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Biomedical subjects

G J Gibson

Publications and source records attributed to G J Gibson.

At least 91 records · Page 5Linked to original sources

Respiratory muscle activity and oxygenation during sleep in patients with muscle weakness.

Patients with respiratory muscle weakness show nocturnal hypoventilation, with oxygen desaturation particularly during rapid eye movement (REM) sleep, but evidence in individuals with isolated bilateral diaphragmatic paresis (BDP) is conflicting. The effect of sleep on relative activity of the different respiratory muscles of such patients and, consequently, the precise mechanisms causing desaturation have not been clarified. We have studied eight patients, four with generalized muscle weakness and four with isolated BDP during nocturnal sleep with measurements including oxygen saturation and surface electromyographic (EMG) activity of various respiratory muscle groups. Nocturnal oxygenation correlated inversely with postural fall in vital capacity, an index of diaphragmatic strength. During REM sleep, hypopnoea and desaturation occurred particularly during periods of rapid eye movements (phasic REM sleep). In most subjects, such events were "central" in type and associated with marked suppression of intercostal muscle activity, but two subjects had recurrent desaturation due to "obstructive" hypopnoea and/or apnoea. Expiratory activity of the external oblique muscle was present whilst awake and during non-rapid eye movement (NREM) sleep in seven of the eight subjects in the semirecumbent posture. This probably represents an "accessory inspiratory" effect, which aids passive caudal diaphragmatic motion as the abdominal muscles relax at the onset of inspiration. Expiratory abdominal muscle activity was suppressed in phasic REM sleep, suggesting that loss of this "accessory inspiratory" effect may contribute to "central" hypopnoea. We conclude that, in patients with muscle weakness, nocturnal oxygenation correlates with diaphragmatic strength.(ABSTRACT TRUNCATED AT 250 WORDS)

Electromyography↗

Breathing pattern awake and asleep in patients with myotonic dystrophy.

Patients with myotonic dystrophy often have an irregular pattern of breathing at rest, implying abnormality of breathing control. No central medullary defect has been found in such patients. We postulated that irregular breathing in myotonic dystrophy due to abnormal central respiratory output would persist during slow-wave sleep. We examined the patterns of breathing whilst awake and asleep in seven patients with myotonic dystrophy, seven similarly weak nonmyotonic subjects and seven normal controls. Polysomnography was performed, and the coefficients of variation (CoV) of the breath intervals were analysed during different stages of sleep. The myotonic group showed significantly greater variation in breath intervals than the other two groups whilst awake (median CoV 37 vs 18% for nonmyotonics) and during light sleep (31 vs 13%). This difference was not evident during slow-wave sleep (median CoV 12 vs 9% in nonmyotonic). We conclude that irregular breathing in patients with myotonic dystrophy whilst awake and during light sleep, does not persist during slow-wave sleep. These results suggest that "behavioural" influences play a role in the abnormal breathing pattern found in myotonic dystrophy. The source of the irregular breathing is unlikely to be found in the medulla, but may originate from forebrain influences.

Adult↗

Immunochemical characterization of feline and human N-acetylgalactosamine 4-sulfatase.

Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI; MPS VI) is a disorder which results from a deficiency in the lysosomal associated enzyme N-acetylgalactosamine 4-sulfatase (4-sulfatase). A feline model of human MPS VI has previously been described and provides a system for the evaluation of enzyme replacement therapy protocols. As a preliminary study to human 4-sulfatase enzyme replacement therapy in feline we have compared the immunochemical properties of human and feline 4-sulfatase. By SDS-PAGE the molecular mass of purified feline and human 4-sulfatase were similar under both reducing and nonreducing conditions. There was, however, a detectable conformation difference between human and feline 4-sulfatase indicating some structural variation. Feline 4-sulfatase reacted weakly with a panel of monoclonal antibodies in an immunobinding assay (interacting with 4-sulfatase in free solution), but the same monoclonal antibodies reacted strongly with feline 4-sulfatase in an immunoquantification assay where the feline 4-sulfatase was bound to a polyclonal antibody (which presumably induces a conformation change in the feline 4-sulfatase to closer approximate the structure of human 4-sulfatase). A monoclonal antibody which selectively reacts with human 4-sulfatase has been used to develop an assay suitable for evaluating human 4-sulfatase enzyme replacement in cat tissues.

Animals↗

Frequency of chronic obstructive airways disease and pulmonary hypertension in patients with acute inferior myocardial infarction with or without right ventricular infarction.

OBJECTIVE: Factors influencing the incidence of right ventricular infarction among patients with acute inferior myocardial infarction have not yet been fully established. Chronic obstructive airways disease and right ventricular hypertrophy were suggested as possible predisposing factors but no definite evidence was shown. This study analyses the frequency of chronic obstructive airway disease and of Doppler assessed pulmonary hypertension among patients with acute inferior myocardial infarction with or without right ventricular infarction. DESIGN AND PATIENTS: Sixty consecutive patients with acute inferior myocardial infarction were prospectively enrolled into the study. MEASUREMENTS: Standard 12-lead ECG with right precordial leads (V3-6R) were recorded on admission to the Coronary Care Unit and on days 2 and 3. Doppler echocardiography was performed within 48 h after the onset of myocardial infarction and repeated 6 weeks later together with a pulmonary function test. Routine biochemical and clinical data were collected. RESULTS: Right ventricular infarction occurred in 35% of patients with acute inferior myocardial infarction. No differences in respiratory indices of chronic obstructive airways disease or in Doppler echocardiography parameters of pulmonary hypertension were revealed among patients with and without right ventricular infarction. Peak total creatine kinase level and creatine kinase myocardial isoenzyme levels were higher in patients with right ventricular infarction than in those without (2925 +/- 1321 vs. 1682 +/- 1216 U/l; P < 0.001 and 207 +/- 108 vs. 127 +/- 102 U/l; P < 0.05, respectively). CONCLUSIONS: In the course of acute inferior myocardial infarction, the frequencies of chronic obstructive airways disease and/or pulmonary hypertension were not higher among patients with right ventricular infarction than among those without right ventricular infarction. Thus, history of chronic obstructive airways disease and/or pulmonary hypertension do not necessitate specific precautions in respect of right ventricular infarction.

Aged↗

The effect of controlled-release salbutamol on sleep and nocturnal oxygenation in patients with asthma and chronic obstructive pulmonary disease.

Patients with asthma or chronic obstructive pulmonary disease (COPD) may have falls in oxygen saturation at night. We have investigated the effect of a long acting beta agonist (salbutamol CR) on nocturnal oxygen saturation (SaO2) in asthma and COPD. Eleven asthmatic and 14 COPD patients in stable condition were randomly allocated to 8 mg salbutamol CR or placebo twice daily in a double-blind, cross-over study. FEV1 at entry was 71.5% predicted in the asthmatic patients and 36% predicted in the COPD group. Each treatment period lasted 7 days, at the end of which measurements of ventilatory function and detailed sleep studies were performed. There was a significant improvement in morning FEV1 in the asthmatic patients when on active treatment and a small, but non-significant improvement in the COPD group. Sleep architecture and oxygenation were similar on placebo and on active treatment in both groups. We conclude that salbutamol CR has no significant effect on nocturnal oxygenation or sleep pattern in patients with mild asthma or moderately severe COPD.

Albuterol↗

Automated measurement of the cyclic activity of respiratory muscles.

A microcomputer-based system developed for the automated analysis of the electromyogram (EMG) recorded from respiratory muscles in a variety of situations is described. In addition, an assessment of the performance of the system is presented, along with data relating intercostal EMG activity to ribcage movement in seated subjects. Studies were performed on sixteen normal subjects--non smokers, mean (+/- SD) age 31 (+/- 6) years, mean (+/- SD) mass 78 (+/- 8) kg--of which fifteen studies proved suitable for analysis. Each study lasted for a period of five minutes, during which time recordings of intercostal EMG, ribcage postero-anterior displacement (RCPA) and airflow were made. For every breath taken by each of the subjects, the peak integrated EMG activity (iEMGpeak) was measured both by hand and by the automated system. The automated and manual measurements of iEMGpeak, which ranged from 0.0 to 91.3 microV, differed by only -0.82 +/- 3.34 microV (mean +/- SD). The index iEMGpeak and two additional indices of iEMG activity (iEMGmean, iEMGarea) were evaluated with respect to RCPA, a measure of overall respiratory activity. The indices of iEMG were observed to show an exponential dependence on RCPAamp, the amplitude of ribcage motion. Following a log transformation to linearise the relationship, the correlation of each index with RCPAamp was evaluated; iEMGpeak and iEMGarea correlated similarly with RCPAamp (no significant difference at 5% level), but iEMGmean was found to be a significantly different (p < 0.001) and poorer correlate. We conclude that the automated analysis of respiratory iEMG as described in this paper can provide results showing consistency with manual measurement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Lack of effect of H2-receptor antagonists on the pharmacokinetics of alcohol consumed after food at lunchtime.

The possibility of a pharmacokinetic interaction between H2-receptor antagonists and alcohol consumed at lunchtime, was investigated in 24 healthy non-alcoholic male subjects, each receiving ranitidine 150 mg four times daily, cimetidine 400 mg four times daily, famotidine 20 mg four times daily and placebo in an open, four-way cross-over study. The subjects consumed 50 g alcohol after a standard lunch on the eighth day of dosing with study medication. Blood samples taken during the 6 h after alcohol consumption were analysed for alcohol concentrations by gas liquid chromatography using head space analysis. None of the H2-receptor antagonists had any statistically significant effects on any of the pharmacokinetic parameters for alcohol. Mean Cmax (95% CI) results for ranitidine were 547 (516, 580), cimetidine 531 (501, 563), famotidine 563 (530, 598) and placebo 529 (499, 561) mg l-1.

Adult↗

The use of sound recording and oxygen saturation in screening snorers for obstructive sleep apnoea.

It is desirable to screen snoring patients for obstructive sleep apnoea (OSA) prior to surgical treatment. We postulated that the addition of a sound profile would increase the value of overnight oxygen saturation (SaO2) as a screening method. Thirty-nine polysomnographic studies including sound level measured by calibrated meter were performed on snorers being considered for uvulopalato-pharyngoplasty (UPPP). Polysomnography showed an apnoea/hypopnoea index (AHI) > or = 15 per hour of sleep in seven subjects. Two experienced observers independently, without knowledge of other data, classified paper records of SaO2 alone and SaO2 plus sound level obtained during polysomnography as OSA 'unlikely', 'equivocal' or 'definite'. The addition of sound to SaO2 reduced the number of equivocal results from 14 to six and increased the number classified as 'definite' or 'unlikely'. The sensitivity of oximetry +/- sound increased as the threshold AHI used in the definition of OSA increased; addition of sound improved recognition of mild OSA without impairing specificity.

Adult↗

Communicating the diagnosis of lung cancer.

In order to assess their reaction to the information given, 50 patients underwent a semi-structured interview with a social worker within 1 week of having been told the diagnosis of lung cancer. There were 32 men and 18 women with a mean age of 63 (range 38-82) years. Thirty-eight (76%) belonged to Registrar General social class IV or V, and 45 (90%) had left school at the age of 15 years. Two patients were unaware of the diagnosis despite having been told that they had lung cancer. Two patients would have preferred not to have been told the diagnosis and two were unsure, while 46 (92%) felt that telling them the diagnosis truthfully had been correct. No patient felt that they had been given too much information, but 13 (26%) indicated a lack of information about prognosis. Despite being told 'bad news', 31 (62%) felt more reassured after their interview with the doctor, 5 (10%) felt less reassured, and 14 (28%) were uncertain. Twenty-one (42%) patients were experiencing a sense of guilt or regret at having smoked. Many patients had concerns about specific symptoms which they expected to suffer. In general, patients wanted to be told their diagnosis truthfully and required a high level of information. Many patients felt reassured by the discussion of such details.

Adult↗

The relationship of quantitative epidermal growth factor receptor expression in non-small cell lung cancer to long term survival.

Increased expression of epidermal growth factor receptor (EGFr) has been reported in non small cell lung cancers (NSCLC) when compared to normal lung. We have examined post-operative survival in 19 surgically treated patients with NSCLC who had full characterisation of EGFr on primary tumour membrane preparations from resection specimens. There were ten squamous, seven adeno and two large cell carcinomas. The median concentration of high affinity sites was 31 fmol per mg of protein (4-1532) and the median dissociation constant (Kd) of these high affinity sites was 2.3 x 10(-10) per mol (1.2-30 x 10(-10)). Seven patients survived over 5 years. Twelve patients died between 8.5 and 55 months from the time of surgery. When > 5 year survivors were compared to non-survivors there was no difference as regards tumour size or stage, or as regards age or sex. The survivors had a median concentration of high affinity EGFr sites of 16.1 fmol mg-1 protein compared to a median concentration of 68.6 fmol mg-1 protein in the non-survivors (P = 0.01 Wilcoxon test). No long term survivor had > 35 fmol mg-1 protein of receptor. Thus EGFr quantitation may give independent prognostic information in NSCLC and help to select patients for adjuvant therapy after surgery. These results need confirmation in a larger prospective study.

Adenocarcinoma↗

Nonstationarity and the measurement of psychophysical response in a visual inspection-time task.

Inspection time (IT) is an index of speed of early visual processing that correlates significantly with measures of higher cognitive ability. An obstacle to the understanding of this important association is the lack of an agreed mechanistic model of the processes involved in IT performance. It is argued here that, whereas in current attempts to model IT processing, stationarity in IT performance is assumed, it is necessary to address this key issue empirically. Two practised subjects undertook 38,400 trials on a standard two-choice visual IT discrimination task. Testing was spread evenly over 60 days. Isotonic regression analysis revealed that both subjects showed nonstationarity in performance over very long periods. The results were not merely due to long-term practice effects; one subject improved in some durations but worsened at others. Therefore, current attempts at modelling in which stationarity in IT performance is assumed must be altered to incorporate the temporal dynamics of IT performance, which might have individual differences.

Cognition↗

Variability in ciliary beat frequency in normal subjects and in patients with bronchiectasis.

BACKGROUND: There is a wide variation in tracheobronchial clearance of inhaled aerosol in normal subjects and in patients with bronchiectasis, but little information is available on the variability in ciliary beat frequency (CBF). METHODS: The variability in CBF was measured in 10 nasal mucosal samples from each of 19 normal controls and 23 stable bronchiectatic subjects. RESULTS: The CBF varied at different mucosal sites in both normal subjects and bronchiectatic patients. Although the CBF of the fastest beating cilia was similar in both groups, the CBF of the slowest beating cilia was, on average, lower and showed greater within subject variation in bronchiectatic than in normal subjects. CONCLUSIONS: There is a wide variation in CBF in nasal mucosal samples and this is significantly wider in bronchiectatic subjects with some cilia beating slowly. This may be a consequence of chronic inflammation or infection.

Adult↗

Ciliary beat frequency in transplanted lungs.

BACKGROUND: Patients with lung transplantation are prone to respiratory infections. Generally this is attributable to the effects of immunosuppressive drugs but mucociliary clearance has been found to be impaired in these subjects. A study was performed to determine whether this finding is accompanied by a reduction in ciliary beat frequency (CBF). METHODS: Six patients who had undergone single lung transplantation for fibrosing lung disease were investigated. CBF was measured in mucosal samples from native and transplanted bronchi by a videophotometry method. RESULTS: The CBF was reduced in the transplanted bronchi in all cases when both fastest and slowest beating cilia were examined. The fastest beating cilia on the native side had a mean (SD) CBF of 12.1 (1.3) Hz compared with 9.6 (2.0) Hz on the transplanted side. The slowest beating cilia also had reduced CBF on the transplanted side. CONCLUSION: In patients with fibrotic lung disease, CBF is reduced in transplanted bronchi in comparison with native bronchi.

Adult↗