Mycobacterium canettii Infection of Adipose Tissues

Adipose tissues were shown to host Mycobacterium tuberculosis which is persisting inside mature adipocytes. It remains unknown whether this holds true for Mycobacterium canettii, a rare representative of the M. tuberculosis complex responsible for lymphatic and pulmonary tuberculosis. Here, we infected primary murine white and brown pre-adipocytes and murine 3T3-L1 pre-adipocytes and mature adipocytes with M. canettii and M. tuberculosis as a positive control. Both mycobacteria were able to infect 18–22% of challenged primary murine pre-adipocytes; and to replicate within these cells during a 7-day experiment with the intracellular inoculums being significantly higher in brown than in white pre-adipocytes for M. canettii (p = 0.02) and M. tuberculosis (p = 0.03). Further in-vitro infection of 3T3-L1 mature adipocytes yielded 9% of infected cells by M. canettii and 17% of infected cells by M. tuberculosis (p = 0.001). Interestingly, M. canettii replicated and accumulated intra-cytosolic lipid inclusions within mature adipocytes over a 12-day experiment; while M. tuberculosis stopped replicating at day 3 post-infection. These results indicate that brown pre-adipocytes could be one of the potential targets for M. tuberculosis complex mycobacteria; and illustrate differential outcome of M. tuberculosis complex mycobacteria into adipose tissues. While white adipose tissue is an unlikely sanctuary for M. canettii, it is still an open question whether M. canettii and M. tuberculosis could persist in brown adipose tissues

Cardiopulmonary Response to Exercise in COPD and Overweight Patients: Relationship between Unloaded Cycling and Maximal Oxygen Uptake Profiles

Cardiopulmonary response to unloaded cycling may be related to higher workloads. This was assessed in male subjects: 18 healthy sedentary subjects (controls), 14 hypoxemic patients with chronic obstructive pulmonary disease (COPD), and 31 overweight individuals (twelve were hypoxemic). They underwent an incremental exercise up to the maximal oxygen uptake (VO 2 max), preceded by a 2 min unloaded cycling period. Oxygen uptake (VO 2 ), heart rate (HR), minute ventilation (VE), and respiratory frequency (fR) were averaged every 10 s. At the end of unloaded cycling period, HR increase was significantly accentuated in COPD and hypoxemic overweight subjects (resp., +14 ± 2 and +13 ± 1.5 min −1 , compared to +7.5 ± 1.5 min −1 in normoxemic overweight subjects and +8 ± 1.8 min −1 in controls). The fR increase was accentuated in all overweight subjects (hypoxemic: +4.5 ± 0.8; normoxemic: +3.9 ± 0.7 min −1 ) compared to controls (+2.5 ± 0.8 min −1 ) and COPDs (+2.0 ± 0.7 min −1 ). The plateau VE increase during unloaded cycling was positively correlated with VE values measured at the ventilatory threshold and VO 2 max. Measurement of ventilation during unloaded cycling may serve to predict the ventilatory performance of COPD patients and overweight subjects during an exercise rehabilitation program

Diaphragmatic motion recorded by M-mode ultrasonography: limits of normality

International audienceChest ultrasonography has proven to be useful in the diagnosis of diaphragm dysfunction. The aim of the present study was to determine the normal values of the motion of both hemidiaphragms recorded by M-mode ultrasonography. Healthy volunteers were studied while in a seated position. Diaphragmatic excursions and diaphragm profiles were measured during quiet breathing, voluntary sniffing and deep breathing. Diaphragmatic excursions were assessed by M-mode ultrasonography, using an approach perpendicular to the posterior part of the diaphragm. Anatomical M-mode was used for the recording of the complete excursion during deep breathing. The study included 270 men and 140 women. The diaphragmatic motions during quiet breathing and voluntary sniffing were successfully recorded in all of the participants. The use of anatomical M-mode was particularly suitable for measurement of the entire diaphragmatic excursion during deep breathing. The statistical analysis showed that the diaphragmatic excursions were larger in men compared to women, supporting the determination of normal values based on sex. The lower and upper limits of normal excursion were determined for men and women for both hemidiaphragms during the three manoeuvres that were investigated. The lower limits of normal diaphragmatic excursions during deep breathing should be used to detect diaphragmatic hypokinesia, i.e. 3.3 and 3.2 cm in women and 4.1 and 4.2 cm in men for the right and the left sides, respectively. The normal values of the diaphragmatic motion and the lower and upper limits of normal excursion can be used by clinicians to detect diaphragmatic dysfunction

Changes in Diaphragmatic Function Induced by an Increased Inspiratory Load Experienced by Military Divers: An Ultrasound Study

International audienceBackground: Inspiratory loading is experienced by military divers when they use rebreather device. Our objective was to assess the changes in diaphragm function induced by an increase in inspiratory load at values similar to those experienced by divers in real life. Methods : We recorded the excursion and the thickness of the right hemidiaphragm in 22 healthy male volunteers under inspiratory load conditions, using ultrasound in B- and M-mode. The measurements were performed at tidal volume and during breathing at 50% of inspiratory capacity. The breathing rate was regulated and similar in the various sessions with and without load. Results: The rebreather device used by French military divers leads to an increase in inspiratory load of close to 30 cmH 2 O. Consequently, the session under load was performed using a device set to this threshold. Significant increases in the excursion and the thickening fraction of the diaphragm were observed between the sessions at tidal volume and at high volume. With addition of the inspiratory load, the excursion of the right hemidiaphragm increased significantly from 2.3 to 3.4cm at tidal volume and from 3.9 to 4.7cm at high volume. The thickening fraction increased significantly from 30.4 to 76.6% at tidal volume and from 70 to 123% at high volume. The statistical analysis demonstrated that assessment of the changes of the thickening fraction during breathing at tidal volume was the most relevant marker to assess the impact of the inspiratory load on the diaphragm. Conclusion: Diaphragm ultrasound can be used to assess the changes in the diaphragm contraction pattern secondary to an increase in the respiratory load that can be generated by use a diving apparatus. The recording of the changes of the motion, and more importantly of the thickness of the diaphragm, during the breathing cycle is able to provide relevant information regarding the inspiratory load

Ultrasound assessment of the respiratory system using diaphragm motion-volume indices

International audienceBackground Although previous studies have determined limit values of normality for diaphragm excursion and thickening, it would be beneficial to determine the normal diaphragm motion-to-inspired volume ratio that integrates the activity of the diaphragm and the quality of the respiratory system. Methods To determine the normal values of selected ultrasound diaphragm motion-volume indices, subjects with normal pulmonary function testing were recruited. Ultrasound examination recorded diaphragm excursion on both sides during quiet breathing and deep inspiration. Diaphragm thickness was also measured. The inspired volumes of the corresponding cycles were systematically recorded using a spirometer. The indices were calculated using the ratio excursion, or percentage of thickening, divided by the corresponding breathing volume. From this corhort, normal values and limit values for normality were determined. These measurements were compared to those performed on the healthy side in patients with hemidiaphragm paralysis because an increase in hemidiaphragm activity has been previously demonstated in such circumstances. Results A total of 122 subjects (51 women, 71 men) with normal pulmonary function were included in the study. Statistical analysis revealed that the ratio of excursion, or percentage of thickening, to inspired volume ratio significantly differed between males and females. When the above-mentioned indices using excursion were normalized by body weight, no gender differences were found. The indices differed between normal respiratory function subjects and patients with hemidiaphragm paralysis (27 women, 41 men). On the paralyzed side, the average ratio of the excursion divided by the inspired volume was zero. On the healthy side, the indices using the excursion and the percentage of thickening during quiet breathing or deep inspiration were significantly increased comparedto patients with normal lung function. According to the logistic regression analysis, the most relevant indice appeared to be the ratio of the excursion measured during quiet breathing to the inspired volume. Conclusion The normal values of the diaphragm motion-volume indices could be useful to estimate the performance of the respiratory system. Proposed indices appear suitable in a context of hyperactivity

Cardiopulmonary Response to Exercise in COPD and Overweight Patients: Relationship between Unloaded Cycling and Maximal Oxygen Uptake Profiles

Cardiopulmonary response to unloaded cycling may be related to higher workloads. This was assessed in male subjects: 18 healthy sedentary subjects (controls), 14 hypoxemic patients with chronic obstructive pulmonary disease (COPD), and 31 overweight individuals (twelve were hypoxemic). They underwent an incremental exercise up to the maximal oxygen uptake (VO2max), preceded by a 2 min unloaded cycling period. Oxygen uptake (VO2), heart rate (HR), minute ventilation (VE), and respiratory frequency (fR) were averaged every 10 s. At the end of unloaded cycling period, HR increase was significantly accentuated in COPD and hypoxemic overweight subjects (resp., +14±2 and +13±1.5 min−1, compared to +7.5±1.5 min−1 in normoxemic overweight subjects and +8±1.8 min−1 in controls). The fR increase was accentuated in all overweight subjects (hypoxemic: +4.5±0.8; normoxemic: +3.9±0.7 min−1) compared to controls (+2.5±0.8 min−1) and COPDs (+2.0±0.7 min−1). The plateau VE increase during unloaded cycling was positively correlated with VE values measured at the ventilatory threshold and VO2max. Measurement of ventilation during unloaded cycling may serve to predict the ventilatory performance of COPD patients and overweight subjects during an exercise rehabilitation program

Staphylococcus aureus Nasal Colonization: An Update on Mechanisms, Epidemiology, Risk Factors, and Subsequent Infections

International audienceUp to 30% of the human population are asymptomatically and permanently colonized with nasal Staphylococcus aureus. To successfully colonize human nares, S. aureus needs to establish solid interactions with human nasal epithelial cells and overcome host defense mechanisms. However, some factors like bacterial interactions in the human nose can influence S. aureus colonization and sometimes prevent colonization. On the other hand, certain host characteristics and environmental factors can predispose to colonization. Nasal colonization can cause opportunistic and sometimes life-threatening infections such as surgical site infections or other infections in non-surgical patients that increase morbidity, mortality as well as healthcare costs

Ultrasound Assessment of Diaphragm Thickness and Thickening: Reference Values and Limits of Normality When in a Seated Position

International audienceBackground: Diagnosing diaphragm dysfunction in the absence of complete paralysis remains difficult. The aim of the present study was to assess the normal values of the thickness and the inspiratory thickening of both hemidiaphragms as measured by ultrasonography in healthy volunteers while in a seated position. Methods: Healthy volunteers with a normal pulmonary function test were recruited. The diaphragmatic thickness was measured on both sides at the zone of apposition of the diaphragm to the rib cage during quiet breathing at end-expiration, end-inspiration, and after maximal inspiration. The thickening ratio, the thickening fraction, and the thickness at end-inspiration divided by the thickness at deep breathing were determined. The mean values and the lower and upper limits of normal were determined for men and women. Results: 200 healthy volunteers (100 men and 100 women) were included in the study. The statistical analysis revealed that women had a thinner hemidiaphragm than men on both sides and at the various breathing times studied. The lower limit of normality of the diaphragm thickness measured at end-expiration was estimated to be 1.3 mm in men and 1.1 mm in women, on both sides. The thickening fraction did not differ significantly between men and women. In men, it ranged from 60 to 260% on the left side and from 57 to 200% on the right side. In women, it ranged from 58 to 264% on the left side and from 60 to 229% on the right side. The lower limits of normality of the thickening fraction were determined to be 40 and 39% in men and 39 and 48% in women for the right and left hemidiaphragms, respectively. The upper limit for normal of the mean of both sides of the ratio thickness at end-inspiration divided by the thickness at deep breathing was determined to be 0.78 in women and 0.79 in men. Conclusion: The normal values of thickness and the indexes of diaphragmatic function should help clinicians with detecting diaphragm atrophy and dysfunction

Role of proinflammatory activity contained in gastric juice from intensive care unit patients to induce lung injury in a rabbit aspiration model

OBJECTIVE: Although aspiration pneumonitis is a severe complication in patients hospitalized in intensive care units, its pathogenesis is poorly understood. The aim of this study was to determine whether the intensity of lung injury and inflammation developing after aspiration during mechanical ventilation differed depending on the inflammatory activity of intensive care unit patients' gastric fluid. DESIGN: In vitro study on human gastric juice and randomized controlled animal study. SETTING: Research laboratories of academic institutions. SUBJECTS: Male New-Zealand white rabbits. INTERVENTIONS: Proinflammatory activity of gastric juice from 17 intensive care unit patients and 12 controls undergoing elective surgery was measured based on a target cell activation assay. Two gastric juices from intensive care unit patients with similar pH but differing for their in vitro proinflammatory activity (high and low) were further instilled into the trachea of ventilated rabbits. Lung function, mechanics, pathology, leukocyte infiltration, and local cytokine levels were measured after 6 hrs. MEASUREMENTS AND MAIN RESULTS: Gastric juice from intensive care unit patients, even buffered at pH 7.4, stimulated human type II-like A549 epithelial cells to up-regulate intercellular adhesion molecule-1 and interleukin-8, significantly more than juice obtained in controls. Gastric juice from an intensive care unit patient supporting high proinflammatory activity in vitro also induced a more severe and persistent drop in PaO2/FIO2 and respiratory system compliance in ventilated rabbits, a worse histologic score, higher lung lavage concentrations of inflammatory cells, interleukin-8 (p < 0.01), and growth-related oncogene-alpha (p < 0.01) than one fluid with low proinflammatory activity. CONCLUSION: Gastric juice from critically ill patients is proinflammatory and stimulates human pulmonary cells in vitro. A human gastric juice with high proinflammatory activity is more "toxic" to the lung than one with low proinflammatory activity in a ventilated rabbit model, an effect that is independent of pH and particulate matter content