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Biomedical subjects

S J Lane

Publications and source records attributed to S J Lane.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of the efficacy of nebulised lignocaine as adjunctive local anaesthesia for fibreoptic bronchoscopy: a randomised, placebo-controlled study.

Optimisation of topical anaesthesia for flexible fibreoptic bronchoscopy (FOB) is becoming increasingly important as a wider range of more complex, and thereby more prolonged, interventional endoscopic procedures are becoming available. Lignocaine is the most commonly used topical anaesthetic agent for bronchoscopy, but there is variability in current practice as to its optimum mode of administration. In this prospective, randomised, placebo-controlled, blinded study, we examine whether there was enhanced effectiveness of additional nebulised lignocaine as compared to our current regime utilising two visual analogue scales as markers of efficacy. Treatment groups were matched in terms of age (p = 0.39), gender, concomitant sedation (p = 0.51 midazolam; p = 0.12 fentanyl) and dose of background administered lignocaine (290 mg). We found no significant additional differences between any of the treatment groups in terms of general ease of procedure (p = 0.09) or in cough severity (p = 0.12). We conclude that this study does not support the hypothesis that additional nebulised lignocaine confers any additional benefit to the ease of procedure or cough severity in patients undergoing fibreoptic bronchoscopy. We suggest that preparation regimes for bronchoscopic examinations need optimization.

Administration, Inhalation↗
PubMed2006

The role of endobronchial electrocautery in the management of malignant airway obstruction.

Bronchoscopy has evolved well beyond a simple look-see examination, with new interventional techniques becoming more commonly employed. So-called interventional bronchoscopy implies the use of bronchoscopy as a therapeutic, in addition to diagnostic, tool. We present 2 cases to illustrate the utility of one such interventional technique, tumour ablation by endobronchial electrocautery and snaring, in the management of airway obstruction by tumour. This procedure, performed via a flexible bronchoscope under local anaesthesia can spare patients time-consuming, expensive treatments with their attendant morbidity, and in some cases can be life-saving. There is minimal morbidity associated with this technique. It is anticipated that interventional bronchoscopy will continue to revolutionise management of such conditions in the future, and become a necessary facility in all pulmonary medicine units.

Aged↗
PubMed2005

Role for macrophage migration inhibitory factor in asthma.

Macrophage migration inhibitory factor (MIF) is an immunologic regulator that is expressed in inflammatory and autoimmune disorders. We investigated MIF's role in asthma using genetic approaches in a mouse model and in a cohort of asthma patients. Mice genetically deficient in MIF that were primed and aerosol-challenged with ovalbumin showed less pulmonary inflammation and lower airway hyperresponsiveness than genetically matched, wild-type controls. MIF deficiency also resulted in lower titers of specific IgE, IgG(1), and IgG(2a), and decreased pulmonary, T(H)2 cytokine levels. IL-5 concentrations were lower and corresponded to decreased eosinophil numbers in bronchoalveolar lavage fluid. T cell studies also showed a lower level of antigen-specific responses in MIF-KO versus wild-type mice. In an analysis of 151 white patients with mild, moderate, or severe asthma (Global Initiative for Asthma criteria), a significant association was found between mild asthma and the low-expression, 5-CATT MIF allele. Pharmacologic inhibition of MIF may be beneficial and could be guided by the MIF genotype of affected individuals.

Adult↗
PubMed2005

COPD: illness severity, resource utilisation and cost.

COPD is a major source mortality and morbidity International evidence suggests the associated financial burden substantial. This research was undertaken to capture the costs associated with COPD in an Irish secondary care setting. 150 COPD patients attending a respiratory clinic were interviewed. Data on healthcare utilisation were collected. Prescription data and clinical severity data were collected from patient notes. The average direct cost of COPD was estimated at 4,730 euros. Secondary care costs accounted for 44% of total costs. Lost productivity averaged 668 euros. The main direct cost driver was in-patient admissions. A positive relationship was found between average direct costs and both clinical and symptom severity. The costs of COPD increased with increasing illness severity driven mainly by secondary care in-patient costs. If illness progression can be slowed and symptom severity can be reduced it may be possible to achieve significant reductions in expenditure and free resources within the healthcare system.

Aged↗
PubMed2005

The implementation of a nurse-provided, ward-based bilevel non-invasive ventilation service.

Bilevel non-invasive ventilation (NIV) is now standard of care for patients with acute hypercapnic respiratory failure (AHRF), and has an increasing role to play in patients with stable chronic hypercapnic respiratory failure (CHRF). The institution of an NIV service in a hospital setting requires major infrastructural and multidisciplinary input to be effective. This paper describes our experiences in setting up a 24-hour, nurse-provided, ward-based NIV service in a new acute teaching hospital in Dublin over a 39-month period. In addition, we provide audit data on 78 patients with AHRF treated with NIV by this service over this time period. The majority of patients (65) had their respiratory acidosis corrected and were discharged home; 11 patients failed NIV and were intubated and mechanically ventilated in the ITU; 13 patients died, 8 from respiratory causes and 5 from non-respiratory causes, indicating the critical nature of this condition.

Adult↗
PubMed2004

Embryonic disc development and subsequent viability of cattle embryos following culture in two media under two oxygen concentrations.

Bovine embryos were produced in vitro using a 2 x 2 design of modified medium (KSOM or SOF) and oxygen concentration (5% or 20%). Day 7 blastocysts were transferred in bulk (n = 11, on average) to recipient heifers and recovered non-surgically at Day 14. In two replications of a Latin square, eight heifers received embryos from each combination of factors. Recovered embryos were evaluated for trophoblast length and width, as well as the presence and diameter of an embryonic disc (ED). An ED was detected in a higher percentage of embryos that had been cultured in KSOM than SOF (72% v. 46%, respectively; P < 0.05). The aim of a second series of experiments was to associate Day 14 morphology with subsequent developmental capacity. In vitro-produced blastocysts were transferred (n = 17-20) on Day 7 to each of eight heifers and recovered at Day 14. Thirty-eight blastocysts were retransferred to heifers following morphological evaluation. Embryos in which an ED with no signs of degeneration had been detected maintained more pregnancies than other embryos in which an ED had either shown signs of degeneration or had not been detected (5/8 v. 2/30, respectively; P < 0.01). Further investigation into ED integrity at the elongating stage may contribute to our understanding of pregnancy establishment and maintenance.

Animals↗
PubMed2004

Auditing a new lung cancer service.

The Adelaide and Meath Hospital (AMNCH) is a new hospital, with the respiratory service established in 1999. We report on our experience with lung cancer in this short time. We conducted a retrospective chart audit, identifying patients from the Oncology Nurse patient list, of lung cancer cases diagnosed in 2001-2002. In 2001, 47 cases were diagnosed, with 71 cases diagnosed in 2002. Time to tissue diagnosis was 14.8, 2-46 (mean, range, one subject skewing the data) days. Diagnosis by tissue type was as follows: non-small cell carcinoma (NSCLC) n=92 (77.9%), small cell lung carcinoma (SCLC) n=17 (14.4%), mesothelioma n=2 (17%), carcinoid n=1 (0.8%) and no tissue diagnosis n=6 (5.1%). Staging of NSCLC: stage 1a n=3 (3.2%), stage 1b n=6 (6.5%), stage 2a n=5 (5.4%), stage 2b n=2 (2.2%), stage 3a n=10 (10.9%), stage 3b n=22 (23.9%) and stage 4 n=44 (47.8%). Staging of SCLC: limited stage n=5 (29.4%), extensive stage n=12 (70.6%). Positive emission tomography (PET) was employed in the staging of 22 patients. In these patients PET up-staged the disease in 8 patients, and management was unchanged in 8 patients. We conclude that 1. the relatively new respiratory service in AMNCH is handling increasing numbers of lung cancer cases, 2. cases are diagnosed within an acceptable time-frame, 3. rate of tissue diagnosis is comparable to national figures, 4. most patients present with advanced disease and 5. PET is a useful imaging modality for detection of cancer spread in selected patients.

Adult↗
PubMed2003

Corticosteroid-insensitive asthma: molecular mechanisms.

Corticosteroids are the most potent anti-inflammatory agents used to treat chronic inflammatory diseases such as bronchial asthma. However, there are a small number (<5%) of asthmatic patients who do not respond well, or at all, to corticosteroid therapy - the corticosteroid-resistant and corticosteroid-dependent patients. Although this phenomenon is relatively uncommon, it poses a difficult therapeutic problem because few alternative therapies are available and these patients account for >50% of the health care costs of asthma. If the mechanisms for corticosteroid insensitivity are understood they may, in turn, provide insight into the key mechanism of corticosteroid action and allow a rational way to treat these individuals whose disease tends to be severe. Corticosteroid insensitivity is not limited to asthma and is a feature of other inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease. Thus, elucidation of the cause for the relative lack of corticosteroid response in this subgroup of asthmatic individuals may have important implications for other diseases.

Adult↗
PubMed2000

Single bead and hard tag decoding using accurate isotopic difference target analysis-encoded combinatorial libraries.

A single fully automated generic microbore liquid chromatography electrospray time-of-flight protocol has been developed for the analysis of single beads, single beads with analytical constructs, and isotopically labelled dialkylamine hard tags. The protocol relies upon the incorporation of an isotopic signature into the linker and/or derivatising molecule to give a specific isotopic ratio together with an accurate isotopic difference. These properties facilitate highly specific and sensitive analysis of beads and hard tags using accurate isotopic difference analysis (AIDA) without prior knowledge of the molecular weight. Three open access methods with automated processing have been developed around a core generic approach.

Amines↗
PubMed2000

Glucocorticoid resistance in asthma is associated with elevated in vivo expression of the glucocorticoid receptor beta-isoform.

BACKGROUND: Glucocorticoid-resistant bronchial asthma is characterized by failure of corticosteroids to suppress key asthma-relevant, cell-mediated inflammatory responses in the airways. OBJECTIVE: The mechanism of this phenomenon is not clear but may involve aberrant expression of the beta-isoform of the glucocorticoid receptor. METHODS: We have measured expression of the alpha- and beta-glucocorticoid receptor isoforms in tuberculin-driven cutaneous cell-mediated inflammatory lesions in people with asthma who are glucocorticoid sensitive and resistant after 9 days of therapy with oral prednisolone (40 mg/day) or matching placebo in a random order, crossover design. RESULTS: After placebo therapy, the mean numbers of cells expressing glucocorticoid receptor alpha immunoreactivity in the lesions evoked in glucocorticoid-sensitive and -resistant patients with asthma were statistically equivalent. The numbers of cells expressing glucocorticoid receptor beta were significantly elevated in the patients who were glucocorticoid resistant, resulting in an 8-fold higher ratio of expression of glucocorticoid receptor alpha/glucocorticoid receptor beta in the patients who were glucocorticoid sensitive. Glucocorticoid receptor alpha/glucocorticoid receptors beta were colocalized to the same cells. Oral prednisolone therapy was associated with a significant decrease in the numbers of cells expressing glucocorticoid receptor alpha but not glucocorticoid receptor beta in the subjects who were glucocorticoid sensitive. No significant change was found in the numbers of cells expressing glucocorticoid receptor alpha and glucocorticoid receptor beta in the patients who were glucocorticoid resistant. Prednisolone therapy reduced the ratio of glucocorticoid receptor alpha/glucocorticoid receptor beta expression for the patients who were glucocorticoid sensitive to a level seen in the patients who were glucocorticoid resistant before therapy. CONCLUSION: Because glucocorticoid receptor beta inhibits alpha-glucocorticoid receptor-mediated transactivation of target genes, the increased expression of glucocorticoid receptor beta in inflammatory cells might be a critical mechanism for conferring glucocorticoid resistance.

Adult↗
PubMed1999

In vivo resistance to corticosteroids in bronchial asthma is associated with enhanced phosyphorylation of JUN N-terminal kinase and failure of prednisolone to inhibit JUN N-terminal kinase phosphorylation.

BACKGROUND: Corticosteroid-resistant (CR) asthma is associated with increased in vitro activity of the proinflammatory transcription factor activating peptide (AP)-1 in PBMCs resulting from increased c-FOS synthesis. Increased AP-1 may sequester the glucocorticoid receptor to produce a CR state. Using the tuberculin-induced inflammatory responses in the skin, we have previously demonstrated that a therapeutically effective dose of prednisolone suppressed T-cell, macrophage, and eosinophil infiltration into purified protein derivative-induced lesional skin of corticosteroid-sensitive (CS), but not CR, individuals. OBJECTIVE: Skin biopsy specimens from a tuberculin-induced model of dermal inflammation have been evaluated for the effect of corticosteroids in regulating components of AP-1 in vivo. METHODS: Immunohistochemical analysis of the tuberculin-mediated cutaneous response has been performed on 9 subjects with CS asthma and 6 subjects with CR asthma for the regulatory components of AP-1 before and after 9 days of either 40 mg prednisolone or placebo. RESULTS: Significantly greater expression of c-FOS, phosphorylated c-JUN, and phosphorylated JUN N-terminal kinase (JNK) protein has been identified in CR than in CS subjects. Corticosteroids suppressed phosphorylation of c-JUN and JNK in the CS Group (P =.004 for both) but enhanced phosphorylation of c-JUN and JNK in the CR group (P =.031 for both). CONCLUSION: Resistance to corticosteroids in asthmatic subjects may be caused, at least in part, by failure to suppress JNK phosphorylation, leading to failure to suppress c-JUN N-phosphorylation. Increased JNK may be one of the mechanisms central to the mechanism of CR asthma.

Animals↗
PubMed1999

Regulation of major histocompatibility complex class II antigens on human alveolar macrophages by granulocyte-macrophage colony-stimulating factor in the presence of glucocorticoids.

Alveolar macrophages (AM) present antigen poorly to CD4+ T cells and respond weakly to interferon-gamma (IFN-gamma) for up-regulation of major histocompatibility complex (MHC) class II and costimulatory molecule expression. In atopic asthma, however, AM exhibit enhanced antigen-presenting cell (APC) activity. Since granulocyte-macrophage colony-stimulating factor (GM-CSF) is increased in the airways of asthmatic patients, we have investigated its role in modulating the APC function of AM. The effects of glucocorticoids were also studied since earlier studies showed optimal induction of MHC antigens on monocytes by GM-CSF in their presence. GM-CSF in the presence, but not the absence, of dexamethasone enhanced the expression of HLA-DR, -DP and -DQ antigens by AM. However AM and monocytes differed in the optimal concentration of steroid required to mediate this effect (10-10 m and 10-7 m, respectively). Induction of MHC antigens was glucocorticoid specific and independent of IFN-gamma. These studies suggest the existence of an IFN-gamma-independent pathway of macrophage activation, which may be important in regulating APC function within the lung.

Adult↗
PubMed1998

Corticosteroid-resistant bronchial asthma is associated with increased c-fos expression in monocytes and T lymphocytes.

Unstimulated peripheral blood mononuclear cells (PBMCs) from corticosteroid-resistant (CR) but not corticosteroid-sensitive (CS) asthmatics demonstrate increased activating peptide-1 (AP-1)- and decreased glucocorticoid receptor (GR)-DNA binding. We test whether these abnormalities are associated with excessive generation of c-fos, the inducible component of AP-1. The c-fos transcription rate, mRNA and protein levels, and GR-DNA binding were quantitated in PBMCs, T cells, and monocytes from CS, CR, and nonasthmatic subjects. There was a 1.7-, 4.2-, and 2.3-fold greater increase in the baseline c-fos transcription rate, mRNA expression, and protein levels, respectively, in PBMCs derived from CR compared with CS patients. At optimal stimulation with PMA, there was a 5.7-, 3.4-, and 2-fold greater increase in the c-fos transcription rate, mRNA accumulation, and protein levels, respectively, in CR compared with CS PBMCs. These abnormalities were detected in both the T cell and monocyte subpopulations. PMA stimulation converted PBMCs from a CS to a CR phenotype and was associated with direct interaction between c-Fos and the GR. Pretreatment of PBMCs from CR patients with c-fos antisense oligonucleotides enhanced GR-DNA binding activity in CR PBMCs stimulated with dexamethasone. We suggest that increased c-fos synthesis provides a major mechanism for the increased AP-1- and decreased GR- DNA binding seen in CR asthma.

Adrenal Cortex Hormones↗
PubMed1998

Endogenous ouabain secretion in man is not regulated by ACTH.

It has been suggested that endogenous ouabain-like substance (OLS) is of adrenal origin and the secretion of OLS may be ACTH dependent. To determine if OLS is influenced by the pituitary-adrenal axis, we studied the effect of adrenal stimulation (0.25 mg Synacthen) and suppression (1 mg Dexamethasone) on two separate groups of nine subjects. Serum OLS was measured by a radioimmunoassay (RIA) developed in our lab, and cortisol and ACTH were measured by commercial assay kits. Dexamethasone significantly (P< 0.001) suppressed serum cortisol and ACTH concentrations, without effecting endogenous OLS concentration (0.64+/-0.17 vs 0.85+/-0.18nmol/l). Synacthen increased the concentration of cortisol in serum (p < 0.001) over the test period; OLS concentration, again, remained unchanged (0.45+/-0.04 vs 0.43+/-0.05 nmol/l). In further studies, serum concentrations of cortisol and OLS were compared between left (LAV) and right (RAV) adrenal veins with that from the inferior vena cava (IVC). Concentration of cortisol in the LAV and RAV was five-fold greater than that in IVC. However, there was no difference in OLS concentration at the corresponding sites. In addition, serum OLS concentrations in patients having undergone bilateral adrenalectomy or diagnosed with Addison's disease (0.62+/-0.19 nmol/l) were similar to concentrations in healthy subjects (0.67+/-0.21 nmol/l). Examination of bovine adrenal, liver, kidney, heart and human placenta demonstrated that OLS content of bovine adrenal was comparable with other tissues analysed. HPLC studies of human serum and bovine adrenal gland produced identical elution profiles, resolving a single peak which coincided with the retention time observed for standard ouabain. We conclude that the adrenal is unlikely to be the source of endogenous OLS, the secretion of which appears to be independent of ACTH.

Addison Disease↗
PubMed1998

Isolation of translactone-containing triterpenes with thrombin inhibitory activities from the leaves of Lantana camara.

Methanolic extracts prepared from the leaves of Lantana camara have been found to inhibit human thrombin. An assay, in which thrombin activity is measured as a function of clot formation from fibrinogen, was used to guide the fractionation and purification of five principal active constituents (1-5), which were all characterized as 5,5-trans-fused cyclic lactone-containing euphane triterpenes.

Carbohydrate Sequence↗
PubMed1997

Enhanced expression of cyclo-oxygenase isoenzyme 2 (COX-2) in asthmatic airways and its cellular distribution in aspirin-sensitive asthma.

BACKGROUND: There are two isoforms of cyclo-oxygenase (COX), namely COX-1 and COX-2. COX-1 is constitutively expressed in most tissues and in blood platelets. The metabolites derived from COX-1 are probably involved in cellular housekeeping functions. COX-2 is expressed only following cellular activation by inflammatory stimuli and is thought to be involved in inflammation. METHODS: The expression of COX-1 and COX-2 isoenzymes has been studied in the bronchial mucosa of 10 normal and 18 asthmatic subjects, 11 of whom had aspirin-sensitive asthma (ASA) and seven had non-aspirin-sensitive asthma (NASA) RESULTS: There was a significant fourfold and 14-fold increase, respectively, in the epithelial and submucosal cellular expression of COX-2, but not of COX-1, in asthmatic patients. There was no significant difference in the total number of cells staining for either COX-1 or COX-2 between subjects with ASA and NASA, but the number and percentage of mast cells that expressed COX-2 was significantly increased sixfold and twofold, respectively, in individuals with ASA. There was a mean fourfold increase in the percentage of COX-2 expressing cells that were mast cells in subjects with ASA and the number of eosinophils expressing COX-2 was increased 2.5-fold in these subjects. CONCLUSION: COX-2-derived metabolites may play an essential part in the inflammatory processes present in asthmatic airways and development of drugs targeted at this isoenzyme may have therapeutic potential in the treatment of asthma. Mast cells and eosinophils may also have a central role in the pathology of aspirin-sensitive asthma.

Adult↗