Biomedical subjects
Publications and source records attributed to Stephen Thomas.
Blood glucose monitoring is important in optimizing long-term outcomes in diabetic patients. Reliance on near-patient testing and the use of longer term measures of glycation are the current cornerstones. However, as this review details, there are significant problems using blood tests as measures of metabolic control in uremic diabetic patients.
This paper explores the policy-making process in the 1990s in two countries, South Africa and Zambia, in relation to health care financing reforms. While much of the analysis of health reform programmes has looked at design issues, assuming that a technically sound design is the primary requirement of effective policy change, this paper explores the political and bureaucratic realities shaping the pattern of policy change and its impacts. Through a case study approach, it provides a picture of the policy environment and processes in the two countries, specifically considering the extent to which technical analysts and technical knowledge were able to shape policy change. The two countries' experiences indicate the strong influence of political factors and actors over which health care financing policies were implemented, and which not, as well as over the details of policy design. Moments of political transition in both countries provided political leaders, specifically Ministers of Health, with windows of opportunity in which to introduce new policies. However, these transitions, and the changes in administrative structures introduced with them, also created environments that constrained the processes of reform design and implementation and limited the equity and sustainability gains achieved by the policies. Technical analysts, working either inside or outside government, had varying and often limited influence. In part, this reflected the limits of their own capacity as well as weaknesses in the way they were used in policy development. In addition, the analysts were constrained by the fact that their preferred policies often received only weak political support. Focusing almost exclusively on designing policy reforms, these analysts gave little attention to generating adequate support for the policy options they proposed. Finally, the country experiences showed that front-line health workers, middle level managers and the public had important influences over policy implementation and its impacts. The limited attention given to communicating policy changes to, or consulting with, these actors only heightened the potential for reforms to result in unanticipated and unwanted impacts. The strength of the paper lies in its 'thick description' of the policy process in each country, an empirical case study approach to policy that is under-represented in the literature. While such an approach allows only a cautious drawing of general conclusions, it suggests a number of ways in which to strengthen the implementation of financing policies in each country.
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Cellular protein trafficking has been studied to date only in vitro or with techniques that are invasive and have a low time resolution. To establish a gentle method for analysis of glucose transporter-4 (GLUT4) trafficking in vivo in fully differentiated rat skeletal muscle fibres we combined the enhanced green fluorescent protein (EGFP) labelling technique with physical transfection methods in vivo: intramuscular plasmid injection or gene gun bombardment. During optimisation experiments with plasmid coding for the EGFP reporter alone EGFP-positive muscle fibres were counted after collagenase treatment of in vivo transfected flexor digitorum brevis (FDB) muscles. In contrast to gene gun bombardment, intramuscular injection produced EGFP expression in only a few fibres. Regardless of the transfection technique, EGFP expression was higher in muscles from 2-week-old rats than in those from 6-week-old rats and peaked around 1 week after transfection. The gene gun was used subsequently with a plasmid coding for EGFP linked to the C-terminus of GLUT4 (GLUT4-EGFP). Rats were anaesthetised 5 days after transfection and insulin given i.v. with or without accompanying electrical hindleg muscle stimulation. After stimulation, the hindlegs were fixed by perfusion. GLUT4-EGFP-positive FDB fibres were isolated and analysed by confocal microscopy. The intracellular distribution of GLUT4-EGFP under basal conditions as well as after translocation to the plasma membrane in response to insulin, contractions, or both, was in accordance with previous studies of endogenous GLUT4. Finally, GLUT4-EGFP trafficking in quadriceps muscle in vivo was studied using time-lapse microscopy analysis in anaesthetised mice and the first detailed time-lapse recordings of GLUT4-EGFP translocation in fully differentiated skeletal muscle in vivo were obtained.
BACKGROUND: The DD genotype of the ACE gene predisposes to faster diabetic nephropathy (DN) progression but its role in DN development is more controversial. We reported previously, in type 1 diabetic patients, an association between faster DN progression and the PC-1 gene Q121 variant, which associates with insulin resistance in non-diabetic subjects. We investigated here whether the combination of the ACE DD genotype and the PC-1 Q121 variant predicts the development and/or progression of DN in type 1 diabetic patients. METHODS: Type 1 diabetic patients either with (n=159) or without (n=122) nephropathy were evaluated in a cross-sectional study. DN was defined as the presence of microalbuminuria or persistent proteinuria in a subject with more than 10-year duration of disease and concomitant diabetic retinopathy, and with no evidence of heart failure or other renal disease. Seventy-five (47 male/28 female) type 1 diabetic patients with nephropathy in whom retrospective information with repeated measurements of serum creatinine was available, were analysed in a longitudinal study. RESULTS: No association of the PC-1 Q121 variant and the ACE D/D genotype with DN development was observed. However, the ACE DD genotype and the PC-1 Q121 variant were associated, both independently (P=0.02 and P=0.025, respectively) or in combination (P=0.02), with a faster rate of glomerular filtration rate decline. An interaction (P=0.03) was observed between the two genes in increasing the individual patient's risk of being a fast progressor. CONCLUSION: Our data suggest that, in type 1 diabetic patients, the ACE and the PC-1 genes interact in increasing the individual risk of having a faster DN progression.
In this article, the authors present the results of the analysis of the baseline data from Keepin' it R.E.A.L.!, an HIV prevention project developed for mothers and their adolescents. Six hundred twelve mostly male (60.6%) and African American (98.2%) adolescents completed baseline assessments. Eleven percent of the adolescent participants reported initiating sexual intercourse. Adolescent participants expressing higher levels of self-efficacy to resist peer pressure, more favorable outcome expectancies, less communication about sex with their mothers, higher levels of self-concept related to their behavior, lower levels of self-concept related to popularity, and less stress reported fewer types of intimate sexual behaviors. Adolescent participants who reported higher self-efficacy to resist peer pressure to have sex and lower levels of stress were less likely to have initiated sexual intercourse. Selected characteristics of mothers did not contribute to understanding factors associated with intimate sexual behaviors or initiation of sexual intercourse among adolescent participants.
A laboratory-based study undertaken to examine the effect of confinement in net bags upon the feeding mechanisms and growth rate of maggots of Lucilia sericata showed that free-range maggots survived better and grew significantly faster than maggots in bags (P<0.005). In a separate study it was also demonstrated that maggots in bags could survive on wound fluid that passed through the net without their having access to any form of solid food. This finding was consistent with clinical experience that suggests that although there may be some aesthetic advantages to the use of maggots in bags, their ability to combat infection or remove necrotic tissue from wounds is greatly reduced.
Platelets play a critical role in both primary and secondary haemostasis. In primary haemostasis, specialised glycoprotein receptors enable platelets to adhere to proteins that are exposed in areas of vascular damage. The process of adhesion, and/or the interaction of soluble agonists with receptors on the platelet, activates the platelets, which are then able to aggregate together. This aggregation creates a platelet plug that seals the breach in the vessel wall and prevents excess blood loss. Activated platelets then facilitate secondary haemostasis, the formation of a fibrin clot, by carrying coagulation factors and providing a catalytic surface for the major interactions of the coagulation cascade. This review briefly describes the adhesion, activation and aggregation of platelets; their role in blood coagulation and clot retraction; and how they may be inhibited in order to prevent thrombosis in at-risk patients.
Mesangial cell proliferation and growth factor over-expression are characteristic features of several glomerular diseases. Vascular endothelial growth factor (VEGF), a potent mitogen, is expressed in podocytes in the glomerulus, and VEGF receptors (flt-1, KDR, and neuropilin-1) are present on endothelial cells and other cell types. This study examined whether human mesangial cells (HMC) express VEGF receptors in vitro and ex vivo and evaluated the effect of VEGF on HMC proliferation. All receptor types were detected in HMC in vitro by immunofluorescence and Western blotting. VEGF(165) induced a dose-responsive increase in (3)H-thymidine incorporation (25 ng/ml VEGF(165) : 2.3-fold increase; 50 ng/ml : 3.8-fold; 100 ng/ml : 4. 8-fold; 200 ng/ml : 3.4-fold; P = 0.016) and in cell number (50 ng/ml VEGF(165) : 1.2-fold increase; 100 ng/ml : 1.6-fold; 200 ng/ml : 1.4-fold; P = 0.005), effects prevented by an anti-VEGF(165) polyclonal neutralizing antibody (100 microg/ml). The proliferative effect was confirmed by a tetrazolium dye-based assay (100 ng/ml VEGF(165) : 1.4-fold increase). In ex vivo experiments, VEGF receptors in biopsy material from normal and diseased kidneys were detected by immunohistochemistry. No mesangial flt-1 receptor staining was seen in normal renal cortical tissue samples, and only weak mesangial KDR staining was detected. In contrast, mesangial flt-1 and KDR receptor staining were both clearly seen in biopsy samples from proliferative renal diseases. In conclusion, flt-1, KDR, and neuropilin-1 are present on cultured HMC, and VEGF(165) induces HMC proliferation. In addition, the flt-1 and KDR receptors are expressed in the mesangium in mesangioproliferative disease.
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