RESUMO
BACKGROUND: Patients with metastatic renal carcinoma (mRCC) treated with first-line pazopanib were not included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. SPAZO (NCT02282579) was a nation-wide retrospective observational study designed to assess the effectiveness and validate the IMDC prognostic model in patients treated with first-line pazopanib in clinical practice. PATIENTS AND METHODS: Data of 278 patients, treated with first-line pazopanib for mRCC in 34 centres in Spain, were locally recorded and externally validated. Mean age was 66 years, there were 68.3% male, 93.5% clear-cell type, 74.8% nephrectomized, and 81.3% had ECOG 0-1. Metastatic sites were: lung 70.9%, lymph node 43.9%, bone 26.3%, soft tissue/skin 20.1%, liver 15.1%, CNS 7.2%, adrenal gland 6.5%, pleura/peritoneum 5.8%, pancreas 5%, and kidney 2.2%. After median follow-up of 23 months, 76.4% had discontinued pazopanib (57.2% due to progression), 47.9% had received second-line targeted therapy, and 48.9% had died. RESULTS: According to IMDC prognostic model, 19.4% had favourable risk (FR), 57.2% intermediate risk (IR), and 23.4% poor risk (PR). No unexpected toxicities were recorded. Response rate was 30.3% (FR: 44%, IR: 30% PR: 17.3%). Median progression-free survival (whole population) was 11 months (32 in FR, 11 in IR, 4 in PR). Median and 2-year overall survival (whole population) were 22 months and 48.1%, respectively (FR: not reached and 81.6%, IR: 22 and 48.7%, PR: 7 and 18.8%). These estimations and their 95% confidence intervals are fully consistent with the outcomes predicted by the IMDC prognostic model. CONCLUSION: Our results validate the IMDC model for first-line pazopanib in mRCC and confirm the effectiveness and safety of this treatment.
Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Terapia de Alvo Molecular , Prognóstico , Pirimidinas/administração & dosagem , Sulfonamidas/administração & dosagem , Adulto , Idoso , Carcinoma de Células Renais/patologia , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Humanos , Indazóis , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Espanha , Sulfonamidas/efeitos adversosRESUMO
BACKGROUND: Parents'/caregivers' quality of life is an important aspect to consider when handling paediatric asthma, but there is a paucity of valid and reliable instruments to measure it. The Family Impact of Childhood Bronchial Asthma (IFABI-R) is a recently developed questionnaire to facilitate the assessment of asthma-related parents'/caregivers' quality of life. This study researches the psychometric properties of IFABI-R. METHODS: Parents/main caregivers of 462 children between 4 and 14 years of age with active asthma were included in the sample. IFABI-R was administered on two different occasions and a number of other variables related to the parents'/caregivers' quality of life were measured: child's asthma control, family functioning, and parents'/caregivers' perception of asthma symptoms in the child. IFABI-R evaluative and discriminative properties were analysed, and the minimal important change in the IFABI-R score was identified. RESULTS: IFABI-R showed high internal consistency (Cronbach's alpha=0.941), cross-sectional construct validity (correlation with the degree of child's asthma control, family functioning and parent/caregiver perception of the child's asthma symptoms), longitudinal construct validity (correlation of changes in the IFABI-R with changes in asthma control and changes in the perception of symptoms), sensitivity to change and test-retest reliability. An absolute change of 0.3 units in IFABI-R related to a minimal significant change in the parents'/caregivers' quality of life. CONCLUSIONS: IFABI-R is a reliable and valid instrument to study the quality of life of parents/caregivers of children with asthma.
Assuntos
Asma/epidemiologia , Cuidadores/estatística & dados numéricos , Qualidade de Vida , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Psicometria/métodos , Reprodutibilidade dos Testes , Espanha/epidemiologia , Inquéritos e Questionários/normasRESUMO
BACKGROUND: Rhabdomyolysis (RB) is a syndrome characterised by decomposition of skeletal muscle that could be life threatening, so the identification of biomarkers of its severity could help us in its treatment. Creatine kinase (CK) is usually taken as a reference in patients with RB in order to stratify prognosis, however that is not probably the most effective parameter. AIMS: The present study was designed to analyse the specific features and mortality of patients with RB and the relation between creatinine, CK and mortality. METHODS: Retrospective cohort analysis among patients admitted to San Pedro Hospital in Logroño (Spain) with RB (CK levels higher than 2000 U/L) diagnosed since 1 January 2009 until 31 December 2; 013 522 patients with RB patients diagnosed of RB were collected. The aetiology and the analytical feature (creatinine, CK, calcium, phosphorus, pH and bicarbonate), as well as 30-year mortality, were investigated. RESULTS: Among the 522 patients, there were 138 deaths. Four patients required renal replacement therapy. The most common cause of RB was trauma (29%). Infectious aetiology had the highest mortality (41.2%). The median CK was 3451 u/L (interquartile range 3348), and the mean creatinine at admission was 132.6 umol/L (±110.5). Initial CK levels do not have predictive ability on mortality or renal dysfunction in contrast to initial creatinine values. Each state of acute kidney injury (AKI) increased mortality compared with those who have not presented this renal dysfunction (P < 0.0001). Age, calcium, phosphorus, bicarbonate and pH are associated with AKI. CONCLUSION: Despite being a diagnostic marker for RB, initial CK levels do not predict mortality. However, creatinine initial levels are related to progression to acute renal injury and mortality at 30 days.
Assuntos
Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/urina , Creatinina/urina , Rabdomiólise/mortalidade , Rabdomiólise/urina , Injúria Renal Aguda/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Valor Preditivo dos Testes , Estudos Retrospectivos , Rabdomiólise/diagnóstico , Espanha/epidemiologiaRESUMO
BACKGROUND: Tajikistan has a high burden of rifampicin-resistant TB (RR-TB), with 2,700 new cases estimated for 2021 (28/100,000 population). TB is spread among household members through close interaction and children exposed through household contact progress to disease rapidly and frequently.METHODS: We retrospectively analysed programmatic data from household contact tracing in Dushanbe over 50 months. We calculated person-years of follow-up, contact tracing yield, number needed to screen (NNS) and number needed to test (NNT) to find one new case, and time to diagnosis.RESULTS: We screened 6,654 household contacts of 830 RR-TB index cases; 47 new RR-TB cases were detected, 43 in Year 1 and 4 in Years 2 or 3. Ten were aged <5 years; 46/47 had TB symptoms, 34/45 had chest radiographs consistent with TB, 11/35 were Xpert Ultra-positive, 29/32 were tuberculin skin test-positive and 28/47 had positive TB culture and phenotypic drug susceptibility results. The NNS to find one RR-TB case was 141.57 and the NNT was 34.49. The yields for different types of contacts were as follows: 0.7% for screened contacts, 2.9% for tested contacts, 17.0% for symptomatic contacts and 12.1% for symptomatic contacts aged below 5 years.CONCLUSION: RR-TB household contact tracing was feasible and productive in Tajikistan, a low middle-income country with an inefficient healthcare delivery system.
Assuntos
Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Criança , Humanos , Tadjiquistão/epidemiologia , Busca de Comunicante , Estudos Retrospectivos , RifampinaRESUMO
Zinc exists in biological systems as bound and histochemically reactive free Zn(2+) in the nanomolar range. Zinc is required as either structural or catalytic component for a large number of enzymes. It also modulates current passage through many ion channels. Here, we reinvestigated the effects of extracellular and intracellular Zn(2+) on the L-type Ca(2+) current (I (CaL)) and its modulation by ß-adrenergic stimulation in rat ventricular cardiomyocytes. In the absence of Ca(2+) ions, Zn(2+) could permeate through the L-type channel at much lower concentrations and at a more positive voltage range, but with a lower permeability than Ca(2+). In the presence of Ca(2+), extracellular Zn(2+) demonstrated strong bimodal inhibitory effects on the I (CaL), with half-inhibition occurring around 30 nM, i.e., in the range of concentrations found in the plasma. Intracellular Zn(2+) also significantly inhibited the I (CaL) with a half-inhibitory effect at 12.7 nM. Moreover, ß-adrenergic stimulation was markedly reduced by intracellular Zn(2+) at even lower concentrations (<1 nM) as a consequence of Zn(2+)-induced inhibition of the adenylyl cyclase. All these effects appeared independent of redox variations and were not affected by dithiothreitol. Thus, both basal intracellular and extracellular Zn(2+) modulate transmembrane Ca(2+) movements and their regulation by ß-adrenergic stimulation. Considering that, in many pathological situations, including diabetes, the extracellular Zn(2+) concentration is reduced and the intracellular one is increased, our results help to explain both Ca(2+) overload and marked reduction in the ß-adrenergic stimulation in these diseases.
Assuntos
Canais de Cálcio Tipo L/fisiologia , Miócitos Cardíacos/fisiologia , Zinco/metabolismo , Agonistas Adrenérgicos beta/farmacologia , Animais , Cálcio/metabolismo , Canais de Cálcio Tipo L/efeitos dos fármacos , Cardiopatias/metabolismo , Ventrículos do Coração/citologia , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Ratos , Zinco/farmacologiaRESUMO
The congenital deficit of FVII of coagulation it's an anomaly of genetic transmission autosomal recessive type, it can occur with clinical manifestations like hematomas and spontaneous bleeding or not. The normal levels of FVII it's found between 70%-130% of the laboratory reference value. For unknown reasons there is a poor correlation between levels of FVII and bleeding risk. During pregnancy coagulation can be significantly altered, there is a no clear consensus and a very few information about how to act during labor in a patient with a FVII deficit. The case of a 35-year-old patient with 35 weeks of gestation and congenital deficit of the coagulation FVII (36%) is presented, epidural analgesia is performed during labor previously administering activated recombinant FVII (rFVIIa) without complications (Spinal hematoma, postpartum bleeding, thrombosis).
Assuntos
Analgesia Epidural , Deficiência do Fator VII , Hemorragia Pós-Parto , Trombose , Adulto , Coagulação Sanguínea , Deficiência do Fator VII/complicações , Deficiência do Fator VII/genética , Feminino , Humanos , Gravidez , Trombose/complicaçõesRESUMO
The congenital deficit of FVII of coagulation it's an anomaly of genetic transmission autosomal recessive type, it can occur with clinical manifestations like hematomas and spontaneous bleeding or not. The normal levels of FVII it's found between 70%-130% of the laboratory reference value. For unknown reasons there is a poor correlation between levels of FVII and bleeding risk. During pregnancy coagulation can be significantly altered, there is a no clear consensus and a very few information about how to act during labor in a patient with a FVII deficit. The case of a 35-year-old patient with 35 weeks of gestation and congenital deficit of the coagulation FVII (36%) is presented, epidural analgesia is performed during labor previously administering activated recombinant FVII (rFVIIa) without complications (Spinal hematoma, postpartum bleeding, thrombosis).
RESUMO
The identification of the presence of genotype by environment interaction effects on important traits in Holstein cattle allows for the use of international genetic evaluations and a more efficient design of regional genetic evaluation programmes. The aim of this study was to determine the genotype × environment interaction effects in Chilean Holstein dairy cattle through the analysis of records corresponding to calvings between 1998 and 2015. Herds were classified in the central and southern regions of Chile based on herd location as well as by high and low levels of production environments based on the fat plus protein yield averages per herd within each region. The central region has a Mediterranean climate and a confined production system while the southern region has a humid temperate climate and a production system based on grazing with supplementation. Traits studied were milk yield (MY), fat yield (FY), protein yield (PY), fat content (FC) and protein content (PC) by lactation, age at first calving (AFC) and calving interval (CI). Several four-trait mixed animal models were applied to environmental category data as different traits, which included herd-year-calving season (herd-year-birth season for AFC) and lactation number as fixed effects, and animal additive genetic, sire-herd, permanent environment and residual effects as random effects. Genetic correlations (rg) for MY, FY, FC, PC and CI were found to decrease as differences between environmental categories increased. The rg between the most extreme environmental categories considered in this study for AFC (0.26) was the only one found statistically lower than 0.60. Genetic correlation values statistically lower than 0.80 (P < 0.05) were observed for AFC, CI, MY, FY and PY between some environmental categories. If separate genetic evaluations are adopted as practical criteria when the value of rg is lower than 0.60, the consequence of improving a multi-trait economic breeding objective in this population is likely to be small unless extreme environmental categories are considered. However, a moderate decrease in selection response and re-ranking of selection candidates is expected for AFC, CI and yield traits when selection is performed in different environmental conditions. Genotype × environment interaction effects involving production systems in a Mediterranean climate and confinement vs. Temperate Oceanic climate and grazing with supplementation, and between two fat plus protein yield level categories within each environment, were at most moderate for the studied traits.
Assuntos
Lactação , Leite , Animais , Bovinos/genética , Feminino , Genótipo , Parto , Fenótipo , GravidezRESUMO
El déficit congénito del factor VII (FVII) de la coagulación es una anomalía de transmisión genética de tipo autosómico recesivo, puede presentarse con manifestaciones clínicas como hematomas y sangrados espontáneos o no. Los niveles normales del FVII se encuentran entre el 70-130% del valor de referencia del laboratorio. Por razones desconocidas existe una pobre correlación entre los niveles del FVII y el riesgo de sangrado. Durante el embarazo se puede alterar notablemente la coagulación, no existe un consenso claro y hay escasa información sobre cómo actuar durante el trabajo de parto en paciente con déficit del FVII. Se presenta el caso de una mujer de 35 años en la semana 35 de gestación y déficit congénito del FVII (36%), se realiza analgesia peridural durante el parto administrando previamente factor VII recombinante activado (rFVIIa) sin complicaciones (hematoma peridural, sangrado posparto, trombosis).(AU)
The congenital deficit of FVII of coagulation it's an anomaly of genetic transmission autosomal recessive type, it can occur with clinical manifestations like hematomas and spontaneous bleeding or not. The normal levels of FVII it's found between 70%-130% of the laboratory reference value. For unknown reasons there is a poor correlation between levels of FVII and bleeding risk. During pregnancy coagulation can be significantly altered, there is a no clear consensus and a very few information about how to act during labor in a patient with a FVII deficit. The case of a 35-year-old patient with 35 weeks of gestation and congenital deficit of the coagulation FVII (36%) is presented, epidural analgesia is performed during labor previously administering activated recombinant FVII (rFVIIa) without complications (Spinal hematoma, postpartum bleeding, thrombosis).(AU)
Assuntos
Humanos , Feminino , Adulto , Analgesia Epidural , Gestantes , Deficiência do Fator VII , Transtornos Hemorrágicos , Doenças Genéticas Inatas , Reanimação Cardiopulmonar , AnestesiologiaRESUMO
Reliable noninvasive estimators of global left ventricular (LV) chamber function remain unavailable. We have previously demonstrated a potential relationship between color-Doppler M-mode (CDMM) images and two basic indices of LV function: peak-systolic elastance (Emax) and the time-constant of LV relaxation (tau). Thus, we hypothesized that these two indices could be estimated noninvasively by adequate postprocessing of CDMM recordings. A semiparametric regression (SR) version of support vector machine (SVM) is here proposed for building a blind model, capable of analyzing CDMM images automatically, as well as complementary clinical information. Simultaneous invasive and Doppler tracings were obtained in nine mini-pigs in a high-fidelity experimental setup. The model was developed using a test and validation leave-one-out design. Reasonably acceptable prediction accuracy was obtained for both Emax (intraclass correlation coefficient Ric, = 0.81) and tau (Ric, = 0.61). For the first time, a quantitative, noninvasive estimation of cardiovascular indices is addressed by processing Doppler-echocardiography recordings using a learning-from-samples method.
Assuntos
Inteligência Artificial , Ecocardiografia Doppler em Cores/métodos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Isquemia Miocárdica/diagnóstico por imagem , Reconhecimento Automatizado de Padrão/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Algoritmos , Animais , Armazenamento e Recuperação da Informação/métodos , Isquemia Miocárdica/complicações , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Volume Sistólico , Suínos , Disfunção Ventricular Esquerda/etiologiaRESUMO
OBJECTIVE: The goal of this research has been to evaluate the survival, in long and short term, of the patient receiving liver transplant for hepatocellular carcinoma (HCC), the risk of post-transplant tumor relapse and factors related to this complication. DESIGN: Retrospective study of a consecutive series of patients having had liver transplant for HCC. PATIENTS AND METHODOLOGY: Transplant patients for HCC from 1989 to November 2003. Patients were selected due to general limitations of nodule size and quantity, which were subsequently published as Milan criteria. Also, criteria agreed in the Conference of Barcelona were followed in the pre-transplant diagnosis. RESULTS: The survival of this 81 patients group was of the 80, 61 and 52% for 1, 5 and 10 years respectively. In the 32% of the cases the HCC was an incidental finding in the explant. In the 12.3%, the tumor relapse was verified. The multivariate research identified the size of the nodule (OR=1,7944) (IC 95%=1,1332-2,8413) and the vascular invasion (OR=6,6346) (IC 95%=1,4624-30,1003) as risk factors of relapse. CONCLUSIONS: The liver transplant in selected patients with HCC has good results in medium and long term. The risk of post-transplant tumor relapse becomes notably reduced and is associated with the size of the nodule and the microscopic vascular invasion.
Assuntos
Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Transplante de Fígado/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Retrospectivos , Risco , Espanha/epidemiologia , Análise de Sobrevida , Taxa de Sobrevida , Resultado do TratamentoRESUMO
In this work, a new open hardware interface based on Arduino to read electromotive force (emf) from potentiometric detectors is presented. The interface has been fully designed with the open code philosophy and all documentation will be accessible on web. The paper describes a comprehensive project including the electronic design, the firmware loaded on Arduino, and the Java-coded graphical user interface to load data in a computer (PC or Mac) for processing. The prototype was tested by measuring the calibration curve of a detector. As detection element, an active poly(vinyl chloride)-based membrane was used, doped with cetyltrimethylammonium dodecylsulphate (CTA(+)-DS(-)). The experimental measures of emf indicate Nernstian behaviour with the CTA(+) content of test solutions, as it was described in the literature, proving the validity of the developed prototype. A comparative analysis of performance was made by using the same chemical detector but changing the measurement instrumentation.
RESUMO
BACKGROUND: The development of metabolic syndrome (MS) after liver transplantation (LT) is a major source of mortality derived from cardiovascular events. The aim of the present study was to determine the prevalence and risk factors of MS after LT. METHODS: One-hundred seventy-four consecutive LT patients from January 2004 to June 2010 surviving longer than 1 year after LT were included. Median follow-up after LT was 48 months. Independent predictors of MS were obtained by means of multivariate logistic regression. RESULTS: At 3 years after LT, 25.5% of patients reached a body mass index (BMI) ≥30 kg/m2, 35.6% of patients developed arterial hypertension, 54.2% showed impaired fasting glucose, 22.5% had serum cholesterol >200 mg/dL, and 22.5% showed hypertriglyceridemia >150 mg/dL. The prevalence of MS ranged from 49% to 86% depending on the considered period. The pre-LT variables associated with MS were age at LT (odds ratio [OR], 1.08; P = .002), BMI of recipient before LT (OR, 1.23; P = .001), serum glucose (OR, 1.02; P = .005), and non-heart-beating donor (OR, 1.02; P = .046). The post-LT predictors of MS were body weight (OR, 1.04; P = .005), arterial hypertension (OR, 1.02; P = .047), and serum glucose (OR, 1.02; P = .011) at 6 months. CONCLUSIONS: LT patients develop MS in a high proportion and progressively despite current efforts (ie, lifestyle modifications and aggressive management of hypertension, diabetes, and hyperlipidemia). The associated risk factors include age, increased BMI, and pre- and post-LT glucose.
Assuntos
Transplante de Fígado/efeitos adversos , Síndrome Metabólica/epidemiologia , Adulto , Índice de Massa Corporal , Diabetes Mellitus , Feminino , Humanos , Hiperlipidemias/complicações , Hipertensão/complicações , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Fatores de RiscoRESUMO
OBJECTIVE: A safety threshold for baseline rhythm R-wave amplitudes during follow-up of implantable cardioverter defibrillators (ICD) has not been established. We aimed to analyse the amplitude distribution and undersensing rate during spontaneous episodes of ventricular fibrillation (VF), and define a safety amplitude threshold for baseline R-waves. METHODS: Data were obtained from an observational multicentre registry conducted at 48 centres in Spain. Baseline R-wave amplitudes and VF events were prospectively registered by remote monitoring. Signal processing algorithms were used to compare amplitudes of baseline R-waves with VF R-waves. All undersensed R-waves after the blanking period (120â ms) were manually marked. RESULTS: We studied 2507 patients from August 2011 to September 2014, which yielded 229 VF episodes (cycle length 189.6±29.1â ms) from 83 patients that were suitable for R-wave comparisons (follow-up 2.7±2.6â years). The majority (77.6%) of VF R-waves (n=13953) showed lower amplitudes than the reference baseline R-wave. The decrease in VF amplitude was progressively attenuated among subgroups of baseline R-wave amplitude (≥17; ≥12 to <17; ≥7 to <12; ≥2.2 to <7â mV) from the highest to the lowest: median deviations -51.2% to +22.4%, respectively (p=0.027). There were no significant differences in undersensing rates of VF R-waves among subgroups. Both the normalised histogram distribution and the undersensing risk function obtained from the ≥2.2 to <7â mV subgroup enabled the prediction that baseline R-wave amplitudes ≤2.5â mV (interquartile range: 2.3-2.8â mV) may lead to ≥25% of undersensed VF R-waves. CONCLUSIONS: Baseline R-wave amplitudes ≤2.5â mV during follow-up of patients with ICDs may lead to high risk of delayed detection of VF. TRIAL REGISTRATION NUMBER: NCT01561144; results.
Assuntos
Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Sistema de Condução Cardíaco/fisiopatologia , Fibrilação Ventricular/terapia , Potenciais de Ação , Adulto , Idoso , Diagnóstico Tardio , Cardioversão Elétrica/efeitos adversos , Eletrocardiografia/métodos , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Valor Preditivo dos Testes , Desenho de Prótese , Sistema de Registros , Tecnologia de Sensoriamento Remoto/métodos , Fatores de Risco , Processamento de Sinais Assistido por Computador , Espanha , Telemetria/métodos , Fatores de Tempo , Resultado do Tratamento , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/fisiopatologiaRESUMO
The properties of the low threshold Ca current (ICaT) in bullfrog (Rana catesbeiana) isolated atrial cardiomyocytes were studied using the whole-cell recording patch-clamp technique and compared with those of the high threshold Ca current (ICaL). In 91% of atrial cells we observed both ICaT and ICaL when collagenase and trypsin were used to dissociate the cells. But when pronase was used, only 30% of the cells exhibited ICaT. ICaT was never found in ventricular cells. ICaT could be investigated more easily when ICaL was inhibited by Cd ions (50 microM). Its kinetics were unchanged by substituting Ba for Ca, or in the presence of high concentrations of Ba. Both ICaT and ICaL exhibited reduced inactivation after high depolarizing prepulses. ICaT was found to be sensitive to dihydropyridines: 1 microM nifedipine decreased this current while 1 microM BAY K 8644 increased it; this occurred without significant variations in the steady-state inactivation curve. ICaT was more sensitive than ICaL to alpha 1-adrenergic and P2-purinergic stimulations, while ICaL was more sensitive to beta-adrenergic stimulation. Isoproterenol was still able to increase ICaT in the presence of high intracellular cAMP. Both currents were increased by 1 microM ouabain (although ICaL only transiently) and decreased by 10 microM ouabain. It is concluded that the two types of Ca channels can be observed in bullfrog atrial cells and that they are specifically altered by pharmacological agents and neuromediators. This may have implications for cardiac behavior.
Assuntos
Canais de Cálcio/fisiologia , Átrios do Coração/citologia , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Animais , Função Atrial , Bário/farmacologia , Cádmio/farmacologia , Cálcio/farmacocinética , Canais de Cálcio/ultraestrutura , Células Cultivadas , Relação Dose-Resposta a Droga , Átrios do Coração/química , Isoproterenol/farmacologia , Níquel/farmacologia , Nifedipino/farmacologia , Ouabaína/farmacologia , Fenilefrina/farmacologia , Propranolol/farmacologia , Rana catesbeianaRESUMO
Three hundred seventeen patients with toxic oil syndrome caused by ingestion of denatured rapeseed oil were followed up after one year. Total mortality for the 317 patients was 4.4%. After 12 months, 3.2% of the surviving patients have a severe motor neuropathy, 52.9% are asymptomatic, and the remaining 39.4% have mild residual myalgia. The cause of death in seven patients during the acute phase of toxic oil syndrome was respiratory failure due to interstitial pneumonitis with cerebral edema. The death of five patients in the second phase was due to motor neuropathy that involved respiratory muscles and was complicated by aspiration pneumonia.
Assuntos
Brassica , Doenças Transmitidas por Alimentos/etiologia , Óleos/intoxicação , Óleos de Plantas , Adolescente , Adulto , Idoso , Compostos de Anilina/intoxicação , Criança , Ácidos Graxos Monoinsaturados , Feminino , Seguimentos , Contaminação de Alimentos , Doenças Transmitidas por Alimentos/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Óleo de Brassica napus , Espanha , SíndromeRESUMO
OBJECTIVE: Deleterious electrical abnormalities evolve during myocardial infarction. The goal of this study was to analyse current changes during the late decompensated phase of heart disease induced by coronary ligation and to compare them in various heart regions. METHODS: Young rats were submitted to left coronary ligature. After 4-6 months, cells were enzymatically dissociated and isolated from the upper part basal region of the left ventricle, as well as from the septum, apex and the right ventricle before being studied under whole-cell patch-clamp. RESULTS: Basal L-type Ca2+ current, ICaL elicited at +10 mV did not exhibit regional dependence neither in control nor after post-myocardial infarction (PMI). ICaL showed both a significantly reduced peak amplitude (17.1 +/- 2.8 pA/pF versus 9.9 +/- 1.4 pA/pF in seven control and seven PMI hearts, n = 32 and 40, respectively) and a slower inactivation, such that the amount of inward charges during a 200 ms-depolarizing pulse was nearly unchanged. beta-Adrenergic stimulation was less effective in increasing ICaL in PMI cells but it slowed inactivation further. Significant differences in the K+ currents were observed. A regional distribution was seen for Ito only, with the largest amplitude in the right ventricle (in pA/pF: 23.1 +/- 2.4, 18.2 +/- 3.9, 14.8 +/- 2.4, 8.3 +/- 1.7 in the right ventricle, apex, septum and left ventricle, respectively n = 8, 7, 8 and 9). This was also true in failing heart cells despite Ito being halved in each of the four regions (in pA/pF: 12.2 +/- 2.5, 11.2 +/- 1.9, 5.1 +/- 1.0 and 4.8 +/- 1.0, respectively n = 12, 12, 11 and 13). IK1 was also significantly reduced by 20% in the PMI cells. Two-way analyses of variance demonstrated the absence of interaction between the topographical origin of the cells and the physiological state of the rats. The alpha 1-adrenergic agonist, methoxamine significantly reduced Ito and IK1 to the same extent in both sham and PMI cells, by about 35% and 20% respectively. CONCLUSIONS: Long-term left coronary occlusion induces significant alterations in both Ca2+ and K+ currents that occur with similar amplitude in both ventricles. They include a marked reduction in Ito amplitude as well as a slowing of ICaL inactivation. Both factors could contribute to the disturbances in cellular electrical behaviour and the occurrence of arrhythmias in the post-myocardial infarcted heart.
Assuntos
Potenciais de Ação , Arritmias Cardíacas/etiologia , Transporte Biológico Ativo , Infarto do Miocárdio/complicações , Remodelação Ventricular , Potenciais de Ação/efeitos dos fármacos , Agonistas alfa-Adrenérgicos/farmacologia , Agonistas Adrenérgicos beta/farmacologia , Análise de Variância , Animais , Arritmias Cardíacas/patologia , Arritmias Cardíacas/fisiopatologia , Transporte Biológico Ativo/efeitos dos fármacos , Western Blotting , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Expressão Gênica , Transporte de Íons , Isoproterenol/farmacologia , Masculino , Metoxamina/farmacologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Nifedipino/farmacologia , Técnicas de Patch-Clamp , Canais de Potássio/efeitos dos fármacos , Canais de Potássio/genética , Ratos , Ratos Wistar , Fatores de TempoRESUMO
The current development of cloud computing is completely changing the paradigm of data knowledge extraction in huge databases. An example of this technology in the cardiac arrhythmia field is the SCOOP platform, a national-level scientific cloud-based big data service for implantable cardioverter defibrillators. In this scenario, we here propose a new methodology for automatic classification of intracardiac electrograms (EGMs) in a cloud computing system, designed for minimal signal preprocessing. A new compression-based similarity measure (CSM) is created for low computational burden, so-called weighted fast compression distance, which provides better performance when compared with other CSMs in the literature. Using simple machine learning techniques, a set of 6848 EGMs extracted from SCOOP platform were classified into seven cardiac arrhythmia classes and one noise class, reaching near to 90% accuracy when previous patient arrhythmia information was available and 63% otherwise, hence overcoming in all cases the classification provided by the majority class. Results show that this methodology can be used as a high-quality service of cloud computing, providing support to physicians for improving the knowledge on patient diagnosis.
Assuntos
Arritmias Cardíacas/classificação , Eletrocardiografia/classificação , Internet , Computação em Informática Médica , Arritmias Cardíacas/terapia , Bases de Dados Factuais , Desfibriladores Implantáveis , Humanos , Aprendizado de Máquina , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Tuberculosis currently represents a serious problem in prison populations. METHODS: With the aim of studying the predictive factors for, and the prevalence of, Mycobacterium tuberculosis infection and pulmonary tuberculosis in a Spanish prison, all those admitted during 1991 and 1992 were included (N = 1314). The tuberculin skin test, HIV serology, chest X-ray and bacteriological examination of sputum were carried out. Statistical analysis was done by univariant tests, stratified analysis and logistic regression. RESULTS: The prevalence of M. tuberculosis infection was 55.5% (95% confidence interval [CI] 52.5-58.5). An association was found with sex, imprisonment more than once, HIV infection and age. The co-infection rate (tuberculosis plus HIV) was 9.2%. Logistic regression showed a greater risk with age (4.4% per year), time spent in prison and for males. The prevalence of pulmonary tuberculosis was 1.26% and an association was found with M. tuberculosis infection, HIV infection (odds ratio [OR] = 13.7), intravenous drug users (OR = 17.2) and imprisonment more than once (OR = 7.3). Logistic regression showed an association with HIV co-infection (OR = 20.2). CONCLUSIONS: The prevalence of M. tuberculosis infection and pulmonary tuberculosis is high when compared with similar studies. The influence of age, time spent in prison and co-infection with HIV is relevant to recommendations for specific tuberculosis prevention programmes in correctional facilities.
Assuntos
Prisioneiros , Tuberculose Pulmonar/epidemiologia , Síndrome da Imunodeficiência Adquirida/complicações , Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Fatores Sexuais , Espanha/epidemiologia , Abuso de Substâncias por Via Intravenosa , Teste Tuberculínico , Tuberculose/epidemiologia , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnósticoRESUMO
The two novel dihydropyridines, oxodipine and elgodipine greatly depressed the KCl-induced contraction of rabbit aorta and decreased the cardiac force of contraction of rat ventricular strips with lower potency. Both compounds markedly shortened cardiac action potentials. In rat cultured neonatal ventricular myocytes, oxodipine and elgodipine decreased the L-type Ca2+ current (I(CaL)) with IC50 of 0.24 and 0.33 microM respectively while oxodipine was slightly more potent on the T-type Ca2+ current (I(CaT)) than elgodipine (IC50 = 0.41 vs. 2.18 microM). Both compounds were less potent in inhibiting I(CaL) of adult cardiomyocytes. Oxodipine exhibited mostly a tonic block of both currents while elgodipine induced mainly a use-dependent block. Oxodipine and elgodipine increased by at least one order of magnitude their inhibitory potency on I(CaT) and I(CaL) when the cells were partially depolarized. We conclude that the mechanisms of inhibition of Ca2+ channels by these two dihydropyridines are different and suggest that the underlying mechanism of vascular selectivity is the voltage-dependent block of I(CaL), with the use-dependent inhibition of Ca2+ currents by elgodipine further contributing to this selectivity.