bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperbaric Oxygen Therapy in Acute Ischemic Stroke
Authors: Rusyniak Daniel E. , Kirk Mark A. , May Jason D. , Kao Louise W. , Brizendine Edward J. , Welch Julie L. , Cordell William H. , Alonso Robert J.
Published: February 2003

Background and Purpose—

Hyperbaric oxygen therapy (HBO) has promise as a treatment for acute stroke. This study was conducted to evaluate the efficacy, safety, and feasibility of using HBO in acute ischemic stroke.

Methods—

We conducted a randomized, prospective, double-blind, sham-controlled pilot study of 33 patients presenting with acute ischemic stroke who did not receive thrombolytics over a 24-month period. Patients were randomized to treatment for 60 minutes in a monoplace hyperbaric chamber pressurized with 100% O
2
to 2.5-atm absolute (ATA) in the HBO group or 1.14 ATA in the sham group. Primary outcomes measured included percentage of patients with improvement at 24 hours (National Institutes of Health Stroke Scale [NIHSS]) and 90 days (NIHSS, Barthel Index, modified Rankin Scale, Glasgow Outcome Scale). Secondary measurements included complications of treatment and mortality at 90 days.

Results—

Baseline demographics were similar in both groups. There were no differences between the groups at 24 hours (
P
=0.44). At 3 months, however, a larger percentage of the sham patients had a good outcome defined by their stroke scores compared with the HBO group (NIHSS, 80% versus 31.3%;
P
=0.04; Barthel Index, 81.8% versus 50%;
P
=0.12; modified Rankin Scale, 81.8% versus 31.3%;
P
=0.02; Glasgow Outcome Scale, 90.9% versus 37.5%;
P
=0.01) with loss of statistical significance in a intent-to-treat analysis.

Conclusions—

Although our HBO protocol appears feasible and safe, it does not appear to be beneficial and may be harmful in patients with acute ischemic stroke.
Effects of Acute Hyperhomocysteinemia on the Neurovascular Coupling Mechanism in Healthy Young Adults
Authors: Rosengarten B. , Osthaus S. , Auch D. , Kaps M.
Published: February 2003

Background and Purpose—

Hyperhomocysteinemia is a vascular risk factor that infers with the nitric oxide signaling pathway of endothelial vasoregulation. Most investigations in young healthy humans on the peripheral vasculature using a standardized methionine challenge demonstrated altered vascular reactivity. In contrast, the cerebral autoregulation mechanism was shown to be unaffected by the same methionine load. To obtain additional insight into the compensatory range of the cerebral vasculature during a methionine challenge, we tested the neurovascular coupling mechanism that adjusts cerebral blood flow in accordance with cortical activity.

Methods—

Fifteen healthy young adults (age, 24.7±2.3 years; 7 men) were tested with a functional transcranial Doppler test before and 3, 8, and 24 hours after administration of placebo, 20 mg folic acid, 20 mg folic acid and 0.1 g/kg body weight
l
-methionine, or
l
-methionine alone. Evoked blood flow response was evaluated according to a control system approach. Plasma concentrations of homocysteine, resting blood flow velocities, and control system parameters of flow velocity change were compared for each time point using a multiple analysis of variance test.

Results—

Homocysteine levels increased significantly compared with baseline (before, 7.6±1.9 μmol/L; 3 hours, 22.2±6.0 μmol/L [
P
<0.0001]; 8 hours, 27.9±8.6 μmol/L [
P
<0.0001]; 24 hours, 12.6±7.8 μmol/L [
P
=NS]). Resting flow velocities and control system parameters remained statistically nonsignificant.

Conclusions—

Compared with the peripheral vasculature, the regulatory mechanisms controlling adequate cerebral blood flow appear to have a wider compensatory range. This is concluded from statistically nonsignificant results comparing the vascular reactivity in young adults undergoing a standardized methionine challenge. Our data confirm indirectly the reports of high concentrations of homocysteine needed to affect the cerebral vasculature in animal experiments.
Intravenous Administration of Bone Morphogenetic Protein-7 After Ischemia Improves Motor Function in Stroke Rats
Authors: Chang Chen-Fu , Lin Shinn-Zong , Chiang Yung-Hsiao , Morales Marisela , Chou Jenny , Lein Pamela , Chen Hui-Ling , Hoffer Barry J. , Wang Yun
Published: February 2003

Background and Purpose—

We and others have previously reported that bone morphogenetic protein-7 (BMP-7), given before middle cerebral artery occlusion (MCAO), reduces ischemic injury in brain. Recent studies have indicated that receptors for BMP are upregulated after brain ischemia. It is possible that this upregulation may facilitate endogenous neurorepair in the ischemic brain. The purpose of this study was to determine the neuroregenerative effects of BMP-7 given parenterally after ischemia/reperfusion injury.

Methods—

Adult Sprague-Dawley rats were anesthetized with chloral hydrate. The middle cerebral artery was transiently occluded by a filament inserted through the right internal carotid artery. The filament was removed after 60-minute ischemia to allow reperfusion. Some animals were killed 24 hours after MCAO to examine BMP-7 mRNA expression. Other animals received a single dose of intravenous BMP-7 or vehicle at 24 hours after MCAO and were used for subsequent behavioral studies and BMP-7 immunostaining.

Results—

BMP-7 mRNA was upregulated 24 hours after MCAO in untreated animals. BMP-7 immunoreactivity was dose-dependently increased on the ischemic side of the hippocampus/dentate on day 6 after MCAO in animals receiving intravenous injection of BMP-7. Animals receiving BMP-7 also showed a decrease in body asymmetry from day 7 to day 14 and an increase in locomotor activity on day 14 after MCAO.

Conclusions—

Our data indicate that BMP-7, given parenterally after stroke, can pass through the blood-brain barrier on the ischemic side and induce behavioral recovery in stroke animals at longer testing times.
Incidence and Risk Factors of Silent Brain Infarcts in the Population-Based Rotterdam Scan Study
Authors: Vermeer Sarah E. , den Heijer Tom , Koudstaal Peter J. , Oudkerk Matthijs , Hofman Albert , Breteler Monique M.B.
Published: February 2003

Background and Purpose—

The prevalence of silent brain infarcts in healthy elderly people is high, and these lesions are associated with an increased risk of stroke. The incidence of silent brain infarcts is unknown. We investigated the incidence and cardiovascular risk factors for silent brain infarcts.

Methods—

The Rotterdam Scan Study is a prospective, population-based cohort study of 1077 participants 60 to 90 years of age. All participants underwent cranial MRI in 1995 to 1996, and 668 participants had a second MRI in 1999 to 2000 (response rate, 70%) with a mean interval of 3.4 years. We assessed cardiovascular risk factors by interview and physical examination at baseline. Associations between risk factors and incident silent infarcts were analyzed by multiple logistic regression.

Results—

Ninety-three participants (14%) had ≥1 new infarcts on the second MRI; of these, 81 had only silent and 12 had symptomatic infarcts. The incidence of silent brain infarcts strongly increased with age and was 5 times higher than that of symptomatic stroke. A prevalent silent brain infarct strongly predicted a new silent infarct on the second MRI (age- and sex-adjusted odds ratio, 2.9; 95% confidence interval, 1.7 to 5.0). Age, blood pressure, diabetes mellitus, cholesterol and homocysteine levels, intima-media thickness, carotid plaques, and smoking were associated with new silent brain infarcts in participants without prevalent infarcts.

Conclusions—

The incidence of silent brain infarcts on MRI in the general elderly population strongly increases with age. The cardiovascular risk factors for silent brain infarcts are similar to those for stroke.
Risk of Stroke Associated With Nonsteroidal Anti-Inflammatory Drugs
Authors: Bak Søren , Andersen Morten , Tsiropoulos Ioannis , García Rodríguez Luis Alberto , Hallas Jesper , Christensen Kaare , Gaist David
Published: February 2003

Background and Purpose—

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with bleeding complications and may affect the risk of hemorrhagic stroke through inhibition of platelet cyclooxygenase-1. We performed a population-based case-control study to estimate the risk of intracerebral hemorrhage, subarachnoid hemorrhage, and ischemic stroke in users of NSAIDs.

Methods—

We used a population-based patient registry to identify all patients with a first-ever stroke discharge diagnosis in the period of 1994 to 1999. All diagnoses were validated according to predefined criteria. We selected 40 000 random controls from the background population. Information on drug use for cases and controls was retrieved from a prescription registry. Odds ratios were adjusted for age, sex, calendar year, and use of other medication. To evaluate the effect of various potential confounders not recorded in the register, we performed separate analyses on data from 2 large population-based surveys with more detailed information on risk factors.

Results—

The cases were classified as intracerebral hemorrhage (n=659), subarachnoid hemorrhage (n=208), and ischemic stroke (n=2717). The adjusted odds ratio of stroke in current NSAID users compared with never users was 1.2 (95% CI, 0.9 to 1.6) for intracerebral hemorrhage, 1.2 (95% CI, 0.7 to 2.1) for subarachnoid hemorrhage and 1.2 (95% confidence interval, 1.0 to 1.4) for ischemic stroke. The survey data indicated that additional confounder control would not have led to an increase in relative risk estimates.

Conclusions—

Current exposure to NSAIDs is not a risk factor for intracerebral hemorrhage or subarachnoid hemorrhage. Furthermore, NSAIDs probably offer no protection against first-ever ischemic stroke.
Tolerability of NXY-059 at Higher Target Concentrations in Patients With Acute Stroke
Authors: Lees K.R. , Barer D. , Ford G.A. , Hacke W. , Kostulas V. , Sharma A.K. , Odergren T.
Published: February 2003

Background and Purpose—

NXY-059 is a nitrone-based free radical–trapping agent in development for acute stroke. In patients with acute stroke, NXY-059 is well tolerated at concentrations known to be associated with neuroprotection in animal models of transient cerebral ischemia; however, higher target concentrations appear necessary on the basis of animal models of permanent ischemia.

Methods—

This was a randomized, double-blind, placebo-controlled, parallel-group, dose-escalation, multicenter study that evaluated safety, tolerability, and plasma concentrations of 2 NXY-059 dosing regimens within 24 hours of acute stroke. NXY-059 was administered as either 915 mg over 1 hour followed by 420 mg/h for 71 hours or 1820 mg for 1 hour followed by 844 mg/h for 71 hours; plasma concentrations were monitored. Neurological and functional outcomes were recorded for up to 30 days.

Results—

One hundred thirty-five patients were recruited, of whom 134 received study treatment and completed assessments (844 mg/h, n=39; 420 mg/h, n=48; placebo, n=47). Mean age was 69 years (range, 34 to 92 years), and baseline National Institutes of Health Stroke Scale score was 8.5 (SD, 6.6). Serious adverse events occurred in 3, 17, and 13 patients, respectively, with deaths in 0, 4, and 3 patients and treatment discontinuations because of adverse events in 0, 1, and 3 patients. Good outcome, defined by modified Rankin Scale score of 0 or 1, was seen in 53%, 29% and 40%, respectively. No safety concern was identified in analysis of body temperature, blood pressure, or other laboratory parameters. The unbound plasma concentration at steady state was 260±79 μmol/L, exceeding the target of 200 μmol/L in the high-dose group.

Conclusions—

NXY-059 was well tolerated in patients with an acute stroke at and above concentrations shown to be neuroprotective in an animal model when initiated 4 hours after onset of permanent focal ischemia.
Risk Factors for Falling in Home-Dwelling Older Women With Stroke
Authors: Lamb S.E. , Ferrucci L. , Volapto S. , Fried L.P. , Guralnik J.M.
Published: February 2003

Background and Purpose—

Much of our knowledge of risk factors for falls comes from studies of the general population. The aim of this study was to estimate the risk of falling associated with commonly accepted and stroke-specific factors in a home-dwelling stroke population.

Methods—

This study included an analysis of prospective fall reports in 124 women with confirmed stroke over 1 year. Variables relating to physical and mental health, history of falls, stroke symptoms, self-reported difficulties in activities of daily living, and physical performance tests were collected during home assessments.

Results—

Risk factors for falling commonly reported in the general population, including performance tests of balance, incontinence, previous falls, and sedative/hypnotic medications, did not predict falls in multivariate analyses. Frequent balance problems while dressing were the strongest risk factor for falls (odds ratio, 7.0). Residual balance, dizziness, or spinning stroke symptoms were also a strong risk factor for falling (odds ratio, 5.2). Residual motor symptoms were not associated with an increased risk of falling.

Conclusions—

Interventions to reduce the frequency of balance problems during complex tasks may play a significant role in reducing falls in stroke. Clinicians should be aware of the increased risk of falling in women with residual balance, dizziness, or spinning stroke symptoms and recognize that risk assessments developed for use in the general population may not be appropriate for stroke patients.
Infection and Risk of Ischemic Stroke
Authors: Paganini-Hill A. , Lozano E. , Fischberg G. , Perez Barreto M. , Rajamani K. , Ameriso S.F. , Heseltine P.N.R. , Fisher M.
Published: February 2003

Background and Purpose—

Although prior studies have demonstrated that 25% to 35% of stroke patients have had a recent infection, the role of infection as a risk factor remains unclear. Our aim was to characterize the effect of infectious/inflammatory syndromes on stroke risk.

Methods—

Case-control and crossover analyses of 233 cases and 363 controls aged 21 to 89 years were performed. Cases were patients hospitalized with a first ischemic stroke at a Los Angeles, California, medical center. Controls were outpatients in the hypertension, diabetes, and general medical clinics. All subjects were administered a neurological examination, an infection/inflammation (I/I) examination, and an interview to elicit recent I/I history at baseline (within several days of stroke onset) and again approximately 2 months later. Three physicians classified subjects by the presence or absence of I/I within 1 month of the index dates, based on findings of the I/I examination, the interview report, and laboratory results.

Results—

Infections, either total or specific, were not found more frequently in cases than controls. However, patients with a recent respiratory tract infection suffered more often from large-vessel atherothromboembolic or cardioembolic stroke than did patients without infection (48% vs 24%,
P
=0.07). The age- and sex-adjusted relative risk estimate for these subtypes was 1.75 (95% CI, 0.86 to 3.55). The risk was notably high for those without stroke risk factors: 4.15 (95% CI, 1.22 to 14.1) for normotensives, 2.71 (95% CI, 1.04 to 7.06) for nondiabetics, and 1.74 (95% CI, 0.74 to 4.07) for nonsmokers. Patients with a recent respiratory infection also had a more severe neurological deficit on admission than those without infection (
P
=0.05).

Conclusions—

Our results suggest that respiratory tract infection may act as a trigger and increase the risk of large-vessel and/or cardioembolic ischemic stroke, especially in those without vascular risk factors.
Mortality From Cerebrovascular Disease in a Cohort of 23 000 Patients With Insulin-Treated Diabetes
Authors: Laing Susan P. , Swerdlow Anthony J. , Carpenter Lucy M. , Slater Stefan D. , Burden Andrew C. , Botha Johannes L. , Morris Andrew D. , Waugh Norman R. , Gatling Wendy , Gale Edwin A.M. , Patterson Christopher C. , Qiao Zongkai , Keen Harry
Published: February 2003

Background and Purpose—

Disease of the cardiovascular system is the main cause of long-term complications and mortality in patients with type I (insulin-dependent) and type II (non-insulin-dependent) diabetes. Cerebrovascular mortality rates have been shown to be raised in patients with type II diabetes but have not previously been reported by age and sex in patients with type I diabetes.

Methods—

A cohort of 23 751 patients with insulin-treated diabetes, diagnosed under the age of 30 years from throughout the United Kingdom, was identified during 1972 to 1993 and followed up for mortality until the end of December 2000. Age- and sex-specific mortality rates and standardized mortality ratios (SMRs) were calculated.

Results—

There were 1437 deaths during the follow-up, 80 due to cerebrovascular disease. Overall, the cerebrovascular mortality rates in the cohort were higher than the corresponding rates in the general population, and the SMRs were 3.1 (95% CI, 2.2 to 4.3) for men and 4.4 (95% CI, 3.1 to 6.0) for women. When stratified by age, the SMRs were highest in the 20- to 39-year age group. After subdivision of cause of death into hemorrhagic and nonhemorrhagic origins, there remained a significant increase in mortality from stroke of nonhemorrhagic origin.

Conclusions—

Analyses of mortality from this cohort, essentially one of patients with type I diabetes, has shown for the first time that cerebrovascular mortality is raised at all ages in these patients. Type I diabetes is at least as great a risk factor for cerebrovascular mortality as type II diabetes.
Possible Role for Vascular Cell Proliferation in Cerebral Vasospasm After Subarachnoid Hemorrhage
Authors: Borel Cecil O. , McKee Andy , Parra Augusto , Haglund Michael M. , Solan Amy , Prabhakar Vikas , Sheng Huaxin , Warner David S. , Niklason Laura
Published: February 2003

Background and Purpose—

During vasospasm after subarachnoid hemorrhage (SAH), cerebral blood vessels show structural changes consistent with the actions of vascular mitogens. We measured platelet-derived vascular growth factors (PDGFs) in the cerebrospinal fluid (CSF) of patients after SAH and tested the effect of these factors on cerebral arteries in vivo and in vitro.

Methods—

CSF was sampled from 14 patients after SAH, 6 patients not suffering SAH, and 8 normal controls. ELISA was performed for PDGF-AB, transforming growth factor-β1, and vascular endothelial growth factor. A mouse model was used to compare cerebral vascular cell proliferation and PDGF staining in SAH compared with sham-operated controls. Normal human pial arteries were incubated for 7 days in vitro, 2 groups with human blood clot and 1 with and 1 without PDGF antibodies.

Results—

PDGF-AB concentrations in CSF from SAH patients were significantly higher than those from non-SAH patients and normal controls, both during the first week after SAH and for all time points measured. Smooth muscle and fibroblast proliferation was observed after SAH in the mouse model, and this cellular replication was observed in conjunction with PDGF protein at the sites of thrombus. In human pial arteries, localized thrombus stimulated vessel wall proliferation, and proliferation was blocked by neutralizing antibodies directed against PDGFs.

Conclusions—

Vascular mitogens are increased in the CSF of patients after SAH. Proliferation of cells in the vascular wall is associated with perivascular thrombus. Cellular proliferation and subsequent vessel wall thickening may contribute to the syndrome of delayed cerebral vasospasm.
Interobserver Agreement in the Classification of Stroke in the Women’s Health Study
Authors: Atiya Monika , Kurth Tobias , Berger Klaus , Buring Julie E. , Kase Carlos S.
Published: February 2003

Background and Purpose—

Accurate classification of stroke events is essential in large cohort studies of risk factor assessment and in treatment trials such as the Women’s Health Study (WHS).

Methods—

Based on medical record review, we assessed interrater reliability in stroke classification and disability status in the WHS using the κ statistic.

Results—

During 7.0 years of follow-up, 271 incident strokes occurred, of which 133 were reclassified. There was excellent interrater agreement in the diagnosis of major stroke types, hemorrhagic subtypes, and degree of disability, as well as substantial agreement in the definition of the vascular territory involved. Only moderate agreement was reached in the classification of ischemic subtypes.

Conclusions—

Major stroke types, degree of disability, and vascular territory involved can be reliably classified on the basis of a review of medical records in the WHS, whereas classification of ischemic stroke subtypes needs further refinement of diagnostic criteria.
Physical and Social Functioning After Stroke
Authors: Lai Sue-Min , Perera Subashan , Duncan Pamela W. , Bode Rita
Published: February 2003

Background and Purpose—

This study evaluated assessments of physical functioning and social functioning using the Stroke Impact Scale (SIS) and Short Form-36 (SF-36) to characterize health-related quality of life for patients after stroke.

Methods—

The SIS and SF-36 were administered to 278 stroke subjects ≈90 days after stroke. The SIS-16 and SF-36 Physical Functioning (PF) domain characterize physical function, whereas the SIS Participation and SF-36 Social Functioning (SF) domains characterize social function. Descriptive statistics and an analysis of variance were used to characterize physical and social functioning after stroke across levels of the modified Rankin Scale (MRS). Rasch analysis was used to compare the hierarchies and ranges of item difficulties in the SIS-16 and the SF-36 PF domains, as well as in the SIS Participation and the SF-36 SF domains.

Results—

Item hierarchies for the SIS-16 and SF-36 PF domain demonstrate that the SIS-16 contains less difficult items that could differentiate physical function among patients with more severe limitations. Compared with the SF-36 SF domain, the item hierarchy for the SIS Participation domain contained more difficult items that could differentiate social function among patients who were more active. In contrast to SIS-16, the SF-36 PF has major floor effects. In contrast to SIS Participation, the SF-36 SF domain has major ceiling effects. Both SIS-16 and SF-36 PF were able to discriminate well among the MRS levels of 0 to 1, 2, 3, and 4. The SIS Participation domain was also able to discriminate across the MRS levels of 0 to 1, 2, and 3 to 4. On the other hand, the SF-36 SF was similar among MRS levels 0, 1, and 2 and among MRS levels 2, 3, and 4.

Conclusions—

Both the physical and participation subscales of the SIS cover a wider range of item difficulty than their counterparts from the SF-36. Compared with the SF-36 PF and SF domains, the SIS-16 and SIS Participation are better able to capture physical functioning and social well-being in patients with strokes.
Obstructive sleep apnoea syndrome: is the "half-night polysomnography" an adequate method for evaluating sleep profile and respiratory events?
Authors: Fanfulla F , Patruno V , Bruschi C , Rampulla C
Published: February 2003

Recently, to reduce the costs of polysomnography, split-night studies have been introduced into routine practice: the first part of the night is used to make the diagnosis of obstructive sleep apnoea syndrome (OSAS) and the second part to achieve an appropriate level of continuous positive airway pressure. Since this split-night protocol has not yet been validated by the comparison of polysomnographic pictures obtained in the first and second parts of the night, the aim of this study was to evaluate sleep profile and respiratory disturbances in the first part (PSG1) and second (PSG2) portion of a standard full-night polysomnographic examination (PSGtot) in a group of OSAS patients. Twenty nine consecutive OSAS patients, aged 54+/-10 yrs; body mass index (BMI) 40+/-6 kg x m(-2) (mean+/-SD values), were studied by separate analyses of PSG1, PSG2 and PSGtot. PSG1 was found to have a low sensitivity value (66%). A significant difference was found between apnoea-hypopnoea indices (AHI) recorded in PSG1, PSG2 and PSGtot (mean+/-SD, AHI1 33+/-27, AHI2 45+/-28, AHItot 40+/-25 events x h(-1), respectively; p<0.01). A strong correlation was observed between AHItot and AHI1 (r=0.89) and between AHItot and AHI2 (r=0.92), but a weaker correlation between AHI1 and AHI2 (r=0.66). These correlations became weaker when patients were subdivided into two different classes on the basis of disease severity. PSG1 was representative of PSGtot and similar to PSG2 only in those patients with rapid eye movement (REM) phase sleep in the first part of the night. We conclude that split-night protocols are not appropriate for evaluating sleep-disordered breathing in obstructive sleep apnoea syndrome patients when rapid eye movement phase sleep does not occur in the first part of the night.
Sleep-related O2 desaturation and daytime pulmonary haemodynamics in COPD patients with mild hypoxaemia
Authors: Chaouat A , Weitzenblum E , Kessler R , Charpentier C , Ehrhart M , Levi-Valensi P , Zielinski J , Delaunois L , Cornudella R , Moutinho dos Santos J
Published: February 2003

It has been hypothesized but not firmly established that sleep-related hypoxaemia could favour the development of pulmonary hypertension in chronic obstructive pulmonary disease (COPD) patients without marked daytime hypoxaemia. We have investigated the relationships between pulmonary function data, sleep-related desaturation and daytime pulmonary haemodynamics in a group of 94 COPD patients not qualifying for conventional O2 therapy (daytime arterial oxygen tension (Pa,O2) in the range 7.4-9.2 kPa (56-69 mmHg)). Nocturnal desaturation was defined by spending > or = 30% of the recording time with a transcutaneous O2 saturation < 90%. An obstructive sleep apnoea syndrome was excluded by polysomnography. Sixty six patients were desaturators (Group 1) and 28 were nondesaturators (Group 2). There was no significant difference between Groups 1 and 2 with regard to pulmonary volumes and Pa,O2 (8.4+/-0.6 vs 8.4+/-0.4 kPa (63+/-4 vs 63+/-3 mmHg)) but arterial carbon dioxide tension (Pa,CO2) was higher in Group 1 (6.0+/-0.7 vs 53+/-0.5 kPa (45+/-5 vs 40+/-4 mmHg); p<0.0001). Mean pulmonary artery pressure (Ppa) was very similar in the two groups (2.6+/-0.7 vs 2.5+/-0.6 kPa (19+/-5 vs 19+/-4 mmHg)). No individual variable or combination of variables could predict the presence of pulmonary hypertension. It is concluded that in these patients with chronic obstructive pulmonary disease with modest daytime hypoxaemia, functional and gasometric variables (with the noticeable exception of arterial carbon dioxide tension) cannot predict the presence of nocturnal desaturation; and that mean pulmonary artery pressure is not correlated with the degree and duration of nocturnal hypoxaemia. These results do not support the hypothesis that sleep-related hypoxaemia favours the development of pulmonary hypertension.
Effect of sputum bacteriology on the quality of life of patients with bronchiectasis
Authors: Wilson CB , Jones PW , O'Leary CJ , Hansell DM , Cole PJ , Wilson R
Published: February 2003

Bronchiectatic patients have impaired health-related quality of life (QoL) and are prone to chronic lower respiratory tract infections. We have investigated whether impaired QoL is related to sputum bacteriology. Eighty seven patients with non-cystic fibrosis (non-CF) bronchiectasis, in a stable phase of their illness, completed three QoL measures, underwent a computed tomography (CT) scan and lung function tests, and provided a fresh sputum sample for microscopy and culture. The QoL of patients colonized by Pseudomonas aeruginosa (Pa group) was significantly worse than all other patients grouped together (non-Pa group), and specifically those infected by Haemophilus influenzae (Hi group) or who had no bacterial growth (NG group) (p<0.05), but not those infected by other bacterial species (O group). The Pa group had worse lung function, but no significant differences were found between the groups for forced expiratory volume in one second (FEV1) and peak expiratory flow rate. The Pa group had significantly worse bronchiectasis scores than the O, NG and non-Pa groups, but not the Hi group. There were no significant differences between the groups with respect to the number of infective exacerbations in the last year, but the Pa group had significantly more hospital admissions. Patients infected by P. aeruginosa for more than 3 yrs had significantly worse FEV1 (p<0.03) and bronchiectasis scores (p<0.05) than those infected with P. aeruginosa for less time, but not significantly worse QoL. We conclude that, overall, patients infected with P. aeruginosa have worse quality of life, and that P. aeruginosa is associated with a greater extent of disease and worse lung function. Although patients infected with H. influenzae had extensive bronchiectasis their quality of life was better than the P. aeruginosa infected group.
Use of the paediatric bronchoscope, flexible and rigid, in 51 European centres
Authors: Barbato A , Magarotto M , Crivellaro M , Novello A , Cracco A , de Blic J , Scheinmann P , Warner JO , Zach M
Published: February 2003

We have undertaken a survey to establish current practices and differences in the use of bronchoscopes in children in European centres. A questionnaire was sent to all 220 members of the Paediatric Assembly of the European Respiratory Society (ERS). The questions concerned the following points: indications for bronchoscopy; site of bronchoscopy; type of sedation; any oxygen supplementation during the procedure; number of procedures performed in the previous 12 months; number of procedures performed in the neonatal intensive care unit; number of bronchoalveolar lavages (BALs); side-effects during and after the procedures; and diagnostic yield. Fifty one European centres (40.8% of the European centres contacted) took part in the study. A total of 7,446 bronchoscopies had been performed in the last 12 months: 4,587 using the flexible bronchoscope and 2,859 using the rigid bronchoscope. At centres using only the fibreoptic bronchoscope, the most frequent indication was "recurrent/persistent pneumonia" (17%); at centres using only the rigid bronchoscope, it was "foreign body inhalation" (36.7%); at centres using both methods, the most frequent indication was "other indications" (23.9%). In 12 months, 2,231 BALs were performed: 1,419 in immunocompetent children and 812 in immunocompromised patients. In centres using only the fibreoptic bronchoscope, the highest yield was for "stridor" (81%); in centres using only the rigid bronchoscope, the highest yield was for "persistent atelectasis" (68%); and in centres using both instruments, it was for "foreign body inhalation" (93%). The results of the study suggest that bronchoscopy in children is now a well-established procedure at several European centres, while others are just beginning to use this technique.
Increased spontaneous release of tumour necrosis factor-alpha by alveolar macrophages from wheezy infants
Authors: Azevedo I , de Blic J , Dumarey CH , Scheinmann P , Vargaftig BB , Bachelet M
Published: February 2003

We determined if alveolar macrophages (AMs) from infants with severe recurrent wheezing episodes release increased amounts of tumour necrosis factor-alpha (TNF-alpha), as described in adults with asthma. We compared TNF-alpha release by unstimulated and lipopolysaccharide-stimulated AMs obtained by bronchoalveolar lavage in 13 wheezy and seven nonwheezy infants (aged 6-36 months) and analysed its regulation by dexamethasone. Metabolites in cell supernatants were quantified by enzyme-linked immunosorbent assay (ELISA) (TNF-alpha) or radioimmunoassay (thromboxane B2 and prostaglandin E2). Comparison of results was performed by the Mann-Whitney U-test and values were expressed as median (interquartile range) in ng x 10(6) cells(-1). Resting AMs from wheezy infants released larger amounts of TNF-alpha and thromboxane B2 as compared to controls: 2.67 (0.89-8.33) vs 0.48 (0.25-1.08) and 75.63 (38.07-158.91) vs 10.03 (7.36-76.08), respectively (p<0.05). When stimulated overnight with bacterial lipopolysaccharide, AMs from both groups released similar amounts of metabolites. Dexamethasone induced a consistent inhibition of the lipopolysaccharide-stimulated release of all the mediators. Our results show that alveolar macrophages from wheezy infants are activated to release increased amounts of tumour necrosis factor-alpha, as in asthma, and suggest that infants with recurrent wheezing may eventually benefit from treatment with glucocorticoids.
In utero exposure to cigarette smoking influences lung function at birth
Authors: Lodrup Carlsen KC , Jaakkola JJ , Nafstad P , Carlsen KH
Published: February 2003

To avoid the possible confounding effects of postnatal exposure to tobacco smoke, we investigated possible effects of uterine tobacco smoke (UTS) exposure upon infant lung function shortly after birth. Infants with no major disease, in one maternity ward in Oslo, Norway, participating in a cohort study established in 1992/1993, were included in the present study (n=803). Exposure information, assessed as maternal active and passive smoking during pregnancy and other personal and environmental factors, was obtained by questionnaire. Tidal flow-volume (TFV) loops (n=802) and compliance (Crs) and resistance (Rrs) of the respiratory system (n=663) were measured at a mean age of 2.7 days. In girls, the TFV ratio (time to reach peak expiratory flow to total expiratory time (tPEF/tE)), and Crs were significantly lower with active as well as passive maternal smoking compared to nonexposure to UTS. Respiratory rate and Rrs were not significantly influenced by UTS exposure. However, in linear regression analysis adjusted for confounding factors (including respiratory rate), tPEF/tE and Crs, but not Rrs, were related to maternal active but not passive daily smoking. One daily cigarette corresponded to a change in tPEF/tE of -0.0021 (95% confidence interval (95% CI) -0.0040 to -0.0002) and a change in Crs of -0.026 mL x cmH2O (95% CI -0.045 to -0.007 mL x cmH2O). The decrease was 0.023 and 0.29, respectively, in infants of an average smoker. Maternal smoking during pregnancy adversely affected tidal flow-volume ratios in healthy newborn babies, as well as the compliance of the respiratory system in girls, independently of the reduced body size also resulting from maternal smoking.
Effect of ageing on peak expiratory flow variability and nocturnal exacerbations in bronchial asthma
Authors: Bellia V , Cuttitta G , Cibella F , Vignola AM , Crescimanno G , D'Accardi P , Catalano F , Bonsignore G
Published: February 2003

The aim of this study was to evaluate the role of ageing on variability of airflow obstruction and on the specific pattern of nocturnal exacerbations ("morning dipping" of peak expiratory flow (PEF)) in asthma. Two groups of stable asthmatics (Group A: 23 patients, aged 14-47 yrs; Group B: 20 patients, aged 53-74 yrs), that were similar for duration of disease, degree of obstruction and response to bronchodilators, were studied. PEF was monitored four times daily for 2 weeks, and amplitude of variation and "morning dip" were calculated. Both PEF amplitude and "morning dip" were greater in the older patients (p<0.005). Amplitude was negatively correlated with baseline forced expiratory volume in one second (FEV1) in both groups (p<0.01); multiple correlation with age, duration of disease, baseline FEV1 and degree of reversibility was significant in the older group only. Morning dip was inversely correlated to baseline FEV1 (p<0.01) and reversibility (p<0.05). Nocturnal symptoms were reported by all of the five Group A "dippers", but by only 6 of the 13 Group B "dippers" (p<0.04). Ageing contributes to increased variability of airway calibre in asthma. Aged patients are potentially at risk because functional evidence of nocturnal asthma may frequently be accompanied by a poor subjective awareness. Therefore, a more extensive practice of PEF monitoring is recommended in aged asthmatics.
Muscarinic contraction in isolated guinea-pig trachea and antagonism by noradrenaline
Authors: Walland A , Hammer R
Published: February 2003

In contrast to other muscarinic agonists, WAL 2014 FU does not induce bronchospasm in laboratory animals. The present investigation was intended to test the hypothesis that this is due to a particular susceptibility of the drug's effect to antagonism by catecholamines, as a result of partial M3-agonism. The tonic activity of the muscarinic agonists, aceclidine, arecoline, carbachol, McN-A-343, RS 86, thiopilocarpine and WAL 2014 FU, was tested in groups of isolated tracheal muscle of the guinea-pig. Susceptibility to functional antagonism by beta-adrenoceptor stimulation was measured by the displacement of the concentration-force curves by 3 microM noradrenaline. Evaluation of the concentration-force relationship revealed differences in potency and intrinsic activity (carbachol-100%) ranging from 114% for arecoline to 36% for thiopilocarpine (WAL 2014 FU-63%). The catecholamine increased the concentration of agonist which induced 5% of the maximum effect achievable (EC05) values fivefold (carbachol) to more than 4,680 fold (thiopilocarpine) (WAL 2014 FU: 2,860 fold). Regression analysis between the intrinsic activity of the seven compounds and the antagonistic effect of noradrenaline revealed a significant correlation (Spearman correlation coefficient (r[s])=-0.79; p=0.036). Inhibition of the effects of endogenous catecholamines by beta-adrenolysis with 50 microM toliprolol increased the maximal contraction induced by 1 mM WAL 2014 FU, but did not affect maximal contraction induced by 30 microM arecoline. Pretreatment with 0.3-1.0 mM dibutyrylcyclic adenosine monophosphate (DBcAMP) shifted the concentration-response curves of arecoline, WAL 2014 FU and thiopilocarpine in a similar manner to noradrenaline. The results exclude an important contribution of adenylate cyclase-coupled M2-receptors to the susceptibility of tracheal contraction by muscarinic agonists to functional antagonism by noradrenaline, but emphasize the importance of intrinsic activity at the M3-receptors. The pronounced susceptibility of WAL 2014 FU-induced contraction to functional antagonism by beta-adrenoceptor activation provides an explanation for the failure of the drug to induce bronchospasm in vivo.
Molecular diagnosis of tuberculosis: current clinical validity and future perspectives
Authors: Roth A , Schaberg T , Mauch H
Published: February 2003

The rapid development and availability of a variety of new molecular genetic technologies present the clinician with an array of options for the accurate diagnosis of infectious diseases. This is particularly the case for tuberculosis, since molecular methods have been rapidly introduced into all working areas of the mycobacteriology laboratory. Nucleic acid amplification methods to detect Mycobacterium tuberculosis in clinical specimens are increasingly used as a tool to diagnose tuberculosis. The bulk of recently available data from clinical evaluations performed under routine laboratory conditions indicate that these molecular methods are rapid and sensitive, but yet inferior, to culture with regard to sensitivity and specificity. Therefore, until gene amplification tests have proved to be reliable and quality control procedures exist, their clinical validity remains controversial. Consequently, definition of selected clinical applications of gene amplification to routine diagnosis of tuberculosis is important and need to be discussed. This review will focus on the clinical role of molecular methods in the direct detection and diagnosis of M. tuberculosis in clinical samples. In addition, molecular genetic approaches designed to determine drug susceptibility and to discriminate strains below the species level will be outlined and discussed in terms of their current and future clinical applicability.
A new interpretation of the date of the ‘Little Ice Age’ glacier maximum at Svartisen and Okstindan, northern Norway
Authors: Winkler Stefan
Published: February 2003

New results concerning the dating of ‘Little Ice Age’ glacier variations at Svartisen and Okstindan, northern Norway, are presented. Measurements of lichens of the Rhizocarpon subgenus on gravestones are used to construct several local sets of lichenometric dating curves. These are partly ‘adjusted’ in relation to well-established lichenometric dating curves from southern Norway. The ‘Little Ice Age’ maximum at Svartisen and Okstindan is thereby dated to the mid-eighteenth century (i.e., in agreement with southern Norway). Pre viously suggested earlier ‘Little Ice Age’ advances are demonstrated to have resulted from an underestimation of the growth rates of the Rhizocarpon subgenus. Synchroneity of ‘Little Ice Age’ maxima in southern Norway and at Svartisen and Okstindan suggest that a north–south migration of latitudinal depressional tracks can be excluded as the main forcing factor. As an alternative, an increased SE–NW trend of moist air‘ ow in winter parallel to the coast of Norway is suggested as the main forcing factor with recent glacier dynamics in response to recent climatic ‘ uctuations supporting this hypothesis.
Assessing the impact of Icelandic volcanism on vegetation systems in the north of Ireland in the fifth and sixth millennia BC
Authors: Hall Valerie A.
Published: February 2003

The ‘Lairg tephras’ comprise two of the three most abundantly represented tephra layers in Irish Holocene peat sequences. The impact of these tephras on the vegetation at two lowland raised bogs in Northern Ireland is investigated through high-resolution pollen percentage and concentration studies. The palynological response of mire and dryland taxa to the tephra falls is assessed. No significant palynological response to either tephra event is recorded.
Reconstructing Holocene water tables in New Zealand using testate amoebae: differential preservation of tests and implications for the use of transfer functions
Authors: Wilmshurst Janet M. , Wiser Susan K. , Charman Dan J.
Published: February 2003

Testate amoebae analysis is used to provide the first quantitative reconstruction of Holocene surface wetness changes from a Southern Hemisphere ombrogenous bog. Water-table depth and surface moisture are the dominant environmental factors influencing testate amoebae species composition in a modern training set of 62 surface samples from 19 bogs in New Zealand. A transfer function based on partial least squares (PLS) performed well in cross-validation of modern samples, but produced unrealistic predictions of water-table depth and moisture for fossil samples. This resulted from poor overlap of species composition between modern and fossil samples. Peat humification data is used to examine decay-related species diversity trends and ordination is used to explore the differences between modern and fossil assemblages. Poor overlap can be explained by differential preservation in the fossil assemblages of those taxa with more robust tests. This enhances their abundance and reduces the overall diversity of the fossil assemblages. Human activities over the last 150 years have also influenced the surface environments and hydrology of the sampled bogs. In this situation, weighted average (WA) and tolerance downweighted weighted average (WA-Tol) models were more robust than PLS, and were applied, along with semi-quantitative scoring, to reconstruct more realistic Holocene surface wetness changes. Selection of the best model for reconstruction of surface wetness changes should be based on the characteristics of the fossil data rather than the predictive power of the model in cross-validation of the modern data alone.
Holocene palaeoenvironmental evolution in the São Paulo State (Brazil), based on anthracology and soil δ13C analysis
Authors: Scheel-Ybert R. , Gouveia S. E. M. , Pessenda L. C. R. , Aravena R. , Coutinho L. M. , Boulet R.
Published: February 2003

This paper presents a reconstruction of the Holocene palaeoenvironmental evolution in the central São Paulo State (Brazil) based on anthracological analyses, in association with soil isotopic composition (δ13C) and radiocarbon dating from four sites. Anatomical identification of charcoal particles allows the reconstitution of past plant associations, and consequently of the vegetation and climate history. Rather precise interpretations may be achieved when associating anthracology and soil δ13C analysis. In the early Holocene, climate was dry and an open cerrado vegetation (savanna) covered most of this area. A cerradão (forested savanna) or a semideciduous forest existed in the more humid localities. After 3500/3000 14C yr BP the climate was more humid, similar to the present, leading to the establishment of forested vegetation in all the studied sites. Com parison of these results with various palaeoenvironmental studies carried out in the Brazilian phytogeographical zone of cerrado and semideciduous forest suggests that at least its greater part presented a similar trend in the climatic evolution during the Holocene. This phytogeographical zone presented a dry climate during the early Holocene, then a more humid climate during the late Holocene. Climatic conditions similar to the present appeared from 5000 to 1000 yr BP, depending on the site.
Lateglacial and Holocene vegetation belts in the Pirin Mountains (southwestern Bulgaria)
Authors: Stefanova Ivanka , Ammann Brigitta
Published: February 2003

Pollen stratigraphy of a core 270 cm long from Lake Dalgoto at 2310 m in the Northern Pirin Mountains, southern Bulgaria, was treated by optimal partitioning and compared to a broken-stick model to reveal statistically significant pollen zones. The vegetational reconstructions presented here are based on pollen percentages and pollen influx, on comparisons of modern and fossil pollen spectra, and on macrofossil dates from other sites in the mountains. During the Younger Dryas (11000–10200 14C yr BP), an open xerophytic herb vegetation with Artemisia and Chenopodiaceae was widely developed around the lake. Deciduous trees growing at lower elevations contributed to the pollen rain deposited at the higher-elevation sampling sites. Specifically, from 10200 to 8500 yr BP, Quercus, Ulmus, Tilia and Betula expanded rapidly at low and intermediate elevations, and between 8500 and 6500 yr BP they extended to higher elevations close to the upper forest limit, which was formed by Betula pendula at about 1900 m. Coniferous species were limited in the region at this time. After 6500 yr BP, the expansion of conifers (Pinus peuce, P. sylvestris, P. mugo, Abies alba) at high elevations forced the deciduous trees downward. Between 6500 and 3000 yr BP, the forest limit at 2200 m was formed by P. peuce, and A. alba had its maximum vertical range up to 1900 m. Later the abundance and vertical range of P. peuce and A. alba were reduced. After 3000 yr BP, Picea expanded.
Palynological evidence for vegetational history in semi-arid areas of the western Mediterranean (Almería, Spain)
Authors: Pantaléon-Cano José , Yll Errikarta-Imanol , Pérez-Obiol Ramon , Roure Joan Maria
Published: February 2003

Three sedimentary sequences from the southeastern littoral of the Iberian Peninsula have been palynologically studied. The results obtained show that during the Holocene no significant forest cover existed in the studied area, so that the different phases identified mainly show an alternation of shrub formations and steppe communities probably determined by limitations that are fundamentally bioclimatic. Highest values of arboreal pollen at the bottom of the San Rafael sequence would correspond to an older period, when the area appears to be dominated by shrub communities with a high proportion of wild olive, whereas at the beginnings of the Holocene it is dominated by steppe formations. Between 7000 and 4500 yr BP the Holocene optimum is recorded, with a significant degree of vegetational cover. This period ends abruptly with a radical transform ation of the landscape that reflects the establishment of the steppe conditions that persist today, which lead to the marginalization of the maquis and the impact of intense erosion processes on a gradually deforested countryside.