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Biomedical subjects

M Fartasch

Publications and source records attributed to M Fartasch.

At least 37 records · Page 2Linked to original sources

Altered lamellar body secretion and stratum corneum membrane structure in Netherton syndrome: differentiation from other infantile erythrodermas and pathogenic implications.

BACKGROUND: The infant with Netherton syndrome (NS) typically displays a generalized erythroderma covered by fine, translucent scales, which can be difficult to distinguish clinically from erythrodermic psoriasis, nonbullous congenital ichthyosiform erythroderma, or other infantile erythrodermas. Some infants with NS develop progressive hypernatremic dehydration, failure to thrive, and enteropathy. Such complications can be fatal. Diagnosis is typically delayed until the appearance of a pathognomonic hair shaft anomaly, trichorrhexis invaginata (bamboo hair). To facilitate the early diagnosis of NS, we obtained biopsy specimens from 7 patients with erythrodermic NS and compared their morphologic findings to those of 3 patients with erythrodermic psoriasis and 2 with congenital ichthyosiform erythroderma. Biopsy specimens were processed for light and electron microscopy using postfixation with osmium tetroxide and ruthenium tetroxide. OBSERVATION: In NS, and often in congenital ichthyosiform erythroderma and erythrodermic psoriasis, the stratum corneum layer was largely replaced by parakeratotic cells. A distinctive feature--premature secretion of lamellar body contents--occurred only in NS. Furthermore, lamellar body-derived extracellular lamellae and stratum corneum lipid membranes were separated extensively by foci of electron-dense material. Finally, transformation of lamellar body-derived lamellae into mature lamellar membrane structures was disturbed in NS. CONCLUSIONS: Premature lamellar body secretion and foci of electron-dense material in the intercellular spaces of stratum corneum, features not observed in other erythrodermic disorders, appear to be frequent and relatively specific markers for NS. These ultrastructural features could permit the early diagnosis of NS before the appearance of the hair shaft abnormality. These abnormalities could explain the impaired permeability barrier in NS, and account for hypernatremia and dehydration in infants with NS.

Child, Preschool↗

[Ulcerative stomatitis as clinical clue to inadvertent methotrexate overdose].

Gastrointestinal side effects and the development of toxic liver fibrosis are well-known side effects of low dose methotrexate therapy. A female patient receiving a long term low dose methotrexate therapy for a seronegative chronic polyarthritis developed an ulcerative stomatitis, as clinical clue to an inadvertently given methotrexate overdose. A summary of other side effects of methotrexate and of oral side effects of other cytostatic agents and immunosuppressive drugs is given.

Aged↗

[Digital ischemia as paraneoplastic marker of metastatic endometrial carcinoma].

Digital ischemia with gangrene of one or several fingertips has been described as a paraneoplastic syndrome associated with various malignant tumors, especially adenocarcinomas. Most often this paraneoplastic syndrome represents the first symptom of an occult neoplasia in an advanced stage. We present the case of an 83 year-old patient with digital ischemia and gangrenous fingertips in association with a latent adenocarcinoma of the uterus and metastatic involvement of the paraaortal lymph nodes. Acute occurrence of digital ischemia and gangrene without pathological laboratory findings and negative past medical history concerning cardiovascular-induced emboli, arteriosclerotic occlusion, or rheumatologic and autoimmune diseases should suggest this paraneoplastic syndrome and lead to thorough search for an underlying tumor.

Aged↗

Normal ultrastructure, but altered stratum corneum lipid and protein composition in a mouse model for epidermolytic hyperkeratosis.

Recently, we established keratin 10-deficient mice, serving as a model for the hyperkeratotic skin disorder epidermolytic hyperkeratosis. The considerable ichthyosis in these mice suggested alterations in terminal differentiation and in the formation of a functional epidermal barrier. Here, we report on the ultrastructural organization and composition of the stratum corneum lipids and on the expression of two major cornified envelope proteins. Electron microscopy of ruthenium tetroxide postfixed skin samples demonstrated a normal extrusion and morphology of lamellar bodies as well as the formation of bona fide lamellar layers in neonatal keratin 10-deficient mice. When we studied the composition of the major stratum corneum lipids, however, we found significant changes. Most importantly, the analysis of ceramide subpopulations revealed that the total amount of ceramide 2 was elevated in keratin 10-deficient mice, whereas ceramides 1, 3, 4, and 5 were decreased among total stratum corneum lipids. The amount of the ceramide precursors sphingomyelin and glucosylceramide was reduced in the stratum corneum without accompanying changes in the mRNA coding for acid sphingomyelinase. Notably, we found an increased mRNA and protein content for involucrin in neonatal keratin 10-deficient mice, whereas the expression of loricrin was not changed. Our data demonstrate that, although the formation of lipid layers in the stratum corneum appeared to be normal, its lipid composition is significantly altered in keratin 10-deficient mice.

Animals↗

Does sodium lauryl sulfate concentration vary with time?

When performing skin irritation tests with sodium lauryl sulfate (SLS), the quality of the test solution is of major importance for the reproducibility and comparability of the results. The influence of 4 different storage parameters (concentration, duration, temperature, material of the storage vials) on the stability of aqueous SLS solutions was investigated under non-sterile conditions. SLS solutions at 5 different concentrations (0.001%, 0.01%, 0.1%, 0.5%, 1%) were analysed by mobile phase ion chromatography. Analyses were performed after a storage time of 3 h, 1 week, and 4 weeks. Storage was carried out at different temperatures: -18 degrees C, 6 degrees C, and 23 degrees C. The storage containers were of 2 different materials (glass and polypropylene). After a storage of 1 week, no decrease in SLS concentration was observed, regardless of the chosen conditions. After 4 weeks at 6 degrees C and 23 degrees C, the SLS concentration was found to be significantly decreased for the 2 lowest concentrations (0.001% and 0.01%). At higher concentrations and lower temperatures, no decrease in SLS concentration had occurred. In parallel to the loss of SLS, contamination with bacteria was found in the solutions, especially at the 2 lowest concentrations. Bacterial growth was not observed at higher concentrations. The possibility of biodegradation of SLS has to be taken into account, especially when dealing with low concentrations of SLS.

Allergens↗

Intra-and inter-individual variations in transepidermal water loss on the face: facial locations for bioengineering studies.

The volar forearm is the favored location for bioengineering studies. However, transepidermal water loss (TEWL), which is an important indicator of the function of the epidermal barrier, shows regional variations, and for the evaluation of cosmetic formulations, facial skin would be more suitable. In this study, we have compared 10 facial locations with 1 test site on the volar forearm for absolute TEWL values, reproducibility, and correlation. Measurements were performed over 3 consecutive days. The TEWL values of the facial test sites were higher compared to forearm values and did not correlate with the forearm. On the face, there was a good correlation between the values of the right compared to the left side of the face. The sites superior to the nervus supraorbitalis, the medial borders of the musculus masseter, and the center of the chin proved to be locations with relatively stable TEWL values. There was a greater variability at the center of the forehead and at the center of the cheeks. It is recommended that TEWL measurements on facial locations with stable TEWL values are used for the evaluation of cosmetic formulations.

Adult↗

Provocative use tests in CAPB-allergic subjects with CAPB-containing product.

Cocamidopropyl betaine (CAPB) has been identified as a cause of contact allergy in personal care products. Furthermore, it has been suggested that chemicals responsible are impurities, especially dimethylaminopropylamine (DMAPA). However, skin contact concentrations with these impurities, especially DMAPA, are very low. The aim of the study was to analyse whether subjects with previous positive patch tests to CAPB would react in provocative use tests of a product containing CAPB. 10 individuals with a clinical history of contact allergy to CAPB (by positive patch test and history) took part in a ROAT which used a CAPB-based shower gel at 25% (DMAPA concentration < 1 ppm). None of the subjects showed positive allergic reactions. 1 of the test subjects did experience a flare of atopic dermatitis at the treatment site. Later, all 10 subjects were patch tested to 3 different concentrations of CAPB and DMAPA (0.1%, 0.3%, 1%) to verify the threshold that was capable of inducing a positive test reaction. 5/10 showed clear + reactions to 1% CAPB (typically at D3), whilst a further 3 gave marginal and/or irritant reactions. Only 1 of the subjects showed an allergic reaction to DMAPA. Finally, in uncontrolled use testing with the shower gel, none of the test subjects reported any adverse skin reactions. Thus, the study confirmed that CAPB-sensitive individuals can use a CAPB-based rinse-off product without the risk of experiencing an allergic reaction to CAPB.

Adult↗

[Value of psychotherapy in expert assessment of skin diseases. Recommendations and indications for additional psychotherapy evaluation in expert assessment from the viewpoint of dermatology].

Skin diseases, the psyche and psychological changes are often intertwined, especially in patients presenting for expert dermatologic opinion. In many cases an additional evaluation provided by psychotherapeutic medicine may be necessary. This resource may help with the diagnosis, explanation of the problem and estimation of the degree of disability. The different legal guidelines of the various evaluation boards must be considered. The role of psychotherapeutic evaluation is demonstrated through case examples. The evaluation of new possibly occupationally-related disorders such as multiple chemical sensitivity and mobbing is considered.

Adult↗

Characterization of detergent-induced barrier alterations -- effect of barrier cream on irritation.

To gain a better understanding of the interaction of the model detergent sodium lauryl sulfate (SLS) with the stratum corneum, we investigated systematically the ultrastructural changes of the epidermal barrier and the nucleated parts of the epidermis after the occluded application of different concentrations of SLS in human. Different application models were investigated. Two of the three irritation procedures (long duration exposure and the repetitive exposure for 3 d) provoked damage of the nucleated parts of the epidermis and alterations of the lower parts of the stratum corneum. Here, the extrusion and transformation of lamellar body derived lipids into lamellar lipid bilayers were disturbed; however, the upper portions of stratum corneum displayed intact intercellular lipid layers that contradict the long-standing belief that surfactants damage the skin by delipidization. Furthermore, we investigated ultrastructurally and by measurement of transepidermal water loss the influence and protective capacity of a lipophilic barrier cream on acute irritant contact dermatitis. The irritant contact dermatitis was induced by the standardized cumulative short application model with two SLS concentrations (0.5% and 0.75%). The cumulative type of exposure simulates daily living more realistically. Because most of the previous tests have been performed on the human forearm or back, we analyzed whether the pattern of response was similar on both sites. The back showed a higher level of irritant reaction, but the pattern of irritant response proved to be similar to the forearm. Application of the barrier cream before and during irritation showed a decrease of transepidermal water loss enhancement with 0.5% SLS by 58% (back) and 49% (arm) and after irritation with 0.75% SLS by 56% (back) and 43% (arm). Because the experimental result correlated with the clinical experience, the development of the cumulative short exposure model might help to predict and to discriminate the efficacy of barrier creams.

Adult↗

Epidermal barrier in disorders of the skin.

The water permeability barrier of the stratum corneum (SC) seems primarily to be regulated by the lamellarly arranged lipid bilayers between the corneocytes, which originate largely from polar lipid precursors provided by the cells of stratum granulosum via exocytosis of the lamellar body (LB) content. In particular, the structural organization of these intercellular lipid lamellae seems to be responsible for the very low water permeability of the intact skin, and these lipid-rich structures might also influence the desquamation process in the SC. The aim of this study was to obtain further insight into the distribution and organization of the epidermal lipids (EL) and the mechanism involved in desquamation and barrier function in normal human skin and scaling skin disorders. Biopsies of healthy human skin (n = 12), of inflammatory skin diseases (atopic dry skin (n = 9), psoriatic skin lesions [n = 2]), and of hereditary keratinization disorders (autosomal recessive ichthyoses congenita (n = 3), X-chromosomal ichthyosis (XCI) [n = 3]) were analyzed utilizing a special fixation protocol with ruthenium tetroxide (RuO4) postfixation. While the atopic dry skin revealed normal barrier structures, the psoriasis lesions were characterized by severe alteration of the lipid structures leading to an abnormal interaction with the desmosomal unit. While the intercellular domains in some of the studied keratinization disorders showed an impaired distribution of the EL (autosomal recessive ichthyoses), X-chromosomal ichthyosis showed normal lipid architecture. Dry and scaly skin disorders are therefore not always accompanied by an impairment of the water permeability barrier.

Dermatitis, Atopic↗

Ultrastructure of the epidermal barrier after irritation.

The stratum corneum (SC) controls the diffusion and penetration of chemical substances and drugs into and through the skin. Surprisingly, knowledge of the SC structure and reaction to the various irritants is still poorly understood. Routine transmission electron microscopy has not been effective in demonstrating the epidermal lipids (EL) of SC which are believed to morphologically represent the water permeability barrier. To gain a better understanding of the interaction of chemically different irritants with the SC, we investigated the ultrastructural changes of epidermal lipids resulting from the topical application of sodium dodecyl sulfate (SDS 0.5% and 1% w/v) and absolute acetone. The disturbance of barrier function by these irritants was determined by the increase of transepidermal water loss (TEWL). Punch biopsies from the treated sites showed a maximum increase of TEWL. To visualize the EL which derive from lamellar body (LB) lipids (sheets), we used a special fixation method utilizing 0.5% ruthenium tetroxide/0.25% KFe(CN)6 as the postfixative. The 0.5% SDS caused cell damage to the nucleated cells of the epidermis with disturbance of LB lipid extrusion and the transformation into the lipid bilayers. However, the upper portions of SC displayed intact intercellular lipid layers. With the acetone treatment, the EL lamellae showed disruption and loss of cohesion between the lamellae at all levels of the SC. The more polar LB lipids appeared more resistant to acetone. The results of this study suggest that different irritants induce distinct and characteristic alterations to reflect the specific interaction with the epidermal permeability barrier.

Acetone↗

Mode of action of glycolic acid on human stratum corneum: ultrastructural and functional evaluation of the epidermal barrier.

Alpha-hydroxy acids (AHA) such as glycolic acid have recently been used extensively in cosmetic and dermatological formulas. In low concentration (2-5%) glycolic acid is believed to facilitate progressive weakening of cohesion of the intercellular material of the stratum corneum (SC), resulting in uniform exfoliation of its outermost layers (the stratum disjunctum). Since thinning of the SC as well as changes of intercellular lipids could theoretically compromise the barrier functions of the skin, we investigated the mode of AHA action on the SC to determine whether enhanced desquamation compromises the barrier structures of the SC and changes transepidermal water loss (TEWL) values. Electron microscopy of the epidermis biopsied from the volar forearm of human volunteers after 3 weeks of treatment with a 4% glycolic acid formulation twice daily was employed to evaluate 1) epidermal morphology and thickness of the SC, (2) the lamellar body and SC lipid bilayer organization, and (3) desquamative events based on degradation of desmosomes. TEWL values and SC hydration were recorded prior to and at the end of the study. Electron microscopy revealed no ultrastructural changes in the nucleated layers of the epidermis. The lamellar body (LB) secretory system in the stratum granulosum (SG), and intercellular lipid lamellae in the SC in both vehicle- and glycolic acid-treated samples were comparable to normal human SC. Within the SC, enhanced desmosomal breakdown, promoting loss of cohesion and desquamation, was restricted to the stratum disjunctum while desmosomes of the stratum compactum were unaffected. Treated areas displayed histologically, a more compact appearing SC. TEWL values remained unchanged in glycolic acid- and vehicle-treated skin. Our findings indicate that the barrier structures of the SC are not disrupted by glycolic acid formulations at the concentration used. One of the mechanism of action of AHA on the SC seemed to be a "targeted" desmosomal (corneosomal) action without compromising the barrier structures of the skin.

Adult↗

Resolution requirements for digital images in dermatology.

BACKGROUND: The digital image has become an important tool in dermatology because of the rapid development of computer hardware, networks, and the World Wide Web. OBJECTIVE: Our purpose was to examine the resolution requirements for digital images. METHODS: Slides of eight selected images showing characteristic lesions were produced in five different resolutions each, ranging from 192 x 128 x 24 (192 pixels x, 128 pixels y, and 24-bit color depth) up to 3072 x 2048 x 24. They were compared side by side by a group of six experienced dermatologists using a standardized questionnaire. RESULTS: Images at the resolution of 768 x 512 x 24 were perceived as equivalent to higher resolutions, whereas a clear difference was visible between 768 x 512 x 24 and 384 x 256 x 24. The slide projector had a significant influence on the rating of the images. CONCLUSION: For digital images in dermatology a resolution of 768 x 512 x 24 is suitable to recognize the relevant details of the source image.

Dermatology↗

Guidelines on sodium lauryl sulfate (SLS) exposure tests. A report from the Standardization Group of the European Society of Contact Dermatitis.

This report reviews the clinical and histopathological reactions caused by sodium lauryl sulfate (SLS), and the non-invasive methods that can characterize these reactions. Furthermore, SLS exposure techniques and factors that may influence the outcome of these exposures are discussed. Finally, guidelines are introduced for each exposure technique in order to have a uniform approach to SLS testing in man. Since different study aims warrant different testing conditions, we have proposed 2 categories, namely susceptibility testing and provocative testing, tailored to the aim with which the study is performed.

Dermatitis, Contact↗

Topical vitamin D3 derivatives impair the epidermal permeability barrier in normal mouse skin.

BACKGROUND: Calcipotriol, 1,25(OH)2D3 and 1,24(OH)2D3 are potent drugs for the treatment of psoriasis. It has recently been published that these compounds induce epidermal hyperproliferation in hairless mouse skin. OBJECTIVE: The aim of our study was to examine the effect of vitamin D3 derivatives on epidermal growth, keratinization and permeability barrier function in vivo. METHODS: Calcipotriol, 1,25(OH)2D3 and 1,24(OH)2D3 in isopropanol or in an ointment formula were applied to normal hairless mouse skin. Transepidermal water loss (TEWL), a marker of cutaneous barrier function, and epidermal proliferation were determined at different time points 0-264 h after treatment. In addition, light and electron microscopy studies were performed. RESULTS: A single treatment in solution led to a transient (2- to 3-fold) increase in TEWL after application of calcipotriol or 1,25(OH)2D3 and to a 3- to 6-fold increase in epidermal proliferation after application of each of the compounds. Repeated applications also resulted in an up to 3-fold increase in TEWL which persisted for 3 days after the end of the treatment. By light microscopy an increase in epidermal thickness was observed. There was no sign of inflammation. Electron microscopy studies showed the formation of a transitional cell zone as a sign of a premature keratinization. CONCLUSION: These results demonstrate that in normal mouse skin vitamin D3 and its analogues disrupt the epidermal permeability barrier by induction of epidermal proliferation and premature keratinization but without morphological signs of inflammation.

1-Propanol↗

Development and validation of diagnostic scores for atopic dermatitis incorporating criteria of data quality and practical usefulness.

No objective classification criteria for atopic dermatitis (AD) exist. Therefore the diagnosis is usually based on many variables including anamnestic, clinical, and laboratory findings. The aim of this study was to develop and validate a diagnostic score to standardize the diagnosis of atopic skin diathesis for clinical and epidemiological studies. In two separate studies, each consisting of cases and controls, 19 atopic binary features were examined by two independent experienced physicians and these features were classified as "objective," respectively, "subjective." On the basis of these criteria and two additional laboratory measures, we developed a score with high discriminative ability, using the logistic regression model and backward elimination. Ignoring "subjective" variables and the two laboratory measures, two additional models were built that had a worse fit in the original data, but still yielded high estimates of sensitivity (approximately 90%) and specificity (approximately 96%). Using the same data as for the model building, it is well known that these estimates are too optimistic. The validation study allows us to obtain unbiased estimates of sensitivity and specificity for the different scores and to investigate the influence of data quality-here given by the assessment of the reproducibility of the features (objective and subjective)-on the usefulness of diagnostic scores. The results of the validation study show that we developed simple and easy-to-use scores offering a base for a broad practical use in epidemiological and clinical research. In addition, we demonstrate that the criteria classified as "subjective" have no influence on the case-control status in the validation study.

Adolescent↗