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Biomedical subjects

K P Wilhelm

Publications and source records attributed to K P Wilhelm.

At least 19 recordsLinked to original sources
PubMed2006

Preliminary testing for normality: some statistical aspects of a common concept.

BACKGROUND: Statistical methodology has become an increasingly important topic in dermatological research. Adequacy of the statistical procedure depends among others on distributional assumptions. In dermatological articles, the choice between parametric and nonparametric methods is often based on preliminary goodness-of-fit tests. AIM: For the special case of the assumption of normally distributed data, the Kolmogorov-Smirnov test is the most popular choice. We investigated the performance of this test on four types of non-normal data, representing the majority of real data in dermatological research. METHODS: Simulations were run to assess the performance of the Kolmogorov-Smirnov test, depending on sample size and severity of violations of normality. RESULTS: The Kolmogorov-Smirnov test performs badly on data with single outliers, 10% outliers and skewed data at sample sizes < 100, whereas normality is rejected to an acceptable degree for Likert-type data. CONCLUSION: Preliminary testing for normality is not recommended for small-to-moderate sample sizes.

Biomedical Research↗
PubMed2001

Comparison of three techniques for evaluating skin erythemal response for determination of sun protection factors of sunscreens: high resolution laser Doppler imaging, colorimetry and visual scoring.

BACKGROUND/PURPOSE: Sun protection factor (SPF) measurement is based on the determination of the minimal erythema dose (MED). The ratio of doses required to induce a minimal erythema between product-treated and untreated skin is defined as SPF. The aim of this study was to validate the conventionally used visual scoring with two non-invasive methods: high resolution laser Doppler imaging (HR-LDI) and colorimetry. Another goal was to check whether suberythemal reactions could be detected by means of HR-LDI measurements. MATERIALS AND METHODS: Four sunscreens were selected. The measurements were made on the back of 10 subjects. A solar simulator SU 5000 (m.u.t., Wedel, Germany) served as radiation source. For the visual assessment, the erythema was defined according to COLIPA as the first perceptible, clearly defined unambiguous redness of the skin. For the colorimetric determination of the erythema, a Chromameter CR 300 (Minolta, Osaka, Japan) was used. The threshold for the colorimetry was chosen according to the COLIPA recommendation as an increase of the redness parameter delta a* = 2.5. For the non-contact perfusion measurements of skin blood flow, a two-dimensional high resolution laser Doppler imager (HR-LDI) (Lisca, Linköping, Sweden) was used. For the HR-LDI measurements, an optimal threshold perfusion needed to be established. RESULTS: For the HR-LDI measurements basal perfusion +1 standard deviation of all basal measurements was found to be a reliable threshold perfusion corresponding to the minimal erythema. Smaller thresholds, which would be necessary for detection of suberythemal responses, did not provide unambiguous data. All three methods, visual scoring, colorimetry and HR-LDI, produced similar SPFs for the test products with a variability of < 5% between methods. The HR-LDI method showed the lowest variation of the mean SPF. Neither of the instrumental methods, however, resulted in an increase of the sensitivity of SPF determination as compared with visual scoring. CONCLUSION: Both HR-LDI and colorimetry are suitable, reliable and observer-independent methods for MED determination. However, they do not provide greater sensitivity and thus do not result in lower UV dose requirements for testing.

Adult↗
PubMed2001

Scale-sensitive fractal analysis using the patchwork method for the assessment of skin roughness.

BACKGROUND/AIMS: As skin roughness and wrinkles are easily perceived by the consumer, quantifying skin surface structures is a vital parameter for cosmetic product development. As more tools are available for measuring three-dimensional (3-D) surface data, instead of two-dimensional (2-D) profile lines, new algorithms are desirable, to take advantage of the information gathered. METHODS: The patchwork method tiles topographic data sets virtually and analyzes the change in apparent area as a function of tile scale. The patchwork method and conventional 2-D profilometric analysis were applied to 24 topographic skin data sets. The data sets were derived before and after application of 15% glycerol solution on the skin of eight volunteers. RESULTS: One hour after application, skin roughness decreased by 20.8%, as measured by conventional analysis, and by 23.3%, as measured by the patchwork method. For both methods, the differences were not significant. CONCLUSIONS: The patchwork method can be applied to skin data and renders results similar in intensity and direction to conventional 2-D analysis. It is advantageous over conventional 2-D analysis in three ways: it makes use of the full topologic information, it requires no high-pass or low-pass filtering, and it is independent of the anisotropy of the skin.

Algorithms↗
PubMed2001

Quantitative assessment of primary skin irritants in vitro in a cytotoxicity model: comparison with in vivo human irritation tests.

BACKGROUND: While great efforts have been made in recent years to develop in vitro methods for assessing skin irritation potential, there are relatively few data that correlate in vitro data with in vivo data. OBJECTIVES: To expand our previously reported investigations on in vitro vs. in vivo correlation of a series of homologous N-alkyl sulphates of different alkyl chain length to include primary skin irritants of different chemical classes. METHODS: Anionic surfactants (three different sodium alkyl sulphonates and sodium lauryl sulphate), cationic surfactants (three alkyl trimethyl ammonium bromides), non-ionic surfactants (polyoxyethylene-20-cetyl ether and Tween 20), benzoic acid, dimethyl sulphoxide and phenol were chosen as model irritants. A spontaneously immortalized human keratinocyte line, HaCaT, was used as an in vitro model to predict the cutaneous irritation. The end-point used to assess toxicity was uptake of the vital dye neutral red (NR) 24 h after dosing. The cytotoxicity data from these assays were compared with the irritant responses (as evaluated by measurement of erythema and transepidermal water loss) obtained after 24-h application of the same compounds (100 microL of 20 mmol L(-1) aqueous solution) to the volar forearm of human volunteers. RESULTS: All tested irritants had cytotoxic effects as demonstrated by a decreased NR uptake, which showed a clear dose-response relationship. Concentrations resulting in 50% inhibition of NR uptake (IC(50)) ranged from 8 micromol L(-1) (hexadecyl trimethyl ammonium bromide) to 328 mmol L(-1) (dimethyl sulphoxide). We found a good overall correlation between in vitro cytotoxicity (NR uptake IC(50) values) and in vivo irritation potential in humans. Only the high molecular weight compounds Tween 20 and polyoxyethylene-20-cethyl ether were problematic, as their irritation potential was overestimated by the in vitro assay. This non-conformity of these high molecular weight (> 1000) compounds was expected, and can be largely attributed to the epidermal permeability barrier. The epidermal barrier, which greatly limits the percutaneous penetration of xenobiotics in vivo, does not exist in cell culture models. CONCLUSIONS: The in vitro cytotoxicity model is a useful screening tool, but data should be interpreted critically and require confirmation by appropriate in vivo studies.

Cell Culture Techniques↗
PubMed2001

Role of flavonoids in controlling the phototoxicity of Hypericum perforatum extracts.

Hypericum perforatum extracts are used mainly as oral antidepressants. Depending on source the extracts contain various amounts of phenylpropanes, flavonol derivates, biflavones, proathocyanidines, xanthones, phloroglucinoles, some amino acids, naphtodianthrones (hypericines) and essential oil constituents. The therapeutic use of Hypericum perforatum extracts however is limited by their phototoxic potential. It was the aim of the present study to investigate the phototoxic potential of 3 Hypericum perforatum extracts from different sources as well as some of its main constituents. In order to systematically study the phototoxic potential we established a modified neutral red assay utilizing an immortalized human keratinocyte cell line (HaCaT cells) as substrate and UVA irradiation. This modified neutral red assay was found to be a simple and reliable method for detecting phototoxic effects of reference agents and plant extracts. The validity of this method was demonstrated with known phototoxic compounds like chloropromazine and psoralenes like 5-MOP. Hypericum perforatum extracts demonstrated cytotoxicity and photocytotoxicity in a dose and UVA-dose dependent manner. Hypericine itself also evoked severe phototoxic effects and was thus identified as the main phototoxic constituent. Among the tested flavonoids quercitrin was found to be cytotoxic, while rutin unexpectedly demonstrated phototoxicity whereas quercitrin was effective to control the phototoxic activity of Hypericum perforatum extracts.

Cell Line↗
PubMed1998

SLS-irritated human skin shows no correlation between degree of proliferation and TEWL increase.

It is well known that cutaneous irritants influence epidermal proliferation but the pathogenesis is poorly understood. Recent investigations have shown that the skin barrier integrity influences the proliferation of the basal keratinocytes. Our question was whether the proliferating activity of keratinocytes is indeed regulated by the degree of skin barrier damage or by a direct toxic action of the irritant on the keratinocytes. Therefore various degrees of skin irritation were induced by the application of 0.1%, 0.5% and 2% sodium lauryl sulphate (SLS) solution to the forearm skin of six healthy volunteers. This experiment was performed to evaluate the relationship between SLS concentration and epidermal proliferation. In a second experiment another 14 volunteers were treated with a single SLS concentration (0.5%) to look for interindividual differences in the patterns of skin reaction and susceptibility to the irritant. Skin barrier function was evaluated by measurements of transepidermal water loss (TEWL) before and after irritation. Punch biopsies were taken after 96 h from exposed areas and from unexposed normal skin. Dividing keratinocytes were identified immunocytochemically using three different monoclonal antibodies: PCNA, MIB 1 and KiS1. Exposure to SLS resulted in concentration-dependent increases in both TEWL and epidermal proliferation. However, no significant correlation could be found between the degree of hyperproliferation and the TEWL changes. The results suggest that epidermal proliferation is modulated by a direct interaction of the surfactant with the keratinocytes and/or by release of mediators rather than the consequence of a barrier disturbance.

Adult↗
PubMed1998

Water diffusion characteristics of human stratum corneum at different anatomical sites in vivo.

Despite its heterogeneity, stratum corneum (SC) has been described as a homogeneous membrane for water diffusion. We measured water flux across the SC, transepidermal water loss (TEWL), in six women, in vivo. At four anatomical sites--back, abdomen, forearm, and thigh--we took measurements during sequential tape stripping. The inverse of TEWL (1/TEWL) and removed SC thickness yielded a highly linear correlation (Pearson's r ranging between 0.88 and 0.99). Applying Fick's law of diffusion, we calculated SC thickness (H), and SC water diffusion coefficient (D). Comparing the results, SC of all women was significantly thicker (p < 0.05) at the extremities (12.7 +/- 4.2 microm, mean +/- SD, n = 12) than the abdomen (7.7 +/- 1.8 microm, n = 6). The calculated diffusion coefficient approximated 2.16 +/- 1.14x10(-9) cm2/s. Compared with the diffusion constant found for SC depleted of lipids, our value was 100-fold lower. In agreement with previous findings that intercellular lipids are a rate determining component of the SC barrier, we suggest that water diffuses mainly through the intercellular space. The calculation of H and/or D, however, is based on several variables: SC density, the water concentration difference, and the partition coefficient of water between viable epidermis and SC. The literature values vary widely. It is desirable to determine these parameters more precisely, especially if discrete differences, such as between anatomical sites, are to be revealed.

Abdomen↗
PubMed1998

Cumulative irritation in older and younger skin: a comparison.

Changes in stratum corneum properties due to sodium lauryl sulfate cumulative irritation were determined as a function of age. We irritated the backs of 7 younger (27.7 +/- 4.6 years, mean +/- standard deviation) and 10 older (69.8 +/- 5.5 years) volunteers on 5 consecutive days with open application of a 7.5% aqueous sodium lauryl sulfate solution. Water- and untreated skin served as controls. Transepidermal water loss, stratum corneum capacitance, Desquamation Index, and skin roughness parameters were evaluated on 5 days of the 1st week, and on 3 days of the 2nd week. All parameters revealed a delayed and decreased reaction of older compared to younger skin and recovery appeared to be prolonged. We conclude that under these test conditions irritancy to repetitive sodium lauryl sulfate exposure of older versus younger skin resembled that previously observed after single occlusive exposure. In neither age group was the recovery effect reduced by repeated irritation, demonstrating sufficient skin barrier and recovery function.

Adult↗
PubMed1997

Interlaboratory evaluation of a human patch test for the identification of skin irritation potential/hazard.

The human 4 hr patch test provides an opportunity to identify substances with significant skin irritation potential without recourse to the use of animals. To demonstrate the validity of the method it must be relevant and reliable. It is self-evident that the method is relevant to the identification of skin irritation hazards to humans. However, it is essential that the results be reproducible. This paper presents data on a number of substances tested by different laboratories. Eight substances were tested by two or more laboratories and the data compared with a standard positive control, 20% sodium dodecyl sulfate. In almost all cases, the outcome of this comparison was identical. Thus, despite the fact that there is known variability among human subjects in terms of skin reactivity to irritants, this simple method showed good reproducibility for the classification of acute skin irritation potential. Therefore, it is argued that this human 4-hr patch test is a valid alternative to the equivalent rabbit test for the assessment of skin irritation hazard to humans.

Adult↗
PubMed1996

Guidelines for measurement of skin colour and erythema. A report from the Standardization Group of the European Society of Contact Dermatitis.

This report reviews individual-related variables (age, sex, race, anatomical site, skin surface properties), intra- and interindividual variation (temporal, physical and mental activity, orthostatic effect, menstrual cycle/menopause), environment-related variables (light conditions, temperature) and various instrument-related variables that influence skin colour. CIE colorimetry (Minolta Chroma Meter) and spectrophotometric measurement (Derma Spectrometer) are considered. The guidelines give recommendations for measuring conditions and procedures.

Adult↗
PubMed1996

Skin permeability barrier and occlusion: no delay of repair in irritated human skin.

It has been reported that occlusive treatment of irritated skin results in a reduction of barrier repair activities in hairless mice. In contrast, the clinically observed benefit of occlusion in the treatment of hand eczema and other chronic skin diseases with a perturbed barrier function is well-known. While the beneficial effect of occlusion has been proven for the treatment of psoriasis there are no controlled clinical studies of the effect of occlusion on irritated human skin. We have therefore evaluated the effect of various occlusive treatments on repair of the human skin permeability barrier under controlled experimental conditions. Barrier perturbation was induced either by application of sodium lauryl sulfate (SLS) or by repeated tape stripping. This was followed by treatment with different occlusive and semipermeable dressings, partly after pre-treatment with petrolatum. Repair of water barrier function was evaluated by daily measurements of transepidermal water loss (TEWL) for 1 week. SLS irritation and tape stripping led to a 6-fold increase in TEWL as a sign of severe water barrier perturbation, followed by a stepwise decrease over the following days. Occlusion did not significantly delay barrier repair as measured by TEWL. Only in tape-stripped skin did TEWL stay at high levels during treatment with self-adhesive dressings. This may be explained by damage of newly formed stratum corneum caused by changing of these membranes. Our results indicate that, in contrast to earlier observations in hairless mouse skin, permeability barrier repair activities are not significantly delayed by occlusive treatment in human skin.

Adult↗
PubMed1996

Individual, ethnic and seasonal variability in irritant susceptibility of skin: the implications for a predictive human patch test.

Since irritants are the major cause of contact dermatitis, it is important to identify those chemicals that possess significant ability to cause skin irritation. This process must then be followed by risk assessment and risk management. Historically, animal tests have played a major rôle in this process, but human volunteer studies are of increasing importance in this field. Where the appropriate safety and ethical controls are in place, human testing can give data that identifies skin irritation hazard. To be of widest value, these human studies must not be flawed due to inter-individual, inter-ethnic or seasonal variation. We conducted a large dose-response study and studied the impact of summer and winter weather on a predictive human assay. Sodium dodecyl sulphate (SDS) was tested at 0.1%-20% in 3 national groups of approximately 100 volunteers, using 25 mm Hill Top chambers loaded with 0.2 ml, solution and applied to the upper outer arm for 4 h. Reactions were scored at 24, 48 and/or 72 h after patch application. The German and Chinese studies were completed in a few weeks under similar winter conditions, whereas the UK work was spread fairly evenly over about a 15-month period. Some relatively minor differences were observed in the dose-response curves obtained, probably due to weather conditions. The effect of the weather on the intensity, but not the pattern, of irritant reactivity was also evident in the smaller specific study that assessed reactions to SDS in summer and in winter. Whereas 45% of the panel reacted to 20% SDS in summer, 91% reacted in the winter. However, in both studies, substantial inter-individual variations in response to SDS dominated the pattern of response. When designing a human patch test to discriminate skin irritant substances from those that are of minimal effect, it is this inter-individual variability, rather than any small inter-ethnic or seasonal variation, which must be taken into account. This can be achieved by the routine inclusion of a suitable positive irritant control, which then calibrates each human volunteer panel.

Adult↗
PubMed1996

Studies on non-immune immediate contact reactions in an unselected population.

Non-immune immediate contact reactions (NIICR) arising from skin contact with a wide range of chemicals have been well described. There is evidence that many, if not all, individuals are susceptible to this effect; it may be just a matter of applying a higher dose to the most resistant types of skin. In this work, we chose to evaluate susceptibility to development of NIICR in a large unselected population. Skin tests were made with 3 known urticants (benzoic acid, trans-cinnamic acid and methyl nicotinate), each at 2 concentrations. In a group of 200 volunteers, it was demonstrated that all 3 chemicals induced NIICR in the majority of people. Approximately 10% of the volunteers appeared particularly sensitive, reacting fairly strongly to 2/3 urticants. In contrast, another subset, also about 10%, failed to respond significantly to any of the chemicals at any dose. However, strong reactivity to one urticant was not predictive of the reaction to the other urticants. In a number of cases, individuals reacting strongly to one urticant reacted very little if at all to the other urticants. Also, the type of response, erythema or oedema, was specific to an individual. There was no significant correlation with age or sex on the degree of NIICR. In conclusion, it has been demonstrated that there is a wide interindividual variation in the response to chemical urticants, which cannot be predicted on the basis of age or sex. The prospect of identifying a panel of individuals generally sensitive to non-immune immediate contact reactions seems limited.

Adult↗
PubMed1995

Skin surface lipid and skin friction: relation to age, sex and anatomical region.

Differences in the skin surface lipid content (SSL) and the dynamic friction coefficient (mu) were investigated with respect to age, sex, and anatomical region in 29 volunteers. The group consisted of (a) 7 young adult females (24.9 +/- 1.1 years old, mean +/- SD), (b) 7 old females (75.3 +/- 2.4 years old), (c) 7 young adult males (28.7 +/- 0.5 years old), and (d) 8 old males (73.8 +/- 1.9 years old). Measurements were obtained on 11 anatomical regions, namely, the forehead, upper arm, volar and dorsal forearm, postauricular, palm, abdomen, upper and lower back, thigh, and ankle. Skin surface lipid content data were compared with mu measurements to determine the relative contribution of the former to frictional properties of skin. mu and SSL were not statistically different between age groups on all regions except for the ankle, where lipid content was lower in the elderly. Similarly, mu did not vary between sex groups. Skin surface lipid content was statistically lower on the forehead, dorsal forearm and postauricular area in females. Both parameters, however, showed considerable regional variability. A significant linear correlation was established between mu and SSL combining all regions from all volunteers. When mu was plotted against SSL among individual anatomic sites, only the forehead and postauricular area showed significant linear correlations between the two parameters. These data suggest that surface lipid content plays a limited role in frictional properties of skin.

Adult↗