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Biomedical subjects

C J Taylor

Publications and source records attributed to C J Taylor.

At least 73 records · Page 4Linked to original sources

HLA-specific antibodies in highly sensitized patients can cause a positive crossmatch against pig lymphocytes.

BACKGROUND: The presence of IgG HLA-specific antibodies in the serum of patients awaiting transplantation indicates T- and B-cell priming and would result in acute rejection of a poorly matched human allograft. Recent advances in xenotransplantation, with the amelioration of hyperacute rejection using transgenic pig kidneys, may benefit such patients. However, accelerated cellular rejection might result from the primed T-cell recognition of antigenic epitopes shared between pig and human MHC molecules. METHODS: We have compared the reactivity of IgG antibodies from 8 nonsensitized (NS) and 13 highly sensitized (HS) patients with human and pig lymphocytes by flow cytometry. Xenoreactive natural antibodies (XNA) were absorbed with pig red blood cells, and HLA class I-specific antibodies were further absorbed with pooled human platelets. RESULTS: Before XNA absorption, 20 of the 21 patients had a positive IgG crossmatch with pig lymphocytes, and there was no difference between NS and HS patients. In contrast, after XNA absorption, none of the 8 NS patients were positive, compared with 9 of the 13 HS patients (mean of the median channel fluorescence values of 7.7 and 86.5, respectively; P=<0.001). For XNA-absorbed HS patient sera, 20 of 30 (67%) pig lymphocyte crossmatch combinations were positive, with a mean median channel fluorescence value of 125 (range 31 to 294) compared with 9.5 (range 7 to 13) for the 10 crossmatch-negative combinations. Platelet absorption resulted in a concomitant reduction in antibody binding to pig lymphocytes in three of six HS patient sera, indicating that HLA class I-specific antibodies are responsible, at least in part, for the positive crossmatch. CONCLUSION: These results suggest that some IgG HLA-specific antibodies can bind to pig lymphocytes, analogous to a positive crossmatch with allogeneic donors.

Animals↗

Automatic construction of eigenshape models by direct optimization.

A new approach to the problem of automatic construction of eigenshape models is presented. Eigenshape models have proved to be successful in a variety of medical image analysis problems. However, automatic construction of eigenshape models has proved to be a difficult problem, and in many applications the models are built by hand-a painstaking process. We show that the fundamental problem is a choice of the correct pose and parametrization of each shape in the training set. Eigenshape models are not invariant under reparametrizations and pose transformations of the training shapes. Since there is no a priori correct choice for the pose and parametrization of each shape, their value should be chosen so as to produce a model that is compact and specific. This problem can be solved by finding an objective function that measures these properties and varying the pose and parametrization of each shape to optimize this function. We show that the appropriate objective function is the determinant of the covariance matrix. We go on to show how this objective function can be optimized by a genetic algorithm (GA) and thus give a practical method for building eigenshape models. The models produced are often better than hand-built ones. The advantages of a GA over other choices of optimization method are that no assumptions about the nature of the shapes being modelled is required and that the global minimum of the objective function can, in principle, be found.

Algorithms↗

Factors affecting behavior toward people with disabilities.

Two field experiments were designed to explore ambivalence-induced behavior toward people with disabilities in low-cost helping situations. In Experiment 1, confederates, who either rode in a wheelchair or walked, asked shoppers for a small sum of money and either provided a reason (positive presentation) or did not provide a reason (negative presentation) for the request. Contrary to prediction, more people with a physical disability than without a physical disability were helped, regardless of their presentation. In Experiment 2, the presence of confederates in wheelchairs resulted in significantly fewer violations of parking spaces reserved for people with handicaps.

Adult↗

The use of dual-isotope imaging to compare the gastrointestinal transit of food and pancreatic enzyme pellets in cystic fibrosis patients.

Cystic fibrosis patients require pancreatic enzyme supplements to aid food digestion. It is suspected that incorrect delivery of this enzyme may result in both significant malabsorption and the development of strictures in the proximal colon caused by the high-dose supplement reaching this region before the food. Investigations into the drug's delivery were performed using dual-isotope imaging; a method was developed to directly label the enteric-coated enzyme pellets with 111In, re-applying the enteric coating afterwards, and this was then ingested with a pancake meal labelled with 99Tcm-tin colloid. Consecutive image data, acquired over a period of > or = 4 h using a dual-headed gamma camera, were analysed to assess intestinal transit. In-vitro stability checks on these labelling techniques were encouraging, showing < 2% 99Tcm and < 7% 111In elution over 90 min in hydrochloric acid. In 5 of the 12 patients studied to date, the pellets were seen to pass through significantly faster than the food, with a mean difference in 50% gastric emptying time of greater than 93 min. The mean absolute difference in emptying time for all 12 patients was > 67 min. Thus, a technique has been developed to effectively radiolabel pancreatic enzyme pellets, and analysis of dual-isotope images using this preparation, together with radiolabelled solid food, has demonstrated significant differences in the transit of these two substances through the gastrointestinal tract of some cystic fibrosis patients.

Adolescent↗

Model-based interpretation of complex and variable images.

The ultimate goal of machine vision is image understanding-the ability not only to recover image structure but also to know what it represents. By definition, this involves the use of models which describe and label the expected structure of the world. Over the past decade, model-based vision has been applied successfully to images of man-made objects. It has proved much more difficult to develop model-based approaches to the interpretation of images of complex and variable structures such as faces or the internal organs of the human body (as visualized in medical images). In such cases it has been problematic even to recover image structure reliably, without a model to organize the often noisy and incomplete image evidence. The key problem is that of variability. To be useful, a model needs to be specific-that is, to be capable of representing only 'legal' examples of the modelled object(s). It has proved difficult to achieve this whilst allowing for natural variability. Recent developments have overcome this problem; it has been shown that specific patterns of variability in shape and grey-level appearance can be captured by statistical models that can be used directly in image interpretation. The details of the approach are outlined and practical examples from medical image interpretation and face recognition are used to illustrate how previously intractable problems can now be tackled successfully. It is also interesting to ask whether these results provide any possible insights into natural vision; for example, we show that the apparent changes in shape which result from viewing three-dimensional objects from different viewpoints can be modelled quite well in two dimensions; this may lend some support to the 'characteristic views' model of natural vision.

Form Perception↗

Human leukocyte antigen compatibility in heart transplantation: evidence for a differential role of HLA matching on short- and medium-term patient survival.

BACKGROUND: Studies of the influence of human leukocyte antigen (HLA) matching on cardiac transplant outcome have proved inconclusive, mainly due to the lack of well-matched grafts. However, a growing number of studies report improved clinical course and patient survival in cases with increased HLA compatibility. Opelz et al. believe these benefits justify the introduction of prospective HLA-matching strategies. METHODS: We performed univariate and multivariate analyses to examine the short- and medium-term influence of HLA matching on 556 consecutive primary heart transplants performed at a single center between 1983 and 1994. Overall graft survival at 1, 3, and 5 years was 80%, 74%, and 67% respectively. Sixteen (2.9%) grafts failed within 5 days and were not considered in the analysis of the HLA matching and graft survival data. RESULTS: Complete HLA-A, -B, and -DR typing data were available on 477 transplant pairs. The results demonstrate a 12% 1-year survival advantage for 31 patients with zero to two HLA antigen mismatches compared with three to six mismatches. The influence of each individual locus was 6.1%, 8.4%, and 5.4% for zero HLA-A, -B, and -DR mismatches, respectively, compared with two mismatches. However, when outcome from 1 to 5 years was considered, analysis of the role of each locus revealed marked differences. HLAA-matched grafts (n=45) had a 24% lower survival rate compared with two-antigen-mismatched grafts (n=148; 88% [SE 3.1] vs. 64% [SE 8.2], respectively; P=0.009). Furthermore, 34% of HLA-A-matched grafts failed between 1 and 5 years, compared with only 5% of HLA-B-matched grafts (P=0.013). CONCLUSIONS: These data suggest that although HLA matching is effective at reducing acute graft loss, in the longer term, HLA-A matching may impair survival. HLA-A may serve as a restriction element for indirect presentation of allopeptides or tissue-specific minor histocompatibility antigens, facilitating chronic graft loss. Therefore, we advocate a differential role for HLA matching over two epochs. A blanket approach to prospective matching for heart transplants may be premature for optimal long-term survival.

Adolescent↗

The use of active shape models for making thickness measurements of articular cartilage from MR images.

Previously reported studied to quantify articular cartilage have used labor-intensive manual or semi-automatic data-driven techniques, demonstrating high accuracy and precision. However, none has been able to automate the segmentation process. This paper describes a fast, automatic, model-based approach to segmentation and thickness measurement of the femoral cartilage in 3D T1-weighted images using active shape models (ASMs). Systematic experiments were performed to assess the accuracy and precision of the technique with in vivo images of both normal and abnormal knees. Segmentation accuracy was determined by comparing the results of the segmentation with the boundaries delineated by a radiologist. The mean error in locating the boundary was 0.57 pixels. To assess the precision of the measurement technique, the mean thickness of the femoral cartilage was calculated for repeated scans of five healthy volunteers. A mean coefficient of variation (CV) of 2.8% was obtained for the thickness measurements.

Cartilage, Articular↗

Contrast-modified gradient echo imaging using rotary echo preparatory pulses.

The use of on-resonance 121 binomial composite pulses in two- or three-dimensional magnetization-prepared gradient-recalled echo magnetic resonance imaging experiments generates rotary echoes, leading to an increase in contrast range that is, in part, determined by the ratio of T2 to T1. In comparison with other fast gradient-recalled echo imaging techniques designed for enhanced T2 contrast, this method is more robust with respect to radiofrequency field inhomogeneity and less sensitive with respect to motion artifacts. Three-dimensional parametric images may be calculated using least-squares fitting based on a simple model for steady-state longitudinal magnetization during the imaging sequences.

Brain↗

Chloride conductance and sodium-dependent glucose transport in rat and human enterocytes.

BACKGROUND & AIMS: In cystic fibrosis intestine, there is an increase in the rate of Na+-dependent glucose absorption. This may result from enterocyte hyperpolarization after defective Cl- channel function, but only if Cl- secretion and Na+/glucose cotransport occur in the same membrane. This study examined the effects of Cl- gradients on Na+/glucose uptake in brush border membrane vesicles from rat and human small intestine. METHODS: Vesicles were prepared by Mg2+-precipitation, and the active uptake of tritiated glucose was measured using a filtration-stop protocol. RESULTS: An outwardly directed Cl- gradient inhibited active glucose uptake in rat vesicles, whereas an inward Cl- gradient stimulated uptake. These effects were sensitive to blockers of the cystic fibrosis transmembrane regulator but not to inhibitors of other Cl- channels. Active glucose uptake into vesicles prepared from normal human intestine was also inhibited by an outward Cl- gradient, whereas uptake into vesicles prepared from a single sample of human cystic fibrosis intestine was not. CONCLUSIONS: A Cl- conductance resembling the cystic fibrosis transmembrane regulator is colocalized with Na+/glucose cotransport in rat and human small intestine, supporting the possibility that abnormalities in glucose absorption in cystic fibrosis may be a secondary effect of defects in Cl- channel function.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Workload management in A&E: counting the uncountable and predicting the unpredictable.

The development of a workload management system for use in the accident and emergency department is described. The system is capable of capturing the work all professional groups, allowing the user to roster staff according to anticipated workload, and gives accurate information on whether staffing requirements are sufficient to provide the desired standard of care.

Emergency Service, Hospital↗

Desktop system for accounting, audit, and research in A&E.

The development of a database for audit, research, and accounting in accident and emergency (A&E) is described. The system uses a desktop computer, an optical scanner, sophisticated optical mark reader software, and workload management data. The system is highly flexible, easy to use, and at a cost of around 16,000 pounds affordable for larger departments wishing to move towards accounting. For smaller departments, it may be an alternative to full computerisation.

Accounting↗

An automated method for assessing routine radiographs of patients with total hip replacements.

This paper describes a new, fully automated method of locating objects on radiographs of patients with total joint replacements (TJRs). A statistical computer model, known as an active shape model, was trained to identify the position of the femur, pelvis, stem and cup marker wire on radiographs of patients with Charnley total hip prostheses. Once trained, the model was able to locate these objects through a process of automatic image searching, despite their appearance depending on the orientation and anatomy of the patient. Experiments were carried out to test the accuracy with which the model was able to fit to previously unseen data and with which reference points could be calculated from the model points. The model was able to locate the femur and stem with a mean error of approximately 0.8 mm and a 95 per cent confidence limit of 1.7 mm. Once the model had successfully located these objects, the midpoint of the stem head could be calculated with a mean error of approximately 0.2 mm. Although the model has been trained on Charnley total hip replacements, the method is generic and so can be applied to radiographs of patients with any TJR. This paper shows that computer models can form the basis of a quick, automatic method of taking measurements from standard clinical radiographs.

Computer Simulation↗

Application of computer texture analysis to the Singh Index.

The Singh Index, which describes trabecular patterns in the proximal femur, has been used as a predictor for hip fractures and as an indicator of osteopenia. Evidence suggests that its contribution to the assessment of hip fracture risk is in its description of the structural properties of the femur. However, subjectivity in its determination may limit its practical value. In this study, we have used computer texture analysis to characterize the textural changes in trabecular bone which occur in osteoporosis. Texture analysis of the proximal femur was used to rank radiographs of 25 cadaver femora by Singh grading. These rankings were compared with those performed by two experienced radiologists. The computer method performed better than the least consistent individual radiologist, but not as well as the two radiologists in combination. The method required no radiologist's time after the system had been 'trained' from a set of example radiographs. The method has potential for use in large studies in which speed and consistency of measurement are important.

Bone Density↗

Immunogenicity and tolerability of a trivalent influenza subunit vaccine (Influvac) in high-risk children aged 6 months to 4 years.

Fifty-two children, aged less than 5 years, with chronic lung disease or congenital heart disease were entered into a two-centre open study to determine the immunogenicity and tolerability of Influvac, a trivalent influenza sub-unit vaccine. Seroresponses were determined following two intramuscular vaccinations with 0.25 ml of Influvac, four weeks apart. Any local or systemic reaction was sought. Seroresponses were age and antigen specific, with children older than 9 months showing better seroresponses to all three antigens. Both A/Taiwan and B/Panama strains met all efficacy criteria. A/Shangdong met two of the three criteria: seroconversion and mean geometric titre increase. Local (23%) and systemic (48%) reactions following either of the two vaccinations were minor in nature and resolved within a few days. The vaccine induced a strong antibody response against all three haemagglutinin antigens and was well tolerated. The incidence of local and systemic reactions was comparable with those reported in healthy adults.

Antibodies, Bacterial↗