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Biomedical subjects

K J Robson

Publications and source records attributed to K J Robson.

At least 19 recordsLinked to original sources

Pilot study into optimisation of viewing conditions for electronically displayed images.

The increased use of soft-copy reporting introduces new concerns over the effect of viewing conditions on the observer's ability to report images. Owing to their lower luminance, electronic display screens may be more susceptible to poor viewing conditions than conventional viewing boxes and there is the potential for images to be displayed in locations not optimised for viewing radiographs. In the present work, the effects of sub-optimal viewing conditions on the observer's performance for images on an electronic display device are investigated. A test object was used to produce a computed radiography image containing a wide range of grey levels. The image was scored under quasi-ideal and sub-optimal conditions and the effect of changing the viewing conditions on the observer's performance determined. Basic photometric quantities were used to characterise the viewing conditions and the degradation in observer performance related to these quantities. The presence of structured reflection had a significant effect on the observer's ability to discern low-contrast objects. The study demonstrates the need for adequate viewing conditions especially when images are displayed on low luminance devices in sub-optimal conditions.

Humans↗

Mammographic image restoration using maximum entropy deconvolution.

An image restoration approach based on a Bayesian maximum entropy method (MEM) has been applied to a radiological image deconvolution problem, that of reduction of geometric blurring in magnification mammography. The aim of the work is to demonstrate an improvement in image spatial resolution in realistic noisy radiological images with no associated penalty in terms of reduction in the signal-to-noise ratio perceived by the observer. Images of the TORMAM mammographic image quality phantom were recorded using the standard magnification settings of 1.8 magnification/fine focus and also at 1.8 magnification/broad focus and 3.0 magnification/fine focus; the latter two arrangements would normally give rise to unacceptable geometric blurring. Measured point-spread functions were used in conjunction with the MEM image processing to de-blur these images. The results are presented as comparative images of phantom test features and as observer scores for the raw and processed images. Visualization of high resolution features and the total image scores for the test phantom were improved by the application of the MEM processing. It is argued that this successful demonstration of image de-blurring in noisy radiological images offers the possibility of weakening the link between focal spot size and geometric blurring in radiology, thus opening up new approaches to system optimization.

Algorithms↗

Hepcidin and its role in iron absorption.

Maintaining the correct iron balance is crucial to good health. Disorders of iron homeostasis have a global distribution. As iron is not actively excreted by the body, understanding the role of proteins involved in regulating iron uptake is essential to our understanding of disease involving iron homeostasis. Over the past 10 years, major advances have been made in understanding the genetics of iron metabolism and this has led to identification of a number of new proteins, including hepcidin, involved in iron homeostasis.

Animals↗

Application of low dose rate pulsed fluoroscopy in cardiac pacing and electrophysiology: patient dose and image quality implications.

The performance of a low dose rate pulsed fluoroscopy option and its successful application to cardiac pacing and electrophysiology is reported. Low dose rate 6.25 frames per second pulsed fluoroscopy was made available in two catheter laboratories at a specialist cardiac centre in February 2003, and was adopted as the standard imaging technique for cardiac pacing procedures. The image quality was found to be considerably poorer than conventional modern units, being very similar to that which would have been accepted as adequate performance 20 years ago, but at less than one-tenth of the dose rate. No problems with the clinical acceptance of this imaging mode for cardiac pacing and electrophysiology have been reported. The already low median patient dose-area product for pacing at this cardiac centre was further reduced by 50% with the introduction of this fluoroscopy option.

Attitude of Health Personnel↗

Short communication: anomalous image quality phantom scores in magnification mammography: evidence of phase contrast enhancement.

Anomalously high image quality scores were noted for images of the Leeds TORMAM phantom obtained using magnification mammography. Comparison of optical density profiles of fibre features in the images with non-magnified images and images previously obtained using an in-line phase contrast geometry showed the presence of phase contrast enhancement in the magnification images. The effect on the phantom score is particularly marked for this design of phantom owing to its use of fibres, which tend to enhance well. A large proportion of the phantom score is associated with fibrous features. It is concluded that direct comparison of TORMAM phantom scores from magnified images with those from non-magnified images is not valid due to the different balance of physical mechanisms forming the two kinds of image.

Breast Neoplasms↗

A prime-boost immunisation regimen using DNA followed by recombinant modified vaccinia virus Ankara induces strong cellular immune responses against the Plasmodium falciparum TRAP antigen in chimpanzees.

Two chimpanzees were vaccinated intramuscularly against malaria using plasmid DNA expressing the pre-erythrocytic antigens thrombospondin related adhesion protein (PfTRAP) and liver stage specific antigen-1 (PfLSA-1) of Plasmodium falciparum together with GM-CSF protein. A recombinant modified vaccinia virus Ankara (MVA) expressing PfTRAP was injected intramuscularly 6 weeks later to boost the immune response. This sequence of antigen delivery induced a specific and long-lasting T cell and antibody response to PfTRAP as detected by ELISPOT assay and ELISA. Antibody responses were detected after four DNA injections, and were boosted by injection of recombinant MVA expressing PfTRAP. Interferon-gamma secreting antigen-specific T cells were detected in both animals, but only after boosting with recombinant MVA. By screening a panel of PfTRAP-derived peptides, an epitope was identified that was recognized by cytotoxic T lymphocytes in one of the chimpanzees studied. T cells specific for this epitope were present in PBMCs and liver-infiltrating lymphocytes at a frequency of between 1 in 200 and 1 in 500. The high immunogenicity of this prime-boost regimen in chimpanzees supports further assessment of this delivery strategy for the induction of protection against P. falciparum malaria in humans.

Animals↗

Receptor dose in digital fluorography: a comparison between theory and practice.

A method of identifying the dose per image when quantum mottle no longer dominates the image statistics is presented as a first step towards quantitative optimization in native and subtracted digital fluorography. The method is based on measurements of threshold contrast over a range of receptor doses and the application of a simple model of the threshold contrast detection task to estimate the magnitude of system noise sources. The point at which system and quantum noise sources are equal in magnitude is proposed as the practical upper limit for dose per image. The method is applied to a typical digital fluorography system and the results are placed into the context of the range of dose per image values found from a regional survey of digital fluorography units. While there is broad agreement between the dose per image values in the survey with values predicted from the experimental method, the considerable spread in survey doses suggests there are instances where the use of a high dose per image is unjustified.

Dose-Response Relationship, Radiation↗

A parametric method for determining mammographic X-ray tube output and half value layer.

In the National Health Service Breast Screening Programme, regular assessment of the mean glandular doses received by a group of women is recognized as an important part of a quality assurance programme. The use of different tube voltages, to improve the beam penetration for thick or dense breasts, and of X-ray units with programmable exposure modes, requires a large number of measurements to ensure that all the values of tube output and half value layer required for the dose calculations are available. In this work, a computer model is used to produce data that allow the calculation of tube output and half value layer for the range of clinically encountered conditions from measurements routinely obtained during quality assurance tests. The data are given as a series of equations and parameters, enabling the calculations to be easily incorporated into a dose calculation spreadsheet. The results of an experimental verification of the model are presented, showing good agreement between the measured and predicted values of half value layer and tube output for a range of combinations of target, filter and tube voltage.

Breast Neoplasms↗

Erythematous plaques due to platelet plugging: a clue to underlying myeloproliferative disorder.

We report a syndrome in a middle-aged woman characterized by tender erythematous plaques with histologic evidence of dramatic dermal vessel occlusion. These cutaneous findings occurred in association with progressive inferior vena cava and portal vein thrombosis while on coumarin anticoagulation, following hepatic transplantation for Budd-Chiari syndrome. The material occluding dermal vessels was proven by immunohistochemical staining to be platelet plugs. These findings led to the diagnosis of an underlying myeloproliferative disorder explaining both her cutaneous and liver abnormalities and institution of appropriate platelet directed anticoagulation with aspirin.

Bone Marrow↗

Pulsed-dye laser versus conventional therapy in the treatment of warts: a prospective randomized trial.

BACKGROUND: The clinical management of verrucae vulgaris is often challenging, and no ideal treatment currently exists. Early studies suggested that pulsed-dye laser (PDL) therapy might be highly effective in the treatment of verrucae, although more recent reports have been less optimistic. Previous studies have been retrospective or have consisted of a series of patients treated with PDL alone. OBJECTIVE: Our objective was to prospectively evaluate the efficacy of PDL therapy versus conventional therapy with liquid nitrogen cryotherapy or cantharidin in the treatment of warts. METHODS: Forty healthy adult patients with verrucae were randomized to receive either PDL (585 nm) therapy or conventional therapy. All enrollees also performed home therapy. Patients were eligible for up to 4 treatment sessions at 1-month intervals. Warts were individually counted and measured at the time of each treatment session. Complete response was defined as complete absence of verrucae with the presence of dermatoglyphics, and partial response was defined as a 50% or greater reduction in wart size. RESULTS: A total of 194 warts were evaluated by the conclusion of the study. Complete response was noted in an average of 70% of the warts treated with conventional therapy and in 66% of those in the PDL group; this was statistically insignificant. Partial response was observed in an average of 82% of the warts in patients treated with conventional therapy and 87% in the PDL group. Verruca vulgaris responded more readily than verruca plantaris in both treatment groups. The mean number of treatments to achieve success was similar in both groups. CONCLUSION: The PDL is an efficacious form of therapy for verrucae, as is conventional therapy. PDL therapy should be considered among the better established approaches in the treatment of warts, although data from this trial suggest that this approach is probably not superior.

Adult↗

Detection of C282Y and H63D in the HFE gene.

The gene for hemochromatosis was identified in 1996 and two mutations were found. Homozygosity for one of these, C282Y, is associated with hemochromatosis in a high percentage of patients. Genetic analysis of patient DNA is, therefore, a very useful tool to aid and confirm diagnosis and to screen asymptomatic relatives of patients to identify those at risk of developing this common, easily treated disease.

DNA Primers↗

Uncommon mutations and polymorphisms in the hemochromatosis gene.

Hereditary hemochromatosis (HH) is a common autosomal recessive disorder of iron metabolism. Iron absorption from the gut is inappropriately high, resulting in increasing iron overload. The hemochromatosis gene (HFE) was identified in 1996 by extensive positional cloning by many groups over a period of about 20 years. Two missense mutations were identified. Homozygosity for one of these, a substitution of a tyrosine for a conserved cysteine (C282Y), has now clearly been shown to be associated with HH in 60-100% of patients. The role of the second mutation, the substitution of an aspartic acid for a histidine (H63D), is not so clear but compound heterozygotes for both these mutations have a significant risk of developing HH. Here we review other putative mutations in the HFE gene and document a number of diallelic polymorphisms in HFE introns.

Amino Acid Substitution↗

Geography of HFE C282Y and H63D mutations.

Hereditary hemochromatosis (HH) is a common autosomal recessive disorder causing inappropriate dietary iron absorption that affects North Europeans. HH is associated with the C282Y mutation of the HFE gene, and the H63D mutation to a lesser degree. Both mutations are abundant in Europe, with H63D also appearing in North Africa, the Middle East, and Asia. Emigration from Europe over the past 500 years has introduced C282Y and H63D to America, Australia, New Zealand, and South Africa in an essentially predictable fashion. The distinctive characteristics of the population genetics of HH are the confined racial distribution and high frequency in North European peoples. C282Y frequencies in North Europeans are typically between 5% and 10%, with homozygotes accounting for between 1/100 and 1/400 of these populations. The scarcity of the C282Y mutation in other populations accounts for the lack of HH in non-Europeans.

Emigration and Immigration↗

The A-domain and the thrombospondin-related motif of Plasmodium falciparum TRAP are implicated in the invasion process of mosquito salivary glands.

Sporozoites from all Plasmodium species analysed so far express the thrombospondin-related adhesive protein (TRAP), which contains two distinct adhesive domains. These domains share sequence and structural homology with von Willebrand factor type A-domain and the type I repeat of human thrombospondin (TSP). Increasing experimental evidence indicates that the adhesive domains bind to vertebrate host ligands and that TRAP is involved, through an as yet unknown mechanism, in the process of sporozoite motility and invasion of both mosquito salivary gland and host hepatocytes. We have generated transgenic P.berghei parasites in which the endogenous TRAP gene has been replaced by either P.falciparum TRAP (PfTRAP) or mutated versions of PfTRAP carrying amino acid substitutions or deletions in the adhesive domains. Plasmodium berghei sporozoites carrying the PfTRAP gene develop normally, are motile, invade mosquito salivary glands and infect the vertebrate host. A substitution in a conserved residue of the A-domain or a deletion in the TSP motif of PfTRAP impairs the sporozoites' ability to invade mosquito salivary glands. Notably, midgut sporozoites from these transgenic parasites are still able to infect mice. Midgut sporozoites carrying a mutation in the A-domain of PfTRAP are motile, while no gliding motility could be detected in sporozoites with a TSP motif deletion.

Animals↗

A retrospective anonymous pilot study in screening newborns for HFE mutations in Scandinavian populations.

We have retrospectively analyzed 837 random anonymized dried blood spot (DBS) samples from neonatal screening programs in Scandinavia for mutations in HFE, the candidate gene for hemochromatosis. We have found C282Y allele frequencies of 2.3% (+2.0%) (-1.3%) in Greenland, 4.5%+/-1.9% in Iceland, 5.1%+/-2.3% in the Faeroe Islands, and 8.2%+/-2.7% in Denmark. The high prevalence of HFE mutations in Denmark suggests that population screening for the C282Y mutation could be highly advantageous in terms of preventive health care. Long-term follow-up evaluation of C282Y homozygotes and H63D/C282Y compound heterozygotes will give an indication of the penetrance of the mutations.

Alleles↗

Broadly distributed T cell reactivity, with no immunodominant loci, to the pre-erythrocytic antigen thrombospondin-related adhesive protein of Plasmodium falciparum in West Africans.

Protective immunity to malaria has been achieved in human volunteers utilizing the pre-erythrocytic Plasmodium falciparum antigen, the circumsporozoite protein (CS). However, T cell reactivity to CS is focused on several highly polymorphic T cell epitope regions, potentially limiting the efficacy of any vaccine to specific malaria strains. Another important pre-erythrocytic malaria antigen, the thrombospondin-related adhesive protein (TRAP), can induce protection in animal models of malaria, but knowledge of human T cell responses is limited to the identification of CD8 T cell epitopes, with no CD4 epitopes identified to date. This comprehensive study assessed reactivity to overlapping peptides spanning almost the whole of P. falciparum TRAP (PfTRAP), as well as peptides selected on the basis of HLA class II-binding motifs. A total of 50 naturally exposed Gambian adults were assessed to define 26 T cell epitopes in PfTRAP capable of inducing rapid IFN-gamma or IL-4 production, as assessed by enzyme-linked immunospot assays. In contrast to the CS protein, this reactivity was broadly distributed along the length of TRAP. Moreover, of the 26 epitopes identified, 10 were found to be conserved in West Africa.

Adult↗

The haemochromatosis gene: a global perspective and implications for the Asia-Pacific region.

Mutations in the haemochromatosis (HFE) gene cause most of the cases of hereditary haemochromatosis among people of Northern European ancestry while remaining a rare cause of iron overload among indigenous persons of the Asia-Pacific region. Advances in understanding of the role of the HFE protein product and other recently cloned iron transporters signify an exciting period, as previously unknown components of the iron metabolism pathway are revealed one by one. Epidemiological studies have shown that this gene is more widespread than its phenotypic expression would suggest and that the heterozygous state may be implicated in the expression of other diseases of the liver such as porphyria cutanea tarda, hepatitis C virus infection and non-alcoholic steatohepatitis. The diagnosis, management and ethical implications for clinical practice in the aftermath of this discovery are discussed.

Asia↗