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1.
J Crit Care ; 56: 197-202, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31945586

RESUMO

PURPOSE: This is a predefined sub-study of the Endothelial Dysfunction in Resuscitated Cardiac Arrest (ENDO-RCA) trial. We aim to investigate Iloprost, a prostacyclin analogue, safety by evaluating change in whole blood platelet aggregometry (Multiplate) in out of hospital cardiac arrest (OHCA) patients from baseline to 96-h post randomization. METHODS: A randomized, placebo controlled double-blinded trial in 46 OHCA patients. Patients were allocated 1:2 to 48 h Iloprost infusion, (1 ng/kg/min) or placebo (saline infusion). Platelet aggregation was determined by platelet aggregation tests ASPI-test (arachidonic acid); TRAP-test (thrombin-receptor activating peptide (TRAP)-6; RISTO test (Ristocetin); ADP test (adenosin diphosphat). RESULTS: There was no significant difference between the iloprost and placebo groups according to ASPI, TRAP, RISTO and ADP platelet aggregation assays. Further, no significant differences regarding risk of bleeding were found between groups (Risk of bleeding: ASPI <40 U; TRAP <92 U; RISTO <35 U; ADP <50 U). CONCLUSIONS: In conclusion, the iloprost infusion did not influence platelet aggregation as evaluated by the ASPI, TRAP, RISTO and ADP assays. There was no increased risk of bleeding or transfusion therapy. A decline in platelet aggregation was observed for the ASPI and ADP assays during the initial 96 h after OHCA. TRIAL REGISTRATION: Trial registration at clinicaltrials.gov (identifier NCT02685618) on 18-02-2016.


Assuntos
Coma/complicações , Iloprosta/administração & dosagem , Parada Cardíaca Extra-Hospitalar/sangue , Parada Cardíaca Extra-Hospitalar/tratamento farmacológico , Inibidores da Agregação Plaquetária/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Idoso , Método Duplo-Cego , Feminino , Humanos , Iloprosta/efeitos adversos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Inibidores da Agregação Plaquetária/efeitos adversos , Testes de Função Plaquetária
3.
Resuscitation ; 131: 24-28, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30053455

RESUMO

INTRODUCTION: Routine EEG is widely used and accessible for post arrest neuroprognostication. Recent studies, using standardised EEG terminology, have proposed highly malignant EEG patterns with promising predictive ability. OBJECTIVES: To validate the performance of standardised routine EEG patterns to predict neurological outcome after cardiac arrest. METHODS: In the prospective multicenter Target Temperature Management trial, comatose cardiac arrest patients were randomised to different temperature levels (950 patients, 36 sites). According to the prospective protocol a routine EEG was performed in patients who remained comatose after the 36 h temperature control intervention. EEGs were retrospectively reviewed blinded to outcome using the standardised American Clinical Neurophysiology Society terminology. Highly malignant, malignant and benign EEG patterns were correlated to poor and good outcome, defined by best achieved Cerebral Performance Category up to 180 days. RESULTS: At 20 sites 207 patients had a routine EEG performed at median 76 h after cardiac arrest. Highly malignant patterns (suppression or burst-suppression with or without discharges) had a high specificity for poor outcome (98%, CI 92-100), but with limited sensitivity (31%, CI 24-39). Our false positive patient had a burst-suppression pattern during ongoing sedation. A benign EEG, i.e. continuous normal-voltage background without malignant features, identified patients with good outcome with 77% (CI 66-86) sensitivity and 80% (CI 73-86) specificity. CONCLUSION: Highly malignant routine EEG after targeted temperature management is a strong predictor of poor outcome. A benign EEG is an important indicator of a good outcome for patients remaining in coma.


Assuntos
Coma/fisiopatologia , Eletroencefalografia , Hipotermia Induzida/métodos , Parada Cardíaca Extra-Hospitalar/terapia , Idoso , Coma/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Neurofisiológica/métodos , Parada Cardíaca Extra-Hospitalar/complicações , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Terminologia como Assunto
4.
Acta Anaesthesiol Scand ; 62(10): 1436-1442, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29926901

RESUMO

BACKGROUND: Admission lactate and lactate clearance are implemented for risk stratification in sepsis and trauma. In out-of-hospital cardiac arrest, results regarding outcome and lactate are conflicting. METHODS: This is a post-hoc analysis of the Target Temperature Management trial in which 950 unconscious patents after out-of-hospital cardiac arrest were randomized to a temperature intervention of 33°C or 36°C. Serial lactate samples during the first 36 hours were collected. Admission lactate, 12-hour lactate, and the clearance of lactate within 12 hours after admission were analyzed and the association with 30-day mortality assessed. RESULTS: Samples from 877 patients were analyzed. In univariate logistic regression analysis, the odds ratio for death by day 30 for each mmol/L was 1.12 (1.08-1.16) for admission lactate, P < .01, 1.21 (1.12-1.31) for 12-hour lactate, P < .01, and 1.003 (1.00-1.01) for each percentage point increase in 12-hour lactate clearance, P = .03. Only admission lactate and 12-hour lactate levels remained significant after adjusting for known predictors of outcome. The area under the receiver operating characteristic curve was 0.65 (0.61-0.69), P < .001, 0.61 (0.57-0.65), P < .001, and 0.53 (0.49-0.57), P = .15 for admission lactate, 12-hour lactate, and 12-hour lactate clearance, respectively. CONCLUSIONS: Admission lactate and 12-hour lactate values were independently associated with 30-day mortality after out-of-hospital cardiac arrest while 12-hour lactate clearance was not. The clinical value of lactate as the sole predictor of outcome after out-of-hospital cardiac arrest is, however, limited.


Assuntos
Ácido Láctico/metabolismo , Parada Cardíaca Extra-Hospitalar/metabolismo , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/mortalidade
5.
Clin Neurophysiol ; 129(8): 1660-1668, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29933239

RESUMO

OBJECTIVE: Investigate the temporal development of EEG and prognosis. METHODS: Prospective observational substudy of the Target Temperature Management trial. Six sites performed simplified continuous EEG-monitoring (cEEG) on comatose patients after cardiac arrest, blinded to treating physicians. We determined time-points of recovery of a normal-voltage continuous background activity and the appearance of an epileptiform EEG, defined as abundant epileptiform discharges, periodic/rhythmic discharges or electrographic seizure activity. RESULTS: 134 patients were included, 65 had a good outcome. Early recovery of continuous background activity (within 24 h) occurred in 72 patients and predicted good outcome since 55 (76%) had good outcome, increasing the odds for a good outcome seven times compared to a late background recovery. Early appearance of an epileptiform EEG occurred in 38 patients and 34 (89%) had a poor outcome, increasing the odds for a poor outcome six times compared to a late debut. The time to background recovery and the time to epileptiform activity were highly associated with outcome and levels of neuron-specific enolase. Multiple regression analysis showed that both variables were independent predictors. CONCLUSIONS: Time to epileptiform activity and background recovery are independent prognostic indicators. SIGNIFICANCE: Patients with early background recovery combined with late appearance of epileptiform activity may have a good outcome.


Assuntos
Coma/diagnóstico , Coma/fisiopatologia , Eletroencefalografia/tendências , Parada Cardíaca/diagnóstico , Parada Cardíaca/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Idoso , Idoso de 80 Anos ou mais , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Tempo
6.
Acta Anaesthesiol Scand ; 62(10): 1412-1420, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29947076

RESUMO

BACKGROUND: Neurological prognostication is an essential part of post-resuscitation care in out-of-hospital cardiac arrest (OHCA). This study aims to assess the use of computed tomography (CT) and magnetic resonance imaging (MR) of the head, electroencephalography (EEG), and somatosensory evoked potentials (SSEP) in neurological prognostication in resuscitated OHCA patients and factors associated with their use in Danish tertiary and non-tertiary centers from 2005 to 2013 and associations with outcome. METHODS: We used the Danish Cardiac Arrest Registry to identify patients ≥18 years of age admitted to intensive care units due to OHCA of presumed cardiac etiology. CT 0-20 days and MR, SSEP, and EEG ≥2-20 days post OHCA were considered related to prognostication. Incidence and factors associated with procedures were assessed by multiple Cox regression with death as competing risk. RESULTS: Use of CT, MR, EEG, and SSEP increased during the study period (CT: 51%-67%, HRCT : 1.06, CI: 1.03-1.08, MR: 2%-5%, P = .08, EEG: 6%-33%, HREEG : 1.25, CI: 1.19-1.30, SSEP: 4%-15%, HRSSEP : 1.23, CI: 1.15-1.32). EEG and SSEP were more used in tertiary centers than non-tertiary (HREEG : 1.86, CI: 1.51-2.29, HRSSEP : 4.44, CI: 2.86-6.89). Use of CT, SSEP, and EEG were associated with higher 30-day mortality, and MR was associated with lower (HRCT : 1.15, CI: 1.01-1.30, HRMR : 0.53, CI: 0.37-0.77, HRSSEP : 1.90, CI: 1.57-2.32, HREEG : 1.75, CI: 1.49-2.05). CONCLUSION: Use of neurological prognostication procedures increased during the study period. EEG and SSEP were more used in tertiary centers. CT, EEG and SSEP were associated with increased mortality.


Assuntos
Eletroencefalografia , Potenciais Somatossensoriais Evocados , Unidades de Terapia Intensiva , Parada Cardíaca Extra-Hospitalar/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Viés , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Tempo , Tomografia Computadorizada por Raios X
8.
Int J Cardiovasc Imaging ; 34(7): 1017-1028, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29383465

RESUMO

Tricuspid annular plane systolic excursion (TAPSE) is a robust measure of RV function, but the performance of transesophageal echocardiography (TEE) measured TAPSE during surgery is not well established. We aim to evaluate feasibility of various TEE views before, during and after surgery. Furthermore, we compare performance of individual TEE measurements depending on view and method (AMM- and M-mode as well as 2D) as well as TAPSE measured using TEE with transthoracic echocardiography (TTE) TAPSE. The study was conducted from January 2015 through September 2016. In 47 patients with normal left ventricular ejection fraction, TEE was prospectively performed during coronary artery bypass grafting surgery. TAPSE and tricuspid annulus tissue Doppler imaging (TDI) were recorded in five different views at pre-specified time points during surgery. Data were analyzed for availability (obtainable/readable images) and reliability (intra-/inter-observer bias and precision). Finally, TEE TAPSE was compared to TTE TAPSE immediately before and after surgery. TAPSE and TDI with TEE was achievable in > 90% of patients in the transgastric view during surgery. The AM- and M-mode had the best reliability and the best correlation with TAPSE measured with TTE. The deep transgastric view was achievable in less than 50% after sternotomy, and TAPSE measured from 2D had a poorer performance compared to the AM- and M-mode. TDI demonstrated a high reliability throughout surgery. RV function can be evaluated by TAPSE and TDI using TEE during surgery. TEE values from the transgastric view demonstrated high performance throughout surgery and a good agreement with TTE TAPSE measurements.


Assuntos
Ponte de Artéria Coronária , Doença das Coronárias/cirurgia , Ecocardiografia Transesofagiana , Valva Tricúspide/diagnóstico por imagem , Disfunção Ventricular Direita/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Doença das Coronárias/diagnóstico por imagem , Ecocardiografia , Estudos de Viabilidade , Feminino , Humanos , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Valva Tricúspide/fisiopatologia , Disfunção Ventricular Direita/fisiopatologia , Função Ventricular Direita/fisiologia
9.
Allergy ; 73(2): 498-504, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28929567

RESUMO

BACKGROUND: Studies have suggested that Bacillus Calmette-Guérin (BCG) vaccination may reduce the risk of allergic diseases, including atopic dermatitis. METHODS: The Danish Calmette Study was conducted 2012-2015. Within 7 days of birth new-borns were randomised 1:1 to BCG or no BCG. Exclusion criteria were gestational age <32 weeks, birth weight <1000 g, known immunodeficiency or no Danish-speaking parent. Data were collected through telephone interviews and clinical examinations until 13 months. RESULTS: Clinical atopic dermatitis was diagnosed in 466/2,052 (22.7%) children in the BCG group and 495/1,952 (25.4%) children in the control group (RR = 0.90 [95% confidence intervals 0.80-1.00]). The effect of neonatal BCG vaccination differed significantly between children with atopic predisposition (RR 0.84 (0.74-0.95)) and children without atopic predisposition (RR 1.09 [0.88-1.37]) (test of no interaction, P = .04). CONCLUSION: Among children with atopic predisposition, the number-needed-to-treat with BCG to prevent one case of atopic dermatitis was 21 (12-76).


Assuntos
Vacina BCG/uso terapêutico , Dermatite Atópica/prevenção & controle , Dermatite Atópica/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Países Baixos/epidemiologia
10.
Eur J Clin Microbiol Infect Dis ; 37(1): 29-41, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28890996

RESUMO

Several studies have shown increased in vitro cytokine responses to non-related pathogens after Bacillus Calmette-Guérin (BCG) vaccination. A total of 158 infants (80 BCG administered within 7 days of birth; 78 controls) were bled 4 days post-randomization, and at age 3 and 13 months. Geometric mean concentrations of IL-1ß, TNF-α, IL-6 (24 h stimulation) and IFN-γ, IL-10, IL-17, IL-22 (96 h stimulation) in response to in vitro stimulation with RPMI, LPS, PHA, Escherichia coli, Streptococcus pneumoniae, Candida albicans and BCG were compared among BCG vaccinated children and controls. BCG vaccination did not affect in vitro cytokine production, except IFN-γ and IL-22 response to BCG. Stratifying for 'age at randomization' we found a potentiating effect of BCG on cytokine production (TNF-α, IL-6, IL-10) in the 4 days post randomization stimulations, among children who were vaccinated at age 2-7 days versus age 0-1 days. BCG vaccination did not potentiate cytokine production to non-BCG antigens. At 4 days post randomization, BCG was associated with higher cytokine production in the later randomized children.


Assuntos
Vacina BCG/imunologia , Citocinas/sangue , Mycobacterium bovis/imunologia , Vacina BCG/administração & dosagem , Candida albicans/imunologia , Escherichia coli/imunologia , Feminino , Humanos , Recém-Nascido , Masculino , Streptococcus pneumoniae/imunologia , Vacinação
11.
BMC Pregnancy Childbirth ; 17(1): 413, 2017 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-29221468

RESUMO

BACKGROUND: In a variety of animal species, hyperthermia in pregnancy has been recognized as teratogenic. Hyperthermia interferes with protein synthesis via heat-shock proteins, which can entail membrane disruption, cell death, vascular disruption, and placental infarction. This can induce severe fetal malformations or death. Fever during pregnancy, especially during embryogenesis, has also been associated with congenital malformations in human offspring. The purpose of this large cohort study of clinically recognized pregnancies was to investigate whether fever during first trimester was associated with an increased risk of congenital malformations in the offspring. METHODS: The Danish National Birth Cohort is a population-based cohort of 100,418 pregnant women and their offspring recruited in 1996 to 2002. Information on fever during pregnancy was collected prospectively by means of two telephone interviews. The study population comprised the 77,344 pregnancies enrolled in the Danish National Birth Cohort where self-reported information on fever during first trimester of pregnancy was available. Pregnancy outcomes were identified through linkage with the National Patient Registry. Congenital malformations within the first three and a half years of life were categorized according to EUROCAT's classification criteria. Logistic regression models were used to estimate the associations between fever in first trimester and overall congenital malformations and congenital malformations by subgroups. RESULTS: Eight thousand three hundred twenty-one women reported fever during first trimester (10.8%) and 2876 infants were diagnosed with a congenital malformation (3.7%). Fever during first trimester did not affect the risk of overall fetal congenital malformation (OR 0.99, 95% CI 0.88-1.12). The subgroup analyses indicated slightly higher risk of congenital anomalies in the eye, ear, face and neck (OR 1.29, 95% CI 0.78-2.12) and in the genitals (OR 1.17, 95% CI 0.79-1.12), whereas lower risk of malformations in the nervous system (OR 0.47, 95% CI 0.21-1.08), the respiratory system (OR 0.56, 95% CI 0.23-1.29) and in the urinary subgroup (OR 0.58, 95% CI 0.35-0.99) was suggested, the latter constituting the only statistically significant finding. CONCLUSIONS: Overall, this study did not show any association between maternal fever in pregnancy and risk of congenital anomalies.


Assuntos
Anormalidades Congênitas/etiologia , Febre/complicações , Complicações Infecciosas na Gravidez/etiologia , Primeiro Trimestre da Gravidez , Adulto , Dinamarca , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
12.
J Clin Monit Comput ; 31(6): 1159-1166, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27987104

RESUMO

Phenylephrine increases mean arterial pressure (MAP) by enhanced total peripheral resistance (TPR) but near-infrared spectroscopy (NIRS) determined muscle oxygenation (SmO2) increases. We addressed that apparent paradox during supine rest and head-up tilt (HUT). Variables were determined ± phenylephrine in males during supine rest (n = 17) and 40° HUT (n = 7). MAP, stroke volume (SV), heart rate (HR), and TPR were derived by Modelflow® and NIRS determined biceps SmO2 and (tibial) bone oxygenation (StibialO2). For ten subjects, cardiac filling and the diameter of the inferior caval vein (ICV collapsibility index: ((ICVexpiration - ICVinspiration)/ICVexpiration) × 100) were assessed by ultrasound. Pancreatic polypeptide (PP) and atrial natriuretic peptide (proANP) in plasma were determined by immunoassay. Brachial artery blood flow was assessed by ultrasound and skin oxygenation (SskinO2) monitored by white light spectroscopy. Phenylephrine increased MAP by 34% and TPR (62%; P < 0.001) during supine rest. The ICV collapsibility index decreased (24%; P < 0.001) indicating augmented cardiac preload although volume of the left atrium and ventricle did not change. SV increased (18%; P < 0.001) as HR decreased (24%; P < 0.001). ProANP increased by 9% (P = 0.002) with unaffected PP. Brachial artery blood flow tended to decrease while SskinO2 together with StibialO2 decreased by 11% (P = 0.026) and 20% (P < 0.001), respectively. Conversely, phenylephrine increased SmO2 (9%) and restored the HUT elicited decrease in SmO2 (by 19%) along with SV (P = 0.02). Phenylephrine reduces skin and bone oxygenation and tends to reduce arm blood flow, suggesting that the increase in SmO2 reflects veno-constriction with consequent centralization of the blood volume.


Assuntos
Músculo Esquelético/metabolismo , Consumo de Oxigênio , Fenilefrina/farmacologia , Pele/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho , Tíbia/metabolismo , Adulto , Fator Natriurético Atrial/sangue , Velocidade do Fluxo Sanguíneo , Volume Sanguíneo , Artéria Braquial , Frequência Cardíaca , Hemodinâmica , Humanos , Imunoensaio , Masculino , Oxigênio/metabolismo , Polipeptídeo Pancreático/sangue , Posicionamento do Paciente , Decúbito Dorsal , Adulto Jovem
14.
Intensive Care Med ; 41(5): 856-64, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25800582

RESUMO

PURPOSE: To investigate whether early coronary angiography (CAG) after out-of-hospital cardiac arrest of a presumed cardiac cause is associated with improved outcomes in patients without acute ST elevation. METHODS: The target temperature management after out-of-hospital cardiac arrest (TTM) trial showed no difference in all-cause mortality or neurological outcome between an intervention of 33 and 36 °C. In this post hoc analysis, 544 patients where the admission electrocardiogram did not show acute ST elevation were included. Early CAG was defined as being performed on admission or within the first 6 h after arrest. Primary outcome was mortality at the end of trial. A Cox proportional hazard model was created to estimate hazard of death, adjusting for covariates. In addition, a propensity score matched analysis was performed. RESULTS: A total of 252 patients (46 %) received early CAG, whereas 292 (54 %) did not. At the end of the trial, 122 of 252 patients who received an early CAG (48 %) and 159 of 292 patients who did not (54 %) had died. The adjusted hazard ratio for death was 1.03 in the group that received an early CAG; 95 % CI 0.80-1.32, p = 0.82. In the propensity score analysis early CAG was not significantly associated with survival. CONCLUSIONS: In this post hoc observational study of a large randomized trial, early coronary angiography for patients without acute ST elevation after out-of-hospital cardiac arrest of a presumed cardiac cause was not associated with improved survival. A randomized trial is warranted to guide clinical practice.


Assuntos
Temperatura Corporal , Angiografia Coronária , Trombose Coronária/complicações , Parada Cardíaca Extra-Hospitalar/diagnóstico por imagem , Parada Cardíaca Extra-Hospitalar/terapia , Idoso , Austrália/epidemiologia , Diagnóstico Precoce , Europa (Continente)/epidemiologia , Feminino , Humanos , Hipotensão Controlada , Masculino , Pessoa de Meia-Idade , Razão de Chances , Parada Cardíaca Extra-Hospitalar/epidemiologia , Parada Cardíaca Extra-Hospitalar/mortalidade , Sobrevida
15.
Hernia ; 14(4): 351-5, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20396920

RESUMO

PURPOSE: The mortality following emergency groin hernia repair in Denmark is more than twice as high (7%) as in comparable countries. This article describes in detail the population that died following emergency herniotomy in order to identify aspects of care that may improve outcome. METHODS: Patients > or =18 years of age who died within 30 days following emergency hernia surgery from June 2003 through June 2008 were identified using the Danish Hernia Database (DHDB) and the Danish National Hospital Registry (n = 158). In total, 156 records were collected and reviewed. RESULTS: The median age of the patients was 83 years (range 54-97) and 80% had co-morbidity. There was an almost equal distribution of men and women and inguinal and femoral hernias. More than 60% of the patients with a hernia upon admission had symptoms lasting > or =48 h prior to admission and 41% were not examined for hernia at admission and had delayed diagnosis. Only 23% underwent surgery within 8 h of admission and 35% of the patients were admitted to a medical or non-abdominal surgical ward. Laparotomy and bowel resections were frequent (53.1 and 49.2%, respectively). CONCLUSION: Delay to admission, diagnosis and surgery are common in patients undergoing emergency groin hernia surgery in Denmark. Patients admitted with acute abdominal symptoms should be examined for a hernia and operated on soon after admission.


Assuntos
Abdome Agudo/etiologia , Herniorrafia , Procedimentos Cirúrgicos Operatórios/mortalidade , Idoso , Idoso de 80 Anos ou mais , Bases de Dados como Assunto , Dinamarca/epidemiologia , Emergências , Feminino , Virilha , Hérnia/complicações , Hérnia/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade
16.
Br J Pharmacol ; 156(2): 297-306, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19076726

RESUMO

BACKGROUND AND PURPOSE: The increased levels of extracellular adenosine in inflamed tissues down-regulate activated immune cells via the A(2A) adenosine receptor. This A(2A) adenosine receptor-mediated immunosuppression is a disqualifying obstacle in cancer immunotherapy as it protects cancerous tissues from adoptively transferred anti-tumour T cells. The aim of this study was to test whether the negative selection of T cells will produce T cells that are resistant to inhibition by extracellular adenosine. EXPERIMENTAL APPROACH: Cytotoxic T lymphocytes (CTL) were developed by mixed lymphocyte culture in the presence or absence of the adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA). The sensitivity of CTL to adenosine analogues was characterized by cAMP induction, interferon-gamma production and cytotoxicity. KEY RESULTS: CTL that could proliferate even in the presence of NECA were less susceptible to inhibition by A(2A) adenosine receptor agonists, as shown by a much smaller accumulation of cAMP and less inhibition of interferon-gamma production compared with control CTL. The successful protocol to produce CTL that are both resistant to adenosine-mediated immunosuppression and maintain strong cytotoxicity and interferon-gamma secretion required NECA to be added only during the expansion stage after the establishment of CTL. In contrast, the priming of resting T cells in the presence of NECA resulted in T cells with impaired effector functions. CONCLUSIONS AND IMPLICATIONS: Adenosine-resistant effector T cells were successfully obtained by exposure of activated T cells to NECA. These in vitro studies form the basis for future attempts to produce anti-tumour T cells that are more effective in adoptive immunotherapy.


Assuntos
Tolerância Imunológica , Receptor A2A de Adenosina/fisiologia , Receptor A2B de Adenosina/fisiologia , Linfócitos T Citotóxicos/citologia , Adenosina/metabolismo , Agonistas do Receptor A2 de Adenosina , Adenosina-5'-(N-etilcarboxamida)/farmacologia , Animais , Linhagem Celular Tumoral , AMP Cíclico/biossíntese , Citotoxicidade Imunológica , Espaço Extracelular/metabolismo , Tolerância Imunológica/efeitos dos fármacos , Interferon gama/biossíntese , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia
17.
J Intern Med ; 264(4): 361-9, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18537871

RESUMO

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is an important differential diagnosis in patients with heart failure (HF). The primary aims were to determine the prevalence of COPD and to test the accuracy of self-reported COPD in patients admitted with HF. Secondary aims were to study a possible relationship between right and left ventricular function and pulmonary function. DESIGN: Prospective substudy. SETTING: Systematic screening at 11 centres. SUBJECTS: Consecutive patients (n = 532) admitted with HF requiring medical treatment with diuretics and an episode with symptoms corresponding to New York Heart Association class III-IV within a month prior to admission. INTERVENTIONS: Forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC) were measured by spirometry and ventricular function by echocardiography. The diagnosis of COPD and HF were made according to established criteria. RESULTS: The prevalence of COPD was 35%. Only 43% of the patients with COPD had self-reported COPD and one-third of patients with self-reported COPD did not have COPD based on spirometry. The prevalence of COPD in patients with preserved left ventricular ejection fraction (i.e. LVEF >or=45%) was significantly higher than in patients with impaired LVEF (41% vs. 31%, P = 0.03). FEV(1) and FVC were negatively correlated with right ventricular end-diastolic diameter and tricuspid annular plane systolic excursion and FVC positively correlated with systolic gradient across the tricuspid valve. CONCLUSION: Chronic obstructive pulmonary disease is frequent in patients admitted with HF and self-reported COPD only identifies a minority. The prevalence of COPD was high in both patients with systolic and nonsystolic HF.


Assuntos
Insuficiência Cardíaca/complicações , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Idoso , Ecocardiografia , Feminino , Humanos , Modelos Logísticos , Masculino , Prevalência , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Testes de Função Respiratória , Sensibilidade e Especificidade , Espirometria
18.
Int J Sports Med ; 29(6): 507-11, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18574873

RESUMO

Injury to the infrapatellar branch of the saphenous nerve (IPBSN), is known to cause regional hypoesthesia of the lower leg after anterior cruciate ligament (ACL) reconstruction. The aim of this study was to determine if the orientation of the graft harvest incision does influence the prevalence of postoperative hypoesthesia. Furthermore,to describe change, if any, of the hypoesthetic area, during the first postoperative year. Our hypothesis was that an oblique incision parallel to the nerve branch would reduce the incidence of this complication and the area with hypoesthesia after ACL reconstruction, compared to the vertical incision. Secondly, that the area with hypoesthesia is reduced over time. Fifty patients underwent a primary ACL reconstruction using hamstring graft. Twenty-five patients were operated using a vertical incision for graft harvest,and 25 were operated using a slightly oblique incision. Twelve days after surgery and at a one year follow-up the patients had their sensibility of the lower leg examined. We found that hypoesthesia is a common complication (88%) after hamstring ACL surgery. Change from vertical to slightly oblique incision did not reduce the morbidity.Furthermore, the area with sensory loss,felt by the patient shortly after surgery, was shown to decrease significantly by 46.3 percent after one year.


Assuntos
Ligamento Cruzado Anterior/cirurgia , Hipestesia/etiologia , Perna (Membro)/inervação , Músculo Esquelético/inervação , Traumatismos dos Nervos Periféricos , Procedimentos de Cirurgia Plástica/efeitos adversos , Transtornos de Sensação/etiologia , Coxa da Perna/inervação , Adolescente , Adulto , Feminino , Humanos , Incidência , Masculino , Complicações Pós-Operatórias , Fatores de Risco
19.
Acta Anaesthesiol Scand ; 51(1): 74-81, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17229231

RESUMO

BACKGROUND: In a previous study, we showed that sustained pulmonary hyperinflation, i.e. a lung recruitment maneuver, after closure of the chest in patients undergoing cardiac surgery had significantly negative effects on the central hemodynamics. As elevated pleural pressure is believed to be a major cause of this cardiovascular impairment, we hypothesized that performing the sustained pulmonary hyperinflation under open chest conditions would affect the circulation less. METHODS: Patients undergoing cardiac by-pass surgery were included and sustained pulmonary hyperinflations (40 cmH(2)O airway pressure for 15 s) were performed immediately before and after closure of the sternum. Pulse contour cardiac output, heart rate, mean arterial pressure and pulse pressure variation were measured before, during and 1 min after the hyperinflations. Left ventricular dimensions were measured using trans-esophageal echocardiography. RESULTS: Cardiac output (CO) and mean arterial blood pressure (MAP) decreased significantly during the sustained pulmonary hyperinflation both with an open and closed chest (in parenthesis): CO by 50 (45)% and MAP by 19 (24)%. The left ventricular end-diastolic area was significantly reduced by 24 (33)%. One minute after the hyperinflation, all measured variables had returned to baseline values. No significant differences in the measured variables were found between the two conditions before, during or 1 min after the hyperinflation. CONCLUSION: Contrary to our hypothesis, sustained pulmonary hyperinflations with the chest open, i.e. before sternal closure, had similar negative effects on central hemodynamics as those performed with the chest closed, i.e. after sternal closure.


Assuntos
Fenômenos Fisiológicos Cardiovasculares , Ponte de Artéria Coronária , Pulmão/fisiologia , Esterno/cirurgia , Idoso , Pressão Sanguínea , Débito Cardíaco , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Função Ventricular Esquerda
20.
Scand J Clin Lab Invest ; 66(8): 647-57, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17101557

RESUMO

OBJECTIVE: Increased left ventricular mass (LVM) and presence of left ventricular hypertrophy (LVH) are predictors of cardiovascular morbidity and mortality, but can be reversed with proper treatment of the underlying cause. Therefore accurate as well as reproducible methods for diagnosis and follow-up are needed. We evaluated different modalities by which to measure LVM in patients with no known LVH using magnetic resonance imaging (MRI) as the gold standard: ECG using the formulae proposed by Sokolow-Lyon and Cornell, 2D echocardiography and 3D echocardiography. METHODS: 34 subjects were included in the study; 17 had a history of myocardial infarction, 7 had pulmonary hypertension and 10 were healthy. All patients and controls had a standard 12-lead ECG, a transthoracic 2D and 3D echocardiographic study and a cardiac MRI. RESULTS: ECG estimates of LVM correlated poorly with LVM by MRI (r = 0.18, NS and 0.16, NS for Sokolow-Lyon and Cornell, respectively), whereas a moderate correlation between 2D and 3D echocardiography and MRI was observed (r = 0.63, p<0.001 and r = 0.74, p<0.001, respectively). All methods were reproducible with no significant bias. CONCLUSION: LVM measured by 3D echocardiography is highly accurate compared to LVM measured by MRI. LVM calculated from 2D echocardiography also proved useful, whereas estimates of LVM by ECG are inaccurate in a non-hypertrophic population.


Assuntos
Ecocardiografia Tridimensional , Hipertensão Pulmonar/diagnóstico , Hipertrofia Ventricular Esquerda/diagnóstico , Imageamento por Ressonância Magnética , Infarto do Miocárdio/diagnóstico , Idoso , Feminino , Humanos , Masculino , Valores de Referência , Reprodutibilidade dos Testes
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