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Biomedical subjects

S Bourke

Publications and source records attributed to S Bourke.

At least 19 recordsLinked to original sources
PubMed2004

Selective modulation of ligand-gated P2X purinoceptor channels by acute hypoxia is mediated by reactive oxygen species.

Purinergic excitatory synapses use ATP to mediate fast synaptic transmission via activation of P2X receptor cation channels, and this response can be altered by acute hypoxia. This study examined the effect of acute hypoxia on cloned homo- and heteromeric P2X2 and P2X3 receptors expressed in human embryonic kidney 293 cells. In cells expressing homomeric P2X2 receptors, perfusion of 5 microM ATP (EC25) induced an inward whole-cell current that showed little desensitization during repeated exposures under continuously normoxic conditions. Exposure to a hypoxic ATP solution (pO2, 25-40 mm Hg) significantly reduced the whole-cell current to 49% of normoxic control. This hypoxic inhibition of P2X2-mediated inward current was maintained across all potentials when a voltage-step protocol was applied. In contrast, currents mediated by homomeric P2X3 receptors or heteromeric P2X(2/3) receptors were insensitive to an acute hypoxic challenge. One mechanism whereby hypoxia may modulate P2X2 channels is via the production of reactive oxygen species (ROS). H2O2 (1.8 mM) reversibly reduced homomeric P2X2 whole-cell currents to 38% of control. Furthermore, H2O2 attenuated the effect of hypoxia on homomeric P2X2 whole-cell currents. Inhibitors of the mitochondrial electron transport chain that reduce (rotenone and myxothiazol) or increase (antimycin A) the production of ROS altered the magnitude of P2X2-mediated currents. In summary, this is the first report indicating that acute hypoxia is able to regulate the activity of any ligand-gated ion channel. Furthermore, our data show that acute hypoxia selectively modulates the P2X2 receptor and that the response of P2X2 receptor subunits to hypoxia is mediated through the mitochondrial production of ROS.

Adenosine Triphosphate↗
PubMed2001

Treatment pathways, resource use and costs in the management of small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) represents about 20% of primary lung tumours and the costs associated with the management of SCLC can be significant. The main objective of this study was to obtain information on current patterns of care and associated resource use and costs for patients with SCLC from initial diagnosis and treatment phase, throughout disease progression and terminal care. METHODS: A 4 year retrospective patient chart analysis (1994-7) was conducted on a consecutive series of 109 patients diagnosed with SCLC in two Newcastle hospitals. For this consecutive series of patients all details about care received including tests and procedures, treatment, and medication from diagnosis till death were recorded. Pathways of care and forms were designed to enable resource use to be captured for different disease phases. Unit costs were determined from a variety of sources including the Newcastle Hospitals NHS Trust Finance Department and the British National Formulary. RESULTS: The average total cost per patient calculated for the full cohort of 109 patients was pound 11,556. Initial treatment was the most resource use intensive constituting 48.2% of the total cost. The major cost element throughout all disease phases was hospitalisation. Twenty eight percent of the total costs of care occur after recurrence of the disease until death, of which 73% are generated by terminal care. CONCLUSION: The results of this retrospective medical chart analysis show that the costs of care of SCLC are considerable, although the variability between patients in terms of the type and quantity of resource use is very high. Analyses such as this provide a useful insight into resources used in actual clinical practice.

Aged↗
PubMed2000

IgG subclass responses to pigeon intestinal mucin in pigeon Fanciers' lung

Pigeon fanciers' lung (PFL) is a form of extrinsic allergic alveolitis caused by exposure to avian antigens. Although the mechanisms involved in the pathogenesis of PFL are unclear it has been suggested that immune complexes formed on the alveolar epithelial surface of the lung initiate the symptoms of the acute stages of discase. Pigeon intestinal mucin has been implicated as an important antigen in the pathogenesis of PFL, and affected fanciers have very high antibody titres against this antigen. In this study we investigated the IgG and IgG subclass responses to both intact and papain digested mucin in 250 pigeon fanciers classified according to the presence of absence of precipitating antibodies and clinical status. Sera were screened by quantitative ELISA for IgG and IgG subclass activity to these antigens. There was no significant difference in the median IgG titre to pigeon mucin in individuals with PFL and asymptomatic antibody positive individuals. IgG1 and IgG2 were the major antibody subclasses against pigeon intestinal mucin with lower titres of IgG3 and negligible IgG4. Patients with PFL had significantly higher titres of anti-mucin IgG1 than asymptomatic antibody positive individuals (p = 0.0019) whilst there was no significant differences in IgG2, IgG3 and IgG4 titres between these two groups. Papain digestion of mucin resulted in a 600 fold decrease in IgG3 titres whilst IgG1 and IgG2 titres were essentially unaffected as compared to undigested mucin. This suggests that both IgG1 and IgG2 are directed against the O-linked oligosaccharides in the papain resistant regions of mucin whilst the majority of IgG3 is directed against papain sensitive protein epitopes (or possibly N-Iinked sugars in the sparsely glycosylated regions). - The difference between symptomatic and asymptomatic sera in the IgG subclass profiles to pigeon intestinal mucin together with the very high titres of anti-mucin antibody in all individuals with PFL confirm pigeon mucin as a major antigen in disease. Differences in antibody subclass profiles are likely to affect the composition and properties of the immune complexes, with consequences for the developmcnt of disease.

Journal Article↗
PubMed1998

Pigeon fanciers' lung: effects of smoking on serum and salivary antibody responses to pigeon antigens.

A reduced prevalence of pigeon fanciers' lung has been reported in pigeon breeders who smoke cigarettes. Serum and salivary antibodies to pigeon intestinal mucin and pigeon serum proteins were investigated in 227 pigeon fanciers, subdivided according to smoking habit and clinical status. Smokers had a lower incidence of precipitating antibodies to pigeon antigens and lower titres of serum IgG and IgA antibodies to mucin and to pigeon serum proteins in ELISA compared with non-smokers and ex-smokers. In contrast, IgG antibody titres to tetanus toxoid were similar in smoking and non-smoking groups. In contrast to serum antibodies, salivary IgA antibody titres to pigeon antigens were similar in smokers and non- or ex-smokers. Approximately one third of the smokers reported symptoms consistent with pigeon fanciers' lung but did not have precipitating antibodies. Only some individuals with precipitating antibodies had disease symptoms, and IgG antibody titres in these individuals were not significantly higher than in many asymptomatic individuals. Salivary IgA titres against pigeon mucin were significantly higher in asymptomatic individuals, consistent with a protective role for these antibodies. The results confirm that smoking is associated with a decreased serum antibody response to inhaled pigeon antigens, affecting IgG1, IgG2 and IgA responses, but this impairment does not extend to salivary IgA or to antibody responses to a parenterally administered protein antigen. The fact that responses to pigeon serum proteins and to pigeon intestinal mucin were similarly affected suggests that cigarette smoking depresses both T-independent and T-dependent responses to inhaled antigens.

Animals↗
PubMed1995

Oxygen desaturation during sleep and exercise in patients with severe chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) have varying degrees of arterial oxyhaemoglobin desaturation during sleep, which have been shown to correlate with awake oxygen levels. We wished to ascertain if exercise desaturation was a better predictor of nocturnal oxygen desaturation than daytime blood gases. We studied 25 COPD patients with PaO2 < 10 kPa (mean = 8.6 kPa), 12 of whom were normocapnic (PaCO2 < or = 6 kPa, Group A), and 13 of whom were hypercapnic (PaCO2 > 6 kPa, Group B), by means of overnight oximetry and maximum treadmill exercise testing. The overall group desaturated significantly more during sleep than exercise [12.9 +/- 10.5 fall in nocturnal oxygen saturation (SaO2) vs. 4.5 +/- 3.7, P < 0.01]. Group B had a lower minimum SaO2 during sleep than Group A (74.3 +/- 13.4 vs. 84.6 +/- 5.8, P < 0.05), despite very similar pre-sleep SaO2 (91.9 +/- 3.2 vs. 92.8 +/- 2.9, P = n.s.). Awake SaO2 correlated well with both mean values (r = 0.7, P < 0.001), and minimum sleep SaO2 (r = 0.44, P < 0.05), but not with the fall in sleep SaO2 (r = 0.21, P = n.s.). Minimum sleep and exercise SaO2 were also significantly correlated (r = 0.44, P < 0.05), but the fall in SaO2 during sleep and exercise was not (P = n.s.). We conclude that exercise studies add no extra information to awake blood gas analysis in predicting the likelihood of nocturnal oxygen desaturation in patients with COPD.

Aged↗
PubMed1993

Reversible hypercapnia in acute exacerbations of chronic obstructive pulmonary disease (COPD).

We prospectively studied emergency hospitalizations due to acute exacerbations of chronic obstructive pulmonary disease (COPD) among 74 hypercapnic patients, in order to determine factors which predict reversal to normocapnia as a result of therapy. Clinical, arterial blood gas and pulmonary function data on presentation were compared to predischarge values among those 58 patients who survived the admission. Patients were divided into those who reverted to normocapnia (reversible, 40% of surviving patients), and those who remained hypercapnic (chronic, 60% of surviving patients). Reversible patients had higher admission arterial oxygen tension (PaO2) levels than those with chronic hypercapnia (6.4 +/- 1.3 kPa (mean +/- SD), as compared to 5.7 +/- 1.1 kPa) better pulmonary function (forced expiratory volume in one second (FEV1) 35 +/- 16% predicted, as compared to 26 +/- 7.9), and a lower prevalence of cor pulmonale (30% as compared to 63% of patients). No admission variable(s) distinguished individual patients as reversible or chronic hypercapnic, and, in particular, admission arterial carbon dioxide tension (PaCO2) and pH levels were similar in both groups. Furthermore, there were no differences between survivors and those 16 patients who died during the admission, apart from a higher urea level among those who died. These findings suggest that reversible patients have milder underlying disease than those with chronic hypercapnia. Our data establish the high prevalence of reversible hypercapnia among patients hospitalized with exacerbations of COPD, and, furthermore, indicate that patients who are normocapnic in the stable state can develop similar levels of hypercapnia during exacerbations as those with chronic hypercapnia.

Acute Disease↗
PubMed1991

The effect of estradiol, trenbolone acetate, or zeranol on growth rate, mammary development, carcass traits, and plasma estradiol concentrations of beef heifers.

The effect of a single implantation (on d 1) with one or two long-acting, biodegradable estradiol implants (1E or 2E) on plasma estradiol concentrations in beef heifers was determined. The growth rates of these (2E) heifers, and of heifers repeatedly implanted with trenbolone acetate (TBA) or zeranol (Z) on d 1, 84, 168, and 252 of the trial, were compared to growth rates of controls. Trenbolone acetate alone was compared to TBA + 2E, and 2E was compared to 1E. At a mean age of 84 d (d 1 of experiment), 81 Hereford x Friesian heifers were allocated at random to the following treatments: Control (n = 15); TBA (n = 15); 1E (n = 12); 2E (n = 15); Z (n = 13); or TBA + 2E (n = 11). Mean live weight (kg) prior to slaughter on d 368 and hot carcass weight (kg) for heifers assigned to treatment Groups 1 to 6, respectively, were 366 and 200, 391 and 212, 374 and 201, 386 and 207, 387 and 210, and 391 and 208 (residual SD = 30.3 and 20.2). Heifers assigned to both the 2E and Z treatments were heavier on d 368 (P less than .05) and had longer teats on d 279 (P less than .05), less pelvic fat (P less than .05), and heavier kidneys (P less than .005) than control heifers. Heifers assigned to the TBA treatment had shorter teats on d 279 (P less than .001) but greater final live weight (P less than .05) and carcass weight than control heifers. Heifers given TBA alone had more pelvic fat (P less than .05) and lighter kidneys (P less than .05) than those given TBA + 2E. Mean estradiol concentrations in both the ipsilateral and contralateral jugular veins of heifers assigned to the 2E and TBA + 2E treatments, and in the ipsilateral jugular veins of heifers given 1E, were greater (P less than .05) than those in control heifers; concentrations did not decline during the experiment.

Adipose Tissue↗
PubMed1989

Percussion of the chest re-visited: a comparison of the diagnostic value of ausculatory and conventional chest percussion.

Percussion of the chest is thought to be insensitive in detecting small or deeply situated chest lesions. A newer technique, ausculatory percussion, has been reported as having a far higher sensitivity. In a controlled blind study the diagnostic value of conventional chest percussion compared with ausculatory percussion was defined using the chest x-ray as a gold standard. The prevalence of disease in 100 lung fields was 26%. The majority of lesions were not detected by either technique resulting in very low sensitivities of 15.4% for conventional percussion and 19.2% for ausculatory percussion. A positive result with ausculatory percussion was twice as likely to be false as true (positive predictive value 31.2%). The technique did not add to the diagnostic value of conventional percussion. Both techniques have major limitations. Patients with suspected lung disease still require chest x-ray examination if percussion is normal.

Auscultation↗
PubMed1989

Chronic simple bronchitis in pigeon fanciers. Relationship of cough with expectoration to avian exposure and pigeon breeders' disease.

The prevalence of chronic bronchitis and its relationship to antigenic exposure was studied in a population of pigeon fanciers. Two hundred and eighty seven fanciers completed a questionnaire regarding symptoms and circumstances of avian exposure and had IgG antibody to pigeon gammaglobulin measured by an enzyme linked immunosorbent assay. Chronic bronchitis occurred in 26.2 percent of nonsmoking fanciers and increased in prevalence as antibody levels rose (p less than 0.001). Although significantly more common (p less than 0.005) in the 85 (29.6 percent) fanciers who also had typical delayed symptoms of pigeon breeders' disease (PBD), chronic bronchitis was the only manifestation of the disease in 24 (8.4 percent) of the population surveyed. Chronic bronchitis was not related to the intensity or duration of avian exposure suggesting that host factors are more important in its pathogenesis. Chronic bronchitis must be considered to be an integral part of the clinical spectrum of PBD.

Adolescent↗
PubMed1988

Induction of parturition in swine with the prostaglandin analogue fenprostalene.

Ninety-one to 100 per cent of pregnant sows injected with 0.25, 0.5 or 1 mg of fenprostalene on days 112, 113 or 114 of gestation began to farrow within 30 hours of treatment, the majority during working hours on the day after injection. Induction of farrowing had no significant effect on the piglets' viability, the litter weight or the subsequent sow or litter performance. Treatment of sows with fenprostalene and oxytocin on day 114 of pregnancy resulted in a reduction in duration of farrowing compared with fenprostalene alone.

Animals↗
PubMed1988

Apical pulmonary fibrosis in psoriasis.

Apical pulmonary fibrosis has been established as a non-articular complication of ankylosing spondylitis. Although psoriasis is frequently associated with arthropathy and spondylitis, there is only one previous report of apical fibrosis occurring in a patient with psoriasis. We report two patients with psoriasis complicated by apical pulmonary disease in whom extensive investigations were negative.

Aged↗