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1.
Anesth Analg ; 120(2): 449-59, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25602455

RESUMO

For the dedicated anesthesiologist, a high level of expertise is needed to deliver good care to patients and to provide excellent service to surgeons, anesthesia colleagues, and others. Expertise helps the anesthesiologist recover from difficult situations and generally makes the practice run more effectively. Expertise also contributes to quality of life through higher self-esteem and long-term career satisfaction. We begin by reviewing the attributes that characterize expert performance and discussing how a specific training format, known as deliberate practice, contributes to acquisition and maintenance of expertise. Deliberate practice involves rehearsal of specific tasks to mastery, ideally under the eye of a mentor to provide feedback. This amounts to an orchestrated effort to improve that enables trainees to progress to expert levels of performance. With few exceptions, people who become recognized experts have pursued deliberate practice on the order of 4 hours per day for 10 to 15 years. In contrast, those who practice their profession in a rote manner see their skills plateau well below the level of top performers. Anesthesiology instruction with attending supervision provides all of the necessary components for deliberate practice, and it can be effective in anesthesia. Using deliberate practice in teaching requires organization in selecting training topics, effort in challenging students to excel, and skill in providing feedback. In this article, we discuss how educational programs can implement deliberate practice in anesthesiology training, review resources for instructors, and suggest how anesthesiologists can continue the practice after residency.


Assuntos
Anestesiologia/normas , Competência Clínica/normas , Anestesiologia/educação , Humanos , Internato e Residência
2.
A A Pract ; 18(7): e01825, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39037074

RESUMO

Mastery learning with fixed end points and variable training time leads to more consistent expertise but is difficult to implement. Here we piloted mastery learning of laryngoscopy with independent practice. 35 learners participated in independent mastery learning on a manikin that provides automated performance feedback. A pre- and postpractice assessment of intubation skills was completed. After an average of 21 minutes of open practice, the percentage of subjects that met mastery criteria improved from 24% to 89% (P < .05). Independent intubation practice with manikin feedback facilitated mastery learning, enhanced procedural education, and may impact clinical care.


Assuntos
Competência Clínica , Laringoscopia , Manequins , Humanos , Laringoscopia/métodos , Laringoscopia/instrumentação , Retroalimentação , Treinamento por Simulação/métodos , Masculino , Intubação Intratraqueal/métodos , Intubação Intratraqueal/instrumentação , Avaliação Educacional/métodos
3.
Anesth Analg ; 113(4): 877-87, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21680861

RESUMO

In population-based research, subjects are frequently in clusters with shared features or demographic characteristics, such as age range, neighborhood, who they have for a physician, and common comorbidities. Classification into clusters also applies at broader levels. Physicians are classified by physician group or by practice site; hospitals can be characterized by size, location, or demographics. Hierarchical, nested structures pose unique challenges in the conduct of research. Data from nested structures may be interdependent because of similarities among subjects in a cluster, while nesting at multiple levels makes it difficult to know whether findings should be applied to the individual or to the larger group. Statistical tools, known variously as hierarchical linear modeling, multilevel modeling, mixed linear modeling, and other terms, have been developed in the education and social science fields to deal effectively with these issues. Our goal in this article is to review the implications of hierarchical, nested data organization and to provide a step-by-step tutorial of how multilevel modeling could be applied to a problem in anesthesia research using current, commercially available software.


Assuntos
Anestesiologia/estatística & dados numéricos , Modelos Estatísticos , Análise por Conglomerados , Interpretação Estatística de Dados , Humanos , Análise dos Mínimos Quadrados , Modelos Lineares , Dinâmica não Linear , Software
4.
Anesth Analg ; 113(4): 862-8, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20966442

RESUMO

BACKGROUND: A problem with learning endotracheal intubation on airway mannequins is poor transfer of direct laryngoscopy skills from model to patient. We developed an airway model with adjustable anatomic features and investigated whether practicing on a model with frequent adjustments improved laryngoscopy skills transfer. METHODS: Fifty-one paramedic students and 18 medical students with minimal previous experience practiced laryngoscopy 25 times with either the novel model with static features, the novel model with variable features, or a Laerdal Adult Intubation mannequin. For the variable group, the configuration changed after every 5 attempts. After training, all subjects performed 10 laryngoscopies on 2 new mannequins to test their competence at skills transfer. A mixed linear model analyzed various predictors of success as a binary outcome, including training group and change in laryngoscopy model. RESULTS: The odds ratio for success after a recent change in mannequin was 0.69 (0.49, 0.96 [95% confidence interval]). Compared with the Laerdal group, subjects with the static trainer did worse (odds ratio 0.46 [0.23, 0.94]), and subjects in the variable group were no different (0.74 [0.36, 1.52]). Change in laryngoscopy model decreased success rate by approximately 30% for all training groups. CONCLUSION: The results verify that proficiency on one model does not guarantee success on another. However, subjects who trained with a laryngoscopy mannequin in multiple configurations did not show better skill transfer than subjects practicing on fixed configuration airway models.


Assuntos
Competência Clínica , Educação Médica/métodos , Intubação Intratraqueal/métodos , Laringoscopia/educação , Manequins , Modelos Anatômicos , Atividade Motora , Humanos , Intubação Intratraqueal/instrumentação , Laringoscópios , Laringoscopia/instrumentação , Curva de Aprendizado , Modelos Lineares , Razão de Chances , Análise e Desempenho de Tarefas
5.
Simul Healthc ; 16(6): e123-e128, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33273420

RESUMO

INTRODUCTION: Multiple attempts and failure at endotracheal intubation (ETI) are common for inexperienced practitioners and can cause patient morbidity. A test to predict a provider's likelihood of success at patient ETI could assist decisions about training. This project investigated whether trainees' performance at laryngoscopy on airway mannequins predicted their laryngoscopy outcomes in patients. METHODS: Twenty-one consenting first-year anesthesiology residents, emergency medicine residents, and medical students enrolled in this prospective, observational study. They performed laryngoscopy and ETI with a curved laryngoscope on 4 airway mannequins. Metrics included peak dental force, procedure duration, esophageal intubation, laryngeal view, and first-pass ETI success on the mannequins. Trainee data from 203 patient ETIs were collected over a roughly 2-month period centered around the simulation test. Multivariable logistic regression analyzed the relationship of mannequin metrics, participant experience, and a patient difficult airway score with trainee ETI outcomes in patients. RESULTS: Median trainee first-pass success rate at patient ETI was 63%, the rate of ETI problems was 16%, and the esophageal intubation rate was 6%. Laryngoscopy peak dental force, first-pass ETI success, and duration on individual mannequins were significant predictors of patient ETI first-pass success. Metrics from 2 of the 4 mannequins predicted ETI problems. DISCUSSION: Performance metrics from simulated laryngoscopy predicted trainee outcomes during patient ETI. First-pass success and ETI problems affect patient safety and are related to trainee skill. Mannequin laryngoscopy tests could identify trainees who would benefit from additional practice. The metrics could be surrogate end points in research to optimize simulated laryngoscopy training.


Assuntos
Intubação Intratraqueal , Laringoscópios , Competência Clínica , Humanos , Laringoscopia , Manequins , Estudos Prospectivos
6.
Am J Physiol Lung Cell Mol Physiol ; 297(4): L578-85, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19633068

RESUMO

Parathyroid hormone-related protein (PTHrP), a paraneoplastic protein expressed by two-thirds of human non-small cell lung cancers, has been reported to slow progression of lung carcinomas in mouse models and to lengthen survival of patients with lung cancer. This study investigated the effects of ectopic expression of PTHrP on proliferation and cell cycle progression of two human lung adenocarcinoma cell lines that are normally PTHrP negative. Stable transfection with PTHrP decreased H1944 cell DNA synthesis, measured by thymidine incorporation, bromodeoxyuridine uptake, and MTT proliferation assay. A substantial fraction of PTHrP-positive cells was arrested in or slowly progressing through G1. Cyclin D2 and cyclin A2 protein levels were 60-70% lower in PTHrP-expressing cells compared with control cells (P < 0.05, N = 3 independent clones per group), while expression of p27(Kip1), a cyclin-dependent kinase inhibitor, was increased by 35 +/- 9% (mean +/- SE, P < 0.05) in the presence of PTHrP. Expression of other cyclins, including cyclins D1 and D3, and cyclin-dependent kinases was unaffected by PTHrP. PTHrP did not alter the phosphorylation state of Rb, but decreased cyclin-dependent kinase (CDK) 2-cyclin A2 complex formation. Ectopic expression of PTHrP stimulated ERK phosphorylation. In MV522 cells, PTHrP had similar effects on DNA synthesis, cyclin A2 expression, pRb levels, CDK2-cyclin A2 association, and ERK activation. In summary, PTHrP appears to slow progression of lung cancer cells into S phase, possibly by decreasing activation of CDK2. Slower cancer cell proliferation could contribute to slower tumor progression and increased survival of patients with PTHrP-positive lung cancer.


Assuntos
Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Ciclo Celular/fisiologia , Proliferação de Células , Regulação da Expressão Gênica/fisiologia , Neoplasias Pulmonares/genética , Proteína Relacionada ao Hormônio Paratireóideo/genética , Adenocarcinoma/patologia , Apoptose , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Quinase 2 Dependente de Ciclina/genética , Quinase 2 Dependente de Ciclina/metabolismo , Citometria de Fluxo , Humanos , Immunoblotting , Imunoprecipitação , Neoplasias Pulmonares/patologia , Fosforilação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor Tipo 1 de Hormônio Paratireóideo/genética , Receptor Tipo 1 de Hormônio Paratireóideo/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas
8.
J Educ Perioper Med ; 20(1): E615, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29928662

RESUMO

BACKGROUND: The goal of this study was to determine whether motion parameters during laryngoscopy in a manikin differed with experienced operators versus novice trainees and whether motion measurements would predict trainee outcomes when intubating patients. METHODS: Motion, force, and duration of laryngoscopy on a manikin were compared in two separate experiments between beginning anesthesiology residents (CA1) and anesthesiologists with more than 24 months of anesthesiology training (CA3 or attendings). In one experiment, CA1 residents were also evaluated for the percentage of their laryngoscope path that followed the route used by attending anesthesiologists. The residents were then observed for patient intubation outcomes for 4 weeks after manikin testing. The relationship between manikin test metrics and patient intubation outcomes was analyzed by multilevel modeling. RESULTS: CA1 residents positioned the laryngoscope blade farther right and with less lift than did experienced anesthesiologists. Endpoint position was 0.6 ± 0.3 cm left of midline for residents (n = 10) versus 2.7 ± 0.3 cm for advanced anesthesiologists (n = 8; P = .0003), and 15.6 ± 0.8 versus 17.7 ± 0.2 cm above the table surface, respectively (P = .033). On average, only 74 ± 6% of the CA1 laryngoscopy trajectory coincided with the Attending Route (P < .001 versus 100%). For each percentage point increase in Attending Route match, residents' odds of intubating a patient's trachea improved by a factor of 1.033 (95% confidence interval [CI] 1.007-1.059, P = .040), and their rate of failed laryngoscopy attempts decreased by a factor of 0.982 (0.969-0.996, P = .045). DISCUSSION: Laryngoscopy motion in manikins may predict which trainees can complete a patient intubation successfully in a few attempts. The assessment could help determine readiness for intubating patients with indirect supervision.

9.
Respir Physiol Neurobiol ; 252-253: 10-15, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29526659

RESUMO

Patients with end-expiratory flow limitation (eEFL) demonstrate a terminal rise in capnography slope. The high slope could represent phase 5, a phenomenon described for single breath N2 tests but previously unreported during capnography. This study evaluated 6 healthy subjects exhaling from total lung capacity to residual volume at several set constant rates. We measured the volumes of flow limitation (VFL) and phase 5 (VP5) for CO2 and N2. A distinct phase 5 occurred shortly after eEFL for both gases. Increased expiratory flow rate resulted in parallel increases in VFL and VP5. The two quantities differed on average by the volume of dead space. These data suggest that phase 5 on capnography identifies eEFL with a small delay resulting from transit of expired gas through dead space. Following phase 5 by volumetric capnography could be useful for monitoring anesthetized patients, who in some circumstances may have lung volumes close to residual volume. eEFL could be treated with lung volume-increasing maneuvers, such as positive end-expiratory pressure.


Assuntos
Capnografia , Expiração , Adulto , Expiração/fisiologia , Feminino , Humanos , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Espirometria , Capacidade Vital
10.
Clin Cancer Res ; 12(2): 499-506, 2006 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-16428492

RESUMO

PURPOSE: Parathyroid hormone-related protein (PTHrP) is commonly expressed in non-small cell lung carcinomas (NSCLC). Expression of the protein could have implications for progression of the disease because it regulates cancer cell growth, apoptosis, and angiogenesis. However, its relationship with survival has not been evaluated in a large-scale investigation. EXPERIMENTAL DESIGN: PTHrP expression was assessed in paraffin-embedded tumor samples from 407 patients with NSCLC by immunohistochemistry. A pathologist unaware of the clinical history classified specimens as PTHrP positive or PTHrP negative. The log-rank test was used to compare survivals of PTHrP-positive and PTHrP-negative groups, and Cox regression was used to adjust for additional covariates. RESULTS: Median survival was 55 versus 22 months (P < 0.001) in female patients with and without tumor PTHrP, respectively. Male survival was 38 months independent of PTHrP status. Stage, histology, age, and smoking history were also associated with increased longevity. PTHrP remained a significant predictor of survival for female patients after controlling for stage, histology, and age. CONCLUSIONS: In this study, PTHrP expression was associated with a survival advantage in female patients. Additional investigations must be done to ascertain whether the result is reproducible and independent of potential confounding covariates. Sex-dependent effects of PTHrP in lung cancer would open new avenues of research into the role of sex in cancer progression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Distribuição por Sexo , Taxa de Sobrevida
11.
Clin Cancer Res ; 12(8): 2602-6, 2006 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-16638872

RESUMO

PURPOSE: Metastatic bone disease is one of the major causes of morbidity and mortality in prostate cancer patients. Bisphosphonates are currently used to inhibit bone resorption and reduce tumor-induced skeletal complications. More effective bisphosphonates would enhance their clinical value. EXPERIMENTAL DESIGN: We tested several bisphosphonates in a green fluorescent protein (GFP)-expressing human prostate cancer nude mouse model. The in vivo effects of four bisphosphonates, including pamidronate, etidronic acid, and olpadronate, on bone tumor burden in mice intratibially inoculated with PC-3-GFP human prostate cancer cells were visualized by whole-body fluorescence imaging and X-ray. RESULTS: The PC-3-GFP cells produced extensive bone lesions when injected into the tibia of immunocompromised mice. The skeletal progression of the PC-3-GFP cell growth was monitored by GFP fluorescence and the bone destruction was evaluated by X-ray. We showed that 3,3-dimethylaminopropane-1-hydroxy-1,1-diphosphonic acid (olpadronate) was the most effective bisphosphonate treatment in reducing tumor burden as assessed by GFP imaging and radiography. The GFP tumor area and X-ray score significantly correlated. Reduced tumor growth in the bone was accompanied by reduced serum calcium, parathyroid hormone-related protein, and osteoprotegerin. CONCLUSIONS: The serum calcium, parathyroid hormone-related protein, and osteoprotegerin levels were significantly correlated with GFP area and X-ray scores. Treatment with olpadronate reduced tumor growth in the bone measured by GFP and X-ray imaging procedures. Imaging of GFP expression enables monitoring of tumor growth in the bone and the GFP results complement the X-ray assessment of bone disease. The data in this report suggest that olpadronate has potential as an effective inhibitor of the skeletal progression of clinical prostate cancer.


Assuntos
Neoplasias Ósseas/prevenção & controle , Difosfonatos/uso terapêutico , Proteínas de Fluorescência Verde/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/secundário , Cálcio/sangue , Linhagem Celular Tumoral , Progressão da Doença , Glicoproteínas/sangue , Proteínas de Fluorescência Verde/genética , Humanos , Masculino , Camundongos , Camundongos Nus , Osteoprotegerina , Pamidronato , Proteína Relacionada ao Hormônio Paratireóideo/sangue , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores Citoplasmáticos e Nucleares/sangue , Receptores do Fator de Necrose Tumoral/sangue , Fatores de Tempo , Resultado do Tratamento
12.
Anesth Analg ; 115(6): 1472; author reply 1472, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23175577
13.
Anesth Analg ; 105(4): 1118-26, table of contents, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17898397

RESUMO

BACKGROUND: The view obtained during direct laryngoscopy is only seen by a single anesthesiologist. The inability of instructors to observe the view poses problems for teaching the technique. The anatomic interactions affecting laryngoscopy are largely internal, hampering efforts to understand why some patients are unexpectedly difficult to intubate. In response, we have constructed a full scale, adjustable, two-dimensional model showing the head and neck in the sagittal plane. In this article, we validate the mannequin and test how various conditions or changes in equipment affect the laryngoscopic view. METHODS: Model parameters were compared with literature values. Glottic exposure was evaluated over a range of jaw lengths and interincisor gaps for Macintosh 3, Miller 2, and Macintosh 4 blades. RESULTS: Thirty segmental airway distances and 10 angles were within 1 standard deviation from published values. Spine and jaw mobilities approximated normal range of motion. Glottic exposure decreased steeply for mouth openings below a threshold. A larger mouth opening was required to obtain a view when the mandible was short. None of the blades exposed the glottis when mouth opening was narrow, 2.4 cm. The Macintosh 4 blade was closest to success, within 7 mm of viewing the posterior cords. CONCLUSIONS: The model reflects an average 16-yr-old male patient in size, proportion, and mobility. It can be used to explicate how anatomic relationships affect laryngoscopy. An objective assessment is necessary to determine the model's utility for teaching and as a tool for researching the mechanisms responsible for laryngoscopic difficulty.


Assuntos
Cabeça/anatomia & histologia , Laringoscopia , Manequins , Pescoço/anatomia & histologia , Adolescente , Cefalometria , Vértebras Cervicais/anatomia & histologia , Humanos , Arcada Osseodentária/anatomia & histologia , Laringe/anatomia & histologia , Masculino , Materiais de Ensino
14.
J Cancer Res Clin Oncol ; 143(8): 1395-1407, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28342003

RESUMO

PURPOSE: Expression of the carboxyl PTHrP region of parathyroid hormone-related protein (PTHrP) is a positive prognostic indicator in women with lung cancer, but amino PTHrP is a negative indicator in other lung cancer patients. This project investigated whether PTHrP could be expressed as predominantly amino PTHrP or carboxyl PTHrP in individual lung carcinomas. It also assessed domain-specific effects on cancer progression and patient survival. METHODS: PTHrP immunoreactivities were analyzed versus survival in a human lung cancer tissue microarray (TMA). Growth was compared in athymic mice for isogenic lung carcinoma xenografts differing in expression of amino and carboxyl PTHrP domains. RESULTS: In the TMA, 33 of 99 patient tumors expressed only one PTHrP domain, while 54 expressed both. By Cox regression, the hazard ratio for cancer-specific mortality (95% confidence interval) was 2.6 (1.28-5.44) for amino PTHrP (P = 0.008) and 0.6 (0-2.58) for carboxyl PTHrP (P = 0.092). Xenografts of H358 lung adenocarcinoma cells that overexpressed amino PTHrP grew twice as fast as isogenic low PTHrP tumors in athymic mice, but growth of tumors expressing amino plus carboxyl PTHrP was not significantly different than growth of the control tumors. In summary, the presence of amino PTHrP signifies worse prognosis in lung cancer patients. In mouse xenografts, this effect was abrogated if carboxyl PTHrP was also present. CONCLUSION: Amino PTHrP and carboxyl PTHrP can vary independently in different lung carcinomas. Carboxyl PTHrP may temper the stimulatory effect of amino PTHrP on cancer progression.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Proteína Relacionada ao Hormônio Paratireóideo/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Adulto , Idoso , Animais , Biomarcadores Tumorais/biossíntese , Carcinoma Pulmonar de Células não Pequenas/patologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Proteína Relacionada ao Hormônio Paratireóideo/biossíntese , Domínios Proteicos/genética , Análise Serial de Tecidos , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Endocrinology ; 147(2): 990-8, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16293661

RESUMO

PTHrP is an oncofetal protein with distinct proliferative and antiapoptotic roles that are affected by nucleocytoplasmic shuttling. The protein's nuclear export is sensitive to leptomycin B, consistent with a chromosome region maintenance protein 1-dependent pathway. We determined that the 109-139 region of PTHrP was involved in its nuclear export by demonstrating that a C-terminal truncation mutant, residues 1-108, exports at a reduced rate, compared with the wild-type 139 amino acid isoform. We searched for potential nuclear export sequences within the 109-139 region, which is leucine rich. Comparisons with established nuclear export sequences identified a putative consensus signal at residues 126-136. Deletion of this region resulted in nuclear export characteristics that closely matched those of the C-terminal truncation mutant. Confocal microscopic analyses of transfected 293, COS-1, and HeLa cells showed that steady-state nuclear levels of the truncated and deletion mutants were significantly greater than levels of wild-type PTHrP and were unaffected by leptomycin B, unlike the wild-type protein. In addition, both mutants demonstrated greatly reduced nuclear export with assays using nuclear preparations and intact cells. Based on these results, we conclude that the 126-136 amino acid sequence closely approximates the structure of a chromosome region maintenance protein 1-dependent leucine-rich nuclear export signal and is critical for nuclear export of PTHrP.


Assuntos
Transporte Ativo do Núcleo Celular/fisiologia , Sinais de Exportação Nuclear/fisiologia , Proteína Relacionada ao Hormônio Paratireóideo/química , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo , Sequência de Aminoácidos , Animais , Células COS , Núcleo Celular/metabolismo , Chlorocebus aethiops , Células HeLa , Humanos , Leucina/análise , Dados de Sequência Molecular , Mutação , Proteína Relacionada ao Hormônio Paratireóideo/genética , Isoformas de Proteínas , Homologia de Sequência de Aminoácidos
16.
Springerplus ; 4: 268, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26090315

RESUMO

Parathyroid hormone-related protein (PTHrP) inhibits proliferation of several lung cancer cell lines, but the signaling mechanism has not been established. This study tested the hypotheses that growth inhibition is mediated through the PTHrP receptor, PTH1R, and that the process is modified by ERK activation. PTHrP-positive and negative clones of H1944 lung adenocarcinoma cells underwent stable PTH1R knockdown with lentiviral shRNA or transient transfection with ERK1 and ERK2 siRNA. Alternatively, cells were treated with 8-CPT cAMP, 8-CPT 2'-O-methyl cAMP, and N-6-phenyl cAMP analogs. H1944 cells expressing ectopic PTHrP showed 20-40% decrease in proliferation compared to the PTHrP-negative cells in the presence of normal levels of PTH1R (P < 0.01). PTH1R knockdown eliminated this difference and increased cell proliferation regardless of PTHrP status. The three cAMP analogs each inhibited proliferation over 5 days by 30-40%. ERK2 knockdown inhibited proliferation of PTHrP-positive cells alone and in combination with ERK1 knockdown. The growth inhibition mediated by cAMP analogs was unaffected by ERK1 knockdown. In conclusion, ectopic expression of PTHrP 1-87 inhibits H1944 cell proliferation. PTH1R knockdown blocks this effect and stimulates proliferation, indicating that the ligand exerts anti-mitogenic effects. cAMP, the second messenger for PTH1R also inhibits proliferation and activates ERK. PTHrP growth inhibition may be opposed by concomitant ERK activation.

18.
Respir Physiol Neurobiol ; 142(2-3): 95-113, 2004 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-15450473

RESUMO

Parathyroid hormone-related protein (PTHrP) is expressed in normal and malignant lung and has roles in development, homeostasis, and pathophysiology of injury and cancer. Its effects in developing lung include regulation of branching morphogenesis and type II cell maturation. In adult lung, PTHrP stimulates disaturated phosphatidylcholine secretion, inhibits type II cell growth, and sensitizes them to apoptosis. In lung cancer, PTHrP may play a role in carcinoma progression, or metastasis. The protein could be a useful marker for assessing lung maturity or type II cell function, predicting risk of injury, and detecting lung cancer. PTHrP-based therapies could also prove useful in lung injury and lung cancer.


Assuntos
Regulação da Expressão Gênica/fisiologia , Pulmão/fisiologia , Proteína Relacionada ao Hormônio Paratireóideo/fisiologia , Animais , Humanos , Pulmão/patologia , Pneumopatias/classificação , Pneumopatias/genética , Pneumopatias/metabolismo , Modelos Biológicos , Proteína Relacionada ao Hormônio Paratireóideo/genética , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo , Receptores de Hormônios Paratireóideos/fisiologia , Fatores de Tempo
19.
Contemp Top Lab Anim Sci ; 38(6): 33-35, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12086445

RESUMO

This report describes a noninvasive method for direct laryngoscopy in mice as small as 20 g by using commercially available equipment. A pediatric otoscope is inserted into the mouth of an anesthetized mouse to provide a clear view of the vocal cords. The procedure takes less than a minute and has been successful without complications in the 65 mice studied to date. The technique can be used to instill test substances into the lungs or to perform oral endotracheal intubation for resuscitation, airway support, or controlled ventilation.

20.
Stud Health Technol Inform ; 94: 45-51, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-15455862

RESUMO

Many medical procedures require fine motor skills, and these skills are developed over years of practice and through performing hundreds to thousands of procedures. However medical training that is based upon gaining this expertise by performing procedures on patients results in unnecessary risk to the patient. In this project expert medical skill is quantified, so that advanced medical simulators can be created to provide a realistic training environment. This approach is applied to airway intubation with a rigid laryngoscope; a procedure that is performed prior to general anesthesia and during emergency situations. A laryngoscope has been instrumented with a 3 dimensional force/torque sensor, and magnetic position sensors have been placed on the laryngoscope and the patient. Measurements are made in the operating room of both experts and novices as they perform laryngoscopy on consenting patients undergoing general anesthesia. The skill of the laryngoscopist is represented by the motion and force trajectories applied to the laryngoscope during the procedure. Preliminary results show that novices often err in the placement of the tip of the laryngoscope blade. However, when two experts perform laryngoscopy on the same patient, both experts perform key elements of the task consistently. The measured consistency among experts indicates that it will be possible to apply algorithms developed for Human Skill Acquisition, and thereby define regions of expert motion relative to patient anatomy. This is the first step in developing advanced training simulators that will simulate the procedure accurately, provide guidance to the trainee, and can be used for assessment of medical skill.


Assuntos
Competência Clínica , Simulação por Computador , Educação Médica/métodos , Laringoscopia , Humanos , Intubação Intratraqueal , Interface Usuário-Computador
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