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3.
AEM Educ Train ; 7(Suppl 1): S58-S67, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37383836

RESUMO

Objectives: Debriefing is an integral component of simulation education, and effective debriefing education is required to maintain effective simulation programs. However, many educators report financial and logistical barriers to accessing formal debriefing training. Due to limited educator development opportunities, simulation program leaders are often compelled to utilize educators with insufficient debriefing training, which can limit the impact of simulation-based education. To address these concerns, the SAEM Simulation Academy Debriefing Workgroup authored the Workshop in Simulation Debriefing for Educators in Medicine (WiSDEM), a freely available, concise, and ready-to-deploy debriefing curriculum with a target audience of novice educators without formal debriefing training. In this study, we describe the development, initial implementation, and evaluation of the WiSDEM curriculum. Methods: The Debriefing Workgroup iteratively developed the WiSDEM curriculum by expert consensus. The targeted level of content expertise was introductory. The curriculum's educational impact was assessed by surveying participants on their impressions of the curriculum and their confidence and self-efficacy in mastery of the material. Additionally, facilitators of the WiSDEM curriculum were surveyed on its content, usefulness, and future applicability. Results: The WiSDEM curriculum was deployed during the SAEM 2022 Annual Meeting as a didactic presentation. Thirty-nine of 44 participants completed the participant survey, and four of four facilitators completed the facilitator survey. Participant and facilitator feedback on the curriculum content was positive. Additionally, participants agreed that the WiSDEM curriculum improved their confidence and self-efficacy in future debriefing. All surveyed facilitators agreed that they would recommend the curriculum to others. Conclusions: The WiSDEM curriculum was effective at introducing basic debriefing principles to novice educators without formal debriefing training. Facilitators felt that the educational materials would be useful for providing debriefing training at other institutions. Consensus-driven, ready-to-deploy debriefing training materials such as the WiSDEM curriculum can address common barriers to developing basic debriefing proficiency in educators.

6.
AEM Educ Train ; 6(Suppl 1): S32-S42, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35783076

RESUMO

Objectives: We identified and quantified the gap between emergency medicine (EM) procedures currently taught using simulation versus those that educators would teach if they had better procedural task trainers. Additionally, we endeavored to describe which procedures were taught using homemade models and the barriers to creation and use of additional homemade models. Methods: Using a modified Delphi process, we developed a survey and distributed it to a convenience sample of EM simulationists via the Society for Academic Emergency Medicine Simulation Academy listserv. Survey items asked participants to identify procedures they thought should be taught using simulation ("most important"), do teach using simulation ("most frequent"), would teach if a simulator or model were available ("most needed"), and do teach using simulation with "homemade" models ("most frequent homemade"). Results: Thirty-seven surveys were completed. The majority of respondents worked at academic medical centers and were involved in simulation-based education for at least 6 years. Three procedures ranked highly in overall teaching importance and currently taught categories. We identified four procedures that ranked highly as both important techniques to teach and would teach via simulation. Two procedures were selected as the most important procedures that the participants do teach via simulation but would like to teach in an improved way. We found 14 procedures that simulationists would teach if an adequate model was available, four of which are of high importance. Conclusions: This study captured data to illuminate the procedural model gap and inform future interventions that may address it and meet the overarching objective to create better and more readily available procedure models for EM simulation educators in the future. It offers an informed way of prioritizing procedures for which additional homemade models should be created and disseminated as well as barriers to be aware of and to work to overcome. Our work has implications for learners, educators, administrators, and industry.

8.
AEM Educ Train ; 5(1): 105-110, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33521496

RESUMO

BACKGROUND: Early-career simulation investigators identify limited mentorship as a common barrier to disseminating scholarship and launching a successful academic career in emergency medicine (EM). Conferences often bridge this gap, but the COVID-19 pandemic has forced their indefinite delay. Virtual solutions are needed to capitalize on the breadth of national simulation research experts and grow mentorship in a postpandemic world. METHODS: We developed two complementary innovations to facilitate scholarship development and minimize COVID-associated career challenges resulting from social distancing requirements. The e-fellows forum (FF) provides a capstone experience for works-in-progress and the e-consultation service (CS) supports simulation research during the earlier project stages of design and development. In conjunction with the Society for Academic Medicine's Simulation Academy, we applied videoconferencing technology for both of these novel, virtual innovations. We analyzed corresponding chat transcripts and detailed field notes for emerging themes. In addition, we collected quantitative data via participant surveys regarding their experiences and impact on their projects. RESULTS: Nine simulation fellows presented at the FF and seven junior simulation investigators participated in the CS sessions. Most preferred the virtual format (56% FF, 66% CS) and found the sessions to be helpful in project advancement (66% FF, 100% CS). COVID-19 affected most projects (89% FF, 67% CS). We identified three themes via qualitative analysis: design concerns and inquiries, validation or support shown by mentors and peers, and professional cohesion. CONCLUSIONS: Participants felt that both virtual mentorship innovations advanced their simulation research projects and fostered a sense of professional cohesion within a greater community of practice. These benefits can be powerful at a time where simulation researchers in EM feel disconnected in an era of social distancing. Our future work will include adaptations to a hybrid model with both virtual and in-person modalities as well as creation of more e-mentorship opportunities, thus broadening the early-career simulation research community of practice.

9.
West J Emerg Med ; 20(1): 145-156, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30643618

RESUMO

INTRODUCTION: Resident remediation is a pressing topic in emergency medicine (EM) training programs. Simulation has become a prominent educational tool in EM training and been recommended for identification of learning gaps and resident remediation. Despite the ubiquitous need for formalized remediation, there is a dearth of literature regarding best practices for simulation-based remediation (SBR). METHODS: We conducted a literature search on SBR practices using the terms "simulation," "remediation," and "simulation based remediation." We identified relevant themes and used them to develop an open-ended questionnaire that was distributed to EM programs with experience in SBR. Thematic analysis was performed on all subsequent responses and used to develop survey instruments, which were then used in a modified two-round Delphi panel to derive a set of consensus statements on the use of SBR from an aggregate of 41 experts in simulation and remediation in EM. RESULTS: Faculty representing 30 programs across North America composed the consensus group with 66% of participants identifying themselves as simulation faculty, 32% as program directors, and 2% as core faculty. The results from our study highlight a strong agreement across many areas of SBR in EM training. SBR is appropriate for a range of deficits, including procedural, medical knowledge application, clinical reasoning/decision-making, communication, teamwork, and crisis resource management. Simulation can be used both diagnostically and therapeutically in remediation, although SBR should be part of a larger remediation plan constructed by the residency leadership team or a faculty expert in remediation, and not the only component. Although summative assessment can have a role in SBR, it needs to be very clearly delineated and transparent to everyone involved. CONCLUSION: Simulation may be used for remediation purposes for certain specific kinds of competencies as long as it is carried out in a transparent manner to all those involved.


Assuntos
Competência Clínica/normas , Consenso , Medicina de Emergência/educação , Internato e Residência , Treinamento por Simulação , Técnica Delphi , Humanos , América do Norte
10.
Acad Emerg Med ; 25(2): 168-176, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28963862

RESUMO

The acquisition and maintenance of individual competency is a critical component of effective emergency care systems. This article summarizes consensus working group deliberations and recommendations focusing on the topic "Simulation-based education to ensure provider competency within the healthcare system." The authors presented this work for discussion and feedback at the 2017 Academic Emergency Medicine Consensus Conference on "Catalyzing System Change Through Healthcare Simulation: Systems, Competency, and Outcomes," held on May 16, 2017, in Orlando, Florida. Although simulation-based training is a quality and safety imperative in other high-reliability professions such as aviation, nuclear power, and the military, health care professions still lag behind in applying simulation more broadly. This is likely a result of a number of factors, including cost, assessment challenges, and resistance to change. This consensus subgroup focused on identifying current gaps in knowledge and process related to the use of simulation for developing, enhancing, and maintaining individual provider competency. The resulting product is a research agenda informed by expert consensus and literature review.


Assuntos
Competência Clínica/normas , Medicina de Emergência/educação , Treinamento por Simulação/organização & administração , Consenso , Prestação Integrada de Cuidados de Saúde/normas , Medicina de Emergência/normas , Humanos
11.
West J Emerg Med ; 18(1): 76-81, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28116012

RESUMO

INTRODUCTION: Feedback, particularly real-time feedback, is critical to resident education. The emergency medicine (EM) milestones were developed in 2012 to enhance resident assessment, and many programs use them to provide focused resident feedback. The purpose of this study was to evaluate EM residents' level of interest in receiving real-time feedback on each of the 23 competencies/sub-competencies. METHODS: This was a multicenter cross-sectional study of EM residents. We surveyed participants on their level of interest in receiving real-time on-shift feedback on each of the 23 competencies/sub-competencies. Anonymous paper or computerized surveys were distributed to residents at three four-year training programs and three three-year training programs with a total of 223 resident respondents. Residents rated their level of interest in each milestone on a six-point Likert-type response scale. We calculated average level of interest for each of the 23 sub-competencies, for all 223 respondents and separately by postgraduate year (PGY) levels of training. One-way analyses of variance were performed to determine if there were differences in ratings by level of training. RESULTS: The overall survey response rate across all institutions was 82%. Emergency stabilization had the highest mean rating (5.47/6), while technology had the lowest rating (3.24/6). However, we observed no differences between levels of training on any of the 23 competencies/sub-competencies. CONCLUSION: Residents seem to ascribe much more value in receiving feedback on domains involving high-risk, challenging procedural skills as compared to low-risk technical and communication skills. Further studies are necessary to determine whether residents' perceived importance of competencies/sub-competencies needs to be considered when developing an assessment or feedback program based on these 23 EM competencies/sub-competencies.


Assuntos
Competência Clínica/estatística & dados numéricos , Medicina de Emergência/normas , Retroalimentação , Internato e Residência/estatística & dados numéricos , Estudos Transversais , Avaliação Educacional/normas , Medicina de Emergência/educação , Humanos , Inquéritos e Questionários , Estados Unidos
12.
MedEdPORTAL ; 13: 10649, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30800850

RESUMO

Introduction: High-fidelity mannequin-based simulation is frequently used to compliment medical student education during clinical clerkships. However, psychiatric educators have not broadly adopted this modality, focusing rather on standardized patient actors. We developed and delivered a simulation case involving a patient with alcohol withdrawal and lithium toxicity followed by a debriefing session to medical students at the end of their psychiatric clerkship. Methods: The case involves a 40-year-old male truck driver with a history of bipolar disorder who presents to the emergency room after a truck accident. The patient is in alcohol withdrawal, which responds to benzodiazepines. A workup reveals that the patient also has lithium toxicity related to the co-ingestion of lithium and naproxen for pain. Participants learn to evaluate and treat alcohol withdrawal, consider medical comorbidities and legal consequences, and complete a brief intervention for substance use. This case requires a simulation mannequin. Results: To date, 150 second-, third-, and fourth-year medical students have participated in this case and 76 have been surveyed. Participants have provided a postsession rating of 4.49 on a 5-point Likert scale (1 = strongly disagree and 5 = strongly agree) on a question about enjoyment, and 3.93 on a question about confidence with evaluation and treatment of patients in alcohol withdrawal. Discussion: Psychiatric education currently underutilizes mannequin-based simulation compared to other medical disciplines. Mannequin simulation is feasible and effective in psychiatric education, especially in cases involving medical complexity, as shown in this novel case involving a patient with alcohol withdrawal and lithium toxicity.


Assuntos
Alcoolismo/complicações , Lítio/toxicidade , Acidentes de Trânsito/psicologia , Adulto , Alcoolismo/tratamento farmacológico , Alcoolismo/psicologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Benzodiazepinas/uso terapêutico , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Estágio Clínico/métodos , Humanos , Lítio/efeitos adversos , Lítio/uso terapêutico , Masculino , Veículos Automotores , Naproxeno/efeitos adversos , Naproxeno/uso terapêutico , Dor/tratamento farmacológico , Simulação de Paciente , Estudantes de Medicina/estatística & dados numéricos , Inquéritos e Questionários
13.
Acad Emerg Med ; 23(9): 1054-60, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27251553

RESUMO

OBJECTIVES: There is currently no consolidated list of existing simulation fellowship programs in emergency medicine (EM). In addition, there are no universally accepted or expected standards for core curricular content. The objective of this project is to develop consensus-based core content for EM simulation fellowships to help frame the critical components of such training programs. METHODS: This paper delineates the process used to develop consensus curriculum content for EM simulation fellowships. EM simulation fellowship curricula were collected. Curricular content was reviewed and compiled by simulation experts and validated utilizing survey methodology, and consensus was obtained using a modified Delphi methodology. RESULTS: Fifteen EM simulation fellowship curricula were obtained and analyzed. Two rounds of a modified Delphi survey were conducted. The final proposed core curriculum content contains 47 elements in nine domains with 14 optional elements. CONCLUSION: The proposed consensus content will provide current and future fellowships a foundation on which to build their own specific and detailed fellowship curricula. Such standardization will ultimately increase the transparency of training programs for future trainees and potential employers.


Assuntos
Currículo , Medicina de Emergência/educação , Bolsas de Estudo , Desenvolvimento de Programas/métodos , Treinamento por Simulação , Consenso , Técnica Delphi , Humanos , Inquéritos e Questionários
14.
MedEdPORTAL ; 12: 10512, 2016 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-30984854

RESUMO

INTRODUCTION: This simulation case was designed to evaluate the ability of third- and fourth-year emergency medicine clerkship students and acting interns to perform the tasks outlined in the Association of American Medical College's Core Entrustable Professional Activity 10, to "recognize a patient requiring urgent or emergent care and initiate evaluation and management." The overarching goal is to assess medical students' ability to recognize and take steps to stabilize a sick patient. METHODS: In this case, students encounter a physician, simulated with a high-fidelity manikin, who has suddenly become confused. Students are expected to recognize that he is acutely ill, call for help, and begin the initial steps of resuscitation. Bedside testing reveals hypoglycemia, which students are expected to treat. Further examination, history gathering, and diagnostic tests reveal that the patient is suffering from gram-negative sepsis. Students are evaluated on their ability to recognize signs of serious illness, call for appropriate help, perform critical assessment and treatment tasks, communicate their findings to an attending physician, and determine the appropriate patient disposition. Outcomes are measured using critical action checklists. RESULTS: Initial trials of this case demonstrated its feasibility. All 13 students who have participated in this session have identified all five critical actions. DISCUSSION: In later iterations, the number of roles was streamlined in order to reduce how many personnel were required. As a result of the very high critical-actions success rates of the first two groups of students tested, our case-specific checklist was revised with the goal of improving its discriminatory power.

15.
MedEdPORTAL ; 12: 10517, 2016 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-30984859

RESUMO

INTRODUCTION: Entrustable professional activities (EPAs) are units of professional practice defined as tasks or responsibilities that trainees are entrusted to perform unsupervised. AAMC Core EPA 10 is defined as the ability to "recognize a patient who requires emergent care and initiate evaluation and management." We designed a simulation scenario to elicit EPA 10-related behaviors for learner assessment to guide entrustment decisions. METHODS: This case presents a 61-year-old male with a complaint of feeling ill. The students need to diagnose an ST segment elevation myocardial infarction that leads to a pulseless ventricular tachycardia arrest. A simulation manikin is used, and students are assessed using a checklist. The tool is a set of critical actions that were proposed by a group of content experts, based on the following EPA 10 functions: recognizing unstable vital signs, asking for help, and determining appropriate disposition. In addition to case-specific behavioral items, an overall entrustment item was added to inform the entrustment decision. RESULTS: This case was implemented in a mandatory fourth-year clerkship for 7 years prior to its adaptation for entrustment on EPA 10. In recent experience from one institution, about 14% of students failed to meet entrustment. Students rated the experience as valuable (average 5.0, on a 5-point Likert scale) and thought that it would change their performance in a clinical setting (average 4.95, on a 5-point Likert scale). DISCUSSION: Faculty raters noted challenges regarding entrustment based on a single simulation and the implications that team role (supporting role vs. leader role) has on entrustment.

16.
Mult Scler ; 20(5): 588-93, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24072721

RESUMO

BACKGROUND: Pediatric multiple sclerosis (MS) represents approximately 5% of the MS population; information regarding clinical features is slowly accumulating. Cognitive and psychiatric impairments frequently occur, but remain poorly understood. OBJECTIVES: To describe psychiatric diagnoses among children with MS referred for psychiatric assessment and their relation to cognitive impairment. METHODS: Forty-five pediatric MS patients (aged 8 to 17 years) were referred for outpatient psychiatric evaluation including a psychiatric interview (K-SADS), a clinician-based global assessment of functioning (Children's Global Assessment Scale, CGAS), a neurologic examination including the Expanded Disability Status Scale (EDSS), and a neuropsychological test battery. RESULTS: The most common categories of psychiatric diagnoses were anxiety disorders (n=15), attention deficit hyperactivity disorder (ADHD, n=12), and mood disorders (n=11). Cognitive impairment was classified in 20/25 (80%) of patients meeting criteria for a psychiatric disorder versus 11/20 (55%) of those without psychiatric disorder (p=0.08). Those diagnosed with anxiety or mood disorder had the highest frequency of cognitive impairment, with a significantly higher rate when compared with those with psychiatric diagnoses in other categories (p=0.05). CONCLUSIONS: A variety of psychiatric diagnoses can occur in children with pediatric MS. Many of these children also had cognitive impairment, particularly those in the mood and anxiety groups.


Assuntos
Ansiedade/psicologia , Transtornos Cognitivos/psicologia , Cognição , Transtornos do Humor/psicologia , Esclerose Múltipla/psicologia , Adolescente , Comportamento do Adolescente , Fatores Etários , Ansiedade/diagnóstico , Criança , Comportamento Infantil , Transtornos Cognitivos/diagnóstico , Avaliação da Deficiência , Feminino , Humanos , Masculino , Transtornos do Humor/diagnóstico , Esclerose Múltipla/diagnóstico , Testes Neuropsicológicos , Fatores de Risco , Inquéritos e Questionários
17.
Neuron ; 70(5): 908-23, 2011 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-21658584

RESUMO

Adult hippocampal neurogenesis has been implicated in cognitive and emotional processes, as well as in response to antidepressant treatment. However, little is known about how the adult stem cell lineage contributes to hippocampal structure and function and how this process is modulated by the animal's experience. Here we perform an indelible lineage analysis and report that neural stem cells can produce expanding and persisting populations of not only neurons, but also stem cells in the adult hippocampus. Furthermore, the ratio of stem cells to neurons depends on experiences of the animal or the location of the stem cell. Surprisingly, social isolation facilitated accumulation of stem cells, but not neurons. These results show that neural stem cells accumulate in the adult hippocampus and that the stem cell-lineage relationship is under control of anatomic and experiential niches. Our findings suggest that, in the hippocampus, fate specification may act as a form of cellular plasticity for adapting to environmental changes.


Assuntos
Hipocampo/citologia , Células-Tronco Neurais/fisiologia , Neurogênese/fisiologia , Análise de Variância , Animais , Antineoplásicos Hormonais/farmacologia , Proteínas de Bactérias/genética , Bromodesoxiuridina/metabolismo , Contagem de Células/métodos , Morte Celular , Irradiação Craniana/métodos , Meio Ambiente , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Hipocampo/efeitos dos fármacos , Hipocampo/efeitos da radiação , Proteínas de Filamentos Intermediários/genética , Proteínas Luminescentes/genética , Camundongos , Camundongos Transgênicos , Modelos Neurológicos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Nestina , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/efeitos da radiação , Neurogênese/efeitos dos fármacos , Neurogênese/efeitos da radiação , Isolamento Social , Tamoxifeno/farmacologia , Fatores de Tempo
18.
Biol Psychiatry ; 68(8): 689-96, 2010 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-20678752

RESUMO

BACKGROUND: We used a positron emission tomography paradigm with the D2/3 radiotracer [¹¹C]raclopride and an alcohol challenge to examine the magnitude of alcohol-induced dopamine release and compare it between young men and women. METHODS: Twenty-one nonalcohol-dependent young social drinkers completed two positron emission tomography scans on separate days following ingestion of a juice mix containing either ethanol (.75 mg/kg body water) or trace ethanol only. The extent of dopamine released after alcohol was estimated by the percentage difference in [¹¹C]raclopride binding potential (ΔBP(ND)) between days. RESULTS: Alcohol administration significantly displaced [¹¹C]raclopride in all striatal subregions, indicating dopamine release, with the largest effect observed in the ventral striatum. Linear mixed model analysis across all striatal subregions of regional ΔBP(ND) with region of interest as repeated measure showed a highly significant effect of sex (p < .001). Ventrostriatal dopamine release in men, but not in women, showed a significant positive correlation to alcohol-induced measures of subjective activation. Furthermore, we found a significant negative correlation between the frequency of maximum alcohol consumption per 24 hours and ventrostriatal ΔBP(ND) (r = .739, p = .009) in men. CONCLUSIONS: This study provides definitive evidence that oral alcohol induces dopamine release in nonalcoholic human subjects and shows sex differences in the magnitude of this effect. The ability of alcohol to stimulate dopamine release may contribute to its rewarding effects and, thereby, to its abuse liability in humans. Our report further suggests several biological mechanisms that may mediate the difference in vulnerability for alcoholism between men and women.


Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Corpo Estriado/metabolismo , Dopamina/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Racloprida/metabolismo , Caracteres Sexuais , Adulto , Consumo de Bebidas Alcoólicas/sangue , Radioisótopos de Carbono , Corpo Estriado/diagnóstico por imagem , Feminino , Humanos , Masculino , Ensaio Radioligante/métodos
19.
Biol Psychiatry ; 68(7): 634-41, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-20673873

RESUMO

BACKGROUND: Alterations in dopamine D(2)/D(3) receptor binding have been reported in schizophrenia, and a meta-analysis of imaging studies has shown a modest elevation in striatum. Newer radioligands now allow the assessment of these receptors in extrastriatal regions. We used positron emission tomography with [(18)F]fallypride to evaluate D(2)/D(3) receptors in both striatal and extrastriatal regions in schizophrenia. METHODS: Twenty-one patients with schizophrenia and 22 matched healthy control subjects were scanned with an ECAT EXACT HR+ camera. Two-tissue compartment modeling and the reference tissue method gave binding potentials relative to nondisplaceable uptake, total plasma concentration, and free plasma concentration. These were compared between groups in five striatal and eight extrastriatal regions. Several regional volumes were lower in the patient group, and positron emission tomography data were corrected for partial volume effects. RESULTS: Binding potential values differed in three regions between groups. Values for binding potential relative to nondisplaceable uptake from two-tissue compartment modeling in patients and control subjects, respectively, were 28.7 ± 6.8 and 25.3 ± 4.3 in postcommissural caudate, 2.9 ± .7 and 2.6 ± .4 in thalamus, and 1.8 ± .5 and 2.1 ± .7 in uncus. Loss of D(2)/D(3) receptors with age was found in striatal and extrastriatal regions and was greater in neocortex. CONCLUSIONS: Our study found selective alterations in D(2)/D(3) receptors in striatal and extrastriatal regions, consistent with some but not all previously published reports. As previously shown for the striatum, a more sensitive imaging approach for studying the role of dopamine in the pathophysiology of schizophrenia might be assessment of neurotransmitter levels rather than D(2)/D(3) receptor levels in extrastriatal regions.


Assuntos
Corpo Estriado/diagnóstico por imagem , Corpo Estriado/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/metabolismo , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia , Adulto , Fatores Etários , Análise de Variância , Antipsicóticos/uso terapêutico , Mapeamento Encefálico , Estudos de Casos e Controles , Corpo Estriado/efeitos dos fármacos , Feminino , Radioisótopos de Flúor/metabolismo , Humanos , Masculino , Tomografia por Emissão de Pósitrons/métodos , Ligação Proteica/efeitos dos fármacos , Escalas de Graduação Psiquiátrica , Esquizofrenia/tratamento farmacológico , Adulto Jovem
20.
Clin Cancer Res ; 13(18 Pt 2): 5629s-5635s, 2007 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-17875799

RESUMO

PURPOSE: The applicability of radioimmunotherapy with organism-specific monoclonal antibodies to treatment of infectious disease in experimental models has been recently shown for fungal, bacterial, and viral infections. To identify the best delivery vehicle for radioimmunotherapy of human pathogenic fungus Cryptococcus neoformans (CN), we have done comparative evaluation of capsular polysaccharide-specific antibodies with IgG1 and IgM isotypes and F(ab')2 and Fab fragments. EXPERIMENTAL DESIGN: 18B7 IgG1 and 13F1 IgM and their isotype-matching controls were radiolabeled with 188Re, and their binding to 24067 and H99 CN strains was evaluated by doing Scatchard and kinetics analyses. The doses delivered during in vitro radioimmunotherapy were estimated using a cellular dosimetry algorithm. The biodistribution of 188Re-labeled 18B7 and 13F1 and of 111In-labeled 18B7 and its F(ab')2 and Fab fragments was done in A/JCr mice systemically infected with 24067 CN strain. RESULTS: 18B7 IgG1 showed superior to 13F1 IgM binding to 24067 CN (Ka=1.7x10(9) mol/L(-1) and 5.4x10(7) mol/L(-1), respectively). Substantial killing of 24067 and H99 CN cells was achieved with 1 microCi 188Re-18B7 (55 cGy dose), whereas no killing was observed for 1 microCi 188Re-13F1 (2 cGy dose). In vivo 188Re-18B7 localized specifically in the lungs of CN-infected mice, whereas uptake of 188Re-13F1 was nonspecific. 111In-F(ab')2 fragments showed higher uptake in the lungs and lower in the liver at the 48-h time point in comparison with intact 111In-18B7. CONCLUSIONS: Comparative evaluation of IgG and IgM and of F(ab')2 and Fab fragments as potential delivery vehicles for radioimmunotherapy of cryptococcal infection strongly suggests that affinity for the target antigen is an important prerequisite for successful targeting of infection in vivo and that in vitro affinity measurements may predict the in vivo efficacy of candidate monoclonal antibodies.


Assuntos
Anticorpos Monoclonais/farmacologia , Criptococose/terapia , Fragmentos Fab das Imunoglobulinas/farmacologia , Imunoglobulina G/farmacologia , Imunoglobulina M/farmacologia , Imunotoxinas/farmacologia , Radioimunoterapia , Animais , Anticorpos Monoclonais/uso terapêutico , Criptococose/imunologia , Criptococose/microbiologia , Cryptococcus neoformans/patogenicidade , Cryptococcus neoformans/efeitos da radiação , Sistemas de Liberação de Medicamentos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Imunoglobulina G/uso terapêutico , Imunoglobulina M/uso terapêutico , Imunotoxinas/uso terapêutico , Radioisótopos de Índio/farmacologia , Pulmão/citologia , Pulmão/metabolismo , Camundongos , Polissacarídeos/imunologia , Rênio/farmacologia
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