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Biomedical subjects

R Thomas

Publications and source records attributed to R Thomas.

At least 73 records · Page 4Linked to original sources
PubMed2003

A randomised controlled trial of breast cancer genetics services in South East Scotland: psychological impact.

This study compared the psychological impact of two models of breast cancer genetics services in South East Scotland. One hundred and seventy general practices were randomised to refer patients to the existing standard regional service or the novel community-based service. Participants completed postal questionnaires at baseline (n=373), 4 weeks (n=276) and 6 months (n=263) to assess perceived risk of breast cancer, subjective and objective understanding of genetics and screening issues, general psychological distress, cancer worry and health behaviours. For participants in both arms of the trial, there were improvements in subjective and objective understanding up to 4 weeks which were generally sustained up to 6 months. However, improvements in subjective understanding for the women at low risk of breast cancer (i.e. not at significantly increased risk) in the standard service arm did not reach statistical significance. Cancer worry was significantly reduced at 6 months for participants in both arms of the trial. The two models of cancer genetics services tested were generally comparable in terms of the participants' psychological outcomes. Therefore, decisions regarding the implementation of the novel community-based service should be based on the resources required and client satisfaction with the service.

Adolescent↗
PubMed2003

Longitudinal assessment of changes in HIV-specific effector activity in HIV-infected patients starting highly active antiretroviral therapy in primary infection.

Both the magnitude and breadth of HIV-specific immunity were evaluated longitudinally on samples collected from six subjects starting highly active antiretroviral therapy (HAART) preseroconversion (group 1), 11 recently infected subjects starting HAART postseroconversion (group 2), five subjects starting HAART in the second half of the first year of infection (group 3), and six persons starting treatment in the chronic phase of infection (group 4). HIV-specific immunity was measured by IFN-gamma ELISPOT, detecting the frequency of cells responding to a panel of HLA-restricted HIV-1 peptides. Intracellular cytokine staining was used to detect the frequency of HIV-1 Gag p55-specific CD4(+) and CD8(+) T cells in a subset of participants. The magnitude and breadth of HIV-specific responses persisted in all group 1 subjects and in 5 of 11 (45%) group 2 subjects. Both of these parameters declined in 6 of 11 (55%) group 2 and in all group 3 and 4 individuals. All persons who maintained detectable numbers of HIV-1 Gag p55-specific CD4(+) and CD8(+) T cells after starting HAART preserved the intensity and breadth of their HIV-specific effector response. Our results show that HIV-specific immunity can be preserved even if HAART is initiated beyond the acute phase of infection.

Adult↗
PubMed2003

A multicenter, randomized, placebo controlled, multiple-dose, safety and pharmacokinetic study of AIT-082 (Neotrofin) in mild Alzheimer's disease patients.

A phase 1, randomized, double-blind, placebo-controlled, dose escalation study of the purine derivative, AIT-082 (Neotrofin, NeoTherapeutics) was conducted in mild Alzheimer's disease (AD) patients to evaluate multiple-dose safety, tolerability, and pharmacokinetics. Possible short-term effects of AIT-082 on cognition and memory were preliminarily investigated. AIT-082 is currently being developed as a potential treatment for Alzheimer's disease and other neurological disorders. Pre-clinical studies indicate that AIT-082 has memory enhancing properties, stimulates neuritogenesis and the production of neurotrophic factors. Patients received an oral dose of AIT-082 or placebo daily for one week. Thirty-six AD patients were divided into three dose cohorts; each dose cohort consisted of twelve patients with 8 patients randomized to AIT-082 and 4 to placebo. The 3 doses of AIT-082 evaluated in this study were 100 mg/day, 500 mg/day, and 2,000 mg/day. There were no serious adverse events at any dose and the drug was well tolerated without significant side effects. AIT-082 was orally and rapidly absorbed, resulting in peak serum concentrations within 2 hours with an elimination half-life of approximately 20 hours. Higher doses resulted in corresponding increases in peak concentrations and areas under the curve (AUC). There was an approximate 2-fold accumulation in AIT-082 with daily dosing (as reflected by the AUC) at steady state. There were no significant differences by treatment arm on the clinical or neuropsychological evaluations. AIT-082 was rapidly absorbed by the oral route with a half-life suitable for dosing once or twice daily. No problems with tolerability or safety were found. AIT-082 appears suitable for testing in larger clinical trials for the treatment of AD and other neurologic disorders.

Administration, Oral↗
PubMed2003

An enhanced cosmic-ray flux towards zeta Persei inferred from a laboratory study of the H3+-e- recombination rate.

The H3+ molecular ion plays a fundamental role in interstellar chemistry, as it initiates a network of chemical reactions that produce many molecules. In dense interstellar clouds, the H3+ abundance is understood using a simple chemical model, from which observations of H3+ yield valuable estimates of cloud path length, density and temperature. But observations of diffuse clouds have suggested that H3+ is considerably more abundant than expected from the chemical models. Models of diffuse clouds have, however, been hampered by the uncertain values of three key parameters: the rate of H3+ destruction by electrons (e-), the electron fraction, and the cosmic-ray ionization rate. Here we report a direct experimental measurement of the H3+ destruction rate under nearly interstellar conditions. We also report the observation of H3+ in a diffuse cloud (towards Persei) where the electron fraction is already known. From these, we find that the cosmic-ray ionization rate along this line of sight is 40 times faster than previously assumed. If such a high cosmic-ray flux is ubiquitous in diffuse clouds, the discrepancy between chemical models and the previous observations of H3+ can be resolved.

Journal Article↗
PubMed2003

An open randomised trial of second-line endocrine therapy in advanced breast cancer. comparison of the aromatase inhibitors letrozole and anastrozole.

It was previously shown that letrozole (Femara) was significantly more potent than anastrozole (Arimidex) in inhibiting aromatase activity in vitro and in inhibiting total body aromatisation in patients with breast cancer. The objective of this study was to compare letrozole (2.5 mg per day) and anastrozole (1 mg per day) as endocrine therapy in postmenopausal women with advanced breast cancer previously treated with an anti-oestrogen. This randomised, multicentre and multinational open-label phase IIIb/IV study enrolled 713 patients. Treatment was for advanced breast cancer that had progressed either during anti-oestrogen therapy or within 12 months of completing that therapy. Patients had tumours that were either positive for oestrogen and/or progesterone receptors (48%) or of unknown receptor status (52%). The primary efficacy endpoint was time to progression (TTP). Secondary endpoints included objective response, duration of response, rate and duration of overall clinical benefit (responses and long-term stable disease), time to treatment failure, and overall survival, as well as general safety. There was no difference between the treatment arms in TTP; median times were the same for both treatments. Letrozole was significantly superior to anastrozole in the overall response rate (ORR) (19.1% versus 12.3%, P=0.013), including in predefined subgroups (receptor status-unknown, and soft-tissue- and viscera-dominant site of disease). There were no significant differences between the treatment arms in the rate of clinical benefit, median duration of response, duration of clinical benefit, time to treatment failure or overall survival. Both agents were well tolerated and there were no significant differences in safety. These results support previous data documenting the greater aromatase-inhibiting activity of letrozole and indicate that advanced breast cancer is more responsive to letrozole than to anastrozole as second-line endocrine therapy.

Adult↗
PubMed2003

Prospective randomised double-blind comparative study of rocuronium and pancuronium in adult patients scheduled for elective 'fast-track' cardiac surgery involving hypothermic cardiopulmonary bypass.

The majority of cardiac anaesthetists in the UK use pancuronium for fast-track cardiac surgery. We compared the duration of action of pancuronium and rocuronium in patients undergoing fast-track hypothermic cardiopulmonary bypass and cardiac surgery. We determined whether patients would have had residual neuromuscular blockade at extubation. Twenty patients were randomly allocated to receive either pancuronium 0.1 mg x kg(-1) or rocuronium 1 mg x kg(-1). Neuromuscular function was assessed by acceleromyography; spontaneous recovery was evaluated by the train-of-four ratio measured at the adductor pollicis longus muscle. Median times to recover train-of-four ratio of 0.9 were 3 h 38 min for rocuronium and 7 h 52 min for pancuronium. The median difference in recovery times was 4 h 15 min (95% CI 2 h 30 min to 6 h 20 min; p = 0.0003 by Mann-Whitney test). None of the patients in the rocuronium group and seven of 10 patients in the pancuronium group had their extubations delayed because of residual neuromuscular blockade. Unless fast-track patients have neuromuscular function assessed before extubation, pancuronium should not be used.

Aged↗
PubMed2003

The overall effectiveness of prophylaxis in severe haemophilia.

The aim of this retrospective review was to assess the overall effectiveness of prophylaxis when compared with on-demand treatment of haemophilic patients. Twenty-five children (22 with severe haemophilia A and three with severe haemophilia B) were evaluated. Five haemophilia A patients received primary prophylaxis (instituted before the onset of any joint bleed) while the other 17 haemophilia A and all three haemophilia B patients were on secondary prophylaxis. We compared factor usage, number of bleeding episodes, emergency room (ER) visits and hospitalizations while on prophylaxis to those while on demand therapy. All subjects were male, the median age at time of review was 11.4 years and at start of prophylaxis was 4.5 years. Thirteen of the 25 patients (52%) required indwelling venous catheters for access, seven of these had one or more (one-six) episodes of line sepsis. Haemophilia A patients received an average of 23.8 U kg(-1) (20-30 U kg(-1)) of recombinant factor VIII three times a week while haemophilia B patients received 50 U kg(-1) recombinant FIX twice weekly. There was a significant reduction in the mean number of major bleeds on prophylaxis from 15.5 to 1.9 per year and a significant decrease in target joints, ER visits and hospitalizations. Although factor usage per year was higher on prophylaxis, there was an overall reduction in number of bleeds and resultant decrease in hospitalizations and ER visits. By preventing new target joints, prophylaxis can lead to reduction in long-term morbidity and a better quality of life despite increased central lines and higher factor usage.

Adolescent↗
PubMed2003

Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis.

Mouse models of the GM2 gangliosidoses [Tay-Sachs, late onset Tay-Sachs (LOTS), Sandhoff] and GM1 gangliosidosis have been studied to determine whether there is a common neuro-inflammatory component to these disorders. During the disease course, we have: (i) examined the expression of a number of inflammatory markers in the CNS, including MHC class II, CD68, CD11b (CR3), 7/4, F4/80, nitrotyrosine, CD4 and CD8; (ii) profiled cytokine production [tumour necrosis factor alpha (TNF alpha), transforming growth factor (TGF beta 1) and interleukin 1 beta (IL1 beta)]; and (iii) studied blood-brain barrier (BBB) integrity. The kinetics of apoptosis and the expression of Fas and TNF-R1 were also assessed. In all symptomatic mouse models, a progressive increase in local microglial activation/expansion and infiltration of inflammatory cells was noted. Altered BBB permeability was evident in Sandhoff and GM1 mice, but absent in LOTS mice. Progressive CNS inflammation coincided with the onset of clinical signs in these mouse models. Substrate reduction therapy in the Sandhoff mouse model slowed the rate of accumulation of glycosphingolipids in the CNS, thus delaying the onset of the inflammatory process and disease pathogenesis. These data suggest that inflammation may play an important role in the pathogenesis of the gangliosidoses.

1-Deoxynojirimycin↗
PubMed2003

Detection of medullary and papillary necrosis at an early stage by multiphasic helical computerized tomography.

PURPOSE: Multiphasic helical computerized tomography (CT) is advocated to identify early manifestations of papillary and medullary necrosis based on decreased enhancement of circumscribed areas in the medullary pyramid. At this stage the devascularizing process can be reversed if causative conditions such as infections or diabetes mellitus are effectively treated. MATERIALS AND METHODS: Multiphasic helical CTs were performed in 31 male and 26 female patients with complaints of microscopic hematuria (41), macroscopic hematuria (2), bacteriuria (39) and pyuria (9). Pre-enhancement, arterial, early corticomedullary, parenchymal and excretory phase helical CTs generated 1.25 to 5 mm. thick slices. Followup examination included multiphasic helical CT at 1 and 3 months, and excretory urography for some patients at 3 months. RESULTS: Bacteriuria was identified as the probable cause of medullary and papillary necrosis in 39 patients, of whom 28 were treated with effective antibiotic therapy, resulting in normalization and re-perfusion of the initial lesion in 16, no change in 5 and progressive disease in 7 at 3-month followup. Of 8 lesions not treated with specific antibiotic therapy 4 progressed and 4 remained unchanged. CONCLUSIONS: Multiphasic helical CT unlike the excretory urogram can identify medullary and papillary necrosis at an early stage when effective treatment of the underlying cause can reverse the process of devascularization and prevent sloughing of medullary tissues.

Adult↗
PubMed2003

Optic disc morphology in south India: the Vellore Eye Study.

AIM: To evaluate the morphology of the optic nerve head in an unselected population group in south India. METHODS: The study included 70 subjects forming a population based sample, selected in a random manner. Mean age was 47.5 (SD 8.7) years, mean refractive error measured -0.07 (1.11) dioptres (range -4.50 to +2.50 dioptres). Optic disc slides were morphometrically analysed. RESULTS: Mean optic disc area measured 2.58 (0.65) mm(2). It was statistically independent of age and refractive error. Optic disc shape was slightly vertically oval. Mean neuroretinal rim area was 1.60 (0.37) mm(2). It was significantly and positively correlated with optic disc size and optic cup size. It was independent of age, sex, refractive error, and axial length. In all subjects included in the study, the rim was smallest in the temporal horizontal optic disc sector. Mean horizontal cup/disc diameter ratio (0.66 (0.07)) was significantly (p<0.001) higher than the mean vertical cup/disc diameter ratio (0.56 (0.08)). Both ratios were highly significantly (p <0.001) and positively correlated with optic disc size. The alpha zone of parapapillary atrophy (0.84 (0.29) mm(2)), and beta zone (0.13 (0.38) mm(2)), respectively, occurred in 69 (98.6%) subjects and in eight (11.4%) subjects, respectively. They were significantly larger in the temporal horizontal sector. The alpha zone was significantly (p<0.001) larger and occurred significantly more often than beta zone. Retinal arterioles and venules were wider, and in spatial correlation, the visibility of the retinal nerve fibre layer was significantly better, in the temporal inferior disc arcade and the temporal superior arcade than in the nasal superior arcade and the nasal inferior vessel arcade. Except for the absolute size measurements these optic nerve head parameters did not differ markedly (p >0.05) from the values found in white people. CONCLUSIONS: South Indians and white people do not show marked differences in the morphology of the optic nerve head as measured by morphometric optic disc parameters, with the possible exception of the absolute optic disc dimensions.

Adult↗
PubMed2003

Five year risk of progression of primary angle closure suspects to primary angle closure: a population based study.

AIM: To report progression of primary angle closure suspects (PACS) to primary angle closure (PAC) at the 5 year follow up of a population based sample. METHODS: 82 of 118 PACS who could be contacted and 110 randomly selected normals from a population based survey in 1995 were invited for a follow up examination in 2000. Progression to PAC was based on the development of raised IOP or synechiae in a PACS. RESULTS: 50 of the 82 PACS contacted were examined. 11 (22%; 95% CI 9.8 to 34.2) developed PAC (seven synechial and four appositional); all were bilateral PACS. Two of 50 people previously diagnosed as PACS were reclassified as normal. One person among the 110 normals progressed to PAC. The relative risk of progression among PACS was 24 (95% CI 3.2 to 182.4). There was no significant difference in axial length, anterior chamber depth, or lens thickness between those who progressed and those who did not. None of the patients developed optic disc or field damage attributable to angle closure. One angle closure suspect was diagnosed to have normotensive glaucoma. CONCLUSION: In this population based study of PACS the 5 year incidence of PAC was 22%; none developed functional damage. Bilateral PACS was a clinical risk factor for progression.

Adult↗
PubMed2003

Isolation and chromosomal assignment of canine genomic BAC clones representing 25 cancer-related genes.

An extensive number of genes have been implicated in the initiation and progression of human cancers, aiding our understanding of the genetic aetiology of this highly heterogeneous disease. In order to facilitate extrapolation of such information between species, we have isolated and physically mapped the canine orthologues of 25 well-characterised human cancer-related genes. The identity of PCR products representing each canine gene marker was first confirmed by DNA sequencing analysis. Each product was then radiolabelled and used to screen a genomic BAC library for the domestic dog. The chromosomal location of each positive clone in the canine karyotype was determined by fluorescence in situ hybridisation (FISH) onto canine metaphase preparations. Of the 25 genes, the FISH localisation of 21 correlated fully with that expected on the basis of known regions of conserved synteny between the human and canine genomes. Three correlated less closely, and the chromosomal location of the remaining marker showed no apparent correlation with current comparative mapping data. In addition to generating useful comparative mapping information, this panel of markers will act as a valuable resource for detailed study of candidate genes likely to be involved in tumourigenesis, and also forms the basis of a canine cancer-gene genomic microarray currently being developed for the study of unbalanced genomic aberrations in canine tumours.

Animals↗
PubMed2003

A canine cancer-gene microarray for CGH analysis of tumors.

As with many human cancers, canine tumors demonstrate recurrent chromosome aberrations. A detailed knowledge of such aberrations may facilitate diagnosis, prognosis and the selection of appropriate therapy. Following recent advances made in human genomics, we are developing a DNA microarray for the domestic dog, to be used in the detection and characterization of copy number changes in canine tumors. As a proof of principle, we have developed a small-scale microarray comprising 87 canine BAC clones. The array is composed of 26 clones selected from a panel of 24 canine cancer genes, representing 18 chromosomes, and an additional set of clones representing dog chromosomes 11, 13, 14 and 31. These chromosomes were shown previously to be commonly aberrant in canine multicentric malignant lymphoma. Clones representing the sex chromosomes were also included. We outline the principles of canine microarray development, and present data obtained from microarray analysis of three canine lymphoma cases previously characterized using conventional cytogenetic techniques.

Animals↗
PubMed2003

Comparison of four techniques for the detection of Clostridium perfringens type D epsilon toxin in intestinal contents and other body fluids of sheep and goats.

Polyclonal capture enzyme-linked immunosorbent assay (PC-ELISA), monoclonal capture ELISA (MC-ELISA), mouse neutralization test (MNT), and counterimmunoelectrophoresis (CIEP), were compared for their ability to detect epsilon toxin in intestinal contents and body fluids of sheep and goats. When used to evaluate intestinal contents of sheep artificially spiked with epsilon prototoxin, PC-ELISA detected 0.075 mouse lethal dose (MLD)50/ml, whereas the MNT, MC-ELISA, and CIEP detected 6, 25, and 50 MLD50/ml, respectively. Amounts of epsilon toxin detected by PC-ELISA, MC-ELISA, MNT, and CIEP in sheep pericardial fluid artificially spiked with epsilon prototoxin were 0.075, 0.75, 6, and 200 MLD50/ml, respectively. For assaying epsilon toxin in aqueous humor, PC-ELISA and MC-ELISA detected 0.075 MLD50/ml, whereas CIEP detected 200 MLD50/ml (MNT was not evaluated). When 51 samples of intestinal contents of sheep and goats (32 positive and 19 negative to MNT) were analyzed by the other 3 techniques, the relative sensitivity of PC-ELISA, MC-ELISA, and CIEP was 93.75, 84.37, and 37.50%, respectively. The specificity of PC-ELISA, MC-ELISA, and CIEP was 31.57, 57.89, and 84.21%, respectively. The absolute sensitivity of PC-ELISA, MC-ELISA, CIEP, and MNT was 90.90, 69.69, 15.15, and 54.54%. The absolute specificity of the 4 techniques was 100%. These results show that there is a marked inconsistency among techniques routinely used to detect Clostridium perfringens epsilon toxin. Until more consistent results are achieved, the diagnosis of enterotoxemia should not only be based solely on epsilon toxin detection, but also on clinical and pathological data.

Animals↗
PubMed2003

The socio-economic impact of telehealth: a systematic review.

We reviewed the socio-economic impact of telehealth, focusing on nine main areas: paediatrics, geriatrics, First Nations (i.e. indigenous peoples), home care, mental health, radiology, renal dialysis, rural/remote health services and rehabilitation. A systematic search led to the identification of 4646 citations or abstracts; from these, 306 sources were analysed. A central finding was that telehealth studies to date have not used socio-economic indicators consistently. However, specific telehealth applications have been shown to offer significant socio-economic benefit, to patients and families, health-care providers and the health-care system. The main benefits identified were: increased access to health services, cost-effectiveness, enhanced educational opportunities, improved health outcomes, better quality of care, better quality of life and enhanced social support. Although the review found a number of areas of socio-economic benefit, there is the continuing problem of limited generalizability.

Bias↗
PubMed2003

Cathepsin K mRNA and protein expression in prostate cancer progression.

Prostate cancer (CaP) is the most commonly diagnosed malignancy in men and is often associated with bone metastases, which cause much of the morbidity associated with CaP. Lesions associated with CaP generally exhibit increased bone formation and resorption. Increased bone resorption may release factors from the extracellular matrix that contribute to tumor growth. Cathepsin K (cat K) is a cysteine protease that exhibits strong degradative activity against the extracellular matrix and is involved in osteoclast-mediated bone destruction. In this study, we analyzed the expression of cat K in CaP cell lines and patient samples. Cat K message was detected in CaP cell lines by reverse transcription-polymerase chain reaction (RT-PCR) and in primary CaP and metastases by in situ hybridization. Immunohistochemistry revealed variable expression of cat K in primary CaP samples, as well as nonosseous metastases, whereas expression in bone metastases was significantly higher than in primary CaP, and normal prostate tissues were negative. Cat K protein was detected in CaP cell lines by Western blotting after immunoprecipitation. Cat K enzymatic activity was also detected in CaP cell lines by a fluorogenic assay and by an assay for degradation of collagen type I. Increased levels of NTx, a marker of bone matrix degradation mediated primarily by cat K, were also detected in sera of patients with CaP bone metastases. We hypothesize that CaP-expressed cat K may contribute to the invasive potential of CaP, while increased expression in bone metastases is consistent with a role in matrix degradation.

Blotting, Western↗