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1.
Respir Physiol Neurobiol ; 276: 103426, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32120011

RESUMO

BACKGROUND: Remote ischemic preconditioning (RIP) may protect target organs from ischemia - reperfusion injury, however, little is known on pulmonary effects of RIP prior to, immediately after and several hours after one-lung ventilation (OLV). The present randomized, controlled, animal experiment was undertaken to analyze these issues. METHODS: After animal ethics committee approval, twelve piglets (26 ± 2 kg) were anesthetized and randomly assigned to a control (n = 6) or to a RIP group (n = 6). For RIP, arterial perfusion of a hind limb was suspended by an inflated blood pressure cuff (200 mmHg for 5 min) and deflated for another 5 min, this was repeated four times. After intubation, mechanical ventilation (MV) was kept constant with tidal volume 10 ml/kg, inspired oxygen fraction (FIO2) 0.40, and positive end-expiratory pressure (PEEP) 5cmH2O. FIO2 was increased to 1 after RIP in the RIP group and after the sham procedure in the control group, respectively, for the time of OLV. OLV was established by left-sided bronchial blockade. After OLV, TLV was re-established until the end of the protocol. Exhaled nitric oxide (NO) was measured by ozon chemiluminiscense and ventilatory and hemodynamic variables were assessed according to the protocol. RESULTS: Hemodynamic and respiratory data were similar in both groups. Arterial pO2 was higher in the RIP group after two hours of OLV. In the control group, exhaled NO decreased during OLV and remained at low levels for the rest of the protocol. In the RIP group, exhaled NO decreased as well during OLV but returned to baseline levels when TLV was re-established. CONCLUSIONS: RIP has no effects on hemodynamic and respiratory variables in juvenile, healthy piglets. RIP improves the oxygenation after OLV and prevents the decline of exhaled NO after OLV.

2.
Sci Rep ; 10(1): 4208, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144345

RESUMO

Respiratory tract infections require early diagnosis and adequate treatment. With the antibiotic overuse and increment in antibiotic resistance there is an increased need to accurately distinguish between bacterial and viral infections. We investigated the diagnostic performance of calprotectin in respiratory tract infections and compared it with the performance of heparin binding protein (HBP) and procalcitonin (PCT). Biomarkers were analyzed in patients with viral respiratory infections and patients with bacterial pneumonia, mycoplasma pneumonia and streptococcal tonsillitis (n = 135). Results were compared with values obtained from 144 healthy controls. All biomarkers were elevated in bacterial and viral infections compared to healthy controls. Calprotectin was significantly increased in patients with bacterial infections; bacterial pneumonia, mycoplasma pneumonia and streptococcal tonsillitis compared with viral infections. PCT was significantly elevated in patients with bacterial pneumonia compared to viral infections but not in streptococcal tonsillitis or mycoplasma caused infections. HBP was not able to distinguish between bacterial and viral causes of infections. The overall clinical performance of calprotectin in the distinction between bacterial and viral respiratory infections, including mycoplasma was greater than performance of PCT and HBP. Rapid determination of calprotectin may improve the management of respiratory tract infections and allow more precise diagnosis and selective use of antibiotics.

3.
Histochem Cell Biol ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32189111

RESUMO

In this article, we present an X-ray tomographic imaging method that is well suited for pulmonary disease studies in animal models to resolve the full pathway from gas intake to gas exchange. Current state-of-the-art synchrotron-based tomographic phase-contrast imaging methods allow for three-dimensional microscopic imaging data to be acquired non-destructively in scan times of the order of seconds with good soft tissue contrast. However, when studying multi-scale hierarchically structured objects, such as the mammalian lung, the overall sample size typically exceeds the field of view illuminated by the X-rays in a single scan and the necessity for achieving a high spatial resolution conflicts with the need to image the whole sample. Several image stitching and calibration techniques to achieve extended high-resolution fields of view have been reported, but those approaches tend to fail when imaging non-stable samples, thus precluding tomographic measurements of large biological samples, which are prone to degradation and motion during extended scan times. In this work, we demonstrate a full-volume three-dimensional reconstruction of an intact rat lung under immediate post-mortem conditions and at an isotropic voxel size of (2.75 µm)3. We present the methodology for collecting multiple local tomographies with 360° extended field of view scans followed by locally non-rigid volumetric stitching. Applied to the lung, it allows to resolve the entire pulmonary structure from the trachea down to the parenchyma in a single dataset. The complete dataset is available online (https://doi.org/10.16907/7eb141d3-11f1-47a6-9d0e-76f8832ed1b2).

4.
J Am Heart Assoc ; 9(5): e014634, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32114892

RESUMO

Background The inflammatory biomarker YKL-40 has previously been studied as a potential risk marker in cardiovascular disease. We aimed to assess the prognostic reclassification potential of serum YKL-40 in patients with stable coronary artery disease. Methods and Results The main study population was the placebo group of the CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) trial. The primary outcome was a composite of acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all-cause mortality. We used Cox proportional hazards regression models adjusted for C-reactive protein level and baseline cardiovascular risk factors. Improvement in prediction by adding serum YKL-40 to the risk factors was calculated using the Cox-Breslow method and c-statistic. A total of 2200 patients were randomized to placebo, with a follow-up duration of 10 years. YKL-40 was associated with an increased risk of the composite outcome (hazard ratio per unit increase in (YKL-40) 1.13, 95% CI 1.03-1.24, P=0.013) and all-cause mortality (hazard ratio 1.32, 95% CI 1.17-1.49, P<0.0001). Considering whether a composite-outcome event was more likely to have, or not have, occurred to date, we found 68.4% of such predictions to be correct when based on the standard predictors, and 68.5% when serum YKL-40 was added as a predictor. Equivalent results were obtained with c-statistics. Conclusions Higher serum YKL-40 was independently associated with an increased risk of adverse cardiovascular outcomes and mortality. Addition of YKL-40 did not improve risk prediction in patients with stable coronary artery disease. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00121550.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32150440

RESUMO

RATIONALE: Tidal expiratory flow limitation (tidal-EFL) is not completely avoidable by applying positive end-expiratory pressure and may cause respiratory and hemodynamic complications in ventilated patients with lungs prone to collapse. During spontaneous breathing, expiratory diaphragmatic contraction counteracts tidal-EFL. We hypothesized that during both spontaneous breathing and controlled mechanical ventilation, external expiratory resistances reduce tidal-EFL. OBJECTIVES: To assess whether external expiratory resistances 1. Affect expiratory diaphragmatic contraction during spontaneous breathing; 2. Reduce expiratory flow and make lung compartments more homogeneous with more similar expiratory time constants; 3. Reduce tidal atelectasis, preventing hyperinflation. METHODS: Three positive end-expiratory pressure levels and four external expiratory resistances were tested in 10 pigs after lung lavage. We analyzed expiratory diaphragmatic electric activity and respiratory mechanics. Based on computed tomography scans, four lung compartments - not (atelectasis), poorly, normally and hyper inflated - were defined. MEASUREMENTS AND MAIN RESULTS: Consequently to additional external expiratory resistances, and mainly in lungs prone to collapse (at low positive end-expiratory pressure), 1. The expiratory transdiaphragmatic pressure decreased during spontaneous breathing by more than 10%; 2. Expiratory flow was reduced and the expiratory time constants became more homogeneous. 3. The amount of atelectasis at end-expiration decreased from 24% to 16% during spontaneous breathing and from 32% to 18% during controlled mechanical ventilation, without increasing hyperinflation. CONCLUSIONS: The expiratory modulation induced by external expiratory resistances preserves the positive effects of the expiratory brake while minimizing expiratory diaphragmatic contraction. External expiratory resistances optimize lung mechanics and limit tidal-EFL and tidal atelectasis, without increasing hyperinflation.

6.
Intensive Care Med Exp ; 8(1): 10, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32086632

RESUMO

BACKGROUND: Real-time bedside information on regional ventilation and perfusion during mechanical ventilation (MV) may help to elucidate the physiological and pathophysiological effects of MV settings in healthy and injured lungs. We aimed to study the effects of positive end-expiratory pressure (PEEP) and tidal volume (VT) on the distributions of regional ventilation and perfusion by electrical impedance tomography (EIT) in healthy and injured lungs. METHODS: One-hit acute lung injury model was established in 6 piglets by repeated lung lavages (injured group). Four ventilated piglets served as the control group. A randomized sequence of any possible combination of three VT (7, 10, and 15 ml/kg) and four levels of PEEP (5, 8, 10, and 12 cmH2O) was performed in all animals. Ventilation and perfusion distributions were computed by EIT within three regions-of-interest (ROIs): nondependent, middle, dependent. A mixed design with one between-subjects factor (group: intervention or control), and two within-subjects factors (PEEP and VT) was used, with a three-way mixed analysis of variance (ANOVA). RESULTS: Two-way interactions between PEEP and group, and VT and group, were observed for the dependent ROI (p = 0.035 and 0.012, respectively), indicating that the increase in the dependent ROI ventilation was greater at higher PEEP and VT in the injured group than in the control group. A two-way interaction between PEEP and VT was observed for perfusion distribution in each ROI: nondependent (p = 0.030), middle (p = 0.006), and dependent (p = 0.001); no interaction was observed between injured and control groups. CONCLUSIONS: Large PEEP and VT levels were associated with greater pulmonary ventilation of the dependent lung region in experimental lung injury, whereas they affected pulmonary perfusion of all lung regions both in the control and in the experimental lung injury groups.

7.
J Diabetes Res ; 2020: 6450742, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31998807

RESUMO

Periodontitis is a chronic inflammatory condition that may contribute to diabetogenesis. The aim was to investigate the levels of glycated proteins and their correlation with periodontal and systemic inflammation. Fifty-one patients with periodontitis and 20 healthy subjects underwent probing pocket depth (PPD) measurements. PPD total and PPD disease with and without tooth adjustment were used as continuous indices. Marginal bone loss (MBL) for mandibular premolars and molars was measured digitally. Body mass index (BMI) and waist circumference (WC) were also analyzed. Glycated hemoglobin (HbA1c) and fructosamine (FrAm) levels were measured in all subjects. A multiplex proximity extension assay (PEA) was used to analyze the serum samples for simultaneous measurement of 92 proteins. Both HbA1c and FrAm inversely correlated with IL-10, FGF-21, MCP-1, and TNF beta amongst 16 proteins. HbA1c correlated directly with OPG. Parameters of disease severity were consistently significant for HbA1c. Adjusted PPD total and number of missing teeth were increased in diabetes whereas levels of RANKL and RANKL to OPG ratio were the highest in nondiabetic periodontitis patients. Hyperglycemic conditions in periodontitis patients are associated with reduced levels of anti-inflammatory proteins as well as dysregulated bone resorption.

8.
Br J Anaesth ; 124(3): 345-353, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31952649

RESUMO

BACKGROUND: Bedside lung volume measurement could personalise ventilation and reduce driving pressure in patients with acute respiratory distress syndrome (ARDS). We investigated a modified gas-dilution method, the inspired sinewave technique (IST), to measure the effective lung volume (ELV) in pigs with uninjured lungs and in an ARDS model. METHODS: Anaesthetised mechanically ventilated pigs were studied before and after surfactant depletion by saline lavage. Changes in PEEP were used to change ELV. Paired measurements of absolute ELV were taken with IST (ELVIST) and compared with gold-standard measures (sulphur hexafluoride wash in/washout [ELVSF6] and computed tomography (CT) [ELVCT]). Measured volumes were used to calculate changes in ELV (ΔELV) between PEEP levels for each method (ΔELVIST, ΔELVSF6, and ΔELVCT). RESULTS: The coefficient of variation was <5% for repeated ELVIST measurements (n=13 pigs). There was a strong linear relationship between ELVIST and ELVSF6 in uninjured lungs (r2=0.97), and with both ELVSF6 and ELVCT in the ARDS model (r2=0.87 and 0.92, respectively). ELVIST had a mean bias of -12 to 13% (95% limits=±17 - 25%) compared with ELVSF6 and ELVCT. ΔELVIST was concordant with ΔELVSF6 and ΔELVCT in 98-100% of measurements, and had a mean bias of -73 to -77 ml (95% limits=±128 - 186 ml) compared with ΔELVSF6 and -1 ml (95% limits ±333 ml) compared with ΔELVCT. CONCLUSIONS: IST provides a repeatable measure of absolute ELV and shows minimal bias when tracking PEEP-induced changes in lung volume compared with CT in a saline-lavage model of ARDS.


Assuntos
Respiração com Pressão Positiva/métodos , Síndrome do Desconforto Respiratório do Adulto/terapia , Animais , Modelos Animais de Doenças , Medidas de Volume Pulmonar/métodos , Testes Imediatos , Reprodutibilidade dos Testes , Síndrome do Desconforto Respiratório do Adulto/diagnóstico por imagem , Síndrome do Desconforto Respiratório do Adulto/etiologia , Síndrome do Desconforto Respiratório do Adulto/fisiopatologia , Solução Salina , Sus scrofa , Tomografia Computadorizada por Raios X
9.
Crit Care Med ; 48(3): e200-e208, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31809278

RESUMO

OBJECTIVES: Determine the intra-tidal regional gas and blood volume distributions at different levels of atelectasis in experimental lung injury. Test the hypotheses that pulmonary aeration and blood volume matching is reduced during inspiration in the setting of minimal tidal recruitment/derecruitment and that this mismatching is an important determinant of hypoxemia. DESIGN: Preclinical study. SETTING: Research laboratory. SUBJECTS: Seven anesthetized pigs 28.7 kg (SD, 2.1 kg). INTERVENTIONS: All animals received a saline-lavage surfactant depletion lung injury model. Positive end-expiratory pressure was varied between 0 and 20 cm H2O to induce different levels of atelectasis. MEASUREMENTS AND MAIN RESULTS: Dynamic dual-energy CT images of a juxtadiaphragmatic slice were obtained, gas and blood volume fractions within three gravitational regions calculated and normalized to lung tissue mass (normalized gas volume and normalized blood volume, respectively). Ventilatory conditions were grouped based upon the fractional atelectatic mass in expiration (< 20%, 20-40%, and ≥ 40%). Tidal recruitment/derecruitment with fractional atelectatic mass in expiration greater than or equal to 40% was less than 7% of lung mass. In this group, inspiration-related increase in normalized gas volume was greater in the nondependent (818 µL/g [95% CI, 729-908 µL/g]) than the dependent region (149 µL/g [120-178 µL/g]). Normalized blood volume decreased in inspiration in the nondependent region (29 µL/g [12-46 µL/g]) and increased in the dependent region (39 µL/g [30-48 µL/g]). Inspiration-related changes in normalized gas volume and normalized blood volume were negatively correlated in fractional atelectatic mass in expiration greater than or equal to 40% and 20-40% groups (r = 0.56 and 0.40), but not in fractional atelectatic mass in expiration less than 20% group (r = 0.01). Both the increase in normalized blood volume in the dependent region and fractional atelectatic mass in expiration negatively correlated with PaO2/FIO2 ratio (ρ = -0.77 and -0.93, respectively). CONCLUSIONS: In experimental atelectasis with minimal tidal recruitment/derecruitment, mechanical inspiratory breaths redistributed blood volume away from well-ventilated areas, worsening PaO2/FIO2.

10.
J Interferon Cytokine Res ; 40(2): 71-74, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31599692

RESUMO

There exists a close relationship between cardiovascular diseases and chronic kidney disease. Apolipoprotein A1 and high-density lipoprotein (HDL) cholesterol are widely used as cardiovascular risk markers but they also have anti-inflammatory properties. The aim of this study was to investigate any associations between HDL levels and cytokine levels in urine. We randomly selected 90 urine samples from the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females). The samples were analyzed with 2 multiplex assays, Multiplex Inflammation I and Cardiovascular II kits (Olink Bioscience, Uppsala, Sweden). We analyzed the correlations between 158 cytokines in urine with apolipoprotein A1, HDL cholesterol, apolipoprotein B, and low-density lipoprotein cholesterol. There were strong correlations for apolipoprotein A1 and HDL cholesterol with individual cytokines. After adjustment for multiplicity testing, there were 33 significant correlations between apolipoprotein A1 and cytokine levels and 14 of these were also significantly correlated with HDL cholesterol. The strongest associations were observed for IL-1α, SPON2, RAGE, PAR-1, TRAIL-R2, IL-4RA, TNFRSF11A, and SCF. A total of 28 out of 33 correlations were negative, indicating a negative relationship between apolipoprotein A1 and urinary cytokines. The study shows a negative correlation between apolipoprotein A1 and HDL cholesterol and urinary cytokine levels. The finding is in agreement with the anti-inflammatory properties of HDL.

11.
Am J Bot ; 107(1): 91-115, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31814117

RESUMO

PREMISE: Phylogenetic trees of bryophytes provide important evolutionary context for land plants. However, published inferences of overall embryophyte relationships vary considerably. We performed phylogenomic analyses of bryophytes and relatives using both mitochondrial and plastid gene sets, and investigated bryophyte plastome evolution. METHODS: We employed diverse likelihood-based analyses to infer large-scale bryophyte phylogeny for mitochondrial and plastid data sets. We tested for changes in purifying selection in plastid genes of a mycoheterotrophic liverwort (Aneura mirabilis) and a putatively mycoheterotrophic moss (Buxbaumia), and compared 15 bryophyte plastomes for major structural rearrangements. RESULTS: Overall land-plant relationships conflict across analyses, generally weakly. However, an underlying (unrooted) four-taxon tree is consistent across most analyses and published studies. Despite gene coverage patchiness, relationships within mosses, liverworts, and hornworts are largely congruent with previous studies, with plastid results generally better supported. Exclusion of RNA edit sites restores cases of unexpected non-monophyly to monophyly for Takakia and two hornwort genera. Relaxed purifying selection affects multiple plastid genes in mycoheterotrophic Aneura but not Buxbaumia. Plastid genome structure is nearly invariant across bryophytes, but the tufA locus, presumed lost in embryophytes, is unexpectedly retained in several mosses. CONCLUSIONS: A common unrooted tree underlies embryophyte phylogeny, [(liverworts, mosses), (hornworts, vascular plants)]; rooting inconsistency across studies likely reflects substantial distance to algal outgroups. Analyses combining genomic and transcriptomic data may be misled locally for heavily RNA-edited taxa. The Buxbaumia plastome lacks hallmarks of relaxed selection found in mycoheterotrophic Aneura. Autotrophic bryophyte plastomes, including Buxbaumia, hardly vary in overall structure.

12.
Clin Nutr ; 39(1): 159-165, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30685298

RESUMO

BACKGROUND & AIMS: Rye consumption has shown beneficial effects on prostate cancer tumors, as indicated by slower initial tumor growth in animal models and lowering of prostate-specific antigen (PSA) in humans. This study evaluated the effects of whole grain/bran rye consumption on low-grade inflammation and endothelial function biomarkers in men with prostate cancer. METHODS: Seventeen men with untreated, low-grade prostate cancer consumed 485 g rye whole grain and bran products (RP) per day or refined wheat products with added cellulose (WP) in a randomized crossover design. Fasting blood samples were taken before and after 2, 4, and 6 weeks of treatment. RESULTS: Concentrations of tumor nuclear factor-receptor 2 (TNF-R2), e-selectin, and endostatin were significantly lower after consumption of the RP diet compared with WP (p < 0.05). Cathepsin S concentration was positively correlated to TNF-R2 and endostatin concentrations across all occasions. Strong correlations were consistently found between intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and between interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1RA). No effect of intervention was found in 92 inflammation-related protein biomarkers measured in a proximity extension assay. CONCLUSIONS: RP diet lowered TNF-R2, e-selectin, and endostatin, compared with WP in men with prostate cancer. These effects were accompanied by a reduction in PSA.

13.
Front Physiol ; 10: 1392, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824326

RESUMO

Background: Whether spontaneous breathing (SB) should be used in early acute respiratory distress syndrome (ARDS) is questioned because it may cause ventilator-induced lung injury (VILI) by tidal high strain/stress and recruitment/derecruitment (R/D). However, SB has shown beneficial effects when used appropriately. We hypothesized that high levels of positive end-expiratory pressure (PEEP), during assisted SB, would prevent tidal R/D, reducing ventilatory variation and respiratory rate while potentially increasing transpulmonary pressure (P TP). The aim was to test this hypothesis in experimental mild ARDS during continuous SB using neurally adjusted ventilator assist (NAVA) and uninterrupted computed tomography (CT) exposure. Methods: Mild experimental ARDS (PaO2/FiO2-ratio of 250) was induced in anesthetized pigs (n = 5), ventilated using uninterrupted NAVA. PEEP was changed in steps of 3 cmH2O, from 0 to 15 and back to 0 cmH2O. Dynamic CT scans, ventilatory parameters, and esophageal pressure were acquired simultaneously. P TP and R/D were calculated and compared among PEEP levels. Results: When increasing PEEP from 0 to 15 cmH2O, tidal R/D decreased from 4.3 ± 5.9 to 1.1 ± 0.7% (p < 0.01), breath-to-breath variability decreased, and P TP increased from 11.4 ± 3.7 to 29.7 ± 14.1 cmH2O (R 2 = 0.96). Conclusion: This study shows that injurious phenomena like R/D and high P TP are present in NAVA at the two extremes of the PEEP spectrum. Willing to titrate PEEP to limit these phenomena, the physician must choose the best compromise between restraining the R/D or P TP.

14.
Shock ; 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31880758

RESUMO

PURPOSE: Lipopolysaccharides (LPS) are presumed to contribute to the inflammatory response in sepsis. We investigated if extracorporeal Alteco® LPS Adsorber for LPS removal in early Gram-negative septic shock was feasible and safe. Also, effect on endotoxin level, inflammatory response and organ function were assessed. METHODS: A pilot, double-blinded, randomized, Phase IIa, feasibility clinical investigation was undertaken in six Scandinavian intensive care units aiming to allocate thirty-two septic shock patients with abdominal or urogenital focus to LPS Adsorber therapy or a Sham Adsorber, therapy without active LPS-binding. The study treatment was initiated within 12 hours of inclusion and given for six hours daily on first two days. LPS was measured in all patients. RESULTS: The investigation was terminated after 527 days with eight patients included in the LPS Adsorber group and seven in the Sham group. Twenty-one adverse effects, judged not to be related to the device, were reported in three patients in the LPS Adsorber group and two in the Sham group. Two patients in the Sham group and no patients in the LPS Adsorber group died within 28 days. Plasma LPS levels were low without groups differences during or after adsorber therapy. The changes in inflammatory markers and organ function were similar in the groups. CONCLUSIONS: In a small cohort of patients with presumed Gram-negative septic shock, levels of circulating endotoxin were low and no adverse effects within 28 days after LPS adsorber-treatment were observed. No benefit compared to a sham device was seen when using a LPS adsorber in addition to standard care. TRIAL REGISTRATION: Clinicaltrials.gov NCT02335723. Registered: November 28, 2014.

15.
Scand J Clin Lab Invest ; : 1-6, 2019 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-31841042

RESUMO

Sepsis is the most frequent cause of death in the intensive care unit (ICU). A rapid and correct diagnosis and initiation of therapy is crucial for improving patient outcomes. The aim of this study was to compare the performance of calprotectin with the more widely used sepsis biomarker procalcitonin (PCT) in ICU patients. The performance of calprotectin and PCT as sepsis and prognostic markers for 30-d mortality was compared in a prospective, observational study in an eight-bed ICU. We investigated concentrations of the biomarkers in plasma collected at admission from all ICU patients admitted during a year (2012-2013, n = 271) together with simplified acute physiology 3 scores (SAPS3) and sequential organ failure assessment (SOFA) scores. The receiver operating characteristic (ROC) analysis showed a higher area under the curve (AUC) value for calprotectin (0.79) than for PCT (0.49) when used as a sepsis marker. The calprotectin concentrations at admission were higher in non-survivors than in survivors at day 30. In our study, calprotectin was superior to PCT for distinguishing between ICU patients with sepsis and non-sepsis patients. Calprotectin also had higher predictive ability regarding 30-d mortality.

16.
Ups J Med Sci ; 124(4): 246-253, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31701794

RESUMO

Background: Acute respiratory distress syndrome (ARDS) is an acute inflammatory condition with pulmonary capillary leakage and lung oedema formation. There is currently no pharmacologic treatment for the condition. The antisecretory peptide AF-16 reduces oedema in experimental traumatic brain injury. In this study, we tested AF-16 in an experimental porcine model of ARDS.Methods: Under surgical anaesthesia 12 piglets were subjected to lung lavage followed by 2 hours of injurious ventilation. Every hour for 4 hours, measurements of extravascular lung water (EVLW), mechanics of the respiratory system, and hemodynamics were obtained.Results: There was a statistically significant (p = 0.006, two-way ANOVA) reduction of EVLW in the AF-16 group compared with controls. However, this was not mirrored in any improvement in the wet-to-dry ratio of lung tissue samples, histology, inflammatory markers, lung mechanics, or gas exchange.Conclusions: This pilot study suggests that AF-16 might improve oedema resolution as indicated by a reduction in EVLW in experimental ARDS.

17.
Intensive Care Med Exp ; 7(1): 59, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676929

RESUMO

BACKGROUND: Dynamic single-slice CT (dCT) is increasingly used to examine the intra-tidal, physiological variation in aeration and lung density in experimental lung injury. The ability of dCT to predict whole-lung values is unclear, especially for dual-energy CT (DECT) variables. Additionally, the effect of inspiration-related lung movement on CT variables has not yet been quantified. METHODS: Eight domestic pigs were studied under general anaesthesia, including four following saline-lavage surfactant depletion (lung injury model). DECT, dCT and whole-lung images were collected at 12 ventilatory settings. Whole-lung single energy scans images were collected during expiratory and inspiratory apnoeas at positive end-expiratory pressures from 0 to 20 cmH2O. Means and distributions of CT variables were calculated for both dCT and whole-lung images. The cranio-caudal displacement of the anatomical slice was measured from whole-lung images. RESULTS: Mean CT density and volume fractions of soft tissue, gas, iodinated blood, atelectasis, poor aeration, normal aeration and overdistension correlated between dCT and the whole lung (r2 0.75-0.94) with agreement between CT density distributions (r 0.89-0.97). Inspiration increased the matching between dCT and whole-lung values and was associated with a movement of 32% (SD 15%) of the imaged slice out of the scanner field-of-view. This effect introduced an artefactual increase in dCT mean CT density during inspiration, opposite to that caused by the underlying physiology. CONCLUSIONS: Overall, dCT closely approximates whole-lung aeration and density. This approximation is improved by inspiration where a decrease in CT density and atelectasis can be interpreted as physiological rather than artefactual.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31722419

RESUMO

OBJECTIVES: We investigated the cell adhesion molecules (CAMs) Vascular CAM 1 (VCAM-1) and Activated Leucocyte CAM (ALCAM) as urinary biomarkers in SLE patients with and without renal involvement. METHODS: Female SLE patients (n = 111) and non-SLE population-based controls (n = 99) were enrolled. We measured renal activity using the renal domain of the BILAG index and urine (U) and plasma (P) concentrations of soluble (s)VCAM 1 and U-sALCAM using ELISA. U-sCAM levels were next corrected by U-creatinine. RESULTS: U-sVCAM-1/creatinine and U-sALCAM/creatinine ratios were higher in SLE patients vs non-SLE controls (P < 0.001 for both), as well as in patients with active/low-active (BILAG A-C; n = 11) vs quiescent (BILAG D; n = 19) LN (P = 0.023 and P = 0.001, respectively). U-sALCAM/creatinine but not U-sVCAM-1/creatinine ratios were higher in patients with nephritis history (BILAG A-D; n = 30) vs non-renal SLE (BILAG E; n = 79) (P = 0.014). Patients with baseline U-sVCAM-1/creatinine ratios ≥75th percentile showed a 23-fold increased risk of a deterioration in estimated glomerular filtration rate by ≥25% during a 10-year follow-up (odds ratio: 22.9; 95% CI: 2.8, 189.2; P = 0.004); this association remained significant after adjustments for age, disease duration and organ damage. Traditional markers including anti-dsDNA antibodies did not predict this outcome. CONCLUSION: While high U-sVCAM-1 levels appear to reflect SLE disease activity, sALCAM might have particular importance in renal SLE. Both U-sVCAM-1 and U-sALCAM showed ability to distinguish SLE patients with active renal involvement from patients with quiescent or no prior nephritis. High U-sVCAM-1 levels may indicate patients at increased risk for long-term renal function loss.

19.
Horm Res Paediatr ; 92(2): 106-114, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31655800

RESUMO

INTRODUCTION: Obesity is increasing among the pregnant population. Leptin has an important role in the regulation of energy balance and hunger. The aim of this study was to investigate the association between maternal leptin levels with maternal obesity, gestational weight gain (GWG), single nucleotide polymorphisms (SNPs) within the leptin gene, and the age-adjusted birth weight of the child. MATERIAL AND METHODS: Maternal leptin levels (n = 740) and SNPs (n = 504) were analyzed in blood samples taken within the Uppsala Biobank of Pregnant women at pregnancy weeks 16-19. RESULTS: Maternal leptin levels differed significantly between body mass index (BMI) groups. Normal weight women had the lowest median leptin levels and levels increased with each BMI group. Leptin SNP genotype was not associated with leptin levels or BMI. There was also no association between maternal leptin levels and age-adjusted birth weight of the child except for a negative association between leptin levels and birth weight in the morbid obese group. DISCUSSION/CONCLUSION: Maternal BMI was identified as the best positive explanatory factor for maternal leptin levels. Leptin was a strong positive explanatory factor for GWG. Birth weight of children of uncomplicated pregnancies was, however, dependent on maternal height, BMI, GWG, and parity but not leptin levels, except for in morbid obese women where a negative association between maternal leptin levels and birth weight was found. We speculate that this indicates altered placental function, not manifested in pregnancy complication. We conclude that maternal leptin levels do not affect the birth weight of the child more than BMI, GWG, and parity.

20.
Sci Rep ; 9(1): 14521, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601945

RESUMO

Immunoassays are widely used for detection and quantification of analytes in biological samples, but are vulnerable to analytical errors caused by interfering sample substances. Of particular interest are endogenous anti-animal antibodies that may bind to the immunoassay antibodies and cause erroneous test results. This phenomenon is a hazard to patient safety in both human and veterinary medicine. Here, we demonstrate that anti-mouse antibodies in dogs bind selectively to different regions of the murine IgG molecule, cross-react with IgG from different species, and consist of all major antibody classes present in canine serum (IgA, IgG and IgM). The antibody characteristics varied among individuals and their prevalence differed between two dog breeds. The selective binding to different IgG regions suggests that the antibodies might not originate from immunization through exposure to mice or other species. These findings show that canine anti-mouse antibodies are highly heterogeneous in nature and therefore require a combination of strategies to be counteracted.

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