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Biomedical subjects

S O'Neill

Publications and source records attributed to S O'Neill.

At least 73 records · Page 4Linked to original sources
PubMed1999

Neutrophil CD11b and soluble ICAM-1 and E-selectin in community acquired pneumonia.

It was hypothesized that there would be an upregulation of systemic neutrophil CD11b expression in pneumonia. Expression of CD11b and concentrations of soluble intercellular adhesion molecule (ICAM)-1 and E-selectin were evaluated as potential surrogate markers of the severity of pneumonia. Possible age-related immunosenescence in relation to neutrophil CD11b expression in elderly patients with pneumonia was examined for. In patients with community-acquired pneumonia (n = 36) neutrophil CD11b expression was measured by flow cytometry and soluble ICAM-1 and E-selectin concentrations by enzyme-linked immunosorbent assay. An upregulation of neutrophil CD11b expression and increased soluble adhesion molecule concentrations on admission were confirmed, but the concentrations did not correlate with patient Acute Physiology and Chronic Health Evaluation II scores. Neutrophil CD11b expression was similar between elderly (age range 70-100 yrs) and younger (age range 18-70 yrs) patients with pneumonia. In conclusion, there is evidence of neutrophil and endothelial cell activation in pneumonia as indicated by upregulation of CD11b and increased soluble intercellular adhesion molecule and E-selectin, however, they do not appear to be good surrogate markers of severity of infection. Advanced age does not influence adhesion molecule expression in pneumonia.

APACHE↗
PubMed1999

Outcome analysis of patients with vasculitis associated with antineutrophil cytoplasmic antibodies.

BACKGROUND: Objective scoring systems of disease activity and disease-associated damage have proven useful in the management of patients with systemic vasculitis. PATIENTS AND METHODS: We used the recently designed Birmingham vasculitis activity score (BVAS; maximum score 63) and vasculitis damage index (VDI; maximum score 59) to assess initial activity and long-term damage, respectively, in ANCA positive patients from one center over a 3-year period. Thirty-two patients with ANCA vasculitis were identified and analyzed as an historic cohort. The median BVAS for all vasculitis patients at first presentation was 19 (range 6 - 36). Patients with Wegener's granulomatosis had a significantly higher total score and respiratory BVAS score compared to the 15 with microscopic polyangiitis. The majority of patients received standard cyclophosphamide/steroid treatment. RESULTS: At the end of follow-up (mean 24.9 months), 4 patients had died; all patients had evidence of permanent organ damage. The median total VDI score at last follow-up was 4.0 (range 0-11), with no differences between patients with Wegener's granulomatosis and microscopic polyangiitis. The VDI was not associated with the number of relapses. A high initial BVAS was found to correlate with a later high vasculitis damage index (r = 0.56). Initial renal or respiratory involvement was also associated with longterm damage in the same organ system. CONCLUSION: Although mortality from ANCA-associated vasculitis has decreased, morbidity remains a common problem. High early-disease activity may identify patients at high risk of long-term organ damage, allowing more effective individualized therapy. This hypothesis requires validation in a prospective, controlled study.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1998

Pathogen-free granulomatous diseases of the central nervous system.

Pathogen-free granulomatous diseases (PFGD) of the central nervous system (CNS) are a group of disorders with protean clinical and pathological findings. Failure to identify a causative organism leads to considerable diagnostic difficulty. The neuropathology records between 1985 and 1995 were retrospectively reviewed, and the medical records of all patients in whom a diagnosis of PFGD of the CNS was made were retrieved. Patients in whom an infective agent was shown either by culture, special staining techniques, or by immunohistochemical methods were excluded. We identified 11 patients (eight male, three female) who fulfilled the pathological criteria for this condition. Average age at diagnosis was 38.7 years (range, 17 to 78). Neurological symptoms were the presenting feature in nine patients. Neuroimaging findings included hydrocephalus (54.5%), meningeal enhancement (45.5%), and mass lesions (45.5%). Seven patients had antemortem CNS biopsies (brain/meninges [n = 6], spinal [n = 1]), which showed noncaseating granulomas. Eight patients died (mortality rate: 72.7%). Postmortem examination showed granulomatous involvement of the leptomeninges and cerebral parenchyma in all cases with systemic involvement in 50%, chiefly in the form of noncaseating granulomas of the hilar nodes. Six patients fulfilled the clinical, radiological, and pathological diagnostic criteria for neurosarcoidosis. The remaining five patients had an unclassifiable pathogen-free granulomatous disease of the CNS. PFGD of the CNS are associated with a poor prognosis. Although neurosarcoidosis may account for some of the cases, there remains an unclassifiable subgroup that continues to be a diagnostic and management challenge.

Adolescent↗
PubMed1996

Effects of ofloxacin administration on the reliability of urine glucose testing.

OBJECTIVE: To study the effects of ofloxacin on the reliability of urine glucose testing. DESIGN: Open-label, nonrandomized. SETTING: A university-affiliated tertiary care hospital, ambulatory clinic. PARTICIPANTS: Ten healthy volunteers (8 men and 2 women) aged 22-39 years. MAIN OUTCOME MEASURES: Phase I (in vitro) involved the addition of selected amounts of ofloxacin to a set of standard 50-mL urine samples prepared to simulate glycosuria. Phase II (in vivo) involved the oral administration of ofloxacin 400 mg to 10 subjects. Urine was collected: (1) immediately predose, (2) pooled 0-4 hours postdose, and (3) pooled 4-8 hours postdose. Known glucose concentrations were then added to these samples. Clinitest and Diastix tests were performed on all samples. The accuracy of these tests in determining glucose concentrations was compared among urine samples taken before and after ofloxacin dosing. RESULTS: None of the ofloxacin concentrations in phase I (0, 25, 50, 100, 200, 400, and 800 micrograms/mL) influenced these testing methods at the urine glucose concentrations of 0.0%, 0.5%, 1%, and 2%. Likewise, the accuracy of these two tests was unaffected by ofloxacin administration in phase II. CONCLUSIONS: In single-dose administration, ofloxacin does not interfere with Clinitest or Diastix for determining urine glucose concentrations.

Adult↗
PubMed1996

Endobronchial hamartoma presenting as massive haemoptysis.

A 53 year old man presented with massive haemoptysis, and chest radiography revealed a left suprahilar mass. At thoracotomy he was found to have a modular mass in the left upper lobe, which was attached to a peripheral bronchus. Histology confirmed a pulmonary hamartoma.

Bronchial Diseases↗
PubMed1996

[Dysphonia and inhalation of corticoids: a prospective study].

Dysphonia or hoarseness is a well recognised but poorly understood complication of inhaled steroid therapy. 20 asthmatics were investigated, using a perceptual rating score of hoarseness, videolaryngoscopy and videostroboscopy, prior to and after three months of high dose inhaled steroid therapy (1 mg/day). A group of 22 healthy volunteers acted as controls. Prior to commencing inhaled steroid therapy six of the asthmatics were hoarse. Erythema and oedema was noted in 10 asthmatics and vocal fold nodules in 2 asthmatics. 4 of the control group had erythema and oedema. There was significantly more vocal fold pathology in the asthmatic group, p = 0.0135. After three months of inhaled steroid therapy, improvement in voice was noted in 2 of the 6 hoarse asthmatics. This was associated with resolution of vocal fold nodules in one case and with resolution of oedema in another. One asthmatic developed a mid glottic chink. This study demonstrates that asthmatics have significantly more vocal fold pathology than healthy controls. These findings improve with commencement of inhaled steroid therapy. The development of steroid induced myopathy of the vocal folds is a possible cause for the development of a mid glottic chink in one of our subjects. Further studies are necessary to investigate this area further.

Administration, Inhalation↗
PubMed1995

Signalling via CD28 of human naive neonatal T lymphocytes.

Accessory molecules play a crucial role in the development of the T cell response to antigenic challenge. We have examined the role of CD28 in modulating the 'naive' neonatal T cell response to anti-CD2-mediated activation. To compare the role of CD28, neonatal and adult T cells were stimulated with a pair of mitogenic anti-CD2 antibodies in the presence or absence of anti-CD28 MoAb. With anti-CD2 alone, neonatal T cells proliferated slightly but produced no detectable IL-2, whereas adult T cells proliferated vigorously, with significant IL-2 production. Costimulation with anti-CD28 MoAb greatly enhanced the proliferative response of neonatal T cells to levels equivalent to those of adult T cells, whereas adult T cells showed only slight increases. Although IL-2 secretion was increased in the presence of anti-CD28 MoAb, neonatal T cell IL-2 production remained lower than in adults. In contrast, enhancement of IL-2 mRNA expression in neonates was similar to adult levels. Anti-CD28 MoAb costimulation increased NF kappa B levels in neonates, albeit to levels lower than that of adults. The cellular mechanism governing the diminished proliferative response of neonatal T lymphocytes to anti-CD2 may therefore be due to decreased NF kappa B induction, reduced IL-2 mRNA expression and deficient IL-2 production. Although anti-CD28 MoAb costimulation enhances all of the above signals, NF kappa B and IL-2 levels remain lower than in adults, suggesting the need for further activation requirements in the neonate.

Adult↗
PubMed1994

Phosphorylated HSP27 associates with the activation-dependent cytoskeleton in human platelets.

The three prominently phosphorylated 29-kD proteins in thrombin-activated human platelets are forms of the mammalian 27-kD heat-shock protein (HSP27). Though the function of HSP27 is not yet known, its phosphorylation is highly correlated with platelet secretion, and recent evidence in nonhematopoietic cells suggests that HSP27 regulates cortical actin filament assembly. Therefore, the subcellular location and phosphorylation state of HSP27 in resting and thrombin-activated platelets was studied. Platelets were fractionated by established Triton X-100 lysis methods followed by differential centrifugation to obtain the 14,000g fraction (low-speed cytoskeleton), 100,000g fraction (membrane skeleton), and the 100,000g supernatant fraction containing soluble cytosolic proteins. In resting platelets, HSP27 was present principally in the 100,000g supernatant fraction. Platelet activation with thrombin led to translocation of the majority of HSP27 to the low-speed cytoskeleton. This association was reversible by DNase, supporting the idea that HSP27 is a specific component of the actin cytoskeleton. Immunofluorescence studies similarly showed HSP27 is cytoplasmic in resting platelets but colocalizes with actin in fully spread, glass-activated platelets. Immunoprecipitation studies showed a small amount of constitutively phosphorylated HSP27 in resting platelets, but phosphorylation of the majority of HSP27 after thrombin activation. After activation, virtually all phosphorylated HSP27 was found in the low-speed cytoskeletal fraction, and each of the three phosphorylated forms of HSP27 were present by two-dimensional autoradiography. Furthermore, in time-course studies, the phosphorylation of HSP27 occurred just before localization of HSP27 to the low-speed pellet. These results show that, after platelet activation, HSP27 is first phosphorylated and then translocated from the cytoplasm to the assembling cytoskeleton, and suggest that HSP27 phosphorylation may be important to the binding of HSP27 to cytoskeletal components and the cytoskeletal rearrangements characteristic of platelet activation.

Actins↗
PubMed1994

Antiglomerular basement membrane disease: the long-term pulmonary outcome.

We have evaluated long-term pulmonary function in 14 patients who were treated for anti-glomerular basement membrane disease at our institution during the last 17 years. Eight of these patients had evidence of pulmonary involvement, as manifested by hemoptysis, pulmonary infiltrates on chest x-ray film, or anemia. These patients were compared with a control group of 15 patients who had renal disease and who were matched for degree and duration of renal disease, age, smoking history, and method of renal replacement. The following variables were measured in each patient: forced vital capacity, forced expiratory volume in 1 minute, vital capacity, total lung capacity, residual volume, functional residual capacity, single-breath carbon monoxide transfer factor, and single-breath carbon monoxide transfer factor corrected for alveolar volume (KCO). These patients also participated in a graded exercise test and measurements of oxygen uptake, carbon dioxide production, minute ventilation, and oxygen saturation were taken. Patients with anti-glomerular basement membrane disease and a prior history of pulmonary hemorrhage had a significantly reduced KCO (46% +/- 10% v 68.7% +/- 14.7%) compared with the control group. There was no difference in any of the other measured parameters.

Adult↗
PubMed1994

Chronic occult intra-alveolar hemorrhage: a rare cause of failure to respond to erythropoietin.

Recombinant human erythropoietin (EPO) is an effective and safe therapy for correction of anemia in end-stage renal disease (ESRD). Clinical trials reported to date suggest that EPO improves anemia in over 90% of hemodialysis patients with anemia (Eschbach 1989). Factors which have been identified that appear to inhibit the effectiveness of EPO are infection [Muirhead N et al. 1990], iron deficiency, hyperparathyroidism, aluminium excess [Casati 1991] and persistent GIT bleeding. The development of reticulocytosis in response to EPO in the absence of a rise in hematocrit should alert the clinician to the possibility of either hemolysis or occult blood loss. We present a case in which, despite the development of a reticulocytosis of 5% in response to EPO and the absence of hemolysis, we had difficulty in identifying the presumed source of blood loss.

Anemia↗
PubMed1993

An Australian experience of transdermal oestradiol patches in a subtropical climate.

Tolerability and efficacy of transdermal oestradiol patches were assessed in 121 menopausal women over a period of 3 months to 2.5 years. Of particular interest, in a subtropical climate such as Brisbane, were the problems associated with adhesiveness and skin irritation during the summer months. We conducted a retrospective study with self-administered questionnaires. All patients had been selected for the nonoral route because of side-effects or relative contraindications to oral therapy. There was, overall, good efficacy and acceptability. The majority of the women found the patch very adequate in relieving symptoms of the menopause (vasomotor, genitourinary and musculoskeletal). Most preferred the patch to oral therapy. The oestradiol patch was well tolerated and few side-effects were reported. Breast tenderness and weight gain were 2 minor problems associated with its use. Skin irritation was minimal, but adhesiveness was a problem during the summer months, especially with swimming or showering. Some practical suggestions were obtained about how to overcome site of application problems.

Adhesiveness↗
PubMed1992

Oestrogen and cyclical progestogen in postmenopausal hormone replacement therapy.

OBJECTIVE: To ascertain the effectiveness, safety and incidence of side effects of a postmenopausal hormone replacement regimen consisting of continuous conjugated equine oestrogens and cyclical medroxyprogesterone acetate given for the first 14 days of each calendar month. DESIGN: A six month, prospective, open label, two centre, outpatient study of continuous Premarin (0.625 mg; Wyeth-Ayerst) and cyclical Provera (10 mg; Upjohn). Dosage adjustment was allowed in one centre. STUDY POPULATION: Seventy-six postmenopausal women in Adelaide and Brisbane. MAIN OUTCOME MEASURES: Menopausal symptom score, serum lipid levels, routine biochemical and haematological indices, endometrial histology and clinical bleeding pattern, blood pressure, weight changes, side effects, withdrawal from the study, compliance and necessary dose adjustment. MAIN RESULTS: Eight women withdrew from the study and nearly 50% experienced some minor side effect. Where dosage adjustment was allowed, almost all side effects were eliminated. Most patients had acceptable regular withdrawal bleeds although some were deemed heavy. There was a statistically highly significant 54% reduction in the menopausal symptoms score at three months and a 62% reduction at six months. Endometrial biopsy at six months showed atrophic or secretory endometrium with no inappropriate proliferation or hyperplasia. Total cholesterol and low density lipoprotein (LDL) cholesterol levels were significantly decreased. The high density lipoprotein (HDL) cholesterol level remained unchanged and triglyceride levels were raised within the normal range. There were no other clinically relevant biochemical, haematological or clinical changes. CONCLUSION: Continuous conjugated equine oestrogens (0.625 mg) and cyclical medroxyprogesterone acetate (10 mg) for the first 14 days of each calendar month proved to be a safe and effective postmenopausal therapy regimen. Initial minor side effects were common but could be readily ameliorated with early follow-up and dose titration.

Adult↗
PubMed1991

The 29-kDa proteins phosphorylated in thrombin-activated human platelets are forms of the estrogen receptor-related 27-kDa heat shock protein.

Thrombin plays a critical role in platelet activation, hemostasis, and thrombosis. Cellular activation by thrombin leads to the phosphorylation of multiple proteins, most of which are unidentified. We have characterized several 29-kDa proteins that are rapidly phosphorylated following exposure of intact human platelets to thrombin. A murine monoclonal antibody raised to an unidentified estrogen receptor-related 29-kDa protein selectively recognized these proteins as well as a more basic, unphosphorylated 27-kDa protein. Cellular activation by thrombin led to a marked shift in the proportion of protein from the 27-kDa unphosphorylated form to the 29-kDa phosphoprotein species. Using this antibody, we isolated and sequenced a human cDNA clone encoding a protein that was identical to the mammalian 27-kDa heat shock protein (HSP27), a protein of uncertain function that is known to be phosphorylated to several forms and to be transcriptionally induced by estrogen. The 29-kDa proteins were confirmed to be phosphorylated forms of HSP27 by immunoprecipitation studies. Thus, the "estrogen receptor-related protein" is HSP27, and the three major 29-kDa proteins phosphorylated in thrombin-activated platelets are forms of HSP27. These data suggest a role for HSP27 in the signal transduction events of platelet activation.

Amino Acid Sequence↗
PubMed1991

Leukotriene receptor blockade reduces bile acid-induced superficial gastric mucosal injury.

Leukotriene C4 and D4 are putative mediators of the severe gastric mucosal injury caused by a variety of topical irritants. The purpose of this present study was (1) to investigate the effect of pretreatment with topical leukotriene C4 and D4 on the more superficial injury caused by low concentrations of bile acid and (2) to determine the effect of leukotriene receptor blockade, alone and during leukotriene pretreatment, on this injury. Prior to injury with topical 5 mM acidified taurocholate (pH 1.2) rat stomachs were pretreated with either normal saline, leukotriene C4 or D4, SKF-104353 (a leukotriene receptor antagonist), SKF-104353/LTC4, or SKF-104353/LTD4. Injury was assessed by measuring hydrogen ion flux and DNA efflux, a marker of gastric mucosal cell exfoliation. Both LTC4 and LTD4 significantly increased bile acid-induced luminal hydrogen ion loss and DNA efflux. Leukotriene receptor blockade not only blocked this effect, but also significantly decreased the injury from bile acid alone. Thus, both LTC4 and LTD4 exacerbate the superficial gastric mucosal injury caused by physiologic concentrations of bile acids. Leukotriene receptor blockade with SKF-104353 completely blocks these effects and reduces injury from bile acid alone.

Animals↗