RESUMO
Background: Adverse reactions, including anaphylaxis, to messenger RNA coronavirus disease 2019 (COVID-19) vaccines rarely occur. Because of the need to administer a timely second dose in subjects who reported a reaction to their first dose, a panel of health-care professionals developed a safe triage of the employees and health care providers (EHCP) at a large health-care system to consider administration of future dosing. Methods: There were 28,544 EHCPs who received their first dose of COVID-19 vaccines between December 15, 2020, and March 8, 2021. The EHCPs self-reported adverse reactions to a centralized COVID-19 command center (CCC). The CCC screened and collected information on the quality of reaction, symptoms, and timing of the onset of the reaction. Results: Of 1253 calls to the CCC, 113 were identified as requiring consideration by a panel of three (American Board of Allergy and Immunology) ABAI-certified allergists for future dosing or formal in-person assessment. Of the 113 EHCPs, 94 (83.2%) were recommended to get their second dose. Eighty of 94 received their second planned dose without a severe or immediate reaction. Of the 14 of 113 identified as needing further evaluation, 6 were evaluated by a physician and subsequently received their second dose without a serious adverse reaction. Eight of 14 did not receive their second dose. Only 5 of the 113 EHCPs reported reactions (4.4%) were recommended to not take the second dose: 3 (2.6%) because of symptoms consistent with anaphylaxis, and 2 because of neurologic complications (seizure, stroke). Conclusion: The panel demonstrated that, by consideration of reaction history alone, the ECHPs could be appropriately triaged to receive scheduled second dosing of COVID-19 vaccines without delays for in-person evaluation and allergy testing.
Assuntos
Anafilaxia/etiologia , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Pessoal de Saúde , Doenças Profissionais/prevenção & controle , Triagem/métodos , Vacinas Sintéticas/efeitos adversos , Adulto , Idoso , Anafilaxia/diagnóstico , Anafilaxia/prevenção & controle , Vacina BNT162 , Vacinas contra COVID-19/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Serviços de Saúde do Trabalhador/métodos , Serviços de Saúde do Trabalhador/normas , Melhoria de Qualidade , Estudos Retrospectivos , Autorrelato , Triagem/normas , Vacinas Sintéticas/administração & dosagem , Vacinas de mRNARESUMO
Thymic stromal lymphopoietin (TSLP) and IL-7 are cytokines that signal via the IL-7 receptor alpha (IL-7Rα) to exert both overlapping and unique functions during early stages of mouse B-cell development. In human B lymphopoiesis, the requirement for IL-7Rα signaling is controversial and the roles of IL-7 and TSLP are less clear. Here, we evaluated human B-cell production using novel in vitro and xenograft models of human B-cell development that provide selective IL-7 and human TSLP (hTSLP) stimulation. We show that in vitro human B-cell production is almost completely blocked in the absence of IL-7Rα stimulation, and that either TSLP or IL-7 can provide a signal critical for the production and proliferation of human CD19(+) PAX5(+) pro-B cells. Analysis of primary human bone marrow stromal cells shows that they express both IL-7 and TSLP, providing an in vivo source of these cytokines. We further show that the in vivo production of human pro-B cells under the influence of mouse IL-7 in a xenograft scenario is reduced by anti-IL-7 neutralizing antibodies, and that this loss can be restored by hTSLP at physiological levels. These data establish the importance of IL-7Rα mediated signals for normal human B-cell production.
Assuntos
Linfócitos B/citologia , Linfócitos B/metabolismo , Citocinas/metabolismo , Interleucina-7/metabolismo , Linfopoese , Receptores de Interleucina-7/metabolismo , Transdução de Sinais , Animais , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Células Cultivadas , Citocinas/farmacologia , Expressão Gênica , Humanos , Interleucina-7/farmacologia , Linfopoese/efeitos dos fármacos , Linfopoese/imunologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Transgênicos , Células Precursoras de Linfócitos B/citologia , Células Precursoras de Linfócitos B/efeitos dos fármacos , Células Precursoras de Linfócitos B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linfopoietina do Estroma do TimoRESUMO
These parameters were developed by the Joint Task Force on Practice Parameters (JTFPP), representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology. The AAAAI and ACAAI have jointly accepted responsibility for establishing "The diagnosis and management of acute and chronic urticaria: 2014 update." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the JTFPP, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. The JTFPP understands that the cost of diagnostic tests and therapeutic agents is an important concern that might appropriately influence the work-up and treatment chosen for a given patient. The JTFPP recognizes that the emphasis of our primary recommendations regarding a medication might vary, for example, depending on third-party payer issues and product patent expiration dates. However, because a given test or agent's cost is so widely variable and there is a paucity of pharmacoeconomic data, the JTFPP generally does not consider cost when formulating practice parameter recommendations. In extraordinary circumstances, when the cost/benefit ratio of an intervention is prohibitive, as supported by pharmacoeconomic data, commentary might be provided. These parameters are not designed for use by pharmaceutical companies in drug promotion. The JTFPP is committed to ensuring that the practice parameters are based on the best scientific evidence that is free of commercial bias. To this end, the parameter development process includes multiple layers of rigorous review. These layers include the workgroup convened to draft the parameter, the task force reviewers, and peer review by members of each sponsoring society. Although the task force has the final responsibility for the content of the documents submitted for publication, each reviewer comment will be discussed, and reviewers will receive written responses to comments, when appropriate. To preserve the greatest transparency regarding potential conflicts of interest, all members of the JTFPP and the practice parameter workgroups will complete a standard potential conflict of interest disclosure form, which will be available for external review by the sponsoring organization and any other interested individual. In addition, before confirming the selection of a Work Group chairperson, the Joint Task Force will discuss and resolve all relevant potential conflicts of interest associated with this selection. Finally, all members of parameter workgroups will be provided a written statement regarding the importance of ensuring that the parameter development process is free of commercial bias. Practice parameters are available online at www.jcaai.org and www.allergyparameters.org.
Assuntos
Urticária/diagnóstico , Urticária/terapia , Doença Aguda , Doença Crônica , Feminino , Humanos , Masculino , Sociedades MédicasRESUMO
A new series of peptidomimetic pseudo-prolyl-homophenylalanylketones were designed, synthesized and evaluated for inhibition of the Plasmodium falciparum cysteine proteases falcipain-2 (FP-2) and falcipain-3 (FP-3). In addition, the parasite killing activity of these compounds in human blood-cultured P. falciparum was examined. Of twenty-two (22) compounds synthesized, one peptidomimetic comprising a homophenylalanine-based α-hydroxyketone linked Cbz-protected hydroxyproline (39) showed the most potency (IC50 80 nM against FP-2 and 60 nM against FP-3). In silico analysis of these peptidomimetic analogs offered important protein-ligand structural insights including the role, by WaterMap, of water molecules in the active sites of these protease isoforms. The pseudo-dipeptide 39 and related compounds may serve as a promising direction forward in the design of competitive inhibitors of falcipains for the effective treatment of malaria.
Assuntos
Antimaláricos/farmacologia , Inibidores de Cisteína Proteinase/síntese química , Inibidores de Cisteína Proteinase/farmacologia , Dipeptídeos/síntese química , Dipeptídeos/farmacologia , Peptídeos/química , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/síntese química , Antimaláricos/química , Sítios de Ligação , Cisteína Endopeptidases/química , Cisteína Endopeptidases/metabolismo , Inibidores de Cisteína Proteinase/química , Dipeptídeos/química , Resistência a Medicamentos , Humanos , Ligação de Hidrogênio , Cetonas/síntese química , Cetonas/química , Cetonas/farmacologia , Simulação de Acoplamento Molecular , Peptidomiméticos , Plasmodium falciparum/enzimologia , Ligação Proteica , Estrutura Terciária de Proteína , Relação Estrutura-Atividade , TermodinâmicaRESUMO
A series of cinnamylideneacetophenones were synthesized via a modified Claisen-Schmidt condensation reaction and evaluated for cytotoxicity against breast cancer cells using the Alamar Blue™ assay. Derivatives 17 and 18 bearing a 2-nitro group on the B ring, exhibited sub-micromolar cytotoxicity in MCF-7 cells (IC50=71 and 1.9 nM), respectively. Derivative 17 also displayed sub-micromolar (IC50=780 nM) cytotoxicity in MDA-MB-468 cells. Additionally, 17 and 18 displayed significantly less cytotoxicity than the chemotherapeutic doxorubicin in non-tumorigenic MCF-10A cells. This study provides evidence supporting the continued development of nitro-substituted cinnamylideneacetophenones as small molecules to treat breast cancer.
Assuntos
Antineoplásicos/farmacologia , Cetonas/farmacologia , Nitrobenzenos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Cetonas/síntese química , Cetonas/química , Células MCF-7 , Estrutura Molecular , Nitrobenzenos/síntese química , Nitrobenzenos/química , Relação Estrutura-AtividadeRESUMO
Patients with urticaria and/or angioedema have several reasons to have a poor quality of life (QoL). The intensity of pruritus and density of involvement compromise a patient's lifestyle as well as aggravate stressors that affect physical and psychiatric conditions. The burden of illness is significant in not only costs for emergent practitioner visits, but, often, unnecessary laboratory testing and medication expenses. Questionnaires that assess a patient's QoL serve to document benefit to therapies. Objectively documenting changes that are important to patients with urticaria and/or angioedema allows the patients and clinician to accurately assess effectiveness of therapies over long periods of time. Specific surveys that address urticaria (CU-Q2oL and UAS) and angioedema (AE-QoL questionnaire) allow simplified and sensitive assessments for patients with the corresponding condition. Common components of appropriate surveys assess not only intensity of pruritus and wheals but also impact on sleep, interpersonal relationships, and appearances. In considering the most important aspects of several surveys, an example of a survey is provided that focuses on the patient's perception of how their urticaria and/or angioedema impacts their QoL.
Assuntos
Angioedema/epidemiologia , Qualidade de Vida , Urticária/epidemiologia , Análise de Variância , Angioedema/diagnóstico , Angioedema/psicologia , Inquéritos Epidemiológicos , Humanos , Administração dos Cuidados ao Paciente/normas , Administração dos Cuidados ao Paciente/estatística & dados numéricos , Fatores de Risco , Inquéritos e Questionários , Urticária/diagnóstico , Urticária/psicologiaRESUMO
These parameters were developed by the Joint Task Force on Practice Parameters (JTFPP), representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma and Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing "A focused parameter update: Hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the JTFPP, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. The Joint Task Force on Practice Parameters understands that the cost of diagnostic tests and therapeutic agents is an important concern that might appropriately influence the work-up and treatment chosen for a given patient. The JTFPP recognizes that the emphasis of our primary recommendations regarding a medication might vary, for example, depending on third-party payer issues and product patent expiration dates. However, because the cost of a given test or agent is so widely variable and there is a paucity of pharmacoeconomic data, the JTFPP generally does not consider cost when formulating practice parameter recommendations. In some instances the cost benefit of an intervention is considered relevant, and commentary might be provided. These parameters are not designed for use by pharmaceutical companies in drug promotion. The Joint Task Force is committed to ensuring that the practice parameters are based on the best scientific evidence that is free of commercial bias. To this end, the parameter development process includes multiple layers of rigorous review. These layers include the Workgroup convened to draft the parameter, the Task Force Reviewers, and peer review by members of each sponsoring society. Although the Task Force has the final responsibility for the content of the documents submitted for publication, each reviewer comment will be discussed, and reviewers will receive written responses to comments when appropriate. To preserve the greatest transparency regarding potential conflicts of interest, all members of the Joint Task Force and the Practice Parameters Workgroups will complete a standard potential conflict of interest disclosure form, which will be available for external review by the sponsoring organization and any other interested individual. In addition, before confirming the selection of a Workgroup chairperson, the Joint Task Force will discuss and resolve all relevant potential conflicts of interest associated with this selection. Finally, all members of parameter workgroups will be provided a written statement regarding the importance of ensuring that the parameter development process is free of commercial bias.
Assuntos
Angioedema/diagnóstico , Angioedema/terapia , Angioedema Hereditário Tipos I e II/diagnóstico , Angioedema/etiologia , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Angioedema Hereditário Tipos I e II/etiologia , Angioedema Hereditário Tipos I e II/terapia , HumanosRESUMO
Graduating student pharmacists who are practice-ready is an essential responsibility of pharmacy programs and heavily emphasized by Accreditation Council of Pharmacy Education (ACPE), pharmacy education's accrediting body. Although several studies have examined students' readiness to engage in advanced pharmacy practice experiences (APPE), few studies examine graduating students' readiness to practice. The objective of this study was to examine national trends in graduating pharmacy students' and preceptors' perceptions of students' pharmacy practice preparedness across a six-year time frame (2016-2021) and trends in graduating students' overall impressions of their program and the pharmacy profession across the same time period. A longitudinal descriptive study to examine trends in graduating student and preceptor perception was conducted utilizing data from the 2016-2021 American Association of Colleges of Pharmacy (AACP) Graduating Student Surveys (GSS) (n = 65,461) and Preceptor Surveys (PS) (n = 41,951). Over six years of survey data analyzed, a large percentage of students at both public and private institutions reported they felt prepared for practice (96.5% vs 95.5% respectively, p < 0.001). There was overall agreement (>90%) among preceptors that graduating students were prepared to enter pharmacy practice based on responses, although preceptors had lower levels of agreement compared to students on most statements. Based on the findings, both graduating pharmacy students and preceptors feel that graduates are prepared to practice pharmacy, with consistent trends in perceptions over the last six years. However, results also indicate that a consistent downward trend in students' willingness to pursue pharmacy again, indicating decreased optimism of graduating students for the profession.
Assuntos
Percepção , Preceptoria , Estudantes de Farmácia , Humanos , Estudantes de Farmácia/estatística & dados numéricos , Estudantes de Farmácia/psicologia , Estudos Longitudinais , Preceptoria/métodos , Preceptoria/estatística & dados numéricos , Preceptoria/tendências , Preceptoria/normas , Inquéritos e Questionários , Feminino , Masculino , Adulto , Educação em Farmácia/métodos , Educação em Farmácia/estatística & dados numéricos , Educação em Farmácia/tendências , Educação em Farmácia/normas , Estados UnidosRESUMO
OBJECTIVE: To assess pharmacy faculty members' perceptions of conditions associated with workload equity and factors that can improve workload equity. METHODS: A 26-item survey instrument was developed and distributed via email to members of the American Association of Colleges of Pharmacy Council of Faculties. Questions pertained to the workload distribution, fairness in assignment, and perception of the conditions associated with workload equity (transparency, context, credit, clarity, norms, and accountability) as well as institutional and individual demographics. RESULTS: A total of 662 responses were obtained (response rate 15.9%). Respondents' demographics were comparable to available national data. Approximately 41% of respondents reported their institutions did not have a written faculty workload policy. Most respondents reported their workload assignment was fair (highest with research/scholarship) but reported only moderate alignment between assigned and actual workloads. The rating level for what domains the primary decision maker uses to assign workload was highest for context, followed by credit, clarity, and transparency. Transparency was reported as the most needed condition to improve faculty perception of workload equity. Respondents also rated increasing trust between leadership and faculty and increasing productivity and accountability as the most important reasons to minimize workload inequities. CONCLUSION: This was the first national survey of pharmacy faculty perceptions around the conditions associated with workload equity. Though additional research is needed in this area, programs can work to implement strategies associated with all of the conditions, particularly transparency, to improve faculty perceptions of equity.
Assuntos
Educação em Farmácia , Docentes de Farmácia , Humanos , Carga de Trabalho , Docentes , Inquéritos e QuestionáriosRESUMO
Importance: Diversity is an essential element of an effective health care system. A key to developing a diverse workforce is establishing a diverse student population in health professions programs. Objective: To examine the diversity of students in Doctor of Medicine (MD), Doctor of Osteopathic Medicine (DO), Doctor of Dental Surgery (DDS), Doctor of Dental Medicine (DMD), and Doctor of Pharmacy (PharmD) programs with emphasis on the trends of underrepresented minoritized groups (American Indian or Alaska Native, Black or African American, Hispanic or Latino, and Native Hawaiian or Other Pacific Islander) and sex relative to the overall age-adjusted US population. Design, Setting, and Participants: This cross-sectional study used deidentified, self-reported data from 2003 to 2019 from the Association of American Medical Colleges, American Association of Colleges of Osteopathic Medicine, American Dental Education Association, American Dental Association, and American Association of Colleges of Pharmacy. Data analysis was performed from 2003 to 2004 and from 2018 to 2019. Exposures: Data on the race, ethnicity, and sex of applicants, matriculants, and degrees conferred by health professions programs were collected and compared with the age-adjusted population in the US Census (aged 20-34 years) over time. Main Outcomes and Measures: The main outcomes were trends in the proportions of underrepresented minoritized groups and sex diversity among applicants, matriculants, and degrees conferred relative to the overall age-adjusted US population. Trends were measured using the representation quotient, which is defined as the ratio of the proportion of each subgroup to the total population of applicants, matriculants, or graduates relative to the proportion for that subgroup within the US Census population of similar age. Regression analysis was used to evaluate the trend over time. Results: A total of 594â¯352 applicants were analyzed across the examined programs. From 2003 to 2019, the proportions of individuals from underrepresented groups increased for DDS and DMD (applicants, from 1003 of 8176 to 1962 of 11â¯298 [5.1%]; matriculants, from 510 of 4528 to 966 of 6163 [4.2%]; degrees awarded, from 484 of 4350 to 878 of 6340 [2.7%]), PharmD (applicants, from 9045 of 71â¯966 to 11â¯653 of 50â¯482 [9.0%]; matriculants, from 5979 of 42â¯627 to 10â¯129 to 62â¯504 [6.3%]; degrees awarded, from 922 of 7770 to 2190 of 14â¯800 [3.0%]), and DO (applicants, from 740 of 6814 to 3478 of 21â¯090 [5.4%]; degrees awarded, 199 of 2713 to 582 of 6703 [1.4%]) programs, but decreased for MD programs (applicants, from 6066 of 34â¯791 to 7889 of 52â¯777 [-2.3%]; matriculants, 2506 of 16â¯541 to 2952 of 21â¯622 [-2.4%]; degrees awarded, from 2167 of 15â¯829 to 2349 of 19â¯937 [-0.1%]). Compared with age-adjusted US Census data, all programs had more Asian students and fewer male, American Indian or Alaska Native, Black or African American, Hispanic or Latino, and Native Hawaiian or Other Pacific Islander students (representation quotient <1). Conclusions and Relevance: In this cross-sectional study, most of the health professions in the study saw increases in underrepresented minority applicants, matriculants, and degrees conferred from 2003 to 2019; however, all programs were below the age-adjusted US Census data. The increased racial, ethnic, and sex diversity in the programs illustrates progress, but additional strategies are needed to achieve a more representative health care workforce.
Assuntos
Ocupações em Saúde , Farmácia , Estados Unidos , Humanos , Masculino , Estudos Transversais , Pessoal de Saúde , EtnicidadeRESUMO
OBJECTIVE: To assess how department chairs/administrators define, measure, and evaluate faculty workload to better understand practices within the Academy. METHODS: An 18-item survey was distributed to department chairs/administrators via American Association of Colleges of Pharmacy Connect. Participants identified if they are a primary decision maker for faculty workload, whether their program has a workload policy, how workload is calculated, and how faculty satisfaction with workload equity is measured. RESULTS: Of 71 participants initiating the survey, data from 64 participants from 52 colleges/schools were eligible for analysis. Leaders of practice departments reported that their faculty spend an average of 38% of their time on teaching (compared to 46% for non-practice departments), 13% on research (vs 37%), 12% on service (vs 16%), and 36% on clinical practice (vs 0%). Most survey participants (n = 57, 89%) are at schools/colleges with a tenure system, and about 24 participants reported that faculty workload metrics differ across departments/divisions. Teaching assignments and service are reportedly negotiable between faculty and supervisors, and workload expectations are widely variable. The majority indicated they do not analyze faculty satisfaction with workload fairness (n = 35) and faculty do not provide evaluative feedback on how supervisors assign faculty workload (n = 34). Of 6 priorities considered when determining workload, 'support college/school strategies and priorities' ranked highest (1.92) and 'trust between the chair and faculty' ranked lowest (4.87). CONCLUSION: Overall, only half of the participants reported having a clear, written process of quantifying faculty workload. The use of workload metrics may be needed for evidence-based decision-making for personnel management and resource allocation.
Assuntos
Educação em Farmácia , Carga de Trabalho , Humanos , Estados Unidos , Liderança , Docentes , Escolaridade , Docentes de FarmáciaRESUMO
PURPOSE: Propofol is an intravenous sedative used in many patient populations and care settings. Although generally considered safe and effective, the drug has historically been avoided in patients with reported allergies to egg, soy, and/or peanut on the basis of the manufacturer's prescribing information. Concerns exist for potential adverse events, increased medication costs, reduced efficacy, and risk of medication errors when using alternative agents. Here we present a critical examination of the literature concerning cross-reactivity of food allergies with propofol to provide evidence-based recommendations for the evaluation and management of potential allergic reactions. SUMMARY: Literature regarding the history of propofol allergy warnings and clinical trial data were assessed to provide an alternative perspective on avoidance of propofol in patients with food allergies. Suspected trigger molecules are discussed, with evaluation of the antigenic potential of excipient ingredients used in the manufacture of multiple propofol formulations. Evidence-based recommendations are provided for pharmacist-led screening of adult patients with reported food allergies to support selection of propofol or alternative therapy. CONCLUSION: There is a lack of definitive evidence that propofol must be routinely avoided in patients with reported allergies to egg, soy, and/or peanut products. Data from clinical trials suggest that propofol is safe for patients with nonanaphylactic food allergies. Patients who do experience allergic reactions following administration of propofol should undergo further testing to definitively identify the specific trigger and prevent future unnecessary avoidance of preferred medication regimens. Pharmacists can play an important role in interviewing patients with reported food allergies to better determine the risk vs benefit of propofol avoidance.
Assuntos
Hipersensibilidade , Propofol , Humanos , Propofol/efeitos adversosRESUMO
There are many conditions that may present with swelling that mimics angioedema. When swelling persists for greater than a few days or is unresponsive to treatment for urticaria/angioedema, other etiologies should be considered. In most instances, a thorough history and physical examination will define other etiologies. However, for more persistent conditions, further laboratory evaluation and a biopsy may be required to define the diagnosis. Rarely is a more aggressive approach required to make the diagnosis. Clinicians should remember that if the swelling does not act like angioedema, it more than likely is not angioedema.
Assuntos
Angioedema/diagnóstico , Angioedema/etiologia , Diagnóstico Diferencial , HumanosRESUMO
We studied the phase-transition induced texture changes and strengthening mechanism for zirconium metal under quasi-hydrostatic compression and uni-axial deformation under confined high pressure using the deformation-DIA (D-DIA) apparatus. It is shown that the experimentally obtained texture for ω-phase Zr can be qualitatively described by combining a subset of orientation variants previously proposed in two different models. The determined flow stress for the high-pressure ω-phase is 0.5-1.2 GPa, more than three times higher than that of the α-phase. Using first-principles calculations, we investigated the mechanical and electronic properties of the two Zr polymorphs. We find that the observed strengthening can be attributed to the relatively strong directional bonding in the ω phase, which significantly increases its shear plastic resistance over the α-phase Zr. The present findings provide an alternate route for Zr metal strengthening by high-pressure phase transformation.
RESUMO
OBJECTIVE: To provide information about risk factors for, diagnosis of, and potential treatments and prevention of avascular necrosis (AVN) in patients frequently given systemic corticosteroid therapy for the management of allergic and/or inflammatory diseases. DATA SOURCES: Articles on AVN cited in PubMed from 1975 through 2008. STUDY SELECTION: Publications consisted of case reports, reviews of osteonecrosis, and animal and human studies (mostly open, nonrandomized, and observational). RESULTS: Case reports of rare and infrequent use of corticosteroids and the development of osteonecrosis are of great concern to physicians, but most patients affected may also be at risk of developing osteonecrosis because of repetitive systemic corticosteroid use with underlying hyperlipidemia, alcoholism, smoking, connective tissue disorders, and/or previous trauma to the affected area. The use of statins for patients with hyperlipidemias may be useful in decreasing the risk of osteonecrosis but is considered investigational. Enhanced magnetic resonance imaging is the most sensitive tool for diagnosing AVN early. Prophylaxis with bisphosphonates may be worthwhile in certain patients for the early management of pain due to AVN, but eventually surgical intervention is warranted in the treatment of osteonecrosis. CONCLUSIONS: Recognition of risk factors and educating (enabling) the patient remain the most effective ways of preventing AVN caused by corticosteroid use.
Assuntos
Corticosteroides/efeitos adversos , Osteonecrose/induzido quimicamente , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Animais , Osso e Ossos/patologia , Causalidade , Humanos , Osteonecrose/diagnóstico , Osteonecrose/epidemiologia , Osteonecrose/terapia , Hipersensibilidade Respiratória/tratamento farmacológicoRESUMO
OBJECTIVE: To define the effects of both parenteral and inhaled corticosteroids on bone growth in children and the development of osteopenia and osteoporosis in children and adults. DATA RESOURCES: Articles in PubMed and MEDLINE published from 1983 to 2008 were searched. Keywords used included corticosteroids and bone growth, osteopenia, osteoporosis, and bisphosphonates. STUDY SELECTION: Publications reviewed include randomized, placebo-controlled studies of both children and adults. RESULTS: Because systemic and high-dose inhaled corticosteroids affect bone growth of children taking these medications, stadiometry should be used to measure the growth of children. Osteoporosis due to repetitive courses of oral or parenteral corticosteroids and inhaled corticosteroids can develop gradually in the aging adult. Prophylaxis against osteoporosis requires an index of suspicion, assessment of bone density, supplemental calcium and vitamin D, and use of bisphosphonates to prevent bone fractures that could compromise the patient's quality of life. CONCLUSION: Preventing corticosteroid-induced effects on bone metabolism can allow effective treatment of allergic disease without long-term adverse effects.
Assuntos
Corticosteroides/efeitos adversos , Corticosteroides/farmacologia , Densidade Óssea/efeitos dos fármacos , Desenvolvimento Ósseo/efeitos dos fármacos , Corticosteroides/administração & dosagem , Adulto , Doenças Ósseas Metabólicas/induzido quimicamente , Doenças Ósseas Metabólicas/tratamento farmacológico , Doenças Ósseas Metabólicas/prevenção & controle , Criança , Humanos , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de RiscoRESUMO
Pruritus is synonymous with itching. Many medical conditions are complicated by chronic pruritus compromising the patient's quality of life. The majority of pruritic stimuli are transmitted through C fibers into the lateral spinothalamic tract and then into the somatic sensory cortex where the itching is detected. Histamine, substance P, and tumor necrosis factor a play significant roles in the perception of pruritus. Medical conditions in adults with significant pruritus will be defined in this review.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Transtornos Mentais/complicações , Prurido/etiologia , Dermatopatias/complicações , Adulto , Dermatite Herpetiforme/complicações , Dermatite Herpetiforme/fisiopatologia , Diagnóstico Diferencial , Histamina/metabolismo , Humanos , Líquen Plano/complicações , Líquen Plano/fisiopatologia , Transtornos Mentais/diagnóstico , Transtornos Mentais/fisiopatologia , Fibras Nervosas Amielínicas/metabolismo , Penfigoide Bolhoso/complicações , Penfigoide Bolhoso/fisiopatologia , Prurido/metabolismo , Prurido/fisiopatologia , Psoríase/complicações , Psoríase/fisiopatologia , Escabiose/complicações , Escabiose/fisiopatologia , Pele/inervação , Dermatopatias/diagnóstico , Dermatopatias/microbiologia , Dermatopatias/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Substância P/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Urticária/complicações , Urticária/fisiopatologiaRESUMO
In patients with chronic and recurrent sinusitis, laryngopharyngeal reflux disease may play a significant role. Laryngopharyngeal reflux disease differs from gastroesophageal reflux disease in the extent of reflux (into the hypopharynx and above) as well as timing (occurring more often when the patient is upright). Most patients are unaware of the extent of their symptoms, and diagnostic tools such as pH probe, multichannel intraluminal impedance, and manometry are required for adequate diagnosis. Although therapy with lifestyle modification and acid-suppressive agents may improve reflux in the majority of patients, for many with persistent symptoms, endoscopic or surgical intervention is required to reduce reflux successfully.
Assuntos
Refluxo Gastroesofágico , Doenças da Laringe , Sinusite , Antiácidos/uso terapêutico , Antiulcerosos/uso terapêutico , Criança , Doença Crônica , Determinação da Acidez Gástrica , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/fisiopatologia , Refluxo Gastroesofágico/terapia , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Doenças da Laringe/complicações , Doenças da Laringe/fisiopatologia , Doenças da Laringe/terapia , Doenças Faríngeas/complicações , Doenças Faríngeas/fisiopatologia , Doenças Faríngeas/terapia , Sinusite/complicações , Sinusite/fisiopatologiaRESUMO
The causes of coughing are multiple. Research into the physiology of coughing has established that interactions amid C-fibers and rapidly activating receptors in humans have the most significant effect on stimulation of coughing. Precipitants of coughing include gastroesophageal reflux and sinusitis. Stimulation of vagal afferents by esophageal irritation and aspiration of acidic gastric contents or vapors are the most frequently cited causes of cough associated with gastroesophageal reflux or laryngopharyngeal reflux. Sinusitis may precipitate coughing from other mechanisms including aspiration of postnasal drainage and sinopulmonary reflex. Taking a lesson on how these conditions affect asthmatic patients, this article will review how these two conditions may also influence cough in normal patients.
Assuntos
Tosse/etiologia , Refluxo Gastroesofágico/complicações , Sinusite/complicações , Hiper-Reatividade Brônquica/fisiopatologia , Doença Crônica , Tosse/fisiopatologia , Diagnóstico Diferencial , Esôfago/fisiopatologia , Refluxo Gastroesofágico/fisiopatologia , Refluxo Gastroesofágico/terapia , Humanos , Doenças da Laringe/etiologia , Doenças Faríngeas/etiologia , Sinusite/fisiopatologia , Traqueia/inervação , Traqueia/fisiopatologia , Nervo Vago/fisiopatologiaRESUMO
The dilemma of treating chronic sinusitis continues to confuse clinicians. When mucosal thickening does not respond to aggressive antibiotic therapy, other etiologies should be considered. Perhaps the most likely is the inflammatory response. In comparison with asthma, chronic sinusitis exhibits amazing similarities. Atopic dermatitis also exhibits similar inflammatory responses that lead to thickening of the skin in a manner not dissimilar to mucosal thickening. The interactions amid eosinophils, lymphocytes, leukotrienes, interleukins, and epithelial cells serve as a reminder that there is one immune response and similarities exist in the pathophysiology of these conditions.