bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety of Dexamphetamine in Acute Ischemic Stroke
Authors: Martinsson Louise , Wahlgren Nils Gunnar
Published: February 2003

Background and Purpose—Amphetamine is reported to enhance recovery after experimental stroke, but results from the first few trials in humans are inconclusive. Limited information is available on treatment safety. This study intended to investigate the safety and tolerability of dexamphetamine in patients with acute cerebral ischemia.

Methods—Forty-five patients with cerebral ischemia were enrolled within 72 hours after onset of symptoms. Patients were randomized to 1 of 3 dose levels (2.5, 5, or 10 mg orally twice daily) or placebo for 5 consecutive days. Adverse events, blood pressure, heart rate, body temperature, consciousness level, and functional outcome measures were followed up daily during treatment. Follow-ups were made at day 7 and 1 and 3 months after stroke.

Results—Mean systolic and diastolic blood pressures and heart rate increased 14 mm Hg, 8 mm Hg, and 9 bpm, respectively, with dexamphetamine treatment compared with placebo (P≤0.01). There was no difference between dexamphetamine and placebo regarding adverse events, body temperature, or consciousness level. During treatment, there was a benefit of dexamphetamine in neurological and functional outcome (P<0.05), but differences were not maintained at follow-up.

Conclusions—Overall, dexamphetamine was safe and well tolerated by patients with acute cerebral ischemia, but blood pressure and heart rate increased during treatment in comparison to placebo. These observations may be important in the future planning of amphetamine trials because changes in these variables have been observed to interfere with clinical outcome. The suggestions of improvement in outcome must be confirmed in further studies.
Patient Selection for Carotid Endarterectomy
Authors: Barth Alain , Bassetti Claudio
Published: February 2003

Background and Purpose—

Risk-factor modeling has been proposed to identify patients with carotid stenosis who will most benefit from surgery. Validation by independent institutions performing carotid endarterectomy is necessary to determine the applicability of such models to the individual patient.

Methods—

A series of patients with a recently symptomatic high-grade carotid stenosis were selected for surgery according to current guidelines and were consecutively operated on in a single institution. In addition, a prognostic model was applied to the patients to analyze the concordance of both selection methods.

Results—

The study included 134 patients operated on between 1999 and 2001. The risk model predicted that 49% of the patients should have been excluded from surgery because the operation was found to be possibly harmful in 1 patient (1%) and not significantly beneficial in 65 patients (48%). This resulted from the predominant negative weight of the surgical risk factors in the model. However, this predominance was negated in our series by the fact that only 1 major complication (0.75%) occurred during follow-up.

Conclusions—

Exclusion of single patients on the basis of risk modeling may be problematic when the rate of perioperative complications is very low.
Measuring Longitudinally the Metabolic Demands of Stroke Patients
Authors: Finestone Hillel M. , Greene-Finestone Linda S. , Foley Norine C. , Woodbury M. Gail
Published: February 2003

Background and Purpose—

Little is known of the acute, subacute, and longer-term energy demands of stroke, information essential to appropriate clinical and nutritional management. The goals of this study were to (1) determine the resting energy expenditure (REE) of stroke patients from stroke onset to 3 months, (2) examine relations between stroke size, type, location, severity, and REE, and (3) evaluate whether estimation of REE from the Harris-Benedict equation (HB) requires the addition of a “stress factor” to capture the possible additional REE imposed by stroke.

Methods—

The REE of new stroke patients was measured prospectively at hospital admission and on days 7, 11, 14, 21, and 90 by indirect calorimetry. Stroke patients’ REEs (Kcal/d) over time and REEs as a percentage of HB were compared with control subjects’ single measurements.

Results—

Mean REE and %HB of stroke patients ranged from 1521±290 to 1663±268 Kcal/d and from 107±14.9 to 114±12.9 %HB, respectively. Mean measurements of control subjects were 1665±265 Kcal/d and 112.9±11.4 %HB (NS). REE was not associated with stroke characteristics (NS). Changes in REE measured longitudinally were not clinically meaningful (4 to 62 Kcal/d) though statistically significant (
P
=0.004).

Conclusions—

The REEs of stroke patients and controls were both ≈10% higher than those predicted by HB. No hypermetabolic response pattern of energy expenditure was evident after stroke. REE did not vary with stroke characteristics, although confirmation with larger subgroups is required.
Lower Endotoxin Immunity Predicts Increased Cognitive Dysfunction in Elderly Patients After Cardiac Surgery
Authors: Mathew Joseph P. , Grocott Hilary P. , Phillips-Bute Barbara , Stafford-Smith Mark , Laskowitz Daniel T. , Rossignol Daniel , Blumenthal James A. , Newman Mark F. ,   the Cardiothoracic Anesthesiology Research Endeavors (CARE†) Investigators of the Duke Heart Center
Published: February 2003

Background and Purpose—

Although coronary artery bypass graft surgery (CABG) improves the quality of life and functional capacity for numerous patients, many also exhibit impairment in cognitive function immediately after surgery. Although the etiology of this cognitive decline is multifactorial, the inflammatory response to the primary insult may modulate the extent of dysfunction. Patients with low preoperative levels of anti-endotoxin core antibody (EndoCAb) are more likely to experience adverse outcomes, suggesting that decreased immunity to endotoxin causes a heightened release of inflammatory mediators. We therefore sought to determine the association of decreased EndoCAb and the incidence of postoperative cognitive decline.

Methods—

EndoCAb levels were measured before surgery in 460 patients undergoing elective CABG. Cognitive function was measured preoperatively and 6 weeks postoperatively. Multivariable analysis accounted for the effects of age, Parsonnet score, sex, body mass index, baseline cognition, years of education, history of hypertension, bypass time, cross-clamp time, and number of grafts.

Results—

At 6-week follow-up, 122 patients (36%) showed cognitive decline. Lower preoperative EndoCAb levels were associated with a greater incidence and severity of postoperative cognitive decline. The elderly with decreased endotoxin immunity are particularly susceptible to this decline (relative risk=1.97 for age >64).

Conclusions—

Reduced preoperative endotoxin immunity is a predictor of increased postoperative cognitive dysfunction in patients undergoing CABG, particularly in those >60 years old. Interventions that increase IgM EndoCAb levels might improve cognitive function after cardiac surgery.
Interleukin-6 Promoter Polymorphism Modulates the Effects of Heavy Alcohol Consumption on Early Carotid Artery Atherosclerosis
Authors: Jerrard-Dunne Paula , Sitzer Matthias , Risley Paul , Steckel Donata A. , Buehler Alexandra , von Kegler Stefan , Markus Hugh S.
Published: February 2003

Background and Purpose—

A J-shaped relationship has been demonstrated between alcohol and both clinical cardiovascular events and carotid atherosclerosis. A similar J-shaped relationship has been found between alcohol intake and inflammatory markers. If inflammation were on the intermediate causal pathway between alcohol intake and atherosclerosis, then genetic determinants of enhanced inflammation would be expected to modify this relationship.

Methods—

In a large community population (n=1000; age, 50 to 65 years), we studied the effects of the interleukin-6 (IL-6)-174 polymorphism and gene-alcohol interactions on common carotid artery intima-media thickness (CCA-IMT) and carotid plaque.

Results—

The CC genotype was associated with significantly higher IL-6 levels; the odds ratio (OR) for IL-6 in the top quartile was 2.07 (95% CI, 1.16 to 3.72;
P
=0.014). Interactions were seen between genotype and alcohol consumption for both IL-6 levels and CCA-IMT. In individuals who drank >30 g/d of alcohol, the CC genotype was associated with higher IL-6 levels, elevated CCA-IMT (
P
=0.001), and increased risk of carotid plaque (OR, 3.64; 95% CI, 1.15 to 11.54;
P
=0.028). The J-shaped relationship between alcohol intake and IMT was seen only for the CC genotype.

Conclusions—

These data suggest that the IL-6-174 promotor polymorphism may modulate the effects of alcohol on carotid atherosclerosis. These data support the hypothesis that inflammation forms part of the intermediate causal pathway between alcohol intake and atherosclerosis.
Baseline Magnetic Resonance Imaging Parameters and Stroke Outcome in Patients Treated by Intravenous Tissue Plasminogen Activator
Authors: Nighoghossian N. , Hermier M. , Adeleine P. , Derex L. , Dugor J.F. , Philippeau F. , Ylmaz H. , Honnorat J. , Dardel P. , Berthezène Y. , Froment J.C. , Trouillas P.
Published: February 2003

Background and Purpose—

We designed a prospective sequential pretreatment and posttreatment MRI study to assess the relation between neuroimaging parameters and clinical outcome in patients treated with intravenous recombinant tissue-type plasminogen activator (rtPA).

Methods—

Patients with symptoms of acute hemispheric ischemic stroke were recruited. The National Institutes of Health Stroke Scale (NIHSS) score was assessed at baseline and at days 1, 7, and 60, and the modified Rankin scale (mRS) at day 60, by which outcome was classified in terms of independence (mRS score 0, 1, or 2) or severe disability or death (mRS score 3 through 6), was assigned. Multimodal stroke MRI was performed at presentation and repeated at day 1. MRI procedures included magnetic resonance angiography, T2* gradient-echo sequence, echoplanar imaging, and isotropic diffusion- (DWI) and perfusion-weighted (PWI) imaging. Patients were treated with intravenous rtPA after MRI completion.

Results—

Twenty-nine patients (16 men and 13 women; mean±SD age, 65±14 years) underwent MRI; the mean time from symptom onset to treatment was 255±62 minutes. Twenty-six patients had a vessel occlusion, and 15 patients experienced a partial (Thrombolysis in Myocardial Infarction [TIMI]-2) or total (TIMI-3) recanalization at day 1, whereas 11 patients had a persistent occlusion. Mean NIHSS scores at day 60 were 5.7±5.4 if recanalization had occurred and 14±2 in cases of persistent occlusion. According to the mRS, 13 patients were independent (mRS 0 through 2), whereas severe disability or death (mRS 3 through 6) was observed in 15 patients. A better outcome was observed when recanalization was achieved (
r
=−0.68,
P
=0.0002). PWI volume and time to peak (TTP) within the DWI lesion assessed before therapy were correlated with day-60 NIHSS score (PWI volume:
r
=0.51,
P
=0.006, TTP:
r
=0.35,
P
=0.07). The day-0 DWI abnormality volume was well correlated with day-60 NIHSS score (
r
=0.58,
P
=0.001). Multiple regression linear analysis showed that 2 factors mainly influenced clinical outcome: (1) recanalization, with a high correlation with NIHSS score at day 60 (
P
=0.0001) and (2) day-0 DWI lesion volume, which is closely associated with day-60 NIHSS score (
P
=0.03).

Conclusions—

Baseline DWI volume and recanalization are the main factors influencing clinical outcome after rtPA for ischemic stroke.
Withdrawal of Statin Treatment Abrogates Stroke Protection in Mice
Authors: Gertz Karen , Laufs Ulrich , Lindauer Ute , Nickenig Georg , Böhm Michael , Dirnagl Ulrich , Endres Matthias
Published: February 2003

Background and Purpose—

Statins (3-hydroxy-3-methylglutaryl–coenzyme A [HMG-CoA] reductase inhibitors) reduce stroke damage independent of lipid lowering by upregulation of endothelial nitric oxide synthase (eNOS). Acute withdrawal of statin treatment may suppress endothelial NO production and impair vascular function.

Methods—

To test this hypothesis, we treated 129/SV mice with atorvastatin (10 mg/kg) for 14 days and then withdrew treatment.

Results—

Treatment with atorvastatin conferred stroke protection by 40% after filamentous occlusion of the middle cerebral artery followed by reperfusion. Withdrawal of statin treatment, however, resulted in the loss of stroke protection after 2 and 4 days. In mouse aortas and brain vasculature, statins upregulated eNOS message 2.3- and 1.7-fold, respectively, as measured by reverse transcription–polymerase chain reaction. Withdrawal of statins resulted in 5- and 2.7-fold downregulation of eNOS in aorta and brain, respectively, after 2 days. Statin treatment decreased RhoA GTPase membrane expression to 48%, while withdrawal of statins resulted in 4-fold increase of RhoA in the membrane. Moreover, platelet factor 4 and β-thromboglobulin in plasma were significantly downregulated by statin treatment, but withdrawal of statins resulted in a 2.9- and 3.1-fold upregulation after 2 days, respectively. Thrombus formation induced by ligature of the inferior vena cava was significantly reduced by statin treatment. When statin treatment was withdrawn, however, protection was lost between 2 and 4 days.

Conclusions—

Acute termination of statin treatment results in a rapid loss of protection in mouse models of cerebral ischemia and thrombus formation independent of lipid lowering. In patients with acute or impending stroke, withdrawal of statins may impair outcome.
Nonaspirin Nonsteroidal Anti-Inflammatory Drugs and Risk of Hospitalization for Intracerebral Hemorrhage
Authors: Johnsen Søren P. , Pedersen Lars , Friis Søren , Blot William J. , McLaughlin Joseph K. , Olsen Jørgen H. , Sørensen Henrik T.
Published: February 2003

Background and Purpose—

Nonsteroidal anti-inflammatory drugs (NSAIDs) have effects on hemostasis and have been associated with an increased risk of bleeding. However, data relating the use of nonaspirin NSAIDs and risk of intracerebral hemorrhage (ICH) are sparse.

Methods—

Using data from the County Hospital Patient Register and the Civil Registration System of North Jutland County, Denmark, we identified 912 cases of first-time ICH and 9059 sex- and age-matched population-based controls in the period of 1991 to 1999. All prescriptions for nonaspirin NSAIDs before the date of admission for ICH were identified through a population-based prescription database. Conditional logistic regression was used to adjust for potential confounding factors, including previous discharge diagnoses of hypertension, chronic bronchitis and emphysema, alcoholism, liver cirrhosis, diabetes mellitus, and prescriptions for insulin or oral hypoglycemic agents, antihypertensive agents, lipid-lowering agents, low-dose aspirin, high-dose aspirin, and oral anticoagulants.

Results—

No overall association was found between prescription for nonaspirin NSAIDs in the preceding 30, 60, or 90 days and risk of ICH; ie, odds ratios ranged from 0.92 (95% CI, 0.70 to 1.21) to 1.13 (95% CI, 0.81 to 1.58). Furthermore, there was no increased risk of ICH associated with prescription for nonaspirin NSAIDs when the study population was stratified by age, sex, and a previous discharge diagnosis of hypertension.

Conclusions—

Patients prescribed nonaspirin NSAIDs were not at an overall increased risk of being hospitalized for ICH. This reassuring finding was seen in all examined subgroups, including the elderly and patients with a previous discharge diagnosis of hypertension.
Essential Role of Gap Junctions in NO- and Prostanoid-Independent Relaxations Evoked by Acetylcholine in Rabbit Intracerebral Arteries
Authors: Ujiie Hiroshi , Chaytor Andrew T. , Bakker Linda M. , Griffith Tudor M.
Published: February 2003

Background and Purpose—

Direct intercellular communication via gap junctions may play a central role in endothelium-dependent relaxations that are mediated by a conducted hyperpolarization and do not involve the synthesis of NO and prostanoids. In the present study, inhibitory peptides homologous to the Gap27 domain of the second extracellular loop of connexin37/connexin43 and connexin40, designated as
37,43
Gap27 and
40
Gap27, respectively, were used to evaluate the role of this mechanism in intracerebral arteries.

Methods—

Isolated rings of rabbit middle cerebral artery were constricted by histamine (10 μmol/L) in the presence of
N
G
-nitro-
l
-arginine methyl ester (300 μmol/L) and indomethacin (10 μmol/L). Concentration-relaxation curves for acetylcholine were constructed in the presence and absence of
37,43
Gap27 and
40
Gap27. Specific antibodies were used to delineate the distribution of connexin37, connexin40, connexin43, and connexin45 within the arterial wall.

Results—

Individually,
37,43
Gap27 and
40
Gap27 minimally affected endothelium-dependent relaxations to acetylcholine at concentrations of 300 μmol/L, whereas their combination (at 300 μmol/L each) inhibited the maximal response by ≈70% and increased the EC
50
value for relaxation by ≈15-fold. In endothelium-denuded rings, this peptide combination did not attenuate responses to sodium nitroprusside, an exogenous source of NO. Gap junction plaques, whose incidence was highest in endothelium, were constructed from connexin40 and connexin43 in the media and connexin37, connexin40, and connexin43 in the endothelium.

Conclusions—

The findings confirm that direct communication via gap junctions contributes to agonist-induced relaxations of intracerebral arteries. More than one connexin subtype appears to participate in such responses.
Reanalysis of the Final Results of the European Carotid Surgery Trial
Authors: Rothwell P. M. , Gutnikov S. A. , Warlow C. P.
Published: February 2003

Background and Purpose—

The European Carotid Surgery Trial (ECST) and North American Symptomatic Carotid Endarterectomy Trial (NASCET) have shown that endarterectomy reduces the risk of stroke in certain patients with recently symptomatic carotid stenosis. However, they differed in the degree of stenosis above which surgery was reported to be effective. This disparity has led to inconsistent clinical recommendations but may have been due to differences between the trials in the methods of measurement of carotid stenosis and definitions of outcome events.

Methods—

To allow direct comparison of analyses from ECST and NASCET, we remeasured the prerandomization ECST carotid angiograms and redefined the outcome events the same way as in NASCET.

Results—

We randomized 3018 patients and followed them up for a mean of 73 months. Surgery reduced the 5-year risk of any stroke or surgical death by 5.7% (95% CI, 0 to 11.6) in patients with 50% to 69% stenosis (n=646,
P
=0.05) and by 21.2% (95% CI, 12.9 to 29.4) in patients with 70% to 99% stenosis without “near occlusion” (n=429,
P
<0.0001). These benefits were maintained at the 10-year follow-up. However, surgery was of no benefit in patients (n=125) with near occlusion. The effect of surgery in this group was highly significantly different from that in patients with 70% to 99% stenosis without near occlusion (
P
=0.002). Surgery was harmful in patients with <30% stenosis (n=1321,
P
=0.007) and of no benefit in patients with 30% to 49% stenosis (n=478,
P
=0.6).

Conclusions—

Results of the ECST and NASCET were consistent when analyzed in the same way. In ECST, surgery was highly beneficial for 70% to 99% stenosis and moderately beneficial for 50% to 69% stenosis. However, contrary to clinical recommendations and current practice, surgery was of little benefit in patients with carotid near occlusion.
Should patients with sleep apnoea/hypopnoea syndrome be diagnosed and managed on the basis of home sleep studies?
Authors: Parra O , Garcia-Esclasans N , Montserrat JM , Garcia Eroles L , Ruiz J , Lopez JA , Guerra JM , Sopena JJ
Published: February 2003

The purpose of this study was to analyse the validity and the economic efficiency of a portable monitor of respiratory parameters (PMRP), used in a home setting for the diagnosis of sleep apnoea/hypopnoea syndrome (SAHS). Eighty nine patients with suspected SAHS were studied in two settings: in the sleep laboratory using full-polysomnography (full-PSG); and at the patient's home using a PMRP. In the home setting, 50 patients were assisted by a technician and 39 set up the equipment themselves. SAHS (apnoea/hypopnoea index (AHI) >10 events x h(-1) by means of full-PSG) was diagnosed in 75 of the 89 patients. An acceptable agreement was obtained between the AHI measured by full-PSG and PMRP, according to the Bland and Altman method of concordance (mean bias 2.56; 95% confidence interval 3.25). Sensitivity and specificity of PMRP were adequate for diagnostic purposes; however, their values rely on the prior PMRP-AHI cut-off point selected with reference to full-PSG-AHI >10. The clinical therapeutic decision taken after PMRP agreed with that taken with full-PSG in 79 patients (89%). Although 10% of the studies with an individual set-up needed repetition, both of the domiciliary modalities (with and without a technician's intervention) were, economically, about three times more efficient than full-PSG. In conclusion, we believe that patients with a suspected sleep apnoea/hypopnoea syndrome should initially be studied in a home setting with a portable monitor of respiratory parameters, since it is a reliable method with an acceptable cost-effective profile.
Expression of complement receptors and regulatory proteins on alveolar CD4+ lymphocytes from human immunodeficiency virus-1 infected individuals
Authors: Aries SP , Schaaf B , Hansen F , Weyrich K , Kurowski V , Dennin R , Dalhoff K
Published: February 2003

Several lines of evidence suggest a dysregulation of the complement system in human immunodeficiency virus-1 (HIV-1) infected patients. The aim of this study was to elucidate whether CD4+ alveolar lymphocytes from HIV-1 infected patients show a loss of complement regulatory proteins that would render these cells susceptible to antibody-dependent complement-mediated cytotoxicity. We investigated the expression of complement regulatory (CD46, CD55, CD59) and complement receptor (CR1, CR2, CR3, CR4) proteins on alveolar cells by flow cytometry. Cells were obtained by bronchoalveolar lavage from 17 HIV-1 infected and 12 HIV-1 negative individuals. Expression of adhesion molecules (leucocyte functional associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1)) and CD30 were evaluated in patient subgroups. In addition, interleukin (IL)-1beta, tumour necrosis factor alpha (TNF-alpha), IL-4 and interferon gamma (IFN-gamma) concentrations were measured in supernatants of alveolar cells. We found a significantly reduced expression of CD46 and CD59 on CD4+ alveolar lymphocytes from HIV-1 infected individuals, whereas the expression of CR3, CR4, ICAM-1 and CD30 was increased. IL-1beta and TNF-alpha concentration in supernatants of alveolar cells was augmented in HIV-1 infected patients, but did not correlate with the expression of surface molecules. IFN-gamma concentration was also increased and showed an inverse relationship to the surface expression of CD30 on CD4+. Our data suggest that in human immunodeficiency virus-1 infection an increased level of activation is associated with a diminished expression of complement regulatory proteins on CD4+ alveolar lymphocytes. This phenomenon might contribute to the depletion of CD4+ lymphocytes and the local immunodeficiency in the pulmonary compartment.
Kinin generation in acute pneumonia and chronic bronchitis
Authors: Zhang M , Peng B , Niehus J , Baumgarten CR , Brunnee T , Thalhofer S , Dorow P , Kunkel G
Published: February 2003

Kinins are potent inflammatory mediators, liberated from kininogens by different kininogenases. The aim of this study was to investigate the kinin generation pathways in acute and chronic inflammation of the lower airways. We studied bronchoalveolar lavage fluid (BALF) of patients with acute pneumonia, patients with chronic bronchitis and healthy controls. Kinins were determined by radioimmunoassay (RIA). Plasma kallikrein (pl-Kal), alpha2-macroglobulin (alpha2-M) and toluenesulphonylarginine methyl ester (TAME) esterase activity (TAME-ea) were studied in BALF before and after gel filtration chromatography. Plasma kallikrein and alpha2-M were measured using two newly developed sandwich enzyme-linked immunosorbent assays (ELISAs). TAME-ea was measured by a radiochemical assay. After gel filtration, inhibition of TAME-ea with benzamidine, soy-bean-trypsin inhibitor (SBTI) and aprotinin was performed. Kinins and TAME-ea did not differ significantly between acute pneumonia and chronic bronchitis, whereas pl-Kal and alpha2-M values were significantly higher in acute pneumonia. Gel filtration revealed the highest TAME-ea peak in acute pneumonia corresponding with the first alpha2-M peak at approximately 800 kDa, whereas in chronic bronchitis the highest peak was found at approximately 40 kDa. The inhibition test showed that the TAME-ea peak at approximately 800 kDa was due to pl-Kal and the TAME-ea peak at approximately 40 kDa was mainly due to tissue kallikrein. High peaks of alpha2-M and pl-Kal were found in pneumonia and only small peaks were seen in chronic bronchitis. We conclude that in acute airway inflammation kinins seem to be mainly generated by plasma kallikrein whereas in chronic inflammation, kininogenases other than plasma kallikrein, such as tissue kallikrein, seem to be more important.
Prevalence of asthma symptoms in video and written questionnaires among children in four regions of Finland
Authors: Pekkanen J , Remes ST , Husman T , Lindberg M , Kajosaari M , Koivikko A , Soininen L
Published: February 2003

The aim of this study was to determine whether there are regional differences in the prevalence of childhood asthma in Finland. A secondary objective was to assess the concordance between a written and a video questionnaire on asthma symptoms. In 1994-1995, the self-reported prevalence of asthma symptoms in four regions of Finland was studied among 11,607 schoolchildren aged 13-14 yrs, as part of the International Study of Asthma and Allergies in Childhood (ISAAC). The ISAAC written and video (AVQ 3,0) questionnaires were administered in the school setting. The prevalences of any wheezing during the previous 12 months in the ISAAC video questionnaire were 10% in East Finland (Kuopio County, n=2,821), 12% in South Finland (Helsinki area, n=2,771), 12% in Southwest Finland (Turku and Pori County, n=2,983), and 11% in North Finland (Lapland, n=3,032). The prevalences in the ISAAC written questionnaire were 13, 20, 15, and 16%, respectively. The surveys were performed during winter, except in Helsinki where the survey was carried out mainly during the spring pollen season. During autumn, the prevalence in the written questionnaire in Helsinki was 16%. In multivariate analysis, boys had a lower prevalence than girls, and smokers a threefold higher prevalence than nonsmokers. In conclusion, the prevalence of childhood asthma is lower in Finland than in other European countries, and may be even lower in the eastern part of the country. In contrast to the results from some other European countries, prevalences were lower in the video than in the written questionnaire, which suggests that translating the word "wheezing" into other languages, including Finnish, may produce results that cannot be compared. The strong association of smoking with wheeze both in the video and written questionnaires should be considered in further analysis of the ISAAC study.
Lung delivery of salbutamol by dry powder inhaler (Turbuhaler) and small volume antistatic metal spacer (Airomir CFC-free MDI plus NebuChamber)
Authors: Lipworth BJ , Clark DJ
Published: February 2003

As a worldwide ban on the use of chlorofluorocarbons (CFCs) in inhaler devices approaches, considerable attention has been focused on the production of CFC-free delivery devices. The aim of our study was to compare the delivery of salbutamol by dry powder inhaler (DPI), Turbuhaler and a CFC-free metered-dose inhaler (MDI), Airomir, used with a novel small volume metal spacer (NebuChamber). Ten healthy volunteers, mean (SEM) age 21 (0.7) yrs were studied in a randomized, single (investigator)-blind cross-over design. Single doses of 1,200 microg salbutamol, from Turbuhaler DPI and Airomir CFC-free MDI via a NebuChamber, were given as 12 sequential 100 microg inhalations over 6 min. The lung delivery of salbutamol was assessed by measuring the plasma salbutamol profile over the first 20 min after inhalation. Plasma salbutamol concentration was expressed as maximal (Cmax) and average (Cav) value. Significant differences (p<0.001) were found between the NebuChamber (N) and the Turbuhaler (T) for salbutamol Cmax and Cav. This amounted to a 1.89 fold difference (95% CI 1.56-2.22) between these devices for Cmax, and a 1.78 fold difference (95% CI 1.42-2.15) for Cav. We have demonstrated that, in vivo, salbutamol from a chlorofluorocarbon-free metered-dose inhaler given via a small volume metal spacer (NebuChamber) produces significantly greater delivery than from an efficient dry powder inhaler (Turbuhaler).
MDR1-Pgp 170 expression in human bronchus
Authors: Lechapt-Zalcman E , Hurbain I , Lacave R , Commo F , Urban T , Antoine M , Milleron B , Bernaudin JF
Published: February 2003

MDR1 P-glycoprotein (Pgp 170), a member of the adenosine triphosphate (ATP) binding cassette transporters, acts as an efflux pump for various hydrophobic agents, particularly for xenobiotics such as benzo(a)pyrene. It has also been shown to regulate cell-volume activated chloride channels. Pgp 170 could, therefore, be of particular importance in cellular mechanisms of defence in the airways and in the control of mucus layer composition. For these reasons, we evaluated the precise localization of Pgp 170 in human adult airways. Fresh non-neoplastic bronchial specimens were collected from 33 patients (26 smokers, four exsmokers and three nonsmokers) who underwent surgery for lung carcinoma. The presence of MDR1 messenger ribonucleic acid (mRNA) was demonstrated by reverse transcriptase chain reaction (RT-PCR) in bronchial epithelial cells collected by gentle scraping from either smokers, exsmokers or nonsmokers. Immunodetection of Pgp 170 using a panel of monoclonal antibodies (MRK16, JSB1, C219, C494) was performed either on cryostat or paraffin-embedded sections of histologically normal bronchial tissue. Pgp 170 was constantly detected with intense labelling at the apical surface of ciliated epithelial cells from the surface epithelium or ciliated collecting ducts, and on apical and lateral surfaces of serous cells from bronchial glands. No staining of mucus-secreting cells was observed. Pgp 170 was also demonstrated at the luminal surface of endothelial cells of bronchial capillaries. In conclusion, the expression of MDR1 P-glycoprotein in bronchial structures, particularly at the epithelial apical surface, suggests important roles for this transmembrane protein in human airways.
Neutral endopeptidase activity in newborn and adult rabbit tracheas
Authors: Haver K , Gerard C , Kobzik L , Shore SA
Published: February 2003

Neutral endopeptidase (NEP, E.C. 3.4.24.11), a widely distributed ectoenzyme, cleaves and inactivates a variety of biologically active peptides, including the tachykinin, substance P (SP). This study was undertaken to determine whether the modulation of SP airway smooth muscle contraction by NEP is age-dependent. We studied the contractile response of isolated tracheal rings from newborn and 120 day old New Zealand white rabbits. We measured NEP activity and determined immunoreactive NEP content in tracheal membrane preparations. NEP activity was then localized histochemically in sections of rabbit tracheas. In the presence of the NEP inhibitor, SCH 32615, the contractile response of isolated tracheal rings to SP was increased both in the newborn and 120 day old rabbits. However, the increase was greatest in the newborn animals. NEP activity in tracheal membrane preparations increased fivefold between the newborn and 120 day old rabbits. Western blot analysis also revealed a significant increase in the immunoreactive NEP content of these tracheal membrane preparations between the newborn and 120 day old rabbits. NEP activity, localized histochemically, was most intense in the epithelial region of the newborn animals, with a shift of activity to the subepithelial region with age. The prominent epithelial localization of neutral endopeptidase in the tracheas of these 1 day old rabbits, which we have shown to have relatively low neutral endopeptidase activity, suggests that the location of neutral endopeptidase in the airway, including proximity to relevant substance P receptors, may be critical to its function.
Alterations of lung structure in experimental diabetes, and diabetes associated with hyperlipidaemia in hamsters
Authors: Popov D , Simionescu M
Published: February 2003

Since hyperglycaemia is known to affect normal pulmonary physiology and biochemistry and few structure-function correlations have been reported, we designed experiments on hamsters subjected to streptozotocin-induced diabetes or diabetes associated with hyperlipidaemia, and investigated the impact of these conditions on the lung structure. At time intervals ranging 2-24 weeks from the inception of disease (without correcting blood glucose with insulin), the animals were sacrificed, and plasma glucose and cholesterol assayed. The lung was processed for electron microscopy, and the structural changes of the capillary and venular endothelium, of epithelial cells, and interstitium were examined. In diabetic animals, especially after 6 weeks of disease, a gradual narrowing of approximately 35% of the capillaries and approximately 30% of the alveoli, and hyperplasia of the extracellular matrix, rich in collagen bundles, were observed. Frequently, capillaries contained adherent intravascular macrophages suggestive of an inflammatory process. The capillary endothelium was characterized by numerous plasmalemmal vesicles, often fused, well-developed synthesizing apparatus (endoplasmic reticulum and Golgi complex) and cytoskeleton, and an uneven distribution of the anionic sites on the luminal plasmalemma. The venular endothelium was particularly rich in Weibel-Palade bodies. The alveolar epithelium was often collapsed, compressing surfactant within the airspace. The lung interstitium was apparently enlarged, and the fibroblasts and contractile interstitial cells frequently contained lipid droplets. These alterations were more pronounced and occurred at a faster rate (4 weeks) in diabetes associated with hyperlipidaemia. The structural modifications reported in this study support the functional disturbances observed in association with hyperglycaemia, sustaining the conclusion that the lung is an organ affected by diabetes.
Laser monitoring of chest wall displacement
Authors: Kondo T , Uhlig T , Pemberton P , Sly PD
Published: February 2003

We developed a prototype laser monitor, consisting of a single laser sensor, to observe chest wall displacement during respiration. With this monitor, respiratory waveforms are expressed as an anterioposterior motion of the chest wall. The purpose of this study was to examine the characteristics and performance of this prototype. Performance was assessed: 1) under static conditions; 2) using a lung model ventilated in both conventional and high frequency oscillation (HFOV) modes; and 3) during spontaneous breathing in normal adults. In vitro, the monitor performed well both under static conditions and during mechanical ventilation. Reliable "respiratory" wave forms, with no frequency-dependent change in the relationship between displacement and volume, were produced during both conventional ventilation and HFOV at 15 Hz. In vivo, abdominal displacement, measured in the midline, was linearly correlated with the tidal volume signal integrated from flow. The waveforms produced by the monitor were adequate for monitoring respiration and for calculating respiratory timing variables. While a single laser sensor is unlikely to be sufficient for monitoring respiration in spontaneously breathing subjects, the performance of the prototype monitor was sufficiently impressive to encourage further development and further study of this type of truly noninvasive respiratory monitor.
Influence of endotracheal tube diameter on forced deflation flow-volume curves in rhesus monkeys
Authors: Hammer J , Newth CJ
Published: February 2003

The forced deflation (FD) technique is the recommended gold standard to generate forced expiratory vital capacity (FVC) curves and to measure maximum expiratory flow-volume (MEFV) relationships in intubated infants and children. However, the influence of the endotracheal tube (ETT) on the site of flow limitation, the shape and the analysis of the resultant MEFV curves have not been defined. Nine anaesthetized (thiopentone, 8 mg x kg(-1) x h(-1)) rhesus monkeys (mean weight (+/-SEM) 10+/-1 kg) were intubated consecutively with ETTs of different internal diameters (ID 3.0-5.5 mm, at intervals of 0.5 mm); the largest representing the appropriate ETT size for the animal. Quadruplicate MEFV curves were generated by FD using the standard +40 cmH2Oinsp/-40 cmH2Oexp pressures and recorded at each ETT diameter. The effect of the different ETT diameters on the FD flow-volume curve was analysed by comparing maximum expiratory flows at isovolume points at 50, 25 and 10% FVC (MEF50, MEF25 and MEF10, respectively). The shape of the resulting MEFV curves could be divided into an initial horizontal part (tube-dependent), and a final descending slope (airway-dependent). No difference in FVC occurred irrespective of the ETT size (p>0.05 by analysis of variance (ANOVA)). MEF50 increased with increasing tube diameter (p<0.05). MEF25 remained unchanged using ETTs which were less than 1.5 mm smaller than the largest ETT. Smaller ETTs resulted in significantly reduced MEF25 (p<0.05). MEF10 was not influenced by the ETT size. We conclude that maximum expiratory flows measured by the forced deflation technique are not influenced by an appropriately sized endotracheal tube at lung volumes below 25% forced vital capacity in our monkey model with normal lungs. We postulate that the effect of endotracheal tubes on maximum expiratory flow volume curves in intubated infants might be of similar or even smaller magnitude, which remains to be established.
Limits of commercial molecular tests for diagnosis of pulmonary tuberculosis
Authors: Lebrun L , Mathieu D , Saulnier C , Nordmann P
Published: February 2003

Several studies report high specificity, but variable sensitivity, of Amplified Mycobacterium tuberculosis Direct Test (AMTDT, Gen-Probe) based on ribosomal ribonucleic acid (rRNA) amplification and Amplicor Mycobacterium tuberculosis test (Amplicor, Roche) based on deoxyribonucleic acid (DNA) amplification for diagnosis of pulmonary tuberculosis. We have retrospectively evaluated these assays on selected acid-fast bacilli (AFB)-positive and -negative smear specimens and compared the results obtained from nucleic acid amplification with those of AFB staining of semi-quantitative cultures as determined by radiometric Bactec and Lowenstein-Jensen cultures. In comparison to cultures, Amplicor and AMTDT assays exhibited identical overall sensitivities of 80%, while the staining had a lower sensitivity of 62%. The sensitivities of Amplicor and AMTDT were 98% and 100%, respectively, for the AFB-positive specimens, and 50 and 46%, respectively for the AFB-negative specimens in comparison to cultures. The sensitivities of both assays appeared similar, and were directly related to the number of bacilli in the specimens studied. The low sensitivity (50%) for smear-negative specimens showed that current amplification assays may be unsuitable to replace cultures for diagnosis of tuberculosis. The decision to perform these molecular techniques should result from close co-operation between clinicians and microbiologists, taking into account the sensitivity results reported here, as well as the expense of the assays.
The role of tachykinin receptor antagonists in the prevention of bronchial hyperresponsiveness, airway inflammation and cough
Authors: Advenier C , Lagente V , Boichot E
Published: February 2003

Several recent observations suggest that tachykinins, such as substance P and neurokinin A, might be involved in the pathogenesis of bronchopulmonary alterations. Progress in investigations on the physiological and pathological roles of tachykinins has been greatly facilitated by the availability of a number of highly selective nonpeptide antagonists for tachykinin neurokinin 1, 2 and 3 (NK1, NK2 and NK3) receptors. The use of selective tachykinin NK2 receptor antagonists suggests that tachykinin NK2 receptor stimulation plays an important role in the development of airway hyperresponsiveness in the guinea-pig. Others studies have also indicated that tachykinin NK1-receptors are involved in immediate or delayed neurogenic inflammation including microvascular leakage and the subsequent increase in plasma protein extravasation. A role for the sensory neuropeptide system has also been proposed in cough, as shown by the observation that the antitussive effect of tachykinin NK2 receptor antagonists has clearly been demonstrated in several experimental conditions, but the effect of tachykinin NK1 receptor antagonists is still debated. Taken together, the results obtained with the various selective receptor antagonists provide pharmacological evidence that tachykinins play a role in delayed bronchopulmonary alterations and suggest that tachykinin receptor antagonists may be useful for investigating mechanisms and possibly reducing airway functional alterations in asthmatic patients.
Lung mucus: a clinician's view
Authors: Kim WD
Published: February 2003

Respiratory mucus represents the products derived from secretion of the submucosal glands and the goblet cells. Accumulation of mucus in the airway tree may be caused by an increased volume of mucus produced, and also by decreased clearance due to defects in the ciliary clearance apparatus. Hypersecretion of mucus contributes to the morbidity of airway diseases by predisposing patients to respiratory infections, and contributing to airflow obstruction and to patients' discomfort. There is a significant association between chronic production of mucus and an increased risk of mortality. Also the degree of airway obstruction is related to the physical properties of the sputum. Observation of chronic bronchitic sputum can reveal important clinical information concerning the type and level of the inflammatory process, the physical properties of the material, the extent of bronchial mucosal damage, and the identification of pathogenic microorganisms that may be present. The management of mucous hypersecretion can be undertaken in two main ways: firstly, improved clearance by physical methods; and, secondly, by pharmacological methods.
Rhinitis caused by ninhydrin develops into occupational asthma
Authors: Piirila P , Estlander T , Hytonen M , Keskinen H , Tupasela O , Tuppurainen M
Published: February 2003

Ninhydrin (2,2-dihydroxy-1,3-indanedione or 1,2,3-triketo-hydrindene hydrate) is a chemical used in the detection of free amino and carboxyl groups in proteins and peptides. Allergic, immunoglobulin E (IgE)-mediated rhinitis caused by ninhydrin was diagnosed earlier in a 41 yr old woman working as a laboratory technician in a forensic laboratory. Despite handling ninhydrin only in a flow cabinet, symptoms of dyspnoea developed 6 months later. Peak flow was found to vary by 20% during working days. In the specific inhalation challenge it was shown that occupational asthma had also developed due to continuing slight exposure to ninhydrin. The titre of ninhydrin-specific IgE also increased from 0.6 to 1.1 kU x L(-1) in the follow-up. This case stresses the importance of cessation of allergen exposure in occupational allergic rhinitis, in order to prevent asthma.
Bilateral diaphragmatic paralysis--a rare cause of acute respiratory failure managed with nasal mask bilevel positive airway pressure (BiPAP) ventilation
Authors: Lin MC , Liaw MY , Huang CC , Chuang ML , Tsai YH
Published: February 2003

A 68 yr old woman presented with acute respiratory failure. She was suspected of having a phrenic-diaphragmatic impairment, without evidence of an intrinsic lung disease or generalized neuromuscular disorder, after 3 weeks of prolonged mechanical ventilation. A series of studies, including fluoroscopy, phrenic nerve stimulation test and diaphragmatic electromyography, was performed before the diagnosis of bilateral diaphragmatic paralysis (BDP) was confirmed. The patient was successfully weaned from the conventional mechanical ventilator, and was placed on nasal mask bi-level positive airway pressure (BiPAP) ventilation. A high degree of clinical suspicion of bilateral diaphragmatic paralysis should always be raised in patients suffering respiratory failure without definite predisposing factors. Weaning with noninvasive nasal mask ventilation should be tried first instead of direct tracheostomy.
Metastatic pulmonary calcification after renal transplantation
Authors: Murris-Espin M , Lacassagne L , Didier A , Voigt JJ , Cisterne JM , Giron J , Durand D , Leophonte P
Published: February 2003

Metastatic pulmonary calcifications, unlike dystrophic calcifications, occur in the normal healthy lung. The radiological pattern is quite specific. The disease is commonly described in chronic renal failure with calcium disorders. The prognosis is totally unpredictable. In 1992, a 50 yr old man underwent a successful renal transplantation during the final stage of chronic renal failure. He subsequently developed asymptomatic diffuse nodular opacities, that were discovered in 1995. An open lung biopsy confirmed the diagnosis of metastatic pulmonary calcification. There was no calcium disorder in this patient. In contrast to the benign course of pulmonary calcification in most patients, some fulminant pulmonary calcifications complicating renal transplantation or hypercalcaemia have been described. Radiographic identification of such entities is important to permit correction of calcium disorders. Otherwise, the condition is a potentially progressive and fatal cause of respiratory failure.
Lung volume equipment and infection control. ERS/ATS Workshop Report Series. European Respiratory Society/American Thoracic Society
Authors: Clausen JL
Published: February 2003

As part of the consensus workshop regarding lung volume measurements for the American Thoracic Society and European Respiratory Society, this background paper reviews mechanisms and risks of cross-infection resultant from performing measurements of absolute lung volumes either by body plethysmography, gas dilution, or gas wash-out techniques. Published reports of infection attributable to the performance of lung volume measurements are extremely rare. Nevertheless, because some infectious agents could be transmitted during measurements of lung volumes, and because of widespread concerns both of patients and some medical personnel about the risks of transmission of infections during inspiration from equipment used by other patients, a variety of measures have been advocated to minimize the risks of cross-infection. Workshop participants were divided in opinion about whether such testing does indeed pose significant risk of cross-infection, and also could not agree regarding optimal measures to prevent cross-infection. Although there is conflicting information regarding the efficacy of particulate filters for protecting cross-contamination of downstream equipment and tubing, the author recommends that such filters be used when making lung volume measurements, but only if the filter has acceptably low resistance (e.g. <0.15 kPa x L(-1) x s (1.5 cmH2O x L(-1) x s)), and the measurements are adjusted for the impact of the added resistance and dead space.