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Biomedical subjects

M Hurley

Publications and source records attributed to M Hurley.

At least 19 recordsLinked to original sources
PubMed2003

Urinary levels of creatine and other metabolites in the assessment of polymyositis and dermatomyositis.

BACKGROUND: A simple and reliable method is needed to assess disease activity and monitor the efficacy of therapy in polymyositis (PM) and dermatomyositis (DM). This study used in vitro proton ((1)H) magnetic resonance spectroscopy (MRS) to explore whether excretion of urinary metabolites can be used as a reliable marker of disease in PM and DM patients. METHODS: Urine samples were obtained from PM/DM patients (n=34), healthy controls (50) and subjects with known muscle-wasting conditions including adult-onset muscular dystrophy (8), stroke patients (10), rheumatoid arthritis (RA) patients on steroids (13) and not on steroids (16) and patients with alcoholic myopathy (12). Levels of urinary metabolites were then correlated with creatine kinase (CK) activities and quadriceps muscle strength. RESULTS: Creatine was detected in the urine in 26 of 35 patients with PM/DM, four of 60 cases with other medical disorders (including one with adult-onset dystrophy, one with a stroke and two with RA who were not on steroids) and 10 of 50 healthy controls. The urinary creatine/creatinine ratio exceeded 0.4 in 20 patients with PM/DM but no patients with other medical disorders and no healthy controls. These differences were highly significant (P<0.001) by Kruskal-Wallis test (comparing all groups) and by Mann-Whitney U-tests (comparing individual groups with PM/DM cases). Citrate, glycine, choline-containing compounds and taurine levels were significantly increased in PM/DM when compared with controls. There were positive correlations between CK activities and choline-containing compounds (r=0.78, P=0.0006) and also between CK activities and betaine (r=0.57, P=0.026). CONCLUSIONS: This study shows significant differences in the urinary levels of creatine, choline-containing metabolites, betaine and citrate in PM/DM subjects compared with controls, although further work is required to elucidate the underlying metabolic processes.

Adult↗
PubMed2001

Anomalous anatomy of speech-language areas in adults with persistent developmental stuttering.

OBJECTIVE: The major aim of this study was to determine whether adults with persistent developmental stuttering (PDS) have anomalous anatomy in cortical speech-language areas. The major postulate was that anomalous cerebral dominance, reflected by anomalous cortical anatomy in various regions, may put an individual at increased risk for the development of stuttering. METHODS: Adults with PDS (n = 16) and controls (n = 16) matched for age, sex, hand preference, and education were studied. Volumetric MRI scans were completed. Frontal (pars triangularis, pars opercularis) and temporo-parietal areas (planum temporale, posterior ascending ramus) were measured in the left and right hemispheres and interhemispheric asymmetries were computed. Gyral variants were assessed within these perisylvian cortical speech-language areas. RESULTS: The right and left planum temporale were significantly larger in the adults with PDS (p = 0.045), and the magnitude of the planar asymmetry was reduced (p = 0.003). Some gyral variants were unique to the adults with PDS, including a second diagonal sulcus and extra gyri along the superior bank of the sylvian fossa. In addition, anatomic subgroups emerged based on sex and hand preference. Overall, the adults with PDS had significantly more gyral variants (mean = 4.19) than controls (mean = 1.31, p < 0.0005). CONCLUSIONS: These results provide strong evidence that adults with PDS have anomalous anatomy in perisylvian speech and language areas. No one anatomic feature distinguished the groups, but multiple loci within a widely distributed neural network differed between groups. These results provide the first evidence that anatomic anomalies within perisylvian speech-language areas may put an individual at risk for the development of stuttering.

Adult↗
PubMed2001

Ultrasound features of blunt testicular injury.

This is a retrospective study of ultrasound examination for patients with blunt scrotal trauma. Fifteen patients were examined over an 18-month period. The purpose of the study was to discover the ultrasonic features of blunt testicular trauma and to distinguish less severe from more severe injury with testicular rupture requiring surgery. Three had ultrasonic findings of acute testicular rupture and this was confirmed by surgery. The ultrasound features of testicular trauma with rupture are irregularity of testicular outline and inhomogeneity of testicular texture. The value of ultrasound in diagnosing patients with testicular rupture and, therefore, requiring urgent surgery is discussed. In our limited study, irregularity of testicular outline was the distinguishing feature of rupture.

Adolescent↗
PubMed2001

Allergic bronchopulmonary aspergillosis: a rare cause of pleural effusion.

Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Allergic bronchopulmonary aspergillosis (ABPA) is a syndrome seen in patients with asthma and cystic fibrosis, and is characterized by hypersensitivity to chronic colonization of the airways with A. fumigatus. We report the case of a patient with ABPA presenting with pleural effusion. A 27-year-old male was referred with recurrent right pleural effusion. Past medical history was remarkable for asthma, allergic sinusitis, and recurrent pleurisy. Investigations revealed peripheral eosinophilia with elevated serum immunoglobulin E and bilateral pleural effusions with bilateral upper lobe proximal bronchiectasis. Precipitating serum antibodies to A. fumigatus were positive and the A. fumigatus immediate skin test yielded a positive reaction. A diagnosis of ABPA associated with bilateral pleural effusions was made and the patient was commenced on prednisolone. At review, the patient's symptoms had considerably improved and his pleural effusions had resolved. ABPA may present with diverse atypical syndromes, including paratracheal and hilar adenopathy, obstructive lung collapse, pneumothorax and bronchopleural fistula, and allergic sinusitis. Allergic bronchopulmonary aspergillosis is a rare cause of pleural effusion and must be considered in the differential diagnosis of patients presenting with a pleural effusion, in particular those with a history of asthma.

Adult↗
PubMed2001

Physical, functional and other non-pharmacological interventions for osteoarthritis.

Non-pharmacological interventions are frequently and widely used in the management of patients with osteoarthritis (OA). However, there is little evidence that most of these interventions are efficacious (i.e. that they work under ideal circumstances) owing to the paucity of research studies on these interventions and the fundamental methodological flaws in published studies. Moreover, the clinical effectiveness of non-pharmacological interventions (i.e. their efficacy under the conditions prevailing in clinical practice) is unknown, and cost-analysis of these interventions has not been carried out. If evidence-based management guidelines were to be constructed solely from firm research studies few could be recommended. Established and developing research methodologies and techniques should be employed to construct and conduct research programmes that appropriately evaluate the clinical and cost effectiveness of these complex non-pharmacological healthcare interventions. Establishing clinical effectiveness will ensure that we have practice-based evidence and are administering relevant, effective and optimal healthcare for patients with OA, maximizing the efficient use of healthcare resources.

Costs and Cost Analysis↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Adult service refusers in the greater Dublin area.

The reclusive behaviour and living conditions of people living in the community can be a source of concern to others, especially when statutory and voluntary support are refused. A cross-sectional observational study of service providers was carried out to profile 'service refusers' in the greater Dublin area and to describe the support offered. Two hundred and thirty three subjects were identified. Most were female (127, 54.5%) and 65 years of age or older (162, 69.5%). Approximately 50% (117, 50.2%) were living in private accommodation. The majority of subjects were considered to exhibit traits of poor personal hygiene (171, 73.4%), suspiciousness (160, 68.7%), secrecy (144, 61.8%) or hoarding (126, 54.1%). Forty-seven per cent of subjects (110) identified met the criteria for 'Diogenes Syndrome'. A wide variety supports had been offered including meals-on-wheels, home-helps and house cleaning. Respondents considered that 51.9% (121) of subjects had not been offered a service which proved successful. Despite the best efforts of agencies, service refusers can remain steadfast in not availing of the help that is on offer.

Adult↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1994

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↗
PubMed1994

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↗