178 research outputs found
Novel topical therapy for mild-to-moderate plaque psoriasis: focus on calcitriol
The benefits of vitamin D derivatives for the treatment of chronic plaque psoriasis are well documented. Of importance is how compatible they are with, and how they compare to, other established treatments for psoriasis. This paper reviews 15 studies with calcitriol 3 μg g−1 ointment (Silkis®/Vectical™ ointment; Galderma Laboratories) applied twice daily for up to 52 weeks. The ointment was found to be effective and safe for the treatment of mild-to-moderate plaque psoriasis including sensitive skin areas. Calcitriol 3 μg g−1 ointment was found to be as effective as, or even superior to, other established treatment modalities and more highly tolerated than other local treatment modalities in most studies’ comparisons. It could be combined with other psoriasis treatment modalities such as ultraviolet B phototherapy or topical corticosteroids in order to achieve a faster response and in order to reduce the risk of adverse events
To change or not to change? Evidence on the steadiness of more hubristic CEOs
To Change or Not to Change? Evidence on the Steadiness of More Hubristic CEOs
Marc Kowalzick Moritz Appels University of Mannheim Extant research on CEO hubris has amassed substantial evidence on the positive association of this prominent managerial disposition and CEOs’ attraction to challenging and consequential strategic activities. Similarly, one may well anticipate more hubristic CEOs to strive for frequent transformations of their firms’ overarching trajectories as they overestimate their ability to reap the fruits of such challenging and highly consequential endeavors. In contrast to these arguments, however, higher levels of hubris might also lead CEOs to see little reason for scrutinizing and adapting extant paths in light of the magnificent prospects under their outstanding leadership. We explicate this theoretical obscurity surrounding the dispositional preference for change
or steadiness associated with higher degrees of CEO hubris by carving out sets of competing hypotheses on the effect of CEO hubris on two key domains of change within the immediate purview of a CEO: strategic change and top management team (TMT) membership change. Empirically, we examine these arguments using a panel data set comprising 1,197 S&P 1500 CEOs and find strong support for a negative effect of CEO hubris on a set of indicators of strategic change as well as on TMT membership change. Our results indicate that, beyond their attraction to manifold and challenging strategic activities, more hubristic CEOs exhibit a preference for steadiness that may prevail in the overall effect of hubris on certain organizational outcomes
Photo(geno)toxicity changes associated with hydroxylation of the aromatic chromophores during diclofenac metabolism
[EN] Diclofenac (DCF) can cause adverse reactions such as gastrointestinal, renal and cardiovascular disorders;
therefore, topical administration may be an attractive alternative to the management of local pain in order to
avoid these side effects. However, previous studies have shown that DCF, in combination with sunlight, displays
capability to induce photosensitivity disorders. In humans, DCF is biotransformed into hydroxylated metabolites
at positions 4¿ and 5 (4¿OH-DCF and 5OH-DCF), and this chemical change produces non negligible alterations of
the drug chromophore, resulting in a significant modification of its light-absorbing properties. In the present
work, 5OH-DCF exhibited higher photo(geno)toxic potential than the parent drug, as shown by several in vitro
assays (3T3 NRU phototoxicity, DNA ssb gel electrophoresis and COMET), whereas 4¿OH-DCF did not display
significant photo(geno)toxicity. This could be associated, at least partially with their more efficient UV-light
absorption by 5OH-DCF metabolite and with a higher photoreactivity. Interestingly, most of the cellular DNA
damage photosensitized by DCF and 5OH-DCF was repaired by the cells after several hours, although this effect
was not complete in the case of 5OH-DCF.This work was supported by the Carlos III Institute of Health (Grants: RD16/0006/0030, PI16/01877), by the MINECO (Grants: CTQ2013-47872, CTQ2016-78875), and by the Generalitat Valenciana (Prometeo 2017/075).García -Laínez, G.; Ana M Marínez-Reig; Limones Herrero, D.; Jiménez Molero, MC.; Miranda Alonso, MÁ.; Andreu Ros, MI. (2018). Photo(geno)toxicity changes associated with hydroxylation of the aromatic chromophores during diclofenac metabolism. Toxicology and Applied Pharmacology. 341:51-55. https://doi.org/10.1016/j.taap.2018.01.005S515534
UVA/UVA1 phototherapy and PUVA photochemotherapy in connective tissue diseases and related disorders: a research based review
BACKGROUND: Broad-band UVA, long-wave UVA1 and PUVA treatment have been described as an alternative/adjunct therapeutic option in a number of inflammatory and malignant skin diseases. Nevertheless, controlled studies investigating the efficacy of UVA irradiation in connective tissue diseases and related disorders are rare. METHODS: Searching the PubMed database the current article systematically reviews established and innovative therapeutic approaches of broad-band UVA irradiation, UVA1 phototherapy and PUVA photochemotherapy in a variety of different connective tissue disorders. RESULTS: Potential pathways include immunomodulation of inflammation, induction of collagenases and initiation of apoptosis. Even though holding the risk of carcinogenesis, photoaging or UV-induced exacerbation, UVA phototherapy seems to exhibit a tolerable risk/benefit ratio at least in systemic sclerosis, localized scleroderma, extragenital lichen sclerosus et atrophicus, sclerodermoid graft-versus-host disease, lupus erythematosus and a number of sclerotic rarities. CONCLUSIONS: Based on the data retrieved from the literature, therapeutic UVA exposure seems to be effective in connective tissue diseases and related disorders. However, more controlled investigations are needed in order to establish a clear-cut catalogue of indications
Treatment of advanced, recurrent, resistant to previous treatments basal and squamous cell skin carcinomas with a synergistic formulation of interferons. Open, prospective study
<p>Abstract</p> <p>Background</p> <p>Aggressive non-melanoma skin cancer (deeply infiltrating, recurrent, and morphea form lesions) are therapeutically challenging because they require considerable tissue loss and may demand radical disfiguring surgery. Interferons (IFN) may provide a non-surgical approach to the management of these tumors. The aim of this work was to evaluate the effect of a formulation containing IFNs-α and -γ in synergistic proportions on patients with recurrent, advanced basal cell (BCC) or squamous cell skin carcinomas (SCSC).</p> <p>Methods</p> <p>Patients with extensive, recurrent, resistant to other procedures BCC or SCSC received the IFN formulation peri- and intralesionally, three times per week for 3 weeks. They had been previously treated with surgery and/or radiotherapy or chemotherapy. Thirteen weeks after the end of treatment, the original lesion sites were examined for histological evidence of remaining tumor.</p> <p>Results</p> <p>Sixteen elder (median 70 years-old) patients were included. They beared 12 BCC and 4 SCSC ranging from 1.5 to 12.5 cm in the longest dimension. At the end of treatment 47% CR (complete tumor elimination), 40% PR (>30% tumor reduction), and 13% stable disease were obtained. None of the patients relapsed during the treatment period. The median duration of the response was 38 months. Only one patient with complete response had relapsed until today. Principal adverse reactions were influenza-like symptoms well known to occur with interferon therapy, which were well tolerated.</p> <p>Conclusion</p> <p>The peri- and intralesional combination of IFNs-α and -γ was safe and showed effect for the treatment of advanced, recurrent and resistant to previous treatments of BCC and SCSC in elder patients. This is the first report of such treatment in patients with advance non-melanoma skin cancer. The encouraging result justifies further confirmatory trials.</p> <p>Trial registration</p> <p>Current Controlled Trials RPCEC00000052.</p
Presence of papillomavirus sequences in condylomatous lesions of the mamillae and in invasive carcinoma of the breast
BACKGROUND: Viruses including Epstein–Barr virus (EBV), a human equivalent of murine mammary tumour virus (MMTV) and human papillomavirus (HPV) have been implicated in the aetiology of human breast cancer. We report the presence of HPV DNA sequences in areolar tissue and tumour tissue samples from female patients with breast carcinoma. The presence of virus in the areolar–nipple complex suggests to us a potential pathogenic mechanism. METHODS: Polymerase chain reaction (PCR) was undertaken to amplify HPV types in areolar and tumour tissue from breast cancer cases. In situ hybridisation supported the PCR findings and localised the virus in nipple, areolar and tumour tissue. RESULTS: Papillomavirus DNA was present in 25 of 29 samples of breast carcinoma and in 20 of 29 samples from the corresponding mamilla. The most prevalent type in both carcinomas and nipples was HPV 11, followed by HPV 6. Other types detected were HPV 16, 23, 27 and 57 (nipples and carcinomas), HPV 20, 21, 32, 37, 38, 66 and GA3-1 (nipples only) and HPV 3, 15, 24, 87 and DL473 (carcinomas only). Multiple types were demonstrated in seven carcinomas and ten nipple samples. CONCLUSIONS: The data demonstrate the occurrence of HPV in nipple and areolar tissues in patients with breast carcinoma. The authors postulate a retrograde ductular pattern of viral spread that may have pathogenic significance
Pattern recognition receptors in immune disorders affecting the skin.
Contains fulltext :
109004.pdf (publisher's version ) (Open Access)Pattern recognition receptors (PRRs) evolved to protect organisms against pathogens, but excessive signaling can induce immune responses that are harmful to the host. Putative PRR dysfunction is associated with numerous immune disorders that affect the skin, such as systemic lupus erythematosus, cryopyrin-associated periodic syndrome, and primary inflammatory skin diseases including psoriasis and atopic dermatitis. As yet, the evidence is often confined to genetic association studies without additional proof of a causal relationship. However, insight into the role of PRRs in the pathophysiology of some disorders has already resulted in new therapeutic approaches based on immunomodulation of PRRs
Phlebologie an deutschen Hautkliniken: eine Bestandsaufnahme im Auftrag der Deutschen Gesellschaft für Phlebologie
Reich-Schupke S, Alm J, Altmeyer P, et al. Phlebologie an deutschen Hautkliniken: Eine Bestandsaufnahme im Auftrag der Deutschen Gesellschaft für Phlebologie. Hautarzt. 2013;64(9):685-694.Phlebologic diseases have become extremely common and have major socio-economic impact. However, the percentage of dermatologists working in phlebology appears to be decreasing according to the data of the German Society of Phlebology (DGP). To investigate the reasons for this development, we-on behalf of the DGP-sent a questionnaire to 120 German Departments of Dermatology in autumn 2012. In 76 returned questionnaires, the number of physicians with additional fellowship training in phlebology averaged 1.5; the average number of those who fulfill the criteria for training fellows in phlebology was 0.9. In 71.1 % of the departments there was a phlebologist. A special phlebologic outpatient clinic existed in 73.7 % of the departments. Sonography with Doppler (89.5 %) and duplex (86.8 %) was used as the most frequent diagnostic tool. For therapy, compression (94.7 %), sclerotherapy (liquid 78.9 %, foam 63.2 %, catheter 18.4 %), endoluminal thermic procedures (radio wave 28.9 %, laser 17.1 %) and surgery (especially crossectomy and stripping 67.1 %, phlebectomy of tributaries 75 %) were used. The average number of treatments was very heterogenous in the different departments. Phlebology definitely plays an important role in dermatology. Most departments fulfill the formal criteria for the license to conduct advanced training in phlebology. A wide spectrum of phlebological diagnostic and therapeutic procedures is available.Hintergrund
Venenleiden sind eine Volkskrankheit und haben eine enorme sozioökonomische Bedeutung. Dennoch scheint der Anteil der phlebologisch tätigen Dermatologen entsprechend den Zahlen der Deutschen Gesellschaft für Phlebologie (DGP) abzunehmen.
Methoden
Um die Ursachen dieser Entwicklung zu untersuchen, führten wir im Herbst 2012 im Auftrag der DGP eine Befragungsstudie zur Phlebologie an 120 deutschen Hautkliniken durch.
Ergebnisse
In 76 antwortenden Klinien gab es im Mittel 1,5 Phlebologen und 0,9 Ärzte mit Voraussetzungen zur Weiterbildungsermächtigung Phlebologie. In 71,1 % der Kliniken gab es einen Phlebologen, in 73,7 % eine phlebologische Sprechstunde. Zur Diagnostik wurden besonders die Doppler- (89,5 %) und Duplexsonographie (86,8 %) eingesetzt. In der Therapie führte die Kompressionstherapie (94,7 %), gefolgt von Sklerosierungstherapien (flüssig 78,9 %, Schaum 63,2 %, Katheter 18,4 %), den endoluminalen thermischen Verfahren (Radiowelle 28,9 %, Laser 17,1 %) und den operativen Eingriffen (vor allem Cross- und Saphenektomie 67,1 %, Seitenastexhairese 75 %). Die durchschnittlichen Behandlungszahlen waren sehr heterogen.
Schlussfolgerung
Die Phlebologie spielt in der Dermatologie weiterhin eine wichtige Rolle. Mehrheitlich sind in den Kliniken die Möglichkeiten zur Weiterbildung Phlebologie gegeben. Es wird ein breites Spektrum an phlebologischen Techniken zur Diagnostik und Therapie angeboten
Vitamin A derivatives in the prevention and treatment of human cancer.
Vitamin A is essential for normal cellular growth and differentiation. A vast amount of laboratory data have clearly demonstrated the potent antiproliferative and differentiation-inducing effects of vitamin A and the synthetic analogues (retinoids). Recent in-vitro work has led to the exciting proposal that protein kinase-C may be centrally involved in many of retinoids' anticancer actions including the effects on ornithine decarboxylase induction, intracellular polyamine levels, and epidermal growth factor receptor number. Several intervention trials have clearly indicated that natural vitamin A at clinically tolerable doses has only limited activity against human neoplastic processes. Therefore, clinical work has focused on the synthetic derivatives with higher therapeutic indexes. In human cancer prevention, retinoids have been most effective for skin diseases, including actinic keratosis, keratoacanthoma, epidermodysplasia verruciformis, dysplastic nevus syndrome, and basal cell carcinoma. Several noncutaneous premaligancies, however, are currently receiving more attention in retinoid trials. Definite retinoid activity has been documented in oral leukoplakia, laryngeal papillomatosis, superficial bladder carcinoma, cervical dysplasia, bronchial metaplasia, and preleukemia. Significant therapeutic advances are also occurring with this class of drugs in some drug-resistant malignancies and several others that have become refractory, including advanced basal cell cancer, mycosis fungoides, melanoma, acute promyelocytic leukemia, and squamous cell carcinoma of the skin and of the head and neck. This report comprehensively presents the clinical data using retinoids as anticancer agents in human premalignant disorders and outlines the ongoing and planned studies with retinoids in combination and adjuvant therapy
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