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Biomedical subjects

Christopher J Taylor

Publications and source records attributed to Christopher J Taylor.

11 recordsLinked to original sources

Improved wrist pannus volume measurement from contrast-enhanced MRI in rheumatoid arthritis using shuffle transform.

BACKGROUND: Contrast-enhanced MRI is of value in assessing rheumatoid pannus in the hand, but the images are not always easy to quantitate. OBJECTIVE: To develop and evaluate an improved measurement of volume of enhancing pannus (VEP) in the hand in human rheumatoid arthritis (RA). METHODS: MR images of the hand and wrist were obtained for 14 patients with RA at 0, 1 and 13 weeks. Volume of enhancing pannus was measured on images created by subtracting precontrast T1-weighted images from contrast-enhanced T1-weighted images using a shuffle transformation technique. Maximum intensity projection (MIP) and 3D volume rendering of the images were used as a guide to identify the pannus and any contrast-enhanced veins. RESULT: Visualisation of pannus was much improved following the shuffle transform. Between 0 weeks and 1 week, the mean value of the within-subject coefficient of variation (CoV) was 0.13 and the estimated total CoV was 0.15. There was no evidence of significant increased variability within the 13-week interval for the complete sample of patients. CONCLUSION: Volume of enhancing pannus can be measured reproducibly in the rheumatoid hand using 3D contrast-enhanced MRI and shuffle transform.

Adult↗

Assessment of lung disease in children with cystic fibrosis using hyperpolarized 3-Helium MRI: comparison with Shwachman score, Chrispin-Norman score and spirometry.

This study assesses the feasibility of hyperpolarized 3-Helium MRI in children with cystic fibrosis (CF) and correlates the findings with standard clinical parameters based on chest radiograph (CXR) and pulmonary function tests (PFT). An uncontrolled, observational study in eighteen children with cystic fibrosis aged 5 - 17 years (median 12.1 years), with different severity of disease was carried out. All subjects underwent routine clinical assessment including PFT and standard auxology; CXR was obtained and Shwachman and Chrispin-Norman scores calculated. Hyperpolarized 3-He magnetic resonance imaging (MRI) was carried out using a spin-exchange polarizer and a whole body 1.5 T scanner. Ventilation distribution images were obtained during a 21-second breath-hold and scored according to previously defined criteria. Spearman's non-parametric correlations test was performed to assess for statistical significance at the p<0.05 level. The children tolerated the procedure well. No desaturation events were observed during 3-He MRI. A significant, albeit moderate, correlation was found between MRI score and FEV1% predicted (r=-0.41; p=0.047) and FVC% predicted (r=-0.42; p=0.04), while there were trends of correlations between Shwachman score and MRI score (r=-0.38; p=0.06) and Shwachman score and FEV1% predicted (r=0.39; p=0.055). The feasibility of hyperpolarized 3-He MRI in children with CF was demonstrated. MRI appears to be able to demonstrate functional lung changes, although correlations with routine clinical tests are only moderate to poor. This non-ionising radiation technique could be useful for monitoring lung disease and assessing therapy in this patient population.

Adolescent↗

Abnormalities of CSF flow patterns in the cerebral aqueduct in treatment-resistant late-life depression: a potential biomarker of microvascular angiopathy.

There is growing evidence that microvascular angiopathy (MVA) plays an important role in the development of dementia and affective disorders in older people. At currently available image resolutions it is not possible to image directly the vascular changes associated with MVA, but the effects on blood and cerebrospinal fluid (CSF) flow may be detectable. The aim of this study was to investigate a potential biomarker for MVA based on MRI of abnormalities in CSF flow. Since there is considerable indirect evidence that treatment resistance in late-onset depressive disorder is related to MVA, we assessed the method in a group of 22 normal volunteers and 29 patients with responsive (N=21) or treatment-resistant (N=8) late-onset depressive disorder. Single-slice quantified phase-contrast (PC) images of cerebral blood and CSF flow were collected at 15 points over a cardiac cycle, and the resulting flow curves were parameterized. Significant differences in the CSF flow (width of systolic flow peak and diastolic flow volume, both P<0.01) through the cerebral aqueduct were observed for the group of treatment-resistant patients when compared to age matched controls. No significant difference was observed for a group of 21 patients with treatment-responsive depression. The findings support the hypothesis that MR measurement of CSF flow abnormalities provides a biomarker of MVA, and thus could have application in a wide range of age-related diseases.

Aged↗

Computerized nailfold video capillaroscopy--a new tool for assessment of Raynaud's phenomenon.

OBJECTIVE: To develop a computer based nailfold video capillaroscopy system with enhanced image quality and to assess its disease-subgroup resolving power in patients with primary and secondary Raynaud's phenomenon (RP). METHODS: Using frame registration software, digitized video images from the microscope were combined to form a panoramic mosaic of the nailfold. Capillary dimensions (apex, arterial, venous, and total width) and density were measured onscreen. Significantly, the new system could guarantee analysis of the same set of capillaries by 2 observers. Forty-eight healthy control subjects, 21 patients with primary RP, 40 patients with limited cutaneous systemic sclerosis (lcSSc), and 11 patients with diffuse cutaneous SSc (dcSSc) were studied. Intra- and interobserver variability were calculated in a subset of 30 subjects. RESULTS: The number of loops/mm was significantly lower, and all 4 capillary dimensions significantly greater, in SSc patients versus controls plus primary RP patients (p < 0.001 for all measures). When comparing control (+ primary RP) patients with SSc patients (lcSSc + dcSSc) the most powerful discriminator was found to be the number of loops/mm. Results for intra- and interobserver reproducibility showed that the limits of agreement were closer when both observers measured the same capillaries. CONCLUSION: The key feature of the newly developed system is that it improves reproducibility of nailfold capillary measurements by allowing reidentification of the same capillaries by different observers. By allowing access to previous measurements, the new system should improve reliability in longitudinal studies, and therefore has the potential of being a valuable outcome measure of microvessel disease/involvement in clinical trials of scleroderma spectrum disorders.

Adult↗

Linear structures in mammographic images: detection and classification.

We describe methods for detecting linear structures in mammograms, and for classifying them into anatomical types (vessels, spicules, ducts, etc). Several different detection methods are compared, using realistic synthetic images and receiver operating characteristic (ROC) analysis. There are significant differences (p < 0.001) between the methods, with the best giving an Az value for pixel-level detection of 0.943. We also investigate methods for classifying the detected linear structures into anatomical types, using their cross-sectional profiles, with particular emphasis on recognising the "spicules" and "ducts" associated with some of the more subtle abnormalities. Automatic classification results are compared with expert annotations using ROC analysis, demonstrating useful discrimination between anatomical classes (Az = 0.746). Some of this discrimination relies on simple attributes such as profile width and contrast, but important information is also carried by the shape of the profile (Az = 0.653). The methods presented have potentially wide application in improving the specificity of abnormality detection by exploiting additional anatomical information.

Algorithms↗

Corresponding articular cartilage thickness measurements in the knee joint by modelling the underlying bone (commercial in confidence).

We present a method for corresponding and combining cartilage thickness readings from a population of patients using the underlying bone structure as a reference. Knee joint femoral bone and cartilage surfaces are constructed from a set of parallel slice segmentations of MR scans. Correspondence points across a population of bone surfaces are defined and refined by minimising an objective function based on the Minimum Description Length of the resulting statistical shape model. The optimised bone model defines a set of corresponding locations from which 3D measurements of the cartilage thickness can be taken and combined for a population of patients. Results are presented for a small group of patients demonstrating the feasibility and potential of the approach as a means of detecting sub-millimetre cartilage thickness changes due to disease progression.

Algorithms↗

Improved lung function and body mass index associated with long-term use of Macrolide antibiotics.

BACKGROUND: A number of studies have suggested that the non-antimicrobial actions of macrolide antibiotics may be valuable in treating patients with cystic fibrosis. The use of long-term macrolide antibiotics for the management of CF patients colonised by Pseudomonas aeruginosa and progressive pulmonary disease was introduced into our clinic in 1997. A retrospective study was undertaken to assess of the impact of this therapy. METHODS: Twenty patients with progressive pulmonary disease (>10% fall in FEV(1) over 12 months despite optimising conventional therapy) were commenced on Azithromycin, 250 mg daily during a 21-month period. At the time of assessment they had remained on therapy for a mean of 0.9 years. Changes in lung function, weight, body mass index (BMI) and frequency of pulmonary exacerbations were assessed. A group of 20 patients with stable lung function and matched as far as possible for age and sex was identified for comparison. RESULTS: Pulmonary function increased significantly in the Azithromycin group with FEV1% predicted increasing from a mean of 50.2-59.1% (P=0.001) while FVC% predicted increase from 64.5 to 76.1% (P=0.002). There was small but non-significant fall in lung function in the comparison group. Body mass index increased by a mean of 1.1 in the Azithromycin group but remained unchanged in the comparison group. The number of pulmonary exacerbations requiring intravenous antibiotics declined by 48.3% in macrolide treated subjects compared to the pre-treatment period (P<0.025); frequency of exacerbations in the control group was unchanged. CONCLUSION: Long-term Azithromycin treatment in patients with progressive deterioration in lung function appears to have led to an improvement in pulmonary function, increased body mass index and decreased the frequency of pulmonary exacerbations requiring intravenous antibiotics.

Adolescent↗

Hyperhomocystinemia in children with inflammatory bowel disease.

OBJECTIVES: Thromboembolism is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). Plasma total homocysteine (tHcy) is a risk factor for vascular disease and has been implicated as a mediator of thromboembolic events in adults with IBD. The authors studied the link between tHcy and IBD in children, in whom associations may be clearer, and investigated associations with plasma von Willebrand factor antigen, a marker of vascular damage. METHODS: This cross-sectional study included 43 patients with IBD (27 Crohn disease, 9 ulcerative colitis, and 7 indeterminate colitis) and 46 control subjects from a pediatric gastroenterology clinic. Plasma tHcy, plasma 5-methyl tetrahydrofolate, red cell folate, plasma vitamin B12, plasma von Willebrand factor antigen, and methylene tetrahydrofolate reductase (MTHFR) genotype (for the C677T mutation) were measured. RESULTS: Plasma tHcy concentrations were higher in children with IBD than in control subjects, when corrected for age (P < 0.05), and plasma tHcy was negatively correlated with plasma 5 methyl tetrahydrofolate (P < 0.0005). Plasma 5 methyl tetrahydrofolate and age were the main predictors of plasma tHcy. Neither MTHFR genotype nor von Willebrand factor showed any association with any other measure, and there were no differences between children with IBD and control subjects. CONCLUSIONS: Elevated plasma tHcy is a consequence of IBD in children, probably mediated by poor folate status associated with diet or the pathophysiology of the disease.

Adolescent↗

Induction of neutrophil apoptosis by the Pseudomonas aeruginosa exotoxin pyocyanin: a potential mechanism of persistent infection.

Pseudomonas aeruginosa colonizes and infects human tissues, although the mechanisms by which the organism evades the normal, predominantly neutrophilic, host defenses are unclear. Phenazine products of P. aeruginosa can induce death in Caenorhabditis elegans. We hypothesized that phenazines induce death of human neutrophils, and thus impair neutrophil-mediated bacterial killing. We investigated the effects of two phenazines, pyocyanin and 1-hydroxyphenazine, upon apoptosis of neutrophils in vitro. Pyocyanin induced a concentration- and time-dependent acceleration of neutrophil apoptosis, with 50 microM pyocyanin causing a 10-fold induction of apoptosis at 5 h (p < 0.001), a concentration that has been documented in sputum from patients colonized with P. aeruginosa. 1-hydroxyphenazine was without effect. In contrast to its rapid induction of neutrophil apoptosis, pyocyanin did not induce significant apoptosis of monocyte-derived macrophages or airway epithelial cells at time points up to 24 h. Comparison of wild-type and phenazine-deleted strains of P. aeruginosa showed a highly significant reduction in neutrophil killing by the phenazine-deleted strain. In clinical isolates of P. aeruginosa pyocyanin production was associated with a proapoptotic effect upon neutrophils in culture. Pyocyanin-induced neutrophil apoptosis was not delayed either by treatment with LPS, a powerfully antiapoptotic bacterial product, or in neutrophils from cystic fibrosis patients. Pyocyanin-induced apoptosis was associated with rapid and sustained generation of reactive oxygen intermediates and subsequent reduction of intracellular cAMP. Treatment of neutrophils with either antioxidants or synthetic cAMP analogues significantly abrogated pyocyanin-induced apoptosis. We conclude that pyocyanin-induced neutrophil apoptosis may be a clinically important mechanism of persistence of P. aeruginosa in human tissue.

Apoptosis↗