This study describes a new model of biofilm study in rabbits. The primary focus of this study was to assess biofilm adhesion to orthopaedic metals in their first 48 h in a femoral intramedullary implantation model. Two previous inoculation methods i.e. that of pre-and direct inoculation were studied with two bacterial isolates namely Staphylococcus uureus and epidermidis, on titanium and stainless steel metallic implants. A method of sonication and log dilution/plating was used to assess biofilm bacteria adhering to implants. Silver coated metals were then compared with their respective control metals in the new model. The direct inoculation model gave larger and more reproducible biofilm adhesion to implanted metals. Staphylococcus epidermidis shows lower adhesion ability to metals, and biofilms adhere in greater numbers to stainless steel over titanium.Silver coated metals show no statistical difference over control metals when exposed to orthopaedic biofilms.

All health care personnel, especially those in the rehabilitation field, are quite familiar with the frustrations that ischemic skin ulcers engender, particularly decubiti. When preventive measures prove unsuccessful, one is faced with the problem of enhancing tissue repair of the resultant lesion. A satisfactory method for the treatment of these lesions has eluded physicians for centuries, and the variety of therapeutic techniques is exceeded only by the number of resistant ulcers.Ischemic ulcers are, by definition, areas of chronic dermal and epidermal erosion in which local hypoxia plays a major role. Aggravating factors include a multitude of pathophysiologic processes; however, most of these ulcers are sequelae of chronic venous stasis with lower extremity varicosities, peripheral arterial insufficiency, or destructive forces that act on decentralized, denervated, or even normally innervated tissue.In the past, these lesions have responded most consistently to avoidance of pressure, cleanliness, and patience. A welcome break in this routine was described by Kanof' who reported the accelerating effect of ordinary gold leaf upon the healing of decubitus ulcers. Although the study was of limited scope, in terms of ulcer type and number of patients, the inherent potential of this unique regimen seemed to warrant further evaluation and investigation.Our evaluation of the gold leaf treatment* indicated a significant acceleration in healing rate. Of particular interest was the electrometric evidence that dissipation of the negative charge from the leaf was complete in about 48 hr and also that infected ulcers were aggravated by the negatively charged gold foil. It was hypothesized that the external application of a negatively charged substance (e.g., gold leaf) forms a dipole configuration with the adjacent tissue, whose polarity thereby becomes relatively more positive and catalyzes anabolism.Armed with this hypothesis, we next evaluated healing with applied direct constant current of known intensity by means of a constant-current generator with an output range of 200-1000 PA. The treatment regimen, which utilized lowintensity direct current (LIDC), produced a healing response clearly superior to that achieved with gold leaf. Subsequent refinement of the treatment protocol has resulted in a substantial improvement in healing rate over our initial results.We were surprised to find that the effects of polarity were the opposite to those

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Basal cell carcinoma (BCC) is the most common cutaneous malignancy in humans. One of the most efficacious drugs used in the management of basal cell carcinoma BCC is the immunomodulator, imiquimod. However, imiquimod has physiochemical properties that limit its permeation to reach deeper, nodular tumour lesions. The use of microneedles may overcome such limitations and promote intradermal drug delivery. The current work evaluates the effectiveness of using an oscillating microneedle device Dermapen ® either as a pre or post-treatment with 5% w/w imiquimod cream application to deliver the drug into the dermis. The effectiveness of microneedles to enhance the permeation of imiquimod was evaluated ex vivo using a Franz cell set up. After a 24-hour permeation experiment, sequential tape strips and vertical cross-sections of the porcine skin were collected and analysed using time-of-flight secondary ion mass spectrometry (ToF-SIMS). In addition, respective Franz cell components were analysed using high performance liquid chromatography (HPLC). Analysis of porcine skin cross-sections demonstrated limited dermal permeation of 5% w/w imiquimod cream. Similarly, limited dermal permeation was also seen when 5% w/w imiquimod cream was applied to the skin that was pre-treated with the Dermapen ® , this is known as poke-and-patch. In contrast, when the formulation was applied first to the skin prior to Dermapen ® application, this is known as patch-and-poke, we observed a significant increase in intradermal permeation of imiquimod. Such enhancement occurs immediately upon microneedle application, generating an intradermal depot that persists for up to 24 hours. Intradermal colocalization of isostearic acid, an excipient in the cream, with imiquimod within microneedle channels was also demonstrated. However, such enhancement in intradermal delivery of imiquimod was not observed when the patch-and-poke strategy used a non-oscillating microneedle applicator, the Dermastamp TM . The current work highlights that using the patch-andpoke approach with an oscillating microneedle pen may be a viable approach to improve the current treatment in BCC patients who would prefer a less invasive intervention relative to surgery.

Chronic hand eczema is a common and often debilitating condition. Alitretinoin, a 9-cis-retinoic acid and pan-retinoic acid agonist, is a new and effective systemic treatment for chronic hand eczema, which provides another treatment option. A “clear” or “almost clear” response can be achieved in up to half of patients within a 24-week course of treatment. Even higher rates of remission can be obtained with a longer duration of treatment. Alitretinoin has a favorable overall profile of adverse effects; however, female patients who are at risk of becoming pregnant should follow a strict pregnancy-prevention program due to the teratogenic effects of this drug.

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Ten µg. of the lipopolysaccharide endotoxin of Salmonella typhosa was given to rabbits intravenously to enhance the subsequent antibody response to an unrelated substance. The spleens were removed 24 hours later, diced, and incubated 1 hour with the antigen, bovine-γ-globulin (BGG), in a protein-free medium. After washing, the tissues either were extracted at once or planted and the fluids and tissues harvested 1 to 3 days later. Antibody was determined by a modification of the Boyden hemagglutination technique. Small amounts of antibody were synthesized as early as 1 hour after the addition of antigen. The antibody formed could be specifically inhibited with BGG, was not dialyzable, and did not sediment at 105,000 g for 2 hours. Dose-response studies revealed no antibody formation when the BGG concentration was 0.005 or 0.05 mg./ml. The best responses were obtained at concentrations of 0.5 to 5.0 mg./ml. These results were found irrespective of whether the animal had previously received BGG in vivo. Forty per cent autologous serum increased antibody formation about 9-fold over that secured with protein-free medium or with 40 per cent homologous serum. Antibody formed with this system could be detected by 50 per cent complement fixation test, although at much lower titer than found by hemagglutination. While spleens from rabbits previously given BGG did not produce more antibody than spleens from normal rabbits, they differed in that they produced antibody without the involvement of endotoxin. Under appropriate circumstances, endotoxin was effective in vitro in enabling spleen fragments to produce antibody to BGG. Cortisone acetate administered to rabbits prior to the removal of the spleen severely inhibited antibody production in vitro. Sodium prednisolone phosphate added in vitro showed a similar irreversible effect at concentrations as low as 2 x 10–5 M. Nitrogen mustard inhibited antibody formation at concentrations as low as 10–4 M.