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M Thomas

Publications and source records attributed to M Thomas.

At least 55 records · Page 3Linked to original sources
PubMed2005

Histocompatibility testing predicts acute rejection risk in early corticosteroid withdrawal regimens.

UNLABELLED: Histocompatibility testing has been shown to predict acute rejection risk in steroid-based immunosuppression. However, little evidence exists of its ability to predict acute rejection risk in corticosteroid-free patients, with no evidence in early corticosteroid withdrawal (CSWD) under modern immunosuppression. The purpose of this study was to evaluate the ability of histocompatibility testing to identify patients at high risk for acute rejection after early CSWD. METHODS: One hundred eighty-one patients were entered into six IRB-approved early CSWD regimens. Histocompatibility testing included serologic PRA, flow cytometric PRA testing by Class I and Class II MHC beads, and B cell crossmatching with pronase treatment. All rejection episodes were biopsy proven, and grading was assigned using Banff criteria. Influence of individual tests was examined using Chi square univariate and multivariate logistic regression analysis. RESULTS: Median follow-up was 23.5 months (range 7-48 months). Of 181 patients, 16% were repeat transplant recipients, 36% received deceased donor renal transplants, 48% received living related donor renal transplants, and 16% received living unrelated transplants. Overall patient survival was 97%, and death-censored graft survival was 96.5%. Acute rejection rates in the entire follow-up period were 17.7%. 12.4% in primary transplant recipients and 37% in repeat transplant recipients. Multivariate analysis revealed that HLA AB and DR locus mismatching were associated with increased acute rejection risk. Similarly, serologic PRA analysis predicted acute rejection risk; however, flow cytometry crossmatching did not predict acute rejection risk. The greatest single influence on acute rejection risk appeared to be a flow cytometric B cell crossmatch (7.94-fold increased risk). In conclusion, histocompatibility testing can identify patients at high risk for acute rejection following early CSWD. HLA matching, serologic PRA testing, and flow cytometry-based B cell crossmatching can all be used to predict acute rejection risk.

Adrenal Cortex Hormones↗
PubMed2005

Quantitative comparison of polyethylenimine formulations and adenoviral vectors in terms of intracellular gene delivery processes.

An objective of designing molecular vehicles exhibiting virus-like transgene delivery capabilities but with low toxicity and immunogenicity continues to drive synthetic vector development. As no single step within the gene delivery pathway represents the critical limiting barrier for all vector types under all circumstances, improvements in synthetic vehicle design may be aided by quantitative analysis of the contributions of each step to the overall delivery process. To our knowledge, however, synthetic and viral gene delivery methods have not yet been explicitly compared in terms of these delivery pathway steps in a quantitative manner. As a first address of this challenge, we compare here quantitative parameters characterizing intracellular gene delivery steps for an E1/E3-deleted adenoviral vector and three polyethylenimine (PEI)-based vector formulations, as well as the liposomal transfection reagent Lipofectamine and naked DNA; the cargo is a plasmid encoding the beta-galactosidase gene under a CMV promoter, and the cell host is the C3A human hepatocellular carcinoma line. The parameters were determined by applying a previously validated mathematical model to transient time-course measurements of plasmid uptake and trafficking (from whole-cell and isolated nuclei lysates, by real-time quantitative PCR), and gene expression levels, enabling discovery of those for which the adenoviral vector manifested superiority. Parameter-sensitivity analysis permitted identification of processes most critically rate-limiting for each vector. We find that the adenoviral vector advantage in delivery appears to reside partially in its import to the nuclear compartment, but that its vast superiority in transgene expression arises predominantly in our situation from postdelivery events: on the basis of per-nuclear plasmid, expression efficiency from adenovirus is superior by orders of magnitude over the PEI vectors. We find that a chemical modification of a PEI-based vector, which substantially improves its performance, appears to do so by enhancing certain trafficking rate parameters, such as binding and uptake, endosomal escape, and binding to nuclear import machinery, but leaves endosomal escape as a barrier over which transgene delivery could be most sensitively increased further for this polymer.

Adenoviridae↗
PubMed2005

[MR-guided core biopsy of the shoulder: possibilities and experience with a vertically open 0.5T system].

PURPOSE: The availability of open whole body MRI magnets and MR-compatible instrumentarium were essential conditions for the progression of interventional MRI. The advantages of an MR-guided biopsy at the musculoskeletal system are the visualization of the puncture site of a representative area for tumor histology, the absence of exposure to radiation and the free selection of imaging planes. The purpose of the study was the development of a new technique of a secure MR-guided biopsy of intraosseus lesions in the humeral head. MATERIAL AND METHODS: MR-guided core biopsy of a intraosseus lesion of the humeral head was performed in five male patients on a vertical open, whole body MRI magnet (SIGNA SP/i 0.5T, GE Medical Systems). The technique using interactive MRI and the MR-compatible instrumentarium are described. RESULTS: A secure core biopsy could be obtained from a representative area for tumor histology in all cases. No complications occurred, especially no nerve or vessel lesion, no rotator cuff lesion and no intra-articular contamination of the shoulder joint were observed. CONCLUSION: A new technique is presented to obtain MR-guided core biopsies of intraosseous lesions of the humeral head. Furthermore, clinical indications of this technique are described.

Adult↗
PubMed2005

Effect of a concomitant diagnosis of allergic rhinitis on asthma-related health care use by adults.

BACKGROUND: Asthma and allergic rhinitis (AR) frequently coexist, but have usually been studied separately in health economic analyses. OBJECTIVE: To determine the incremental effect of documented AR on health care resource use in adults with asthma. METHODS: A retrospective cohort study using data from a UK general practice database for the period 1998-2001 enrolled subjects 16-55 years of age, with one or more asthma-related general practitioner (GP) visits during a 12-month follow-up period. The study outcomes were asthma-related hospitalizations, GP visits, and prescription drug costs during the 12-month follow-up period for patients with and without physician-diagnosed AR. RESULTS: Concomitant AR was documented in 4,611 (16.9%) of the total sample of 27,303 adults with asthma. Compared with those with asthma alone, patients with concomitant AR experienced more GP visits (5.2 vs. 4.2; P<0.0001) and more of them were hospitalized for asthma (0.76% vs. 0.45%; P<0.01) during the 12-month follow-up period. In multi-variable regression analyses, AR was predictive of hospitalization for asthma (odds ratio 1.52, 95% confidence interval (CI) 1.03-2.24) and was associated with an increase in the annual number of asthma-related GP visits (mean increase per patient 0.42, 95% CI 0.42-0.43) and annual asthma-related drug costs (mean increase GBP 5.1, 95% CI 5.0-5.3). CONCLUSION: Adults with asthma and documented concomitant AR experienced more asthma-related hospitalizations and GP visits, and incurred higher asthma drug costs than did adults with asthma alone. A unified treatment strategy for asthma and AR might reduce the costs of treating these conditions.

Adolescent↗
PubMed2005

Are outcomes the same with all dry powder inhalers?

Most clinicians and patients would intuitively say that the inhaler device used influences the outcome achieved in asthma. However, it is important to have objective evidence to support or refute this view. Systematic reviews have suggested that there is no difference in clinical effectiveness between dry powder inhalers and metered-dose inhalers. However, the studies included in the review were randomised clinical trials and not studies based on real-life clinical practice. In the real world, the efficacy of products as determined in a specified and well-monitored population is only one aspect of product performance--patient characteristics and behaviour are critical. Observational studies in real-world primary care settings suggest that the choice of inhaler device has an important impact on asthma outcomes. The IMS Mediplus database has now been used to compare outcomes among patients receiving initial maintenance therapy with beclometasone dipropionate administered via different dry powder inhalers. Patients using the DISKHALER dry powder inhaler used significantly less short-acting beta(2)-agonist than those using the ROTAHALER dry powder inhaler. This suggests a difference in the level of asthma control with the different devices, even when the same chemical entity is delivered. Real-world studies suggest, therefore, that outcomes are not always the same with all dry powder inhalers. This indicates the need for further studies to investigate the impact of inhaler device choice and the impact of switching between devices.

Administration, Inhalation↗
PubMed2005

Trends in age at diagnosis of Turner syndrome.

The age at diagnosis of 242 girls with Turner syndrome (TS) treated in Belgium with growth hormone between 1991 and 2002 was evaluated. The median (range) age at diagnosis was 6.6 (0-18.3) years. Patients with 45,X karyotype were diagnosed earlier than patients with other karyotypes. Compared to a previous survey, performed on 100 patients 12 years earlier, more patients were diagnosed during infancy and childhood, and less during adolescence. However, in 22% of the girls the diagnosis was made after the age of 12 years; these girls showed the largest height deficit. As early diagnosis has several potential advantages we recommend that a cytogenetic analysis should be considered in all girls with unexplained short stature with height below -2 SD of the mean for age or below the parent specific lower limit of height.

Adolescent↗
PubMed2005

ANCA associated pauci-immune retinal vasculitis.

BACKGROUND: Antinuclear cytoplasmic antibodies (ANCA) are useful diagnostic serological markers for the most common forms of necrotising vasculitis. ANCA associated vasculitides represent distinctive clinicopathological categories--for example, Wegener's granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis, and idiopathic necrotising crescentic glomerulonephritis, collectively known as the small vessel pauci-immune vasculitides. METHOD: Three cases of ANCA associated pauci-immune retinal vasculitis are described. Their systemic features are described and the clinical significance of ANCA as a diagnostic test in relation to retinal vasculitis discussed. RESULTS: These three cases represent a spectrum of clinical features associated with retinal vasculitis. Two cases have evolved into clinical recognisable entities as microscopic polyangiitis. Adherence to the international consensus statement on testing and reporting of ANCA is recommended and the authors speculate that the incidence of microscopic polyangiitis may be underestimated because of the under-recognition of systemic involvement in patients with retinal vasculitis. CONCLUSION: The receipt of a positive ANCA result should always raise the suspicion of a pauci-immune systemic vasculitis and prompt appropriate investigation. The authors emphasise the importance of the evaluation of systemic features in these patients with retinal vasculitis, enabling earlier recognition and thereby preventing significant morbidity and mortality.

Adult↗
PubMed2005

Relapse with transformation of lupus nephritis in a transplant kidney.

Lupus nephritis is a constellation of different renal histologies, characterized by an immune complex mediated glomerular disease. Histological transformation in lupus nephritis usually occurs from a mild mesangial proliferative glomerulonephritis to a more aggressive diffuse proliferative lesion. We present a case of relapsed systemic lupus erythematosus (SLE) in a renal transplant recipient in which there was a histological transformation from the original diffuse proliferative lupus nephritis in the native kidneys to a membranous lupus nephritis in the renal transplant.

Adult↗
PubMed2005

Dietary palm olein oil augments cardiac antioxidant enzymes and protects against isoproterenol-induced myocardial necrosis in rats.

Wistar rats, 150-200 g, of either sex, were fed daily with commercial rat diet supplemented with palm olein oil in two doses (5% v/w (n = 16) and 10% v/w (n = 16) of diet) for 30 days. Control rats (n = 16) were fed with normal diet. On the 29(th) and 30(th) days, 8 rats from each group were administred isoproterenol (85 mg/kg, s.c., 24-h interval). On the 31(st) day, all rats were sacrificed and myocardial tissues were studied for thiobarbituric acid reactive substances (TBARS), antioxidant enzymes and light microscopic changes, along with the ferric-reducing ability of plasma (FRAP). A significant rise in myocardial superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activity and FRAP level were observed in rats fed with palm olein oil. Isoproterenol caused an increase in myocardial oxidative stress in control rats, as evidenced by an increase in myocardial TBARS level, reduction in FRAP and myocardial SOD, catalase and GPx activity, along with focal necrosis of cardiac muscle fibres on light microscopy. The rise in myocardial TBARS and depletion of SOD and catalase activity following isoproterenol administration were prevented in palm-olein-oil-supplemented diet-fed rats at both doses. Isoproterenol-induced myocardial light-microscopic changes were also prevented in the treated groups. The results suggest that dietary palm olein oil caused augmentation of myocardial antioxidant enzymes and protected against isoproterenol-induced myocardial necrosis and associated oxidative stress.

Animals↗
PubMed2005

Shoulder hemiarthroplasty in patients with juvenile idiopathic arthritis.

Replacement of the shoulder in juvenile idiopathic arthritis is not often performed and there have been no published series to date. We present nine glenohumeral hemiarthroplasties in eight patients with systemic or polyarticular juvenile idiopathic arthritis. The mean follow-up was six years (59 to 89 months). The mean age at the time of surgery was 32 years. Surgery took place at a mean of 27 years after diagnosis. The results indicated excellent relief from pain. There was restoration of useful function which deteriorated with time, in part because of progression of the systemic disease in this severely affected group. No patient has required revision to date and there has been no radiological evidence of loosening or osteolysis around the implants. We discuss the pathoanatomical challenges unique to this group. There was very little space for a prosthetic joint and, in some cases, bony deformity and the small size necessitated the use of custom-made implants.

Adult↗
PubMed2005

Protein phosphorylation and signal transduction modulation: chemistry perspectives for small-molecule drug discovery.

Protein phosphorylation has been exploited by Nature in profound ways to control various aspects of cell proliferation, differentiation, metabolism, survival, motility and gene transcription. Cellular signal transduction pathways involve protein kinases, protein phosphatases, and phosphoprotein-interacting domain (e.g., SH2, PTB, WW, FHA, 14-3-3) containing cellular proteins to provide multidimensional, dynamic and reversible regulation of many biological activities. Knowledge of cellular signal transduction pathways has led to the identification of promising therapeutic targets amongst these superfamilies of enzymes and adapter proteins which have been linked to various cancers as well as inflammatory, immune, metabolic and bone diseases. This review focuses on protein kinase, protein phosphatase and phosphoprotein-interacting cellular protein therapeutic targets with an emphasis on small-molecule drug discovery from a chemistry perspective. Noteworthy studies related to molecular genetics, signal transduction pathways, structural biology, and drug design for several of these therapeutic targets are highlighted. Some exemplary proof-of-concept lead compounds, clinical candidates and/or breakthrough medicines are further detailed to illustrate achievements as well as challenges in the generation, optimization and development of small-molecule inhibitors of protein kinases, protein phosphatases or phosphoprotein-interacting domain containing cellular proteins.

Drug Design↗
PubMed2005

Surface models for coupled modelling of runoff and sewer flow in urban areas.

Traditional methods fail for the purpose of simulating the complete flow process in urban areas as a consequence of heavy rainfall and as required by the European Standard EN-752 since the bi-directional coupling between sewer and surface is not properly handled. The new methodology, developed in the EUREKA-project RisUrSim, solves this problem by carrying out the runoff on the basis of shallow water equations solved on high-resolution surface grids. Exchange nodes between the sewer and the surface, like inlets and manholes, are located in the computational grid and water leaving the sewer in case of surcharge is further distributed on the surface. Dense topographical information is needed to build a model suitable for hydrodynamic runoff calculations; in urban areas, in addition, many line-shaped elements like houses, curbs, etc. guide the runoff of water and require polygonal input. Airborne data collection methods offer a great chance to economically gather densely sampled input data.

Cities↗
PubMed2005

Assessment of urban flooding by dual drainage simulation model RisUrSim.

The European research project in the EUREKA framework, RisUrSim is presented with its overall objective to develop an integrated planning tool to allow cost effective management for urban drainage systems. The project consortium consisted of industrial mathematics and water engineering research institutes, municipal drainage works as well as an insurance company. The paper relates to the regulatory background of European Standard EN 752 and the need of a more detailed methodology to simulate urban flooding. The analysis of urban flooding caused by surcharged sewers in urban drainage systems leads to the necessity of a dual drainage modeling. A detailed dual drainage simulation model is described based upon hydraulic flow routing procedures for surface flow and pipe flow. Special consideration is given to the interaction between surface and sewer flow during surcharge conditions in order to most accurately compute water levels above ground as a basis for further assessments of possible damage costs. The model application is presented for a small case study in terms of data needs, model verification and first simulation results.

Cities↗
PubMed2005

Quantification of tension in Thera-Band and Cando tubing at different strains and starting lengths.

AIM: Elastic resistance exercise is frequently used in rehabilitation programs. Precise quantification using color coded bands is not possible. A method to predict forces for any length of mostly used elastic tubings and thereby a general equation for the comparison of elastic material is presented. METHODS: In an in vitro-series the tubing tension in relation to elongation of 6 colors of Thera-Band and Cando tubings was directly measured. The relation between tension and elongation was determined depending on different resting lengths. In clinical practice tension and elongation are prescribed. Two mathematical methods to calculate the resting length as regulatory variable are presented. One is based on the construction of iso-tension curves, the 2nd on the general mathematical relation delta % tension=K* % length change+n. RESULTS: 1. The tension/elongation relation is linear beyond a threshold in the early part of elongation. 2. The iso-tension method works graphically and facilitates the precise determination of resting length. 3. The double % relation between tension and elongation method describes the general properties of all tubings, where K=0.75 is a general constant. To calculate absolute values for the resting length, corresponding to a given tension and elongation, special ''color constants'' are presented. CONCLUSIONS: The prediction of maximum tension values for any given elongation is possible by simple variation of resting length. These findings may improve the usefulness of elastic tubings in rehabilitation programs. The mathematical method further may be used for the comparison of elastic materials with linear characteristics.

Algorithms↗
PubMed2004

Incidence of self-reported occupational injuries in seafaring--an international study.

AIMS: Seafaring is known as a high-risk industry. The aims were to describe the incidence of non-fatal injuries among seafarers, including testing the hypothesis that long working hours might result in higher injury rates. METHODS: A questionnaire study of injury on the latest tour of duty was carried out among seafarers in 11 countries with 6461 participants. The seafarers were asked if they were injured during the latest tour of duty and what was the number of hours worked. RESULTS: During the latest tour of duty, 9.1% of all seafarers were injured and 4.3% had an injury with at least 1 day of incapacity. The injury incidence rates for cargo ships and tankers: 39.5 per 1 million work hours and 37.6 per 100,000 days. Multivariate analyses: incidence rate ratios (IRR) for >70 working hours per week compared with <57 h: 0.90 [95% confidence interval (95% CI) = 0.61-1.32]; non-officers compared with officers: IRR = 1.57 (95% CI = 1.14-2.15); seafarers <35 years compared with > or =35 years of age: IRR = 2.11 (1.57-2.86); tour lengths > or =117 days compared with <117 days: IRR = 0.27 (0.19-0.39). Main work area on the deck and in the service area compared with work in the engine room: IRR = 0.37 (0.27-0.52) and IRR = 0.49 (0.26-0.91), respectively. CONCLUSIONS: There was no evidence that long working hours alone resulted in higher injury rates. Low self-perceived health, lack of use of personal protection and lack of occupational safety on board were significantly related to an increase in the injury risk.

Accidents, Occupational↗
PubMed2004

Cocaine-induced potentiation of synaptic strength in dopamine neurons: behavioral correlates in GluRA(-/-) mice.

Synaptic plasticity in the mesolimbic dopamine (DA) system is thought to contribute to the neural adaptations that mediate behavioral sensitization, a model for core aspects of addiction. Recently, it has been demonstrated that multiple classes of drugs of abuse, as well as acute stress, enhance strength at excitatory synapses on midbrain DA neurons. Here, we show that both the cocaine- and stress-induced synaptic enhancement involves an up-regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. This enhancement requires the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluRA as evidenced by its absence in mice lacking this subunit. The cocaine-elicited, but not the stress-elicited, synaptic potentiation in DA neurons was blocked by a D1-like receptor antagonist, indicating that the in vivo triggering mechanisms differ for these forms of experience-dependent synaptic modification. Surprisingly, behavioral sensitization to cocaine was elicited in GluRA(-/-) mice, indicating that potentiation of excitatory synaptic transmission in DA neurons is not necessary for this form of behavioral plasticity. However, GluRA(-/-) mice did not exhibit a conditioned locomotor response when placed in a context previously paired with cocaine, nor did they exhibit conditioned place preference in response to cocaine. We suggest that the drug-induced enhancement of excitatory synaptic transmission in midbrain DA neurons, although not required for behavioral sensitization per se, may contribute to the attribution of incentive value to drug-associated cues.

Animals↗