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Biomedical subjects

P O'Byrne

Publications and source records attributed to P O'Byrne.

At least 19 recordsLinked to original sources
PubMed2006

An unusual case of suicidal asphyxia by smothering.

A case is presented of a 30-year-old man suffering from borderline personality disorder who committed suicide by means of smothering. He was hospitalized at the psychiatric department of a public hospital for several months and was found dead in the seclusion room. The death resulted from an obstruction of the upper aerodigestive tract after ingurgitation of pellets of toilet paper. A literature review revealed several cases of suicidal asphyxia by smothering of patients with a history of psychiatric illness. Our patient's operating process had not been reported before to our knowledge.

Adult↗
PubMed2006

[Suspected non-accidental trauma in children: pseudofracture of the parietal bone].

We reported the case of a three month old child who was suspected of abuse syndrome because of a possible parietal bone fracture during radiographic investigation. At autopsy, the parietal bone abnormalities were not fractures, but proved to be unossified membranous strips. A review of the literature about normal variants of parietal suture on roentgenograms was made to avoid the diagnosis of non-accidental trauma in children, especially in live children where autopsy cannot be made.

Child Abuse↗
PubMed2001

Design and analytic considerations in determining the cost-effectiveness of early intervention in asthma from a multinational clinical trial.

Demand for economic and outcomes data in support of drug formulary listing in private and government-sponsored health programs has led to fundamental changes in drug development. In part as a response to these pressures, the pharmaceutical industry has begun to include economic and quality-of-life endpoints in clinical trials with the hope of providing information to answer health policy questions on the economic value of its products. Here, the design and health economic techniques that will be used to analyze the START (inhaled Steroid Treatment As Regular Therapy in early asthma) study-a multinational (31 countries), randomized, placebo-controlled trial of 7240 patients with mild asthma over 3 years-will be presented. START compares the effect of once-daily administration of an inhaled glucocorticosteroid (Pulmicort Turbuhaler to conventional therapy in the management of newly diagnosed asthma, for which the use of this therapy is currently not the standard. The START study will examine both clinical effectiveness (measured as symptom-free days) and asthma-related costs for both treatment arms, aggregated for all patients across all countries. We believe that presenting the analytical plan prior to disseminating the results is an important way of increasing the credibility of economic evaluations. However, using clinical trials for collecting economic data poses several challenges, and the methods for conducting such evaluations are being developed. This paper will present and discuss several methodological options and the current state of the art for conducting economic evaluations alongside multinational clinical trials.

Administration, Inhalation↗
PubMed2000

Eosinophilopoiesis in a murine model of allergic airway eosinophilia: involvement of bone marrow IL-5 and IL-5 receptor alpha.

The airway inflammation in asthma is dominated by eosinophils. The aim of this study was to elucidate the contribution of newly produced eosinophils in airway allergic inflammation and to determine mechanisms of any enhanced eosinophilopoiesis. OVA-sensitized BALB/c mice were repeatedly exposed to allergen via airway route. Newly produced cells were identified using a thymidine analog, 5-bromo-2'-deoxyuridine, which is incorporated into DNA during mitosis. Identification of IL-5-producing cells in the bone marrow was performed using FACS. Bone marrow CD3+ cells were enriched to evaluate IL-5-protein release in vitro. Anti-IL-5-treatment (TRFK-5) was given either systemically or directly to the airways. IL-5R-bearing cells were localized by immunocytochemistry. Repeated airway allergen exposure caused prominent airway eosinophilia after three to five exposures, and increased the number of immature eosinophils in the bone marrow. Up to 78% of bronchoalveolar lavage (BAL) granulocytes were 5-bromo-2'-deoxyuridine positive. After three allergen exposures, both CD3+ and non-CD3 cells acquired from the bone marrow expressed and released IL-5-protein. Anti-IL-5 given i.p. inhibited both bone marrow and airway eosinophilia. Intranasal administration of anti-IL-5 also reduced BAL eosinophilia, partly via local effects in the airways. Bone marrow cells, but not BAL eosinophils, displayed stainable amounts of the IL-5R alpha-chain. We conclude that the bone marrow is activated by airway allergen exposure, and that newly produced eosinophils contribute to a substantial degree to the airway eosinophilia induced by allergen. Airway allergen exposure increases the number of cells expressing IL-5-protein in the bone marrow. The bone marrow, as well as the lung, are possible targets for anti-IL-5-treatment.

Administration, Intranasal↗
PubMed2000

Cyclooxygenase metabolites play a different role in ozone-induced pulmonary function decline in asthmatics compared to normals.

Indomethacin has been used to demonstrate that cyclooxygenase (COX) metabolites of arachidonic acid play a mechanistic role in ozone-induced spirometric decline in normals (Nm). Since the weight of evidence suggests that asthmatics (Asth) do not differ substantially from Nm subjects in the magnitude of their spirometric response to ozone, we sought to determine whether COX metabolites play a similar role in the asthmatic response to ozone. Thirteen (n = 13) Asth and nine (n = 9) Nm volunteers were pretreated with indomethacin or placebo (3 days, 75 mg/day), then exposed for 2 h to 400 ppb ozone or clean air while performing mild intermittent exercise (Vi(min) = 30 L/min.). Baseline changes in spirometry (FVC, FEV(1), FEF(25), FEF(50), FEF(60p), FEF(75)) and soluble markers of COX metabolism (prostaglandin [PG] F2-alpha) were measured from induced sputum samples. Results showed similar reductions in FVC (Asth = 12%, Nm = 10%) and FEV(1) (Asth = 13%, Nm = 11%) in Asth and Nm following ozone. Variables representing small-airways function demonstrated the greatest ozone-induced decline in Asth (FEF(75) = 25%). Indomethacin pretreatment significantly attenuated ozone-induced decreases in FVC and FEV(1) in Nm, but not in Asth. Marked attenuation of ozone-induced decrements in FEF(75) and FEF(60p) was observed in Asth but not in Nm. PGF2-alpha levels were similar in both groups prior to ozone exposure with indomethacin (Asth = 65 pg/ml, Nm = 59 pg/ml), but postexposure levels in Asth were significantly elevated (118 pg/ml) compared to Nm (54 pg/ml). We conclude that COX metabolites, such as PGF2-alpha, play an important but different role in asthmatics than normals with respect to ozone-induced pulmonary function decline. Specifically, COX metabolites contribute to restrictive-type changes in normals and obstructive-type changes in small airways in asthmatics.

Adolescent↗
PubMed1998

Asthma pathogenesis and allergen-induced late responses.

Increases in airway eosinophils occur during the late asthmatic response, 7 hours after allergen inhalation, and these can persist for 3 days. Also, increases in airway metachromatic cells occur which are most marked after 7 hours. These increases in airway cells are associated with increases in bone marrow progenitors, which are caused by an increased responsiveness of the bone marrow to IL-5 after allergen because of an increased expression of the IL-5 receptor on the progenitors. These studies suggest that after allergen inhalation, signals are sent from the airways to the bone marrow, which increase production of progenitors and make more cells available to be recruited into the airways.

Allergens↗
PubMed1998

Induced sputum, bronchoalveolar lavage and blood from mild asthmatics: inflammatory cells, lymphocyte subsets and soluble markers compared.

Airway inflammation in asthma can be measured directly by invasive bronchoalveolar lavage (BAL), directly and relatively noninvasively by induced sputum and indirectly from peripheral blood. We compared cellular and fluid phase indices of inflammation in induced sputum, BAL and blood from 11 adults with mild stable asthma. On one day, induced sputum selected from saliva was collected and on the next, blood and BAL. Median results of sputum compared with BAL showed a higher number of nonsquamous cells (53 versus 0.8 x 10(6) cells x mL(-1), p=0.003), more neutrophils (34.3 versus 1.0%, p<0.001), CD4+ and CD19+ T-cells (76.5 versus 54.7%, p=0.01 and 5.2 versus 1.1%, p=0.03, respectively), fewer macrophages (603 versus 95.0%, p=0.002) and markedly higher levels of eosinophil cationic protein (ECP) (264 versus 2.0 microg x L(-1), p<0.001), tryptase (17.6 versus 2.2 UI x L(-1), p<0.001) and fibrinogen (1,400 versus 150 microg x L(-1), p=0.001). Sputum and BAL neutrophils and CD4+ T-cells were strongly correlated. Sputum and BAL differed from blood by having higher proportions of T-cells (94.9 and 98.9% versus 87.7%, p=0.002) and lower proportions of CD19+ T-lymphocytes (p=0.04 and 0.006). Sputum also differed from blood by having higher proportions of CD4+ T-cells (76.5 versus 51.4%, p=0.001), lower proportions of CD8+ cells (24.0 versus 403%, p=0.04) and a higher CD4+/CD8+ ratio (3.3 versus 1.4, p=0.01). We conclude that in mild asthmatics, sputum, bronchoalveolar lavage and blood measure different compartments of inflammation. Induced selected sputum has the advantage over bronchoalveolar lavage of higher density of cell recovery and stronger signal for fluid-phase markers.

Adult↗
PubMed1997

Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group.

BACKGROUND: The role of long-acting, inhaled beta2-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide. METHODS: After a four-week run-in period of treatment with budesonide (800 microg twice daily), 852 patients being treated with glucocorticoids were randomly assigned to one of four treatments given twice daily by means of a dry-powder inhaler (Turbuhaler): 100 microg of budesonide plus placebo, 100 microg of budesonide plus 12 microg of formoterol, 400 microg of budesonide plus placebo, or 400 microg of budesonide plus 12 microg of formoterol. Terbutaline was permitted as needed. Treatment continued for one year; we compared the frequency of exacerbations of asthma, symptoms, and lung function in the four groups. A severe exacerbation was defined by the need for oral glucocorticoids or a decrease in the peak flow to more than 30 percent below the base-line value on two consecutive days. RESULTS: The rates of severe and mild exacerbations were reduced by 26 percent and 40 percent, respectively, when formoterol was added to the lower dose of budesonide. The higher dose of budesonide alone reduced the rates of severe and mild exacerbations by 49 percent and 37 percent, respectively. Patients treated with formoterol and the higher dose of budesonide had the greatest reductions -- 63 percent and 62 percent, respectively. Symptoms of asthma and lung function improved with both formoterol and the higher dose of budesonide, but the improvements with formoterol were greater. CONCLUSIONS: In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids, the addition of formoterol to budesonide therapy or the use of a higher dose of budesonide may be beneficial. The addition of formoterol to budesonide therapy improves symptoms and lung function without lessening the control of asthma.

Administration, Inhalation↗
PubMed1996

Transforming growth factor beta 1 (TGF beta 1) gene expression by eosinophils in asthmatic airway inflammation.

The increase in thickness of bronchial walls by such structural changes as subepithelial fibrosis contributes to the severity and chronicity of asthma by amplifying airway narrowing. However, the pathogenesis of this structural alteration is not known. Transforming growth factor beta 1 (TGF beta 1) is known to have biologic activities relevant to the cellular and molecular events in subepithelial fibrosis, such as the deposition of collagen I and III and the increase of myofibroblasts beneath the epithelial basement membrane. Therefore, we examined TGF beta 1 gene expression in bronchial biopsy tissues from five severe asthmatics, five mild asthmatics, and five normal subjects using in situ hybridization combined with histochemical staining. Cells expressing TGF beta 1 mRNA were detected in tissues from four normal subjects, one mild asthmatic, and five severe asthmatics. The density of positive cells in severe asthmatic tissues (52.1 +/- 22.7, mean +/- SD/mm2) was significantly greater than that in mild asthmatic tissues (1.0 +/- 1.9/mm2, P < 0.01) or normal tissues (10.5 +/- 10.6/mm2, P < 0.02). The density in mild asthmatic tissues was not significantly different from that in normal tissues. The vast majority of positive cells in severe (99.1 +/- 1.7%) and mild (100%) asthmatic tissues were identified as eosinophils. In contrast, eosinophils constituted a small portion of positive cells (20.8 +/- 21.6%) in normal tissues. These results indicated that TGF beta 1 mRNA was overexpressed in severe asthmatics and that the main source of the mRNA was eosinophils, suggesting that eosinophils play an important role in the pathogenesis not only of inflammation but also of structural changes, such as subepithelial fibrosis, in asthmatic airways.

Adult↗
PubMed1995

Distinct immunohistochemical localization of IL-4 in human inflamed airway tissues. IL-4 is localized to eosinophils in vivo and is released by peripheral blood eosinophils.

Nasal polyposis and asthma are inflammatory conditions of the airways characterized by infiltration of activated inflammatory cells, particularly eosinophils. IL-4 is a multifunctional cytokine considered to play an important role in eosinophilic inflammation. We examined the cellular distribution of immunoreactive IL-4 in nasal polyps, as well as in the bronchial mucosa of both nonasthmatic control subjects (n = 6) and patients with well-characterized mild asthma (n = 6) subjected to a diluent or an allergen challenge. To determine eosinophilic contribution, tissue sections were counterstained with FITC after IL-4 immunostaining. No eosinophils were observed in the bronchial mucosa of nonasthmatic subjects. Nasal polyp tissues contained approximately 15 times more eosinophils per mm2 compared with bronchial tissues from asthmatics after a diluent challenge. Allergen challenge resulted in a marked increase in eosinophil density in bronchial tissues. A negligible number of cells immunostaining IL-4 was observed in bronchial tissues from nonasthmatic control subjects. The density of IL-4-positive cells in nasal polyp tissues was almost three times greater compared with asthmatics bronchial tissues after a diluent challenge. Approximately 90% of the IL-4-positive cells in bronchial tissues did not exhibit fluorescence after FITC counterstaining; in contrast, about 80% of the IL-4-positive cells in nasal polyp tissues did. We also show that peripheral blood eosinophils from allergic subjects express IL-4 mRNA by Northern blot analysis, particularly on stimulation with secretory IgA immune complexes. Finally, the supernatant of stimulated eosinophils contained approximately 50 pg/10(6) cells of IL-4 as determined by ELISA. These data demonstrate that eosinophils express the message and release IL-4 in vitro, and that these cells are the primary source of immunoreactive IL-4 in tissues undergoing chronic severe mucosal inflammation.

Adult↗
PubMed1995

Prostanoid enhancement of interleukin-6 production by rat peritoneal mast cells.

Mast cells are traditionally associated with an acute response involving the short-term release of mediators such as histamine. We have shown previously that mast cells can produce IL-6 without prior histamine release. In this study we examined the hypothesis that mast cell IL-6 production can be selectively regulated by PGs. Highly purified rat peritoneal mast cells were cultured in the presence of PGE1, PGE2, or PGD2 alone or in combination with anti-IgE or bacterial LPS. Histamine release was assessed after 10 min; IL-6 and TNF-alpha production was measured in supernatants after 18 h. Mast cell IL-6 production was induced by PGE1 and PGE2 to a similar level to that observed in anti-IgE-activated cells. In contrast, constitutive production of TNF-alpha was inhibited by PGE1 and PGE2, but not by PGD2. PGE2 had a synergistic effect, inducing IL-6 in the presence of LPS, whereas an additive effect was observed in the presence of anti-IgE. None of the prostanoids alone induced significant histamine release at the 10-min time point. However, PGE2 significantly increased histamine release when added concurrently with anti-IgE. Flurbiprofen in the context of anti-IgE or LPS activation did not alter mast cell IL-6 or TNF-alpha production. IL-6 production in response to each of the stimuli was significantly inhibited by the corticosteroid dexamethasone. These observations of selective modulation of mast cell cytokine production are important to understand the mechanisms by which mast cells interact with other cells during an inflammatory process involving prostanoid synthesis.

Alprostadil↗
PubMed1995

Eosinophils as a potential source of platelet-derived growth factor B-chain (PDGF-B) in nasal polyposis and bronchial asthma.

Tissue remodeling in bronchial tissues from asthmatics as well as in nasal polyp (NP) tissues includes sub-basement membrane deposition of collagen, stromal deposition of extracellular matrix protein, and hypertrophy/hyperplasia of airway smooth muscle cells, which are relevant to the cellular and molecular events induced by platelet-derived growth factor (PDGF). Therefore, we investigated the localization of mRNA and protein of PDGF-B chain (PDGF-B) in NP tissues and bronchial tissues from mild and severe asthmatics by in situ hybridization and immunohistochemistry, respectively. Cells expressing PDGF-B mRNA were found in all nine NP tissues and in bronchial tissues from 2 of 6 normal subjects, 2 of 5 mild asthmatics, and all of 6 severe asthmatics examined. The vast majority of cells expressing PDGF-B mRNA were eosinophils in NP (99.7 +/- 0.2%, mean +/- SD) and asthmatic bronchial tissues (75.0 and 77.8% in mild asthma, and 92.7 +/- 8.1% in severe asthma), but no cells expressing PDGF-B mRNA were eosinophils in normal bronchial tissues. The number of cells expressing the gene in severe asthma tissues (122.3 +/- 32.2/mm2) was similar to that in NP tissues (152.8 +/- 73.9/mm2) and greater than that in mild asthma tissues (4.7 +/- 7.6/mm2, P < 0.01), which was not significantly greater than that in normal bronchial tissues (3.4 +/- 5.2/mm2). Furthermore, we detected immunolocalization of PDGF-B in NP tissues and in asthmatic bronchial tissues. The eosinophils purified from peripheral blood were demonstrated to express PDGF-B gene transcript and immunoreactivity after stimulation with A23187.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Interleukin 10 inhibits lipopolysaccharide-induced survival and cytokine production by human peripheral blood eosinophils.

In this study we have investigated the effects of interleukin 10 (IL-10) on human peripheral blood eosinophils stimulated with granulocyte/macrophage colony stimulating factor (GM-CSF) and lipopolysaccharide (LPS). We show that LPS was able to enhance eosinophil survival in a dose-dependent manner, as well as release of the cytokines GM-CSF, tumor necrosis factor alpha, and IL-8. LPS-induced eosinophil survival was largely inhibited by an anti-GM-CSF neutralizing antibody and completely blocked by polymyxin B, suggesting GM-CSF involvement in the survival enhancing mechanism and LPS specificity, respectively. IL-10 significantly inhibited survival of, and cytokine production from, eosinophils induced by LPS, but did not inhibit the survival induced by GM-CSF. These observations suggest a novel activation mechanism of eosinophils and, also, that IL-10 may participate in the regulation of diseases characterized by eosinophil infiltration.

Antibodies↗
PubMed1992

Formoterol compared with beclomethasone and placebo on allergen-induced asthmatic responses.

Formoterol is a new long-acting beta 2-agonist. We compared the protective effect of 24 micrograms formoterol with 200 micrograms beclomethasone and placebo on inhaled allergen-induced asthmatic responses in mild stable asthmatic subjects. We measured airflow rates, histamine airway responsiveness, cell counts from sputum and peripheral blood, and markers of lymphocyte and eosinophil activation. Adjustments were made for the confounding effect of bronchodilatation produced by formoterol in comparisons using a control inhalation of normal saline. Formoterol caused bronchodilation and inhibition of histamine airway responsiveness for at least 24 h. It completely inhibited the early asthmatic responses when beclomethasone had no effect. Control comparisons of the effect of formoterol and beclomethasone on the allergen-induced late asthmatic response and increase in histamine responsiveness showed each to be equally effective but not to inhibit the responses completely. Formoterol caused bronchodilation in addition to preventing bronchoconstriction. Both drugs inhibited the rise in serum eosinophil cationic protein 24 h after allergen, but neither inhibited the allergen-induced increases in sputum or blood eosinophils or CD25+ lymphocytes. These results suggest that formoterol modifies allergen-induced airway responses through functional antagonism rather than the inhibition of inflammatory cell infiltration.

Adult↗