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Inhaled budesonide reduces lung hyperinflation in children with asthma.

Previous studies have shown that asthmatics have hyperinflation as defined by larger total lung capacity. The present study was set up in order to document changes in asthma clinic, airway calibre, airway reactivity and lung volumes after budesonide treatment. After a 2-week run-in period, 28 children with moderate persistent asthma were treated in a double-blind manner either with budesonide (0.4 mg/day) or placebo for 8 weeks and, thereafter, all patients were treated with open-label budesonide for a further 20 weeks. Symptoms, bronchodilator requirements and airway calibre improved significantly after 8 weeks of treatment (p < 0.05 for each) and prolonged treatment did not cause any further improvement. Reduction in hyperreactivity was apparent only after 20-28 weeks of treatment. Total lung capacity decreased along with budesonide treatment in both groups suggesting that early introduction of an inhaled corticosteroid may be useful in the prevention of asthma-related remodelling of the lung and thoracic cage.

Administration, Inhalation↗

[Lung function, gas exchange and regulation of ventilation in patients with portocaval encephalopathy (author's transl)].

In 17 patients, breathing room air and pure oxygen, with histologically proven cirrhosis of the liver and portocaval encephalopathy grade I, static and dynamic lung volumes, closing capacity and arterial blood gases were determined. Furthermore, CO2, response curves were provided and mouth occlusion pressure measurements were carried out. The residual volume was found to be increased (130 +/- 8% of predicted) which resulted in decreased vital capacity (79 +/- 2% of predicted) with total lung capacity being normal (94 +/- 2% of predicted). Closing capacity was increased to 134 +/- 5% of the predicted value. Gas exchange for oxygen was impaired (AaDO2 = 262 +/- 30% of predicted). Arterial PO2, however, was within normal range PaO2 = 84 +/- 3.6 mm Hg) due to hyperventilation (PaCO2 = 28.1 +/- 0.8 mm Hg). Hypoxic ventilatory stimulation could be excluded because inspiration of pure oxygen caused no change of PaCO2 (PaCO2 = 27.3 + 0.7 mm Hg and PaO2 = 465 + 16.9 mm Hg with FIO2 = 1.0). The slope of the CO2 response curves was normal, the mouth occlusion pressures, however, were higher than the predicted value: up to PaCO2 of 55 mm Hg. The slope of these curves being smaller than predicted. The results show that in patients with portocaval encephalopathy the lung function is disturbed due to premature airway closure with consequently decreased regional ventilation: perfusion ratios and that regulation of ventilation is impaired by a loss of sensitivity for CO2 with high basal output of the respiratory centers not related to CO2.

Blood Gas Analysis↗

The role of respiratory muscles in the hyperinflation of bronchial asthma.

To examine the mechanism of hyperinflation in bronchial asthma we studied lung and chest wall mechanics in 7 asymptomatic patients in whom progressive bronchoconstriction was induced by doubling the amount of inhaled aerosolized histamine. An increase in pulmonary resistance (RL) from 2.5 +/- 0.3 cmH2O . 1-1 . s (mean, +/- 1 SE) to 12.3 +/- 0.9 cmH2 was associated with a linear increase in functional residual capacity (FRC) up to 74.7 +/- 1.7% of control total lung capacity (TLCc). The mean regression coefficient was 2.3% TLCc . cmH2O-1 . 1 . s-1. At each level of hyperinflation the most positive expiratory pleural pressures measured during spontaneous breathing were generally less than the predicted chest wall relaxation pressures, indicating persistent inspiratory muscle contraction throughout expiration. This was predominantly due to inspiratory intercostal and accessory muscle activity, because measurements of transdiaphragmatic pressure indicated complete diaphragmatic relaxation early in expiration. Recruitment of abdominal muscles during expiration, inferred from measurements of gastric pressure (Pg) and abdominal antero-posterior (A-P) diameter, was progressively more apparent with increasing bronchoconstriction. We concluded that the increase in FRC in induced asthma is substantially influenced by persistent inspiratory intercostal and accessory muscle activity during expiration. Concomitant abdominal muscle recruitment results in a chest wall configuration that tends to optimize diaphragmatic function.

Abdomen↗

Pleural and parenchymal fibrosis mainly affecting the upper lung lobes in persons exposed to asbestos.

From the County of Uppsala, Sweden, more than 1600 persons with pleural plaques and/or asbestos-related pleural thickening have been seen at the Uppsala University Hospital during a period of about 15 years. During the observation time, 40 patients developed lesions mainly affecting the upper lobes of the lung. They were all men, 41 to 78-years-old, and all had been occupationally exposed to asbestos. The mean latency time from the first exposure was 34 years. The mean width of the apical pleural thickening was 21 mm. In 21 patients the lesions were on the right side, in 15 they were bilateral, and in only four patients was the left side alone affected. Biopsies from the pleura were available in twelve patients and from the lung parenchyma in eight. The biopsies of the lungs all showed varying degrees of asbestosis and of the pleura nonspecific pleuritis. The lesions tended to progress and in all cases except one they were part of a diffuse pleural and parenchymal fibrosis involving the rest of the lung. Consequently, the pulmonary function was impaired, with the vital capacity reduced to an average of 62% and total lung capacity to 68% of the predicted value. In many patients there was contraction of the upper lobe and deviation of the trachea towards the same side. Upper lobe changes are a relatively rare complication of exposure to asbestos but are important to recognise. Other possible causes of upper lobe changes such as tuberculosis must always be excluded before the diagnosis is made.

Adult↗

Cough stress rib fractures in two obstetric patients: case report and pathophysiology.

The clinical presentation of fractured ribs and physiology of cough in two obstetric patients are described to explain why a rib fracture, not a pneumothorax, occurred on coughing in these patients. At total lung capacity the outward expansion of the lower thorax (flare) during a cough is limited. The costal angles are widened at term pregnancy, and flare may then be almost impossible at total lung capacity. The insertional action of the diaphragm is virtually nil. A direct expiratory action of abdominal muscles predominates over their indirect inspiratory action. The lower ribs are pulled down by the cough and may even fracture from the enormous intrapleural cough pressures which are generated before the glottis opens.

Journal Article↗

Mechanism of action of ozone on the human lung.

Fourteen healthy normal volunteers were randomly exposed to air and 0.5 ppm of ozone (O3) in a controlled exposure chamber for a 2-h period during which 15 min of treadmill exercise sufficient to produce a ventilation of approximately 40 l/min was alternated with 15-min rest periods. Before testing an esophageal balloon was inserted, and lung volumes, flow rates, maximal inspiratory (at residual volume and functional residual capacity) and expiratory (at total lung capacity and functional residual capacity) mouth pressures, and pulmonary mechanics (static and dynamic compliance and airway resistance) were measured before and immediately after the exposure period. After the postexposure measurements had been completed, the subjects inhaled an aerosol of 20% lidocaine until response to citric acid aerosol inhalation was abolished. All of the measurements were immediately repeated. We found that the O3 exposure 1) induced a significant mean decrement of 17.8% in vital capacity (this change was the result of a marked fall in inspiratory capacity without significant increase in residual volume), 2) significantly increased mean airway resistance and specific airway resistance but did not change dynamic or static pulmonary compliance or viscous or elastic work, 3) significantly reduced maximal transpulmonary pressure (by 19%) but produced no changes in inspiratory or expiratory maximal mouth pressures, and 4) significantly increased respiratory rate (in 5 subjects by more than 6 breaths/min) and decreased tidal volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Abdominal distension alters regional pleural pressures and chest wall mechanics in pigs in vivo.

Abdominal distension (AD) occurs in pregnancy and is also commonly seen in patients with ascites from various causes. Because the abdomen forms part of the "chest wall," the purpose of this study was to clarify the effects of AD on ventilatory mechanics. Airway pressure, four (vertical) regional pleural pressures, and abdominal pressure were measured in five anesthetized, paralyzed, and ventilated upright pigs. The effects of AD on the lung and chest wall were studied by inflating a liquid-filled balloon placed in the abdominal cavity. Respiratory system, chest wall, and lung pressure-volume (PV) relationships were measured on deflation from total lung capacity to residual volume, as well as in the tidal breathing range, before and 15 min after abdominal pressure was raised. Increasing abdominal pressure from 3 to 15 cmH2O decreased total lung capacity and functional residual capacity by approximately 40% and shifted the respiratory system and chest wall PV curves downward and to the right. Much smaller downward shifts in lung deflation curves were seen, with no change in the transdiaphragmatic PV relationship. All regional pleural pressures increased (became less negative) and, in the dependent region, approached 0 cmH2O at functional residual capacity. Tidal compliances of the respiratory system, chest wall, and lung were decreased 43, 42, and 48%, respectively. AD markedly alters respiratory system mechanics primarily by "stiffening" the diaphragm/abdomen part of the chest wall and secondarily by restricting lung expansion, thus shifting the lung PV curve as seen after chest strapping. The less negative pleural pressures in the dependent lung regions suggest that nonuniformities of ventilation could also be accentuated and gas exchange impaired by AD.

Abdomen↗

Vital prognosis in intrathoracic sarcoidosis with special reference to pulmonary function and radiological stage.

A follow-up of 254 patients with intrathoracic sarcoidosis has been carried out after a median of 27 yrs from the diagnostic admission. All patients could be traced. At the end of follow-up there was no excess mortality (80 deaths observed versus 65.5 expected). However, during the first 20 yrs of follow-up a slight excess mortality was seen. Thirty three out of the 80 deaths were related to sarcoidosis. No excess number of deaths from lung cancer or lymphoma was observed. Erythema nodosum was of no prognostic significance concerning survival. X-ray stage was related to survival with a significant excess mortality for stage 3. Early clearing of X-ray changes gave a favourable vital prognosis. Survival was related to lung function, and for forced expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC) index and total lung capacity (TLC) this relationship reached levels of statistical significance. In multivariate Cox regression models, with age and sex entered as covariates, the same parameters were found to be significant predictors of mortality. Patients with FEV1 < or = 50% predicted had an increased mortality risk of 4.2 (95% confidence interval 1.8-9.6) when compared to patients with FEV1 > 80% predicted. Likewise, patients with TLC < or = 80% predicted had a mortality risk of 2.6 (1.5-4.5) when compared to patients with TLC > 80% predicted. In conclusion, a modest excess mortality was observed during the first 20 yrs of follow-up. Furthermore, both X-ray staging and lung function at the time of diagnosis influenced long-term mortality in patients with intrathoracic sarcoidosis.

Adult↗

Estimation of lung volumes from chest radiographs using shape information.

The cross-sectional shapes of the chest and its contained structures have been assessed in post-mortem anatomical sections and from computerised tomographic scans in living subjects. These shapes are described by simple equations that can be used to increase the accuracy of measuring lung volumes from chest radiographs. Radiographic estimates of total lung capacity, using the equations, were compared with plethysmographic and single-breath helium dilution measurements in 35 normal subjects. The postures commonly used for taking chest radiographs were found, on average, to decrease total lung capacity (TLC) and to increase residual volume by about 200 ml when compared with the sitting positions used for the other two measurements (studies made in 18 of the subjects). After correction for this effect, the radiographic estimates of TLC, which measure the displacement volume of the lung, exceeded the plethysmographic estimates of contained gas volume by a mean of 720 ml, which was taken as the volume of tissue, blood, and water in the lungs. The single-breath dilution estimates of TLC fell short of the plethysmographic values by a mean of 480 ml, taken as the volume of contained gas that was inaccessible to helium in 10 seconds. The tomographic studies suggested that the radiographic technique of measuring lung displacement volumes has an accuracy of +/- 210 ml. The method is rapid and simple to use and has intra- and inter-observer variabilities of less than 1% and less than 5% respectively.

Helium↗

Pulmonary function in Sardinian fire fighters.

Our study examined the respiratory function of 92 firemen whose main activity is fire fighting in forests and open country. Such fire fighting activities are to be considered a risk to the respiratory tract, taking into account studies already in the literature that have evaluated the nature and quantity of inhalable toxins present in activities of this kind. The control group was composed of 51 Carabinieri (policemen), who were asked to fill in a questionnaire about their work activities. Forced expiratory volume and flow, total lung capacity, respiratory volume, and the permeability of the alveolar-capillary barrier were measured. Firemen and Carabinieri (policemen) showed FVC rates higher than the European Community for Coal and Steel standards. The firemen showed a significant reduction in forced expiratory volume in 1 second (FEV1)[3.90 (0.50) vs. 4.04 (0.44); p < 0.05] and forced expiratory flow at 75% of forced vital capacity (FVC) (FEF75) [8.37 (4.11) vs. 8.38 (1.67) p < 0.05] and more markedly in the FEV 1/FVC relationship [80.07 (5.89) vs. 83.89 (1.67) p < 0.001] and in FEF50 [4.73 (1.34) vs. 5.54 (1.44) p < 0.01] and FEF25[1.58 (.47) vs. 1.99 (.69) p < 0.001]. There were no marked differences in air-blood exchanges. No correlation was found between respiratory function data and years of service or the number of fires extinguished during work experience.

Adult↗

Acute and chronic pulmonary function changes in allergic bronchopulmonary aspergillosis.

Pulmonary functions of patients with allergic bronchopulmonary aspergillosis were studied during an acute episode (n = 6); during a mean follow-up period of 44 months (range four months--14.8 years) (n = 16); and for any correlation between duration of ABPA and asthma with the total lung capacity (helium dilution), 1 second forced expiratory volume (FEV1), vital capacity, 1 second forced expiratory volume-forced vital capacity ratio (FEV1:FVC per cent) and diffusing capacity of carbon monoxide (DL:CO) (single breath) for the entire group (n = 22). All patients were treated with corticosteroids (intermittent or continuous) and bronchodilators. For the 16 patients, slopes using linear regression analysis were determined from the function as per cent predicted versus time in months from diagnosis and then analyzed for significance. Significant functional loss was shown in three of 16 patients for FEV1, two of 16 patients for vital capacity, one of 16 patients for FEV1:FVC per cent, none of 10 patients for DL:CO and one of 10 patients for total lung cital capacity, FEV1:FVC per cent and the duration of asthma or allergic bronchopulmonary aspergillosis was found by multiple regression analysis correcting for age and smoking (mean 4.24 years; range 0.3 to 14.8 years). Roentgenographic criteria and blood eosinophilia were used to define a "flare" of allergic bronchopulmonary aspergillosis. The six patients during a flare showed a significant reduction in total lung capacity (P less than 0.001), vital capacity (P less than 0.05), FEV1 (P less than 0.01) and DL:CO (P less than 0.001) which uniformly returned to baseline values during steroid therapy. The FEV1:FVC per cent remained unaltered. These findings, contrary to suggestions in the literature, indicate that in the majority of our patients there was no significant progressive functional deterioration after diagnosis. However, during acute episodes of allergic bronchopulmonary aspergillosis, transient reduction of volumes and DL:CO were uniformly present.

Adolescent↗

Changes in rib cage shape during quiet breathing, hyperventilation and single inspirations.

We measured the relative changes in upper and lower rib cage volume (delta RCU and delta RCL, respectively) using an induction coil plethysmograph (Respitrace) in seven normal seated subjects during relaxed passive expiration from total lung capacity, during quiet breathing, rapid breathing at 60 breaths/min (RB), during exercise-induced hyperventilation (EH) and during single fast inspirations. The plot of the RCU vs RCL was slightly curvilinear during relaxation from total lung capacity in all subjects. However, the inferred changes in rib cage shape were similar during RB and EH to those observed during quiet breathing and the relaxation manoeuvres. In contrast, single rapid inspirations were associated with marked and variable changes in rib cage shape, being most prominent in the first part of the breath. Our results suggest that during cyclic breathing respiratory muscle activity is so co-ordinated that the pattern of rib cage shape change is similar to that observed during relaxation. In contrast, single rapid inspirations are associated with markedly different and variable shape changes of the rib cage, presumably due to different patterns of inspiratory muscle recruitment. The results are consistent with the observation that during tidal breathing regional ventilation distribution is flow independent.

Adult↗

Effect of lung inflation in vivo on airways with smooth muscle tone or edema.

Fibrous attachments to the airway wall and a subpleural surrounding pressure can create an external load against which airway smooth muscle must contract. A decrease in this load has been proposed as a possible cause of increased airway narrowing in asthmatic individuals. To study the interaction between the airways and the surrounding lung parenchyma, we investigated the effect of lung inflation on relaxed airways, airways contracted with methacholine, and airways made edematous by infusion of bradykinin into the bronchial artery. Measurements were made in anesthetized sheep by using high-resolution computed tomography to visualize changes in individual airways. During methacholine infusion, airway area was decreased but increased minimally with increases in transpulmonary pressure. Bradykinin infusion caused a 50% increase in airway wall area and an small decrease in airway luminal area. In contrast to airways contracted with methacholine, the luminal area after bradykinin increased substantially with increases in transpulmonary pressure, reaching 99% of the relaxed area at total lung capacity. Thus airway edema by itself did not prevent full distension of the airway at lung volumes approaching total lung capacity. Therefore, we speculate that if a deep inspiration fails to relieve airway narrowing in vivo, this must be a manifestation of airway smooth muscle contraction and not airway wall edema.

Animals↗

Association of esophageal dysfunction and pulmonary function impairment in systemic sclerosis.

OBJECTIVE: The aim of this study was to investigate the relationship between esophageal dysfunction and pulmonary involvement in patients with systemic sclerosis (SSc). METHODS: Pulmonary function parameters were compared between groups of patients with and without manometric evidence for SSc-induced esophageal dysmotility. RESULTS: Twenty-six of 43 patients (60.5%) exhibited a marked hypo- or aperistalsis of the smooth muscle portion of the esophagus. Total lung capacity, inspiratory vital capacity, and forced vital capacity were significantly lower in patients with esophageal dysfunction compared with those with normal esophageal peristalsis (p < 0.001). Patients with the diffuse form of SSc (n = 20) had significantly lower values for total lung capacity and inspiratory vital capacity compared with patients with the limited type of SSc (n = 23; p < 0.05). CONCLUSION: There is a significant association of esophageal dysmotility with reduced lung volumes in SSc. Possible explanations for these findings are pulmonary damage due to increased gastroesophageal reflux and, more likely, simultaneous involvement of the lungs and the esophagus in the disease process.

Esophageal Motility Disorders↗

Functional analysis in single-lung transplant recipients: a comparative study of high-resolution CT, 3He-MRI, and pulmonary function tests.

OBJECTIVE: To develop and evaluate a postprocessing tool to quantify ventilated split-lung volumes on the basis of (3)He-MRI and to apply it in patients after single-lung transplantation (SLTX). High-resolution CT (HRCT) was employed as a reference modality providing split air-filled lung volumes. Lung volumes derived from pulmonary function test results served as clinical parameters and were used as the "gold standard." MATERIAL AND METHODS: Eight patients (mean age, 54 years) with emphysema and six patients (mean age, 58 years) with idiopathic pulmonary fibrosis. All patients were evaluated following SLTX. HRCT was performed during inspiration (slice thickness, 1 mm; increment, 10 mm). For correlation with (3)He-MRI, HRCT images were reconstructed in coronal orientation to match the same anatomic levels. Aerated lung was determined by threshold-based segmentation of CT. (3)He-MRI was performed on a 1.5-T scanner using a two-dimensional, fast low-angle shot sequence in coronal orientation covering the whole lung after inhalation of a 300-mL bolus of hyperpolarized (3)He gas followed by normal room air for the rest of the tidal volume. Lung segmentation on (3)He-MRI was done using different thresholds. RESULTS: In emphysematous patients, (3)He-MRI showed excellent correlation (r = 0.9) with vital capacity, while CT correlated (r = 0.8) with total lung capacity. (3)He-MRI correlated well with CT (r > 0.8) for grafts and native fibrotic lungs. In emphysematous lungs, MRI showed a good correlation (r = 0.7) with the nonemphysematous lung volume from CT. Increasing thresholds in (3)He-MRI reveal differences between aerated and ventilated lung areas with a different distribution in emphysema and fibrosis. CONCLUSIONS: (3)He-MRI is superior to CT in emphysema to demonstrate ventilated lung areas that participate in gas exchange. In fibrosis, (3)He-MRI and CT have a similar impact. The decrease pattern and the intraindividual ratio between ventilation of native and transplanted lungs will have to be investigated as a new surrogate for the ventilatory follow-up in patients undergoing SLTX.

Female↗

Lung volume and pleural pressure in the anesthetized hamster.

Lung volumes and respiratory pressures were measured in anesthetized male hamsters weighing an average 117 g. In 16 supine animals functional residual capacity (FRC) determined by body plethysmograph was 1.12 +/- 0.23 (SD) ml (about 20% total lung capacity, TLC) slightly and significantly larger than the FRC measured by saline displacement, 1.01 +/- 0.15 ml. Similar results were found in six prone animals. Paralysis did not significantly alter supine FRC. Contrary to published reports, pleural pressure (Ppl) estimated from esophageal pressure was negative at FRC. The fact that lung volume decreased by 0.2 ml (about 4% TLC) when the chest was opened at FRC provided additional evidence of negative Ppl at FRC. No consistent changes in the lung pressure-volume curve were found after the chest was opened. Deflation chest wall compliance just above FRC was about twice lung compliance. The vital capacity and reserve volumes in this study agreed with values reported in the literature. However, absolute lung volumes (TLC, FRC, and residual volume) were lower by about 1.4 ml, possibly because of earlier overestimates of box FRC.

Animals↗

Bronchial airway deposition and retention of particles in inhaled boluses: effect of anatomic dead space.

The fractional deposition of particles in boluses delivered to shallow lung depths and their subsequent retention in the airways may depend on the relative volume and size of an individual's airways. To evaluate the effect of variable anatomic dead space (ADS) on aerosol bolus delivery we had healthy subjects inhale radiolabeled, monodisperse aerosol (99mTc-iron oxide, 3.5 micron mean mondispersed aerosol diameter) boluses (40 ml) to a volumetric front depth of 70 ml into the lung at a lung volume of 70% total lung capacity end inhalation. By using filter techniques, aerosol photometry, and gamma camera analysis, we estimated the fraction of the inhaled boluses deposited in intrathoracic airways (IDF). ADS by single-breath N2 washout was also measured from 70% total lung capacity. Results showed that among all subjects IDF was variable (range = 0.04-0.43, coefficient of variation = 0.54) and increased with decreasing ADS (r = -0.76, P = 0.001, n = 16). We found significantly greater deposition in the left (L) vs. right (R) lungs; mean L/R (ratio of deposition in L lung to R lung, normalized to ratio of L-to-R lung volume) was 1.58 +/- 0.42 (SD; P < 0.001 for comparison with 1.0). Retention of deposited particles at 2 h was independent of ADS or IDF. There was significant retention of particles at 24 h postdeposition (0.27 +/- 0.05) and slow clearance of these particles continued through 48 h postdeposition. Finally, analysis of central-to-peripheral ratios of initial deposition and 24-h-retention gamma-camera images suggest significant retention of insoluble particles in large bronchial airways at 24 h postdeposition (i.e., 24 h central-to-peripheral ratio = 1.40 +/- 0. 44 and 1.82 +/- 0.54 in the R and L lung, respectively; P < 0.02 for comparison with 1.0). These data may prove useful for 1) designing aerosol delivery techniques to target bronchial airways and 2) understanding airway retention of inhaled particles.

Adult↗

The National Institutes of Health Intermittent Positive Pressure Breathing trial--pathology studies. III. The diagnosis of emphysema.

In an attempt to predict the severity of emphysema in patients with moderately severe and severe chronic air-flow obstruction, antemortem pulmonary function data, including spirometry, subdivisions of lung volumes, diffusing capacity (transfer factor) for carbon monoxide, and elastic recoil were assessed in 46 patients who were autopsied during the National Institutes of Health Intermittent Positive Pressure Breathing Clinical Trial and we compared these to the morphologic severity of emphysema. The severity of emphysema was graded by the panel grading method using whole lung, paper-mounted (Gough-Wentworth) sections and the mean linear intercept (Lm). The FEV1 and FEF25-75 of the FVC, the DLCO, the diffusing capacity for carbon monoxide, and subdivisions of lung volumes showed significant but low order correlations with the emphysema score and Lm. Total lung capacity, determined by plethysmography, was better related to emphysema in this study than in others in which TLC was measured by helium dilution. Volume-pressure data fitted to the exponential equation (V = A - Be-KP) yielded a low order, but a significant relationship between Lm and the exponential constant (K), but not between K and the panel emphysema score. We conclude that the recognition of the presence and severity of emphysema continues to require a multivariate approach including clinical history, assessment of air-flow obstruction via routine spirometry, radiologic assessment of the lung with emphasis on total lung capacity, and evaluation of the diffusing capacity for carbon monoxide.

Biomechanical Phenomena↗