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Biomedical subjects

G M McCarthy

Publications and source records attributed to G M McCarthy.

At least 19 recordsLinked to original sources
PubMed2026

EDucation and eXercise for gluteal tendinopathy in an Irish context (EDX-Ireland): findings from the LEAP-Ireland feasibility randomised controlled trial.

OBJECTIVE: To assess feasibility of a randomised controlled trial (RCT) investigating effectiveness of 6 sessions of an EDucation and eXercise intervention delivered over 8 weeks (EDX-Ireland) for gluteal tendinopathy, against usual care. EDX-Ireland was modified from a 14-session EDucation and eXercise intervention (EDX), delivered over 8 weeks, previously evaluated in an Australian RCT. DESIGN: Feasibility parallel RCT. METHODS: Participants were randomly assigned to physiotherapist-led EDX-Ireland or usual care. EDX-Ireland comprised 6 sessions of education, hip abductor strengthening and functional loading over 8 weeks, supported by a home exercise programme. Primary outcomes included success of different recruitment strategies and recruitment/retention rates. Secondary outcomes measured global rating of change and other clinical outcomes. Descriptive statistics (percentage, mean, standard deviations and 95% confidence intervals (CI)) are presented. RESULTS: Of 323 individuals who expressed interest in study participation, 119 completed physical examination screening, and 65 met criteria and consented to participate (recruitment rate 55%). Sixty-five people (89% women; mean age 53.1 ± 9.3 years), were randomised to EDX-Ireland (n = 32) or usual care (n = 33). Eighty-three percent (n = 54) were recruited via social media/community, 3% (n = 2) from general practitioners and 14% (n = 9) from orthopaedic/rheumatology. Retention was 92% (95% CI 82-97%, n = 60) at 8-weeks, and 89% (95% CI 79-96%, n = 58) at 3-months. Feasibility thresholds were met. Effect size estimates indicate that 134 participants would be required for a future RCT. CONCLUSION: Pre-defined recruitment and retention thresholds were met, indicating that a RCT evaluating 6 sessions of physiotherapist-delivered education and exercise against usual care for gluteal tendinopathy is feasible. TRIAL REGISTRATION: Clinicaltrials.gov (NCT05516563).

Humans↗
PubMed2006

BCP crystals increase prostacyclin production and upregulate the prostacyclin receptor in OA synovial fibroblasts: potential effects on mPGES1 and MMP-13.

OBJECTIVE: To investigate the potential involvement of prostacyclin in basic calcium phosphate (BCP) crystal-induced responses in osteoarthritic synovial fibroblasts (OASF). METHODS: OASF grown in culture were stimulated with BCP crystals. Prostacyclin production was measured by enzyme immunoassay. Expression of messenger RNA (mRNA) transcripts was assessed by real-time polymerase chain reaction (PCR). Expression of prostacyclin synthase (PGIS) and the prostacyclin (IP) receptor was measured. The effects of iloprost, a prostacyclin analogue, on expression of genes implicated in osteoarthritis such as microsomal prostaglandin E2 synthase 1 (mPGES1) and matrix metalloproteinases (MMPs) were also studied. FPT inhibitor II, a farnesyl transferase inhibitor, was used to antagonize iloprost-induced responses. RESULTS: BCP crystal stimulation led to a five-fold increase in prostacyclin production in OASF compared to untreated cells. This induction was attenuated by cyclooxygenase (COX)-2 and COX-1 inhibition at 4 and 32h, respectively. PGIS and IP receptor transcripts were constitutively expressed in OASF. BCP crystals upregulated IP receptor expression two-fold. While iloprost diminished BCP crystal-stimulated IP receptor upregulation, the inhibitory effect of iloprost was blocked by the farnesyl transferase inhibitor. In addition, iloprost upregulated mPGES1 and downregulated MMP-13 expression in BCP crystal-stimulated OASF, effects that were not influenced by the farnesyl transferase inhibitor. CONCLUSIONS: These data showed for the first time that BCP crystals can increase prostacyclin production and upregulate expression of the IP receptor in OASF. The potential of prostacyclin to influence BCP crystal-stimulated responses was supported by the effects of iloprost on the expression of the IP receptor, mPGES1 and MMP-13. These data demonstrate the potential involvement of prostacyclin in BCP crystal-associated osteoarthritis (OA) and suggest that inhibition of PG synthesis with non-steroidal anti-inflammatory drugs may have both deleterious and beneficial effects in BCP crystal-associated OA.

Calcium Phosphates↗
PubMed2006

Calcium crystal deposition diseases: update on pathogenesis and manifestations.

Basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate crystals are the most common types of pathologic calcium-containing crystals. Although these crystals long have been associated with a variety of rheumatic syndromes, recent evidence implicates BCP crystals in the pathogenesis of breast cancer and atherosclerosis. Although understanding of molecular mechanisms involved in generating these pathologic effects has been advanced significantly in recent years, they still are understood incompletely. Such advances are essential to the ongoing search for effective therapies for crystal-associated diseases.

Calcium Phosphates↗
PubMed2001

A genomewide linkage study of age at onset in schizophrenia.

There is strong evidence for a genetic contribution to age at onset of schizophrenia, which probably involves both susceptibility loci for schizophrenia and modifying loci acting independent of disease risk. We sought evidence of linkage to loci that influence age at onset of schizophrenia in a sample of 94 affected sibling pairs with DSM-IV schizophrenia or schizoaffective disorder, and age at first psychiatric contact of 45 years or less. Individuals were genotyped for 229 microsatellite markers spaced at approximately 20 cM intervals throughout the genome. Loci contributing to age at onset were sought by a quantitative maximum-likelihood multipoint linkage analysis using MAPMAKER/SIBS. A nonparametric multipoint analysis was also performed. The genomewide significance of linkage results was assessed by simulation studies. There were six maximum-likelihood LOD score peaks of 1.5 or greater, the highest being on chromosome 17q (LOD = 2.54; genomewide P = 0.27). This fulfils Lander and Kruglyak's [1995: Nat Genet 11:241-247] criteria for suggestive linkage in that it would be expected to occur once or less (0.3 times) per genome scan. However, this finding should be treated with caution because the LOD score appeared to be almost solely accounted for by the pattern of ibd sharing at one marker (D17S787), with virtually no evidence of linkage over flanking markers. None of the linkage results achieved genomewide statistical significance, but the LOD score peak on chromosome 13q (LOD = 1.68) coincided with the region showing maximum evidence for linkage in the study by Blouin et al. [1998: Nat Genet 20:70-73] of categorical schizophrenia.

Age of Onset↗
PubMed2001

Calcium hydroxyapatite promotes mitogenesis and matrix metalloproteinase expression in human breast cancer cell lines.

Radiographic mammary microcalcifications are one of the most pertinent diagnostic markers of breast cancer. Breast tissue calcification in the form of calcium hydroxyapatite (HA) is strongly associated with malignant disease. We tested the hypothesis that calcium HA may exert biological effects on surrounding cells, thereby facilitating breast cancer progression. Our findings showed that HA crystals enhanced mitogenesis in breast cancer cell lines MCF-7 and Hs578T and also in normal human mammary epithelial cells. HA crystals were also found to upregulate the production of a variety of matrix metalloproteinases (MMPs), including MMP-2, -9, and -13 in MCF-7 and MMP-9 in human mammary epithelial cell lines. HA crystals were found to greatly augment prostaglandin E(2) levels in Hs578T cells, and treatment with a cyclooxygenase inhibitor, aspirin, abrogated the HA-induced mitogenesis. These results suggest that calcium HA crystals may play an active role in amplifying the pathological process involved in breast cancer.

Breast Neoplasms↗
PubMed2001

Basic calcium phosphate crystals activate human osteoarthritic synovial fibroblasts and induce matrix metalloproteinase-13 (collagenase-3) in adult porcine articular chondrocytes.

OBJECTIVE: To determine the ability of basic calcium phosphate (BCP) crystals to induce (a) mitogenesis, matrix metalloproteinase (MMP)-1, and MMP-13 in human osteoarthritic synovial fibroblasts (HOAS) and (b) MMP-13 in cultured porcine articular chondrocytes. METHODS: Mitogenesis of HOAS was measured by [3H]thymidine incorporation assay and counts of cells in monolayer culture. MMP messenger RNA (mRNA) accumulation was determined either by northern blot analysis or reverse transcriptase-polymerase chain reaction (RT-PCR) of RNA from chondrocytes or HOAS treated with BCP crystals. MMP-13 secretion was identified by immunoprecipitation and MMP-1 secretion by western blot of conditioned media. RESULTS: BCP crystals caused a 4.5-fold increase in [3H]thymidine incorporation by HOAS within 20 hours compared with untreated control cultures (p< or =0.05). BCP crystals induced MMP-13 mRNA accumulation and MMP-13 protein secretion by articular chondrocytes. In contrast, in HOAS, MMP-13 mRNA induced by BCP crystals was detectable only by RT-PCR, and MMP-13 protein was undetectable. BCP crystals induced MMP-1 mRNA accumulation and MMP-1 protein secretion by HOAS. MMP-1 expression was further augmented when HOAS were co-incubated with either BCP and tumour necrosis factor alpha (TNFalpha; threefold) or BCP and interleukin 1alpha (IL1alpha; twofold). CONCLUSION: These data confirm the ability of BCP crystals to activate HOAS, leading to the induction of mitogenesis and MMP-1 production. MMP-13 production in response to BCP crystals is substantially more detectable in porcine articular chondrocytes than in HOAS. These data support the active role of BCP crystals in osteoarthritis and suggest that BCP crystals act synergistically with IL1alpha and TNFalpha to promote MMP production and subsequent joint degeneration.

Animals↗
PubMed2001

Aggressive behaviour in patients with schizophrenia is associated with catechol-O-methyltransferase genotype.

BACKGROUND: Evidence exists for an association between aggression and schizophrenia. Although the aetiology of aggression is multifactorial, three studies have reported associations between polymorphisms of the catechol-O-methyltransferase (COMT) gene and aggression in schizophrenia. AIMS: To replicate these findings in a larger sample using the Overt Aggression Scale (OAS). METHOD: A sample of 180 people with DSM-IV schizophrenia were rated for aggression using the OAS. Kruskal-Wallis and contingency table analyses were applied to the OAS results. RESULTS: The high-activity homozygotes showed significantly higher scores of aggression, whereas the heterozygotes showed significantly lower scores. The odds ratio for aggression for the high-activity homozygotes was 2.07 (95% Cl=1.03-4.15), whereas that for the heterozygotes was 0.54 (95% Cl=0.30-1.00). CONCLUSIONS; The high-activity COMT homozygote confers a higher risk of recorded aggression in schizophrenia. Heterozygotes had a significantly lower risk, which may represent an example of heterosis/heterozygote advantage.

Aggression↗
PubMed2000

Primary pulmonary artery leiomyosarcoma in an adult dog.

A 7-year-old neutered female English Setter presented with syncope, anemia, and weight loss. Clinical examination revealed a systolic murmur and echocardiography demonstrated a mass on the pulmonic valve. Postmortem examination confirmed the presence of a pulmonic valve mass that extended along the pulmonary trunk and into the left pulmonary artery. Multiple pale nodules were observed in the right lung. Microscopic examinations of the pulmonary artery mass and the lung nodules revealed a pleomorphic population of spindle cells often arranged in broad bands containing strap-like nuclei and eosinophilic cytoplasm devoid of cross striations. The neoplastic cells expressed vimentin and alpha-smooth muscle actin but did not express desmin, CD31, factor VIII, or S100. The presentation, histological features, immunocytochemical profiles, and behavior of this tumor were indicative of a primary pulmonary artery leiomyosarcoma with lung metastasis.

Animals↗
PubMed2000

Sociodemographic and workload characteristics of dentists who participated in national survey, 1995.

Comprehensive, standardized data on the sociodemographic characteristics and workload of dentists in different provinces and territories in Canada are not available. The authors mailed a survey to a stratified random sample of dentists (n = 6,444) with three follow-up attempts. The response rate was 66.4%. Significant provincial and territorial differences in sociodemographic characteristics included gender, age, years since graduation, marital status, population size of town or city where primary practice is located and patient load. There was considerable variation in dentists' workload: more than 10% of dentists from New Brunswick and Prince Edward Island reported seeing > or = 30 patients per day. The majority of respondents reported seeing patients for 25 to 40 hours per week. British Columbia, Ontario, Saskatchewan and Newfoundland had a greater proportion of respondents > or = 60 years of age compared with other provinces/territories, indicating that there may be more opportunities in these provinces for younger dentists as a result of retirements.

Adult↗
PubMed1999

Cellular responses to whitlockite.

Whitlockite crystals have been observed in both degenerating and normal articular cartilages. To determine their potential for inducing cartilage degeneration, we studied their ability to induce mitogenesis and synthesis and secretion of metalloproteases in vitro. Whitlockite crystals were found to stimulate cell proliferation and to stimulate synthesis and secretion of stromelysin and collagenase. However, they were less stimulatory than crystals that contained calcium (Ca) and phosphate without magnesium substitution for Ca. Whitlockite crystals elicit biologic cellular responses that suggest potential pathogenicity in arthritis, but are less potent than Ca phosphate crystals without magnesium.

Calcium Phosphates↗
PubMed1999

Crystal-induced inflammation and cartilage degradation.

In the past year, there have been advances in our understanding of the induction of cartilage damage by calcium-containing crystals. Mechanisms of deposition and the biologic effects of crystals have been further characterized, as has the interaction between crystals and leukocytes. Studies of the clinical diagnosis of crystal deposition diseases suggest that accuracy with microscopy needs to be enhanced. Normal values for serum NTPPPHase have been established and optimal diagnostic imaging strategies for calcium pyrophosphate deposition disease have been suggested. There are still no available drugs to inhibit deposition or effect reabsorption of calcium-containing crystals.

Calcinosis↗
PubMed1999

Compliance with recommended infection control procedures among Canadian dentists: results of a national survey.

OBJECTIVES: The objective of this study was to investigate compliance with recommended infection control (IC) practices by dentists in Canada in 1995. DESIGN: A mailed survey of a stratified random sample of dentists (N = 6444), with 3 follow-up attempts. Weighted analyses included multiple logistic regression to identify the best predictors of "excellent" compliance (18 items). RESULTS: The adjusted response rate was 66.4%. Respondents reported use of an IC manual (52%); postexposure protocol (41%); biologic monitoring of heat-sterilizers (71%); hepatitis B immunization of dentists (91%: of these 72% had post-immunization screening; natural immunity 3%) all hygienists (78%), and all other clinical staff (70%); handwashing (before treating patients 76%, after degloving 63%); always wearing gloves (95%); changing gloves after each patient (97%); masks (82%); protective eyewear (82%); protective uniform (48%); puncture-proof container for sharps (94%); recapping needles with scoop technique/device (60%); flushing waterlines (55%); heat-sterilizing handpieces (94%; after each patient 77%); high-volume suction (92%) and "excellent" compliance (6%). Significant predictors of "excellent compliance" included attending continuing education about IC (>/=10 hours, odds ratio [OR] = 6.3; 6-10 hours, OR = 3.3), treating 20 to 29 patients per day (OR = 2.8), being women (OR = 2.7), and population of city in which practice is located (>500,000, OR = 2.5). CONCLUSION: Improvements in IC are necessary in dental practice. The introduction of mandatory continuing education about IC may improve compliance with recommended IC procedures, which is important because of concerns related to transmission of bloodborne pathogens and drug-resistant microorganisms.

Adult↗
PubMed1999

Occupational injuries and exposures among Canadian dentists: the results of a national survey.

OBJECTIVES: To measure the frequency of occupational exposures reported by dentists in Canada and to identify factors associated with occupational exposure. DESIGN: A national mailed survey of a stratified random sample of 6,444 dentists with three follow-up attempts. Weighted data were analyzed using t tests, analysis of variance, and multiple logistic regression. RESULTS: The response rate was approximately 66%. Occupational exposures, percutaneous injuries, and mucous membrane exposures in the last year were reported by 67%, 62%, and 29% of respondents, respectively. Fewer than 1% reported exposure to human immunodeficiency virus or hepatitis B virus (HBV). Respondents reported means of 1.5 mucous membrane and 3.0 percutaneous exposures per year. HBV immunization was reported by 91% of dentists, but of these 28% reported no post-immunization serology. Other reports of suboptimal compliance included use of a postexposure protocol by only 41% and HBV vaccination of all assistants or of hygienists by 74% and 77% of respondents, respectively. Factors associated with percutaneous exposure included non-use of postexposure protocol or puncture-proof containers for sharps disposal, treating > or =20 patients per day, and male gender. Risk factors for mucous membrane exposure included non-use of eye protection or masks. CONCLUSION: This study provides evidence of the protective effect of puncture-proof containers, eye protection, and masks and raises concerns related to HBV post-immunization serology and postexposure protocols. To reduce risk of infection, educational interventions are required to improve compliance with Universal Precautions, with emphasis on comprehensive HBV immunization and post-immunization serology, the use of barriers, puncture-proof containers for sharps disposal, and postexposure protocols.

Adult↗
PubMed1999

The role of age- and population-based differences in the attitudes, knowledge and infection control practices of Canadian dentists.

OBJECTIVES: To investigate age- and population-based differences in dentists' infection control practices and willingness and refusal to treat patients with HIV. METHODS: A national mailed survey of a stratified random sample of dentists in Canada (n = 6444) with three follow-up attempts. Pearson's chi-square test and multiple logistic regression were used for data analysis. Predictor variables included population, age, gender, marital status, specialty, number of patients treated per day and continuing education on HIV/AIDS. RESULTS: The adjusted response rate was 66.4%. The best predictors of willingness to treat patients with HIV were younger age (compared with dentists > or = 60 years of age: < 30 years, OR = 8.6, 30-39, OR = 3.4; 40-49, OR = 2.7; 50-59, OR = 1.6), attending continuing education on HIV/AIDS in the past 2 years (> 10 hours, OR = 1.6 compared with zero hours), practicing in small population centres < 10,000 (OR = 1.6 compared with > 500,000) and gender (male OR = 1.3). The best predictors of refusal to treat patients with HIV were older age (compared with dentists < 30 years of age: > or = 60, OR = 6.1; 50-59, OR = 4.1; 40-49, OR = 3.0; 30-39, OR = 2.6); and practicing in population centres > 500,000 (OR = 1.5 compared with < 10,000). However, the latter group also reported treating more HIV patients than respondents in smaller communities. Infection control practices varied significantly with age and population centre. Dentists in communities of < 10,000 were more compliant with HBV vaccination, but less compliant with handwashing after degloving and the use of infection control manuals. Similarly, dentists > 60 years of age were the least compliant with HBV immunization, routine use of barriers and sterilization of handpieces, but reported the highest compliance with handwashing. CONCLUSIONS: Age- and population-based differences need to be considered in planning educational interventions to improve both access to care for patients with HIV and dentists' compliance with recommended infection control procedures.

Adult↗