bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling and assessment of accidental subsea gas leakage using a coupled computational fluid dynamics and machine learning approaches
Authors: Ellethy Ahmed M , Shehata Ahmed S , Shehata Ali I , Mehanna Ahmed
Published: November 2022

All over the world, the oil and gas industries are the most important source of energy. The likelihood of subsea gas and oil leakage is increasing, which can cause threats and harmful impacts on the marine environment and potentially catastrophic events such as fires, explosives, and the loss of structural integrity of subsea infrastructure. Also, Physical models have usually been used to predict sea currents, but they are unstable to disturbances and hence incorrect over long periods of time. Machine learning approaches are more resistant than the physical models that have usually been used to predict sea currents. Also, Physical models have usually been used to predict sea currents. Nonetheless, they are not stable to disturbances and thus are not correct for long periods of time. Machine learning approaches are more resistant than the physical models that have usually been used to predict sea currents. Machine learning approaches are more resistant to change and perturbation. Therefore, the goal of this research is to assess the potential of hazards of the gas plume from subsea pipeline rupture till reaching the sea surface by changing the influence parameters on gas plume to assist petroleum companies in developing risk assessment strategies by assessing and simulating subsea gas release in order to contain the leakage by developing coupling models one for machine learning code which can predict the upcoming water current speed by using Multiple Linear Regression algorithm and hooked it by UDF to a second model which implements Computational Fluid Dynamics (CFD) model to study subsea gas release under current effects. Engebretsen’s Rotvoll experiment data is being used to validate the numerical computational fluid dynamics model. The rising time and fountain height and horizontal migration for gas release are the essential factors to be considered while evaluating the gas dispersion through our study by changing the influencing parameters such as leakage hole sizes, water current speeds, gas velocity, and water depths in the presence of water current in all cases. Also, applied our simulation to real case parameters for one of the Egyptian Petroleum Companies. These findings might aid in evaluating the hazards and response planning in the event of subsea gas leakage.
A stiffness-based method for damage detection in 3-D offshore jacket platforms using inverse vibration problem (IVP) technique
Authors: Tabeshpour Mohammad Reza , Abbaspour Madjid , Ahmadi Ali
Published: November 2022

More attention has been paid to Damage detection in offshore jacket platforms (OJP) because of repair and maintenance issues. Damage detection using modal data from a few sensors is one of the main important subjects that researchers have paid attention to it. The inverse Vibration Problem (IVP) technique does not need modal data in all nodes of OJP but first modal data in different levels of platform and principal degrees of freedom could be sufficient. Since the complex structural model becomes a reduced shear building by implementing this technique, there must be a reduced equivalent stiffness matrix for the healthy structure to make the comparison for damage detection. This paper deals with the formulation and implementation of IVP technique in corporation of the proper method for calculation of equivalent level stiffness. The proper method was selected based on a comparison of modal data obtained from full and reduced models using comparison tools like the MAC coefficient. Also, damage detection in a typical OJP model under a specific damage scenario was investigated numerically and experimentally and the results show the reliable performance of the methodology. A damage detection flowchart is suggested to detect damage location properly. It is developed mainly based on geometrical couplings in OJP structure in damaged conditions and the method leads to damage location exactly and maximum error in damage prediction is obtained at about 12%.
Virtual and Augmented Reality in Management of Phantom Limb Pain: A Systematic Review
Authors: Eldaly Abdullah S. , Avila Francisco R. , Torres-Guzman Ricardo A. , Maita Karla C. , Garcia John P. , Serrano Luiza Palmieri , Emam Omar S. , Forte Antonio J.
Published: November 2022

Upper and lower limb amputations are frequently associated with phantom limb pain (PLP). Recently, virtual reality (VR) and augmented reality (AR) have been reported as a potential therapy of PLP. We have conducted a systematic review of literature to evaluate the efficacy of VR and AR in managing PLP. Four databases were searched: PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and Web of Science. We utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for our organization. The initial search resulted in 164 results. After title, abstract, and full-text screening, 9 studies were included. One study was of good quality and 8 studies were of fair to poor quality. Seven studies utilized VR and 2 studies utilized AR. The number of treatment sessions ranged from 1 to 28 and the duration ranged from 10 minutes to 2 hours. Several pain scales were used to evaluate PLP pre- and postintervention including Numeric Rating Scale, Pain Rating Index, McGill Pain Questionnaire, and Visual Analog Scale. All the studies reported improvement of PLP on one or more of pain scales after one or more sessions of VR or AR. Despite the promising results reported by literature, we cannot recommend using VR or AR for PLP. Most of the studies are of poor design and have limited sample size with high bias levels. Therefore, no substantial evidence can be derived from them. However, we do believe further research with high-quality randomized controlled trials should take place to increase the knowledge of the potential advantages.
Anterior Scalene Muscle Block Response Predicts Outcomes Following Thoracic Outlet Decompression
Authors: Beason Austin M. , Thayer Jacob A. , Arras Norma , Franke Jacob D. , Mailey Brian A.
Published: November 2022

Background:

There is no definitive objective measure for diagnosis of thoracic outlet syndrome (TOS), and functional capacity testing on standardized rehabilitation exercises before and after an anterior scalene muscle block (ASMB) has the potential to serve as a predictor of response to surgery and to improve diagnostic accuracy in these cases.

Methods:

Patients evaluated for TOS underwent ASMB as a diagnostic test and were retrospectively reviewed. Functional capacity scores were recorded for patients performing repetitive motion exercises immediately before ASMB, 15 minutes after ASMB, and at a minimum of 6 weeks after thoracic outlet decompression (TOD). The primary outcome of interest was correlation between the pre- to post-ASMB difference and the pre-ASMB to postoperative difference with respect to 3 functional work capacity scores.

Results:

The average change in time-to-fatigue and work product between pre- and post-ASMB of all exercises was an increase of 39.5% and 53.8%, respectively. The greatest pre-ASMB to post-TOD difference was seen for the Extremity Abduction Stress Test with an average improvement of 109.7% and 150.4% for time-to-fatigue and work product, respectively. The degree of percent improvement post-ASMB correlated positively with the degree of percent improvement post-TOD for all exercises with respect to work product and time-to-fatigue.

Conclusions:

Patient response to ASMB as measured by functional capacity on rehabilitation exercises predicted objective functional outcomes following TOD. Post-ASMB outcomes correlated with post-TOD outcomes. The ASMB can be used to assist in diagnosing TOS and provide a surrogate for expectation in patients considering undergoing neurogenic TOD.
Risk Factors for 30-Day Complications and Unplanned Reoperation Following Surgical Treatment of Distal Radius Fractures
Authors: Newton William N. , Johnson Charles A. , Daley Dane N.
Published: November 2022

Background:

The purpose of this study was to identify demographic data, medical comorbidities, and perioperative factors that are associated with increased risk of overall surgical complications, wound complications, and reoperation within 30 days of open reduction and internal fixation (ORIF) of distal radius fractures.

Methods:

All adult patients undergoing ORIF of distal radius fractures in the National Surgical Quality Improvement Program database between 2005 and 2020 were identified. Patients were excluded for secondary procedures, open/infected injuries, or inpatient surgical setting. Demographic data, medical comorbidities, and perioperative data were examined for each patient, and patients were grouped by the presence or absence of any surgical complication. Univariate analysis and multivariate logistic regression were used to identify risk factors.

Results:

A total of 20 301 patients from between 2005 and 2020 met the inclusion criteria, of which 219 complications (1.1% of cases) were identified. Following multivariate analysis, independent risk factors found to be associated with surgical complications included male sex, smoking, heart failure, longer operative time, and American Society of Anesthesiologists (ASA) classification of 3 or higher.

Conclusion:

Male sex, smoking, heart failure, prolonged operative time, and ASA status of 3 or higher are associated with an increased risk of surgical complications following ORIF of distal radius fractures. These complications, with the exception of heart failure, were also associated with an increased risk of wound complications. Finally, male sex, nonwhite race, smoking, dialysis, prolonged operative time, and 3 or higher ASA class were associated with reoperations. Understanding these risk factors allows surgeons to better predict and prevent complications in high-risk populations.
Adapting Cognitive Remediation Group Therapy as an Online or Hybrid Intervention for People Aging With HIV and Cognitive Concerns: Focus Group Protocol
Authors: Eaton Andrew D. , Hui Jenny , Muchenje Marvelous , Murzin Kate , Chan Carusone Soo , Ibáñez-Carrasco Francisco , Novik Nuelle , McCullagh John W. , Nicolay Susanne , Walmsley Sharon L.
Published: November 2022

Cognitive impairment is a significant health issue for people aging with HIV/AIDS. Cognitive challenges can include forgetfulness, trouble concentrating, and increasing struggles to learn new skills, all of which contribute to poorer mental health and decreased quality of life. Although there is no specific drug therapy that can reverse the brain impairment, group therapies may help people aging with HIV and cognitive challenges to better cope with their symptoms when combined with their usual medical treatment and follow-up. This community-based study will involve peer-led focus groups to discuss cognitive remediation group therapy – a combination of mindfulness-based stress reduction and brain training activities tested in a pilot randomized, controlled trial – as an in-person intervention for people aging with HIV in 2019. Via a brief demographic survey and technology-mediated focus groups ( n = 40) in Ontario and Saskatchewan, we will determine how the intervention could be adapted in an online or hybrid format considering the ongoing COVID-19 pandemic. Content analysis will be employed whereby a team of independent coders will code the focus group transcripts in line with the co-design framework and “Double Diamond” model of developing interventions, including intervention structure, content, and mode of delivery. Given the aging of the HIV population in Canada, increasing support will be required in addition to medical care to improve quality of life, and proactively address concerns about cognition. This protocol provides a roadmap for adapting in-person psychosocial interventions using community-based and technology-mediated methods.
What role for climate pact ambassadors? A policy process perspective
Authors: Tosun Jale
Published: November 2022

The European Green Deal puts forth an ambitious agenda for a transition towards sustainable development. To this end, it embraces participatory governance and has even created a new tool for it: climate pact ambassadors (CPAs). CPAs either act on their own behalf or represent organisations that have made a publicly accessible pledge. They are expected to provide information on and support for climate action, as well as ‘inspire’ others in their networks and communities. Despite only being launched in December 2020, the European Commission has endorsed more than 850 CPAs (as of October 2022). What role can the CPAs play at the different stages of the policy cycle? How could their participation in pertinent policy processes become more effective? These are the two questions that guide this explorative analysis.
Is the two-step test set out in LM and L and P English Supreme Court’s best option in post-Brexit Britain for EAW requests made by States with structural deficiencies?
Authors: Stirone Angelo , Mumolo Giovanna
Published: November 2022

This article briefly introduces the European arrest warrant (‘EAW’) system, analysing the context in which it develops and how this procedure interacts with both the intricate post-Brexit universe and the current instability of the Polish judiciary. Paragraph 2 assesses the relevant case law of the European Court of Justice (‘CJEU’) in cases of EAW requested by States with generalised deficiencies and asserts that the legal approach developed in LM and L and P proves correct in the abstract. Though it argues that the safeguarding mechanisms set out in the EAW Framework Decision can be paralysed by instruments that are ontologically political in nature, it thus proposes a new legal approach that consists of a three-step test which would effectively guarantee the protection of fundamental rights. The article concludes by arguing that if English Courts were to follow this new approach, departing from LM and L and P, they would effectively implement the protection of fundamental rights in EAW procedures.
Liposomal Daunorubicin and Cytarabine, a Potential Therapy for Blastic Plasmacytoid Dendritic Cell Neoplasm
Authors: Ashok Kumar Prashanth , Ombada Mulham , Pemmasani Gayatri , Tambe Ajay , Banki Katalin , Gentile Teresa
Published: November 2022

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive malignancy with poor outcomes. Although novel options like tagraxofusp, a CD123-directed cytotoxin, has emerged and is promising, treatment options are very limited in the relapsed and recurrent setting. We present a case of refractory BPDCN in a 62-year-old man who showed a complete bone marrow response to liposomal daunorubicin and cytarabine (vyxeos).
Pulmonary hypertension in obstructive sleep apnoea
Authors: Laks L , Lehrhaft B , Grunstein RR , Sullivan CE
Published: November 2022

To determine the frequency and correlates of pulmonary hypertension in sleep-disordered breathing, pulmonary artery pressure, lung function and arterial blood gases were measured in 100 consecutive patients with obstructive sleep apnoea (OSA) (respiratory disturbance index (RDI) of > 20 episodes.h-1). Twenty six of the patients had significant chronic airflow limitation (CAL). Overall, 42% of patients had awake pulmonary artery pressure > 20 mmHg. Patients with pulmonary hypertension were older, had higher arterial carbon dioxide tension (PaCO2), lower arterial oxygen tension (PaO2) and lower forced expiratory volume in one second (FEV1) values compared with normotensive patients. Pao2, PaCO2 and FEV1 were correlated with the levels of pulmonary artery pressure (correlation coefficient (r2) 0.50, 0.46 and 0.49, respectively). These three factors combined could explain 33% of the variability in pulmonary artery pressure. Six patients had pulmonary hypertension despite a PaO2 in excess of 10.7 kPa (80 mmHg). We conclude that pulmonary hypertension is common in patients with moderate and severe sleep apnoea, especially those with coexisting chronic airflow limitation. The presence of daytime hypoxaemia is not a prerequisite in the development of pulmonary hypertension in these patients.
Post-transplant obstructive lung disease ("bronchiolitis obliterans"): a clinical comparative study of bone marrow and lung transplant patients
Authors: Philit F , Wiesendanger T , Archimbaud E , Mornex JF , Brune J , Cordier JF
Published: November 2022

Patients at a single pulmonary centre who developed obstructive lung disease after bone marrow transplantation (BMT) and lung transplantation (LT) were studied, in order to compare the clinical expression of post-transplant obstructive lung disease (PTOLD) (bronchiolitis obliterans) in these two conditions, which have so far been studied separately. Nine out of 179 patients surviving more than 100 days after BMT (5%) and 9 out of 44 patients surviving more than 100 days after LT (20%) developed post-transplant obstructive lung disease. This was defined by an irreversible airflow obstruction, as characterized by a forced expiratory volume in one second divided by forced vital capacity (FEV1/FVC) of less than 70%, and a FEV1 of less than 70% of predicted value. The mean interval between transplantation and the diagnosis of post-transplant obstructive lung disease was 262 days and 217 days for BMT and LT patients, respectively. In all cases, pulmonary symptoms consisted of dyspnoea and progressively productive cough. Bronchial dilatation on high-resolution computed tomography scans was the main imaging feature present in both groups of patients at the onset of post-transplant obstructive lung disease. The mean FEV1/FVC ratio was 51 and 54% for BMT and LT patients, respectively. All BMT and LT patients had normal transfer coefficient. Clinical chronic graft-versus-host disease was present in all BMT patients before or concurrent with the onset of post-transplant obstructive lung disease, and all LT patients had presented at least one episode of acute lung rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
High dose fluticasone propionate, 1 mg daily, versus fluticasone propionate, 2 mg daily, or budesonide, 1.6 mg daily, in patients with chronic severe asthma. International Study Group
Authors: Ayres JG , Bateman ED , Lundback B , Harris TA
Published: November 2022

Airway inflammation is now regarded as fundamental in the pathogenesis of asthma and treatment with inhaled corticosteroids has proved effective. There is a need for drugs in this category with higher topical potency but fewer side-effects than those presently available. A double-blind, parallel group study was conducted in 671 patients with severe asthma (already taking between 0.8-2.0 mg of inhaled corticosteroid daily) to compare the safety and efficacy of 6 weeks of treatment with inhaled fluticasone propionate (FP), 1 mg daily, to fluticasone propionate, 2 mg daily, and budesonide (BUD), 1.6 mg daily, delivered via a metered-dose inhaler. Peak expiratory flow (PEF), asthma symptoms, and usage of rescue medication were recorded daily by the patient. At each clinic visit (-2, 0, 3 and 6 weeks) morning serum cortisol levels, bone markers and spirometry were assessed. The changes in mean morning PEF from baseline (weeks 1-6) were: FP 2 mg daily +24 l.min-1; FP 1 mg daily +21 l.min-1; BUD 1.6 mg daily +13 l.min-1. A similar rank order for the three treatments was seen for evening PEF, clinic spirometry, reduction of diurnal PEF variation, symptom scores, and requirement for rescue bronchodilators. The mean serum cortisol levels remained well within the normal range in all three groups. Analysis of the geometric mean cortisol ratio (treatment/baseline ratio after 6 weeks treatment) showed a changed rank order, the values being: FP 1 mg daily 1.04; BUD 1.6 mg daily 0.97; FP 2 mg daily 0.88.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of ipratropium bromide and/or sodium cromoglycate pretreatment on water-induced bronchoconstriction in asthma
Authors: Tranfa CM , Vatrella A , Parrella R , Bariffi F
Published: November 2022

The mechanisms underlying water-induced bronchoconstriction are still not fully understood. Cholinergic reflexes and mast cell mediator release are currently believed to play an important pathogenetic role. In order to evaluate the relative contribution of each of these mechanisms, we studied the effect of ipratropium bromide (80 micrograms), a muscarinic antagonist, and sodium cromoglycate (20 mg), an inhibitor of mast cell mediator release, administered alone and in combination, in the prevention of bronchospasm induced by ultrasonic mist of distilled water (UMDW). Fifteen patients with documented atopic asthma and hyperresponsiveness to distilled water were selected for this randomized, placebo-controlled, double-blind study. Airway responses to pharmachological agents and bronchial challenge were measured by change in specific airways conductance (sGaw). Sodium cromoglycate had no effect on bronchial calibre, whilst ipratropium bromide and the combination of the two drugs produced a significant bronchodilation 30, 60 and 90 min after treatments. The maximal increase in sGaw (mean % +/- SD) was observed at 90 min: 63 +/- 28% and 58 +/- 22% after ipratropium bromide and the combined drugs respectively. UMDW (2, 4, 8, 16 ml water) caused a -36 +/- 19%, -42 +/- 19%, -49 +/- 18%, -56 +/- 15% mean % +/- SD fall in sGaw after placebo. Pretreatment with sodium cromoglycate abolished the bronchoconstriction to 2 ml (fall sGaw -5 +/- 23% NS) and significantly reduced the effect of 4 (-15 +/- 22%), 8 (-21 +/- 20%) and 16 ml (-24 +/- 18%) water.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in mucociliary clearance during and after isocapnic hyperventilation in asthmatic and healthy subjects
Authors: Daviskas E , Anderson SD , Gonda I , Chan HK , Cook P , Fulton R
Published: November 2022

Hyperpnoea with dry air could lead to a reduction in depth and hyperosmolarity of the periciliary fluid layer (PFL) as a consequence of evaporative water loss. We investigated whether mucociliary clearance (MCC) is likely to be affected by dry air hyperpnoea, which also results in airway narrowing in asthmatics. MCC was measured by radioaerosol technique, for about 1 h, in 10 asthmatic and 8 healthy subjects on 3 separate days: 1) nasal resting breathing with ambient air; 2) isocapnic hyperventilation (ISH) with dry air; and 3) ISH with warm humid air. Analysis of the initial and post-intervention lung radioactivity for the whole right lung and for defined regions of interest showed that, compared to ISH with warm humid air and nasal resting breathing, MCC was reduced during and increased post-ISH with dry air in the whole right lung of both groups. The mean reduction in clearance (+/- 95% confidence interval (95% CI)) was -9.3% (-3.1 to -15.6%) and -3.6% (-2.0 to -9.1%), and the mean increase (+/- 95% CI) was 19.2% (11.8 to 26.6%) and 14.8% (7.1 to 22.5%), compared to warm humid air, in asthmatic and healthy subjects, respectively. However, regional analysis showed that the changes were present in all lung regions of the asthmatics, whilst only in the central region of the healthy subjects. The duration of the increased clearance rates post-ISH was also different in both groups. The changes in mucociliary clearance during and after isocapnic hyperventilation with dry air was probably related to the water content of the inspired air, causing transient changes in the periciliary fluid layer.
Spirometric standards for healthy adult lifetime nonsmokers in Australia
Authors: Gore CJ , Crockett AJ , Pederson DG , Booth ML , Bauman A , Owen N
Published: November 2022

The aim of this study was to develop suitable spirometric prediction equations for asymptomatic Caucasian adults in the Australian population. These equations were compared with those of previous studies and constants were presented which, when associated with the prediction equations, permitted the calculation of 5% tolerance intervals for lung function. The 1,302 subjects (aged 18-78 yrs) who underwent pneumotachograph spirometry, using techniques recommended by the American Thoracic Society, were a sample from metropolitan Adelaide, South Australia. The variables recorded were sex, age, height, mass, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), forced mid-expiratory flow (FEF25-75%) and FEV1/FVC ratio. Complete data were obtained for 614 females and 621 males, but the sample was reduced to 249 females and 165 males when only lifetime nonsmokers with no adverse bronchial symptoms were selected. Prediction equations of normal lung function were obtained from the reduced sample by multiple regression, with age, height and functions of both age and height as predictors. The derived equations did not differ significantly from the majority of previously reported equations and were generally superior in their ability to predict the lung function of the asymptomatic ex-smokers who were part of the original sample. Analysis of the sensitivity, specificity and predictive power of 5% tolerance limits for the presence of symptoms revealed the important roles of FEV1, FEV1/FVC and FEF25-75% in diagnostic testing. The present prediction equations are recommended for use on the Australian population and on populations with similar Caucasian characteristics.
Cytokines and cytokine network in silicosis and coal workers' pneumoconiosis
Authors: Vanhee D , Gosset P , Boitelle A , Wallaert B , Tonnel AB
Published: November 2022

The alveolar macrophage (AM) is a critically important cell playing a prominent role in lung inflammation via the production of oxygen radicals, enzymes, arachidonic acid metabolites, and also a large panel of cytokines. Among interstitial lung disorders, silicosis and coal workers' pneumoconiosis (CWP) are the most widespread fibrotic lung diseases. Although their pathophysiology remains incompletely understood, several lines of evidence suggest the participation of cytokines produced by AMs at least in the initiation of the alveolitis. In vitro exposure of AMs (obtained from healthy subjects) to coal dust particles triggered a significant release of tumour necrosis factor (TNF) and interleukin-6, by comparison with titanium dioxide used as a biologically inert control dust. Moreover, it appeared that coal mine dust was more aggressive than similar concentrations of pure silica, suggesting that cytokine secretion induced by coal mine dust was not exclusively related to the presence of silica but resulted from a complex interaction between the different components. In silicosis and CWP, bronchoalveolar lavage showed a large influx of mononuclear phagocytes, with an increased spontaneous production of oxidants, fibronectin, neutrophil chemotactic factor, and also of interleukin-6 and TNF-alpha. This spontaneous cytokine release was associated with an increased cytokine messenger ribonucleic acid (mRNA) expression in the lungs of coal miners.(ABSTRACT TRUNCATED AT 250 WORDS)
The isolation and characterization of non-typeable Haemophilus influenzae from the sputum of adult cystic fibrosis patients
Authors: Bilton D , Pye A , Johnson MM , Mitchell JL , Dodd M , Webb AK , Stockley RA , Hill SL
Published: November 2022

The role of non-typeable Haemophilus influenzae in cystic fibrosis (CF) remains unclear. We wanted, therefore, to determine the presence and characteristics of non-typeable H. influenzae in sputum samples from patients with CF. In order to do this, we have assessed sputum samples from 55 consecutive clinically stable patients seen routinely at an adult CF out-patient clinic. Quantitative bacterial culture was performed using a selective media containing cefsoludin, and isolates were characterized by biotyping and outer membrane protein profile analysis. In 17 (30%) of these samples, non-typeable H. influenzae was isolated and was present in similar viable numbers (mean 7.7 x 10(8) colony-forming units (cfu).mL-1; SEM 3.1) to Pseudomonas aeruginosa (mean 8 x 10(8) cfu.mL-1: SEM 2.4). All non-typeable H. influenzae isolates recovered were beta-lactamase negative and sensitive to a range of antibiotics. Several biotypes and outer membrane protein profiles were observed, with no apparent association between these two phenotypic characteristics. The study showed that large numbers of non-typeable H. influenzae are often present in sputum from adult patients with CF. Further longitudinal studies of outer-membrane protein profile analysis are required to determine the dynamics of non-typeable H. influenzae colonization in individual patients and the clinical significance.
Theophylline and selective phosphodiesterase inhibitors as anti-inflammatory drugs in the treatment of bronchial asthma
Authors: Banner KH , Page CP
Published: November 2022

Theophylline has been in clinical use for the treatment of bronchial asthma and other respiratory diseases for well over 50 yrs. Over this time, a considerable body of evidence has accumulated to show that this drug has a wide range of pharmacological actions, in addition to the well-recognized action on airway smooth muscle function. Current evidence suggests that part of the therapeutic value of theophylline in the treatment of asthma is by virtue of an anti-inflammatory or immunomodulatory effect, although the actual mechanism of action remains unclear. It has been proposed that the observed anti-inflammatory effects of theophylline could be attributed to phosphodiesterase (PDE) inhibition, and recently the type III and IV isoenzymes have been characterized in a number of inflammatory cells. This article reviews the evidence that theophylline and the newer more selective type IV PDE isoenzyme inhibitors can inhibit the activation of inflammatory cell types, such as T-lymphocytes, eosinophils, mast cells and macrophages, in vitro. The evidence supporting the ability of theophylline and selective PDE IV isoenzyme inhibitors to modify allergic inflammation both in animal models and clinical asthma is also discussed. We conclude that theophylline possesses important anti-inflammatory and immunomodulatory activity and that, in light of this evidence, it is timely to reconsider the place of theophylline in the treatment of asthma.
Blood eosinophil leukotriene C4 production in asthma of different severities
Authors: Laviolette M , Ferland C , Comtois JF , Champagne K , Bosse M , Boulet LP
Published: November 2022

In asthma, activation and recruitment of eosinophils to the bronchial mucosa amplifies many cellular functions. The blood eosinophil count and the number of hypodense eosinophils increase with asthma severity. Eosinophils produce numerous proinflammatory mediators in response to a variety of agonists, notably the peptido-leukotriene (LT) C4, a potent bronchoconstrictor. In this study, we have evaluated blood eosinophil LTC4 release and its modulation by cytokines in normal individuals and in subjects with asthma of various severities: mild (beta 2-agonist on demand); moderate (inhaled steroids on a regular basis); and severe (inhaled and oral steroids on a regular basis). Eosinophils were isolated using a modified Percoll gradient technique, which recovers both hypodense and normodense eosinophils in a global cell population. Eosinophils released detectable amounts of LTC4 only in the presence of the stimulus (calcium ionophore A23187, 2 microM). The ionophore-induced LTC4 release was greater in moderate asthmatics (mean +/- SEM 5.7 +/- 1.3 pg x 10(3)/250,000 eosinophils) than in normal individuals (1.6 +/- 0.4 pg x 10(3)/250,000 eosinophils), mild asthmatics (1.8 +/- 0.3 pg x 10(3)/250,000 eosinophils) and severe asthmatics (2.0 +/- 0.3 pg x 10(3)/250,000 eosinophils). Granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-5 (IL-5) amplified the ionophore-induced LTC4 release in the four groups from 1.9 to 2.6 and 1.9 to 2.8 fold, respectively. Interleukin-3 (IL-3) did not increase LTC4 production except by the eosinophils of the severe asthmatics whose ionophore-induced LTC4 production was enhanced by 1.9 fold. These data demonstrate that the asthmatic bronchial inflammatory process may modify blood eosinophil LTC4 release and its modulation by cytokines according to asthma severity and treatment.
FK506 and cyclosporin A inhibit granulocyte/macrophage colony-stimulating factor production by mononuclear cells in asthma
Authors: Sano T , Nakamura Y , Matsunaga Y , Takahashi T , Azuma M , Okano Y , Shimizu E , Ogushi F , Sone S , Ogura T
Published: November 2022

Bronchial asthma is associated with eosinophilic inflammation and expression of T-cell-derived cytokines, which influence eosinophilic function. FK506, a newly established immunosuppressive agent, may have potential as a therapeutic instrument for asthma because of its suppressive effect on T-cell activation. To assess this, we compared the inhibitory effects of FK506 and cyclosporin A on production of granulocyte/macrophage colony-stimulating factor and interleukin-5 by interleukin-2- or Dermatophagoides farinae-stimulated mononuclear cells from patients with asthma, and their contribution to proliferation and survival of eosinophils in vitro. FK506 inhibited granulocyte/macrophage colony-stimulating factor production by stimulated mononuclear cells from asthma patients at lower concentrations than cyclosporin A. Both drugs inhibited eosinophil proliferation and survival activity from mononuclear cells at comparable concentrations. Interleukin-5 production by stimulated mononuclear cells was also inhibited both by FK506 and cyclosporin A. We conclude that both FK506 and cyclosporin A have potential for therapy of bronchial asthma.
Salmeterol xinafoate in asthmatic patients under consideration for maintenance oral corticosteroid therapy. UK Study Group
Authors: Boyd G
Published: November 2022

In severe chronic asthma, long-term oral steroids may be necessary to control symptoms. In patients in whom such treatment was under consideration, the efficacy and safety of salmeterol xinafoate 100 micrograms b.i.d. was investigated in a randomized, double-blind, placebo-controlled parallel-group, multicentre study. One hundred and nineteen chronic symptomatic asthmatics were randomized to receive either salmeterol, 100 micrograms b.i.d. (n = 55; baseline % predicted morning peak expiratory flow (PEF) 59%; forced expiratory volume in one second (FEV1) 66%) or placebo (n = 64; baseline % predicted morning PEF 63%; FEV1 66%) both via the Diskhaler. Morning and evening PEF and asthma symptoms were recorded in daily record booklets by the patient over a 12 week period. A significant improvement in morning PEF was achieved after 1 month in the salmeterol treated group; this persisted throughout the treatment period (estimated treatment difference 22 L.min-1). There was a significant increase in the proportion of symptom-free nights experienced by the salmeterol treated group (33 (SD 32) %) compared with placebo (13 (26) %), and a significant decrease in daily use of relief medication (mean decrease 5.1 (4.7) doses per day with salmeterol, 2.5 (4.0) doses with placebo). Both treatments were well-tolerated, with no evidence of any difference in the side-effects associated with beta 2-agonists. In conclusion, the addition of salmeterol (100 micrograms daily) to the existing treatment of chronic asthmatics under consideration for maintenance oral corticosteroid therapy is well-tolerated, improves lung function and provides additional symptom control.
Prostanoids and cough response to capsaicin in asthma and chronic bronchitis
Authors: Fujimura M , Kamio Y , Kasahara K , Bando T , Hashimoto T , Matsuda T
Published: November 2022

Cyclooxygenase products are released by chronic airway inflammation. Our working hypothesis for the present study was that prostanoids augment airway cough sensitivity. The effects of a cyclooxygenase inhibitor, indomethacin (100 mg.day-1 for 4 days), and a thromboxane synthesis inhibitor, OKY-046 (400 mg.day-1 for 4 days), on cough response to inhaled capsaicin were examined in eight patients with asthma, 10 patients with chronic bronchitis, and 10 normal subjects. Capsaicin cough threshold, the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough sensitivity. In asthmatics, the cough thresholds with indomethacin treatment (15.7 (GSEM 1.38) microM) and OKY-046 (10.2 (GSEM 1.20) microM) were significantly greater than the value with placebo (6.05 (GSEM 1.25) microM). In patients with chronic bronchitis, the cough threshold was significantly greater with indomethacin (5.94 (GSEM 1.50) microM) than with placebo (3.41 (GSEM 1.33) microM and OKY-046 2.97 (GSEM 1.43) microM). In normal subjects, the capsaicin cough threshold was not altered by indomethacin or OKY-046 treatment. These results support our hypothesis and suggest that thromboxane A2 may be one of the cyclooxygenase products augmenting airway cough sensitivity in asthma, but not in chronic bronchitis.
Electrically-activated dilator muscles reduce pharyngeal resistance in anaesthetized dogs with upper airway obstruction
Authors: Bishara H , Odeh M , Schnall RP , Gavriely N , Oliven A
Published: November 2022

There is current controversy as to whether electrical stimulation of upper airway musculature can be used us a beneficial treatment modality in patients with obstructive sleep apnoea syndrome. Increased upper airway (UAW) muscle activity decreases UAW resistance (Ruaw) in isolated UAW of dogs. In the present study, we evaluated the effect of UAW muscle contraction on UAW patency in anaesthetized dogs in vivo breathing spontaneously through partially and completely obstructed UAW. Airflow and supraglottic pressure were measured to obtain Ruaw. Ruaw could be regulated by inhalation of a rubber balloon implanted transcutaneously in the pharyngeal submucosa to produce partial or complete obstruction. Wire electrodes were implanted bilaterally into the genioglossus (GG), geniohyoid (GH), sternothyroid (ST), and sternohyoid (SH) muscles for electrical stimulation (ES), and into the alae nasi for electromyographic (EMG) recording. Three levels of electrical stimulation were delivered to each muscle before and during partial or complete UAW obstruction. Genioglossus and geniohyoid stimulation both resulted in a significant reduction in Ruaw, which was most pronounced during partial obstruction, reducing Ruaw from 54 +/- 11 to 14 +/- 3 and from 74 +/- 12 to 31 +/- 5 cmH2O.L-1.s, respectively. At low voltage, stimulation of the genioglossus was more effective than stimulation of the geniohyoid in reducing Ruaw. Furthermore, electrical stimulation of the genioglossus but not of the geniohyoid released total obstruction. In contrast, electrical stimulation of the sternohyoid and sternothyroid produced no significant change in Ruaw. These findings demonstrate that selective UAW dilatory muscle contraction in spontaneously breathing anaesthetized dogs reduces Ruaw in the presence of UAW obstruction and releases UAW occlusion, with the genioglossus being the most effective muscle. This favours further attempts to investigate the benefits of electrical stimulation of selected upper airway muscles in the treatment of obstructive sleep apnoea syndrome.
Clinical characteristics and outcome of Pneumocystis carinii pneumonia in HIV-infected and otherwise immunosuppressed patients
Authors: Ewig S , Bauer T , Schneider C , Pickenhain A , Pizzulli L , Loos U , Luderitz B
Published: November 2022

The factors contributing to unequal mortality rates following Pneumocystis carinii pneumonia (PCP) in different groups at risk are poorly understood. We therefore compared the first episodes of PCP without prophylaxis in human immunodeficiency virus infected (HIV) and otherwise immunosuppressed patients in this retrospective study. A total of 58 HIV-infected and 16 otherwise immunosuppressed patients were analysed. The comparison included epidemiological, clinical, laboratory, radiological and microbiological data, as well as therapy and clinical course. A prognostic analysis was performed using a logistic regression model. The mortality was significantly different in the two groups (HIV group 17 versus non-HIV group 50%). Renal transplant patients had a higher survival rate as compared to malignancy or collagen vascular disease as underlying diseases at risk. Acute respiratory failure was more common in the non-HIV group. Variables found to be significantly associated with lethal outcome in univariate analysis were alveolar to arterial pressures difference for oxygen (P(A-a),O2), haemoglobin, platelet count, total protein, serum albumin, and gamma-globulins in the HIV-group, and serum albumin in the non-HIV group. In the multivariate analysis of the HIV group, platelet count and gamma-globulins remained independent prognostic factors. In conclusion, in the HIV-group, mortality is closely related to the severeness of PCP as well as to the severeness of the acquired immune deficiency syndrome (AIDS) disease. In the non-HIV group, malignancy and collagen vascular disease as underlying conditions at risk account for the high mortality rate. Its severeness was mainly reflected by serum albumin, which represented the only variable found to be significantly associated with death in both groups.
Predictive value of serum III procollagen for diagnosis of pulmonary involvement in patients with scleroderma
Authors: Diot E , Diot P , Valat C , Boissinot E , Asquier E , Lemarie E , Guilmot JL
Published: November 2022

High resolution computed tomography (HRCT) was recently demonstrated to be as good as open lung biopsy for the diagnosis of pulmonary involvement in patients with scleroderma. Nevertheless, in view of its price and related irradiation, HRCT cannot be recommended as a screening test. Serum III procollagen (sPIIINP) is an aminopropeptide of type III collagen, which is released during conversion into collagen by specific proteases. Increased levels of sPIIINP have been observed in patients with scleroderma. The aim of the present study was to assess the relationship between sPIIINP measurement and pulmonary involvement defined according to HRCT and pulmonary function tests (PFT) with single-breath carbon monoxide transfer capacity (TL,CO) in 28 patients suffering from scleroderma. Patients were divided into two groups for analysis, Group A comprising 16 patients without pulmonary scleroderma and Group B comprising 12 patients with pulmonary scleroderma. All patients had stable cutaneous disease and normal renal and hepatic function. The level of sPIIINP was determined by radioimmunoassay (RIA-gnost P-III-P, Prod. Nr. ODMT; Behring, Marburg, Germany). Mean +/- SD sPIIINP level in Group A was 0.85 +/- 0.21 U.mL-1. Individual values ranged 0.6-1.3 U.mL-1. Mean +/- SD sPIIINP value was 1.30 +/- 0.40 U.mL-1 in Group B and individual values ranged 0.7-1.9 U.mL-1. The difference in mean sPIIINP level between Group A and Group B was significant. Using a cut-off at 1.1 U.mL-1, sensitivity of sPIIINP was 0.66, specificity 0.94, positive predictive value 0.89, negative predictive value 0.79, false positive rate 0.06, and false negative rate 0.33. The value of sPIIINP correlated with HRCT score but not with PFT. This study confirms the relationship between sPIIINP and scleroderma with interstitial lung disease. We suggest that sPIIINP could be measured in patients with scleroderma to screen those patients requiring HRCT. Further studies are necessary to determine the value of sPIIINP in terms of prognosis and follow-up of patients under treatment.
Manifestations and consequences of obstructive sleep apnoea
Authors: Peter JH , Koehler U , Grote L , Podszus T
Published: November 2022

Over the last two decades the diagnostic tools used in sleep medicine have developed enormously, making it possible to study the interaction of sleep-related breathing disorders (SRBD) with cardiovascular function and the autonomic nervous system, as well as the effects of SRBD on a variety of physiological processes during wakefulness. Different modes of nasal ventilation are now available, allowing all forms of SRBD to be treated. If early diagnosis and treatment are provided, the acute and long-term sequelae of SRBD can be prevented. In addition to the care and treatment of patients with severe obstructive sleep apnoea syndrome (OSAS), future patient management will need to focus on patients with milder forms of obstructive sleep apnoea (OSA). In particular, the consequences of SRBD on cardiac arrhythmias, arterial hypertension and hypersomnolence are discussed, considering epidemiological, clinical, diagnostic and therapeutic aspects. Some economical issues arising from SRBD are also discussed, and the authors conclude that a Europewide programme for early detection, treatment and prevention of SRBD is required. This could make a large contribution to the reduction of cardiovascular morbidity and mortality and also reduce the incidence of "human error catastrophes" due to hypersomnolence.
Physical examination of the adult patient with respiratory diseases: inspection and palpation
Authors: Maitre B , Similowski T , Derenne JP
Published: November 2022

Inspection of the thorax identifies the breathing position adopted by the patient, the shape of the thorax, the dynamics of respiration (breathing pattern, symmetry of expansion, mechanics and synchrony of rib cage and abdominal movements). Inspection of the neck adds useful information, particularly with respect to the dynamics of breathing. Palpation ascertains the signs suggested by inspection with respect to the mechanics of breathing. It also assesses the state of the pleura and pulmonary parenchyma by studying the tactile fremitus. It integrates extrarespiratory signs, such as enlarged lymph nodes or breast abnormalities. Extrathoracic respiratory signs should also be systematically looked for, including cyanosis, finger deformation, pulsus paradoxus, and pursed lips breathing. Interobserver agreement about respiratory signs has repeatedly been studied, and generally found to be low, as are clinical-functional correlations. However, some data on chronic obstructive pulmonary disease (COPD), asthma or pulmonary embolism are available. From the description of some signs and the current knowledge about their operative values, it appears that much clinical research remains necessary to better define the precise diagnostic value of a given sign. The impact of training on diagnostic performance also has to be defined. Both of these aspects should allow clinicians to optimize the way in which they use their hands and eyes to conduct respiratory diagnosis, as well as the way they teach respiratory symptomatology.
Pulmonary fibrosis and sea-blue histiocyte infiltration in a patient with primary myelofibrosis
Authors: Yamauchi K , Shimamura K
Published: November 2022

The authors present the case of a 73 year old man with primary myelofibrosis, pulmonary fibrosis, and acquired sea-blue histiocytosis, who died of respiratory failure. Pathology of the lungs revealed infiltration by sea-blue histiocytes, and fibrosis in the alveolar septa, and clumps of these cells filling the alveolar spaces. Megakaryocytes were also occasionally observed in the alveolar capillaries.