Self-Reported Psychosomatic Complaints and Conduct Problems in Swedish Adolescents.

Physical conditions in children and adolescents are often under reported during mainstream school years and may underlie mental health disorders. Additionally, comparisons between younger and older schoolchildren may shed light on developmental differences regarding the way in which physical conditions translate into conduct problems. The aim of the current study was to examine the incidence of psychosomatic complaints (PSC) in young and older adolescent boys and girls who also report conduct problems. A total of 3132 Swedish adolescents (age range 15-18 years, 47% boys) completed the Uppsala Life and Health Cross-Sectional Survey (LHS) at school. The LHS question scores were categorised by two researchers who independently identified questions that aligned with DSM-5 conduct disorder (CD) criteria and PSC. MANOVA assessed the effects of PSC, age, and gender on scores that aligned with the DSM criteria for CD. The main effects of gender, age, and PSC on the conduct problem scores were observed. Adolescents with higher PSC scores had higher conduct problem scores. Boys had higher serious violation of rules scores than girls, particularly older boys with higher PSC scores. Psychosomatic complaints could be a useful objective identifier for children and adolescents at risk of developing conduct disorders. This may be especially relevant when a reliance on a child's self-reporting of their behavior may not help to prevent a long-term disturbance to their quality of life.

An obesity-associated risk allele within the FTO gene affects human brain activity for areas important for emotion, impulse control and reward in response to food images.

Understanding how genetics influences obesity, brain activity and eating behaviour will add important insight for developing strategies for weight-loss treatment, as obesity may stem from different causes and as individual feeding behaviour may depend on genetic differences. To this end, we examined how an obesity risk allele for the FTO gene affects brain activity in response to food images of different caloric content via functional magnetic resonance imaging (fMRI). Thirty participants homozygous for the rs9939609 single nucleotide polymorphism were shown images of low- or high-calorie food while brain activity was measured via fMRI. In a whole-brain analysis, we found that people with the FTO risk allele genotype (AA) had increased activity compared with the non-risk (TT) genotype in the posterior cingulate, cuneus, precuneus and putamen. Moreover, higher body mass index in the AA genotype was associated with reduced activity to food images in areas important for emotion (cingulate cortex), but also in areas important for impulse control (frontal gyri and lentiform nucleus). Lastly, we corroborate our findings with behavioural scales for the behavioural inhibition and activation systems. Our results suggest that the two genotypes are associated with differential neural processing of food images, which may influence weight status through diminished impulse control and reward processing.

Regional pulmonary inflammation in an endotoxemic ovine acute lung injury model.

The regional distribution of inflammation during acute lung injury (ALI) is not well known. In an ovine ALI model we studied regional alveolar inflammation, surfactant composition, and CT-derived regional specific volume change (sVol) and specific compliance (sC). 18 ventilated adult sheep received IV lipopolysaccharide (LPS) until severe ALI was achieved. Blood and bronchoalveolar lavage (BAL) samples from apical and basal lung regions were obtained at baseline and injury time points, for analysis of cytokines (IL-6, IL-1ß), BAL protein and surfactant composition. Whole lung CT images were obtained in 4 additional sheep. BAL protein and IL-1ß were significantly higher in injured apical vs. basal regions. No significant regional surfactant composition changes were observed. Baseline sVol and sC were lower in apex vs. base; ALI enhanced this cranio-caudal difference, reaching statistical significance only for sC. This study suggests that apical lung regions show greater inflammation than basal ones during IV LPS-induced ALI which may relate to differences in regional mechanical events.

Impact of positive end-expiratory pressure during heterogeneous lung injury: insights from computed tomographic image functional modeling.

Image Functional Modeling (IFM) synthesizes three dimensional airway networks with imaging and mechanics data to relate structure to function. The goal of this study was to advance IFM to establish a method of exploring how heterogeneous alveolar flooding and collapse during lung injury would impact regional respiratory mechanics and flow distributions within the lung at distinct positive end-expiratory pressure (PEEP) levels. We estimated regional respiratory system elastance from computed tomography (CT) scans taken in 5 saline-lavaged sheep at PEEP levels from 7.5 to 20 cmH(2)O. These data were anatomically mapped into a computational sheep lung model, which was used to predict the corresponding impact of PEEP on dynamic flow distribution. Under pre-injury conditions and during lung injury, respiratory system elastance was determined to be spatially heterogeneous and the values were distributed with a hyperbolic distribution in the range of measured values. Increases in PEEP appear to modulate the heterogeneity of the flow distribution throughout the injured lung. Moderate increases in PEEP decreased the heterogeneity of elastance and predicted flow distribution, although heterogeneity began to increase for PEEP levels above 12.5-15 cmH(2)O. By combining regional respiratory system elastance estimated from CT with our computational lung model, we can potentially predict the dynamic distribution of the tidal volume during mechanical ventilation and thus identify specific areas of the lung at risk of being overdistended.

Dynamic assessment of paranasal sinus ventilation using xenon-enhanced computed tomography.

Disease of the paranasal sinuses is a common and costly condition. Evaluation of the efficacy of either medical or surgical methods of treatment is limited by the lack of quantitative methods to characterize sinus ventilation, which may be an important determinant of the baseline physiological state of the sinuses. Xenon-enhanced computed tomography (Xe-CT) measurement of sinus ventilation provides a noninvasive method of quantifying maxillary sinus ventilation using the nonradioactive, radiodense gas Xe as a tracer. Study subjects breathed a mixture of Xe gas and oxygen through a close-fitting nasal mask during serial CT imaging of a single radiographic plane through the maxillary sinuses--a generally well-tolerated protocol. Analysis of the sinus density-time curves allowed calculation of first-order exponential time constants from which specific ventilation rates could be determined for individual sinuses. Previously developed data analysis techniques were used to assess the statistical significance of the data and determine confidence intervals, allowing examination of the effects of noise in the data, and to demonstrate areas for further study protocol refinement. We conclude that Xe-CT measurement of sinus ventilation is a potentially valuable noninvasive technique for the diagnostic imaging of the human maxillary sinus.

Distribution of pulmonary ventilation using Xe-enhanced computed tomography in prone and supine dogs.

Xe-enhanced computed tomography (CT; Xe-CT) is a method for the noninvasive measurement of regional pulmonary ventilation in intact subjects, determined from the washin and washout rates of the radiodense, nonradioactive gas Xe, as measured in serial CT scans. We used the Xe-CT ventilation method, along with other quantitative CT measurements, to investigate the distribution of regional lung ventilation and air content in healthy, anesthetized, mechanically ventilated dogs in the prone and supine postures. Vertical gradients in regional ventilation and air content were measured in five mongrel dogs in both prone and supine postures at four axial lung locations. In the supine position, ventilation increased with dependent location, with a mean slope of 7.3%/cm lung height, whereas no ventilation gradients were found at any location in the prone position. These results agree quantitatively with other published studies. In addition, six different animals were studied (3 supine, 3 prone) to examine the longitudinal distribution of ventilation and air content. The prone lungs were more uniformly inflated compared with the supine, which were less well expanded at the base than apex. Ventilation index, a measure of regional ventilation relative to whole lung ventilation, increased steeply from apex to base in the supine animals, whereas it was again more uniform in the prone condition. We conclude that the Xe-CT method provides a reasonable, quantitative measurement of regional ventilation and promises to be a valuable tool for the noninvasive determination of regional lung function.

Biologic variability in mechanical ventilation rate and tidal volume does not improve oxygenation or lung mechanics in canine oleic acid lung injury.

Mechanical ventilation in patients with acute respiratory distress syndrome and acute lung injury (ALI) remains a difficult challenge because of the conflict between maintaining adequate gas exchange and furthering lung injury via overdistention. In a recent study, Lefevre and colleagues (Am. J. Respir. Crit. Care Med. 1996;154: 1567-1572) suggested that mechanical ventilation with natural biologic variability (BV) in breath-to-breath respiratory frequency (f) and VT could reduce lung injury and improve gas exchange without increases in mean airway pressure (Paw) or peak inspiratory pressure (PIP). However, significant differences in cardiac output (CO), Pa(CO(2)), pH, and delivered VT between the treatment groups in their study could have influenced these results. Because of the potential implications of these findings for patient care, we attempted to confirm these findings by Lefevre and colleagues in a canine model of oleic acid-induced lung injury. Eighteen mongrel dogs were anesthetized in the supine position, paralyzed, and mechanically ventilated with 50% O(2) at f = 15 breaths/min, and VT was adjusted to achieve an end-tidal CO(2) of 30 to 35 mm Hg. Lung injury was produced by infusion of 0.06 ml/kg oleic acid solution into the right atrium over a 30-min period. Animals were then randomized to either conventional ventilation at the baseline settings (n = 9) or to BV at the same mean VT and f (n = 9). Both groups received comparable degrees of injury, and hemodynamic and ventilatory parameters were closely matched, with no differences in mean VT, PIP, mean Paw, Pa(CO(2)), pH, CO, pulmonary artery occlusion pressure, or arterial pressure (Pa). However, no differences between the two groups were found in Pa(O(2)), shunt, or static compliance over a 4-h period. When hemodynamic and ventilatory parameters were well matched in a canine model of ALI, BV showed no advantage over conventional ventilation at constant VT and f.

Xenon-enhanced computed tomography quantifies normal maxillary sinus ventilation.

OBJECTIVE: The purpose of this study was to determine the applicability, safety, and normal parameters of a xenon-enhanced CT technique to quantify maxillary sinus ventilation. PATIENTS AND METHODS: Nine healthy subjects inhaled a xenon-oxygen-air mixture through their noses while repeated CT scans were performed through the same section of their sinuses. Images were obtained every 1 to 3 minutes and analyzed to measure the density of the gas in the maxillary sinus as a function of time. RESULTS: Individual nasal cavity time constants ranged from 0.5 to 18 minutes. Studies performed after decongestion showed poorer sinus ventilation. CONCLUSIONS: The xenon-CT washin/washout technique is safe, effective, and gives representative data.

Non-invasive imaging of regional lung function using x-ray computed tomography.

The use of imaging technologies has progressed beyond the depiction of anatomic abnormalities to providing non-invasive regional structure and functional information in intact subjects. These data are particularly valuable in studies of the lung, since lung disease is heterogeneous and significant loss of function may occur before it is detectable by traditional whole lung measurements such as oxygenation, compliance, or spirometry. While many imaging modalities are available, X-ray computed tomography (CT) is emerging as the preferred method for imaging the lung because of its widespread availability, resolution, high signal/noise ratio for lung tissue, and speed. Utilizing the quantitative density and dimensional information available from conventional CT images, it is possible to measure whole and regional lung volumes, distribution of lung aeration and recruitment behavior under various clinical conditions and interventions, and important regional mechanical properties. In addition, using the radiodense gas xenon (Xe) as a contrast agent, regional ventilation or gas transport may also be obtained. This communication will review recent advances in CT based techniques for the measurement of regional lung function.

Pulmonary vascular endothelial responses are differentially modulated after cardiopulmonary bypass.

The aim of this study was to characterize the mechanisms underlying pulmonary vascular dysfunction after cardiopulmonary bypass (CPB) by examining responses of isolated pulmonary arteries to selective endothelium-dependent and -independent activators in control and post-CPB dogs. Adult male mongrel dogs were placed on closed-chest, hypothermic CPB for 2.5 h, and then allowed to recover. Anatomically matched pulmonary arterial rings were isolated and suspended for isometric tension recording. Contractile responses to the alpha1-adrenergic agonist phenylephrine were similar in endothelium-containing arteries from control and CPB animals. Endothelium denudation increased contractions to phenylephrine to a similar extent in both groups. Endothelium-dependent relaxation to acetylcholine was decreased 4 days after CPB compared with controls. In contrast to acetylcholine, endothelium-dependent relaxation to bradykinin or to A23187 were not impaired 4 days after CPB. Inhibition of nitric oxide synthase (NOS) with L-NAME depressed the response to acetylcholine in control vessels, confirming that a component of the response to acetylcholine was nitric oxide (NO) dependent. At lower concentrations of acetylcholine, this component of the response was abolished after CPB. The residual relaxation evoked by acetylcholine in the presence of L-NAME also was impaired in CPB compared with control arteries. This suggests that the CPB-induced impairment of acetylcholine-evoked relaxation may not involve both an NO-mediated and an NO-independent component. L-NAME depressed the response to bradykinin to a similar degree in control and CPB arteries. Vascular smooth-muscle dilatation to the NO donor, SIN-1, or to the K+ATP-channel opener, cromakalim, were similar in endothelium-denuded arteries from CPB and control animals. These results suggest that CPB causes a selective impairment in endothelial dilator function without changing the vascular smooth-muscle response to vasodilator or vasoconstrictor stimuli.

A comprehensive equation for the pulmonary pressure-volume curve.

Quantification of pulmonary pressure-volume (P-V) curves is often limited to calculation of specific compliance at a given pressure or the recoil pressure (P) at a given volume (V). These parameters can be substantially different depending on the arbitrary pressure or volume used in the comparison and may lead to erroneous conclusions. We evaluated a sigmoidal equation of the form, V = a + b[1 - e-(P-c)/d]-1, for its ability to characterize lung and respiratory system P-V curves obtained under a variety of conditions including normal and hypocapnic pneumoconstricted dog lungs (n = 9), oleic acid-induced acute respiratory distress syndrome (n = 2), and mechanically ventilated patients with acute respiratory distress syndrome (n = 10). In this equation, a corresponds to the V of a lower asymptote, b to the V difference between upper and lower asymptotes, c to the P at the true inflection point of the curve, and d to a width parameter proportional to the P range within which most of the V change occurs. The equation fitted equally well inflation and deflation limbs of P-V curves with a mean goodness-of-fit coefficient (R2) of 0.997 +/- 0.02 (SD). When the data from all analyzed P-V curves were normalized by the best-fit parameters and plotted as (V-a)/b vs. (P-c)/d, they collapsed into a single and tight relationship (R2 = 0.997). These results demonstrate that this sigmoidal equation can fit with excellent precision inflation and deflation P-V curves of normal lungs and of lungs with alveolar derecruitment and/or a region of gas trapping while yielding robust and physiologically useful parameters.

Parameter estimation and confidence intervals for Xe-CT ventilation studies: a Monte Carlo approach.

Xenon-enhanced computed tomography (Xe-CT) is a technique for the noninvasive measurement of regional pulmonary ventilation from the washin and/or washout time constants of radiodense stable xenon gas, determined from serial computed tomography scans. Although the measurement itself is straightforward, there is a need for methods for the estimation of variability and confidence intervals so that the statistical significance of the information obtained may be evaluated, particularly since obtaining repeated measurements is often not practical. We present a Monte Carlo (MC) approach to determine the 95% confidence interval (CI) for any given measurement. This MC method was characterized in terms of its unbiasedness and coverage of the CI. In addition, 10 identical Xe-CT ventilation runs were performed in an anesthetized dog, and the time constant was determined for several regions of varying size in each run. The 95% CI, estimated from these repeated measurements as the mean +/- 2 x SE, compared favorably with the CI obtained by the MC approach. Finally, a simulation was performed to compare the performance of three imaging protocols in estimating model parameters.

Effect of hypoxia on respiratory system impedance in dogs.

The effects of hypoxia on lung and airway mechanics remain controversial, possibly because of the confounding effects of competing reflexes caused by systemic hypoxemia. We compared the effects of systemic hypoxemia with those of unilateral alveolar hypoxia (with systemic normoxemia) on unilateral respiratory system impedance (Z) in intact, anesthetized dogs. Independent lung ventilation was obtained with a Kottmeier endobronchial tube. Individual left and right respiratory system Z was measured during sinusoidal forcing with 45 ml of volume at frequencies of 0.2-2.1 Hz during control [100% inspired O2 fraction (FIO2)], systemic hypoxemia (10% FIO2), and unilateral alveolar hypoxia (0% FIO2 to left lung, 100% FIO2 to right lung). During systemic hypoxemia, there was a mean Z magnitude increase of 18%. This change was entirely attributable to a decrease in the imaginary component of Z; there was no change in the real component of Z. Administration of atropine (0.2 mg/kg) did not block the increase in Z with systemic hypoxemia. In contrast, there was no change in Z in the lung subjected to unilateral alveolar hypoxia. We conclude that alveolar hypoxia has no direct effect on lung mechanical properties in intact dogs. In contrast, systemic hypoxemia does increase lung impedance, apparently through a noncholinergic mechanism.

Selective endothelial dysfunction in conscious dogs after cardiopulmonary bypass.

It has previously been demonstrated that cardiopulmonary bypass (CPB) causes prolonged pulmonary vascular hyperreactivity (D.P. Nyhan, J.M. Redmond, A.M. Gillinov, K. Nishiwaki, and P.A. Murray. J. Appl. Physiol. 77: 1584-1590, 1994). This study investigated the effects of CPB on endothelium-dependent (acetylcholine and bradykinin) and endothelium-independent (sodium nitroprusside) pulmonary vasodilation in conscious dogs. Continuous left pulmonary vascular pressure-flow (LP-Q) plots were generated in conscious dogs before CPB and again in the same animals 3-4 days post-CPB. The dose of U-46619 used to acutely preconstrict the pulmonary circulation to similar levels pre- and post-CPB was decreased (0.13 +/- 0.01 vs. 0.10 +/- 0.01 mg.kg-1.min-1, P < 0.01) after CPB. Acetylcholine, bradykinin, and sodium nitroprusside all caused dose-dependent pulmonary vasodilation pre-CPB. The pulmonary vasodilator response to acetylcholine was completely abolished post-CPB. For example, at left pulmonary blood flow of 80 ml.kg-1.min-1 acetylcholine (10 micrograms.kg-1.min-1) resulted in 72 +/- 15% reversal (P < 0.01) of U-46619 preconstriction pre-CPB but caused no change post-CPB. However, the responses to bradykinin and sodium nitroprusside were unchanged post-CPB. The impaired pulmonary vasodilator response to acetylcholine, but not to bradykinin, suggests a selective endothelial defect post-CPB. The normal response to sodium nitroprusside indicates that cGMP-mediated vasodilation is unchanged post-CPB.

Changes in regional lung mechanics and ventilation distribution after unilateral pulmonary artery occlusion.

Regional pneumoconstriction induced by alveolar hypocapnia is an important homeostatic mechanism for optimization of ventilation-perfusion matching. We used positron imaging of 13NN-equilibrated lungs to measure the distribution of regional tidal volume (VT), lung volume (VL), and lung impedance (Z) before and after left (L) pulmonary artery occlusion (PAO) in eight anesthetized, open-chest dogs. Measurements were made during eucapnic sinusoidal ventilation at 0.2 Hz with 4-cmH2O positive end expiratory pressure. Right (R) and L lung impedances (ZR and ZL) were determined from carinal pressure and positron imaging of dynamic regional VL. LPAO caused an increase in magnitude of ZL relative to magnitude of ZR, resulting in a shift in VT away from the PAO side, with a L/R magnitude of Z ratio changing from 1.20 +/- 0.07 (mean +/- SE) to 2.79 +/- 0.85 after LPAO (P < 0.05). Although mean L lung VL decreased slightly, the VL normalized parameters specific admittance and specific compliance both significantly decreased with PAO. Lung recoil pressure at 50% total lung capacity also increased after PAO. We conclude that PAO results in an increase in regional lung Z that shifts ventilation away from the affected area at normal breathing frequencies and that this effect is not due to a change in VL but reflects mechanical constriction at the tissue level.

Permissive hypercapnia with high-frequency oscillatory ventilation and one-lung isolation for intraoperative management of lung resection in a patient with multiple bronchopleural fistulae.

We report the use of high-frequency oscillatory ventilation in the operating room during repair of multiple bronchopleural fistulae in a 9-year-old boy. In addition, we used principles of permissive hypercapnia to further minimize barotrauma. There were no cardiovascular consequences due to either the high-frequency ventilation or the permissive hypercapnia. Our goals in employing this strategy were to minimize barotrauma, minimize gas flow through the fistulae, and optimize the surgical results.

Ventilation distribution and regional lung impedance during partial unilateral bronchial obstruction.

Significant degrees of main-stem bronchial obstruction may not have a detectable effect on ventilation distribution at normal breathing frequencies. We determined the effect of graded left main-stem bronchial obstruction (area reduction of 50 and 70%) on the distribution of tidal volume (VT) and mean lung volume (VL) using radioactive 13NN and two-dimensional planar positron imaging in six supine anesthetized tracheotomized dogs. Measurements were made during eucapnic high-frequency oscillatory ventilation at frequencies (f) of 0.2, 1, 5, and 10 Hz. Right and left lung respiratory system complex impedance (Z) values were assessed by simultaneous measurements of dynamic regional lung volume by positron imaging and carinal pressure. The results show a progressive shift of VT away from the obstruction at f > 1 Hz, with VT left-to-right (L/R) ratios of 0.9, 0.9, 0.58, and 0.46 at f of 0.2, 1, 5, and 10 Hz, respectively, for 70% obstruction. VT shifts with f for 50% obstruction were similar but of lesser magnitude. VL L/R ratio was 0.88 and did not change with f or obstruction. The real part of Z was frequency dependent and increased at low f independent of obstruction. The real part of Z L/R ratio increased with obstruction at 5 and 10 Hz. At low f there was a difference between left and right imaginary parts of Z due to the difference in VL. There was no significant change in the imaginary part of Z as a result of obstruction. We conclude that up to a 70% unilateral bronchial obstruction is not detectable by distribution of ventilation at f < or = 1 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)

Analyzing 13NN lung washout curves in the presence of intraregional nonuniformities.

The use of 13NN and positron imaging provides a powerful noninvasive means of assessing regional pulmonary function. Current techniques for analyzing lung washout curves, however, are subject to error due to intraregional nonuniformities, particularly in the presence of areas with very long time constants or gas trapping. This paper presents a simple "hybrid" method for analyzing 13NN-washout studies that addresses the problems of regions of air trapping and long time constants within a region of interest. This method assumes an exponential washout form for the slow regions, estimates their fractional volume, and subtracts their contribution from the overall washout curve. The modified Stewart-Hamilton method is then applied to the remaining washout curve to calculate its ventilation. The over-all specific ventilation of the region is calculated as the volume-weighted average of the specific ventilations of the two compartments. The performance of the hybrid method is compared with other currently used correction techniques by using a simulated two-compartment lung washout in which there is a variable amount of gas trapping. The analysis techniques are also applied to washout data with intraregional nonuniformities obtained during experimentally created unilateral bronchial obstruction. This new approach has the advantages of automatically correcting for washout truncation, estimating the relative size of the trapped or slow region while eliminating its bias on the regional ventilation, and yet retaining the unrestricted and robust nature of the Stewart-Hamilton method in the analysis of the well-ventilated regions.

A mass balance model for the Mapleson D anaesthesia breathing system.

A mathematical model is described which calculates the alveolar concentration of CO2(FACO2) in a patient breathing through a Mapleson D anaesthesia system. The model is derived using a series of mass balances for CO2 in the alveolar space, dead space, breathing system limb volume and reservoir. The variables included in the model are tidal volume (VT), respiratory rate, fresh gas flow rate (Vf), dead space volume, I:E ratio, and expiratory limb volume (Vl) time constant of lung expiration, and carbon dioxide production rate. The model predictions are compared with measurements made using a mechanical lung simulator in both spontaneous and controlled ventilation. Both the model and the experimental data predict that at high fresh gas flow rates and low respiratory rates, FACO2 is independent of Vf; at low fresh gas flow rates and high respiratory rates, FACO2 is independent of respiratory rate. The model and the data show that the VT influences FACO2, independent of minute ventilation alone, during both partial re-breathing and non-rebreathing operation. Therefore, describing the operation in terms of minute ventilation is ambiguous. It is also shown that Vl influences FACO2 such that, for any combination of patient and breathing-system variables, there is a Vl that minimizes the Vf required to maintain FACO2. In addition, expiratory resistance can increase the fresh gas flow rate required to maintain a given FACO2. The respiratory patterns observed with spontaneous and controlled ventilation are responsible for the difference in Vf required with each mode of ventilation.