Search PubMed⌕ Search

Biomedical subjects

M Hurley

Publications and source records attributed to M Hurley.

At least 19 recordsLinked to original sources

The ultrasound investigation of scrotal swelling.

The objectives of this study were to: (1) establish the causes of scrotal swelling in the hospital catchment population; (2) define the role of high frequency ultrasound examination in the management of scrotal swelling. A retrospective study of 582 patients who had high frequency ultrasound examination was carried out. Those requiring more information on perfusion had colour doppler examination. Forty-four per cent of examinations were performed for scrotal swelling. The cause of the scrotal swelling was mainly extratesticular (75% of all scrotal swellings), hydrocele being the commonest. Of the intratesticular causes, infection (50.8%) and tumour (20.6%) were the commonest. In conclusion ultrasound examination distinguishes extratesticular (almost always benign) from intratesticular (potentially malignant) causes of scrotal swelling. Infection, trauma and torsion mimic the ultrasound appearance of tumour as do rare benign entities.

Cysts↗

Rectus sheath haematoma: an unusual diagnosis.

Rectus sheath haematoma is a very rare occurrence. There were four cases in this hospital within a three month period. In this article, these cases, their investigation and management arc reported. A review of the literature was undertaken to ascertain how best to diagnose and treat this condition.

Adult↗

A pilot study of cervical screening in an inner city area--lessons for a national programme.

The objectives of this study were to examine aspects of organization of a proposed national screening programme based in general practice. The target population of women aged 25-59 years and their general practitioners (GPs), in a defined inner city area, was identified from a population register of persons eligible for free medical services; a computerized system was developed for invitations and record linkage of cytology results. Smears were examined in one laboratory and follow up of women with abnormal smears was undertaken by one gynaecologist. A random sample of non-responders was surveyed by questionnaire. Response following two invitations was only 20%. Practices with male doctors only had significantly lower response rates (P < 0.001) than those with a female doctor/nurse. A survey of non-responders showed that over 20% of addresses were incorrect and 16% of those interviewed were ineligible for smear tests. A preference for a female to undertake smears was expressed by 67%, and 77% believed that the purpose of the cervical smear was to detect cancer. An accurate population register, health promotion, support for GP practices, provision of alternative venues for smear tests, development of computer systems, accurate data entry and fail-safe follow up are aspects of a cervical screening service which must be addressed prior to setting up a national service.

Adult↗

Intact insulin-like growth factor binding protein-5 (IGFBP-5) associates with bone matrix and the soluble fragments of IGFBP-5 accumulated in culture medium of neonatal mouse calvariae by parathyroid hormone and prostaglandin E2-treatment.

We examined the distribution of insulin-like growth factor binding proteins (IGFBPs) in cultured neonatal mouse calvariae. IGFBP-3 and -4 were predominantly found in the conditioned medium. IGFBP-2 was partitioned between conditioned medium and bone and extracellular matrix (BECM), while intact (31-kDa) IGFBP-5 was most abundant in BECM extracts. After treatment with parathyroid hormone (PTH, 10(-8) M) or prostaglandin E2 (PGE2, 10(-6) M), immunoreactive IGFBP-5 accumulated in the conditioned medium in a 21-kDa form which did not bind IGF-I on Western ligand blots. PTH and PGE2 did not alter the level of steady-state IGFBP-5 mRNA, nor markedly stimulate IGFBP-5 synthesis in the calvariae, and thus accumulation of 21-kDa IGFBP-5 was largely due to release from BECM. This accumulation of truncated IGFBP-5 in the conditioned medium was not dependent on osteoclastic bone resorption, since it was not blocked by calcitonin or a bisphosphonate which inhibited PTH- and PGE2-stimulated 45Ca-release. The conditioned medium from PTH- or PGE2-treated cultures degraded recombinant human IGFBP-5 into lower molecular weight fragments. Addition of IGF-1 at 10(-8) M into the culture resulted in accumulation of native 31-kDa IGFBP-5. However, even in the presence of IGF-1, the native IGFBP-5 was degraded and the 21-kDa product accumulated in the culture medium. These results suggested a possible proteolytic mechanism for 21-kDa IGFBP-5 accumulation, responsive to PTH and PGE2. Aprotinin, leupeptin, cystatin, and bestatin did not inhibit the effects of PTH and PGE2 in the cultures. The localization of IGFBP-5 in BECM and its release and proteolysis induced by PTH and PGE2 could play a role in the local regulation of bone metabolism.

Animals↗

Effector mechanisms responsible for gamma interferon-mediated host resistance to Legionella pneumophila lung infection: the role of endogenous nitric oxide differs in susceptible and resistant murine hosts.

To facilitate identification of the effector mechanism(s) responsible for gamma interferon (IFN-gamma)-mediated host resistance to Legionella pneumophila, a murine model of legionellosis in BALB/c mice with a targeted disruption in the IFN-gamma gene (gamma knockout [GKO] mice) was developed. Immunocompetent BALB/c mice and GKO mice were inoculated intratracheally with virulent L. pneumophila (10(6) bacteria per mouse), and bacterial clearance and the pulmonary inflammatory response were assessed. L. pneumophila did not replicate in, and was rapidly cleared from, the lungs of immunocompetent BALB/c mice, demonstrating that immunocompetent BALB/c mice are resistant to replicative L. pneumophila pulmonary infections. In contrast, similarly infected GKO mice developed persistent, replicative intrapulmonary L. pneumophila infections with extrapulmonary dissemination of the bacteria to the spleen. Histopathologic and flow cytometric analysis of L. pneumophila-infected lung tissue demonstrated that while immunocompetent BALB/c mice develop multifocal pneumonitis which resolves, similarly infected GKO mice develop diffuse pneumonitis with persistent neutrophil recruitment into the lung. Intratracheal administration of exogenous IFN-gamma to L. pneumophila-infected GKO mice facilitated intrapulmonary clearance of the bacteria, confirming the pivotal role of IFN-gamma in innate host defenses to L. pneumophila lung infection in this murine host. The potential role of endogenous reactive nitrogen intermediates, including nitric oxide (NO), in IFN-gamma-mediated resistance to L. pneumophila pulmonary infections in immunocompetent BALB/c mice was subsequently assessed. Macrophage inducible nitric oxide synthetase (an enzyme responsible for the production of NO) was induced in alveolar cells from L. pneumophila-infected immunocompetent BALB/c mice (with maximal expression at 48 h postinfection) but was not induced in similarly infected GKO mice. However, administration of the NO synthetase inhibitor N-monomethyl-L-arginine did not significantly inhibit clearance of L. pneumophila from the lung of immunocompetent BALB/c mice (compared with that in similarly infected mice not administered N-monomethyl-L-arginine). In contrast, we have previously demonstrated that IFN-gamma-induced host resistance to replicative L. pneumophila lung infections in a susceptible murine host (A/J mice) is mediated, in part, by endogenous NO. Taken together, these studies identify a differing role of endogenous NO in IFN-gamma-mediated resistance to L. pneumophila pulmonary infection in susceptible and resistant murine hosts.

Animals↗

Coinoculation with Hartmannella vermiformis enhances replicative Legionella pneumophila lung infection in a murine model of Legionnaires' disease.

The effect of inhaled amoebae on the pathogenesis of Legionnaires' disease was investigated in vivo. A/J mice, which are susceptible to replicative Legionella pneumophila infections, were inoculated intratracheally with L. pneumophila (10(6) bacteria per mouse) or were coinoculated with L. pneumophila (10(6) bacteria per mouse) and Hartmannella vermiformis (10(6) amoebae per mouse). The effect of coinoculation with H. vermiformis on bacterial clearance, histopathology, cellular recruitment into the lung, and intrapulmonary levels of cytokines including gamma interferon and tumor necrosis factor alpha was subsequently assessed. Coinoculation with H. vermiformis significantly enhanced intrapulmonary growth of L. pneumophila in A/J mice. Histopathologic and flow cytometric analysis of lung tissue demonstrated that while A/J mice inoculated with L. pneumophila alone develop multifocal pneumonitis which resolves with minimal mortality, mice coinoculated with H. vermiformis develop diffuse pneumonitis which is associated with diminished intrapulmonary recruitment of lymphocytes and mononuclear phagocytic cells and significant mortality. Furthermore, coinoculation of mice with H. vermiformis resulted in a fourfold enhancement in intrapulmonary levels of gamma interferon and tumor necrosis factor alpha compared with mice infected with L. pneumophila alone. The effect of H. vermiformis on intrapulmonary growth of L. pneumophila in a resistant host (i.e., BALB/c mice) was subsequently evaluated. While BALB/c mice do not develop replicative L. pneumophila infections following inoculation with L. pneumophila alone, there was an eightfold increase in intrapulmonary L. pneumophila in BALB/c mice coinoculated with H. vermiformis. These studies, demonstrating that intrapulmonary amoebae potentiate replicative L. pneumophila lung infection in both a susceptible and a resistant host, have significant implications with regard to the potential role of protozoa in the pathogenesis of pulmonary diseases due to inhaled pathogens and in the design of strategies to prevent and/or control legionellosis.

Animals↗

Stimulatory effect of a phorbol ester on expression of insulin-like growth factor (IGF) binding protein-2 and level of IGF-I receptors in mouse osteoblastic MC3T3-E1 cells.

We examined the relationship between signal transduction and the expression of insulin-like growth factor I (IGF-I), IGF-I receptor level, and IGF binding proteins (IGFBPs) in murine clonal osteoblastic MC3T3-E1 cells. 12-O-Tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, decreased the secretion of immunoreactive IGF-I into the medium, whereas dibutyryl cAMP (Bt2cAMP) augmented the secretion. In contrast, TPA increased the level of type I IGF receptor on the cells. Furthermore, MC3T3-E1 cells produced and secreted at least three different IGFBPs with molecular masses of 24, 30, and 34 kDa, and the 24-kDa IGFBP was predominant under normal conditions. However, TPA specifically increased the secretion of the 34-kDa IGFBP. The N-terminal amino acid sequence of the purified 34-kDa IGFBP was nearly identical with that of rat IGFBP-2. Furthermore, the 34-kDa IGFBP was immunoreactive to anti-IGFBP-2 antiserum. The level of IGFBP-2 mRNA in the cells was increased by TPA, indicating that the increase in IGFBP-2 secretion results from the stimulation of IGFBP-2 production. In contrast, Bt2cAMP affected neither IGF-I receptor number nor the IGFBP secretion. These results indicate that the production of IGF-I and the expression of IGF-I receptors and IGFBP-2 are up-regulated by the activation of adenylate cyclase and protein kinase C, respectively, in osteoblastic MC3T3-E1 cells.

Adenylyl Cyclases↗

Replicative Legionella pneumophila lung infection in intratracheally inoculated A/J mice. A murine model of human Legionnaires' disease.

The role of host immune responses in the pathogenesis of Legionnaires' disease is incompletely understood, due in part to the current lack of an animal model that is both susceptible to replicative Legionella pneumophila-induced lung infection and for which species-specific immunological reagents are available. We have developed a model of replicative L. pneumophila lung infection in intratracheally inoculated A/J mice. L. pneumophila was obtained in the exponential growth phase and inoculated into the trachea of 6- to 8-week-old female A/J mice. Microbiological and histopathological evidence of infection was demonstrated in mice inoculated with 10(6) colony-forming units. Development of an acute pneumonia that resembled human Legionnaires' disease coincided with exponential growth of the bacteria in the lung 24 to 48 hours after intratracheal inoculation of L. pneumophila. This was associated with increased plasma levels of interferon-gamma at 24 hours after inoculation. After 48 hours, the bacteria were gradually eliminated from the lung over the next 5 days, corresponding with resolution of the inflammatory response in the lung, thereby mimicking the outcome frequently seen in the immunocompetent human host. Treatment of animals with anti-interferon-gamma antibody enhanced bacterial replication and disease progression, indicating an important role of host immune response in resolution of the infection. Because of the availability of murine-specific reagents, this model of replicative L. pneumophila lung infection in A/J mice after intrapulmonary inoculation of L. pneumophila potentially provides an important tool for future studies investigating the role of host immune responses in the pathogenesis of Legionnaires' disease in the immunocompetent host.

Animals↗

Contact sports and injury.

A year long survey of sports injuries in the accident and emergency department of St. Luke's Hospital, Kilkenny revealed 864 injuries, with hurling and soccer accounting for 41% and 23% respectively. In hurling, lacerations to face and scalp, and fractures of the wrist and hand, accounted for a large number of the injuries seen, while in soccer bruising and sprains of the lower limbs accounted for the majority of the injuries. We make some recommendations for avoidance of these injuries. We show clearly that non-accidental or deliberately inflicted injury forms a significant proportion of sport injuries and recommended steps to curb non-accidental injuries.

Adolescent↗