Search PubMed⌕ Search

Biomedical subjects

S L Hill

Publications and source records attributed to S L Hill.

At least 19 recordsLinked to original sources

Modelling Southern Ocean ecosystems: krill, the food-web, and the impacts of harvesting.

The ecosystem approach to fisheries recognises the interdependence between harvested species and other ecosystem components. It aims to account for the propagation of the effects of harvesting through the food-web. The formulation and evaluation of ecosystem-based management strategies requires reliable models of ecosystem dynamics to predict these effects. The krill-based system in the Southern Ocean was the focus of some of the earliest models exploring such effects. It is also a suitable example for the development of models to support the ecosystem approach to fisheries because it has a relatively simple food-web structure and progress has been made in developing models of the key species and interactions, some of which has been motivated by the need to develop ecosystem-based management. Antarctic krill, Euphausia superba, is the main target species for the fishery and the main prey of many top predators. It is therefore critical to capture the processes affecting the dynamics and distribution of krill in ecosystem dynamics models. These processes include environmental influences on recruitment and the spatially variable influence of advection. Models must also capture the interactions between krill and its consumers, which are mediated by the spatial structure of the environment. Various models have explored predator-prey population dynamics with simplistic representations of these interactions, while others have focused on specific details of the interactions. There is now a pressing need to develop plausible and practical models of ecosystem dynamics that link processes occurring at these different scales. Many studies have highlighted uncertainties in our understanding of the system, which indicates future priorities in terms of both data collection and developing methods to evaluate the effects of these uncertainties on model predictions. We propose a modelling approach that focuses on harvested species and their monitored consumers and that evaluates model uncertainty by using alternative structures and functional forms in a Monte Carlo framework.

Animals↗

Evaluation of the AMPLATZER vascular plug for embolization of peripheral vascular malformations associated with congenital heart disease.

OBJECTIVE: The purpose of this study is to evaluate the recently FDA-approved AMPLATZER Vascular Plug in the embolization of vascular lesions associated with congenital heart disease (CHD). BACKGROUND: Fistulas and arteriovenous malformations have been occluded using various devices. The AMPLATZER Vascular Plug is a self-expandable, cylindrical device, used for embolization in the peripheral vasculature. METHODS: A total of 84 vessels in 52 patients with CHD from 11 centers were occluded with 89 AMPLATZER Vascular Plugs, delivered through a coronary guide catheter in various vascular sites, including collaterals, pulmonary arterio-venous and coronary artery fistulas, transhepatic tracts, central shunts, patent ductus arteriosus (PDA), and excluded hepatic vein. Complete vessel occlusion was demonstrated within 10 min in 94% of patients. RESULTS: There was no device embolization, vascular disruption, or procedure-related complication. One vascular plug implanted in a large type C PDA required surgical removal followed by PDA ligation, after 5 weeks from successful implant because of significant residual flow through the device. CONCLUSIONS: The AMPLATZER Vascular Plug is an effective transcatheter occlusion device in the embolization of a wide variety of vascular lesions associated with CHD. Based on our early experience, caution should be used when considering the Vascular Plug as a closure device for large PDA.

Adolescent↗

Exercise training and inspiratory muscle training in patients with bronchiectasis.

BACKGROUND: Bronchiectasis is a chronic suppurative lung disease often characterised by airflow obstruction and hyperinflation, and leading to decreased exercise tolerance and reduced health status. The role of pulmonary rehabilitation (PR) and inspiratory muscle training (IMT) has not been investigated in this group of patients. METHODS: Thirty two patients with idiopathic bronchiectasis were randomly allocated to one of three groups: PR plus sham IMT (PR-SHAM), PR plus targeted IMT (PR-IMT), or control. All patients (except the control group) underwent an 8 week training programme of either PR or PR plus targeted IMT. Exercise training during PR was performed three times weekly at 80% of the peak heart rate. IMT was performed at home for 15 minutes twice daily over the 8 week period. RESULTS: PR-SHAM and PR-IMT resulted in significant increases in the incremental shuttle walking test of 96.7 metres (95% confidence interval (CI) 59.6 to 133.7) and 124.5 metres (95% CI 63.2 to 185.9), respectively, and in endurance exercise capacity of 174.9% (95% CI 34.7 to 426.1) and 205.7% (95% CI 31.6 to 310.6). There were no statistically significant differences in the improvements in exercise between the two groups. Significant improvements in inspiratory muscle strength were also observed both in the PR-IMT group (21.4 cm H2O increase, 95% CI 9.3 to 33.4; p = 0.008) and the PR-SHAM group (12.0 cm H2O increase, 95% CI 1.1 to 22.9; p = 0.04), the magnitude of which were also similar (p = 0.220). Improvements in exercise capacity were maintained in the PR-IMT group 3 months after training, but not in the PR-SHAM group. CONCLUSION: PR is effective in improving exercise tolerance in bronchiectasis but there is no additional advantage of simultaneous IMT. IMT may, however, be important in the longevity of the training effects.

Breathing Exercises↗

Haemophilus parainfluenzae infection of respiratory mucosa.

The pathogenicity of Haemophilus parainfluenzae (Hpi) in the respiratory tract is unclear, in contrast to the accepted pathogenicity of its close relative non-typable H. influenzae. We have investigated the interaction of two Hpi isolates with the mucosa of adenoid and bronchial tissue organ cultures. The adherence of bacteria to the mucosa of organ cultures, the effect of broth culture filtrates on human nasal epithelium, and interleukin (IL)-8 production by A549 cell cultures was investigated. Hpi 4846 adhered infrequently in clusters of pleomorphic cocco-bacilli to areas of epithelial damage, mucus and unciliated cells in adenoid organ culture experiments at 24 h, but not bronchial mucosa. Hpi 3698 was seen in only one adenoid and no bronchial organ cultures at 24 h. In separate experiments, Hpi 3698 was cleared more rapidly from the centre of the adenoid organ culture and was not cultured at 24 h. Although not adhering to the mucosa at 24 h, Hpi 3698, but not Hpi 4846, caused an increase in the amount of epithelial damage in both types of organ culture. Broth culture filtrates of both strains caused immediate slowing of ciliary beat frequency that progressed, and disrupted epithelial integrity. Dialysed culture filtrates of both strains stimulated IL-8 production by A549 cells, with the culture filtrate of Hpi 3698 being most potent. We conclude that two strains of Hpi varied in their adherence to adenoid tissue, and neither adhered to bronchial tissue. These results lead us to speculate that Hpi is only likely to be a pathogen in the lower respiratory tract when impaired airway defences delay bacterial clearance.

Bronchi↗

Resolution of bronchial inflammation is related to bacterial eradication following treatment of exacerbations of chronic bronchitis.

BACKGROUND: Recent studies of the role of bacteria in chronic bronchitis have shown that bacterial colonisation is associated with enhanced inflammation and that purulent acute exacerbations of chronic bronchitis (AECB) are associated with bacteria and characterised by increased inflammation. Changes in bronchial inflammation in response to the success or failure of bacterial eradication following AECB were therefore studied. METHODS: Bacterial quantitative culture and sputum markers of inflammation (myeloperoxidase (MPO), neutrophil elastase, leukotriene B4 (LTB4), sol:serum albumin ratio, and secretory leukoprotease inhibitor) were measured in patients presenting with culture positive purulent AECB and repeated 10 days and 2 months later. 41 patients provided sputum sufficient for both bacteriology and assessment of inflammation at baseline and day 10, and 46 provided sufficient sample for bacteriology, 40 of which could also be analysed for inflammation at 2 months (when clinically stable). RESULTS: At day 10, 17 of the 41 patient samples had a positive bacterial culture. In the stable state, 18 of the 46 samples had a positive culture, but with a significantly lower bacterial load than at presentation. Although there was no difference between the groups at presentation, the concentration of MPO was lower (p<0.05) in those in whom bacteria were eradicated by day 10 than in those with persisting bacteria. The LTB4 concentration was similarly lower (p<0.001) in those in whom bacteria were eradicated than in those with persistent bacteria. In the stable clinical state the concentrations of both MPO and LTB4 were lower in those in whom bacteria were eradicated than in patients with persisting bacteria. CONCLUSION: Resolution of bronchial inflammation following AECB is related to bacterial eradication. Those in whom bacteria continue to be cultured in their sputum have partial resolution of inflammation which may reflect continued stimulation by the reduced bacterial load.

Adult↗

The incremental shuttle walking test in elderly people with chronic airflow limitation.

BACKGROUND: There is a concern that comorbidity or frailty in older people could limit the usefulness of currently available exercise tests for chronic lung disease. This study evaluated the feasibility and reproducibility of the incremental shuttle walking test (SWT) in people aged 70 years or over, compared exercise tolerance with other disability markers, and assessed whether the SWT is responsive to change after bronchodilators. METHODS: Fifty elderly patients with chronic airflow limitation (CAL) and 32 controls without airflow limitation attempted the SWT before and after combined nebulised salbutamol/ipratropium bromide. Subjects also completed the Nottingham Extended Activities of Daily Living index (NEADL) and the London Handicap score (LHS). RESULTS: Forty four subjects with CAL (88%) and 29 controls (84%) completed the SWT, including many with co-morbidities. Two week repeatability was good and the SWT was strongly associated with EADL (r=0.51, p<0.001) and LHS (r=0.43, p<0.004), but only weakly with forced expiratory volume in 1 second (FEV1) (r=0.31, p=0.05). Subjects with CAL walked a mean distance of 177.7 m compared with 243.3 m in controls (p<0.001); following bronchodilator therapy the distance walked increased in the CAL group by 13.2% (p=0.009). CONCLUSION: The SWT is a feasible and reproducible measure of exercise tolerance in elderly people with and without airflow obstruction and correlates with other markers of disability. It is sensitive to change following bronchodilation in subjects with CAL, although the change correlates less well with improvements in FEV1. Overall, these results suggest that the SWT might be an appropriate measure to assess interventions in elderly people.

Administration, Inhalation↗

Experimental autoimmune myocarditis in A/J mice is an interleukin-4-dependent disease with a Th2 phenotype.

Myocarditis in humans is often associated with an autoimmune process in which cardiac myosin (CM) is a major autoantigen. Experimental autoimmune myocarditis (EAM) is induced in mice by immunization with CM. We found that EAM in A/J mice exhibits a Th2-like phenotype demonstrated by the histological picture of the heart lesions (eosinophils and giant cells) and by the humoral response (association of IgG1 response with disease and up-regulation of total IgE). Blocking interleukin (IL)-4 with anti-IL-4 monoclonal antibody (mAb) reduced the severity of EAM. This reduction in severity was associated with a shift from a Th2-like to a Th1-like phenotype represented by a reduction in CM-specific IgG1; an increase in CM-specific IgG2a; an abrogation of total IgE response; a decrease in IL-4, IL-5, and IL-13; as well as a dramatic increase in interferon (IFN)-gamma production in vitro. Based on the latter finding, we hypothesized that IFN-gamma limits disease. Indeed, IFN-gamma blockade with a mAb exacerbated disease. The ameliorating effect of IL-4 blockade was abrogated by co-administration of anti-IFN-gamma mAb. Thus, EAM represents a model of an organ-specific autoimmune disease associated with a Th2 phenotype, in which IL-4 promotes the disease and IFN-gamma limits it. Suppression of IFN-gamma represents at least one of the mechanisms by which IL-4 promotes EAM.

Animals↗

Vascular surgeons--do they make a difference in peripheral vascular disease?

BACKGROUND: The purpose of this study was to quantitate the effect of surgeons with added qualifications in general vascular surgery on aortic and peripheral vascular surgery performed in a community hospital. METHODS: We performed a retrospective study covering a 22-year period and comparing indications, procedures, and results of surgeons who had added qualifications in general vascular surgery with those of board certified general and thoracic surgeons in a private hospital. In Period I (1975-1982), there were 702 vascular procedures all performed by thoracic (65%) and general (35%) surgeons. In Period II (1982-1997), there were 2590 vascular procedures performed by vascular surgeons (73%), general surgeons (7%), and thoracic surgeons (20%). A further comparison was done to examine the results of surgeons with added qualifications in general vascular surgery with board certified general and thoracic surgeons within Period II. RESULTS: The volume and frequency of different types of vascular surgery changed significantly from Period I to Period II with lower extremity prosthetic reconstructions decreasing from 12% to 8.2% and autogenous lower extremity bypasses increasing from 15% to 36%. The percentage of distal reconstructions increased significantly from 27% of the total vascular surgeries in Period I to 44.3% in Period II. In Period II, vascular surgeons operated on older patients, had decreased mortality, decreased length of stay, and performed more distal bypasses than board certified general and thoracic surgeons. CONCLUSIONS: The development of vascular surgery as a separate specialty appears to have had a beneficial effect on the types of vascular surgery and the results when compared in a contemporaneous or retrospective fashion.

Age Factors↗

Incremental shuttle walk test in the assessment of patients for heart transplantation.

OBJECTIVE: To compare the incremental shuttle walk test (ISWT) with treadmill exercise testing (TT) derived measurement of peak oxygen consumption (peak VO(2)) in patients undergoing assessment for cardiac transplantation. DESIGN: Prospective comparison. All investigations occurred during a single period of admission for transplant assessment. SETTING: Single UK cardiothoracic transplantation unit. PATIENTS: 25 patients recruited (21 men). Mean age was 53 years. INTERVENTIONS: Patients underwent two TT of peak VO(2) using the modified Naughton protocol and three (one practice) ISWT. Investigations were performed on consecutive days. MAIN OUTCOME MEASURES: Main outcome measures were repeatability of TT and ISWT assessments; relation between peak VO(2) and distance walked in the ISWT; and receiver operating characteristic (ROC) analysis to establish a distance walked in the ISWT that predicted which patients would have a peak VO(2) greater than 14 ml/min/kg. RESULTS: Both the ISWT and the TT were highly reproducible. Following the first practice walk, mean (SD) ISWT distances were 400.0 (146) m (ISWT2) and 401.3 (129) m (ISWT3), r = 0.90, p < 0.0001. Mean peak VO(2) by TT was 15.2 (4.4) ml/kg/min (TT1) and 15.0 (4.4) ml/kg/min (TT2), r = 0.83, p < 0.0001. The results revealed a strong correlation between distance covered in the ISWT and peak VO(2) obtained during TT (r = 0.73, p = 0.0001). ROC analysis showed that a distance walked of 450 m allowed the selection of patients with a peak VO(2) of over 14 ml/min/kg. CONCLUSIONS: This work confirms the utility of the ISWT in the assessment of exercise capacity in patients with severe heart failure undergoing assessment for cardiac transplantation. ISWT may provide a widely applicable surrogate measure for peak VO(2) estimation in this population. Shuttle distance walked may therefore allow the convenient, serial assessment of patients with heart failure before referral for transplantation.

Exercise Test↗

Relationship between airway inflammation and the frequency of exacerbations in patients with smoking related COPD.

BACKGROUND: Patients with more frequent exacerbations of chronic obstructive pulmonary disease (COPD) may have increased bronchial inflammation. Airway inflammation was measured in patients who had been thoroughly investigated with full pulmonary function testing, thoracic HRCT scanning, and sputum microbiology to examine further the relationship between exacerbation frequency and bronchial inflammation. METHODS: Airway inflammation (spontaneous sputum sol phase myeloperoxidase (MPO), elastase, leukotriene (LT)B(4), interleukin (IL)-8, secretory leukoprotenase inhibitor (SLPI), protein leakage) and serum levels of C reactive protein (CRP) were compared in 40 patients with stable, smoking related COPD, divided into those with frequent (> or =3/year) or infrequent (< or =2/year) exacerbations according to the number of primary care consultations during the preceding year. The comparisons were repeated after excluding eight otherwise clinically indistinguishable patients who had tubular bronchiectasis on the HRCT scan. RESULTS: Patients with frequent (n=12) and infrequent (n=28) exacerbations were indistinguishable in terms of their clinical, pulmonary function, and sputum characteristics, CRP concentrations, and all of their bronchial inflammatory parameters (p>0.05). The patients without evidence of tubular bronchiectasis (n=32) were equally well matched but the sputum concentrations of SLPI were significantly lower in the frequent exacerbators (n=8) in this subset analysis (p<0.05). CONCLUSIONS: There are several clinical features that directly influence bronchial inflammation in COPD. When these were carefully controlled for, patients with more frequent reported exacerbations had lower sputum concentrations of SLPI. This important antiproteinase is also known to possess antibacterial and antiviral activity. Further studies are required into the nature of recurrent exacerbations and, in particular, the regulation and role of SLPI in affected individuals.

Aged↗

Symptom resolution assessed using a patient directed diary card during treatment of acute exacerbations of chronic bronchitis.

BACKGROUND: Acute exacerbations of chronic bronchitis are common and the presenting symptoms vary, although it is not clear how this should influence management. From a health care perspective, an understanding of the speed of symptom resolution is of importance to determine the success of treatment or when a change is indicated because of treatment failure. METHODS: The response of 63 patients treated at home for exacerbations of chronic bronchitis was assessed using a patient directed diary card incorporating sputum characteristics and symptoms. Treatment was given according to the nature of the sputum at presentation; patients with purulent sputum received an antibiotic for 5 or 10 days (randomised, double blind) whereas patients with mucoid sputum received high dose inhaled steroid or placebo for 14 days (randomised, double blind). RESULTS: The mean (SE) total diary card score at presentation was significantly higher in the purulent group than in the mucoid group (19.7 (0.9) v 16.3 (0.9); mean difference -3.4 (95% CI -6.1 to -0.7), p<0.05). In the purulent group sputum colour and volume improved rapidly and in both groups the mean (SE) total diary card score had improved by the fifth day of treatment to 13.0 (0.7) in the purulent group (mean difference -6.6 (95% CI -8.8 to -4.4), p<0.001) and 14.6 (0.8) in the mucoid group (mean difference -1.7 (95% CI -4.0 to 0.8), p<0.05), which was no longer significantly different from the stable state. Diary card scores did not differ significantly between patients who received antibiotics for 5 or 10 days in the purulent group or between patients who received inhaled fluticasone or placebo in the mucoid group. CONCLUSIONS: Exacerbations of chronic bronchitis associated with purulent sputum have significantly worse symptoms at presentation than those with mucoid sputum. In both groups these symptoms resolve rapidly so that by the fifth day of treatment they are no different from the stable state. No significant effect was found on symptom resolution of antibiotic duration (5 v 10 days) in the purulent group or of inhaled fluticasone in the mucoid group, which resolved without antibiotics. Larger numbers may be required to demonstrate a statistically (if not clinically) significant difference.

Acute Disease↗

Assessment of airway neutrophils by sputum colour: correlation with airways inflammation.

BACKGROUND: Airway inflammation, with recruitment of neutrophils to the airway lumen, results in purulent secretions and a variety of potential adverse consequences for patients with chronic bronchitis and bronchiectasis. We hypothesised that gradations of sputum colour would correlate directly with the myeloperoxidase content of sputum and with various other indicators of the activity and consequences of bronchial diseases. METHODS: To test this hypothesis, we quantified sputum colour by reference to a sensitive nine point colour chart and correlated this assessment with indices of a number of inflammatory mediators in sputum. RESULTS: The results indicate that standardised visual measurements of sputum colour correlated strongly with myeloperoxidase, interleukin 8, leucocyte elastase (both activity and total quantity), sputum volume, protein leak, and secretory leucocyte proteinase inhibitor (p<0.001 for all). In addition, there was a strong direct correlation between leucocyte elastase and both myeloperoxidase (p<0.003) and sputum volume (p<0.001), but a strong negative correlation with secretory leucocyte proteinase inhibitor (p<0.001). CONCLUSIONS: These results indicate that sputum colour graded visually relates to the activity of the underlying markers of bronchial inflammation. The results of this simple visual analysis of sputum provides guidance concerning underlying inflammation and its damaging potential. It also provides a useful scientific tool for improving the monitoring of chronic airways diseases and response to treatment.

Biomarkers↗

Exercise capacity predicts health status in alpha(1)-antitrypsin deficiency.

Resting lung function is only weakly related to health status in chronic obstructive pulmonary disease, reflecting the multifactorial causes of impairment and the heterogeneous nature of the condition. The current study examined whether density mask analysis of high-resolution computed tomography (HRCT) or exercise capacity were better surrogates for health status in a well-defined, homogeneous group of patients with alpha(1)-antitrypsin deficiency (PiZ). Twenty-nine patients with predominantly lower zone emphysema on HRCT were studied. Exercise was assessed by incremental treadmill (V O(2) peak) and shuttle walking tests (ISWT) and health status by the St. George's Respiratory Questionnaire (SGRQ) and SF-36. Although lower zone expiratory HRCT was related to exercise capacity (rho = -0.64 and -0.63 for V O(2) peak and ISWT, respectively, p < 0.001), multiple regression analysis suggested that FEV(1) was a marginally better predictor (rho = -0.64 and -0.65, p < 0.001). HRCT also related significantly to health status (rho = -0.37 for SGRQ activity, p < 0.05), although again FEV(1) showed a stronger relationship (rho = -0.43, p = 0.01). However, exercise capacity was the best predictor of health status with the ISWT accounting for up to 55% of the variability seen in SGRQ total and up to 53% of the SF-36 domain scores (physical functioning). Although both HRCT and lung function relate to health status, exercise capacity is the best predictor of patients disability in these patients with predominantly lower zone emphysema.

Exercise Test↗

Effect of pre-loading oral glucosamine HCl/chondroitin sulfate/manganese ascorbate combination on experimental arthritis in rats.

The therapeutic effect of a nutritional supplement consisting of a combination of glucosamine hydrochloride (FCHG49), purified sodium chondroitin sulfate (TRH122), and manganese ascorbate (GCM)3 was investigated in the rat model of collagen-induced autoimmune arthritis (CIA). The GCM compound was mixed with a palatable nutritional paste (Nutri-cal [NC]). Oral administration of the NC/GCM compound was initiated in 26 rats 10 days before immunization and continued until the day of sacrifice. One group of 12 control rats was given no oral agents; a second group of 12 control rats received NC only. Evaluations included arthritis index (AI) scoring by three independent evaluators, histologic index (HI) scoring of lesions, T-cell proliferation, and serological studies for antibody classes and subclasses. Both the AI and HI criteria showed a statistically significant reduction in the prevalence of CIA in rats pretreated with the NC/GCM (54%) compared to the combined control groups (96%, chi2 analysis P = 0.001). Rats fed the NC/GCM also exhibited a significant decrease in the severity of autoimmune arthritis in both the AI and HI compared to control Group 2 (immunized-NC) (chi2 analysis P < 0.05). Histological studies verified the decreased incidence of arthritis in the NC/GCM group compared to control Group 2. GCM treatment failed to alter T-cell proliferation and antibody production to bovine type-II collagen, indicating that its effects are not due to alteration of the antigen-specific immune response.

Animals↗

High-resolution computed tomography scanning in alpha1-antitrypsin deficiency: relationship to lung function and health status.

The development of computed tomography (CT) has enabled emphysema to be assessed noninvasively. Objective quantification of lung density correlates well with lung function in patients with chronic obstructive pulmonary disease and has been shown to be a sensitive tool for monitoring disease progression. In order to determine the clinical impact of changes seen on high-resolution computed tomography (HRCT), the relationship between the objective quantification of emphysema on HRCT, lung function and health status in 111 patients with alpha1-antitrypsin deficiency was examined (PiZ). The degree of HRCT scan abnormality correlated well (p<0.001 for all comparisons) with forced expiratory volume in one second (r = -0.60- -0.75), specific airway conductance (r = -0.67-0.76), residual volume/total lung capacity (r = 0.46-0.58) and transfer factor of the lung for carbon monoxide (r = -0.64- -0.81). In addition, the CT scans correlated (p<0.001) with health status as assessed by the St. George's Respiratory Questionnaire (SGRQ total: r = -0.38-0.50) and the Short-Form health survey (e.g. physical functioning: r = -0.39-0.54). In summary, other workers have shown high-resolution computed tomography to be a sensitive indicator of disease progression. This study confirms the relationship between high-resolution computed tomography and lung physiology, and suggests the relationship is even stronger in patients with predominantly lower zone pan-lobular emphysema than in usual chronic obstructive pulmonary disease. High-resolution computed tomography also relates to patients disability and impairment as defined by health status questionnaires and, therefore, should be considered as an alternative outcome measure particularly in alpha1-antitrypsin deficiency.

Adult↗

Changes in bronchial inflammation during acute exacerbations of chronic bronchitis.

There are little data describing noncellular changes in bronchial inflammation during exacerbations of chronic bronchitis. The relationship between sputum colour and airway inflammation at presentation has been assessed during an exacerbation in patients with chronic bronchitis and a primary care diagnosis of chronic obstructive pulmonary disease. Sputum myeloperoxidase, neutrophil elastase, leukotriene B4 (LTB4), interleukin-8 (IL-8), sol:serum albumin ratio and serum C-reactive protein were measured in patients presenting with an exacerbation and mucoid (n = 27) or purulent sputum (n = 42). Mucoid exacerbations were associated with little bronchial or systemic inflammation at presentation, and sputum bacteriology was similar to that obtained in the stable state. Purulent exacerbations were associated with marked bronchial and systemic inflammation (p < 0.025 for all features) and positive sputum cultures (90%). Resolution was related to a significant reduction in LTB4 (p < 0.01), but no change in IL-8, suggesting that LTB4 may be more important in neutrophil recruitment in these mild, purulent exacerbations. In the stable state, IL-8 remained higher in patients who had experienced a purulent exacerbation (2p < 0.02). The presented results indicate that exacerbations of chronic bronchitis, defined by sputum colour, differ in the degree of bronchial and systemic inflammation. Purulent exacerbations are related to bacterial infection, and are associated with increased neutrophilic inflammation and increased leukotriene B4 concentrations.

Acute Disease↗

The transition from viral to autoimmune myocarditis.

Myocarditis offers a unique opportunity to study the factors contributing to its transition from a viral infection to an autoimmune disease. In this article, we review recent studies on the role of nitric oxide (NO), gamma interferon (IFN-gamma) and interleukin 12 (IL-12) in the progression from early (viral) to late (autoimmune) phases of myocarditis induced by Coxsackievirus B3 (CB3) in highly susceptible (A.CA) and moderately susceptible (B10.M) mice. NO plays a paradoxical role, being protective in early stages but detrimental later in the course of disease. Treatment with antibody to IFN-gamma reduced early disease, but had little effect on the severity of cardiac lesions at later times. Treatment with recombinant (r) IL-12 significantly reduced the autoimmune cardiac lesions in moderately susceptible B10.M mice, but had no measurable effect in highly susceptible A.CA animals. These studies provide evidence that the profile of inflammatory mediators produced early in the course of viral infection determines the later development of autoimmune disease.

Animals↗

Nasal administration of cardiac myosin suppresses autoimmune myocarditis in mice.

OBJECTIVES: This study was designed to examine whether myocarditis induced in a mouse model can be effectively suppressed by nasal administration of cardiac myosin (CM). BACKGROUND: Myocarditis in humans often follows viral infection and is accompanied by evidence of an autoimmune response to CM. Treatment has been hampered by the fact that measures undertaken to reduce the autoimmune response often enhance the viral infection. Delivery of antigen via nasal route has been shown to induce antigen-specific tolerance and suppress certain autoimmune diseases in animal models. METHODS: Myocarditis was induced in A/J mice by two subcutaneous injections of CM emulsified in complete Freund's adjuvant. Nasal instillation of CM (200 microg/mouse) or vehicle buffer was carried out three days before the first subcutaneous injection (day -3). The effect of nasal instillation of CM on cardiac histopathology, cytokine production by splenocytes, and antibody response was examined three weeks after the first subcutaneous injection (day 21). RESULTS: Nasal administration of CM effectively reduced the severity of myocarditis. Consistent with the histological findings, the levels of interleukin-2 (IL-2), tumor necrosis factor-alpha, and IL-1beta produced by splenocytes in response to CM were significantly decreased. In addition, the serum levels of IgE and IgG1 anti-myosin antibodies were suppressed. However, the levels of transforming growth factor-beta (TGF-beta) and CM-specific IgA antibodies were not affected. CONCLUSIONS: Taken together, our results do not support active suppression through upregulation of TGF-beta, IL-4, and IL-10 as a mechanism of tolerance, but favor anergy or deletion of both Th1 and Th2 autoreactive T cells.

Administration, Intranasal↗