Quasi-periodic ripples in high latitude electron content, the geomagnetic field, and the solar wind.

In this study we present evidence for the existence of quasi-periodic ripples in the F-region electron content at high latitude, the magnetic flux density at geosynchronous orbit, and the solar wind dynamic pressure and IMF flux density at L1. The ripples are shown to be continually present during all 14 days of observations in different years and seasons, and at all local times, though they are generally small in magnitude relative to the background. The frequencies of all the parameters are, on average, remarkably similar, and the amplitudes of the selected peaks of some parameters show strong correlations for which regression formulae are given. These results support the proposition that the ripples propagate from the solar wind to the F-region, and that they are a related, persistent phenomenon.

Technical report: Inter- and intra-rater reliability of regional gastrointestinal transit times measured using the 3D-Transit electromagnet tracking system.

BACKGROUND: The 3D-Transit electromagnet tracking system is an emerging tool for the ambulatory assessment of gastrointestinal (GI) transit times and motility patterns, based on the anatomical localization of ingestible electromagnetic capsules. Currently, 3D-Transit recordings are manually analyzed to extract GI transit times. As this is a subjective method, there is some inherent variability in the measurements, which may be experience-dependent. We therefore assessed inter- and intra-rater reliability of GI transit times from 3D-Transit recordings. METHODS: Thirty-six 3D-Transit recordings (17 female; median age: 34 years [range: 21-80]) were analyzed twice by 3 raters with varying experience. Each rater manually identified the timestamps when a capsule progressed from antrum to duodenum, and from ileum to right colon. These timestamps, along with the ingestion and expulsion times, were used to determine whole gut (WGTT), gastric emptying (GET), small intestinal (SITT) and colonic (CTT) transit times. Reliability was determined using interclass correlation coefficients (ICCs). KEY RESULTS: For capsule progression timestamps, the most and mid-experienced raters had fair to good inter- and excellent intra-rater reliability (ICCmin-max  = 0.61-1.00), whereas the inexperienced rater had poor to fair inter- and poor intra-rater reliability (ICCmin-max  = 0.28-0.55). GET and SITT reliability between the most and mid-experienced raters was fair (ICCmin-max  = 0.61-0.73), while reliability between these raters and the inexperienced rater was poor to fair (ICCmin-max  = 0.28-0.55). CTT reliability was excellent between and within all raters (ICCmin-max  = 0.92-0.99). CONCLUSIONS & INFERENCES: Inexperienced raters provide the least reliable measurements from 3D-Transit recordings, which confirms requirement for adequate training. Automation may improve the reliability of measurements.

Characterisation of Elastic and Acoustic Properties of an Agar-Based Tissue Mimicking Material.

As a first step towards an acoustic localisation device for coronary stenosis to provide a non-invasive means of diagnosing arterial disease, measurements are reported for an agar-based tissue mimicking material (TMM) of the shear wave propagation velocity, attenuation and viscoelastic constants, together with one dimensional quasi-static elastic moduli and Poisson's ratio. Phase velocity and attenuation coefficients, determined by generating and detecting shear waves piezo-electrically in the range 300 Hz-2 kHz, were 3.2-7.5 ms(-1) and 320 dBm(-1). Quasi-static Young's modulus, shear modulus and Poisson's ratio, obtained by compressive or shear loading of cylindrical specimens were 150-160 kPa; 54-56 kPa and 0.37-0.44. The dynamic Young's and shear moduli, derived from fitting viscoelastic internal variables by an iterative statistical inverse solver to freely oscillating specimens were 230 and 33 kPa and the corresponding relaxation times, 0.046 and 0.036 s. The results were self-consistent, repeatable and provide baseline data required for the computational modelling of wave propagation in a phantom.

Sensiprobe--a miniature thermal device incorporating Peltier technology as a diagnostic tool for studying human oesophageal sensitivity.

Heightened perception of gastrointestinal sensation is termed visceral hypersensitivity (VH) and is commonly observed in patients with gastrointestinal disorders. VH is thought to be a major contributory factor in oesophageal disease, particularly gastro-oesophageal reflux disease that does not respond to standard (proton pump inhibitor) treatment, and in functional heartburn. Clinical tools that can help phenotype according to the mechanism of chronic pain and thus allow targeted drug treatment (e.g. with pain modulator therapy) would be very desirable. A technique that produces repeatable and controllable thermal stimuli within the oesophagus could meet this need. The aims of this study were to develop a method for linear control of the heat stimulation in the oesophagus, to assess the reproducibility of this method, and obtain normal thermal sensitivity values in the distal and proximal oesophagus. The 7 mm diameter Peltier-based thermal device was investigated on 27 healthy subjects using a heating ramp of 0.2 °C s(-1). The pain detection threshold (PDT) temperature was recorded. To assess the reproducibility of the device, each subject underwent the procedure twice, with a minimum of two weeks between each procedure. The mean PDT temperature measured in the distal oesophagus, was 53.8 ± 2.9 °C and 53.6 ± 2.6 °C, for visits 1 and 2 respectively. The mean PDT temperature measured in the proximal oesophagus was 54.1 ± 2.4 °C and 54.0 ± 2.8 °C, for visits 1 and 2 respectively. The reproducibility of the PDT temperature in the distal and proximal oesophagus, was good (intra-class correlation >0.6). Future studies should be aimed to determine whether oesophageal thermal sensitivity can act as a biomarker of transient receptor potential vallanoid 1 upregulation.

Carotid atherosclerotic plaque characterisation by measurement of ultrasound sound speed in vitro at high frequency, 20 MHz.

This study aimed to utilise a tissue mimicking material (TMM) in order to embed in vitro carotid plaque tissue so that its acoustic properties could be assessed. Here, an International Electrotechnical Commission (IEC) agar-based TMM was adapted to a clear gel by removal of the particulates. This clear TMM was measured with sound speed at 1540 ms(-1) and an attenuation coefficient of 0.15 dB cm(-1)MHz(-1). Composite sound speed was then measured through the embedded material using a scanning acoustic microscope (SAM). Both broadband reflection and transmission techniques were performed on each plaque specimen in order to ensure the consistency of the measurement of sound speed, both at 21 °C and 37 °C. The plaque was measured at two temperatures to investigate any effect on the lipid content of the plaque. The contour maps from its associated attenuation plots were used to match the speed data to the photographic mask of the plaque outline. This physical matching was then used to derive the sound speed from the percentage composition seen in the histological data by solution of simultaneous equations. Individual speed values for five plaque components were derived; TMM, elastin, fibrous/collagen, calcification and lipid. The results for derived sound speed in the TMM were consistently close to the expected value of soft tissue, 1540 ms(-1). The fibrous tissue showed a mean value of 1584 ms(-1) at 37 °C. The derived sound speeds for elastic and lipid exhibited large inter-quartile ranges. The calcification had higher sound speed than the other plaque components at 1760-2000 ms(-1). The limitations here lay in the difficulties in the matching process caused by the inhomogeneity of the plaque material and shrinkage during the histological process. Future work may concentrate on more homogeneous material in order to derive sound speed data for separate components. Nevertheless, this study increases the known data ranges of the individual components within a plaque. This information may be used help to assess the mechanical properties and structural integrity and its associated vulnerability or risk of embolization in future diagnostic ultrasound techniques.

Palate lengthening by buccinator myomucosal flaps for velopharyngeal insufficiency.

OBJECTIVE : To assess the outcome of palate lengthening by myomucosal buccinator flaps for velopharyngeal insufficiency both in terms of speech and changes in palate length. DESIGN : Thirty-two consecutive patients who underwent the buccinator flap procedure were reviewed retrospectively. Palate length and the presence or absence of a velopharyngeal gap were assessed on pre- and postoperative videofluoroscopic recordings using a calibrated image analysis system. Hypernasality, nasal emission, nasal turbulence, and passive cleft type articulation errors were evaluated blindly by a speech-language pathologist external to the team using pre- and postoperative speech recordings. SETTING : Multidisciplinary cleft team based in a tertiary referral center. Results : In 81% of patients, speech outcome was such that no further velopharyngeal surgery was considered necessary at the time of follow-up. The buccinator flap procedure resulted in a mean palate lengthening of 7.5 mm (±5.5 SD). After the operation, there was a complete elimination of the velopharyngeal gap on lateral videofluoroscopy in 77% of patients. There were significant decreases in hypernasality ratings and passive cleft type articulation errors postoperatively. CONCLUSION: Palatal lengthening with myomucosal buccinator flaps in patients with velopharyngeal insufficiency is effective and safe. It has become one of our routinely practiced procedures for velopharyngeal insufficiency.

Towards clinical assessment of velopharyngeal closure using MRI: evaluation of real-time MRI sequences at 1.5 and 3 T.

OBJECTIVE: The objective of this study was to demonstrate soft palate MRI at 1.5 and 3 T with high temporal resolution on clinical scanners. METHODS: Six volunteers were imaged while speaking, using both four real-time steady-state free-precession (SSFP) sequences at 3 T and four balanced SSFP (bSSFP) at 1.5 T. Temporal resolution was 9-20 frames s(-1) (fps), spatial resolution 1.6 × 1.6 × 10.0-2.7 × 2.7 × 10.0 mm(3). Simultaneous audio was recorded. Signal-to-noise ratio (SNR), palate thickness and image quality score (1-4, non-diagnostic-excellent) were evaluated. RESULTS: SNR was higher at 3 T than 1.5 T in the relaxed palate (nasal breathing position) and reduced in the elevated palate at 3 T, but not 1.5 T. Image quality was not significantly different between field strengths or sequences (p=NS). At 3 T, 40% acquisitions scored 2 and 56% scored 3. Most 1.5 T acquisitions scored 1 (19%) or 4 (46%). Image quality was more dependent on subject or field than sequence. SNR in static images was highest with 1.9 × 1.9 × 10.0 mm(3) resolution (10 fps) and measured palate thickness was similar (p=NS) to that at the highest resolution (1.6 × 1.6 × 10.0 mm(3)). SNR in intensity-time plots through the soft palate was highest with 2.7 × 2.7 × 10.0 mm(3) resolution (20 fps). CONCLUSIONS: At 3 T, SSFP images are of a reliable quality, but 1.5 T bSSFP images are often better. For geometric measurements, temporal should be traded for spatial resolution (1.9 × 1.9 × 10.0 mm(3), 10 fps). For assessment of motion, temporal should be prioritised over spatial resolution (2.7 × 2.7 × 10.0 mm(3), 20 fps). Advances in knowledge Diagnostic quality real-time soft palate MRI is possible using clinical scanners and optimised protocols have been developed. 3 T SSFP imaging is reliable, but 1.5 T bSSFP often produces better images.

Finite element analysis animated simulation of velopharyngeal closure.

OBJECTIVE: To use finite element analysis animated simulations to investigate factors affecting velopharyngeal closure. DESIGN: A coronal section multicomponent finite element analysis model of a human soft palate was created in Simulia Abaqus 6.5-1 from high resolution MRI images of a single adult female subject, interpreted by reference to published anatomic dissections. Tissues were assigned hyperelastic property coefficients for neo-Hookean behavior, with gravity at 9.8 ms(-2) in the y-axis. Vector forces based on estimations in previous publications were applied throughout levator veli palatini and palatopharyngeus muscles, using a nonlinear analysis algorithm, to produce animated simulations of velopharyngeal space closure. Variation of levator veli palatini angle from 60° to 49°, the contribution of palatopharyngeus muscle, and the effect of submucous cleft were investigated for their effects on velopharyngeal closure. RESULTS: The animated simulations showed anthropomorphic behavior and supported the previously suggested effects of the levator veli palatini angle, with reduced effectiveness of velopharyngeal closure as levator veli palatini angle decreases. Palatopharyngeus action reduced the efficiency of closure for a levator veli palatini angle of 60°, and a submucous cleft reduced this for both our normal subject and for a levator veli palatini angle of 60°, but both palatopharyngeus action and a submucous cleft enhanced closure for a levator veli palatini angle of 49°. CONCLUSIONS: This study advances soft palate finite element analysis to a real-subject-based multicomponent hyperelastic model that demonstrates anthropomorphic behavior. Animated simulations using the model demonstrate the possible effects of levator veli palatini angle, a submucous cleft, and the contribution of the palatopharyngeus.

Biomechanical properties of the human soft palate.

OBJECTIVE: To measure biomechanical properties of the human soft palate and the variation across anatomic regions. DESIGN: Ex vivo analysis of human tissue. PATIENTS/PARTICIPANTS: Ten palates harvested from 10 normal adult human cadavers (age range, 37 to 90 years). INTERVENTIONS: Computer-controlled uniaxial stress-relaxation mechanical properties tested in physiological saline at 37 degrees C. MAIN OUTCOME MEASURES: Measurement of Young modulus, Poisson ratio, and determination of viscoelastic constants c, tau(1), and tau(2) by curve-fitting of the reduced relaxation function to the data. RESULTS: One hundred sections were tested from the 10 palates, representative of 10 anatomic zones. The mean Young modulus range was 585 Pa at the posterior free edge to 1409 Pa at regions of attachment. The mean Poisson ratio in the inferior-superior direction was 0.45 (SD 0.26) and in the lateral direction, was 0.30 (SD 0.21). The mean viscoelastic constants for 1-mm extensions were C = -0.1056 (+/-0.1303), tau(1) = 11.0369 (+/-9.1865) seconds, and tau(2) = 0.2128 (+/-0.0792) seconds, and for 2-mm extensions were C = -0.1111 (+/-0.1466), tau(1) = 14.3725 (+/-5.2701) seconds, and tau(2) = 0.2094 (+/-0.0544) seconds. CONCLUSIONS: The results show agreement with values of the Young modulus estimated by authors (Ettema and Kuehn, 1994; Berry et al., 1999) undertaking finite element modeling of the palate. However, other modulus measurements based on closing pressure are considerably different. The spatial distribution of viscoelastic parameters across the palate shows good consistency.

Comparison of simulated and experimental results from helical antennas within a muscle-equivalent phantom.

Miniature microwave helical antennas for use in thermal therapy applications are usually investigated using muscle-equivalent phantoms. In this paper, an alternative method using an electromagnetic solver based on the finite integration technique is used to simulate a range of 915 MHz helical antennas within a medium with the dielectric properties of muscle. By avoiding the stair-casing effect associated with many solvers, this method enables accurate simulations of non-orthogonal geometric objects such as helical antennas to be achieved. The effects of coil-spacing and insertion depth on the SAR distribution produced by the antennas were characterized and showed good agreement with previously published results obtained using a muscle phantom and a thermographic camera. The simulations confirm that the performance of helical antennas depends on insertion depth. Modification of the coil density demonstrated improvement of the return loss characteristics and changes to the resulting SAR profile.

The acoustic properties, centered on 20 MHZ, of an IEC agar-based tissue-mimicking material and its temperature, frequency and age dependence.

The purpose of this study was to characterize the ultrasonic properties of agar-based tissue-mimicking materials (TMMs) at ultrasound frequencies centered around 20 MHz. The TMM acoustic properties measured are the amplitude attenuation coefficient alpha (dB cm(-1)MHz(-1)), the speed of sound (ms(-1)) and the backscattered power spectral density (distribution of power per unit frequency normalized to the total received power) characteristics of spectral slope (dB MHz(-1)), y-axis intercept (dB) and reflected power (dB). The acoustic properties are measured over a temperature range of 22 to 37 degrees C. An intercomparison of results between two independent ultrasound measurement laboratories is also presented. A longitudinal study of the acoustic properties over a period of two years is also detailed, and the effect of water immersion on the acoustic properties of TMM is measured. In addition, the physical parameters of mass density rho (kg m(-3)) and specific heat capacity C (J kg(-1) K(-1)) are included. The measurement techniques used were based on the substitution technique using both broadband and narrowband pulses centered on 20 MHz. Both the attenuation coefficient and speed of sound (both group and phase) showed good agreement with the expected values of 0.5 dB cm(-1) MHz(-1) and 1540 ms(-1), respectively, with average values over the three-year period of 0.49 dBcm(-1)MHz1 (SD +/- 0.05) and 1540.9 ms(-1) (SD +/- 8.7). These results also showed agreement between the two independent measurement laboratories. Speed of sound and attenuation coefficient were shown to change with temperature with rates of + 2.1 m s(-1) degrees C(-1) and -0.005 dB cm(-1) MHz(-1) degrees C(-1), respectively. Attenuation changed linearly with frequency at the high frequency range of 17 to 23 MHz, and speed of sound was found to be independent of frequency in this range. The spectral slope of relative backscattered power for the material increased with frequency at typically 1.5 dB MHz(-1). This compared favorably with theoretical spectral slope values, calculated for a variety of scatterer sizes, albeit at a lower frequency range. It is also noticed that, on extrapolation back to lower frequencies, the backscatter is comparable with that measured at 7 MHz. Overall, this non-commercial agar-based TMM is shown to perform as expected at the higher frequency range of 17 to 23 MHz and is seen to retain its acoustic properties of attenuation and speed of sound over a three-year period.

Quality of surgical instruments.

INTRODUCTION: Many surgeons will have encountered the scissors that would not cut, and the artery clip that comes off in a deep difficult location, but it would be reasonable to assume that new instruments should be of assured quality. This study reports the surprising findings of a local quality control exercise for new instruments supplied to a single trust. MATERIALS AND METHODS: Between January 2004 and June 2004, all batches of new surgical instruments ordered by the Central Sterile Supplies Department of St Bartholomew's and the Royal London Hospitals were assessed by three clinical engineers, with reference to British Standards (BS) requirements. RESULTS: Of 4800 instruments examined, 15% had potential problems. These included 116 with machining burrs and debris in the teeth of the tissue-holding regions, 71 defects of ratcheted instruments, 34 scissors with deficient cutting action, and 35 tissue forceps protruding guide pins. In addition, 254 instruments did not have a visible manufacturer's mark. CONCLUSIONS: This study demonstrates the value of local quality control for surgical instruments. This is of importance in an increasingly hazard-conscious environment, where there are concerns over instrument sterilisation, surgical glove puncture and the potential for transmission of blood-borne and prion diseases.

Preliminary findings from tests of a microwave applicator designed to treat Barrett's oesophagus.

Barrett's oesophagus is considered to increase the risk of cancer 30-fold. Helical microwave antennas have been developed for ablative treatment of Barrett's. A microwave balloon applicator was tested in an initial animal study using adult white pigs. For treatment, a balloon filled with tissue-equivalent material encapsulated the antenna. A range of different treatment temperatures and durations was used to investigate a range of thermal ablations of the oesophageal epithelium. Eight animals were investigated, five non-survival and three with a 1-week survival period. The balloon was fitted with an array of temperature sensors, which gave an indication of the treatment in situ and allowed modifications to be performed in real time. Temperature data were recorded from all four quadrants of the balloon throughout and test sites were collected and analysed histologically. All experiments were successfully completed without perforation, serious adverse effects or death. Sites of discrete ulceration were induced in the survival tests, whereas the non-survival tests yielded little reproducible tissue modification. Results suggested that an activation temperature of approximately 55 degrees C needed to be reached during the treatment for tissue damage to be induced. Once damage had been triggered the severity was related to the mean temperature attained during the treatment period. A mean temperature of 52 degrees C or more resulted in substantial damage, whilst a mean temperature of approximately 50 degrees C resulted in the desired surface damage with sparing of subjacent tissues.

First report of a new ultrasound velocity based system for atherosclerotic plaque characterisation.

PURPOSE: To built an experimental system that can create ultrasound velocity maps for human tissues. METHODS AND RESULTS: We describe a new experimental system and its use to examine ex vivo specimens of carotid atherosclerotic plaque. CONCLUSION: This new ultrasound system is promising but requires further testing and development in the laboratory.

Effect of insertion depth on helical antenna performance in a muscle-equivalent phantom.

Barrett's oesophagus is considered to increase the risk of cancer 30 fold. A set of helical microwave antennas was designed to investigate their potential use in the thermal therapy of Barrett's oesophagus. For treatment, a balloon filled with muscle-equivalent material encapsulates the antenna. The effects of insertion depth and coil-spacing on the thermal distribution produced by the antennas (20-35 mm) were characterized. The 35 mm helical antenna, with a coil-spacing of 3.6 mm resulted in uniform heating for an insertion depth of 40 mm. It was observed that the resultant temperature distribution produced, by the antennas, was dependent on the insertion depth within the phantom. For all antennas studied, deeper insertion resulted in two high intensity regions, approximately 1/4 and 3/4 along the antenna length. In contrast, shallow insertion resulted in predominant tip heating with undesirable heating at the phantom entry point. However, by manipulating the coil-spacing of the helix, uniform temperature profiles were achieved for a range of insertion depths.

A study of the measurement errors associated with the analysis of velar movements assessed from lateral videofluoroscopic investigations.

OBJECTIVE: The analysis of lateral videofluoroscopic images of velar movements during speech is a commonly used tool in the management of the cleft palate patient. This study tests the general hypothesis that measurements of velar movements taken from lateral videofluoroscopic images are accurate and reliable. METHOD: A measurement system was used that allowed for the rapid assessment of velopharyngeal distance, soft palate velocity during the closure cycle, extension of the soft palate at maximum closure, and the angular lift of the soft palate above the plane of the hard palate. Ten recordings of soft palate movement during speech were randomly chosen from lateral X-rays of 27 normal adults. The video recordings were captured by digital frame grabber for subsequent analysis by three operators using a standard PC that was running image-analysis software. The uncertainties associated with the above measurements were analyzed in terms of the errors introduced by the inherent calibration and nonlinearity of the imaging system, the inaccuracy of the patient setup, and the operator-dependent measurement error. RESULTS: For both absolute dimensions and ratiometric measurements, the measurement uncertainties related to the inherent nonlinearity in the imaging system were shown to be less than 2%. Typical patient misalignments as a result of a 10 degree head rotation and a 10-mm translation out of the measurement plane introduced errors of between 2% and 3%. Results showed that the average standard deviation for measurement of gap size was 1.2 mm, extension ratio was 0.11, angular lift was 3.1 degrees, and soft palate velocity was 15.5 mm/second. The intra-class correlation coefficient generally showed a good agreement between operators, typically in the range 0.8 to 0.9. CONCLUSION: Measurements of velopharyngeal distance, extension of the soft palate at maximum closure, and the angular lift of the soft palate above the plane of the hard palate assessed from lateral videofluoroscopic images are reliable and accurate. The soft palate velocity during the closure cycle can also be determined, but clinical interpretations based on this parameter should be constrained by the measurement uncertainties.

Design of a microwave system for endoscopy: an experimental study of energy, tissue contact, and hemostatic efficacy.

BACKGROUND: A microwave generator and delivery system for endoscopic use was built. Using a 650-W, 2450-MHz magnetron, 0-160 W were generated from the tip of a 180-cm flexible coaxial cable (2.1 mm diameter). METHODS: Three methods of achieving hemostasis with microwaves were identified studying standard bleeding canine ulcers: (1) interstitial method: inserting the coaxial tip into the tissue and heating slowly until bleeding stopped; (2) contact method: tip held in contact, light pressure applied; (3) noncontact method: microwave-induced sparking (dielectric breakdown) with tip held 1 mm from tissue. RESULTS: Studies of optimal energy levels for hemostasis showed that high power (70 W) noncontact methods required significantly less energy to stop bleeding than contact or interstitial methods. The noncontact method was more effective than the contact method, stopping 20 of 20 bleeding ulcers vs. 10 of 20 (P < 0.001) and was more rapidly effective causing less tissue damage (P < 0.05) than the interstitial method. CONCLUSIONS: In a randomized comparison using a non-contact method, microwave coagulation was superior (P < 0.001) to a polidocanol 1% + adrenaline 1:10,000 injection and control treatment stopping 40 of 40 vs. 0 of 20 and 0 of 20 standard bleeding ulcers. Microwaves stopped bleeding from 10 of 10 severed mesenteric vessels, whereas injection was ineffective (0 of 10, P < 0.001). Microwaves look promising for hemostasis at flexible endoscopy.

Effect of bronchodilators on the cough response to inhaled citric acid in normal and asthmatic subjects.

Coughing was induced in seven normal and eight asthmatic subjects by giving successive inhalations of citric acid aerosols of progressively higher concentration (range 0.5-32%). A baseline cough response was obtained on each of four experimental days, and there was no significant difference between days in this respect. Then the subjects received by inhalation either a bronchodilator (salbutamol 5 mg or ipratropium 1 mg) or placebo, in a paired double blind crossover design. A second citric acid run followed and was used for paired drug-placebo comparisons. In the asthmatic subjects the cough response was diminished by both bronchodilators (p less than 0.05), and the cough threshold was significantly higher after ipratropium but not salbutamol. In normal subjects no significant effects were found. Airways calibre was assessed, by an oscillatory technique that measures the resistance of the respiratory system (Siemens Siregnost FD 5), in four of the seven normal and all eight asthmatic subjects. The mean respiratory resistance was higher in asthmatic than in normal subjects, and fell significantly after both bronchodilators. In normal subjects smaller decreases in respiratory resistance occurred, significant only with salbutamol. The simplest hypothesis which explains the results relates change in cough response to altered neuroreceptor sensitivity associated with rapid changes in bronchial calibre.