Guidelines of care for vascular lasers and intense pulse light sources from the European Society for Laser Dermatology.

AIM: Lasers and non-coherent intense pulse light sources (IPLS) are based on the principle of selective photothermolysis and can be used for the treatment of many vascular skin lesions. A variety of lasers has been developed for the treatment of congenital and acquired vascular lesions which incorporate these concepts into their design. Although laser and light sources are very popular due to their non-invasive nature, caution should be considered by practitioners and patients to avoid permanent side-effects. The aim of these guidelines is to give evidence-based recommendations for the use of lasers and IPLS in the treatment of vascular lesions. METHODS: These guidelines were produced by a Consensus Panel made up of experts in the field of vascular laser surgery under the auspices of the European Society of Laser Dermatology. Recommendations on the use of vascular lasers and IPLS were made based on the quality of evidence for efficacy, safety, tolerability, cosmetic outcome, patient satisfaction/preference and, where appropriate, on the experts' opinion. The recommendations of these guidelines 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: Lasers and IPLS are very useful and sometimes the only available method to treat various vascular lesions. It is of a paramount importance that the type of laser or IPLS and their specific parameters are adapted to the indication but also that the treating physician is familiar with the device to be used. The crucial issue in treating vascular lesions is to recognize the immediate end-point after laser treatment. This is the single most important factor to ensure both the efficacy of the treatment and avoidance of serious side-effects.

Early granulomatous foreign body reactions to a novel alginate dermal filler: the system's failure?

BACKGROUND: Cutaneous granulomas after a soft filler injection represent one of the worst scenarios for both patient and injector. OBJECTIVES: To present clinical and histopathological features of granulomatous nodular reactions induced by a new alginate-based dermal filler (Novabel(®)), and put it in context of the process of injectable soft tissue fillers approval and promotion in the EU. METHODS: A case series of four patients injected with Novabel(®) for volume restoration of the face and hands, who developed severe foreign body reactions. RESULTS: Four patients injected with Novabel(®) into tear troughs and/or dorsa of hands developed severe granulomatous reactions within months after injections. As we injected with the new filler into a total of 10 patients, a high incidence of 40% of the disfiguring adverse effect was observed. The inadequate response of manufacturer to our reporting the side-effects along with the available data on registration process of dermal fillers confirmed that the area is not well-regulated. CONCLUSIONS: The status of dermal fillers as class III medical devices, and the process of their approval and marketing in the EU need to be seriously reconsidered to avoid unnecessary and serious adverse reactions.

Subcutaneous injection of liquid and foamed polidocanol: extravasation is not responsible for skin necrosis during reticular and spider vein sclerotherapy.

BACKGROUND: Cutaneous necrosis is one of the most annoying complications of reticular and spider vein sclerotherapy. The precise incidence of the complication is not known, although various sources reported incidence between 0.2% and 1.2%. Among a few mechanisms proposed to explain it, extravasation of the sclerosant into the perivascular tissue has been cited as the major cause. OBJECTIVES: The aim of the experimental study in rats was to examine the potential of various concentrations and volumes of polidocanol in both liquid and foam forms to cause cutaneous necrosis after superficial subcutaneous injection. METHODS: Twenty-four female Sprague Dawley rats were injected subcutaneously different concentrations (0.5%, 1%, 2% and 3%) of polidocanol as well as different preparations of polidocanol (liquid vs. foam) and volumes (0.1-0.5 mL). The animals were sacrificed 10 days after injections and biopsy specimens were obtained. RESULTS: Cutaneous necrosis was not seen at volumes <0.5 mL regardless of the concentration or form of polidocanol injected. Foam preparation was shown to be less potent in inducing necrosis with a minimal strength being 2% in comparison with the liquid form where 1% was sufficient to produce overt cutaneous necrosis. CONCLUSIONS: This experimental study shows that extravasation of polidocal in usual circumstances of sclerotherapy of spider and reticular veins cannot be a significant cause of cutaneous necrosis rarely observed in this setting. It is particularly true for the foamed polidocanol where 1% strength seems safe if injected extravascularly in volumes up to 0.5 mL.

Pre-operative ultrasound with a 12-15 MHz linear probe reliably differentiates between melanoma thicker and thinner than 1 mm.

BACKGROUND: Pre-operative determination of primary melanoma thickness could be a tool to identify those patients who could be treated with radical primary tumour excision and sentinel lymph node biopsy in a single procedure. An excellent correlation between sonographic and histological measurement of maximal tumour thickness has been achieved using 20-MHz transducers. OBJECTIVE: To show that widely available high resolution ultrasound with 12-15 MHz linear probe could also reliably assess the thickness of primary melanoma. METHODS: Sixty-nine patients underwent ultrasound evaluation of 70 clinically and dermoscopically suspicious pigmented skin lesions before surgical excision. RESULTS: The sensitivity, specificity, positive and negative predictive values of ultrasound to detect melanoma > 1 mm were 92%, 92%, 95% and 81% respectively. The correlation between ultrasound and histological tumour thickness was very good [Pearson's correlating index 0.823 (P < 0.001)]. Mean difference between sonographic and histological measurements was 0.045 mm with limits of agreement estimated at -1.4 and +1.49, and a bias between two methods 45 microm. CONCLUSION: Ultrasound examination with a 12-15 MHz linear transducer can reliably differentiate primary melanoma > 1 mm from those

Epidemiology and diagnostics of visceral leishmaniasis in Serbia.

A retrospective epidemiological and diagnostic study of visceral leishmaniasis (VL) was carried out during the period 2001-2007 and included patients suspected of VL who had been diagnosed at the Parasitological Laboratory at the Institute for Infectious and Tropical Diseases, Belgrade. Diagnosis of VL was confirmed by microscopic examination of Giemsa-stained bone marrow (BM) smears. BM smears from 134 patients were examined; 22 cases of VL were diagnosed, the majority of which involved individuals who had been on holiday at the Montenegrian sea coast. The sensitivity of the initial BM smears was inadequate; this required the application of a serological test, adapted for routine use, for the diagnosis of VL.

Expression of heat shock protein 70 (HSP70) in patients with colorectal adenocarcinoma--immunohistochemistry and Western blot analysis.

The role of heat shock protein 70 (HSP70) expression has been investigated in various types of tumors. There are only little and controversial data about its clinical relevance in colorectal carcinoma, one of the most common carcinomas observed in humans. In this study we investigated expression of HSP70 in human colonic carcinoma and possible correlation with clinicopathology. To assess patterns (cytosolic and membrane) of HSP70 expression, the 48 surgically removed colorectal adenocarcinomas and 12 normal colonic and rectal mucosal samples were examined by immunohistochemistry and Western-blot. According to results of immunohistochemistry, expression of cytoplasmic HSP72 was significantly higher in colorectal carcinoma compared with normal and adjacent mucosa (p<0.01). In addition, there was significant increase in HSP72 expression in lymph node-positive compared to node-negative group (p<0.001). Dukes C2 stage of colonic cancer showed significantly higher immunohistochemical score than Dukes B2 and B1 stage groups (p< 0.05 i.e. p< 0.02). There was no relation between expression of HSP72 and degree of tumor differentiation. Using Western blot analyses, we noticed elevated levels of cytosolic HSP70 in colorectal cancer cells compared to normal. Densitometric analysis of blots of plasma membrane HSP70 expression has shown decrease in colorectal cancer cells compared to normal mucosa. According to our results, overexpression of HSP72 in malignant tissues of patients with colorectal carcinoma is related to tumor progression, suggesting that these proteins could play an important role not only in tumorigenesis but also in the development of drug resistance. Further research is necessary to clarify the mechanisms responsible for differential HSP70 expression as well as its definitive role in colorectal cancer.

Lupus band test and disease activity in systemic lupus erythematosus: does it still matter?

BACKGROUND: Lupus band test still has no clearly defined position within either diagnostic or disease activity measuring tools for systemic lupus erythematosus (SLE). OBJECTIVES: We tested the hypothesis that positive LBT correlates with global activity of SLE measured by the SLE Disease Activity Index (SLEDAI) score. METHODS: In total, 90 SLE patients who underwent biopsy of sunprotected non-lesional (SPNL) skin were studied prospectively. The skin specimen was processed for standard direct immunofluorescence. The patients were classified into groups as negative and positive LBT, and the latter were further subdivided on the basis of the type and morphology of the deposits. Every patient was thoroughly examined and assigned a SLEDAI score. The relationship between LBT findings and SLEDAI score was analysed. RESULTS: The disease was significantly more active in patients with positive LBT and in those with a higher number of deposited immunoreactants. Almost all patients with renal involvement had a positive LBT. CONCLUSIONS: LBT on SPNL skin may be a good marker of severe disease at presentation, particularly when three immunoglobulins are found at the dermoepidermal junction.

Persistent erythema multiforme: a report of three cases.

Three cases of persistent erythema multiforme, two of unknown aetiology and one precipitated by influenza are reported. Lesions were widespread, mostly atypical in appearance and regressed in response to immunosuppressants (systemic steroids and/or azathioprine) or, in one case, to dapsone. One patient developed erythroderma responding eventually to etretinate. Histology in all patients was consistent with the mixed, epidermodermal pattern of erythema multiforme. There were no significant laboratory abnormalities nor marked symptomatology apart from itching. The persistent form appears to belong to the spectrum of erythema multiforme being heterogeneous with respect to inducing stimuli, including viral antigens, neoplastic or inflammatory disease or unknown causes. Whenever it is possible, treatment should be adjusted depending on the causative agent.

Bullous delayed pressure urticaria; pressure testing may produce a systemic reaction.

We report a patient with bullous delayed pressure urticaria (DPU) and chronic idiopathic urticaria (CIU) in whom a systemic reaction occurred. The reaction occurred 18 h after a pressure test had been performed on the right forearm. Blood histamine levels were more elevated in the sample taken from the forearm on which the test had be applied. Skin biopsy revealed both intraepidermal and subepidermal bullae with a sparse dermal inflammatory infiltrate and direct immunofluorescence showed linear deposition of fibrinogen along the epidermodermal basement membrane. As far as we are aware this is only the third case of bullous DPU reported and the first associated with generalized urticaria and angioedema and severe broncho-obstruction. Possible pathophysiological mechanisms are discussed.

Role of beta 2 integrins in the binding of thymocytes to rat thymic macrophages.

A role of beta 2 integrins and one of their ligands, ICAM-1, in thymic macrophage (TMF)/thymocyte interactions was studied. TMF were isolated as adherent cells from 4-day old culture of thymic-cell suspensions either from normal or hydrocortisone-treated rats. Adherent cells were 94-98% positive with ED1 (a pan-macrophage marker). The majority of them (75-95%) expressed the CD11b and CD18 molecules, and 60-70% expressed CD54 (ICAM-1). A low proportion of TMF (10-20%) expressed CD11a (LFA-1). The expression of all these antigens was upregulated by IFN-gamma and TNF-alpha. The effect of these mAbs on TMF/thymocyte binding was studied using a simple rosette assay by incubating unstimulated or IFN-gamma or TNF-alpha stimulated TMF, grown on microscopic slides with resting or ConA+IL-2 activated thymocytes. It was found that LFA-1/CD18 and ICAM-1 play a significant role in the TMF/thymocyte adhesion. In addition, a LFA-1-dependent/ICAM-1-independent adhesion pathway was observed, suggesting that LFA-1 might use another ligand. The inhibitory effect of anti-CD18 mAb (WT-3) was higher than the effect of anti-LFA-1 mAb (WT-1) and was a consequence of blocking the CD18 chain both on thymocytes and TMF. No significant difference in the expression and function of adhesion molecules was found between TMF obtained from normal or hydrocortisone-treated rats. The involvement of CD11b in these processes was of lesser importance than the role of the CD11a molecule. By using mAbs to different epitopes of the CD11b molecule, such as OX-42 (anti-CD11b/CD11c), ED7, and ED8 (anti-CD11b), it was found that they were either slightly or moderately inhibitory under certain experimental conditions or did not significantly modulate TMF/thymocyte binding. OX-42 was slightly stimulatory in some experiments. Cumulatively, these results show that beta 2 integrins play a significant role in TMF/thymocyte interactions and probably contribute to T-cell development in vivo.

Two novel monoclonal antibodies reactive with different components of the rat thymic epithelium.

Two novel monoclonal antibodies (mAbs) (PT10B7 and PT13D11) have been raised against molecules of rat thymic epithelial cells (TEC). Streptavidin-biotin immunoperoxidase staining and double immunofluorescence using these mAbs and anti-cytokeratin (CK) antibodies showed that PT10B7 and PT13D11 mAbs bound to different components of rat TEC. PT10B7 mAb reacted with cortical and a subset of medullary TEC, whereas PT13D11 mAb labeled subcapsular/perivascular and most medullary TEC, including TE-R 2.5 TEC line of medullary origin. Their staining patterns were different from those seen using mAbs to CK10, CK18 and CK19 polypeptides and other anti-rat TEC mAbs produced so far. The differences in immunoreactivity of these two mAbs on rat thymus during ontogeny and on other epithelial cells of adult rats were also seen. Namely, PT13D11 stained ectoderm-derived epithelia, whereas PT10B7 stained some cells of simple epithelia. Cumulatively, these results reveal a fine phenotypic heterogeneity within rat thymic epithelium.