Biomedical subjects

A Dowling

Publications and source records attributed to A Dowling.

At least 19 recordsLinked to original sources

PubMed2006

Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide.

Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28-81 years), male 81%, Child-Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0-9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways.

Adult↗

PubMed2006

A study to validate the method based on DIMOND quality criteria for cardiac angiographic images.

A method based on image quality criteria (QC) for cine-angiography was developed to measure the quality of cine-angiograms (CA). A series of 30 CA for left ventriculography (LV) and left and right coronary angiography (LCA, RCA) have been scored and 172 readings were obtained. Standard deviation of quality scores indicated the reproducibility of the method. Each part of CA was examined separately, giving scores for LV, LCA and RCA and a total score (TS), with clinical (C) and technical (T) criteria defined and examined separately. In 83% of the studies TS was >0.8 and with standard deviation from 0.02 to 0.21. In general, LV had a lower score and greater disagreement compared with RCA and LCA. Disagreement was greater in T, compared with C. In conclusion, these results indicate that QC, translated into a scoring system, yields reproducible data on the quality of cardiac images.

Cineangiography↗

PubMed2006

Correlation of patient and staff doses in interventional cardiology.

The purpose of this study was to measure staff radiation doses in representative institutions of five European countries performing coronary angiographies (CA) and percutaneous transluminal coronary angioplasties (PTCA), as well as to investigate any correlation with patient doses. Patient doses were recorded in terms of dose-area product (DAP). Staff doses were measured by thermoluminescence dosemeters placed on the operator's left shoulder and left foot. Radiation protection measures were also recorded. Third quartile shoulder and foot doses were 90 and 66 microSv in CA, and 157 and 173 microSv in PTCA, respectively. Shoulder dose was poorly correlated with DAP in CA (R2 = 0.29) and only moderately correlated in PTCA (R2 = 0.69). DAP and foot dose correlation was poor both in CA (R2 = 0.16) and in PTCA (R2 = 0.02). Protective measures taken by staff varied between countries, which may explain the poor correlation of patient and staff radiation doses.

Angioplasty, Balloon, Coronary↗

PubMed2006

Subjective and objective measures of image quality in digital fluoroscopy.

There are numerous methods for assessing image quality in diagnostic X ray. In our study we assessed how imaging quality assurance methods perform in practice. Physics assessments were based on IPEM protocols using Leeds test objects. Clinical assessment was based on a questionnaire. A total of 15 systems in three European locations were assessed, covering a range of image intensifier-TV digital fluoroscopy units. Analysis of 274 clinical questionnaires showed that clinical and physics assessments did not place systems in the same order, based on a given image quality parameter. In almost all the comparisons, low level correlation was measured for statistical comparison of rank order (rs < 0.3). However, broad agreement was observed between physics and clinical assessments for image quality associated with contrast and noise. This study emphasises the importance of maintaining links with clinical assessment, when developing quality assurance metrics, and measuring the mutual performance of clinical and physical assessments of image quality.

Europe↗

PubMed2006

Reference levels in PTCA as a function of procedure complexity.

The multicentre assessment of a procedure complexity index (CI) for the introduction of reference levels (RLs) in percutaneous transluminal coronary angioplasties (PTCA) is presented here. PTCAs were investigated based on methodology proposed by Bernardi et al. Multiple linear stepwise regression analysis, including clinical, anatomical and technical factors, was performed to obtain fluoroscopy time predictors. Based on these regression coefficients, a scoring system was defined and CI obtained. CI was used to classify dose values into three groups: low, medium and high complexity procedures, since there was good correlation (r = 0.41; P < 0.001) between dose-area product (DAP) and CI. CI groups were determined by an ANOVA test, and the resulting DAP and fluoroscopy time third quartiles suggested as preliminary RLs in PTCA, as a function of procedure complexity. PTCA preliminary RLs for DAP are 54, 76 and 127 Gy cm2, and 12, 20 and 27 min for fluoroscopy time, for the three CI groups.

Analysis of Variance↗

PubMed2006

Equipment standards for interventional cardiology.

Interventional radiology has seen rapid growth in cardiology and represents an alternative to hazardous surgery. Recently there has been a substantial growth in the number of procedures being performed and interventional cardiology (IC) procedures are the most common interventional procedures in Europe. Advances in imaging technology have facilitated the development of increasingly complex radiological IC equipment. Currently, the technology is developing at a rate ahead of supporting research, equipment standards and a regulatory framework. International standards play a key role in the design, manufacture and performance of radiological IC equipment. A survey of 12 IC systems (15 imaging chains) was conducted in Irish hospitals. The aim of the study was to assess the imbalance between rapidly advancing technology and existing standards and to propose recommendations for new IC equipment standards. The results demonstrate the need for definitive equipment requirements and standardisation in the design, manufacture, acceptance and maintenance of IC equipment.

Cardiology↗

PubMed2006

On the use of DICOM cine header information for optimisation: results from the 2002 European DIMOND cardiology survey.

The paper explores the level of information contained within the DICOM header in images from various cardiology systems. Data were obtained in the European DIMOND survey on image quality (Italy, Ireland, Belgium, Greece and Spain). Images from five standard diagnostic cardiology procedures carried out in six European hospitals have been analysed. DICOM header information was extracted to a database in order to analyse how it could help in the optimisation of the procedures. The level of data contained in the headers differs widely between cardiology systems. None of the X-ray systems in the 2002 survey archives the dosimetric data in the DICOM header. The mean number of runs per procedure ranges between 7.5 and 15.4 and the mean number of frames per procedure between 575 and 1417. Differences in kVp, mA, pulse time, distances and C-arm angulations are substantial and suggest that there exists a wide range for optimisation.

Cardiology↗

PubMed2006

Commissioning and quality assurance protocol for dual energy X-ray absorptiometry (DEXA) systems.

This study reports on the development and evaluation of a protocol for testing DEXA systems, which can be incorporated into a routine medical physics/engineering service. Methodologies are reported for (1) scatter measurement, (2) estimation of reference dose and (3) enquiry into potential sources of overexposure. Results show that fan-beam and cone-beam systems require shielding if the walls or operator are within 1 m of the table. Patient reference dose was estimated using the dose-area product (DAP). This varied over an order of magnitude from 2 to 36 mGy cm2 in the range of systems studied. The inquiry into potential sources of overexposure revealed some weaknesses in current practise including a design which prevents the inclusion of DAP metres; beam non-uniformity; incorrect specification of patient dose and the risk of overexposure when tube operates during patient positioning.

Absorptiometry, Photon↗

PubMed2006

Image quality criteria in cardiology.

Image quality evaluation plays a key role in the process of optimisation in radiological procedures. Image quality criteria for cardiac cine-angiography were recently agreed as part of a European Research Project, and a scoring system based on these criteria has been developed to allow an 'objective' measurement of the quality of cardiac angiograms. Two studies aimed at the evaluation of the methodology have been completed, demonstrating that the method can be applied to cardiac images and translated into a scoring system that yields reproducible data. Based on the results of these studies, quality criteria have been further reviewed by DIMOND III panel and the updated version is presented in this paper.

Cardiology↗

PubMed2005

Potentiation and cellular phenotypes of the insecticidal Toxin complexes of Photorhabdus bacteria.

The toxin complex (tc) genes of bacteria comprise a large and growing family whose mode of action remains obscure. In the insect pathogen Photorhabdus, tc genes encode high molecular weight insecticidal toxins with oral activity against caterpillar pests. One protein, TcdA, has recently been expressed in transgenic plants and shown to confer insect resistance. These toxins therefore represent alternatives to toxins from Bacillus thuringiensis (Bt) for deployment in transgenic crops. Levels of TcdA expression in transgenic plants were, however, low and the full toxicity associated with the native toxin was not reconstituted. Here we show that increased activity of the toxin TcdA1 requires potentiation by either of two pairs of gene products, TcdB1 and TccC1 or TcdB2 and TccC3. Moreover, these same pairs of proteins can also cross-potentiate a second toxin, TcaA1B1. To elucidate the likely functional domains present in these large proteins, we expressed fragments of each 'toxin' or 'potentiator' gene within mammalian cells. Several domains produced abnormal cellular morphologies leading to cell death, while others showed specific phenotypes such as nuclear translocation. Our results prove that the Tc toxins are complex proteins with multiple functional domains. They also show that both toxin genes and their potentiator pairs will need to be expressed to reconstitute full activity in insect-resistant transgenic plants. Moreover, they suggest that the same potentiator pair will be able to cross-potentiate more than one toxin in a single plant.

Animals↗

PubMed2004

Pathophysiological and immune cell responses in calves prior to and following lung challenge with formalin-killed Pasteurella multocida biotype A:3 and protection studies involving subsequent homologous live challenge.

Pneumonic pasteurellosis is a common respiratory infection in cattle that has major economic and welfare implications world-wide and the incidence in the UK due to Pasteurella multocida, currently the same as that associated with Mannheimia haemolytica, is increasing. Whereas much is known regarding the pathogenesis of M. haemolytica infections little information is available on the pathogenic process of pasteurellosis initiated by P. multocida. In the present work calf systemic and innate immune responses to intratracheal challenge with formalin-killed P. multocida biotype A:3 and to subsequent experimental lung infection with live P. multocida were investigated. Eight-week-old calves were challenged intratracheally on day 0 with either 10(9) colony forming units (cfu) of formalin-killed P. multocida biotype A:3 in 300 ml saline (n = 10) or 300 ml saline alone (n = 10), followed, at day 21, by challenge with 10(9) cfu live P. multocida. Pathophysiological and lung phagocyte responses were assessed by clinical monitoring, sequential lung lavage and blood sampling. Results for samples obtained before, during and after challenge showed clinical and acute phase protein responses to both bacterial culture and saline control treatments, although higher responses were associated with bacterial challenge. Phagocytosis of P. multocida during 1h incubation periods with lavaged cells in vitro was unaffected by exposure in vivo to killed P. multocida and there was evidence that P. multocida was able to survive intracellularly during this assay. There was no indication that lung exposure to formalin-killed P. multocida conferred protection against subsequent homologous live challenge.

Animals↗

PubMed2003

Preliminary reference levels in interventional cardiology.

This article describes the European DIMOND approach to defining reference levels (RLs) for radiation doses delivered to patients during two types of invasive cardiology procedures, namely coronary angiography (CA) and percutaneous transluminal coronary angioplasty (PTCA). Representative centres of six European countries recorded patients' doses in terms of dose-area product (DAP), fluoroscopy time and number of radiographic exposures, using X-ray equipment that has been subject to constancy testing. In addition, a DAP trigger level for cardiac procedures which should alert the operator to possible skin injury, was set to 300 Gyxcm2. The estimation of maximum skin dose was recommended in the event that a DAP trigger level was likely to be exceeded. The proposed RLs for CA and PTCA were for DAP 45 Gyxcm2 and 75 Gyxcm2, for fluoroscopy time 7.5 min and 17 min and for number of frames 1250 and 1300, respectively. The proposed RLs should be considered as a first approach to help in the optimisation of these procedures. More studies are required to establish certain "tolerances" from the proposed levels taking into account the complexity of the procedure and the patient's size.

Angioplasty, Balloon, Coronary↗

PubMed2003

Anatomical and possible clinical relationships between the calcaneofibular ligament and peroneus brevis--a pilot study.

The authors have observed in their clinical practice patients presenting with chronic retromalleolar pain following lateral ankle injuries. It has been hypothesized that persistent retromalleolar pain following a supination sprain may be due to peroneus brevis (PB) tendon tears (Boruta et al. 1990). The aims of this study were to investigate whether an anatomical relationship exists between the calcaneofibular ligament (CFL) and PB, and if so, the significance of this relationship in the positions of supination sprain and talar tilt test. Seven out of eight cadaveric ankles demonstrated fibrous connecting tissue between the tendon of PB and CFL. Four of the eight ankles demonstrated PB tendon abnormalities. The presence of connecting tissue between CFL and PB suggests an anatomical basis for concomitant damage to the PB tendon with a supination sprain, thus supporting the hypothesis that there may be an anatomical basis for persistent retromalleolar pain subsequent to injury to the lateral ankle complex.

Ankle Injuries↗

PubMed2002

Experimental induction of pneumonic pasteurellosis in calves by intratracheal infection with Pasteurella multocida biotype A:3.

The study aimed to establish an experimental model to investigate the pathogenesis of lung infection by Pasteurella multocida, an important cause of bovine respiratory disease. An experimental model is required to assist the development of an effective vaccine. Sixteen 8-week-old calves were challenged intratracheally with 10(9) or 10(10) colony forming units of P. multocida in either 60 or 300 ml saline in a 2 x 2 factorial experiment. All animals became dull within 2-6h post-infection (p.i.) and two calves were killed humanely because of suspected endotoxic shock. Remaining animals showed increased respiratory rates by 15-20 h p.i. and, at 23 h p.i., calves given the high dose, high volume challenge showed higher (P < 0.05) rectal temperatures. From 24 to 36 h p.i., clinical signs decreased in a majority of animals. Plasma haptoglobin concentrations increased (P < 0.05) in calves given the high volume challenge irrespective of the number of bacteria. At post-mortem examination (4d p.i.), lung lesions, mainly in the apical lobes, were found in all calves. Histopathological examination showed areas of purulent pneumonia with a tendency to abscessation and inflamed interlobular septa characterised by accumulation of neutrophils and oedema. The clinical and pathological responses described were typical of bovine pneumonic pasteurellosis.

Animals↗

PubMed2001

Developmental and functional evidence of a role for Zfhep in neural cell development.

The rat Zfhep gene encodes a member of the Zfh family of transcription factors having a homeodomain-like sequence and multiple zinc fingers. We examined expression of Zfhep in the rat forebrain during embryonic and postnatal development. Zfhep mRNA was strongly expressed in the progenitor cells of the ventricular zone around the lateral ventricles on E14 and E16, but showed little expression in cells that had migrated to form the developing cortex. Dual labeling with PCNA demonstrated expression of Zfhep mRNA in proliferating cells. Expression of Zfhep in the ventricular zone decreases during late development as the population of progenitor cells decreases. This pattern is distinctly different from other members of the Zfh family. We also examined the expression of Zfhep protein during retinoic acid-induced neurogenesis of P19 embryonal carcinoma cells. Zfhep is highly expressed in P19 neuroblasts, and expression decreases by the time of morphological neurogenesis. Hence, both P19 cells and embryonic brain demonstrate a loss of Zfhep expression during the transition from proliferating precursor to differentiated neural cells. We investigated a possible link between Zfhep and proliferation by treating human glial cell lines with Zfhep antisense phosphorothioate oligodeoxynucleotides. Two Zfhep antisense oligonucleotides repressed proliferation of either U-138 or U-343 glioblastoma cells more than control oligonucleotides. Based on the expression patterns of Zfhep in vivo and in the P19 cell model of neurogenesis, we suggest that Zfhep may play a role in proliferation or differentiation of neural cells.

Animals↗

PubMed2001

Medical exposures directive: implications for interventional radiology.

The new European Directive on Medical Exposures (97/43/EURATOM) specifically mentions 'high dose procedures' among the areas requiring special attention. This is universally interpreted as including the interventional procedures in radiology, cardiology and many of the special procedures involving fluoroscopy in these and related areas. This communication will focus on a definition of interventional procedures. It will examine the equipment, processes and patient and staff risks involved. From this examination it will be evident that new development is rapid in these areas and proceeding at a rate that is well ahead of both supporting research and regulatory framework. It will further note that the level of patient risk which is acceptable may be higher than in many other procedures. Finally it will note where the general provisions of the new Directive must be brought to bear on this new and developing field.

European Union↗

PubMed2001

A critical overview of acceptance testing using various measured indices.

It is a requirement of the new European directive on health protection of individuals against the dangers of ionising radiation in relation to medical exposure (97/43/EURATOM), that acceptance testing is carried out on all radiological equipment before its first use for clinical purposes. This directive must be implemented into member state law. In accordance with this requirement, thirteen digital fluorography systems were acceptance tested by the Department of Medical Physics and Bioengineering, St James's Hospital, Dublin. The equipment tested was in six Irish hospitals and included nine systems intended for interventional use, two of which were dedicated cardiac catheterisation laboratories and two of which were dedicated vascular laboratories. Testing was performed in line with current published international guidelines and standards and involved the measurement and analysis of various indices including X ray tube and generator performance, operating dose levels, image quality and electrical, mechanical and radiation safety aspects. The results are presented and compared with international standards and recommendations. Problems were identified with all systems tested with approximately 70% of all systems demonstrating significant problems. This study emphasises the importance of acceptance testing radiological equipment.

European Union↗

PubMed2001

Oral toxicity of Photorhabdus luminescens W14 toxin complexes in Escherichia coli.

Previous attempts to express the toxin complex genes of Photorhabdus luminescens W14 in Escherichia coli have failed to reconstitute their oral toxicity to the model insect Manduca sexta. Here we show that the combination of three genes, tcdA, tcdB, and tccC, is essential for oral toxicity to M. sexta when expression in E. coli is used. Further, when transcription from native toxin complex gene promoters is used, maximal toxicity in E. coli cultures is associated with the addition of mitomycin C to the growth medium. In contrast, the expression of tcdAB (or the homologous tcaABC operon) with no recombinant tccC homolog in a different P. luminescens strain, K122, is sufficient to confer oral toxicity on this strain, which is otherwise not orally toxic. We therefore infer that P. luminescens K122 carries a functional tccC-like homolog within its own genome, a hypothesis supported by Southern analysis. Recombinant toxins from both P. luminescens K122 and E. coli were purified as high-molecular-weight particulate preparations. Transmission electron micrograph (TEM) images of these particulate preparations showed that the expression of tcdAB (either with or without tccC) in E. coli produces visible approximately 25-nm-long complexes with a head and tail-like substructure. These data are consistent with a model whereby TcdAB constitutes the majority of the complex visible under TEM and TccC either is a toxin itself or is an activator of the complex. The implications for the potential mode of action of the toxin complex genes are discussed.

Administration, Oral↗