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The persistent use of MLCs through VMAT and IMRT is causing additional wear and tear on these mechanical parts, leading to an increase in MLC interlocks, breakdowns and failures. This study investigates the effect of an MLC clean and service procedure on MLC performance and positional accuracy demonstrated through in-house service logbook reports, Varian MLC backlash test results, daily MLC position QC results and Varian TrueBeam trajectory log file data. A service and clean of each individual MLC leaf was carried out on 3 standard MLC and 2 high definition MLC (HDMLC) Varian TrueBeam linacs. In-house service logbook reports, Varian backlash test results, daily MLC picket fence QC results and beam hold data from patient delivery trajectory log files were analysed for up to 6 months pre and 2 years post the MLC service/clean to assess the impact on unplanned MLC maintenance work and MLC performance. The median (range) of hardware faults reduced from 12 (1–17) pre clean to 0 (0–1) and 4 (1–11) at 12 and 24 months respectively for all linacs with the exception of a HDMLC linac where faults increased from 4 pre-clean to 13 and 20 again at 12 and 24 months respectively. The reduction in faults in the alternative 4 linacs was consistent with the reduction in the number of MLCs reaching the 0.3 mm and the 0.4 mm backlash recommendations in the first 12 and 24 months following the service/clean. The increase in faults in the HDMLC linac was also consistent with the increase in MLCs reaching the 0.3 mm backlash recommendation in the first 12 and 24 months. The median (range) of MLCs reaching a daily picket fence QC position tolerance of 0.25 mm reduced from 14 (1–40) pre clean to 0 (0) at both 12 and 24 months post-clean. This demonstrates the improvement in MLC performance caused by the MLC service/clean but also reveals factors other than MLC position accuracy influence hardware faults. Additionally, the number of beam hold-offs determined from patient delivery trajectory log files were found to have no correlation with the MLC service/clean. The MLC service/clean improves MLC performance and MLC position accuracy, reducing reactive repair work for engineering and physics staff. The results were maintained for 1 year post the MLC service/clean, with a trend back towards pre-clean levels in the subsequent 12–24 months. This suggests this preventative maintenance work could be performed at a frequency of > 2 years. This period of reduced faults and improved performance is significant given the 10 year expected lifespan of a linac.

Paid community health workers screened for hypertension in the community, referred cases to the clinic for diagnosis and initial treatment by a physician, and then monitored patients who had well-controlled blood pressure including dispensing maintenance medications prescribed by the physician. Blood pressure control was successful in the majority of such patients., Poor blood pressure control results in tremendous morbidity and mortality in India where the leading cause of death among adults is from coronary heart disease. Despite having little formal education, community health workers (CHWs) are integral to successful public health interventions in India and other low- and middle-income countries that have a shortage of trained health professionals. Training CHWs to screen for and manage chronic hypertension, with support from trained clinicians, offers an excellent opportunity for effecting systemwide change in hypertension-related burden of disease. In this article, we describe the development of a program that trained CHWs between 2014 and 2015 in the tribal region of the Sittilingi Valley in southern India, to identify hypertensive patients in the community, refer them for diagnosis and initial management in a physician-staffed clinic, and provide them with sustained lifestyle interventions and medications over multiple visits. We found that after 2 years, the CHWs had screened 7,176 people over age 18 for hypertension, 1,184 (16.5%) of whom were screened as hypertensive. Of the 1,184 patients screened as hypertensive, 898 (75.8%) had achieved blood pressure control, defined as a systolic blood pressure less than 140 and a diastolic blood pressure less than 90 sustained over 3 consecutive visits. While all of the 24 trained CHWs reported confidence in checking blood pressure with a manual blood pressure cuff, 4 of the 24 CHWs reported occasional difficulty documenting blood pressure values because they were unable to write numbers properly. They compensated by asking other CHWs or members of their community to help with documentation. Our experience and findings suggest that a CHW blood pressure screening system linked to a central clinic can be a promising avenue for improving hypertension control rates in low- and middle-income countries.

Background Patients treated with radiotherapy for head and neck (H&N) cancer often experience anatomical changes. The potential compromises to Planning Target Volume (PTV) coverage or Organ at Risk (OAR) sparing has prompted the use of adaptive radiotherapy (ART) for these patients. However, implementation of ART is time and resource intensive. This study seeks to define a clinical trigger for H&N re-plans based on spinal cord safety using kV Cone-Beam Computed Tomography (CBCT) verification imaging, in order to best balance clinical benefit with additional workload. Methods Thirty-one H&N patients treated with Volumetric Modulated Arc Therapy (VMAT) who had a rescan CT (rCT) during treatment were included in this study. Contour volume changes between the planning CT (pCT) and rCT were determined. The original treatment plan was calculated on the pCT, CBCT prior to the rCT, pCT deformed to the anatomy of the CBCT (dCT), and rCT (considered the gold standard). The dose to 0.1 cc (D0.1cc) spinal cord was evaluated from the Dose Volume Histograms (DVHs). Results The median dose increase to D0.1cc between the pCT and rCT was 0.7 Gy (inter-quartile range 0.2–1.9 Gy, p Conclusions An adaptive re-plan can be triggered using spinal cord doses calculated on the CBCT/dCT. Implementing this trigger can reduce patient appointments and radiation dose by eliminating up to 90% of additional un-necessary CT scans, reducing the workload for radiographers, physicists, dosimetrists, and clinicians.

OBJECTIVE:: To assess the accuracy and efficiency of four different techniques, thus determining the optimum method for recalculating dose on cone beam CT (CBCT) images acquired during radiotherapy treatments.METHODS:: Four established techniques were investigated and their accuracy assessed via dose calculations: (1) applying a standard planning CT (pCT) calibration curve, (2) applying a CBCT site-specific calibration curve, (3) performing a density override and (4) using deformable registration. Each technique was applied to 15 patients receiving volumetric modulated arc therapy to one of three treatment sites, head and neck, lung and prostate. Differences between pCT and CBCT recalculations were determined with dose volume histogram metrics and 2.0%/0.1 mm gamma analysis using the pCT dose distribution as a reference.RESULTS:: Dose volume histogram analysis indicated that all techniques yielded differences from expected results between 0.0 and 2.3% for both target volumes and organs at risk. With volumetric gamma analysis, the dose recalculation on deformed images yielded the highest pass-rates. The median pass-rate ranges at 50% threshold were 99.6-99.9%, 94.6-96.0%, and 94.8.0-96.0% for prostate, head and neck and lung patients, respectively.CONCLUSION:: Deformable registration, HU override and site-specific calibration curves were all identified as dosimetrically accurate and efficient methods for dose calculation on CBCT images.ADVANCES IN KNOWLEDGE:: With the increasing adoption of CBCT, this study provides clinical radiotherapy departments with invaluable information regarding the comparison of dose reconstruction methods, enabling a more accurate representation of a patient's treatment. It can also integrate studies in which CBCT is used in image-guided radiation therapy and for adaptive radiotherapy planning processes.

The objective of this study is to identify promising strategies for improving drinking-water access and consumption among children aged 0 to 5 years. MEDLINE/PubMed, Embase, ERIC, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched in this review. Studies included peer-reviewed, full-text studies from high-income countries, published in English between January 1, 2000, and January 12, 2018, that evaluated interventions to increase water access or consumption in children aged 0 to 5 years. Twenty-five studies met inclusion criteria; 19 used an effective intervention strategy to increase water access or water consumption. Three studies addressed both water access and consumption. Frequently used strategies included policy and practice changes, increasing water access and convenience, and education, training, or social support for caregivers. Studies were of fair methodological quality (average score: 18.8 of 26) for randomized studies and of moderate quality (5.1 of 9) for non-randomized studies. To date, few high-quality studies with objectively measured outcomes have clearly demonstrated strategies that may influence water intake and consumption among young children aged 0 to 5 years.

Wavelet entropy assesses the degree of order or disorder in signals and presents this complex information in a simple metric. Relative wavelet entropy assesses the similarity between the spectral distributions of two signals, again in a simple metric. Wavelet entropy is therefore potentially a very attractive tool for waveform analysis. The ability of this method to track the effects of pharmacologic modulation of vascular function on Doppler blood velocity waveforms was assessed. Waveforms were captured from ophthalmic arteries of 10 healthy subjects at baseline, after the administration of glyceryl trinitrate (GTN) and after two doses of NG-nitro-L-arginine-methyl ester (L-NAME) to produce vasodilation and vasoconstriction, respectively. Wavelet entropy had a tendency to decrease from baseline in response to GTN, but significantly increased after the administration of L-NAME (mean: 1.60 ± 0.07 after 0.25 mg/kg and 1.72 ± 0.13 after 0.5 mg/kg vs. 1.50 ± 0.10 at baseline, p < 0.05). Relative wavelet entropy had a spectral distribution from increasing doses of L-NAME comparable to baseline, 0.07 ± 0.04 and 0.08 ± 0.03, respectively, whereas GTN had the most dissimilar spectral distribution compared with baseline (0.17 ± 0.08, p = 0.002). Wavelet entropy can detect subtle changes in Doppler blood velocity waveform structure in response to nitric-oxide-mediated changes in arteriolar smooth muscle tone.

The motivation for this study was to reduce physics workload relating to patient- specific quality assurance (QA). VMAT plan delivery accuracy was determined from analysis of pre- and on-treatment trajectory log files and phantom-based ionization chamber array measurements. The correlation in this combination of measurements for patient-specific QA was investigated. The relationship between delivery errors and plan complexity was investigated as a potential method to further reduce patient-specific QA workload. Thirty VMAT plans from three treatment sites - prostate only, prostate and pelvic node (PPN), and head and neck (H&N) - were retrospectively analyzed in this work. The 2D fluence delivery reconstructed from pretreatment and on-treatment trajectory log files was compared with the planned fluence using gamma analysis. Pretreatment dose delivery verification was also car- ried out using gamma analysis of ionization chamber array measurements compared with calculated doses. Pearson correlations were used to explore any relationship between trajectory log file (pretreatment and on-treatment) and ionization chamber array gamma results (pretreatment). Plan complexity was assessed using the MU/ arc and the modulation complexity score (MCS), with Pearson correlations used to examine any relationships between complexity metrics and plan delivery accu- racy. Trajectory log files were also used to further explore the accuracy of MLC and gantry positions. Pretreatment 1%/1 mm gamma passing rates for trajectory log file analysis were 99.1% (98.7%-99.2%), 99.3% (99.1%-99.5%), and 98.4% (97.3%-98.8%) (median (IQR)) for prostate, PPN, and H&N, respectively, and were significantly correlated to on-treatment trajectory log file gamma results (R = 0.989, p < 0.001). Pretreatment ionization chamber array (2%/2 mm) gamma results were also significantly correlated with on-treatment trajectory log file gamma results (R = 0.623, p < 0.001). Furthermore, all gamma results displayed a significant correlation with MCS (R > 0.57, p < 0.001), but not with MU/arc. Average MLC position and gantry angle errors were 0.001 ± 0.002 mm and 0.025° ± 0.008° over all treatment sites and were not found to affect delivery accuracy. However, vari- ability in MLC speed was found to be directly related to MLC position accuracy. The accuracy of VMAT plan delivery assessed using pretreatment trajectory log file fluence delivery and ionization chamber array measurements were strongly correlated with on-treatment trajectory log file fluence delivery. The strong corre- lation between trajectory log file and phantom-based gamma results demonstrates potential to reduce our current patient-specific QA. Additionally, insight into MLC and gantry position accuracy through trajectory log file analysis and the strong cor- relation between gamma analysis results and the MCS could also provide further methodologies to both optimize the VMAT planning and QA process.

Purpose The dose delivery accuracy of 30 clinical step and shoot intensity modulated radiation therapy plans was investigated using the single integrated multileaf collimator controller of the Varian Truebeam linear accelerator (linac) (Varian Medical Systems, Palo Alto, CA) and compared with the dose delivery accuracy on a previous generation Varian 2100CD C-Series linac. Methods and Materials Ten prostate, 10 prostate and pelvic node, and 10 head-and-neck cases were investigated in this study. Dose delivery accuracy on each linac was assessed using Farmer ionization chamber point dose measurements, 2-dimensional planar ionization chamber array measurements, and the corresponding Varian dynamic log files. Absolute point dose measurements, fluence delivery accuracy, leaf position accuracy, and the overshoot effect were assessed for each plan. Results Absolute point dose delivery accuracy increased by 1.5% on the Truebeam compared with the 2100CD linac. No improvement in fluence delivery accuracy between the linacs, at a gamma criterion of 3%/3 mm was measured using the 2-dimensional ionization chamber array, with median (interquartile range) gamma passing rates of 98.99% (97.70%-99.72%) and 99.28% (98.26%-99.75%) for the Truebeam and 2100CD linacs, respectively. Varian log files also showed no improvement in fluence delivery between the linacs at 3%/3 mm, with median gamma passing rates of 99.97% (99.93%-99.99%) and 99.98% (99.94%-100%) for the Truebeam and 2100CD linacs, respectively. However, log files revealed improved leaf position accuracy and fluence delivery at 1%/1 mm criterion on the Truebeam (99.87%; 99.78%-99.94%) compared with the 2100CD linac (97.87%; 91.93%-99.49%). The overshoot effect, characterized on the 2100CD linac, was not observed on the Truebeam. Conclusions The integrated multileaf collimator controller on the Varian Truebeam improves clinical treatment delivery accuracy of step and shoot intensity modulated radiation therapy fields compared with delivery on a Varian C-series linac.

The aim of this work was to track and verify the delivery of respiratory-gated irradiations, performed with three versions of TrueBeam linac, using a novel phantom arrangement that combined the OCTAVIUS(®) SRS 1000 array with a moving platform. The platform was programmed to generate sinusoidal motion of the array. This motion was tracked using the real-time position management (RPM) system and four amplitude gating options were employed to interrupt MV beam delivery when the platform was not located within set limits. Time-resolved spatial information extracted from analysis of x-ray fluences measured by the array was compared to the programmed motion of the platform and to the trace recorded by the RPM system during the delivery of the x-ray field. Temporal data recorded by the phantom and the RPM system were validated against trajectory log files, recorded by the linac during the irradiation, as well as oscilloscope waveforms recorded from the linac target signal. Gamma analysis was employed to compare time-integrated 2D x-ray dose fluences with theoretical fluences derived from the probability density function for each of the gating settings applied, where gamma criteria of 2%/2 mm, 1%/1 mm and 0.5%/0.5 mm were used to evaluate the limitations of the RPM system. Excellent agreement was observed in the analysis of spatial information extracted from the SRS 1000 array measurements. Comparisons of the average platform position with the expected position indicated absolute deviations of 0.5 mm for all four gating settings. Differences were observed when comparing time-resolved beam-on data stored in the RPM files and trajectory logs to the true target signal waveforms. Trajectory log files underestimated the cycle time between consecutive beam-on windows by 10.0 ± 0.8 ms. All measured fluences achieved 100% pass-rates using gamma criteria of 2%/2 mm and 50% of the fluences achieved pass-rates 90% when criteria of 0.5%/0.5 mm were used. Results using this novel phantom arrangement indicate that the RPM system is capable of accurately gating x-ray exposure during the delivery of a fixed-field treatment beam.

This study aims to evaluate the use of Varian radiotherapy dynamic treatment log (DynaLog) files to verify IMRT plan delivery as part of a routine quality assurance procedure. Delivery accuracy in terms of machine performance was quantified by multileaf collimator (MLC) position errors and fluence delivery accuracy for patients receiving intensity modulated radiation therapy (IMRT) treatment. The relationship between machine performance and plan complexity, quantified by the modulation complexity score (MCS) was also investigated. Actual MLC positions and delivered fraction of monitor units (MU), recorded every 50 ms during IMRT delivery, were extracted from the DynaLog files. The planned MLC positions and fractional MU were taken from the record and verify system MLC control file. Planned and delivered beam data were compared to determine leaf position errors with and without the overshoot effect. Analysis was also performed on planned and actual fluence maps reconstructed from the MLC control file and delivered treatment log files respectively. This analysis was performed for all treatment fractions for 5 prostate, 5 prostate and pelvic node (PPN) and 5 head and neck (H&N) IMRT plans, totalling 82 IMRT fields in ∼5500 DynaLog files. The root mean square (RMS) leaf position errors without the overshoot effect were 0.09, 0.26, 0.19 mm for the prostate, PPN and H&N plans respectively, which increased to 0.30, 0.39 and 0.30 mm when the overshoot effect was considered. Average errors were not affected by the overshoot effect and were 0.05, 0.13 and 0.17 mm for prostate, PPN and H&N plans respectively. The percentage of pixels passing fluence map gamma analysis at 3%/3 mm was 99.94 ± 0.25%, which reduced to 91.62 ± 11.39% at 1%/1 mm criterion. Leaf position errors, but not gamma passing rate, were directly related to plan complexity as determined by the MCS. Site specific confidence intervals for average leaf position errors were set at −0.03–0.12 mm for prostate and −0.02–0.28 mm for more complex PPN and H&N plans. For all treatment sites confidence intervals for RMS errors with the overshoot was set at 0–0.50 mm and for the percentage of pixels passing a gamma analysis at 1%/1 mm a confidence interval of 68.83% was set also for all treatment sites. This work demonstrates the successful implementation of treatment log files to validate IMRT deliveries and how dynamic log files can diagnose delivery errors not possible with phantom based QC. Machine performance was found to be directly related to plan complexity but this is not the dominant determinant of delivery accuracy.

Background: Flow-mediated dilatation (FMD) of the brachial artery is commonly measured as a surrogate marker of endothelial function. Its measurement is, however, technically demanding and reports regarding its reproducibility have not always been favourable. Aim: Two Type I diabetes and control group comparator studies were conducted to assess the reproducibility of FMD and to analyse blood flow data normally discarded during FMD measurement. Design: The studies were sequential and differed only with regard to operator and ultrasound machine. Seventy-two subjects with diabetes and 71 controls were studied in total. Methods: Subjects had FMD measured conventionally. Blood velocity waveforms were averaged over 10 pulses post forearm ischaemia and their component frequencies analysed using the wavelet transform, a mathematical tool for waveform analysis. The component frequencies were grouped into 11 bands to facilitate analysis. Results: Subjects were well-matched between studies. In Study 1, FMD was significantly impaired in subjects with Type I diabetes vs. controls (median 4.35%, interquartile range 3.10–4.80 vs. 6.50, 4.79–9.42, P

Clinical and experimental studies indicate that structural and functional changes in the microvasculature can predate or accompany risk factors for cardiovascular disease at the earliest stages in the disease process. In the current work, both simulated and actual Doppler ultrasound maximum blood velocity waveform envelopes recorded from the ophthalmic artery were analysed using a root-MUSIC and least squares fitting approach to determine amplitude frequency spectra. Both amplitude and frequency components of noise contaminated simulated waveforms were reliably determined indicating the robustness of the technique. The technique was then used to compare the spectral content of the ophthalmic artery blood velocity waveforms of normal controls in three test states: at baseline, following administration of GTN, a nitric oxide donor, and following administration of L-Name, a nitric oxide inhibitor. Principal components derived from root-MUSIC analysis discriminated between waveforms in baseline and non-baseline test states (p < 0.00001) and between GTN and non-GTN test states (p = 0.0002).

Deposition distribution variability strongly influences data from radioaerosol mucus clearance measurements. We investigated how one clearance measurement-the area under the 0-6 h tracheobronchial retention curve (AUC)-relates to three different indices characterizing initial particle distribution. These indices were a conventional penetration index (PI), retention at 24 h (R(24)) and an Airways Penetration Index (API). API is an estimate of an outer to inner zone ratio for "tracheobronchial" (short-term cleared) deposition. Data were analyzed from "control" tests on 35 normal nonsmoking volunteers (16 females, 19 males, age 18-72 years). The strongest clearance-deposition correlation (r = 0.84, p0.0001) was obtained with API, yielding a narrower normal range than those with PI or R(24). No influence of age was detected. Data from repeat tests on 17 subjects demonstrated AUC changes correlating closely with API changes (r = 0.92, p0.0001), confirming the potential value of API as a "predictor" of clearance changes resulting simply from a changed distribution of initial deposition along the tracheobronchial airway generations. Additional data from 19 "placebo" tests on normal subjects gave AUC values within or close to suggested normal confidence limits derived from the control subject plots of AUC against, respectively, PI, R(24), and API. Quantitative attention to the influence of depositionclearance relationships should help in analyzing data from studies where posttreatment aerosol distribution cannot be exactly matched to the pretreatment situation. Deposition-corrected clearance provides an approach to improved estimation of clearance "normality."

To demonstrate the benefit of complexity metrics such as the modulation complexity score (MCS) and monitor units (MUs) in multi-institutional audits of volumetric-modulated arc therapy (VMAT) delivery.39 VMAT treatment plans were analysed using MCS and MU. A virtual phantom planning exercise was planned and independently measured using the PTW Octavius(®) phantom and seven29(®) 2D array (PTW-Freiburg GmbH, Freiburg, Germany). MCS and MU were compared with the median gamma index pass rates (2%/2 and 3%/3 mm) and plan quality. The treatment planning systems (TPS) were grouped by VMAT modelling being specifically designed for the linear accelerator manufacturer's own treatment delivery system (Type 1) or independent of vendor for VMAT delivery (Type 2). Differences in plan complexity (MCS and MU) between TPS types were compared.For Varian(®) linear accelerators (Varian(®) Medical Systems, Inc., Palo Alto, CA), MCS and MU were significantly correlated with gamma pass rates. Type 2 TPS created poorer quality, more complex plans with significantly higher MUs and MCS than Type 1 TPS. Plan quality was significantly correlated with MU for Type 2 plans. A statistically significant correlation was observed between MU and MCS for all plans (R = -0.84, p 0.01).MU and MCS have a role in assessing plan complexity in audits along with plan quality metrics. Plan complexity metrics give some indication of plan deliverability but should be analysed with plan quality.Complexity metrics were investigated for a national rotational audit involving 34 institutions and they showed value. The metrics found that more complex plans were created for planning systems which were independent of vendor for VMAT delivery.

Purpose To provide a tool to enable gamma analysis software algorithms to be included in a quality assurance (QA) program. Methods Four image sets were created comprising two geometric images to independently test the distance to agreement (DTA) and dose difference (DD) elements of the gamma algorithm, a clinical step and shoot IMRT field and a clinical VMAT arc. The images were analysed using global and local gamma analysis with 2 in-house and 8 commercially available software encompassing 15 software versions. The effect of image resolution on gamma pass rates was also investigated. Results All but one software accurately calculated the gamma passing rate for the geometric images. Variation in global gamma passing rates of 1% at 3%/3mm and over 2% at 1%/1mm was measured between software and software versions with analysis of appropriately sampled images. Conclusion This study provides a suite of test images and the gamma pass rates achieved for a selection of commercially available software. This image suite will enable validation of gamma analysis software within a QA program and provide a frame of reference by which to compare results reported in the literature from various manufacturers and software versions.

To assess the effects of tiotropium on lung mucociliary clearance in COPD.Randomized, double-blind, placebo-controlled, parallel-group study.Outpatients of an urban-area university teaching hospital.Thirty-four patients with COPD aged 40 to 75 years classified equally into two groups.Single (18 microg) daily dose of tiotropium inhalation capsules or of placebo for 21 days.Six-hour tracheobronchial clearance of inhaled 99mTc-labeled polystyrene particles using a 48-h retention measurement to determine the "nontracheobronchial" deposition fraction.Test radioaerosol penetration into the lungs increased significantly (p0.003) as did FEV1 (p0.006) in the tiotropium-treated patients, but measured mucociliary clearance was not significantly changed despite the increased pathway length for clearance (mean +/- SE area under the tracheobronchial retention curve changed from 442 +/- 22 to 453 +/- 20%/h). Smaller (nonsignificant) decreases of radioaerosol penetration and FEV1 occurred in the placebo group together with a small (nonsignificant) decrease in the area under the retention curve.Twenty-one days of inhaled tiotropium, 18 microg/d, as a dry powder does not retard mucus clearance from the lungs.

Lung mucociliary clearance is impaired in stable asthma. The long-acting beta2-agonist salmeterol has been shown in vitro to cause a significant increase in ciliary beat frequency. It seemed possible therefore that salmeterol may also have a favourable effect on lung mucociliary transport in asthmatic patients. Fourteen patients with asthma participated in a double-blind, placebo-controlled, crossover study to assess the effect of 2 weeks of treatment with salmeterol MDI (50 microg b.d.) on lung mucociliary clearance. The 11 patients who completed the study (seven males, four females) had a mean +/- SE age of 50 +/- 4 years, % predicted FEV1 of 74 +/- 8% and a tobacco consumption history of 13 +/- 7 pack-years (seven non-smokers, four exsmokers). Lung mucociliary transport was measured by a radioaerosol technique. Pulmonary function indices (FEV1, FVC, and PEF) were significantly improved on salmeterol relative to placebo. The main radioaerosol finding was a significant increase in the penetration of radioaerosol into the lung with 24-h radioaerosol rising from 40 +/- 5% on placebo to 49 +/- 4% (P0.01) on salmeterol. Despite this increased penetration, a slight favourable change occurred in tracheobronchial aerosol clearance. This study demonstrates that 2 weeks salmeterol treatment influences deposition of particles within the lung by increasing airway patency and indicates a beneficial effect of MDI salmeterol on lung mucociliary clearance.

Complementary and alternative medicine have become an increasingly topical theme in respiratory medicine. Aromatics are a commonly used ingredient in a number of proprietary medicines. It is well established that lung mucus clearance is impaired in patients with chronic airways obstruction. This study investigated whether aromatics delivered by inunction could be objectively shown to enhance lung clearance.We studied 12 patients with chronic bronchitic with a mean standard error (SE) age of 67 (2) years (mean [SE] tobacco consumption history of 64 [12] pack-years). We used a randomized, single-blinded, placebo-controlled crossover trial within patient design assessing the effect of 7.5 g of aromatics inunction (compared to a "no-treatment baseline" and to a petrolatum "placebo") on lung mucus clearance measured by a standard radioaerosol technique.Aromatic treatment significantly enhanced clearance at two time points 30 (p0.05) and 60 (p0.02) minutes postradioaerosol inhalation but had no demonstrable further effect over the following 5 hours despite further application of the inunction. The clearance improvement (relative to a baseline) observed during the first hour of testing was significantly correlated (p0.01) with the concentration level of aromatics.Our data, thus, provide objective evidence of a positive effect of aromatics inunction on mucus clearance in chronic airways obstruction.

It has been well established that lung mucociliary clearance is depressed in patients with chronic obstructive pulmonary disease. This study examines whether oral antibiotics have a detectable effect on this clearance mechanism during exacerbation in patients with such disease. Twelve patients with a mean ± se age of 63 ± 2 years participated in a randomized, double-blind, parallel group study to assess the effect of 1 week of treatment with amoxycillin (500 mg t.d.s.) or ciprofloxacin (500 mg b.d.) on lung mucociliary clearance during exacerbation. Lung mucociliary clearance rates were measured by a non-invasive radioaerosol technique. Both drugs on average resulted in small, non-significant, enhancement of mucociliary clearance. Following treatment, the numbers of coughs were reduced in both groups and significantly (P

In this study the Octavius detector 729 ionization chamber (IC) array with the Octavius 4D phantom was characterized for flattening filter (FF) and flattening filter free (FFF) static and rotational beams. The device was assessed for verification with FF and FFF RapidArc treatment plans.The response of the detectors to field size, dose linearity, and dose rate were assessed for 6 MV FF beams and also 6 and 10 MV FFF beams. Dosimetric and mechanical accuracy of the detector array within the Octavius 4D rotational phantom was evaluated against measurements made using semiflex and pinpoint ionization chambers, and radiochromic film. Verification FF and FFF RapidArc plans were assessed using a gamma function with 3%∕3 mm tolerances and 2%∕2 mm tolerances and further analysis of these plans was undertaken using film and a second detector array with higher spatial resolution.A warm-up dose of6 Gy was required for detector stability. Dose-rate measurements were stable across a range from 0.26 to 15 Gy∕min and dose response was linear, although the device overestimated small doses compared with pinpoint ionization chamber measurements. Output factors agreed with ionization chamber measurements to within 0.6% for square fields of side between 3 and 25 cm and within 1.2% for 2 × 2 cm(2) fields. The Octavius 4D phantom was found to be consistent with measurements made with radiochromic film, where the gantry angle was found to be within 0.4° of that expected during rotational deliveries. RapidArc FF and FFF beams were found to have an accuracy of97.9% and90% of pixels passing 3%∕3 mm and 2%∕2 mm, respectively. Detector spatial resolution was observed to be a factor in determining the accurate delivery of each plan, particularly at steep dose gradients. This was confirmed using data from a second detector array with higher spatial resolution and with radiochromic film.The Octavius 4D phantom with associated Octavius detector 729 ionization chamber array is a dosimetrically and mechanically stable device for pretreatment verification of FF and FFF RapidArc treatments. Further improvements may be possible through use of a detector array with higher spatial resolution (detector size and∕or detector spacing).

Many different inhalation devices are now available for the treatment of asthma. Pressures towards the elimination of chlorofluorocarbon propellants are driving forward development of new devices-as are obvious commercial pressures, including the increased availability of generic formulations. We still, however, often cannot tell exactly where within the lung we want to target a particular medication, be it a bronchodilator or a steroid. The basic processes of aerosol deposition are readily comprehensible. Nevertheless, even under carefully supervised inhalation conditions, one can only roughly estimate where the medication is deposited. We can, however, hope to give our patients good guidance on how to make the best use of a metered-dose inhaler or a jet nebuliser. From the array of available devices, we will increasingly be able to select the most comfortable and convenient for the patient-and therefore most likely to encourage good compliance.

Lung mucociliary clearance (LMC) depends on age and it is adversely affected by cigarette smoking. When using the radioaerosol technique for measuring LMC the initial site of deposition of the radioaerosol within the lungs affects its rate of removal. Whether there is a difference in gender for LMC is still an open question. Forty-one (20 female, 21 male) healthy, non-smoking subjects had their lung mucociliary clearance measured using an objective, non-invasive radioaerosol technique. The male and female groups were closely matched for initial distribution of the radioaerosol. There was no statistical significant difference between males and females in the rate of clearance of inhaled radioaerosol over a 6 h observation period. When comparing the LMC of two groups although it is important to match them for age, smoking habits and initial topographical distribution of the tracer radioaerosol it does not seem essential to also match the two groups for gender.

Inhaled frusemide has been shown to protect against the bronchoconstrictor effect of several inhaled agents in asthmatic subjects by mechanism(s) that are unclear. Since loop diuretics can modulate Cl- transport in the airway epithelium, frusemide may alter the quality and/or the quantity of the periciliary layer, which in turn may affect lung mucociliary transport. We investigated the effect of a single inhalation of nebulized frusemide (40 mg) on lung mucociliary clearance in four healthy subjects and in seven stable, mild asthmatics using an objective radioaerosol technique. Frusemide or placebo was inhaled in a double-blind, randomized, cross-over manner half an hour after the inhalation of 5 microns polystyrene particles labelled with 99mTc, used for assessing mucociliary clearance. The pulmonary function and initial radioaerosol distribution were similar between frusemide and placebo runs within each of the two study groups. The areas under the tracheobronchial retention curves over the 6 h observation period were similar between frusemide and placebo runs for both groups. Our findings show inhaled frusemide, at a dose known to inhibit bronchoconstrictor responses, does not affect lung mucociliary clearance.

BACKGROUND--In vitro studies have suggested that both the viscoelastic properties of lung secretions and the peak flow attained during simulated cough influence clearance. This study examines the possible association of the viscoelastic properties of sputum and maximum expiratory flow with measured effectiveness of mucus clearance induced by instructed cough and by forced expiration technique (FET) in patients with airways obstruction. METHODS--Nineteen patients (11 men and eight women) of mean (SE) age, % predicted FEV1, and daily sputum wet weight of 64 (2) years, 52 (6)%, and 37.5 (7.9) g respectively participated in the study. Mucus movement from proximal and peripheral lung regions was measured by an objective non-invasive radioaerosol technique. Each patient underwent three assessments: control, cough, and FET. During cough and FET, maximum expiratory flow was measured at the mouth level. Apparent viscosity and elasticity of the expectorated sputum samples were measured with a viscometer. RESULTS--Compared with the control run (mean (SE) clearance: 16 (3)%) there was an increase in clearance from the whole lung during cough (44 (5)%) and FET (42 (5)%), and also an enhanced clearance of inhaled, deposited radioaerosol from the trachea, inner and intermediate regions of the lungs, but not from the outer region. There were, however, no differences in regional clearance between cough and FET. Neither regional nor total clearance correlated with maximum expiratory flow, apparent viscosity, elasticity, or daily sputum wet weight. CONCLUSIONS--These results confirm that cough and FET both promote effective clearance but suggest that, unlike in vitro studies, sputum production and viscoelasticity, as well as maximum expiratory flow, provide no guide to clearance efficacy in humans.

It has previously been shown that unproductive coughing in both healthy subjects and patients with airways obstruction is not effective in clearing lung secretions. This study investigates the regional mucus transport in a group of subjects with airways obstruction who failed to expectorate following instructed cough and forced expiration technique. Fourteen patients (mean +/- SEM age: 68 +/- 2 years) with airways obstruction (mean +/- SEM percent predicted. FEV1: 54 +/- 5; daily wet weight sputum: 9.1 +/- 2.0 g) took part in the study which was a randomized, three-way crossover within-patient design. Each patient underwent three treatment maneuvers: control, cough (30 coughs over a 10-min period), and forced expiration (30 forced expirations over a 10-min period). An objective radioaerosol technique was used to monitor regional mucus movement within the lungs of the patients. The lungs were divided arbitrarily into four regions of interest: tracheal, inner, intermediate, and outer. Peak expiratory flow rate during cough and forced expiration was measured at the mouth. There was no correlation between the radioaerosol clearance from all regions and (1) mean peak flow during cough and forced expiration, and (2) mean 24-h sputum production prior to the study day. There were no differences in regional radioaerosol clearance between cough and forced expiration. However, both cough and forced expiration resulted in significant clearance compared with control for all regions with the exception of the forced expiration in the outer region. To our knowledge, this study is the first to demonstrate that unproductive cough and forced expiration result in movement of secretions proximally from all regions of the lung in patients with airways obstruction.

Waveform analysis has been used to assess vascular resistance and predict cardiovascular events. We aimed to identify microvascular abnormalities in patients with IGT using ocular waveform analysis. The effects of pioglitazone were also assessed.Forty patients with IGT and 24 controls were studied. Doppler velocity recordings were obtained from the central retinal, ophthalmic, and common carotid arteries, and sampled at 200 Hz. A discrete wavelet-based analysis method was employed to quantify waveforms. The RI was also determined. Patients with IGT were randomized to pioglitazone or placebo, and measurements were repeated after 12-week treatment.In the ocular waveforms, significant differences in power spectra were observed in frequency band 4 (corresponding to frequencies between 6.25 and 12.50 Hz) between groups (p0.05). No differences in RI occurred. No association was observed between waveform parameters and fasting glucose or insulin resistance. Pioglitazone had no effect on waveform structure, despite significantly reducing insulin resistance, fasting glucose, and triglycerides (p0.05).Analysis of ocular Doppler flow waveforms using the discrete wavelet transform identified microvascular abnormalities that were not apparent using RI. Pioglitazone improved glucose, insulin sensitivity, and triglycerides without influencing the contour of the waveforms.

Impaired FMD (flow-mediated dilatation) has traditionally been recognized as an indirect marker of NO bioactivity, occurring in disease states such as DM (diabetes mellitus). Endothelium-dependent FMD is a homoeostatic response to short-term increases in local shear stress. Microvascular dysfunction in DM influences blood flow velocity patterns. We explored the determinants of the FMD response in relation to evoked DSS (diastolic shear stress) and forearm microcirculation haemodynamics by quantifying changes in Doppler flow velocity waveforms between groups. Forty patients with uncomplicated Type 1 DM and 32 controls underwent B-mode and Doppler ultrasound scanning to interrogate the brachial artery. Postischaemic Doppler velocity spectral envelopes were recorded and a wavelet-based time-frequency spectral analysis method was employed to track change in distal microcirculatory haemodynamics. No difference in baseline brachial artery diameter was evident between the groups (4.15 compared with 3.94 mm, P =0.23). FMD was significantly impaired in patients with Type 1 DM (3.95 compared with 7.75%, P

The earliest signs of cardiovascular disease occur in microcirculations. Changes to mechanical and structural properties of these small resistive vessels alter the impedance to flow, subsequent reflected waves, and consequently, flow waveform morphology. In this paper, we compare two frequency analysis techniques: 1) rootMUSIC and 2) the discrete wavelet transform (DWT) to extract features of flow velocity waveform morphology captured using Doppler ultrasound from the ophthalmic artery (OA) in 30 controls and 38 age and sex matched Type I diabetics. Conventional techniques for characterizing Doppler velocity waveforms, such as mean velocity, resistive index, and pulsatility index, revealed no significant differences between the groups. However, rootMUSIC and the DWT provided highly correlated results with the spectral con tent in bands 2-7 (30-0.8 Hz) significantly elevated in the diabetic group (p

Lung mucociliary clearance was measured using an objective, noninvasive radioaerosol technique in 13 patients with pulmonary sarcoidosis and 13 matched, healthy control subjects. Four of the sarcoid patients had never received any steroid therapy, five were currently receiving oral corticosteroids, and the remaining four were using inhaled corticosteroids only. A statistically significant retardation in tracheobronchial clearance (p less than 0.02) was observed in the sarcoid patients compared to the control subjects. The sarcoid patients using inhaled corticosteroids appeared to demonstrate the greatest degree of mucociliary transport impairment. The sarcoid patients in apparent remission and those receiving oral corticosteroid therapy had clearances better than those using inhaled corticosteroids, but they were still reduced compared to the control subjects. This study demonstrates that lung mucociliary clearance is adversely affected in patients with pulmonary sarcoidosis and raises the question of the possible consequences that could follow long-term inhaled immunosuppressive therapy on the prime clearance defense mechanism within the human lungs.

The study was designed to ascertain the movement of mucus from proximal and peripheral regions within the human lungs during cough and the forced expiration technique (FET). Mucus movement was measured using a radioaerosol technique. Seven patients (mean +/- SEM age: 63 +/- 3 years) with airways obstruction (% predicted FEV1: 44 +/- 4) participated in the study. Each patient underwent three assessments in a randomized manner: control/cough/FET. Peak expiratory flow rate (PEFR) was measured at the mouth during cough and FET. None of the patients produced sputum during the assessment periods. Both cough and FET compared with control increased, on average, mucus clearance from all regions; statistical significance was achieved only for central lung regions with cough (P less than 0.05). There was no significant correlation between PEFR during cough/FET and regional lung clearance.

Tracheobronchial clearance was measured in seven patients with bilateral diaphragmatic weakness using a noninvasive objective radioaerosol technique. The data were compared with those from seven healthy nonsmoking control subjects matched for physical characteristics and studied under the same experimental conditions; the control subjects were drawn from a data bank of healthy subjects and were matched to the patients for age, sex, and the initial distribution of their radioaerosol deposition. Pulmonary function indices (FEV1, FVC, PEFR, and MMFR25-75) for the patients were all significantly (p less than 0.01) reduced compared with those for the control subjects. The initial topographic distribution of the radioaerosol within the lungs of the patients and control groups was similar: alveolar deposition [mean (SD)] was 36.4 (6.7) versus 41.0 (4.0)%, and penetration index was 0.56 (0.08) versus 0.56 (0.03), respectively. Tracheobronchial clearance of deposited radioaerosol over a 6-h observation period after inhalation showed a marked reduction (p less than 0.02) in the patients: area under the clearance curve (between zero and 6 h) was 262 (80)% h for the patients and 142 (41)% h for the healthy control subjects. These data suggest that in patients with bilateral diaphragmatic weakness, mucociliary clearance is depressed, or that reduced mechanical movement of the lungs can itself impair clearance of secretions from the lungs. Impaired clearance from either cause may contribute to an increased incidence of chest infections in severe respiratory muscle weakness.

In addition to breathlessness and cough, excessive mucus production is one of the main symptoms of chronic obstructive pulmonary disease (COPD). Excess mucus coupled with deteriorating mucociliary clearance is associated with a decline in lung function and an increased risk of death from pulmonary infection. The effect of Viozan (Sibenadet HCl, AR-C68397AA), a novel dual D2 dopamine receptor, beta2-adrenoceptor agonist, on mucociliary clearance was investigated together with that of a beta2-adrenoceptor agonist, salbutamol. Using a double blind, parallel group study design, 15 patients with COPD, all habitual smokers, were randomised to receive nebulised sidenadet (3mg tid; n = 7) or salbutamol (5mg tid; n = 8) for 10 days. Lung mucociliary clearance rates were measured, by a standard radioaerosol technique, before and after the treatment period, as were 24-h sputum volumes. Both sibenadet and salbutamol therapies resulted in significant (P0.02) enhancement of lung mucociliary clearance. The 24-h sputum volume was significantly reduced following sibenadet therapy (P0.03) whereas salbutamol therapy had no effect. Our results, in addition to illustrating the effects of a standard beta2 agonist on mucociliary clearance, strongly suggest the potential dual benefit of dual-agonist compounds in lessening sputum production whilst simultaneously enhancing mucociliary clearance. For reasons unconnected with the present study, development work on this specific formulation is no Longer proceeding.

This research examined the performance of 80 children aged 9–12 years with either a mild and moderate intellectual disability when recalling an innocuous event that was staged in their school. The children actively participated in a 30-min magic show, which included 21 specific target items. The first interview (held 3 days after the magic show) provided false and true biasing information about these 21 items. The second interview (held the following day) was designed to elicit the children's recall of the target details using the least number of specific prompts possible. The children's performance was compared with that of 2 control groups; a group of mainstream children matched for mental age and a group of mainstream children matched for chronological age. Overall, this study showed that children with either a mild or moderate intellectual disability can provide accurate and highly specific event-related information. However, their recall is less complete and less clear in response to free-narrative prompts and less accurate in response to specific questions when compared to both the mainstream age-matched groups. The implications of the findings for legal professionals and researchers are discussed.

As with all places of employment, nuclear medicine, medical physics and research departments in the United Kingdom which use radiation are required by legislation to make risk assessments associated with their work. Many have been slow to complete these, finding little guidance as to the best approach to take for departments which handle ionizing radiation. The Royal Free Hospital has set up a project to examine the whole procedure and approach to risk assessments in departments which use ionizing radiations, and has produced a standardized approach using matched risk assessment forms for both general risks and ionizing radiation risks. A worked example is included to illustrate the methodology and the standardized risk assessment forms.

BACKGROUND: Tracheobronchial clearance of mucus from the lungs is reduced during sleep and, usually, by the administration of opiates. It seemed possible therefore that temazepam, a widely used potent benzodiazepine, retarded clearance. METHODS: The effect of 10 mg temazepam on mucociliary clearance was studied in eight healthy volunteers, aged 18-50 (mean 30) years, in a randomised, placebo controlled, double blind, cross-over study. Six subjects were female and two male. Six were non-smokers and two were light current smokers. Clearance was assessed from the change in radio-activity in the lungs after inhalation of 5 microns diameter polystyrene particles, labelled with technetium-99m, under controlled conditions. RESULTS: Tracheobronchial clearance was reduced by 22% after temazepam by comparison with placebo during the first three hours after drug ingestion; this is the period when circulating drug concentrations are highest. CONCLUSION: Temazepam should be prescribed with caution in patients with impaired lung mucociliary transport.

15-(s)-Hydroxyeicosatetraenoic acid (15-HETE) is the predominant metabolite of arachidonic acid in normal and asthmatic human airways and a potent mucus secretagogue in canine and human airways. A study was carried out on the effect of inhaled 15-HETE on tracheobronchial clearance, measured for six hours by a radioaerosol technique, in 10 normal subjects. Subjects inhaled 80 nmol 15-HETE or the diluent (sodium phosphate buffer) on two occasions at least two weeks apart in a double blind and randomised fashion (20 minutes after radioaerosol inhalation. Tracheobronchial clearance after inhaled 15-HETE was almost identical to that after placebo for all measurements up to six hours. It is concluded that 15-HETE has no effect on tracheobronchial clearance in normal human airways and is unlikely to account for the impaired mucociliary clearance seen in asthma.

We have previously shown a high incidence of osteopenia and osteoporosis in patients with thalassaemia major. These bone changes, were more severe in males than females, in those with diabetes mellitus and with hypogonadal-hypogonadism. Our recent studies concern the relationship of erythroid activity, assessed by serum transferrin receptors as an overall measure of anaemia, to osteoporosis. Serum transferrin receptor levels correlated with the mean pre-transfusion haemoglobin level, but there was no correlation with the incidence of osteopenia and osteoporosis. As osteoporosis has a strong genetic component we have also studied the COLIA1 and COLIA2 genes which code for the major protein of bone (type 1 collagen). Studies by others have shown in non-thalassaemic patients that a polymorphism G--T or TT in a regulatory region of COLIA1 at the recognition site for transcription factor Sp1 is associated with the presence of osteoporosis. Our studies suggest that Sp1 polymorphism is not specific to any one ethnic group; the polymorphism occurs more commonly in females (female to male ratio 2:1). In male thalassaemia major patients the presence of the Sp1 mutation was associated with more severe osteoporosis of the spine and the hip compared with female patients. There is failure of improvement in spinal osteoporosis with bisphosphonate therapy (intravenous Pamidronate) in male patients with the Sp1 mutation.

Cooley's original description of beta-thalassaemia major included marked bone deformities as a characteristic feature. These were thought to be due to expansion of haemopoiesis attempting to compensate for the congenital anaemia. Regular blood transfusions from infancy prevents these skeletal problems. Nevertheless, symptoms due to bone disease frequently occur in adult patients. Osteoporosis has not previously been reported as a cause of severe morbidity in thalassaemia major. The present study shows a high prevalence of low bone mass among thalassaemia major patients and analyses the predisposing causes. Bone density scans were performed in 82 patients with transfusion-dependent beta thalassaemia. Factors known to be associated with low bone mass such as gender, endocrine disorders and lifestyle activities, together with factors specific to the thalassaemia and its management, were included in a series of univariate analyses to ascertain any significant associations. 42 (51%) of the patients had severely low bone mass and a further 37 (45%) had low bone mass. The three factors showing a statistically significant association with severely low bone mass were male sex, 24/38 (63%) males had severely low bone mass, compared with 18/44 (41%) females, the lack of spontaneous puberty, 22/32 (69%) who required therapeutic induction of pubertal development had severely low bone mass, compared with 19/47 (40%) with spontaneous puberty and diabetes, 8/10 (80%) diabetic patients had severely low bone mass, compared with 23/56 (41%) with normal glucose tolerance. There was no association between the bone mineral density measurements and the haematological characteristics or treatment details of these patients. Severely low and low bone mass are common findings in patients with beta-thalassaemia major despite optimal transfusion and iron chelation. The associated features suggest that the severely low bone mass is due to endocrine abnormalities, in contrast to the haematological causes of bone disease characteristically seen in untreated thalassaemics.

Kinins may affect lung mucociliary clearance in man by interacting with specific surface receptors designated B1 and B2. To evaluate this possibility, we have compared the effect of inhaled bradykinin and [desArg9]-bradykinin on mucociliary clearance in healthy volunteers. Four subjects attended the laboratory on three separate occasions to undertake tracheobronchial clearance studies, by a noninvasive radioisotopic technique, followed by inhalation with either bradykinin (8 mg.mL-1), [desArg9]-bradykinin (8 mg.mL-1), or vehicle placebo 30 min after radioaerosol inhalation. Half-hourly whole lung counts were measured for 6 h with two collimated scintillation counters and a tracheobronchial clearance curve was plotted for each subject on each occasion. In all the subjects studied, mucociliary clearance, expressed as the area under the tracheobronchial radioaerosol retention curve calculated for the first 6 h (AUCo-6h) was enhanced after inhaling bradykinin and prolonged following exposure with [desArg9]-bradykinin when compared to placebo. The median values (range) for AUCo-6h were significantly reduced from 123 (83-152)%.h to 92 (51-133)%.h with placebo and bradykinin, respectively, and significantly augmented to 269 (144-331)%.h after exposure with [desArg9]-bradykinin. This small study suggests that acute exposure with inhaled bradykinin accelerates, whilst [desArg9]-bradykinin delays, tracheobronchial clearance in normal human airways.

Interregional sequential filling potentially affects lung ventilation imaging, depending on the distribution of the tracer within the inspired volume. We investigated its importance quantitatively under near tidal breathing conditions in the upright lung using a short-lived radioactive tracer. Ten normal volunteers performed two runs of 900-ml breaths (from functional residual capacity) in which 100 ml of 81mKr boli were delivered "early" or "late" in inspiration, i.e., 50 ml or 450 ml volumetric depth. Apex-to-base gradients in the vertical profile were -106 +/- 22 (s.e.) counts/cm (early) and -187 +/- 24 (s.e.) counts/cm (late). Ratios of upper-to-lower regional ventilation (U/L) were 0.88 +/- 0.01 (s.e.) (early) and 0.81 +/- 0.01 (s.e.) (late). Simulations with a compartment model show that a simple pattern of sequential filling can by itself account for the experimental results observed. Control over 81mKr delivery can be important to physiologically accurate assessment of ventilation-perfusion matching. Controlled delivery techniques could also modify effectiveness and targeting of other inhaled agents including therapeutic aerosols.

BACKGROUND--The inability to match lung perfusion to ventilation because of a reduced cardiac output on exercise contributes to reduced exercise capacity in chronic heart failure. OBJECTIVE--To quantify ventilation to perfusion matching at rest and at peak exercise in patients with chronic heart failure and relate this to haemodynamic and ventilatory variables of exercise capacity. DESIGN--Eight men in New York Heart Association class II underwent maximal bicycle ergometry with expired gas analysis. MAIN OUTCOME MEASURES--On separate days, ventilation and perfusion gamma camera imaging was performed at rest, and at 80% of previous peak exercise heart rate during bicycle ergometry. The vertical distribution of mismatch between ventilation and perfusion (V/Q) was estimated from subtracted profiles of activity (ventilation and perfusion) to derive a numerical index of global mismatch. RESULTS--Maximal mean (SD) oxygen consumption on bicycle ergometry was 16.0 (4.5) ml min-1 kg-1. There was a reduction in the global V/Q mismatch index from 23.96 (5.90) to 14.88 (7.90) units (p < 0.01) at rest and at peak exercise. Global V/Q mismatch index at peak exercise correlated negatively with maximal minute ventilation (R = -0.90, p < 0.01) and with maximal mean arterial pressure (R = -0.79, p < 0.05), although no relation was seen with maximal oxygen consumption. The reduction in global V/Q mismatch index from rest to peak exercise correlated with maximal oxygen consumption (R = 0.88, p < 0.01), and with maximal minute ventilation (R = 0.87, p < 0.01). CONCLUSIONS--During exercise in patients with chronic heart failure, there is a reduction in the global V/Q mismatch index. A lower global V/Q mismatch index at peak exercise is associated with higher maximal ventilation. The reduction in global V/Q mismatch index on exercise correlates well with maximal exercise capacity. This may imply that the inability to perfuse adequately all regions of lung on exercise and match this to ventilation is a factor determining exercise capacity in chronic heart failure.

BACKGROUND: Lung mucociliary clearance rates are reduced during sleep in patients with asthma. Methylxanthines and beta 2 agonists have been shown to enhance rates of lung mucociliary clearance. This study examined whether oral slow release bronchodilators may also have an effect on this clearance mechanism during sleep in patients with asthma. METHODS: Nine patients with asthma with a mean(SE) age of 65(5) years and percentage predicted forced expiratory volume in one second (FEV1 of 61(9)% participated in a double blind, placebo controlled, within subject crossover study to assess the effect of two weeks of treatment with salbutamol (Volmax; 8 mg twice daily) or theophylline (Phyllocontin; 350 mg twice daily) on lung mucociliary clearance during sleep. Lung mucociliary clearance rates were measured by a radioaerosol technique. RESULTS: The observation period for radioaerosol clearance was approximately 0.3 hours before sleep, 6.0 hours during sleep and 0.6 hours after sleep. Mean mucociliary clearance rates for theophylline, placebo and salbutamol before sleep were: 39, 39, and 32%/hour respectively; during sleep: 11, 10, and 9%/hour respectively; and after sleep: 39, 32, and 35%/hour respectively. CONCLUSION: During sleep lung mucociliary clearance in stable asthma was reduced, which is in agreement with the group's previous findings. Treatment with controlled/slow release oral bronchodilators had no effect on this reduced rate of clearance associated with sleep.

BACKGROUND: Bradykinin, a nonapeptide that contributes as a mediator to the pathogenesis of asthma, may affect lung mucociliary clearance, as it has been shown to be a potent secretagogue in canine airways and in human nasal mucosa in vivo. To evaluate this possibility the effect of inhaled bradykinin on mucociliary clearance has been studied in 10 healthy volunteers. METHODS: Subjects attended the laboratory on two occasions to take part in tracheobronchial clearance studies using a non-invasive radioisotopic technique. Inhalation of radioaerosol was followed 30 minutes later by inhalation of either bradykinin (8 mg/ml) or vehicle placebo in a randomised, double blind fashion. After each inhalation the number of coughs was recorded. Whole lung radioactivity was measured every half hour for six hours with two collimated scintillation counters, and a tracheobronchial clearance curve was plotted for each subject on each occasion. RESULTS: Mucociliary clearance, expressed as the area under the tracheobronchial radioaerosol retention curve calculated for the first six hours (AUC0-6h), was greater in nine out of 10 subjects after inhalation of bradykinin than after placebo. The median values (range) for AUC0-6h were significantly reduced from 126% (78-232%)/h with placebo to 87% (51-133%)/h with bradykinin. CONCLUSION: It is concluded that acute exposure to inhaled bradykinin accelerates tracheobronchial clearance in normal human airways.

Lung mucociliary clearance was measured in 15 pigeon fanciers. The study group was subdivided into two: a precipitin-positive group (n = 10; mean +/- SEM age 45 +/- 5 years) with circulating blood precipitins and a precipitin-negative group (n = 5; mean +/- SEM age 40 +/- 3 years) without. Clearance was measured using an objective, noninvasive radioaerosol technique. The data for both groups were compared with those of matched control groups of healthy subjects. The mean +/- SEM area under the tracheobronchial retention curves (AUC) over the 6-h observation period was 257 +/- 27 %h for the precipitin-positive group compared with 177 +/- 16 %h for its control group (p = 0.02)--a high AUC value denoting slow clearance. That for the precipitin-negative group was 282 +/- 34 %h compared with 150 +/- 15 %h for its control group (p = 0.02). Our study illustrates in pigeon fanciers involvement of the conducting airways in that a major defense mechanism of the airways--namely, mucociliary clearance--is substantially compromised. The presence or absence of precipitins appears not to be related to the degree of mucociliary clearance impairment.

Nasal and tracheobronchial mucociliary clearance have been compared in 10 healthy subjects. Nasal clearance was measured by monitoring the rate of removal of 2 microns diameter Teflon particles, labelled with 99mTc, which had been placed in the anterior part of the nose. Tracheobronchial clearance was measured with an objective radioaerosol technique, 5 microns diameter polystyrene particles being used. With these comparable techniques there was a close correlation between the nasal mucociliary clearance rate and both the area under the tracheobronchial clearance curve from 0 to 6 hours after radioaerosol inhalation (rs = -0.94, p less than 0.001) and the area under the tracheobronchial clearance curve from 0 to 2.5 hours after inhalation (rs = -0.79, p less than 0.01). The rate of clearance of small particles from the nose may thus be a useful guide to tracheobronchial clearance in healthy individuals.

The effect of a single dose of carbamazepine (CBZ), 10 mg kg-1, on a battery of simple psychomotor tests was investigated in 12 healthy subjects (6 male, 6 female) in a balanced randomised double blind placebo controlled cross-over study. Psychomotor testing and blood sampling for total and free plasma CBZ, and CBZ 10, 11 epoxide concentration were performed at 10, 12, 14, 16, 18 and 34 h after oral dosing (23.00 h the previous evening). CBZ impaired i) critical flicker fusion threshold frequency at all time points up to 18 h (p less than 0.005); ii) total choice reaction time at 10 h (p less than 0.005) and 18 h (p less than 0.008); iii) card sorting at 14 h (p less than 0.001). No significant effect on finger tapping was noted. Subjects adjudged themselves more sedated on CBZ as compared to placebo at 12, 14 and 16 h (p less than 0.008). Plasma total and free CBZ concentrations (mean +/- SD) peaked at 10 h (8.8 +/- 0.2 mg 1-1) and 16 h (1.88 +/- 0.3 mg 1-1) after dosing respectively. CBZ 10, 11 epoxide values were all less than 10% of total CBZ concentrations and, therefore, were unlikely to contribute to the pharmacodynamic effect. Total choice reaction time was significantly more impaired in females (p less than 0.05) but no sex difference occurred with the other tests or CBZ concentrations at any time point. No significant correlations were found between individual total or free CBZ concentrations and corresponding test performances at each time point.(ABSTRACT TRUNCATED AT 250 WORDS)