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1.
J Am Coll Surg ; 236(6): 1093-1103, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36815715

RESUMO

BACKGROUND: Surgical risk prediction models traditionally use patient attributes and measures of physiology to generate predictions about postoperative outcomes. However, the surgeon's assessment of the patient may be a valuable predictor, given the surgeon's ability to detect and incorporate factors that existing models cannot capture. We compare the predictive utility of surgeon intuition and a risk calculator derived from the American College of Surgeons (ACS) NSQIP. STUDY DESIGN: From January 10, 2021 to January 9, 2022, surgeons were surveyed immediately before performing surgery to assess their perception of a patient's risk of developing any postoperative complication. Clinical data were abstracted from ACS NSQIP. Both sources of data were independently used to build models to predict the likelihood of a patient experiencing any 30-day postoperative complication as defined by ACS NSQIP. RESULTS: Preoperative surgeon assessment was obtained for 216 patients. NSQIP data were available for 9,182 patients who underwent general surgery (January 1, 2017 to January 9, 2022). A binomial regression model trained on clinical data alone had an area under the receiver operating characteristic curve (AUC) of 0.83 (95% CI 0.80 to 0.85) in predicting any complication. A model trained on only preoperative surgeon intuition had an AUC of 0.70 (95% CI 0.63 to 0.78). A model trained on surgeon intuition and a subset of clinical predictors had an AUC of 0.83 (95% CI 0.77 to 0.89). CONCLUSIONS: Preoperative surgeon intuition alone is an independent predictor of patient outcomes; however, a risk calculator derived from ACS NSQIP is a more robust predictor of postoperative complication. Combining intuition and clinical data did not strengthen prediction.


Assuntos
Intuição , Cirurgiões , Humanos , Estados Unidos , Prognóstico , Medição de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Fatores de Risco , Estudos Retrospectivos , Melhoria de Qualidade
2.
Am Surg ; : 31348221146932, 2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36564886

RESUMO

BACKGROUND: Trainees and attending surgeons alike have concerns about resident and fellow operative volume/breadth, competency, and overall readiness for practice. This is an important topic within surgical graduate medical education. Our goal was to analyze the change in general surgery trainee operative experience over time by postgraduate year. METHODS: Institutional operative records from two corresponding three-month time periods in 2009 and 2018 at the residency program's main hospital site were reviewed. Cases assisted on by general, vascular, or thoracic surgery trainees were included. The number of cases per level, combination of trainees in each case, and categories of cases were compared over time. RESULTS: There were 1940 cases in 2009 and 1967 cases in 2018 over the respective time periods. The distribution of trainees was different (P < .001), with a similar number of PGY-1 and fellow cases, a decrease in PGY-2 and PGY-5 cases, and an increase in PGY-3 and PGY-4 cases. The number of cases with two trainees, double scrubbed cases, increased from 19.6% to 26.8% (P < .001). In addition, there were differences in the resident years that double scrubbed cases together, an increase in robotic and endovascular surgery, and a decrease in open cases. CONCLUSIONS: This analysis of cases shows that resident operative volume over approximately a decade has been largely preserved, with some change in the distribution of cases based on trainee level, an increase in cases with more than one trainee, and a rise of minimally invasive surgery with a corresponding decrease in open cases.

3.
Am Surg ; 88(6): 1137-1145, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33522831

RESUMO

BACKGROUND: Though many trauma patients are on anticoagulation or antiplatelet therapy (AAT), there are few generalizable data on the risks for these patients. The purpose of this study was to analyze the impact of anticoagulation (AC) and antiplatelet (AP) therapy on mortality and length of stay (LOS) in general trauma patients. METHODS: A retrospective review was performed of patients in the institutional trauma registry during 2019 to determine AAT use on admission and discharge. Outcomes were compared using standard statistics. RESULTS: Of 2261 patients who met the inclusion criteria, 2 were excluded due to an incomplete medication reconciliation, resulting in 2259 patients. Patients on AAT had a higher mortality (4.5% vs 2.1%). On multivariable analysis, preadmission AC (odds ratio OR, 3.325, P = .001), age (OR 1.040, P < .001), and injury severity score ((ISS) 1.094, P < .001) were associated with mortality. Anticoagulation use was also associated with longer LOS on multivariable analysis (OR: 1.626, P = .005). Antiplatelet use was not associated with higher mortality or longer LOS. More patients on AAT were unable to be discharged home. However, patients on AAT did not have a greater blood transfusion requirement or need more hemorrhage control procedures. Lastly, 23.7% of patients on preadmission AAT were not discharged on any AAT. DISCUSSION: These data demonstrate that patients on AC, but not AP, have greater mortality and longer hospital LOS. This may provide guidance for those being newly started on AAT. Further work to determine which patients benefit most from restarting AAT would lead to improvement in the care of trauma patients.


Assuntos
Anticoagulantes , Hemorragia , Anticoagulantes/uso terapêutico , Hemorragia/induzido quimicamente , Humanos , Escala de Gravidade do Ferimento , Tempo de Internação , Estudos Retrospectivos
5.
Neurosurgery ; 88(4): 773-778, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33469647

RESUMO

BACKGROUND: Routine follow-up head imaging in complicated mild traumatic brain injury (cmTBI) patients has not been shown to alter treatment, improve outcomes, or identify patients in need of neurosurgical intervention. We developed a follow-up head computed tomography (CT) triage algorithm for cmTBI patients to decrease the number of routine follow-up head CT scans obtained in this population. OBJECTIVE: To report our experience with protocol implications and patient outcome. METHODS: Data on all cmTBI patients presenting from July 1, 2018 to June 31, 2019, to our level 1, tertiary, academic medical center were collected prospectively and analyzed retrospectively. Descriptive analysis was performed. RESULTS: Of the 178 patients enrolled, 52 (29%) received a follow-up head CT. A total of 27 patients (15%) were scanned because of initial presentation and triaged to the group to receive a routine follow-up head CT. A total of 151 patients (85%) were triaged to the group without routine follow-up head CT scan. Protocol adherence was 89% with 17 violations. CONCLUSION: Utilizing this protocol, we were able to safely decrease the use of routine follow-up head CT scans in cmTBI patients by 71% without any missed injuries or delayed surgery. Adoption of the protocol was high among all services managing TBI patients.


Assuntos
Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/terapia , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Testes Diagnósticos de Rotina/métodos , Feminino , Seguimentos , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
6.
Intensive Care Med ; 46(10): 1884-1893, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32885276

RESUMO

PURPOSE: ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine, an oral α1-adrenergic agonist, as adjunct to standard treatment shortens the duration of intravenous vasopressor requirement. METHODS: In this multicentre, randomised, controlled trial including three tertiary referral hospitals in the US and Australia, we enrolled adult patients with hypotension requiring a single-agent intravenous vasopressor for ≥ 24 h. Subjects received oral midodrine (20 mg) or placebo every 8 h in addition to standard care until cessation of intravenous vasopressors, ICU discharge, or occurrence of adverse events. The primary outcome was time to vasopressor discontinuation. Secondary outcomes included time to ICU discharge readiness, ICU and hospital lengths of stay, and ICU readmission rates. RESULTS: Between October 2012 and June 2019, 136 participants were randomised, of whom 132 received the allocated intervention and were included in the analysis (modified intention-to-treat approach). Time to vasopressor discontinuation was not different between midodrine and placebo groups (median [IQR], 23.5 [10-54] vs 22.5 [10.4-40] h; difference, 1 h; 95% CI - 10.4 to 12.3 h; p = 0.62). No differences in secondary endpoints were observed. Bradycardia occurred more often after midodrine administration (5 [7.6%] vs 0 [0%], p = 0.02). CONCLUSION: Midodrine did not accelerate liberation from intravenous vasopressors and was not effective for the treatment of hypotension in critically ill patients.


Assuntos
Hipotensão , Midodrina , Adulto , Austrália , Humanos , Hipotensão/tratamento farmacológico , Unidades de Terapia Intensiva , Vasoconstritores/uso terapêutico
7.
Int J Crit Illn Inj Sci ; 9(2): 87-90, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31334051

RESUMO

Gallbladder volvulus is a rare condition that most commonly occurs in elderly women and often mimics acute cholecystitis in its presentation. This condition is a surgical emergency requiring cholecystectomy as it can lead to gallbladder perforation and bilious peritonitis with high morbidity to the patient. An 85-year-old woman with chronic lymphocytic leukemia presented with acute-onset right upper-quadrant abdominal pain and associated nausea with emesis. After admission to the surgical service and initiation of intravenous antibiotics, the patient was taken to the operating room for surgical management due to the persistence of symptoms. Intraoperative findings included a necrotic appearing gallbladder that was twisted on the cystic duct. Laparoscopic cholecystectomy was performed, which was complicated by bile leak requiring endoscopic retrograde cholangiopancreatography with bile duct stenting followed by operative washout. Gallbladder volvulus can be challenging to diagnose. This condition should be suspected in elderly women with acute-onset abdominal pain and imaging concerning for acute cholecystitis. Emergent cholecystectomy is the treatment of choice for gallbladder volvulus.

8.
Am J Surg ; 218(3): 613-618, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30928019

RESUMO

BACKGROUND: We piloted a curriculum combining a flipped classroom with two-stage narration, role-play, and partial task trainer simulation to teach this critical skill to trainees. METHODS: This "flipped classroom" module (2012-2018) for open and percutaneous cricothyroidotomy (OC and PC) required participants to watch two 4 min training videos for OC and PC. The simulation session consisted of a 45-min hands-on simulation of OC and PC in which participants rotated between the roles of operator, narrator, and critiquer. Median performance scores were calculated. RESULTS: 103 trainees were evaluated. The median performance score was 14 out of maximum 14 (range: 9-14) across all trainees for OC. The median performance score was 13 out of maximum 13 (range: 3-13) across all trainees for PC. CONCLUSION: A multi-modality approach including the flipped classroom, role-play, and partial task trainer simulation is an efficient and effective method for teaching trainees proficiency in short, single operator procedures.


Assuntos
Modelos Educacionais , Treinamento por Simulação , Traqueotomia/educação , Currículo , Projetos Piloto
9.
Int J Surg Case Rep ; 33: 79-83, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28285209

RESUMO

PURPOSE: Atrophic visceral myopathy is a pathological diagnosis characterized by atrophy of the smooth muscle layers of the viscera with intact ganglia. Rarely, it can present acutely as an intestinal pseudo-obstruction. We describe a rare case report and explore how this diagnosis can be distinguished from other forms of intestinal obstruction. CASE DESCRIPTION: A 60-year-old male with a past medical history of hypothyroidism presented to the emergency department with a two-day history of worsening abdominal distention and pain associated with nausea and vomiting. Upon evaluation patient was found to have tachycardia, with abdominal distention and localized tenderness with peritonitis. Computed tomography demonstrated large bowel obstruction, likely caused by sigmoid volvulus. The patient underwent emergent laparotomy. Intra-operatively, the entire colon was found to be extremely dilated and redundant. With a working diagnosis of recurrent sigmoid volvulus causing intermittent large bowel obstruction, a sigmoid colectomy and primary anastomosis was performed. Pathology revealed atrophic visceral myopathy, with an extremely thin colonic wall and atrophic circumferential and longitudinal muscularis propria without inflammation or fibrosis. The ganglion cells and myenteric plexus were unaffected. Post-operatively, the patient developed prolonged ileus requiring nasogastric decompression and parenteral nutrition. The ileus resolved with pro-kinetic agents, and patient was discharged home on post-operative day fifteen. CONCLUSIONS: Atrophic visceral neuropathy is a rare cause of intestinal pseudo-obstruction. While often presenting with chronic obstruction in younger populations, we present a rare late-onset acute presentation that may have been secondary to underlying hypothyroidism.

10.
Tissue Eng Part C Methods ; 22(8): 725-39, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27310581

RESUMO

BACKGROUND: A novel potential approach for lung transplantation could be to utilize xenogeneic decellularized pig lung scaffolds that are recellularized with human lung cells. However, pig tissues express several immunogenic proteins, notably galactosylated cell surface glycoproteins resulting from alpha 1,3 galactosyltransferase (α-gal) activity, that could conceivably prevent effective use. Use of lungs from α-gal knock out (α-gal KO) pigs presents a potential alternative and thus comparative de- and recellularization of wild-type and α-gal KO pig lungs was assessed. METHODS: Decellularized lungs were compared by histologic, immunohistochemical, and mass spectrometric techniques. Recellularization was assessed following compartmental inoculation of human lung bronchial epithelial cells, human lung fibroblasts, human bone marrow-derived mesenchymal stromal cells (all via airway inoculation), and human pulmonary vascular endothelial cells (CBF) (vascular inoculation). RESULTS: No obvious differences in histologic structure was observed but an approximate 25% difference in retention of residual proteins was determined between decellularized wild-type and α-gal KO pig lungs, including retention of α-galactosylated epitopes in acellular wild-type pig lungs. However, robust initial recellularization and subsequent growth and proliferation was observed for all cell types with no obvious differences between cells seeded into wild-type versus α-gal KO lungs. CONCLUSION: These proof of concept studies demonstrate that decellularized wild-type and α-gal KO pig lungs can be comparably decellularized and comparably support initial growth of human lung cells, despite some differences in retained proteins. α-Gal KO pig lungs are a suitable platform for further studies of xenogeneic lung regeneration.


Assuntos
Células Epiteliais/citologia , Fibroblastos/citologia , Galactosiltransferases/fisiologia , Pulmão/citologia , Células-Tronco Mesenquimais/citologia , Regeneração/fisiologia , Animais , Animais Geneticamente Modificados , Proliferação de Células , Células Epiteliais/enzimologia , Matriz Extracelular/enzimologia , Fibroblastos/enzimologia , Humanos , Pulmão/enzimologia , Células-Tronco Mesenquimais/enzimologia , Suínos
11.
J Appl Psychol ; 100(1): 40-55, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24820926

RESUMO

In this temporally lagged study of employees in a service organization, we examined the ways in which feedback regarding organizational citizenship behavior (OCB) may affect employees' motives to continue performing OCBs over time. Building on the self-regulation approach to citizenship (Bolino, Harvey, & Bachrach, 2012), we propose and test an overall model of OCB motive, others' attribution and feedback, and motive fulfillment to determine their impact on continuing OCB. Using a total sample of 213 employees and structural equation modeling, we found support for most of our model, indicating that instances of OCB initiate a chain of events that can ultimately lead individuals to alter their OCB patterns, based on their own motives, others' motive attributions, and feedback. We also find that feedback regarding OCB can influence motive fulfillment and the motivations to engage in future OCB, although this feedback is most powerful when it comes from peers, as opposed to managers.


Assuntos
Emprego/psicologia , Retroalimentação Psicológica , Motivação , Cultura Organizacional , Autocontrole , Comportamento Social , Adulto , Humanos
12.
J Surg Educ ; 71(6): e16-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25001063

RESUMO

BACKGROUND: The frenetic pace of inpatient care on surgical services can create barriers to resident teaching of students. Students are often concerned that busy surgical residents will not be able to adequately evaluate their performance at the end of a clerkship. OBJECTIVE: To determine whether the addition of a resident preceptor would increase the satisfaction of students rotating through the general surgery portion of the required third-year surgery clerkship. STUDY DESIGN: Before implementing a resident preceptor model, third-year students rotating on general surgery were administered a 24-item web-based survey regarding their experience on the general surgery portion of the surgery clerkship. General surgery residents were similarly surveyed. A resident preceptor model was then introduced. Subsequent students and residents were surveyed. Presurveys and postsurveys were compared and mean responses analyzed. RESULTS: The addition of a resident preceptor made students more comfortable with asking residents questions (p = 0.02), increased the time students felt was available for developing relationships with residents (p = 0.03), and improved the feeling that residents would be able to accurately evaluate the student's effectiveness as a team member (p = 0.05). The students felt resident teaching on afternoon rounds was increased with the resident preceptor model (p = 0.05). Residents reported spending more time teaching students on morning rounds (p = 0.03). CONCLUSIONS: Implementation of a resident preceptor model resulted in significant improvement in medical students' perceptions of resident teaching effectiveness and ability to accurately evaluate a student's performance.


Assuntos
Estágio Clínico/organização & administração , Cirurgia Geral/educação , Modelos Educacionais , Preceptoria/organização & administração , Adulto , Feminino , Humanos , Internato e Residência , Relações Interprofissionais , Masculino , Desenvolvimento de Programas
13.
Biomaterials ; 35(9): 2664-79, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24411675

RESUMO

Acellular scaffolds from complex whole organs such as lung are being increasingly studied for ex vivo organ generation and for in vitro studies of cell-extracellular matrix interactions. We have established effective methods for efficient de and recellularization of large animal and human lungs including techniques which allow multiple small segments (∼ 1-3 cm(3)) to be excised that retain 3-dimensional lung structure. Coupled with the use of a synthetic pleural coating, cells can be selectively physiologically inoculated via preserved vascular and airway conduits. Inoculated segments can be further sliced for high throughput studies. Further, we demonstrate thermography as a powerful noninvasive technique for monitoring perfusion decellularization and for evaluating preservation of vascular and airway networks following human and porcine lung decellularization. Collectively, these techniques are a significant step forward as they allow high throughput in vitro studies from a single lung or lobe in a more biologically relevant, three-dimensional acellular scaffold.


Assuntos
Pneumopatias/fisiopatologia , Pulmão/patologia , Pulmão/fisiopatologia , Regeneração , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Animais , Cadáver , Células Endoteliais/citologia , Células Epiteliais/citologia , Matriz Extracelular/metabolismo , Fibroblastos/citologia , Humanos , Raios Infravermelhos , Pulmão/ultraestrutura , Pneumopatias/patologia , Espectrometria de Massas , Células-Tronco Mesenquimais/citologia , Perfusão , Sus scrofa , Termografia
14.
Biomaterials ; 35(10): 3281-97, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24461327

RESUMO

Acellular whole human lung scaffolds represent a unique opportunity for ex vivo tissue engineering. However, it remains unclear whether lungs from individuals with chronic lung diseases such as chronic obstructive pulmonary disease (COPD) can be appropriately decellularized and recellularized. To assess this, cadaveric human lungs from normal (non-smoking) patients and from patients with COPD (smoking history) were decellularized and found by histochemical and immunohistochemical staining, electron microscopy, and mass spectrometry to retain characteristic histological architecture and extracellular matrix components (ECM) reflecting either normal or COPD, particularly emphysematous, origin. Inoculation of human bronchial epithelial cells, endothelial progenitor cells, bone marrow-derived mesenchymal stem cells, and lung fibroblasts via airway or vascular routes into small, excised segments of the decellularized lungs demonstrated that normal lung scaffolds robustly supported initial engraftment and growth of each cell type for up to one month. In contrast, despite initial binding, all cell types inoculated into decellularized emphysematous lungs did not survive beyond one week. However, cell attachment and proliferation on solubilized ECM homogenates of decellularized normal and emphysematous lungs coated onto tissue culture plates was comparable and not impaired, suggesting that the 3-dimensional decellularized emphysematous scaffolds may lack the necessary ECM architecture to support sustained cell growth.


Assuntos
Enfisema/patologia , Pulmão/patologia , Linhagem Celular , Proteínas da Matriz Extracelular/metabolismo , Humanos , Espectrometria de Massas , Microscopia Eletrônica
15.
J Nematol ; 41(1): 84-91, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22661780

RESUMO

We studied soil nematode communities from the surface of granite flatrock outcrops in the eastern Piedmont region of the United States. The thin soils that develop here experience high light intensity and extreme fluctuations in temperature and moisture and host unique plant communities. We collected soils from outcrop microsites in Virginia (VA) and North Carolina (NC) in various stages of succession (Primitive, Minimal, and Mature) and compared soil properties and nematode communities to those of adjacent forest soils. Nematodes were present in most outcrop soils, with densities comparable to forest soils (P > 0.05). Nematode communities in Mature and Minimal soils had lower species richness than forest soils (P < 0.05) and contained more bacterial-feeders and fewer fungal-feeders (P < 0.05). Primitive soils contained either no nematodes (NC) or only a single species (Mesodorylaimus sp., VA). Nematode communities were similar between Mature and Minimal soils, according to trophic group representation, MI, PPI, EI, SI, and CI (P > 0.05). Forest soils had a higher PPI value (P < 0.05), but otherwise community indices were similar to outcrop soils (P > 0.05). Outcrop nematode communities failed to group together in a Bray-Curtis cluster analysis, indicating higher variability in community structure than the Forest soils, which did cluster together. A high proportion of the nematodes were extracted from outcrop soils in coiled form (33-89%), indicating that they used anhydrobiosis to persist in this unique environment.

16.
J Appl Psychol ; 92(3): 865-75, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17484566

RESUMO

In this study, the authors examined how individual gender-related attitudes and beliefs affect the reactions of men and women to gender diversity management programs in organizations. They found that whereas there were no significant between-sex differences in the effects of gender diversity management on organizational attractiveness, there were strong within-sex differences based on individual attitudes and beliefs. Specifically, within the sexes, centrality of one's gender identity, attitudes toward affirmative action for women, and the belief that women are discriminated against in the workplace moderated the effects of gender diversity management on organizational attractiveness. The findings, combined with prior research, suggest that it is critical for organizations to incorporate efforts to manage perceptions of gender diversity management programs into their diversity management strategies.


Assuntos
Atitude , Cultura , Emprego/psicologia , Cultura Organizacional , Percepção Social , Adulto , Feminino , Humanos , Masculino , Fatores Sexuais , Inquéritos e Questionários
17.
Am J Respir Cell Mol Biol ; 36(2): 191-200, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16980557

RESUMO

Beryllium (Be)-antigen presentation to Be-specific CD4(+) T cells from the lungs of patients with chronic beryllium disease (CBD) results in T cell proliferation and TNF-alpha secretion. We tested the hypothesis that Be-induced, CBD bronchoalveolar lavage (BAL) T cell, transcription-dependent, TNF-alpha secretion was accompanied by specific transcription factor upregulation. After 6 h of Be stimulation, CBD BAL cells produced a median of 883 pg/ml TNF-alpha (range, 608-1,275 pg/ml) versus 198 pg/ml (range, 116-245 pg/ml) by unstimulated cells. After 12 h CBD BAL cells produced a median of 2,963 pg/ml (range, 99-9,424 pg/ml) TNF-alpha versus 55 pg/ml (range, 0-454) by unstimulated cells. Using real-time RT-PCR, Be-stimulated TNF-alpha production at 6 h was preceded by a 5-fold increase in TNF-alpha pre-mRNA copy number:beta-actin copy number (Be median ratio 0.21; unstimulated median ratio 0.04). The median ratio of mature TNF-alpha mRNA:beta-actin mRNA was upregulated 1.4-fold (Be median ratio 0.17; unstimulated median ratio 0.12). Be exposure in the presence of the transcription inhibitor pentoxifylline (PTX) decreased CBD BAL cell TNF-alpha pre-mRNA levels > 60%, whereas treatment with the mRNA splicing inhibitor 2-aminopurine (2AP) decreased levels 40% relative to Be exposure alone. PTX treatment decreased mature TNF-alpha mRNA levels 50% while 2AP decreased levels > 80%, relative to Be exposure alone. Beryllium exposure specifically upregulated transcription factors AP-1 and NF-kappaB. The data suggest that Be exposure induces transcription-dependent TNF-alpha production, potentially due to upregulation of specific transcription factors.


Assuntos
Beriliose/genética , Berílio/farmacologia , Transcrição Gênica/efeitos dos fármacos , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genética , Adulto , Líquido da Lavagem Broncoalveolar/citologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Separação Celular , Feminino , Dosagem de Genes , Humanos , Cinética , Lipopolissacarídeos/farmacologia , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Proteínas Nucleares/metabolismo , Precursores de RNA/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição AP-1/metabolismo , Fatores de Transcrição/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
18.
Am J Respir Cell Mol Biol ; 31(1): 122-30, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-14975942

RESUMO

Beryllium (Be) presentation to CD4+ T cells from patients with chronic beryllium disease (CBD) results in T cell activation, and these Be-specific CD4+ T cells undergo clonal proliferation and T-helper 1-type cytokine production. In exposed workers, genetic susceptibility to this granulomatous disorder is associated with particular HLA-DPB1 alleles. We hypothesized that these HLA-DP molecules could mediate Be-stimulated tumor necrosis factor-alpha (TNF-alpha) messenger RNA (mRNA) and protein production. Using intracellular cytokine staining, we found that treatment with an anti-HLA-DP, but not anti-HLA-DR, monoclonal antibody inhibited Be-stimulated TNF-alpha expression in lung CD3+ CD4+ T cells. This monoclonal antibody also blocked Be-specific T cell proliferation, increased production of TNF-alpha mature-mRNA transcripts, and increased TNF-alpha protein production by Be-stimulated CBD peripheral blood mononuclear cells and bronchoalveolar lavage (BAL) cells. The Be-stimulated upregulation of TNF-alpha mature-mRNA levels with TNF-alpha protein production was a unique property of CBD BAL cells, and did not occur in BAL cells from Be-sensitized patients without CBD, or sarcoidosis BAL cells. This study identifies HLA-DP as a regulatory component in the activation of T cell receptors on Be-specific CD4+ T cells from CBD patients resulting in proliferation and proinflammatory cytokine production.


Assuntos
Beriliose/imunologia , Berílio/efeitos adversos , Linfócitos T CD4-Positivos/metabolismo , Antígenos HLA-DP/imunologia , Antígenos HLA-DP/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Anticorpos Monoclonais/farmacologia , Beriliose/metabolismo , Beriliose/fisiopatologia , Líquido da Lavagem Broncoalveolar/citologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/imunologia , Citocinas/genética , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Antígenos HLA-DP/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Receptores de Antígenos de Linfócitos T/efeitos dos fármacos , Receptores de Antígenos de Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Regulação para Cima/imunologia
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