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Biomedical subjects

C McSharry

Publications and source records attributed to C McSharry.

At least 37 records · Page 2Linked to original sources
PubMed1999

Sputum endothelin-1 is increased in cystic fibrosis and chronic obstructive pulmonary disease.

Many patients with cystic fibrosis (CF) have airflow obstruction, with peribronchial and peribronchiolar fibrosis. Endothelin (ET)-1 is a potent bronchoconstrictor with mitogenic activity for airway smooth muscle. Do the levels of ET-1 in sputum support the putative role of ET-1 in contributing to airway remodelling with airflow obstruction in CF? The levels of ET-1 in plasma, saliva and sputum from 12 adult patients with CF not in exacerbation (spontaneous sputum), 17 normal control subjects (induced sputum) and as an additional control population, nine patients with stable chronic obstructive pulmonary disease (COPD) (seven spontaneous sputum) were measured. Total and differential sputum cell counts were performed. Median (interquartile range) sputum ET-1 level was elevated in CF (77.6 (29.0-122.8) pg x mL(-1)) compared to normal subjects (6.00 (2.8-14.8) pg x mL(-1)) and COPD (16.4 (6.8-38.2) pg x mL(-1)), and in COPD compared to normal subjects. There was a slight elevation of plasma ET-1 level in CF (5.3 (3.2-6.0) pg x mL(-1)) compared to normal subjects (3.1 (1.7-4.4) pg x mL(-1)) and COPD (3.3 (2.7-4.2) pg x mL(-1)). Sputum and saliva ET-1 levels were significantly higher than plasma levels in all groups, suggesting local production or release in the respiratory tract. Sputum differential cell counts revealed pronounced neutrophilia in CF and COPD compared to normal subjects. Sputum endothelin-1 concentrations are elevated in cystic fibrosis sputum compared to chronic obstructive pulmonary disease, and in cystic fibrosis and chronic obstructive pulmonary disease compared to normal subjects. The role of endothelin-1 in contributing to airflow obstruction through bronchoconstriction and mitogenesis in cystic fibrosis needs now to be explored.

Adolescent↗
PubMed1998

Fucose-specific adhesins on germ tubes of Candida albicans.

Lectin-like adhesins of hyphal-form Candida albicans were investigated by conventional fluorescence microscopy, fluorescence microscopy with image analysis, spectrofluorimetry and flow cytometry. Labelling was done with neoglycoprotein probes consisting of sugars (fucose, mannose, glucose, galactose, lactose) covalently linked to bovine serum albumin (BSA), which itself was labelled with fluorescein. The fucose probe bound to both the yeast and germ-tube portions of hyphal-form cells, not especially at the tip, but in the adjacent region of the germ-tube portion. Probes with the other sugars did not label the hyphal-form cells. Fucose-probe binding to the cells was optimal at pH 5.0 in citrate buffer, and was a time-dependent reaction requiring 30-60 min and reaching saturation concentration at 100 microg ml(-1). Each hyphal-form cell of C. albicans grown in 199 medium was calculated to have about 2 x 10(7) fucose probe-binding sites. There appeared to be no requirement for Ca2+ or Mg2+ in binding. Binding of the fucose probe to the hyphal-form cells was higher at 37 degrees C than at 22 degrees C or 4 degrees C. Fluorescence intensity of the fucose-labelled yeast forms was not increased over the hyphal-form cells. A germ-tube-deficient mutant when exposed to hyphal-form growth conditions for 2 h showed much less binding of the fucose probe than the wild-type which produced germ tubes. Confirmation of specificity and the need for a carrier molecule was obtained by showing that Fuc-BSA (without fluorescein) effectively inhibited the binding of the fucose probe, although L-fucose itself was inactive, as was Gal-BSA.

Candida albicans↗
PubMed1998

The recent impact of antiretroviral combination therapy on CD4 counts, AIDS and death in HIV-infected persons: routine HIV surveillance in Scotland.

Our aim was to investigate if the clinical benefits of combination antiretroviral therapy recently reported from clinical trials are reproduced in a population-based HIV surveillance scheme. This surveillance scheme is estimated to cover 90% of the HIV-positive population currently under immunological monitoring in Scotland. Our results showed a considerable reduction in new AIDS cases among this group from 107 in 1995 to 59 in 1996 and an estimated 58 in 1997 (allowing for reporting delay). There was a similar fall in deaths from 75 in 1995 to 59 in 1996 and an estimated 24 in 1997. These observations are temporally associated with increasing prescription of antiretroviral therapy in Scotland throughout 1996 and 1997. Examination of those individuals monitored in both 1996 and 1997 showed that from their first CD4 count in 1996 to their first count in 1997 there has been a median gain of 6 CD4 cells/mm3 (95%CI 0-12) compared with a median fall of 27 CD4 cells/mm3 (95%CI -35, -17) for those monitored in both 1995 and 1996. Highest median gains in CD4 cell counts from 1996 to 1997 were seen in those receiving triple or quadruple therapy (median gain 32CD4 cells/mm3). These results are further strengthened by the results of a separate longitudinal analysis showing a highly significant (P < 0.001) effect of treatment on CD4 cell loss with the highest mean CD4 gains being seen in those in triple or quadruple therapy. Our results indicate that the benefits of combination antiretroviral therapy previously seen in clinical trials are being reproduced at a population level. It remains to be seen if these benefits can be sustained in the long term.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Role of heat shock proteins in the pathogenesis of cystic fibrosis arthritis.

BACKGROUND: Arthritis is a well recognised complication of cystic fibrosis. The cause of this arthritis is not yet clear but it is likely to be an immunological reaction to one of the many bacterial antigens to which the lungs are exposed. One such group, the heat shock proteins, (hsp), was investigated. These are immunodominant antigens of a wide variety of infectious microorganisms and have varying amino acid chain sequences, some of which are similar to those found in human tissues. METHODS: Antibodies to human hsp 27 and hsp 90 in the serum of patients with cystic fibrosis, with and without arthritis, and in normal age and sex matched healthy controls were measured. The severity of the cystic fibrosis was assessed by lung function tests and chest radiographs. The nature of the organisms colonising the lungs was determined by bacteriological examination of sputum. RESULTS: Higher mean titres of serum IgG anti-human hsp 27 and hsp 90 antibodies were found in 50 patients with cystic fibrosis than in healthy controls (hsp 27, 0.25 (95% CI 0.19 to 0.33) versus 0.05 (95% CI 0.04 to 0.07); hsp 90, 0.27 (95% CI 0.22 to 0.32) versus 0.11 (95% CI 0.08 to 0.14)). These antibodies were higher in patients in whom the lungs were colonised with Pseudomonas aeruginosa than in those without infection (hsp 27, 0.41 (95% CI 0.17 to 0.63) versus 0.18 (95% CI 0.10 to 0.27); hsp 90, 0.37 (95% CI 0.18 to 0.57) versus 0.22 (95% CI 0.16 to 0.29)). The eight patients with cystic fibrosis with arthritis had higher anti-hsp 27 antibodies (0.48 (95% CI 0.13 to 0.92)) than the 42 patients without arthritis (0.22 (95% CI 0.17 to 0.30)). CONCLUSIONS: These findings suggest that the arthritis associated with cystic fibrosis, despite being seronegative for rheumatoid factor, was associated with more severe lung disease and with a greater inflammatory response to heat shock proteins.

Adolescent↗
PubMed1997

Endothelin-1 levels in induced sputum samples from asthmatic and normal subjects.

BACKGROUND: Endothelin-1 (ET-1) is a potent bronchoconstrictor which may have a role in the pathogenesis of asthma. The levels of ET-1 in saliva, induced sputum, and plasma from asthmatic and non-asthmatic subjects were compared. METHODS: Sputum induction was performed on 28 asthmatic subjects and nine normal volunteers. ET-1 levels were measured in plasma, saliva, and sputum samples and reversed phase high performance liquid chromatography (RP-HPLC) was performed on saliva and sputum samples. RESULTS: ET-1 was present in the following order of concentration in both normal and asthmatic subjects: saliva > sputum > plasma (saliva, median 30.1 and 23.9 pg/ ml, respectively; sputum, median 15.5 and 11.2 pg/ml; plasma, median 3.1 and 3.6 pg/ ml). There were no differences between asthmatic and normal subjects in the levels of ET-1 in each fluid. The levels of ET-1 in asthmatic subjects were not influenced by whether or not they were taking inhaled steroids. RP-HPLC of sputum and saliva confirmed the presence of ET-1 in these fluids. CONCLUSIONS: Levels of ET-1 can be measured in saliva and sputum obtained by sputum induction in asthmatic and healthy subjects and, although no difference was found in basal levels of ET-1 in sputum, saliva and plasma between normal subjects and asthmatics without bronchoconstriction, it is apparent that ET-1 is produced or released locally within the respiratory tract in concentrations higher than those in plasma.

Adult↗
PubMed1997

Investigations on the renin-angiotensin system in acute severe asthma.

The renin-angiotensin system is activated in acute severe asthma. The precise mechanism of activation is at present unknown, but may involve, beta2-agonists, catecholamines or proteases released in airway inflammation. This study aims to identify potential factors involved in the activation of the renin-angiotensin system in acute asthma. Forty asthmatics with severe exacerbations of asthma, assessed by measurement of peak expiratory flow rate (mean (SD) 35 (18)% predicted), oxygen saturation (94 (4)%) and pulse rate (108 (16) beats x min(-1)) were recruited. Nineteen (48%) asthmatics had elevated plasma angiotensin II levels (median (interquartile range) 10.9 (4.3-23.5) pg x mL(-1) (normal range 3-12 pg x mL(-1))) and 10 (25%) had elevated plasma renin concentration (22.0 (10.0-50.0) microU x mL(-1) (normal range 9-50 microU x mL(-1))). Plasma renin and angiotensin II correlated strongly, implying renin-dependent angiotensin II formation. No correlation was found between plasma salbutamol, adrenaline, nor-adrenaline, endothelin-1, histamine, eosinophilic cationic protein, serum angio-tensin-converting enzyme (ACE) activity, total immunoglobulin E (IgE), urea and electrolytes, indicators of the severity of the attack, atopic status, blood pressure and renin or angiotensin II levels. We conclude that although a subpopulation of asthmatics appear to have raised renin and angiotensin II during attacks of acute, severe asthma, the mechanism of activation of the renin-angiotensin system remains unclear.

Acute Disease↗
PubMed1997

Feather mites are potentially an important source of allergens for pigeon and budgerigar keepers.

BACKGROUND: Previous studies on allergy to feathers have not addressed whether organisms living on feathers (mites, lice, moulds) are a source of allergens. OBJECTIVE: To investigate whether feather mites produced allergens of clinical relevance to bird keepers. METHODS: We examined serum IgE responses of 96 pigeon breeders to an extract of feather mites from pigeons (predominantly Diplaegidia columbae), using Western blotting, specific IgE assay using AlaSTAT EIA and RAST inhibition. RESULTS: Feather mites are a major source of soluble proteins derived from feathers, accounting for up to 10% of the total weight of the feather. Forty-three sera had a negative score (0) for anti-feather mite IgE, 27 were weakly positive (1-2) and 26 had strongly positive scores (3-4). Fewer pigeon breeders with scores > or = 3 were asymptomatic than those with negative scores (12 versus 40%), more had late onset symptoms (with or without early onset symptoms: 77% versus 44%) and had IgE antibody against house dust mite (89% versus 23%). Western blotting of eight sera against the extract of Diplaegidia columbae revealed 20 IgE-binding components ranging from 22 to 200 kDa. A high diversity of components was recognized by each serum: arithmetic mean 7 (range 2-14). RAST inhibition indicated feather mites had species-specific epitopes as well as ones that cross-reacted with Dermatophagoides pteronyssinus. CONCLUSION: Strongly-positive AlaSTAT scores to pigeon feather mite were associated with allergic symptoms of late onset in pigeon breeders. We conclude that feather mites are a major source of clinically-relevant allergens for pigeon breeders.

Allergens↗
PubMed1995

Occupational asthma caused by automated salmon processing.

Within 3 months of the opening of a salmon-processing plant in the UK, some workers complained of symptoms suggestive of occupational asthma. A survey of all 291 employees identified 24 (8.2%) with occupational asthma. The employees worked near machines which generated respirable aerosols containing salmon-serum proteins. The IgE response to these proteins was associated with occupational asthma (p < 0.001), with increasing severity of symptoms (p < 0.001), and with working distance from the aerosol source (p = 0.037). The main factor which predisposed to IgE-antibody production and asthma was cigarette smoking (p < 0.001), whereas atopy and a previous allergic history did not. The affected employees were reallocated to a low-exposure worksite and factory ventilation was improved. Eleven showed significant clinical and pulmonary function improvement, and continued in employment. Thirteen who still had symptoms were advised to leave, thereafter becoming symptom-free, and regaining normal respiratory function. Early recognition of symptoms and prompt action to reduce aerosol exposure avoided the long-term reduction in pulmonary functions often associated with occupational asthma.

Adult↗
PubMed1994

Is evidence for homoeopathy reproducible?

We tested, under independent conditions, the reproducibility of evidence from two previous trials that homoeopathy differs from placebo. The test model was again homoeopathic immunotherapy. 28 patients with allergic asthma, most of them sensitive to house-dust mite, were randomly allocated to receive either oral homoeopathic immunotherapy to their principal allergen or identical placebo. The test treatments were given as a complement to their unaltered conventional care. A daily visual analogue scale of overall symptom intensity was the outcome measure. A difference in visual analogue score in favour of homoeopathic immunotherapy appeared within one week of starting treatment and persisted for up to 8 weeks (p = 0.003). There were similar trends in respiratory function and bronchial reactivity tests. A meta-analysis of all three trials strengthened the evidence that homoeopathy does more than placebo (p = 0.0004). Is the reproducibility of evidence in favour of homoeopathy proof of its activity or proof of the clinical trial's capacity to produce false-positive results?

Adult↗
PubMed1994

The IgE and IgG antibody responses to aerosols of Nephrops norvegicus (prawn) antigens: the association with clinical hypersensitivity and with cigarette smoking.

Raised levels of serum IgE antibodies to prawn antigens were found in 15 of 26 seafood factory process workers with respiratory symptoms and in one of 26 case-matched asymptomatic controls (P < 0.001). Raised IgG antibody titres against the same antigens were found in 18 subjects in each symptom grouping, and the median titres of this antibody did not differ significantly between the groups. The prawn-specific IgE antibody response was significantly associated with atopy (IgE antibody response to common allergens) and with a history of cigarette smoking, confirmed by level of serum cotinine, a major nicotine metabolite. Non-atopic non-smokers were unlikely to become sensitized. The titre of the prawn-specific IgE antibody correlated with the duration of exposure and with the duration of symptoms. Discriminant analysis of the serological profile (anti-prawn IgE, total IgE and cotinine) was sufficient to assign individuals correctly into symptomatic or asymptomatic categories in 77% of subjects. The titres of the IgE and IgG antibody responses to prawn antigens did not correlate, and the main factor which seemed to determine the antibody isotype response to these inhaled antigens was cigarette smoking. IgE antibody was produced mainly by smokers, whereas IgG antibody was the predominant isotype produced by non-smokers.

Adolescent↗
PubMed1994

Computed tomographic scanning of the lung in patients with allergic bronchopulmonary aspergillosis and in asthmatic patients with a positive skin test to Aspergillus fumigatus.

BACKGROUND: Allergic bronchopulmonary aspergillosis is a disease of asthmatic patients which may follow a protracted course and result in chronic lung damage such as central bronchiectasis. In asthma uncomplicated by allergic bronchopulmonary aspergillosis, in particular in asthmatic patients with immediate hypersensitivity type skin reactions to Aspergillus fumigatus, the incidence of bronchiectasis is uncertain. METHODS: Computed tomographic (CT) scans were performed in 17 asthmatic patients of mean (SE) age 60.1 (2.5) years, FEV1 49.4 (5.8)% predicted with allergic bronchopulmonary aspergillosis (all with current or previous positive precipitins to A fumigatus) and in 11 asthmatic patients of mean (SE) age 49.5 (5.8) years, FEV1 75.5 (6.5)% predicted, skin test positive for A fumigatus, but without the clinical or serological features of allergic bronchopulmonary aspergillosis (non-allergic bronchopulmonary aspergillosis group). RESULTS: Bronchial dilatation was more common in the group with allergic bronchopulmonary aspergillosis, affecting 14 patients compared with two in the non-allergic bronchopulmonary aspergillosis group. Evidence of bronchiectasis was found in 43 of a possible 102 lobes of patients with allergic bronchopulmonary aspergillosis, compared with three of a possible 66 in the non-allergic bronchopulmonary aspergillosis group. Bronchial wall thickening was common to both, affecting 16 and nine patients respectively. Pleural thickening on CT scanning was common in the group with allergic bronchopulmonary aspergillosis, being noted in 14 patients compared with only three in the non-allergic bronchopulmonary aspergillosis group. CONCLUSIONS: Bronchiectasis is common in allergic bronchopulmonary aspergillosis but occurs only occasionally in asthmatic patients with a positive skin test to A fumigatus but without other features of the disease.

Aspergillosis, Allergic Bronchopulmonary↗
PubMed1993

Measurement of serum arabinitol by gas-liquid chromatography: limitations for detection of systemic candida infections.

The measurement of serum arabinitol in the diagnosis of systemic candidosis was evaluated using a gas-liquid chromatography technique in a cohort of at risk patients. The prevalence of seropositivity was low and did not correlate with evidence of infection. This technique is unlikely to achieve acceptance because it does not discriminate between patients with and without infection; it requires specialised equipment and it is expensive.

Candidiasis↗
PubMed1993

Discriminant analysis of symptom pattern and serum antibody titres in humidifier related disease.

BACKGROUND: The heterogeneous patterns of symptoms among factory workers exposed to aerosols from contaminated air humidifiers were analysed to assess the association between specific symptoms and the serum IgG antibody response to the humidifier water contaminants, and to test the ability of specific symptoms to predict this antibody response. METHODS: Symptoms from 88 factory workers were surveyed by a doctor administered questionnaire and compared with their serum IgG antibody titres to humidifier water contaminants quantified by enzyme immunoassay. RESULTS: The strength of association between individual symptoms and antibody showed that fever, shivering or chills, influenza-like symptoms, or headache were individually significantly associated with the presence and higher titres of antibody. This was also true for those subjects whose symptoms were most pronounced during the first day of the working week. Within each subject's full symptom profile there were significant associations between the description of chest tightness, breathlessness, and wheeze; between headache and influenza like symptoms; between fever and shivering or chills; and between intermittent onset and general tiredness. Discriminant analysis of the full symptom profiles showed that there was maximum information content in five independent parameters, namely, the descriptions of fever, headache, and chest tightness, the timing of their onset, and the readiness to describe miscellaneous symptoms in addition to those in the questionnaire. On the basis of these criteria 72% of subjects could be classified according to their antibody state. Cluster analysis with these five independent parameters described four symptom clusters: one associated with high median antibody levels, one with low, and two with zero median levels. These were, respectively: (1) fever with headache and chest tightness; (2) either no or few symptoms; (3) chest tightness and headache with intermittent onset; (4) headache and miscellaneous symptoms with intermittent onset. CONCLUSIONS: The association between serum antibody titres and specific symptom patterns may identify different categories of disease which constitute the spectrum known as humidifier related disease, and strengthens the hypothesis that antibody may be involved in the pathogenesis of some components of the disease.

Antibodies↗
PubMed1992

Heterogeneity of peripheral blood monocyte populations in human immunodeficiency virus-1 seropositive patients.

Monocytes from human immunodeficiency virus (HIV) patients have an increased heterogeneity of phenotype and function. In a study of 120 HIV patients we have demonstrated that they have normal monocyte differential counts but that with progression of the disease an increasing proportion of monocytes show phenotypic and functional evidence for activation or maturation. A proportion of the monocytes are larger, with increased expression of CD11b, HLA-DR, CD45 and CD16. Concomitantly there was increased expression of TNF-alpha, high constitutive synthesis of PGE2 and high plasma IL-6 levels. This suggested that there exists a more dynamic situation of recruitment, activation and maturation of peripheral blood monocytes driven by HIV infection which results in a broader phenotypic profile.

Antigens, CD↗