bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation of airway obstruction and patient-reported endpoints in clinical studies
Authors: Shingo S. , Zhang J. , Reiss T.F.
Published: July 2002

To establish the correlation among asthma efficacy parameters over a long period, data from over 1500 patients in two one-year asthma clinical trials with montelukast, a Cys-LT1antagonist, were analysed. Airway obstruction measurements, forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF), were measured at clinic visits. Patients recorded daytime symptom score, “as-needed” β-agonist use, and PEF on a daily basis.

Relationships among these parameters at baseline and during the one-year treatment period were established by correlation analyses. Multiple correlations between the airway obstruction (FEV1and PEF) and patient-reported measurements were evaluated by canonical correlation analysis.

Pairwise correlations of the efficacy parameters over a one-year time period were stable. Canonical correlation between the airway obstruction and patient-reported asthma efficacy endpoints was low, indicating that each category of endpoints measures a distinctively different aspect of the disease.

It appears that at least one endpoint from each category should be used in asthma clinical studies.
Interlobar differences in bronchoalveolar lavage fluid from children with cystic fibrosis
Authors: Gutierrez J.P. , Grimwood K. , Armstrong D.S. , Carlin J.B. , Carzino R. , Olinsky A. , Robertson C.F. , Phelan P.D.
Published: July 2002

Bronchoalveolar lavage (BAL) performed in specialist centres has improved the understanding of infant cystic fibrosis (CF) lung disease. As most researchers sample from a single lobe, it was determined whether BAL results could be generalized to other lung segments.

Thirty-three CF children, aged 1.5–57 months, underwent in random order sequential BAL of their right middle and lingula lobes. Specimens from each lobe had separate quantitative bacteriology, cytology and cytokine analysis.

Bacterial counts ≥1×105colony forming units (cfu)·mL−1were observed in nine (27%) subjects, including six involving only the right middle lobe. These six children had similar inflammatory indices in their right middle and lingula lobes, and interleukin (IL)-8 concentrations in the latter were significantly higher than that observed within the lingula lobes of the 24 CF children with bacterial counts <1×105 cfu·mL−1. Lingula neutrophil and IL-8 levels correlated best with right middle lobe bacteria numbers.

This observational study in cystic fibrosis children suggests that while inflammation is detected in both lungs, bacterial distribution may be more inhomogeneous. Bronchoalveolar lavage microbiological findings from a single lobe may therefore, not be generalized to other lung segments. When performing bronchoalveolar lavage in cystic fibrosis children, it is important to sample from multiple sites.
Acute psychosis after CPAP treatment in a schizophrenic patient with sleep apnoea­hypopnoea syndrome
Authors: Chiner E. , Arriero J.M. , Signes-Costa J. , Marco J.
Published: July 2002

A 52-yr-old man with a residual phase of schizophrenia developed sleep apnoea­hypopnoea syndrome (SAHS). After five days of continuous positive airway pressure (CPAP) treatment, the patient developed an aggressive mood with incoherence, prominent hallucinations and agitation, and attempted to hit his relatives. He was finally admitted to the hospital with an acute psychotic episode. Withdrawal of CPAP, and neuroleptic treatment controlled the episode, and clinical symptoms of SAHS reappeared 10 days later.

Schizophrenia associated to sleep apnoea­hypopnoea syndrome has rarely been reported, but, to the authors' knowledge, the induction of a psychotic episode by continuous positive airway pressure treatment in a patient with sleep apnoea­hypopnoea syndrome and coexisting schizophrenia has never been previously reported.
Inhaled corticosteroid therapy reduces the risk of rehospitalization and all-cause mortality in elderly asthmatics
Authors: Sin D.D. , Tu J.V.
Published: July 2002

Elderly patients with asthma have relatively high rates of hospitalization and mortality. Although inhaled corticosteroids have been shown to improve outcomes among younger patients with asthma, their usefulness in elderly patients has not been established. Therefore, a population-based study of patients 65 yrs of age or older, who have been hospitalized at least once with asthma in Ontario, Canada was conducted to determine the impact of inhaled corticosteroids on rehospitalization for asthma and all-cause mortality rates.

Data from the Canadian Institute of Health Information was used to capture all patients 65 yrs of age and older who were hospitalized at least once, with the most responsible diagnosis of asthma in Ontario, Canada between fiscal year 1992 and 1996. This database was then linked with drug claims, physician billing and mortality databases.

In total, 6,254 consecutive elderly patients with asthma were identified. Sixty percent of these patients were given at least one prescription for inhaled corticosteroids within 90 days postdischarge from their index hospitalization for asthma. Users of inhaled corticosteroids postdischarge were 29% (95% confidence interval (CI) 20%–38%) less likely to be readmitted to hospital for asthma and 39% (95% CI, 20%–53%) less likely to experience all-cause mortality compared to those who did not receive these drugs postdischarge over a one year follow-up period.

These findings suggest that inhaled corticosteroids are beneficial in reducing the risk for rehospitalization and all-cause mortality in elderly patients with asthma who have recently been hospitalized for their disease.
Gas and dust exposure in underground construction is associated with signs of airway inflammation
Authors: Ulvestad B. , Lund M.B. , Bakke B. , Djupesland P.G. , Kongerud J. , Boe J.
Published: July 2002

Exposure to gases and dust may induce airway inflammation. It was hypothesized that heavy construction workers who had been exposed to dust and gases in underground construction work for 1 yr, would have early signs of upper and lower airway inflammation, as compared to outdoor workers.

A study group comprising 29 nonsmoking underground concrete workers (mean± sd age 44±12 yrs), and a reference group of 26 outdoor concrete workers (39±12 yrs) were examined by acoustic rhinometry, nasal and exhaled nitric oxide spirometry and a questionnaire on respiratory symptoms. Exposure measurements were carried out.

The underground workers had higher exposure to total and respirable dust, α‐quartz and nitrogen dioxide than the references (p<0.001). The occurrence of respiratory symptoms was higher in the underground workers than in the references (p<0.05). Exhaled nitric oxide (NO) (geometric mean±sem) was higher in the underground workers than in the references (8.4±1.09versus5.6±1.07 parts per billion (ppb), p=0.001), whereas spirometric values were comparable. The underground workers had smaller nasal cross-sectional area and volume than the references, and more pronounced increases after decongestion (p<0.001).

To conclude the exposure in underground construction may cause nasal mucosal swelling and increased levels of exhaled nitric oxide, indicating signs of upper and lower airway inflammation.
Assessment of passive respiratory mechanics in infants: doubleversussingle occlusion?
Authors: Goetz I. , Hoo A.F. , Lum S. , Stocks J.
Published: July 2002

The single breath or occlusion technique (SOT) is widely used to assess passive respiratory mechanics in infants, but depends on various underlying assumptions. Recently, it has been proposed that such measurements could be internally validated by performing two brief airway occlusions during the same expiration. The aim of this study was to evaluate the use of the double occlusion technique (DOT) using a new commercially available program (Jaeger MasterScreen BabyBody Erich Jaeger GmbH, Würzburg, Germany).

Paired measurements of respiratory system compliance (Crs) and resistance (Rrs) using both SOT and DOT were obtained in 18 healthy sedated infants (age range 4–41 weeks, weight 2.7–9.9 kg).

There was close agreement between both methods of assessingCrsin all infants, the mean within-subject difference (95% confidence interval (CI)) for DOT−SOT being −0.06 (−0.55–+0.42) mL·kPa−1·kg−1. By contrast, estimates ofRrs,DOwere on average 20% lower than those forRrs,SO, (mean within-subject difference (95% CI) being −0.67 (−1.04–−0.31) kPa·L−1·s; p<0.01).

The relatively lower values obtained forRrs,DOmay reflect the higher mean lung volume at which it was calculated. Further work is required to investigate the clinical and epidemiological relevance of this new approach, and whether there are any advantages of using both techniques when assessing passive mechanics in infants.
Diagnostic significance of surfactant proteins A and D in sera from patients with radiation pneumonitis
Authors: Takahashi H. , Imai Y. , Fujishima T. , Shiratori M. , Murakami S. , Chiba H. , Kon H. , Kuroki Y. , Abe S.
Published: July 2002

Radiation pneumonitis (RP) is the most common complication of radiotherapy for thoracic tumours. The aim of this study was to evaluate the significance of pulmonary surfactant proteins (SP)‐A and SP‐D as new serum markers for RP.

Twenty-five patients with lung tumour, who had received radiotherapy, were studied. At the completion of radiotherapy, the presence of RP was judged by chest plain radiography and chest high resolution computed tomography (HRCT).

RP findings detected on chest plain radiography were seen in only three of 12 patients in whom RP was detected by HRCT. Nevertheless, both SP‐A and SP‐D concentrations in sera from the patients with RP were significantly higher than those from the 13 patients without RP (p=0.0065, p=0.0011, respectively). As with SP‐A, ratios of SP‐D at the completion, compared to at the initiation (1 week post/pre ratio), were also significantly higher in patients with RP than in patients without RP. When a post/pre ratio>1.6 was considered positive, the SP‐A and SP‐D assays showed an 83% and 85% specificity, respectively.

In conclusion, serum assays of surfactant proteins A and D may be of diagnostic value for detection of radiation pneumonitis, even when the radiographic change is faint.
Airway resistance measured by the interrupter technique: expiration or inspiration, mean or median?
Authors: Bridge P.D. , McKenzie S.A.
Published: July 2002

The measurement of airway resistance by the interrupter technique (Rint) needs standardization. Should measurements be made be during the expiratory or inspiratory phase of tidal breathing? In reported studies, the measurement of Rinthas been calculated as the median or mean of a small number of values, is there an important difference?

Subjects were 2.5–5.0 yrs (median 4.0 yrs) who had previous respiratory symptoms. The Rintin expiration (RintE) and inspiration (RintI) pre and postsalbutamol, the coefficient of variation (CV) of values contributing to measurements, and bronchodilator responsiveness (BDR) in both phases were compared. Measurements using median and mean were compared.

RintE was higher than RintI by 4% (p<0.01). The CV of values making up RintE and RintI, and BDR measured in expiration and inspiration were similar. The median difference between means and medians of values making up measurements was 0.6% (range −6–11%).

RintE has been shown to be consistently greater then RintI but the difference in this study is small. It is suggested that one or the other is chosen as the standard. In the present data the mean of a set of values contributing to a measurement was not significantly different from the median. However, the use of the median has been recommended since it is less affected by possible outlying values such as might be included by fully automated equipment.
Urinary excretion reflects lung deposition of aminoglycoside aerosols in cystic fibrosis
Authors: Dequin P-F. , Faurisson F. , Lemarié E. , Delatour F. , Marchand S. , Valat C. , Boissinot E. , de Gialluly C. , Diot P.
Published: July 2002

Using nebulization to deliver aminoglycosides may be of benefit in cystic fibrosis (CF) patients colonized byPseudomonas aeruginosa. However, one problem with this route is the absence of clinical parameters allowing estimation of the mass of drug deposited in the lungs (MDL). The aim of this study was to assess whether aminoglycoside excretion in the urine reflects the MDL.

Fourteen studies were performed in seven CF patients. Amikacin was mixed with albumin labelled with99mTc and nebulized with an ultrasonic nebulizer. The MDL was determined by the mass-balance technique. Urine was collected during the 24 h following inhalation and was assayed for amikacin by fluorescence polorization immunoassay (FPIA).

The mean±sem MDL was 14.0±2.2% of the nebulizer charge. The mean±sem amount of amikacin excreted in the urine was 20.9±4.5 mg and correlated with the MDL (r=0.93; p=0.0001). There was, however, wide intersubject variability in both deposition and excretion in the urine.

Monitoring excretion of aminoglycosides in the urine allows noninvasive estimation of the mass of drug deposited in the lung in cystic fibrosis patients, which might be useful to assess the dose-response relationship in groups of patients, but intersubject variability prevents its use for individual follow-up.
Interpretation of quality of life scores from the St George's Respiratory Questionnaire
Authors: Ferrer M. , Villasante C. , Alonso J. , Sobradillo V. , Gabriel R. , Vilagut G. , Masa J.F. , Viejo J.L. , Jiménez-Ruiz C.A. , Miravitlles M.
Published: July 2002

The aim of the study was to obtain the general population norms for the St. George's Respiratory Questionnaire (SGRQ), a specific questionnaire for respiratory diseases.

The IBERPOC project was a cross-sectional study of representative samples of the general population aged between 40–69 yrs. The study sample was composed of 862 individuals. All participants considered as “probable cases” of chronic obstructive pulmonary disease (COPD) (n=460) were eligible to complete the SGRQ and among the rest of the nonprobable COPD participants (n=3,571), 10 individuals from each defined age and sex group were eligible (n=402). Weights were applied to restore general population representativity of the sample.

Mean forced expiratory volume in one second (FEV1) predicted was 89.4% (sd=16.5%; range: 16–131%). Chronbach's alpha coefficients were >0.7 in the symptoms, activity and impact scales, and >0.9 in the overall scale. Symptom scale score was significantly higher among males (11.6versus7.8; p<0.01) and activity scale score was significantly higher among females (12.2versus14.6; p=0.04). In a multiple linear regression model, respiratory diseases (asthma and COPD) and FEV1% over pred showed the strongest association with the SGRQ total score. Smoking, sex, age and education were independently associated with the total SGRQ score.

These results indicate that individuals from the general population presented some of the problems that are important when measuring health-related quality of life in respiratory patients, and provide St George's Respiratory Questionnaire norms, a useful method for interpreting the St George's Respiratory Questionnaire score in a given patient or study samples.
Misuse of corticosteroid metered-dose inhaler is associated with decreased asthma stability
Authors: Giraud V. , Roche N.
Published: July 2002

This study assessed whether the improper use of pressurized metered-dose inhalers (pMDIs) is associated with decreased asthma control in asthmatics treated by inhaled corticosteroids (ICS).

General practitioners (GPs) included consecutive asthmatic outpatients treated by pMDI-administered ICS and on-demand, short-acting β2-agonists. They measured an asthma instability score (AIS) based on daytime and nocturnal symptoms, exercise-induced dyspnoea, β2-agonist usage, emergency-care visits and global perception of asthma control within the preceding month; the inhalation technique of the patient also was assessed.

GPs (n=915) included 4,078 adult asthmatics; 3,955 questionnaires were evaluable. pMDI was misused by 71% of patients, of which 47% was due to poor coordination. Asthma was less stable in pMDI misusers than in good users (AIS: 3.93versus2.86, p<0.001). Among misusers, asthma was less stable in poor coordinators (AIS: 4.38versus3.56 in good coordinators, p<0.001).

To conclude, misuse of pressurized metered-dose inhalers, which is mainly due to poor coordination, is frequent and associated with poorer asthma control in inhaled corticosteroid-treated asthmatics. This study highlights the importance of evaluating inhalation technique and providing appropriate education in all patients, especially before increasing inhaled corticosteroid dosage or adding other agents. The use of devices which alleviate coordination problems should be reinforced in pressurized metered-dose inhaler misusers.
Regular follow-up after curative resection of nonsmall cell lung cancer: a real benefit for patients?
Authors: Egermann U. , Jaeggi K. , Habicht J.M. , Perruchoud A.P. , Dalquen P. , Solèr M.
Published: July 2002

Even though complete resection is regarded as the only curative treatment for nonsmall cell lung cancer (NSCLC), >50% of resected patients die from a recurrence or a second primary tumour of the lung within 5 yrs. It remains unclear, whether follow-up in these patients is cost-effective and whether it can improve the outcome due to early detection of recurrent tumour.

The benefit of regular follow-up in a consecutive series of 563 patients, who had undergone potentially curative resection for NSCLC at the University Hospital, was analysed. The follow-up consisted of clinical visits and chest radiography according to a standard protocol for up to 10 yrs. Survival rates were estimated using the Kaplan-Meier analysis method and the cost-effectiveness of the follow-up programme was assessed.

A total of 23 patients (6.4% of the group with lobectomy) underwent further operation with curative intent for a second pulmonary malignancy. The regular follow-up over a 10-yr period provided the chance for a second curative treatment to 3.8% of all patients.

The calculated costs per life-yr gained were 90,000 Swiss Francs. The cost-effectiveness of the follow-up protocol was far above those of comparable large-scale surveillance programmes. Based on these data, the intensity and duration of the follow-up was reduced.
A novel clinical test of respiratory muscle endurance
Authors: Hart N. , Hawkins P. , Hamnegård C-H. , Green M. , Moxham J. , Polkey M.I.
Published: July 2002

Impaired respiratory muscle endurance (RME) could reduce exercise tolerance and contribute to ventilatory failure. The aim of the present study was to develop a clinically-feasible method to measure RME using negative-pressure inspiratory-threshold loading. It was hypothesized that endurance time (tlim) could be predicted by normalizing oesophageal pressure-time product (PTP) per total breath cycle (PTPoes) for maximum oesophageal pressure (Poes,max); the load/capacity ratio. The corresponding mouth pressures, PTPmouthandPmouth,maxwere also measured.

The RME test was performed on 30 healthy subjects exposed to the same target pressure (70% ofPoes,max). Eight patients with systemic sclerosis/interstitial lung disease were studied to assess the validity and acceptability of the technique.

Normal subjects showed a wide intersubject variation intlim(coefficient of variation, 69%), with a linear relationship demonstrated between logtlimand PTPoes/Poes,max(r=0.88). All patients with systemic sclerosis/interstitial lung disease had normal respiratory muscle strength, but six out of eight had a reduction in RME.

In conclusion, endurance time can be predicted from the load/capacity ratio, over a range of breathing strategies; this relationship allows abnormal respiratory muscle endurance to be detected in patients. Oesophageal and mouth pressure showed a close correlation, thus suggesting that the test could be applied noninvasively.
Effects of inducible nitric oxide synthase and xanthine oxidase inhibitors on SEB-induced interstitial pneumonia in mice
Authors: Miyakawa H. , Sato K. , Shinbori T. , Okamoto T. , Gushima Y. , Fujiki M. , Suga M.
Published: July 2002

The authors have previously reported that intratracheal instillation of staphylococcal enterotoxin‐B (SEB) induced interstitial pneumonia (IP) in autoimmune-prone mice. SEB-reactive T‐cells were critically involved in the development of IP in this model. Concern has arisen about the hazards of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the process of lung injury and fibrosis.

Therefore, the involvement of nitric oxide (NO) and superoxide anion (O2−) in the pathogenesis of IP in this autoimmune-prone model has been investigated.

Nitrite/nitrate levels were increased in bronchoalveolar lavage (BAL) fluid and serum from SEB-injected mice. The signal of the NO-(N‐(dithiocarboxy) sarcosine)2-Fe2+complex was detected in the SEB-injected lung and whole blood by electron paramagnetic resonance (EPR) spectroscopy. NO production was significantly decreased by aminoguanidine (AG) treatment. Xanthine oxidase (XO) activity in the lung, BAL fluid, and plasma was increased with instillation of SEB, and 4‐amino‐6‐hydroxypyrazolo(3,4‐d)‐pyrimidine (AHPP) significantly inhibited XO activity. Moreover, both AG and AHPP significantly decreased production of pro-inflammatory cytokines, numbers of infiltrated cells in BAL fluid, and the area of thickened alveolar septa in the SEB-injected lung.

In conclusion, the overproduction of nitric oxide and super oxide anion were implicated in the pathogenesis of interstitial pneumonia, and inducible nitric oxide synthase and xanthine oxidase inhibitors had protective effects against interstitial pneumonia in this model.
Is waking electroencephalographic activity a predictor of daytime sleepiness in sleep-related breathing disorders?
Authors: Sforza E. , Grandin S. , Jouny C. , Rochat T. , Ibanez V.
Published: July 2002

No data are available in the literature assessing the potential use of waking electroencephalographic (EEG) activity in the detection of excessive daytime sleepiness (EDS) in patients with sleep-related breathing disorders (SRBD). The aim of this study was to evaluate whether waking EEG spectral power reflects the level of EDS in SRBD patients.

The study was performed in 48 patients in whom quantitative EEG analysis, including the alpha attenuation coefficient (AAC), was performed. Sleepiness was assessed by the Epworth Sleepiness Scale, the Stanford Sleepiness Scale, the Visual Analogue Scale and the maintenance of wakefulness test.

Although AAC and EEG spectral power tended to vary throughout the day, none of these variations correlated with EDS measures. Waking EEG measures were not different between snorers and apnoeic patients. Compared to nonsleepy patients, sleepy patients had greater theta and slow alpha powers, but the differences did not reach statistical significance. The EEG slowing was independent of hypoxaemia, severity of SRBD, or degree of sleep disruption.

The authors conclude that waking electroencephalographic measures are not sensitive enough to predict variation in alertness or to differentiate sleepy from nonsleepy sleep-related breathing disorders patients. The degree of electrocephalographic slowing was related neither to sleep disruption nor to severity of sleep-related breathing disorders.
Prostaglandin D2inhibits fibroblast migration
Authors: Kohyama T. , Liu X.D. , Wen F.Q. , Kim H.J. , Takizawa H. , Rennard S.I.
Published: July 2002

Fibroblasts play an important role in the repair and remodelling processes following injury. Prostaglandin D2(PGD2) is a potent mediator in inflammatory processes.

In this study, the effect of the PGD2on human foetal lung fibroblasts (HFL‐1) chemotaxis induced by human plasma fibronectin (HFn) was investigated using the blindwell chamber technique.

PGD2inhibited HFL‐1 chemotaxis to HFn (20 µg·mL−1) by 20.8±3.8% (p<0.05). Checkerboard analysis of HFn-directed migration confirmed that PGD2inhibited both chemotaxis and chemokinesis. The effect of PGD2was concentration-dependent and the inhibitory effect diminished with time. The PGD2receptor (DP) agonist BW245C (500 nM) had a similar effect, inhibiting chemotaxis to 39.4±6.3%. The inhibitory effects of both PGD2and BW245C on HFL‐1 chemotaxis were blocked by the DP receptor antagonist AH6809 (2 µM). The inhibitory effect of PGD2on fibroblast chemotaxis was also blocked by the cyclic adenosine monophosphate (cAMP)‐dependent protein kinase (PKA) inhibitor, KT5720, suggesting a DP receptor-initiated, cAMP‐dependent effect mediated by PKA.

Prostaglandin D2appears to inhibit fibroblast chemotaxis, perhaps by modulating the rate of fibroblast migration. Such an effect may contribute to regulation of the wound healing response following injury in asthma patients.
The role of thrombophilic risk factors in the severity of pulmonary thromboembolism
Authors: Oguzulgen I.K. , Ekim N.N. , Akar N. , Demirel K. , Kitapci M.
Published: July 2002

High plasma factor-VIIIc concentration, presence of factor‐V 1691 G‐A (FVL) and prothrombin20210A(PT20210A) mutations were shown to be significant risk factors for venous thromboembolism (VTE) and recurrent VTE. The objective of this study was to investigate the role of these thrombotic risk factors in the severity of pulmonary thromboembolism (PTE).

The plasma concentrations of factor VIIIc, presence of FVL and PT20210Amutations were studied in 32 patients with PTE. Eleven of the patients had documented recurrent VTE. Lung perfusion scans were scored according to the percentage of vascular obstruction. Patients who had a pulmonary vascular obstruction score (PVOs) >50% were compared to those with PVOs<50%.

There was no significant difference between the patients with PVOs >50% and those with PVOs <50%, with regard to the presence of FVL and PT20210Amutation. However, patients with PVOs >50% had a significantly higher factor-VIIIc concentration than those with PVOs <50% (factor-VIIIc levels were 253.3±29.1 International Units (IU)·dL−1and 138.5±16.2 IU·dL−1, respectively; p<0.005). Factor-VIIIc concentrations were significantly correlated with PVOs (r=0.52, p<0.005). Patients with recurrent VTE had significantly higher factor-VIIIc concentrations than those in which it occurred for the first time (factor-VIIIc concentrations were 232.6±30.9 IU·dL−1and 158.3±20.6 IU·dL−1, respectively; p<0.05).

The authors conclude that in addition to being a risk factor for venous thromboembolism, high factor-VIIIc concentration is an important factor in the severity of pulmonary thromboembolism.
Do hormonal contraceptives influence asthma severity?
Authors: Forbes L , Jarvis D , Burney P
Published: July 2002

There is some evidence that endogenous progesterone and oestrogen levels influence asthma severity in females, but little is known about the effects of hormonal contraceptives. This study aimed to describe how females with asthma perceived the effects of hormonal contraceptives on symptom severity, and to describe the association between asthma severity and current use of hormonal contraceptives. A questionnaire was sent to 891 females with asthma aged 20-30 yrs recruited from general practice registers in South London, UK. It asked about perceptions of the effects of hormonal contraceptives on asthma severity, about current use of hormonal contraceptives, and included an asthma quality of life questionnaire as a measure of asthma severity. About 6% of respondents who had ever used hormonal contraceptives reported that these had influenced asthma severity, -4% reporting worsening and 2% an improvement. There were no significant differences in asthma quality of life score between females currently taking hormonal contraceptives and those not, between those taking combined and progesterone-only preparations, or between users of different progestagen types. This study found no evidence of any important effect of hormonal contraceptives or their components on asthma severity in a group of females with relatively mild asthma.
Epinastine (WAL 801CL) inhibits the electrical field stimulation-induced cholinergic contraction in guinea pig and human airways in vitro
Authors: Dupont LJ , Pype JL , Meade CJ , DeLeyn P , Deneffe G , Demedts MG , Verleden GM
Published: July 2002

Epinastine is an antihistamine drug with binding affinities at 5-hydroxytryptamine (5-HT) receptors. The current study was performed to investigate whether epinastine could modulate the cholinergic contraction in guinea pig and human airways in vitro. Isolated guinea pig and human airway preparations were suspended in organ baths containing modified Krebs-Henseleit solution. Electrical field stimulation was applied to elicit cholinergic contractions. Epinastine produced a concentration-dependent inhibition of the cholinergic contraction in guinea pig airways and pretreatment with methysergide (5-HT1/2/7 antagonist) significantly attenuated these inhibitory effects of epinastine. Pretreatment with tropisetron (5-HT3/4 antagonist), ketanserin (5-HT2 antagonist), SDZ216-525 (5-HT1A antagonist) or phentolamine (alpha-adrenergic antagonist) had no effect. Epinastine did not displace the concentration-response curve to acetylcholine. These results suggest that epinastine inhibits the cholinergic contraction in guinea pig airways through stimulation of prejunctional 5-hydroxytryptamine receptors, located to postganglionic cholinergic nerves. Inhibitory effects of epinastine on the cholinergic contraction in human airways in vitro were also demonstrated, which suggests that a similar mechanism might be present in human airways. The pharmacological profile of epinastine, which shows binding affinity at the 5-hydroxytryptamine7 receptor but not at the 5-hydroxytryptamine1 receptor subtypes corroborates the hypothesis that the inhibitory prejunctional 5-hydroxytryptamine receptor on cholinergic nerves is of the 5-hydroxytryptamine7 subtype.
Effects of long-term administration of erythromycin on cytokine production in rat alveolar macrophages
Authors: Sugiyama Y , Yanagisawa K , Tominaga SI , Kitamura S
Published: July 2002

Low-dose long-term erythromycin treatment has recently been reported to be very effective in patients with chronic respiratory infection and inflammation. This effect of erythromycin was thought to be not antibacterial but anti-inflammatory. However, the exact mechanism of the effect of erythromycin has not yet been clarified. The aims of this study were to investigate the effects of erythromycin on cytokine production and its mechanisms of actions in rat alveolar macrophages. Using rats with or without administration of erythromycin for 3 months, the production of the cytokines tumour necrosis factor-or (TNF-alpha), cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-2alpha by enzyme-linked immunosorbent assay and the expression of TNF-alpha and CINC-1 messenger ribonucleic acid (mRNA) by Northern blotting in rat alveolar macrophages were analysed. CINC-1 is the rat counterpart of human interleukin-8, and CINC-2alpha of human macrophage inflammatory peptide-2. Erythromycin reduced cytokine production and secretion when cytokines was induced by lipopolysaccharide treatment. Conversely, erythromycin slightly upregulated the expression of cytokine mRNA. These results suggest that erythromycin inhibits cytokine production and exhibits anti-inflammatory effects by means of a translational and/or posttranslational mechanism.
Cytokine expression in bronchial biopsies of cystic fibrosis patients with and without acute exacerbation
Authors: Wojnarowski C , Frischer T , Hofbauer E , Grabner C , Mosgoeller W , Eichler I , Ziesche R
Published: July 2002

In patients with cystic fibrosis (CF), the progression of pulmonary disease differs considerably, even in identical cystic fibrosis transmembrane conductance regulator-genotypes which could reflect an additional influence of the host's immune response. This study therefore measured cytokine expression patterns in CF patients with different clinical presentation. Expression of interleukin (IL)-8, interferon gamma (IFN-gamma), IL-4, IL-10, and transforming growth factor (TGF)beta(I) was assessed in bronchial mucosal biopsies of eight CF patients with acute exacerbation (age 6.0-14.2 yrs), eight CF patients with chronic stable disease (age 7.3-17.4 yrs), and in five normal control subjects by semiquantitative and quantitative reverse transcriptase polymerase chain reaction combined with histopathological assessment and immunohistochemical staining. All CF patients expressed IL-8. In acute exacerbation, expression of TGF-beta1 and IFN-gamma was either absent or extremely low. In contrast, all patients with stable disease strongly expressed TGF-beta1. The highest expression of TGF-beta1 and IFN-gamma was found in CF patients with mild disease and a history of infrequent exacerbations. No correlation was found between the expression of IL-4 and IL-10 and patient history. In normal control subjects, only a weak expression of TGF-beta1 was observed. These results show a remarkable correlation between cytokine pattern and the clinical course of cystic fibrosis. High expression of transforming growth factor-beta1 and interferon gamma was associated with mild disease, whereas no or very weak expression of these cytokines was typical for patients with acute disease and frequent exacerbations suggesting a contribution of the immune response to the progression of pulmonary disease in cystic fibrosis.
Effects of short-term inhaled fluticasone on oxidative burst of sputum cells in cystic fibrosis patients
Authors: Dauletbaev N , Viel K , Behr J , Loitsch S , Buhl R , Wagner TO , Bargon J
Published: July 2002

Inhaled corticosteroids have been proposed to decrease pulmonary inflammation in cystic fibrosis (CF). In this study the effects of therapy with inhaled fluticasone on clinical and sputum outcomes (leukocyte count, activity of myeloperoxidase, superoxide anion release) in adult CF patients were investigated in an open label design. Twenty-six stable patients (median+/-SD forced expiratory volume in one second (FEV1) 58.1+/-19.9% pred.) were randomly assigned to the study group (500 microg b.i.d., for three weeks) or the control group (n=14; nonsteroid medication). Sputum samples were obtained during inhalation of hypertonic saline (3%, 20 min), which was found not to alter the investigated sputum parameters. No significant changes in clinical parameters, sputum leukocyte count, activity of myeloperoxidase, and baseline superoxide anion release where observed following therapy. Surprisingly, stimulated superoxide anion release increased significantly after therapy (34.1+/-17.7 versus 25.2+/-17.4 nmol x hr(-1) x 10(6) cells, p<0.03) and exceeded spontaneous variability of this parameter (p=0.02 versus control group). In conclusion, in adult cystic fibrosis patients short-term fluticasone therapy had no evident effect on clinical and sputum parameters. Further investigations are necessary to evaluate whether the observed up-regulation of oxidative capacity of inflammatory cells is of concern or benefit in these patients.
Methacholine-induced volume dependence of respiratory resistance in preschool children
Authors: Marchal F , Loos N , Monin P , Peslin R
Published: July 2002

Enhanced negative volume dependence of airway resistance is associated with bronchoconstriction in tracheostomized paralysed open-chest animals. Significant upper airways responses may be associated with bronchoconstriction and could thereby alter the pattern of volume dependence in spontaneously breathing subjects. The aim of the study was to test whether volume dependence of respiratory resistance (Rrs) could be demonstrated in preschool children undergoing routine methacholine challenge. The volume dependence of respiratory oscillation resistance at 12 and 20 Hz (Rrs,12 and Rrs,20) was examined in eight 4-5.5-yr-old children showing a positive response to methacholine. Multiple linear regression analysis was also used to account for flow dependence during tidal breathing (Rrs,12 or Rrs,20=K1+K2 inverted question markV' inverted question mark+K3V). Rrs,12 and Rrs,20 yielded similar results. Negative volume dependence was present at baseline and significantly enhanced by methacholine (p<0.01). For instance, the mean+/-SD inspiratory K3 at 20 Hz was 4.1+/-1.3 hPa x s x L(-2) at baseline and -15.0+/-4.3 hPa x s x L(-2) after methacholine, in which case it was also larger on expiration than on inspiration (p<0.05), possibly as a result of upper airway responses. A significant increase in the negative volume dependence of respiratory resistance may thus be shown in preschool children in response to methacholine. The volume dependence (K3) during inspiration may be particularly useful in detecting bronchoconstriction, because it is less likely to be affected by upper airway mechanisms than during expiration.
Lack of a late asthmatic response after hypertonic saline challenge in children
Authors: Eder W , Schreuer M , Riedler J
Published: July 2002

Hypertonic saline challenge has become a standardized method for measuring airway responsiveness. However, there is still uncertainty about the occurrence of a late asthmatic response. Therefore, the present study was designed to assess a possible late asthmatic response after hypertonic saline challenge in children. Twenty-one children with mild to moderate bronchial hyperresponsiveness were studied. On days 1 and 2, forced expiratory volume in one second (FEV1) was measured hourly from 10:00 h to 22:00 h to assess diurnal variation of lung function. On the third study day, a hypertonic saline challenge was performed and FEV1 was measured as on control days. The possibility of a late asthmatic response was tested by comparing FEV1 levels up to 12 h after the challenge on the intervention day to FEV1 levels on control days. In no subjects were the FEV1 values following the challenge found to be considerably below the individual mean of the control days. Furthermore, a nonparametric approach was applied for each child and the population looked into as a whole. Again, no late asthmatic response was detectable. The results of this study suggest that in children with mild to moderate bronchial hyperresponsiveness a late asthmatic response does not occur 4-12 h after a 4.5% saline challenge.
Alexander Pope (1688-1744): his spinal deformity and his doctors
Authors: Sharma OP
Published: July 2002

Alexander Pope was the towering figure of 18th century England. A poet and a wit he commanded unswerving loyalty from his friends and penetrating hatred from his enemies. His spinal deformity, either due to tuberculosis, trauma or congenital weakness, shaped his career. This brief report highlights the illness and the medical men who were involved in treating Alexander Pope.
Permeability prediction in shaly formations: The fuzzy modeling approach
Authors: Finol Jose , Jing Xu‐Dong D.
Published: July 2002

This paper shows how fuzzy rule‐based systems help predict permeability in sedimentary rocks using well‐log responses. The fuzzy rule‐based approach represents a global nonlinear relationship between permeability and a set of input log responses as a smooth concatenation of a finite family of flexible local submodels. The fuzzy inference rules expressing the local input‐output relationships are obtained automatically from a set of observed measurements using a fuzzy clustering algorithm. This approach simplifies the process of constructing fuzzy systems without much computation effort. The benefits of the methodology are demonstrated with a case study in the Lake Maracaibo basin, Venezuela. Special core analyses from three early development wells provide the data for the learning task. Core permeability and well‐log data from a fourth well provide the basis for model validation. Numerical simulation results show that the fuzzy system is an improvement over conventional empirical methods in terms of predictive capability.
Lifestyle Intervention Requirements for Novel Antiobesity Medications—Necessary Adjunct or Harmful Gatekeeper?
Authors: Golovaty Ilya , Hagan Scott
Published: November 2024

This Viewpoint discusses how prerequisite comprehensive lifestyle interventions for novel antiobesity medications may disproportionately impact patients at highest risk of obesity-related complications and perpetuate disparities in care.
Isocyanates, Organic
Authors: Richter Frank , Karafilidis Christos , Darmandeh Heidar
Published: November 2024

The article contains sections titled:1Introduction2Physical Properties3Chemical Properties3.1Reaction with Nucleophiles3.2Cycloaddition Reactions4Production4.1Phosgenation of Free Amines4.2Other Phosgenation Procedures4.2.1Phosgenation of Amine Hydrochlorides4.2.2Phosgenation of Carbamate Salts4.2.3Phosgenation in the Gas Phase4.2.4Phosgenation of Ureas4.3Non‐phosgene Processes5Environmental Protection6Quality Specifications and Analysis7Storage and Transportation8Uses9Economic Aspects10Toxicology and Occupational HealthReferences
Adaptive Bounded Bilinear Control of a Parallel‐Flow Heat Exchanger
Authors: Mechhoud Sarah , Belkhatir Zehor
Published: November 2024

This work investigates the adaptive constrained control design for a parallel‐flow heat exchanger represented by a system of two coupled linear first‐order hyperbolic partial differential equations (PDEs). This system incorporates structured uncertainty involving unknown in‐domain parameters that characterize neglected dynamics in the heat exchanger model. These parameters may encompass unmodeled heat transfer phenomena, variations in fluid properties, and modeling simplifications. The objective is to regulate the internal fluid outlet temperature to track a desired reference trajectory by adjusting the external fluid velocity. Due to inherent physical constraints, this manipulated variable is upper and lower‐bounded. Accordingly, the control problem is bounded and bilinear. Using the set‐invariance principle and an energy‐like framework, we first develop a bounded state‐feedback controller. Then, since the measurements are considered only at the boundaries, we propose an adaptive boundary observer using a swapping scheme and a recursive least squares identifier. The proposed adaptive observer provides online estimates of the distributed state and the unknown parameters. Next, the state‐feedback controller is associated with the boundary observer and parameter identifier, and the exponential stability of the closed‐loop system is guaranteed using Lyapunov's stability theory. Finally, we provide numerical simulations to demonstrate the efficiency of the proposed control scheme.
Command Filter‐Based Prescribed Performance Adaptive Control for Fractional Order Non‐Strict System With Unmodeled Dynamics and Input Delay
Authors: Zhu Xinfeng , Du Shaofeng , Song Jian
Published: November 2024

This article focuses on adaptive control of a class of non‐strict feedback nonlinear fractional order systems with input delay and unmodeled dynamics under prescribed performance constraints. Command filtering backstepping design method is employed to avoid explosion of computation. Additionally, an error compensation mechanism is established to mitigate any errors introduced by the command filter. Radial basis function neural network is utilized to approximate the nonlinear function. Auxiliary signal processing variables are introduced to handle unmodeled dynamics. To address the input delay problem, a Pade approximation technique is employed. The stability analysis of the controller is conducted using Lyapunov stability theory, ensuring that the tracking error converges within a narrow predefined performance range. Finally, simulation results are presented to demonstrate the effectiveness of the proposed controller.
Inflammatory Microenvironment‐Responsive Nanomotors with NIR Photothermal Effect for Deep Inflammation Elimination and Infection Inhibition
Authors: Wang Wentao , Gao Yumeng , Lin Yan , Qian Yuxin , Shen Jian , Zhou Ninglin , Tang Ben Zhong , Zhang Ming
Published: November 2024

The infected chronic wound area has a unique microenvironment featuring hypoxia, excessive reactive oxygen species (ROS), and inflammatory conditions. Bacteria‐formed biofilms limit the anti‐inflammation efficiency of most therapeutics by hindering their penetration into deep infected wound tissues and increasing drug resistance. The unitary modulation of pro‐inflammatory M1 macrophage polarization cannot relieve inflammation immediately. Here, the “all in one” folic acid‐modified small organic molecule‐based nanoparticles (2TT‐mC6B@CeO2@FA, PCFs) are developed, which possess dual‐targeting to bacteria and M1 macrophages, double modulation to M1 macrophages, photothermal therapy (PTT), and enzymatic‐like activities. Based on the considerable catalase‐ and superoxide dismutase‐like activities, PCFs can efficiently scavenge ROS and produce oxygen (O2). The generated O2 can automatically drive PCFs movement as nanomotors to further promote deep penetration and rescue hypoxia. The scavenging of ROS promotes M1 macrophages polarized into anti‐inflammatory M2 macrophages. The study also identifies that FA‐modified PCFs can target bacteria and M1 macrophages to selectively eliminate M1 macrophages and bacteria through PTT, which relieves inflammation and chronic wound healing. Transcriptome analysis confirms that PCFs inhibit the expression of inflammatory‐related genes while increasing the expression of anti‐inflammatory cytokines. In vivo experiments identify that PCFs benefit neovascularization in neonatal tissues and tissue generation at wound sites.
Zeolitic Imidazolate Frameworks Derived Magnetic Nanocage/MXene/Nanocellulose Bilayer Aerogels for Low Reflection Electromagnetic Interference Shielding and Light‐to‐Heat Conversion
Authors: Mai Tian , Chen Lei , Liu Qi , Guo Zhong‐Hui , Ma Ming‐Guo
Published: November 2024

To cope with the increasingly serious electromagnetic pollution, the demand for electromagnetic interference (EMI) shielding materials with low electromagnetic wave reflection ability has become urgent. Controlling electrical components, magnetic components, and designing the EMI material structure can effectively improve electromagnetic shielding performance, but this remains a significant challenge. Besides, extreme cold weather conditions also do considerable potential damage to the normal work of outdoor electronic equipment. Integrated light‐to‐heat conversion capability on electromagnetic shielding materials can further improve the stability and reliability of the equipment. Herein, the novel bilayer aerogels composed of zeolitic imidazolate frameworks derived hollow CoNi carbon nanocage/MXene Ti3C2Tx/nanocellulose (BZMN) are prepared by a two‐step freezing method. BZMN aerogels exhibit good EMI shielding effectiveness (SE) with low reflection coefficient (R coefficients): 35.1 dB (R coefficient = 0.28) and 21.2 dB (R coefficient = 0.25). The unique structures of bilayer aerogels demonstrate the ability to absorb more electromagnetic waves through interfacial polarization and multiple scattering. The green shielding index (gs) of BZMN aerogels can reach 2.88. Moreover, BZMN aerogels show remarkable and unique light‐to‐heat conversion performance on different surfaces. Under 2.0 sun intensity, temperatures can reach 109.3 °C in the upper layer and 102.3 °C in the lower layer. Under 0.8 W cm−2 near‐infrared (NIR) laser intensity, the temperatures can rise to 234.1 °C in the upper layer and 167.4 °C in the lower layer. In addition, the size and shape of BZMN aerogels can be customized according to the mold. These features present BZMN aerogels as advanced potential low reflection EMI shielding device candidates, useful for future telecommunication and electronic equipment protection.