Inaccurate risk perceptions contribute to treatment gaps in secondary prevention of cardiovascular disease.

BACKGROUND: All patients with cardiovascular disease (CVD) are at high risk of recurrent events. Despite strong evidence, large treatment gaps exist in CVD secondary prevention. We hypothesise that patients' self-perception and general practitioner's (GP) assessment of future cardiovascular (CV) risk may influence secondary prevention behaviours. AIM: To examine in patients with known CVD the perceived risk of future CV events and its relationship with use of secondary prevention medications and risk factor control. METHODS: We examined patient and practitioner's perceived risk and its relationship with the uptake of secondary prevention recommendations in adults with CVD participating in the Australian Hypertension and Absolute Risk Study. RESULTS: Among the 1453 participants, only 11% reported having a high absolute risk and 29% reported high relative risk of recurrent events. The GP categorised only 30% as having a 5-year risk ≥15%. After adjusting for covariates, hospitalisation within the preceding 12 months was the only significant predictor of patients' accurate risk perception. Conventional CV risk factors were predictive of the GP's risk estimates. Patients who accurately understood their risk reported higher smoking cessation rates (7 vs 3%, P = 0.003) and greater use of antiplatelet, blood pressure lowering therapy and statins (P ≤ 0.01). However, there was no relationship between GP's risk perception and secondary prevention treatments. CONCLUSION: Both patients and GP have optimistic bias and underestimate the risk of future CV events. Patients' accurate self-perception, but not GP risk perception, was associated with improved secondary preventative behaviours. This suggests that helping patients to understand their risk may influence their motivation towards secondary prevention. Providing support to GP or programmes to help patients better understand their risks could have potential benefit on secondary prevention behaviours.

Higher mortality in patients with right hemispheric intracerebral haemorrhage: INTERACT1 and 2.

BACKGROUND AND PURPOSE: Controversy exists over the prognostic significance of the affected hemisphere in stroke. We aimed to determine the relationship between laterality of acute intracerebral haemorrhage (ICH) and poor clinical outcomes. METHODS: A subsidiary analysis of the INTERACT Pilot and INTERACT2 studies--randomised controlled trials of patients with spontaneous acute ICH with elevated systolic blood pressure (BP), randomly assigned to intensive (target systolic BP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Outcomes were the combined and separate end points of death and major disability (modified Rankin scale (mRS) scores of 3-6, 6 and 3-5, respectively) at 90 days. RESULTS: A total of 2708 patients had supratentorial/hemispheric ICH and information on mRS at 90 days. Patients with right hemispheric ICH (1327, 49%) had a higher risk of death at 90 days compared to those with left hemispheric ICH after adjustment for potential confounding variables (OR, 1.77 (95% CI 1.33 to 2.37)). There were no differences between patients with right and left hemispheric ICH regarding the combined end point of death or major disability or major disability in the multivariable-adjusted models (1.07 (0.89 to 1.29) and 0.85 (0.72 to 1.01), respectively). CONCLUSIONS: Right hemispheric lesion was associated with increased risk of death in patients with acute ICH. The laterality of the ICH does not appear to affect the level of disability in survivors. TRIAL REGISTRATION NUMBER: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00226096 and NCT00716079.

A randomised controlled trial of a consumer-focused e-health strategy for cardiovascular risk management in primary care: the Consumer Navigation of Electronic Cardiovascular Tools (CONNECT) study protocol.

INTRODUCTION: Fewer than half of all people at highest risk of a cardiovascular event are receiving and adhering to best practice recommendations to lower their risk. In this project, we examine the role of an e-health-assisted consumer-focused strategy as a means of overcoming these gaps between evidence and practice. Consumer Navigation of Electronic Cardiovascular Tools (CONNECT) aims to test whether a consumer-focused e-health strategy provided to Aboriginal and Torres Strait Islander and non-indigenous adults, recruited through primary care, at moderate-to-high risk of a cardiovascular disease event will improve risk factor control when compared with usual care. METHODS AND ANALYSIS: Randomised controlled trial of 2000 participants with an average of 18 months of follow-up to evaluate the effectiveness of an integrated consumer-directed e-health portal on cardiovascular risk compared with usual care in patients with cardiovascular disease or who are at moderate-to-high cardiovascular disease risk. The trial will be augmented by formal economic and process evaluations to assess acceptability, equity and cost-effectiveness of the intervention. The intervention group will participate in a consumer-directed e-health strategy for cardiovascular risk management. The programme is electronically integrated with the primary care provider's software and will include interactive smart phone and Internet platforms. The primary outcome is a composite endpoint of the proportion of people meeting the Australian guideline-recommended blood pressure (BP) and cholesterol targets. Secondary outcomes include change in mean BP and fasting cholesterol levels, proportion meeting BP and cholesterol targets separately, self-efficacy, health literacy, self-reported point prevalence abstinence in smoking, body mass index and waist circumference, self-reported physical activity and self-reported medication adherence. ETHICS AND DISSEMINATION: Primary ethics approval was received from the University of Sydney Human Research Ethics Committee and the Aboriginal Health and Medical Research Council. Results will be disseminated via the usual scientific forums including peer-reviewed publications and presentations at international conferences CLINICAL TRIALS REGISTRATION NUMBER: ACTRN12613000715774.

The second (main) phase of an open, randomised, multicentre study to investigate the effectiveness of an intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT2).

RATIONALE: The INTERACT pilot study demonstrated the feasibility of the protocol, safety of early intensive blood pressure lowering and effects on haematoma expansion within 6 h of onset of intracerebral haemorrhage. This article describes the design of the second, main phase, INTERACT2. AIMS: To compare the effects of a management strategy of early intensive blood pressure lowering with a more conservative guideline-based blood pressure management policy in patients with acute intracerebral hemorrhage. DESIGN: INTERACT2 is a prospective, randomized, open label, assessor-blinded end-point (PROBE). Patients with a systolic blood pressure greater than 150 mmHg and no definite indication for or contraindication to blood pressure-lowering treatment are centrally randomised to either of two treatment groups within 6 h onset of intracerebral haemorrhage. Those allocated to intensive blood pressure lowering will receive primarily intravenous, hypotensive agents to achieve a systolic blood pressure target of <140 mmHg within 1 h of randomisation and to maintain this level for up to 7 days in hospital. The control group will receive blood pressure-lowering treatment to a target systolic blood pressure of <180 mmHg. Both groups are to receive similar acute stroke unit care, therapy and active management. Oral antihypertensive therapy is recommended in patients before hospital discharge with a long-term systolic blood pressure goal of 140 mmHg according to secondary stroke prevention guidelines. A projected 2800 subjects are to be enrolled from approximately 140 centres worldwide to provide 90% power (alpha 0.05) to detect a 14% difference in the risk of death and dependency between the groups, which equates to one or more cases of a poor outcome prevented in every 15 patients treated. STUDY OUTCOMES: The primary outcome is the combined end-point of death and dependency according to the modified Rankin Scale at 90 days. The secondary outcomes are the separate components of the primary end-point in patients treated <4 hours of ICH onset, grades of physical function on the modified Rankin Scale, health-related quality of life on the EuroQoL, recurrent stroke and other vascular events, days of hospitalisation, requirement for permanent residential care and unexpected serious adverse events.

Significance of perihematomal edema in acute intracerebral hemorrhage: the INTERACT trial.

BACKGROUND: Uncertainty surrounds the effects of cerebral edema on outcomes in intracerebral hemorrhage (ICH). METHODS: We used data from the INTERACT trial to determine the predictors and prognostic significance of "perihematomal" edema over 72 hours after ICH. INTERACT included 404 patients with CT-confirmed ICH and elevated systolic blood pressure (BP) (150-220 mm Hg) who had the capacity to commence BP lowering treatment within 6 hours of ICH. Baseline and repeat CT (24 and 72 hours) were performed using standardized techniques, with digital images analyzed centrally. Predictors of growth in edema were determined using generalized estimating equations, and its effects on clinical outcomes were estimated using a logistic regression model. RESULTS: Overall, 270 patients had 3 sequential CT scans available for analyses. At baseline, there was a highly significant correlation between hematoma and perihematomal edema volumes (r(2) = 0.45). Lower systolic BP and baseline hematoma volume were independently associated with absolute increase in perihematomal edema volume. History of hypertension, baseline hematoma volume, and earlier time from onset to CT were independently associated with relative increase in edema volume. Both absolute and relative increases in perihematomal edema growth were significantly associated with death or dependency at 90 days after adjustment for age, gender, and randomized treatment, but not when additionally adjusted for baseline hematoma volume. CONCLUSIONS: The degree of, and growth in, perihematomal edema are strongly related to the size of the underlying hematoma of acute intracerebral hemorrhage, and do not appear to have a major independent effect in determining the outcome from this condition.

Identification and evaluation of a possible signal of exacerbation of colitis during rofecoxib treatment, using Prescription-Event Monitoring data.

BACKGROUND: Identifying previously unrecognized adverse drug reactions (signals) is an important part of post-marketing surveillance. Automated signal generation now forms part of routine surveillance of spontaneous adverse drug reactions reported to the UK Yellow Card system. The Drug Safety Research Unit (DRSU) provides an additional post-marketing drug surveillance scheme in the UK, using the non-interventional observational cohort technique of Prescription-Event Monitoring (PEM), and systematically collects data on patients who were prescribed selected newly licensed drugs in primary care clinical practice. The introduction of a new computer system in January 2000 enabled the development of an automated signal generation system to compliment the process of identification of possible safety signals in drug data collected using PEM. AIMS: To use incidence rate ratios (IRRs) as a form of signal generation in the DSRU database, with particular interest in rofecoxib, plus further evaluation of any signal(s) of interest by requesting additional information from the general practioner (GP) of each relevant case. METHODS: Crude IRRs were calculated for each event term of interest by comparing the incidence rate for each lower term event reported in rofecoxib users with the comparable incidence rate for the whole PEM database (77 drugs of various therapeutic classes) from the total person-exposure time up to 180 days after starting the drug. To investigate a possible class effect, IRRs were also calculated using a second comparator cohort including only those PEM study drugs within the same therapeutic class (non-steroidal anti-inflammatory drugs, NSAIDs) and used for similar indications. Cases arising out of potential signals were followed up for additional information. RESULTS: A potential signal of 'colitis' was identified when rofecoxib was compared with the rest of the database, IRR 5.8 (95% CI 2.7,11.3; z statistic 5.6), and when the comparator group was changed to include only the other four NSAIDs, IRR 4.3 (95% CI 1.4,14.5; z statistic 2.8). Other possible signals, compared with the rest of the database, included events deemed to be related to the underlying condition, labelled adverse events and events describing effectiveness of treatment. Further evaluation of this signal revealed that there were 11 reports of colitis (two reports for one patient) that occurred while taking rofecoxib and within 180 days of exposure. A causality assessment for these 10 patients did not confirm an association with newly developing colitis, but showed that the events were 'possible' exacerbations of pre-existing colitis during treatment with rofecoxib. CONCLUSIONS: The use of IRRs for signal generation using PEM data is worthwhile and enables time to be taken into account. Previously unrecognized adverse events require further evaluation to confirm that a possible safety signal exists. In this study, the number of patients reported to have colitis was small but compared with other drugs on the database, the incidence rate was relatively high. Follow-up revealed a possible relationship between exacerbation of pre-existing colitis and treatment with rofecoxib. Hypotheses arising from signal generation require evaluation and cannot be taken as a conclusive evidence for clinical differences in the safety profiles of drugs.

The new materials processing beamline at the SRS Daresbury, MPW6.2.

A new beamline (MPW6.2) has been designed and built for the study of materials during processing where three synchrotron techniques, SAXS, WAXS and XAS, are available simultaneously. It has been demonstrated that Rietveld refinable data can be collected from silicon SRM 640b over a 60 degrees range in a time scale of 1 s. The data have been refined to a chi(2) of 2.4, the peaks fitting best to a Pearson VII function or with fundamental parameters. The peak halfwidths have been found to be approximately constant at 0.06 degrees over a 120 degrees angular range indicating that the instrumental resolution function has matched its design specification. A quantitative comparison of data sets collected on the same isotactic polypropylene system on MPW6.2 and DUBBLE at the ESRF shows a 17% improvement in angular resolution and a 1.8 improvement in peak-to-background ratio with the RAPID2 system; the ESRF data vary more smoothly across detector channels. The time-dependent wide-angle XRD was tested by comparing a hydration reaction of gypsum-bassanite-anhydrite with energy-dispersive data collected on the same system on the same time scale. Three sample data sets from the reaction were selected for analysis and gave an average chi(2) of 3.8. The Rietveld-refined lattice parameters are a good match with published values and the corresponding errors show a mean value of 3.3 x 10(-4). The data have also been analysed by the Pawley decomposition phase-modelling technique demonstrating the ability of the station to quickly and accurately identify new phases. The combined SAXS/WAXS capability of the station was tested with the crystallization and spinodal decomposition of a very dilute polymer system. Our measurements show that the crystallization of a high-density co-polymer (E76B38) as low as 0.5% by weight can be observed in solution in hexane. The WAXS and SAXS data sets were collected on the same time scale. The SAXS detector was calibrated using a collagen sample that gave 30 orders of diffraction in 1 s of data collection. The combined XRD and XAS measurement capability of the station was tested by observing the collapse and re-crystallization of zinc-exchanged zeolite A (zeolite Zn/Na-A). Previous studies of this material on station 9.3 at the SRS were compared with those from the new station. A time improvement of 38 was observed with better quality counting statistics. The improved angular resolution from the WAXS detector enabled new peaks to be identified.

Comparison of the incidence rates of thromboembolic events reported for patients prescribed rofecoxib and meloxicam in general practice in England using prescription-event monitoring (PEM) data.

BACKGROUND: Rofecoxib and meloxicam are classified as cyclo-oxygenase (COX)-2 selective inhibitors. The Drug Safety Research Unit (DSRU) monitored the post-marketing safety of these drugs in England using the non-interventional observational cohort technique of prescription-event monitoring (PEM). OBJECTIVES: To compare the incidence rates of selected thromboembolic (TE)(cardiovascular, cerebrovascular and peripheral venous thrombotic) events reported for patients prescribed rofecoxib and meloxicam in general practice. METHODS: Patients were identified from dispensed prescriptions written by general practitioners (GPs) for meloxicam (December 1996 to March 1997) and rofecoxib (July to November 1999). Simple questionnaires requesting details of events recorded during/after treatment, indication and potential risk factors (including age, sex and NSAIDs prescribed within 3 months of treatment) were posted to prescribing GPs approximately 9 months after the first prescription for each patient. Incidence rates of the first event within each TE group were calculated; crude and age- and sex-adjusted rate ratios (RR) obtained using regression modelling. RESULTS: During the 9 months after starting treatment, 21 (0.14%) and 19 (0.10%) patients were reported to have cardiovascular TE events, and 74 (0.48%) and 52 (0.27%) cerebrovascular TE events, and 6 (0.05%) and 20 (0.10%) were reported to have peripheral venous thrombotic events for rofecoxib and meloxicam, respectively. Regarding time to first event, there was a persistent divergence between the two drugs from the start of treatment for both the cerebrovascular TE event group (log rank test P = 0.0063) and the peripheral venous thrombotic event group (log rank test P = 0.0264). Indication and use of a NSAID within 3 months prior to starting treatment had no statistically significant effect on the relative risk estimates of the event groups and was excluded from subsequent analyses. Adjusting for the two identified risk factors of age (age2) and sex, for rofecoxib the adjusted cerebrovascular TE event group rate was higher than for meloxicam [RR 1.68 (95% CI 1.15, 2.46)]; lower than meloxicam for the peripheral venous thrombotic event group [RR 0.29 (95% CI 0.11, 0.78)], and not different for the cardiovascular TE event group [RR 1.38 (95% CI 0.71, 2.67)]. CONCLUSIONS: This study reports a relative increase in the rate of cerebrovascular TE events and a relative reduction in peripheral venous thrombotic events in users of rofecoxib compared with meloxicam. There was no difference in the rate of cardiovascular thromboembolic events. The incidence of these three groups of events reported in each of these two drug cohorts was low (less than 0.5%), therefore the relevance of our findings needs to be taken into consideration with other clinical and pharmacoepidemiological studies.

Comparison of the incidence rates of selected gastrointestinal events reported for patients prescribed rofecoxib and meloxicam in general practice in England using prescription-event monitoring data.

BACKGROUND: and objectives. Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with gastrointestinal (GI) toxicity. Rofecoxib and meloxicam are classified as cyclooxygenase (COX)-2 selective inhibitors. The Drug Safety Research Unit monitored the safety of these drugs immediately after their launch in England using the non-interventional observational cohort technique of prescription-event monitoring (PEM). Our objective was to investigate whether there is a clinically relevant difference in the incidence of reported symptomatic (acid/peptic) and complicated upper GI conditions (perforations/bleeding) between rofecoxib and meloxicam during use in general practice. METHODS: Patients were identified from dispensed prescriptions written by general practitioners (GPs) for meloxicam (between December 1996 and March 1997) and rofecoxib (between July and November 1999). Simple questionnaires requesting details of events occurring during/after treatment and potential risk factors (including age, sex, history of upper GI problems, and NSAIDS prescribed within 3 months of treatment) were posted to prescribing GPs approximately 9 months after the first prescription for each patient. Incidence rates of the first event were calculated, and crude and adjusted rate ratios were obtained using regression modelling. RESULTS: For rofecoxib and meloxicam respectively, 1127 (7.4%) and 1376 (7.2%) patients had symptomatic (acid/peptic) upper GI events, whereas 57 (0.4%) and 67 (0.4%) had complicated upper GI conditions (perforations/bleeding). A past medical history of upper GI problems was an important risk factor only for symptomatic (acid/peptic) upper GI events for both drugs, despite a two-fold difference in the proportion reporting previous GI problems (48.4 and 25.1% for rofecoxib and meloxicam respectively). The adjusted rate ratio of symptomatic (acid/peptic) upper GI events or complicated upper GI conditions (perforations/bleeding) for rofecoxib compared with meloxicam was 0.71 (95% confidence interval 0.65, 0.79) and 0.91 (95% confidence interval 0.59, 1.42) respectively. CONCLUSIONS: This study reports a relative reduction (29%) in the incidence rate of symptomatic (acid/peptic) GI events, and no difference in the incidence rate of complicated upper GI conditions (perforations/bleeding) for rofecoxib compared with meloxicam.

Prescription-event monitoring and reporting of adverse drug reactions.

Newly marketed drugs in the UK are marked with a black triangle, indicating that doctors should report all adverse drug reactions associated with them to the Committee on Safety of Medicines (CSM). However, under-reporting of adverse reactions is frequent. Our aim was to establish what types of adverse reactions are under-reported to the CSM by family doctors who work in England. We used prescription-event monitoring data obtained for 15 newly marketed drugs. Only 9% (376) of 4211 events found on prescription-event monitoring were reported to the CSM. However, 53% (27) of 51 events classified as serious adverse drug reactions were reported. Overall, serious events were five times more likely to be reported to the CSM than non-serious events. Our results should not be extrapolated to calculate incidence rates of adverse drug reactions in the community from spontaneous reports.

Comparative study of mortality rates and cardiac dysrhythmias in post-marketing surveillance studies of sertindole and two other atypical antipsychotic drugs, risperidone and olanzapine.

Sertindole (Serdolect), an atypical antipsychotic, was voluntarily suspended in the European Union in 1998 following regulatory concerns over reports of serious cardiac dysrhythmias and sudden unexpected deaths. The reported causes of death, their frequency, prolongation of the rate corrected QT interval (QTc) and cardiac dysrhythmias in patients prescribed sertindole were compared with those for patients treated with two other atypical antipsychotics. All patients in England, prescribed atypical antipsychotics by general practitioners during each drug's immediate post-marketing period, were identified using an observational cohort technique, prescription-event monitoring. Mortality rates in the sertindole cohort were compared with those in a comparator cohort using standardized mortality ratios and incidence rate ratios. Cardiovascular events were reviewed and followed up to identify cases of prolongation of QTc interval. There was no statistically significant difference in mortality rates between sertindole and the comparator cohort, although confidence intervals (CI) were wide due to small numbers in the sertindole cohort. A much smaller number of patients were prescribed sertindole than the other antipsychotics. Six cases of prolongation of QTc interval were identified in 462 patients (1.3%, 95% CI 0.5-2.8) treated with sertindole and one with unspecified electrocardiogram changes in the comparator cohort of 16,542 patients. This study contributes to the understanding of the occurrence of prolongation of QTc interval during clinical use of sertindole, the incidence of which was similar to that in clinical trials. Although no statistically significant difference was shown in mortality rates between sertindole and comparator cohort, the sertindole cohort was too small to rule out an association between the use of this drug and cardiovascular deaths.

A comparison of the molecular species compositions of mammalian lung surfactant phospholipids.

While dipalmitoyl phosphatidylcholine (PC16:0/16:0) is essential for pulmonary surfactant function, roles for other individual molecular species of surfactant phospholipids have not been established. If any phospholipid species other than PC16:0/16:0 is important for surfactant function, then it may be conserved across animal species. Consequently, we have quantified, by electrospray ionisation mass spectrometry, molecular species compositions of phosphatidylcholine (PC), phosphatidylglycerol (PG) and phosphatidylinositol (PI) in surfactants from human, rabbit, rat and guinea pig lungs. While PC compositions displayed only relatively minor variations across the animal species studied, there were wide variations of PG and PI concentrations and compositions. Human surfactant PG and PI were enriched in the same three monounsaturated species (PG16:0/18:1, PG18:1/18:1 and PG18:0/18:1) with minimal amounts of PG16:0/16:0 or polyunsaturated species, while all animal surfactant PG contained increased concentrations of PG16:0/16:0 and PG16:0/18:2. Animal surfactant PIs were essentially monounsaturated except for a high content of PI18:0/20:4 (29%) in the rat. As these four surfactants all maintain appropriate lung function of the respective animal species, then all their varied compositions of acidic phospholipids must be adequate at promoting the processes of adsorption, film refinement, respreading and collapse characteristic of surfactant. We conclude that this effectively monounsaturated composition of anionic phospholipid molecular species is a common characteristic of mammalian surfactants.

Bacterial cell membrane hydrolysis by secreted phospholipases A(2): a major physiological role of human group IIa sPLA(2) involving both bacterial cell wall penetration and interfacial catalysis.

The ability of human group IIa secreted phospholipase A(2) (human sPLA(2)) to hydrolyse the phospholipid membrane of whole cell suspensions of Gram-positive bacteria is demonstrated in real time using a continuous fluorescence displacement assay. Micrococcus luteus is used as a model system and demonstrates an almost absolute specificity for this human enzyme compared with porcine pancreatic and Naja naja venom sPLA(2)s. This specificity is due to selective penetration of the highly cationic human sPLA(2)50%) phospholipid hydrolysis was observed and this was confirmed by electrospray mass spectrometry that allowed the identification of several molecular species of phosphatidylglycerol as the targets for hydrolysis. However, the bactericidal activity of the human enzyme under these assay conditions was low, highlighting the capacity of the organism to survive a major phospholipid insult. In addition to pure enzyme, the human sPLA(2) activity in tears was demonstrated using M. luteus as substrate. In comparison to M. luteus, cell suspensions of Staphylococcus aureus were highly resistant to hydrolysis by human sPLA(2) as well as to the pancreatic and venom enzymes. Treatment of this organism with the specific cell wall protease lysostaphin resulted in a dramatic enhancement in cell membrane phospholipid hydrolysis by all three sPLA(2)s. Overall, the results highlight the potential of the human sPLA(2) as a selective antimicrobial agent against Gram-positive bacteria in vivo because this enzyme is essentially inactive against mammalian plasma membranes. However, the enzyme will be most effective in combination with other antimicrobial agents that enhance the permeability of the bacterial cell wall and where potentiation of the effectiveness of other antibiotics would be expected.

Phospholipid molecular species of bronchoalveolar lavage fluid after local allergen challenge in asthma.

Electrospray ionization mass spectrometry was used to quantify phosphatidylcholine (PC) and phosphatidylglycerol (PG) molecular species in bronchoalveolar lavage fluid (BALF) from control and mild asthmatic subjects after local allergen challenge. BALF was obtained from 5 control and 13 asthmatic subjects before and 24 h after segmental allergen and saline challenge. There were no differences in the ratio of total PC to total PG or in the molecular species composition of PC or PG between the asthmatic and control groups under basal conditions. Allergen challenge in asthmatic but not in control volunteers caused a significant increase in the PC-to-PG ratio because of increased concentrations of PC species containing linoleic acid (16:0/18:2 PC, 18:0/18:2 PC, and 18:1/18:2 PC). These molecular species were characteristic of plasma PC analyzed from the same subjects, strongly suggesting that the altered PC composition in BALF in asthmatic subjects after allergen challenge was due to infiltration of plasma lipoprotein, not to catabolism of surfactant phospholipid. Interactions between surfactant and lipoprotein infiltrate may contribute to surfactant dysfunction and potentiate disease severity in asthma.

Time-Resolved Simultaneous SAXS/WAXS of the Drawing of Polyethylene at the Daresbury SRS.

A system has been developed which represents a significant advance in the quality and extent of small- and wide-angle X-ray scattering data (SAXS and WAXS) that can be recorded simultaneously with strain data during the drawing and annealing of polymer materials. WAXS data are recorded using a Photonic Science charge-coupled-device area detector and SAXS data using a gas-filled multiwire area detector. Strain data, for the region of the specimen from which the SAXS/WAXS data are collected, are calculated from an accurately synchronized continuously recorded video image of the specimen. The system allows X-ray and video image data to be collected as a series of frames with essentially no ;dead-time' between frames. The data are fully two-dimensional and can be collected for a wide range of d spacings. The use of this system to investigate the stress-induced orientation and phase changes during the drawing of a range of grades of commercially available polyethylene is described.