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Biomedical subjects

M Doyle

Publications and source records attributed to M Doyle.

At least 19 recordsLinked to original sources
PubMed2005

Low incidence of retained common bile duct stones using a selective policy of biliary imaging.

AIM: Biliary imaging has decreased since the advent of laparoscopic cholecystectomy. This study aimed to examine the incidence of retained common bile duct (CBD) stones, using a selective policy of biliary imaging. METHODS: A prospective computerised database was used to study patients who underwent laparoscopic cholecystectomy by one surgeon over 36 months. Two hundred and thirty-five patients (191 female, 44 male) were operated on. Ages ranged from 15 to 82 years (mean 47 years). Follow-up periods ranged from six to 39 months (mean 23.3 months). Selection for pre-operative endoscopic retrograde cholangiopacreatogram (ERCP), intraoperative cholangiography (IOC) or neither depended on liver function tests (LFTs) and CBD diameter on ultrasound prior to surgery. If LFTs were persistently raised and/or the CBD was dilated on ultrasound, patients underwent pre-operative ERCP. If LFTs were raised, and returned to normal promptly, IOC was performed. RESULTS: Of 235 patients, 26 had pre-operative ERCP, 62 had IOC and 157 had neither. Ten patients had both ERCP and IOC. To date, one patient (0.43%) has radiologically-proven unsuspected retained CBD stones; these were successfully treated with ERCP. CONCLUSION: Selective biliary imaging in patients undergoing laparoscopic cholecystectomy is safe. This process identifies the majority of patients with ductal calculi and minimises the need for unnecessary ERCP and peroperative cholangiography.

Algorithms↗
PubMed2005

Can the stem cell mobilization technique influence CD34+ cell collection efficiency of leukapheresis procedures in patients with hematologic malignancies?

A total of 415 leukaphereses in 201 patients stimulated with growth factor (GF; n = 119) or chemotherapy-GF (n = 296) were studied to determine CD34+ cell collection efficiency (CE). The pre-apheresis leukocyte count was 1-93 x 10(9)/l (median 20), and peripheral blood CD34 count (PBCD34) was 1-1104/microl (median 19). The total number of CD34+ cells collected was 4-6531 x 10(6) (median 151); corresponding to 0.1-111.4 x 10(6) (median 2.3) per kg. There was strong correlation between PBCD34 and the number of CD34+ cells collected (r = 0.9; P < 0.0001). CE was 7-145% (median 46). On multiple regression analysis, a higher leukocyte count (P < 0.0001) was the most important predictor of lower CE. CE with leukocytes < 20 was 7-145% (median 53%) compared to 10-132% (median 40%) with leukocyte > or = 20 (P < 0.0001). In all, 61% of the apheresis procedures performed after chemotherapy-GF occurred when leukocytes were < 20 compared to 21% of those performed after GF alone (P < 0.0001). We conclude that mobilizing patients with the combination of chemotherapy and GF rather than GF alone leads to leukapheresis being performed when the leukocyte count is low -- in a range that results in optimum CD34+ cell CE. Autologous stem cells should be mobilized with chemotherapy-GF rather than GF alone whenever possible.

Adult↗
PubMed2003

Shigella flexneri 2a strain 2457T expresses three members of the H-NS-like protein family: characterization of the Sfh protein.

Shigella flexneri 2a is known to express the H-NS nucleoid-structuring protein and the paralogous protein StpA. Using bioinformatic analysis we have now discovered a third member of the H-NS protein family, Sfh (Shigella flexneri H-NS-like protein), in strain 2457T. This protein is encoded by the sfh gene, which is located on a high-molecular-mass plasmid that is closely related to the self-transmissible plasmid R27. When expressed in Escherichia coli, the Sfh protein can complement an hns null mutation, restoring wild-type Bgl, porin protein, and mucoidy phenotypes, and wild-type expression of the fliC and proU genes. While a knockout mutation in the sfh gene alone had no effect on the expression of virulence genes in S. flexneri, an additive effect on virulence gene derepression was seen when the sfh lesion was combined with a mutation in hns. Over-expression of the sfh gene repressed expression of the VirB virulence regulatory protein and transcription of a VirB-dependent structural gene promoter. The purified Sfh protein bound specifically to DNA sequences containing the promoters of the virF and virB virulence regulatory genes. These findings show that Sfh has the ability to influence genetic events beyond the genetic element that encodes it, including the expression of the S. flexneri virulence genes. They raise the possibility of a triangular relationship among three closely related proteins with broad consequences for genetic events in the bacterium that harbours them.

Bacterial Proteins↗
PubMed2003

All-terrain vehicles--unstable, unsafe and unregulated. A prospective study of ATV-related trauma in rural Ireland.

All-terrain vehicles (ATVs) are fast, powerful machines that pose a significant threat to public safety. In the USA, ATVs are responsible for 273 deaths and over 68,000 injuries each year. As the incidence of ATV-related accidents in Britain and Ireland is unknown we carried out a prospective audit of all patients presenting to our Accident and Emergency Departments with ATV-related trauma over a 1-year period. Of 32 patients with ATV-associated injuries, 10 were under 16 years of age and 23 had no previous experience of operating an ATV. We documented 24 fractures (2 open) and 1 tension pneumothorax. Helmet usage was high and head injuries were few and not of a serious nature. Two-thirds of injuries occurred on commercial adventure sports courses. Since ATVs are off-road vehicles, they are exempt from safety regulations that apply to other forms of transport. As care-providers to trauma victims, we must make prevention of these injuries a priority and campaign for both voluntary and legislative controls to make ATV use a safer leisure pursuit.

Accidents, Traffic↗
PubMed2003

Minimally displaced Colles' fractures: a prospective randomized trial of treatment with a wrist splint or a plaster cast.

Sixty-six adult patients with minimally displaced distal radial fractures were randomly assigned to treatment with either a plaster cast or a lightweight removable wrist splint. Outcome assessment was by clinical and radiological evaluation and an independent physiotherapy assessment. There were significant differences between the treatments for cast satisfaction, cast problems and the functional assessment score at 6 weeks, with the removable splint scoring better in all cases.

Activities of Daily Living↗
PubMed2002

Violence risk assessment: combining actuarial and clinical information to structure clinical judgements for the formulation and management of risk.

Throughout history most societies have assumed a link between mental disorder and violence to others. In recent times there has been increasing concern in the United Kingdom over law and order, specifically the risk of violence, and these issues are now high on the political and mental health agenda. Nurses and staff working in National Health Service Mental Health Service Trusts are the groups most at risk of violence. Many clinical decisions are based on risk. Mental health nurses play a pivotal role in the assessment and management of risk and it is argued that they need to adopt a clear structured approach to violence risk assessment and management, which is evidence-based. The advantages of clinical and actuarial approaches to risk assessment are briefly reviewed and a structured clinical judgement approach is proposed that combines these approaches. A method of linking the assessment process with the management plan via a risk formulation is discussed.

Humans↗
PubMed2001

Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability.

Histone H3 lysine 9 methylation has been proposed to provide a major "switch" for the functional organization of chromosomal subdomains. Here, we show that the murine Suv39h histone methyltransferases (HMTases) govern H3-K9 methylation at pericentric heterochromatin and induce a specialized histone methylation pattern that differs from the broad H3-K9 methylation present at other chromosomal regions. Suv39h-deficient mice display severely impaired viability and chromosomal instabilities that are associated with an increased tumor risk and perturbed chromosome interactions during male meiosis. These in vivo data assign a crucial role for pericentric H3-K9 methylation in protecting genome stability, and define the Suv39h HMTases as important epigenetic regulators for mammalian development.

Aneuploidy↗
PubMed2001

Initial sequencing and analysis of the human genome.

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

Animals↗
PubMed2001

Curved saccade trajectories: voluntary and reflexive saccades curve away from irrelevant distractors.

In this study we examined the impact of irrelevant distractors upon trajectories of reflexive and voluntary saccades. Observers made saccades to visual targets above and below fixation as directed by target appearance (reflexive) or by a central directional cue (voluntary) in the presence of an irrelevant distractor stimulus (a cross) whose appearance was simultaneous with target onset. We recorded saccade latency, amplitude and the magnitude of saccade curvature relative to the direct route from the start-to-end of the saccade. Previous studies of saccades curvature have used distractors to provide information about the saccade task and, as a result, have only examined trajectories of voluntary saccades. However, we have shown that both reflexive and voluntary saccades curved away from irrelevant distractors. The effect of irrelevant distractors indicates that observers do not need to attend to distractors in a voluntary fashion for distractors to modify saccade trajectories. Furthermore, it highlights an important parallel in curvature of saccades and reach trajectories, namely that both curve away from irrelevant distractors. The second important observation was that reflexive, as well as voluntary, saccades curved away from distractors. This suggests that curvature is not solely a consequence of voluntary control. These results have been considered within the context of inhibition-based theories of curvature derived from studies of saccade and manual reach trajectories.

Adolescent↗
PubMed2001

Mother-to-child transmission of the human immunodeficiency virus in Texas.

BACKGROUND: The Pediatric Spectrum of HIV Diseases (PSD) project has been collecting data on HIV-exposed children in Texas since 1989. These data have now been analyzed to describe mother-to-child transmission in Texas and to provide much needed information on the magnitude of the pediatric HIV epidemic in the state. METHODS: We examined trends in the numbers of perinatally exposed children and perinatally acquired cases of HIV in the Texas PSD cohort. We calculated transmission rates and relative risks for 656 children born from January, 1995, to July, 1998, that received all or part of the ACTG 076 regimen. RESULTS: Only a small proportion (38%) of pairs of an HIV-infected mother and her HIV-exposed child received the full AIDS Clinical Trial Group 076 (ACTG 076) regimen; only 73% of the mothers received at least some prenatal care. In recent years, however, the numbers of perinatally exposed children and perinatally acquired cases of HIV have decreased in Texas. Univariate analyses showed that a reduction in the vertical transmission of HIV was associated with receipt of a full ACTG 076 regimen, receipt of a partial ACTG 076 regimen and residence in Dallas County. CONCLUSIONS: Findings identify a gap in meeting the health care needs of pregnant HIV-infected women and suggest missed opportunities to prevent mother-to-child transmission of HIV. At the same time this study confirms progress in prevention efforts to reduce mother-to-child transmission of HIV in Texas.

Anti-HIV Agents↗
PubMed2001

Validation of rapid velocity encoded cine imaging of a dynamically complex flow field using turbo block regional interpolation scheme for k space.

Block regional interpolation scheme for k space (BRISK) is a sparse sampling approach to allow rapid magnetic resonance imaging of dynamic events. Rapid velocity encoded cine (VEC) imaging with Turbo BRISK is potentially an important clinical diagnostic technique for cardiovascular diseases. Previously we applied BRISK and Turbo BRISK to imaging pulsatile flow in a straight tube. To evaluate the capabilities of Turbo BRISK imaging in more complex dynamic flow fields such as might exist in the human vasculature, an in vitro curved tube model, similar in geometry to the aortic arch, was fabricated and imaged under pulsatile flow conditions. Velocity maps were obtained using conventional VEC and Turbo BRISK (turbo factors 1 through 5). Comparison of the flow fields obtained with each higher order turbo factor showed excellent agreement with conventional VEC with minimal loss of information. Similarly, flow maps showed good agreement with the profiles from a laser Doppler velocimetry model. Turbo-5 BRISK, for example, allowed a 94% savings in imaging time, reducing the conventional imaging time from over 8 min to a near breath-hold imaging period of 31 s. Turbo BRISK shows excellent promise toward the development of a clinical tool to evaluate complex dynamic intravascular flow fields.

Biomedical Engineering↗
PubMed2001

Ventilator-patient dyssynchrony induced by change in ventilation mode.

Patient-ventilator interactions may be coordinated (synchronous) or uncoordinated (dyssynchronous). Ventilator-patient dyssynchrony increases the work of breathing by imposing a respiratory muscle workload. Respiratory centre output responds to feedback from respiratory muscle loading. Mismatching of respiratory centre output and mechanical assistance results in dyssynchrony. We describe a case of severe patient-ventilator dyssynchrony and hypothesize that dyssynchrony was induced by a change in mode of ventilation from pressure-cycled to volume-cycled ventilation, due to both ventilator settings and by the patient's own respiratory centre adaptation to mechanical ventilation. The causes, management and clinical implications of dyssynchrony are discussed.

Aged↗
PubMed2001

A mathematical treatment of AIDS and condom use.

In this paper we examine the impact of condom use on the sexual transmission of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) amongst a homogeneously mixing male homosexual population. We first derive a multi-group SIR-type model of HIV/AIDS transmission where the homosexual population is split into subgroups according to frequency of condom use. Both susceptible and infected individuals can transfer between the different groups. We then discuss in detail an important special case of this model which includes two risk groups and perform an equilibrium and stability analysis for this special case. Our analysis shows that this model can exhibit unusual behaviour. As normal, if the basic reproduction number, R0, is greater than unity then there is a unique disease-free equilibrium which is locally unstable and a unique endemic equilibrium. However, when R0 is less than unity two endemic equilibrium solutions can also co-exist simultaneously with the disease-free solution which is locally stable. Numerical simulations using realistic parameter values confirm this and we find that in certain circumstances the disease-free solution and one of the endemic solutions are both locally asymptotically stable, while the other endemic solution is unstable. This unusual behaviour has important implications for control of the disease as reducing R0 to less than unity no longer guarantees eradication of the disease. For a restricted special case of this two-group model we show that there is only the disease-free equilibrium for R0 < or = 1 which is globally stable. For R0 > 1 the disease-free equilibrium is unstable and there is a unique endemic equilibrium which is locally stable. We then attempt to fit the model to HIV and AIDS incidence data from San Francisco, USA. The paper concludes with a brief discussion.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Regulation of protein kinase Ctheta function during T cell activation by Lck-mediated tyrosine phosphorylation.

Protein kinase C theta (PKCtheta) is a novel Ca(2+)-independent PKC isoform, which is selectively expressed in skeletal muscle and hematopoietic cells, especially T cells. In T cells, it colocalizes with the T cell antigen receptor (TCR).CD3 complex in antigen-stimulated T cells and is involved in the transcriptional activation of the interleukin-2 gene. In the present study, we report that PKCtheta is tyrosine phosphorylated in Jurkat T cells upon TCR.CD3 activation. The Src family protein-tyrosine kinase, Lck, was critical in TCR-induced tyrosine phosphorylation of PKCtheta. Lck phosphorylated and was associated with the regulatory domain of PKCtheta both in vitro and in intact cells. This association was constitutive, but it was enhanced by T cell activation, with both Src-homology 2 and Src-homology 3 domains of Lck contributing to it. Tyrosine 90 (Tyr-90) in the regulatory domain of PKCtheta was identified as the major phosphorylation site by Lck. A constitutively active mutant of PKCtheta (A148E) could enhance proliferation of Jurkat T cells and synergized with ionomycin to induce nuclear factor of T cells activity. However, mutation of Tyr-90 into phenylalanine markedly reduced (or abolished) these activities. These results suggest that Lck plays an important role in tyrosine phosphorylation of PKCtheta, which may in turn modulate the physiological functions of PKCtheta during TCR-induced T cell activation.

Humans↗
PubMed2000

Antioxidant levels in the cord blood of term fetus.

The aim of this study was to compare the differences in the total antioxidant levels in the cord blood after a normal vaginal delivery and after an elective caesarean section. This was a prospective study approved by the Wirral Hospital ethical research committee. The study was carried out in a district general hospital. We investigated 96 healthy pregnant women who had normal antenatal period with singleton pregnancies between 37 and 42 completed weeks of gestation. Sixty-five women had a spontaneous normal vaginal delivery and 31 underwent elective caesarean section. Umbilical cord blood was obtained immediately after delivery. Antioxidants such as glutathione peroxidase (GPX) and superoxide dismutase (SOD) were measured and compared between the normal vaginal delivery and elective ceasarean sections. The mean values for GPx in umbilical cord arterial blood (95; 86-103, n=74) was found to be significantly higher (P=0.0133) than that found in umbilical cord venous blood (84; 80-88, n=95). The arterial SOD values were found to be significantly higher (P=0.0337) in infants who had been delivered by caesarean section (1188; 1065-1311, n=22) than by vaginal delivery (1021;958-1083, n=39). The differences in the levels of GPX between the arterial and venous systems is not well documented but may be due to differences in the level of selenium, hydroperoxides or glutathione. In addition, why infants delivered by ceasarian section have a higher level of arterial SOD than those delivered by vaginal delivery remains unclear, but it may be a reflection of a relatively low level in infants subjected to the stress of labour.

Journal Article↗
PubMed2000

Fertility after abdominal myomectomy.

This study aimed to evaluate the morbidity and pregnancy outcome of myomectomy in infertile women with uterine fibroids. This was a cross-sectional study. Records were reviewed for 100 consecutive women in the Rotunda Hospital who underwent myomectomy in the years 1995-1996. A questionnaire regarding subsequent fertility was sent. The study was carried out in the infertility unit at the Rotunda Hospital, Dublin, Ireland. Seventy-five women responded. Multiple myomectomy was performed in 52 (70%). Mean fibroid size was 6.8 cm (range 2-14.5 cm). Nine women (12%) developed complications; five had menstrual problems, two had wound discomfort and two had abdominal discomfort. Twenty-five women (33%) became pregnant. Seven (28%) were IVF pregnancies. Overall six (24%) miscarried. In 19 of 25, pregnancy occurred where fibroids were the only identifiable cause of infertility. We conclude that abdominal myomectomy is associated with a favourable outcome in infertile women particularly if no other confounding variable is present.

Journal Article↗
PubMed2000

Mouse staufen genes are expressed in germ cells during oogenesis and spermatogenesis.

The Drosophila melanogaster staufen gene encodes an RNA binding protein (Dm Stau) required for the localization and translational repression of mRNAs within the Drosophila oocyte. In mammals translational repression is important for normal spermatogenesis in males and storage of mRNAs in the oocytes of females. In the present study we identified two mouse cDNA expressed sequence tags (ESTs), encoding proteins with significant homology to Dm Stau and used these firstly to screen a mouse kidney cDNA library and secondly to determine whether staufen mRNAs are expressed in the ovaries and testes of mice and rats. Sequence analysis of the cDNAs revealed that they originated from two different genes. Using Northern blots of RNAs from kidneys, ovaries and testes, both cDNAs hybridized to mRNA species of approximately 3 kb in all three tissues. On sections of mouse ovaries, staufen mRNA was localized specifically to oocytes. On sections of mouse testes, staufen mRNA was expressed in spermatocytes found in seminiferous tubules at stages VI-XII of the spermatogenic cycle. In conclusion, we have shown that the mammalian homologues of Dm stau are expressed in germ cells in both male and female mice, consistent with a role for these RNA binding proteins in mammalian gametogenesis.

Amino Acid Sequence↗