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Biomedical subjects

W Taylor

Publications and source records attributed to W Taylor.

At least 19 recordsLinked to original sources
PubMed2006

The association of homocysteine and its determinants MTHFR genotype, folate, vitamin B12 and vitamin B6 with bone mineral density in postmenopausal British women.

We studied the association between plasma total homocysteine (tHcy), its determinants folate, vitamin B(12), vitamin B(6) and MTHFR genotype, and bone mineral density (BMD) in 328 postmenopausal British women. When the subjects were assigned to one of 3 groups (control, osteopenic or osteoporotic) according to their BMD at the os calcis, those in the osteoporotic group had, compared with the controls, a significantly lower serum folate concentration, a significantly higher % of current smokers and a significantly higher incidence of recent fracture. In the population as a whole, we found significant associations of BMD with tHcy (r=-0.130, p=0.033, log tHcy) and folate (r=0.132, p=0.025, log folate). The association of folate with BMD was maintained after correction for age, weight and height (r=0.124, p=0.042, log folate), but the association of tHcy with BMD weakened after correction for age, weight, height and creatinine (r=-0.117, p=0.059, log tHcy). Vitamins B(12) and B(6) were not associated with BMD, but were significantly associated with tHcy, vitamin B(12) (r=-0.34, p<0.0001), vitamin B(6) (r=-0.16, p=0.007), as was folate (r=-0.41, p<0.0001). There was an increasing frequency of the MTHFR TT genotype across the 3 BMD groups, but this did not attain significance. Individuals with the TT genotype had significantly higher plasma tHcy but there was no difference between the genotypes (CC, CT, TT) for folate or BMD. Smoking was associated with a highly significant reduction in BMD and lower weight, and a significant reduction in circulating folate and vitamin B(6) concentrations, but no change in tHcy or vitamin B(12) concentrations when compared with non-smokers. We conclude that low serum folate is a significant risk factor for osteoporosis, with plasma tHcy having a lesser effect. Both vitamins B(12) and B(6), by acting through tHcy, may also have an effect on the skeleton, albeit a weaker one than folate. Cigarette smoking is a strong determinant of BMD, and may act through effects on folate and vitamin B(6).

Aged↗
PubMed2006

Cyclic stretch-induced reorganization of the cytoskeleton and its role in enhanced gene transfer.

Cyclic stretch is known to alter a number of cellular and subcellular processes, including those involved in nonviral gene delivery. We have previously shown that moderate equibiaxial cyclic stretch (10% change in basement membrane area, 0.5 Hz, 50% duty cycle) of human pulmonary A549 cells enhances gene transfer and expression of reporter plasmid DNA in vitro, and that this phenomena may be due to alterations in cytoplasmic trafficking. Although the path by which plasmid DNA travels through the cytoplasm toward the nucleus is not well understood, the cytoskeleton and the constituents of the cytoplasm are known to significantly hinder macromolecular diffusion. Using biochemical techniques and immunofluorescence microscopy, we show that both the microfilament and microtubule networks are significantly reorganized by equibiaxial cyclic stretch. Prevention of this reorganization through the use of cytoskeletal stabilizing compounds mitigates the stretch-induced increase in gene expression, however, depolymerization in the absence of stretch is not sufficient to increase gene expression. These results suggest that cytoskeletal reorganization plays an important role in stretch-induced gene transfer and expression.

Actin Cytoskeleton↗
PubMed2005

An unusual case of Turcot's syndrome associated with ileal adenocarcinoma, intestinal non-Hodgkin's lymphoma, and duodenal adenocarcinoma. Review of the classification and genetic basis of Turcot's syndrome.

A 38-year-old man with a history of colonic and small bowel polyposis and glioblastoma was investigated for dyspepsia. Upper GI endoscopy identified an abnormal area in the duodenum, confirmed by histology as high grade non-Hodgkin's B cell MALT lymphoma. Although cases of Turcot's syndrome (TS) (colonic polyposis and primary brain tumour occurring in the same patient) have been previously described, association with haematological malignancy is rare. This is the first report of intestinal lymphoma occurring in an adult with TS.

Adenocarcinoma↗
PubMed2005

Insulin resistance and inflammatory activation in older patients with systolic and diastolic heart failure.

OBJECTIVE: To evaluate insulin resistance and systemic inflammation in older patients with systolic (SHF) or diastolic heart failure (DHF). PATIENTS: 52 non-diabetic patients (> 70 and < 90 years old) with chronic heart failure (CHF) and hospitalised within the previous six months for heart failure were studied, together with a control group of older healthy volunteers (n = 26). On the basis of Doppler echocardiographic criteria patients were classed as having SHF (n = 27) or DHF (n = 25). MAIN OUTCOME MEASURES: Fasting glucose, insulin, C reactive protein, interleukin 6, and tumour necrosis factor alpha soluble receptor II (TNF-alphaSRII) concentrations were determined. Insulin resistance was estimated by the homeostasis model assessment (HOMA). RESULTS: HOMA index (median, interquartile range) was higher in patients with DHF (1.77, 1.06-2.26) than in patients with SHF (0.97, 0.81-1.85) or healthy volunteers (1.04, 0.76-1.44; p = 0.01). After adjustment for body mass index, age, and use of angiotensin converting enzyme inhibitors, both groups of patients with CHF were more insulin resistant than were healthy volunteers (p = 0.02). C reactive protein, interleukin 6, and TNF-alphaSRII were all significantly (p < 0.001) higher in patients with DHF and SHF than in healthy volunteers. All markers of systemic inflammation were independently associated with the presence of clinical CHF. CONCLUSION: Insulin resistance and inflammatory activation are present in older patients with SHF and DHF.

Aged↗
PubMed2004

Artesunate combinations for treatment of malaria: meta-analysis.

BACKGROUND: Addition of artemisinin derivatives to existing drug regimens for malaria could reduce treatment failure and transmission potential. We assessed the evidence for this hypothesis from randomised controlled trials. METHODS: We undertook a meta-analysis of individual patients' data from 16 randomised trials (n=5948) that studied the effects of the addition of artesunate to standard treatment of Plasmodium falciparum malaria. We estimated odds ratios (OR) of parasitological failure at days 14 and 28 (artesunate combination compared with standard treatment) and calculated combined summary ORs across trials using standard methods. FINDINGS: For all trials combined, parasitological failure was lower with 3 days of artesunate at day 14 (OR 0.20, 95% CI 0.17-0.25, n=4504) and at day 28 (excluding new infections, 0.23, 0.19-0.28, n=2908; including re-infections, 0.30, 0.26-0.35, n=4332). Parasite clearance was significantly faster (rate ratio 1.98, 95% CI 1.85-2.12, n=3517) with artesunate. In participants with no gametocytes at baseline, artesunate reduced gametocyte count on day 7 (OR 0.11, 95% CI 0.09-0.15, n=2734), with larger effects at days 14 and 28. Adding artesunate for 1 day (six trials) was associated with fewer failures by day 14 (0.61, 0.48-0.77, n=1980) and day 28 (adjusted to exclude new infections 0.68, 0.53-0.89, n=1205; unadjusted including reinfections 0.77, 0.63-0.95, n=1958). In these trials, gametocytes were reduced by day 7 (in participants with no gametocytes at baseline 0.11, 0.09-0.15, n=2734). The occurrence of serious adverse events did not differ significantly between artesunate and placebo. INTERPRETATION: The addition of 3 days of artesunate to standard antimalarial treatments substantially reduce treatment failure, recrudescence, and gametocyte carriage.

Adolescent↗
PubMed2003

Spinal epidural abscess: a diagnostic challenge.

The objective of the study was to highlight the diagnostic challenge of this elusive rare disease. A retrospective study of non-tuberculous spinal epidural abscesses (SEA) was carried out in Southern General Hospital, Glasgow, University Hospital of Wales, Cardiff, and Morriston Hospital, Swansea, from 1990 to 2000. Thirty-nine patients, consisting of 20 females and 19 males, with an age range from 20 to 85 years (mean: 61.1) were identified. Thirty-eight had localized back/neck pain. Eighteen were apyrexial. Twenty-nine demonstrated neurological deficit. All patients had raised inflammatory markers and gadolinium-enhanced magnetic resonance imaging (MRI) was diagnostic in 34. The most commonly identified organism was Staphylococcus aureus. All underwent surgical decompression, of which 13 required stabilization. Three died, seven lacked sphincter control and nine had motor deficit at the end of 1 year. It was concluded that fever is not mandatory for the diagnosis of SEA. Patients with localized back/neck pain and raised inflammatory markers need urgent MRI.

Adult↗
PubMed2002

Dual technique for obliteration of small arteriovenous malformations.

A 17-year-old man underwent an incomplete excision of a left fronto-parietal arterio-venous malformation (AVM), under image guidance. An initial attempt to treat the residual AVM by embolization was unsuccessful. The craniotomy was then re-opened in the angiography suite and the residual AVM was excised by, first, following the microcatheter within the arterial feeding vessel to the AVM and, secondly, by using metallic clips as radiographic markers to locate the position of the AVM during superselective angiography. The dual technique described is likely to be useful in selected cases with small residual AVMs and AVMs near eloquent areas of the brain, where the extent of surgical dissection and postoperative morbidity can be minimized by the precise localization of the AVM.

Adolescent↗
PubMed2001

Epidemiology of the insulin-like growth factor system in three ethnic groups.

The insulin-like growth factor (IGF) system, comprising insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), and their binding proteins (IGFBPs), is linked to cell growth, the development of cardiovascular disease, and several cancers. Little is known about its epidemiology. The authors studied relations of the IGF system to anthropometric and metabolic variables in three population-based ethnic groups in Manchester, England, in 1994-1998 with differing disease risks: African Caribbean (n = 193), Pakistani (n = 130), and local Europeans(n = 142). Standardized anthropometry, glucose tolerance tests, and serum assays were performed. Body mass indices (BMIs) were high in all groups. IGF-I levels were highest in normoglycemic African Caribbeans and declined with age (r = -0.28). IGF-II levels were greatest in Europeans. IGFBP-1 concentrations increased with age in Pakistanis (r = 0.20) and Europeans (r = 0.29), but not in African Caribbeans (r = 0.06), and were inversely related to BMI (r = -0.37). Age- and sex-adjusted IGFBP-1 was inversely related to fasting insulin and proinsulin in all groups; participants with newly detected diabetes were relatively insulinopenic but had higher IGFBP-1 concentrations. Nonesterified (free) fatty acid (NEFA) concentrations increased with declining glucose tolerance. In multiple regression analysis, IGFBP-1 was independently and negatively related to fasting insulin, BMI, and African-Caribbean compared with European ethnicity but positively related to age, fasting glucose, and NEFA. IGF-I was inversely related only to age, NEFA, and Pakistani ethnicity. IGF-II showed a strong ethnic difference but was unrelated to other variables. These data indicate considerable potential for exploring disease-IGF system relations in population samples.

Adult↗
PubMed2001

Rehabilitation that works--vocational outcomes following rehabilitation for occupational musculoskeletal pain.

AIMS: To describe the short term vocational outcome for accident compensation claimaints with disabling musculoskeletal pain following a comprehensive, interdisciplinary rehabilitation programme. METHODS: A telephone follow-up audit of clients who had undertaken a rehabilitation programme characterised by a cognitive-behavioural approach with self-management, reconditioning, vocational rehabilitation and psychological pain management. RESULTS: Of 62 clients who had undergone a rehabilitation programme, we obtained follow-up information on 49 (79%). These were predominantly male, aged in their mid 30s, manual workers with low back pain and a median sick leave of twelve months. At a median of five months a vocational success was achieved in 75%: working full time (47%), part time (12%) or actively looking for work (16%). Of those in work, 48% went back to the same job, 7% went back to the same job but with a different employer and 15% went to a different job that used the same skills. Logistic regression analysis showed that duration of work disability was the major predictor of vocational success (OR 0.36, 95% CI 0.18 to 0.78, for a difference of twelve months). CONCLUSION: Despite the uncontrolled nature of these results, it is likely that the rehabilitation programme had a significant impact in getting compensation claimants back to work. Only a minority require substantive retraining and early intervention is associated with a better outcome.

Adult↗
PubMed2001

Close relation of fasting insulin-like growth factor binding protein-1 (IGFBP-1) with glucose tolerance and cardiovascular risk in two populations.

AIMS/HYPOTHESIS: Insulin resistance/hyperinsulinaemia is implicated in the development of cardiovascular disease and diabetes but its role and causal pathways are not clear. We tested the hypothesis that the insulin-like growth factor system is independently associated with cardiovascular risk within susceptible populations based on previous reports of the links between low circulating insulin-like growth factor binding protein-1 concentrations and increased macrovascular disease in Type II (non-insulin-dependent) diabetes mellitus. METHODS: In a population-based study 272 subjects (142 subjects of European and 130 Pakistani of origin) underwent a 75 g oral glucose tolerance test and standardised anthropometry. Fasting concentrations of insulin-like growth factor binding protein-1 (IGFBP-1), insulin-like growth factor-I (IGF-I), insulin-like growth factor-II (IGF-II), intact insulin and lipids were measured and were related to 2-h glucose tolerance test status. Insulin sensitivity was calculated using the homeostasis model assessment (HOMA). RESULTS: Insulin-like growth factor binding protein-1 was significantly lower in subjects with impaired glucose tolerance when compared with normal glucose tolerance in both ethnic groups (Europeans F = 6.7, p = 0.002 and Pakistanis F = 4.4, p = 0.01). Multiple linear regression modelling showed that insulin-like growth factor binding protein-1 was independently associated with 2-h glucose (beta = 0.16, p = 0.009) and logistic regression indicated a 40% reduction in risk of impaired glucose tolerance for every 2.7 ng/ml increase in the insulin-like growth factor binding protein-1 concentration [odds ratio 0.6 (CI = 0.49-0.71), p = 0.001)]. In addition, insulin-like growth factor binding protein-1 was significantly correlated negatively with several established cardiovascular factors, and positively with insulin sensitivity. CONCLUSIONS/INTERPRETATION: Insulin-like growth factor binding protein-1 is closely related to risk factors for diabetes and cardiovascular disease in people of European and Pakistani origin. It has potential use as a marker of (hepatic) insulin resistance in clinical intervention studies and further implicates the insulin-like growth factor system in the development of macrovascular disease.

Blood Glucose↗
PubMed2001

Concepts and data model for a co-operative neurovascular database.

BACKGROUND: Problems of clinical management of neurovascular diseases are very complex. This is caused by the chronic character of the diseases, a long history of symptoms and diverse treatments. If patients are to benefit from treatment, then treatment decisions have to rely on reliable and accurate knowledge of the natural history of the disease and the various treatments. METHODS: Recent developments in statistical methodology and experience from electronic patient records are used to establish an information infrastructure based on a centralized register. RESULTS: A protocol to collect data on neurovascular diseases with technical as well as logistical aspects of implementing a database for neurovascular diseases are described. The database is designed as a co-operative tool of audit and research available to co-operating centres. CONCLUSION: When a database is linked to a systematic patient follow-up, it can be used to study prognosis. Careful analysis of patient outcome is valuable for decision-making.

Adult↗
PubMed2001

Evidence for inadequate construct validity of the Disease Repercussions Profile in people with rheumatoid arthritis.

OBJECTIVE: To re-evaluate the construct validity of the Disease Repercussions Profile (DRP), a measure of handicap in arthritis populations. METHODS: We used the multitrait-multimethod approach to determine convergent and discriminant validity in a postal survey of randomly selected patients with rheumatoid arthritis who had attended the Wellington Regional Rheumatology Unit since 1988. Respondents (n=142) completed the following self-report instruments: Disease Repercussions Profile, EuroQol EQ-5D, Health Assessment Questionnaire, London Handicap Scale and WHOQOL-BREV. RESULTS AND CONCLUSIONS: The pattern of correlation supported the construct validity of the dichotomous response question (DRP domain affected or not) for the activity and relationships domain, provided ambiguous support for the appearance and emotion domain and no support for the social and financial domains. There was no support for construct validity of any of the domains on the importance rating part of the DRP. We suggest that the DRP be interpreted cautiously in aggregated group data.

Arthritis, Rheumatoid↗
PubMed2001

Paroxysmal alternating skew deviation and nystagmus after partial destruction of the uvula.

A patient with suspected brain stem glioma involving the area of the left vestibular nuclei and cerebellar peduncle, developed paroxysmal alternating skew deviation and direction changing nystagmus after biopsy of the inferior cerebellar vermis resulting in destruction of the uvula. Between attacks she had right over left skew deviation with asymptomatic right beating horizontal nystagmus. Slow phases of the resting nystagmus showed increasing velocity, similar to congenital nystagmus. At intervals of 40-50 seconds, paroxysmal reversal of her skew deviation occurred, accompanied by violent left beating horizontal torsional nystagmus lasting 10-12 seconds and causing severe oscillopsia. It is proposed that this complex paroxysmal eye movement disorder results from (1) a lesion in the left vestibular nuclei causing right over left skew and right beating resting nystagmus and (2) a disruption of cerebellar inhibition of vestibular nuclei, causing alternating activity in the vestibular system with intermittent reversal of the skew deviation and paroxysmal nystagmus towards the side of the lesion.

Adult↗
PubMed2001

Characterization of 5'-regulatory region of human myostatin gene: regulation by dexamethasone in vitro.

We cloned and characterized a 3.3-kb fragment containing the 5'-regulatory region of the human myostatin gene. The promoter sequence contains putative muscle growth response elements for glucocorticoid, androgen, thyroid hormone, myogenic differentiation factor 1, myocyte enhancer factor 2, peroxisome proliferator-activated receptor, and nuclear factor-kappaB. To identify sites important for myostatin's gene transcription and regulation, eight deletion constructs were placed in C(2)C(12) and L6 skeletal muscle cells. Transcriptional activity of the constructs was found to be significantly higher in myotubes compared with that of myoblasts. To investigate whether glucocorticoids regulate myostatin gene expression, we incubated both cell lines with dexamethasone. On both occasions, dexamethasone dose dependently increased both the promoter's transcriptional activity and the endogenous myostatin expression. The effects of dexamethasone were blocked when the cells were coincubated with the glucocorticoid receptor antagonist RU-486. These findings suggest that glucocorticoids upregulate myostatin expression by inducing gene transcription, possibly through a glucocorticoid receptor-mediated pathway. We speculate that glucocorticoid-associated muscle atrophy might be due in part to the upregulation of myostatin expression.

Base Sequence↗
PubMed2001

The 14-3-3 cerebrospinal fluid immunoassay lacks utility in the diagnosis of clinical scrapie.

This study determined whether the immunoassay for cerebrospinal fluid 14-3-3 protein concentration was sensitive and specific in the diagnosis of naturally occurring clinical scrapie in sheep. Cerebrospinal fluid was collected from 9 sheep with the confirmed diagnosis of scrapie. Additionally, cerebrospinal fluid was collected from 13 clinically normal sheep, which originated from a closely monitored flock with no history of scrapie. Sensitivity and specificity were calculated using standard epidemiological methods. Cerebrospinal fluid immunoassay results did not differ significantly between positive and negative sheep. Test sensitivity varied from 0.55 to 0.66, depending on the choice of test endpoint. Test specificity varied from 0.30 to 0.77, depending on the choice of test endpoint. The 14-3-3 cerebrospinal fluid immunoassay appears to have no value in the diagnosis of clinical scrapie in sheep.

14-3-3 Proteins↗