Microdialysis in cutaneous pharmacology: kinetic analysis of transdermally delivered nicotine.

Direct measurements of cutaneous drug levels and kinetics have long been hampered by lack of appropriate methods. Recently, studies have indicated that microdialysis, a method of continuous in vivo sampling of extracellular fluid, may also be performed in human skin. The present study was designed to evaluate this technique for kinetic analyses of cutaneous drug levels. Using a transdermal nicotine delivery system with 35 mg of nicotine as a model, nicotine levels were determined in the dialysate of human skin by means of high performance liquid chromatography. In vitro studies demonstrated that nicotine levels in the dialysate strictly correlated with nicotine concentrations in the dialyzed medium. In nine healthy male volunteers receiving nicotine by transdermal delivery, nicotine was detectable within 90-180 min, and peak levels of approximately 1000 ng/ml were detected within 240-360 min of patch application. Correlation analyses of the individual data from our subjects revealed that nicotine kinetics were independent of skin barrier function, as assessed by transepidermal water loss, but indicated that the detectable maximum nicotine levels may depend on the location of the probe. In summary, the present study demonstrates that microdialysis may be a novel, powerful tool to study cutaneous pharmacology in vivo.

Limitations of high frequency ultrasound in determining the invasiveness of cutaneous malignant melanoma.

Preoperative assessment of melanoma invasion by sonometry has been reported to exhibit a high correlation with postoperative histometry based on the determination of a regression coefficient. We believe that this approach is not adequate and that it can be misleading. We therefore applied an appropriate statistical approach to our data to re-examine this issue. Preoperative measurements by sonometry were compared with postoperative histometry in 71 consecutive patients with the clinical diagnosis of malignant melanoma. Patients with the histological diagnosis of melanoma in situ (n = 13) were excluded from this comparison, as sonometry cannot distinguish structures restricted to the epidermis and Breslow thickness is not routinely determined in Clark level I melanomas. The agreement between sonometry and histometry was analysed by plotting the mean of the two methods against their difference. By linear regression analysis the correlation coefficient (r) in the invasive melanomas (n = 58) was found to be 0.92. The median thickness of the invasive tumours by sonometry was 1.36 mm, and by histometry 0.89 mm. In 95% of the cases sonometry differed by 37% above to 48% below the values obtained by histometry. Thus, we conclude that the accuracy of sonometry in predicting preoperative tumour thickness- and tumour invasiveness-is far lower than previously reported.

Statistical evaluation of epiluminescence microscopy criteria in the differential diagnosis of malignant melanoma and pigmented basal cell carcinoma.

Pigmented basal cell carcinoma (PBCC) is a tumour with distinct clinical features which occasionally may be difficult to differentiate from malignant melanoma (MM). The purpose of this study was to re-examine the epiluminescence microscopy (ELM) criteria for PBCC and to determine their statistical significance in the differential diagnosis of MM. Fifty histologically verified pigmented skin lesions (25 PBCCs and 25 MMs) were investigated using ELM for the presence of ELM criteria; their significance was determined by calculating the odds ratios. We found that individual ELM criteria have different weights of significance in the differential diagnosis of PBCC (leaf-like distribution of diffuse pigmentation, gradual thinning at the periphery and telangiectasia) and MM (pigment network, black and grey pigmentation, radial streaming, pseudopods, brown globules and black dots). Selected patterns of ELM criteria adjusted to the distinct types of pigmented skin lesions are characteristic features for preoperative diagnosis. The prevalence of distinct ELM criteria in PBCC and MM is of critical value in differentiating between the two types of lesions.

European guidelines for sclerotherapy in chronic venous disorders.

AIM: Sclerotherapy is the targeted chemical ablation of varicose veins by intravenous injection of a liquid or foamed sclerosing drug. The treated veins may be intradermal, subcutaneous, and/or transfascial as well as superficial and deep in venous malformations. The aim of this guideline is to give evidence-based recommendations for liquid and foam sclerotherapy. METHODS: This guideline was drafted on behalf of 23 European Phlebological Societies during a Guideline Conference on 7-10 May 2012 in Mainz. The conference was organized by the German Society of Phlebology. These guidelines review the present state of knowledge as reflected in published medical literature. The regulatory situation of sclerosant drugs differs from country to country but this has not been considered in this document. The recommendations of this guideline are graded according to the American College of Chest Physicians Task Force recommendations on Grading Strength of Recommendations and Quality of Evidence in Clinical Guidelines. RESULTS: This guideline focuses on the two sclerosing drugs which are licensed in the majority of the European countries, polidocanol and sodium tetradecyl sulphate. Other sclerosants are not discussed in detail. The guideline gives recommendations concerning indications, contraindications, side-effects, concentrations, volumes, technique and efficacy of liquid and foam sclerotherapy of varicose veins and venous malformations.

Compression stockings for treating venous leg ulcers: measurement of interface pressure under a new ulcer kit.

OBJECTIVES: The aim of this study was to measure the interface pressure of a newly designed two-layer compression stocking (Mediven ulcer kit Medi QMBH, Bayreuth, Germany) in different body positions and to compare the values with those obtained with another two-layer product. METHODS: Interface pressure was measured on the distal medial leg in 16 legs of volunteers, with the basic layer alone and with the whole stocking kit in the supine, sitting and standing position for both stocking systems. The literature concerning ulcer-healing rates is reviewed. RESULTS: Mediven ulcerkit produced statistically significant higher pressure values than the ulcer stocking with a median resting value of 35.5 mmHg in the supine and 42.5 mmHg in the standing position. The pressure while standing comes close to values exerted by bandages. The basic layer alone applies a pressure of 20.5 mmHg. CONCLUSIONS: Especially designed compression stockings exerting sufficient interface pressure may be indicated in patients with small ulcers of short duration.

[Tobacco and the skin]. / Tabak und Haut.

Various skin changes are undoubtedly caused or at least promoted by smoking. The present literature seems to concentrate mainly on active cigarette smokers, rather than on other kinds of nicotine consumption or on the effects of passive smoking. Unquestionable sequelae of cigarette smoking are the occurrence of yellow fingers, enhanced wrinkling especially in the faces of females, precancerous lesions and squamous cell carcinomas on lips and oral mucosa, vasospasms and obliterations of large arteries as well as of small skin vessels. The toxicomania is often associated with other addictions as e.g. alcoholism. The main emphasis in medical care of our population should lie in facilitating smoking cessation as well as in an effective prevention.

Granulocyte/macrophage colony-stimulating factor increases wound-fluid interleukin 8 in normal subjects but does not accelerate wound healing.

Granulocyte/macrophage colony-stimulating factor (GM-CSF) is thought to play an important part under conditions of impaired wound healing. This is not confirmed and it is also unknown whether GM-CSF affects wound healing in healthy subjects. We conducted a randomized, double-blind, placebo-controlled pilot study in 10 healthy volunteers. Triplicate wounds (10 x 10 x 0.5 mm) on the right and left upper thigh were made by a razor blade and injected with GM-CSF or a solvent control. Four of the 10 volunteers were re-examined after 2 months by investigating the healing of a new set of triplicate wounds injected with solvent control alone (controls). Factors measured were wound healing time, wound-fluid cytokines by enzyme-linked immunosorbent assay, wound-fluid inflammatory cells and dermal thickness by ultrasonography. Intradermal injection with 20 micrograms GM-CSF per wound caused significantly higher wound-fluid GM-CSF and interleukin 8 (IL-8) levels than in controls, but did not affect the time needed for wound closure (mean 11 days in all groups), dermal thickness, wound-fluid inflammatory cells or other wound-fluid cytokines, e.g. vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). Transforming growth factor (TGF) beta 1 and beta 2, epidermal growth factor (EGF), and beta-fibroblast growth factor (beta-FGF) were not measurable in any wound fluid. The lack of efficacy of exogenously delivered GM-CSF on wound healing in healthy subjects is probably based on the failure of GM-CSF to induce 'wound-healing cytokines' like PDGF, FGF, TGF, EGF or VEGF. However, GM-CSF increases IL-8 release, which is a potent chemotactic cytokine, indicating that GM-CSF might be of therapeutic value under conditions of impaired chemotaxis.

Retrospective study of hospitalized patients with chronic leg ulcers in Hawaii.

The authors describe 226 patients with chronic leg ulcers at a community hospital over a 14-year period. Most leg ulcers were ischemic or venous in origin and located below the ankle. Fifty-five percent of patients were diabetic and the majority of patients were hypertensive. The cases required prolonged hospitalization for systemic antibiotics and vascular surgery. Only 2.3% of patients required above the knee amputation, and 7% needed below-the-knee amputation.