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Biomedical subjects

D Vaughan

Publications and source records attributed to D Vaughan.

At least 19 recordsLinked to original sources

Surface characterization of precious alloys treated with thione metal primers.

OBJECTIVES: To characterize the effect of two thione metal primers with phosphate groups on the surface morphology and composition of two noble prosthodontic alloys. METHODS: Cast specimens from Argen 81(Au-Pd) and Argipal (Hi-Pd) alloys which were ground, polished and ultrasonicated in water, were divided in two groups (2 x 3) and treated with single layers of Alloy Primer (AP) and Metal Primer II (MP) primers respectively. The treated alloy surfaces were washed off with acetone and then examined by polarized light microscopy (PLM), reflection FTIR microspectroscopy (FTIRM) and X-ray photoelectron spectroscopy (XPS). RESULTS: After AP treatment, PLM revealed a crystalline phase (VBATDT) dispersed in an amorphous phase (MDP plus soluble VBATDT) on both the alloys tested. MP demonstrated a fibrial arrangement with the most dense structure found on the Hi-Pd alloy. FTIRM failed to clearly resolve the presence of SH peaks on alloy surfaces. Moreover, NH and PS peaks were identified denoting the presence of original thione tautomers. In both primers, phosphates were detected in a dissociative state (-PO(3)(2-)). FTIR molecular mapping confirmed separation of VBATDT from MDP and MEPS from residual MMA. XPS showed that on alloy surfaces approximately 50% of sulphur was in the sulphide state, the rest being organic sulphur. AP showed higher sulphide percentage than MP on both alloys and higher sulphide percentage on the Au-Pd alloy (p<0.05). CLINICAL SIGNIFICANCE: Phase separation of the primer components on alloy surfaces may adversely affect their clinical performance. Sulphide formation on alloy surfaces was confirmed only by XPS under ultra-high vacuum and not by environmental techniques like FTIR; this poses serious questions on the chemical bonding capacity of these primers with the noble alloys tested under environmental conditions.

Crystallization↗

A new guide to mandibular resection for oral squamous cell carcinoma based on the Cawood and Howell classification of the mandible.

A new guide for mandibular resection in the management of oral squamous cell carcinoma based on the Cawood and Howell classification of the jaws is suggested. This was a retrospective review of case records and pre-operative orthopantomograms (OPG), bone scintigraphy and magnetic resonance imaging (MRI). The classification of the mandible was based on the residual bone height as measured in the molar region of the OPG to be equivalent to the Cawood and Howell classification of the mandible (Class I-II dentate or immediate post-extraction), Class III-IV >20mm well-rounded or knife-edge ridge, and Class V-VI <20mm (flat or depressed ridge form). Of the 77 patients, 58% (22/38) of Class I-II, 43% (9/23) of Class III-IV and 6% (1/16) of Class V-VI were treated with a marginal (rim) resection of the mandible. The predictability of the pre-operative investigations was more accurate in the edentulous mandible (Class III-VI). A simple guide is suggested for mandibular resection taking into account the pre-operative investigations, the estimation of invasion clinically, and the Cawood and Howell classification of ridge resorption.

Adult↗

Fear of recurrence and possible cases of anxiety and depression in orofacial cancer patients.

Recurrence risk in orofacial cancer patients is relatively high in comparison to other cancers. Little information exists on whether patients are unduly concerned over the possibility of recurrence and the association of this concern with psychological morbidity. Aim of study was to assess fear of recurrence and psychological morbidity in orofacial cancer patients. Two samples of patients with orofacial cancer were followed prospectively. First sample (n = 87) were consecutively drawn 3 months and 7 months following initial treatment. Second sample (n = 100) were cross-sectionally drawn from out-patient list and followed 2 years later. A single question item was employed to assess fear of recurrence used in previous work. Hospital Anxiety and Depression Scale was adopted as the measure of psychological morbidity. A prospective survey design was employed. Over 80% of patients expressed concern over the possibility of recurrence at 3 months post treatment. This level reduced to 72% at 7 months (P=0.06). Approximately two-thirds of patients sampled cross-sectionally were concerned at both assessment occasions. Psychological morbidity was greatest at 3 months post treatment (possible cases: anxiety 37% and depression 28%). Women were more likely to report anxiety (at possible case level) than men 3 months following treatment (P<0.05). Patients aged 65 or more years were less concerned about recurrence. This effect was significant on both occasions that sample two patients were assessed (P's<0.002). Very few patients who expressed no concern about recurrence, at 3 months, were found to report anxiety or depression sufficient to be recognized as a possible case (3 and 0% respectively). The positive association between psychological morbidity and fears of recurrence was significant at the majority of data collection points, with the exception that depression was more independent of these concerns.

Age Factors↗

Long-term (7 to 8-year) experience with finasteride in men with benign prostatic hyperplasia.

OBJECTIVES: To evaluate the effects of finasteride, a specific type II 5-alpha-reductase inhibitor, on symptoms of benign prostatic hyperplasia, prostate volume, and urinary flow during a 7 to 8-year period. METHODS: A total of 190 men with symptomatic benign prostatic hyperplasia and enlarged prostates entered one of two Phase II double-blind 3 to 6-month studies. Of these, 156 patients continued taking open-label finasteride, and more than 70 patients completed 7 to 8 years of treatment. The symptoms were scored using a patient self-administered modified Boyarsky symptom questionnaire. Prostate volume was measured by magnetic resonance imaging or ultrasonography, and the maximal urinary flow rate was assessed noninvasively. RESULTS: Treatment with finasteride for 7 to 8 years led to sustained improvement in symptoms, reduction in prostate volume (28% from baseline), and increased urinary flow (median 2.5 mL/s from baseline). Decreases in dihydrotestosterone (86%) and prostate-specific antigen (54%) levels were also maintained. Long-term finasteride treatment was safe and generally well tolerated. CONCLUSIONS: Long-term treatment with finasteride was well tolerated and resulted in durable symptom relief and improvement in prostate volume and urinary flow.

Adult↗

The relevance of tissue angiotensin-converting enzyme: manifestations in mechanistic and endpoint data.

Angiotensin-converting enzyme (ACE) is primarily localized (>90%) in various tissues and organs, most notably on the endothelium but also within parenchyma and inflammatory cells. Tissue ACE is now recognized as a key factor in cardiovascular and renal diseases. Endothelial dysfunction, in response to a number of risk factors or injury such as hypertension, diabetes mellitus, hypercholesteremia, and cigarette smoking, disrupts the balance of vasodilation and vasoconstriction, vascular smooth muscle cell growth, the inflammatory and oxidative state of the vessel wall, and is associated with activation of tissue ACE. Pathologic activation of local ACE can have deleterious effects on the heart, vasculature, and the kidneys. The imbalance resulting from increased local formation of angiotensin II and increased bradykinin degradation favors cardiovascular disease. Indeed, ACE inhibitors effectively reduce high blood pressure and exert cardio- and renoprotective actions. Recent evidence suggests that a principal target of ACE inhibitor action is at the tissue sites. Pharmacokinetic properties of various ACE inhibitors indicate that there are differences in their binding characteristics for tissue ACE. Clinical studies comparing the effects of antihypertensives (especially ACE inhibitors) on endothelial function suggest differences. More comparative experimental and clinical studies should address the significance of these drug differences and their impact on clinical events.

Angiotensin-Converting Enzyme Inhibitors↗

Susceptibility of Canadian isolates of Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae to oral antimicrobial agents.

We measured the susceptibility of Canadian isolates of three respiratory tract pathogens (Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae) to several currently approved antimicrobial agents by two different methods. We also measured the susceptibility of isolates to seven fluoroquinolones. Beta-lactamase was produced by 123/566 (21.7%) of H. influenzae isolates compared with 178/200 (89%) of M. catarrhalis isolates. For S. pneumoniae 83/374 (22.2%) isolates were penicillin resistant and of these 2.1% (8/374) showed high level resistance (MIC > or = 2 mg/l). Regardless of methodology, all fluoroquinolones were highly active against H. influenzae (MIC(90) < or = 0.031 mg/l) and M. catarrhalis (MIC(90) < or = 0.064 mg/l) isolates. Susceptibility of H. influenzae to cefuroxime and amoxycillin/clavulanic acid was 99-100% whereas 84-85.5% were susceptible to cefaclor and cefprozil. Azithromycin susceptibility ranged from 82.6 to 99.2% depending on the method. M. catarrhalis isolates were uniformly susceptible to all agents tested except amoxycillin. Cross-resistance in S. pneumoniae to all non-quinolone agents was concurrent with increasing penicillin resistance as shown by increasing MIC90 values. For the fluoroquinolones tested, the rank order of potency based on MIC(90) values was as follows: gemifloxacin (0.031-0.063 mg/l), trovafloxacin (0.125 mg/l), moxifloxacin (0.125-0.25 mg/l), grepafloxacin (0.125-0.25 mg/l), gatifloxacin (0.5 mg/l), levofloxacin (1 mg/l) and ciprofloxacin (2 mg/l). Our study confirms either a high or increasing prevalence of antimicrobial resistant respiratory pathogens in Canada and also compares the new and old fluoroquinolones and their potential role as therapy for community-acquired infections. The prevalence of beta-lactamase positive H. influenzae may have decreased from levels reported in previous studies.

Administration, Oral↗

The effects of local administration of lactoferrin on inflammation in murine autoimmune and infectious arthritis.

OBJECTIVE: To determine whether lactoferrin can modify articular inflammation in murine models of autoimmune and septic arthritis. METHODS: Collagen arthritis was induced in DBA/1 mice and Staphylococcus aureus septic arthritis in Swiss mice. Joints with established inflammation were injected periarticularly with 0.5 mg or 1 mg of human lactoferrin, and arthritis was monitored for 3 days. RESULTS: DBA/1 mice injected with lactoferrin showed significantly suppressed local inflammation for up to 3 days, achieving up to 71% of the effect of corticosteroid. Periarticular injection of 125I-lactoferrin confirmed that 25% of lactoferrin was retained in paws after 6 hours. Serum levels of interleukin-6, however, were not significantly reduced, suggesting a predominantly local antiinflammatory effect. Similarly, local, periarticular administration of lactoferrin into S aureus-infected Swiss mice significantly suppressed paw inflammation and did not enhance bacterial survival. CONCLUSION: Lactoferrin may have clinical utility in reducing articular inflammation, particularly in septic arthritis, in which antiinflammatory effects may be achieved without promoting bacterial survival.

Administration, Topical↗

In vitro activity of 19 antimicrobial agents against 3513 nosocomial pathogens collected from 48 Canadian medical centres. The Canadian Antimicrobial Study Group.

Antimicrobial resistance is a global concern. Differentiation between susceptibility rates for nosocomial versus community pathogens is important epidemiologically because it impacts on the appropriate empirical selection of antimicrobial therapy for infected patients. We studied resistance rates for 3513 nosocomial pathogens from 48 Canadian medical centres tested against 19 antimicrobial agents. The following are percent susceptibility for ceftazidime, ceftriaxone, ciprofloxacin, imipenem, netilmicin, and ticarcillin/clavulanic acid, respectively: Enterobacteriaceae 95, 95, 97, 99 98, 89; Escherichia coli, all 99 except ticarcillin/clavulanic acid (91); Enterobacter spp. 78, 78, 96, 99, 99, 71; Citrobacter spp. 79, 80, 89, 100, 94, 73; Proteus spp. 99, 88, 99, 88, 99, 98; Pseudomonas aeruginosa 88, 20, 82, 88, 81, 36; Staphylococcus aureus, all > 95; Enterococcus spp. 4, 9, 62, 95, 43, 38. Susceptibility rates for other species of microorganisms and agents tested varied considerably. Some institutions had higher than average resistance rates for some pathogens (i.e. P. aeruginosa) and some agents. Detection and continued surveillance of antimicrobial resistance amongst nosocomial pathogens is vital to patient care and health care resources. The control of antimicrobial resistance can help maintain antibiotic usage and costs associated with the use of ever more potent drugs and the treatment of increasingly resistant infections.

Canada↗

Pharmacology of ACE inhibitors versus AT1 blockers.

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 (AT1) receptor blockers share a number of common properties, including their ability to lower blood pressure. However, they can be differentiated based on their individual effects on the renin-angiotensin system, the fibrinolytic system and the actions of bradykinin. They act at different points in the cascade of events that constitute the renin-angiotensin system. In animal models of atherosclerosis, ACE inhibition was associated with a significant reduction in the percentage surface area of lesions, while no similar effect was evident with AT1 receptor blockade. In the fibrinolytic system, both ACE inhibition and AT1 receptor blockade were associated with reduced aldosterone levels, although the effect was greater with ACE inhibition; only ACE inhibition was associated with a significant reduction in plasminogen activation inhibitor-1. By blocking the degradation of bradykinin, ACE inhibitors potentiate the ability of bradykinin to reduce blood pressure and stimulate the release of tissue-type plasminogen activator from the vasculature, an effect not seen with AT1 receptor blockers.

Angiotensin Receptor Antagonists↗

A review of antimicrobial resistance in Canada.

Antimicrobial resistance is a global concern. Over the past 10 years, considerable efforts and resources have been expended to detect, monitor, and understand at the basic level the many different facets of emerging and increasing resistance. This review summarizes our current understanding of bacterial antimicrobial resistance issues in Canada with particular emphasis given to the Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus, Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Streptococcus pyogenes. In addition, future concerns and programs for ongoing surveillance are discussed.

Anti-Bacterial Agents↗

Two-state mixed renewal processes for chronic disease.

We develop a model based on a two-state mixed renewal process and propose its use for modelling disease activity in studies of chronic conditions. We specify Weibull forms for the conditional transition intensities to allow for time trends, and bivariate frailties to accommodate subject-to-subject variability in the disease process. Extensions of this model are considered for stratified analyses in which strata are defined by the number of past exacerbations. Data from a motivating study of chronic bronchitis are analysed to illustrate the methodology.

Anti-Infective Agents↗

Low rates of Helicobacter pylori reinfection in children.

BACKGROUND & AIMS: Reinfection after treatment for Helicobacter pylori is uncommon in adults. It is more likely to occur in children because they acquire primary infection. The aim of this study was to determine whether children are likely to become reinfected with H. pylori and if there are any risk factors for reinfection. METHODS: A prospective study of children who had documented evidence of successful treatment for H. pylori infection was performed. Sixty children were eligible for inclusion; results for 52 are presented. Children, parents, and siblings underwent [(13)C]urea breath tests. Details of family size and socioeconomic status were documented. Cox logistic regression analysis was used to determine the risk factors for reinfection. RESULTS: The duration of follow-up was 103.8 patient-years (mean +/- SD, 24 +/-14.0 months). Forty-six (88.5%) of the index children remained clear of infection, and 6 (11.5%) children were reinfected. The mean age of those who became reinfected was 5.8 +/- 5.6 years compared with 12.3 +/- 3.0 years for those who remained clear of infection (P = 0.00001). Only 2 of 46 (4.3%) children older than 5 years of age were reinfected, although 80.8% had 1 infected parent and 65% of siblings were infected. Reinfection rate was 2.0% per person per year in children older than 5 years. Living with infected parents and siblings and low socioeconomic status were not risk factors for reinfection. In logistic regression analysis, age was the only risk factor for reinfection. CONCLUSIONS: Reinfection with H. pylori occurs rarely in children older than 5 years of age regardless of socioeconomic group or number of infected family members. These findings also indicate that it is not necessary to treat all family members to achieve long-term eradication of H. pylori.

Adolescent↗

In-vitro susceptibility of 1982 respiratory tract pathogens and 1921 urinary tract pathogens against 19 antimicrobial agents: a Canadian multicentre study. Canadian Antimicrobial Study Group.

A total of 3903 pathogens from 48 Canadian medical centres were tested against 19 antimicrobial agents. Five agents showed activity against > or = 90% of all 1982 respiratory tract pathogens tested (ciprofloxacin, 90%; cefoperazone, 91%; ticarcillin/clavulanate, 92%; ceftazidime and imipenem, 93% each). Nine agents had > or = 90% activity against Enterobacteriaceae from respiratory tract infection (cefotaxime and ticarcillin/clavulanate, 90% each; aztreonam, ceftizoxime and ceftriaxone, 91% each; ceftazidime, 93%; ciprofloxacin, 97%; imipenem and netilmicin, 98% each). Similarly, five agents had activity against > or = 90% of all 1921 urinary tract pathogens tested (ciprofloxacin and ticarcillin/clavulanate, 90% each; cefoperazone and netilmicin, 91% each; imipenem, 99%). Nine agents had > or = 95% activity against Enterobacteriaceae from urinary tract infection (ciprofloxacin, 95%; cefotetan, 97%; aztreonam, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone and netilmicin, 98% each; imipenem, 99%). Seventeen agents had activity against > or = 95% of Staphylococcus aureus strains. Susceptibility of Pseudomonas aeruginosa isolates ranged from 2% to 91%.

Acinetobacter↗

Oral bioequivalence of three ciprofloxacin formulations following single-dose administration: 500 mg tablet compared with 500 mg/10 mL or 500 mg/5 mL suspension and the effect of food on the absorption of ciprofloxacin oral suspension.

The oral bioequivalence and tolerability of two ciprofloxacin formulations (tablet and suspension) and the effect of food on the absorption of ciprofloxacin oral suspension were investigated. Sixty-eight young, healthy male subjects participated in two separate, randomized, crossover studies. In study 1, ciprofloxacin as a single 500 mg tablet or as 500 mg/10 mL oral suspension was administered in a fasted state on day 1. In study 2, subjects participated in a three-way crossover study in which ciprofloxacin suspension was administered as 500 mg/10 mL in a fasted state, or 500 mg/10 mL with food, or 500 mg/5 mL in a fasted state. Plasma ciprofloxacin concentrations were measured by high-performance liquid chromatography. Standard pharmacokinetic parameters were estimated using non-compartmental methods. In study 1, geometric mean Cmax values of ciprofloxacin following the single 500 mg tablet and 500 mg/10 mL suspension doses were 2.36 and 2.18 mg/L, respectively; corresponding geometric mean t(max) values were 1.1 and 1.6 h, respectively. Geometric mean AUC(0-infinity) values were 12.0 and 11.8 mg x h/L, respectively. In study 2, geometric least squares mean Cmax values following ciprofloxacin 500 mg/10 mL and 500 mg/5 mL suspension during fasted conditions were 1.54 and 1.59 mg/L, respectively. Corresponding geometric least squares mean AUC(0-infinity) values were 7.3 and 8.0 mg x h/L. Administration of ciprofloxacin 500 mg/10 mL suspension, in either a fasted or fed state, was not associated with significant changes in Cmax (1.54 mg/L for fasted vs 1.37 mg/L for fed) or AUC(0-infinity) values (7.28 mg x h/L for fasted vs 8.19 mg x h/L for fed). Each ciprofloxacin formulation was well tolerated for the duration of each study. These studies demonstrated bioequivalence between ciprofloxacin 500 mg tablet and two strengths of ciprofloxacin suspension (500 mg/10 mL and 500 mg/5 mL). Bioavailability was unaltered by food.

Administration, Oral↗