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Global signal regression (GSR) is a controversial analysis method, since its removal of signal has been observed to reduce the reliability of functional connectivity estimates. Here, we used test-retest reliability to characterize potential differences in spatial patterns between conventional, static GSR (sGSR) and a novel dynamic form of GSR (dGSR). In contrast with sGSR, dGSR models the global signal at a time delay to correct for blood arrival time. Thus, dGSR accounts for greater variation in global signal, removes blood-flow-related nuisance signal, and leaves higher quality neuronal signal remaining. We used intraclass correlation coefficients (ICCs) to estimate the reliability of functional connectivity in 462 healthy controls from the Human Connectome Project. We tested across two factors: denoising method used (control, sGSR, and dGSR), and interacquisition interval (between days, or within session while varying phase encoding direction). Reliability was estimated regionally to identify topographic patterns for each condition. sGSR and dGSR provided global reductions in reliability compared with the non-GSR control. Test-retest reliability was highest in the frontoparietal and default mode regions, and lowest in sensorimotor cortex for all conditions. dGSR provides more effective denoising in regions where both strategies greatly reduce reliability. Both GSR methods substantially reduced test-retest reliability, which was most evident in brain regions that had low reliability prior to denoising. These findings suggest that reliability of interregional correlation is likely inflated by the global signal, which is thought to primarily reflect dynamic blood flow.

Forced vital capacity (FVC) decline is predictive of mortality in patients with idiopathic pulmonary fibrosis (IPF) and has been used as a clinical trial endpoint to define disease progression. How to interpret FVC findings in an individual patient with IPF in the real-world setting amid uncertainty about the measurement accuracy and variability has not been well established.This review highlights the challenges and limitations of using FVC in the clinic to monitor disease progression in patients with IPF. Spirometry is noninvasive, relatively simple, and inexpensive. FVC measurements provide evidence for trends over time in patients with IPF. When using FVC in the clinic, several important challenges and limitations, including visit-to-visit variability, dependence on patient effort, inconsistent quality control, limitations on accuracy, and the influence of comorbidities and pretest factors, must be considered. Recent studies suggest the potential for home spirometry devices to facilitate more frequent collection of data and perhaps demonstrate more accurate trends.Measuring FVC decline in the clinic has an important role in monitoring disease progression in patients with IPF, but additional measures of disease progression should be considered along with FVC to facilitate decision-making about disease management.

Coronavirus disease 2019 (COVID-19) has negatively affected the delivery of respiratory diagnostic services across the world due to the potential risk of disease transmission during lung function testing. Community prevalence, reoccurrence of COVID-19 surges and the emergence of different variants of SARS-CoV-2 have impeded attempts to restore services. Finding consensus on how to deliver safe lung function services for both patients attending and for staff performing the tests are of paramount importance.This international statement presents the consensus opinion of 23 experts in the field of lung function and respiratory physiology balanced with evidence from the reviewed literature. It describes a robust roadmap for restoration and continuity of lung function testing services during the COVID-19 pandemic and beyond.Important strategies presented in this consensus statement relate to the patient journey when attending for lung function tests. We discuss appointment preparation, operational and environmental issues, testing room requirements including mitigation strategies for transmission risk, requirement for improved ventilation, maintaining physical distance and use of personal protection equipment. We also provide consensus opinion on precautions relating to specific tests, filters, management of special patient groups and alternative options to testing in hospitals.The pandemic has highlighted how vulnerable lung function services are and forces us to re-think how long-term mitigation strategies can protect our services during this and any possible future pandemic. This statement aspires to address the safety concerns that exist and provide strategies to make lung function tests and the testing environment safer when tests are required.

The slow wave late positive potential (LPP) is one of the most dependable measures of emotional processing in human neuroscience. While LPP positivity shows modest malleability by emotional regulation and competing tasks, its fundamental enhancement by emotional scene perception is extremely reliable. Here we assess the impact of emotional scene frequency (67%, 50% and 17%) on the strength of LPP modulation, across 3 groups of participants, using consistent presentation and analysis methods. The results demonstrate strong consistency in the strength of emotional modulation across frequent, equiprobable, and rare emotion conditions. However, a small enhancement of LPP positivity was found during unpleasant scenes in the rare emotion condition. The LPP thus appears to be largely insensitive to contextual features such as scene frequency and predictability, suggesting that strong emotional cues persistently engage orienting and evaluation processes because this tendency was selected in phylogeny.

Background: The American Thoracic Society committee on Proficiency Standards for Pulmonary Function Laboratories has recognized the need for a standardized reporting format for pulmonary function tests. Although prior documents have offered guidance on the reporting of test data, there is considerable variability in how these results are presented to end users, leading to potential confusion and miscommunication.Methods: A project task force, consisting of the committee as a whole, was approved to develop a new Technical Standard on reporting pulmonary function test results. Three working groups addressed the presentation format, the reference data supporting interpretation of results, and a system for grading quality of test efforts. Each group reviewed relevant literature and wrote drafts that were merged into the final document.Results: This document presents a reporting format in test-specific units for spirometry, lung volumes, and diffusing capacity that can be assembled into a report appropriate fo...

Recently, this international task force reported the general considerations for bronchial challenge testing and the performance of the methacholine challenge test, a “direct” airway challenge test. Here, the task force provides an updated description of the pathophysiology and the methods to conduct indirect challenge tests. Because indirect challenge tests trigger airway narrowing through the activation of endogenous pathways that are involved in asthma, indirect challenge tests tend to be specific for asthma and reveal much about the biology of asthma, but may be less sensitive than direct tests for the detection of airway hyperresponsiveness. We provide recommendations for the conduct and interpretation of hyperpnoea challenge tests such as dry air exercise challenge and eucapnic voluntary hyperpnoea that provide a single strong stimulus for airway narrowing. This technical standard expands the recommendations to additional indirect tests such as hypertonic saline, mannitol and adenosine challenge that are incremental tests, but still retain characteristics of other indirect challenges. Assessment of airway hyperresponsiveness, with direct and indirect tests, are valuable tools to understand and to monitor airway function and to characterise the underlying asthma phenotype to guide therapy. The tests should be interpreted within the context of the clinical features of asthma.

The measurement of lung volume is as old as the spirometer. Measurements of lung volume and its subdivisions yield critical diagnostic information about the principle cause of disease, either restrictive with decreased volume or obstructive with increased volume. There are numerous simple and complex techniques for measuring lung volume including simple spirometry, body plethysmography, and the CT scan.

A cortico-limbic network consisting of the amygdala, medial prefrontal cortex (mPFC), and ventral striatum (vSTR) has been associated with altered function in emotional disorders. Here we used rapidly sampled functional magnetic resonance imaging and Granger causality analyses to assess the directional connectivity between these brain structures in a sample of healthy and age-matched participants endorsing moderate to severe depressive symptomatology as they viewed a series of natural scene stimuli varying systematically in pleasantness and arousal. Specifically during pleasant scene perception, dysphoric participants showed reduced activity in mPFC and vSTR, relative to healthy participants. In contrast, amygdala activity was enhanced to pleasant as well as unpleasant arousing scenes in both participant groups. Granger causality estimates of influence between mPFC and vSTR were significantly reduced in dysphoric relative to control participants during all picture contents. These findings provide direct evidence that during visual perception of evocative emotional stimuli, reduced reward-related activity in dysphoria is associated with dysfunctional causal connectivity between mPFC, amygdala, and vSTR.

D.C. Johnson proposed that an adjustment of the predicted value for the diffusing capacity of the lung for carbon monoxide (DLCO) based on the measured and predicted lung volume be included in the report of DLCO test results. An interpretation algorithm is also proposed., A correction of the predicted value for DLCO based on the measured lung volume is not recommended http://ow.ly/KFn730cPJ9n

Electrocortical and hemodynamic measures reliably identify enhanced activity in the ventral and dorsal visual cortices during the perception of emotionally arousing versus neutral images, an effect that may reflect directive feedback from the subcortical amygdala. However, other brain regions strongly modulate visual attention, such as frontal eye fields (FEF) and intraparietal sulcus (IPS). Here we employ rapid sampling of BOLD signal (4 Hz) in the amygdala, fusiform gyrus (FG), FEF and IPS in 42 human participants as they viewed a series of emotional and neutral natural scene photographs balanced for luminosity and complexity, to test whether emotional discrimination is evident in dorsal structures prior to such discrimination in the amygdala and FG. Granger causality analyses were used to assess directional connectivity within dorsal and ventral networks. Results demonstrate emotionally-enhanced peak BOLD signal in the amygdala, FG, FEF, and IPS, with the onset of BOLD signal discrimination occurring between 2 and 3s after stimulus onset in ventral structures, and between 4 and 5s in FEF and IPS. Granger causality estimates yield stronger directional connectivity from IPS to FEF than the reverse in this emotional picture paradigm. Consistent with a reentrant perspective of emotional scene perception, greater directional connectivity was found from the amygdala to FG compared to the reverse. These data support a perspective in which the registration of emotional scene content is orchestrated by the amygdala and rostral inferotemporal visual cortex.

Behavioral and physiological sex differences in emotional reactivity are well documented, yet comparatively few neural differences have been identified. Here we apply quantitative activation likelihood estimation (ALE) meta-analysis across functional brain imaging studies that each reported clusters of activity differentiating men and women as they participated in emotion-evoking tasks in the visual modality. This approach requires the experimental paradigm to be balanced across the sexes, and thus may provide greater clarity than previous efforts. Results across 56 emotion-eliciting studies (n=1907) reveal distinct activation in the medial prefrontal cortex, anterior cingulate cortex, frontal pole, and mediodorsal nucleus of the thalamus in men relative to women. Women show distinct activation in bilateral amygdala, hippocampus, and regions of the dorsal midbrain including the periaqueductal gray/superior colliculus and locus coeruleus. While some clusters are consistent with prevailing perspectives on the foundations of sex differences in emotional reactivity, thalamic and brainstem regions have not previously been highlighted as sexually divergent. These data strongly support the need to include sex as a factor in functional brain imaging studies of emotion, and to extend our investigative focus beyond the cortex.

This document summarises an update to the European Respiratory Society (ERS)/American Thoracic Society (ATS) technical standards for single-breath carbon monoxide uptake in the lung that was last updated in 2005. The full standards are also available online as https://doi.org/10.1183/13993003.00016-2016. The major changes in these technical standards relate to DLCO measurement with systems using rapidly responding gas analysers for carbon monoxide and the tracer gas, which are now the most common type of DLCO instrumentation being manufactured. Technical improvements and the increased capability afforded by these new systems permit enhanced measurement of DLCO and the opportunity to include other optional measures of lung function.

This document provides an update to the European Respiratory Society (ERS)/American Thoracic Society (ATS) technical standards for single-breath carbon monoxide uptake in the lung that was last updated in 2005. Although bothDLCO(diffusing capacity) andTLCO(transfer factor) are valid terms to describe the uptake of carbon monoxide in the lung, the termDLCOis used in this document. A joint taskforce appointed by the ERS and ATS reviewed the recent literature on the measurement ofDLCOand surveyed the current technical capabilities of instrumentation being manufactured around the world. The recommendations in this document represent the consensus of the taskforce members in regard to the evidence available for various aspects ofDLCOmeasurement. Furthermore, it reflects the expert opinion of the taskforce members on areas in which peer-reviewed evidence was either not available or was incomplete. The major changes in these technical standards relate toDLCOmeasurement with systems using rapidly responding gas analysers for carbon monoxide and the tracer gas, which are now the most common type ofDLCOinstrumentation being manufactured. Technical improvements and the increased capability afforded by these new systems permit enhanced measurement ofDLCOand the opportunity to include other optional measures of lung function.

Definitions et subdivisions du volume pulmonaire 17S48 Preparation du patient 17S49 Determination des subdivisions pulmonaires ........ 17S49 Mesure de la CRF par plethysmographie corporelle 17S50 Introduction et theorie 17S50 Materiel 17S50 Technique de mesure 17S50 Controle qualite 17S51 Calculs 17S52 Mesure de la CRF par rincage de l’azote 17S52 Introduction et theorie 17S52 Materiel 17S52 Technique de mesure 17S53 Controle qualite 17S53 Calculs 17S54 Mesure de la Crf par dilution de l’helium 17S54 Introduction et theorie 17S54 Materiel 17S54 Technique de mesure 17S55 Controle qualite 17S56 Calculs 17S56 Mesure des volumes pulmonaires par des techniques d’imagerie 17S56 Radiographies conventionnelles 17S57 Tomodensitometrie 17S57 Imagerie par resonance magnetique 17S57 Controverses et questions critiques 17S57 Valeurs de reference 17S58 Prevention des infections 17S58 Abreviations 17S58

Generalites 17S80 Spirometrie 17S81 Volumes pulmonaires 17S83 Capacite de diffusion du monoxyde de carbone 17S85 Les differents types d’anomalies respiratoires 17S86

Udgivelsesdato: 2007-Mar

FG-3019 is a fully human monoclonal antibody that interferes with the action of connective tissue growth factor, a central mediator in the pathogenesis of fibrosis.This open-label phase 2 trial evaluated the safety and efficacy of two doses of FG-3019 administered by intravenous infusion every 3 weeks for 45 weeks in patients with idiopathic pulmonary fibrosis (IPF). Subjects had a diagnosis of IPF within the prior 5 years defined by either usual interstitial pneumonia (UIP) pattern on a recent high-resolution computed tomography (HRCT) scan, or a possible UIP pattern on HRCT scan and a recent surgical lung biopsy showing UIP pattern. Pulmonary function tests were performed every 12 weeks, and changes in the extent of pulmonary fibrosis were measured by quantitative HRCT scans performed at baseline and every 24 weeks.FG-3019 was safe and well-tolerated in IPF patients participating in the study. Changes in fibrosis were correlated with changes in pulmonary function.Further investigation of FG-3019 in IPF with a placebo-controlled clinical trial is warranted and is underway.

[⇓][1] SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING” Edited by V. Brusasco, R. Crapo and G. Viegi Number 4 in this Series [1]: #F4

This international task force report updates general considerations for bronchial challenge testing and the performance of the methacholine challenge test. There are notable changes from prior recommendations in order to accommodate newer delivery devices. Rather than basing the test result upon a methacholine concentration (provocative concentration (PC20) causing a 20% fall in forced expiratory volume in 1 s (FEV1)), the new recommendations base the result upon the delivered dose of methacholine causing a 20% fall in FEV1(provocative dose (PD20)). This end-point allows comparable results from different devices or protocols, thus any suitable nebuliser or dosimeter may be used, so long as the delivery characteristics are known. Inhalation may be by tidal breathing using a breath-actuated or continuous nebuliser for 1 min (or more), or by a dosimeter with a suitable breath count. Tests requiring maximal inhalations to total lung capacity are not recommended because the bronchoprotective effect of a deep breath reduces the sensitivity of the test.

Field walking tests are commonly employed to evaluate exercise capacity, assess prognosis and evaluate treatment response in chronic respiratory diseases. In recent years, there has been a wealth of new literature pertinent to the conduct of the 6-min walk test (6MWT), and a growing evidence base describing the incremental and endurance shuttle walk tests (ISWT and ESWT, respectively). The aim of this document is to describe the standard operating procedures for the 6MWT, ISWT and ESWT, which can be consistently employed by clinicians and researchers. The Technical Standard was developed by a multidisciplinary and international group of clinicians and researchers with expertise in the application of field walking tests. The procedures are underpinned by a concurrent systematic review of literature relevant to measurement properties and test conduct in adults with chronic respiratory disease. Current data confirm that the 6MWT, ISWT and ESWT are valid, reliable and responsive to change with some interventions. However, results are sensitive to small changes in methodology. It is important that two tests are conducted for the 6MWT and ISWT. This Technical Standard for field walking tests reflects current evidence regarding procedures that should be used to achieve robust results. The realisation of this Technical Standard would not have been possible without the financial support of the European Respiratory Society and American Thoracic Society. Sally J. Singh is supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care East Midlands (CLAHRC EM), and work took place at the University Hospitals of Leicester NHS Trust. Support was also provided by the NIHR Leicester Respiratory Biomedical Research Unit. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Dept of Health.

Measurement of DL(CO) remains a clinically useful way to assess transfer of gases across the lung. It is important, however, to be vigilant in controlling the sources of variation and to be aware of those that remain when interpreting the measured values.

To the Editors: A few questions have been raised following the publication in 2005 of the joint American Thoracic Society (ATS)/European Respiratory Society (ERS) series of documents on standardising lung function testing and these are answered below. The following questions and answers pertain to the standardisation document for spirometry 1. ### Start of test criteria Should blows be rejected solely on the basis of a poor back extrapolated volume (EV)? #### Reply Usually. The forced vital capacity (FVC) may be usable, but the forced expiratory volume in 1 s (FEV1) is likely to be falsely high or low. #### Rationale The acceptability criteria for spirometry were designed to help technologists improve the subject’s technique in order to get the best and most reliable result. EV is important for determining that a fast start to the blow was achieved and this is crucial for getting the best values for FEV1 and peak expiratory flow (PEF). ### End of test criteria In the original document, there was an error in table 5. #### Reply In table 5, the within-manoeuvre criteria for a satisfactory completion of a blow should have read “Duration of ≥6 s (3 s for children) and a plateau in the volume–time curve, or if the subject cannot or should not continue to exhale.” The original table had “or” in twice, whereas the accompanying text was correct, as above. #### Rationale The end of test (EOT) criteria are applied in order to ensure that efforts are made to achieve the best estimate of FVC. When a subject cannot meet the plateau criterion (

Study objective The lower limit for the baseline value to initiate methacholine bronchial hyperresponsiveness testing has not been well established. Recommendations have varied from >1 L to above 80% of predicted. The objective was to determine if an FEV 1 Design Retrospective analysis of challenges in 88 patients with a baseline FEV 1 of Setting Academic institutions. Results There were only four individuals whose FEV 1 did not return to >90% of baseline following one poststudy s 2 -agonist treatment. All four responded to a second treatment. There were no adverse sequelae following challenge in any individual. Neither age (up to 79 years) nor gender influenced outcome. Conclusions In chronic moderate to severe asthma, it appears that bronchial hyperresponsiveness testing can be safely performed even in those patients with a low baseline FEV 1 .

We studied the effect of breath holding and inspiratory speed on airflow during the FVC maneuver in seven healthy subjects and eight patients with asthma. The purpose of the study was to determine whether the effects of inspiratory speed and breath holding on expiratory flow were greater in patients with asthma than in healthy individuals; whether these effects were lessened by inhalation of aerosolized bronchodilator in the patients with asthma; and whether were was a relationship between the lung elastic recoil pressure and the expiratory flow achieved during four different maneuvers. We found that peak expiratory flow rate (PEFR) was significantly lower after both a slow inspiration and a breath hold than after a fast inspiration without a breath hold. In addition, a breath hold was associated with a significantly lower FEV1. The effects of inspiratory speed and breath holding in the patients with asthma were not significantly different from those observed in the healthy subjects. There was a significant relationship between lung elastic recoil pressure at the point of onset of the FVC maneuvers (Pel Blow) and expiratory flow in both healthy and asthmatic subjects. Also, the decrease in Pel Blow with equivalent breath-hold time was greater in asthmatic subjects, which is consistent with an increase in viscoelastic elements in the lung. These findings corroborate previous suggestions that inspiratory speed and the duration of breath holding have significant implications in the performance of spirometry and peak flow measurements, and indicate the importance of standardization of the preceding inspiration when determining FEV1 and PEFR.

A methacholine challenge test is one of the methods to assess bronchial hyperresponsiveness (BHR). BHR is one of the features that can contribute to the diagnosis of asthma. The test is reported as a PC-20 value; the inhaled provocative concentration causing a 20% drop or more in the pretest FEV1. This patient had a PC-20 of 16 mg/ml, 4-16 mg/mL is considered borderline and 1-4 mg/mL is mild BHR according to the ATS guidelines.

To the Editors: In 1986, the American Thoracic Society (ATS) first suggested a fixed ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC)

Udgivelsesdato: 2007-Mar

SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING” Edited by V. Brusasco, R. Crapo and G. Viegi Number 5 in this Series This section is written to provide guidance in interpreting pulmonary function tests (PFTs) to medical directors of hospital-based laboratories that perform PFTs, and physicians who are responsible for interpreting the results of PFTs most commonly ordered for clinical purposes. Specifically, this section addresses the interpretation of spirometry, bronchodilator response, carbon monoxide diffusing capacity ( D L,CO) and lung volumes. The sources of variation in lung function testing and technical aspects of spirometry, lung volume measurements and D L,CO measurement have been considered in other documents published in this series of Task Force reports 1–4 and in the American Thoracic Society (ATS) interpretative strategies document 5. An interpretation begins with a review and comment on test quality. Tests that are less than optimal may still contain useful information, but interpreters should identify the problems and the direction and magnitude of the potential errors. Omitting the quality review and relying only on numerical results for clinical decision making is a common mistake, which is more easily made by those who are dependent upon computer interpretations. Once quality has been assured, the next steps involve a series of comparisons 6 that include comparisons of test results with reference values based on healthy subjects 5, comparisons with known disease or abnormal physiological patterns ( i.e. obstruction and restriction), and comparisons with self, a rather formal term for evaluating change in an individual patient. A final step in the lung function report is to answer the clinical question that prompted the test. Poor choices made during these preparatory steps increase the risk of misclassification, i.e. a falsely negative or falsely positive interpretation for a lung function abnormality or a change …

[⇓][1] SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING” Edited by V. Brusasco, R. Crapo and G. Viegi Number 3 in this Series [1]: #F7

To assess the effect of megestrol acetate (MA), a progestational appetite stimulant commonly used in patients with AIDS and cancer, on body weight and composition, respiratory muscle strength, arterial blood gas levels, and subjective perceptions in COPD patients.Prospective, double-blind, randomized, placebo-controlled trial conducted on an outpatient basis at 18 sites.Underweight (95% ideal body weight) COPD patientsor = 40 years old.Either MA, 800 mg/d oral suspension, or placebo at a 1:1 ratio for 8 weeks.Of 145 randomized patients (63% men), 128 patients completed the trial. Body weight increased by 3.2 kg in the MA group and 0.7 kg in the placebo group (p0.001). Anthropometric and dual-energy radiograph absorptiometry assessments confirmed that weight gain was mainly fat. Spirometry and maximal voluntary ventilation showed no significant changes from baseline in either group, and the difference in the change in maximum inspiratory pressure between groups was not significant. The 6-min walk distances did not differ statistically between groups at week 2 and week 4, but were greater in the placebo group at week 8 (p = 0.012). Consistent with the known ability of MA to stimulate ventilation, PaCO(2) decreased (4.6 mm Hg, p0.001) and PaO(2) increased (2.8 mm Hg, p0.04) in the MA group. Questionnaires revealed that body image and appetite improved in the MA group but not the placebo group. Adverse event frequency and type were similar in both groups, but cortisol and testosterone (in men) levels decreased substantially in the MA group.We conclude that MA safely increased appetite and body weight, stimulated ventilation, and improved body image in underweight COPD patients, but did not improve respiratory muscle function or exercise tolerance.

Every pulmonary function laboratory should develop and implement a quality assurance program to minimize various technical sources of variation. This article has discussed six major components. First, the education and training of the technologists in the pulmonary function laboratory is probably the most important factor in obtaining accurate and reproducible results. A college-level education with an emphasis on math and science is recommended. After an appropriate training program, continued evaluation and feedback are important. Second, instrument maintenance should be performed on a scheduled basis to reduce or prevent instrument malfunctions. Corrective maintenance, which is usually unscheduled, should be performed by knowledgeable individuals and any repairs should be documented. Third, a procedure manual is very important to any successful quality assurance program. It should contain a broad range of information including administrative issues, quality-control procedures, stepwise instructions on test performance, and infection-control policies and procedures. Fourth, the procedures should be performed using published guidelines to help minimize the effects of the many variables. Fifth, a method to quality control each test procedure should be developed. The specific method(s) will vary according to the type of instrumentation and the manufacturer. Finally, the well-run quality assurance program must properly analyze and store the data collected. Sound statistical methods should be applied and various logs and lists should be developed.

STUDY OBJECTIVES: To assess the effect of megestrol acetate (MA), a progestational appetite stimulant commonly used in patients with AIDS and cancer, on body weight and composition, respiratory muscle strength, arterial blood gas levels, and subjective perceptions in COPD patients. DESIGN AND SETTING: Prospective, double-blind, randomized, placebo-controlled trial conducted on an outpatient basis at 18 sites. PATIENTS: Underweight (

We have observed that the results of pulmonary function tests obtained at one site, in general, may not be considered 'acceptable' at another site--in part because of known or suspected variability in equipment and techniques. We sought to document the presence or absence of such variability in our metropolitan area.We compared the test results from 5 trained healthy subjects (3 men and 2 women) studied in 13 Denver-area pulmonary function laboratories in a randomized order and at approximately the same time of day.We performed analysis of variance on commonly reported parameters and found no significant difference for FVC (p = 0.11), FEV1 (p = 0.075), FEF25-75% (p = 0.41), and FRC by helium dilution (p = 0.22). However, marked differences between certain sites could be clinically important. In addition, we found a statistically significant difference for DLCO (p less than 0.001) and TLC (p = 0.024). Six different brands of pulmonary function equipment were used by the 13 hospitals, and differences in the number of trials performed, sequence of testing (eg, FRC determinations were sometimes done first, sometimes last), and calculation of the DLCO breath-hold time.We conclude that although the FVC, FEV1, FEF25-75%, and FRC measured by helium dilution were not statistically different in healthy trained subjects in the 13 hospitals studied, clinically important differences may exist. The DLCO and TLC were statistically different. To minimize variability and improve comparability, hospitals in a given area should give consideration to adopting standardized techniques, using comparable equipment, and adopting common reference equations.

Mit Hilfe eines Torsionspendels wurde die Nachwirkung des Elastizitatsmoduls nach plastischer Verformung an Cu und Ni gemessen. Die mechanische Nachwirkung wird durch die beim Verformen erzeugten Hantel-Zwischengitteratome verursacht, welche im Spannungsfeld einer Versetzung zu einer versetzungsinduzierten Umorientierung (Orientierungsnachwirkung) und Diffusion (Diffusionsnachwirkung) angeregt werden. Aus der Orientierungsnachwirkung ergibt sich die Aktivierungsenergie fur die Umorientierung der Hantel-Zwischengitteratome im Fall von Cu zu 0,67 eV und fur Ni zu 0,87 eV. Die Wanderungsenergie der Zwischengitteratome folgt aus der Diffusionsnachwirkung und betragt fur Cu ebenfalls 0,67 eV, fur Ni hingegen 0,99 eV. Die Ergebnisse der mechanischen Nachwirkungsmessungen sind in voller Ubereinstimmung mit den Resultaten aus inneren Reibungsund magnetischen Nachwirkungsmessungen. By means of a torsion pendulum the after effect of the elastic modulus has been measured on cold-worked Cu and Ni. The mechanical after effect is caused by dumb-bell self-interstitials generated by plastic deformation which are capable of lowering their interaction energy with the dislocation strain fields by reorientation of the dumb-bell axis (orientation after effect) and by diffusion (diffusion after effect). The activation energy for dumbbell reorientation obtained from the orientation after effect is 0.67 eV for Cu and 0.87 eV for Xi. From the diffusion after effect the energy of dumb-bell migration is derived to 0.67 eV for Cu and 0.99 eV for Ni. The results of the mechanical after effect measurements are in complete agreement with internal friction and magnetic after effect experiments.

Durch Verwendung genugend kleiner Frequenzen (f ≈ 10−1 Hz) konnte die versetzungsunabhangige Umorientierung der Hantel-Zwischengitteratome (Hantel-ZGA) getrennt von der versetzungsinduzierten Umorientierung beobachtet werden. Der versetzungsunabhangige Prozes besitzt die von der Theorie vorhergesagte Orientierungsabhangigkeit und last sich nur mit dem Bild des Hantel-ZGA mit 〈100〉-Vorzugsrichtung verstehen. Beim Anlassen der Proben baut sich die versetzungsinduzierte Umorientierung der Hantel-ZGA auf. Dieser Prozes zeigt keine wesentliche Orientierungsabhangigkeit. Bei hoheren Frequenzen (f ≈ 1 Hz) tritt er gleichzeitig mit der versetzungsunabhangigen Umorientierung der Hantel-ZGA auf und maskiert dadurch teilweise deren Orientierungsabhangigkeit. Experimentelle Ergebnisse fruherer Arbeiten finden durch die versetzungsinduzierte Umorientierung der Hantel-ZGA ihre Erklarung. In the low-frequency regime (f ≈ 10−1 Hz) it was possible to study the dislocation-independent and the dislocation-induced reorientation of dumbbell interstitials separately. The dislocation-independent relaxation process shows an orientation dependence as predicted by the theory. This dependence is only explainable in terms of a reorientation of dumb-bells with 〈100〉-axes. Annealing of the specimens gives rise to the occurrence of the dislocation-induced reorientation of dumbbells. This effect shows practically no orientation dependence. At higher frequencies (f ≈ 1 Hz) both the dislocation-independent and dislocation-induced relaxation processes occur simultaneously. Therefore, the measured damping peak is composed of two single relaxation peaks. In this way the orientation dependence of the dislocation-independent process is partially masked. Experimental results of previous papers are explained on the basis of dislocation-induced dumbbell reorientation.

The acute pulmonary and cardiovascular effects of single doses of theophylline 130 mg and terbutaline 2.5 mg administered alone and in combination were compared with placebo over a period of seven hours in 16 stable asthmatic subjects. Terbutaline 2.5 mg produced significant bronchodilatation that peaked at three hours and lasted for four to six hours. Theophylline 130 mg produced small increments in serum theophylline concentration (1.5-4.5 microgram/ml), did not produce greater bronchodilatation than placebo and did not provide additional bronchodilatation when combined with terbutaline 2.5 mg. The clinical implications of these findings with respect to the possible utility of combining low doses of theophylline with low doses of a beta-adrenergic stimulant are discussed.

I. UNTOWARD EFFECTS OF RAPID INJECTION ("SPEED SHOCK") The rapid intravenous introduction of pharmacologically active or inert chemicals, drugs and biologic fluids may frequently give rise to immediate and far-reaching nonspecific sequelae, at times serious, and occasionally fatal. 1 This "speed shock" is a hazard to the clinician and annoys and baffles the laboratory worker (charts 1, 2, 3, 4 and 5). In this article we shall describe, localize and discuss the possible mechanism of the deleterious effects of the rapid introduction into the blood stream of relatively innocuous substances. MATERIAL AND TECHNIC Our observations were made on anesthetized and unanesthetized animals. For the work without anesthesia, dogs and rabbits were used, and the injections were made with the hand syringe. The rate of injection could not be accurately measured, but usually from 2 to 5 cc. was introduced as rapidly as the plunger could be pressed. Under anesthesia, sixty-two animals