RESUMO
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with enhanced NETosis and impaired degradation of neutrophil extracellular traps (NETs). Galectin-3 is a ß-galactoside binding protein and is associated with neutrophil functions as well as involved in mediating autoimmune disorders. In this study, we plan to examine the associations of galectin-3 with the pathogenesis of SLE and NETosis. Galectin-3 expression levels were determined in peripheral blood mononuclear cells (PBMCs) of SLE patients for the association with lupus nephritis (LN) or correlation of SLE disease activity index 2000 (SLEDAI-2K). NETosis was observed in human normal and SLE and murine galectin-3 knockout (Gal-3 KO) neutrophils. Gal-3 KO and wild-type (WT) mice induced by pristane were used to evaluate disease signs, including diffuse alveolar haemorrhage (DAH), LN, proteinuria, anti-ribonucleoprotein (RNP) antibody, citrullinated histone 3 (CitH3) levels, and NETosis. Galectin-3 levels are higher in PBMCs of SLE patients compared with normal donors and positively correlated with LN or SLEDAI-2K. Gal-3 KO mice have higher percent survival and lower DAH, LN proteinuria, and anti-RNP antibody levels than WT mice induced by pristane. NETosis and citH3 levels are reduced in Gal-3 KO neutrophils. Furthermore, galectin-3 resides in NETs while human neutrophils undergo NETosis. Galectin-3-associated immune complex deposition can be observed in NETs from spontaneously NETotic cells of SLE patients. In this study, we provide clinical relevance of galectin-3 to the lupus phenotypes and the underlying mechanisms of galectin-3-mediated NETosis for developing novel therapeutic strategies targeting galectin-3 for SLE.
Assuntos
Armadilhas Extracelulares , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Animais , Humanos , Camundongos , Autoantígenos/metabolismo , Armadilhas Extracelulares/metabolismo , Galectina 3/metabolismo , Hemorragia/metabolismo , Leucócitos Mononucleares/metabolismo , Nefrite Lúpica/patologia , Neutrófilos/metabolismo , Proteinúria/metabolismoRESUMO
BACKGROUND: Cardiovascular waveforms contain information for clinical diagnosis. By learning and organizing the subtle change of waveform morphology from large amounts of raw waveform data, unsupervised manifold learning helps delineate a high-dimensional structure and display it as a novel 3-dimensional (3D) image. We hypothesize that the shape of this structure conveys clinically relevant inner dynamics information. METHODS: To validate this hypothesis, we investigate the electrocardiography (ECG) waveform for ischemic heart disease and arterial blood pressure (ABP) waveform in dynamic vasoactive episodes. We model each beat or pulse to be a point lying on a manifold-like a surface-and use the diffusion map (DMap) to establish the relationship among those pulses. The output of the DMap is converted to a 3D image for visualization. For ECG datasets, first we analyzed the non-ST-elevation ECG waveform distribution from unstable angina to healthy control in the 3D image, and we investigated intraoperative ST-elevation ECG waveforms to show the dynamic ECG waveform changes. For ABP datasets, we analyzed waveforms collected under endotracheal intubation and administration of vasodilator. To quantify the dynamic separation, we applied the support vector machine (SVM) analysis and reported the total accuracy and macro-F1 score. We further performed the trajectory analysis and derived the moving direction of successive beats (or pulses) as vectors in the high-dimensional space. RESULTS: For the non-ST-elevation ECG, a hierarchical tree structure comprising consecutive ECG waveforms spanning from unstable angina to healthy control is presented in the 3D image (accuracy = 97.6%, macro-F1 = 96.1%). The DMap helps quantify and visualize the evolving direction of intraoperative ST-elevation myocardial episode in a 1-hour period (accuracy = 97.58%, macro-F1 = 96.06%). The ABP waveform analysis of Nicardipine administration shows interindividual difference (accuracy = 95.01%, macro-F1 = 96.9%) and their common directions from intraindividual moving trajectories. The dynamic change of the ABP waveform during endotracheal intubation shows a loop-like trajectory structure, which can be further divided using the manifold learning knowledge obtained from Nicardipine. CONCLUSIONS: The DMap and the generated 3D image of ECG or ABP waveforms provides clinically relevant inner dynamics information. It provides clues of acute coronary syndrome diagnosis, shows clinical course in myocardial ischemic episode, and reveals underneath physiological mechanism under stress or vasodilators.
Assuntos
Bases de Dados Factuais , Eletrocardiografia/métodos , Frequência Cardíaca/fisiologia , Imageamento Tridimensional/métodos , Aprendizado de Máquina não Supervisionado , Análise de Ondaletas , Humanos , Processamento de Sinais Assistido por ComputadorRESUMO
Most surgical procedures involve structures deeper than the skin. However, the difference in surgical noxious stimulation between skin incision and laparoscopic trocar insertion is unknown. By analyzing instantaneous heart rate (IHR) calculated from the electrocardiogram, in particular the transient bradycardia in response to surgical stimuli, this study investigates surgical noxious stimuli arising from skin incision and laparoscopic trocar insertion, and their difference. Thirty-five patients undergoing laparoscopic cholecystectomy were enrolled in this prospective observational study. Sequential surgical steps including umbilical skin incision (11 mm), umbilical trocar insertion (11 mm), xiphoid skin incision (5 mm), xiphoid trocar insertion (5 mm), subcostal skin incision (3 mm), and subcostal trocar insertion (3 mm) were investigated. IHR was derived from electrocardiography and calculated by the modern time-varying power spectrum. Similar to the classical heart rate variability analysis, the time-varying low frequency power (tvLF), time-varying high frequency power (tvHF), and tvLF-to-tvHF ratio (tvLHR) were calculated. Prediction probability (PK) analysis and global pointwise F-test were used to compare the statistical performance between indices and the heart rate readings from the patient monitor. Analysis of IHR showed that surgical stimulus elicits a transient bradycardia, followed by the increase of heart rate. Transient bradycardia is more significant in trocar insertion than skin incision (p < 0.001 for tvHF). The IHR change quantifies differential responses to different surgical intensity. Serial PK analysis demonstrates de-sensitization in skin incision, but not in laparoscopic trocar insertion. Quantitative indices present the transient bradycardia introduced by noxious stimulation. The results indicate different effects between skin incision and trocar insertion.
Assuntos
Bradicardia/diagnóstico , Colecistectomia/instrumentação , Eletrocardiografia/instrumentação , Laparoscopia/instrumentação , Pele/patologia , Instrumentos Cirúrgicos , Ferida Cirúrgica , Adulto , Idoso , Colecistectomia/métodos , Eletrocardiografia/métodos , Feminino , Frequência Cardíaca , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Probabilidade , Estudos Prospectivos , Resultado do TratamentoRESUMO
Inhaled anesthetics, such as isoflurane, may cause side effects, including short-term immunosuppression and DNA damage. In contrast, low molecular weight fucoidan (LMF), derived from brown seaweed, exhibits promising immunomodulatory effects. In this study, we determined the effect of isoflurane on telomeres and examined the potential of LMF to ameliorate the harmful effects of isoflurane. Male Lewis rats, the mouse lymphoma cell line YAC-1, and the human nature killer cell line NK-92 MI were exposed to isoflurane. The relative telomere length (T/S) ratio and mRNA expression were determined by quantitative PCR. The viability assay was used to assess cell viability. In vivo, 2% isoflurane exposure, which is a clinically relevant concentration, reduced telomere length, and correlated with exposure frequency and duration. Isoflurane concentrations above 2% shortened YAC-1 telomeres, with minimal impact on cell viability. LMF pre-treatment enhanced NK-92 MI cell survival resulting from isoflurane exposure and exerted superior telomere protection compared with LMF post-treatment. Furthermore, adding LMF during isoflurane exposure resulted in a significant increase in IFN-γ, TNF-α, and IL-10 mRNA compared with the untreated group. LMF protected against isoflurane-induced telomere shortening, enhanced NK cell viability, and modulated cytokine expression, thus mitigating postoperative immune suppression and risk of tumor metastasis.
Assuntos
Isoflurano , Células Matadoras Naturais , Polissacarídeos , Animais , Polissacarídeos/farmacologia , Isoflurano/farmacologia , Isoflurano/toxicidade , Camundongos , Masculino , Humanos , Ratos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Anestésicos Inalatórios/toxicidade , Anestésicos Inalatórios/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Telômero/efeitos dos fármacos , Ratos Endogâmicos Lew , Peso Molecular , Linhagem Celular Tumoral , Homeostase do Telômero/efeitos dos fármacosRESUMO
Pneumomediastinum is the presence of air within the mediastinum. It is usually caused by a respiratory tract disorder, esophageal erosion, bowel perforation, or gastrointestinal tract endoscopic procedure. Pneumomediastinum following urological endoscopic surgery is very uncommon. Here, we report an unusual case of pneumomediastinum in a 55-year-old female following percutaneous nephrolithotomy for renal and ureteral stones. The patient recovered well with supportive treatment with oxygen.
RESUMO
Peripheral infusion of intravenous agents is a daily routine in hospitals. Extravasation is an unintended complication associated with intravenous infusion where accidental injection or leakage of fluid occurs into the perivascular or subcutaneous space. Extravasation is fairly common but is usually without serious consequences. This has led clinicians to underestimate the potentially serious consequences of extravasation. Extravasation injury results from a combination of factors, including cytotoxicity of the solution, osmolality, vasoconstrictor effects, infusion pressure and other factors. We describe a case of upper extremity localised bullous eruptions resulting from the pressurised infusion of crystalloid solutions through an intravenous catheter, placed in the operating room during left ventricular device-assisted surgery. Peri-operative management of acute localised bullous eruptions requires surveillance for unforeseen consequences. Early recognition, diagnosis and intervention averted potential complications and morbidity.
Assuntos
Vesícula/etiologia , Cardiomiopatia Dilatada/terapia , Extravasamento de Materiais Terapêuticos e Diagnósticos/etiologia , Hidratação/efeitos adversos , Coração Auxiliar , Implantação de Prótese , Cloreto de Sódio/efeitos adversos , Extremidade Superior/irrigação sanguínea , Vesícula/diagnóstico , Vesícula/terapia , Extravasamento de Materiais Terapêuticos e Diagnósticos/diagnóstico , Extravasamento de Materiais Terapêuticos e Diagnósticos/terapia , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Cloreto de Sódio/administração & dosagemRESUMO
Acute aortic dissection is not common but usually presents with a severe, sharp chest pain and high blood pressure. Widening of the mediastinum is usually also evident on chest X-ray. Although acute onset of severe chest or back pain is the most common presenting symptom, some patients may present with atypical symptoms and signs. Establishing a diagnosis of aortic dissection can be difficult in the presence of atypical symptoms, especially in the absence of pain. Such presentation of aortic dissection is easily ignored. We report a case of painless aortic dissection with normal blood pressure, which resulted in acute isolated lower limb ischaemia at presentation. Atypical presentation of isolated limb arterial occlusions in an older patient without the classic symptoms are seldom reported as aortic dissection. However, aortic dissection should be included in the differential diagnosis of patients with arterial occlusive disease without chest pain and with normal blood pressure.
Assuntos
Aneurisma da Aorta Torácica/diagnóstico , Dissecção Aórtica/diagnóstico , Isquemia/diagnóstico , Perna (Membro)/irrigação sanguínea , Dissecção Aórtica/complicações , Aneurisma da Aorta Torácica/complicações , Diagnóstico Diferencial , Humanos , Isquemia/etiologia , Masculino , Pessoa de Meia-Idade , Exame Físico , Radiografia Torácica , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: This study observed midterm results of vascular ring connectors in surgery for aortic dissection. METHODS: Vascular ring connectors were used as stents in vascular grafts to achieve quick, sutureless anastomoses. Tapes were used to secure ringed vascular grafts from outside the aorta. RESULTS: From November 2007 to February 2011, 113 consecutive patients with aortic dissection, except 3 in preoperative profound shock, underwent open surgery. All underwent aortic reconstruction with vascular grafts and vascular ring connectors: ascending aorta in 29, descending thoracic aorta in 20, distal hemiarch plus descending thoracic aorta in 22, total arch in 14, ascending aorta plus total arch in 12, total arch plus descending thoracic aorta in 7, ascending aorta plus arch plus descending thoracic aorta in 8, and thoracoabdominal aorta in 1. Concomitant operations were 19 Bentall procedures, 14 coronary bypasses, 2 mitral valve replacements, 1 aortic valve replacement, and 1 heart transplant. We used sternotomy to repair 77% of type B dissections, 83% with elephant trunks. Time to extubation was 9.0 ± 6.2 hours. Average blood loss was 345 ± 195 mL. Half the patients needed no blood transfusion. In-hospital mortality was 5.3%; late mortality was 2.7%. CONCLUSIONS: Use of vascular ring connectors in surgical repair for aortic dissection might reduce risks and improve early and midterm results. With addition of elephant trunk, most type B dissections could be repaired through sternotomy. With the improved surgical results, we can suggest open repair for most uncomplicated type B dissections; however, more long-term follow-up is needed.
Assuntos
Aorta Torácica , Doenças da Aorta/cirurgia , Implante de Prótese Vascular/métodos , Stents , Adulto , Idoso , Implante de Prótese Vascular/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do TratamentoRESUMO
A 36-year-old male had spontaneous intracranial hypotension (SIH) presenting with refractory headache for 4 months. Multiple epidural blood patches (EBPs) yielded relief of symptoms, but the course was complicated, with asymptomatic intracranial subdural hematoma (SDH). Except for SDH, other radiological diagnostic signs of SIH were resolved and the patient's headaches improved after EBP. Owing to a mass effect and persistent cerebrospinal fluid (CSF) leakage, surgical repair of the spinal leakage was performed, but no cranial procedures were carried out. Postoperatively, the SDH completely resolved, but there was still CSF leakage at the level where surgery was performed. The patient has remained free of headache or other events for 3 years. It was reduction rather than elimination of the spinal CSF leak that yielded remission of SIH. In summary, intracranial SDH can be a complication of inadequately treated SIH (i.e. persistent minor CSF leakage). Management of SDH should focus on correction of the underlying SIH rather than craniotomy for hematoma evacuation.
Assuntos
Placa de Sangue Epidural , Hematoma Subdural Intracraniano/complicações , Hipotensão Intracraniana/complicações , Adulto , Humanos , Hipotensão Intracraniana/terapia , MasculinoRESUMO
Methylphenidate, a central stimulant, is used in the treatment of individuals who have attention-deficit hyperactivity disorder (ADHD). ADHD is a notorious worldwide disorder with a prevalence rate of 8-12% in schoolchildren, which is characterized by hyperactivity, impulsivity, and inattention. Currently, there have been few reports in the anesthetic literature examining ADHD patients who have had long-term use of methylphenidate, especially the extended-release formulation. Here, we report a case of a 14-year-old boy with ADHD treated chronically with the long-acting form of methylphenidate (Concerta), and who was scheduled to receive orthopedic surgery under general anesthesia. No significant problems or fluctuations in hemodynamics were encountered during anesthesia induction, maintenance, and emergence. The patient made an uncomplicated recovery and was discharged 3 days later without incident.
Assuntos
Anestesia Geral , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Metilfenidato/uso terapêutico , Interações Medicamentosas , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Biting the laryngeal mask airway during general anesthesia in the absence of a bite block as a forestallment is a common but usually uncomplicated event. We report a young healthy adult female patient who underwent removal of fixation implant in the right elbow under general anesthesia, during the emergence of which she bit and severed the airway tube of the laryngeal mask airway (LMA) after cuff deflation and developed upper airway obstruction in consequence of air blockade by the displaced deflated LMA cuff remaining inside the mouth. Removal of residual part of the LMA in the mouth was successful with propofol re-anesthetization without molestation of 02 saturation. We discuss the management of this critical airway condition resulting from fracture of deflated LMA in the closed mouth.