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1.
J Med Virol ; 95(8): e29010, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37537755

RESUMO

The aim of this study is to investigate the effectiveness of prolonged versus standard course oseltamivir treatment among critically ill patients with severe influenza. A retrospective study of a prospectively collected database including adults with influenza infection admitted to 184 intensive care units (ICUs) in Spain from 2009 to 2018. Prolonged oseltamivir was defined if patients received the treatment beyond 5 days, whereas the standard-course group received oseltamivir for 5 days. The primary outcome was all-cause ICU mortality. Propensity score matching (PSM) was constructed, and the outcome was investigated through Cox regression and RCSs. Two thousand three hundred and ninety-seven subjects were included, of whom 1943 (81.1%) received prolonged oseltamivir and 454 (18.9%) received standard treatment. An optimal full matching algorithm was performed by matching 2171 patients, 1750 treated in the prolonged oseltamivir group and 421 controls in the standard oseltamivir group. After PSM, 387 (22.1%) patients in the prolonged oseltamivir and 119 (28.3%) patients in the standard group died (p = 0.009). After adjusting confounding factors, prolonged oseltamivir significantly reduced ICU mortality (odds ratio [OR]: 0.53, 95% confidence interval [CI]: 0.40-0.69). Prolonged oseltamivir may have protective effects on survival at Day 10 compared with a standard treatment course. Sensitivity analysis confirmed these findings. Compared with standard treatment, prolonged oseltamivir was associated with reduced ICU mortality in critically ill patients with severe influenza. Clinicians should consider extending the oseltamivir treatment duration to 10 days, particularly in higher-risk groups of prolonged viral shedding. Further randomized controlled trials are warranted to confirm these findings.


Assuntos
Influenza Humana , Oseltamivir , Adulto , Humanos , Oseltamivir/uso terapêutico , Influenza Humana/tratamento farmacológico , Antivirais/uso terapêutico , Estudos Retrospectivos , Estado Terminal
2.
Am J Physiol Regul Integr Comp Physiol ; 317(6): R814-R817, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31596107

RESUMO

In our present studies, we seek to determine whether increased osmolarity stimulates deflation-activated receptors (DARs). In anesthetized, open-chest, and mechanically ventilated rabbits, we recorded single-unit activities from typical slowly adapting receptors (SARs; responding only to lung inflation) and DAR-containing SARs (DAR-SARs; responding to both lung inflation and deflation) and identified their receptive fields in the lung. We examined responses of these two groups of pulmonary sensory units to direct injection of hypertonic saline (8.1% sodium chloride; 9-fold in tonicity) into the receptive fields. Hypertonic saline decreased the activity in most SAR units from 40.3 ± 5.4 to 34.8 ± 4.7 imp/s (P < 0.05, n = 12). In contrast, it increased the activity in DAR-SAR units quickly and significantly from 15.9 ± 2.2 to 43.4 ± 10.0 imp/s (P < 0.01, n = 10). Many units initially had increased activity, mainly in the deflation phase. DAR-SAR activities largely returned to the control level 30 s after injection. Since hypertonic saline stimulated DAR-SAR units but not SAR units, we conclude that hypertonic saline activates DARs.


Assuntos
Pulmão/fisiologia , Receptores Pulmonares de Alongamento/fisiologia , Solução Salina Hipertônica/farmacologia , Nervo Vago/efeitos dos fármacos , Animais , Masculino , Coelhos , Respiração
3.
Diabetologia ; 59(9): 1985-94, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27344312

RESUMO

AIMS/HYPOTHESIS: In mammals, the evolutionary conserved family of Mg(2+)-dependent phosphatidate phosphatases (PAP1), involved in phospholipid and triacylglycerol synthesis, consists of lipin-1, lipin-2 and lipin-3. While mutations in the murine Lpin1 gene cause lipodystrophy and its knockdown in mouse 3T3-L1 cells impairs adipogenesis, deleterious mutations of human LPIN1 do not affect adipose tissue distribution. However, reduced LPIN1 and PAP1 activity has been described in participants with type 2 diabetes. We aimed to characterise the roles of all lipin family members in human adipose tissue and adipogenesis. METHODS: The expression of the lipin family was analysed in adipose tissue in a cross-sectional study. Moreover, the effects of lipin small interfering RNA (siRNA)-mediated depletion on in vitro human adipogenesis were assessed. RESULTS: Adipose tissue gene expression of the lipin family is altered in type 2 diabetes. Depletion of every lipin family member in a human Simpson-Golabi-Behmel syndrome (SGBS) pre-adipocyte cell line, alters expression levels of adipogenic transcription factors and lipid biosynthesis genes in early stages of differentiation. Lipin-1 knockdown alone causes a 95% depletion of PAP1 activity. Despite the reduced PAP1 activity and alterations in early adipogenesis, lipin-silenced cells differentiate and accumulate neutral lipids. Even combinatorial knockdown of lipins shows mild effects on triacylglycerol accumulation in mature adipocytes. CONCLUSIONS/INTERPRETATION: Overall, our data support the hypothesis of alternative pathways for triacylglycerol synthesis in human adipocytes under conditions of repressed lipin expression. We propose that induction of alternative lipid phosphate phosphatases, along with the inhibition of lipid hydrolysis, contributes to the maintenance of triacylglycerol content to near normal levels.


Assuntos
Adipócitos/metabolismo , Fosfatidato Fosfatase/metabolismo , Triglicerídeos/metabolismo , Células 3T3-L1 , Adipogenia/genética , Adipogenia/fisiologia , Tecido Adiposo/metabolismo , Animais , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Células Cultivadas , Estudos Transversais , Feminino , Humanos , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Metabolismo dos Lipídeos/genética , Metabolismo dos Lipídeos/fisiologia , Lipodistrofia/genética , Lipodistrofia/metabolismo , Masculino , Camundongos , Proteínas Associadas a Pancreatite , Fosfatidato Fosfatase/genética , RNA Interferente Pequeno/genética
4.
Am J Emerg Med ; 34(12): 2402-2407, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27793503

RESUMO

BACKGROUND: It is unclear whether anteroposterior (AP) or posteroanterior with lateral (PA/Lat) chest radiographs are superior in the early detection of clinically relevant parapneumonic effusions (CR-PPEs). The objective of this study was to identify which technique is preferred for detection of PPEs using chest computed tomography (CCT) as a reference standard. METHODS: A secondary analysis of a pneumonia database was conducted to identify patients who received a CCT within 24 hours of presentation and also received AP or PA/Lat chest radiographs within 24 hours of CCT. Sensitivity and specificity were then calculated by comparing the radiographic diagnosis of PPEs of both types of radiographs compared with CCT by using the existing attending radiologist interpretation. Clinical relevance of effusions was determined by CCT effusion measurement of >2.5 cm or presence of loculation. RESULTS: There was a statistically significant difference between the sensitivity of AP (67.3%) and PA/Lat (83.9%) chest radiography for the initial detection of CR-PPE. Of 16 CR-PPEs initially missed by AP radiography, 7 either required drainage initially or developed empyema within 30 days, whereas no complicated PPE or empyema was found in those missed by PA/Lat radiography. CONCLUSIONS: PA/Lat chest radiography should be the initial imaging of choice in pneumonia patients for detection of PPEs because it appears to be statistically superior to AP chest radiography.


Assuntos
Derrame Pleural/diagnóstico por imagem , Pneumonia/complicações , Radiografia Torácica/métodos , Tórax/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Bases de Dados Factuais , Drenagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X
5.
J Emerg Med ; 49(3): 318-25, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26113379

RESUMO

BACKGROUND: The predictive role of lactate in critically ill patients with acute upper gastrointestinal bleeding (UGIB) remains to be elucidated. OBJECTIVE: The primary objective of this study was to assess the value of lactate level on admission to predict in-hospital death in patients with UGIB admitted to the intensive care unit (ICU). The secondary objective was to assess whether lactate level adds predictive value to the clinical Rockall score in these patients. METHODS: This was a retrospective cohort study that included 133 patients with acute UGIB admitted to the ICU. Inclusion criteria were age > 18 years and presence of UGIB on admission to the ICU. RESULTS: Mean age was 55.4 years old and 64.7% were male. The most common cause of gastrointestinal bleeding was peptic ulcer disease, followed by erosive esophagitis/gastritis. The in-hospital mortality was 22.6%. Median lactate level in survivors and nonsurvivors was 2.0 (interquartile range [IQR] 1.2-4.2 mmol/L) and 8.8 (IQR 3.4-13.3 mmol/L; p < 0.01), respectively. The receiver operating characteristic (ROC) area to predict in-hospital death for clinical Rockall score and lactate level (0.82) was significantly higher than the ROC area for the clinical Rockall score alone (0.69) (p < 0.01). CONCLUSIONS: In patients admitted to the ICU with acute UGIB, lactate level on admission has a high sensitivity but low specificity for predicting in-hospital death. Lactate level adds to the predictive value of the clinical Rockall score. Given its high sensitivity, lactate level can be used in addition to other prediction tools to predict outcomes in patients with UGIB.


Assuntos
Estado Terminal , Hemorragia Gastrointestinal/sangue , Hemorragia Gastrointestinal/mortalidade , Mortalidade Hospitalar , Lactatos/sangue , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade
6.
Respiration ; 88(4): 339-44, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25171767

RESUMO

BACKGROUND: Positive end-expiratory pressure (PEEP) is commonly used in clinical settings. It is expected to affect the input from slowly adapting pulmonary stretch receptors (SARs), leading to altered cardiopulmonary functions. However, we know little about how SARs behave during PEEP application. OBJECTIVES: Our study aimed to characterize the behavior of SARs during PEEP application. METHODS: We recorded single-unit activities from 18 SARs in the cervical vagus nerve and examined their response to an increase of PEEP from 3 to 10 cm H2O for 20 min in anesthetized, open-chest and mechanically ventilated rabbits. RESULTS: The mean activity of the units increased immediately from 35.7 to 80.5 impulses per second at the fifth breath after increasing PEEP (n = 14, p < 0.001) and then gradually returned to 56.5 impulses per second at the end of 20 min of PEEP application (p < 0.001). In the meantime, peak airway pressure increased from 9.3 to 32.7 cm H2O, and then gradually returned to 29.4 cm H2O (n = 18; p < 0.05) after 20 min. The remaining four units ceased firing at 34.7 s (range 10-56 s) after their initial increased activity upon 10 cm H2O PEEP application. The unit activity resumed as the PEEP was returned to 3 cm H2O. CONCLUSIONS: High PEEP stimulates SARs and SAR activity gradually returns towards the baseline via multiple mechanisms including receptor deactivation, neural habituation and mechanical adaptation. Understanding of the sensory inputs during PEEP application will assist in developing better strategies of mechanical ventilation.


Assuntos
Respiração com Pressão Positiva/métodos , Receptores Pulmonares de Alongamento/fisiologia , Sistema Respiratório/inervação , Adaptação Fisiológica , Animais , Fenômenos Biomecânicos , Modelos Animais , Coelhos
7.
Med Intensiva (Engl Ed) ; 48(3): 142-154, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37923608

RESUMO

OBJECTIVE: To evaluate the impact of obesity on ICU mortality. DESIGN: Observational, retrospective, multicentre study. SETTING: Intensive Care Unit (ICU). PATIENTS: Adults patients admitted with COVID-19 and respiratory failure. INTERVENTIONS: None. PRIMARY VARIABLES OF INTEREST: Collected data included demographic and clinical characteristics, comorbidities, laboratory tests and ICU outcomes. Body mass index (BMI) impact on ICU mortality was studied as (1) a continuous variable, (2) a categorical variable obesity/non-obesity, and (3) as categories defined a priori: underweight, normal, overweight, obesity and Class III obesity. The impact of obesity on mortality was assessed by multiple logistic regression and Smooth Restricted cubic (SRC) splines for Cox hazard regression. RESULTS: 5,206 patients were included, 20 patients (0.4%) as underweight, 887(17.0%) as normal, 2390(46%) as overweight, 1672(32.1) as obese and 237(4.5%) as class III obesity. The obesity group patients (n = 1909) were younger (61 vs. 65 years, p < 0.001) and with lower severity scores APACHE II (13 [9-17] vs. 13[10-17, p < 0.01) than non-obese. Overall ICU mortality was 28.5% and not different for obese (28.9%) or non-obese (28.3%, p = 0.65). Only Class III obesity (OR = 2.19, 95%CI 1.44-3.34) was associated with ICU mortality in the multivariate and SRC analysis. CONCLUSIONS: COVID-19 patients with a BMI > 40 are at high risk of poor outcomes in the ICU. An effective vaccination schedule and prolonged social distancing should be recommended.


Assuntos
COVID-19 , Sobrepeso , Adulto , Humanos , Sobrepeso/complicações , Sobrepeso/epidemiologia , Estado Terminal , Estudos Retrospectivos , Magreza/complicações , COVID-19/complicações , Obesidade/complicações , Obesidade/epidemiologia
8.
Intensive Care Med ; 48(8): 1009-1023, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35723686

RESUMO

PURPOSE: Severe community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We hypothesized that downregulation of systemic and pulmonary inflammation with prolonged low-dose methylprednisolone treatment would accelerate pneumonia resolution and improve clinical outcomes. METHODS: This double-blind, randomized, placebo-controlled clinical trial recruited adult patients within 72-96 h of hospital presentation. Patients were randomized in 1:1 ratio; an intravenous 40 mg loading bolus was followed by 40 mg/day through day 7 and progressive tapering during the 20-day treatment course. Randomization was stratified by site and need for mechanical ventilation (MV) at the time of randomization. Outcomes included a primary endpoint of 60-day all-cause mortality and secondary endpoints of morbidity and mortality up to 1 year of follow-up. RESULTS: Between January 2012 and April 2016, 586 patients from 42 Veterans Affairs Medical Centers were randomized, short of the 1420 target sample size because of low recruitment. 584 patients were included in the analysis. There was no significant difference in 60-day mortality between the methylprednisolone and placebo arms (16% vs. 18%; adjusted odds ratio 0.90, 95% CI 0.57-1.40). There were no significant differences in secondary outcomes or complications. CONCLUSIONS: In patients with severe CAP, prolonged low-dose methylprednisolone treatment did not significantly reduce 60-day mortality. Treatment was not associated with increased complications.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Adulto , Infecções Comunitárias Adquiridas/tratamento farmacológico , Estado Terminal/terapia , Humanos , Metilprednisolona/uso terapêutico , Pneumonia/tratamento farmacológico , Respiração Artificial , Resultado do Tratamento
9.
Exp Physiol ; 96(9): 966-76, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21622966

RESUMO

We have reported that airway nociceptors [C fibre receptors (CFRs) and high-threshold Aδ fibre receptors (HTARs)] are activated during oleic acid (OA)-induced acute lung injury. In the present studies, we tested the hypothesis that this nociceptor activation is mediated by arachidonic acid products. In anaesthetized, open-chest, mechanically ventilated rabbits, we examined the response of the nociceptors to intravenous injection of OA before and after blocking the cyclo-oxygenase pathways with indomethacin. Pretreatment with indomethacin (20 mg kg(-1)) decreased the background activities of both CFRs (from 0.48 ± 0.12 to 0.25 ± 0.08 impulses/s, n = 7, P < 0.05) and HTARs (from 0.54 ± 0.14 to 0.23 ± 0.08 impulses/s, n = 10, P < 0.01). It also blocked the response of the nociceptors to OA. Likewise, pretreatment with thromboxane synthase inhibitor (ketoconazole) also blocked the nociceptor response to OA. In addition, local microinjection or intravenous injection of a thromboxane mimetic stimulated CFRs and HTARs. The present results clearly indicate that arachidonic acid metabolites mediate airway nociceptor activation during OA-induced acute lung injury and suggest that thromboxane may be a key mediator.


Assuntos
Lesão Pulmonar Aguda/fisiopatologia , Ácido Araquidônico/metabolismo , Nociceptores/efeitos dos fármacos , Nociceptores/fisiologia , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Indometacina/farmacologia , Cetoconazol/farmacologia , Masculino , Ácido Oleico , Coelhos , Tromboxano-A Sintase/antagonistas & inibidores
10.
Am J Med Sci ; 361(4): 411-419, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33563417

RESUMO

Aspergillus species are ubiquitous in the environment. Aspergillosis is acquired by inhalation of Aspergillus spores. In normal hosts, spore inhalation rarely causes lung disease. Pulmonary Aspergillosis covers a wide spectrum of clinical syndromes depending on the interaction between Aspergillus and the host (immune-status, prior bronchopulmonary disease). It runs the gamut from invasive Aspergillosis to Aspergillus bronchitis. Invasive Aspergillosis usually occurs in severely immunocompromised patients, typically in neutropenic but also in non-neutropenic patients. Chronic pulmonary Aspergillosis affects patients with chronic structural lung disease such as COPD or previous mycobacterial lung disease, but without other significant immunocompromise. Aspergillus bronchitis affects patients with bronchial disease such as bronchiectasis. Allergic bronchopulmonary Aspergillosis affects patients with bronchial asthma or cystic fibrosis, and is due to an allergic response to Aspergillus.


Assuntos
Aspergilose Pulmonar/microbiologia , Humanos , Aspergilose Pulmonar/complicações , Aspergilose Pulmonar/patologia
11.
Int J Med Inform ; 145: 104327, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33220573

RESUMO

BACKGROUND: Quality indicators (QIs) are being increasingly used in medicine to compare and improve the quality of care delivered. The feasibility of data collection is an important prerequisite for QIs. Information technology can improve efforts to measure processes and outcomes. In intensive care units (ICU), QIs can be automatically measured by exploiting data from clinical information systems (CIS). OBJECTIVE: To describe the development and application of a tool to automatically generate a minimum dataset (MDS) and a set of ICU quality metrics from CIS data. METHODS: We used the definitions for MDS and QIs proposed by the Spanish Society of Critical Care Medicine and Coronary Units. Our tool uses an extraction, transform, and load process implemented with Python to extract data stored in various tables in the CIS database and create a new associative database. This new database is uploaded to Qlik Sense, which constructs the MDS and calculates the QIs by applying the required metrics. The tool was tested using data from patients attended in a 30-bed polyvalent ICU during a six-year period. RESULTS: We describe the definitions and metrics, and we report the MDS and QI measurements obtained through the analysis of 4546 admissions. The results show that our ICU's performance on the QIs analyzed meets the standards proposed by our national scientific society. CONCLUSIONS: This is the first step toward using a tool to automatically obtain a set of actionable QIs to monitor and improve the quality of care in ICUs, eliminating the need for professionals to enter data manually, thus saving time and ensuring data quality.


Assuntos
Unidades de Terapia Intensiva , Indicadores de Qualidade em Assistência à Saúde , Cuidados Críticos , Confiabilidade dos Dados , Humanos , Sistemas de Informação
12.
Antibiotics (Basel) ; 10(4)2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33810263

RESUMO

Background: Procalcitonin (PCT) and C-Reactive protein (CRP) are well-established sepsis biomarkers. The association of baseline PCT levels and mortality in pneumonia remains unclear, and we still do not know whether biomarkers levels could be related to the causative microorganism (GPC, GNB). The objective of this study is to address these issues. Methods: a retrospective observational cohort study was conducted in 184 Spanish ICUs (2009-2018). Results: 1608 patients with severe influenza pneumonia with PCT and CRP available levels on admission were included, 1186 with primary viral pneumonia (PVP) and 422 with bacterial Co-infection (BC). Those with BC presented higher PCT levels (4.25 [0.6-19.5] versus 0.6 [0.2-2.3]ng/mL) and CRP (36.7 [20.23-118] versus 28.05 [13.3-109]mg/dL) as compared to PVP (p < 0.001). Deceased patients had higher PCT (ng/mL) when compared with survivors, in PVP (0.82 [0.3-2.8]) versus 0.53 [0.19-2.1], p = 0.001) and BC (6.9 [0.93-28.5] versus 3.8 [0.5-17.37], p = 0.039). However, no significant association with mortality was observed in the multivariate analysis. The PCT levels (ng/mL) were significantly higher in polymicrobial infection (8.4) and GPC (6.9) when compared with GNB (1.2) and Aspergillus (1.7). The AUC-ROC of PCT for GPC was 0.67 and 0.32 for GNB. The AUROC of CRP was 0.56 for GPC and 0.39 for GNB. Conclusions: a single PCT/CRP value at ICU admission was not associated with mortality in severe influenza pneumonia. None of the biomarkers have enough discriminatory power to be used for predicting the causative microorganism of the co-infection.

13.
ERJ Open Res ; 7(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33718494

RESUMO

BACKGROUND: The relationship between early oseltamivir treatment (within 48 h of symptom onset) and mortality in patients admitted to intensive care units (ICUs) with severe influenza is disputed. This study aimed to investigate the association between early oseltamivir treatment and ICU mortality in critically ill patients with influenza pneumonia. METHODS: This was an observational study of patients with influenza pneumonia admitted to 184 ICUs in Spain during 2009-2018. The primary outcome was to evaluate the association between early oseltamivir treatment and ICU mortality compared with later treatment. Secondary outcomes were to compare the duration of mechanical ventilation and ICU length of stay between the early and later oseltamivir treatment groups. To reduce biases related to observational studies, propensity score matching and a competing risk analysis were performed. RESULTS: During the study period, 2124 patients met the inclusion criteria. All patients had influenza pneumonia and received oseltamivir before ICU admission. Of these, 529 (24.9%) received early oseltamivir treatment. In the multivariate analysis, early treatment was associated with reduced ICU mortality (OR 0.69, 95% CI 0.51-0.95). After propensity score matching, early oseltamivir treatment was associated with improved survival rates in the Cox regression (hazard ratio 0.77, 95% CI 0.61-0.99) and competing risk (subdistribution hazard ratio 0.67, 95% CI 0.53-0.85) analyses. The ICU length of stay and duration of mechanical ventilation were shorter in patients receiving early treatment. CONCLUSIONS: Early oseltamivir treatment is associated with improved survival rates in critically ill patients with influenza pneumonia, and may decrease ICU length of stay and mechanical ventilation duration.

14.
Sheng Li Xue Bao ; 62(3): 191-5, 2010 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-20571734

RESUMO

Lung cancer is a major medical problem. Despite advances in molecular biology and pharmacology, the outcome of lung cancer treatment is unsatisfactory. Clinically, inflammation and cancer are closely associated, and, genetically, these two processes are regulated by the same gene loci. Inflammation promotes cancer formation. Increasing evidence shows that neuroimmune interaction involving inflammatory disease and the vagus nerves are crucial in the interaction. Airway sensory receptors are biosensors that detect the lung inflammatory process through various mediators and cytokines. This information is transmitted through vagal afferents to the brain and produces a host of responses that regulate the extent and intensity of inflammation. Tumor cells express receptors for neurotransmitters and provide a substrate for direct interaction with neurons. Thus, neural regulation of the immune response is targeted towards inflammation as well as tumors. The airway sensors can detect cancer-related cytokines, which provides a direct pathway to inform the brain of tumor growth. The knowledge of how these sensors may monitor tumor progression and provide neuroimmune interaction in the control of tumor development and metastasis will improve our treatment of lung cancer.


Assuntos
Inflamação/patologia , Neoplasias Pulmonares/patologia , Pulmão/inervação , Carcinogênese , Citocinas/fisiologia , Humanos , Pulmão/patologia , Células Receptoras Sensoriais/fisiologia , Nervo Vago/fisiologia
15.
Am J Physiol Regul Integr Comp Physiol ; 297(3): R853-8, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19605767

RESUMO

We attempted to determine whether intrapulmonary sensory receptors are nourished by the pulmonary or the systemic circulation. Single-unit activity from the cervical vagus nerve was recorded in anesthetized, open chest, mechanically ventilated rabbits, comparing responses to right or left ventricular injection of 2% lidocaine (at 4 mg/kg). Airway mechanosensors [slowly adapting receptor (SARs) and rapidly adapting receptors] were inhibited by lidocaine, whereas chemosensors (C-fiber receptors and high-threshold A delta-receptors) were stimulated. Furthermore, all types of airway sensors were perfused preferentially by the pulmonary circulation. For example, 14 of the 15 tested SARs ceased discharge at 4.1 +/- 0.6 s after lidocaine injection into the right ventricle. The blocking effect lasted 35 +/- 6.2 s. In contrast, none of the 15 SARs ceased their activity after lidocaine injection into the left ventricle. Our data show that intrapulmonary sensors are mainly nourished by the pulmonary circulation. Their very short latency indicates that these sensors receive ample blood supply. Thus, intrapulmonary sensors rely on the pulmonary circulation to detect bioactive agents in the blood.


Assuntos
Anestésicos Locais/farmacologia , Células Quimiorreceptoras/efeitos dos fármacos , Lidocaína/farmacologia , Pulmão/irrigação sanguínea , Pulmão/inervação , Mecanorreceptores/efeitos dos fármacos , Mecanotransdução Celular/efeitos dos fármacos , Resistência das Vias Respiratórias/efeitos dos fármacos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/sangue , Animais , Pressão Sanguínea/efeitos dos fármacos , Ventrículos do Coração , Injeções , Lidocaína/administração & dosagem , Lidocaína/sangue , Circulação Pulmonar/efeitos dos fármacos , Coelhos , Fatores de Tempo , Nervo Vago/efeitos dos fármacos
16.
J Crit Care ; 52: 186-192, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31096099

RESUMO

There is controversy regarding the mean arterial pressure (MAP) goals that should be targeted in the treatment of hepatorenal syndrome (HRS.) We conducted a study to assess different MAP targets in HRS in the intensive care unit (ICU). MATERIALS AND METHODS: This is a prospective randomized controlled pilot trial. ICU patients had target mean arterial pressure (MAP) ≥ 85 mmHg (control arm) or 65-70 mmHg (study arm). Urine output and serum creatinine were trended and recorded. RESULTS: A total of 18 patients were enrolled. The day four urine output in the high and low MAP group was 1194 (SD = 1249) mL/24 h and 920 (SD = 812) mL/24 h, respectively. The difference in day four - day one urine output was -689 (SD = 1684) mL/24 h and 272 (SD = 582) mL/24 h for the high and low MAP groups. The difference in serum creatinine at day four - day one was -0.54 (SD = 0.63) mg/dL and - 0.77 (SD = 1.14) mg/dL in the high and low MAP groups, respectively. CONCLUSION: In this study, we failed to prove non-inferiority between a low and high target MAP in patients with HRS. TRIAL REGISTRATION: This trial was registered with and approved by the University of Louisville Internal Review Board and hospital research review committees (IRB # 14.1190). The trial was registered with ClinicalTrials.gov (ID # NCT02789150). The IRB committee roster 7/21/2014-2/26/2015 is registered with IORG (IORG # IORG0000147; OMB # 0990-0279) and is available at http://louisville.edu/research/humansubjects/about-the-irb/rosters/RosterEffective20140721thru20150226.pdf.


Assuntos
Síndrome Hepatorrenal/fisiopatologia , Hipertensão/fisiopatologia , Hipotensão/fisiopatologia , Pressão Arterial/fisiologia , Creatinina/sangue , Cuidados Críticos , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos
17.
Chest ; 133(6): 1410-1414, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18339777

RESUMO

BACKGROUND: Pulmonary vasoconstriction in response to hypoxia is unusual inasmuch as local exposure of nonpulmonary vasculature to hypoxia results in vasodilation. It has been suggested that pulmonary artery smooth-muscle cells may relax in response to intracellular generation of reactive oxygen species (ROS) and that the production of ROS decreases under hypoxia. However, other workers report increased ROS production in human pulmonary artery smooth-muscle cells (HPASMC) during hypoxia. METHODS: Using dihydrodichlorofluorescein diacetate, dihydroethidium, and Amplex Red (Molecular Probes; Eugene, OR), we estimated ROS generation by confluent primary cultures of HPASMC and human coronary artery smooth-muscle cells (HCASMC) under normoxia (20%) and acute hypoxia (5%). RESULTS: All three assay systems showed that HPASMC production of ROS is decreased under hypoxia and to a greater extent than the decrease in ROS production by HCASMC. A substantially greater percentage of normoxic ROS production by HPASMC is mitochondrial (> 60%) compared to HCASMC (< 30%). CONCLUSIONS: These results support the conclusion that ROS generation decreases, rather than increases, in HPASMC during hypoxia. However, as ROS production also decreases in HCASMC during hypoxia, the reason for the opposite change in vascular tone is not yet apparent.


Assuntos
Hipóxia/metabolismo , Músculo Liso Vascular/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células Cultivadas , Vasos Coronários , Humanos , Técnicas In Vitro , Artéria Pulmonar , Vasoconstrição
19.
Case Rep Pulmonol ; 2018: 2123140, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30345137

RESUMO

An aortic aneurysm is a permanent localized arterial dilation with more than 50% of the artery diameter. Among the complications of an aortic aneurysm, one of the rarest is the aorto-bronchial fistula, which presents with massive hemoptysis; this condition is lethal if not treated surgically. We report a 90-year-old man with no significant medical history who presented to the emergency department with abrupt onset of hemoptysis; his chest X-ray displayed left upper lobe opacity with widened mediastinum. CT chest revealed aneurysmatic dilatation of the aorta, left upper lobe opacity suspicious of pulmonary aortic fistula. Thoracic surgery was consulted but due to his poor functional status surgery was deferred. On the second day of hospitalization, the patient developed another episode of massive hemoptysis resulting in hypovolemic shock and expired. This case epitomizes the relevance of broad differential diagnosis for hemoptysis and the prompt assessment and management of the patients with this condition.

20.
Am J Med Sci ; 355(2): 168-173, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29406045

RESUMO

BACKGROUND: Determining volume responsiveness in critically ill patients is challenging. We sought to determine if passive leg raise (PLR) induced changes in pulsed wave Doppler of the carotid artery flow time could predict fluid responsiveness in critically ill patients. MATERIALS AND METHODS: Medical intensive care unit patients ≥18 years old with a radial arterial line and FloTrac/Vigileo monitor in place were enrolled. Pulsed wave Doppler of the carotid artery was performed to measure the change in carotid flow time (CFTC) in response to a PLR. Patients were categorized as fluid responders if stroke volume increased by ≥15% on a Vigileo monitor. The main outcome measure was the accuracy of CFTC to detect a change in response to a PLR. We also calculated the percentage increase in CFTC that could predict fluid responsiveness. RESULTS: We enrolled 22 patients. Using an increase of ≥24.6% in the CFTC in response to PLR to predict fluid responsiveness there was a sensitivity of 60%, specificity of 92%, positive likelihood ratio of 7.2, negative likelihood ratio of 0.4, positive predictive value of 86%, negative predictive value of 73% and receiver operating characteristic of 0.75 (95% CI: 0.54-0.96). CONCLUSIONS: CFTC performs well compared to stroke volume measurements on a Vigileo monitor. The use of CFTC is highlighted in resource-limited environments and when time limits the use of other methods. CFTc should be validated in a larger study with more operators against a variety of hemodynamic monitors.


Assuntos
Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/fisiopatologia , Unidades de Terapia Intensiva , Postura , Volume Sistólico , Ultrassonografia Doppler de Pulso , Idoso , Velocidade do Fluxo Sanguíneo , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
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