The use of topical anaesthesia during repair of minor lacerations in Departments of Emergency Medicine:a literature review

There are currently a number of different methods available to obtain anaesthesia in minor dermatological procedures. Although intradermal infiltration of 1% lidocaine is the favoured method for anaesthesia induction in laceration repair, it can cause significant pain in itself. Topical anaesthesia has been investigated as an alternative to infiltration anaesthesia, with the majority of studies looking at preparations of either TAC (tetracaine, adrenaline and cocaine) or LAT (lidocaine, adrenaline and tetracaine).

Long-Term Recurrence of Nonmelanoma Skin Cancer after Topical Methylaminolevulinate Photodynamic Therapy in a Dermato-Oncology Department

BACKGROUND: Most available studies on the efficacy of topical photodynamic therapy focus on short-to medium-term results. Long-term data are scarce. OBJECTIVE: To evaluate the long-term efficacy of photodynamic therapy with topical methylaminolevulinate to treat Bowen's disease and basal cell carcinoma in the clinical practice setting of a dermato-oncology department. METHODS: The study included patients diagnosed with Bowen's disease or basal cell carcinoma, and who received photodynamic therapy from 2004 to 2008. Treatment protocol and clinical follow-up were standardized. The primary endpoint was clinically observed recurrence in a previous photodynamic therapy-treated area. Descriptive and survival analyses were performed. RESULTS: A total of 31 Bowen's disease lesions and 44 superficial basal cell carcinoma were treated, with a median follow-up of 43.5 months. Recurrence was observed in 14 Bowen's disease lesions (53.8%) and in 11 superficial basal cell carcinoma (33.3%). Significantly higher estimates for recurrence rates were found in patients with Bowen's disease (p=0.0036) or those aged under 58 years (p=0.039). The risk of recurrence was higher in patients with Bowen's disease than in those with superficial basal cell carcinoma and younger patients. CONCLUSIONS: Recurrence should be considered when choosing to treat non-melanoma skin cancer with photodynamic therapy. Younger age and Bowen's disease were independent predictors for long-term recurrence, suggesting the need to establish an extended period of follow-up for this subset of patients.

Inclusion complex of piroxicam with beta-cyclodextrin and incorporation in cationic microemulsion. In vitro drug release and in vivo topical anti-inflammatory effect

Topical formulations of piroxicam were evaluated by determination of their in vitro release and in vivo anti-inflammatory effect. The in vitro release assay demonstrated that the microemulsion (ME) systems provided a reservoir effect for piroxicam release. However, the incorporation of the ME into carboxyvinilic gel provoked a greater reduction in the release of piroxicam than the ME system alone. Anti-inflammatory activity was carried out by the cotton pellet granuloma inhibition bioassay. Topical anti-inflammatory effect of the piroxicam inclusion complex/ME contained in carboxyvinilic gel showed significant inhibition of the inflammation process (36.9%, P < 0.05). Subcutaneous administration of the drug formulations showed a significant effect on the inhibition of inflammation, 68.8 and 70.5%, P <0.05, when the piroxicam was incorporated in ME and in the combined system beta -cyclodextrin (B-CD)/ME, respectively, relative to the buffered piroxicam (42.2%). These results demonstrated that the ME induced prolonged effects, providing inhibition of the inflammation for 9 days after a single dose administration. (C) 2001 Elsevier B.V. B.V. All rights reserved.

Use of topical mitomycin C in myoplasty of the medial rectus muscle of rabbits

To possibly reduce postoperative adhesions that occur after ocular myoplasties, we investigated the topical effects of 0.04% mitomycin C on the repaired areas of the medial rectus muscle using an equine renal capsule preserved in 98% glycerin for reinforcement of the sutures. Twenty-four rabbits, divided into two groups of 12 animals each [untreated (control) and treated group (MMC)], were submitted to surgical rupture of the medial rectus muscle of one eye and repair of the defect 24 h later with sutures and an equine renal capsule. Post-operative prophylactic treatment of the two groups consisted of the administration of eye drops containing neomycin, polymyxin B and dexamethasone at regular 6-h intervals for eight consecutive days and daily rinsing with physiological saline. MMC animals received additional treatment with topical 0.04% mitomycin C every 6 h for 14 consecutive days. Slit lamp biomicroscopy showed greater irritation of the ocular surface in MMC animals during the first days post operatively. Adhesions were observed at 15 and 30 days of assessment in the two groups, but were more extensive in control animals at 60 days. Histopathology revealed inflammatory exudation in both groups, which was greater in MMC animals. Mitomycin C (0.04%) instilled at 6-h intervals for 14 consecutive days reduced the occurrence of fibrosis in the myoplastic areas. However, the equine renal capsule was found to be of little benefit for the reinforcement of myoplasties.

Pyrethroid residues in milk and blood of dairy cows following single topical applications

The presence of the pyrethroid insecticides flumethrin, deltamethrin, cypermethrin and cyhalothrin in milk and blood of 10 cows was determined after single dermal applications of recommended doses. Milk and blood samples were collected every 7 days over a 35 d period and analyzed by high performance liquid chromatography. The highest residues in milk were found on day 28 for flumethrin and day 1 for deltamethrin, cypermethrin and cyhalothrin, while in blood the highest concentrations were present on day 28 for flumethrin and deltamethrin, the first day for cypermethrin, and day 14 for cyhalothrin.

Fluoride release by restorative materials before and after a topical application of fluoride gel

The release of fluoride from restorative materials (Vitremer, Ketac-Fil, Fuji II LC and Freedom) was evaluated during two 15-day periods, before and after a topical application of acidulated phosphate fluoride gel (APF). For each material, 6 specimens were made, which were immersed in 2 ml of deionized water. The fluoride concentration dosages in the solutions were read at intervals of 24 hours for 15 days. After this period, the specimens of each material received treatment with APF gel for 4 minutes and the fluoride released was analyzed at 24-hour intervals during the following 15 days. The analysis of variance and the Tukey test (p < 0.05) showed that the total mean fluoride released during the initial 15 days was greater for Vitremer and Ketac-Fil and lower for Fuji II LC and Freedom; and in the final 15 days there was a difference in release readings, with the greatest value for Vitremer, followed by Fuji II LC, Ketac-Fil and Freedom. The comparison of the results between the 1st day and the 16th day (after gel application) showed a greater fluoride release on the 16th day for Vitremer, Fuji II LC and Freedom and was equal for Ketac-Fil. Although all the materials evaluated gained fluoride with the application of APF, the data suggest that the resin-modified ionomers are more efficient in releasing fluoride to the medium than the other materials.

Immunohistochemical expression of HLA-DR in the conjunctiva of patients under topical prostaglandin analogs treatment

PURPOSE: Subclinical inflammation may be observed in patients using topical antiglaucomatous drugs. The objective of this study was to investigate inflammation in conjunctiva of glaucoma patients using prostaglandin analogs, by the detection of an immunogenetic marker (HLA-DR) and compare the effect of 3 different drugs: latanoprost, bimatoprost, and travoprost in the induction of this inflammation. SUBJECTS AND METHODS: Thirty-three patients with primary open-angle glaucoma were evaluated without and with prostaglandin analogs topical therapy. Imprints of conjunctival cells were obtained, fixed on glass slides, and prepared for immunohistochemical analysis. RESULTS: Before the use of prostaglandin analogs, 4 of the 33 patients evaluated presented expression of HLA-DR in the conjunctiva (mild). After 1 month on prostaglandin analog treatment, all but 1 patient presented HLA-DR staining. HLA-DR expression of these 32 patients was scored as mild (19 patients), medium (11 patients), or intense (2 patients). The differences were statistically significant both when the presence and the increased expression of HLA-DR were considered (P<0.001). When the 3 different groups were analyzed (latanoprost, bimatoprost, and travoprost) no statistically significant difference was found (P=0.27). CONCLUSIONS: The use of prostaglandin analogs eye drops provokes a subclinical inflammatory reaction, observed by HLA-DR expression, even after a short period of treatment, independently of the class of the prostaglandin analogs used. © 2009 Lippincott Williams & Wilkins, Inc.

Design and Characterization of Silicone and Surfactant Based Systems for Topical Drug Delivery

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Subconjunctival and topical application of recombinant tissue plasminogen activator in rabbits

To quantify fibrin degradation products after topical and subconjunctival administration of recombinant tissue plasminogen activator in rabbits. Methods: Fibrin formation was induced in the anterior chamber in 25 rabbits. Subsequently, five rabbits received an injection of r-TPA (positive control) in the anterior chamber, another 10 received a subconjunctival injection of r-TPA, and the remaining 10 received instillations of topical r-TPA. Afterwards, samples of aqueous humor were collected and semi-quantitative analysis of fibrin degradation products (FDP) was performed. Results: No statistical differences were noted between the treatment and control groups at any time point. Fibrin degradation products semi-quantification showed statistical improvement in the control group and the subconjunctival group. Conclusion: Fibrin degradation products were observed in the anterior chamber after subconjunctival administration of r-TPA. However, it was probably not sufficient to cause fibrin degradation. Topical r-TPA did not effectively absorb anterior chamber fibrin.

Topical caspofungin for treatment of keratitis caused by Candida albicans in a rabbit model

Candida albicans is the most frequent cause of fungal keratitis in temperate regions. Caspofungin has potent activity against Candida spp. in a variety of clinical settings. Little is known, however, about its activity against fungal keratitis. We compared the efficacy of topical caspofungin with that of topical amphotericin B (AMB) in a rabbit model of experimental keratomycosis. Keratitis was induced with a standardized inoculum of Candida albicans (SC 5314) placed on the debrided cornea. Twenty-four hours after infection, animals were randomly assigned to treatment with 0.15% caspofungin, 0.5% caspofungin, 0.15% AMB, and a saline control (n = 12 rabbits in each group). For the first 12 h, treatment was repeated every 30 min and, after a 12-h pause, was resumed at hourly intervals for another 12 h. The animals were examined and killed 12 h after administration of the last dose. Treatment effects were evaluated by clinical assessment, fungal culture, and histopathology. Drug treatment significantly reduced corneal fungal recovery from 3.78 log10 CFU in saline-treated animals to 2.97, 1.76, and 1.18 log10 CFU in animals treated with 0.15% caspofungin, 0.5% caspofungin, and 0.15% AMB, respectively. By histopathology, the mean hyphal density was significantly lower in the corneas of treated animals than in those of the controls; there was no difference in hyphal densities between the different treatment groups. The depth of corneal invasion was not significantly reduced by the antifungal treatments. By clinical assessment, keratitis progressed in animals treated with saline, whereas disease progression was inhibited by all drug treatment regimens. In our rabbit model, 0.5% caspofungin was as effective as 0.15% AMB for the topical treatment of Candida keratitis. The potential clinical efficacy of caspofungin awaits further investigation.

Epidermal penetration of a therapeutic peptide by lipid conjugation; Stereo-selective peptide availability of a topical diastereomeric lipopeptide

In inflammatory disorders (e.g. psoriasis), local concentrations of human neutrophil elastase (HNE), also known as polymorphonuclear leukocyte elastase (HLE), possibly overwhelm its natural inhibitors leading to extracellular matrix degradation. Elevated levels of HNE have been reported in a variety of inflammatory disorders, including psoriasis. Peptidic HNE inhibitors have a common hydrophobic sequence (Ala-Ala-Pro-Val). This peptide sequence inhibits HNE competitively; however the stratum corneum presents an effective barrier to the delivery of this tetrapeptide across the skin. The current work investigates the delivery of the modified peptide whereby the tetrapeptide was lipidated to enhance its ability to penetrate the stratum The tetrapeptide Was Coupled to a racaemic mixture of a short chain lipoamino acid (LAA) resulting in two diastereomers of the lipoamino acid-modified tetrapeptide. The penetration of the lipopeptide mixture was assessed across human epidermis in vitro. The percentage of applied dose penetrating to the receptor over 8 h following administration was 2.53% for the D-LAA conjugate and 1.47% for the L-diastereomer, compared to 0% for the peptide. The D-diastereomer appears to be relatively stable but the L-diastereomer appears to degrade releasing possibly the tetrapeptide and peptide fragment(s). Therefore the results clearly indicate that coupling the tetrapeptide to a short chain LAA enhances its delivery across human epidermis.

The use of presidential executive orders to control the management and administration of the federal government

As long as governmental institutions have existed, efforts have been undertaken to reform them. This research examines a particular strategy, coercive controls, exercised through a particular instrument, executive orders, by a singular reformer, the president of the United States. The presidents studied-- Johnson, Nixon, Ford, Carter, Reagan, Bush, and Clinton--are those whose campaigns for office were characterized to varying degrees as against Washington bureaucracy and for executive reform. Executive order issuance is assessed through an examination of key factors for each president including political party affiliation, levels of political capital, and legislative experience. A classification typology is used to identify the topical dimensions and levels of coerciveness. The portrayal of the federal government is analyzed through examination of public, media, and presidential attention. The results show that executive orders are significant management tools for the president. Executive orders also represent an important component of the transition plans for incoming administrations. The findings indicate that overall, while executive orders have not increased in the aggregate, they are more intrusive and significant. When the factors of political party affiliation, political capital, and legislative experience are examined, it reveals a strong relationship between executive orders and previous executive experience, specifically presidents who served as a state governor prior to winning national election as president. Presidents Carter, Reagan, and Clinton (all former governors) have the highest percent of executive orders focusing on the federal bureaucracy. Additionally, the highest percent of forceful orders were issued by former governors (41.0%) as compared to their presidential counterparts who have not served as governors (19.9%). Secondly, political party affiliation is an important, but not significant, predictor for the use of executive orders. Thirdly, management strategies that provide the president with the greatest level of autonomy--executive orders--redefine the concept of presidential power and autonomous action. Interviews of elite government officials and political observers support the idea that executive orders can provide the president with a successful management strategy, requiring less expenditure of political resources, less risk to political capital, and a way of achieving objectives without depending on an unresponsive Congress. ^

The use of presidential executive orders to control the management and administration of the federal government

As long as governmental institutions have existed, efforts have been undertaken to reform them. This research examines a particular strategy, coercive controls, exercised through a particular instrument, executive orders, by a singular reformer, the president of the United States. The presidents studied- Johnson, Nixon, Ford, Carter, Reagan, Bush, and Clinton-are those whose campaigns for office were characterized to varying degrees as against Washington bureaucracy and for executive reform. Executive order issuance is assessed through an examination of key factors for each president including political party affiliation, levels of political capital, and legislative experience. A classification typology is used to identify the topical dimensions and levels of coerciveness. The portrayal of the federal government is analyzed through examination of public, media, and presidential attention. The results show that executive orders are significant management tools for the president. Executive orders also represent an important component of the transition plans for incoming administrations. The findings indicate that overall, while executive orders have not increased in the aggregate, they are more intrusive and significant. When the factors of political party affiliation, political capital, and legislative experience are examined, it reveals a strong relationship between executive orders and previous executive experience, specifically presidents who served as a state governor prior to winning national election as president. Presidents Carter, Reagan, and Clinton (all former governors) have the highest percent of executive orders focusing on the federal bureaucracy. Additionally, the highest percent of forceful orders were issued by former governors (41.0%) as compared to their presidential counterparts who have not served as governors (19.9%). Secondly, political party affiliation is an important, but not significant, predictor for the use of executive orders. Thirdly, management strategies that provide the president with the greatest level of autonomy-executive orders redefine the concept of presidential power and autonomous action. Interviews of elite government officials and political observers support the idea that executive orders can provide the president with a successful management strategy, requiring less expenditure of political resources, less risk to political capital, and a way of achieving objectives without depending on an unresponsive Congress.

Enhancement of DNA repair using topical T4 endonuclease V does not inhibit melanoma formation in Cdk4R24C/R24C/Tyr-NrasQ61K mice following neonatal UVR

To further investigate the use of DNA repair-enhancing agents for skin cancer prevention, we treated Cdk4R24C/R24C/NrasQ61K mice topically with the T4 endonuclease V DNA repair enzyme (known as Dimericine) immediately prior to neonatal ultraviolet radiation (UVR) exposure, which has a powerful effect in exacerbating melanoma development in the mouse model. Dimericine has been shown to reduce the incidence of basal-cell and squamous cell carcinoma. Unexpectedly, we saw no difference in penetrance or age of onset of melanoma after neonatal UVR between Dimericine-treated and control animals, although the drug reduced DNA damage and cellular proliferation in the skin. Interestingly, epidermal melanocytes removed cyclobutane pyrimidine dimers (CPDs) more efficiently than surrounding keratinocytes. Our study indicates that neonatal UVR-initiated melanomas may be driven by mechanisms other than solely that of a large CPD load and/or their inefficient repair. This is further suggestive of different mechanisms by which UVR may enhance the transformation of keratinocytes and melanocytes.