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Biomedical subjects

G McColl

Publications and source records attributed to G McColl.

At least 19 recordsLinked to original sources
PubMed2005

Tumour necrosis factor antagonists improve disease activity but not arterial stiffness in rheumatoid arthritis.

OBJECTIVES: Systemic inflammation may play an important role in the accelerated atherosclerosis and increased cardiovascular mortality of rheumatoid arthritis (RA). Atorvastatin reduced arterial stiffness in RA patients after only 6 weeks, an effect that may be partially mediated by the immunomodulatory effects of this drug. Suppression of inflammation with tumour necrosis factor (TNF) antagonists may therefore also improve vascular function in RA; however, TNF antagonists have also been shown to cause or exacerbate congestive heart failure in patients with RA and heart failure. The aim of the present study was to examine the effect of treatment with TNF antagonists on arterial stiffness in RA patients with active disease. METHODS: Fourteen RA patients (age 55.1 +/- 3.8 yr; disease duration 7.9 +/- 1.3 yr) with high disease activity [disease activity score (DAS28) 7.1 +/- 0.3] commencing treatment with TNF antagonists for the first time were studied. Clinical status and arterial stiffness were measured before and after 6 weeks of TNF antagonist therapy (etanercept, adalimumab or infliximab). RESULTS: Arterial stiffness did not change during the study period (the mean augmentation index was 29.1 +/- 2.2% at baseline vs 30.1 +/- 1.8% at week 6; P = 0.504). The DAS28 improved significantly from 7.1 +/- 0.3 to 4.3 +/- 0.4 (P < 0.0001). The erythrocyte sedimentation rate and C-reactive protein [median (range)] were reduced from 44 (12-85) to 15 (3-82) mm/h (P = 0.02) and from 34 (3-95) to 10 (2-61) mg/l (P = 0.007), respectively. CONCLUSIONS: Despite significant reductions in synovitis and inflammatory markers in these RA patients, arterial stiffness was not improved by 6 weeks of treatment with TNF antagonists. This result is of relevance given recent reports of potential adverse cardiovascular effects of TNF antagonists in some RA patients.

Adalimumab↗
PubMed2005

Efficacy of physiotherapy management of knee joint osteoarthritis: a randomised, double blind, placebo controlled trial.

OBJECTIVE: To determine whether a multimodal physiotherapy programme including taping, exercises, and massage is effective for knee osteoarthritis, and if benefits can be maintained with self management. METHODS: Randomised, double blind, placebo controlled trial; 140 community volunteers with knee osteoarthritis participated and 119 completed the trial. Physiotherapy and placebo interventions were applied by 10 physiotherapists in private practices for 12 weeks. Physiotherapy included exercise, massage, taping, and mobilisation, followed by 12 weeks of self management. Placebo was sham ultrasound and light application of a non-therapeutic gel, followed by no treatment. Primary outcomes were pain measured by visual analogue scale and patient global change. Secondary measures included WOMAC, knee pain scale, SF-36, assessment of quality of life index, quadriceps strength, and balance test. RESULTS: Using an intention to treat analysis, physiotherapy and placebo groups showed similar pain reductions at 12 weeks: -2.2 cm (95% CI, -2.6 to -1.7) and -2.0 cm (-2.5 to -1.5), respectively. At 24 weeks, pain remained reduced from baseline in both groups: -2.1 (-2.6 to -1.6) and -1.6 (-2.2 to -1.0), respectively. Global improvement was reported by 70% of physiotherapy participants (51/73) at 12 weeks and by 59% (43/73) at 24 weeks. Similarly, global improvement was reported by 72% of placebo participants (48/67) at 12 weeks and by 49% (33/67) at 24 weeks (all p>0.05). CONCLUSIONS: The physiotherapy programme tested in this trial was no more effective than regular contact with a therapist at reducing pain and disability.

Aged↗
PubMed2004

Atorvastatin reduces arterial stiffness in patients with rheumatoid arthritis.

BACKGROUND: Chronic systemic inflammation may contribute to accelerated atherosclerosis and increased arterial stiffness in patients with rheumatoid arthritis (RA). In addition to lowering cholesterol, statins have immunomodulatory effects which may be especially beneficial in patients with RA who have systemic immune activation. OBJECTIVE: To investigate the effect of atorvastatin on the augmentation index (AIx: a measure of arterial stiffness) and systemic inflammation in RA. METHODS: 29 patients with RA (mean (SD) age 55 (13) years) with moderately active disease of long duration were studied. AIx, lipid levels, serum inflammatory markers, and disease activity score were measured before and after 12 weeks of atorvastatin 20 mg daily. RESULTS: AIx improved significantly from 34.1 (11.6)% to 29.9 (11)% (p = 0.0002), with the greatest improvements in AIx occurring in those subjects with the highest disease activity scores (r = -0.5, p = 0.007). Total and LDL cholesterol were reduced from 5.5 (0.9) to 3.9 (0.7) mmol/l and 3.3 (0.8) to 1.9 (0.6) mmol/l, respectively (p = 0.0001). Serum inflammatory markers remained unchanged during the study. CONCLUSIONS: Atorvastatin significantly reduced arterial stiffness in patients with RA. The greatest improvements were seen in patients with more active disease, suggesting that, in addition to the beneficial effects of cholesterol reduction, immune modulation may contribute to the cardioprotective effect of statins.

Adult↗
PubMed2003

Screening for atherosclerosis in patients with rheumatoid arthritis: comparison of two in vivo tests of vascular function.

OBJECTIVE: Inflammation appears to play a central role in atherosclerosis, and endothelial damage mediated by systemic inflammation may contribute to the increased cardiovascular mortality in rheumatoid arthritis (RA). Brachial artery flow-mediated dilatation (FMD) and pulse wave analysis (PWA) are measures of vascular function. The aim of this study was to determine if FMD and PWA are abnormal in patients with RA. METHODS: Twenty-five RA patients and 25 matched healthy controls were studied. All were free of traditional cardiovascular risk factors. FMD was measured in all subjects. PWA was performed in 18 RA patients and 18 controls, with results expressed as large and small artery compliance (C1 and C2). Modified Sharp scores were calculated in 13 RA patients. RESULTS: Results (mean +/- SD) in RA patients and controls, respectively, were as follows: FMD 107.6 +/- 4.6% versus 108.5 +/- 4.1% (P = 0.49), C1 14.8 +/- 2.8 ml/mm Hg x 10 versus 17.9 +/- 3.1 ml/mm Hg x 10 (P = 0.0033), C2 4.5 +/- 2.3 ml/mm Hg x 100 versus 7.7 +/- 3.7 ml/mm Hg x 100 (P = 0.0039). There was an inverse correlation between C2 and modified Sharp scores in the RA patients (Spearman's rho -0.69, P = 0.0085). CONCLUSION: FMD was normal in these RA patients, whereas arterial compliance was markedly reduced. PWA appears to be a more sensitive measure of vascular dysfunction than FMD in RA and may be the preferred surrogate marker of vascular dysfunction in longitudinal studies of RA patients. The inverse correlation between C2 and the modified Sharp score, a measure that reflects disease activity over time, supports the notion that chronic inflammation plays a role in RA-associated atherosclerosis.

Adult↗
PubMed2003

The effect of ball carrying method on sprint speed in rugby union football players.

Different methods of ball carrying can be used when a player runs with the ball in rugby union. We examined how three methods of ball carrying influenced sprinting speed: using both hands, under the left arm and under the right arm. These methods were compared with running without the ball. Our aim was to determine which method of ball carrying optimizes sprinting speed. Altogether, 48 rugby union players (age 21 +/- 2 years, height 1.83 +/- 0.1 m, body mass 85.3 +/- 12 kg, body fat 14 +/- 5%; mean +/- s) were recruited. The players performed twelve 30-m sprints in total (each player performed three trials under each of three methods of carrying the ball and sprinting without the ball). The design of the study was a form of Latin rectangle, balanced across the trial order for each of the methods and for pairwise combinations of the methods in blocks of four per trial. Each sprint consisted of a 10-m rolling start, followed by a 20-m timed section using electronic timing gates. Compared with sprinting 20 m without the ball (2.58 +/- 0.16 s), using both hands (2.62 +/- 0.16 s) led to a significantly slower time (P < 0.05). Sprinting 20 m with the ball under the left arm (2.61 +/- 0.15 s) or under the right arm (2.60 +/- 0.17 s) was significantly quicker than when using 'both hands' (P < 0.05), and both these methods were significantly slower than when running without the ball (P < 0.05). Accordingly, running with the ball in both hands led to the greatest decrement in sprinting performance, although carrying the ball under one arm also reduced the players' sprinting ability. Our results indicate that to gain a speed advantage players should carry the ball under one arm.

Acceleration↗
PubMed2001

Heat shock protein accumulation is upregulated in a long-lived mutant of Caenorhabditis elegans.

We present evidence for elevated levels of heat shock protein 16 (HSP16) in an intrinsically thermotolerant, long-lived strain of Caenorhabditis elegans during and after heat stress. Mutation of the age-1 gene, encoding a phosphatidylinositol 3-kinase catalytic subunit, results in both extended life span (Age) and increased intrinsic thermotolerance (Itt) in adult hermaphrodites. We subjected age-synchronous cohorts of worms to lethal and nonlethal thermal stress and observed the accumulation of a small (16-18 kd) heat-shock-specific polypeptide detected by an antibody raised against C. elegans HSP16. Strains carrying the mutation hx546 consistently accumulated HSP16 to higher levels than a wild-type strain. Significantly, overaccumulation of HSP16 in the age-1(hx546) strain following heat was observed throughout the adult life span. A chimeric transgene containing the Escherichia coli beta-galactosidase gene fused to a C. elegans HSP16-41 transcriptional promoter was introduced into wild-type and age-1(hx546) backgrounds. Heat-inducible expression of the transgene was elevated in the age-1(hx546) strain compared with the wild-type strain under a wide variety of heat shock and recovery conditions. These observations are consistent with a model in which Age mutations exhibit thermotolerance and extended life span as a result of elevated levels of molecular chaperones.

Aging↗
PubMed2001

Prolonged prodrome, systemic vasculitis, and deafness in Cogan's syndrome.

Cogan's syndrome is a rare, multisystem disease which occurs predominantly in children and young adults. It was originally described as the combination of interstitial keratitis and audiovestibular disturbance, but other forms of ocular disease, as well as systemic vasculitis, have since been recognised as part of the syndrome. Diagnosis can be difficult if the various manifestations occur separately, but early recognition is important because prompt treatment may prevent deafness. Two cases are presented here illustrating the features of this disease, and providing histological evidence of systemic vasculitis in both.

Adult↗
PubMed2000

SAPHO: rare or just not recognized?

OBJECTIVE: The SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome describes an association between musculoskeletal disorders, in particular hyperostosis involving the bones and joints of the anterior chest wall, and various dermatologic conditions. It has been reported in Europe and Japan, but no Australian series have been published. We describe the clinical, laboratory, and radiographic features of a group of patients with the SAPHO syndrome and compare this with the literature. METHODS: We performed a retrospective review of patients seen in our department between 1990 and 1998 who met the proposed diagnostic criteria for SAPHO. Information regarding age, sex, disease duration, skeletal site(s) of disease, presence of skin disease, previous treatment, and response to treatment was collected. Laboratory tests were reviewed, as was all available radiology and bone scintigraphy. RESULTS: Six women with a mean age of 40 years fulfilled the criteria for SAPHO. The skeletal manifestations were similar to those reported in the literature, with hyperostosis of the anterior chest wall being the central feature. Cervical spine and pubic bone were other sites of involvement, whereas sacroiliitis and peripheral joint synovitis were not seen. Skin disease was less frequent in our population than has been reported in other series. Nonsteroidal anti-inflammatory drugs were frequently prescribed as first-line treatment but had limited efficacy. Intravenous pamidronate was administered to two patients, resulting in complete resolution of pain in one patient and 50% reduction in pain in the other. CONCLUSIONS: The SAPHO syndrome may be underrecognized as the skin manifestations in our patients were mild or absent. Although optimal treatment for these patients remains unclear, it is important to make the diagnosis of SAPHO to avoid unnecessary investigations and treatment.

Acquired Hyperostosis Syndrome↗
PubMed2000

Splenic infarction in Wegener's granulomatosis.

We describe a case of severe Wegener's granulomatosis associated with asymptomatic splenic infarction. The 4 previous case reports are reviewed and the implication of this finding for preventive strategies is highlighted.

Adult↗
PubMed1999

The Drosophila heat shock hsr-omega gene: an allele frequency cline detected by quantitative PCR.

The hsr-omega gene of Drosophila melanogaster produces RNA products both constitutively and at elevated levels in response to heat stress. A single-nucleotide difference in this gene that has been detected using denaturing gradient gel electrophoresis (DGGE) is responsible for an hsr-omegaa/b polymorphism, and selection experiments have indicated an association between the hsr-omegaa allele and susceptibility to heat stress. Since allele frequency estimates for population surveys using PCR and DGGE for single flies would be relatively time-consuming and expensive, we here develop a quantitative competitive-PCR method using mass-grind genomic DNA preparations for this purpose. Geographical and temporal variation of allele frequency at the hsr-omega locus in Australian populations of D. melanogaster are examined. Regular samples from a southern population through a summer season suggested stability of hsr-omegaa frequency. Field populations sampled from a approximately 2,250 km north-south transect along eastern Australia revealed a strong positive association between the frequency of hsr-omegaa and latitude, and marked spatial autocorrelation. Using appropriate analyses, strong association between population differences in hsr-omegaa frequencies and differences in temperature and rainfall measures, after controlling for latitudinal differences, support the idea that the cline in hsr-omegaa frequency may be attributable to some form of climatic selection.

Alleles↗
PubMed1998

Both allelic variation and expression of nuclear and cytoplasmic transcripts of Hsr-omega are closely associated with thermal phenotype in Drosophila.

Inducible heat shock genes are considered a major component of the molecular mechanisms that confer cellular protection against a variety of environmental stresses, in particular high temperature extremes. We have tested the association between expression of the heat shock RNA gene hsr-omega and thermoresistance by generating thermoresistant lines of Drosophila melanogaster after application of two distinct regimes of laboratory selection. One set of lines was selected for resistance to knockdown by heat stress and the other was similarly selected but before selection a mild heat exposure known to increase resistance (heat hardening) was applied. A cross between resistant and susceptible lines confirmed our earlier observation that increased thermal tolerance cosegregates with allelic variation in the hsr-omega gene. This cosegregating variation is attributed largely to two haplotype groups. Using quantitative reverse transcription-PCR, we find evidence for divergent phenotypic responses in the two selection regimes, involving both structural and regulatory changes in hsr-omega. Lines selected after hardening showed increased levels of the cytoplasmic transcript but decreased levels of the nuclear transcript. Lines selected without hardening showed decreased levels of the cytoplasmic transcript. The allelic frequency changes at hsr-omega could not by themselves account for the altered transcription patterns. Our results support the idea that the functional RNA molecules transcribed from hsr-omega are an important and polymorphic regulatory component of an insect thermoresistance phenotype.

Alleles↗
PubMed1997

Direct evidence for the expression of multiple endogenous retroviruses in the synovial compartment in rheumatoid arthritis.

OBJECTIVE: Circumstantial evidence links retroviruses (RVs) with human autoimmune diseases. The aim of the present study was to obtain direct evidence of RV gene expression in rheumatoid arthritis (RA). METHODS: Synovial samples were obtained from patients with RA, patients with osteoarthritis (OA), and normal control subjects. Reverse transcription-polymerase chain reaction (RT-PCR) was performed using synovial RNA and primers to conserved sequences in the polymerase (pol) genes of known RVs. RESULTS: PCR products (n = 857) were cloned and sequenced. Multiple pol transcripts, many with open reading frames, were expressed in every sample. Sequences were aligned and classified into 6 families (F1-F6) that contained 33 groups of known and unknown endogenous RVs (ERVs), each distinguished by a specific, deduced peptide motif. The frequency of sequences in each family was similar between RA, OA, and normal synovial tissue, but differed significantly in RA synovial fluid cells. F1 sequences (undefined, but related to murine and primate type C RVs) were lower in frequency, F2 (ERV-9-related), F4 (HERV-K-related), and F6 (HERV-L-related) sequences were higher in frequency, and F3 (RTVL-H-related) sequences were not detected, in the RA synovial fluid cells compared with the RA synovial tissues. CONCLUSION: Multiple ERVs are expressed in normal and diseased synovial compartments, but specific transcripts can be differentially expressed in RA.

Adult↗
PubMed1997

Use of monoclonal antibodies to detect disease associated HLA-DRB1 alleles and the shared epitope in rheumatoid arthritis.

OBJECTIVE: To use a panel of monoclonal antibodies (Mab) which recognise HLA class II alleles associated with rheumatoid arthritis for fluorescence activated cell sorter (FACS) analysis of peripheral blood mononuclear cells (PBMNC) from patients with early and established rheumatoid arthritis and to compare these results against DNA oligotyping of HLA class II molecules in the same patients. METHODS: 27 patients (18 from an early arthritis clinic, nine with established rheumatoid arthritis) were studied using both techniques. PBMNC were stained with Mab which recognise the shared epitope, the HLA-DRB1*04 molecule and its* 0401, *0404 subtypes in the presence of bound peptide. Mab stained cells were analysed by FACS. Genomic DNA was prepared from PBMNC and use for DNA oligotyping and sequencing by standard methods. RESULTS: FACS analysis of Mab stained PBMNC gave identical results to those obtained by DNA oligotyping in 26/27 patients. The antibodies identified the shared epitope in 14/14 cases and the presence of an HLA-DRB1*04 molecule in 12/12 cases. HLA-DRB1*0404 was identified in 4/4 cases. HLA-DRB1*0401 was identified in 5/6 cases. One patient oligotyped as HLA-DRB1*0401, but consistently failed to react with the *0401 Mab. DNA sequencing of the second exon of the HLA-DRB1*0401 allele in this patient confirmed a normal HLA-DRB1*0401 genotype. CONCLUSIONS: FACS analysis of PBMNC stained with Mab recognising the shared epitope and rheumatoid arthritis associated HLA susceptibility molecules provides a rapid, reliable, and more accessible alternative to DNA oligotyping. The apparent discordance between phenotypic and genetic analysis of HLA-DRB1*0401 in one patient, may reflect variability in HLA-DRB1*0401 gene expression or in class II peptide presentation.

Alleles↗
PubMed1996

Response of two heat shock genes to selection for knockdown heat resistance in Drosophila melanogaster.

To identify genes involved in stress resistance and heat hardening, replicate lines of Drosophila melanogaster were selected for increased resistance to knockdown by a 39 degrees heat stress. Two selective regimes were used, one with and one without prior hardening. Mean knockdown times were increased from approximately 5 min to > 20 min after 18 generations. Initial realized heritabilities were as high as 10% for lines selected without hardening, and crosses between lines indicated simple additive gene effects for the selected phenotypes. To survey allelic variation and correlated selection responses in two candidate stress genes, hsr-omega and hsp68, we applied denaturing gradient gel electrophoresis to amplified DNA sequences from small regions of these genes. After eight generations of selection, allele frequencies at both loci showed correlated responses for selection following hardening, but not without hardening. The hardening process itself was associated with a hsp68 frequency change in the opposite direction to that associated with selection that followed hardening. These stress loci are closely linked on chromosome III, and the hardening selection established a disequilibrium, suggesting an epistatic effect on resistance. The data indicate that molecular variation in both hsr-omega and.hsp68 contribute to natural heritable variation for hardened heat resistance.

Alcohol Dehydrogenase↗