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Biomedical subjects

L McLean

Publications and source records attributed to L McLean.

At least 19 recordsLinked to original sources

Using myoelectric signal parameters to distinguish between computer workers with and without trapezius myalgia.

Complaints of chronic trapezius muscle pain among computer workers have increased in prevalence during the last decade. Currently there is no clear understanding of the pathophysiological mechanisms involved in affected muscles. The major objective of this work was to determine if measurable electrophysiological differences exist between the trapezius muscles in individuals suffering from trapezius myalgia (TM) and occupation-matched pain-free control subjects. Myoelectric signal (MES) data were recorded from the upper trapezius muscle while subjects with and without myalgia performed a standardized series of postural and arm-holding tasks. MES variables reflecting muscle fatigue, muscle tension and motor control strategies were analyzed to determine their potential ability to distinguish between the two groups. One variable, RestTime, was found to be significantly different between the groups but it was not specific enough to predict group association. A multivariate logistic regression analysis yielded a model that separated the two groups with better than 70% sensitivity and 70% specificity. The variables included in the model reflect differences in trapezius muscle activity between the groups, particularly related to motor control and/or active muscle tension, but not fatigue. The model was tested using a small sample of new data, which again produced a good sensitivity (85.7%) but not specificity (42.9%). To the authors' knowledge, this is the first objective MES-based model that has successfully classified subjects with or without TM based on a simple clinical test. Further work with this model might result in understanding the pathophysiology of TM, assisting with clinical diagnosis, and testing the effect of various treatment interventions.

Adult↗

Haematological cancers in the breast and axilla: a drop in an ocean of breast malignancy.

We have reviewed imaging findings of 32 female patients with a proven haematological malignancy in the breast and axilla presenting to two breast units over a 13-year period. Nineteen patients had screen-detected lesions, and 13 presented to symptomatic services. The most common histological diagnosis was of non-Hodgkins lymphoma. Of the 12 patients who presented with disease in the breast, six (all with primary breast lymphoma) presented with a well-defined mass on mammography. The range of radiological appearances is, however, highly variable.

Aged↗

Using chlamydia positivity to estimate prevalence: evidence from the Chlamydia Screening Pilot in England.

Studies have suggested that positivity can be used to estimate the prevalence of Chlamydia trachomatis in large-scale chlamydia screening programmes. A recent pilot of opportunistic screening in England estimated that the prevalence among 16-24-year-old women in Portsmouth and Wirral was 9.8% and 11.2%, respectively. This study assessed the continued validity of positivity as an approximate for prevalence. We re-analysed data from the Chlamydia Screening Pilot to estimate positivity,calculated as total positive tests divided by total tests, and compared these estimates with the previously reported prevalence, measured as the number of women testing positive divided by the total number of women screened. Overall positivity was 9.4% in Portsmouth and 11.0% in the Wirral; these estimates were not statistically different from prevalence, regardless of health-care setting, age group or symptoms. We conclude that positivity can be used as a proxy for prevalence.

Adolescent↗

Evidence for negative association of the chemokine receptor CCR5 d32 polymorphism with rheumatoid arthritis.

BACKGROUND: Ligands of chemokine receptor CCR5, including MIP-1 alpha, MIP-1 beta, and RANTES, have been implicated in rheumatoid arthritis. OBJECTIVE: To test whether CCR5 d32 polymorphism has a negative association with rheumatoid arthritis in a New Zealand cohort. METHODS: 516 white patients with rheumatoid arthritis and 985 healthy controls were investigated by PCR amplification of the region flanking the known CCR5 d32 deletion, and the frequencies of CCR5 d32 compared. An early rheumatoid arthritis (ERA) cohort of 92 patients was followed prospectively for two years; disease severity and outcome were correlated with CCR5 d32 status. RESULTS: 12 control subjects (1.2%) were homozygous for d32; no d32 homozygous rheumatoid patients were detected (p = 0.012); 56 patients (10.9%) were heterozygous for the d32 polymorphism (d32/wt), compared with 169 controls (17.2%) (p = 0.0011). The CCR5 d32 allele frequency was lower in the rheumatoid patients than in the controls (frequencies of 0.054 and 0.098, respectively; p = 3.7 x 10(-5)). The frequency of CCR5 d32 did not differ significantly according to disease severity or outcome in the prospective ERA cohort, nor with HLA-DRB1 status. CONCLUSIONS: This study provides further evidence for a protective effect of the CCR5 d32 variant on rheumatoid arthritis, consistent with a role for CCR5 and its ligands in disease pathogenesis.

Arthritis, Rheumatoid↗

8-oxo-7,8-dihydroguanine is removed by a nucleotide excision repair-like mechanism in Porphyromonas gingivalis W83.

A consequence of oxidative stress is DNA damage. The survival of Porphyromonas gingivalis in the inflammatory microenvironment of the periodontal pocket requires an ability to overcome oxidative stress caused by reactive oxygen species (ROS). 8-oxo-7,8-dihydroguanine (8-oxoG) is typical of oxidative damage induced by ROS. There is no information on the presence of 8-oxoG in P. gingivalis under oxidative stress conditions or on a putative mechanism for its repair. High-pressure liquid chromatography with electrochemical detection analysis of chromosomal DNA revealed higher levels of 8-oxoG in P. gingivalis FLL92, a nonpigmented isogenic mutant, than in the wild-type strain. 8-oxoG repair activity was also increased in cell extracts from P. gingivalis FLL92 compared to those from the parent strain. Enzymatic removal of 8-oxoG was catalyzed by a nucleotide excision repair (NER)-like mechanism rather than the base excision repair (BER) observed in Escherichia coli. In addition, in comparison with other anaerobic periodontal pathogens, the removal of 8-oxoG was unique to P. gingivalis. Taken together, the increased 8-oxoG levels in P. gingivalis FLL92 could further support a role for the hemin layer as a unique mechanism in oxidative stress resistance in this organism. In addition, this is the first observation of an NER-like mechanism as the major mechanism for removal of 8-oxoG in P. gingivalis.

DNA Damage↗

Relationship between serum hyaluronic acid level and disease activity in early rheumatoid arthritis.

OBJECTIVES: To measure hyaluronic acid (HA) levels, which are raised in active rheumatoid arthritis (RA), in patients with early RA, and to assess the correlation with clinical and laboratory indices of disease activity and with subsequent radiographic erosive status. PATIENTS AND METHODS: Patients fulfilling ACR criteria were recruited into a prospective cohort within 6 months of disease onset and reviewed every 6 months. An HA binding protein based sandwich ELISA was used to measure HA in 240 sera from 82 patients at regular intervals. RESULTS: Patients had higher HA levels than age matched healthy blood donor controls (median 37.4 v 29.1 ng/ml, respectively, p<0.02), which increased with more prolonged disease. Baseline HA level correlated with measures of disease activity, including swollen and tender joint counts, HAQ, global assessments, ESR, and CRP; was higher in men; and increased with age. There was no relationship with HLA-DRB1 shared epitope or rheumatoid factor status. At 6 and 12 month follow up visits, HA levels were higher in patients who later developed erosions. However, a raised HA level was not a good predictor of erosions. CONCLUSIONS: Serum HA level correlates with clinical and laboratory measures of disease activity in early RA, but is unlikely to be of practical use in clinical practice.

Adult↗

Transforming growth factor-beta1 genotype and susceptibility to chronic obstructive pulmonary disease.

BACKGROUND: Only a few long term smokers develop symptomatic chronic obstructive pulmonary disease (COPD) and this may be due, at least in part, to genetic susceptibility to the disease. Transforming growth factor beta1 (TGF-beta1) has a number of actions that make it a candidate for a role in the pathogenesis of COPD. We have investigated a single nucleotide polymorphism at exon 1 nucleotide position 29 (T-->C) of the TGF-beta1 gene that produces a substitution at codon 10 (Leu-->Pro). METHODS: The frequency of this polymorphism was determined in 165 subjects with COPD, 140 healthy blood donors, and 76 smokers with normal lung function (resistant smokers) using the polymerase chain reaction and restriction enzyme fragment length polymorphism. RESULTS: The distribution of genotypes was Leu-Leu (41.8%), Leu-Pro (50.3%), and Pro-Pro (7.9%) for subjects with COPD, which was significantly different from the control subjects (blood donors: Leu-Leu (29.3%), Leu-Pro (52.1%) and Pro-Pro (18.6%), p=0.006; resistant smokers: Leu-Leu (28.9%), Leu-Pro (51.3%) and Pro-Pro (19.7%), p=0.02). The Pro10 allele was less common in subjects with COPD (33%) than in blood donors (45%; OR=0.62, 95% CI 0.45 to 0.86, p=0.005) and resistant smokers (45%; OR=0.59, 95% CI 0.40 to 0.88, p=0.01). CONCLUSIONS: The proline allele at codon 10 of the TGF-beta1 gene occurs more commonly in control subjects than in individuals with COPD. This allele is associated with increased production of TGF-beta1 which raises the possibility that TGF-beta1 has a protective role in COPD.

Adult↗

The effect of head position, electrode site, movement and smoothing window in the determination of a reliable maximum voluntary activation of the upper trapezius muscle.

Quantitative measures derived from raw myoelectric signal (MES) data must be normalized to allow for comparisons both within and between subjects. The most common method of normalization involves dividing the root mean square (RMS) amplitude of the MES recorded during a given activity by the RMS of the MES elicited during a maximal voluntary isometric contraction (MVIC) of that particular muscle. The objective of this study was to use surface-recorded MES amplitude to determine the combination of electrode site, test position, head posture, and smoothing window that elicits the highest and most reliable MES amplitudes during an MVIC of the upper trapezius (UT) muscle. Ten volunteers had surface electrodes positioned at five sites on the UT of their dominant side. Three trials of each of three MVIC test positions were performed both with the head in neutral and rotated 45 degrees to the contralateral side. A repeated-measures ANOVA was used for statistical hypothesis testing. Coefficients of variation were used to quantify the between-factor variability introduced in each case. In addition, the data were re-analyzed using moving windows of 100 to 500 ms in length, and an ANOVA was used to determine the effect of window length on both the amplitude and variability of the estimates of maximum voluntary activation (MVE). Head position had no significant effect on RMS amplitude of the MVIC in any of the test positions. There was a significant electrode site by test position interaction effect. Bonferroni post-hoc analyses were performed on this interaction by fixing test position and testing electrode site, revealing that Sites 1 (2 cm lateral to the midpoint between C7 spinous process and the posterolateral border of the acromion) and 4 (2 cm posterior to Site 1) recorded significantly higher RMS values for all test positions, and were not significantly different from each other. Fixing electrode site, the test position analysis revealed that abduction of the humerus, and abduction with external rotation of the humerus produced significantly higher RMS values than shoulder elevation at both Sites 1 and 4, and that abduction produced a significantly higher RMS amplitude than abduction in external rotation at Site 1. The results confirmed that Sites 1 and 4 consistently produced the highest MES amplitudes for all movements. Pure abduction consistently elicited maximal RMS values; however there is concern regarding supraspinatus cross talk during this movement. Site 1 was found to produce the most reliable data. A moving window of 100 ms was found to generate MVE estimates that were significantly higher than windows ranging from 200 ms to 500 ms in length. There was no effect of window length on the reliability of the MVEs. Based on this study, it was concluded that abduction or abduction with the arms in lateral rotation should be used as normalization contraction positions for the upper trapezius muscle. During this movement, Site 1 data smoothed with a moving window of 100 ms produces the highest amplitude MVE data but window lengths greater than 200 ms produce more stable estimates in terms of being able to compare studies in which moving windows are used to compute RMS.

Adult↗

Radiology review of the UKCCCR Breast Screening Frequency Trial: potential improvements in sensitivity and lead time of radiological signs.

AIM: To review all previous mammograms of breast cancer cases diagnosed during a randomized trial comparing 3 yearly to annual mammographic screening with a view to identifying and quantifying cases that might potentially have been diagnosed earlier. METHODS: Mammograms of 602 breast cancer cases (399 screen-detected and 203 interval cases) were reviewed in chronological order and suspicious radiological features noted for each mammogram, up to and including the diagnostic mammogram. RESULTS: Of the 602 cases, 79 (13%) had features at diagnosis that were visible on previous mammograms, suggesting a sensitivity of interpretation of 87%. A similar proportion of screen-detected (14%) and interval cancers (11%) had signs at diagnosis that were visible on previous mammograms. The potential for improvement was particularly noted for asymmetric density (sensitivity = 77%, average time visible before diagnosis 14 months) and parenchymal deformity/stellate lesion (sensitivity = 81%, average time visible before diagnosis 12 months). CONCLUSION: The highest sensitivity was observed for comedo-type microcalcifications (sensitivity = 97%, average time visible before diagnosis 5 months). By improvements in sensitivity to asymmetric density and parenchymal deformity/stellate lesion, 4% of tumours could have their time of diagnosis advanced substantially.

Adult↗

Opportunistic screening for genital chlamydial infection. I: acceptability of urine testing in primary and secondary healthcare settings.

OBJECTIVES: To determine the acceptability of opportunistic screening for Chlamydia trachomatis in young people in a range of healthcare settings. DESIGN: An opportunistic screening programme (1 September 1999 to 31 August 2000) using urine samples tested by ligase chain reaction (LCR). Data on uptake and testing were collected and in-depth interviews were used for programme evaluation. SETTING: General practice, family planning, genitourinary medicine clinics, adolescent sexual health clinics, termination of pregnancy clinics, and women's services in hospitals (antenatal, colposcopy, gynaecology and infertility clinics) in two health authorities (Wirral and Portsmouth and South East Hampshire). Main participants: Sexually active women aged between 16 and 24 years attending healthcare settings for any reason. MAIN OUTCOME MEASURES: Uptake data: proportion of women accepting a test by area, healthcare setting, and age; overall population coverage achieved in 1 year. Evaluation data: participants' attitudes and views towards opportunistic screening and urine testing. RESULTS: Acceptance of testing by women (16-24 years) was 76% in Portsmouth and 84% in Wirral. Acceptance was lower in younger women (Portsmouth only) and varied by healthcare setting within each site. 50% of the target female population were screened in Portsmouth and 39% in Wirral. Both the opportunistic offer of screening and the method of screening were universally acceptable. Major factors influencing a decision to accept screening were the non-invasive nature of testing and treatment, desire to protect future fertility, and the experimental nature of the screening programme. CONCLUSIONS: An opportunistic model of urine screening for chlamydial infection is a practical, universally acceptable method of screening.

Adolescent↗

Opportunistic screening for genital chlamydial infection. II: prevalence among healthcare attenders, outcome, and evaluation of positive cases.

OBJECTIVES: To determine the prevalence and treatment outcomes among young women screened opportunistically for genital Chlamydia trachomatis and to evaluate the impact of screening in those participating. DESIGN: An opportunistic screening programme (1 September 1999 to 31 August 2000) using urine samples, tested by ligase chain reaction (LCR). In-depth interviews were used for programme evaluation. SETTING: Screening was offered in two health authorities at general practice, family planning, genitourinary medicine (GUM), adolescent sexual health, termination of pregnancy clinics and women's services in hospitals (antenatal, colposcopy, gynaecology and infertility clinics). Main participants: Sexually active women (16-24 years) attending for any reason. MAIN OUTCOME MEASURES: Screening data: prevalence of infection by age and healthcare setting; proportion of positive patients attending for treatment. Evaluation data: participants' attitudes and views towards screening and follow up. RESULTS: In total, 16 930 women (16-24 years) were screened. Prevalence was higher in younger women (16-20) than those aged 21-24 years and was highly variable at different healthcare settings (range 3.4%-17.6%). Prevalence was approximately 9% in general practice. The role of the project health advisers in managing results and coordinating treatment of positive individuals was essential; the vast majority of all positives were known to be treated. Women felt that screening was beneficial. Improving awareness and education about sexually transmitted infections is required to alleviate negative reactions associated with testing positive for infection. CONCLUSIONS: Prevalence of infection outside GUM clinics is substantial and opportunistic screening using urine samples is an acceptable method of reaching individuals with infection who do not normally present at specialist clinics.

Adolescent↗

Audit of the management of suspected giant cell arteritis in a large teaching hospital.

BACKGROUND: The diagnosis of giant cell arteritis (GCA) is often confirmed by an early temporal artery (TA) biopsy of adequate length. Treatment of this condition with high-dose corticosteroids may be associated with significant morbidity, including osteoporosis. AIM: To audit current management of patients with suspected GCA at Auckland Healthcare, a large teaching hospital. METHODS: We performed a retrospective chart review of all TA biopsies from January 1996 to June 2000. A total of 117 biopsies from 111 patients was audited. Of these patients, 37/111 (33%) had a final clinical diagnosis of GCA (GCA patients). The areas of interest for audit were waiting time for TA biopsy, length of sample, initial corticosteroid therapy and osteoporosis prophylaxis. RESULTS: The mean waiting time for biopsy for all patients was 5.6 days (range 0-42 days). This time varied from 9.3 days for rheumatology patients to 2.6 days for ophthalmology patients (P = 0.003). Only 44/117 (37.6%) specimens measured more than 10 mm. For GCA patients, the median initial oral prednisone dose was 60 mg/day. Osteoporosis prophylaxis was prescribed in 24/37 (65%) GCA patients, most commonly cyclical etidronate. CONCLUSIONS: There is significant variation in the management of GCA within our institution. This audit has highlighted several areas where improvement could be made, particularly in streamlining the process of obtaining TA biopsy and in promoting the use of osteoporosis prophylaxis.

Aged↗

The sensitivity of the assessment process in screening mammography.

A follow-up of 3143 women from four screening centres, who were assessed after screening mammography, showed that 371 had breast cancer diagnosed at that assessment and 62 developed a breast cancer in the following 6 years. Of these, 32 were judged to be false-negatives at assessment, with 23 of the 32 at the site originally suspected. The results show that the assessment process is not infallible and that the scale of the problem only becomes clear when an exhaustive search is made for missed cancers.

Journal Article↗

The UK national study of magnetic resonance imaging as a method of screening for breast cancer (MARIBS).

The UK national study of magnetic resonance imaging as a method of screening for breast cancer (MARIBS) is in progress. The study design, accrual to date, and related research projects are described. Revised accrual rates and expected recruitment are given. 15 cancers have been detected to date, from a total of 1236 screening measurements. This event rate and the tumour grades reported are compared with recent reports from other studies in women at high risk of breast cancer.

Adult↗

Interferon-gamma microsatellite and rheumatoid arthritis.

Several non-HLA genes contribute to the susceptibility to rheumatoid arthritis (RA). A recent report noted an allele (126 bp [CA(13)]) of the interferon-gamma intron A microsatellite repeat strongly associated with both the occurrence and the severity of RA. We assessed this locus in an independent set of 128 controls and 93 prospectively recruited patients with early RA. The reported association could not be confirmed. This discrepancy might be due to technical problems, which could be avoided by the use of reference samples.

Arthritis, Rheumatoid↗