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Biomedical subjects

Stephen Thomas

Publications and source records attributed to Stephen Thomas.

At least 19 recordsLinked to original sources
PubMed2006

Maggot therapy: the science and implication for CAM part II-maggots combat infection.

Maggot therapy employs the use of freshly emerged, sterile larvae of the common green-bottle fly, Phaenicia (Lucilia) sericata, and is a form of artificially induced myiasis in a controlled clinical situation. Maggot therapy has the following three core beneficial effects on a wound: debridement, disinfection and enhanced healing. In part II of this review article, we discuss clinical infections and the evidence supporting the potent antibacterial action of maggot secretions. Enhancement of wound healing by maggots is discussed along with the future of this highly successful, often controversial, alternative treatment.

Journal Article↗
PubMed2006

Maggot Therapy: The Science and Implication for CAM Part I-History and Bacterial Resistance.

It is now a universally acknowledged fact that maggot therapy can be used successfully to treat chronic, long-standing, infected wounds, which have previously failed to respond to conventional treatment. Such wounds are typically characterized by the presence of necrotic tissue, underlying infection and poor healing. Maggot therapy employs the use of freshly emerged, sterile larvae of the common green-bottle fly, Phaenicia (Lucilia) sericata, and is a form of artificially induced myiasis in a controlled clinical situation. In this review article, we will discuss the role of maggots and their preparation for clinical use. Maggot therapy has the following three core beneficial effects on a wound: debridement, disinfection and enhanced healing. In part I we explore our current understanding of the mechanisms underlying these effects.

Journal Article↗
PubMed2006

Second symposium on the definition and management of anaphylaxis: summary report--second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium.

There is no universal agreement on the definition of anaphylaxis or the criteria for diagnosis. In July 2005, the National Institute of Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network convened a second meeting on anaphylaxis, which included representatives from 16 different organizations or government bodies, including representatives from North America, Europe, and Australia, to continue working toward a universally accepted definition of anaphylaxis, establish clinical criteria that would accurately identify cases of anaphylaxis with high precision, further review the evidence on the most appropriate management of anaphylaxis, and outline the research needs in this area.

Journal Article↗
PubMed2006

Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium.

There is no universal agreement on the definition of anaphylaxis or the criteria for diagnosis. In July 2005, the National Institute of Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network convened a second meeting on anaphylaxis, which included representatives from 16 different organizations or government bodies, including representatives from North America, Europe, and Australia, to continue working toward a universally accepted definition of anaphylaxis, establish clinical criteria that would accurately identify cases of anaphylaxis with high precision, further review the evidence on the most appropriate management of anaphylaxis, and outline the research needs in this area.

Anaphylaxis↗
PubMed2006

Health reform, equity and primary healthcare: taking off the make-up.

The prioritisation approach at the heart of the health reform movement not only failed to improve access to services for the very poor but was based on poor methods. Its notion of efficiency ignored local contexts, the interaction of interventions and local specification of needs. The authors argue that a more efficient strategy for prioritisation involves resuscitating the primary healthcare approach and its emphasis on procedural, as well as distributive, equity. A growing body of evidence supports the link between enhancing the voice of local communities and improving the allocation and impact of resources in health service provision.

Health Care Reform↗
PubMed2006

Serum lipids and the progression of nephropathy in type 1 diabetes.

OBJECTIVE: Dyslipidemia contributes to the progression of microvascular disease in diabetes. However, different lipid variables may be important at different stages of nephropathy. This study examines the pattern of dyslipidemia associated with the progression of nephropathy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 152 patients with type 1 diabetes were recruited in order to represent various phases of nephropathy. Patients were followed for 8-9 years, during which time they received standard care. Renal progression was defined a priori as a doubling in albumin excretion (in patients with normo- or microalbuminuria) or a decline in creatinine clearance (in those with macroalbuminuria). A panel of lipid variables was determined and correlated with indexes of progression. RESULTS: In patients with normoalbuminuria (n = 66), progression was associated with male sex (P < 0.05), borderline albuminuria (P = 0.02), and LDL-free cholesterol (P = 0.02). In patients with microalbuminuria (n = 51), progression was independently associated with triglyceride content of VLDL and intermediate-density lipoprotein (both P < 0.05). In patients with macroalbuminuria (n = 36), a significant decline in the renal function (>3 ml x min(-1) x year(-1)) was independently associated with poor glycemic control, hypertension, and LDL size (P < 0.05). When all patients with progressive nephropathy were analyzed together, only LDL cholesterol was predictive on multivariate analysis (P < 0.05), which masked the importance of triglyceride enrichment in microalbuminuria. CONCLUSIONS: Lipid variables are associated with progression of diabetic kidney disease, but the relationship is not the same at all stages. This finding has implications for the design of renoprotective strategies and the interpretation of clinical trials in type 1 diabetes.

Adult↗
PubMed2005

Quantification of particle number emission factors for motor vehicles from on-road measurements.

The database on particle number emission factors has been very limited to date despite the increasing interest in the effects of human exposure to particles in the submicrometer range. There are also major questions on the comparability of emission factors derived through dynamometer versus on-road studies. Thus, the aims of this study were (1) to quantify vehicle number emission factors in the submicrometer (and also supermicrometer) range for stop-start and free-flowing traffic at about 100 km h(-1) driving conditions through extensive road measurements and (2) to compare the emission factors from the road measurements with those obtained previously from dynamometer studies conducted in Brisbane. For submicrometer particles the average emission factors for Tora Street were estimated at (1.89 +/- 3.40) x 10(13) particles km(-1) (mean +/- standard error; n = 386) for petrol and (7.17 +/- 2.80) x 10(14) particles km(-1) (diesel; n = 196) and for supermicrometer particles at 2.59 x 10(9) particles km(-1) and 1.53 x 10(12) particles km(-1), respectively. The average number emission factors for submicrometer particles estimated for Ipswich Road (stop-start traffic mode) were (2.18 +/- 0.57) x 10(13) particles km(-1) (petrol) and (2.04 +/- 0.24) x 10(14) particles km(-1) (diesel). One implication of the conclusion that emission factors of heavy duty diesel vehicles are over 1 order of magnitude higher than emission factors of petrol-fueled passenger cars is that future control and management strategies should in particular target heavy duty vehicles, as even a moderate decrease in emissions of these vehicles would have a significant impact on lowering atmospheric concentrations of particles. The finding that particle number emissions per vehicle-km are significantly larger for higher speed vehicle operation has an important implication on urban traffic planning and optimization of vehicle speed to lower their impact on airborne pollution. Additionally, statistical analysis showed that neither the measuring method (dynamometer or on-road), nor data origin (Brisbane or elsewhere in the world), is associated with a statistically significant difference between the average values of emission factors for diesel, petrol, and vehicle fleet mix. However, statistical analyses of the effect of fuel showed that the mean values of emission factors for petrol and diesel are different at a 5% significance level.

Air Pollutants↗
PubMed2005

The longevity of Caenorhabditis elegans in soil.

Relatively simple model organisms such as yeast, fruit-flies and the nematode, Caenorhabditis elegans, have proven to be invaluable resources in biological studies. An example is the widespread use of C. elegans to investigate the complex process of ageing. An important issue when interpreting results from these studies is the similarity of the observed C. elegans mortality pattern in the laboratory to that expected in its natural environment. We found that the longevity of C. elegans under more natural conditions is reduced up to 10-fold compared with standard laboratory culture conditions. Additionally, C. elegans mutants that live twice as long as wild-type worms in laboratory conditions typically die sooner than wild-type worms in a natural soil. These results indicate that conclusions regarding extended longevity drawn from standard laboratory assays may not extend to animals in their native environment.

Animals↗
PubMed2005

Short-term oral folic acid supplementation enhances endothelial function in patients with type 2 diabetes.

BACKGROUND: Endothelial dysfunction and arterial stiffening are commonly observed in type 2 diabetes. These abnormalities might be secondary to increased plasma concentrations of homocysteine. We sought to determine whether oral folic acid supplementation, by lowering homocysteine levels, enhanced endothelial function and reduced arterial stiffness in type 2 diabetes. METHODS: Twenty-six type 2 diabetic patients (age 56.5 +/- 0.9 years, diabetes duration 5.5 +/- 0.6 years, means +/- SEM) with no history of cardiovascular disease received 5 mg/d of oral folic acid or placebo for 4 weeks in a double-blind, randomized controlled, parallel group trial. The following parameters were measured before and after treatment: 1) endothelial function (forearm arterial blood flow during local intra-arterial administration of endothelium-dependent [acetylcholine 1.5, 4.5, and 15 microg/min] and endothelium-independent [sodium nitroprusside 1, 2, and 4 microg/min] vasodilators); and 2) carotid-radial and carotid-femoral pulse wave velocity. RESULTS: Folic acid reduced plasma homocysteine concentrations and enhanced endothelium-dependent vasodilatation during each acetylcholine infusion rate (mean and 95% confidence interval post versus pretreatment differences in forearm arterial blood flow ratio between the infused and control arm +0.19 (0.03-0.35), P < .01; +0.39 (0.02-0.81), P < .05; and +0.40 (0.09-0.89), P < .05, respectively). Endothelium-independent vasodilatation and pulse wave velocity were not affected. No significant changes in forearm arterial blood flow and pulse wave velocity were observed in the placebo group. Multiple regression analysis showed that changes in folic acid, but not homocysteine, concentrations independently described changes in maximal endothelium-dependent vasodilatation. CONCLUSIONS: Short-term oral folic acid supplementation significantly enhances endothelial function in type 2 diabetic patients, independent of homocysteine lowering.

Acetylcholine↗
PubMed2005

Targeting albumin excretion rate in the treatment of the hypertensive diabetic patient with renal disease.

Combination of an angiotensin-converting enzyme inhibitor (ACEI) with an angiotensin II receptor blocker is advocated as a treatment option in diabetic patients with nephropathy and residual albuminuria while on antihypertensive therapy. Abrogation of albuminuria is a key treatment goal to prevent disease progression. The assumption is that albuminuria reduction is the result of more complete blockade of the renin angiotensin system; thus, the ACEI-angiotensin II receptor blocker combination would have a greater albuminuria-lowering effect than the combination of an ACEI with a calcium channel blocker such as amlodipine, which causes similar reductions in BP but does not affect the renin angiotensin system. Twenty-eight patients who had type 1 diabetes and known diabetic renal disease and had a persistently elevated albumin creatinine ratio (ACR) > 10 mg/mmol despite office BP recordings < or = 140/80 mmHg on maximal recommended dose of the ACEI lisinopril were studied. Patients were allocated to receive either candesartan (16 mg/d) or amlodipine (10 mg/d) in addition to preexisting ACEI inhibition and followed for 24 wk in a randomized, double-blind, parallel-group trial. By week 24, ACR fell by 56% with candesartan and 54% with amlodipine (P < 0.01 versus baseline for both) with no significant difference between groups. Mean arterial BP fell between 3 and 6 mmHg similarly in both groups. In neither group was a significant correlation found between the change in ACR and the change in BP. Candesartan and amlodipine lowered ACR and BP by a similar degree. The fall in ACR was disproportionate to the fall of systemic BP and independent of it. The mechanism of the reduction in albuminuria seen with these agents in combination with an ACEI remains to be elucidated.

Adult↗
PubMed2005

Barriers to the equitable funding of primary healthcare in South Africa.

Over 25 years after Alma-Ata, available evidence suggests that in low- and middle-income countries (LMIC) the funding and coverage of primary care is still inequitable. This article reviews the progress that has been made towards the equitable funding of primary healthcare (PHC) in South Africa and evaluates barriers to future progress. The South African experience is assessed to consider implications for other LMIC. The results show that substantial inequities in funding persist (albeit using a narrow definition of PHC). Underlying causes relate to fiscal austerity, the lack of protection of PHC funding, incremental resource allocation and the belief that poorer districts are not able to use extra funds effectively. These results match the experience in other LMIC. Central governments have a critical role to play in lobbying for and protecting resources for PHC, maintaining more control over decentralised resource allocation and building capacity to benefit in poorer areas.

Financing, Government↗
PubMed2004

Gastric volvulus as a complication of liver transplant.

We report a patient who developed mesenteroaxial gastric volvulus after a liver transplantation. We hypothesize that this complication may have been related to the ligation of the hepatogastric ligament done to mobilize the liver during hepatectomy.

Female↗
PubMed2004

Detection and partial characterisation of two antibacterial factors from the excretions/secretions of the medicinal maggot Lucilia sericata and their activity against methicillin-resistant Staphylococcus aureus (MRSA).

Maggot therapy is a simple and highly successful method for cleansing infected and necrotic wounds. The use of maggots has become increasingly important in the treatment of non-healing wounds, particularly those infected with the multidrug-resistant pathogen, methicillin-resistant Staphylococcus aureus (MRSA). The increasing challenge concerning the treatment of MRSA infections and the recent finding of vancomycin-resistant strains of MRSA have elicited the search for novel antibacterial compounds and, in particular, investigations into the potent antibacterial mechanism(s) behind maggot therapy. In this study, we report that excretions/secretions (ES) from the blowfly, Lucilia sericata, exhibit potent, thermally stable, protease resistant antibacterial activity against MRSA in vitro. We describe the initial characterisation of two antibacterial factors from native ES of L. sericata. A small, <500 Da factor with significant antibacterial activity against MRSA was partially isolated using ultrafiltration techniques. The potent activity of this factor was comparable to that of native excretions/secretions. A larger, 0.5-3-kDa factor with significant activity against S. aureus was also partially characterised.

Animals↗
PubMed2004

Actor management in the development of health financing reform: health insurance in South Africa, 1994-1999.

Health reform is inherently political. Sound technical analysis is never enough to guarantee the adoption of policy. Financing reforms aimed at promoting equity are especially likely to challenge vested interests and produce opposition. This article reviews the Health Insurance policy development in South Africa between 1994 and 1999. Despite more than 10 years of debate, analysis and design, no set of social health insurance (SHI) proposals had, by 1999, secured adequate support to become the basis for an implementation plan. In contrast, proposals to re-regulate the health insurance industry were speedily developed and implemented at the end of this period. The processes of actor engagement and management, set against policy goals and design details, were central to this experience. Adopting a grounded approach to analysis of primary interview data and a range of documentary material, this paper explores the dynamics between reform drivers engaged in directing policy change and a range of other actors. It describes the processes by which actors were drawn into health insurance policy development, the details of their engagement with each other, and it identifies where deliberate strategies of actor management were attempted and the results for the reform process. The primary drivers of this process were the Minister of Health and the unit responsible for health financing and economics in the national Department of Health Directorate of Health Financing and Economics, with support from members of the South African academic community. These actors worked within and through a series of four ad hoc policy advisory committees which were the main fora for health insurance policy development and the regulation of private health insurance. The different experiences in each committee are reviewed and contrasted through the lens of actor management. Differences between these drivers and opposition from other actors ultimately derailed efforts to establish adequate support for any form of SHI, even as regulatory proposals received sufficient support to be enacted in legislation. Drawing on this South African experience together with a simple analytical framework, the authors highlight five potential strategies by which reform drivers of any policy process could create alliances of support sufficient to overcome potential opposition to proposed policy changes. As little is currently known on how to manage the process of engaging actors in reform processes, these findings provide a foundation for further analysis of this issue.

Government Agencies↗
PubMed2004

The virtual advisor program: linking students to mentors via the world wide web.

BACKGROUND: Emergency medicine (EM) is a popular specialty for medical students choosing a career. Many attend medical schools without an affiliated EM residency and lack both the formal mentorship and informal guidance provided by medical school advisors (or faculty) involved in an accredited EM training program. Others desire specialized advice based on geographic or specific academic interest. OBJECTIVE: The authors describe user characteristics of a Web-based virtual advisor program that paired medical students with EM faculty advisors. METHODS: Prospective users access the system from a link on the Society for Academic Emergency Medicine (SAEM) home page. On the initial visit, demographic information is collected. Faculty and student guidelines are provided. Students desiring individual advice may register for a virtual advisor who can assess career goals and qualifications. Volunteer faculty mentors are assigned on the basis of the student's geographic and demographic preferences and career aspirations. Encounters rely primarily on electronic and/or voice correspondence to suit the needs of the pair. A frequently asked question (FAQ) section provides answers to common questions and does not require registration. RESULTS: Two hundred sixty-four students (183 males, 75 females, 6 unspecified) from North American (87) and international (25) medical schools requested a virtual advisor. One hundred twenty-one faculty advisors from 56 U.S. medical schools participated (86 [71%] males; 35 [29%] females). Students indicated reasons they sought a virtual advisor. Qualitative feedback was generally positive from advisors and advisees. CONCLUSION: The implementation of the virtual advisor program enabled medical students to have access to experienced EM faculty career mentors.

Education, Medical, Undergraduate↗
PubMed2003

GLUT-1 overexpression: Link between hemodynamic and metabolic factors in glomerular injury?

Mesangial matrix deposition is the hallmark of hypertensive and diabetic glomerulopathy. At similar levels of systemic hypertension, Dahl salt-sensitive but not spontaneously hypertensive rats (SHR) develop glomerular hypertension, which is accompanied by upregulation of transforming growth factor beta1 (TGF-beta1), mesangial matrix expansion, and sclerosis. GLUT-1 is ubiquitously expressed and is the predominant glucose transporter in mesangial cells. In mesangial cells in vitro, GLUT-1 overexpression increases basal glucose transport, resulting in excess fibronectin and collagen production. TGF-beta1 has been shown to upregulate GLUT-1 expression. We demonstrated that in hypertensive Dahl salt-sensitive (S) rats fed 4% NaCl (systolic blood pressure [SBP]: 236+/-9 mm Hg), but not in similarly hypertensive SHR (SBP: 230+/-10 mm Hg) or their normotensive counterparts (Dahl S fed 0.5% NaCl, SBP: 145+/-5 mm Hg; and Wistar-Kyoto, SBP: 137+/-3 mm Hg), there was an 80% upregulation of glomerular GLUT-1 protein expression (P< or =0.03). This was accompanied by a 2.7-fold upregulation of TGF-beta1 protein expression in glomeruli of DSH compared with DSN rats (P=0.02). TGF-beta1 expression was not upregulated and did not differ in the glomeruli of Wistar-Kyoto and SHR rats. As an in vitro surrogate of the in vivo hemodynamic stress imposed by glomerular hypertension, we used mechanical stretching of human and rat mesangial cells. We found that after 33 hours of stretching, mesangial cells overexpressed GLUT-1 (40%) and showed an increase in basal glucose transport of similar magnitude (both P< or =0.01), which could be blocked with an anti TGF-beta1-neutralizing antibody. These studies suggest a novel link between hemodynamic and metabolic factors that may cooperate in inducing progressive glomerular injury in conditions characterized by glomerular hypertension.

Animals↗
PubMed2003

IGF-I induces vascular endothelial growth factor in human mesangial cells via a Src-dependent mechanism.

BACKGROUND: Both insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) have been implicated in the pathogenesis of early renal dysfunction in diabetes. We investigated whether IGF-I affects VEGF gene expression and protein secretion in human mesangial cells. Furthermore, we studied the intracellular signaling pathway involved and the interaction of IGF-I with mechanical stretch, a known VEGF inducer. METHODS: Human mesangial cells were exposed to IGF-I in the presence and in the absence of (1) anti-IGF-I type I receptor antibody (alpha IR3) (1 microg/mL), a monoclonal antibody blocking the IGF-I type I receptor; (2) wortmannin (600 nmol/L), a phosphatidylinositol 3-kinase (PI3K) inhibitor; (3) 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), a specific Src inhibitor (10 micromol/L); and (4) cyclic stretch (approximately 10% elongation). RESULTS: IGF-I induced a dose-dependent increase in VEGF protein levels (10(-11) mol/L, 5%; 10(-10) mol/L, 14%; 10(-9) mol/L, 46%; 10(-8) mol/L, 66%; 10(-7) mol/L, 68%; P < 0.001). IGF-I-induced VEGF production rose by 6 hours with a peak at 12 hours, and declined by 24 hours (52%, 72%, and 34%, respectively; P < 0.01 at 12 hours). A corresponding 50% increase in VEGF mRNA levels was seen at 6 hours (P < 0.01). IGF-I-induced VEGF protein secretion was not affected by the addition of wortmannin (IGF-I, 76% vs. IGF-I + wortmannin, 79% increase over control; P = NS), but was abolished by alpha IR3 (IGF-I, 69% vs. IGF-I +alpha IR3, 0%; P < 0.001) and significantly reduced by PP2 (IGF-I, 50% vs. IGF-I + PP2, 14%; P < 0.01). Simultaneous exposure of human mesangial cells to both IGF-I and stretch failed to further increase VEGF production (IGF-I, 1.49 +/- 0.05; stretch, 1.76 +/- 0.05; and IGF-I + stretch, 1.83 +/- 0.11). CONCLUSION: IGF-I induces VEGF gene expression and protein secretion in human mesangial cells via a Src-dependent mechanism.

Cells, Cultured↗