Fatigue, depression, and physical activity in patients with malignant hyperthermia: a cross-sectional observational study

Abstract Background Malignant Hyperthermia (MH) is a pharmacogenetic disorder triggered by halogenated anesthesia agents/succinylcholine and characterized by hypermetabolism crisis during anesthesia, but also by day-to-day symptoms, such as exercise intolerance, that may alert the health professional. Objective The study aimed to analyze the incidence of fatigue in MH susceptible patients and the variables that can impact perception of fatigue, such as the level of routine physical activity and depression. Methods A cross-sectional observational study was carried out with three groups - 22 patients susceptible to MH (positive in vitro muscle contracture test), 13 non-susceptible to MH (negative in vitro muscle contracture test) and 22 controls (no history of MH). Groups were assessed by a demographic/clinical questionnaire, a fatigue severity scale (intensity, specific situations, psychological consequences, rest/sleep response), and the Beck depression scale. Subgroups were re-assessed with the Baecke habitual physical exercise questionnaire (occupational physical activity, leisure physical exercise, leisure/locomotion physical activity). Results There were no significant differences among the three groups regarding fatigue intensity, fatigue related to specific situations, psychological consequences of fatigue, fatigue response to resting/sleeping, depression, number of active/sedentary participants, and the mean time and characteristics of habitual physical activity. Nevertheless, unlike the control sub-group, the physically active MH-susceptible subgroup had a higher fatigue response to resting/sleeping than the sedentary MH susceptible subgroup (respectively, 5.9 ± 1.9 vs. 3.9 ± 2, t-test unpaired, p< 0.05). Conclusion We did not detect subjective fatigue in MH susceptible patients, although we reported protracted recovery after physical activity, which may alert us to further investigation requirements.

Patient suspected susceptibility to malignant hyperthermia: impact of the disease

Abstract Introduction Malignant Hyperthermia (MH) is an inherited hypermetabolic syndrome triggered by exposure to halogenated anesthetics/succinylcholine. The lack of knowledge regarding this condition might be associated with the rare occurrence of MH reaction and symptoms. Methods This observational study evaluated 68 patients from 48 families with confirmed or suspected MH susceptibility due to medical history of MH reaction or idiopathic increase of creatine kinase or MH-related myopathies. Participants were assessed by a standardized questionnaire and submitted to physical/neurological examination to assess the characteristics of patients with MH, their knowledge about the disease, and the impact suspected MH had on their daily lives. Results Suspected MH impacted the daily life of 50% of patients, creating difficulties in performing surgical/clinical/dental treatment and problems related to their family life/working/practicing sports. The questionnaire on MH revealed a correct answer score of 62.1 ± 20.8 (mean ± standard deviation) on a scale 0 to 100. Abnormal physical/neurological examination findings were detected in 92.6% of susceptible patients. Conclusions Suspected MH had impacted the daily lives of most patients, with patients reporting problems even before MH investigation with IVCT. Patients showed a moderate level of knowledge about MH, suggesting the need to implement continuing education programs. MH susceptible patients require regular follow-up by a health team to detect abnormalities during physical and neurological examination.

Impacto da COVID-19 nos Programas de Reabilitação Cardiovascular no Brasil: Um Estudo Transversal Baseado em uma Pesquisa Online / Impact of COVID-19's on Cardiovascular Rehabilitation Programs in Brazil: An Online Survey-Based Cross-Sectional Study

Resumo Fundamento A pandemia da COVID-19 teve um impacto sobre os programas de reabilitação cardiovasculares (RC) no Brasil. Objetivos Descrever características dos programas de RC no Brasil, os impactos da primeira onda epidemiológica da COVID-19 (primeiros 60 dias) sobre os programas, e apresentar as iniciativas usadas para superar esses impactos. Métodos Este estudo transversal e retrospectivo usou um questionário online específico. Os participantes eram coordenadores de programas de RC. As variáveis foram apresentadas por região geográfica do Brasil, como as seguintes categorias: característica demográficas, clínicas e operacionais. O nível de significância estatística foi definido em 5%. Resultados Cinquenta e nove programas de RC atendiam 5349 pacientes, dos quais somente 1817 eram pacientes após eventos cardiovasculares agudos, o que correspondia a 1,99% dos pacientes internados no mês anterior à pesquisa (n=91.231). O maior impacto foi a suspensão das atividades presenciais, o que ocorreu de maneira similar em áreas com as taxas mais altas e áreas com as taxas mais baixas de COVID-19 no período. Quarenta e quatro (75%) programas foram interrompidos de forma breve, e três (5%) foram encerrados. Todos os 42 programas que já utilizavam estratégias de reabilitação remota notaram aumento substancial nas atividades, baseadas principalmente no uso da mídia e chamadas por vídeo. Somente três (5%) consideraram seguro atender pacientes durante os primeiros 60 dias. Conclusões Houve redução no número de programas de RC devido a pandemia da COVID-19. Atividades de telerreabilitação aumentaram durante os primeiros dois meses da pandemia da COVID-19, mas que não foi suficiente para superar a redução nas atividades dos programas de RC no Brasil.

Abstract Background The COVID-19 pandemic had an impact on cardiovascular rehabilitation (CR) programs in Brazil. Objectives To describe the characteristics of CR programs in Brazil, the impacts of the first epidemiological wave of COVID-19 (first 60 days) on the programs and present the initiatives used to overcome the impacts. Method This cross-sectional and retrospective study utilized a specific online survey. Participants were coordinators of CR programs. Variables were presented by Brazilian geographic region and as the following categories: demographic, clinical and operational characteristics. The significance level for statistical analysis was set at 5%. Results Fifty-nine CR programs were responsible for 5,349 patients, of which only 1,817 were post-acute cardiovascular events, which corresponded to 1.99% of hospitalized patients in the month prior to the survey (n=91,231). The greatest impact was the suspension of on-site activities, which occurred similarly in areas with the highest and the lowest rates of COVID-19 in the period. Forty-five programs (75%) were shortly interrupted, while three (5%) were ended. All 42 programs that already used remote rehabilitation strategies noticed a substantial increase in activities, based primarily on the use of media and video calling. Only three (5%) considered safe to see patients during the first 60 days. Conclusions There was a reduction in the number of CR programs with the COVID-19 pandemic. Telerehabilitation activities increased during the first two months of the COVID-19 pandemic, but this was not enough to overcome the reduction in CR program activities across Brazil.

Anesthesia for muscle biopsy to test susceptibility to malignant hyperthermia / Anestesia durante biópsia muscular para teste de suscetibilidade à hipertermia maligna

Abstract Introduction Malignant hyperthermia is an autosomal dominant pharmacogenetic disorder, characterized by hypermetabolic crisis triggered by halogenated anesthetics and/or succinylcholine. The standard method for diagnosing malignant hyperthermia susceptibility is the in vitro muscle contracture test in response to halothane-caffeine, which requires muscle biopsy under anesthesia. We describe a series of anesthetic procedures without triggering agents in malignant hyperthermia, comparing peripheral nerve block and subarachnoid anesthesia. Method We assessed the anesthetic record charts of 69 patients suspected of malignant hyperthermia susceptibility who underwent muscle biopsy for in vitro muscle contracture in the period of 7 years. Demographic data, indication for malignant hyperthermia investigation, in vitro muscle contracture test results, and surgery/anesthesia/recovery data were analyzed. Results Sample with 34 ± 13.7 years, 60.9% women, 65.2% of in vitro muscle contracture test positive. Techniques used: peripheral nerve blocks — lateral femoral and femoral cutaneous, latency 65 ± 41 min — (47.8%); subarachnoid anesthesia (49.3%), and total venous anesthesia (1.4%). There was 39.4% failure of peripheral nerve block and 11.8% of subarachnoid anesthesia. Adverse events (8.7%) occurred only with subarachnoid blockade (bradycardia, nausea, and transient neurological syndrome). All patients remained in the post-anesthesia care unit until discharge. Age and weight were significantly higher in patients with blockade failure (ROC cut-off point of 23.5 years and 59.5 kg) and blockade failure was more frequent in the presence of increased idiopathic creatine kinase. Conclusion Anesthesia with non-triggering agents has been shown to be safe in patients with malignant hyperthermia susceptibility. Variables such as age, weight, and history of increased idiopathic creatine kinase may be useful in selecting the anesthetic technique for this group of patients.

Resumo Introdução Hipertermia maligna é uma doença farmacogenética autossômica dominante, caracterizada por crise hipermetabólica desencadeada por anestésicos halogenados e/ou succinilcolina. O padrão para diagnóstico da suscetibilidade à hipertermia maligna é o teste de contratura muscular in vitro em resposta ao halotano-cafeína, para o qual é necessária biopsia muscular sob anestesia. Descrevemos uma série de anestesias sem agentes desencadeantes na hipertermia maligna e comparamos bloqueios de nervo periférico e anestesias subaracnóideas. Método Foram analisados os prontuários/fichas anestésicas de 69 pacientes suspeitos de susceptibilidade à hipertermia maligna, submetidos à biópsia muscular para teste de contratura muscular in vitro durante sete anos. Analisamos dados demográficos, indicação para investigação de hipertermia maligna, resultado do teste de contratura muscular in vitro e dados da cirurgia/anestesia/recuperação. Resultados Amostra com 34 ± 13,7 anos, 60,9% mulheres, 65,2% de teste de contratura muscular in vitro positivos. Técnicas empregadas: 47,8% bloqueios de nervo periférico (femoral e cutâneo femoral lateral, latência 65 ± 41 minutos), 49,3% anestesias subaracnóideas e 1,4% anestesia venosa total. Falha em 39,4% dos bloqueios de nervo periférico e 11,8% das anestesias subaracnóideas. Eventos adversos (8,7%) como bradicardia, náuseas e síndrome neurológica transitória só ocorreram com bloqueio subaracnóideo. Todos os pacientes permaneceram na sala de recuperação pós-anestésica até liberação. Idade e peso foram significativamente maiores nos pacientes com falha no bloqueio (ponto de corte da curva ROC de 23,5 anos e 59,5 Kg) e esta foi mais frequente na presença de aumento idiopático de creatinoquinase. Conclusão Anestesia com agentes não desencadeantes mostrou-se segura em pacientes suscetíveis à hipertermia maligna. Variáveis como idade, peso e antecedente de aumento idiopático de creatinoquinase podem ser úteis para selecionar a técnica anestésica nesse grupo.

Risk factors for the progression of chronic kidney disease after acute kidney injury / Fatores de risco para a progressão da doença renal crônica após a lesão renal aguda

Abstract Introduction: The incidence of chronic kidney disease (CKD) is increasing with the increasing age of the population and the increasing number of elderly survivors of acute kidney injury (AKI). The risk factors for the progression of CKD after AKI are unclear. Objective: To investigate the association between AKI and its progression to CKD and the risk factors involved. Methods: An observational, retrospective study of AKI patients followed from 2009 to 2012 was carried out. We evaluated the etiology of AKI, the use of vasoactive drugs and mechanical ventilation, the need for dialysis, the presence of comorbidities, the glomerular filtration rate (GFR), the length of stay and the progression of CKD. Statistical analyses, including the Chi-square test and Pearson's correlation, were performed using SPSS. Results: The 207 patients analyzed had a mean age of 70.1 ± 13.1, and 84.6% of the male patients exhibited decreased renal function and CKD (vs. 60.4% of the female patients). The progression of AKI to CKD was more frequent in patients admitted to wards (63.8%), cancer patients (74.19%), patients with sepsis (67.18%) and patients with obstruction (91.66%). Dialyses were performed in 16.4% of the patients, but this was not correlated with the progression of CKD. Conclusions: Being an elderly male patient with AKI due to sepsis and obstruction was correlated with progression to CKD following discharge.

Resumo Introdução: A incidência da doença renal crônica (DRC) está aumentando com o aumento da idade da população e o número crescente de idosos sobreviventes da lesão renal aguda (LRA). Os fatores de risco para a progressão da DRC após a lesão renal aguda (LRA) não são claros. Objetivos: Investigar a associação entre a LRA e sua progressão para a DRC e os fatores de risco envolvidos. Métodos: Foi realizado estudo observacional, retrospectivo de pacientes com LRA acompanhados de 2009 a 2012. Foram avaliados a etiologia da LRA, o uso de drogas vasoativas, ventilação mecânica, necessidade de diálise, presença de morbidades associadas, ritmo de filtração glomerular estimado (eGFR), duração da internação e a progressão da DRC. As análises estatísticas incluíram o teste Qui-quadrado e a correlação de Pearson utilizando o programa do SPSS. Resultados: Os 207 pacientes analisados apresentaram idade de 70,1 ± 13,1 anos, 84,6% eram do sexo masculino e que apresentaram redução da função renal e DRC (vs. 60,4% dos pacientes do sexo feminino). A progressão da LRA para DRC foi mais frequente em pacientes internados em enfermarias (63,8%), pacientes com câncer (74,19%), com sepse (67,18%) e com obstrução do trato urinário (91,66%). As dialises foram realizadas em 16,4% dos pacientes, mas isso não foi correlacionado com a progressão da DRC. Conclusões: Pacientes idosos com LRA devido à sepse e obstrução do trato urinário foram correlacionados com a progressão para DRC após a alta.

Epidemiological and clinical factors impact on the benefit of riluzole in the survival rates of patients with ALS / Impacto de fatores epidemiológicos e clínicos sobre o benefício do riluzol nas taxas de sobrevida de pacientes com ELA

ABSTRACT Objective To investigate the impact of epidemiological and clinical factors on the benefit of riluzole in patients with amyotrophic lateral sclerosis (ALS). Methods The survival rate of 578 patients with ALS (1999-2011) was analyzed by descriptive statistics and Kaplan-Meier curves. Considering the median of the sample survival time (19 months), patients were divided in two groups: below (B19) and above the median (A19). Kaplan-Meier curves compared the survival rates of patients treated with riluzole and with patients who did not take the medication. Results Riluzole increased the survival rates of patients with lower limb onset who were diagnosed after the first appointment in B19. Patients with bulbar onset and diagnosed on the first, or after the first appointment showed higher survival rates in A19. Males lived longer than females in both groups. Conclusion Epidemiological and clinical factors influenced the benefit of riluzole in the survival rates of patients with ALS.

RESUMO Objetivo Investigar o impacto de fatores epidemiológicos e clínicos sobre o benefício do riluzole em pacientes com esclerose lateral amiotrófica (ELA). Métodos A sobrevida de 578 pacientes com ELA (1999-2011) foi analisada por estatística descritiva e curvas de Kaplan-Meier. Considerando a mediana do tempo de sobrevida (19 meses), a amostra foi subdividida em dois grupos: sobrevida abaixo (B19) e acima de 19 meses (A19). As curvas de Kaplan-Meier compararam a sobrevida de pacientes tratados com riluzole e com pacientes que não receberam tratamento. Resultados O riluzole aumentou a sobrevida de pacientes com início nos membros inferiores e diagnosticados após a primeira consulta no grupo B19. Pacientes com início bulbar e diagnosticados na primeira/ após a primeira consulta apresentaram maior sobrevida em A19. Os homens apresentaram sobrevida maior do que as mulheres. Conclusão Foram encontradas diferenças epidemiológicas e clínicas no benefício do riluzole em pacientes com ELA.

Late onset multiple sclerosis: concerns in aging patients / Esclerose múltipla de início tardio: atenção a uma população que envelhece

ABSTRACT Late onset multiple sclerosis (LOMS) is when the first symptom starts after 50 years of age, representing 4.5% of multiple sclerosis (MS) patients. This study describes the clinical characteristics of patients with LOMS followed at a specialized MS center in São Paulo. Data was obtained from medical records of 742 patients with MS. The LOMS frequency was 4.18%, median age at onset was 54 years and the predominant disease course was primary progressive (64.3%). The patients reached the disability landmarks of EDSS grades 3.0, 6.0 and 7.0 in the following proportion and time: EDSS 3.0: 77.42% of patients in 3.7 years; EDSS 6.0: 58.06% in 5.1 years and EDSS 7.0: 32.26% in 5.7 years. The comparative analysis with a matched control group of patients with early onset MS showed that late onset, associated with a progressive course, were predictors of reaching EDSS 3.0 and 6.0 in a shorter time.

RESUMO Esclerose múltipla de inicio tardio (EMIT) caracteriza-se pelo início de sintomas aos 50 ou mais anos de idade, representando 4,5% dos pacientes com esclerose múltipla (EM). Este estudo descreve as características clínicas de pacientes com EMIT acompanhados num centro de EM em São Paulo. Dados foram obtidos através de análise de prontuário de 742 pacientes com EM. A frequência de EMIT foi de 4,18%, a mediana da idade de início foi de 54 anos e a forma clínica predominante a primariamente progressiva (64,3%). Os pacientes atingiram os marcos de incapacidade EDSS 3, 6 e 7 nas respectivas proporções e tempo: EDSS 3.0, 77,42% de pacientes em 3.7 anos; EDSS 6.0, 58,06% em 5.1 anos e EDSS 7.0, 32,26% em 5.7 anos. A análise comparativa a um grupo controle de jovens com EM, mostrou que o início tardio associado a forma primariamente progressiva foram preditores para atingir EDSS 3 e 6 num período menor.

The effects of individually ventilated cages on the respiratory systems of male and female Wistar rats from birth until adulthood

OBJECTIVE: To evaluate the respiratory systems of male and female rats maintained in individually ventilated cages (IVCs) from birth until adulthood. METHODS: Female Wistar rats were housed in individually ventilated cages or conventional cages (CCs) and mated with male Wistar rats. After birth and weaning, the male offspring were separated from the females and kept in cages of the same type until 12 weeks of age. RESULTS: The level of food consumption was lower in male offspring (IVC=171.7±9; CC=193.1±20) than in female offspring (IVC=100.6±7; CC=123.4±0.4), whereas the water intake was higher in female offspring (IVC=149.8±11; CC=99.2±0) than in male offspring (IVC=302.5±25; CC=249.7±22) at 11 weeks of age when housed in IVCs. The cage temperature was higher in individually ventilated cages than in conventional cages for both male (IVCs=25.9±0.5; CCs=22.95±0.3) and female (IVCs=26.2±0.3; CCs=23.1±0.3) offspring. The respiratory resistance (IVC=68.8±2.8; CC=50.6±3.0) and elastance (IVC=42.0±3.9; CC=32.4±2.0) at 300 µm/kg were higher in the female offspring housed in ventilated cages. The ciliary beat values were lower in both the male (IVCs=13.4±0.2; CC=15±0.4) and female (IVC=13.5±0.4; CC=15.9±0.6) offspring housed in individually ventilated cages than in those housed in conventional cages. The total cell (IVC=117.5±9.7; CC=285.0±22.8), neutrophil (IVC=13.1±4.8; CC=75.6±4.1) and macrophage (IVC=95.2±11.8; CC=170.0±18.8) counts in the bronchoalveolar lavage fluid were lower in the female offspring housed in individually ventilated cages than in those housed in conventional cages. CONCLUSIONS: The environmental conditions that exist in individually ventilated cages should be considered when interpreting the results of studies involving laboratory animals. In this study, we observed gender dimorphism in both the water consumption and respiratory mechanics of rats kept in ventilated cages.

Lesão renal aguda no pós-operatório de cirurgias não cardíacas em pacientes com recuperação na unidade de terapia intensiva / Non-cardiac postoperative acute kidney injuryin patients requiring intensive care

Objetivo: Caracterizar os fatores de risco para lesão renal aguda em pacientes submetidos a cirurgias não cardíacas na unidade de terapia intensiva e sua influência na evolução clínica no pós-operatório. Métodos: Estudo clínico, prospectivo, observacional com 98 pacientes na unidade de terapia intensiva de pós-operatório do Hospital Servidor Público Estadual entre novembro de 2012 e fevereiro de 2013. As variáveis estudadas foram idade, sexo, risco pré-operatório, tipo de cirurgia e anestesia, comorbidades, necessidade de ventilação mecânica, drogas vasoativas, transfusão, diálise e sobrevida em 30 dias. O diagnóstico da lesão renal aguda foi estabelecido pelos critérios Acute Kidney Injury Network (AKIN). Na análise estatística, variáveis categóricas foram avaliadas pelo teste qui quadrado e níveis de p<0,05 foram considerados significantes. Resultados: Os pacientes apresentavam idade de 70,7±13,8 anos, 57,1% eram do sexo masculino e 88,8% estavam em pós-operatório de cirurgia eletiva. Desenvolveram lesão renal aguda 35 (35,7%) pacientes e, destes, 20 (59,2%) eram AKIN 1, (3) 8,6% AKIN 2 e 12 (34,2%) AKIN 3. Necessitaram de diálise 24 (68,57%) pacientes. Risco anestésico elevado nas cirurgias eletivas, intercorrências no intraoperatório e presença da doença renal crônica foram fatores que influenciaram no aparecimento da lesão renal aguda especialmente nos idosos. A mortalidade nos pacientes com lesão renal aguda foi 46% vs. 11% daqueles sem lesão renal aguda. Conclusão: A lesão renal aguda apresentou alta mortalidade em idosos submetidos à cirurgia eletiva com risco pré-operatório elevado e doença renal crônica prévia. É importante a identificação precoce destes fatores de risco e da lesão renal aguda nesses pacientes.

Objectives: To characterize risk factors for acute kidney injury in patients undergoing non-cardiac surgeries in Intensive Care Unit (ICU), and their influence on clinical outcomes postoperatively. Methods: Clinical, prospective, observational study of 98 patients admitted to the Intensive Care Unit after surgery at Hospital do Servidor Público Estadual from November/2012 to February/2013. The variables studied were: age, gender, preoperative anesthetic risk, type of surgery and anesthesia, comorbidities, need for mechanical ventilation, use of vasoactive drugs, need for blood transfusion, renal replacement therapy (RRT) and survival at 30 days. The diagnosis of acute kidney injury has been established through the Acute Kidney Injury Network (AKIN) criteria. At statistical analysis, categorical variables were analyzed using the chi-square test and p levels <0.05 were considered significant. Results: Patients were 70.7 ± 13.8 years old; 57.1% were male, and 88.8% were in postoperative period of elective surgery. Thirty-five patients (35.7%) had an acute kidney injury, with 20 (59.2%) being AKIN1, 8.6% AKIN2 (3), and 12 (34.2%) AKIN3. High anesthetic risk in elective surgeries, complications during surgery, and the presence of chronic kidney disease were factors that influenced the onset of acute kidney injury, especially in the elderly. Mortality in patients with acute kidney injury was of 46%, versus 11% of those without acute kidney injury. Conclusion: Acute kidney injury showed high mortality in the elderly patients undergoing elective surgery with a high preoperative risk and previous chronic kidney disease. The early identification of these risk factors, as well as the early diagnosis of acute kidney injury in these patients is important.

The impact of interleukin-13 receptor expressions in cell migration of astrocytomas / O impacto da expressão dos receptores de interleucina-13 na migração celular em astrocitomas

INTRODUCTION: Astrocytomas are common brain tumors. Increased expression levels of Interleukin-13 Receptor α2 (IL-13RA2) have been reported in astrocytomas. The Interleukin-13 signaling pathway may be associated with cell migration when binding to Interleukin-13 Receptor α1. OBJECTIVE: To investigate Interleukin-13 Receptor α1 (IL-13RA1) and IL13RA2 expression levels in human diffusely infiltrative astrocytomas and test the involvement of Interleukin-13 levels in cell migration in two glioblastoma cell lines. METHODS: IL13RA expression levels were accessed by quantitative real time PCR in 128 samples of astrocytomas and 18 samples of non-neoplastic brain tissues from temporal lobe epilepsy surgery. The impact of IL-13 levels (10 and 20 ng/mL) on cell migration was analyzed by the wound assay in U87MG and A172 cells. RESULTS: Glioblastoma presented higher IL13RA1 and IL13RA2 expression levels compared to lower grades astrocytomas and to non-neoplastic cases. U87MG and A172 cells presented higher expression levels of IL-13RA1 vs. IL-13RA2. A significant difference in migration rate was observed in A172 cells treated with 10 ng/mL of IL-13 vs. control: treated cells presented slower migration than non-treated cells. U87MG cells treated with IL-13 20ng/mL presented slower migration than non-treated cells. This indicates that the IL13Rα1 signaling pathway was not activated, indeed inhibited by the decoy IL-13Rα2, slowing cell migration. This impact occurred with a lesser concentration of IL-13 on the A172 than on the U87MG cell line, because A172 cells have a higher IL-13RA2/A1 ratio. CONCLUSION: The present results suggest IL-13 receptors as possible targets to decrease tumor cell migration.

INTRODUÇÃO Astrocitomas são os tumores cerebrais mais frequentes. Nestes tumores foi observada maior expressão do receptor de Interleucina-13 α2 (IL13RA2). A cascata de sinalização da Interleucina-13 pode estar associada com a migração celular, após sua ligação com o receptor de Interleucina-13 α1 (IL13Rα1). OBJETIVO: Investigar os níveis de expressão dos receptores de Interleucina-13 (IL13RA1 e IL13RA2) em astrocitomas difusamente infiltrativos e avaliar o envolvimento da Interleucina-13 na migração celular de duas linhagens de glioblastoma. MÉTODOS: A expressão dos receptores IL13RA foi analisada por PCR em tempo real, em 128 amostras de astrocitomas e 18 amostras de tecido cerebral não neoplásico, provenientes de cirurgia de epilepsia do lobo temporal. E o impacto da quantidade de IL-13 (10ng/ml e 20ng/ml) em ensaio de migração celular. RESULTADOS: As amostras de Glioblastoma apresentaram maior expressão de IL13RA1 and IL13RA2 comparados com astrocitomas de baixo grau e os casos não-neoplásicos. Nas células U87MG e A172 foi observado maior nível de expressão de IL-13RA1 do que IL-13RA2. Uma diferença significativa na taxa de migração foi obtida em células A172 tratadas com 10 ng/mL comparadas com o controle: as células tratadas apresentaram menor migração que as células não tratadas. As células U87MG tratadas com 20ng/mL de IL-13 apresentaram menor migração celular que as células não tratadas. A diferença na migração celular indica que o caminho de sinalização de IL13Rα1 não foi ativado e foi inibido pelo IL-13Rα2, diminuindo a migração celular. Esse impacto ocorreu com uma concentração menor de IL-13 nas células A172 ao contrário da U87MG, porque as células A172 possuem uma razão IL-13RA2/A1 maior. CONCLUSÃO: os resultados sugerem que os receptores de IL-13 podem ser utilizados como possíveis alvos para a diminuição da migração celular tumoral.

Study of the incidence of dialysis in São Paulo, the largest Brazilian city

OBJECTIVES: Chronic kidney disease is a major public health problem worldwide. In Brazil, approximately 100,000 patients (January 2012) receive renal replacement therapy. Nevertheless, data on dialysis incidence in the Brazilian population are scarce. This study aims to analyze the incidence of patients starting dialysis therapy in São Paulo City, the largest Brazilian metropolis. METHOD: This cohort study analyzed data from 9,994 patients starting hemodialysis or peritoneal dialysis funded by the Brazilian Public Health System during a 5-year period (2007-2011). Patient data for this study (recorded as electronic files) were obtained from the São Paulo City's Dialysis Regulatory Bureau, which regulates the allocation of patients requiring dialytic therapy. RESULTS: The dialysis incidence rates were 178, 174, 170, 185 and 188 per million population for the years 2007, 2008, 2009, 2010 and 2011, respectively. The incidence rates increased with age. Hypertension and diabetes were the main etiologies diagnosed. Hemodialysis was the chosen dialysis modality in the majority of patients (92.6%), whereas the percentage of patients referred for peritoneal dialysis decreased from 10.1% to 5.5%. CONCLUSION: The incidence of patients starting renal replacement therapy from 2007-2011 in São Paulo was stable but higher than the projected incidence for the entire country. The authors emphasize the need for further studies of the incidence of dialysis in the Brazilian population and for the creation of a Brazilian registry of dialysis patients, which would be a valuable tool for developing healthcare policies and renal replacement therapy strategies. .

Diabetes subdiagnosticado e necrose miocárdica: preditores de hiperglicemia no infarto do miocárdio / Unrecognized diabetes and myocardial necrosis: predictors of hyperglycemia in myocardial infarction

FUNDAMENTO: Hiperglicemia na fase aguda do infarto do miocárdio é importante fator prognóstico. Entretanto, sua fisiopatologia não está completamente elucidada. OBJETIVO: Analisar simultaneamente correlação entre hiperglicemia e marcadores bioquímicos relacionados ao estresse,metabolismo glicídico e lipídico, coagulação, inflamação e necrose miocárdica. MÉTODOS: Oitenta pacientes com infarto agudo do miocárdio foram incluídos prospectivamente. Os parâmetros analisados foram: glicose, hormônios do estresse (cortisol e norepinefrina), fatores do metabolismo glicídico [hemoglobina glicada (HbA1c), insulina], lipoproteínas (colesterol total, LDL, HDL, LDL eletronegativa minimamente modificada e adiponectina), glicerídeos (triglicérides, VLDL e ácido graxo), fatores da coagulação (fator VII, fibrinogênio,inibidor do ativador do plasminogênio-1), inflamação (proteína C reativa ultrassensível) e necrose miocárdica (CK-MB e troponina). Variáveis contínuas foram convertidas em graus de pertinência por intermédio de lógica fuzzy. RESULTADOS: Houve correlação significativa entre hiperglicemia e metabolismo glicídico (p < 0,001), lipoproteínas (p = 0,03) e fatores de necrose (p = 0,03). Na análise multivariada, somente metabolismo glicídico (OR = 4,3; IC = 2,1-68,9 e p < 0,001) e necrose miocárdica (OR = 22,5; IC = 2-253 e p = 0,012) mantiveram correlação independente e significativa.Para análise da influência da história de diabetes mellitus , modelo de regressão, incluindo somente pacientes sem diabetes mellitus foi desenvolvido, e os resultados não alteraram. Finalmente, no modelo ajustado para idade, sexo e variáveis clínicas(história de diabetes mellitus, hipertensão arterial e dislipidemia), três variáveis mantiveram associação significativa e independente com hiperglicemia: metabolismo glicídico (OR = 24,1; IC = 4,8-122,1 e p < 0,001) necrose miocárdica (OR = 21,9; IC = 1,3-360,9 e p = 0,03) e história de DM (OR = 27, IC = 3,7-195,7 e p = 0,001). CONCLUSÃO: Marcadores do metabolismo glicídico e necrose miocárdica foram os melhores preditores de hiperglicemia em pacientes com infarto agudo do miocárdio.

BACKGROUND: Hyperglycemia in the acute phase of myocardial infarction is an important prognostic factor. However, its pathophysiology is not fully understood. OBJECTIVE: To analyze simultaneously the correlation between hyperglycemia and biochemical markers related to stress, glucose and lipid metabolism, coagulation, inflammation, and myocardial necrosis. METHODS Eighty patients with acute myocardial infarction were prospectively included. The following parameters were analyzed: blood glucose; stress hormones (cortisol and norepinephrine); glucose metabolism factors [glycated hemoglobin (HbA1c); insulin]; lipoproteins (total cholesterol, LDL, HDL, minimally modified electronegative LDL, and adiponectin); glycerides (triglycerides, VLDL and fatty acids); coagulation factors (factor VII, fibrinogen, plasminogen activator inhibitor-1); inflammation (high-sensitivity C reactive protein); and myocardial necrosis (CK-MB and troponin). Continuous variables were converted into degrees of relevance using fuzzy logic. RESULTS: Significant correlation was observed between hyperglycemia and glucose metabolism (p < 0.001), lipoproteins (p = 0.03), and necrosis factors (p = 0.03). In the multivariate analysis, only glucose metabolism (OR = 4.3; CI = 2.1-68.9; and p < 0.001) and myocardial necrosis (OR = 22.5; CI = 2-253; and p = 0.012) showed independent and significant correlation. For the analysis of the influence of history of diabetes mellitus, a regression model including only patients without diabetes mellitus was developed, and the results did not change. Finally, in the model adjusted for age, gender, and clinical variables (history of diabetes mellitus, hypertension and dyslipidemia), three variables maintained a significant and independent association with hyperglycemia: glucose metabolism (OR = 24.1; CI = 4.8-122.1; and p < 0.001), myocardial necrosis (OR = 21.9; CI = 1.3-360.9; and p = 0.03), and history of DM (OR = 27; CI = 3.7-195.7; and p = 0.001). CONCLUSION: Glucose metabolism and myocardial necrosis markers were the best predictors of hyperglycemia in patients with acute myocardial infarction.

Late recognition and illness severity are determinants of early death in severe septic patients

OBJECTIVE: To identify the independent variables associated with death within 4 days after the first sepsis-induced organ dysfunction. METHODS: In this prospective observational study, severe sepsis and septic shock patients were classified into 3 groups: Group 1, survivors; Group 2, late non-survivors; and Group 3, early non-survivors. Early death was defined as death occurring within 4 days after the first sepsis-induced organ dysfunction. Demographic, clinical and laboratory data were collected and submitted to univariate and multinomial analyses. RESULTS: The study included 414 patients: 218 (52.7%) in Group 1, 165 (39.8%) in Group 2, and 31 (7.5%) in Group 3. A multinomial logistic regression analysis showed that age, Acute Physiology and Chronic Health Evaluation II score, Sepsis-related Organ Failure Assessment score after the first 24 hours, nosocomial infection, hepatic dysfunction, and the time elapsed between the onset of organ dysfunction and the sepsis diagnosis were associated with early mortality. In contrast, Black race and a source of infection other than the urinary tract were associated with late death. Among the non-survivors, early death was associated with Acute Physiology and Chronic Health Evaluation II score, chronic renal failure, hepatic dysfunction Sepsis-related Organ Failure Assessment score after 24 hours, and the duration of organ dysfunction. CONCLUSION: Factors related to patients' intrinsic characteristics and disease severity as well as the promptness of sepsis recognition are associated with early death among severe septic patients. .

Influência da temperatura e da umidade relativa do ar e determinação do estado trófico em Tillandsia stricta Lindl: (Bromeliaceae), ocorrente no Parque Estadual da Ilha Anchieta, Ubatuba-SP / Influence of temperature and relative humidity of air and the determination of the trophic state in Tillandsia stricta Lindl: (Bromeliaceae) in State park of Anchieta Island / La influencia de la temperatura y de la humedad relativa del aire y la determinación del estado trófico en Tillandsia stricta Lindl: (Bromeliaceae) en el parque estatal de Isla Anchieta

A Bromeliaceae Tillandsia stricta é uma epífita vascular caracterizada como espécie atmosférica, devido à sua capacidade de absorver os nutrientes que necessita diretamente do ar, pelas folhas. Essa bromélia encontra-se distribuída em abundância ao longo de alguns forófitos encontrados no Parque Estadual da Ilha Anchieta em Ubatuba (SP) sendo rara em outros. Neste trabalho procurou-se determinar a existência de possíveis diferenças quanto à temperatura e umidade relativa do ar em três locais (Praia do Presídio, Trilha do Saco Grande e Praia das Palmas), onde essa espécie apresenta distribuição irregular. Além disso, avaliou-se o estado trófico, através da análise de macro e micronutrientes presentes nas folhas. Foram encontradas diferenças significativas de umidade relativa do ar que é maior na Praia do Presídio e Saco Grande e menor na Praia das Palmas. Quanto aos nutrientes, na Praia do Presídio, T. stricta apresentou maiores concentrações de ferro quando comparadas aos outros dois locais. As diferenças nesses fatores abióticos podem explicar a maior concentração de indivíduos de T. stricta existente na Praia do Presídio.

Bromeliaceae Tillandsia stricta is a vascular epiphyte characterized as an atmospheric species due to its capacity of absorbing the nutrients it needs directly from the air through its leaves. This bromeliad is distributed in abundance along some phorophytes found in the State Park of Anchieta Island in Ubatuba (SP), being rare in others. In this work we tried to establish the existence of possible differences regarding temperature and relative humidity of air in three places (Praia do Presídio, Trilha do Saco Grande e Praia das Palmas), where this species presents irregular distribution. Besides, the trophic state was evaluated through the analysis of macro and micronutrients present in the leaves. We found significant differences of relative humidity of air that are greater in Praia do Presídio and Saco Grande and lesser in Praia das Palmas. As for the nutrients, in Praia do Presídio T. stricta presented higher concentrations of iron when compared to the other two places. The differences in these abiotic factors may explain the highest concentration of T. stricta individuals in Praia do Presídio.

La Bromeliaceae Tillandsia stricta es un epifito vascular caracterizado como una especie atmosférica debido a su capacidad de absorber los nutrientes que necesita directamente del aire de promedio sus hojas. Esta bromelia se distribuí en abundancia a lo largo de algúnos forofitos encontrados en el Parque Estatal de Isla Anchieta en Ubatuba (SP), siendo rara en otros. Con este trabajo, tratamos de establecer laexistencia de diferencias posibles en cuanto a la temperaturas y la humedad relativa del aire en tres sitios (Praia del Presídio, Trilha do Saco Grande y Praia das Palmas), donde esta especie presenta distribución irregular. Además, el estado trófico fue evaluado por el análisis de macro y de micronutrientes en las hojas. Encontramos diferencias significativas de humedad relativa del aire que son mayores en Praia del Presídio y Saco Grande y menores en Praia das Palmas. En cuanto a los nutrientes, en Praia del Presídio T. stricta presentó concentraciones más altas de hierro en comparación con los dos otros sitios. Las diferencias en estos factores abióticos pueden explicar la concentración más alta de individuos T. stricta en Praia del Presídio.

Correlation between serum tumor necrosis factor alpha levels and clinical severity of tuberculosis

This study verified the correlation between the serum levels of TNF alpha and different clinical forms of tuberculosis. We described a group of 24 patients presenting several clinical forms of tuberculosis and a control group of 13 healthy individuals. The levels of TNF alpha were measured by bioassay method. The levels of TNF-alpha had significant differences between the tuberculosis and control groups. The patients with abnormal chest X-Ray findings had higher TNF alpha levels (15328.48 ± 4602.19 pg/mL) when compared to patients with normal X-Rays (3353.18 ± 1495.29 pg/mL) (p<0.05). Patients that lost weight had higher TNF alpha levels (15468.54 ± 4580.54 pg/mL) than those that didn't loose weight (2904.98 ± 1367.89) (p<0.05). The levels of TNF alpha were higher in patients with a positive PPD skin test than in those with a negative PPD test (p<0.05). There was a positive correlation between patients' clinical severity and the serum levels of TNF alpha. In patients with successive measurements of TNF alpha, we observed that there was a drop in cytokine levels, and also a clinical improvement concomitantly. We concluded that there was a correlation between serum TNF alpha levels and chest X-Ray alterations, loss of weight, positive PPD skin test and clinical severity in patients with tuberculosis. There was evidence of a worse clinical outcome in patients with tuberculosis that presented higher TNF alpha serum levels.

Estudo da toxicidade das peçonhas crotálicas e botrópicas, no acidente ofídico, com ênfase a toxicidade renal / Study on the Toxicity of Crotalic and Bothropic Venoms in Snake-Related Accidents, with Emphasis on Renal Toxicity

Os acidentes ofídicos possuem uma taxa de letalidade mundial de 2,3 no Brasil chega a 6. Nos acidentes crotálicose botrópicos podem ocorrer insuficiência renal aguda (IRA) causada principalmente por necrose tubular aguda (NTA). As princiapiasfrações tóxicas no veneno crotálico é a crotoxina e a fosfolipase A2, no veneno botrópico são as metaloproteinases e a botropsina. Oveneno crotálico pode levar a alterações glomerulares e nos túbulos proximais, entre as principais causas da IRA por NTA consta a arabdomiólise, já o veneno botrópico pode levar a formaçãode trombos, levando o rim a isquemia pela diminuição da perfusão sanguínea.O comprometimento renal por acidentes ofídicos por apresentar comprometimento sistêmico, deixa ainda obscura sobre a patogênesea ação direta do veneno, bem como da terapia com soro antiofídico que da mesma forma ainda não está esclarecido em sua ação emdiminuir uma potencial ação direta do veneno em tecido renal.

Adaptaçäo intestinal com uso do hormônio de crescimento e da glutamina após ressecçäo extensa do intestino delgado em ratos / Small bowel adaptation with growth hormone and glutamine after massive resection of rat's intestinal small bowel

O uso de glutamina (GLM) e hormônio de crescimento (GH) pode auxiliar a adaptaçäo intestinal em síndrome do intestino curto(SIC). O objetivo deste trabalho foi determinar a atuaçäo de uma dieta rica em GLN associada ao uso de GH sobre a adaptaçäo intestinal em SIC grave em ratos. 80 ratos Wistar(240g) foram randomizados em seis grupos: 1-RGLN (20) - ressecçäo intestinal de 95 porcento do intestino delgado (R) e dieta com glutamina; 2- RGLNGH (20) - RGLN com ministraçäo de GH; 3- RC (10) - R e dieta controle pobre em glutamina; 4- RCGH (10) - R com dieta controle e ministraçäo de GH; 5- TAGLN - transecçäo intestinal na transiçäo jejuno-ileal(TA) seguida de anastomose e dieta rica em glutamina; TAGLNGH - TAGLN e ministraçäo de GH. O GH foi ministrado na dose de 0,14 mg/kg/dia por via subcutânea. Diáriamente foram obtidos o peso corpóreo e o balanço nitrogenado. Após 15 dias os ratos foram sacrificados e a proliferaçäo celular da mucosa intestinal foi estudada com o anticorpo policlonal PC10. Análise estatística apropriada foi efetuada. Em relaçäo ao peso inicial, todos os animais com ressecçäo intestinal perderam peso (8 a 13,9 porcento). O GH favoreceu o ganho de peso nos ratos com transecçäo intestinal. O uso da dieta com GLN e GH promoveu balanço nitrogenado positivo nos ratos com ressecçäo intestinal em relaçäo à diete controle. O uso de GLN e GH potencializou o crescimento do intestino delgado (37,5 porcento), mas näo favoreceu a proliferaçäo celular intestinal. Em conclusäo, a utilizaçäo de dieta enriquecida com glutamina e a ministraçäo de GH favorecem a adaptaçäo intestinal em ratos com ressecçäo maciça do intestino delgado.(au)