Biomedical subjects

A Guz

Publications and source records attributed to A Guz.

At least 109 records · Page 6Linked to original sources

PubMed1989

Does the abnormal pattern of breathing in patients with interstitial lung disease persist in deep, non-rapid eye movement sleep?

Patients with interstitial lung disease (ILD) characteristically exhibit an increased ventilation and breathing frequency when awake. We wanted to see if these increases persisted during deep non-REM sleep. Using noninvasive techniques, we have quantified the pattern of breathing, arterial oxygen saturation, and transcutaneous PCO2 (PtcCO2) during standardized conditions of relaxed wakefulness and during Stage 4 (S4) sleep in eight patients with ILD and eight age-matched normal control subjects. The patients were given supplemental oxygen in order to prevent hypoxic ventilatory stimulation. The data were compared between the two groups during each of these states and also between states within each group. During wakefulness in the patients, respiratory frequency (f) and PtcCO2 were higher (p less than 0.001 and p less than 0.05, respectively) and inspiratory time (TI) and expiratory time (TE) were shorter (p less than 0.05 and p less than 0.001, respectively) than in the normal subjects. However, during S4 sleep, there were no significant differences between groups. Comparing wakefulness with S4 sleep: in the normal subjects during sleep, f and PtcCO2 were increased (p less than 0.01 and p less than 0.05, respectively), TE was shortened (p less than 0.01), and ventilation (VI) was unchanged. In contrast, in the patients, f decreased (p less than 0.001), TE lengthened (p less than 0.01), VI decreased (p less than 0.05), and the rise in PtcCO2 seen in the normal subjects during sleep did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1989

Pharyngeal size and shape during wakefulness and sleep in patients with obstructive sleep apnoea.

Computed tomography has been used to study the pharyngeal airway during tidal breathing in wakefulness and during obstructive apnoeas in Non-REM sleep in patients with obstructive sleep apnoea. In supine subjects, contiguous transverse 10 mm sections were taken perpendicular to the posterior pharyngeal wall with a 2.1 s scan time. Studies during wakefulness showed that the narrowest section of the pharyngeal airspace was in the region posterior to the soft palate and that the minimal airway cross-sectional areas were significantly reduced in the group of patients with obstructive sleep apnoea compared to the group of control subjects without obstructive sleep apnoea. The studies during sleep showed that in all patients, the airspace posterior to the soft palate was a site of obstructive apnoeas. The length of the obstructed segment varied between patients, extending below the level of the soft palate in half the patient group. Airway narrowing and obstruction was due to posterior displacement of the soft palate and the tongue in the majority of patients, although lateral displacement of the pharyngeal walls was also observed. No occlusion was observed in the laryngopharynx although there was narrowing of oro- and laryngopharyngeal apertures below the site of obstruction during obstructive apnoeas. The size of the oropharyngeal airspace during wakefulness did not predict the presence of airway occlusion below the level of the soft palate when asleep. The variability between patients in the site(s) of upper airway obstruction during obstructive apnoeas have important implications for the choice of appropriate treatment in patients with obstructive sleep apnoea.

Adult↗

PubMed1989

Assessment of breathlessness.

In summary, breathlessness is an important symptom in a number of disease states. The most appropriate techniques for assessment of the symptom depend on the circumstances, ranging from the time-honoured clinical interview by a skilled observer, through questionnaires for epidemiological use, to direct scaling of the sensation by subjects under experimental conditions. The use of direct scaling techniques has enabled researching into mechanisms of breathlessness in recent years, resulting in an increased understanding of the sensation, but no significant therapeutic advances as yet. An area of current research interest is study of the different descriptors for the sensation used by different subjects. This may have great practical importance because it may be that, as with pain, different types of breathlessness will respond to different types of treatment.

Dyspnea↗

PubMed1989

Sites and sizes of fat deposits around the pharynx in obese patients with obstructive sleep apnoea and weight matched controls.

It has been suggested that deposition of fat in the soft tissues surrounding the upper airway may be an important factor in the pathogenesis of obstructive sleep apnoea (OSA) in obese subjects. We have used magnetic resonance imaging to determine the site(s) and size(s) of fat deposits around the upper airway in six obese patients with OSA (116-153% of ideal body weight) and five weight-matched controls without OSA (107-152% of ideal body weight). In all subjects, large deposits of fat were present postero-lateral to the oropharyngeal airspace at the level of the soft palate. Significantly more fat was present in these regions in the patients with OSA (p = 0.03). Fat deposits in the soft palate were observed in 4 of the 6 patients with OSA but none of the controls. Fatty streaks were observed in the tongue in 2 of the 5 controls and 3 of the 6 patients with OSA. Fat deposits were observed anterior to the laryngopharyngeal airspace, in submental regions, in all obese subjects. This study shows that more fat is present in those areas surrounding the collapsable segment of the pharynx in patients with OSA, compared to equally obese control subjects without OSA.

Adipose Tissue↗

PubMed1989

The acute effect of cigarette smoking on the neutrophil elastase inhibitory capacity of peripheral lung lavage from asymptomatic volunteers.

Cigarette smoke-induced emphysema is thought to involve reduction of antielastolytic capacity, resulting in elevated elastase activity and lung tissue damage. Peripheral lavage collected from ten asymptomatic subjects immediately before and 20 min after smoking two high tar cigarettes was analysed for neutrophil elastase (NE) inhibitory capacity (IC), alpha 1-proteinase inhibitor (PI) function, elastolytic activity and immunoreactive levels of PI and bronchial inhibitor (BI). The only change found was a small fall in mol immunoreactive PI/mol albumin after smoking (approximately 17%, p less than 0.05) which did not affect NEIC, since PI contributed less than 50% of the NEIC. There was often more NEIC than mol BI + functional PI, suggesting the presence of other NE inhibitors. Thoracic computerized tomography scans of eight of these subjects highlighted two with emphysematous regions of lung; lavage from these two subjects contained either undetectable BI or inactive BI and this suggests a protective role for BI in emphysema.

Adult↗

PubMed1988

Fluorescence-quenching-resolved spectra of fluorophores in mixtures and micellar solutions.

The application of a new fluorescence-quenching-resolved spectroscopic method [Wasylewski, Z., Kołoczek, H. and Waśniowska, A. (1988) Eur. J. Biochem. 172, 719-724] for resolving fluorescence emission spectra of a mixture of fluorophores into components is described. Contrary to fluorescence lifetime measurements, in this method the overlapping spectra can be decomposed even if the components have similar or the same fluorescence lifetimes, but differ in bimolecular-rate-quenching constants. Using this technique, we have resolved the emission spectra of a two-component mixture of fluorescein and riboflavin, which have very similar fluorescence lifetimes. To illustrate the utility of this approach in the study of fluorophores in compartmentalized biological systems such as lipid bilayers, we have also used the method to resolve the emission spectra of a two-component mixture of fluorophores commonly used in biological studies which undergo partition between water and a micellar phase.

Fluorescein↗

PubMed1988

Emphysema in the Blotchy mouse: a morphometric study.

Inheritance of the Blotchy allele at the X-chromosomal Mottled locus of mice results in changes in the lung which resemble emphysema. Previous studies using measurements of mean linear intercept have recognized emphysema in the hemizygous, Blo/Y, male and homozygous, Blo/Blo, female, but not in the heterozygous, Blo/+, female. The aim of this study was to develop a rapid, accurate method for analysis of emphysema and to establish whether it would identify emphysema in the heterozygote. Lungs from wild type and outbred Blo mice were inflated with fixative at a pressure of 25 cm and then sectioned and stained. Transect lengths across air spaces were measured using computerized image analysis and the results were plotted as histograms. Data were also expressed as cumulative frequencies (ogives) and subjected to statistical analysis by the non-parametric Kolmogorov-Smirnov test. Emphysema was shown by significantly increased (P less than 0.001) transect lengths in the Blo/Blo female and Blo/Y male compared with the wild type controls. The heterozygous Blo/+ mice form an intermediate group significantly different (P less than 0.001) from the wild and blotchy mice. The sensitivity of the method is illustrated by the fact that the Blo/+ female formed an intermediate group between wild type and the Blo/Y male and Blo/Blo female.

Animals↗

PubMed1988

Comparison of elastolytic activity in lung lavage from current, ex- and non-smokers.

Cigarette smokers have an increased risk of developing a wide variety of lung diseases compared to non-smokers, and there have been many studies of the possible biochemical changes underlying this increased susceptibility. However, although epidemiological and physiological studies have shown that in the ex-smoker, the risk of smoking-related lung diseases falls between that of current and non-smokers, the biochemical and cellular mechanisms responsible for this intermediate status have not been investigated. In the present study, therefore, the extracellular elastolytic activities in lung lavage fluid from current, ex- and non-smokers have been compared. Elastolytic enzyme activity was investigated, since it is significantly elevated in lung lavage from smokers, and because it has been implicated in the development of pulmonary emphysema. In the subjects studied, extracellular elastolytic activities in lung lavage from ex-smokers were intermediate between those from current and non-smokers. There was no correlation between the time of abstinence from smoking, or the number of pack-years smoked and the extracellular elastolytic activities in ex-smokers' lung lavage. Elastolytic activity may remain elevated in ex-smokers' lungs for a number of reasons, including the persistence of particulate matter which may activate phagocytic cells on the lung surface. The possible significance of the raised elastolytic activity remains to be fully determined.

Adolescent↗

PubMed1988

The effect of human heart-lung transplantation upon breathing at rest and during sleep.

We have assessed the contribution of intrathoracic pulmonary nerves to the control of breathing in humans. During relaxed wakefulness and during sleep the level, pattern and variability of breathing have been quantified in 8 healthy patients 1 month to 2 years after combined heart--lung transplantation. These data have been compared with similar data from both of 2 matched control groups; either healthy normal controls, or healthy patients after heart transplantation alone. We found no significant differences in the mean levels of respiratory variables between the 3 groups either during relaxed wakefulness or sleep. There were no significant differences between groups (other than would be expected by chance alone) either in the variability of breathing, or in the shapes of the frequency distributions of respiratory variables during these states. There were no respiratory disorders associated with sleep nor any disturbances in blood gases in any group. We conclude that in man breathing is remarkably normal, during relaxed wakefulness and during sleep, after chronic pulmonary denervation. When the ventilatory demands are minimal the human ventilation system functions normally in the absence of a control loop involving pulmonary proprioceptors and the medullary respiratory centres.

Adolescent↗

PubMed1988

The effect of lung inflation on breathing in man during wakefulness and sleep.

To determine whether the Hering-Breuer inflation reflex could be demonstrated in the presence and absence of behavioral influences on breathing, lung inflation was performed via the tracheal stoma in eleven laryngectomized subjects: seven seated at rest with their eyes closed and six recumbent during their deepest non-rapid eye movement sleep. Laryngectomized subjects were chosen for study since their permanent tracheal stoma and absence of a glottis abolished the sensation of inflation in the upper airways, avoided problems with glottic closure and allowed simple, airtight connection to respiratory apparatus. At rest awake, inflation volumes of 500-3050 ml caused no reproducible apnea. During EEG-documented sleep, the inflation reflex was tested on 75 occasions using inflation volumes of 540-2100 ml. On the 66 occasions not associated with subject arousal inflations exceeding approximately 1 L produced apnea terminated by inspiration; greater volumes gave longer apneas. At the end of the study the subjects were woken and retested; no reproducible apnea was found. We conclude that the Hering-Breuer inflation reflex can be demonstrated above the resting tidal volume range in adult man in the absence of the behavioral control of breathing.

Humans↗

PubMed1988

Ventilation and breathlessness on maximal exercise in patients with interstitial lung disease after local anaesthetic aerosol inhalation.

1. The ventilatory response to maximal incremental exercise and the accompanying sensation of breathlessness were studied after the inhalation of 0.9% sodium chloride (saline) and 5% bupivacaine aerosols in six patients with interstitial lung disease. 2. The adequacy of airway anaesthesia induced by bupivacaine aerosol was confirmed by the absence of the cough reflex to 5% citric acid aerosol on completion of exercise. 3. All subjects first performed a trial exercise test to familiarize them with the procedure and to assess the degree of arterial oxygen desaturation on exercise. In subsequent tests, supplementary oxygen was given to maintain the saturation at 95% or above. 4. Airway anaesthesia had no effect on the ability to perform exercise as assessed by maximum workload, CO2 production or heart rate. No significant changes were seen on the pattern of breathing, minute ventilation or end-tidal PCO2 on exercise. There was, however, a small but statistically significant increase in ventilation related to CO2 production (VE/VCO2) at the end of exercise. 5. There was a tendency for breathlessness to be increased by airway anaesthesia but this did not reach statistical significance. 6. These results provide no evidence that vagal afferent activity is responsible for the abnormal ventilatory response to exercise in patients with interstitial lung disease. The perception of breathlessness in these patients was not diminished by anaesthesia of the airway.

Aerosols↗

PubMed1988

Effect of hyperoxia and hypoxia on exercise-induced breathlessness in normal subjects.

1. The subjective changes accompanying alterations in inspired oxygen concentration during heavy exercise have been investigated single blind, in normal subjects. 2. In particular, the intensity of the sensation of breathlessness was quantified using a visual analogue scale and changes were compared with those in objective ventilatory measures. 3. Eleven subjects performed three steady-state work-load exercise tests on different days and 100% O2, 15% O2 or air were randomly administered for a fixed interval during each test. 4. Compared with air breathing, all subjects felt less breathless during 100% O2 breathing, and ten of them felt more breathless when inspiring 15% O2; these changes were reversed on return to air breathing. 5. During and after 100% O2, the time course of changes in breathlessness was similar to those for ear arterial oxygen saturation and minute ventilation such that it could be a secondary response to either. However, during and after inspiration of 15% O2, changes in breathlessness occurred relatively more quickly than those in ventilation, more closely reflecting changes in oxygen saturation; this suggests that hypoxia, per se, could contribute to the genesis of this sensation. 6. Individual variability in breathlessness responses to exercise and changes in inspired oxygen concentration did not correlate with objective ventilatory changes; neither were changes in breathlessness in the group particularly associated with changes in respiratory frequency or tidal volume.

Adult↗

PubMed1988

Interleukin-1 and tumour necrosis factor cause hypotension in the conscious rabbit.

1. The cardiovascular effects of intravenous injections of interleukin-1 (IL-1) and tumour necrosis factor (TNF) have been investigated in the conscious rabbit. They have been compared with the effects of bacterial lipopolysaccharide (LPS) because both IL-1 and TNF are released from macrophages by LPS. 2. IL-1, TNF and Escherichia coli J5-LPS all caused hypotension when given intravenously in a dose with low mortality. The time course of the hypotension caused by IL-1 and LPS was similar, although the maximal fall in mean blood pressure occurred earlier after IL-1. TNF produced a more sustained fall in blood pressure. Hypotension was not accompanied by a compensatory tachycardia after any of the test substances. Hypotension was associated with a fever after TNF, hypothermia after LPS and no significant change in temperature after IL-1. 3. The packed cell volume did not change during hypotension in any of the study groups, implying that the hypotension was not due to fluid loss resulting from increased capillary permeability. 4. IL-1 and TNF are candidates for the role of effectors of LPS-induced hypotension.

Animals↗

PubMed1988

The effects of exercise and subject age on pulsed Doppler measurements of left ventricular ejection in normal man.

Pulsed Doppler measurements of ascending aortic blood velocity and acceleration were made in a group of normal subjects on exercise. The aims of the study were: (1) to document the normal response to exercise and its variability at various ages as a baseline for future studies in abnormal subjects, and (2) to investigate the accuracy and reproducibility of these noninvasive measurements. Doppler measurements were related to oxygen consumption in normal subjects aged between 22 and 69 years, during a submaximal 4 min incremental cycle exercise protocol. Computer-aided ensemble averaging of digital spectral data was used to reduce the effects of noise and respiratory variations in the signals. The mean relationship between cardiac output (Q) and oxygen consumption (Vo2) was Q = 5.75 Vo2 + 4.22 1 min-1, r = 0.84 in subjects aged under 45 years, compared to Q = 6.16 Vo2 + 3.87 1 min-1, r = 0.65 in older subjects; this difference was not significant. These values are similar to those previously described in invasive studies. There was a wide range of individual responses especially in the older subjects. These inter-subject differences probably reflect true physiological differences between subjects rather than methodological errors because they were consistent on repeated testing in the same individual, similar differences occurred in heart-rate responses between individuals where Doppler errors do not apply, and inter-subject variability of similar magnitude was found in comparable studies using invasive methods. Peak velocity (PV) rose from 73 +/- 10 cm s-1 at a Vo2 of 0.4 1 min-1 to 101 +/- 11 cm s-1 at a Vo2 of 1.21 min-1 in subjects aged under 45 years; corresponding values in the older subjects were significantly lower at 48 +/- 12 and 64 +/- 10 cm s-1 respectively. Maximum acceleration was also significantly higher at rest and on exercise in subjects under 45 years compared to older subjects. Despite these differences, stroke volume and cardiac output responses showed no significant age dependence, suggesting that differences in ejection velocity are due to increasing aortic cross-sectional area with age. The wide variety of individual responses found suggests an underlying variability in the arteriovenous oxygen difference on exercise between subjects.

Adult↗

PubMed1988

Ventilatory and circulatory responses at the onset of exercise in man following heart or heart-lung transplantation.

1. Ventilatory and cardiovascular responses to the onset of voluntary and electrically induced leg exercise were studied in six patients following heart transplantation and five following heart-lung transplantation; the results were compared between the patient groups and also with responses from a group of normal subjects. 2. Oxygen consumption, carbon dioxide production and ventilation and its components were measured over two 30 s periods prior to, and two 30 s periods following, the onset of exercise. Relative changes in stroke volume and cardiac output were derived from ensemble-averaged Doppler measurements of ascending aortic blood velocity over the same 30 s periods. 3. None of the groups of subjects showed any significant differences in responses to voluntary exercise compared to electrically induced exercise of similar work pattern and intensity. 4. Compared to normal controls, the transplanted subjects showed higher resting heart rates which did not increase at the onset of exercise; stroke volume increased, but less than in the normal subjects. The resulting cardiac output increases in the transplanted subjects were minimal compared to the normal subjects. 5. Ventilation and oxygen uptake increased immediately and with similar magnitude in all three groups. 6. These results show that in the same individual it is possible to have an appropriate ventilatory response to the onset of exercise in the presumed absence of a normal corticospinal input to the exercising muscles (electrically induced exercise) and afferent neural information from the lungs and heart, and in the absence of a normal circulatory response to exercise. The mechanisms underlying this ventilatory response remain undetermined.

Adult↗

PubMed1988

Is neutrophil elastase associated with elastic tissue in emphysema?

To test the role of elastase in the pathogenesis of emphysema human neutrophil elastase (HNE) was localised by electron microscopy using an immunogold staining technique. Specific localisation of HNE to elastic tissue in emphysema did not occur, but non-specific binding of immunoglobulin G (IgG) to elastic tissue in emphysematous and normal lung tissue, which was completely blocked by the non-immune serum that was homologous to the gold labelled second antibody, was found. HNE was also present, however, in the granules of neutrophils in the same sections. Non-specific labelling associated with elastin was probably due to binding of IgG to the high numbers of hydrophobic and charged regions known to be present in this molecule, and it is concluded that our findings do not support the existence of high concentrations of elastase in association with elastin in emphysematous lung tissue.

Aged↗

PubMed1988

Bronchial reactivity to methacholine after combined heart-lung transplantation.

The operation of combined heart-lung transplantation results in acute denervation of the heart, lungs, and airways below the level of the trachea. The bronchoconstrictor response to inhaled methacholine of 12 recipients of heart-lung transplants was compared with that of 12 recipients of heart transplants having similar medication and 12 normal subjects. The median dose of methacholine that produced a reduction of at least 20% in the FEV1 (PC20) for the recipients of heart-lung transplants (8 mg/ml) was significantly lower than that for the recipients of heart transplants (64 mg/ml) and normal subjects (greater than 64 mg/ml). The increased airway reactivity may be related to the effects of chronic pulmonary denervation or subclinical inflammation in the airways. The effect of denervation on the response to full inspiration during bronchoconstriction was studied in six patients with heart-lung transplants by means of partial and maximal forced expiratory manoeuvres. Four showed bronchodilation after a deep breath, indicating that this response can occur after extrinsic pulmonary denervation in man. The patients with heart-lung transplants described a "tight" sensation in the anterior chest during bronchoconstriction, indicating that this sensation is not dependent on pulmonary innervation.

Adolescent↗

PubMed1988

Abolition of methacholine induced bronchoconstriction by the hyperventilation of exercise or volition.

Total pulmonary resistance was measured from continuous records of flow and oesophageal pressure in five normal subjects on three separate days before and after inhalation of methacholine. The dose of methacholine produced, on average, a fivefold increase in airway resistance. Immediately after methacholine inhalation the subjects underwent a progressive exercise test on a cycle ergometer (day 1) or voluntary hyperventilation (day 2) or remained resting (day 3). On the first day during exercise pulmonary resistance fell rapidly to baseline levels within two to three minutes and remained there for the 10 minute duration of the exercise. On day 2 voluntary reproduction of the same level and pattern of ventilation as during exercise resulted in a similar fall of resistance. On the third day, when the subjects remained at rest, pulmonary resistance remained raised for 10 minutes. It is concluded that the bronchodilator effects of exercise can be explained by the increased ventilation rather than the exercise itself, but with much smaller tidal volumes than have previously been thought necessary to reduce drug induced bronchoconstriction.

Adult↗