Effectiveness of a standardized skin care regimen to prevent atopic dermatitis in infants at risk for atopy: a randomized, pragmatic, parallel-group study.

BACKGROUND: It has been proposed that regular emollient application in early life could enhance skin barrier function and prevent atopic dermatitis (AD) especially in predisposed infants. This hypothesis was supported by evidence from exploratory and pilot trials showing protective effects in terms of reduced cumulative atopic dermatitis incidence with the use of daily emollient therapy starting immediately after birth. OBJECTIVES: To investigate the effectiveness of a standardized skin care regimen for infants on the development of AD compared to not structured skin care regimen in infants with atopic predisposition. METHODS: Prospective, parallel group, randomized, pragmatic, investigator-blinded intervention trial including 160 infants with 52 weeks intervention and 52 weeks follow up phase up to the age of two years. Infants were randomly assigned to receive a standardized skin care regimen including once daily leave-on product application (lipid content 21%) or skin care as preferred by the parents. RESULTS: Using the intention to treat approach, the cumulative AD incidence was 10.6% after one year, and 19.5% after two years in the total sample. There were no statistical significant differences between intervention and control groups. Skin barrier parameters between the intervention and control groups were comparable. AD severity was higher and quality of life was more affected in the control group. CONCLUSIONS: Regular emollient application during the first year of life does not prevent the development of atopic dermatitis. A standardized skin care regimen does not delay skin barrier development or causes side effects.

A mechanism-based group-psychotherapy approach to aggressive behaviour in borderline personality disorder: findings from a cluster-randomised controlled trial.

BACKGROUND: Aggressive behaviour is a prevalent and harmful phenomenon in patients with borderline personality disorder (BPD). However, no short-term, low-cost programme exists that specifically focuses on aggression. AIMS: Attuning therapy modules to pathogenetic mechanisms that underlie reactive aggression in BPD, we composed a 6 week mechanism-based anti-aggression psychotherapy (MAAP) approach for the group setting, which we tested against a non-specific supportive psychotherapy (NSSP). METHOD: A cluster-randomised two-arm parallel-group phase II trial of N = 59 patients with BPD and overt aggressive behaviour was performed (German Registry for Clinical Trials, DRKS00009445). The primary outcome was the externally directed overt aggression score of the Modified Overt Aggression Scale (M-OAS) post-treatment (adjusted for pre-treatment overt aggression). Secondary outcomes were M-OAS irritability, M-OAS response rate and ecological momentary assessment of anger post-treatment and at 6 month follow-up, as well as M-OAS overt aggression score at follow-up. RESULTS: Although no significant difference in M-OAS overt aggression between treatments was found post-treatment (adjusted difference in mean 3.49 (95% CI -5.32 to 12.31, P = 0.22), the MAAP group showed a clinically relevant decrease in aggressive behaviour of 65% on average (versus 33% in the NSSP group), with particularly strong improvement among those with the highest baseline aggression. Most notably, significant differences in reduction in overt aggression between MAAP and NSSP were found at follow-up. CONCLUSIONS: Patients with BPD and aggressive behaviour benefited from a short group psychotherapy, with improvements particularly visible at 6 month follow-up. Further studies are required to show whether these effects are specific to MAAP.

[Impact of early life maltreatment of women on the mother-child relationship : Data from mother-child dyads from Heidelberg and Berlin]. / Einfluss früher Gewalterfahrungen von Frauen auf die Mutter-Kind-Beziehung : Daten von Heidelberger und Berliner Mutter-Kind-Dyaden.

Early life maltreatment can have severe and long-lasting consequences for the directly affected individual as well as for the next generation. Data from our research including mother-child dyads from Heidelberg and Berlin show that early life maltreatment is associated with behavioral and neural changes including personality traits and attachment style of the affected mothers that negatively affect their relationship with their child. The children of these mothers affected by early life maltreatment have an elevated risk to be maltreated and to develop mental disorders. They also show a heightened cortisol concentration and a reduced inhibition control. It seems to be of importance whether the mother has experienced early life maltreatment but is resilient, meaning that she has not developed a mental disorder (up to the time of examination) or whether in addition to the early life maltreatment she has developed a mental disorder later in life. Children of mothers with early life maltreatment and a lifetime mental disorder seem to be especially exposed to stress and show the greatest impairments and risks. Based on the existing data from our research practical and clinical implications are discussed and one possible intervention in the form of a training of mentalization competencies for parents is presented.

Sensitivity to change of the Dermatology Life Quality Index in adult females with facial acne vulgaris: a validation study.

BACKGROUND: The postadolescent form of acne papulopustulosa, also referred to as 'acne tarda' can have substantial negative impact on Quality of Life, especially in adult female patients. OBJECTIVE: Although the Dermatology Life Quality Index (DLQI) is widely used, empirical evidence about its performance in adult female acne patients is lacking. METHODS: In this prospective cohort study, we have investigated the sensitivity to change of the DLQI in 53 female adult acne patients with mild to moderate facial acne treated with azelaic acid (AzA) 15% gel twice daily over 24 weeks. RESULTS: Mean Investigator Static Global Assessment (ISGA) score was 2.3 (SD 0.5) at baseline and ranged from 0.9 (SD 0.3) to 2.1 (SD 0.4) at the end of the study in the 'Highly Improved' and 'Unchanged' responder groups respectively. The mean baseline DLQI score was 5.1 (SD 4.2). The Effect Size in the responder group 'Highly Improved' was 0.66; in group 'Improved' 0.62 and 0.23 in group 'Unchanged'. At the end of study, the mean DLQI score ranged from 1.1 (SD 1.5) in the 'Highly Improved' group to 3.7 (SD 6.0) in the 'Unchanged' group. CONCLUSION: The results support the sensitivity to change of the DLQI in this population.

Effect of minoxidil topical foam on frontotemporal and vertex androgenetic alopecia in men: a 104-week open-label clinical trial.

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.

Evaluation of trichodynia (hair pain) during chemotherapy or tamoxifen treatment in breast cancer patients.

INTRODUCTION: In women receiving antineoplastic therapy, hair loss is often accompanied by distressing hair or scalp sensations, such as hair pain (trichodynia) and pruritus. A scientific approach to objectively evaluate the course and characteristics of these unpleasant sensations is of great importance for the establishment of treatment strategies. METHODS: An observational cohort study was conducted in 34 female breast cancer patients, postoperatively undergoing chemotherapy (group C, n = 17) or endocrine therapy with tamoxifen (group T, n = 17). For 28 weeks after therapy initiation, patients experiencing hair pain and/or scalp pruritus were required to complete a specially developed diary, based on a modification of pain questionnaires. Sensations were journalized in terms of time of onset, duration, intensity on a numeric rating scale, dependence on touching the scalp or hair and character of the sensation, chosen from given descriptors or using own words. RESULTS: In group C, all patients who completed the questionnaire experienced hair and scalp sensations: 87% both trichodynia and pruritus, 13% trichodynia only. Reported intensities ranged between 1 and 10. In group T, 31% of participants reported hair and scalp sensations: 12% both trichodynia and pruritus, 12% pruritus only, 7% trichodynia only. Intensities were rated between 1 and 5. No sensations were reported after week 11 in either group. CONCLUSIONS: Hair and scalp sensations in group C were significantly more common, lasted longer, and were of greater intensity and more differentiated qualities than in group T. The occurrence of trichodynia in chemotherapy patients corresponded with the onset and duration of hair loss, thus suggesting a possible correlation.

Analysis of quantitative changes in hair growth during treatment with chemotherapy or tamoxifen in patients with breast cancer: a cohort study.

BACKGROUND: In women with breast cancer, chemotherapy-induced alopecia is a highly feared but common side-effect of antineoplastic treatment. The onset, pattern and amount of hair loss differ depending on the therapy regimen and have not yet been quantified using standardized techniques. OBJECTIVES: To evaluate objectively and compare the effect of antineoplastic therapy with chemotherapy or tamoxifen on hair loss, quantifying trichological parameters. METHODS: Female patients with breast cancer were included (n = 34), who were receiving chemotherapy (group C, n = 17) or tamoxifen (group T, n = 17) after surgery. Trichological parameters were evaluated once before [week 0 (w0)], twice during (w3, w6) and twice after (w18, w28) the normal 16-week course of chemotherapy, or at corresponding time points during continuous tamoxifen intake. At each visit, anagen and telogen hairs and hair density were quantified by automated phototrichogram in two defined areas: frontal and occipital. RESULTS: Group T generally showed no changes in anagen and telogen hairs or hair density. In group C, anagen hairs and hair density generally followed the same course, decreasing until w6, remaining at a low level during w6-18 and increasing after cessation of chemotherapy, reaching values comparable with or higher than baseline at w28. Telogen hairs increased until w3 then decreased until w6, remaining stable afterwards. CONCLUSIONS: Diffuse hair loss begins shortly after initiation of chemotherapy, mainly as anagen effluvium, with a proportion of anagen to telogen conversion. Hair loss is most prominent after 6 weeks of chemotherapy. Within 3 months after cessation of chemotherapy, hair growth rate returns to baseline values. Tamoxifen did not affect hair growth parameters.

Characterisation of epidermal regeneration in vivo: a 60-day follow-up study.

OBJECTIVE: To characterise the long-term course of epidermal regeneration in a suction-blister wound model in healthy humans. METHOD: A single-centre, prospective cohort study was conducted. Suction blister wounds of 8mm diameter were created on the volar forearms of healthy volunteers. Planimetry was used to measure the wound surface area. Transepidermal water loss was estimated to characterise the skin barrier function. Skin brightness was measured using the chromametric luminance L* parameter and skin (visco)elastic properties were measured by a controlled suction device. RESULTS: Thirty-two subjects (mean age 28.6 years) participated. Epithelisation was nearly completed after 8 days, but it took approximately 3 weeks for complete skin barrier restoration. Post-inflammatory hyperpigmentation was observed at the end of day 60 in the majority of skin areas. Elastic and viscoelastic deformation and recovery at the end of the follow-up period did not reach baseline values. CONCLUSION: Newly formed epidermis requires considerable time before reaching complete recovery of the skin barrier function. Up to 2 months after the injury, regenerated epidermis in junction with the reticular dermis is stiffer compared to before. Under mechanical loading increased local stiffness might increase the risk for subsequent injuries at the same or adjacent skin areas. Due to its increased vulnerability it is recommended to protect or to offload the epidermal tissue as long as possible to support the structural long-term regeneration. Artificial suction blister wounds are well standardised and controlled models for a wide range of clinical studies and they offer advantages over uncontrolled patient conditions in wound healing studies. DECLARATION OF INTEREST: This study was funded by La Roche-Posay Laboratoire Pharmaceutique (Asnieres, France). The sponsor had no influence on the design, conduct, and analysis and presentation of the data and on the content of this manuscript. The authors have no financial interest in this article.

Hair shaft abnormalities after chemotherapy and tamoxifen therapy in patients with breast cancer evaluated by optical coherence tomography.

BACKGROUND: Antineoplastic treatment for breast cancer is frequently associated with alopecia. Increasingly, changes in the texture and shape of regrowing hair after chemotherapy have been reported, without evaluation on a scientific basis. Optical coherence tomography (OCT) provides highly reproducible measurements of hair shaft parameters. OBJECTIVES: This study aims to evaluate hair shaft alterations using OCT in chemotherapy-induced alopecia and in patients taking tamoxifen. METHODS: The measurements of this prospective case series were performed on women aged 29-68 years, receiving either tamoxifen (n = 17) or chemotherapy (n = 17) prior to (T1) and after (T2) treatment. Each time, 20 hairs from two different sites of the scalp (frontal, occipital) were examined by OCT. The hair parameters were characterized by cross section (CS) and form factor (FF). The ratio of maximal to minimal hair diameters determined the FF. RESULTS: After chemotherapy, the CS of hairs was significantly lower compared with hairs taken at T1. The FF did not vary between T1 and T2 for the frontal area, but it did for the occipital area. In patients treated with tamoxifen, changes were observed neither in CS nor in FF. However, comparing both therapeutic groups, there were significant differences in CS and FF for T2, but not for T1. CONCLUSIONS: Reported changes in hair structure after chemotherapy may be due to reduction of hair shaft calibre and increase of FF in regrowing hair. The OCT technique is a promising method to gain more insight into chemotherapy-induced changes of hair morphology.

Calculating acoustical properties of cells: influence of surface topography and liquid layer between cell and substrate.

In this paper, a mathematical formulation is presented to compute the V(z) of a tapering layered solid and applying this formulation to the determination of acoustic properties of biological cells and tissues. The formulation is adopted in the simplex inversion algorithm to obtain the acoustic properties of a tapering cell from its V(z) values. The influence of two parameters had been considered: The tapering angle and the presence of a thin liquid layer present between cells and the substratum to which they adhere. Up to a tapering angle less than 10 degrees, it can be safely neglected. However, if a larger angle is neglected, then the acoustic wave velocity in the cell is overestimated. Cell thickness estimation is not affected significantly when the tapering angle is ignored. The calculations of acoustic properties of cells are considerably influenced by the introduction of a thin fluid layer between the solid substratum and the overlying cell, neglecting the presence of at least a very thin layer (20-30 nm), in general, results in a considerable overestimation of sound velocity. The reliability of the data calculated from V(z) values was ascertained using an independent method to determine cell thickness by calculating it from the interference fringe pattern obtained with the reflection-interference light microscope. The shape of the glutaraldehyde-fixed cells was similar to fried eggs. The highest sound velocities were found close to the periphery of the dome-shaped cell center. In the very center and over most of the area of the thin periphery, sound velocity was close to that in saline.

Acoustic microscopy of cultured cells. Distribution of forces and cytoskeletal elements.

The scanning acoustic microscope (SAM) allows one to measure mechanical parameters of living cells with high lateral resolution. By analyzing single acoustic images' sound attenuation and sound velocity, the latter corresponding to stiffness (elasticity) of the cortical cytoplasm can be determined. In this study, measurements of stiffness distribution in XTH-2 cells were compared with the organization of F-actin and microtubules. Single XTH-2 cells exhibit relatively high stiffness at the free margins; toward the cell center this value decreases and reaches a sudden minimum where the slope of the surface topography enlargens at the margin of the dome-shaped cell center. The steepness of the increase in slope is linearly related to the decrease in sound velocity at this site. Thus, a significant determinant of cell shape is paralleled by an alteration of stiffness. In the most central parts, no interferences could be distinguished, therefore, this region had to be excluded from the calculations. Stiffness distribution roughly coincided with the distribution of F-actin, but no correlation to microtubule arrangement was found. Following the treatment of XTH-2 cells with ionomycin in the presence of calcium (in the culture medium), the cell cortex first contracted as indicated by shape changes and by a marked increase in stiffness (deduced from sound velocity). This contraction phase was followed by a phase of microtubule and F-actin disassembly. Concomittantly, sound velocity decreased considerably, indicating the loss of elasticity in the cell cortex. No structural equivalent to sound attenuation has been identified.

Measuring elastic properties of cells by evaluation of scanning acoustic microscopy V(Z) values using simplex algorithm.

In this paper a new technique is proposed to determine the acoustic properties as well as the thickness (and volume) of biological cells. Variations of thickness, density, acoustic wave velocity, stiffness, and attenuation coefficient of a living or dead cell are obtained by scanning the cell by an acoustic microscope. The distance between the cell and the microscope lens is varied and several voltage curves are thus obtained. These curves are then inverted by simplex optimization technique to obtain the cell parameters. The spatial resolution of the method is limited to the resolution of the scanning acoustic microscope. It allows to take advantage of the full range of frequencies and amplification of the microscope. Characteristic distributions of stiffness are exemplified with an endothelial cell in culture. The main part of the thin, lamellar cytoplasm has high stiffness, which drops close to the lamella/cell body transition region and only slightly increases again through the central part of the cell. Acoustic attenuation seems to be related to two factors, cytoplasm accumulation (in the lamellar parts) and scattering in the central part rich in organelles.