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Any experiment involving living organisms requires justification of the need and moral defensibleness of the study. Statistical planning, design, and sample size calculation of the experiment are no less important review criteria than general medical and ethical points to consider. Errors made in the statistical planning and data evaluation phase can have severe consequences on both results and conclusions. They might proliferate and thus impact future trials-an unintended outcome of fundamental research with profound ethical consequences. Unified statistical standards are currently missing for animal review boards in Germany. In order to accompany, we developed a biometric form to be filled and handed in with the proposal at the concerned local authority on animal welfare. It addresses relevant points to consider for biostatistical planning of animal experiments and can help both the applicants and the reviewers in overseeing the entire experiment(s) planned. Furthermore, the form might also aid in meeting the current standards set by the 3+3R's principle of animal experimentation: Replacement, Reduction, Refinement as well as Robustness, Registration, and Reporting. The form has already been in use by the concerned local authority of animal welfare in Berlin, Germany. In addition, we provide reference to our user guide giving more detailed explanation and examples for each section of the biometric form. Unifying the set of biostatistical aspects will help both the applicants and the reviewers to equal standards and increase quality of preclinical research projects, also for translational, multicenter, or international studies.

Background The present paper aims to assess the lower threshold of vascular flow rate on the heat sink effect in bipolar radiofrequency ablation (RFA) ex vivo. Methods Glass tubes (vessels) of 3.4 mm inner diameter were introduced in parallel to bipolar RFA applicators into porcine liver ex vivo. Vessels were perfused with flow rates of 0 to 1,500 ml/min. RFA (30 W power, 15 kJ energy input) was carried out at room temperature and 37°C. Heat sink effects were assessed in RFA cross sections by the decrease in ablation radius, area and by a high-resolution sector planimetry. Results Flow rates of 1 ml/min already caused a significant cooling effect (P ≤ 0.001). The heat sink effect reached a maximum at 10 ml/min (18.4 mm/s) and remained stable for flow rates up to 1,500 ml/min. Conclusions Minimal vascular flows of ≥1 ml/min cause a significant heat sink effect in hepatic RFA ex vivo. A lower limit for volumetric flow rate was not found. The maximum of the heat sink effect was reached at a flow rate of 10 ml/min and remained stable for flow rates up to 1,500 ml/min. Hepatic inflow occlusion should be considered in RFA close to hepatic vessels.

Background Topical minoxidil formulations have been shown to be effective in treating androgenetic alopecia (AGA) for 12 months. Efficacy and safety in both frontotemporal and vertex regions over longer application periods have not been studied so far. Objectives To evaluate the effect of 5% minoxidil topical foam (5% MTF) in the frontotemporal and vertex areas in patients with moderate AGA over 104 weeks. Methods An 80-week, open-label extension phase was performed, following a 24-week randomized, double-blind, placebo-controlled study in men with AGA grade IIIvertex to VI. Group 1 (n = 22) received ongoing 5% MTF for 104 weeks, Group 2 (n = 23) received placebo topical foam (plaTF) until week 24, followed by 5% MTF until week 104 during the extension phase. Frontotemporal and vertex target area non-vellus hair counts (f-TAHC, v-TAHC) and cumulative hair width (f-TAHW, v-TAHW) were assessed at baseline and at weeks 24, 52, 76 and 104. Results In Group 1, f-TAHW and f-TAHC showed a statistically significant increase from baseline to week 52 and week 76, respectively, returning to values comparable to baseline at week 104. No significant differences were found between baseline and week 104 in v-TAHC in Group 1 as well as f-TAHC, v-TAHC, f-TAHW and v-TAHW values in Group 2. Conclusions 5% MTF is effective in stabilizing hair density, hair width and scalp coverage in both frontotemporal and vertex areas over an application period of 104 weeks, while showing a good safety and tolerability profile with a low rate of irritant contact dermatitis.

The effect of different diaper care procedures on skin barrier function in infants has been minimally investigated and may be assessed using objective methods. In a single-center, prospective trial, 89 healthy 9-month-old infants (±8 wks) were randomly assigned to three diaper care regimens: group I used water-moistened washcloths at diaper changes (n = 30), group II additionally applied diaper cream twice daily (n = 28), and group III used wet wipes and diaper cream twice daily (n = 31). Transepidermal water loss (TEWL), skin hydration (SCH), skin pH, interleukin 1α (IL-1α) levels, and microbiologic colonization were measured in diapered skin (upper outer quadrant of the buttocks), nondiapered skin (upper leg), and if diaper dermatitis (DD) occurred, using the most affected skin area at day 1 and weeks 4 and 8. Skin condition was assessed utilizing a neonatal skin condition score and diaper rash grade. On diapered skin, SCH decreased in groups II and III, whereas TEWL values were reduced in group II only. Skin pH increased in groups II and III. In general, SCH, skin pH, and IL-1α levels were higher in healthy diapered skin than in nondiapered skin. The incidence and course of DD was comparable in all groups. Areas with DD had greater TEWL and skin pH than unaffected skin areas. Infants who received diaper cream had lower SCH and TEWL and higher pH levels in the diapered area than on nondiapered skin. No correlation with the occurrence of DD was found.

Aims Intramyocardial inflammation is considered an adverse prognostic factor in inflammatory cardiomyopathy (CMi). However, the precise nature of immune system factors relevant for the prediction of long-term course remains elusive. The aim of this study was to analyse the prognostic relevance of perforin in a large cohort of patients with CMi. Methods and results We investigated 495 consecutive patients with suspected CMi, undergoing endomyocardial biopsies (EMBs), and examined haemodynamic measurements after a long follow-up period (interquartile range 10.2–37.1 months). In EMBs, myocardial inflammation was assessed by histology and immunohistology. At follow-up, 388 patients (Group I) showed stable mild dysfunction or significant improvement, with LVEF rising from 46.2 ± 14.8% to 64.3 ± 12.3% (P

Summary Background Management of patients with lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) is rendered difficult as robust epidemiologic data, insights on pathogenesis, associated diseases, possible relevance of concomitant medications or environmental factors are lacking. Patients and Methods Retrospective analysis of demography, skin status, concomitant medication and diagnostic procedures were performed on 104 medical records (71 classic LPP, 32 FFA, and one Graham-Little-Piccardi-Lassueur syndrome). Results Women were more often affected (distribution F: M classic LPP 4.9: 1; FFA: 31: 1). Compared to LPP patients, patients with FFA were significantly older (p < 0.001), more often postmenopausal, and more frequently on hormone replacement therapy. No other specific associations were identified. An association with lichen planus, other autoimmune diseases, or hepatitis virus infection was found only in individual patients. Clinically, FFA patients were significantly more often reported to have reduced eyebrows (p < 0.005), axillary, and/or pubic hair (p = 0.050). Conclusions The findings obtained from this study, with currently largest LPP/FFA patient cohort in Germany, encouraged us to set up a national FFA patient registry. Prospective data collected from larger numbers of patients with standardized questionnaires will help to assess assumed associations and influencing factors and to develop, in the long-term, recommendations for diagnosis and treatment.

Transcutaneous immunization (TCI) requires targeting of a maximum number of skin antigen-presenting cells as non-invasive as possible on small skin areas. In two clinical trials, we introduced cyanoacrylate skin surface stripping (CSSS) as a safe method for TCI. Here, using ex vivo human skin, we demonstrate that one CSSS procedure removed only 30% of stratum corneum, but significantly increased the penetration of 200 nm polystyrene particles deep into vellus and intermediate hair follicles from where they could not been retrieved by conventional tape stripping. Two subsequent CSSS had no striking additional effect. CSSS increased particle penetration in superficial stratum corneum and induced Langerhans cell activation. Formulation in amphiphilic ointment or massage did not substantially influences the interfollicular penetration profiles. Hair follicle (HF) targeting by CSSS could become a highly effective tool for TCI when combined with carrier-based delivery and is gaining new attention as our understanding on the HF immune system increases.

Angioimmunoblastic T cell lymphoma (AITL) belongs to the subgroup of mature T cell lymphomas according to the World Health Organization and is one of the common T cell lymphomas in Western countries. Particularly in cases in which histological confirmation cannot be easily achieved, immunophenotyping of peripheral blood can give important information for the differential diagnosis of AITL. sCD3− CD4+ T cells are a typical feature of AILT in flow cytometry of peripheral blood. In this retrospective study, the diagnostic value of flow cytometry for the diagnosis ‘AITL’ was assessed by comparing the frequency of sCD3− CD4+ T cells in leukemic AITL patients and in patients with other leukemic CD4+ T cell lymphomas. Immunophenotyping of peripheral blood by flow cytometry was performed in a lymphocyte gate using fluorochrome-labelled antibodies against CD3, CD2, CD4, CD5, CD7, CD8, CD10, CD14, CD16, CD19, CD56, CD57 and T cell receptor. In 17/17 leukemic AITL patients, a small but distinct population of sCD3− CD4+ T cells was detected (mean percentage of sCD3− CD4+ T cells in the lymphocyte gate: 11.9 ± 15.4%, range 0.1–51.8%). In contrast, sCD3− CD4+ T cells were found in only 1/40 patients with other leukemic CD4+ T cell lymphomas (one patient with mycosis fungoides). sCD3− CD4+ T cells have a high positive predictive value (94%) for the diagnosis ‘AITL’. Flow cytometry is particularly useful in the differential diagnosis of AITL, even if the aberrant T cell population has a very low frequency. Further biological characterization of this subfraction of lymphoma cells is warranted. Copyright © 2013 John Wiley & Sons, Ltd.

Summary Background: Skin care is important especially in infancy as the skin barrier matures during the first year of life. We studied the effects of baby swimming and baby lotion on the skin barrier function of infants. Subjects and methods: 44 infants aged 3–6 months were included in this mono-center prospective study. The healthy infants swam four times and were randomized to groupL: baby lotion was applied after swimming all over the body and to groupWL: no lotion was used. Transepidermal water loss, stratum corneum hydration, skin-pH and sebum were measured on four body regions using non-invasive methods. Results: In groupL, sebum and pH remained stable. In groupWL, significant decrease in sebum was noted on forehead and thigh, and for pH on thigh and buttock. GroupL had fewer infants with at least one adverse event compared to groupWL. Location-dependent gender differences in skin barrier function were observed. Conclusions: Reaction of skin barrier function to baby swimming and skin care regimens showed typical regional variability between body areas. Influence of baby lotion on skin barrier and gender differences in skin functional parameters were demonstrated for the first time in healthy infants participating in baby swimming.

Chemokine receptors are thought to be involved in the process of cancer metastases. When investigating cell lines and tissues from colorectal cancer (CRC), the CCR7 protein unexpectedly was confined to the cytoplasm and not present on the cell surface. This study investigated at the DNA, mRNA and protein level, the mechanism and the consequences of the failure of CCR7 to localize to the cell membrane. In all 15 CRC cell lines tested, no surface CCR7 was detected and no chemotactic response was elicited upon in-vitro exposure to CCR7 chemokine ligands (CCL) 19 and CCL21. Integrity of CCR7 DNA and mRNA was examined with respect to signal peptide expression in cell lines and CRC tissues by real-time RT-PCR and sequencing. Nine of 15 CRC cell lines and 8 of 14 CRC tissues revealed a truncated CCR7 mRNA species containing various incomplete signal peptide encoding sequences, while the corresponding DNA was intact. These results indicate in CRC frequent alternative splicing or post-transcriptional mRNA modification resulting in a CCR7 molecule lacking an intact signal peptide prohibiting membrane translocation. Further studies would be necessary to identify a potential intracellular role of the truncated CCR7, abundantly present in the cytoplasm.