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Biomedical subjects

G J Gibson

Publications and source records attributed to G J Gibson.

At least 19 recordsLinked to original sources
PubMed1996

Automated recognition of EEG changes accompanying arousal in respiratory sleep disorders.

Daytime sleepiness and impaired cognitive function can be a consequence of recurrent transient arousal from sleep, associated with abrupt changes in the electroencephalogram (EEG). EEG is normally assessed by trained observers from paper records, but automation offers the advantages of speed and objectivity. We assessed 10 automated indices of EEG activity as potential indicators of arousal. Arousals from light, slow wave and rapid eye movement sleep were studied in 30 subjects. Segments of EEG recorded immediately before and after each arousal were analyzed by automated measurement of 10 EEG indices using a personal computer. We investigated the ability of each index to recognize arousal while rejecting change due to variability during sleep. Nine of the 10 indices showed significant changes with arousal (p < 0.001); the better indices were related to EEG frequency, and 3 were chosen for further study. In these indices, the mean changes with arousal were 3.8 Hz (ZeroCross), 1.7 Hz (Hjorth's Mobility) and 1.2 Hz (FrqMean, an index of central EEG frequency). With none of these three indices were significant differences in performance due to base sleep stage or subject group found. We conclude that detection of arousal is feasible using automated methods that measure simple indices related to the frequency of the EEG waveform.

Adult↗
PubMed1996

British Thoracic Society Sarcoidosis study: effects of long term corticosteroid treatment.

BACKGROUND: Corticosteroids suppress disease activity in pulmonary sarcoidosis and their use produces symptomatic, radiographic, and functional improvement. There is, however, uncertainty regarding their effects on the overall natural history of the condition and long term benefit is unproven. METHODS: Patients with pulmonary radiographic shadowing due to sarcoidosis were recruited in a multicentre study. Those who, in the first six months after entry to the study, neither required prednisolone for symptoms nor showed radiographic improvement were allocated at six months to receive either long term steroid treatment (group L) or selective treatment (group S), with regular assessment over the subsequent five years. Patients in group L were scheduled to receive steroid treatment for at least 18 months with the policy of achieving and maintaining maximal radiographic clearing, while in group S treatment was reserved for use only if warranted by later development of symptoms or deteriorating lung function. Symptoms, radiographic appearances, and respiratory function were assessed periodically during the study. RESULTS: One hundred and forty nine patients were followed: 33 required prednisolone for troublesome symptoms within six months of entry and 58 showed radiographic improvement over this period. The remaining 58 patients were allocated to groups L (n = 27) and S (n = 31). Patients in group L showed greater improvements in symptoms, respiratory function, and radiographic appearances than those in group S, although the differences were not large. After adjusting for differences at the time of allocation, the average difference in vital capacity between groups L and S at final assessment was 9% of the predicted value. Side effects of treatment were frequent but usually mild, necessitating withdrawal in only two individuals. CONCLUSIONS: After excluding those individuals who required steroids for control of symptoms, approximately half of the remaining patients with sarcoidosis and pulmonary shadowing showed spontaneous radiographic improvement during six months of observation. In those in whom the radiograph failed to improve, prolonged steroid treatment with the aim of optimising radiographic appearances resulted in a significantly better long term functional outcome.

Adult↗
PubMed1996

Identification, expression, and biochemical characterization of N-acetylgalactosamine-4-sulfatase mutations and relationship with clinical phenotype in MPS-VI patients.

Maroteaux-Lamy syndrome, or mucopolysaccharidosis type VI (MPS-VI), is a lysosomal storage disorder characterized by the defective degradation of dermatan sulfate due to the deficiency of N-acetylgalactosamine-4-sulfatase (4S). The clinical severity of MPS-VI ranges in a continuum from mildly affected to severely affected patients. Mutations in MPS-VI patient samples were identified by chemical cleavage and direct DNA sequencing of PCR products derived from patient cDNA. Five amino acid substitutions were identified (T92M, R95Q, Y210C, H393P, and L498P), individually introduced into the wild-type 4S cDNA by site-directed in vitro mutagenesis, and transfected into Chinese hamster ovary cells. Three of the five mutations (R95Q, Y210C, and H393P) were observed in >1 of 25 unrelated MPS-VI patients; however, the mutations were not found in 20 control individuals. The residual 4S activity and protein (biochemical phenotype) were determined for each mutant in order to confirm their identity as mutations and to dissect the contribution of each mutant allele to the overall clinical phenotype of the patient. For each patient, the combined biochemical phenotypes of the two 4S mutant alleles demonstrated a good correspondence with the observed clinical phenotype (with the possible exception of a patient who was a compound heterozygote for T92M and L498P). This preliminary correspondence between genotype and the phenotype in MPS-VI may, with further refinement, contribute to the assessment of therapeutic approaches for MPS-VI patients.

Adolescent↗
PubMed1995

Chondrocyte apoptosis in endochondral ossification of chick sterna.

In the process of endochondral ossification, chondrocytes progress through a series of maturational changes, including division and hypertrophy, that culminate in chondrocyte loss and cartilage resorption. From an investigation of morphology, DNA fragmentation and collagen synthesis in the developing chick sterna we have characterized chondrocytes death in this process. Light microscopy of resorbing sterna demonstrated chondrocyte condensation at the interface with the invading vasculature and electron microscopy demonstrated a range of chondrocyte morphologies, including retraction from the pericellular matrix, cytoplasmic and nuclear condensation, and vesiculation suggestive of sequential changes characteristic of apoptosis. Isolation and end-labeling of DNA from chick primary ossification centers demonstrated fragmentation to nucleosome sized units, only in primary ossification centers exhibiting active resorption, and in situ detection of DNA fragmentation showed a restriction to chondrocytes at the interface with invading blood. We conclude that terminal differentiation of chondrocytes results in death by an apoptotic process prior to resorption of the tissue and invasion by blood vessels. The extent of DNA fragmentation correlated closely with the proportion of cells displaying a condensed phenotype in contralateral primary ossification centers and peaked at an early stage of resorption, suggesting that chondrocyte apoptosis may be an initiating event in tissue resorption and vascular invasion. Comparison of DNA fragmentation with expression of the hypertrophic chondrocyte phenotype, as indicated by type X collagen synthesis, suggested that DNA fragmentation was a late event in the process of chondrocyte hypertrophy and probably corresponded with chondrocyte condensation

Animals↗
PubMed1995

Endochondral resorption of chick sterna in culture.

Endochondral resorption is most clearly recognized at the metaphyseal interface of the growth plate with the adjacent vasculature; however, apparently identical processes of endochondral resorption are seen in sites of primary and secondary ossification of the cartilaginous anlage of bones and in ossifying fracture callus. Recent evidence of the expression of the hypertrophic phenotype in osteoarthrotic articular cartilage suggests that endochondral resorption also may be a factor in the loss of articular cartilage in this condition. To investigate the mechanism of endochondral resorption, a model culture system was developed and characterized. The two primary centers of ossification with surrounding cartilage were dissected from embryonic chick sterna prior to (18-day-old embryos) or after (20-day-old embryos) the initiation of resorption. They were cultured either in plastic culture dishes or on chorioallantoic membranes, and resorption was detected by analysis of the loss of types II and X collagen and by histological characterization. Only sterna showing active resorption in vivo were resorbed when cultured on chorioallantoic membrane. The histological appearance of the resorption site and the specificity of resorption to the primary ossification center, seen from both the analysis of loss of collagen and histological observation, suggested that the resorption of sterna cultured on chorioallantoic membrane was similar to that observed in vivo. These studies further indicated that both vascular cells and viable chondrocytes were required for resorption. Susceptibility to resorption could be induced in resistant primary ossification centers by prior culture in the absence of vascular cells, and it is suggested that it results from the accumulation of resorption-susceptible cells and matrix as a result of continued chondrocyte development.

Allantois↗
PubMed1995

Comparison of methods for assessing snoring.

Objective measurements of several sound level indices were made on 32 subjects referred because of snoring and who subsequently underwent uvulopalatopharyngoplasty (UPPP). The measurements were repeated approximately 6 months post-UPPP. The indices were compared with the subjective assessment of snoring by both the subject and his/her bed partner. Correlations between objective and subjective assessments were generally weak and were strongest when the supine posture only was considered. The index which correlated best with subjective assessment was the level which 1% of the sound level samples exceeded.

Abdomen↗
PubMed1995

Objective measurement of the results of uvulopalatopharyngoplasty.

Thirty-two patients undergoing uvulopalatopharyngoplasty (UPPP) for snoring have been studied prospectively using objective measurement of snoring levels. A significant reduction was found, especially in the supine posture. The quantitative reduction was small and correlations between subjective and objective changes in snoring volume were weak.

Adult↗
PubMed1995

Respiratory muscle activity during rapid eye movement (REM) sleep in patients with chronic obstructive pulmonary disease.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD) periods of hypopnoea occur during rapid eye movement (REM) sleep, but the mechanisms involved are not clear. METHODS: Ten patients with stable COPD were studied during nocturnal sleep. Detailed measurements were made of surface electromyographic (EMG) activity of several respiratory muscle groups and the accompanying chest wall motion using magnetometers. RESULTS: Hypopnoea occurred in association with eye movements during phasic rapid eye movement (pREM) sleep. During pREM sleep there were reductions in EMG activity of the intercostal, diaphragm, and upper airway muscles compared with non-REM sleep. Episodic hypopnoea due to partial upper airway occlusion ("obstructive" hypopnoea) was seen consistently in four subjects while the others showed the pattern of "central" hypopnoea accompanied by an overall reduction in inspiratory muscle activity. Although activity of the intercostal muscles was reduced relatively more than that of the diaphragm, lateral rib cage paradox (Hoover's sign) was less obvious during pREM-related hypopnoea than during wakefulness or non-REM sleep. CONCLUSIONS: Hypopnoea during REM sleep in patients with COPD is associated with reduced inspiratory muscle activity. The pattern of hypopnoea may be either "obstructive" or "central" and is generally consistent within an individual. Relatively unopposed action of the diaphragm on the rib cage during REM sleep is not accompanied by greater lateral inspiratory paradox.

Aged↗
PubMed1995

Hormonal and metabolic profiles in subjects with obstructive sleep apnea syndrome and the acute effects of nasal continuous positive airway pressure (CPAP) treatment.

Nocturnal secretion of growth hormone is impaired in patients with obstructive sleep apnea (OSA), but the metabolic consequences have not been reported. We measured blood levels of the hormones insulin, C-peptide, growth hormone, cortisol and glucagon together with the intermediary metabolites of carbohydrate (glucose, pyruvate, lactate, alanine) and lipid metabolism [glycerol, nonesterified fatty acids (NEFA), 3-hydroxybutyrate] in six obese nondiabetic men with OSA on two nights. In the first study, the untreated subjects showed frequent apneas and consequent hypoxemia. The hormone and metabolite concentrations were compared with those obtained on the following night when the subjects were treated effectively with nasal continuous positive airway pressure (CPAP). There were no significant differences in the concentrations of insulin, C-peptide, cortisol or glucagon. We confirmed a marked reduction in growth hormone concentrations in OSA, with a significant increase on the CPAP night. The nocturnal profiles of glucose, pyruvate, lactate, alanine and glycerol showed no differences between the two nights, but concentrations of NEFA and 3-hydroxybutyrate, both products of lipolysis, were significantly greater on the treatment night. Because growth hormone has a lipolytic action, the results suggest that suppression of secretion of growth hormone in untreated OSA results in impaired lipolysis, which is rapidly reversed by nasal CPAP.

Adult↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗