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Biomedical subjects

D S Jones

Publications and source records attributed to D S Jones.

At least 19 recordsLinked to original sources

Controlled release of a model antibacterial drug from a novel self-lubricating silicone biomaterial.

There is considerable interest in developing medical devices that provide controlled delivery of biologically active agents, for example, to reduce the incidence of device-related infection. Silicone elastomers are one of the commonest biomaterials used in medical device production. However, they have a relatively high coefficient of friction and the resulting lack of lubricity can cause pain and tissue damage on device insertion and removal. Novel silicone cross-linking agents have recently been reported that produce inherently 'self-lubricating' silicone elastomers with very low coefficients of friction. In this study, the model antibacterial drug metronidazole has been incorporated into these self-lubricating silicone elastomers to produce a novel bioactive biomaterial. The in vitro release characteristics of the bioactive component were evaluated as a function of cross-linker composition and drug loading. Although conventional matrix-type release kinetics were observed for metronidazole from the silicone systems, it was also observed that increasing the concentration of the cross-linking agent responsible for the lubricious character (tetra(oleyloxy)silane) relative to that of the standard non-lubricious cross-linking agent (tetrapropoxysilane) produced an increase in the metronidazole flux rate by up to 65% for a specified drug loading. The results highlight the potential for developing lubricious silicone medical devices with enhanced drug release characteristics.

Anti-Bacterial Agents↗

Randomized trial of novel tetracaine patch to provide local anaesthesia in neonates undergoing venepuncture.

BACKGROUND: Procedures such as venepuncture or heel prick are painful and may cause considerable stress to newborn infants. Topical local anaesthetics are effective for venepuncture but need to be applied for at least 60 min and the delivered dose will vary. We assessed a novel tetracaine-based self-adhesive patch in providing controlled local anaesthesia before venepuncture. METHODS: A placebo-controlled, double-blind trial was conducted using a tetracaine patch formulated from hydroxypropylcellulose discs (0.283 cm(2)) containing tetracaine (1 mg x cm(-2)) surrounded by a low tack pressure-sensitive adhesive backing layer. Thirty-two newborn infants of gestation 32-42 weeks (median 36 weeks), aged 3-18 days (median 6 days) were randomized to receive a tetracaine-containing patch or a placebo device applied to the dorsum of the hand 30 min before venepuncture to obtain blood samples. Pain was assessed in response to needle insertion using a validated adaptation of the neonatal facial coding score (NFCS) and the presence of crying. RESULTS: Of 15 tetracaine-treated neonates, 14 (93%) presented little or no pain in response to the procedure compared with six of 17 (35%) who had the placebo patch applied (P=0.01). CONCLUSIONS: The tetracaine patch produced effective pain relief during the venepuncture procedure in both term and pre-term infants. There were no adverse effects, either local or systemic.

Administration, Cutaneous↗

Eradication of endotracheal tube biofilm by nebulised gentamicin.

OBJECTIVE: To compare the efficacy of gentamicin, nebulised via the endotracheal tube (ET), with that of parenteral cefotaxime or parenteral cefuroxime in preventing the formation of ET biofilm. SETTING: General intensive care units in two university teaching hospitals. DESIGN: The microbiology of ET biofilm from 36 ICU patients eligible to receive antibiotic prophylaxis was examined. Peak and trough tracheal concentrations of gentamicin, cefotaxime or cefuroxime were measured in each patient group, on the 2nd day of intubation. PATIENTS: Twelve patients received gentamicin (80 mg) nebulised in 4 ml normal saline every 8 h, 12 cefotaxime (1 g, 12 hourly) and 12 cefuroxime (750 mg, 8 hourly). Prophylaxis was continued for the duration of intubation. MEASUREMENTS AND RESULTS: Samples of tracheal secretions were taken on the 2nd day of ventilation for determination of antibiotic concentrations. Following extubation, ETs were examined for the presence of biofilm. Pathogens considered to be common aetiological agents for VAP included Staphylococcus aureus, enterococci, Enterobacteriaceae and pseudomonads. While microbial biofilm was found on all ETs from the cephalosporin group, microbial biofilm of these micro-organisms was found on 7 of the 12 ET tubes from patients receiving cefotaxime [ S. aureus (4), pseudomonads (1), Enterobacteriaceae (1), enterococcus (1)] and 8 of the 12 ET tubes from patients receiving cefuroxime [Enterobacteriaceae (6), P. aeruginosa (1) and enterococcus (1)]. While microbial biofilm was observed on five ETs from patients receiving nebulised gentamicin, none of these were from pathogens for ventilator-associated pneumonia (VAP). Tracheal concentrations of both cephalosporins were lower than those needed to inhibit the growth of pathogens recovered from ET tube biofilm. The median (and range) concentrations for cefotaxime were 0.90 (<0.23-1.31) mg/l and 0.28 (<0.23-0.58) mg/l for 2 h post-dose and trough samples, respectively. Two hours post-dose concentrations of cefuroxime (median and range) were 0.40 (0.34-0.83) mg/l, with trough concentrations of 0.35 (<0.22-0.47) mg/l. Tracheal concentrations (median and range) of gentamicin measured 1 h post-nebulisation were 790 (352-->1250) mg/l and then, before the next dose, were 436 (250-1000) mg/l. CONCLUSION: Nebulised gentamicin attained high concentrations in the ET lumen and was more effective in preventing the formation of biofilm than either parenterally administered cephalosporin and therefore may be effective in preventing this complication of mechanical ventilation.

Administration, Inhalation↗

Rheological characterization of bioadhesive, antimicrobial, semisolids designed for the treatment of periodontal diseases: transient and dynamic viscoelastic and continuous shear analysis.

This study examined the creep behavior and oscillatory and flow properties of tetracycline-containing, bioadhesive semisolid formulations, designed for localized treatment of periodontal disease. Formulations were prepared containing hydroxyethylcellulose (HEC, 1, 3, or 5% w/w), poly(vinylpyrrolidone) (PVP, 2 or 3% w/w), polycarbophil (PC, 1 or 3% w/w), and tetracycline (5% w/w, as the hydrochloride). In creep analysis, each formulation exhibited several distinct regions that were mathematically modelled using a multi-element Voigt model with a residual spring and dashpot. Increasing the concentrations of each polymeric component decreased the elastic compliance (J(0)) yet increased the residual viscosity. In oscillatory analysis, increased polymer concentrations increased the storage modulus (G'), the loss modulus (G") and the dynamic viscosity (eta'), yet decreased the loss tangent (tan delta). The relationships between G' or G" and frequency were observed to plateau at higher frequencies, which is indicative of polymer chain entanglement and network formation. With the exception of formulations containing 1% HEC, the formulations were elastic (tan delta < 1), with large G' and small J(0) values. All formulations exhibited pseudoplastic flow with thixotropy. Increasing concentrations of each polymeric component increased the zero-shear viscosity (determined using the Cross model) and was further evidence of polymer chain entanglement. Formulations containing 1% w/w HEC possessed excellent flow properties, however, their thixotropic behavior and essentially elastoviscous nature (large J(0) and tan delta) would be disadvantageous for use in the treatment of periodontal disease because of rapid removal from the pocket and relatively uncontrolled drug release. Despite their advantageous viscoelastic properties, the flow properties of formulations containing 5% w/w HEC were inappropriate, rendering administration through a periodontal syringe potentially difficult. Based on their rheological behavior, formulations containing HEC (3% w/w), PVP (2 or 3% w/w), and PC (1 or 3% w/w) would be suitable for clinical application. However, consideration of other physicochemical properties (e.g., bioadhesion, drug release kinetics) must be performed prior to selection of the most suitable formulation for clinical examination. This study has highlighted the successful complimentary application of creep analysis and oscillatory and flow rheometry for the characterization and development of bioadhesive semisolid formulations for the treatment of periodontal disease.

Adhesives↗

The concomitant development of poly(vinyl chloride)-related biofilm and antimicrobial resistance in relation to ventilator-associated pneumonia.

Ventilator-associated pneumonia is a major cause of death in intensive care patients and the endotracheal tube, commonly fabricated from poly(vinyl chloride) (PVC), is acknowledged as a significant factor in this. Bacteria colonise the biomaterial, thereby adopting a sessile mode of growth that progresses to the establishment of an antibiotic-resistant biofilm by the accretion of a protective glycocalyx. This study examined the sequential steps involved in the formation of biofilm on PVC by atomic force microscopy and the concomitant development of resistance to an antibiotic (ceftazidime) and to a non-antibiotic antimicrobial agent (hexetidine). Staphylococcus aureus and Pseudomonas aeruginosa isolated from ET tube biofilm were employed. The surface microrugosity of bacteria growing in sessile mode on PVC decreased significantly (p < 0.05) over the period 4, 24, 48 h and 5 d. The progressive accretion of bacterial glycocalyx was readily visualised in micrographs leading to a smoother surface topography with time. The minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) for ceftazidime and hexetidine against planktonic (suspension) S. aureus were lower than for Ps. aeruginosa. Furthermore, sessile populations of S. aureus and Ps. aeruginosa on PVC exhibited greater resistance to both ceftazidime and hexetidine when compared to planktonic bacterial growth. The efficacy of the agents, determined by kill kinetics, against sessile bacteria was dependent on age, with established biofilms (> or = 24 h) significantly more resistant (p < 0.05) than early sessile populations (< or = 4 h). Importantly, for practice, even newly colonised bacteria (1 h) were significantly more resistant to antibiotic than planktonic bacteria. Hexetidine was significantly more active (p < 0.05) than ceftazidime on biofilms of both isolates, irrespective of age, with total kill within 24 h treatment. Hexetidine may offer promise in the resolution of infection associated with PVC endotracheal tubes.

Anti-Bacterial Agents↗

Conditioning film and environmental effects on the adherence of Candida spp. to silicone and poly(vinylchloride) biomaterials.

The reported incidence of colonization of oropharyngeal medical devices with Candida spp. has increased in recent years, although few studies that have systematically examined the adherence of yeast cells to such biomaterials, the primary step in the process of colonization. This study, therefore, examined the effects of oropharyngeal atmospheric conditions (5% v/v carbon dioxide) and the presence of a salivary conditioning film on both the surface properties and adherence of Candida albicans, Candida krusei and Candida tropicalis to PVC and silicone. Furthermore, the effects of the salivary conditioning film on the surface properties of these biomaterials are reported. Growth of the three Candida spp. in an atmosphere containing 5% v/v CO2 significantly increased their cell surface hydrophobicity and reduced the zeta potential of C. albicans and C. krusei yet increased the zeta potential of C. tropicalis (p<0.05). Furthermore, growth in 5% v/v CO2 decreased the adherence of C. tropicalis and C. albicans to both PVC and silicone, however, increased adherence of C. krusei (p<0.05). Pre-treatment of the microorganisms with pooled human saliva significantly decreased their cell surface hydrophobicity and increased their adherence to either biomaterial in comparison to yeast cells that had been pre-treated with PBS (p<0.05). Saliva treatment of the microorganisms had no consistent effect on microbial zeta potential. Interestingly, adherence of the three, saliva-treated Candida spp. to saliva-treated silicone and PVC was significantly lower than whenever the microorganisms and biomaterials had been treated with PBS (p<0.05). Treatment of silicone and PVC with saliva significantly altered the surface properties, notably reducing both the advancing and receding contact angles and, additionally, the microrugosity. These effects may contribute to the decreased adherence of saliva-treated microorganisms to these biomaterials. In conclusion, this study has demonstrated the effects of physiological conditions within the oral cavity on the adherence of selected Candida spp. to biomaterials employed as oropharyngeal medical devices. In particular, this study has ominously shown that these materials act as substrates for yeast colonization, highlighting the need for advancements in biomaterial design. Furthermore, it is important that physiological conditions should be employed whenever biocompatibility of oropharyngeal biomaterials is under investigation.

Journal Article↗

Design of a simulated urethra model for the quantitative assessment of urinary catheter lubricity.

Catheters designed for intermittent urological catheterization should possess appropriate lubricity and mechanical properties to ensure optimal clinical performance. However, the lack of a reproducible in vitro method that simulates clinical use makes it difficult to evaluate the lubricity of urinary catheters and other devices for urethral insertion. Therefore, this study describes a suitable method based on use of a Texture Analyzer to characterize the lubricity of such devices. The novel method was susequently applied to the evaluation of commercially-available intermittent urinary catheters. In addition, other important physicochemical properties of these catheters were examined, namely Young's modulus, degree of hydration and morphology. Catheter lubricity was quantified, using a Texture Analyzer, by measurement of the forces required for insertion and removal of the device from two model substrates, agar and mucin-coated silicone tubing. Significant differences in lubricity were identified between the commercially-available catheters, with Aquacath and Lofric exhibiting the lowest forces of insertion and removal. There were no significant differences between the extent of hydration between the catheters, with the exception of Uro-flo which exhibited the lowest hydration. Therefore, the differences in lubricity were not directly related to the extent of hydration. The forces required for insertion/removal of all catheters were markedly greater in the simulated mucin model than in the agar substrate and the former, simulated urethra model, was accepted to mimic more accurately, the in vivo situation. Significant differences were observed between the Young's Moduli of the catheter biomaterials, with Aquacath possessing the largest value. In conclusion, this study has described the use of a texture analyzer and polymeric substrates for the evaluation of biomaterial lubricity. Using these methods, Aquacath and Lofric catheters exhibited greatest lubricity. However, following additional consideration of the mechanical properties of these biomaterials, Aquacath possessed the most appropriate physicochemical properties for use in intermittent catheterization.

Journal Article↗

The depression puzzle. Do the pieces fit?

BACKGROUND: Depression is a common problem in the Australian community. It results in considerable disability. Currently screening tools promoted for detection of depression are nonspecific. They are not diagnostic tools. While people identified by screening are, by definition, at higher risk of depression, the diagnosis still needs to be based on interview findings. Screening tools do not substitute for time spent with patients developing rapport and an understanding of the causes of the depression and formulating possible management steps. Screening alone has not been shown to improve outcomes for people with depression. OBJECTIVE: This article examines the current prevalence of depression in Australia and whether screening tools ultimately contribute to a reduction in morbidity. DISCUSSION: Screening instruments have arbitrary cut off points for identifying patients with depression and their findings regarding prevalence should be applied with caution. If the thresholds are low then 'prevalences' are raised. It is unclear whether all 'cases' detected using screening instruments require clinical intervention.

Australia↗

Rheological, mechanical and membrane penetration properties of novel dual drug systems for percutaneous delivery.

In this study it has been demonstrated that mixtures of two solid drugs, ibuprofen and methyl nicotinate, with different but complementary pharmacological activities and which exist as a single liquid phase over a wide composition range at skin temperature, can be formulated as o/w emulsions without the use of an additional hydrophobic carrier. These novel dual drug systems provided significantly enhanced in vitro penetration rates through a model lipophilic barrier membrane compared to conventional individual formulations of each active. Thus, for ibuprofen, drug penetration flux enhancements of three- and 10-fold were observed when compared to an aqueous ibuprofen suspension and a commercial alcohol-based ibuprofen formulation, respectively. Methyl nicotinate penetration rates were shown to be similar for aqueous gels and emulsified systems. Mechanisms explaining these observations are proposed. Novel dual drug formulations of ibuprofen and methyl nicotinate, formulated within the liquid range at skin temperature, were investigated by oscillatory rheology and texture profile analysis, demonstrating the effects of drug and viscosity enhancer concentrations, and disperse phase type upon the rheological, mechanical and drug penetration properties of these systems.

Administration, Topical↗

Design, characterisation and preliminary clinical evaluation of a novel mucoadhesive topical formulation containing tetracycline for the treatment of periodontal disease.

This study describes the formulation, characterisation and preliminary clinical evaluation of mucoadhesive, semi-solid formulations containing hydroxyethylcellulose (HEC, 1-5%, w/w), polyvinylpyrrolidine (PVP, 2 or 3%, w/w), polycarbophil (PC, 1 or 3%, w/w) and tetracycline (5%, w/w, as the hydrochloride). Each formulation was characterised in terms of drug release, hardness, compressibility, adhesiveness (using a texture analyser in texture profile analysis mode), syringeability (using a texture analyser in compression mode) and adhesion to a mucin disc (measured as a detachment force using the texture analyser in tensile mode). The release exponent for the formulations ranged from 0.78+/-0.02 to 1. 27+/-0.07, indicating that drug release was non-diffusion controlled. Increasing the concentrations of each polymeric component significantly increased the time required for 10 and 30% release of the original mass of tetracycline, due to both increased viscosity and, additionally, the unique swelling properties of the formulations. Increasing concentrations of each polymeric component also increased the hardness, compressibility, adhesiveness, syringeability and mucoadhesion of the formulations. The effects on product hardness, compressibility and syringeability may be due to increased product viscosity and, hence, increased resistance to compression. Similarly, the effects of these polymers on adhesiveness/mucoadhesion highlight their mucoadhesive nature and, importantly, the effects of polymer state (particularly PC) on these properties. Thus, in formulations where the neutralisation of PC was maximally suppressed, adhesiveness and mucoadhesion were also maximal. Interestingly, statistical interactions were primarily observed between the effects of HEC and PC on drug release, mechanical and mucoadhesive properties. These were explained by the effects of HEC on the physical state of PC, namely swollen or unswollen. In the preliminary clinical evaluation, a formulation was selected that offered an appropriate balance of the above physical properties and contained 3% HEC, 3% PVP and 1% PC, in addition to tetracycline 5% (as the hydrochloride). The clinical efficacy of this (test) formulation was compared to an identical tetracycline-devoid (control) formulation in nine periodontal pockets (>/=5 mm depth). One week following administration of the test formulation, there was a significant improvement in periodontal health as identified by reduced numbers of sub-gingival microbial pathogens. Therefore, it can be concluded that, when used in combination with mechanical plaque removal, the tetracycline-containing semi-solid systems described in this study would augment such therapy by enhancing the removal of pathogens, thus improving periodontal health.

Acrylic Resins↗

Examination of the physical state of chlorhexidine within viscoelastic, bioadhesive semisolids using raman spectroscopy.

This study examined the effects of polymeric components on the physical state of chlorhexidine within bioadhesive, semisolid formulations using Raman spectroscopy. Semisolid formulations were prepared in which chlorhexidine base (CHX, 5%w/w, particle size <63 microm) was dispersed in aqueous (phosphate-buffered saline, pH 6.8) polymer matrices consisting of one or more polymeric components, namely HEC (3%w/w), PVP (3%), and PC (PC, 3%). Raman spectra were recorded using 785-nm excitation and were typically accumulated for 360 s. The Raman spectra were dominated by the presence of CHX. The spectra of CHX in HEC and in HEC/PVP gels were indistinguishable from that for solid CHX as a result of the insolubility of CHX in these formulations. However, in systems containing PC and CHX, there was a shift in the strongest band from 1564 cm(-1) to 1608 cm(-1), which may be accredited to protonation of the basic CHX by the numerous carboxylic acidic groups on PC. Identical shifts in the band positions were observed when this protonation was modeled using ethanoic acid, supporting the view that there was a simple acid base reaction between PC and CHX. However, there were notable differences in the relative intensities of the peaks from these samples, with the spectrum of CHX in the PC matrix displaying properties intermediate between those of CHX dissolved in ethanoic acid and solid CHX diacetate. This may be accredited to the limited solubility of the CHX-PC ion pair. In matrices containing HEC and PC, no peak was observed at 1564 cm(-1), whereas the intensity of the peak at 1608 cm(-1) was increased. Therefore, in these formulations CHX was completely converted to the di-cation as a result of the synergistic effects of PC (which protonated CHX) and HEC (which solubilized the di-cation). In the absence of either HEC or PC, complete protonation was not achieved. It is suggested that this enhancement of solubility of H(2)CHX(2+) may be due to hydrogen bonding, given the hydroxylated nature of HEC. In conclusion, this study has shown the applicability of Raman spectroscopy for both the analysis of opaque, semisolid formulations and, additionally, for the examination of the state of therapeutic agents within such matrices. In particular, using Raman spectroscopy, it was uniquely possible to identify the roles of various polymeric components on both the ionization and solubilization of CHX within aqueous semisolid systems.

Chemistry, Pharmaceutical↗

Visions of a cure. Visualization, clinical trials, and controversies in cardiac therapeutics, 1968-1998.

In the early 1970s physicians engaged in fierce debates over the most appropriate method of evaluating the efficacy of coronary artery bypass grafting (CABG). With millions of patients and billions of dollars at stake, CABG sparked fierce controversy. Skeptics demanded that randomized controlled trials (RCTs) be performed, while enthusiasts argued that they already had visual proof of CABG's efficacy. When RCTs appeared, they did not settle the controversy. Participants simply reasserted their preconceptions, defending a trial's strengths or exploiting its flaws. The debate centered on standards of knowledge for the evaluation of therapeutic efficacy. Specifically, cardiologists and cardiac surgeons struggled to assess the relevance of different measures of therapeutic success: physiological or clinical, visual or statistical. Many factors contributed to participants' decisions, including disciplinary affiliation, traditions of research, personal experience with angiography, and assessments of the history of cardiac therapeutics. Physicians had to decide whether angiography provided a meaningful representation of the disease and its treatment or whether demonstrations of therapeutic success could come only from long-term statistical evaluation of mortality data.

Attitude of Health Personnel↗

Determination of the salivary retention of hexetidine in-vivo by high-performance liquid chromatography.

The non-antibiotic antimicrobial agent hexetidine is widely used at a concentration of 0.1% w/v as an oral rinse to reduce the number of viable microorganisms within the oral cavity. However, following use, the available concentration of hexetidine in the oral cavity declines with time, thus compromising the resultant antimicrobial activity. It is, therefore, desirable to determine the persistence of the agent in the oral cavity by quantification of the drug concentration in saliva, thus enabling prediction of its antimicrobial activity in the oral environment. A rapid reverse-phase HPLC method was therefore developed and validated for hexetidine in aqueous solution (Oraldene) and in saliva samples collected from volunteers post-rinsing with 15 mL of hexetidine oral rinse for 30s. The HPLC assay was sufficiently sensitive to accurately detect hexetidine in saliva up to 25 min after in-vivo use of a commercial oral rinse. Furthermore, it was possible to detect hexetidine below the published minimum inhibitory concentrations (MICs) for a selection of microorganisms. From these data a first-order elimination rate constant of hexetidine from the oral cavity was determined post-rinsing in each of six volunteers. The validated HPLC assay method presented is useful for the assay of hexetidine in the oral cavity both at and below MICs. The first-order elimination rate constant shows significant variation between volunteers.

Adult↗

Aging is associated with endothelial dysfunction in the human forearm vasculature.

OBJECTIVE: Our objective was to examine the role of the endothelium in maintaining vascular tone in the basal as well as in the contracted state during aging. DESIGN/PARTICIPANTS: Responses to brachial artery infusion of acetylcholine in presence and absence of NG-nitro-L-arginine methyl ester (L-NAME) and to angiotensin II were studied in 11 young and 12 old white subjects. MEASUREMENTS: Strain gauge plethysmography was used to measure forearm vascular resistance (FVR). The dose of acetylcholine at 50% maximal observed decrease in forearm vascular resistance (EC50) was significantly higher (11.0 +/- 1.59 vs 7.07 +/- .65 microg/min, respectively; mean +/-SEM; P < .05) and the FVR at maximal acetylcholine effect (Emax) remained greater (12.6 +/- 1.75 vs 7.15 +/- 1.25 mm Hg/100 mL tissue volume/min; P < .02) in old compared with young subjects. Acetylcholine effect was significantly reversed by concomitant administration of L-NAME, as indicated by the increase in EC50 (old, 20.2 +/- 3.69; young, 11.9 +/- 1.68 microg/min). RESULTS: There was no age-related difference in sodium nitroprusside-induced decrease in FVR. The EC50 and Emax for angiotensin II-mediated increase in FVR were 7.87 +/- 1.15 and 8.36 +/- 1.00 ng/min (EC50) and 5.30 +/- .67 vs 6.56 +/-1.25 mm Hg/100 mL tissue volume/min (Emax), and these were not different in old and young subjects, respectively. CONCLUSIONS: These data indicate that aging is associated with impaired endothelial- dependent vascular relaxation and that this is selective, with no age-related change in endothelial-independent vascular relaxation or angiotensin II-mediated vascular contraction.

Acetylcholine↗

Local delivery of chlorhexidine using a tooth-bonded delivery system.

Films containing 20% w/w chlorhexidine base (particle size 63-125 microm) in poly(epsilon-caprolactone), MW 35,000-45,000, were prepared by solvent evaporation and sections attached to the mesio-lingual and mesio-buccal surfaces of the lower first molar in healthy volunteers. Saliva (<1.5 microl) was collected on Periopaper and chlorhexidine concentrations measured by HPLC were typically higher in the area immediately adjacent to the tooth-bonded film sections and lower at more distant sites. Analysis of variance of chlorhexidine concentrations, adjacent to the film sections, showed concentrations were significantly different on the buccal and lingual sides of the tooth and depended on the time of sampling (n=5, P<0.05).

Administration, Oral↗

Dynamic mechanical analysis of polymeric systems of pharmaceutical and biomedical significance.

Dynamic mechanical analysis (DMA) is an analytical technique in which an oscillating stress is applied to a sample and the resultant strain measured as functions of both oscillatory frequency and temperature. From this, a comprehensive knowledge of the relationships between the various viscoelastic parameters, e.g. storage and loss moduli, mechanical damping parameter (tan delta), dynamic viscosity, and temperature may be obtained. An introduction to the theory of DMA and pharmaceutical and biomedical examples of the use of this technique are presented in this concise review. In particular, examples are described in which DMA has been employed to quantify the storage and loss moduli of polymers, polymer damping properties, glass transition temperature(s), rate and extent of curing of polymer systems, polymer-polymer compatibility and identification of sol-gel transitions. Furthermore, future applications of the technique for the optimisation of the formulation of pharmaceutical and biomedical systems are discussed.

Elasticity↗

Implications of endotracheal tube biofilm for ventilator-associated pneumonia.

OBJECTIVE: To determine the relationship between, and antibiotic resistance of, endotracheal tube (ET) biofilm and pulmonary pathogens in ventilator-associated pneumonia (VAP). SETTING: General intensive care units in two university teaching hospitals. DESIGN: The microbiology of ET biofilm and tracheal samples from patients with and without VAP were compared. For individual patients, matching pairs of pathogens were confirmed as identical and characterised for antibiotic susceptibility. PATIENTS: 40 intensive care unit patients - 20 with VAP, 20 without VAP as control. The duration of intubation (median and range) was 6.5 days (3-17) and 5 days (2-10), respectively. MEASUREMENTS AND RESULTS: Samples of tracheal secretions were taken during ventilation for bacteriological culture. Following extubation, ETs were examined for the presence of biofilm. Isolates of high pathogenic potential included Staphylococcus aureus, enterococci, Enterobacteriaceae, pseudomonads and Candida spp. Where the same microorganism was found on tracheal and ET samples by phenotyping, these were confirmed as identical by genotyping and characterised for antibiotic susceptibility in both the free floating and biofilm forms. Seventy per cent of patients with VAP had identical pathogens isolated from both ET biofilm and tracheal secretions. No pairing of pathogens was observed in control patients (p < 0.005). Susceptibility data for these pairs show that the ET acts as a reservoir for infecting microorganisms which exhibit significantly greater antibiotic resistance than their tracheal counterparts. CONCLUSION: This investigation provides further evidence for the role of ET biofilm in VAP. The difficulty in eradicating an established microbial biofilm using antibiotics implies that increased attention must be directed towards modification of the ET to prevent or substantially reduce biofilm formation.

Adolescent↗