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Biomedical subjects

J Mason

Publications and source records attributed to J Mason.

At least 91 records · Page 5Linked to original sources
PubMed1999

A systematic review of foot ulcer in patients with Type 2 diabetes mellitus. II: treatment.

AIM: To assess the value of treatments for foot ulcers in patients with Type 2 diabetes mellitus. METHODS: A systematic review of interventions to treat diabetic foot ulcers. RESULTS: The evidence base for treating infections and dressing wounds is poor. A number of new and potentially promising treatments are being developed but currently available studies are often small, inadequately powered and use different methods and outcomes. CONCLUSIONS: Given the prevalence, morbidity and healthcare costs of diabetic foot disease, it is surprising that available trials provide inadequate evidence to improve upon current empirically based treatment approaches. Substantial effort and resources should be deployed in order to investigate both new and existing treatments in a co-ordinated, systematic and consistent manner, so that a proper evidence base can be established for this important disease area.

Diabetes Mellitus, Type 2↗
PubMed1999

Cartilage tissue engineering: current limitations and solutions.

Articular cartilage repair remains one of the most intensely studied orthopaedic topics. To date the field of tissue engineering has ushered in new methodologies for the treatment of cartilage defects. The authors' 10-year experience using principles of tissue engineering applied to resurfacing of cartilage defects is reported. Which cell type to use, chondrocytes versus chondroprogenitor cells, and their inherent advantages and disadvantages are discussed. Chondrocytes initially were used as the preferred cell type but were shown to have long term disadvantages in models used by the authors. Mesenchymal stem cells can be used effectively to overcome the limitations experienced with the use of differentiated chondrocytes. The use of mesenchymal stem cells as platforms for retroviral transduction of genes useful in cartilage repair introduces the concept of gene modified tissue engineering. The fundamental conditions for promoting and conducting a viable cartilage repair tissue, regardless of which cell type is used, also were studied. Placement of a synthetic porous biodegradable polymer scaffold was found to be a requirement for achieving an organized repair capable of functionally resurfacing a cartilage defect. A new modular device for intraarticular fixation of various graft composites has been developed. This new cartilage repair device is composed of bioabsorbable polymers and is capable of being delivered by the arthroscope.

Animals↗
PubMed1999

Designing evaluations of interventions to change professional practice.

The design and interpretation of experimental studies to examine the effectiveness and efficiency of implementation strategies intended to change professional practice are gaining increasing attention. It has been argued that variations of the simple randomised design are most appropriate in this setting. The principles of block designs and their applicability in this field are reviewed critically, as are the choice of outcomes and approaches to economic analysis. We conclude that more complex designs are not superior per se, and that the design, choice of implementation method and topic, and analysis of such experiments should reflect the circumstances of the study.

Bias↗
PubMed1999

Challenges to the economic evaluation of new biotechnological interventions in healthcare.

The next century is likely to bring unforeseen genetic and biotechnological discoveries, with new benefits, risks and costs. This paper explores some of the problem areas that healthcare biotechnologies are likely to encounter. Biotechnological interventions may present particular difficulties when they promise a major breakthrough in therapy, since economic evaluation early in the development of such technologies is inherently uncertain. Given the structure of the biotechnology industry, the perception of the high cost of new products and unknown uncertainties, governments may need to be proactive to ensure that meaningful clinical and economic data are generated in the product research phase and to manage the introduction and diffusion stages with further evaluation and surveillance. Progress usually comes at a price: both governments and the industry should prepare for this rather than offering bland reassurances about safety.

Antibodies, Monoclonal↗
PubMed1999

Deriving treatment recommendations from evidence within randomized trials. The role and limitation of meta-analysis.

Meta-analysis is commonly used in reviews of the effectiveness of medical technologies, but this approach has not been used in direct support of guidelines development groups. This paper describes the approach of the North of England Guidelines Development Project in describing the evidence using meta-analyses that were conducted explicitly to address questions on the choice of therapy raised by the guidelines development groups. Particular emphasis is placed on the context within which the contributing trials were conducted and the extent to which systematic differences between trials (heterogeneity) was observed, described, and explained. There is a trade-off between internal and external validity for different metrics when presenting the results of trials. More interpretable metrics, such as risk differences or weighted mean differences, are confounded by study design issues and strong assumptions. More robust measures such as odds ratios or standardized weighted mean differences are difficult to interpret physically. Individual patient data may prove particularly helpful in addressing pivotal questions on the magnitude of effects of interventions, though accessing and reanalyzing these data requires a substantial investment in time and other resources.

Bias↗
PubMed1998

Novel cyclic compounds as potent phosphodiesterase 4 inhibitors.

The synthesis and biological activity of a novel series of 2, 2-disubstituted indan-1,3-dione-based PDE4 inhibitors are described. This structurally unique class of PDE4 inhibitors is markedly different from the known PDE4 inhibitors such as RP 73401 (2) and CDP 840 (3). Structure-activity relationship (SAR) studies led to the identification of inhibitors with nanomolar potency and oral activity in a murine endotoxemia model for TNF-alpha inhibition. Unlike other classical PDE4 inhibitors, several analogues were found to be nonemetic in a canine emesis model at intravenous doses of up to 3 mg/kg.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Histochemical and ultrastructural modification of mucosal mast cell granules in parasitized mice lacking the beta-chymase, mouse mast cell protease-1.

The soluble beta-chymases mouse mast cell protease-1 (mMCP-1) and rat mast cell protease-II are predominantly expressed by intestinal mucosal mast cells (IMMCs) and may promote mucosal epithelial permeability when released during intestinal allergic hypersensitivity responses. To study the function of these chymases, we generated mice with a homozygous null mutation of the mMCP-1 gene and investigated their response to infection with the intestinal nematode Nippostrongylus brasiliensis. Whereas mMCP-2, -4, and -5 were transcribed normally, there was no transcription of the mMCP-1 gene in null (-/-) mice, nor was mature mMCP-1 protein detected in (-/-) jejunal mucosa. In contrast, levels of mMCP-1 in wild-type (+/+) jejunal mucosa increased 200- to 350-fold from 0.66 microg mMCP-1/g wet weight in uninfected mice to 129 and 229 microg/g wet weight on days 8 and 10 of infection, respectively. The kinetics of IMMC recruitment differed in -/- mice compared with +/+ controls on days 8 (P < 0.05) and 10 (P < 0.03) of infection. The IMMCs in infected -/- mice stained poorly, if at all, for esterase with naphthol AS-D chloroacetate compared with the intense staining observed in +/+ controls. Ultrastructurally, the prominent crystal intragranular structures that are found in intraepithelial +/+ IMMCs were absent from -/- IMMCs. These data show that disruption of the mMCP-1 gene leads to profound histochemical and ultrastructural changes in IMMC granules.

Animals↗