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Biomedical subjects

A D Woolfson

Publications and source records attributed to A D Woolfson.

At least 55 records · Page 3Linked to original sources

In vivo assessment of percutaneous local anaesthetic preparations.

This study has demonstrated greater efficacy of a new percutaneous amethocaine preparation relative to Eutectic Mixture of Local Anaesthetics (EMLA). Initially, a double-blinded trial was undertaken on each preparation individually against placebo, as the recommended method of application was different for EMLA (2.5 g applied for 60 min under an occlusive dressing) and the amethocaine formulation (0.5 g applied for 30 min). Thereafter, the two preparations were compared directly, in a double-blinded study using a standardized application for both formulations. The results indicated that both preparations provided significant (chi-square; P less than 0.001) percutaneous local anaesthesia when compared with placebo. The amethocaine preparation produced significant anaesthesia (chi-square, P less than 0.001) after 30 min application. Furthermore, the amethocaine formulation demonstrated both increased rapidity of action and increased duration of effect, as determined by a two-tailed unpaired t test, in comparison with EMLA when application times of both 30 and 60 min were used for each preparation. The results of this study indicate that the amethocaine preparation provided more rapid and prolonged anaesthesia than EMLA.

Administration, Cutaneous↗

Local anaesthesia of the skin.

Local anaesthesia of intact skin is of growing importance given the increased use of minor surgical procedures on an out-patient basis. Specific pain receptors (nociceptors) are responsible for sensing cutaneous pain. Mechanisms of pain perception and the role of local anaesthetics in reversibly blocking nociception are considered. Effective routes of administration are dermal infiltration or, more recently, anaesthesia by topical application of specifically formulated preparations which promote percutaneous absorption of the drug (percutaneous local anaesthesia). Although many other topical anaesthetic products are also available these do not permit the anaesthetic to reach the nociceptors underlying the stratum corneum and are therefore only suitable for mucosal anaesthesia or for application to damaged skin. The chemical characteristics of local anaesthesia drugs are identified. Those agents suitable for cutaneous anaesthesia are reviewed with respect to potency, onset and duration of anaesthesia and possible systemic or local adverse reactions.

Anesthesia, Local↗

Pain-free cutting of split skin grafts by application of a percutaneous local anaesthetic cream.

The use of a novel percutaneous anaesthetic preparation for the pain-free cutting of split skin grafts has been assessed in a series of 80 patients, age range 12 to 96 years. The technique was completely successful in 80% of these cases, with complete analgesia established within one hour of initial application. Duration of anaesthesia was such that pain-free cutting of the skin was possible up to 5 hours after initial application of the preparation. Failures of the technique were largely attributed to a loss of anaesthetic potency in the preparation, application of an inadequate amount to the site or patient anxiety. The use of the percutaneous anaesthetic preparation was found to offer considerable advantages over conventional infiltration anaesthesia for this type of surgery. Several additional surgical applications of percutaneous anaesthesia are also considered.

Administration, Cutaneous↗

Comparative in vivo and in vitro assessment of the percutaneous absorption of local anaesthetics.

The percutaneous absorption of local anaesthetics in a standard formulation has been compared in vitro and in vivo. In vitro data were obtained with a modified Sartorius absorption system and silastic as a lipophilic barrier membrane. With this system the greatest steady-state flux values and permeability coefficients were obtained with amethocaine and lignocaine. These drugs also performed best in an in vivo volunteer trial. However, statistical analysis revealed that amethocaine was significantly better at producing full-depth anaesthesia to the challenge of insertion of a sterile needle. An optimized amethocaine formulation may therefore be expected to meet most closely the ideal profile for a percutaneous local anaesthetic preparation.

Anesthesia, Local↗

Concentration-response analysis of percutaneous local anaesthetic formulations.

The percutaneous absorption of amethocaine has been measured for different concentrations of the drug in three different formulations, A, B and C. Statistical analysis indicated that a concentration of 4% produced effective percutaneous local anaesthesia to pin-prick, together with an acceptable onset time of approximately 40 min. Increasing the concentration did not reduce the onset time further, although there was some increase in the duration of anaesthesia. Formulations A and B were hydrophilic, whereas C was an oil-in-water cream. Effective anaesthesia with formulation C required a higher drug concentration (12%), perhaps because of partitioning of the lipophilic anaesthetic into the lipid phase of the vehicle. The rate-limiting step was considered to be diffusion by the lipophilic anaesthetic through the stratum corneum, shown by onset of anaesthesia after removal of the formulation from the test site.

Administration, Cutaneous↗

Methods for the determination of trace aluminium contamination in dialysis fluids.

The problems associated with aluminium contamination of dialysis fluids are reviewed. The major sources of such contamination are generally the water supply or salts used in the manufacture of the fluids. It is generally desirable to keep the aluminium concentration of the dialysate below 15 micrograms/l. This trace level of aluminium results in problems of analysis. Literature methods, notably atomic absorption spectroscopy with electrothermal atomization, neutron activation analysis and inductively coupled plasma atomic emission spectroscopy are considered. Results from these methods are not always in agreement. It is concluded that graphite furnace atomic absorption spectroscopy (GF-AAS) is the most suitable technique. However, it is necessary to consider the effect of matrix interferences, notably chloride, on the determination of aluminium in dialysis fluids by this method. Reliable results for trace aluminium determinations by GF-AAS can be obtained using a suitable furnace programme together with matrix adjusters such as nitric or orthophosphoric acids.

Aluminum↗

On the statistical evaluation of adherence assays.

Parametric (unpaired t-test) and non-parametric (Mann-Whitney U-test) methods have been used in the evaluation of adherence assays on the non-antibiotic antimicrobial agent, Taurolin. In all but one case, where the anti-adherence effect was known to be marginal, both statistical methods gave similar results although there were some minor differences in the levels of significance achieved. The effect of the agent on the deviation of adherence data from normality was quantified by calculation of the skewness coefficient for each data set. A significant anti-adherence effect appears to result in a decrease in the skewness of the adherence assay data. It was concluded that either parametric or non-parametric statistical evaluation of adherence assay data is valid for large numbers of observations. In future studies of this type it is suggested that attention should also be given to the effect of the anti-adherence agent on the deviation of adherence data from normality as denoted by the skewness coefficient.

Adhesiveness↗

Reduced adherence of micro-organisms to human mucosal epithelial cells following treatment with Taurolin, a novel antimicrobial agent.

Taurolin, a non-antibiotic antimicrobial agent, significantly reduced the adherence of buccal and vaginal strains of Candida albicans blastospores and urine isolates of Escherichia coli and Staphylococcus saprophyticus to epithelial cells. Light microscopy and radio-isotopic counting methods were used to quantify the adherence of the micro-organisms to either uroepithelial or buccal epithelial cells. A maximum reduction in adherence of approximately 65% was obtained. The anti-adherence capacity was time-dependent, requiring a contact time of 30 min to achieve maximum effect. Taurolin at sub-minimum inhibitory concentrations (MIC) significantly reduced the adherence of Candida and E. coli. A concentration slightly higher than the MIC was required for Staph. saprophyticus. Treatment of either epithelial cells or micro-organisms with Taurolin resulted in reduced adherence of microorganisms.

Anti-Bacterial Agents↗

Drug assays--the role of modern voltammetric techniques.

Modern voltammetric techniques, e.g. differential pulse polarography and voltammetry, anodic/cathodic stripping voltammetry and electrochemical detection for high performance liquid chromatography or flow injection analysis, are reviewed with respect to their basic theory, design and usage of available instrumentation and applications to drug assays in formulation and body fluid matrices.

Electrochemistry↗

A comparative study of the microbial antiadherence capacities of three antimicrobial agents.

The antimicrobioal agents, taurolidine, chlorhexidine and povidone-iodine were examined for microbial anti-adherence activity. Two adherence systems were investigated using light microscopic and radio-isotopic assay methods: that of an oral isolate of Candida albicans to human buccal epithelial cells and of a urine isolate of Escherichia coli to human uroepithelial cells. Each of the three agents exhibited significant anti-adherence activity which was concentration dependent. The activity was expressed at subminimum inhibitory concentrations of the agents. Treatment of either the microbial or epithelial cells resulted in significant reductions in adhering micro-organisms. Consideration of the data in respect of the skewness coefficient and percentage clear epithelial cells indicated that the agents exhibited a broadly based anti-adherence capacity.

Anti-Bacterial Agents↗

Decrease in adherence of bacteria and yeasts to human mucosal epithelial cells by noxythiolin in vitro.

Adherence of buccal and vaginal isolates of Candida albicans to buccal epithelial cells and the adherence of urine isolates of Escherichia coli and Staphylococcus saprophyticus to uroepithelial cells was quantified by light microscopy. The antimicrobial agent noxythiolin reduced the adherence of these micro-organisms in both exponential and stationary growth phases. Adherence of both the blastospore and pseudohyphal forms of C. albicans was reduced. Treatment of epithelial cells and/or micro-organisms with noxythiolin resulted in decreased adherence. No anti-adherence effect was observed with formaldehyde and N-methylthiourea, the degradative products of noxythiolin.

Adhesiveness↗

Inhibition of hyphal development and kill of Candida albicans blastospores by noxythiolin in vitro.

The cidal activity of the antimicrobial agent, noxythiolin, was investigated against a laboratory strain and a fresh isolate of Candida albicans. The order of resistance to noxythiolin was hyphal form (isolate) greater than or equal to 25 degrees C-grown blastospores (isolate) greater than 37 degrees C-grown blastospores (isolate) greater than laboratory strain blastospores. Noxythiolin activity was superior to that of 'equivalent' formaldehyde concentrations. Mycelial transformation in C. albicans was examined by light and scanning electron microscopy and measured in terms of percentage germination and hyphal extension. Noxythiolin, 2.5%, in contact for 30 min prevented germination of the blastospore population whereas the decomposition products, formaldehyde and N-methylthiourea, showed no appreciable effect in the expected concentrations. The implications of these results are discussed in relation to the observed clinical efficacy of noxythiolin.

Candida albicans↗

Differential pulse polarographic determination of formaldehyde in stored noxythiolin solutions.

A differential pulse polarographic method has been developed for the determination of formaldehyde, by means of its kinetic current, in noxythiolin solutions. The assay conditions have been optimized so that the noxythiolin decomposition reaction was not affected. The method had the advantage of rapidity with an analysis time of about 10 min per sample. Thus formaldehyde was determined in noxythiolin solutions prepared and stored under typical clinical conditions. The low concentrations of formaldehyde present in all solutions were insufficient to account for the known cidal action of noxythiolin. There must therefore be some doubt that the mode of action of noxythiolin is simply due to formaldehyde produced as a result of the decomposition of noxythiolin in aqueous solution.

Drug Stability↗

A comparison of the antimicrobial activities of noxythiolin and formaldehyde solutions.

The availability of a rapid and highly specific polarographic method of analysis for formaldehyde enabled investigation of the rate of formaldehyde release from noxythiolin solutions and actual concentrations of formaldehyde in solutions during clinical use and storage. The antimicrobial activity of noxythiolin solutions, equivalent pure formaldehyde solutions and N-methylthiourea individually or in combination was examined against standard bacteriological strains and clinical isolates. Several interesting observations were made. Clinical isolates were found to be relatively susceptible to noxythiolin in contrast to laboratory strains. The growth phase of the organism radically affects activity, early exponential phase cells being susceptible to 1.0% noxythiolin. Levels of formaldehyde detected in fresh noxythiolin solutions are extremely low and would not appear to be solely responsible for the antimicrobial activity observed.

Bacteroides fragilis↗

A comparative assessment of a new antacid formulation based on magaldrate.

A new antacid formulation (Dynese) based on magaldrate, a discrete chemical entity with marked antacid properties, has been compared in vitro with several commercially available antacid preparations. All preparations were tested for their ability to maintain gastric pH within acceptable limits and to effectively bind bile acids. Sodium concentrations were also determined. Dynese was shown to compare very favourably with existing preparations in that it had a prolonged even neutralization profile, efficient bile acid binding properties and a low sodium content.

Aluminum Hydroxide↗

A comparison of log P and molecular connectivity in the structure-activity analysis of some antimicrobial agents.

Several congeneric series of antimicrobial agents previously studied by Hansch analysis have been investigated using molecular connectivity as the descriptor of molecular structure. In all cases connectivity gave comparable or improved correlations compared with log P, particularly where the pattern of molecular substitution was more complex. It was concluded that the use of computer-generated connectivity terms had advantages over calculated log P values in its ease of application and should be considered at least for initial screening of structure-activity data.

Anti-Bacterial Agents↗