Biomedical subjects

T Donovan

Publications and source records attributed to T Donovan.

At least 19 recordsLinked to original sources

PubMed2006

Intracortically distributed neurovascular coupling relationships within and between human somatosensory cortices.

The coupling of neuronal cellular activity to its blood supply is of critical importance to the physiology of the human brain and has been under discussion for more than a century. Linearity in this relationship has been demonstrated in some animal studies, but evidence is lacking in humans. In this study, we compared scalp evoked potentials and the functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) signal from healthy human volunteers with changes in the intensity of a somatosensory stimulus. By weighting the fMRI images according to the evoked potential amplitude at corresponding intensities, we tested for positive and negative covariation between these 2 data sets and the extent to which these were linear. Hemodynamic changes in primary somatosensory cortex covaried positively with neuronal activity in a predominantly linear manner, with a small quadratic contribution. Simultaneously, other cortical areas corresponding to the nonstimulated limbs were found to covary negatively and linearly in the hemispheres ipsilateral and contralateral to the stimulus. These concurrent and bilateral cortical dynamics, as well as the intraregional features of this neurovascular coupling, are both more complex than had been considered to date, with considerable implications.

Adult↗

PubMed2006

Time-dependent observer errors in pulmonary nodule detection.

The work was carried out to investigate differences in visual search characteristics between groups of observers with different levels of experience in the task of pulmonary nodule detection in chest radiology and we report here on these differences in respect of time related decisions. Volunteer observers were divided into three groups depending on their level of expertise. There were eight radiologists, eight radiographers and eight novices. Their task was to detect pulmonary nodules in a test bank of 120 digitized posteroanterior (PA) chest radiographs. Five of the eight radiographers were tested twice: once before and once after a 6-month training programme in interpretation of the adult chest radiograph. During each test session the observers' eye movements were tracked. Data on the observers' decisions through Alternate Free Response Operating Characteristic (AFROC) methodology were correlated to their eye-movement and fixation patterns. True negative decisions from all observers were associated with shorter fixation times than false negative decisions. No correct negative decisions were made after fixations exceeding 3 s.

Adult↗

PubMed2005

Redescription of Besnoitia bennetti (Protozoa: Apicomplexa) from the donkey (Equus asinus).

Besnoitia bennetti tissue cysts were found in four naturally-infected donkeys (Equus asinus) from the USA. Infectivity of its bradyzoites and tachyzoites to animals and cell culture was studied. The bradyzoites were not infectious to out-bred Swiss Webster mice, rabbits or gerbils. When fed tissue cysts, cats did not excrete oocysts. However, the parasite was infectious to interferon-gamma gene knock out mice. The parasite from tissues of two donkeys was grown successfully in bovine monocyte monolayers for the first time. Non-dividing, uninucleate tachyzoites were approximately 6 x 1.5 microm in size. Longitudinally-cut bradyzoites in tissue sections measured 8.7 x 1.9 microm. Ultrastructurally, tachyzoites and bradyzoites were similar to those in other Besnoitia species, and in particular to parasites described from cattle (Besnoitia besnoiti) and reindeer (Besnoitia tarandi), in that their bradyzoites lacked enigmatic bodies. Based on comparative analysis of three portions of nuclear ribosomal DNA (the small and large subunits and the first internal transcribed spacer) B. bennetti was found to be more closely related to the other congeners described from ungulates. The parasite was formally redescribed and specimens deposited in the US National Parasite Collections.

Animals↗

PubMed2004

Acute ketamine administration alters the brain responses to executive demands in a verbal working memory task: an FMRI study.

We have used functional MRI to determine the effects of ketamine on brain systems activated in association with a working memory task. Healthy volunteers received intravenous infusions of placebo, ketamine at 50 ng/ml plasma concentration, and ketamine at 100 ng/ml. They were scanned while carrying out a verbal working memory task in which we varied the executive requirements (manipulation vs maintenance processes) and the mnemonic load (three vs five presented letters). We previously showed that ketamine produces a specific behavioral impairment in the manipulation task. In the current study, we modified tasks in order to match performance across drug and placebo conditions, and used an event-related fMRI design, allowing us to remove unsuccessful trials from the analysis. Our results suggest a task-specific effect of ketamine on working memory in a brain system comprising frontal cortex, parietal cortex, and putamen. When subjects are required to manipulate presented letters into alphabetical order, as opposed to maintaining them in the order in which they were presented, ketamine is associated with significantly greater activity in this system, even under these performance-matched conditions. No significant effect of ketamine was seen in association with increasing load. This suggests that our findings are not explicable in terms of a nonspecific effect of ketamine when task difficulty is increased. Rather, our findings provide evidence that the predominant effects of low, subdissociative doses of ketamine are upon the control processes engaged by the manipulation task. Furthermore, we have shown that ketamine's effects may be elucidated by fMRI even when overt behavioral measures show no evidence of impairment.

Adult↗

PubMed2004

Detection or decision errors? Missed lung cancer from the posteroanterior chest radiograph.

A test bank of verified chest radiographs was compiled for visual search experiments to investigate radiology performance in the detection of early lung cancer. A measure of the physical characteristics of the lesions was derived to determine the conspicuity (chi) of the nodules and to investigate possible causes of failed detection. Observer performance was measured by alternate free response operating characteristic (AFROC) methodology and was supplemented with visual search recording. Correlation of AFROC scores and the chi values was poor but inspection of the visual search recordings showed that most nodules were fixated. Fixations on missed lesions produced average dwell times greater than three times the minimum duration thought to be associated with detection. We conclude that the majority of errors were failures of decision rather than detection and comment on the implications of this for strategies to improve diagnostic effectiveness.

Clinical Competence↗

PubMed2003

Diffusion tensor imaging of brain tumours at 3T: a potential tool for assessing white matter tract invasion?

AIM: To determine whether diffusion tensor imaging (DTI) of brain tumours can demonstrate abnormalities distal to hyperintensities on T2-weighted images, and possibly relate these to tumour grade. MATERIALS AND METHODS: Twenty patients with histologically confirmed supratentorial tumours, both gliomas (high and low grade) and metastases, were imaged at 3T using T2-weighted and DTI sequences. Regions of interest (ROI) were drawn within the tumour, in white matter at various distances from the tumour and in areas of abnormality on DTI that appeared normal on T2-weighted images. The relative anisotropy index (RAI)-a measure of white matter organization, was calculated for these ROI. RESULTS: The abnormality on DTI was larger than that seen on T2-weighted images in 10/13 patients (77%) with high-grade gliomas. New abnormalities were seen in the contralateral white matter in 4/13 (30%) of these cases. In these high-grade tumours the RAI in areas of white matter disruption with normal appearance on T2-weighted images was reduced (0.19+/-0.04). Even excluding patients with previous radiotherapy this difference remains significant. In all non high-grade tumours (WHO grade II gliomas and metastases) the tumour extent on DTI was identical to the abnormalities shown on T2-weighted imaging and RAI measurements were not reduced (0.3+/-0.04). CONCLUSIONS: Subtle white matter disruption can be identified using DTI in patients with high-grade gliomas. Such disruption is not identified in association with metastases or low-grade gliomas despite these tumours producing significant mass effect and oedema. We suggest the changes in DTI may be due to tumour infiltration and that the DTI may provide a useful method of detecting occult white matter invasion by gliomas.

Adult↗

PubMed2003

Assessment of the Ventrix parenchymal intracranial pressure monitoring probe (NL950-P) and Monitor (NL950-100) in a 3 Tesla magnetic resonance scanner.

Magnetic resonance (MR) imaging and spectroscopy provide important information in patients with acute head injury. However, optimal patient management requires intracranial pressure (ICP) monitoring. There are few reports on the use of ICP sensors in an MR environment. We tested the Ventrix parenchymal intracranial pressure monitoring probe and monitor (Integra Neurosciences, USA), modified by the use of a fibre-optic extension cable, within a 3 Tesla MR system. The device performed well in the MR environment, but one element within the fibre-optic extension was significantly ferromagnetic. The ICP probe produced a small susceptibility artefact on spin echo images, and a larger artefact on gradient echo images. The MR safety of the integrated system is probably acceptable, but could be easily improved with minor modifications. Although the system is MR compatible and produces generally acceptable imaging even at 3 Tesla, there is significant degradation of image quality during gradient echo sequences.

Artifacts↗

PubMed2003

Using simulated patients in a multiprofessional communications skills programme: reflections from the programme facilitators.

This paper discusses a multiprofessional, 4-day communication skills programme in which participants explore the challenges of communicating with cancer patients and their families. Effective communication and skilled emotional support are essential prerequisites for high quality care in oncology and palliative care settings. This aspect of care presents major challenges to nurses and other health care professionals. It is acknowledged that health professionals often lack the requisite skills to communicate meaningfully with this patient group and that tangible benefits accrue from training in this area. Using simulated patients, structured feedback and small group discussions, this multiprofessional programme seeks to provide a forum that enables participants to acquire confidence and competence in a safe, comfortable and non-threatening environment. The programme structure presents several challenges in terms of providing a learning experience that addresses the diverse educational of a heterogeneous learning group. Participants' comments and programme facilitators reflections suggest that the programme is successful in addressing these challenges and providing a meaningful learning experience.

Clinical Competence↗

PubMed2003

Stereotactic MR imaging for planning neural transplantation: a reliable technique at 3 Tesla?

The purpose of this study was to assess the accuracy of high field (3 Tesla) MR in target localization for stem cell transplantation. Three patients with Huntington's disease were imaged with a stereotactic frame in place for both MRI and CT. Quality assurance procedures and manual shimming were performed before each MRI study to minimize image distortion. The images were fused using multi-modality rigid body image registration software. Image fusion demonstrated the MR images to be in agreement with CT to within 1.5 mm, as assessed by measuring the coordinates of markers on the frame and on the shape and size of the lateral ventricles. Target coordinates for transplantation were selected from the MR images. Postoperative imaging confirmed accurate graft placement.

Brain Tissue Transplantation↗

PubMed2003

Cerebrovascular pressure reactivity is related to global cerebral oxygen metabolism after head injury.

BACKGROUND: After head injury, impaired cerebrovascular autoregulation has been associated with abnormally high or low cerebral blood flow. The physiological relevance of cerebral blood flow levels is difficult to assess in these patients, whose cerebral metabolic rate for oxygen (CMRO(2)) is known to be abnormal. Investigation of these relations requires quantitative measures of cerebral blood flow and CMRO(2), to allow assessment of oxygen supply and demand relations. OBJECTIVES: To investigate the relation between dysautoregulation and global cerebral oxygen metabolism following head injury. METHODS: Using positron emission tomography, global cerebral blood flow, CMRO(2), and oxygen extraction fraction were determined in 22 patients who were investigated in 26 examinations on days 1 to 11 (mean (SD), 3.5 (2.3)) after head injury. Cerebrovascular pressure reactivity was assessed using a pressure reactivity index, calculated as the moving linear correlation coefficient between mean arterial blood pressure and intracranial pressure. Outcome was assessed six months after injury using the Glasgow outcome scale. RESULTS: Low CMRO(2) was associated with disturbed pressure reactivity (inverse function, R(2) = 0.21, p = 0.018) and there was a correlation between disturbed pressure reactivity and oxygen extraction fraction (quadratic function, R(2) = 0.55, p = 0.0001). There was no significant relation between pressure reactivity and cerebral blood flow. An unfavourable outcome was associated with disturbed pressure reactivity. There was no significant relation between outcome and CMRO(2) or oxygen extraction fraction. CONCLUSIONS: There is a close relation between dysautoregulation and abnormal cerebral metabolism but not blood flow. Further studies are needed to determine whether metabolic dysfunction is a result of or a cause of disturbed pressure reactivity, and to establish if there is a relation between cerebral oxygen metabolism and outcome.

Adolescent↗

PubMed2003

The sacroiliac joints: evaluation using nuclear scintigraphy. Part 1: The normal horse.

REASONS FOR PERFORMING STUDY: Sacroiliac (SI) disease is recognised as a cause of poor hindlimb action but differential diagnosis is often difficult. HYPOTHESES: That in clinically normal horses there would be a significant difference in the ratio of radiopharmaceutical uptake (RU) between the fifth lumbar vertebra (L5) and each tuber sacrale (TS) and between L5 and each SI joint; and that these ratios would alter with age, but ratios would be bilaterally symmetrical. METHODS: Dorsal scintigraphic images of the SI region of 15 horses, selected randomly from the clinic database, were analysed by 2 of the authors, comparing noncorrected and motion-corrected images. To determine scintigraphic anatomy, the scintigraphic images of 10 Thoroughbred horses were superimposed over a ventrodorsal radiographic image of an isolated pelvis. Dorsal scintigraphic images of 40 clinically normal horses age 3-16 years were evaluated using subjective examination, profile analysis and quantification using regions of interest. RESULTS: The tubera sacrale were seen as 2 well-defined oval regions immediately to the left and right of the midline, abaxial to which were larger, approximately oval areas with less RU, representing uptake in the SI joints. The definition between the SI region and the TS was more obvious in younger horses. Nonmotion-corrected images were often not of diagnostic quality or could be misinterpreted as abnormal. There were significant differences in RU between the TS and SI joints compared to L5, and decreased RU in the tubera sacrale with increasing age, but no change of uptake in the SI joint region and no effect of gender on RU. There was a high degree of left-right symmetry of the TS and SI joint regions. CONCLUSIONS AND POTENTIAL RELEVANCE: The scintigraphic images of horses with suspected sacroiliac joint disease should be compared with images of normal horses of comparable age. In normal horses, there was a high degree of symmetry; therefore, marked left-right asymmetry is likely to be abnormal.

Age Factors↗

PubMed2003

Evaluation of an MRI-based protocol for cell implantation in four patients with Huntington's disease.

The purpose of this study was to evaluate our surgical protocol for the preparation and delivery of suspensions of fetal tissue into the diseased human brain. We implanted suspensions of human fetal striatal anlage into the right caudate and putamen of four patients with Huntington's disease. Postoperative 3 tesla MR imaging confirmed accurate graft placement. Variability in graft survival was noted and the MR signal changes over 6 months revealed persistent hyperintense signal on T2-weighted images. Our results are consistent with those described by other groups and indicate that our surgical protocol is safe, accurate, and reproducible.

Brain↗

PubMed2002

Assessment of the Caradyne WhisperFlow for administration of continuous positive airway pressure in a 3 Tesla magnetic resonance scanner.

Demand for magnetic resonance investigations in critically ill patients is increasing. While these patients frequently need ventilatory support, not all of them require controlled ventilation and many may be treated with continuous positive airway pressure. Controlled ventilation, with the concurrent need for sedation, may be inappropriate when airway physiology is being studied and may retard weaning. No commercially available ventilator designed for the magnetic resonance environment can deliver high flow continuous positive airway pressure. We tested the Caradyne Whisperflow flow generator and five Whisperflow valves (2.5-15 cmH2O airway pressure) within a 3 Tesla environment for safety and possible dysfunction. All components had minimal ferromagnetic properties and tests showed no clinically relevant change in flow delivery or oxygen concentration in the magnetic field. In addition, the airway pressure generated by the valves was not affected by the magnetic field. We conclude that the tested system can be safely used in a 3 Tesla magnetic resonance environment.

Critical Care↗

PubMed2001

Responses of human frontal cortex to surprising events are predicted by formal associative learning theory.

Learning depends on surprise and is not engendered by predictable occurrences. In this functional magnetic resonance imaging (fMRI) study of causal associative learning, we show that dorsolateral prefrontal cortex (DLPFC) is associated specifically with the adjustment of inferential learning on the basis of unpredictability. At the outset, when all associations were unpredictable, DLPFC activation was maximal. This response attenuated with learning but, subsequently, activation here was evoked by surprise violations of the learned association. Furthermore, the magnitude of DLPFC response to a surprise event was sensitive to the relationship that had been learned and was predictive of subsequent behavioral change. In short, the physiological response properties of right DLPFC satisfied specific predictions made by associative learning theory.

Adult↗

PubMed2001

Age dependence of cerebrospinal pressure-volume compensation in patients with hydrocephalus.

OBJECT: The dynamics of both drainage and storage capacity become altered during the sequential pathological processes that lead to hydrocephalus. Cerebrospinal fluid (CSF) formation and drainage rate have been reported to be age dependent. The aim of this study was to investigate whether CSF compensatory parameters are dependent on age in patients who have symptoms of hydrocephalus and apparently normal intracranial pressure (ICP). METHODS: Forty-six patients who presented with ventriculomegaly, the clinical symptoms of hydrocephalus, and normal ICPs underwent a computerized CSF infusion test. Parameters used to describe CSF compensation were calculated and correlated with the age of each patient. The mean ICPs were found to be independent of the age of the patient. Resistance to CSF outflow (Rcsf), however, demonstrated a nonlinear increase with advancing age (r = -0.57; p < 0.0001) and was associated with a decrease in the CSF production rate, which also occurred with increasing age (r = 0.49; p < 0.002). Both the pulse amplitude of the ICP waveform and the slope of the amplitude-ICP regression line increased significantly with advancing age (r = 0.39; p < 0.01 and r = 0.43, p < 0.004, respectively). The nonlinear increase in the elastance coefficient indicated increasing brain stiffness, which acompanies older ages (r = -0.31; p < 0.04). CONCLUSIONS: In a study of patients with symptoms of hydrocephalus, but normal ICPs, the increase in Rcsf and decrease in CSF production were most pronounced in patients who were older than 56 years of age. This relationship was more significant than previously suggested.

Adaptation, Physiological↗

PubMed2000

Guidelines for the microbiological quality of some ready-to-eat foods sampled at the point of sale. PHLS Advisory Committee for Food and Dairy Products.

These guidelines for the microbiological quality of ready-to-eat foods represent a revision and expansion of guidelines first published by the PHLS in September 1992 and revised in March 1996. The latest guidelines incorporate many of the constructive comments received from food examiners and other microbiologists within and outside the PHLS and from environmental health officers throughout the United Kingdom. This document reviews the changes and the reasons they were made and sets out the new guidelines. It also clarifies the role of food examiners in interpreting the microbiological results of formal samples.

Colony Count, Microbial↗

PubMed1999

Population pharmacokinetics of enterally administered cisapride in young infants with gastro-oesophageal reflux disease.

AIMS: To investigate the pharmacokinetics of enterally administered cisapride suspension in young infants being treated for gastro-oesophageal reflux disease. METHODS: Plasma cisapride concentrations in 49 subjects (weight: 825-5010 g; n=108 samples, median two per patient; concentration: 14.8-170 ng ml-1 ) were fitted to a one-compartment model with first-order absorption and elimination in the NONMEM program using a logarithmic transformation of the observed and predicted concentrations. Fitting was achieved using the first order conditional estimation (FOCE) method with interaction between the interpatient and intrapatient variabilities. The interpatient variance of clearance (CL/F ) and volume of distribution (V /F ) and their covariance were estimated using an exponential error model. Intrapatient (residual) variance was estimated using an additive model. RESULTS: The clearance of cisapride was shown to be linearly related to current body weight, slope: 0.538. The typical population values of CL/F, V /F and Ka (absorption rate constant) were 0.538 l h-1 kg-1, 21.9 l, and 2.58 h-1, respectively. The population coefficients of variation (CV%) for CL/F and V/F were 34.4% and 84.3%, respectively. The squared coefficient of correlation between random effects for CL/F and V /F was 0.45. The intrapatient variance was 0.15. V /F and Ka were not influenced significantly by any patient characteristic. CONCLUSIONS: Cisapride pharmacokinetics in infants with reflux disease were satisfactorily described by a one-compartment model. Current weight should be taken into account when calculating maintenance cisapride doses in these infants.

Analysis of Variance↗

PubMed1998

The diagnosis of lameness associated with distal limb pathology in a horse: a comparison of radiography, computed tomography and magnetic resonance imaging.

A cadaver limb from an eight-year-old horse with right forelimb lameness that was relieved with an intra-articular distal interphalangeal joint block was imaged with radiographs, spiral computed tomography (CT) and magnetic resonance imaging (MRI). Spiral CT demonstrated several lucencies within the deep digital flexor tendon immediately proximal to the navicular bone. On MRI these areas had increased signal and there was enlargement of the tendon at this site. Effusion in the proximal interphalangeal joint and navicular bursa and thinning of the fibrocartilage of the navicular bone were also observed on MRI images. These changes were not detected on radiographs. Histopathology confirmed that there were focal areas of collagen necrosis within the deep digital flexor tendon with thinning and degenerative changes in the fibrocartilage of the navicular bone.

Animals↗