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Biomedical subjects

A Bell

Publications and source records attributed to A Bell.

At least 19 recordsLinked to original sources
PubMed2006

Low-loss passive alignment of single-mode fibers in low-temperature cofired ceramics using CO2 laser fabricated U-grooves.

We report a step toward optoelectronic integration on low-temperature cofired ceramics substrates in the form of fiber alignment U-grooves. The precision of the CO2 laser machining of green state ceramic for this purpose is investigated. The groove-writing process with a speed of 1 mm/s was carried out in air at room temperature and ambient pressure. The process is to a large extent self-cleaning without any gas jet assist. By analysis of groove profiles after firing of a near-zero shrinkage green tape formulation, it is shown that the cutting accuracy is approximately 2 microm, which is at the fundamental limit set by the particle size (1-5 microm). We demonstrate low-loss butt coupling of <1 dB for single-mode fibers using the laser written U-grooves. The technique exhibits a potential for fabrication of low-cost fiber ribbon and fiber array connectors.

Journal Article↗
PubMed2006

Influence of the Plasmodium falciparum P-glycoprotein homologue 1 (pfmdr1 gene product) on the antimalarial action of cyclosporin.

BACKGROUND AND OBJECTIVES: The immunosuppressant cyclosporin A and a number of other cyclosporins have potent and selective antimalarial activity. Their exact mechanism of antimalarial action is unknown but the structure-activity relationships for malarial parasite inhibition and immunosuppression differ markedly. The 3'-keto derivative of cyclosporin D (valspodar) is particularly potent against the human malarial parasite Plasmodium falciparum in culture but causes negligible immunosuppression. Multidrug resistance in mammalian cancer cells, the result of overproduction of the P-glycoprotein, can be reversed by certain cyclosporins, particularly valspodar. We therefore investigated the possibility that the antimalarial target of cyclosporin might be a P-glycoprotein homologue. P. falciparum P-glycoprotein homologue 1 (Pgh1; the pfmdr1 gene product) is located in the digestive vacuole (DV) membrane of the parasite. Its function is unknown but it modulates the susceptibility of parasites to quinolines and related antimalarial drugs, including quinine, mefloquine, halofantrine and chloroquine, and to artemisinin. METHODS AND RESULTS: Here we demonstrate that (i) sequence polymorphisms in pfmdr1 altered the susceptibility of parasites to cyclosporin A and (ii) pfmdr1-overexpressing strains were slightly less susceptible to the drug. Furthermore, we found synergistic antimalarial interactions between cyclosporin A and quinine, mefloquine or halofantrine and antagonism between cyclosporin A and chloroquine. However, we were unable to detect a direct interaction between cyclosporin and Pgh1. CONCLUSIONS: The amino acid sequence and copy number of Pgh1 may influence cyclosporin susceptibility as a result of a direct interaction between the drug and the protein, or via indirect effects on the physiology of the DV.

Animals↗
PubMed2006

Studies on cell-cycle synchronization in the asexual erythrocytic stages of Plasmodium falciparum.

Multiplication of Plasmodium parasites within human erythrocytes is essential to malarial disease. The cell-division cycle of this organism, however, is still poorly understood. In other eukaryotes, various techniques for (apparent) cell-cycle synchronization have been used to shed light on the mechanisms involved in cell division and its control. Thus far there is no technique for cell-cycle synchronization (as opposed to selection of parasites of a limited age-range) in Plasmodium. We therefore investigated the possibility that inhibitors of DNA synthesis, the mitotic spindle, or cell-cycle control elements (such as cyclin-dependent kinases) could be used to synchronize P. falciparum cultures to a particular cell-cycle phase. Surprisingly, most of these compounds did not cause a block at a specific phase. Three compounds, Hoechst 33342, roscovitine and L-mimosine, did block development at the trophozoite-schizont transition (S or G2 phase). The block caused by the latter 2 inhibitors was reversible, suggesting that they might be used as synchronizing agents. However, a consideration of the perturbing effects of inhibitors and problems with 'batch' synchronization techniques in general lead us to believe that any results obtained using roscovitine- or L-mimosine-treated parasites may not be reflective of the normal cell cycle.

Animals↗
PubMed2006

Physician Response Unit -- a feasibility study of an initiative to enhance the delivery of pre-hospital emergency medical care.

OBJECTIVES: To describe the rationale, development and initial results of a collaborative pre-hospital pilot project designed to enhance the emergency care needs of an inner city population. METHODS: Retrospective descriptive analysis of emergency calls attended by a rapid response car staffed by a pre-hospital care physician and ambulance service technician or paramedic. RESULTS: Seven hundred and forty-eight consecutive patients over a 13-month period are described. Six hundred and thirty-eight (82%) patients underwent clinical consultation with a physician within 8 min of emergency call. The Physician Response Unit (PRU) also provided an additional vehicle responding to emergency calls, reaching the national 8 min target response time in 638 (82%) of all cases. Two hundred and eighty-nine (39%) of the patients attended had medical therapy initiated by the PRU physician. Nearly two-thirds of this group, 189 (65%), received medical therapy outside current ambulance service protocols. A physician medical escort was provided for 142 (25%) of patients attending hospital. Of all patients seen 577 (77%) attended the emergency department via ambulance, and 136 (18%) patients were assessed, treated and prevented from attending the emergency department. CONCLUSIONS: The PRU provided clinical care beyond that delivered by the ambulance service. It also contributed positively to local ambulance service response times. The service was able to prevent unnecessary ambulance journeys and attendance at hospital. It demonstrates that traditional working practices can be altered to improve the delivery of emergency medical care.

Algorithms↗
PubMed2006

Tuberculosis screening in migrants in selected European countries shows wide disparities.

Well-established tuberculosis screening units in Western Europe were selectively sampled. Three screening units in Norway, two in the UK, one in the Netherlands and one in Switzerland were evaluated. The aim of this study was to describe a range of service models used at a number of individual tuberculosis units for the screening of new entrants into Europe. Semi-structured interviews were conducted with clinicians, nurses and administrators from a selected sample of European tuberculosis screening units. An outline of key themes to be addressed was forwarded to units ahead of scheduled interviews. Themes included the history of the unit, structure, processes and outputs involved in screening new entrants for tuberculosis. Considerable variation in screening services exists in the approaches studied. Units are sited in transit camps or as units within hospital facilities. Staff capacity and administration varies from one clinic per week with few dedicated staff to fully dedicated units. Only one site recorded symptoms; tuberculin testing was universal in children, but varied in adults; chest radiograph screening was universal except at one site where a positive tuberculin skin test or symptoms were required in those <35 yrs of age before ordering a radiograph. Few output data are routinely and systematically collected, which hinders comparison and determination of effectiveness and efficiency. Service models for screening new immigrants for tuberculosis appear to vary in Western Europe. The systematic collection of data would make international comparisons between units easier and help draw conclusions that might usefully inform service development.

Adult↗
PubMed2006

Hand arthritis in systemic lupus erythematosus: an ultrasound pictorial essay.

A small minority of systemic lupus erythematosus (SLE) patients may develop a deforming arthritis, typically with a non-erosive (Jaccoud's) pattern, although erosive features indistinguishable from rheumatoid arthritis may also occur. High-resolution ultrasonography (HRUS) allows detailed 'real time' imaging of joint and tendon morphostructural changes involving the hand in patients with several rheumatic diseases. The main aim of this pictorial essay is to provide the first descriptive HRUS and power Doppler (PD) findings of joint and tendon involvement of the hand and wrist in patients with SLE arthritis. Seventeen patients with SLE and hand involvement were examined. HRUS of the wrist, 2nd and 3rd MCP joints, 3rd PIP joint and 2nd, 3rd and 4th finger flexor tendons were studied in the dominant hand for each patient. Sixteen (94%) patients had joint effusion or synovial hypertrophy in the wrist. Twelve (71%) patients had joint effusion or synovial hypertrophy in 2nd or 3rd MCPJs. Eight (47%) patients had erosion at 2nd or 3rd MCPJs. In three cases erosions were not present radiologically. Eleven (65%) patients had evidence of tenosynovitis. In SLE, HRUS with PD detects a high prevalence of inflammatory pathology in the tendons and synovium of the hand and wrist, and a high prevalence of MCP joint erosions. HRUS offers a sensitive, real-time and readily repeatable assessment of soft-tissue, inflammatory and bony changes in SLE hands.

Adult↗
PubMed2005

Musculoskeletal ultrasound training in rheumatology: the Belfast experience.

OBJECTIVES: Despite the increasing use of musculoskeletal ultrasound (MSUS) as a clinical tool in rheumatology, there is no consensus yet regarding the standards required to achieve a basic level of competence in the use of this imaging technique. A number of sonographers worldwide are developing curricula and standardizing teaching methods in order to improve training in MSUS for rheumatologists. In the meantime, clinicians are devising informal means of training in order to acquire these new skills. Here we describe the informal team approach to MSUS training adopted by a group of rheumatologists from the Regional Rheumatology Centre in Belfast, UK. METHODS: Over a 5-yr period, eight rheumatologists from Musgrave Park Hospital in Belfast used a variety of means to learn the basic skills of MSUS. RESULTS: Seven of the team underwent a formal assessment of their competency in a practical examination devised by an experienced sonographer. All were judged to have attained a basic competency in MSU. CONCLUSIONS: This Belfast experience shows what can be achieved despite the absence of formal MSUS training. Nevertheless, the development of recognized training programmes and international standards of competency are important goals on the way to achieving more widespread acceptance of MSUS as a useful tool in everyday clinical practice.

Clinical Competence↗
PubMed2005

Rheumatologists' judgements about the efficacy of anti-TNF therapy in two neighbouring regions.

OBJECTIVES: The requirement in Northern Ireland to prescribe biological agents according to National Institute for Clinical Excellence/British Society for Rheumatology (NICE/BSR) guidelines and within a fixed budget has created a waiting list for treatment that has no parallel in the Republic of Ireland. The study investigated the bearing this situation may have had on consultants' judgements in the respective areas. METHODS: Seventy-eight case vignettes created from the data on real patients with RA treated with biologicals in the north and south of Ireland were appraised by nine southern and eight northern consultants, who judged the clinical benefit and significance of the patients' condition after a trial of therapy. Quantitative (clinical judgement analysis) and qualitative (focus groups) techniques were used. RESULTS: Northern consultants perceived a slightly greater degree of clinical benefit after a trial of therapy than southern consultants. Judgement models of northern and southern consultants were broadly comparable. The latter tended to be more uniform in their judgements than the southern group. Focus group discussions with consultants largely validated the findings of the quantitative analysis but revealed how clinical judgement analysis might be misled by gaming strategies. CONCLUSIONS: Despite the absence of overt rationing in the south of Ireland, as far as the judgement of therapeutic benefit from biologicals was concerned, the clinical judgement policies of practitioners were very similar to those in the north. The adoption of NICE/BSR guidelines in the north may have improved the uniformity of clinical practice in Northern Ireland.

Antibodies, Monoclonal↗
PubMed2005

The effects of mosquito transmission and population bottlenecking on virulence, multiplication rate and rosetting in rodent malaria.

Malaria parasites vary in virulence, but the effects of mosquito transmission on virulence phenotypes have not been systematically analysed. Using six lines of malaria parasite that varied widely in virulence, three of which had been serially blood-stage passaged many times, we found that mosquito transmission led to a general reduction in malaria virulence. Despite that, the between-line variation in virulence remained. Forcing serially passaged lines through extreme population bottlenecks (<5 parasites) reduced virulence in only one of two lines. That reduction was to a level intermediate between that of the virulent parental and avirulent ancestral line. Mosquito transmission did not reverse the increased parasite replication rates that had accrued during serial passage, but it did increase rosetting frequencies. Re-setting of asexual stage genes during the sexual stages of the life cycle, coupled with stochastic sampling of parasites with variable virulence during population bottlenecks, could account for the virulence reductions and increased rosetting induced by mosquito transmission.

Animals↗
PubMed2004

Screening programmes for tuberculosis in new entrants across Europe.

Screening foreign-born groups with high rates of tuberculosis may help to ensure that they can benefit from early treatment and minimise onward transmission. In January 2003, we surveyed new entrant screening programmes in Europe. Of the 26 countries from whom a response was received, 13 (50%) conducted no specific tuberculosis screening. Of 13 countries with programmes, none conducted pre-entry screening, three conducted screening at ports of entry, and nine screened in other centres. All 13 principally screened refugees. All programmes used chest X-rays as a screening tool, but no two countries took the same specific clinical approach.

Europe↗
PubMed2003

Effects of the antimitotic natural product dolastatin 10, and related peptides, on the human malarial parasite Plasmodium falciparum.

Microtubule inhibitors from several chemical classes can block the growth and development of malarial parasites, reflecting the importance of microtubules in various essential parasite functions. With the spread of antimalarial drug resistance, there is an urgent need for new approaches to the chemotherapy of this devastating disease. We investigated the effects of two naturally occurring marine peptides, dolastatin 10 and dolastatin 15, and 10 synthetic dolastatin 10-based compounds (auristatins), on cultured malarial parasites of the species most lethal to humans, Plasmodium falciparum. Dolastatin 10 was a more potent inhibitor of P. falciparum than any other previously described microtubule inhibitor, with a median inhibitory concentration (IC50) of 10-10 M. Dolastatin 15 was less active, and compounds of the auristatin series had various potencies. Comparison of the concentrations required to inhibit P. falciparum and mammalian cell proliferation showed that the orders of potency were not the same. Dolastatin 10 and auristatin PE caused arrested nuclear division and apparent disassembly of mitotic microtubular structures in the parasite. The effects of these agents were, superficially at least, similar to those of vinblastine but different from those of paclitaxel. These studies indicate that compounds binding in the 'Vinca domain' of tubulin can be highly potent antimalarial agents.

Animals↗
PubMed2003

Polymorphisms in the interferon-gamma/interleukin-26 gene region contribute to sex bias in susceptibility to rheumatoid arthritis.

OBJECTIVE: To determine whether polymorphisms in the interferon-gamma (IFNgamma)/interleukin-26 (IL-26; formerly, AK155) gene cluster contribute to sex-based differential susceptibility to rheumatoid arthritis (RA). METHODS: Four microsatellite markers, located in a 118-kb interval that contains both the IFNgamma and IL-26 genes on chromosome 12q15, were typed in 251 patients with RA and 198 unrelated healthy controls (all of whom lived in Northern Ireland) by means of polymerase chain reaction-based fragment analysis. RESULTS: Marker D12S2510, which is located 3 kb 3' from the IL-26 gene, was significantly associated with RA in women (corrected P [P(corr)] = 0.008, 2 degrees of freedom [2 df]) but not in men (P = 0.99, 2 df). A 3-marker haplotype, IFNGCA*13;D12S2510*8;D12S2511*9, was inferred that showed significant underrepresentation in women with RA (odds ratio 0.50, 95% confidence interval 0.32-0.78; P = 0.002, P(corr) = 0.03) but not in men with RA. CONCLUSION: Our results demonstrate that common polymorphisms in the IFNgamma/IL-26 gene region may contribute to sex bias in susceptibility to RA, by distorting the propensity of female carriers versus male carriers to contract this disease. These results conform to our recent observations of a role for this gene cluster in sex-based differential susceptibility to another Th1-type inflammatory disease, multiple sclerosis.

Adult↗
PubMed2003

Assessment of the accuracy of a three-dimensional imaging system for archiving dental study models.

OBJECTIVE: The use of stone and plaster study models is an integral part of any dental practice and is required for research. Storage of study models is problematic in terms of space and cost. Ayoub et al.(1) introduced a new technique based on the recent advances in stereophotogrammetry for archiving dental study models in a digital format. However, assessment of the accuracy of the generated three-dimensional (3D) models has not been carried out yet. It was the aim of this study to evaluate the accuracy of this technique. DESIGN: A comparative assessment between direct measurements of dental study models and measurements of computer generated 3D images of the same study models was performed. MATERIALS AND METHODS: Twenty-two dental study models stored at Glasgow Dental Hospital and School for the purposes of research were used in the study. The models were captured in three dimensions using a photostereometric technique and stored in digital format. MAIN OUTCOME MEASURES: Measurements were conducted directly on dental study models and on the computer generated 3D images using Euclidean Distance Matrix Analysis.(2) The difference between the two sets of measurements was statistically analysed using a two-sample t-test. RESULTS: The average difference between measurements of dental casts and 3D images was 0.27 mm. This difference was within the range of operator errors (0.10-0.48 mm) and was not statistically significant (P < 0.05). CONCLUSION: This study shows that it is possible to use 3D imaging to store dental study models for treatment monitoring and research with a satisfactory degree of accuracy.

Archives↗
PubMed2002

Analysis of CHK2 in vulval neoplasia.

Structure and expression of the Rad53 homologue CHK2 were studied in vulval neoplasia. We identified the previously described silent polymorphism at codon 84 (A>G at nucleotide 252) in the germ-line of six out of 72, and somatic mutations in two out of 40 cases of vulval squamous cell carcinomas and none of 32 cases of vulval intraepithelial neoplasia. One mutation introduced a premature stop codon in the kinase domain of CHK2, whereas the second resulted in an amino acid substitution in the kinase domain. The two squamous cell carcinomas with mutations in CHK2 also expressed mutant p53. A CpG island was identified close to the putative CHK2 transcriptional start site, but methylation-specific PCR did not detect methylation in any of 40 vulval squamous cell carcinomas, irrespective of human papillomavirus or p53 status. Consistent with this observation, no cancer exhibited loss of CHK2 expression at mRNA or protein level. Taken together, these observations reveal that genetic but not epigenetic changes in CHK2 occur in a small proportion of vulval squamous cell carcinomas.

Adult↗
PubMed2002

E7 proteins from oncogenic human papillomavirus types transactivate p73: role in cervical intraepithelial neoplasia.

In common with other E2F1 responsive genes such as p14(ARF) and B-myb, the promoter of p73 is shown to be positively regulated in cell lines and primary human keratinocytes by E7 proteins from oncogenic human papillomavirus (HPV) types 16, 18, 31 and 33, but not HPV 6. Mutational analysis revealed that transactivation of the p73 promoter by HPV 16E7 requires association with pRb. Expression of p73 in normal cervical epithelium is confined to the basal and supra-basal layers. In contrast, expression in neoplastic lesions is detected throughout the epithelium and increases with grade of neoplasia, being maximal in squamous cell cancers (SCC). Deregulation of expression of the N-terminal splice variant p73Delta2 was observed in a significant proportion of cancers, but not in normal epithelium. The frequent over-expression of p73Delta2, which has recognized transdominant properties, in malignant and pre-malignant lesions suggests a role in the oncogenic process in cervical epithelium.

Carcinoma, Squamous Cell↗