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J Clin Immunol ; 2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-29882021


The pathogenesis of life-threatening influenza A virus (IAV) disease remains elusive, as infection is benign in most individuals. We studied two relatives who died from influenza. We Sanger sequenced GATA2 and evaluated the mutation by gene transfer, measured serum cytokine levels, and analyzed circulating T- and B-cells. Both patients (father and son, P1 and P2) died in 2011 of H1N1pdm IAV infection at the ages of 54 and 31 years, respectively. They had not suffered from severe or moderately severe infections in the last 17 (P1) and 15 years (P2). A daughter of P1 had died at 20 years from infectious complications. Low B-cell, NK- cell, and monocyte numbers and myelodysplastic syndrome led to sequence GATA2. Patients were heterozygous for a novel, hypomorphic, R396L mutation leading to haplo-insufficiency. B- and T-cell rearrangement in peripheral blood from P1 during the influenza episode showed expansion of one major clone. No T-cell receptor excision circles were detected in P1 and P3 since they were 35 and 18 years, respectively. Both patients presented an exuberant, interferon (IFN)-γ-mediated hypercytokinemia during H1N1pdm infection. No data about patients with viremia was available. Two previously reported adult GATA2-deficient patients died from severe H1N1 IAV infection; GATA2 deficiency may predispose to life-threatening influenza in adulthood. However, a role of other genetic variants involved in immune responses cannot be ruled out. Patients with GATA2 deficiency can reach young adulthood without severe infections, including influenza, despite long-lasting complete B-cell and natural killer (NK) cell deficiency, as well as profoundly diminished T-cell thymic output.

Biochem Pharmacol ; 154: 1-9, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29674001


Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) widely used as a component of High Active Antiretroviral Therapy (HAART) since it is inexpensive, readily absorbed after oral administration and non-teratogenic. In the present work, the mechanism of a previously described pharmacokinetic interaction between NVP and the antidepressant drug nortriptyline (NT) was studied using rat hepatic microsomes. The obtained results showed a competitive inhibition of the NVP metabolism by NT. The three main NVP metabolites (2-OH-NVP, 3-OH-NVP and 12-OH-NVP) where competitively inhibited with similar inhibitory constant values (Ki = 4.01, 3.97 and 4.40 µM, respectively). Time-dependent inhibition of the NVP metabolism was also detected, with a 2.5-fold reduction in the IC50 values of NT for 2-, 3-, and 12-OH-NVP formation when NT was preincubated with the microsomal suspension in the presence of an NADPH-generating system. A concentration-dependent inhibition of the formation of NVP metabolites by the main NT metabolite (10-OH-NT) was also observed, however, the inhibitory potency of 10-OH-NT was much lower than that of the parent drug. The apparent hepatic intrinsic clearance of NVP determined in these in vitro experiments was used to predict the in vivo clearance of NVP using the "well-stirred" and the "parallel-tube" models, resulting in values close to those previously observed in vivo clearance. Finally, a good prediction of the increase in the plasma concentrations of NVP when co-administered with NT was obtained employing the inhibitory constant of NT determined in vitro and the estimated plasma concentration of NT entering the liver.

Circulation ; 137(21): e645-e660, 2018 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-29483084


The American Heart Association previously recommended implementation of cardiac resuscitation systems of care that consist of interconnected community, emergency medical services, and hospital efforts to measure and improve the process of care and outcome for patients with cardiac arrest. In addition, the American Heart Association proposed a national process to develop and implement evidence-based guidelines for cardiac resuscitation systems of care. Significant experience has been gained with implementing these systems, and new evidence has accumulated. This update describes recent advances in the science of cardiac resuscitation systems and evidence of their effectiveness, as well as recent progress in dissemination and implementation throughout the United States. Emphasis is placed on evidence published since the original recommendations (ie, including and since 2010).

Rev. esp. quimioter ; 29(5): 259-264, oct. 2016.
Artigo em Inglês | IBECS | ID: ibc-156281


Background. The clinical response to ertapenem in community-acquired pneumonia (CAP) at the setting of routine hospital practice has been scarcely evaluated. Methods. We retrospectively compared CAP cases treated with ertapenem or with other standard antimicrobials (controls) at a tertiary 1,434-bed center from 2005 to 2014. Results. Out of 6,145 patients hospitalized with CAP, 64 (1%) ertapenem-treated and 128 controls were studied (PSI IV-V 72%, mean age 73 years.). A significant higher proportion of bedridden patients (41% vs. 21%), residence in nursing homes (19% vs. 7%), previous use of antibiotics (39% vs. 29%) and necrotizing (13% vs. 1%) or complicated (36% vs. 19%) pneumonia, was observed in the ertapenem vs. non-ertapenem patients. Initial treatment with ertapenem was independently associated with an earlier resolution of signs of infection. In patients aged 65 or older the independent risks factors for mortality were: PSI score (7.0, 95%CI 1.8-27.7), bedridden status (4.6, 95%CI 1.1-20.9) and Health Care Associated Pneumonia (HCAP) (4.6, 95%CI 1.3-16.5). First-line treatment with ertapenem was an independent protector factor in this subgroup of patients (0.1, 95%CI 0.1-0.7). Conclusions. Ertapenem showed a superior clinical response in frail elderly patients with complicated community- acquired pneumonia, and it may be considered as a firstline therapeutic regimen in this setting (AU)

Introducción. La respuesta clínica a ertapenem en la neumonía adquirida en la comunidad (NAC) en el contexto de la práctica clínica diaria ha sido evaluada de forma insuficiente. Material y Métodos. Estudio retrospectivo, comparativo de pacientes con NAC tratados con ertapenem o con otros antimicrobianos en un hospital terciario de 1.434 camas en el período 2005-2014. Resultados. De los 6.145 pacientes hospitalizados con NAC, 64 (1%) tratados con ertapenem y 128 controles fueron incluidos en el estudio (PSI IV-V 72%, edad media 73 años). Se observó una proporción significativamente mayor de pacientes encamados (41% vs. 21%), institucionalizados (19% vs. 7%), con antibioterapia previa (39% vs. 29%) y con neumonías necrotizantes (13% vs. 1%) o complicadas (36% vs. 19%) en el grupo de ertapenem vs. no-ertapenem. El tratamiento inicial con ertapenem se asoció de forma independiente con una resolución más temprana de los signos de infección. En el subgrupo de pacientes con 65 años o más, los factores independientes de riesgo de mortalidad fueron: PSI score (7,0 IC95% 1,8-27,7), encamamiento (4,6 IC95% 1,1-20,9) y la Neumonía Asociada a Cuidados Sanitarios (NACS) (4,6 IC95% 1,3-16,5). El tratamiento en primera línea con ertapenem fue un factor protector independiente en este grupo de pacientes (0,1 IC95% 0,1-0,7). Conclusiones. El tratamiento con ertapenem se asoció a una respuesta clínica superior en el paciente anciano frágil con NAC complicada y se podría considerar como un régimen terapéutico de primera línea en este contexto (AU)

Humanos , Pneumonia/tratamento farmacológico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Antibacterianos/uso terapêutico , Estudos de Coortes , Estudos Retrospectivos , Idoso Fragilizado/estatística & dados numéricos , Fatores de Risco , Hospitalização/estatística & dados numéricos
West J Emerg Med ; 16(5): 736-42, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26587099


INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) is a leading cause of death. The 2010 American Heart Association Emergency Cardiovascular Care (ECC) Guidelines recognize emergency dispatch as an integral component of emergency medical service response to OHCA and call for all dispatchers to be trained to provide telephone cardiopulmonary resuscitation (T-CPR) pre-arrival instructions. To begin to measure and improve this critical intervention, this study describes a nationwide survey of public safety answering points (PSAPs) focusing on the current practices and resources available to provide T-CPR to callers with the overall goal of improving survival from OHCA. METHODS: We conducted this survey in 2010, identifying 5,686 PSAPs; 3,555 had valid e-mail addresses and were contacted. Each received a preliminary e-mail announcing the survey, an e-mail with a link to the survey, and up to three follow-up e-mails for non-responders. The survey contained 23 primary questions with sub-questions depending on the response selected. RESULTS: Of the 5,686 identified PSAPs in the United States, 3,555 (63%) received the survey, with 1,924/3,555 (54%) responding. Nearly all were public agencies (n=1,888, 98%). Eight hundred seventy-eight (46%) responding agencies reported that they provide no instructions for medical emergencies, and 273 (14%) reported that they are unable to transfer callers to another facility to provide T-CPR. Of the 1,924 respondents, 975 (51%) reported that they provide pre-arrival instructions for OHCA: 67 (3%) provide compression-only CPR instructions, 699 (36%) reported traditional CPR instructions (chest compressions with rescue breathing), 166 (9%) reported some other instructions incorporating ventilations and compressions, and 92 (5%) did not specify the type of instructions provided. A validation follow up showed no substantial difference in the provision of instructions for OHCA by non-responders to the survey. CONCLUSION: This is the first large-scale, nationwide assessment of the practices of PSAPs in the United States regarding T-CPR for OHCA. These data showing that nearly half of the nation's PSAPs do not provide T-CPR for OHCA, and very few PSAPs provide compression-only instructions, suggest that there is significant potential to improve the implementation of this critical link in the chain of survival for OHCA.

Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar/terapia , Telefone , Reanimação Cardiopulmonar/métodos , Serviços Médicos de Emergência/estatística & dados numéricos , Humanos , Inquéritos e Questionários , Estados Unidos
Circulation ; 132(16 Suppl 1): S40-50, 2015 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-26472858


The process for evaluating the resuscitation science has evolved considerably over the past 2 decades. The current process, which incorporates the use of the GRADE methodology, culminated in the 2015 CoSTR publication, which in turn will inform the international resuscitation councils' guideline development processes. Over the next few years, the process will continue to evolve as ILCOR moves toward a more continuous evaluation of the resuscitation science.

Reanimação Cardiopulmonar/normas , Consenso , Serviços Médicos de Emergência/normas , Medicina Baseada em Evidências , Parada Cardíaca/terapia , Guias de Prática Clínica como Assunto , Viés , Reanimação Cardiopulmonar/métodos , Emergências , Serviços Médicos de Emergência/métodos , Humanos , Estudos Observacionais como Assunto , Projetos de Pesquisa
Crit Care ; 18(3): R127, 2014 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-24950659


INTRODUCTION: Inherited variability in host immune responses influences susceptibility and outcome of Influenza A virus (IAV) infection, but these factors remain largely unknown. Components of the innate immune response may be crucial in the first days of the infection. The collectins surfactant protein (SP)-A1, -A2, and -D and mannose-binding lectin (MBL) neutralize IAV infectivity, although only SP-A2 can establish an efficient neutralization of poorly glycosylated pandemic IAV strains. METHODS: We studied the role of polymorphic variants at the genes of MBL (MBL2), SP-A1 (SFTPA1), SP-A2 (SFTPA2), and SP-D (SFTPD) in 93 patients with H1N1 pandemic 2009 (H1N1pdm) infection. RESULTS: Multivariate analysis showed that two frequent SFTPA2 missense alleles (rs1965708-C and rs1059046-A) and the SFTPA2 haplotype 1A(0) were associated with a need for mechanical ventilation, acute respiratory failure, and acute respiratory distress syndrome. The SFTPA2 haplotype 1A(1) was a protective variant. Kaplan-Meier analysis and Cox regression also showed that diplotypes not containing the 1A(1) haplotype were associated with a significantly shorter time to ICU admission in hospitalized patients. In addition, rs1965708-C (P = 0.0007), rs1059046-A (P = 0.0007), and haplotype 1A(0) (P = 0.0004) were associated, in a dose-dependent fashion, with lower PaO2/FiO2 ratio, whereas haplotype 1A(1) was associated with a higher PaO2/FiO2 ratio (P = 0.001). CONCLUSIONS: Our data suggest an effect of genetic variants of SFTPA2 on the severity of H1N1pdm infection and could pave the way for a potential treatment with haplotype-specific (1A(1)) SP-A2 for future IAV pandemics.

Vírus da Influenza A Subtipo H1N1 , Influenza Humana/genética , Proteína A Associada a Surfactante Pulmonar/genética , Adulto , Pressão Sanguínea , Feminino , Haplótipos , Hospitalização , Humanos , Influenza Humana/fisiopatologia , Masculino , Mutação de Sentido Incorreto , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Estudos Retrospectivos , Índice de Gravidade de Doença
Angiología ; 58(3): 231-238, mayo-jun. 2006. tab
Artigo em Espanhol | IBECS | ID: ibc-046266


Objetivos. Interrogar al personal quirúrgico, médico y de enfermería sobre su conocimiento de los distintos hábitos quirúrgicos de los cirujanos zurdos, sus posibles problemas de adaptación, así como sobre las posibilidades de complementariedad que puede suponer operar con un cirujano zurdo. Sujetos y métodos. Entre enero y mayo de 2003 se encuestó a 145 médicos cirujanos y a 17 enfermeros instrumentistas. La encuesta se componía de 15 preguntas con respuestas múltiples. Se realizó un análisis descriptivo de las respuestas y se comprobó si existían diferencias estadísticamente significativas entre las respuestas de los distintos grupos con el test de chi al cuadrado. Resultados. La muestra presenta igual prevalencia de cirujanos zurdos y ambidextros (6,2% frente a 6,8%). El 100% de la enfermería instrumentista y el 72% de los cirujanos de staff han instrumentado o ayudado a un cirujano zurdo. El 93% de los encuestados opina que los cirujanos zurdos operan igual que los diestros. El 65% opina que el instrumental estándar no es igualmente útil para diestros y zurdos. El 45% de los encuestados desconoce la existencia de instrumental específico para zurdos, si bien el 80% cree que mejoraría su capacidad quirúrgica. Es opinión mayoritaria que la implementación de material específico para zurdos no se produce por problemas de costes. Conclusiones. Existe un desconocimiento notable de la problemática del cirujano zurdo, y no se valoran las posibles ventajas que puede aportar su ayuda. La implementación de instrumental diseñado para cirujanos zurdos sería, en opinión general, una ayuda valiosa (AU)

Aims. To question members of surgical, medical and nursing staff about their knowledge of the different surgical habits of left-handed surgeons, the possible problems they may have as regards adaptation, and also about the chances of complementarity that may be required when operating with a left-handed surgeon. Subjects and methods. Between January and May 2003 a survey was conducted on 145 surgeons and 17 instrument nurses. The survey consisted of 15 questions with multiple-choice answers. Responses were submitted to a descriptive analysis and the chi squared test was use to determine whether there were statistically significant differences between the answers given by the different groups. Results. The prevalence of left-handed and ambidextrous surgeons in the sample was the same (6.2% versus 6.8%). 100% of the instrument nurses and 72% of the staff surgeons have assisted or acted as scrub nurses with a left-handed surgeon. 93% of the respondents stated that left-handed surgeons operate in the same way as their right-handed colleagues. 65% said that standard instruments are not as easy to use for left- and right-handers. 45% of the respondents did not know that there are instruments specifically designed for left-handed users, although 80% thought that they would improve their surgical capacity. The majority said that specific left-handed material was not implemented due to the extra cost involved. Conclusions. The problems left-handed surgeons face are something that is largely unknown and the possible advantages that could be gained by helping them are not taken into account. In general respondents thought that implementing instruments designed for left-handed surgeons would be a valuable aid (AU)

Masculino , Feminino , Adulto , Humanos , Hábitos , Auxiliares de Cirurgia , Salas Cirúrgicas , Cirurgia Geral , Cirurgia Geral/métodos , Adaptação , Conhecimentos, Atitudes e Prática em Saúde , Coleta de Dados/métodos , Instrumentos Cirúrgicos/classificação , Instrumentos Cirúrgicos/provisão & distribução , Condicionamento Operante/ética , Equipamentos de Laboratório , Instrumentos Cirúrgicos , Relações Médico-Enfermeiro , Papel do Profissional de Enfermagem