Reduction of telogen rate and increase of hair density in androgenetic alopecia by a cosmetic product: Results of a randomized, prospective, vehicle-controlled double-blind study in men.

BACKGROUND: Considerable parts of the global population are affected by androgenetic alopecia (AGA). AIMS: The efficacy of a foam containing nicotinic acid hexyl ester, polyphenols, zinc, glycine, and caffeine in comparison with a vehicle control foam was assessed in a double-blind vehicle-controlled study in men with AGA over 6 months. PATIENTS/METHODS: Sixty-two men with AGA were assigned either to the active ingredients (verum) or the vehicle group. They applied the products twice daily on affected scalp areas over 6 months. Automated phototrichograms were obtained at baseline, after 3 and 6 months. In addition, a clinical rating by a dermatologist and by the subjects themselves was documented using standardized questionnaires. RESULTS: The reduction of the telogen rate from T0 to T6 was significantly stronger in the verum group compared to the vehicle group. The reduction was significant from T0 to T3 and T6 in the verum group, but in the vehicle group only from T0 to T3, not to T6. Significantly increased hair density was noticed in both groups at all time points, but the change from T0 to T6 did not differ significantly between the groups. Cosmetic acceptance of the foam and its application regimen was generally good in both groups. Slight reddening and burning after application of verum in six cases was probably due to the presence of hexyl nicotinate. CONCLUSION: The study demonstrated a reduction of the telogen rate by a cosmetic foam in men affected by AGA, indicating a benefit for cosmetic intervention against male pattern hair loss.

Nanomechanical Characterization of Vertical Nanopillars Using an MEMS-SPM Nano-Bending Testing Platform.

Nanomechanical characterization of vertically aligned micro- and nanopillars plays an important role in quality control of pillar-based sensors and devices. A microelectromechanical system based scanning probe microscope (MEMS-SPM) has been developed for quantitative measurement of the bending stiffness of micro- and nanopillars with high aspect ratios. The MEMS-SPM exhibits large in-plane displacement with subnanometric resolution and medium probing force beyond 100 micro-Newtons. A proof-of-principle experimental setup using an MEMS-SPM prototype has been built to experimentally determine the in-plane bending stiffness of silicon nanopillars with an aspect ratio higher than 10. Comparison between the experimental results and the analytical and FEM evaluation has been demonstrated. Measurement uncertainty analysis indicates that this nano-bending system is able to determine the pillar bending stiffness with an uncertainty better than 5%, provided that the pillars' stiffness is close to the suspending stiffness of the MEMS-SPM. The MEMS-SPM measurement setup is capable of on-chip quantitative nanomechanical characterization of pillar-like nano-objects fabricated out of different materials.

A metrological large range atomic force microscope with improved performance.

A metrological large range atomic force microscope (Met. LR-AFM) has been set up and improved over the past years at Physikalisch-Technische Bundesanstalt (PTB). Being designed as a scanning sample type instrument, the sample is moved in three dimensions by a mechanical ball bearing stage in combination with a compact z-piezostage. Its topography is detected by a position-stationary AFM head. The sample displacement is measured by three embedded miniature homodyne interferometers in the x, y, and z directions. The AFM head is aligned in such a way that its cantilever tip is positioned on the sample surface at the intersection point of the three interferometer measurement beams for satisfying the Abbe measurement principle. In this paper, further improvements of the Met. LR-AFM are reported. A new AFM head using the beam deflection principle has been developed to reduce the influence of parasitic optical interference phenomena. Furthermore, an off-line Heydemann correction method has been applied to reduce the inherent interferometer nonlinearities to less than 0.3 nm (p-v). Versatile scanning functions, for example, radial scanning or local AFM measurement functions, have been implemented to optimize the measurement process. The measurement software is also improved and allows comfortable operations of the instrument via graphical user interface or script-based command sets. The improved Met. LR-AFM is capable of measuring, for instance, the step height, lateral pitch, line width, nanoroughness, and other geometrical parameters of nanostructures. Calibration results of a one-dimensional grating and a set of film thickness standards are demonstrated, showing the excellent metrological performance of the instrument.

Hamamelis in children with skin disorders and skin injuries: results of an observational study.

Published clinical experience with hamamelis ointment in children is limited. This observational study included children (age 27 days to 11 years) with minor skin injuries, diaper dermatitis, or localized inflammation of skin. The children received either hamamelis ointment or dexpanthenol ointment in groups at a 3-to-1 ratio. Baseline and post-treatment assessments compared the total scores of predefined signs and symptoms for each condition. Physicians and parents were asked for a global assessment of efficacy and tolerability of the respective treatments at the end of therapy. A total of 309 children were treated (hamamelis n = 231; dexpanthenol n = 78). The treatment groups were comparable regarding demographic data and baseline total scores of signs and symptoms. In all three diagnosis groups, the efficacy of hamamelis and dexpanthenol was shown by a statistically significant and clinically relevant decrease of total scores from baseline to endpoint (p < 0.0001 for each group, Wilcoxon signed-rank test). Overall, the results for the hamamelis and the dexpanthenol groups were similar. Descriptive advantages for the hamamelis group were observed for a number of parameters and diagnosis groups. Both treatments were well tolerated. Ratings of the tolerability of hamamelis were "excellent" or "good" in 99.1% (physicians) and 98.2% (parents) of cases, respectively. The corresponding ratings for dexpanthenol were 97.4 and 92.3%. In conclusion, hamamelis ointment is an effective and safe treatment for certain skin disorders in children up to the age of 11 years. The observed effects are similar to dexpanthenol.

Differential role for mitogen-activated protein kinases in IgE-dependent signaling in human peripheral blood basophils: in contrast to p38 MAPK, c-Jun N-terminal kinase is poorly expressed and does not appear to control mediator release.

BACKGROUND: Exposure of human basophils to allergens results in a rapid secretion of histamine, LTC(4), IL-4 and IL-13, which dominate both the symptomology of allergic diseases and support the underlying Th2/IgE predominance associated with these reactions. The IgE-dependent release of these mediators in basophils crucially involves PI 3-kinase and the subsequent activation of p38 MAPK and ERK1&2. Here, we investigated the role of the third major member of the mitogen activated kinase family, namely the c-Jun amino terminal kinase (JNK), which is rapidly activated following IgE receptor cross-linking in murine mast cells. METHODS: Human basophils were highly purified by magnetic cell sorting. The activities of various intracellular signaling components, in basophils that had been stimulated under various conditions, were assessed by Western blotting. Mediator secretions were also determined using either spectrofluorometric analysis (histamine) or ELISA (LTC(4), IL-4 and IL-13). RESULTS: Our results show that while JNK is moderately expressed in human basophils, it is not consistently phosphorylated upon anti-IgE stimulation. Phosphorylation of the transcription factor c-Jun, a downstream target of JNK, was also undetected in contrast to p38 MAPK and ERK1&2, which were clearly activated following anti-IgE stimulation of the cells. Additionally, inhibitors of the JNK pathway failed to prevent basophil mediator release and had no effect on the phosphorylation of p38 MAPK or ERK1&2 at concentrations which were specific for JNK blockade. CONCLUSIONS: These data suggest major differences in utilizing various members of the mitogen-activated kinase family in the signal transduction cascade of IgE-receptor-bearing cells.

[Syphilis maligna in an HIV-negative patient]. / Syphilis maligna bei einem HIV-negativen Patienten.

A 21-year-old patient with a history of drug addiction presented with generalized, centrally-ulcerated papules and haemorrhagic crusts. Initially, differential diagnostic considerations included pityriasis lichenoides et varioliformis acuta and syphilis. Biopsy and serological testing confirmed the latter diagnosis. Syphilis maligna is a rare form of secondary syphilis; symptoms include a papulonecrotic exanthem and general malaise with fevers and wasting. In the past the disease was described in connection with tuberculosis; today it is most often seen in association with HIV.

Prospective randomized trial of interferon alfa-2b and interleukin-2 as adjuvant treatment for resected intermediate- and high-risk primary melanoma without clinically detectable node metastasis.

PURPOSE: Low-dose interferon alfa (IFNalpha) has been shown to have limited effects in the adjuvant treatment of patients with intermediate- and high-risk primary melanoma. We hypothesized that a combination regimen with low-dose interleukin-2 (IL-2) may improve survival prospects in these patients. PATIENTS AND METHODS: After wide excision of primary melanoma without clinically detectable lymph node metastasis (pT3 to 4, cN0, M0), 225 patients from 10 participating centers were randomly assigned to receive either subcutaneous low-dose IFNalpha2b (3 million international units [MU]/m2/d, days 1 to 7, week 1; three times weekly, weeks 3 to 6, repeated all 6 weeks) plus IL-2 (9 MU/m2/d, days 1 to 4, week 2 of each cycle) for 48 weeks, or observation alone. The primary end point was prolongation of a relapse-free interval. RESULTS: Of the 225 enrolled patients, 223 were found to be eligible. Median follow-up time was 79 months. All evaluated prognostic factors were well balanced between the two arms of the study. Relapses were noticed in 36 of 113 patients treated with IFNalpha2b plus IL-2 and in 34 of 110 patients with observation alone. Five-year disease-free survival of those who had routine surgery supplemented by IFNalpha2b and IL-2 treatment was 70.1% (95% confidence interval [CI], 61.3% to 78.9%), compared with 69.9% in those receiving surgery and observation alone (95% CI, 60.7% to 79.1%) in the intention-to-treat analysis. Evaluation of the overall survival did not show any difference between treated and untreated melanoma patients (P =.93). CONCLUSION: Adjuvant treatment of intermediate- and high-risk melanoma patients with low-dose IFNalpha2b and IL-2 is safe and well tolerated by most patients, but it does not improve disease-free or overall survival.

Optical coherence tomography in contact dermatitis and psoriasis.

Optical coherence tomography (OCT) is a new noninvasive imaging technique. In this study, it was used for the investigation of contact dermatitis and psoriasis. In these common inflammatory skin diseases the value of OCT for quantification and monitoring of the changes in comparison with other bioengineering methods was evaluated. Repeated measurements were performed in healthy volunteers after experimental induction of irritant contact dermatitis and in patients with psoriasis. In the OCT images, the thickness of the epidermis and the signal attenuation coefficient in the upper dermis were evaluated. The changes were compared with measurements of transepidermal water loss, hydration, skin colour and surface roughness, and with high-frequency ultrasound measurements. In irritant dermatitis and psoriasis, thickening of the epidermis was detected and could be monitored over time. The light scattering in the upper dermis was lower than in healthy skin. This was interpreted to be due to the inflammation and oedema, leading to a less-dense arrangement of the collagen fibres. The changes in the OCT images did not significantly correlate with the changes shown by the other methods. OCT is an interesting tool for investigation of inflammatory skin diseases. It is a simple method for determination of epidermal thickness and therefore provides, in addition to other methods, information on the severity of the disease and on treatment effects.

[Vibrio vulnificus sepsis]. / Vibrio-vulnificus-Sepsis

A 59-year-old female patient with a history of malignant lymphoma presented with symptoms of septicaemia. The skin of the extremities showed bullous, necrotizing plaques. Blood culture revealed Vibrio vulnificus as the causative organism. The infection was most likely acquired while swimming in the unusually warm Baltic Sea through inadvertent swallowing of sea water. The disease is rare in Europe. It is discussed in view of its typical clinical and histological picture.

[Scleroderma-like skin changes following administration of paclitaxel for the treatment of ovarian carcinoma]. / Sklerodermiforme Hautveränderungen bei Therapie eines Ovarialcarcinoms mit Paclitaxel.

A 61-year-old women with ovarian carcinoma was treated with surgery followed by 6 cycles of paclitaxel (Taxol) and carboplatin, producing a complete remission. During the course of therapy, she developed diffuse cutaneous sclerosis and thickening along with edema, weight gain and malaise. While antinuclear antibodies were elevated, specific antibodies against Scl 70 were not found. Other routine laboratory investigations were normal or negative. 20 MHz sonography showed a thickened, echo-rich dermis, while the Cutometer documented decreased cutaneous elasticity. Esophageal manometry identified abnormal motility. Additional screening and imaging studies showed no further evidence of systemic involvement. A skin biopsy showed dermal sclerosis. Treatment with immunosuppressive agents - prednisolone, azathioprine, cyclophosphamide- and phototherapy, including both UVA-1 and PUVA combined with penicillin, produced no definite improvement. One year after the administration of paclitaxel, the sclerosis and malaise are only minimal improved. This case is the second documented association of scleroderma-like cutaneous changes with paclitaxel therapy. Similar cases have been more often described following treatment with the analog substance docetaxel (Taxotere).

Regulation of mediator secretion in human basophils by p38 mitogen-activated protein kinase: phosphorylation is sensitive to the effects of phosphatidylinositol 3-kinase inhibitors and calcium mobilization.

Although human basophils modulate allergic diseases by secreting histamine, leukotriene C(4), interleukin (IL)-4, and IL-13, the intermediary signals controlling the release of these mediators are poorly understood. Here, we show that p38 mitogen-activated protein kinase (MAPK) crucially affects basophil activation following stimulation with various secretagogues. Phosphorylation of p38 MAPK occurred within 5 min following anti-immunoglobulin (Ig)E stimulation, but was more rapidly activated in basophils stimulated with formyl-Met-Leu-Phe or A23187. Additionally, activation of p38 MAPK to the above stimuli was dependent on extracellular influx and intracellular mobilization of calcium. SB 203580, a specific p38 MAPK inhibitor, blocked anti-IgE-induced secretion of all basophil mediators and reduced not only p38 MAPK, but also extracellular signal-regulated kinases 1 and 2 activity, whereas the MAPK antagonist, PD 098059, did not affect p38 MAPK. IgE-dependent activation of p38 MAPK and MKK3/6 was affected by LY 294002 and wortmannin, suggesting that these kinases are targets for phosphatidylinositol 3 kinase (PI 3-K). We conclude that p38 MAPK is a pivotal regulator of basophil function downstream of PI 3-K activation and calcium mobilization.