Subnanosecond phase transition dynamics in laser-shocked iron.

Iron is one of the most studied chemical elements due to its sociotechnological and planetary importance; hence, understanding its structural transition dynamics is of vital interest. By combining a short pulse optical laser and an ultrashort free electron laser pulse, we have observed the subnanosecond structural dynamics of iron from high-quality x-ray diffraction data measured at 50-ps intervals up to 2500 ps. We unequivocally identify a three-wave structure during the initial compression and a two-wave structure during the decaying shock, involving all of the known structural types of iron (α-, γ-, and ε-phase). In the final stage, negative lattice pressures are generated by the propagation of rarefaction waves, leading to the formation of expanded phases and the recovery of γ-phase. Our observations demonstrate the unique capability of measuring the atomistic evolution during the entire lattice compression and release processes at unprecedented time and strain rate.

[Current aspects of pain management during and after dermatologic surgery]. / Aktuelle Aspekte zum Schmerzmanagement während und nach dermatologischen Operationen.

The project "Pain-free Hospital" was the first attempt to improve the level of postoperative care by standardizing pain therapy standards (concepts) in the individual surgical disciplines. Dermatosurgery is no exception. In addition to drug therapy, it is also important to consider biopsychosocial aspects of the symptom pain, as this is the only way to prevent chronification of acute pain in the further course of a disease. Drug therapy should not only be adapted to the classic WHO system (only considering pain intensity), but should also address aspects of pain quality. In this article, we discuss these aspects in more detail and present our treatment concept for dermatosurgery.

[Postmenopausal lichen planopilaris also known as fibrosing frontotemporal alopecia Kossard : An evidence-oriented practical guide to treatment from the University of the Saarland, Hair Research Center of the Dr. Rolf M. Schwiete Foundation]. / Postmenopausaler Lichen planopilaris alias fibrosierende frontotemporale Alopezie Kossard : Ein evidenzorientierter "practical guide to treatment" des Haarforschungszentrums der Dr. Rolf M. Schwiete Stiftung an der Universität des Saarlandes.

Postmenopausal lichen planopilaris (PLPP), also known as fibrosing frontotemporal alopecia Kossard (FFAK), is a not uncommon inflammatory scalp disease affecting approximately 5% of patients at specialized hair centers. The overall incidence of sporadic occurrence is believed to be just under 1% in the older, predominantly female, general population. Since the disease is often undiagnosed, it is statistically likely to be underrepresented. It especially occurs in postmenopausal women who are in the 6th and 7th decade of life (90%), but also in about 10% of premenopausal women, and in men it is documented only in isolated cases. The result is a permanent scarring hair loss accentuated at the front hairline with backward movement towards the neck mostly accompanied by a typical loss of the eyebrows. The disease therefore often leads to significant mental distress and social anxiety in those affected. This is the basis for a compelling need to develop evidence-based therapeutic concepts. While numerous retrospective case series have characterized the phenomenology of FFAK very well, to date there are no randomized controlled trials on evidence-based therapy. Here, we present the Homburger Evidence-Oriented Therapy Algorithm, which is oriented along the available case series evidence: It may (1) serve as a therapy guide for practice and (2) can be used as a basis for working out reliable data based on study evidence. The article contains detailed practical information on photo documentation, biopsy and histological processing up to the practical implementation of, for example, intralesional steroid therapy as well as information on selection criteria for suitable systemic therapies.

[Melasma : An update on the clinical picture, treatment, and prevention]. / Melasma : Ein Update zu Klinik, Therapie und Prävention.

Melasma, also known as chloasma or mask of pregnancy, presents clinically as hyperpigmented skin areas, which develop mostly in the face as a consequence of increased synthesis of melanin. The established treatment options, including topically applied agents and the use of various laser systems, mostly result in improvement but not in complete remission of the lesions. Because of its significant impact on quality of life and the limited effectivity of available treatment options, the management of melasma is challenging for the treating physician. Although many risk factors, including pregnancy and UV exposure, have been identified, the pathogenesis is not yet fully understood. Avoiding solar or artificial UV exposure is of high importance both for the prevention of melasma and for the clinical outcome of existing lesions. In order to avoid vitamin D deficiency, oral vitamin D supplementation should be recommended. In this review, we give an update on clinical aspects, epidemiology, pathogenesis and therapy of melasma and give an outlook on future developments.

Following the stability of amphiphilic nanoaggregates by using intermolecular energy transfer.

An intermolecular energy transfer system is developed for studying the stability of nanoaggregate(s) (NAs) in complex solution and cell culture by one- and two-photon fluorescence microscopy and optical imaging. The system allows facile addition of one or more tumor targeting molecules, one of which is exemplified here. NAs functionalized with an MRI and optical probe, with and without folic acid, remain stable in fetal bovine serum for at least 4 hours. HeLa cell cultures showed a clear difference between NAs non-targeted and targeted to folate receptors, with both NAs appearing to be taken up by the cells through different mechanisms. An MRI relaxivity, r1, of 9 mM-1 s-1 at 310 K and 1.4 T was measured associated with the increased rotational correlation time of the NAs. These NAs may have application in the targeted drug delivery of hydrophobic drugs such as doxorubicin (DOX).

Adjuvant treatment with pegylated interferon α-2a versus low-dose interferon α-2a in patients with high-risk melanoma: a randomized phase III DeCOG trial.

BACKGROUND: Adjuvant treatment with interferon (IFN)-α-2a improved disease-free survival (DFS) and showed a trend for improving overall survival (OS) in melanoma. This trial was designed to examine whether PEG-IFN is superior to IFN with regard to distant metastasis-free survival (DMFS), DFS and OS. PATIENTS AND METHODS: In this multicenter, open-label, prospective randomized phase III trial, patients with resected cutaneous melanoma stage IIA(T3a)-IIIB (AJCC 2002) were randomized to receive PEG-IFN (180 µg subcutaneously 1×/week; 24 months) or IFN α-2a (3MIU subcutaneously 3×/week; 24 months). Randomization was stratified for stage, number of metastatic nodes, age and previous IFN treatment. The primary end point was DMFS; secondary end points were OS, DFS, quality of life (QoL) and tolerability. RESULTS: A total of 909 patients were enrolled (451 PEG-IFN versus 458 IFN). Neither 5-year DMFS [PEG-IFN 61.0% versus IFN 67.3%; hazard ratio (HR) 1.16, P = 0.21] nor 5-year OS (PEG-IFN 73.2% versus IFN 75.2%; HR 1.05, P = 0.70) nor 5-year DFS (PEG-IFN 57.3% versus IFN 60.9%; HR 1.09, P = 0.40) showed significant differences. Subgroup analyses in patients ± ulcerated primaries and of different tumor stages did not find differences in DMFS, OS or DFS between the treatment groups. One hundred and eighteen patients (26.2%) in the PEG-IFN and 61 patients (13.3%) in the IFN population did not receive the full dosage and length of treatment due to adverse events (P < 0.001). Leukopenia and elevation of liver enzymes were more common in the PEG-IFN arm (56% versus 23.5% LCP; 19.1% versus 9.4% AST; 33.0% versus 16.5% ALT). QoL was identical for nearly all domains. CONCLUSION: PEG-IFN did not improve the outcome over IFN. A higher percentage of patients under PEG-IFN discontinued treatment due to toxicity. CLINICAL TRIALSGOV IDENTIFIER: NCT00204529.

Same Site Recurrence is More Frequent After Endovenous Laser Ablation Compared with High Ligation and Stripping of the Great Saphenous Vein: 5 year Results of a Randomized Clinical Trial (RELACS Study).

OBJECTIVE: To compare the long-term clinical efficacy of endovenous laser ablation (EVLA) with high ligation and stripping (HLS) as standard treatment for great saphenous vein (GSV) incompetence. DESIGN: Investigator initiated two centre randomized controlled trial with 5 year follow up. MATERIALS AND METHODS: Interventions were performed on ambulatory and hospitalized patients at two vein centres, a university dermatology department (EVLA) and a specialized vein clinic (HLS). Four hundred patients suffering from GSV incompetence were assigned to EVLA or HLS of the GSV. One hundred and eighty five and 161 patients (=limbs), respectively, were treated per protocol. Main outcome measures were clinically recurrent varicose veins after surgery (REVAS classification, primary study objective), Duplex detected saphenofemoral recurrence, clinical venous severity scoring (Homburg Varicose Vein Severity Score), quality of life (Chronic Venous Insufficiency Questionnaire 2), side effects, and patient satisfaction 5 years after treatment. RESULTS: Two hundred and eighty one legs (81% of the study population) were evaluated with a median follow up of 60.4 (EVLA) and 60.7 months (HLS). Overall, REVAS was similarly observed in both groups: 45% (EVLA) and 54% (HLS), p = .152. Patients of the EVLA group showed significantly more clinical recurrences in the operated region (REVAS: same site): 18% vs. 5%, p = .002. In contrast, more different site recurrences were observed in the HLS group: 50% vs. 31%, p = .002. Duplex detected saphenofemoral refluxes occurred more frequently after EVLA: 28% vs. 5%, p < .001. Both treatments improved disease severity and quality of life without any difference. CONCLUSIONS: EVLA and HLS are comparably effective concerning overall REVAS, improvement of disease severity, and quality of life. In terms of same site clinical recurrence and saphenofemoral refluxes, HLS is superior to EVLA 5 years after treatment. CLINICAL TRIAL REGISTRATION: ISRCTN18322872.

[Malignant head and neck melanoma : Part 1: Diagnosis and histological particularities]. / Maligne Melanome im Kopf-Hals-Bereich : Teil 1: Diagnostik und histologische Besonderheiten.

About 15% of all cutaneous melanomas develop in the head and neck region. Mucosal melanomas are rare and represent only 1% of all melanomas, however, most frequently, these are located in the nose, the paranasal sinuses and the oral cavity. Visual diagnosis and reflected-light microscopy are relevant for the evaluation of melanoma-suspect lesions. Histological investigation of resected tumors need special skills of the histopathologist and includes in case of high-risk tumors investigations of mutations in the tumor tissue concerning NRAS, BRAF and KIT. The risk of lymphatic or hematogeneous spread rises with increasing tumor thickness and the presence of further prognostic risk factors such as ulceration of the primary tumor or the presence of mitoses within the tumor.

[Malignant head and neck melanoma: Part 2: Therapy]. / Maligne Melanome im Kopf-Hals-Bereich: Teil 2: Therapie.

Resection margins of melanomas in the head and neck region often have to be adapted according anatomical circumstances. In the case of thicker primary tumors or after complete resection of locoregional lymph node metastases, adjuvant therapy with interferon-α can be performed; in some cases, adjuvant radiotherapy may also be indicated. In the case of inoperable lymph node or distant metastases, systemic treatment is required. Beside well-established mono- or polychemotherapy regimens, newer targeted therapies with BRAF inhibitors (vemurafenib, dabrafenib), mitogenic-activated protein kinase (MEK) inhibitors (trametinib, binimetinib, and cobimetinib), and kinase inhibitors (imatinib, sunitinib, nilotinib, dasatinib) are also available.

[Monosystemic, oligolesional Langerhans cell histiocytosis. A rare congenital dermatosis]. / Monosystemische, oligoläsionale Langerhans-Zell-Histiozytose der Haut. Eine seltene kongenitale Dermatose.

A five-day-old female infant presented with congenital red-livid papules and nodules on the head, chest, back and left arm. The nodule on the chest was ulcerated at birth. The pregnancy and delivery were uneventful. There was no history of birth trauma to account for the ulcerated lesion. The parents and the three older siblings were healthy without similar skin lesions. The skin biopsy showed in the deep layer of the dermis a multinodular, granulomatous histiocytic infiltrate. The histiocytic cells expressed S-100 and CD1a. There were additionally many eosinophils. The suspected diagnosis Langerhans cell histiocytosis was confirmed by the histologic results. The patient was referred to pediatric hematology-oncology where evaluation showed no evidence of systemic involvement. The clinical, radiological, sonographic and histological results led to the diagnosis of a congenital, monosystemic, oligolesional Langerhans cell histiocytosis of the skin. In addition to the case presentation, we review the current stand of knowledge of the pathogenesis, the clinical classification and the therapy of the Langerhans cell histiocytosis.

[Disseminated infiltrated cutaneous pruritis]. / Disseminierte infiltrierte juckende Läsionen am Körper.

The diagnosis of scabies is clinically not always simple without the detection of mites. Histology can be difficult, particularly without clinico-pathologic correlation. [corrected] Even after adequate antiscabies treatment the dermatological symptoms and complaints can persist and necessitate an [corrected] intensive follow-up treatment. The case example described here underlines that in consideration of the multifaceted clinical appearance and the sometimes difficult detection of mites, scabies should always be considered as a differential diagnosis in cases of persistent pruritis.

[Reticulated teleangiectatic erythema after implantation of medical devices. An increasingly occurring phenomenon?]. / Retikuläre teleangiektatische Erytheme nach Implantation von elektrischen medizinischen Geräten. Ein an Häufigkeit zunehmendes Phänomen?

Reticulated telangiectatic erythema (RTE) is a rare skin reaction to extraneous materials. We present three cases in which asymptomatic persistent erythemas developed in the area of implantation after medical devices were inserted. Topical and systemic treatment did not improve the skin changes. Patch testing including applied materials showed negative results in all cases. Histological investigation of punch biopsy specimens showed moderate dilatated vessels and a slight lymphocytic infiltrate. Due to our findings and in synopsis with the clinical impression we diagnosed RTE. As RTE is asymptomatic in most cases, the devices need not be removed.

Lichen striatus and blaschkitis: reappraisal of the concept of blaschkolinear dermatoses.

BACKGROUND: Blaschkitis (BL) and lichen striatus (LS) are rare dermatoses occurring along the Blaschko lines of the skin with preferential occurrence in distinct age categories. Controversy exists regarding the pathogenesis and classification of BL and LS within the spectrum of blaschkolinear dermatoses. OBJECTIVES: To describe the clinicopathological characteristics of six cases of BL/LS with special emphasis on immunophenotyping the inflammatory infiltrate. Additionally, we review and critically discuss current concepts of the blaschkolinear dermatoses. METHODS: Skin biopsies from six patients with BL and LS were analysed retrospectively. The immunophenotypes of the inflammatory cells were determined and related to clinical features. RESULTS: The clinical characteristics of the diseases occurred equally in both genders and all ages. BL and LS had similar histopathological findings with respect to epidermal changes and composition of the inflammatory infiltrates. Characteristically, a lichenoid lymphocytic infiltrate with exocytosis of inflammatory cells and obvious alterations of the interface zone was observed. CONCLUSIONS: We characterize the two main blaschkolinear dermatoses BL and LS sensu stricto morphologically and open new insights into the pathogenesis of these diseases. We propose the concept of a wide spectrum of blaschkolinear dermatoses with BL and LS located somewhere within the spectrum. We do not think that it is helpful for clinicians to enlarge the spectrum of blaschkolinear diseases and to create numerous 'new' entities. Rather, our aim was to unify diseases with similar clinical and histopathological features and common genetic pathomechanisms underlying phenotypic variations.

RNAi-mediated germline knockdown of FABP4 increases body weight but does not improve the deranged nutrient metabolism of diet-induced obese mice.

OBJECTIVE: To investigate the impact of reduced adipocyte fatty acid-binding protein 4 (FABP4) in control of body weight, glucose and lipid homeostasis in diet-induced obese (DIO) mice. METHODS: We applied RNA interference (RNAi) technology to generate FABP4 germline knockdown mice to investigate their metabolic phenotype. RESULTS: RNAi-mediated knockdown reduced FABP4 mRNA expression and protein levels by almost 90% in adipocytes of standard chow-fed mice. In adipocytes of DIO mice, RNAi reduced FABP4 expression and protein levels by 70 and 80%, respectively. There was no increase in adipocyte FABP5 expression in FABP4 knockdown mice. The knockdown of FABP4 significantly increased body weight and fat mass in DIO mice. However, FABP4 knockdown did not affect plasma glucose and lipid homeostasis in DIO mice; nor did it improve their insulin sensitivity. CONCLUSION: Our data indicate that robust knockdown of FABP4 increases body weight and fat mass without improving glucose and lipid homeostasis in DIO mice.

Expression of CD30 antigen in superficial mycotic infections of the skin: a possible non-specific finding without clinical relevance.

Expression of CD30 is a distinct marker of lymphocytic activation, originally described in Reed-Sternberg cells of Hodgkin's disease. Recently, the first two cases in which CD30 was expressed in tissue samples derived from superficial cutaneous fungal infections have been reported. The objective of this study was to investigate the expression of CD30 in tinea corporis and to discuss the clinical relevance of CD30. Twenty-three skin biopsies from 23 patients with mycotic infections of the skin were analysed retrospectively. The immunophenotypic expression of CD30 was investigated. In the series investigated, some large CD30-positive cells located in the upper dermal infiltrate were noted in two of 23 biopsy specimens (8.7%). The existence of CD30-positive cells was independent of the density and composition of the accompanying inflammatory infiltrate. We showed that the expression of CD30 in dermatophytoses is not a consistent finding. Instead, as a sign of lymphocytic activation, CD30 expression is observed coincidentally in cutaneous fungal infections. Our data confirm the observation that CD30 antigen is expressed in a variety of benign and malignant skin disorders, including cutaneous fungal infections, probably as an epiphenomenon without clinical relevance.

[Of bugs and joints. Oligoarthritis caused by Tropheryma whipplei]. / Oligoarthritis durch Tropheryma whipplei. "Of bugs and joints".

Whipple's disease is a rare, chronic infection caused by Tropheryma whipplei, an ubiquitary gram positive bacterium. The disease is associated with a high mortality in absence of an antibiotic treatment. The disease can be detected in affected tissues and body fluids by light and electron microscopy, as well as by polymerase chain reaction (PCR). Musculoskeletal symptoms such as arthralgia and arthritis frequently represent the first manifestation of this multi-system disease; typical subsequent symptoms are weight loss, diarrhea, and abdominal pain. Symptoms of central nervous system involvement are present in 10-40% of cases. We report on a 67 year-old male with a history of migratory oligoarthritis over three decades in whom the causative agent was detected by PCR in synovial fluid only. This case illustrates that searches for the characteristic PAS-positive macrophages and PCR in biopsies from the duodenum may be insufficient and that diagnostic efforts should be complemented with PCR assays from affected tissues or body fluids. It is recommended that antibiotic treatment be carried out with an agent that penetrates well into the cerebrospinal fluid, e.g. ceftriaxone, followed by cotrimoxazole. Antibiotics should be maintained over several months to years. It is prudent to document the disappearance of the pathogen in the affected compartments prior to the discontinuation of the antibiotic therapy.

Plaque-Like Sclerodermiform Localized Mucinosis Rapidly Responsive to Topical Tacrolimus.

We report the successful treatment of plaque-like sclerodermiform mucinosis using tacrolimus ointment topically. We present a 70-year-old male with a large chronic erythema and hardening of the nuchal skin and shoulder area. Subjective symptoms were a moderate pruritus and a rather disabling stiffness. A biopsy specimen revealed typical features of lichen myxedematosus. In a subsequent clinical examination, no associated illnesses such as hypothyroidism or gammopathy were found. Since no established therapy exists for this condition, and as there was a lack of response to potent topical glucocorticosteroids, tacrolimus 0.03% ointment was used off-label twice daily. Surprisingly, this resulted in a rapid, almost complete clearance of the skin within three weeks of treatment.