A repetitive movement detector used for automatic monitoring and quantification of scratching in mice.

We have designed an economical non-invasive movement detector for small animal studies and used it for monitoring and quantifying itch in mice. The system is based on a sensitive force transducer positioned below a recording platform holding a lightweight polystyrene recording box in which an animal is placed. A programmed micro-controller is used to discriminate between non-specific movement, grooming behaviour, and scratching movements made by the animal's hind limb. Following sub-dermal injection of histamine receptor agonists into the neck of a mouse, dose-related scratching occurred which was detected and quantified. There was 91% correlation between bouts of scratching as counted manually from playback of the video recording and recorded by the detector. The detector was also able rapidly to count the individual scratch movements of the hind limb that comprise a bout, with 95% accuracy in comparison with manual counting during slow motion playback of video tape, something that is impossible for an unaided observer to achieve because individual scratch movements are too fast to discriminate by eye. Separate detectors were used for the efficient non-invasive study of four animals simultaneously, and this number could easily be increased by adding more platforms. The system could also be modified to record the animal's position within the box, which would be of value in studies involving exploratory behaviour. In summary, the non-invasive multichannel repetitive movement detector will be very useful for accurate measurement of scratching during pruritus studies in small animals, with considerable savings in staff time and effort. It should therefore be a valuable tool for helping to investigate pruritus and in the evaluation of anti-pruritic drugs.

Metachronous pulmonary and cerebral inflammatory pseudotumor in a child.

An 8-year-old boy had a right pneumonectomy performed for a large inflammatory pseudotumor. Over the subsequent 8 years he developed multiple similar lesions in the meninges and bilateral cerebral hemispheres as well as new growths within the ipsilateral pleural cavity and contralateral lung. Metachronous pulmonary and intracranial inflammatory pseudotumor has been reported only once. These lesions probably represent a multifocal, exaggerated inflammatory response to some as yet unidentified stimuli.

Ageing and balance: the measurement of spontaneous sway by posturography.

Sway was measured by static posturography in 74 healthy subjects. Four age groups were investigated: 20-40, 40-60, 60-70 and over 70 years with equal numbers of males and females in each group. Sway increased linearly with age but was not affected by gender at any age. All age groups were more dependent on proprioception than vision in the maintenance of balance, but when reliable pressoreceptor information was removed, dependence on vision increased. The relative contributions of the sensory systems to balance did not alter with advancing age. The increase in sway demonstrated with normal ageing does not appear due to altered peripheral sensibility. It is more likely that it is due to slowing of central integrative processes.

Computerised system for the continuous measurement of azygos venous blood flow.

A computer assisted apparatus for the continuous measurement of azygos blood flow is described. The system was validated in vitro and changes in flow which occur with respiration and Valsalva manoeuvre are illustrated. This apparatus allows real time inspection of flow values which enables changes in flow over short periods to be readily studied.

Hypoglycaemia unawareness in type 1 diabetes: a lower plasma glucose is required to stimulate sympatho-adrenal activation.

To investigate the relationship between awareness of symptoms and the autonomic reaction of hypoglycaemia, acute hypoglycaemia was induced with intravenous insulin (2.5 mU kg-1 min-1) in diabetic and non-diabetic subjects, all of whom had normal cardiovascular autonomic function tests. Three groups were studied: (1) nine patients with Type 1 diabetes with loss of awareness of hypoglycaemia; (2) eight patients who had normal awareness of hypoglycemia, matched for duration of diabetes and blood glucose control; (3) eleven non-diabetic volunteers. The onset of the acute autonomic reaction was identified objectively by the sudden and rapid responses of heart rate and sweating. Cognitive function and hypoglycaemia symptom scores were estimated serially. Acute autonomic activation was observed to occur in all subjects in response to hypoglycaemia. In the 'unaware' diabetic patients, onset of the reaction occurred at a significantly lower plasma glucose (1.0 +/- 0.1 mmol l-1) than in the 'aware' diabetic patients (1.6 +/- 0.2 mmol l-1) (p less than 0.05) or in the non-diabetic control group (1.4 +/- 0.1 mmol l-1) (p less than 0.05). Obvious neuroglycopenia was observed only in the 'unaware' diabetic group and developed when plasma glucose had declined to approximately 1.4 +/- 0.1 mmol l-1, and thus preceded the reaction (p less than 0.02 vs the autonomic threshold). The maximal rise in plasma adrenaline was of similar magnitude in all three groups but a lower plasma glucose was required to stimulate this hormonal response in the 'unaware' patients, in whom the plasma adrenaline concentration was lower at the time of the reaction. Thus, the plasma glucose at which activation of the autonomic reaction was observed was lower in the diabetic patients with unawareness of hypoglycaemia.

Regional distribution of ventilation in chronic obstructive lung disease and the effect of salbutamol.

Regional distribution of ventilation was assessed in 5 normal volunteers, and 19 patients with symptomatic chronic obstructive lung disease (COAD) using the technique of gated lung ventilation imaging with 127Xe. The results of this technique were compared with the more conventional assessment of regional ventilation by analysis of 127Xe wash-out curves. Both techniques demonstrate loss of the normal gravitational distribution of ventilation in patients with severe COAD which is significantly reduced from normals in upper, middle and lower zones of each lung, being most marked in the lower zones (p less than 0.01). Gated lung imaging also shows a significant reduction of regional ventilation in patients with mild to moderate COAD compared to normals but only in the lower zones (p less than 0.05). Gated lung imaging provides a better quantitative method of assessing regional lung function than wash-out analysis and confirms loss of the normal gravitational distribution of ventilation in patients with obstructive lung disease and relates this to severity of disease. The distribution of ventilation was also assessed in 6 patients with severe COAD before and after placebo or salbutamol. There was a significant improvement of the distribution of ventilation to the lung bases after salbutamol (p less than 0.05).

Regional tidal volume assessed by gated lung imaging.

We have measured regional lung tidal volumes and functional residual capacities by accumulating and framing iso-volumic images while the patient rebreathes 127Xe. As the lung changes shape during ventilation corrections for changes in geometry were obtained by simultaneous collection of 99Tcm counts from the gated perfusion scan. Regions of interest were made to vary throughout the respiratory cycle so that a region had always the same value of 99Tcm counts. From the corrected 127Xe counts regional tidal volumes (TVr) and functional residual capacities (FRCr) were derived. In patients with established chronic bronchitis and emphysema FRCr were greater and the ratio TVr/FRCr decreased compared with patients with relatively normal static and dynamic lung volumes. Preliminary studies suggest that this ratio was a better discriminator between normal and abnormal regional function than estimates of regional xenon washout. Studies with xenon-133 have contributed to our understanding of the physiology of ventilation but have contributed somewhat less to routine clinical practice. This results in part from the unsatisfactory physical properties of xenon-133. Its relatively low gamma ray energy of 80 keV results in significant self-absorption losses and the activity which may be administered is limited by the radiation dose from the associated beta particles so that relatively poor counting statistics are obtained. With inhaled technetium-99m (99Tcm) microspheres imaging conditions are greatly improved but the distribution of these particles may not equate with the distribution of ventilation particularly if wet particles are used. Moreover, simultaneous microsphere perfusion scans with technetium-99m as a label are impossible. Krypton-81m gas has a suitable energy but the short half-life of the rubidium-81m generator (4.7 h) makes supply difficult and the ultrashort half-life of the krypton-81m gas (13 s) leads to problems in calculating the indices of ventilation. Xenon-127 (127Xe) gas has a more favourable dosimetry profile than xenon-133 because it does not have associated beta particles. Further it has an energy (203 keV) suitable for modern gamma cameras and may be used in the presence of injected 99Tcm microspheres to provide simultaneous ventilation/perfusion imaging. Conventional techniques have assumed that a static image of a dynamic process is adequate. As the lungs move during imaging, some account of this respiratory movement should be made.(ABSTRACT TRUNCATED AT 250 WORDS)

Nocturnal cough in patients with chronic bronchitis and emphysema.

Patients with respiratory disease commonly report that their sleep is disrupted by nocturnal cough. We have recorded cough during the night in 10 patients with severe chronic bronchitis and emphysema (forced expiratory volume in one second, 1.0 +/- SEM 0.1/L) who complained of nocturnal cough and correlated cough with electroencephalographic sleep stage and arterial oxygenation. Cough was recorded using a directional microphone and an auto-editing tape recorder system. Each cough was subsequently verified by a listener. There was a mean of 14.6 +/- 4.5 bouts of coughing per patient per night, each bout lasting on average 3.9 +/- 0.2 s. Eighty-five percent of coughing bouts occurred during electroencephalographically confirmed wakefulness (p less than 0.02 versus sleep), and coughs during true sleep were rare, with only 1 patient coughing during rapid eye movement sleep and none during Stages 3 and 4 sleep. Cough was only once followed by arousal. There was no correlation between cough and either apneas or hypoxemia during sleep. We conclude that spontaneous cough is suppressed during sleep and only rarely awakens patients.

Increased sensitivity of rabbit carotid body chemoreceptors to dopamine after chronic treatment with domperidone.

An increase in specific dopamine D2 receptor binding sites was observed in membranes prepared from the carotid bodies of rabbits treated for 8 weeks and then withdrawn for 4-9 days from the D2 antagonist domperidone (2-5 mg/kg per day). Recordings of chemoreceptor afferent discharge from the carotid body also revealed that this change in receptor density was accompanied by an increased sensitivity to the chemodepressant effects of exogenous dopamine. The chemoreceptor responsiveness of the carotid body to hypoxia is blunted in rabbits treated chronically with domperidone, but this can be restored to normal by an acute dose of the D2 antagonist. These experiments provide evidence that is compatible with a chemo-inhibitory role for endogenous dopamine in the rabbit's carotid body. Furthermore, these results suggest that the carotid body provides a useful model for the functional studies of dopamine D2 receptors.

Transient hypoxemia during sleep in chronic obstructive pulmonary disease is not a sleep apnea syndrome.

We measured ear oxygen saturation (SaO2), chest wall movement, and oronasal air flow, and took electroencephalographic tracings during nocturnal sleep in 20 healthy subjects and 20 similarly aged patients with chronic obstructive pulmonary disease (COPD), none of whom was obese. Thirteen of the patients with COPD were persistently hypoxemic and hypercapnic when awake ("blue and bloated", Type B); the remaining 7 maintained relatively normal arterial gas tensions when awake despite equally severe airways obstruction ("pink and puffing", Type A). Hypoxemic episodes (HE) (SaO2 falls of greater than 10%) occurred during sleep in all the blue bloaters but in only 3 of 7 pink puffers and 3 of 20 normal subjects. However, the maximal change in arterial oxygen tension (PaO2) (calculated from SaO2 values assuming normal pH) was similar in all 3 groups, averaging 24 mmHg. Furthermore, the cumulative duration of apnea and hypopnea was the same in each group. Only one patient COPD had more than 2 apneas per night, and obstructive apnea was seen only in the healthy subjects. Sleep apnea syndromes thus appear to be rare in nonobese patients with COPD. Of the 40 HE in patients with COPD, 29 occurred during periods of hypoventilation. In 10 blue bloaters whose arterial blood was sampled during sleep, the measured fall in PaO2 during the HE (mean, 11.2 mmHg) was greater than the rise in PaCO2 (mean, 4.2 mmHg). Although these changes in arterial gas tensions could be produced by an increase in ventilation-perfusion imbalance during the HE, it is suggested that unsteady-state gas exchange during transient hypoventilation could provide an alternative explanation.

Preservation of the hypoxic drive to breathing in diabetic autonomic neuropathy.

1. Unexplained cardiorespiratory arrests have been reported in patients with diabetic autonomic neuropathy and these could be due to denervation of the carotid chemoreceptors. 2. We have studied the ventilatory response to transient hypoxia (Ve/Peto2) during exercise in 22 male diabetic patients, six with symptomatic and cardiovascular evidence to suggest diabetic autonomic neuropathy (DAN+) and 12 without these features (DAN-). 3. There was no difference in the ventilatory response to transient hypoxia between the different groups of diabetic patients (Ve/Peto2 in DAN+ patients = -0.9 +/- 0.2 litre min-1 kPa-1; Ve/Peto2 in DAN- patients = -1.2 +/- 0.6 litres min-1 kPa-1) even allowing for differences in the level of exercise achieved (CO2 production in DAN+ patients = 743 +/- 103 ml/min; CO2 production in DAN- patients = 800 +/- 144 ml/min). These results fell within our normal range for ventilatory response to transient hypoxia at this level of exercise. 4. The heart rate response to transient hypoxia varied within the groups but was significantly (P less than 0.05) less in the patients with established diabetic autonomic neuropathy. 5. We conclude that the peripheral chemoreceptors are intact in diabetic autonomic neuropathy and that other mechanisms must be implicated in the unexpected cardiorespiratory arrests seen in these patients.

Irregular breathing and hypoxaemia during sleep in chronic stable asthma.

Breathing patterns, ear oxygen saturation (SaO2), and EEG sleep-stage throughout an undisturbed night's sleep were compared in ten adult stable asthmatics and ten age-matched healthy subjects. The two groups slept equally long (5.0-7.2, mean 6.2 h), but the asthmatics slept less well; they had more periods of wakefulness and drowsiness and irregular breathing than did the healthy subjects. They also had greater and more frequent falls in SaO2. Most hypoxaemic episodes occurred in the rapid-eye movement phase of sleep and were associated with hypopnoea or apnoea, but no patient had a classical sleep-apnoea syndrome. The severity of nocturnal hypoxaemia was related to the level of SaO2 when the subjects were awake, but did not correlate with the fall in forced expiratory volume recorded in eight out of ten asthmatics after sleep.

Effect of exercise and isoprenaline on left ventricular ejection fraction in patients with angina pectoris as assessed by radionuclide angiography.

The effect of supine leg exercise and an infusion of isoprenaline (2 micrograms/min) have been compared in 9 patients with angina pectoris and 8 normal control subjects. Left ventricular ejection fraction was measured by radionuclide angiography using the gated blood pool technique. The normal subjects increased their ejection fraction from 0.57 +/- 0.02 at rest to 0.71 +/- 0.02 during exercise, and 0.76 +/- 0.03 during isoprenaline infusion. In patients with angina pectoris, the resting ejection fraction of 0.47 +/- 0.04 decreased to 0.35 +/- 0.04 during exercise but increased to 0.63 +/- 0.06 during isoprenaline infusion. Our results suggest that the changes in ejection fraction probably depend on the changes in left ventricular segmental wall motion. When dyskinesia is increased, as with exercise, the ejection fraction declines, but when dyskinesia is unaffected or improved, as with isoprenaline, the ejection fraction increases.

Computer measurement of dynamic compliance: technique and reproducibility in man.

A computer program was developed to calculate the frequency dependence of dynamic compliance (Cdyn) using continuous data analysis. Cdyn was measured repeatedly in eight normal human subjects over a 2-yr period. Comparison with Cdyn results measured manually showed that the computer program improved 10-fold the ratio of variance within subjects to between subjects of the compliance at specific frequencies, but there was only slight improvement in indices of the slope of the frequency dependence of compliance. We suggest that the absolute compliance at specific frequencies merits further consideration as a pathophysiological measurement and that, if the frequency dependence of compliance continues to be used, standardization of its calculation should be applied and the wide normal range should be more widely appreciated. Measurements of Cdyn in subjects breathing 80% helium-20% oxygen confirm that inertia is insignificant when breathing with tidal volumes of less than 500 ml and frequency of less than 1.5 Hz.

The influence of ectopic heart beats in gated ventricular blood-pool studies.

Direct data collection from ventricular blood-pool studies were stored in frame mode in a computer and by means of a modified tape recorder, the blood-pool image and ECG were recorded on tape. At the end of the study the tape data were replayed into the computer. The ECG signal was passed through a trigger circuit that detected the R wave which was sampled by the computer once every msec. Contractions outside of the desired range could be rejected along with the subsequent contraction. Of seven patients whose calculated ejection fractions were changed by more than 0.03, all had frequent (one in 20) ectopic contractions. The distorted ventricular volume curves were effectively restructured by the constraining procedure, changing the end-systolic volume and EF. Computer modeling showed a linear relationship between the percent of ectopic contractions and the underestimate of ejection fraction. One ectopic beat in ten led to a 5% underestimate of EF.