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Biomedical subjects

Christopher A Smith

Publications and source records attributed to Christopher A Smith.

9 recordsLinked to original sources
PubMed2006

Comparison of protective effects of aspirin, D-penicillamine and vitamin E against high glucose-mediated toxicity in cultured endothelial cells.

This study compared the protective effects of three different anti-glycation compounds, aspirin, D-penicillamine and vitamin E, against high glucose and advanced glycation endproduct (AGE) mediated toxicity in cultured bovine aortic endothelial cells using two approaches. Their proliferation was assessed in culture in different concentrations of glucose (5.5-100 mmol/l) with and without these inhibitors. A monolayer of cultured endothelial cells was wounded and recovery at the wound site was measured following exposure to different concentrations of glucose with and without inhibitors. The ability of these compounds to protect cultured endothelial cells following exposure to bovine serum albumin-derived advanced glycation endproducts (BSA-AGE) was also studied. Addition of glucose to cultured endothelial cells inhibited their proliferation in a dose dependent manner. All three compounds protected against the anti-proliferative effects of high glucose, with vitamin E being the most effective. The migration of cultured endothelial cells following wounding was inhibited by increasing concentrations of glucose but was maintained in the presence of all three anti-glycation compounds with vitamin E, again giving the greatest protection. Vitamin E was also the most effective at protecting against the anti-proliferative effects of BSA-AGE. D-penicillamine was not as effective as vitamin E whereas aspirin offered no significant protection against AGE-induced cellular toxicity. Our studies suggest that compounds, such as vitamin E, with combined antiglycation and antioxidant properties offer maximum therapeutic potential in protection against high glucose and AGE-mediated cellular toxicity.

Animals↗
PubMed2006

Teaching cardiac examination skills. A controlled trial of two methods.

OBJECTIVE: To determine if structured teaching of bedside cardiac examination skills improves medical residents' examination technique and their identification of key clinical findings. DESIGN: Firm-based single-blinded controlled trial. SETTING: Inpatient service at a university-affiliated public teaching hospital. PARTICIPANTS: Eighty Internal Medicine residents. METHODS: The study assessed 2 intervention groups that received 3-hour bedside teaching sessions during their 4-week rotation using either: (1) a traditional teaching method, "demonstration and practice" (DP) (n=26) or (2) an innovative method, "collaborative discovery" (CD) (n=24). The control group received their usual ward teaching sessions (n=25). The main outcome measures were scores on examination technique and correct identification of key clinical findings on an objective structured clinical examination (OSCE). RESULTS: All 3 groups had similar scores for both their examination technique and identification of key findings in the preintervention OSCE. After teaching, both intervention groups significantly improved their technical examination skills compared with the control group. The increase was 10% (95% confidence interval [CI] 4% to 17%) for CD versus control and 12% (95% CI 6% to 19%) for DP versus control (both P<.005) equivalent to an additional 3 to 4 examination skills being correctly performed. Improvement in key findings was limited to a 5% (95% CI 2% to 9%) increase for the CD teaching method, CD versus control P=.046, equivalent to the identification of an additional 2 key clinical findings. CONCLUSIONS: Both programs of bedside teaching increase the technical examination skills of residents but improvements in the identification of key clinical findings were modest and only demonstrated with a new method of teaching.

Cardiology↗
PubMed2005

Understanding the new human genetics: a review of scientific editorials.

Developments in genetics are expected to have a profound impact on health and health care, yet much remains to be learned about how leaders of the research and clinical communities view and frame these expectations. We conducted a comprehensive review of editorials about developments in genetic medicine published in scientific journals, to understand what this elite group of commentators anticipate. Editorials are an important resource for understanding how the new genetics is understood and portrayed. They allow leaders of the research and clinical communities to communicate to each other and informed publics, and are a forum for the expression of widely shared elite beliefs and opinions. We analyzed selected editorials for content and metaphoric language to explore attitudes and expectations concerning developments in genetic science and technology. Our analysis suggests that a diverse group of leaders of the research and clinical communities are remarkably uniform in their discourse about the future of genetic medicine. Editorialists have great expectations for developments in basic science and in the comprehension and management of disease. They also anticipate important effects on health care, notably the health care professions, and on wider society. Yet editorialists do not discuss these prospects in a consistently positive or optimistic manner, and they utilize metaphoric imagery that emphasizes the inexorable nature of progress, and the sometimes ominous manner in which developments emerge. The dominant discourse of editorialists claims authority for clinicians and researchers and asserts a broad sphere of expertise, but it also positions these leaders as handmaidens of a science they do not control, and insists that their ultimate contribution is to prepare themselves and others for the inexorable march of progress.

Genetics, Medical↗
PubMed2004

Dental pulp cells provide neurotrophic support for dopaminergic neurons and differentiate into neurons in vitro; implications for tissue engineering and repair in the nervous system.

Glial cell line-derived neurotrophic factor (GDNF) mRNA is highly expressed by dental pulp cells (DPCs) prior to the initiation of dental pulp innervation. We show that radioactively labelled exogenous GDNF is retrogradely transported from neonatal teeth and vibrissae to the trigeminal neurons, indicating that GDNF acts as a classical neurotrophic factor in the trigeminal system. We also show that DPCs from both rats and humans produce nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and GDNF mRNAs in vitro, promote the survival and phenotypic characteristics of embryonic dopaminergic (DA) neurons and protect DA neurons against the neurotoxin 6-hydroxy-dopamine (6-OHDA) in vitro. By using inhibitory antibodies to NGF, BDNF and GDNF, we show that the promotion of DA neuron survival relates to the production and release of neurotrophic proteins by DPCs in vitro. We suggest that in vivo production of neurotrophic factors by DPCs play roles in tooth innervation. However, continued production of neurotrophic factors by the DPCs might have wider implications. We propose that the dental pulp is a viable source of easily attainable cells with possible potential for development of autologous cell transplantation therapies. We also show that a population of neural crest-derived dental pulp cells acquire clear neuronal morphology and protein expression profile in vitro, indicating the presence of a cell population in the dental pulp with neuronal differentiation capacity that might provide additional benefits when grafted into the CNS.

Adolescent↗
PubMed2004

Evaluating the performance of inpatient attending physicians: a new instrument for today's teaching hospitals.

OBJECTIVE: Instruments available to evaluate attending physicians fail to address their diverse roles and responsibilities in current inpatient practice. We developed a new instrument to evaluate attending physicians on medical inpatient services and tested its reliability and validity. DESIGN: Analysis of 731 evaluations of 99 attending physicians over a 1-year period. SETTING: Internal medicine residency program at a university-affiliated public teaching hospital. PARTICIPANTS: All medical residents (N= 145) and internal medicine attending physicians (N= 99) on inpatient ward rotations for the study period. MEASUREMENTS: A 32-item questionnaire assessed attending physician performance in 9 domains: evidence-based medicine, bedside teaching, clinical reasoning, patient-based teaching, teaching sessions, patient care, rounding, professionalism, and feedback. A summary score was calculated by averaging scores on all items. RESULTS: Eighty-five percent of eligible evaluations were completed and analyzed. Internal consistency among items in the summary score was 0.95 (Cronbach's alpha). Interrater reliability, using an average of 8 evaluations, was 0.87. The instrument discriminated among attending physicians with statistically significant differences on mean summary score and all 9 domain-specific mean scores (all comparisons, P <.001). The summary score predicted winners of faculty teaching awards (odds ratio [OR], 17; 95% confidence interval [CI], 8 to 36) and was strongly correlated with residents' desire to work with the attending again (r =.79; 95% CI, 0.74 to 0.83). The single item that best predicted the summary score was how frequently the physician made explicit his or her clinical reasoning in making medical decisions (r(2)=.90). CONCLUSION: The new instrument provides a reliable and valid method to evaluate the performance of inpatient teaching attending physicians.

Clinical Competence↗
PubMed2004

The impact of evidence on physicians' inpatient treatment decisions.

OBJECTIVE: Previous studies have shown that most medical inpatients receive treatment supported by strong evidence (evidence-based treatment), but they have not assessed whether and how physicians actually use evidence when making their treatment decisions. We investigated whether physicians would change inpatient treatment if presented with the results of a literature search. DESIGN: Before-after study. SETTING: Large public teaching hospital. PARTICIPANTS: Random sample of 146 inpatients cared for by 33 internal medicine attending physicians. INTERVENTIONS: After physicians committed to a specific diagnosis and treatment plan, investigators performed standardized literature searches and provided the search results to the attending physicians. MEASUREMENTS AND MAIN RESULTS: The primary study outcome was the number of patients whose attending physicians would change treatment due to the literature searches. These changes were evaluated by blinded peer review. A secondary outcome was the proportion of patients who received evidence-based treatment before and after the literature searches. Attending physicians changed treatment for 23 (18%) of 130 eligible patients (95% confidence interval, 12% to 24%) as a result of the literature searches. Overall, 86% of patients (112 of 130) received evidence-based treatments before the searches and 87% (113 of 130) after the searches. Changes were not related to whether patients were receiving evidence-based treatment before the search (P =.6). Panels of peer reviewers judged the quality of patient care as improved or maintained for 18 (78%) of the 23 patients with treatment changes. CONCLUSIONS: Searching the literature could improve the treatment of many medical inpatients, including those already receiving evidence-based treatment.

Adult↗
PubMed2003

Aminosalicylic acid reduces the antiproliferative effect of hyperglycaemia, advanced glycation endproducts and glycated basic fibroblast growth factor in cultured bovine aortic endothelial cells: comparison with aminoguanidine.

Hyperglycaemia reduces proliferation of bovine aortic endothelial cells in vitro. A similar effect in vivo may contribute to long-term complications of diabetes such as impaired wound-healing and retinopathy. We report the effect of increased glucose concentrations, glycated basic fibroblast growth factor (FGF-2) and bovine serum albumin-derived advanced glycation endproducts (BSA-AGE) on the proliferation of bovine aortic endothelial cells. Glucose (30 and 50 mmol/l) had an antiproliferative effect on endothelial cells. This effect may be mediated through reduced mitogenic activity of FGF-2. The glycation of FGF-2 with 250 mmol/l glucose-6-phosphate led to reduced mitogenic activity compared to native FGF-2. BSA-AGE at concentrations of 10, 50 and 250 microg/ml had an antiproliferative effect on cultured endothelial cells. Aminosalicylic acid at a concentration of 200 micromol/l proved to be more effective than equimolar concentrations of aminoguanidine in protecting endothelial cells against the antiproliferative effects of both high (30 mmol/l) glucose and 50 microg/ml BSA-AGE. FGF-2 glycated in the presence of 4 mmol/l aminosalicylic acid or aminoguanidine retained mitogenic activity compared to that glycated in their absence. Compounds like aminoguanidine and, in particular, aminosalicylic acid protect endothelial cells against glucose-mediated toxicity and may therefore have therapeutic potential.

Aminosalicylic Acids↗
PubMed1995

Evolution of the korA-oriV segment of promiscuous IncP plasmids.

Plasmids belonging to Escherichia coli incompatibility group P are of particular interest because they can transfer between, and be stably maintained in, almost all Gram-negative bacterial species. The segment of the IncP alpha plasmid genome between the key regulatory gene korA and the vegetative replication origin, oriV, encodes a series of operons co-regulated with replication and transfer functions by the KorA protein. To determine which of these genes are likely to have an important role in IncP plasmid survival the equivalent region of the distantly related IncP beta plasmid R751 was sequenced. Sequence comparisons show that the kla operon (formerly the kilA locus, which is also responsible for a cryptic tellurite-resistance determinant) is completely absent from R751. Similarly in the kle region, which encodes genes associated with the KilE+ phenotype of unknown function, kleC and kleD, which we proposed arose by a duplication of kleA and kleB, are also completely absent. The genes that are conserved are klcA (formerly kilC, responsible for the KilC+, and recently proposed to be involved in overcoming restriction barriers during transfer), klcB (an ORF interrupted by Tn1 insertion in RK2), korC (a transcriptional repressor which controls the klcK and kle operons), and kleA, kleB, kleE and kleF. A striking feature of the organization in R751 is the lack of the strong transcriptional termination signals which are present in IncP alpha plasmids. The degree of divergence between the plasmids facilitates the identification of motifs of probable functional importance in the primary protein sequences.

Amino Acid Sequence↗