Alexithymia in patients with alopecia areata: educational background much more important than traumatic events.

BACKGROUND: Recent studies suggest a higher prevalence of alexithymia in patients with alopecia areata (AA). Some authors link alexithymia with the presence of early traumatic events, such as dysfunctional parent-child relationships. However, until today, no studies have been carried out on the association of alexithymia and early traumatic events in AA patients. OBJECTIVE: The primary aim of this study was to explore if an association exists between the presence of traumatic childhood experiences and alexithymia in AA patients. A secondary aim was to confirm earlier observations indicating that the occurrence and/or degree of alexithymia is higher in patients with AA compared with individuals from the general population. METHODS: We enrolled 90 patients with AA. Data on alexithymia and traumatic events were collected with two self-report questionnaires: the Toronto Alexithymia Scale-20 and the Traumatic Experiences Checklist. These data were compared with data obtained from control patients without AA randomly selected from patients presenting for dermatological surgery. RESULTS: In adult AA patients, we found no evidence for a significant association between Toronto Alexithymia Scale (TAS) scores and emotional neglect or childhood traumatic experiences. We found a significant association with educational level, higher levels of education being associated with lower TAS-20 scores (P = 0.002). The mean TAS-20 score of 51.22 (SD 11.90) in our adult AA patient group was significantly higher compared with control patients from the same setting (44.00, SD 10.33, P < 0.001). CONCLUSION: In adult AA patients, higher levels of education are significantly associated with lower alexithymia scores. Somewhat unexpectedly, we found no association between alexithymia score and emotional neglect or childhood traumatic experiences. Our results also confirm that alexithymia scores are significantly higher in adult patient with AA compared with control patients.

Seasonal effects on the nasolabial skin condition.

In the present work, nasolabial skin condition and the influence of seasonal changes during autumn and winter were studied in 16 healthy female volunteers. Apart from visual scoring of erythema and skin scaliness, transepidermal water loss (TEWL), skin hydration, apparent skin pH, skin colour and skin desquamation were biophysically measured. The study results showed that nasolabial TEWL was significantly higher during wintertime than in autumn. Also skin colour measurements and squamometry scorings revealed higher values, indicating a more reddish and scaly nasolabial skin during winter compared to autumn. Results from tape stripping and skin surface lipid analysis by high-performance thin-layer chromatography demonstrated significant differences for triglycerides and cholesterol esters, indicating a functionally inferior hydrolipidic layer during the winter season.

LEKTI-1 in sickness and in health.

The stratum corneum (SC) is a biosensor that mediates responses to a variety of exogenous insults through various signalling mechanisms, including the activation of SC serine proteases (SP) kallikrein cascade. The SPINK5 gene encodes an SP inhibitor, the lympho-epithelial-Kazal-type-1 inhibitor (LEKTI-1), which in turn will buffer the excess of SP cascade initiation, key in the maintenance of permeability barrier homeostasis. We demonstrate that LEKTI processing can occur within the SC after secretion from stratum granulosum keratinocytes at least partially by klk7, an SC-specific chymotryptic SP. Unlike the recently described LEKTI-2, neither recombinant full-length LEKTI-1 nor recombinant LEKTI-1 fragments exhibit antimicrobial activity. Finally, we discuss the pathophysiological implications of LEKTI-1 in skin biology as well as its contribution to the pathogenesis of Netherton Syndrome and its potential involvement in atopic dermatitis.

Trichothiodystrophy-like hair abnormalities in a child with keratitis ichthyosis deafness syndrome.

Keratitis ichthyosis deafness syndrome is a rare congenital ectodermal disorder. It appears to be genetically heterogeneous and may be caused by mutations in the connexin 26 (Cx26) gene (GJB2) or in the connexin 30 gene. It is characterized by the association of ichthyosis-like skin lesions, hearing loss, and vascularizing keratitis. We report the clinical and molecular findings in a 5-year-old girl with keratitis ichthyosis deafness syndrome. DNA sequencing in our patient revealed a p.Ser17Phe mutation in GJB2. Besides the typical clinical features of keratitis ichthyosis deafness syndrome, a peculiar intriguing finding not previously described in the literature in this condition was that polarizing light microscopy of the scalp hair in our patient revealed striking bright and dark bands as seen in trichothiodystrophy. Amino acid analysis of the hair sample also disclosed a reduced cysteine index. We emphasize that it would be of great benefit to examine hair shafts in other patients with keratitis ichthyosis deafness syndrome for trichothiodystrophy-like abnormalities.

Access to bacteriophage therapy: discouraging experiences from the human cell and tissue legal framework.

Cultures of human epithelial cells (keratinocytes) are used as an additional surgical tool to treat critically burnt patients. Initially, the production environment of keratinocyte grafts was regulated exclusively by national regulations. In 2004, the European Tissues and Cells Directive 2004/23/EC (transposed into Belgian Law) imposed requirements that resulted in increased production costs and no significant increase in quality and/or safety. In 2007, Europe published Regulation (EC) No. 1394/2007 on Advanced Therapy Medicinal Products. Overnight, cultured keratinocytes became (arguably) 'Advanced' Therapy Medicinal Products to be produced as human medicinal products. The practical impact of these amendments was (and still is) considerable. A similar development appears imminent in bacteriophage therapy. Bacteriophages are bacterial viruses that can be used for tackling the problem of bacterial resistance development to antibiotics. Therapeutic natural bacteriophages have been in clinical use for almost 100 years. Regulators today are framing the (re-)introduction of (natural) bacteriophage therapy into 'modern western' medicine as biological medicinal products, also subject to stringent regulatory medicinal products requirements. In this paper, we look back on a century of bacteriophage therapy to make the case that therapeutic natural bacteriophages should not be classified under the medicinal product regulatory frames as they exist today. It is our call to authorities to not repeat the mistake of the past.

Allogeneic cultured epidermal grafts heal chronic ulcers although they do not remain as proved by DNA analysis.

To investigate whether allogeneic cultured keratinocytes are rejected or not, and to find out how beneficial their effect on wound healing could be, patients with chronic ulcers were grafted with allogeneic cultured human keratinocytes. In order to examine the epidermal origin of the healed wound, DNA analysis was performed and compared to donor and recipient blood-cell DNA. Healing was observed in 84% of the grafted ulcers by granulation tissue stimulation and would edge effect. In little time 60% of the grafted chronic ulcers healed completely. Although no rejection was observed, DNA analysis revealed that the grafted allogeneic keratinocytes were finally replaced by the patient's own epidermis. This study confirmed that cultured allogeneic keratinocytes that have been grafted on ulcers, play an important role in the wound healing process.

Healing of full-thickness wounds in pigs: effects of occlusive and non-occlusive dressings associated with a gel vehicle.

This study, based upon a pig model, was conducted to investigate the effects of moist and dry healing conditions on wound closure (epithelialization, granulation tissue, contraction) of full-thickness wounds. Thirty-two full-thickness square wounds (3 cm x 3 cm) covered with either an occlusive polyurethane dressing (Tegaderm) or a non-occlusive dressing (Melolin) were evaluated. The effect of the presence or the absence of a gel (3% Idroramnosan) was also investigated with both dressings. The dressings were renewed twice a week. The time required for wound closure was 19.2 +/- 1.6 days for Tegaderm and 26.6 +/- 3.0 days (means +/- SD) for Melolin, respectively. The healing time of the full-thickness porcine wounds was significantly (P < 0.001) reduced by the occlusive dressing. Equivalent results were found with the 3% gel, indicating that the gel can be used as a neutral vehicle. The healing rate, calculated according to Gilman's method, was also significantly (P < 0.001) enhanced by the occlusive dressing. This progression was 0.073 +/- 0.004 cm/day and 0.050 +/- 0.009 cm/day (means +/- SD) for Tegaderm and Melolin, respectively. The contribution of contraction to wound closure was similar in all wounds, indicating that the occlusive dressing did not have an effect on wound contraction. Histological evaluation was performed on full-thickness skin biopsies of whole wound harvested from the time of wound closure to 3 months after. At any time point, no significant histological variations were observed between the different treated wounds. This study demonstrates in a porcine model that for full-thickness wounds, as for split-thickness wounds, occlusive dressing enhances healing rate and shortens the time for wound repair. The shortened healing time is a function primarily of the effect of occlusive dressing on epithelialization, especially the third phase of wound resurfacing.

Antifungal pulse therapy for onychomycosis. A pharmacokinetic and pharmacodynamic investigation of monthly cycles of 1-week pulse therapy with itraconazole.

BACKGROUND AND DESIGN: In the treatment of onychomycosis, oral therapies have generally been given as a continuous-dosing regimen. For example, the suggested dose of itraconazole for the treatment of onychomycosis has thus far been 200 mg/d for 3 months. Based on the advances in our understanding of the pharmacokinetics of itraconazole, we investigated the efficacy and nail kinetics of intermittent pulse-dosing therapy with oral itraconazole in patients who were suffering from onychomycosis. Fifty patients with confirmed onychomycosis of the toenails, predominantly Trichophyton rubrum, were recruited and randomly assigned to three (n = 25) or four (n = 25) pulses of 1-week itraconazole therapy (200 mg twice daily for each month). Clinical and mycological evaluation of the infected toenails, and determination of the drug levels in the distal nail ends of the fingernails and toenails, were performed at the end of each month up to month 6 and then every 2 months up to 1 year. RESULTS: In the three-pulse treatment group, the mean concentration of itraconazole in the distal ends of the toenails ranged from 67 (month 1) to 471 (month 6) ng/g, and in the distal ends of the fingernails, it ranged from 103 (month 1) to 424 (month 6) ng/g. At month 11, the drug was still present in the distal ends of the toenails at an average concentration of 186 ng/g. The highest individual concentrations of 1064 and 1166 ng/g were reached at month 6 for toenails and fingernails, respectively. At end-point follow-up, toenails in 84% of the patients were clinically cured with a negative potassium hydroxide preparation and culture in 72% and 80% of the patients, respectively. In the four-pulse treatment group, the mean concentration of itraconazole in the distal ends of the toenails ranged from 32 (month 1) to 623 (month 8) ng/g, and in the distal ends of the fingernails, it ranged from 42 (month 1) to 380 (month 6) ng/g. The highest individual concentrations of 1549 and 946 ng/g were reached at month 7 for toenails and at month 9 for fingernails, respectively. At month 12, the drug was still present in the distal ends of the toenails at an average concentration of 196 ng/g. At end-point follow-up, toenails in 76% of the patients were clinically cured with a negative potassium hydroxide preparation and culture in 72% and 80% of the patients, respectively. There were no significant intergroup differences between the three- and four-pulse treatment groups for the primary efficacy parameters. The drug was well tolerated with no significant side effects in either patient group. CONCLUSIONS: Following pulse therapy with itraconazole (400 mg/d given for 1 week each month for 3 to 4 months), the drug has been detected in the distal ends of nails after the first pulse, and it has reached therapeutic concentrations with further therapy. After stopping the last pulse, the drug remains in the nail plate at levels above 300 ng/g for several months. Clinical cure rates between 76% and 84% and negative mycological examination findings between 72% and 80%, respectively, were observed in toenail onychomycosis. The data suggest that pulse therapy with itraconazole is an effective and safe treatment option for onychomycosis.

Magnitude of ornithine decarboxylase induction by epidermal mitogens: effect of the assay technique.

The polyamines, putrescine, spermidine and spermine, as well as ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis, are increased in the blood, urine and skin of psoriasis patients. A study of the association between stimulated epidermal cell proliferation and induction of ODC activity was done using both an intact, living cell ODC assay and the routinely used homogenized cell supernate assay. 10(-6) to 10(-8) mol/l of the tumor promoter, tetradecanoyl phorbol acetate (TPA), 10(-3) mol/l 8-BrcAMP, 10(-6) mol/l cholera toxin and 10(-3) mol/l MIX, which are epidermal cell mitogens, were used to stimulate basal cells in short-term suspension cultures, freshly plated monolayers, or up to 8-day-old cultures. The results showed that the ODC enzyme must be assayed in supernates from disrupted epidermal cells in order for significant ODC induction by hyperplastic agents to be observed.

Intact epidermal cell assay for ornithine decarboxylase activity.

A procedure measuring the ornithine decarboxylase (ODC) activity and polyamine formation of intact neonatal mouse epidermal cells in culture has been developed and tested. Basal cells prepared from neonatal mouse epidermis were plated on round 15-mm Lux coverslips, placed in Costar 24 well culture clusters and grown at 32 degrees C in M-199 + 13% fetal bovine serum. Before assay the cells were rendered permeable to ornithine 14C and ODC inhibitors using the buffer described by Berger et al. [3]. The slides, covered with adhering cell layers, were then placed in vials, covered with assay buffer and assayed intact for ODC activity. The ODC reaction was terminated by addition of citric acid to the buffer and the amount of 14CO2 released was determined by scintillation counting of a center well filled with trapping agent. The baseline ODC activity of the intact cells was 500-1,000 pmol 14CO2/mg protein/45 min. The validity of this ODC assay procedure using intact neonatal mouse keratinocytes was tested by use of three specific ODC inhibitors and by measuring the formation of polyamines from uniform labeled ornithine. The results indicated that authentic ODC activity was measured and preserved in this intact neonatal mouse epidermal cell assay. This technique holds promise for future studies of epidermal cell regulation of ODC and polyamine synthesis and studies of the multiple ornithine metabolites and conjugates formed, using a highly manipulable in vitro system.

Microrelief of the skin using a light transmission method.

The recently developed Skin Visiometer, based on light transmission through blue-coloured silicone replicas, was used to study skin microrelief. Calibrated metal plates displaying lines with depths between 6 and 361 microns, were used to determine the accuracy, sensitivity and reproducibility of the technique as well as the parameters of importance during measurement. The precision of the measurements was particularly good between 10 microns and 361 microns. The sensitivity of the method was between 10 and 20 microns. Replicas of volar forearm skin were taken from four groups (n = 15) of male and female volunteers in the age ranges 20 to 30 years and 55 to 65 years. In addition to the instrumental roughness parameters (Rz, Rt, Rm and Ra), the surface of the furrows, the number of primary and secondary lines and the number of intersections were determined. For both sexes, significantly lower values were observed for Rz, Rm and Rt in the younger age group than in the older age group. In addition, the numbers of primary and secondary lines and the number of intersections were higher, pointing to a more structured microrelief in younger forearm skin. Diurnal rhythm, the relative humidity of the measuring room and the position of the forearm were found to be significant factors, while room temperature and precleansing of the skin with mild products were not. Following the application of a hydrating cream (twice daily for 14 days) to the forearm skin of the older female age group, the Rz, Rt, Rm and Ra decreased, while the other parameters measured, except for the surface taken in by the lines, increased, indicating that the microrelief was modified towards the typical pattern observed in young skin.

Fresh and cryopreserved cultured keratinocyte allografts for wound healing.

The use of cultured human epithelium for skin grafting has recently been developed and used successfully to treat burns and various smaller skin defects. Cultured epidermal allografts are replaced by the recipient's own skin. The use of cultured allografts has a healing effect in chronic ulcerations and in burn wounds, probably by releasing growth factors. We have recently demonstrated that cryopreserved allografts can also induce wound healing. Both an edge effect and complete healing were found in ulcers treated with fresh or cryopreserved cultured epidermal allografts. These findings could be important in patient care, since in wound-healing problems, cryopreserved allografts could be immediately available. The cryopreservation of human keratinocyte sheets may also open new perspectives in pharmacotoxicological research on topically applied substances.

[Facial nerve palsy in syphilitic meningitis. Treatment of syphilitic meningitis (author's transl)]. / Paralysie faciale périphérique et syphilis secondaire. Problème du traitement des méningites syphilitiques.

The authors are presenting a case of meningitis with facial nerve palsy due to early syphilis. The frequency, symptomatology and treatment of this meningeal invasion during the septicaemic phase of secundary syphilis are discussed.

Pulse therapy with one-week itraconazole monthly for three or four months in the treatment of onychomycosis.

In an open study, twenty-eight patients with toenail onychomycosis were treated with monthly cycles of 400 mg itraconazole daily for one week for three (n = 5) or four (n = 23) consecutive months. In this patient sample, a total of seventy-one toenails were affected, with a mean nail-plate involvement of 55 percent (range, 20 to 100 percent). Trichophyton rubrum was the most frequently isolated pathogen, followed by T. mentagrophytes. After active therapy, patients were evaluated for a maximum period of two years (mean, twelve months). A total of twenty-six of twenty-eight patients (93 percent) were considered as clinically cured. Of the remaining two patients, one was markedly improved and one appeared to have relapsed. Only three of seventy-one nails still exhibited some pathologic involvement. Of the twenty-six patients considered cured, mycologic examination at the final visit was performed on thirteen and the results were negative in all of them. The remaining clinically cured patients had no mycologic examination at the last visit. This short treatment was well tolerated; the only adverse reaction being a mild headache in one patient. Patients preferred this regimen to receiving daily treatment for three months. Pulse therapy consisting of monthly one-week cycles of 400 mg itraconazole daily for three to four months may offer a new option for treatment of onychomycosis. Further large-scale studies are required to confirm these findings.

Oral R115866 in the treatment of moderate to severe facial acne vulgaris: an exploratory study.

BACKGROUND: R115866 (Rambazole; Barrier Therapeutics NV, Geel, Belgium), a new-generation retinoic acid metabolism-blocking agent, is a nonretinoid compound enhancing intracellularly the endogenous levels of all-trans-retinoic acid by blocking its catabolism. By virtue of this property, and the proven positive effects of retinoids in the treatment of acne, R115866 could potentially be a useful drug for acne. OBJECTIVES: To explore the efficacy, safety and tolerability of systemic R115866 in male patients with moderate to severe facial acne vulgaris (at least 15 papules and/or pustules and at least two nodulocystic lesions). METHODS: In this exploratory trial, 17 patients were treated with oral R115866 1 mg once daily for 12 weeks, followed by a 4-week treatment-free period. RESULTS: At the end of treatment (week 12, n = 16) a mean reduction in inflammatory lesion count of 77.4% (P < 0.001), in noninflammatory lesion count of 58.3% (P < 0.001) and in total lesion count of 76.0% (P < 0.001) was observed as compared with baseline. All lesion counts were significantly reduced from week 4 onwards. Mild side-effects were reported occasionally. CONCLUSIONS: The current data indicate that treatment with oral R115866 1 mg once daily for 12 weeks in patients with moderate to severe facial acne vulgaris is efficacious and well tolerated and merits further investigation.

Distinct phenotypic changes between the superficial and deep component of giant congenital melanocytic naevi: a rationale for curettage.

BACKGROUND: Giant congenital melanocytic naevi (GCMN) convey a 14-fold increased melanoma risk. In contrast, medium congenital melanocytic naevi (MCMN) are rarely associated with malignant transformation. Management of patients with GCMN is challenging and there is no consensus on the most appropriate strategy for treating these patients. OBJECTIVES: To provide a rationale for performing curettage of GCMN in the neonatal period in order to reduce the risk of malignant transformation to melanoma. METHODS: Twenty-six infants with GCMN who underwent biopsies before excisional surgery (n = 7) or curettage (n = 19) during the past 14 years (Academic Hospital, Vrije Universiteit Brussel) and 10 MCMN patients who underwent excision biopsies (Radboud University Nijmegen Medical Centre) were included in this study. Using these biopsies, we performed genetic and detailed immunohistochemical evaluations of changes that are associated with malignant transformation. Variables of interest included melanoma-associated BRAF mutations, proliferative activity, vascularity, cellular context and extracellular matrix architecture. RESULTS: GCMN and MCMN did not show oncogenic BRAF mutation and displayed similar features with respect to the amount of nonmelanocytic cells within the naevus and matrix architecture. Naevus cells in the superficial component of the GCMN, however, were more proliferative, and this component was more vascular compared with its deep component and with MCMN. In this study, none of the 19 newborn patients who underwent curettage developed a melanoma within a mean follow-up time of 7 years. CONCLUSIONS: The data presented here support the idea that curettage of GCMN in neonates has the potential for lowering the risk of developing cutaneous melanoma by not only obtaining an important numerical reduction of naevus cells but also removing the 'active' melanocytes.

The treatment of basal skin carcinomas in two sisters with xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder that causes defects in the DNA repair system. It is characterized by a marked sensitivity to sunlight, and sufferers develop serious sunburns with onset of poikilodermia in the light-exposed skin. Squamous cell carcinomas, basal cell carcinomas (BCCs) and malignant melanomas appear in childhood. Two sisters with XP presented with previously treated facial BCCs. They were treated with imiquimod 5% cream three times weekly, one for 6 weeks and the other for 10 weeks. Although both sisters temporarily discontinued treatment due to severe erythema and erosion, successful long-term clearance was observed with no recurrences in both cases.