Search PubMed⌕ Search

Biomedical subjects

A D Woolfson

Publications and source records attributed to A D Woolfson.

At least 37 records · Page 2Linked to original sources

In vivo ac impedance spectroscopy of human skin. Theory and problems in monitoring of passive percutaneous drug delivery.

The use of impedance spectroscopy to evaluate transdermal drug delivery is discussed and new techniques and protocols are suggested to avoid or minimize potential problems. A novel multichannel impedance analyzer, exploiting the advantages of the "three-electrode" configuration, was employed to measure the effects of differing topically applied concentrations of the percutaneous local anesthetic amethocaine on the electrical properties of the treated skin sites. Each measured impedance spectrum was modeled by an equivalent circuit consisting of a resistor in series with the parallel combination of a pseudocapacitance and a resistor. Due to differences in skin sites and to the finite times taken to apply each electrode, it was difficult to satisfactorily compare and contrast the results obtained from adjacent skin sites. Normalization of data highlighted differences in relative impedance changes and aided the meaningful comparison of treated skin sites.

Administration, Cutaneous↗

Physicochemical characterization and preliminary in vivo efficacy of bioadhesive, semisolid formulations containing flurbiprofen for the treatment of gingivitis.

In this study, the physicochemical properties and preliminary in vivo clinical performance of formulations containing hydroxyethylcellulose (HEC; 3, 5, 10% w/w), poly(vinylpyrrolidone) (PVP; 3, 5% w/w), polycarbophil (PC; 1, 3, 5% w/w), and flurbiprofen (5% w/w) were examined. Flurbiprofen release into PBS pH 7.4 was performed at 37 degrees C. The mechanical properties (hardness, compressibility, adhesiveness, initial stress) and syringeability of formulations were determined using a texture analyzer in texture profile analysis (TPA) and compression modes, respectively. In general, the time required for release of 10 and 30% of the original mass of flurbiprofen (t10%, t30%) increased as the concentration of each polymeric component increased. However, in the presence of either 5 or 10% HEC and 5% PC, increased PVP concentration decreased both t10%, t30% due to excessive swelling (and disintegration) of these formulations. Increased concentrations of HEC, PVP, and PC significantly increased formulation hardness, compressibility, work of syringe expression, and initial stress due to the effects of these polymers on formulation viscoelasticity. Similarly, increased concentrations of PC (primarily), HEC, and PVP increased formulation adhesiveness due to the known bioadhesive properties of these polymers. Clinical efficacies of formulations containing 3% HEC, 3% PVP, 3% PC, and either 0% (control) or 5% (test) flurbiprofen, selected to offer optimal drug release and mechanical properties, were evaluated and clinically compared in an experimental gingivitis model. The test (flurbiprofen-containing) formulation significantly reduced gingival inflammation, as evaluated using the gingival index, and the gingival crevicular fluid volume, whereas, these clinical parameters were generally increased in volunteers who had received the control formulation. There were no observed differences in the plaque indices of the two subject groups, confirming that the observed differences in gingival inflammation could not be accredited to differences in plaque accumulation. This study has shown both the applicability of the in vitro methods used, particularly TPA, for the rational selection of formulations for clinical evaluation and, additionally, the clinical benefits of the topical application of a bioadhesive semisolid flurbiprofen-containing formulation for the treatment of experimental gingivitis.

Acrylic Resins↗

Breaking out of the ivory tower: from academia to clinic.

This paper considers the relationship between academic research and industry in terms of the commercial exploitation of product or process driven programmes originating in academic institutions. The commercial exploitation of pharmaceutical research is the only practical means of achieving the desired end-point of all research programmes in the pharmaceutical sciences-achieving patient benefits. The requirements for generating intellectual property rights (IPR), types of IPR likely to be encountered, time scales, costs, potential partnerships and commercial routes for exploitation are discussed. The ability to link up with industry to exploit new pharmaceutical products or processes is exemplified through two models. Model 1 involves out-licensing of IPR generated wholly within an academic setting and is illustrated by reference to the development of Ametop Gel, a novel percutaneous anaesthetic preparation. Model 2 involves a partnership with industry in a risk-sharing format, with both partners contributing expertise to the project. This latter model is illustrated by reference to a new controlled and sustained release intravaginal ring delivery system for oestrogen replacement therapy.

Clinical Trials as Topic↗

Viscoelastic properties of bioadhesive, chlorhexidine-containing semi-solids for topical application to the oropharynx.

PURPOSE: This study examined the viscoelastic properties of bioadhesive, chlorhexidine-containing semi-solid formulations, designed for topical application to the oropharynx. METHODS: Oscillatory rheometry was performed using a Carri-Med CSL2-100 rheometer at 20.0 +/- 0.1 degrees C in conjunction with parallel plate geometry (2 cm diameter, 0.5 mm sample thickness). Samples were subjected to a constant strain (6.5 x 10(-3) rad) and defined viscoelastic parameters, namely storage modulus (G'), loss modulus (G"), loss tangent (tan delta) and dynamic viscosity (eta'), measured over a defined frequency range (0.01-1.0 Hz). RESULTS: As the oscillatory frequency was increased, G' G" of all formulations increased, whereas both eta' and tan delta significantly decreased. The magnitude of increase of G' and G" as a function of frequency was relatively small, indicating that, in general, the formulations were non-cross-linked elastic systems. Increasing concentrations of HEC, PVP and PC significantly increased G', G", eta' yet decreased tan delta, observations that may be attributed to the physical state of each polymer in the formulations. Formulation elasticity increased (i.e. tan delta decreased) as a result of increased entanglement of polymeric chains of dissolved components (i.e. HEC and PVP) and the restrained extension of swollen, cross-linked chains of PC. Additionally, in formulations where the saturation solubility of PVP was exceeded and/or insufficient "free-water" was available for maximal swelling of PC, formulation elasticity increased as a result of the increasing mass of dispersed solid particles of PVP and/or PC. Formulation eta' increased due to the attendant effects of polymer chain entanglement and polymer state on overall formulation viscosity. CONCLUSIONS: Following application to the oropharynx, the formulations will behave as elastic systems. Thus, these formulations would be expected to offer advantageous clinical properties, e.g., prolonged drug release, increased bioadhesion. However, it is noteworthy that the final choice of formulation for clinical evaluation will involve a compromise between viscoelastic characteristics and acceptable textural properties, e.g. ease of product application. This study has shown the applicability of oscillatory rheometry for both the characterisation and selection of candidate, topical bioadhesive formulations for clinical evaluation.

Acrylic Resins↗

Role of physiological conditions in the oropharynx on the adherence of respiratory bacterial isolates to endotracheal tube poly(vinyl chloride).

Pneumonia is a major problem in intensive care patients and can be induced by pathogenic bacteria adhering to poly(vinyl chloride) (PVC) endotracheal (ET) tubes. This study examines the influence of surface properties on the adherence of the respiratory isolates Staphylococcus aureus and Pseudomonas aeruginosa to PVC. In particular, the influence of respiratory tract physiological conditions, 5% CO2 and saliva, on adherence was investigated. In general, decreased adherence to PVC was observed when bacteria were grown in CO2. When these CO2-grown bacteria were treated with saliva their adherence to PVC significantly increased; however, their adherence was significantly reduced to saliva-treated PVC. Treatment of both bacterial isolates with saliva decreased their negative zeta potential, a factor which may directly contribute to the observed increased microbial (saliva pretreated) adherence to PVC. Cell surface hydrophobicity (CSH) was evaluated by measuring the initial rates of microbial removal from a buffered aqueous phase, to ensure the absence of electrostatic interactions, to an organic phase (xylene). Under physiological conditions, CSH did not appear to be a dominant factor in biomaterial adherence as the CSH of S. aureus was decreased by saliva treatment but was unchanged for Ps. aeruginosa. Additionally, CSH also differed for the two isolates when grown in CO2, significantly decreasing with S. aureus but remaining unaltered with Ps. aeruginosa. Saliva treatment of PVC also decreased the advancing and receding contact angles of the biomaterial and its surface roughness, which may be a factor in the decreased adherence of saliva-treated bacteria to this surface. Alternative biomaterials or surface modifications appear necessary for the desired improvements in ET tube effectiveness. This study highlights the influence of physiological conditions on biomaterial and bacterial surface characteristics and subsequent interactions. It is imperative that the physiological conditions predominating in the clinical area of biomaterial use be considered when investigating device biocompatibility.

Bacterial Adhesion↗

Textural analysis and flow rheometry of novel, bioadhesive antimicrobial oral gels.

PURPOSE: This study examined the rheological and textural characteristics (hardness, compressibilty, adhesiveness and cohesiveness) of bioadhesive oral gels containing the antimicrobial agent chlorhexidine. METHODS: Textural analysis was performed using a Stable Micro Systems texture analyser (model TA-XT 2) in texture profile analysis (TPA) mode. In this, an analytical probe was twice compressed into each formulation to a defined depth (15 mm) and at defined rates (2, 4, 6, 8, 10 mm s-1), allowing a delay period (15 s) between the end of the first and beginning of the second compressions. Flow rheograms were performed using a Carri-Med CSL2-100 rheometer with parallel plate geometry under controlled shearing stresses at 20.0 +/- 0.1 degrees C. RESULTS: All formulations exhibited pseudoplastic flow with thixotropy. Increasing concentrations of each polymer significantly increased formulation hardness, compressibility, adhesiveness and zero-rate viscosity. Increased hardness and compressibility were due to the attendent increased viscosities of these formulations. Increased adhesiveness was related to the concentrations of the (bioadhesive) polymers employed in these formulations and, in addition, was dependent on the physical state of polycarbophil. Formulation viscosity contributed to product adhesiveness, reflecting the importance of product rheology on this parameter. Decreased formulation cohesiveness, observed as the concentrations of the PVP, PC and HEC (3-5% w/w) were increased, was due an increase in semi-solid character. Numerical values of hardness, compressibility and adhesiveness were affected by the choice of probe speed, a parameter related to rate of shear in flow rheometry. Statistical interactions were observed and were assigned to the effects of HEC on the physical state of PVP (dissolved or dispersed) and PC (swollen or unswollen). CONCLUSIONS: This study has demonstrated both the applicability of textural analysis for the mechanical characterisation of bioadhesive semi-solid gel systems and, additionally, the direct influence of viscosity on the parameters defined by textural analysis, namely, hardness, compressibility and adhesiveness.

Adhesives↗

The effects of hexetidine (Oraldene) on the adherence of Candida albicans to human buccal epithelial cells in vitro and ex vivo and on in vitro morphogenesis.

PURPOSE: This study reports the effects of hexetidine (Oraldene) on two virulence attributes of Candida albicans, namely, in vitro and ex vivo adherence of yeast cells to buccal epithelial cells (BEC) and in vitro morphogenesis. METHODS: The effects of hexetidine treatment of either yeast cells (stationary and exponential phases) or BEC on Candidal adherence, in terms of viable and non-viable adherent yeast cells, were evaluated using an acridine orange stain in conjunction with fluorescence microscopy. Ex vivo anti-adherence effects were determined by rinsing BEC in vivo with hexetidine (0.1%), removal of BEC after defined periods and inclusion in the adherence assay. The effects of hexetidine on morphogenesis were evaluated using light microscopy. Yeast cell viability following exposure to a range of concentration of hexetidine (0.005-0.1% v/v) for defined periods was determined following serial dilution and enumeration on solid media. RESULTS: Treatment of stationary and exponential phase yeast cells or BEC with hexetidine (0.1%) for a range of times (10-300 s) or, alternatively, with a range of concentrations of hexetidine (0.005-0.1%) for a fixed time (30s) significantly decreased the resultant Candidal/ epithelial adhesion. No correlations were observed between reduced adherence and either time of treatment or hexetidine concentration. In vivo treatment of BEC with hexetidine (0.1%) for 30s resulted in prolonged and significant reductions in the ex vivo adherence of both viable and non-viable yeast cells for periods of up to (and including) four hours post-rinsing. Treatment of C. albicans blastospores with hexetidine (0.05, 0.1% v/v) for 10s and 30s totally inhibited Candida morphogenesis, whereas treatment with lower antiseptic concentrations significantly reduced the extent of Candida morphogenesis and the rate of hyphal development. The effects of hexetidine on yeast cell viability were both concentration and time-dependent. CONCLUSIONS: The reduced adherence of C. albicans to BEC and the modification or inhibition of morphogenesis following exposure to hexetidine suggests a clinical role for hexetidine in the prophylaxis of both superficial candidosis and the systemic complications resulting from invasion of sub-epithelial tissue.

Antifungal Agents↗

Effect of percutaneous local anaesthetics on pain reduction during pulse dye laser treatment of portwine stains.

We have used EMLA, 4% amethocaine gel and placebo for facial portwine stains, for a period of 1 h, in a double-blind study. After removal of the preparations from the skin surface, each area was treated with six pulses of the laser, each 5 mm in diameter. Any pain noted immediately after treatment was recorded using both visual analogue (VAS) and verbal rating (VRS) scores. Twenty nine patients completed the study and statistical analysis of the results indicated that both EMLA and 4% amethocaine gel were superior to placebo (P < 0.001). However, when EMLA and 4% amethocaine gel were compared, the amethocaine preparation was significantly better (P < 0.05, VAS; P < 0.005 VRS) than EMLA in reducing pain caused by the laser treatment.

Adolescent↗

A randomised controlled trial evaluating a novel cytotoxic drug delivery system for the treatment of cervical intraepithelial neoplasia.

OBJECTIVE: To investigate the efficacy of a novel method for the treatment of cervical intraepithelial neoplasia. A cytotoxic drug delivery system using a bilaminar bioadhesive polymeric film was applied directly to the cervix. This cytotoxic drug delivery system allowed the dose, the site and the duration of application of the cytotoxic drug (5-fluorouracil) to be controlled. DESIGN: A prospective, double-blind randomised controlled trial. SETTING: The Departments of Obstetrics and Gynaecology and Pathology of Belfast City Hospital and The Queen's University of Belfast, and the Department of Pharmacy of The Queen's University of Belfast. PARTICIPANTS: One hundred and four patients who had been referred to the colposcopy outpatient clinic because of abnormal cervical cytology were recruited into the trial. They were assessed colposcopically and biopsies for histopathology were obtained. Only patients with cervical intraepithelial neoplasia lesions Grades 1 and 2 were recruited. INTERVENTIONS: All patients were re-assessed one, three, and six months after application of the cytotoxic drug delivery system by colposcopy. Clinical endpoints were noted. MAIN OUTCOME MEASURES: Pre-treatment histopathological biopsy results were compared with those obtained after treatment. RESULTS: The cytotoxic drug delivery system fulfilled the requirements for treatment of cervical intraepithelial neoplasia without causing any architechtural damage, but the chemotherapeutic agent, 5-fluorouracil, did not provide effective treatment of disease. CONCLUSIONS: This study showed that the delivery system was effective, and further studies using this mechanism are now possible.

Administration, Topical↗

Development and mechanical characterization of bioadhesive semi-solid, polymeric systems containing tetracycline for the treatment of periodontal diseases.

PURPOSE: This study examined the mechanical characteristics and release of tetracycline from bioadhesive, semi-solid systems which were designed for the treatment of periodontal diseases. METHODS: Tetracycline release into phosphate buffered saline (pH 6.8, 0.03 M) was examined using a Caleva 7ST dissolution apparatus at 37 degrees C. The mechanical properties of each formulation (hardness, compressibility, adhesiveness, elasticity and cohesiveness) were determined using texture profile analysis. Syringeability was measured using the texture analyser in compression mode as the work of syringeability i.e. the force required to express the product from a periodontal syringe over a defined distance. RESULTS: Tetracycline release from all formulations was zero-order for 24-54 h and ranged from 1.59 +/- 0.20 to 15.80 +/- 0.50 mg h-1. Increased concentrations of hydroxyethylcellulose (HEC) decreased the rate of release of tetracycline, due to the concomitant increase in product viscosity and the subsequent decreased rate of penetration of dissolution fluid into the formulation. Conversely, an increased polyvinylpyrrolidone (PVP) concentration increased tetracycline release rates, due to an increased formulation porosity following dissolution of this polymer. Increased concentrations of HEC and PVP increased the hardness, compressibility and work of syringeability of the semi-solid formulations, due to increased product viscosity. An increase in formulation adhesiveness, a parameter related to bioadhesion, was observed as the concentrations of HEC and PVP were increased, illustrating the adhesive nature of these polymers. Increased concentrations of HEC and PVP enhanced the semi-solid nature of the product, resulting in decreased product elasticity and cohesiveness. Several statistically significant interactions between polymeric formulation components were observed within the factorial design, with respect to rate of release and all mechanical properties. These interactions arose because of variations in the physical states (dissolved or dispersed) of polymeric formulation components. CONCLUSIONS: The optimal choice of bioadhesive formulation for use in periodontal disease will involve a compromise between achieving the necessary release rate of tetracycline and the mechanical characteristics of the formulation, as these factors will affect clinical efficacy and the ease of product application into the periodontal pocket.

Acrylic Resins↗

Efficacy of bioadhesive patches in the treatment of recurrent aphthous stomatitis.

This study evaluated the efficacy of bioadhesive hydrogel patches, made of a pharmaceutical grade cellulose derivative, in the control of pain and as an aid to healing of aphthous ulceration. Patients kept a twice daily ulcer diary to record their pain level on a visual analogue scale. The sensitivity of the test ulcer was assessed by a challenge with pure orange juice as a stimulant before and after application of the patch by the patient. A significant reduction in stimulated pain was recorded following application of the patches to the ulcers (P < 0.01). The patches were found to adhere longer to large ulcers in the early stages of ulceration, when they achieved their maximum protective and pain-attenuating effects. The ulcer size was recorded daily by the patient and patients claimed a reduction in healing time following patch therapy.

Adhesiveness↗

Frequency distribution of Candida albicans blastospores adhered to mucosal epithelial cells in-vitro.

Although several methods are available for examination of microbial adherence to epithelial cells, these do not distinguish between adherence of viable and non-viable micro-organisms. This study reports the use of acridine orange-stained blastospores of Candida albicans in conjunction with direct epifluorescence microscopy to determine viable (orange-fluorescing) and non-viable (green-fluorescing) blastospore adherence to buccal epithelial cells. The method was also employed to examine the effects of chlorhexidine treatment at subminimum inhibitory concentrations on the adherence of viable and non-viable blastospores. There was good correlation in the assessment of blastospore viability between the direct epifluorescence microscopy technique and the standard serial dilution and plating method for viable counting, confirming the reliability of direct epifluorescence microscopy. Chlorhexidine treatment before acridine orange staining did not alter this assessment of viability. Blastospore adherence to buccal epithelial cells resulted in a similarly skewed distribution whether examined using a crystal violet stain in conjunction with light microscopy or using direct epifluorescence microscopy, therefore validating the direct epifluorescence microscopy technique for the enumeration of blastospore adherence. Chlorhexidine treatment (0.0005% v/v, 30 min) of either blastospores or buccal epithelial cells altered the distribution of adherent blastospores per epithelial cell by increasing the number of epithelial cells having no adherent blastospores. No differences in adherence were, however, observed between blastospore or epithelial cells after treatment with this agent. Examination of the adherence of viable and non-viable blastospores to buccal epithelial cells using direct epifluorescence microscopy revealed a greater adherence capacity of non-viable than viable blastospores for buccal epithelial cells. Treatment of blastospores with chlorhexidine altered the frequency distributions of viable and non-viable blastospores with lower numbers of blastospores adherent per epithelial cell. The larger reduction in adherent viable blastospores in comparison with their non-viable counterparts is, however, an important observation which might have clinical relevance. Microbial cells adhere to epithelial cells resulting in a skewed distribution; study of this distribution gives useful information about the adherence process. Viable and non-viable components of a microbial population have different adherence capabilities and treatment of such populations with an antimicrobial agent exerting anti-adherent activity at sub-minimum inhibitory concentrations reduces the amount of adherence of these viable/non-viable components to different extents.

Adhesiveness↗

Autoradiographic imaging of the distribution of 5-fluorouracil through cervical tissue following in vitro surface application of a bioadhesive cervical patch.

The distribution of 5-fluorouracil through cervical tissue has been assessed following the in vitro application of a bioadhesive patch to excised human cervix. The bioadhesive matrix contained a total of 20 mg of 5-fluorouracil spiked with 5-fluorouracil-6-3H and was applied for fixed periods of either 4 or 24 hours. Tissue slices were sectioned perpendicular to the plane of the applied patch and the autoradiographic image developed by placing a frozen tissue slice on Hyperfilm with subsequent instant thawing and refreezing, the resulting bilayer being maintained at -18 degrees C for 24 hours. The developed image was analysed by scanning densitometry and raster scans were visualised with three-dimensional contouring software. The autoradiograms showed darker areas surrounding tissue ducts, suggesting that 5-FU was spilling from the lumen into the surrounding stroma. Transport of 5FU via aqueous channels may thus make an important contribution to the rapid penetration of the drug through the cervical stroma. Three-dimensional autoradiographic images showed that, for a 4-hour patch application, there were areas of relatively low drug concentration within the upper 5 mm of tissue, where CIN lesions can exist in the glandular tissue or cervical crypts. However, extending the application time to 24 hours produced areas of high drug concentration extending throughout this region.

Antimetabolites, Antineoplastic↗

Liquid scintillation spectrometry of 5-fluorouracil in cervical tissue following in vitro surface application of a bioadhesive cervical patch.

The potential use of bioadhesive technology for the treatment of cervical intraepithelial neoplasia was investigated. A cervical patch was designed containing 5-fluorouracil in a bioadhesive matrix and polyvinyl chloride as the backing layer. The concentration of 5-fluorouracil at specified tissue depths from the cervical surface was determined in vitro in relation to the ability of the drug to reach precancerous foci in cervical crypts up to 4 mm below the tissue surface. Thus, tissue was exposed to drug-loaded patches spiked with 5-fluorouracil-6-3H and subsequently sectioned to obtain tissue slices at different depths. The concentration of 5-fluorouracil was determined by liquid scintillation spectrometry. Drug penetration into cervical tissue exceeded a depth of 5.5 mm. Furthermore, the concentration in the tissue depended on the drug loading in the patch. Patches containing 10 and 20 mg of 5-fluorouracil produced a linear drug gradient that was established after a 4 hour application of the patch and persisted over 24 hours. However, patches containing 3.5 mg of 5-fluorouracil displayed signs of drug exhaustion after 24 hours. The penetration characteristics of 5-fluorouracil through cervical tissue using the cervical patch delivery system were sufficiently favourable to warrant further clinical investigations.

Adhesives↗

New patch delivery system for percutaneous local anaesthesia.

We have assessed the release of amethocaine from a new patch delivery system and subsequent drug diffusion through human stratum corneum and whole skin. We found that the patch system was more efficient than an amethocaine gel preparation. It was also observed, both in vitro and in vivo, that the stratum corneum acted as a reservoir for amethocaine. A double-blinded clinical trial, using 30- and 60-min application times, indicated that there was no statistical difference between patch and gel formulations in onset of percutaneous local anaesthesia. Furthermore, a 30-min application of the patch was sufficient to provide profound and prolonged topical anaesthesia in all volunteers. In contrast, although a 60-min application of EMLA was necessary to ensure satisfactory onset of percutaneous anaesthesia, the duration of action was much shorter than that of the amethocaine patch.

Administration, Cutaneous↗

The effects of three non-antibiotic, antimicrobial agents on the surface hydrophobicity of certain micro-organisms evaluated by different methods.

The effects of three non-antibiotic, antimicrobial agents (taurolidine, chlorhexidine acetate and providone-iodine) on the surface hydrophobicity of the clinical strains Escherichia coli, Staphylococcus saprophyticus, Staphylococcus epidermidis and Candida albicans were examined. Three recognized techniques for hydrophobicity measurements, Bacterial Adherence to Hydrocarbons (BATH), the Salt Aggregation Test (SAT) and Hydrophobic Interaction Chromatography (HIC) were compared. At concentrations reported to interfere with microbial-epithelial cell adherence, all three agents altered the cell surface hydrophobicity. However, these effects failed to exhibit a uniform relationship. Generally, taurolidine and povidone-iodine treatments decreased the hydrophobicity of the strains examined whereas chlorhexidine acetate effects depended upon the micro-organism treated. Subsequently, the exact contribution of altered cell surface hydrophobicity to the reported microbial anti-adherence effects is unclear. Comparison of the three techniques revealed a better correlation between the results obtained with the BATH test and HIC than the results obtained with the BATH and SAT or SAT and HIC. However, these differences may be due to the inaccuracy associated with the visual assessment of results employed by the SAT.

Anti-Bacterial Agents↗

Clinical experiences with a novel percutaneous amethocaine preparation: prevention of pain due to venepuncture in children.

1. The efficacy and safety of a novel percutaneous anaesthetic preparation based on amethocaine has been investigated in the paediatric clinical environment. 2. There were 1241 recorded applications on a named patient basis made to patients from infant to age 16 years. Of these, 88.7% had satisfactory anaesthesia to venepuncture challenge, rising to approximately 90% when the infant group was excluded. 3. A 30 min application time was found to be adequate for reliable topical anaesthesia. 4. There were no serious adverse reactions to the preparation. Of the total 6.9% recorded reactions, 6.3% were of a mild, transient erythema later identified as due to the vasodilator action of the drug. 5. A total of 123 patients received more than one application of the preparation. There was no evidence of sensitisation on subsequent exposure to the preparation. 6. The short application time required was found to be advantageous to ward and clinic routines.

Adolescent↗