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Biomedical subjects

G J Gibson

Publications and source records attributed to G J Gibson.

At least 55 records · Page 3Linked to original sources
PubMed2001

A novel autosomal dominant distal myopathy with early respiratory failure: clinico-pathologic characteristics and exclusion of linkage to candidate genetic loci.

We describe a novel autosomal dominant myopathy presenting in mid-adult life with tibialis anterior weakness. We carried out a detailed clinical assessment of 24 individuals spanning three generations, documenting pathologic features of the muscles in 7 of the 11 affected individuals, including an autopsy study on one case. The second generation of affected individuals presented at an earlier age, and the disease progressed more rapidly than in the first generation. Lung function tests revealed progressive global respiratory muscle weakness detectable from the time of presentation, with preferential diaphragmatic involvement in some cases. Hip girdle and shoulder girdle weakness appeared later in the disease course. We observed a striking correlation between the clinical and pathological features. Clinically unaffected muscles had minimal pathologic change. Fiber splitting, eosinophilic inclusions, and vacuoles with basophilic rims were seen in moderately affected muscles, and fat and fibrous connective tissue replaced muscle fibers in the severely involved muscles. The inclusions were Congophilic and reacted with antibodies to desmin, beta-amyloid, and phosphorylated tau protein. The disease was not linked to any of the known loci associated with distal myopathies, confirming that the disorder in this family is both genetically and phenotypically distinct.

Adult↗
PubMed2000

Tests of airway function in detecting and monitoring treatment of obliterative bronchiolitis after lung transplantation.

BACKGROUND: This study evaluated different tests of airway function in detection of obliterative bronchiolitis. It included analysis of spirogram within the time domain in patients with and without obliterative bronchiolitis (OB) after heart lung and lung transplantation. The purpose of this analysis is to evaluate which tests are of greatest value for early recognition of OB. METHODS: The coefficient of variation of different airway function tests was calculated in 13 patients who had no evidence of OB and 12 patients who developed OB post-transplantation. In the patients with OB the effect of treatment with total lymphoid irradiation (TLI) was investigated by comparing the rate of change of lung function before and after TLI. Several lung function tests were used. RESULTS: The measurements that showed the least variation were FEV(1), FVC, PEF, FEV(1)/FVC ratio and the Moment Ratio, while those which became abnormal earlier were FEV(1), FEV(1)/FVC, MEF(50), and the first moment. Additionally, the tests that became abnormal in a higher proportion of patients were MMEF, MEF(50), MEF(75), and the first moment. CONCLUSIONS: The results o thi support the use of simple spirometric indices for the detection of OB. In the patients with OB the rates of decline of lung function were significantly attenuated by treatment with TLI as determined by several different tests. KEYWORDS: obliterative bronchiolitis, lung transplantation, moments analysis, airway function tests, total lymphoid irradiation

Adolescent↗
PubMed2000

Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo.

As a result of fatigue, bone sustains microdamage, which is then repaired by bone-remodeling processes. How osteoclastic activity is targeted at the removal of microdamaged regions of bone matrix is unknown. In the current studies, we tested the hypothesis that changes in osteocyte integrity, through the initiation of regulated cell death (apoptosis), are associated with fatigue-related microdamage and bone resorption. Ulnae of adult rats were fatigue-loaded to produce a known degree of matrix damage. Osteocyte integrity was then assessed histomorphometrically from terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labeling (TUNEL)-stained sections to detect cells undergoing DNA fragmentation associated with apoptosis; toluidine blue-stained sections were used for secondary morphological confirmation. Ten days after loading, large numbers of TUNEL-positive osteocytes were found in bone surrounding microcracks and in bone surrounding intracortical resorption spaces (approximately 300% increases over controls, p < 0.005). TUNEL labeling in loaded ulnae at sites distant from microcracks or resorption foci did not differ from that in control bone. Osteocytes in toluidine blue-stained sections showed equivalent trends to TUNEL-stained sections, with significant increases in pyknotic nuclei and empty lacunae associated with microcracks and intracortical resorption spaces. TUNEL-positive osteocytes were observed around bone microdamage by 1 day after loading (p < 0.01 relative to baseline), and their number remained elevated throughout the entire experimental period. Increases in empty lacunae and decreases in normal osteocyte numbers were observed over time as well. These studies show that (1) osteocyte apoptosis is induced by bone fatigue, (2) this apoptosis is localized to regions of bone that contain microcracks, and (3) osteoclastic resorption after fatigue also coincides with regions of osteocyte apoptosis. The strong associations between microdamage, osteocyte apoptosis, and subsequent bone remodeling support the hypothesis that osteocyte apoptosis provides a key part of the activation or signaling mechanisms by which osteoclasts target bone for removal after fatigue-induced matrix injury.

Animals↗
PubMed1999

Predicting variability in biological control of a plant-pathogen system using stochastic models.

A stochastic model for the dynamics of a plant-pathogen interaction is developed and fitted to observations of the fungal pathogen Rhizoctonia solani (Kühn) in radish (Raphanus sativus L.), in both the presence and absence of the antagonistic fungus Trichoderma viride (Pers ex Gray). The model incorporates parameters for primary and secondary infection mechanisms and for characterizing the time-varying susceptibility of the host population. A parameter likelihood is developed and used to fit the model to data from microcosm experiments. It is shown that the stochastic model accounts well for observed variability both within and between treatments. Moreover, it enables us to describe the time evolution of the probability distribution for the variability among replicate epidemics in terms of the underlying epidemiological parameters for primary and secondary infection and decay in susceptibility. Consideration of profile likelihoods for each parameter provides strong evidence that T. viride mainly affects primary infection. By using the stochastic model to study the dependence of the probability distribution of disease levels on the primary infection rate we are therefore able to predict the effectiveness of a widely used biological control agent.

Models, Biological↗
PubMed1999

Objective benefit of laser palatoplasty for non-apnoeic snoring.

Laser palatoplasty (LPP) is widely used for the treatment of non-apnoeic snoring, despite the lack of objective data supporting its use. We report measurements of snoring in a prospective study of LPP, and we compare the results with a previous study of uvulopalatopharyngoplasty (UPPP). Twenty patients with an apnoea/hypopnoea index < 20 h-1 underwent LPP for habitual snoring. Overnight sound recordings were compared before and 6 months after operation using three objective indices; L, (the level exceeded by the loudest 1% of sound), L5 (the level exceeded by the loudest 5% of sound) and P50 (% total sleep time above 50 dBA). The subjective impression of snoring severity (Wilcoxon test, P < 0.001), and objective indices L1 and P50 (t-test, P < 0.001) showed significant reductions after LPP. The mean change in L1 was 4.2 dBA, comparable to that we previously reported for UPPP, while P50 was reduced to less than one-third its preoperative value. No other sleep variables changed significantly following LPP. We conclude that LPP results in reduced snoring volume comparable to that following UPPP.

Acoustics↗
PubMed1999

Psychometric performance before and after laser palatoplasty for non-apnoeic snoring.

Psychometric tests are an objective way of examining cognitive functioning, and have shown impairment in patients with obstructive sleep apnoea. Non-apnoeic snoring may cause reduced concentration, but psychometric tests have been used rarely in this population. We investigate whether their use can demonstrate an improvement in cognitive performance in 20 non-apnoeic snorers following Laser Palatoplasty (LPP). The subjects completed psychometric tests, Beck Anxiety and Depression Inventories and an Epworth Sleepiness Scale on two occasions before LPP and once postoperatively. The only index to show any significant change with LPP was the Beck Depression Inventory (P < 0.005), which was reduced by a mean of 1.6 units following surgery. There was also a highly significant improvement in information processing between the preoperative tests, for which no explanation could be found. Our results suggest that commonly applied psychometric tests are unable to demonstrate significant improvements following surgery for non-apnoeic snoring. However, we have demonstrated for the first time a significant reduction in depression following surgery, which is evidence that snoring is more than a social nuisance.

Cognition↗
PubMed1998

Comparison of the functional results of single lung transplantation for pulmonary fibrosis and chronic airway obstruction.

BACKGROUND: Single lung transplantation (SLT) is now a treatment option for patients with both pulmonary fibrosis and advanced chronic airway obstruction. Lung function after transplantation might be expected to be different in these two groups of patients because of the effect of the remaining native lung, but the implications of these differences have not been fully explored. METHODS: The functional results of a stable population of 20 patients (13 chronic airway obstruction, seven pulmonary fibrosis) after SLT with no evidence of obliterative bronchiolitis were analysed. The differences between the two populations in the interrelations between and determinants of total lung capacity (TLC), subdivisions of lung volume, airway function (spirometry, maximum expiratory flow volume curves, and moments analysis of the spirogram) respiratory mechanics (PV curves and maximal respiratory pressures), CO transfer factor (TLCO) and the distribution of perfusion, ventilation and volume of the transplanted and native lungs were compared. RESULTS: Total lung capacity after SLT (TLCpost) was normal in the patients with pulmonary fibrosis (mean (SE) 103.9 (6.9)% predicted) but remained significantly elevated in patients with airway obstruction (126.4 (4.4)%. Forced expiratory volume in one second (FEV1) and vital capacity (VC) improved to similar values after SLT in both groups with a final VC of 76.8 (5.9)% and 66.7 (3.9)% in patients with fibrosis and airway obstruction, respectively. Maximum expiratory flows were generally lower and moments analysis of the spirogram showed slower lung emptying with significantly greater second and third moments (alpha 2 and alpha 3) in patients with airway obstruction. Relative ventilation and perfusion of the transplanted lung were both greater in both populations but relative ventilation of the transplanted lung was significantly greater in patients treated for airway disease than in those with pulmonary fibrosis. TLCO was also significantly higher in patients who had received a transplant for chronic airway obstruction. CONCLUSIONS: These results suggest that differences in the functional results of SLT for airway disease and pulmonary fibrosis are relatively minor. In this series the native hyperinflated lung in chronic airway disease was not more disadvantageous to overall function than the native lung in pulmonary fibrosis. However, tests of lung function based on the terminal portion of the forced spirogram are likely to be less sensitive for the detection of obliterative bronchiolitis in patients who have received a transplant for advanced airway obstruction than in those with pulmonary fibrosis.

Female↗
PubMed1998

Airway hyperresponsiveness in asthma. Not just a problem of smooth muscle relaxation with inspiration.

Airway hyperresponsiveness in asthma has been attributed to impaired ability of deep inspiration (DI) to stretch airway smooth muscle. We have retested this hypothesis by comparing the responses to methacholine of 10 asthmatic and 10 control subjects. After each dose subjects breathed tidally without deep inspiration for 4 min, followed by a forced partial expiration from which flow was measured at a constant volume, 35% baseline VC (Vp 35). This index is independent of both DI and increases in end-inspiratory lung volume (EILV). EILV increased significantly more in the asthmatic group than in the control group (15.0 versus 2.5% of baseline VC, p = 0. 019), a factor that if not taken into account would tend to mask the difference in the two responses. Comparisons were made after a cumulative dose of 50 microg methacholine, which was the highest dose common to all subjects. The asthmatic response was significantly greater than that seen in the control group, with reductions to 25.9 and 72.1% of baseline Vp 35, respectively (p = 0. 0007). We conclude that the sensitivity of asthmatic airways to methacholine is greater than that of normal airways even when DI is prohibited. Therefore, the hyperresponsiveness of asthmatic airways is not attributable simply to an inability of DI to stretch airway smooth muscle.

Adult↗
PubMed1998

Interobserver variability in recognizing arousal in respiratory sleep disorders.

Daytime sleepiness is a common consequence of repeated arousal in obstructive sleep apnea (OSA). Arousal indices are sometimes used to make decisions on treatment, but there is no evidence that arousals are detected similarly even by experienced observers. Using the American Sleep Disorders Association (ASDA) definition of arousal in terms of the accompanying electroencephalogram (EEG) changes, we have quantified interobserver agreement for arousal scoring and identified factors affecting it. Ten patients with suspected OSA were studied; three representative EEG events during each of light, slow-wave, and rapid-eye-movement (REM) sleep were extracted from each record (90 events total) and evaluated by experts in 14 sleep laboratories. Observers differed (ANOVA, p < 0.001) in the number of events scored as arousal (totals ranged from 23 to 53 of the 90 events). Overall agreement was moderate (kappa = 0.47), but it was best for events during slow-wave sleep, moderate for REM, and poor for light sleep (kappa = 0.60, 0.52, and 0.28, respectively). Agreement was unrelated to arousal duration. We conclude that the ASDA definition of arousal is only moderately repeatable. Account should be taken of this variability when results from different centers are compared.

Adult↗