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Biomedical subjects

D Thomas

Publications and source records attributed to D Thomas.

At least 415 records · Page 23Linked to original sources

Stability of reamed and unreamed intramedullary tibial nails: a biomechanical study.

We examined the correlation of bone mineral density and bone strength in the cadaver tibia, and looked in vitro at the relative stability of tibial fractures fixed with either reamed or unreamed tibial nails. Bone-mineral density correlated well with bone strength (r = 0.946), but paired tibias did not correlate closely. The unreamed nail-bone construct was less stable than the reamed construct in each pair tested (P < 0.05), and a comparison of all bones showed it to be less stable at all levels of our testing regimen, including failure (P < 0.01). Bending and breakage was seen in four of the smaller unreamed interlocking screws (4 mm).

Biomechanical Phenomena↗

Buprenorphine increases intake of freely available and operant-contingent food in satiated rats.

Opiate administration increases short-term free feeding in satiated rats. The feeding effects of the mixed opioid receptor agonist/antagonist buprenorphine were examined in both free-feeding and operant chamber paradigms. Buprenorphine (0.1 and 0.3 mg/kg) produced significant increases in short-term free feeding (i.e., 4 h), an effect enhanced by repeated administration. Buprenorphine's effects on operant responding were examined in satiated rats using a fixed ratio (FR) 80 (initial pellet) FR 3 (subsequent pellets) reinforcement schedule. Buprenorphine (0.03-0.3 mg/kg) decreased latency to begin responding for food, and increased total number of pellets consumed in a 1-h session. Increases in food intake relative to control were caused by continued responding for food as sessions progressed. Naloxone suppressed both the free-feeding and operant-contingent intake induced by buprenorphine. Thus, buprenorphine increases both freely available and lever-press contingent food intake.

Animals↗

Screening for colorectal cancer: what are the costs?

We examined a screening program for colorectal cancer in South Australia in terms of its overall direct costs to society and costs to participants. The best estimate of the cost per cancer detected was $18,924 (Australian dollars). Potential improvements in health outcome through screening are discussed in light of these costs.

Colorectal Neoplasms↗

Expression of retinoblastoma gene product and p53 protein in bladder carcinoma: correlation with Ki67 index.

OBJECTIVES: To determine whether loss of the tumour suppressor gene retinoblastoma (Rb) and increased expression of the p53 protein were associated with increased tumour cell growth fraction. PATIENTS AND METHODS: Tumours from 105 patients (72 men, 33 women; median age 69 years, range 35-89) with newly diagnosed primary transitional cell bladder carcinoma were studied. Tumour samples were taken by means of cystoscopic resection. Expression of the retinoblastoma (Rb) and p53 gene products was assessed immunohistochemically in 98 of the carcinomas. The proportion of cells expressing the Ki67 antigen (Ki67 index which is a measure of growth fraction) was determined in 64 cases. RESULTS: p53 protein was detectable in 50% and Rb protein in 82% of the tumours. Staining for p53 and lack of staining for Rb protein were associated with muscle-invasive growth and high tumour grade (G3). The Ki67 index varied over a wide range (1-47%), but there were significant differences between mean indices for poorly differentiated (G3) and well or moderately differentiated (G1/G2) tumours, and between indices for muscle-invasive and the remaining tumours. The mean Ki67 indices for Rb-negative tumours and p53-positive tumours were approximately twice those for Rb-positive and p53-negative tumours. Only 10% of the tumours expressed high levels of p53 protein and failed to express Rb. CONCLUSION: These observations are consistent with the hypothesis that loss of Rb and mutation and overexpression of p53 are associated with an increased tumour cell growth fraction and that such changes may play a role in the de-regulation of cell proliferation in transitional cell carcinoma of the bladder.

Adult↗

Activity of synchronized cells of a steady-state biofilm recirculated reactor during xenobiotic biodegradation.

The maintenance of a steady-state biofilm in a continuous-flow fixed-bed reactor, as a consequence of the reproduction-detachment of cells (an interfacial cell physiology phenomenon of steady-state biofilm) during the biodegradation of 2,4,6-trichlorophenol by Pseudomonas cells, was determined. After cell adhesion on an open-pore glass support, the biofilm was formed in a packed-bed recirculated reactor. After the steady-state biofilm was reached, the mechanisms of the interfacial cell detachment (at the biofilm-liquid interface) were determined. It was established that (i) the hydrophobicity of immobilized sessile cells (parent cells) increased (from 50 to 80%) as the dilution rate increased, while the hydrophobicity of detached suspended cells (daughter cells) remained constant (about 45%); and (ii) the immediately detached suspended cells showed a synchronized growth in about three generations. These results indicate that (i) the immobilized sessile and suspended detached cells grew synchronically at the end and at the beginning of the cell cycle, respectively; and (ii) the hydrophobicity difference of immobilized sessile and suspended detached cells permitted the cells detachment. Therefore, it is probable that independent of shear stress (due to recirculated flow), the synchronized growth and hydrophobicity of cells (which vary during the cell cycle) are the main factors permitting the maintenance of a steady-state xenobiotic-degrading biofilm reactor (in which the overall accumulation of biofilm is determined by the average growth rate of the biofilm cells minus the rate of detachment of cells from the biofilm).

Bacterial Adhesion↗

Functional analysis of Met4, a yeast transcriptional activator responsive to S-adenosylmethionine.

Transcription of the genes necessary for sulfur amino acid biosynthesis in Saccharomyces cerevisiae is dependent on Met4, a transcriptional activator that belongs to the basic region-leucine zipper protein family. In this report, we show that one mechanism permitting the repression of the sulfur network by S-adenosylmethionine (AdoMet) involves inhibition of the transcriptional activation function of Met4. Using a wide array of deleted LexA-Met4 fusion proteins as well as various Gal4-Met4 hybrids, we identify the functional domains of Met4 and characterize their relationship. Met4 appears to contain only one activation domain, located in its N-terminal part. We demonstrate that this activation domain functions in a constitutive manner and that AdoMet responsiveness requires a distinct region of Met4. Furthermore, we show that when fused to a heterologous activation domain, this inhibitory region confers inhibition by AdoMet. Met4 contains another distinct functional domain that appears to function as an antagonist of the inhibitory region when intracellular AdoMet is low. On the basis of the presented results, a model for intramolecular regulation of Met4 is proposed.

Basic-Leucine Zipper Transcription Factors↗

Met30p, a yeast transcriptional inhibitor that responds to S-adenosylmethionine, is an essential protein with WD40 repeats.

A specific repression mechanism regulates the biosynthesis of sulfur amino acids in Saccharomyces cerevisiae. When the intracellular S-adenosylmethionine (AdoMet) concentration increases, transcription of the sulfur genes is repressed. Using a specific reporter system, we have isolated mutations impairing the AdoMet-mediated transcriptional regulation of the sulfur network. These mutations identified a new gene, MET30, and were shown to also affect the regulation of the methyl cycle. The MET30 gene was isolated and sequenced. Sequence analysis reveals that Met30p contains five copies of the WD40 motif within its carboxy-terminal part, like the yeast transcriptional repressors Hir1p and Tup1p. We identified one target of Met30p as Met4p, a transcriptional activator regulating the sulfate assimilation pathway. By the two-hybrid method, we showed that Met30p interacts with Met4p and identified a region of Met4p involved in this interaction. Further analysis reveals that expression of Met30p is essential for cell viability.

Amino Acid Sequence↗

Inducible nuclear expression of newly synthesized I kappa B alpha negatively regulates DNA-binding and transcriptional activities of NF-kappa B.

The transcription factor NF-kappa B is exploited by many viruses, including the human immunodeficiency virus, for expression of viral genes, but its primary role appears to be in the rapid induction of cellular genes during immune and inflammatory responses. The inhibitor protein I kappa B alpha maintains NF-kappa B in an inactive form in the cytoplasms of unstimulated cells, but upon cell activation, I kappa B alpha is rapidly degraded, leading to nuclear translocation of free NF-kappa B. However, NF-kappa B-dependent transcription of the I kappa B alpha gene leads to rapid resynthesis of the I kappa B alpha protein and inhibition of NF-kappa B-dependent transcription. Here we demonstrate a new regulatory function of I kappa B alpha exerted on NF-kappa B in the nuclear compartment. Although normally found in the cytoplasm, I kappa B alpha, newly synthesized in response to tumor necrosis factor or interleukin I, is transported to the nucleus. In the nucleus I kappa B alpha associates with the p50 and p65 subunits of NF-kappa B, inhibiting DNA binding of the transcription factor. Furthermore, nuclear expression of I kappa B alpha correlates with transcription termination of transfected NF-kappa B-dependent luciferase genes. Following the appearance of I kappa B alpha in the nuclei of activated cells, a dramatic reduction in the amount of nuclear p50 occurs, suggesting that NF-kappa B-I kappa B alpha complexes are cleared from the nucleus.

Cell Nucleus↗

Addressing the inevitable conflicts in reforming teacher education: one department's story.

Embracing a transformative philosophy of special education teacher education, the Department of Special Education at the University of South Florida has undergone significant change over the past several years. Perspectives on the foundational knowledge for this change and the values guiding its realization are shared in this article. Dilemmas arising from the encounter between traditional practice and emerging views are described, along with approaches aimed at understanding and addressing these conflicts.

Child↗

The demand for primary dental care at a dental teaching hospital, 1989 and 1993.

The demand for, and provision of, primary dental care was investigated in a teaching hospital setting in 1989 and 1993 - a period which saw the introduction of the new dental contract and the publication of the Poswillo report on general anaesthesia and sedation. Five hundred patients who attended the primary care department for the first time at the University of Wales Dental Hospital were interviewed in May/June 1989, and a further 520 patients were interviewed in May/June 1993. Self-referrals increased from 260 patients (52%) in 1989 to 352 patients (68%) in 1993. The proportion of patients who did not have a general dental practitioner (GDP) increased from 32% (160) in 1989 to 39% (202) in 1993. More patients registered with a dentist self-referred in 1993 compared to those in 1989, reportedly because of inability to obtain an appointment with their own GDP (88), rather than because of cost (17). Over the four-year period there was an increase in demand for treatment of early stage (pulpitic) dental infection from 32% to 40%, and a decrease in relation to end-stage infection (dentoalveolar abscess) from 11% to 6%. This 'safety net' role of dental hospitals needs to be taken into account when contracting for services.

Adolescent↗

[Coronary restenosis: the cardiologist facing problems of definitions].

Many angiographic definitions have been proposed to define restenosis after coronary angioplasty. The utility of each remains poorly defined. The aims of this study were: a) to analyse groups of patients defined by each of three criteria: > 50% stenosis (definition 1), loss > or = 50% of initial gain in diameter (definition 2), loss > or = 0.52 mm of minimal luminal diameter based on the variability of the angiographic measurement (definition 3) and, b) to compare the immediate attitude of the interventional cardiologist with the deferred quantitative angiographic analysis. The angiographic follow-up included 89 patients. The angiographic restenosis rate was 37% (definition 1), 48% (definition 2) and 43% (definition 3). Restenosis as defined by criterion 1 was associated with the greatest degree of postangioplasty residual stenosis (p = 0.02) whereas, with criteria 2 and 3, it was associated with less severe residual stenosis (p = 0.03 and p = 0.007). Definition 2 and 3 are the most similar and definitions 1 and 3 the most complementary. The sensitivity, specificity positive and negative predictive values for recurrence of angina with respect to angiographic restenosis (definition 1) were respectively 63.6%, 77.8%, 63.6%, and 77.8% and are not significantly improved by associated analysis of exercise testing. Discordances between the decision of the interventional cardiologist and the results of quantitative angiography (definition 1) were noted in 12.4% of the stenosis studied, there measuring 44 to 64%. The judgement of the cathetiser of these intermediary stenoses was essentially influenced by the recurrence of angina during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗

Enhancement of clinician workflow with computer order entry.

Physician-operated order entry systems can bring great benefits to an institution. Such systems can improve the consistency, accuracy, safety, and cost-effectiveness of orders. When building or selecting order entry for an institution, consideration must be given to the many different scenarios in which orders are written and communicated. Transfer, post-op, pre-admission and discharge orders have different communication requirements from standard inpatient orders. In certain services, orders from a very limited set (such as warfarin orders) must be written frequently for a large number of patients. Intensive-care patients, chemotherapy patients, and others have particular requirements for ordering. A computerized order entry system should respond to these requirements in order to promote correct and efficient ordering. We present a number of these issues, their specific requirements, and the approach we have taken to ensure that the system both supports and enhances workflow.

Clinical Pharmacy Information Systems↗

[What dose of aspirin should be prescribed in patients with coronary disease?].

Aspirin is prescribed in almost all coronary patients. However, the prescription modalities tend to vary, partly because of the absence of phase II development of this molecule as an antithrombotic agent in coronary patients. The dose of 162.5 mg has been shown to be effective during the acute phase of myocardial infarction, but we do not know whether this is the most effective dose. A higher dose, in particular 500 mg to 1 g, would have the advantage of more rapidly and more completely blocking platelets during an acute thrombotic phase. After this first high dose, lower doses, less than 100 mg, could be administered in the long term. These low doses of aspirin, generally 75 mg, have been demonstrated, in stable angina, to decrease infarction and sudden death by more than 30%. This dose has also been demonstrated to be effective in the long-term in unstable angina, but once again this low dose should be introduced after an initial higher dose for this acute coronary syndrome. A primary prevention study is currently underway using the dose of 75 mg per day following the trial in American physicians using a dose of 320 mg every second day. Long-term low doses have a clearly demonstrated efficacy in chronic prevention and have the advantage of inducing much fewer adverse effects, particularly gastrointestinal haemorrhage. In conclusion, a high initial dose should be recommended in acute coronary syndromes and a low dose, less than 100 mg, should be recommended for chronic prevention. Buffered forms, protecting the stomach, and sustained-release forms are impatiently awaited to further improve the benefit/risk ratio of aspirin, which is nevertheless already excellent.

Aspirin↗

[Indium III monoclonal antimyosin antibody scintigraphy for the detection of chronic myocardial infarction apart from the acute phase].

Fab antimyosin scintigraphy has been shown to be sensitive and specific in detecting acute myocardial necrosis. This study was designed to evaluate the preoperative frequency of Indium-111 (In-111) antimyosin myocardial uptake in patients scheduled for coronary artery bypass surgery. The scintigraphic results were compared with other criteria of myocardial infarction (MI). Sixteen consecutive patients were included. Recent MI (1 to 3 months) were detected in four patients, with an accurate localization in three cases when compared to the classic criteria for MI. Two more patients had old Q wave MI: one did not show any uptake in the territory of MI whereas the second patient with a 21 year old infarct without recent acute coronary events showed an intense uptake consistent with the ECG and angiographic localization. Four other patients with stable angina showed limited uptakes that were unexpected, since there were no acute coronary events in their medical history, and ECG. Their left ventricle angiography were considered as normal. In these four cases, the scintigraphic location corresponded to a territory supplied by an occluded coronary artery (n = 2) or by a coronary artery with a tight stenosis requiring a bypass graft (n = 2). These antimyosin uptakes are probably related to small necroses which did not modify the ECG and did not alter the ventricular segmental wall motion. We conclude: 1) recent MI are detected by In-111 antimyosin scintigraphy; 2) In-111 antimyosin uptake may occur in patients without a diagnosis of recent myocardial infarction and correspond to older MI or limited necroses without detectable changes of the ECG and left ventricle angiography.

Aged↗

Endothelin-1 in patients with coronary heart disease undergoing cardiac catheterization.

OBJECTIVES: This study examined the possible association between endothelin and coronary atherosclerosis and evaluated the synthesis and release of endothelin in the presence of various stimuli that occur during cardiac catheterization. BACKGROUND: Circulating endothelin has been reported to be increased in diffuse atherosclerosis and acute myocardial infarction. However, the relation between coronary artery disease and endothelin release remains unclear. METHODS: We measured the plasma and urinary concentrations of endothelin immunoreactivity in 45 patients and 10 healthy control subjects. RESULTS: In group IA (n = 9), simultaneous blood sampling in the coronary sinus and femoral artery during coronary angioplasty of the left anterior descending coronary artery demonstrated no immediate changes in plasma immunoreactive endothelin-1 (ir-ET-1) levels. In 11 patients in group IB undergoing coronary angioplasty of a major artery, we did not detect changes in peripheral plasma concentrations of ir-ET-1 within 24 h, but urinary ir-ET-1 levels increased from 9.2 +/- 2.3 to 18.6 +/- 4.9 pg/mg of creatinine a few hours after coronary angioplasty (mean +/- SEM, p < 0.05). This increase in urinary endothelin excretion persisted 24 h later. Group II patients (n = 12) had coronary angiography without coronary angioplasty. Levels of both plasma and urinary ir-ET-1 did not change during the 24-h follow-up period. There was no relation between the severity of coronary atherosclerosis and the plasma or urinary concentrations of ir-ET-1. Systolic aortic pressure correlated with basal urinary excretion of endothelin (r = 0.54, p = 0.03, n = 15). In group III (n = 13), levels of ir-ET-1 in patients undergoing right heart catheterization without angiography did not differ from those in the control group. CONCLUSIONS: The presence or the severity, or both, of coronary atherosclerosis is not associated with a detectable increase in endothelin release. The diagnostic procedures of catheterization do not modify endothelin concentrations in plasma and urine. Vascular stretch or injury, or both, during coronary angioplasty increases urinary ir-ET-1 levels a few hours after the procedure. This increase persists for at least 24 h but is not detectable by brief sampling of peripheral or coronary sinus blood.

Angioplasty, Balloon, Coronary↗