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Biomedical subjects

L Gray

Publications and source records attributed to L Gray.

At least 19 recordsLinked to original sources
PubMed2006

Increased levels of SNAP-25 and synaptophysin in the dorsolateral prefrontal cortex in bipolar I disorder.

OBJECTIVE: In order to identify whether the mechanisms associated with neurotransmitter release are involved in the pathologies of bipolar disorder and schizophrenia, levels of presynaptic [synaptosomal-associated protein-25 (SNAP-25), syntaxin, synaptophysin, vesicle-associated membrane protein, dynamin I] and structural (neuronal cell adhesion molecule and alpha-synuclein) neuronal markers were measured in Brodmann's area 9 obtained postmortem from eight subjects with bipolar I disorder (BPDI), 20 with schizophrenia and 20 controls. METHODS: Determinations of protein levels were carried out using Western blot techniques with specific antibodies. Levels of mRNA were measured using real-time polymerase chain reaction. RESULTS: In BPDI, levels of SNAP-25 (p < 0.01) and synaptophysin (p < 0.05) increased. There were no changes in schizophrenia or any other changes in BPDI. Levels of mRNA for SNAP-25 were decreased in BPDI (p < 0.05). CONCLUSION: Changes in SNAP-25 and synaptophysin in BPDI suggest that changes in specific neuronal functions could be linked to the pathology of the disorder.

Antibodies↗
PubMed2006

Airway management in patients with a broadcomplex tachycardia requiring electrical cardioversion: a postal survey.

This study was to determine whether or not ED and ICU consultants would intubate an unstarved, haemodynamically unstable patient with a BCT requiring electrical cardioversion, and to determine the incidence of complications for both intubating and not intubating based on the responders personal experience. 174 postal questionnaires were sent to ED and ICU consultants in the Wessex and South West regions of England. They were asked whether or not they would intubate a patient that required electrical cardioversion for a BCT with hypotension. 139 responded: 77 (56%) elected to intubate the patient always or most of the time, 34 (24%) would rarely or never intubate the patient, and 28 (20%) would only do so sometimes. Responders were aware of significant complications from both intubating and not intubating such a patient. Intubation for an unstarved patient with a haemodynamically compromising BCT would seem to occur on a variable basis. ED consultants were more likely to sedate such a patient without intubation whereas ICU consultants were more likely to intubate them.

Consultants↗
PubMed2003

Toxicity, recurrence and survival after adjuvant radiotherapy treatment for FIGO stage I cancer of the endometrium.

We conducted a retrospective observational study to determine the rate of toxicity, pattern of tumour recurrence and survival associated with radiotherapy treatment for FIGO stage I cancer of the endometrium. All patients had undergone definitive surgery and had been referred to the oncology department of the University Hospital Birmingham, U.K. Two hundred and forty-five women were included in the study; 228 patients were treated with radiotherapy; 160 had external beam radiation alone; 32 had vaginal vault brachytherapy alone; 36 patients had both modalities; and 17 patients were not given radiotherapy. There were nine cases of Grade 3 and 4 radiation reactions, of which four were acute, four were late and one was acute and late toxicity. The severity of both acute and late radiation effects was significantly associated with the delivery of vault brachytherapy (external beam radiotherapy alone compared with brachytherapy alone (1/158 vs 3/32; P = 0.02). Thirty-four patients were diagnosed with tumour recurrence (11 distant, 14 local, 4 patients had both distant and local disease and 5 patients had recurrence diagnosed at the time of death). Patients who received no radiotherapy were at greater risk of local pelvic tumour recurrence (P < 0.0001; hazard ratio [HR] 9.6, 95% confidence interval (CI) 3.5-26.3). Vaginal vault brachytherapy had no discernible effect on the pattern of tumour recurrence. Forty-six patients died during the follow-up period, 28 of these were attributable to carcinoma of the endometrium. There was no difference in survival between the four treatment groups (P = 0.68). The overall 5-year survival rate in our study group was 89.6% (85.4-93.8%). In a proportional hazards model, tumour grade (HR 2.0 per level [1.25, 3.17]; P = 0.004]) and age (HR 1.74 per 10 years [1.12, 2.69]; P = 0.01) were the only factors found to have an independent influence on survival. This study suggests that, although pelvic radiation may not alter overall survival, it does reduce the risk of local disease recurrence. In this study population, vaginal vault brachytherapy using a vaginal stock/dobbie showed no additional benefits compared with external beam radiotherapy; it was, however, associated with a higher rate of both acute and late radiation effects.

Adult↗
PubMed2003

The effect of biological effective dose on time to symptom progression in metastatic renal cell carcinoma.

AIMS: Renal cell carcinoma is commonly thought to be a radioresistant malignancy. Retrospective studies report conflicting results on the effect of radiotherapy dose escalation on response and time to progression in symptomatic metastatic disease; studies using the linear quadratic model have used alpha/beta ratios that are inappropriate for slow growing tumours. We aim to describe our experience with palliative radiotherapy in this context, relating Biological Effective Dose to outcome. MATERIALS AND METHODS: From December 1995 to April 2001, 143 independent palliative radiotherapy treatments were delivered to 78 patients in a single institution. Retrospective data was obtained on the radiotherapy schedule used, symptom response and time to symptom progression. The biological effective dose (BED) was calculated using alpha/beta ratios of 3 and 7 Gy (BED3 and BED7). The Log-Rank test was used to assess any differences in time to progression, and the Cox Proportional Hazards analysis to determine prognostic factors of time to progression. RESULTS: Overall symptomatic response rate was 73%, with most responses being partial (67%). Forty-three (38%) patients had symptomatic progression after a median follow-up of 425 days. BED (BED3 or BED7) was not significantly different across response types (complete, partial or no response; P=0.90 and 0.88, respectively) and was not predictive for time to symptomatic progression (P=0.99 for BED3 and P=0.70 for BED7). Patients with bone metastases received less total dose (P=0.001), less BED (BED3, P=0.0013, and BED7, P=0.0005) and had a significantly longer time to progression than other sites of metastases (hazard ratio (HR) 0.4; 95% confidence interval (CI) 0.2-0.7; P=0.004). Initial treatment with interferon-alpha alone in patients presenting with metastatic disease, before palliative radiotherapy, was also associated with a shorter time to symptom progression (HR 4.6; 95% CI 1.5-14.1; P=0.007). On removal of these criteria, brain metastases became a significant predictor of progression time, with an HR of 2.5 (95% CI 1.0-5.9; P=0.05), showing an increased risk of progression with brain metastases compared with metastases elsewhere. Time from primary diagnosis to development of metastatic disease was not predictive of time to symptom progression (P=0.29). CONCLUSION: Despite the widespread assumption that renal cell carcinoma is radioresistant, retrospective assessment showed high response rates to palliative radiotherapy. On the basis of our data, higher BED does not seem to be a predictor of response or of duration of response in the palliative treatment of renal cell carcinoma. Palliation of bone pain seems to be particularly durable compared with the palliation of symptoms at other sites of metastases. A trend for shorter duration of palliative effect of whole-brain radiotherapy was noted.

Adult↗
PubMed2003

The effect of Epstein-Barr virus status on outcome in age- and sex-defined subgroups of patients with advanced Hodgkin's disease.

BACKGROUND: Conflicting data on the effect of the Epstein-Barr virus (EBV) on outcome in Hodgkin's disease (HD) might be due to the heterogeneous nature of this disease. In this study we have investigated whether the effect of EBV status on outcome is different between aetiologically defined age groups (15-34, 35-44, 45+ years) and also between males and females. PATIENTS AND METHODS: Paraffin-embedded sections from 273 patients with advanced HD from two related clinical trials were analysed for the presence of EBV using in situ hybridisation. RESULTS: EBV was detected in 78 (29%) of cases. For all patients, after a median follow-up of 5 years, there were no significant differences in survival by EBV status although there was a trend towards longer failure-free survival times for EBV-positive patients. Multivariate analyses suggested that EBV and sex, when in combination, were prognostic factors for failure-free survival (P = 0.06 for both). For subgroups, the effect of EBV on failure-free survival was significant for males and 15-34 years age group (P = 0.05 and P = 0.03, respectively). CONCLUSION: This study suggests that with a median follow-up of 5 years, EBV status does not affect survival but being EBV-positive may be beneficial in terms of failure-free survival, particularly for males and younger adults.

Adolescent↗
PubMed2003

Management of vertically HIV-infected children in Europe.

AIM: To describe policies for the therapeutic management of vertically HIV-infected children, and to compare these with practice, using children enrolled in a cohort study in the same setting. METHODS: A postal questionnaire survey of clinicians in the paediatric centres of the European Collaborative Study (ECS) was used. Prospective data collected within the ECS on the treatment and clinical status of infected children seen in these centres in 1999-2001 were analysed and compared with the year 2000 policies reported. RESULTS: In 3 of the 10 centres, the policy was routinely to administer antiretroviral therapy (ART) to infants upon confirmation of infection, and in 7 centres initiation of therapy was delayed until specific clinical, virological and immunological criteria were reached. Evidence of disease progression was a reason for treatment modification in all centres; other considerations included adherence problems and side effects. However, practice did not always match policy. For the 84 children with at least 5 y of follow-up (73 treated and 11 untreated), overall, 69% of the 420 person-years lived were spent without treatment, and 72% without any HIV-related symptoms. Untreated children were without symptoms for 94% of these 5 y, whereas treated children spent nearly a third of their time with mild or moderately severe symptoms. CONCLUSIONS: Therapeutic management of paediatric HIV disease requires a balance between preventing disease progression and minimizing adherence problems and side effects. This is important, as most infected children are without symptoms most of the time. Recent European consensus guidelines for the treatment of infected children will facilitate management.

Adolescent↗
PubMed2002

Retrospective study of acute toxicity following short-course preoperative radiotherapy.

BACKGROUND: The use of short-course preoperative radiotherapy (25 Gy in five fractions over 1 week) in resectable rectal cancer reduces local recurrence but is associated with an increased risk of postoperative complications and late toxicity. This study aimed to identify those patients who are unlikely to benefit from short-course preoperative radiotherapy and the factors associated with acute toxicity. METHODS: All patients who received short-course preoperative radiotherapy at a university hospital in 1998 and 1999 were included in this retrospective study. The association between complications occurring within 3 months and patient demographics, radiotherapy technique, surgical details and overall treatment time (OTT) was assessed by univariate and multivariate analysis. RESULTS: The mortality rate at 30 days was 6 per cent in the 177 patients identified. Thirty-seven per cent of patients had either Dukes' A tumours, surgically incurable disease or positive circumferential margins. One or more complications occurred in 38 per cent of patients. On multivariate analysis an OTT of more than 13 days (P = 0.03), age (P = 0.02) and length of the radiotherapy field (P = 0.05) were associated with an increased risk of complications. CONCLUSION: Surgery within 1 week of completing short-course preoperative radiotherapy improved preoperative staging and use of an optimal radiotherapy technique will result in fewer patients at risk of acute toxicity.

Acute Disease↗
PubMed2002

The G2 chromosomal radiosensitivity assay.

Although requiring stringent experimental conditions to achieve good reproducibility, the G2 assay has potential as a sensitive marker for cancer susceptibility, and is particularly useful in population studies. Immediate culture of blood is preferable, but overnight storage of blood either at ambient temperature or at 4 degrees C does not appear significantly to affect G2 scores. Transport of blood may lead to additional variability in assay results and should be well controlled. Although reproducibility is generally good, G2 scores on blood from certain individuals appear to show significant variability in repeat samples. Thus, determination of an individual's radiosensitivity may require multiple assays on different occasions. While it is recognized that the distinction between aligned and mis-aligned discontinuities has no scientific basis, some laboratories have decided for the purpose of record-keeping to score all aligned discontinuities as gaps, and mis-aligned discontinuities as breaks. In all cases the final G2 score should comprise the sum of all gaps and breaks.

Carcinogenicity Tests↗
PubMed2001

Observation of high-energy neutrinos using Cerenkov detectors embedded deep in Antarctic ice.

Neutrinos are elementary particles that carry no electric charge and have little mass. As they interact only weakly with other particles, they can penetrate enormous amounts of matter, and therefore have the potential to directly convey astrophysical information from the edge of the Universe and from deep inside the most cataclysmic high-energy regions. The neutrino's great penetrating power, however, also makes this particle difficult to detect. Underground detectors have observed low-energy neutrinos from the Sun and a nearby supernova, as well as neutrinos generated in the Earth's atmosphere. But the very low fluxes of high-energy neutrinos from cosmic sources can be observed only by much larger, expandable detectors in, for example, deep water or ice. Here we report the detection of upwardly propagating atmospheric neutrinos by the ice-based Antarctic muon and neutrino detector array (AMANDA). These results establish a technology with which to build a kilometre-scale neutrino observatory necessary for astrophysical observations.

Journal Article↗
PubMed2001

Assessment of aspiration risk in stroke patients with quantification of voluntary cough.

BACKGROUND: Dysphagia and subsequent aspiration are serious complications of acute stroke that may be related to an impaired cough reflex. It was hypothesized that aspirating stroke patients would have impaired objective measures of voluntary cough as compared with both nonstroke control subjects and nonaspirating stroke patients. METHODS: Swallowing was evaluated by standard radiologic or endoscopic methods, and stroke patients were grouped by aspiration severity (severe, n = 11; mild, n = 17; no aspiration, n = 15). Airflow patterns and sound pressure level (SPL) of voluntary cough were measured in stroke patients and in a group of normal control subjects (n = 18). Initial stroke severity was determined retrospectively with the Canadian Neurological Scale. RESULTS: All cough measures were altered in stroke patients as a group relative to nonstroke control subjects. Univariate analysis showed that peak flow of the inspiration phase (770.6 +/- 80.6 versus 1,120.1 +/- 148.4 mL/s), SPL (90.0 +/- 3.1 versus 100.2 +/- 1.6 dB), peak flow of the expulsive phase (875.1 +/- 122.7 versus 1,884.1 +/- 221.6 mL/s), expulsive phase rise time (0.34 +/- 0.1 versus 0.09 +/- 0.01 s), and cough volume acceleration (5.5 +/- 1.3 versus 27.8 +/- 3.9 mL/s/s) were significantly impaired in severe aspirators as compared with nonaspirators. Aspirating patients had more severe strokes than nonaspirators (mean Canadian Neurological Scale score 7.7 +/- 0.7 versus 9.8 +/- 0.3). Multivariate logistic regression found only expulsive phase rise time values during cough correlated with aspiration status. CONCLUSION: Objective analysis of cough may provide a noninvasive way to identify the aspiration risk of stroke patients.

Aged↗
PubMed2001

Perinatal transmission of human immunodeficiency virus type 1 by pregnant women with RNA virus loads <1000 copies/ml.

In a collaboration of 7 European and United States prospective studies, 44 cases of vertical human immunodeficiency virus type 1 (HIV-1) transmission were identified among 1202 women with RNA virus loads <1000 copies/mL at delivery or at the measurement closest to delivery. For mothers receiving antiretroviral treatment during pregnancy or at the time of delivery (or both), there was a 1.0% transmission rate (8 of 834; 95% confidence interval [CI], 0.4%-1.9%), compared with 9.8% (36 of 368; 95% CI, 7.0%-13.4%) for untreated mothers (risk ratio, 0.10; 95% CI, 0.05-0.21). In multivariate analysis adjusting for study, transmission was lower with antiretroviral treatment (odds ratio [OR], 0.10; P<.001), cesarean section (OR, 0.30; P=.022), greater birth weight (P=.003), and higher CD4 cell count (P=.039). In 12 of 44 cases, multiple RNA measurements were obtained during pregnancy or at the time of delivery or within 4 months after giving birth; in 10 of the 12 cases, the geometric mean virus load was >500 copies/mL. Perinatal HIV-1 transmission occurs in only 1% of treated women with RNA virus loads <1000 copies/mL and may be almost eliminated with antiretroviral prophylaxis accompanied by suppression of maternal viremia.

Anti-HIV Agents↗
PubMed2001

Perception of voice and tone onset time continua in children with dyslexia with and without attention deficit/hyperactivity disorder.

Tasks assessing perception of a phonemic contrast based on voice onset time (VOT) and a nonspeech analog of a VOT contrast using tone onset time (TOT) were administered to children (ages 7.5 to 15.9 years) identified as having reading disability (RD; n = 21), attention deficit/hyperactivity disorder (ADHD; n = 22), comorbid RD and ADHD (n = 26), or no impairment (NI; n = 26). Children with RD, whether they had been identified as having ADHD or not, exhibited reduced perceptual skills on both tasks as indicated by shallower slopes on category labeling functions and reduced accuracy even at the endpoints of the series where cues are most salient. Correlations between performance on the VOT task and measures of single word decoding and phonemic awareness were significant only in the groups without ADHD. These findings suggest that (a) children with RD have difficulty in processing speech and nonspeech stimuli containing similar auditory temporal cues, (b) phoneme perception is related to phonemic awareness and decoding skills, and (c) the potential presence of ADHD needs to be taken into account in studies of perception in children with RD.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

Sensitivity of spiral computed tomography scanning for detecting intraocular foreign bodies.

OBJECTIVE: The purpose of this study is to determine whether 3-mm computed tomography (CT) cuts are equivalent to 1-mm CT cuts for detecting small intraocular foreign bodies (IOFBs). DESIGN: Experimental instrument validation study. PARTICIPANTS: Seventy-two porcine eyes were divided into three groups. Each group had 0.5 ml of human blood injected into the vitreous cavity and were surgically implanted with IOFBs. INTERVENTION: Each eye was surgically implanted with 0.5-mm metallic, 0.5-mm glass, or 0.5-mm stone IOFBs. Two additional eyes were left without IOFBs to serve as negative controls. MAIN OUTCOME MEASURES: Axial CT images of both 3-mm and 1-mm thickness were obtained and analyzed in masked fashion by two separate neuroradiologists. RESULTS: The sensitivity for detecting 0.5-mm metallic, 0.5-mm glass, and 0.5-mm stone IOFBs with 3-mm CT images was 100%. The sensitivity for detecting 0.5-mm metallic, 0.5-mm glass, and 0.5-mm stone IOFBs with 1-mm CT images was also 100% (confidence interval, 95%; range, 0.88-1.00). Two negative control eyes without IOFBs were also correctly evaluated by the neuroradiologists. CONCLUSIONS: With modern spiral CT scanning, 3-mm cuts are as sensitive as 1-mm cuts for detecting small metallic, glass, and stone IOFBs.

Animals↗
PubMed2001

Thoracic and lumbar spine trauma.

Complete thoracolumbar trauma evaluation incorporates radiographs, computed tomography, and magnetic resonance imaging. Primarily to localize the level of injury, diagnosis of thoracolumbar spine trauma begins with radiographs. Computed tomography with sagittal reformatted images is more sensitive for identifying the full extent of injury and the degree of involvement of the bony posterior elements. Magnetic resonance imaging is used for evaluating the extent of soft tissue injury, including damage to ligaments, discs, and epidural spaces. Magnetic resonance imaging is most frequently performed when radiographs and computed tomography do not explain the patients' symptoms and when there is a possibility of epidural hematoma, traumatic disc herniation, or spinal cord injury.

Diagnostic Imaging↗
PubMed2001

Utility of three-dimensional computed tomographic angiography for assessment of relationships between the vertebrobasilar system and the cranial base.

OBJECTIVE: The optimal surgical exposure for basilar tip aneurysms is dictated by the relationship of the basilar bifurcation to the cranial base. This study was designed to evaluate three-dimensional computed tomographic angiography as a means of obtaining detailed anatomic information on the basilar artery and the surrounding cranial base in individual patients before surgery. METHODS: We studied 30 patients using three-dimensional computed tomographic angiographic reconstructions from 1-mm computed tomographic slices. Detailed anatomic measurements were performed to define the relationship between the basilar artery and the cranial base. Particular attention was paid to the height of the dorsum sellae and its relationship to the basilar bifurcation. RESULTS: The heights of the basilar apex and the vertebrobasilar junction, relative to the cranial base, were extremely variable. Considerable asymmetries in the heights of the left and right posterior clinoid processes were identified; in one case, this difference was more than 1 cm (mean difference in height, 0.9 mm; range, 0-10.3 mm). The heights of the posterior clinoid processes above the sellar floor ranged from 5.8 to 14.1 mm (mean height, 9.5 mm). We were able to determine the feasibility of the pterional/orbitozygomatic, middle fossa/ anterior petrosal, and presigmoid retrolabyrinthine approaches to an individual basilar bifurcation. We also estimated the amount of bone removal required and determined the operative distances via those approaches. CONCLUSION: Three-dimensional computed tomographic angiography is a useful tool for assessing critical anatomic relationships and represents an adjunct to conventional angiography in the planning of individualized, precisely tailored, cranial base approaches to the vertebrobasilar system.

Adult↗
PubMed2001

Three-dimensional computed tomographic cranial base measurements for improvement of surgical approaches to the petrous carotid artery and apex regions.

OBJECTIVE: The bony and vascular anatomic features in the region of the petrous apex can vary significantly. These variations affect the operative view obtained via extended subtemporal or anterior transpetrosal approaches to cranial base lesions for individual patients. The goal of this study was to evaluate three-dimensional computed tomography as a means of obtaining detailed preoperative anatomic information regarding bony and vascular landmarks and spatial relationships in the region of the petrous carotid artery and petrous apex. METHODS: We radiographically studied 15 patients (30 sides), using 0.8- to 1-mm-thick, reconstructed, computed tomographic images. Special attention was given to the course of the petrous carotid artery. RESULTS: The petrous carotid artery was located lateral to the trigeminal impression. The size of the petrous apex medial to the horizontal petrous carotid artery was observed to be variable. The width of bone from the trigeminal impression to the wall of the internal auditory canal averaged 9.6 mm (range, 5.2-16.1 mm). A variable amount of bone overlying the internal auditory canal (4.5 mm) was also present. Multiple other relationships among key landmarks were quantified. CONCLUSION: There is significant variability in the anatomic features of the petrous apex among patients. For each patient, detailed preoperative information regarding the amount of bone to be removed during a cranial base procedure can be obtained using three-dimensional computed tomography. This information may be critical for determination of the amount of extra exposure that can be achieved via an anterior petrosectomy for each patient.

Adult↗