bluuebunny/crossref_metadata_2025 huggingface dataset:
The maraca plot: A novel visualization of hierarchical composite endpoints
Authors: Karpefors Martin , Lindholm Daniel , Gasparyan Samvel B
Published: November 2022

Background:

Hierarchical composite endpoints are complex endpoints combining outcomes of different types and different clinical importance into an ordinal outcome that prioritizes the clinically most important (e.g. most severe) event of a patient. Hierarchical composite endpoint can be analysed with the win odds, an adaptation of win ratio to include ties. One of the difficulties in interpreting hierarchical composite endpoint is the lack of proper tools for visualizing the treatment effect captured by hierarchical composite endpoint, given the complex nature of the endpoint which combines events of different types.

Methods:

Hierarchical composite endpoints usually combine time-to-event outcomes and continuous outcomes into a composite; hence, it is important to capture not only the shift from more severe categories to less severe categories in the active group in comparison to the control group (as in any ordinal endpoint), but also changes occurring within each category. We introduce the novel maraca plot which combines violin plots (with nested box plots) to visualize the density of the distribution of the continuous outcome and Kaplan–Meier plots for time-to-event outcomes into a comprehensive visualization.

Conclusion:

The novel maraca plot is suggested for visualization of hierarchical composite endpoints consisting of several time-to-event outcomes and a continuous outcome. It has a very simple structure and therefore easily communicates both the overall treatment effect and the effect on individual components.
Seeing like a driver: How workers repair, resist, and reinforce the platform's algorithmic visions
Authors: Qadri Rida , D’Ignazio Catherine
Published: November 2022

This article theorizes the relationship between two ways of “seeing” and organizing urban mobility markets: the abstract, algorithmic vision of the mobility platform and the experiential, relational vision of the platform driver. Using the case of mobility platforms in Jakarta, we empirically demonstrate how drivers experience the limitations of the platform's visions and how they deploy their own alternative visions of work and the city. We offer this drivers’ “View from Within” as a counterpoint to the visions of the platform, decentering the platform's visions as the sole arbiter of change and optimization in the city. At the same time, we disrupt the assumed binary between these views, showing how they exist in a complex dance of complementarity and contestation. We conclude with a discussion on the opportunities this entanglement presents for worker agency in the algorithmic market, the hurdles toward more “worker centered design” in platform economies and the tensions between globalizing technological solutions and their localized instantiations. Through this article, we argue for seeing deep, embedded relationships as culturally and historically important modes of urban life which technology has to interact with but cannot fully capture nor do away with.
Need for cognition and burnout in teachers – A replication and extension study
Authors: Zerna Josephine , Engelmann Nicole , Strobel Anja , Strobel Alexander
Published: November 2022

Burnout has become more prevalent, mainly in social jobs, and there is evidence that certain personality traits protect against burnout. Only recently, studies have focused on investment traits like Need for Cognition (NFC), the stable intrinsic motivation to seek out and enjoy effortful cognitive activities. This study had three aims: First, the replication of findings by Grass et al. (2018), who investigated NFC and the burnout subscale reduced personal efficacy in student teachers, in a sample of 180 teachers. Second, investigating the role of perceived demands and resources in the context of NFC and burnout. And finally, creating an exploratory model for further research. The results indicated that unlike the student sample, the teachers’ association of NFC and reduced personal efficacy was mediated by self-control but not reappraisal. Teachers with higher NFC and self-control also had lower burnout because they experienced their resources as fitting to the demands.
The Meanings of Social Media Use in Everyday Life: Filling Empty Slots, Everyday Transformations, and Mood Management
Authors: Bengtsson Stina , Johansson Sofia
Published: November 2022

Since their emergence in the early 2000s, social media have continued to increase in popularity, particularly among adolescents and young adults. Even though they have been studied in relation to a wide range of topics, including their role in politics, social relationships, activism, identity construction, and youth cultures, the rise of social media is also connected to a number of less dramatic, yet pervasive, shifts relating to their integration into the mundane practices of day-to-day life. In this article, we explore the uses of social media as part of everyday life, a perspective that has gained less attention in research about social media. We take an interest in how young adults create meaning around their daily practices, involving many different social media platforms. Doing so, we draw on in-depth individual and small group interviews with 67 young adults, aged 18–26, conducted in Sweden during 2019–2021. We approach social media as a joint environment, consisting of a wide range of different platforms traversed by the user. The empirical analysis identifies three significant meanings of social media: filling empty slots, everyday transformations, and mood management. These three different meanings are shaped by different temporal, spatial, and technological characteristics and emphasize the importance of social media use in the lives of the young adults.
Dyslipidemia is Associated with an Increased Risk of Achilles Tendinopathy and Tendon Rupture to a Greater Extent in Underweight Than in Obese Subjects
Authors: Choi Jun Young
Published: November 2022

Category:

Ankle

Introduction/Purpose:

The association between dyslipidemia and Achilles tendinopathy (AT) or Achilles tendon rupture (ATR) remains controversial, although some studies have been reported on the subject. This study aimed to evaluate the correlation of dyslipidemia and the risk of AT or ATR, and its association with body mass index (BMI), by assessing data from a nationwide population-based cohort.

Methods:

We used the National Health Insurance database, which includes the entire South Korean population to follow-up subjects who participated in the National Health Screening Program (NHSP) from January 2009 to December 2010. Participants diagnosed with AT or ATR before December 31, 2017, were selected. The variables were age, sex, frequency of high-intensity exercise per week, BMI, waist circumference, low-density lipoprotein cholesterol (LDL-C) levels, triglyceride (TG) levels, high- density lipoprotein cholesterol (HDL-C) levels, fasting blood glucose levels, and systolic blood pressure. Multivariate Cox proportional hazards regression was used for data analysis.

Results:

A total of 16,830,532 subjects were included. Of these, 125,814 and 31,424 subjects developed AT and ATR, respectively. A higher level of LDL-C was associated with an increased risk of both AT (adjusted hazard ratio [HR], 1.16) and ATR (adjusted HR, 1.18). A slightly increased risk of AT was observed in subjects with higher TG levels (adjusted HR, 1.03), whereas higher HDL-C level was associated with a slight risk reduction for AT (adjusted HR, 0.95). However, no significant association was observed between higher TG or HDL-C levels and ATR. In the underweight group (BMI < 18.5 kg/m2), a higher LDL-C level was associated with an increased risk of AT and ATR by 37 and 116%, respectively, compared with lower LDL-C. Higher LDL-C levels was associated with an increased risk of AT and ATR by 10 and 16%, respectively, in the obese group (BMI >= 25 kg/m2).

Conclusion:

Our results support the hypothesis that dyslipidemia was related to the development of AT and ATR. The association of higher LDL-C levels with AT and ATR risk was more pronounced in underweight than in overweight and obese subjects.
Impact of COVID-19 on emergency department visits among palliative home care recipients: a retrospective population-based cohort study in the Piedmont region, Italy
Authors: Scacchi Alessandro , Conti Alessio , Politano Gianfranco , Dalmasso Marco , Ostellino Sofia , Gianino Maria Michela
Published: November 2022

Background:

Integrated palliative home care (IHPC) is delivered to patients with progressive end-stage diseases. During the COVID-19 pandemic, IHPC needed to provide high-quality home care services for patients who were treated at home, with the goal of avoiding unnecessary care, hospital admissions, and emergency department (ED) visits. This study aimed to compare the ED visits of IHPC recipients in a large Italian region before and during the first two waves of the COVID-19 pandemic and to find sociodemographic or clinical characteristics associated with changes in ED visits during the first two waves of COVID-19 pandemic, compared with the period before.

Methods:

Administrative databases were used to identify sociodemographic and clinical variables of IHPC recipients admitted before and during the pandemic. The obtained data were balanced by applying a propensity score. The average number of ED visits before and during the pandemic was calculated by using the Welch’s t test and stratified by all the variables.

Results:

Before and during the pandemic, 5155 and 3177 recipients were admitted to IHPC, respectively. These individuals were primarily affected by neoplasms. ED visits of IHPC recipients reduced from 1346 to 467 before and during the pandemic, respectively. A reduced mortality among IHCP patients who had at least one ED visit during the pandemic (8% during the pandemic versus 15% before the pandemic) was found. The average number of ED visits decreased during the pandemic [0.143, confidence interval (CI) = (0.128–0.158) versus 0.264, CI = (0.242–0.286) before the pandemic; p < 0.001] for all ages and IHPC duration classes. The presence of a formal caregiver led to a significant decrease in ED use. Medium and high emergency ED admissions showed no difference, whereas a decrease in low-level emergency ED admissions during the pandemic [1.27, CI = (1.194–1.345) versus 1.439, CI = (1.3–1.579) before the pandemic; p = 0.036] was found.

Conclusion:

ED visits among IHPC recipients were significantly decreased during the first two waves of the COVID-19 pandemic, especially in those individuals characterized by a low level of emergency. This did not result in an increase in mortality among IHPC recipients. These findings could inform the reorganization of home care services after the pandemic.
Eco-friendly hybrid materials made from Tunisian clay and natural flowers
Authors: Amraoui Amira , Gamoudi Safa , Baenas Nieves , Periago Maria Jesus , Srasra Ezzeddine
Published: November 2022

Clay minerals are used widely in health products both as cosmetic and pharmaceutical ingredients. To optimize use, natural compounds are mixed with clay powder. The aim of the present study was to synthesize new, coloured hybrids based on purified Tunisian clay and powders of natural flowers: Malva sylvestris, Chrysanthemum coronarium, Silene dioica, Anagallis monellin and Pelargonium × hortorum. The floral pigments in Tunisian flowers were studied. The chlorophylls (a and b), total flavonoids (TF), total phenolic compounds (TPC), and carotenoids were analyzed using UV-Vis spectrophotometry and high-performance liquid chromatography (HPLC-DAD). In addition, the antioxidant capacity was determined using the oxygenated radical absorption capacity assay (ORAC) and the antioxidant capacity to reduce ferric ion assay (FRAP). The properties of the studied clay were evaluated by means of pharmaceutical and microbiological tests. The coloured hybrids were prepared by solid–solid reaction and analyzed using X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Chlorophyll a is present in large quantities in the Malva flower which presents the smallest antioxidant capacity. Chlorophyll b and the TPC are more abundant in the Pelargonium × hortorum. The TF appears in large quantities in the Anagallis flower. The carotenoids are present in the largest amounts in the Chrysanthemum. The results of the clay characterization justify its use as a pharmaceutical and cosmetic agent. The mixture of dried flowers and purified clay is used in the synthesis of new and biocoloured hybrids; these can be used as biocosmetic products without negative side effects on human health or the environment.
Targeting platelet GPVI with glenzocimab: a novel mechanism for inhibition
Authors: Billiald Philippe , Slater Alexandre , Welin Martin , Clark Joanne C. , Loyau Stéphane , Pugnière Martine , Jiacomini Isabella G. , Rose Nadia , Lebozec Kristell , Toledano Elie , François Déborah , Watson Steve P. , Jandrot-Perrus Martine
Published: November 2022

Platelet glycoprotein VI (GPVI) is attracting interest as a potential target for the development of new antiplatelet molecules with a low bleeding risk. GPVI binding to vascular collagen initiates thrombus formation and GPVI interactions with fibrin promote the growth and stability of the thrombus. In this study, we show that glenzocimab, a clinical stage humanized antibody fragment (Fab) with a high affinity for GPVI, blocks the binding of both ligands through a combination of steric hindrance and structural change. A cocrystal of glenzocimab with an extracellular domain of monomeric GPVI was obtained and its structure determined to a resolution of 1.9 Å. The data revealed that (1) glenzocimab binds to the D2 domain of GPVI, GPVI dimerization was not observed in the crystal structure because glenzocimab prevented D2 homotypic interactions and the formation of dimers that have a high affinity for collagen and fibrin; and (2) the light variable domain of the GPVI-bound Fab causes steric hindrance that is predicted to prevent the collagen-related peptide (CRP)/collagen fibers from extending out of their binding site and preclude GPVI clustering and downstream signaling. Glenzocimab did not bind to a truncated GPVI missing loop residues 129 to 136, thus validating the epitope identified in the crystal structure. Overall, these findings demonstrate that the binding of glenzocimab to the D2 domain of GPVI induces steric hindrance and structural modifications that drive the inhibition of GPVI interactions with its major ligands.
A one year double blind follow-up of blood gas tensions and haemodynamics in almitrine bismesylate therapy
Authors: Prefaut C , Bourgouin-Karaouni D , Ramonatxo M , Michel FB , Macabies J
Published: November 2022

Almitrine bismesylate, a chemoreceptor agonist, improves blood gases in chronic obstructive lung disease (COLD). Some authors have observed an increase in pulmonary artery pressure (Ppa) after single doses of almitrine bismesylate (A). This led to the present one year double blind placebo (P) controlled study to assess haemodynamic effects of long-term oral treatment in COLD (1.5 mg/kg/day for one year), together with clinical benefit and blood gas improvement. Twenty moderately severe patients entered the study, fifteen of whom completed it (eight in group (A), seven in group (P]. Blood gas values, minute ventilation (VE), mean pulmonary artery pressure (Ppa) and cardiac output (Qc) were periodically measured. Ppa and Qc remained unchanged in both groups throughout the study. We observed relevant clinical improvement without side effects and no significant increase in VE in group (A). Arterial oxygen tension (PaO2) showed a 1.2 kPa (9 mmHg) mean increase in group (A) and remained unchanged in group (P). These data and those from the literature seem to indicate that almitrine induces a vascular effect, especially after a single dose. However, as long as PaO2 improves simultaneously no long-term haemodynamic consequence is apparent. The discrepancy between immediate and long-term vascular effects of almitrine might be explained by the improvement in gas exchange which could reduce and/or counter-balance the vasoactive response. In conclusion, after one year of therapy almitrine bismesylate results in considerable clinical and blood gas improvements without significant haemodynamic change.
Radiographic bilateral cavitary lesions in lipoid pneumonia
Authors: Casademont J , Xaubet A , Lopez-Guillermo J , Agusti C , Ramirez J
Published: November 2022

We report a case of lipoid pneumonia with pulmonary bilateral cavitated lesions. The diagnosis was based on the finding of abundant lipid-laden alveolar macrophages in bronchoalveolar lavage and the presence of histologic changes indicative of lipoid pneumonia in transbronchial lung biopsy.
The transfer factor and its subdivisions in patients with pulmonary emboli
Authors: Fennerty AG , Gunawardena KA , Smith AP
Published: November 2022

The carbon monoxide transfer factor and its subdivisions, the pulmonary membrane diffusing capacity and the pulmonary capillary volume were measured in fourteen subjects following submassive pulmonary emboli, as demonstrated by a ventilation-perfusion scan, and in fourteen matched controls. Transfer factor and alveolar volume were significantly lower in patients with pulmonary emboli (p less than 0.02). Patients were given six weeks anticoagulant therapy and the measurements repeated three months later. There was a significant increase in the transfer factor and the alveolar volume (p less than 0.01) and the membrane diffusing capacity (p less than 0.05). It has previously been assumed that the reduction in the transfer factor following a pulmonary embolus is due to a reduction in the pulmonary capillary volume. Results of this study however, suggest that it is more likely to be due to a loss of alveolar volume, at least in subjects with submassive emboli.
Lung function changes following Legionnaires' disease
Authors: Gea J , Rodriguez-Roisin R , Torres A , Roca J , Agusti-Vidal A
Published: November 2022

Eleven out of thirteen patients hospitalized because of severe pneumonia caused by Legionella Pneumophila were evaluated over a period of 53 months. During the acute phase, all but one patient manifested severe hypoxaemia, needing either supplementary oxygen or, in the case of three, mechanical ventilation and one died. Following recovery, two patients complained of mild shortness of breath alone. However, most of the individuals showed subclinical mild to moderate ventilatory and/or gas exchange abnormalities a few months after discharge (less than 6 months). Despite the fact that some of these functional findings in part persisted at long-term (6-33 months), a significant overall improvement in lung function was noticed. The main pulmonary functional sequelae following Legionnaires' Disease might include a restrictive ventilatory defect, a low transfer factor and hypoxaemia.
The alveolar carbon monoxide uptake fraction: a simple, alternative measure of carbon monoxide transfer
Authors: Ameratunga R , Harris EA
Published: November 2022

The measurement and interpretation of "diffusing capacity" by either single-breath or steady-state methods are complicated by both technical and conceptual difficulties. The CO uptake fraction is less complex but, as originally described, it is unacceptably sensitive to dead-space ventilation. A modification (the "alveolar CO uptake fraction", UA) largely removes this factor. We have measured UA in thirteen healthy subjects and 100 patients with a variety of pulmonary disorders. It is reproducible and appears sensitive to clinical abnormality. Its technical and interpretative simplicity suggest its use as an alternative to other measures of CO transfer.
Changes in respiratory muscle function after neostigmine injection in patients with myasthenia gravis
Authors: Radwan L , Strugalska M , Koziorowski A
Published: November 2022

In sixteen patients with myasthenia gravis, the weakness of respiratory muscles, especially of expiratory, caused some disturbances in lung function. Thirty minutes after injection of neostigmine, general improvement of muscle function was accompanied by an increase of strength and endurance of respiratory muscles. The mean value of maximal inspiratory mouth pressure (PImax) increased by 33%, maximal expiratory mouth pressure (PEmax) by 23.5% and maximal voluntary ventilation (MVV) by 21%. As a consequence of these changes amelioration of lung function indices was found, vital capacity increasing on average by 13% and residual volume decreasing by 12.5%. We concluded that patients with generalized myasthenia gravis have disturbances in lung function which may be partially improved by neostigmine injection or other anticholinesterase agents.
Bronchoconstriction due to exercise combined with cold air inhalation does not generally influence bronchial responsiveness to inhaled histamine in asthmatic subjects
Authors: Tessier P , Cartier A , Ghezzo H , Martin RR , Malo JL
Published: November 2022

We investigated immediate and late changes in airway responsiveness to histamine, after bronchoconstriction due to exercise combined with inhalation of cold air, in ten asthmatic subjects who came on six days. On the first visit, the provocation concentration producing 20% fall in FEV1 (PC20) histamine was obtained. After functional recovery, each subject walked on a treadmill whilst breathing dry, cold air. This resulted in an immediate fall greater than 15% (mean +/- SD = 31.9 +/- 11.0%) in forced expiratory volume in one second (FEV1). Following recovery, PC20 was measured again. FEV1 was then monitored for up to 6-8 h. PC20 was measured then and on the two following days at the same time of the day. Subjects were studied on three control days using the same design except that a resting period replaced the exercise with cold air. The mean changes in PC20 at each interval after exercise combined with cold air were not statistically significant. Physiologically significant changes were obtained in only two subjects, reaching a maximum 8 h after the manoeuvre. In these subjects, changes in PC20 were reproducible during a second series of visits. It is concluded that bronchial responsiveness to histamine is not generally influenced by the bronchoconstriction due to exercise combined with cold air.
Failure to demonstrate complement activation during bronchial challenge test
Authors: Michel O , Duchateau J , Sergysels R
Published: November 2022

In order to demonstrate a possible complement activation during early bronchospastic reaction in asthma, we have measured plasmatic C3d (a split product of C3) and the C3d/C3 index, both of which are sensitive indices of complement activation. Twenty-nine allergenic bronchial challenge tests were accomplished, with an absence of response in six cases, an early reaction in sixteen cases and a dual reaction in seven cases. Changes in plasmatic C3d or C3d/C3 five min after an early reaction, or five min after the last dose of allergen (in the six cases without bronchial response) were insignificant. However, complement activation in the lungs during asthmatic reaction cannot be completely excluded without studies using the bronchoalveolar technique.
No effect of oral N-acetylcysteine on the bioavailability of erythromycin and bacampicillin
Authors: Paulsen O , Borgstrom L , Kagedal B , Walder M
Published: November 2022

In vitro studies with N-acetylcysteine (NAC) solutions used for inhalation treatment have demonstrated inactivation of some antibiotics by NAC. Oral NAC treatment is increasingly common for long-term prophylaxis in chronic bronchitis. During exacerbations, treatment with oral antibiotics will often be given simultaneously. We assessed the effect of simultaneous oral administration of NAC on the bioavailability of two antibiotics in ten healthy volunteers. No effect of NAC was found on the bioavailability of ampicillin, after administration of the prodrug bacampicillin. A slight, but not significant statistical increase in erythromycin serum levels was seen with NAC. Acetylator phenotype did not influence the absorption of NAC, which seemed slightly reduced by bacampicillin, but significantly increased by erythromycin. No decrease of antibacterial activity of sera was found in vitro after the addition of NAC or the related thiol glutathione, employing micrococcus luteus and staphylococcus aureus as indicator organisms.
Nocturnal asthma: effects of slow-release terbutaline on spirometry and arterial blood-gases
Authors: Eriksson L , Jonson B , Eklundh G , Persson G
Published: November 2022

The effect of terbutaline, in a slow-release preparation, on spirometry and arterial blood-gases, was studied in fourteen patients with nocturnal asthma. The patients were treated with either 15 mg of slow-release terbutaline or placebo given as a single dose at 10 pm for eight days in a double-blind crossover trial. The patients were studied in the hospital for one night at the end of each treatment period. During active treatment the patients had a significantly higher FEV1 and PaO2 compared with placebo. Tolerance to the high single dose was good and none of the patients discontinued treatment because of side-effects. In patients with nocturnal asthma treatment with a high dose of slow-release terbutaline given as a single dose in the evening appears to be effective.
The validity of the static charge sensitive bed in detecting obstructive sleep apnoeas
Authors: Polo O , Brissaud L , Sales B , Besset A , Billiard M
Published: November 2022

The demand for polysomnographic recordings associated with respiratory control exceeds the capacity of the few existing sleep disorder centres and therefore a simple and inexpensive method is needed for screening and diagnosing sleep-related breathing disorders. The static charge sensitive bed (SCSB) permits long-term recordings of body movements, respiratory movements and the ballistocardiogram (BCG) without electrodes or cables being attached to the subject. The aim of the present study was to test the validity of this particular method in detecting obstructive sleep apnoeas without airflow measurements. Simultaneous SCSB and spirometer recordings were compared in fourteen sleep apnoea patients and six controls. The mean sensitivity of the SCSB method to detect the obstructive apnoeas was 0.92-0.98. The specificity to detect 2 min apnoea epochs was 0.61-0.68 in the apnoea group, while in the control group it was 0.99-1.00. According to this study, the SCSB detects the obstructive events without always distinguishing between severe periodic hypopnoeas and obstructive apnoeas. The sensitivity of the SCSB makes it valuable for screening subjects suspected of having obstructive sleep apnoeas. Further studies will concentrate on a more detailed analysis of the various respiratory, BCG and body movement patterns, which may lead to additional information on the severity of the upper airway obstruction.
Effects of clonidine on bronchial responses to histamine in normal and asthmatic subjects
Authors: Dinh Xuan AT , Regnard J , Matran R , Mantrand P , Advenier C , Lockhart A
Published: November 2022

Our aim was to examine the effects of clonidine (C), an agonist of central and peripheral alpha-2 adrenoceptors, on bronchomotor responsiveness to histamine (H). In a double-blind study, we compared on two different days the effects of pretreatment with placebo (P) and with 200 micrograms or 150 micrograms of C given orally, in ten normal (NS) and eight asymptomatic asthmatic subjects (AS) respectively, the response to inhalation of serially increasing doses of H. On each day, five doubling doses of H (first dose = 3.5 and 1.1 mumol in NS and AS, respectively) were administered every 5 min; forced expiratory volume in one second (FEV1) was measured after each dose. The dose-response curves were compared by an analysis of variance. Clonidine caused hypotension with bradycardia in all subjects. Baseline values and pre-challenge values of FEV1 after P and C were identical on the two study days. Compared to P, C did not modify the response to H in NS but significantly increased it in AS (p less than 0.01). Our results suggest that the neural control of the airways differs in AS compared to NS and could be explained either by a decrease in sympathetic inhibitory activity or a greater responsiveness of the airways to parasympathetic stimulation and/or a higher parasympathetic tone in AS.
Nasal response to substance P and methacholine in subjects with and without allergic rhinitis
Authors: Devillier P , Dessanges JF , Rakotosihanaka F , Ghaem A , Boushey HA , Lockhart A , Marsac J
Published: November 2022

We compared the rise in nasal airway resistance (NAR) provoked by topical application of substance P (SP) and of methacholine (MCH) in seventeen patients suffering from rhinitis and fourteen control subjects. Challenges with SP or MCH were separated by a week or more. NAR was measured by posterior rhinomanometry before and 10 min after intranasal administration of SP (10-40 nmol) or MCH (3-12 mumol). The two groups of subjects had similar baseline levels of NAR and similar small responses to buffered saline. Substance P but not MCH provoked cutaneous flushing in all subjects. Both SP and MCH provoked a significantly greater increase in NAR in patients suffering from rhinitis than in control subjects. The increase in NAR was dose-dependent, and on a molar basis, SP was 375-500-fold more potent than MCH. Pretreatment with 200 micrograms of a topically active anticholinergic agent, oxytropium bromide, prevented the rise in NAR caused by 12 mumol of MCH but not that caused by 40 nmol of SP in six patients suffering from rhinitis. We conclude that SP is absorbed across the nasal mucosa and causes cutaneous vasodilation, that MCH and SP cause a greater rise in NAR in patients suffering from rhinitis than in control subjects, that SP is about 500-fold more potent than MCH in increasing NAR, and that the rise in NAR caused by SP is not mediated by postganglionic parasympathetic mechanisms.
Variability and reproducibility in the measurement of tracheobronchial clearance in healthy subjects and patients with different obstructive lung diseases
Authors: Del Donno M , Pavia D , Agnew JE , Lopez-Vidriero MT , Clarke SW
Published: November 2022

The purpose of this study was to establish the inter- and intra-subject/patient variability of tracheobronchial clearance, measured for 6 h, using a radioaerosol technique. Inter-subject variability was evaluated in five groups: 33 healthy non-smokers (NS); 19 asymptomatic smokers (S); 40 asthmatics (A); 27 chronic bronchitics (CB) and 12 bronchiectatics (B). Intra-subject variability was evaluated in 16 A and 27 CB who were studied twice. The inter-subject/patient coefficient of variation (CoV) of tracheobronchial clearance was 13% for NS and 28-39% for the remaining four groups. The intra-patient CoV was about half of the inter-patient CoV. Inter-subject CoV (for A and CB) appeared to be independent of initial tracheobronchial deposition of radioaerosol and frequency of cough. We were also able to estimate the approximate number of patients required for a crossover study in order to avoid statistical, type II errors when investigating the effect of a drug or of a therapeutic intervention on tracheobronchial clearance.
Response of nasal ciliated cells of the guinea-pig during allergic reactions in human blood
Authors: Ohashi Y , Nakai Y , Ikeoka H , Koshimo H , Esaki Y
Published: November 2022

Nasal mucosal samples from thirty-five guinea-pigs were placed in a chamber, containing the medium RPMI 1640. Ciliary activity (beats.s-1) of the most active cell in each mucosal culture was measured using a photoelectric method. The RPMI 1640 was then replaced by 2 ml of RPMI 1640 and 1 ml of heparinized human blood from a non-allergic patient, with a ragweed-sensitive nasal allergy, or patients with D. farinae-sensitive nasal allergy: the ciliary activity of the same ciliated cell in each culture did not change significantly. We then added 1 micrograms of D. farinae extracts to evoke an in vitro allergic reaction. Ciliary excitation was induced when D. farinae extracts were added to the blood from D. farinae-sensitive subjects but not when added to blood from subjects without sensitivity to D. farinae. The peak and plateau of such an event occurred after 20-30 min. Ciliary stimulations were correlated with D. farinae-induced histamine release from whole blood. Thus, in vitro allergic reactions stimulate activity in cilia from normal nasal mucosa.
The role of physiological deadspace and shunt in the gas exchange of patients with pulmonary hypertension: a study of exercise and prostacyclin infusion
Authors: Otulana B , Higenbottam T
Published: November 2022

Haemodynamic and gas exchange measurements were made at rest, on supine exercise and on acute vasodilatation with intravenous prostacyclin in eight patients with pulmonary hypertension. This enabled an assessment of the contribution of V/Q imbalance to the abnormal gas exchange on the condition. At rest arterial oxygen tension, PaO2 (mean 8.1 +/- 1.7 kPa) and mixed venous oxygen tension, PVO2 (3.6 +/- 0.4) were reduced. The physiological shunt, Qs/Qt (15 +/- 17%) and the dead space, Vd/Vt (0.47 +/- 0.11) were elevated above normal. Exercise produced an increase in cardiac index, a fall in PVO2, no significant change in PaO2 and also no appreciable changes in the Vd/Vt and Qs/Qt. Intravenous prostacyclin increased the cardiac index and raised the PVO2 and the PaO2 but again with no significant changes in Vd/Vt and Qs/Qt. We conclude that ventilation-perfusion imbalance as shown by increased Vd/Vt and Qs/Qt, contributes significantly to the abnormal gas exchange in pulmonary hypertension. But neither index was altered by exercise or vasodilation; the latter improves the hypoxemia by increasing the PVO2 from an increase in the cardiac output.
Comparison of human lung surface protein profiles from the central and peripheral airways sampled using two regional lavage techniques
Authors: Smith SF , Guz A , Winning AJ , Cooke NT , Burton GH , Tetley TD
Published: November 2022

This study describes two new techniques of lung lavage which selectively remove material from the central airways, or from the lung below the seventh generation. Bronchograms confirmed that discrete regions of the lung were washed by central lavage (CL; maximum airway diameter approximately 6.5 mm) and peripheral lavage (PL; maximum airway diameter approximately 1.3 mm), and that both could be clearly distinguished from conventional bronchoalveolar lavage (BAL). These techniques were used to establish whether or not large-airway proteins made a major contribution to the protein profile of BAL. Twenty consecutive patients undergoing routine fibreoptic bronchoscopy were investigated. More bronchial mucus proteinase inhibitor per unit albumin and per unit total measured antiproteinase was present in CL than PL or BAL. In contrast alpha 1-proteinase inhibitor per unit albumin and as a percentage of total measured antiproteinase was lower in CL than in other lavage types. There were no differences in elastase activity, irrespective of the way in which the data were expressed. As no differences were found between BAL and PL for any of the variables measured, it was concluded that in the subjects studied the contribution of CL proteins to BAL was minimal.
Interaction between allopurinol and pyrazinamide
Authors: Lacroix C , Guyonnaud C , Chaou M , Duwoos H , Lafont O
Published: November 2022

Pyrazinamide (PZA) is increasingly used with isoniazid and rifampicin, in short-course antituberculous chemotherapy in service programme conditions. Complicating arthralgias occur due to hyperuricaemia induced by the inhibition of renal tubular secretion of uric acid by pyrazinoic acid, the main PZA metabolite. Allopurinol (Al), a hypouricaemic agent, provides no substantial clinical improvement. Pharmacokinetics of PZA and its metabolites were studied in six healthy volunteers, in a cross-over design, after a single oral dose of PZA alone and, in a second trial, after the same dose together with Al. Plasma and urinary concentrations were measured by high pressure liquid chromatography with a column of cation exchange resin. Analysis of the pharmacokinetic parameters showed that Al induced marked changes in levels of PZA metabolites and accumulation of pyrazinoic acid. Despite decreasing uric acid synthesis, allopurinol increased plasma concentrations of pyrazinoic acid, which is directly responsible for the inhibition of renal urate secretion. Other drugs, which do not involve xanthine oxidase inhibition, should be used in the treatment of this side effect of chemotherapy.
Electron microscopic analysis of asbestos body cores from the Belgian urban population
Authors: Moulin E , Yourassowsky N , Dumortier P , De Vuyst P , Yernault JC
Published: November 2022

Typical ferruginous bodies considered as asbestos bodies (AB) were collected from the lungs of 19 asbestos-exposed and 25 non-exposed urban subjects. Of the 319 body cores analysed by energy dispersive spectrometry (EDS), 315 were asbestos. The non-asbestos cores were talc and crystalline silica. 89.2% of the asbestos cores were commercial amphiboles (amosite/crocidolite), 7% were chrysotile and 3.8% were non-commercial amphiboles (anthophyllite/tremolite). The commercial amphibole bodies were found in exposed and non-exposed subjects and chrysotile bodies mostly in exposed subjects. The non-commercial amphibole bodies were detected in non-exposed patients with low lung AB levels; this background contamination would be more difficult to detect in lungs containing large amounts of bodies due to occupational exposure. Chrysotile bodies and tremolite/anthophyllite bodies were not observed together. We suggest that in Belgium the source of non-commercial amphiboles exposure is not contamination by chrysotile.
Nocturnal asthma: snoring, small pharynx and nasal CPAP
Authors: Guilleminault C , Quera-Salva MA , Powell N , Riley R , Romaker A , Partinen M , Baldwin R , Nino-Murcia G
Published: November 2022

We studied two populations of patients who snored and had frequent nocturnal asthma attacks: ten overweight men presenting with typical obstructive sleep apnoea syndrome, and a group of five adolescents with regular snoring and an increase in negative inspiratory oesophageal pressure during stage II non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. All subjects presented cranio-mandibular abnormalities at cephalometric evaluation, with a narrow space behind the base of the tongue. Both populations were treated with nasal continuous positive airway pressure (CPAP) during sleep. Snoring and partial or complete airway obstruction were eliminated, as were the nocturnal asthma attacks. Two adolescents treated with upper airway surgery after nasal CPAP showed no nocturnal asthma at short-term follow-up. Nasal CPAP had no effect on daytime asthma. One hypothesis is that a subgroup of asthmatic patients with small pharynxes may have enhanced vagal stimulation during sleep compared with other asthmatic patients. This enhancement would be related to the repetitive Muller manoeuvres noted with airway obstruction during sleep. Combined with the local effects of snoring, this extra vagal stimulation would be a precipitating factor in nocturnal asthma attacks.
Bacteraemic Haemophilus influenzae pneumonia
Authors: Allen MB , Prowse K
Published: November 2022

Bacteraemia with Haemophilus pneumonia is uncommon. To determine its incidence and features case notes of patients in whom Haemophilus spp. were isolated from blood and pleural fluid over a five-year period were reviewed. Eight adult patients with H. influenzae bacteraemia were identified, five of whom had pneumonia on clinical and radiographic criteria. Only one patient had a predisposing factor, chronic obstructive lung disease. Two patients had beta-lactamase producing isolates, one of whom developed an empyema, following treatment with ampicillin, which required surgical drainage. Four patients were elderly, aged 69-80 yrs and were clinically in shock at the time of diagnosis. Seven of the eight patients survived.
A national register for long-term oxygen therapy in chronic hypoxia: preliminary results
Authors: Strom K , Boe J
Published: November 2022

A national register of patients undergoing long-term oxygen therapy in Sweden was started in 1987. Of the population of 8.4 million, 560 patients (267 males) were registered as undergoing domiciliary oxygen treatment on January 1, 1987. These registered patients, aged between 2-86 yrs (mean age 65 yrs), constituted some 90% of all patients receiving domiciliary oxygen therapy because of chronic hypoxaemia on that date. The chronic respiratory diseases leading to hypoxaemia (more than one diagnosis could be registered for each patient) were: chronic obstructive pulmonary disease (COPD) (393), sequelae from pulmonary tuberculosis (92), thoracic deformity (97), interstitial fibrosis (44), benign pleural disease (22) and others (84). Concentrators were used by 253 patients and high-pressure compressed gas cylinders by 307. Arterial blood gas analyses were registered for 547 patients. The mean arterial oxygen tension (PaO2) when breathing air was 6.5 +/- 1.1 kPa and 9.0 +/- 1.4 kPa when breathing oxygen. The mean arterial carbon dioxide tension (PaCO2) without oxygen was 6.5 +/- 1.5 kPa and 6.8 +/- 1.5 kPa with oxygen. The register forms a data-base which can be used for the evaluation of different home oxygen systems, regional differences in the access to treatment and treatment performance and decisions relating to health care economics.
Role of lung volumes in sleep apnoea-related oxygen desaturation
Authors: Series F , Cormier Y , La Forge J
Published: November 2022

We studied the influence of lung volumes on apnoea-induced desaturation in ten subjects with sleep apnoea syndrome. Lung volumes were measured by helium dilution in the sitting and supine position and closing volume with the single-breath nitrogen washout test. To characterize the severity of apnoea-induced desaturations, we determined a desaturation curve for each patient. This curve was obtained by plotting the fall in arterial oxygen saturation (SaO2) reached at the end of each apnoea against the apnoea duration. From this curve we selected two indices: 1) the SaO2 fall following 30 s of obstructive apnoea (delta SaO2 30); and 2) the desaturation surface between 10-30 s of obstructive apnoea (DS 10-30). Both the delta SaO2 30 and the DS 10-30 were significantly correlated with the expiratory reserve volume (ERV), measured in the sitting (r = 0.77 and 0.65, respectively; p less than 0.05) and the supine positions (r = 0.96 and 0.87; p less than 0.005). A strong correlation was also observed with the difference between the supine ERV and the seated closing volume CV) (r = 0.99 with delta SaO2 30 and 0.89 with DS 10-30; p less than 0.005). Obesity influenced sitting and supine ERV values. We conclude that, among lung volumes, supine ERV and supine ERV-seated CV are the best indicators of the severity of apnoea-induced desaturation.
The effect of breath size and posture on calibration of the respiratory inductive plethysmograph by multiple linear regression
Authors: Verschakelen JA , Deschepper K , Clarysse I , Demedts M
Published: November 2022

The accuracy of the respiratory inductive plethysmograph (Respitrace) for estimation of lung volume changes during quiet breathing and vital capacity (VC) manoeuvres was evaluated using a variant of the multiple linear regression (MLR) technique. We applied this technique successively on quiet breathing, on the whole VC, and on each of the four quarters of the VC separately. This was carried out in six body positions. The best estimation of tidal volumes was obtained when calibration factors calculated during quiet breathing were used. The best estimation of VC was obtained when the calibration factors were adapted to the level of lung inflation. These results indicate that, using a single position MLR calibration method, the Respitrace measures tidal and VC mouth volumes very accurately. The accuracy of this MLR method for estimation of the rib cage and abdominal contributions was validated by comparison with isovolume calibration factors. Both techniques gave very similar results during tidal breathing. However, the MLR calibration factors may have no physiological meaning (i.e. for volume partitioning) when they are calculated from VC manoeuvres, in which more than two degrees of freedom are involved.
Protection against pulmonary O2 toxicity by N-acetylcysteine
Authors: Wagner PD , Mathieu-Costello O , Bebout DE , Gray AT , Natterson PD , Glennow C
Published: November 2022

N-acetylcysteine (NAC) is a known antioxidant. We therefore investigated NAC as an agent protective against O2 toxicity in the lung. Twelve dogs were anaesthetized with sodium pentobarbital and ventilated with 100% O2 for 54 h. Five were given diluent and 7 intravenous NAC (loading dose prior to 100% O2 ventilation of 150 mg.kg-1 and maintenance dose of 20 mg.kg-1.h-1). Every 6 h, physiological evaluation of the pulmonary circulation, mechanical properties, and gas exchange was performed. Post-mortem evaluation consisted of gross examination and weighing followed by light and electron microscopy. By both functional and structural criteria, NAC protected against the effects of 100% O2. The NAC group developed significantly less increase in pulmonary vascular resistance, arterial carbon dioxide tension (PaCO2) and lung wet weight, while dynamic compliance was greater. NAC also delayed the development of abnormal ventilation-perfusion relationships and was associated with reduced pulmonary white cell accumulation, with less evidence of alveolar and interstitial oedema. NAC may well be worthy of evaluation as a therapeutic agent in human diseases characterized by oxidant damage.
V/Q and alveolar gas exchange in pulmonary sarcoidosis
Authors: Eklund A , Broman L , Broman M , Holmgren A
Published: November 2022

Eleven patients with pulmonary sarcoidosis of type II or III were investigated with regard to regional distribution of ventilation and perfusion (V/Q), alveolar gas exchange and diffusion limit at rest and during exercise. Lung volumes were 50-65% of normal values. Flow-volume curves indicated obstructive changes. The transfer factor was 75% (range 16-120%) of predicted. Perfusion scintigraphy showed marked defects in 7 out of 11 patients. Radiospirometry showed matching ventilation and perfusion defects and washout of xenon was prolonged. There was a venous admixture at rest of 9%. Arterial oxygen tension (Pao2) averaged 9.7 kPa. V/Q analyses indicated the presence of a small shunt (1%), regions with low V/Q in 4 out of 11 patients, regions with high V/Q in 5 out of 11 patients and increased wasted ventilation. At rest measured Pao2 was lower (0.6 kPa) than predicted from the V/Q distribution. During mild supine exercise causing significant dyspnoea, pulmonary vascular resistance rose to abnormal values, 5.2 mmHg.l.-1 min-1.m2 BSA. The venous admixture decreased to 5.4%. The shunt was unchanged, as was the perfusion of regions with low V/Q. The regions with abnormally high V/Q disappeared. Measured Pao2 decreased to 9.1 kPa, while calculated Pao2 remained unchanged. Thus the P(A-a)o2 at rest (4.2 kPa) was 70% caused by shunt and V/Q mismatch. During exercise alveolar-arterial pressure difference for oxygen measured P(A-a)o2 rose further to 5.1 kPa, while calculated P(A-a)o2 remained unchanged and was only 50% caused by shunt and V/Q disturbances. The difference between calculated and measured Pao2 indicated significant diffusion limitation both at rest and during mild exercise.