Development and validation of an ultra-performance liquid chromatography/electrospray ionization-tandem mass spectrometry bioanalytical method for quantifying clonazepam in human plasma.

A sensitive, selective, and rapid ultra-performance LC (UPLC)/MSIMS method was validated for the confirmation and quantification of clonazepam in human plasma. The analyte was extracted from human plasma with diethyl ether, reaching an average recovery of 64.02 and 66.48% for clonazepam and the internal standard, respectively. The separation was performed on a Waters ACQUITY UPLC BEH C18 column (50 x 2.1 mm id, 1.7 microm particle size) with gradient elution at a flow rate of 0.25 mL/min using a 0.5% formic acid solution (mobile phase A) and acetonitrile-methanol-formic acid (75+25 + 0.5, v/v/v; mobile phase B). Detection was performed on a triple-quadruple tandem mass spectrometer in the multiple reaction monitoring mode via electrospray ionization. Linear calibration curves were obtained in the concentration range of 0.3-50.0 ng/mL, with an LOQ of 0.3 ng/mL. The intraday and interday precision (CV) values were below 10%, and accuracy (relative error) ranged from -2.6 to 6.6% at all QC levels. The suggested method was successfully applied for the determination of clonazepam in human plasma in a bioequivalence study.

Increased S100B serum levels in dilated cardiomyopathy patients.

BACKGROUND: The S100B protein is considered a biochemical marker for brain injuries. However, our group demonstrated that the isolated rat heart releases S100B. In this study, we investigated the serum levels of S100B in dilated cardiomyopathy (DCM) patients to evaluate its levels in heart disease. METHODS AND RESULTS: We selected DCM patients, excluding any condition that could influence S100B serum levels. Control individuals were sex and age matched. Both groups were submitted to clinical evaluation and echocardiography. We measured the S100B and NT-proBNP serum levels (expressed as median [interquartile range]). NT-proBNP levels in patients group (1462 pg/mL [426-3591]) were higher than in controls (35 pg/mL [29-55]), P < .001. S100B serum levels were higher in patients group (0.051 microg/L [0.022-0.144]) than in controls (0.017 microg/L [0.003-0.036]), P = .009. Additionally, we found a positive correlation between S100B and NT-proBNP serum levels only in patients group (Spearman's coefficient r = 0.534; P = .013). CONCLUSIONS: Although we cannot rule out the influence of S100B from brain, the positive correlation between S100B and NT-proBNP levels in DCM patients points to the myocardium as the main source for the rise in S100B serum levels.

The ischemic rat heart releases S100B.

S100B is an astrocytic protein assessed in cerebrospinal fluid and serum as a biochemical marker of cerebral injuries. However, increasing evidences suggest the influence of extra cerebral sources on its serum levels. Since it was reported that the injured myocardium expresses S100B, we investigated whether the isolated heart releases this protein. The rat hearts were excised and perfused by the Langendorff technique of isolated heart perfusion. After stabilization, 10 hearts (ischemic group) were submitted to 20 minutes of ischemia and 30 minutes of reperfusion, and 5 hearts (control group) were submitted to 50 minutes of perfusion. The perfusion fluid was collected at pre-ischemia, and 0, 5, 10, 15 and 30 min after ischemia (or equivalent in controls) for S100B and cardiac troponin T (a heart injury marker) assays. In the ischemic group, S100B and troponin T levels increased significantly at time 0 min: S100B values [mug/L, median (IQ25/IQ75)] increased from < or = 0.02 (< or = 0.02/0.03) to 0.38 (0.22/0.84), while troponin T values [mug/L, median (IQ25/IQ75)] increased from 0.31 (0.15/0.45) to 2.84 (2.00/3.63). Our results point to the ischemic heart as an extra cerebral source of S100B.

Coping strategies after heart transplantation: psychological implications.

OBJECTIVES: To investigate coping strategies used by patients submitted to heart transplantation and whether they are related to the perception of the disease and transplantation. METHODS: Cross-sectional study with quantitative and qualitative analysis. The sample of 32 patients was assessed by the Ways of Coping Scale and socio-demographic questionnaire, and five of them were selected for interviews. The internal consistency of the scale was assessed, the variables and strategies involved were crossed and content analysis of interviews, investigating the existence of a relationship with the speech of the participants. RESULTS: The individuals have used all coping styles, with a predominance of the problem-focused strategy. Psychologically prepared patients showed a statistically significant increase in the use of problem-focused coping and seek for social support. However, a significant increase in the use of emotion-focused coping was observed in patients who were not prepared. Analysis through the method of Bardin showed as categories: disease; reaction to call; transplantation; fantasies; postoperative; team and coping. CONCLUSION: Patients with a transplanted heart make use of all coping strategies, with a predominance of the problem-focused strategy. Psychologically prepared individuals used more active coping strategies, which highlights the importance of psychological support during the process.

Summary of the II Brazilian Guideline update on Acute Heart Failure 2009/2011.

In the past two years we observed several changes in the diagnostic and therapeutic approach of patients with acute heart failure (acute HF), which led us to the need of performing a summary update of the II Brazilian Guidelines on Acute Heart Failure 2009. In the diagnostic evaluation, the diagnostic flowchart was simplified and the role of clinical assessment and echocardiography was enhanced. In the clinical-hemodynamic evaluation on admission, the hemodynamic echocardiography gained prominence as an aid to define this condition in patients with acute HF in the emergency room. In the prognostic evaluation, the role of biomarkers was better established and the criteria and prognostic value of the cardiorenal syndrome was better defined. The therapeutic approach flowcharts were revised, and are now simpler and more objective. Among the advances in drug therapy, the safety and importance of the maintenance or introduction of beta-blockers in the admission treatment are highlighted. Anticoagulation, according to new evidence, gained a wider range of indications. The presentation hemodynamic models of acute pulmonary edema were well established, with their different therapeutic approaches, as well as new levels of indication and evidence. In the surgical treatment of acute HF, CABG, the approach to mechanical lesions and heart transplantation were reviewed and updated. This update strengthens the II Brazilian Guidelines on Acute Heart Failure to keep it updated and refreshed. All clinical cardiologists who deal with patients with acute HF will find, in the guidelines and its summary, important tools to help them with the clinical practice for better diagnosis and treatment of their patients.

Perioperative variables of ventilatory function and physical capacity in heart transplant patients.

INTRODUCTION: Heart transplantation is currently the only widely accepted surgical alternative to treat patients with severe heart failure (HF) drug therapy cannot maintain optimal quality of life appropriate. OBJECTIVE: To describe and to compare the values between pre-and postoperative physical capacity and pulmonary patients who underwent heart transplantation. METHODS: A retrospective cohort composed of patients undergoing heart transplantation between January 2001 to March 2005 in IC-FUC/RS. RESULTS: Were included in the 21 individuals. We observed decreased levels of volume and lung capacity (FEV1 and FVC) in the first days after surgery compared to preoperatively (P <0.001) and recovery of these values in the 14th postoperative day (P <0.001). The values of muscle strength showed similar trends in reducing post-operative period compared to preoperative (P <0.001) and recovered on the 14th postoperative day (P <0.001). A useful functional capacity, measured by testing 6-minute walk test (T6') showed improvement in the 14th postoperative day in relation to pre-operatively (P <0.001). CONCLUSION: Changes in ventilatory function of subjects undergoing cardiac transplantation are predictable, but these recover respiratory muscle strength and lung capacity within two weeks, and improve functional capacity useful in relation to pre-operative, the transplantation, when indicated, associated with good functional rehabilitation is very god treatment strategy.

Coping strategies after heart transplantation: psychological implications / Estratégias de enfrentamento pós-transplante cardíaco: implicações psicológicas

OBJECTIVES: To investigate coping strategies used by patients submitted to heart transplantation and whether they are related to the perception of the disease and transplantation. METHODS: Cross-sectional study with quantitative and qualitative analysis. The sample of 32 patients was assessed by the Ways of Coping Scale and socio-demographic questionnaire, and five of them were selected for interviews. The internal consistency of the scale was assessed, the variables and strategies involved were crossed and content analysis of interviews, investigating the existence of a relationship with the speech of the participants. RESULTS: The individuals have used all coping styles, with a predominance of the problem-focused strategy. Psychologically prepared patients showed a statistically significant increase in the use of problem-focused coping and seek for social support. However, a significant increase in the use of emotion-focused coping was observed in patients who were not prepared. Analysis through the method of Bardin showed as categories: disease; reaction to call; transplantation; fantasies; postoperative; team and coping. CONCLUSION: Patients with a transplanted heart make use of all coping strategies, with a predominance of the problem-focused strategy. Psychologically prepared individuals used more active coping strategies, which highlights the importance of psychological support during the process.

OBJETIVOS: Verificar as estratégias de enfrentamento utilizadas por indivíduos que tiveram o coração transplantado e suas relações com percepção da doença e do transplante. MÉTODOS: Estudo transversal com análise quantitativa e qualitativa. A amostra de 32 pacientes foi avaliada pela Escala Modos de Enfretamento de Problemas e questionário sociodemográfico; e cinco deles foram sorteados para entrevista. Realizou-se a avaliação da consistência interna da escala, cruzamentos entre as variáveis e os estilos de enfrentamento e a análise de conteúdo das entrevistas, relacionando os resultados ao discurso dos participantes. RESULTADOS: Os indivíduos utilizaram todos os estilos de enfrentamento, predominando o focalizado no problema. Nos participantes que receberam preparo psicológico, houve aumento estatisticamente significativo dos enfrentamentos focalizados no problema e na busca de suporte social. Entretanto, naqueles que não receberam preparo, houve aumento significativo da utilização do enfrentamento focalizado na emoção. Através do método de Bardin, revelaram-se como categorias: doença, reação ao chamado, transplante, fantasias, pós-operatório, equipe e enfrentamento. CONCLUSÕES: Os participantes utilizaram todos os estilos de enfrentamento, predominando a estratégia focalizada no problema. Os que receberam preparo psicológico usaram maior número de estratégias de enfrentamento ativas, o que evidencia a importância do acompanhamento psicológico durante o processo.

Variáveis perioperatórias de função ventilatória e capacidade física em indivíduos submetidos a transplante cardíaco / Perioperative variables of ventilatory function and physical capacity in heart transplant patients

INTRODUÇÃO: O transplante cardíaco é atualmente a única alternativa cirúrgica amplamente aceita para tratar pacientes com insuficiência cardíaca (IC) grave que a terapia medicamentosa otimizada não consiga manter qualidade de vida adequada. OBJETIVO: Descrever e comparar os valores entre pré e pós-operatório, das capacidades física e pulmonar de pacientes que realizaram transplante cardíaco. MÉTODOS: Estudo de coorte retrospectivo composto por indivíduos submetidos ao transplante cardíaco, entre janeiro de 2001 a março de 2005, no IC-FUC/RS. RESULTADOS: Foram incluídos na análise 21 indivíduos. Observou-se redução dos valores de volumes e capacidades pulmonares (VEF1 e CVF) no 1º dia de pós-operatório em relação ao pré-operatório (P<0,001) e recuperação destes valores no 14º dia de pós-operatório (P<0,001). Os valores de força muscular inspiratória demonstraram tendências semelhantes, reduzindo no 1º dia de pós-operatório em relação ao pré-operatório (P< 0,001) e recuperando no 14º pós-operatório (P< 0,001). A capacidade funcional útil, mensurada por meio do teste de caminhada de 6 minutos (T6') mostrou melhora no 14º pós-operatório em relação ao pré-operatório (P< 0,001). CONCLUSÃO: Alterações na função ventilatória de indivíduos submetidos a transplante cardíaco são previsíveis, porém estes recuperam a força de músculos ventilatórios e capacidades pulmonares dentro de duas semanas, além de melhorar a capacidade funcional útil em relação ao préoperatório, sendo o transplante, quando indicado, associado à reabilitação funcional boa estratégia terapêutica.

INTRODUCTION: Heart transplantation is currently the only widely accepted surgical alternative to treat patients with severe heart failure (HF) drug therapy cannot maintain optimal quality of life appropriate. OBJECTIVE: To describe and to compare the values between pre-and postoperative physical capacity and pulmonary patients who underwent heart transplantation. METHODS: A retrospective cohort composed of patients undergoing heart transplantation between January 2001 to March 2005 in IC-FUC/RS. RESULTS: Were included in the 21 individuals. We observed decreased levels of volume and lung capacity (FEV1 and FVC) in the first days after surgery compared to preoperatively (P <0.001) and recovery of these values in the 14th postoperative day (P <0.001). The values of muscle strength showed similar trends in reducing post-operative period compared to preoperative (P <0.001) and recovered on the 14th postoperative day (P <0.001). A useful functional capacity, measured by testing 6-minute walk test (T6') showed improvement in the 14th postoperative day in relation to pre-operatively (P <0.001). CONCLUSION: Changes in ventilatory function of subjects undergoing cardiac transplantation are predictable, but these recover respiratory muscle strength and lung capacity within two weeks, and improve functional capacity useful in relation to pre-operative, the transplantation, when indicated, associated with good functional rehabilitation is very god treatment strategy.

A importância de medidas preventivas na profilaxia de infecções em pacientes submetidos a transplante cardíaco nos primeiros 30 dias de pós-operatório / The importance of preventive measures in the prophylaxis of infections in patients submitted to heart transplant during the first thirty postoperative days

OBJETIVO: Descrever a incidência de infecções apresentadas pelos pacientes submetidos a transplante cardíaco, durante os primeiros 30 dias da cirurgia, quanto à topografia e agente etiológico e, comparar a incidência de infecções no pós-operatório imediato ao transplante cardíaco com as medidas preventivas adotadas no controle de infecções. MÉTODO: Estudo descritivo de séries históricas numa população de 125 pacientes submetidos a transplante cardíaco, de junho de 1984 a janeiro de 2004. A coleta de dados foi realizada mediante a análise dos prontuários dos pacientes submetidos a transplante, com o auxílio de um roteiro investigativo específico. A idade da população variou de 9 dias a 71 anos, com mediana de 47 anos. A predominância foi do sexo masculino (75,2 por cento). RESULTADOS: Apresentaram infecção, nos primeiros 30 dias pós-cirurgia, 32,8 por cento dos pacientes. Houve predominância das infecções bacterianas (32 por cento), seguindo as fúngicas (5,6 por cento) e as causadas por vírus (4 por cento). Não se observou diferença na incidência de infecção, quando comparadas em duas situações: (1) na assistência de enfermagem ao paciente com uso de isolamento protetor (29,9 por cento); e (2) sem isolamento protetor (36,2 por cento) - p= 0,835. CONCLUSÃO: As infecções bacterianas predominaram nesta população, seguidas das fúngicas e virais. Observou-se que não houve diferença na incidência de infecções, quando comparadas as distintas medidas preventivas, com e sem uso de isolamento protetor, confirmando pesquisas norte-americanas. Esses dados mostram-se úteis para orientação de protocolos, visto que apresentam particularidades do nosso meio.

OBJECTIVE: To describe the rate of infections presented by patients submitted to heart transplant during the first thirty days after surgery, in respect to the topography and etiological agent and to compare the rate of infection during the immediately postoperative period with the preventive measures adopted by infection control. METHODS: A retrospective study was made of a population consisting of 125 patients submitted to heart transplant from June 1984 to January 2004. Data were collected by analyzing the patients' records following a specific investigative sequence. The ages of the patients ranged from 9 days to 71 years old, with a median of 47 years. There was a predominance of men (75.2 percent). RESULTS: During the first thirty postoperative days, 32.8 percent of the patients presented with infections. There were predominantly bacterial infections (32 percent), followed by fungal infections (5.6 percent) and those caused by viruses (4 percent). No difference was observed in the rate of infection comparing two situations: (1) in nursing care of patients using protective isolation (29.9 percent); and (2) without protective isolation (36.2 percent) ( p = 0.835). CONCLUSION: Bacterial infections predominated followed by fungal and viral infections. The protective isolation initially used in post-heart transplant patients proved unnecessary as a measure to prevent or reduce rates of infection, confirming data obtained mainly in North American studies. These data are useful to guide protocols as they take specificities of our environment into account.

Gestaçäo pós transplante cardíaco. Relato de caso e revisäo / Pregnancy after cardiac transplantation. Report of one case and review

A 14-year-old female patient became pregnant 6 years after heart transplantation. The pregnancy evolved uneventfully, and the newborn infant was healthy. Five months after delivery, the mother was in good condition with preserved ventricular function, and the baby had normal neuro-psychomotor development. Even though the case reported here was a success, pregnancy following cardiac transplantation is considered a high-risk condition and remains contraindicated

Resultado clínico tardio da anuloplastia mitral sem suporte em crianças e adolescentes / Late outcome of unsupported mitral annuloplasty in children and adolescents

O resultado clínico pós-operatório (p.o.) tardio da reconstruçao da valva mitral sem suporte em crianças e adolescentes é analisado através da observaçao de uma série de 70 pacientes operados. Objetivou-se acompanhar a evoluçao clínica tardia após o tratamento de insuficiência mitral pelas técnicas reparadoras nos pacientes em fase de crescimento, avaliar a eficácia, a durabilidade e a reprodutibilidade do procedimento, bem como morbidade e mortalidade nas fases hospitalar e tardia. Consideraram-se, ainda, os resultados em relaçao à etiologia da doença e as causas de falha do método. De 1977 a 1995, foram operados 70 pacientes, sendo 36 casos do sexo feminino e 34 do masculino. A média de idade foi de 12,4 ñ 4,8 anos (6m a l8a). Houve predomínio da etiologia reumática (71,4 por cento) sobre a congênita (l8,6 por cento), a degeneraçao mixomatosa (8,6 por cento) e a infecciosa (l,4 por cento). A classe funcional pré-operatória era II em 32 (45,7 por cento) casos, III em 18 (25,7 por cento) casos e IV em 20 (28,6 por cento) casos. A técnica cirúrgica utilizada foi a anuloplastia simples tipo Wooler isolada em 58 (82,9 por cento) casos e associadas encurtamento de cordoalha em 12 (l7,1 por cento). Em 21 (30 por cento) pacientes foram realizados procedimentos associados. O período de acompanhamento foi de 7 m a 17 anos, no p.o. A mortalidade hospitalar foi 4,3 por cento. Regurgitaçao mitral foi descrita no intra-operatório em 21,4 por cento. Sopro sistólico de regurgitaçao mitral residual foi notado em 35 (49,9 por cento) pacientes, a maioria sem repercussao hemodinâmica. A classe funcional pós-operatória foi I em 73,9 por cento, II em 21,7 por cento e III em 4,4 por cento. As curvas de análise atuarial mostraram aos 5 e l0 anos, respectivamente, probabilidade de sobrevida global de 89 por cento e 79 por cento e estimativa de permanecer livre de eventos cirúrgicos no período de 87 por cento e 61 por cento no grupo total, 88 por cento e 56 por cento no grupo de etiologia reumática e 91 por cento no grupo de etiologia congênita para 5 e lO anos. A insuficiência mitral pode ser tratada efetivamente por anuloplastia sem suporte anular protético, com resultados tardios comparáveis àqueles obtidos por técnicas mais complexas. Isto tem importância no tratamento de crianças e adultos jovens, especialmente no sexo feminino, quando se deseja evitar o implante de próteses mecânicas.

O papel da biopsia pulmonar na indicaçäo cirúrgica de cardiopatias congênitas / The role of pulmonary biopsy in the surgical indication of congenital cardiopathies

Objetivando relacionar o aspecto morfológico dos vasos pulmonares com os dados clínicos para auxiliar na decisao da cirurgia de cardiopatias congênitas com hipertensao pulmonar severa, em casos previamente avaliados por critérios clínicos, angiográficos e/ou hemodinámicos, foram realizadas, de 1980 a 1991, no Instituto de Cardiologia do Ria Grande do Sul, 49 biopsias pulmonares. As idades dos pacientes variaram de 5m a 28a6m (média = 7a7m) e os diagnósticos foram: CIV (l6), PCA (3), CIV e ESubAo (1), PCA e CIV (2), PCA e CIA (1) DSAV (7), DSAV incompl. e PCA (1), PCA e CoAo (1), Inter Arco Ao com PCA e CIV e/ou ESupraM e Anel SubAo (2), DVSVD com CIV e/ou PCA (6), DVSVE e EP (1), AT e ESubP. (1), TGV (1), TGV corrigida e CIV (l) e truncus arteriosus (5). Houve 3 (6,1 por cento) óbitos no pós-operatório da biopsia. Baseado na classificaçao de Heath-Edwards, foram para correçao cirúrgica 1l pacientes com cardiopatias simples (CIV, PCA, DSAV), cuja mortalidade foi 36,4 por cento. Dez pacientes com cardiopatias complexas (DVSVD, DVSVE, TGV, truncus, inter arco Ao) foram para cirurgia, com mortalidade de 30 por cento. A evoluçao pós-operatória tardia foi favorável em 13 (62 por cento) pacientes. Conclui-se que a biopsia pulmonar pode ser útil na indicaçao cirúrgica das cardiopatias congênitas com hipertensao pulmonar severa e, por envolver riscos, sua utilizaçao deve ser criteriosa. É valiosa para os pacientes que apresentam dúvidas quanto ao grau de doença vascular pulmonar ou quanto à natureza das lesoes e o estudo clínico e hemodinâmico nao sao esclarecedores, ou mesmo quando apontarem para a contra-indicaçao cirúrgica.