Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 44
Filtrar
1.
N Engl J Med ; 387(19): 1759-1769, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36278971

RESUMO

BACKGROUND: Invasive mechanical ventilation in critically ill adults involves adjusting the fraction of inspired oxygen to maintain arterial oxygen saturation. The oxygen-saturation target that will optimize clinical outcomes in this patient population remains unknown. METHODS: In a pragmatic, cluster-randomized, cluster-crossover trial conducted in the emergency department and medical intensive care unit at an academic center, we assigned adults who were receiving mechanical ventilation to a lower target for oxygen saturation as measured by pulse oximetry (Spo2) (90%; goal range, 88 to 92%), an intermediate target (94%; goal range, 92 to 96%), or a higher target (98%; goal range, 96 to 100%). The primary outcome was the number of days alive and free of mechanical ventilation (ventilator-free days) through day 28. The secondary outcome was death by day 28, with data censored at hospital discharge. RESULTS: A total of 2541 patients were included in the primary analysis. The median number of ventilator-free days was 20 (interquartile range, 0 to 25) in the lower-target group, 21 (interquartile range, 0 to 25) in the intermediate-target group, and 21 (interquartile range, 0 to 26) in the higher-target group (P = 0.81). In-hospital death by day 28 occurred in 281 of the 808 patients (34.8%) in the lower-target group, 292 of the 859 patients (34.0%) in the intermediate-target group, and 290 of the 874 patients (33.2%) in the higher-target group. The incidences of cardiac arrest, arrhythmia, myocardial infarction, stroke, and pneumothorax were similar in the three groups. CONCLUSIONS: Among critically ill adults receiving invasive mechanical ventilation, the number of ventilator-free days did not differ among groups in which a lower, intermediate, or higher Spo2 target was used. (Supported by the National Heart, Lung, and Blood Institute and others; PILOT ClinicalTrials.gov number, NCT03537937.).


Assuntos
Estado Terminal , Oxigênio , Respiração Artificial , Adulto , Humanos , Estado Terminal/terapia , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Oxigênio/administração & dosagem , Oxigênio/sangue , Oxigênio/uso terapêutico , Respiração Artificial/métodos , Cuidados Críticos/métodos , Estudos Cross-Over , Serviço Hospitalar de Emergência , Centros Médicos Acadêmicos , Oximetria
2.
BMJ Open ; 11(10): e052013, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34711597

RESUMO

INTRODUCTION: Mechanical ventilation of intensive care unit (ICU) patients universally involves titration of the fraction of inspired oxygen to maintain arterial oxygen saturation (SpO2). However, the optimal SpO2 target remains unknown. METHODS AND ANALYSIS: The Pragmatic Investigation of optimaL Oxygen Targets (PILOT) trial is a prospective, unblinded, pragmatic, cluster-crossover trial being conducted in the emergency department (ED) and medical ICU at Vanderbilt University Medical Center in Nashville, Tennessee, USA. PILOT compares use of a lower SpO2 target (target 90% and goal range: 88%-92%), an intermediate SpO2 target (target 94% and goal range: 92%-96%) and a higher SpO2 target (target 98% and goal range: 96%-100%). The study units are assigned to a single SpO2 target (cluster-level allocation) for each 2-month study block, and the assigned SpO2 target switches every 2 months in a randomly generated sequence (cluster-level crossover). The primary outcome is ventilator-free days (VFDs) to study day 28, defined as the number of days alive and free of invasive mechanical ventilation from the final receipt of invasive mechanical ventilation through 28 days after enrolment. ETHICS AND DISSEMINATION: The trial was approved by the Vanderbilt Institutional Review Board. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. TRIAL REGISTRATION NUMBER: The trial protocol was registered with ClinicalTrials.gov on 25 May 2018 prior to initiation of patient enrolment (ClinicalTrials.gov identifier: NCT03537937).


Assuntos
COVID-19 , Humanos , Oxigênio , Estudos Prospectivos , Respiração Artificial , SARS-CoV-2
3.
AJOB Empir Bioeth ; 10(4): 215-221, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31593523

RESUMO

Introduction: Patient advocacy organizations (PAOs) provide patient education, raise public awareness, and influence health policy for a wide range of diseases. These organizations frequently receive financial support form from drug, device, and biotechnology companies. Though PAOs often develop policies to address institutional conflicts of interest arising from industry relations, little is known about the substance of these policies. Methods: We sampled all PAOs that are members of the National Health Council. Using a standardized search strategy, all policies were obtained from each organization if publicly available. We reviewed policies for content related to restrictions on corporate partnerships, disclosure of corporate funding, and governance and monitoring of corporate partnerships. Results: We found that 24 of 47 (51%) organizations had policies that addressed institutional conflict of interest. A total of 9 of those 24 (38%) policies placed any restriction on the types of corporations that the PAO would or would not partner with. While 16 of the 24 (67%) outlined some process for disclosure of the organization's corporate donors, only 5 of 24 (21%) specified a manner for disclosing the financial value of those donations. Further, 15 of the 24 (63%) policies identified the person or persons responsible for approving corporate partnerships. However, 17 (71%) failed to address or specify the person(s) responsible for ongoing review of those partnerships. Conclusion: Nearly half of the organizations studied did not have publicly available conflict of interest policies. Among those that did, few policies had a substantial level of detail or limitations to guard against conflicts of interest.


Assuntos
Conflito de Interesses , Revelação/ética , Disseminação de Informação/ética , Defesa do Paciente/ética , Defesa do Paciente/estatística & dados numéricos , Pesquisa Biomédica , Revelação/estatística & dados numéricos , Indústria Farmacêutica/ética , Humanos , Política Organizacional , Confiança
4.
J Bone Joint Surg Am ; 96(9): e71, 2014 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-24806017

RESUMO

BACKGROUND: We hypothesized that a novel surgical method, in which three-dimensional (3-D) preoperative planning software is generated to create a patient-specific surgical model that is used with a reusable and adjustable tool, could substantially improve the positioning accuracy of the glenoid guide pin used in total shoulder arthroplasty. We tested this method using bone models from patients with shoulder pathology and compared the results with those achieved using surgical methods representing the current standard of care. METHODS: Three surgeons with a variety of surgical experience placed a guide pin in nine bone models from patients with a variety of glenohumeral arthritis severity using (1) standard instrumentation alone, (2) standard instrumentation and 3-D preoperative surgical planning, and (3) the reusable transfer device and 3-D preoperative surgical planning. A postoperative 3-D computed tomography scan of the bone model was made and registered to the preoperative plan, and the differences between the actual and planned pin locations and trajectories were measured. RESULTS: Use of the standard instrumentation combined with 3-D preoperative planning software improved guide pin positioning compared with standard instrumentation and preoperative planning using 2-D imaging. The accuracy of pin positioning increased by 4.5° ± 1.0° in version (p < 0.001), 3.3° ± 1.3° in inclination (p = 0.013), and 0.4 ± 0.2 mm in location (p = 0.042). Use of the adjustable and reusable device and the 3-D software improved pin positioning by a further 3.7° ± 0.9° in version, 8.1° ± 1.2° in inclination, and 1.2 ± 0.2 mm in location (p < 0.001 for all) compared with standard instrumentation and the 3-D software; the improvement compared with use of standard instrumentation with 2-D imaging was 8.2° ± 0.9° in version, 11.4° ± 1.2° in inclination, and 1.7 ± 0.2 mm in location (p < 0.001 for all). CONCLUSIONS: Use of 3-D preoperative planning and use of the patient-specific bone model and transfer device both improved the positioning accuracy of the pin used to guide placement of the glenoid component in total shoulder arthroplasty. CLINICAL RELEVANCE: Proper positioning of the glenoid component would be expected to improve the function and durability of the joint replacement.


Assuntos
Artroplastia de Substituição/métodos , Cavidade Glenoide/cirurgia , Articulação do Ombro/cirurgia , Software , Pinos Ortopédicos , Simulação por Computador , Humanos , Imageamento Tridimensional/métodos , Informática Médica , Modelos Anatômicos , Planejamento de Assistência ao Paciente , Cuidados Pré-Operatórios/métodos , Análise de Regressão , Cirurgia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X
5.
Apoptosis ; 18(5): 566-77, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23456624

RESUMO

Apoptotic injury participates in hepatic fibrosis, but the molecular mechanisms are not well understood. The present study aimed to investigate the role of inducible TIMP1 in the pathogenesis of hepatic apoptosis-fibrosis. Apoptosis was induced with GCDC, LPS, and alcohol in precision-cut liver slices or bile duct ligation (BDL) in rats, as reflected by caspase-3 activity, TUNEL assay, and apoptosis-related gene profiles. The hepatic fibrosis was detected with Picrosirius staining, hydroxyproline determination, and expression profiling of fibrosis-related genes. Levels of TIMP1 were upregulated by the hepatic apoptosis, but downregulated by caspase inhibitor. The inducible TIMP1 was apoptosis-dependent. Once TIMP1 was inhibited with treatment of TIMP1-siRNA, the fibrotic response was reduced as demonstrated by hydroxyproline assay. In addition, the expression of fibrosis-related genes aSMA, CTGF, and TGFb2r were down-regulated subsequent to the treatment of TIMP1-siRNA. TIMP1 could mediate the expression of fibrosis-related genes. TIMP1 was transcriptionally regulated by nuclear factor c-Jun as demonstrated by EMSA and ChIP assay. The treatment of c-Jun siRNA could significantly decrease the expression of TIMP1 induced by alcohol, GCDC, or LPS treatment. Hepatic apoptosis induces the expression of TIMP1. Inducible TIMP1 can modulate the expression of fibrosis-related genes in liver. TIMP1 pathway is a potential target for therapeutic intervention of fibrotic liver diseases.


Assuntos
Apoptose/genética , Cirrose Hepática/metabolismo , Fígado/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genética , Actinas/genética , Actinas/metabolismo , Animais , Biomarcadores/metabolismo , Inibidores de Caspase/farmacologia , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Etanol , Regulação da Expressão Gênica , Ácido Glicoquenodesoxicólico , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Cirrose Hepática/patologia , Microtomia , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais , Técnicas de Cultura de Tecidos , Inibidor Tecidual de Metaloproteinase-1/antagonistas & inibidores , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Crescimento Transformador beta2/genética , Fator de Crescimento Transformador beta2/metabolismo
6.
Cell Signal ; 25(4): 867-74, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23275033

RESUMO

UNLABELLED: Hepatocyte apoptosis is a ubiquitous feature of chronic liver injury, but the molecular mechanism remains to be determined. The liver-enriched Foxa2 transcription factor has been implicated in inflammation and neoplasia. Foxa2 may play a role in the regulation of apoptosis. This study aimed to investigate the relationship between Foxa2 and hepatic apoptosis. Apoptosis was induced with different causative factors as measured by caspase activity and TUNEL assay. Results showed that the apoptotic injury was associated with a downregulation of Foxa2. Foxa2-expressing vectors decreased apoptosis, whereas siRNA silencing of Foxa2 increased apoptosis in HepG2 cells. Foxa2 was correlated with expression profiling of anti-apoptotic genes cIAP1, cIAP2, XIAP, and survivin. Significantly, the cIAP1 expression was decreased by siRNA silencing of Foxa2, but increased by Foxa2-expressing vectors. The promoter of cIAP1 had specific DNA sequences that could be bound by Foxa2 nuclear protein as demonstrated by EMSA and gel supershift assay. The cIAP1 promoter was also occupied by Foxa2 nuclear factor through ChIP assay. Deletion of putative Foxa2 binding domains in cIAP1 promoter significantly reduced its promoter activity. CONCLUSION: A mechanism by which Foxa2 transcription factor modulates hepatic apoptosis may be through cIAP1 signaling pathway. Foxa2 can be a potential target for therapeutic intervention in liver diseases.


Assuntos
Apoptose , Fator 3-beta Nuclear de Hepatócito/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Animais , Células Cultivadas , Regulação para Baixo , Ensaio de Desvio de Mobilidade Eletroforética , Células Hep G2 , Fator 3-beta Nuclear de Hepatócito/antagonistas & inibidores , Fator 3-beta Nuclear de Hepatócito/genética , Hepatócitos/citologia , Hepatócitos/metabolismo , Humanos , Proteínas Inibidoras de Apoptose/genética , Fígado/lesões , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Survivina , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo
7.
J Bone Joint Surg Am ; 94(23): 2167-75, 2012 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-23224387

RESUMO

BACKGROUND: Glenoid component malposition for anatomic shoulder replacement may result in complications. The purpose of this study was to define the efficacy of a new surgical method to place the glenoid component. METHODS: Thirty-one patients were randomized for glenoid component placement with use of either novel three-dimensional computed tomographic scan planning software combined with patient-specific instrumentation (the glenoid positioning system group), or conventional computed tomographic scan, preoperative planning, and surgical technique, utilizing instruments provided by the implant manufacturer (the standard surgical group). The desired position of the component was determined preoperatively. Postoperatively, a computed tomographic scan was used to define and compare the actual implant location with the preoperative plan. RESULTS: In the standard surgical group, the average preoperative glenoid retroversion was -11.3° (range, -39° to 17°). In the glenoid positioning system group, the average glenoid retroversion was -14.8° (range, -27° to 7°). When the standard surgical group was compared with the glenoid positioning system group, patient-specific instrumentation technology significantly decreased (p < 0.05) the average deviation of implant position for inclination and medial-lateral offset. Overall, the average deviation in version was 6.9° in the standard surgical group and 4.3° in the glenoid positioning system group. The average deviation in inclination was 11.6° in the standard surgical group and 2.9° in the glenoid positioning system group. The greatest benefit of patient-specific instrumentation was observed in patients with retroversion in excess of 16°; the average deviation was 10° in the standard surgical group and 1.2° in the glenoid positioning system group (p < 0.001). Preoperative planning and patient-specific instrumentation use resulted in a significant improvement in the selection and use of the optimal type of implant and a significant reduction in the frequency of malpositioned glenoid implants. CONCLUSIONS: Novel three-dimensional preoperative planning, coupled with patient and implant-specific instrumentation, allows the surgeon to better define the preoperative pathology, select the optimal implant design and location, and then accurately execute the plan at the time of surgery.


Assuntos
Artroplastia de Substituição/métodos , Diagnóstico por Computador/instrumentação , Imageamento Tridimensional/métodos , Articulação do Ombro/diagnóstico por imagem , Software , Idoso , Feminino , Seguimentos , Humanos , Prótese Articular , Masculino , Pessoa de Meia-Idade , Medição da Dor , Cuidados Pós-Operatórios/métodos , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos , Desenho de Prótese , Radiografia , Amplitude de Movimento Articular/fisiologia , Medição de Risco , Articulação do Ombro/fisiopatologia , Articulação do Ombro/cirurgia , Instrumentos Cirúrgicos/normas , Resultado do Tratamento
8.
Cell Signal ; 23(10): 1677-85, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21693187

RESUMO

Inducible nitric oxide synthase (iNOS) and nitric oxide (NO) can ameliorate apoptosis induced by toxic glycochenodeoxycholate (GCDC) in hepatocytes. However, the underlying molecular mechanisms are not yet understood in detail. This study is to clarify the function of iNOS/NO and its mechanisms during the apoptotic process. The apoptosis was brought about by GCDC in rat primary hepatocytes. iNOS/NO signaling was then investigated. iNOS inhibitor 1400W enhanced the GCDC-induced apoptosis as reflected by caspase-3 activity and TUNEL assay. Exogenous NO regulated the apoptosis subsequent to NO donor S-nitroso-N-acetyl-penicillamine (SNAP) or sodium nitroprusside (SNP). The GCDC-induced apoptosis was decreased with 0.1mM SNAP or 0.15mM SNP, while it was increased with 0.8mM SNAP or 1.2mM SNP. The endogenous iNOS inhibited apoptosis, but the exogenous NO played a dual role during the GCDC-induced apoptosis. There was a potential iNOS/Akt/survivin axis that inhibited the hepatocyte apoptosis in low doses of NO donors. In contrast, high doses of NO donors activated CHOP through p38MAP-kinase (p38MAPK), upregulated TRAIL receptor DR5, and suppressed survivin. Consequently the high doses of NO donors promoted the apoptosis in hepatocytes. Our data suggest that the iNOS/NO signaling can modulate Akt/survivin and p38MAPK/CHOP pathways to mediate the GCDC-induced the apoptosis in hepatocytes. These signaling pathways may serve as targets for therapeutic intervention in cholestatic liver disease.


Assuntos
Apoptose , Ácido Glicoquenodesoxicólico/farmacologia , Hepatócitos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/farmacologia , Transdução de Sinais , Amidinas/farmacologia , Animais , Benzilaminas/farmacologia , Western Blotting , Células Cultivadas , Ensaio de Desvio de Mobilidade Eletroforética , Inibidores Enzimáticos/metabolismo , Hepatócitos/metabolismo , Imidazóis/farmacologia , Proteínas Associadas aos Microtúbulos/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Nitroprussiato/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , S-Nitroso-N-Acetilpenicilamina/farmacologia , Survivina , Transfecção , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
Biochim Biophys Acta ; 1813(8): 1395-403, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21539866

RESUMO

Inducible nitric oxide synthase (iNOS) and nitric oxide (NO) involve many pathophysiologic conditions. The expression of iNOS is regulated at multiple stages. Presently, the regulatory details of iNOS signaling are still unclear. This study aimed to investigate the regulatory role of C/EBPα and C/EBPß in iNOS signaling pathway. By employing the techniques such as EMSA, ChIP assay, site-directed mutagenesis, and siRNA silencing, the relationship between iNOS and C/EBPα/C/EBPß in rat hepatocytes was clarified. iNOS promoter was the direct transcriptional targets of the C/EBPα, C/EBPß, and NF-κB binding proteins. There was the interactive influence between NF-κB and C/EBPα/C/EBPß. The expression of iNOS was modulated by C/EBPα/C/EBPß transcription factors. Moreover, the iNOS expression mediated glycochenodeoxycholate (GCDC)-induced apoptosis in hepatocytes. C/EBPα/C/EBPß binding proteins could affect the GCDC-induced apoptosis through iNOS cascade. These findings indicate that C/EBPα and C/EBPß regulate the iNOS expression, which may further modify cell responses such as apoptosis and cell survival.


Assuntos
Apoptose/fisiologia , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Hepatócitos/citologia , Hepatócitos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Sequência de Bases , Sítios de Ligação/genética , Proteína alfa Estimuladora de Ligação a CCAAT/antagonistas & inibidores , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/antagonistas & inibidores , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteínas de Transporte/metabolismo , Primers do DNA/genética , Ácido Glicoquenodesoxicólico/farmacologia , Hepatócitos/efeitos dos fármacos , Técnicas In Vitro , Mutagênese Sítio-Dirigida , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Regiões Promotoras Genéticas , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
11.
Angiology ; 62(1): 46-8, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20529976

RESUMO

PURPOSE: To describe the safety and efficacy of percutaneous transluminal angioplasty and stent placement in patients presenting with suprahepatic inferior vena cava (IVC) outflow compromise in the early postoperative period following orthotopic liver transplantation. METHODS AND RESULTS: Between October 2002 and April 2009, 3 patients presented with IVC outflow compromise in the first 2 months following orthotopic liver transplantation. All 3 underwent percutaneous transluminal angioplasty and stent placement without complication and showed significant clinical improvement at short and intermediate term follow-up. CONCLUSION: Percutaneous transluminal angioplasty and Gianturco stent placement is a safe and effective treatment for IVC outflow compromise in the early postoperative period following orthotopic liver transplantation.


Assuntos
Angioplastia , Transplante de Fígado/efeitos adversos , Stents , Doenças Vasculares/etiologia , Doenças Vasculares/terapia , Veia Cava Inferior , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segurança
12.
Biochim Biophys Acta ; 1803(12): 1368-75, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20816704

RESUMO

UNLABELLED: Hepatocytes in primary culture undergo apoptosis upon exposure to glycochenodeoxycholate (GCDC). The signaling mechanisms of GCDC-induced apoptosis remain unclear. To investigate the role of antiapoptotic genes, we compared apoptotic response in primary hepatocytes following GCDC treatment. The hepatocytes from adult Sprague-Dawley rats were cultured in collagen-coated dishes and treated with GCDC in varying concentrations, or the same concentration at different time intervals. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, DNA fragmentation assay, and caspase assays. Expression of apoptosis-related genes and proteins was evaluated by RT-PCR, quantitative real-time PCR (qRT-PCR), and Western blotting, respectively. The DNA-binding property of a nuclear protein was assessed by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay. An interesting result was that GCDC caused hepatocyte apoptosis to display a biphasic phenomenon at a dosage of 50µM, whereas it was not found at higher dosages such as 200µM. GCDC stimulated the expression of antiapoptotic Survivin, which also presented a biphasic response. The activation of nuclear factor-kappaB (NF-κB) corresponded with the up-regulation of Survivin. The inhibitor of NF-κB, BAY 11-7082, suppressed the expression of Survivin and simultaneously eliminated the biphasic response. The expression of Survivin was transcriptionally mediated by the activation of NF-κB, as shown by EMSA and ChIP assay. CONCLUSIONS: These results demonstrated that a low dosage of GCDC induced the hepatocyte apoptosis to exhibit the biphasic response, which was regulated by the expression of Survivin through NF-κB signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Ácido Glicoquenodesoxicólico/toxicidade , Proteínas Associadas aos Microtúbulos/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Animais , Ratos , Ratos Sprague-Dawley , Survivina
13.
J Shoulder Elbow Surg ; 19(8): 1243-9, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20558091

RESUMO

HYPOTHESIS: This study evaluated the intra-rater and inter-rater correlation of 3 commonly used x-ray image classifications and defined the clinical factors most correlated with a surgical recommendation for a hemiarthroplasty or a reverse total shoulder arthroplasty (RSA) for treatment of rotator cuff tear arthropathy (CTA). We hypothesized that specific radiographic criteria and clinical criteria would be most important and consistently used among experienced shoulder surgeons when determining the best surgical option for a particular patient. METHODS: Four experienced orthopedic surgeons evaluated standard anteroposterior radiographs and the clinical examination of 37 shoulders with CTA. On each reading, they classified the grade of pathology using the Seebauer, Favard, and Hamada classifications. Using radiographic criteria alone, or with the clinical findings, each evaluator determined the recommended prosthetic treatment for each shoulder. RESULTS: Intra-rater correlations for surgical recommendations using radiographic criteria ranged from 0.39 to 1.0 and improved in 3 of 4 evaluators when the clinical examination was included in the clinical decision. The inter-rater reliability using these same criteria were fair, at 0.32 for radiographic and .35 for radiographic and clinical data. The most significant radiographic factors associated with a surgical decision were the degree of humeral head superior migration and the escape of the humeral head from the coracoacromial arch. Clinical factors most associated with the decision for RSA were advanced age, loss of shoulder elevation, superior humeral head escape, and pseudoparalysis of the shoulder. Radiographic findings had a less significant effect on surgical recommendations when clinical factors were included. CONCLUSION: Clinical and radiographic criteria are needed for a decision for hemiarthroplasty or RSA in the treatment of CTA. A treatment algorithm based upon radiographic and clinical criteria is proposed.


Assuntos
Artrite/diagnóstico por imagem , Lesões do Manguito Rotador , Idoso , Idoso de 80 Anos ou mais , Artrite/classificação , Artrite/cirurgia , Artroplastia , Artroplastia de Substituição , Tomada de Decisões , Feminino , Humanos , Prótese Articular , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Radiografia , Estudos Retrospectivos , Manguito Rotador/diagnóstico por imagem
15.
J Bone Joint Surg Am ; 90(11): 2438-45, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18978413

RESUMO

BACKGROUND: Arthritic changes to glenoid morphology can be difficult to fully characterize on both plain radiographs and conventional two-dimensional computer tomography images. We tested the hypothesis that three-dimensional imaging of the shoulder would increase inter-rater agreement for assessing the extent and location of glenoid bone loss and also would improve surgical planning for total shoulder arthroplasty. METHODS: Four shoulder surgeons independently and retrospectively reviewed the preoperative computed tomography scans of twenty-four arthritic shoulders. The blinded images were evaluated with conventional two-dimensional imaging software and then later with novel three-dimensional imaging software. Measurements and preoperative judgments were made for each shoulder with use of each imaging modality and then were compared. The glenoid measurements were glenoid version and bone loss. The judgments were the zone of maximum glenoid bone loss, glenoid implant fit within the glenoid vault, and how to surgically address abnormal glenoid version and bone loss. Agreement between observers was evaluated with use of intraclass correlation coefficients and the weighted kappa coefficient (kappa), and we determined if surgical decisions changed with use of the three-dimensional data. RESULTS: The average glenoid version (and standard deviation) measured -17 degrees +/- 2.2 degrees on the two-dimensional images and -19 degrees +/- 2.4 degrees on the three-dimensional images (p < 0.05). The average posterior glenoid bone loss measured 9 +/- 2.3 mm on the two-dimensional images and 7 +/- 2 mm on the three-dimensional images (p < 0.05). The average anterior bone loss measured 1 mm on both the two-dimensional and the three-dimensional images. However, the intraclass correlation coefficients for anterior bone loss increased significantly with use of the three-dimensional data (from 0.36 to 0.70; p < 0.05). Observers were more likely to locate mid-anterior glenoid bone loss on the basis of the three-dimensional data (p < 0.05). The use of three-dimensional data provided greater agreement among observers with regard to the zone of glenoid bone loss, glenoid prosthetic fit, and surgical decision-making. Also, when the judgment of implant fit changed, observers more often determined that it would violate the vault walls on the basis of the three-dimensional data (p < 0.05). CONCLUSIONS: The use of three-dimensional imaging can increase inter-rater agreement for the analysis of glenoid morphology and preoperative planning. Important considerations such as the extent and location of glenoid bone loss and the likelihood of implant fit were influenced by the three-dimensional data.


Assuntos
Artroplastia de Substituição/métodos , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Osteoartrite/diagnóstico por imagem , Osteoartrite/cirurgia , Estudos Retrospectivos
16.
J Shoulder Elbow Surg ; 17(4): 575-7, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18440832

RESUMO

To our knowledge, no independent analysis of the inter-rater agreement of the widely used Walch classification for osteoarthritic glenoid morphology has been performed. The computed tomography scans of 24 shoulders with primary osteoarthritis were used by 4 experienced shoulder surgeons to classify the glenoids independently according to Walch et al. The weighted kappa statistic was calculated to determine the inter-rater and intrarater agreement among observers. The overall inter-rater agreement for the Walch classification was fair (kappa = 0.37) when classified into the 5 types (A1, A2, B1, B2, and C). Agreement for the various subclassifications was as follows: A1, kappa = 0.22; A2, kappa = 0.33; B1, kappa = 0.17; B2, kappa = 0.32; and C, kappa = 0.86. When the classification system was simplified to just the 3 major types (A, B, and C), overall agreement was moderate (kappa = 0.44). Agreement for each type was moderate for A (kappa = 0.59) and B (kappa = 0.59) and almost perfect for C (kappa = 0.89). Overall intrarater agreement was fair (kappa = 0.37). We conclude that only fair agreement was found among experienced shoulder surgeons when classifying arthritic shoulders using the classification system of Walch et al. A glenoid classification scheme that relies more upon glenoid morphology and less upon humeral head position may demonstrate greater observer agreement and, therefore, may offer greater value.


Assuntos
Artrite Reumatoide/classificação , Osteoartrite/classificação , Articulação do Ombro/diagnóstico por imagem , Idoso , Artrite Reumatoide/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Osteoartrite/diagnóstico por imagem , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X
17.
J Shoulder Elbow Surg ; 17(3): 471-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18328741

RESUMO

Current glenoid implants are designed to be secured to the articular surface. When the articular surface is compromised, a glenoid component could be implanted if it obtained fixation from the endosteal surface of the glenoid vault. The first step for designing such a glenoid implant is to define the normal three-dimensional anatomy of the glenoid vault. The purpose of this study was to define the variations in glenoid vault shape in a large group of cadaver scapula. Computed tomographic (CT) scans of 61 normal scapulae (mean, 25-34 years) from the Haman-Todd Osteological Collection, with a wide range of sizes, were examined to define the normal glenoid vault anatomy. A custom software program was used to manipulate and measure the scans to determine the morphologic variations among the different glenoid vaults. From these data, we defined a unique glenoid vault shape and empirically developed 5 sizes to represent the study population of the 61 scapulae. A second group of 11 cadaver scapulae were used to validate the shape defined using the other 61. Prototype implants were placed into the real 11 scapulae using standard surgical techniques and then CT-scanned to analyze the shape of the glenoid vault. In the 61 scapulae, 85% of the points defining the endosteal surfaces vary among scapulae by less than 2 mm. For each of the 11 cadaver scapulae, the implant size used in the virtual computer implantation was the same size used for the plastic components placed into the cadaver scapulae. Fifty percent of the measured distances between the outer dimensions of the plastic models was within 2.4 mm of the glenoid endosteal surface. Eighty percent of the surface area of the plastic models was within 3.1 mm of the glenoid endosteal surface. Five percent of the dimensions were less than 1 mm and were considered to be areas of point contact. Before designing implants that can be used in pathologic glenoids, the shape of the normal glenoid vault must first be defined. This study defined a normal glenoid vault shape that can accommodate different sized scapula with 5 sizes. This glenoid shape may be used as a template to design a glenoid implant that obtains fixation within the glenoid vault.


Assuntos
Prótese Articular , Desenho de Prótese , Articulação do Ombro/anatomia & histologia , Adulto , Cadáver , Feminino , Humanos , Masculino , Escápula/diagnóstico por imagem , Articulação do Ombro/diagnóstico por imagem , Tomografia Computadorizada por Raios X
18.
Cleve Clin J Med ; 75(1): 50-6, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18236730

RESUMO

Nonspinal musculoskeletal disorders frequently cause neck and back pain and thus can mimic conditions of the spine. Common mimics are rotator cuff tears, bursitis in the hip, peripheral nerve compression, and arthritis in the shoulder and hip. A thorough history and physical examination, imaging studies, and ancillary testing can usually help determine the source of pain.


Assuntos
Dor nas Costas/etiologia , Doenças Musculoesqueléticas/diagnóstico , Doenças da Coluna Vertebral/diagnóstico , Dor nas Costas/diagnóstico , Diagnóstico Diferencial , Humanos , Doenças Musculoesqueléticas/complicações , Doenças Musculoesqueléticas/patologia , Síndromes de Compressão Nervosa , Fatores de Risco , Doenças da Coluna Vertebral/patologia
19.
J Shoulder Elbow Surg ; 17(2): 328-35, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18218326

RESUMO

The 3-dimensional (3D) shape of the glenoid vault has been defined previously and shown to be a complex, yet consistent, shape in individuals without glenoid pathology. We proposed assessing whether this conserved shape could be used as a template to measure glenoid bone loss in subjects with glenohumeral osteoarthritis. Computed tomography (CT) scans of both shoulders were obtained from 12 subjects with unilateral glenohumeral osteoarthritis. The paired scapulae were reconstructed 3-dimensionally, using a previously developed graphic software package. Two methods of estimating glenoid bone loss were performed. First, using the software, a stereolithography model of the standardized vault shape was implanted into each glenoid and measurements made of the volume of the implant not contained within each vault. Second, direct measurements of the paired glenoid vault volumes were performed. The volume of the nonarthritic glenoid was used as a subject-specific template for normal glenoid vault volume for each pair. The glenoid bone volumes measured by each method were compared and Pearson's correlation coefficient determined. The average measurement of glenoid bone loss using the vault implant was within 0.8% (SD +/- 1.5%) of the measurement made using the contralateral, normal glenoid. For all patients, Pearson's correlation coefficient was .99, indicating a very high correlation between the two methods of measuring bone loss (P < .0001). The intricate, yet consistent 3D shape of the glenoid vault can be used as an accurate and reliable template to measure glenoid bone loss in glenohumeral osteoarthritis.


Assuntos
Doenças Ósseas/diagnóstico por imagem , Osteoartrite/diagnóstico por imagem , Articulação do Ombro/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA