PubMed Health⌕ Search

Biomedical subjects

M O'Donnell

Publications and source records attributed to M O'Donnell.

At least 19 recordsLinked to original sources
PubMed2006

Doppel: more rival than double to prion.

Conversion of normal cellular prion protein to the diseased form plays an essential role in transmissible spongiform encephalopathies such as mad cow disease and Creutzfeldt-Jakob disease. However, the normal physiological function of prion protein remains elusive. Doppel, a German synonym of double, was initially identified as a prion-like protein due to its structural and biochemical similarities. However, emerging evidence suggests that function of prion protein is more antagonistic to Doppel than synergistic. In this review, basic biochemical and structural similarities of prion protein and Doppel are introduced; evidence demonstrating antagonistic interaction of prion protein with Doppel is presented; and a potential novel activity of Doppel and prion protein in spermatogenesis, which could stimulate new avenues for research, is discussed.

Animals↗
PubMed2006

Clinical trials of new anticoagulants.

Shortcomings of the existing anticoagulants, vitamin K antagonists and heparins, have led to the development of newer anticoagulant therapies. In particular, Vitamin K antagonists' slow onset of action, numerous drug interactions, narrow therapeutic window and need for frequent monitoring make it the most obvious target for replacement. Targeting specific coagulation enzymes or steps in the coagulation pathway, new anticoagulants have been or are under evaluation in clinical trials for a number of clinical indications, namely the prevention and treatment of venous thromboembolism, the prevention of ischemic stroke in patients with atrial fibrillation, and in acute coronary syndromes. Following a brief review of pharmacological aspects, this article will summarize the results of Phase III clinical trials evaluating the novel anticoagulants fondaparinux, ximelagatran and idraparinux. At present, most attention is directed at developing an oral anticoagulant to replace vitamin K antagonists for prevention of systemic thromboembolism. A number of newer agents are in both early and advanced stages of investigation.

Anticoagulants↗
PubMed2005

Renal advances in ultrasound elasticity imaging: measuring the compliance of arteries and kidneys in end-stage renal disease.

BACKGROUND/AIMS: Ultrasound elasticity imaging visually represents tissue hardness measurements using high-resolution ultrasound speckle-tracking algorithms. This method has recently been applied in the renal setting to measure arterial compliance in end-stage renal disease (ESRD) and the mechanical properties of transplant kidneys in vivo. METHODS: Ultrasound radio-frequency signal measurements were made of the brachial artery in 5 ESRD subjects and 5 healthy controls and renal transplant measurements in 2 subjects, 1 with chronic allograft nephropathy (CAN) and 1 with normal graft function. RESULTS: Maximal brachial artery percent strain measurements for healthy controls were 32.9 +/- 10.2% (mean +/- SD) and for ESRD subjects maximal percent strains were 4.9 +/- 1.8%. Transplant renal cortical strain for the subject with CAN was approximately one third that of the healthy transplant recipient. CONCLUSION: Ultrasound elasticity imaging offers the potential to noninvasively measure the mechanical properties of structures within the body.

Adult↗
PubMed2005

3-D correlation-based speckle tracking.

Widely-used 1-D/2-D speckle tracking techniques in elasticity imaging often experience significant speckle decorrelation in applications involving large elevational motion (i.e., out of plane motion). The problem is more pronounced for cardiac strain rate imaging (SRI) since it is very difficult to confine cardiac motion to a single image plane. Here, we present a 3-D correlation-based speckle tracking algorithm. Conceptually, 3-D speckle tracking is just an extension of 2-D phase-sensitive correlation-based speckle tracking. However, due to its high computational cost, optimization schemes, such as dynamic programming, decimation and two-path processing, are introduced to reduce the computational burden. To evaluate the proposed approach, a 3-D bar phantom under uniaxial compression was simulated for benchmark tests. A more sophisticated 3-D simulation of the left ventricle of the heart was also made to test the applicability of 3-D speckle tracking in cardiac SRI. Results from both simulations clearly demonstrated the feasibility of 3-D correlation-based speckle tracking. With the ability to follow 3-D speckle in 3-D space, 3-D speckle tracking outperforms lower-dimensional speckle tracking by minimizing decorrelation caused by pure elevational translation. In other words, 3-D tracking can push toward solely deformation-limited, decorrelation-optimized speckle tracking. Hardware implementation of the proposed 3-D speckle tracking algorithm using field programmable gate arrays (FPGA) is also discussed.

Algorithms↗
PubMed2005

Injection-moulded models of major and minor arteries: the variability of model wall thickness owing to casting technique.

Cardiovascular disease of major and minor arteries is a common cause of death in Western society. The wall mechanics and haemodynamics within the arteries are considered to be important factors in the disease formation process. This paper is concerned with the development of an efficient computer-integrated technique to manufacture idealized and realistic models of diseased major and minor arteries from radiological images and to address the issue of model wall thickness variability. Variations in wall thickness from the original computer models to the final castings are quantified using a CCD camera. The results found that wall thickness variation from the major and minor idealized artery models to design specification were insignificant, up to a maximum of 16 per cent. In realistic models, however, differences were up to 23 per cent in the major arterial models and 58 per cent in the minor arterial models, but the wall thickness variability remained within the limits of previously reported wall thickness results. It is concluded that the described injection moulding procedure yields idealized and realistic castings suitable for use in experimental investigations, with idealized models giving better agreement with design. Wall thickness is variable and should be assessed after the models are manufactured.

Anatomy, Cross-Sectional↗
PubMed2005

Periods of low atmospheric pressure are associated with high abdominal aortic aneurysm rupture rates in Northern Ireland.

Seasonal and circadian variation in the incidence of ruptured abdominal aortic aneurysm (RAAA) has been reported. We explored the role of atmospheric pressure changes on rupture incidence and its relationship to cardiovascular risk factors. During a three year-period, 1st April 1998 and 31st March 2001, data was prospectively acquired on 144 Ruptured Abdominal Aortic Aneurysm (RAAA) presenting to the Regional Vascular Surgery Unit at the Royal Victoria Hospital, Belfast, Northern Ireland. For each patient the chronology of acute onset of symptoms and presentation to the regional vascular unit was recorded, along with details of standard cardiovascular risk factors. During the same period meteorological data including atmospheric pressure and air temperature were recorded daily at the regional meteorological research unit, Armagh. We then analyzed the monthly mean values for daily rupture incidence in relation to the monthly values for atmospheric pressure, pressure change and temperature. Furthermore atmospheric pressure on the day of rupture, and day preceding rupture, were also analyzed in relation to days without rupture presentation and between individual ruptures for various cardiovascular risk factors. Data demonstrated a significant monthly variation in aneurysm rupture frequency, (p<0.03, ANOVA). There was also a significant monthly variation in mean barometric atmospheric pressure, (p<0.0001, ANOVA), months with high rupture frequency also exhibiting low average pressures in the months of April (0.24 +/- 0.04 ruptures per day and 1007.78 +/- 1.23 mB) and September (0.16 +/- 0.04 ruptures per day and 1007.12 +/- 1.14 mB), respectively. The average barometric pressures were found to be significantly lower on those days when ruptures occurred (n=1127) compared to days when ruptures did not occur (n=969 days), (1009.98 +/- 1.11 versus 1012.09 +/- 0.41, p<0.05). Full data on risk factors was available on 103 of the 144 rupture patients and was further analyzed. Interestingly, RAAA with a known history of hypertension, (n=43), presented on days with significantly lower atmospheric pressure than those without, (n=60), (1008.61 +/- 2.16 versus 1012.14 +/- 1.70, p<0.05). Further analysis of ruptures grouped into those occurring on days above or below mean annual atmospheric pressure 1013.25 (approximately 1 atmosphere), by Chi-square test, revealed three cardiovascular risk factors significantly associated with low-pressure rupture, (p<0.05). Data represents mean +/- SEM, statistical comparisons with Student t-test and ANOVA. These data demonstrate a significant association between periods of low barometric pressure and high incidence of ruptured aneurysm, especially in those patients with known hypertension. The association between rupture incidence and barometric pressure warrants further study as it may influence the timing of elective AAA repair.

Adult↗
PubMed2004

Help-seeking behaviour and associated factors among women with urinary incontinence in France, Germany, Spain and the United Kingdom.

OBJECTIVES: To assess the proportion of women who consult their doctor about urinary incontinence (UI), and explore factors associated with help-seeking in France, Germany, Spain and the UK. METHODS: A representative sample of 29,500 women received a 13 item postal questionnaire to identify those with UI. A randomly selected sub-sample of 2953 women with UI received a more detailed follow-up questionnaire. RESULTS: There was a response rate of 58% in the initial survey and 53% in the second. Thirty-one percent of all women had consulted a doctor about their UI symptoms with more women consulting in France and Germany than in the UK and Spain. A number of factors relating to general health care, UI and women's attitudes were found to be associated with help-seeking after adjusting for women's age, UI duration and frequency, and 'bothersomeness' of UI; factors traditionally associated with help-seeking. After adjusting for these factors, willingness to take long-term medication and having spoken to others about UI were found to be strong predictors of help-seeking in all four countries.

Female↗
PubMed2004

Vascular intramural strain imaging using arterial pressure equalization.

Peripheral vascular strain imaging has limited strain dynamic range because arterial wall deformations only exhibit small strains under physiologic pressures. A noninvasive freehand ultrasound (US) scanning procedure was performed to apply external force, comparable to the force generated in measuring a subject's blood pressure, to achieve higher strains by equalizing the internal arterial baseline pressure. When the applied pressure matched the internal baseline diastolic pressure, intramural strain and strain rate increased by a factor of 10 over a cardiac cycle. Radial arterial strain was assessed within the vessel wall over the entire deformation procedure using a phase-sensitive 2-D speckle-tracking algorithm. The feasibility of this technique to assess vascular nonlinear elastic properties is demonstrated in an ex vivo experiment and further supported by in vivo measurements. With some uncertainty associated with the elastic properties of surrounding tissue, an elastic modulus reconstruction procedure was developed to estimate the nonlinear elastic properties of the vascular wall.

Adult↗
PubMed2003

Microwave-induced thermal imaging of tissue dielectric properties.

A new imaging method, microwave-induced thermal imaging (MITI), was developed to differentiate tissue based on thermal and dielectric properties. Image contrast depends on temporal strain in tissue, which was determined by one-dimensional speckle tracking using a phase-sensitive, correlation-based technique. The underlying mechanisms were analyzed and experimental results on biologic tissue agreed well with theoretical predictions. Because of its strong contrast between water-bearing and lipid-bearing tissue, the technique may enhance existing intravascular ultrasound (IVUS) imaging systems to identify vulnerable arterial plaque.

Adipose Tissue↗
PubMed2003

Blood flow estimation error with intravascular ultrasound due to in-plane component of flow.

Previously, we presented a real-time method to measure blood flow perpendicular to the image plane of an intravascular ultrasound (IVUS) imaging system using a slow-time FIR (finite impulse response) filter bank. Any in-plane flow introduces error in the flow measurement using the filter bank algorithm. Simulations show that for a flow angle of +/- 10 degrees and velocities between 200 mm/s and 300 mm/s, the energy within the lowest frequency band filter is 6.92 to 7.80 times higher than for perpendicular flow in the worst case. We present a variation of the FIR filter bank algorithm, applying filter coefficients in a tilted fashion to slow-time signals (i.e., combining slow-time and fast-time). An appropriate tilt, which depends on the flow angle and velocity, corrects for the increased energy under the frequency bands. In this case, the energy under the lowest frequency band filter for an angle of +/- 10 degrees and velocities ranging from 200 mm/s to 300 mm/s is 2.09 to 2.94 times higher than for perpendicular flow, yielding greater than a factor of three improvement in the worst case over the original slow-time method. Moreover, the average energy over the vessel determined with the appropriate tilt is within 2-3% of the true value.

Algorithms↗
PubMed2003

The value of digital imaging in diabetic retinopathy.

OBJECTIVES: To assess the performance of digital imaging, compared with other modalities, in screening for and monitoring the development of diabetic retinopathy. DESIGN: All imaging was acquired at a hospital assessment clinic. Subsequently, study optometrists examined the patients in their own premises. A subset of patients also had fluorescein angiography performed every 6 months. SETTING: Research clinic at the hospital eye clinic and optometrists' own premises. PARTICIPANTS: Study comprised 103 patients who had type 1 diabetes mellitus, 481 had type 2 diabetes mellitus and two had secondary diabetes mellitus; 157 (26.8%) had some form of retinopathy ('any') and 58 (9.9%) had referable retinopathy. INTERVENTIONS: A repeat assessment was carried out of all patients 1 year after their initial assessment. Patients who had more severe forms of retinopathy were monitored more frequently for evidence of progression. MAIN OUTCOME MEASURES: Detection of retinopathy, progression of retinopathy and determination of when treatment is required. RESULTS: Manual grading of 35-mm colour slides produced the highest sensitivity and specificity figures, with optometrist examination recording most false negatives. Manual and automated analysis of digital images had intermediate sensitivity. Both manual grading of 35-mm colour slides and digital images gave sensitivities of over 90% with few false positives. Digital imaging produced 50% fewer ungradable images than colour slides. This part of the study was limited as patients with the more severe levels of retinopathy opted for treatment. There was an increase in the number of microaneurysms in those patients who developed from mild to moderate. There was no difference between the turnover rate of either new or regressed microaneurysms for patients with mild or with sight-threatening retinopathy. It was not possible in this study to ascertain whether digital imaging systems determine when treatment is warranted. CONCLUSIONS: In the context of a national screening programme for referable retinopathy, digital imaging is an effective method. In addition, technical failure rates are lower with digital imaging than conventional photography. Digital imaging is also a more sensitive technique than slit-lamp examination by optometrists. Automated grading can improve efficiency by correctly identifying just under half the population as having no retinopathy. Recommendations for future research include: investigating whether the nasal field is required for grading; a large screening programme is required to ascertain if automated grading can safely perform as a first-level grader; if colour improves the performance of grading digital images; investigating methods to ensure effective uptake in a diabetic retinopathy screening programme.

Diabetes Mellitus, Type 1↗
PubMed2002

Triplex ultrasound: elasticity imaging to age deep venous thrombosis.

Deep venous thrombosis (DVT), and its sequela, pulmonary embolism (PE), is the leading cause of preventable in-hospital mortality in the USA and other developed countries. After it is detected, acute clots must be differentiated from chronic DVT for appropriate treatment. However, there are no reliable thrombus staging methods presently available in clinical practice. In this study, we tested the hypothesis that blood clots can be detected and staged using a triplex ultrasound (US) test. Triplex US is based on a "gold standard" duplex US technique augmented by US-based reconstructive elasticity imaging. Fibrin-composed blood clots harden with development and organization. By imaging clot elasticity, it may be possible to both detect and differentiate clots and, therefore, provide an urgently needed noninvasive means of DVT staging.

Animals↗
PubMed2002

Evaluation of liquid-based cytology in cervical screening of high-risk populations: a split study of colposcopy and genito-urinary medicine populations.

A split study evaluated the ThinPrep(R) PapTesttrade mark (TP; Cytyc Corp., Boxborough, MA) compared with current methodologies of cervical cytology in two high-risk cohorts. One thousand, three hundred cases from a colposcopy clinic and a genito-urinary medicine outpatient clinic were examined. The TP reported increased detection of all grades of dyskaryosis (mild, moderate and severe; + 4.5%) and a decrease in borderline and unsuitable cases (- 4.9%). Four cases of high-grade dyskaryosis (moderate or severe) were detected only using the TP, while an additional four cases classified as high-grade dyskaryosis with the TP were reported as borderline by our conventional methods. The split-study finding of increased sensitivity with the TP provides for improved clinical management of patients in our high-risk cohorts.

Cell Nucleus↗
PubMed2002

Cytokeratin 7: a useful adjunct in the diagnosis of chromophobe renal cell carcinoma.

AIMS: The histopathological diagnosis of chromophobe renal cell carcinoma can present a diagnostic challenge, as these tumours can resemble either conventional renal cell carcinoma or oncocytoma. The aim of this study was to determine whether cytokeratin 7 expression is of practical use in the distinction of these three entities. METHODS AND RESULTS: A total of 40 cases previously diagnosed as either chromophobe renal cell carcinoma, conventional renal cell carcinoma or oncocytoma were identified. A representative section of each was stained with H&E and cytokeratin 7. Following independent review of the cases by three pathologists, a consensus diagnosis for each case was reached and the pattern of cytokeratin 7 staining was assessed. There were 12 cases of chromophobe renal cell carcinoma in the study, all of which showed a characteristic peripheral membrane pattern of staining for cytokeratin 7. Seventeen of the 18 cases of conventional renal cell carcinoma studied were negative for cytokeratin 7, while one case showed weak focal staining of <5% of the cells. The 10 cases of oncocytoma showed patchy weak to moderate cytoplasmic expression of cytokeratin 7, without the characteristic peripheral membrane accentuation seen in the chromophobe carcinomas. CONCLUSIONS: Immunohistochemical staining for cytokeratin 7 appears to be a useful adjunct in the diagnosis of chromophobe renal cell carcinoma, and in distinguishing this tumour from both oncocytoma and conventional renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed2001

Clamp loader structure predicts the architecture of DNA polymerase III holoenzyme and RFC.

Recent determinations of the crystal structure of the Escherichia coli gamma complex and delta-beta assembly have shed light on the bacterial clamp loading reaction. In this review, we discuss the structures of delta-beta and the gamma(3)deltadelta' complex and its mechanism of action as a clamp loader of the E. coli beta sliding clamp. We also expand upon the implications of the structural findings to the structure and function of the eukaryotic clamp loader, RFC, and the structure of E. coli DNA polymerase III holoenzyme.

Animals↗
PubMed2001

Interplay of clamp loader subunits in opening the beta sliding clamp of Escherichia coli DNA polymerase III holoenzyme.

The Escherichia coli beta dimer is a ring-shaped protein that encircles DNA and acts as a sliding clamp to tether the replicase, DNA polymerase III holoenzyme, to DNA. The gamma complex (gammadeltadelta'chipsi) clamp loader couples ATP to the opening and closing of beta in assembly of the ring onto DNA. These proteins are functionally and structurally conserved in all cells. The eukaryotic equivalents are the replication factor C (RFC) clamp loader and the proliferating cell nuclear antigen (PCNA) clamp. The delta subunit of the E. coli gamma complex clamp loader is known to bind beta and open it by parting one of the dimer interfaces. This study demonstrates that other subunits of gamma complex also bind beta, although weaker than delta. The gamma subunit like delta, affects the opening of beta, but with a lower efficiency than delta. The delta' subunit regulates both gamma and delta ring opening activities in a fashion that is modulated by ATP interaction with gamma. The implications of these actions for the workings of the E. coli clamp loading machinery and for eukaryotic RFC and PCNA are discussed.

Adenosine Triphosphate↗