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Biomedical subjects

Torkil Menné

Publications and source records attributed to Torkil Menné.

At least 19 recordsLinked to original sources

Bioequivalence of topical formulations in humans: evaluation by dermal microdialysis sampling and the dermatopharmacokinetic method.

The aim of this study was to evaluate the relationship between dermal microdialysis (DMD) sampling and the dermatopharmacokinetic method when employed simultaneously for bioequivalence (BE) investigations of topical formulations. Topical lidocaine cream and ointment (both 5%) was investigated in eight healthy human volunteers (four male, four female). On one forearm, four microdialysis probes in two penetration areas sampled for 5 hours, and on the other arm, tape stripping was performed 30 and 120 minutes after product application. Lidocaine content in samples was analyzed by HPLC-mass spectrometry. The two methods were in agreement showing 3- to 5-fold higher lidocaine penetration from cream formulation than from ointment. A rank-order correlation between the two methods was demonstrated for lidocaine contents in microdialysates versus tape strip at 120 minutes, significant for the ointment formulation and for both formulations analyzed together. Analysis of variance demonstrated reproducible lidocaine concentrations in microdialysates with an intrasubject variability of 19% between probes and 20% between the two penetration areas. Thus, intersubject variability accounted for 61% of the variance. DMD sampling proved effective and variability analyses demonstrated the feasibility of BE studies in as little as 18 subjects.

Administration, Topical↗

ROAT: morphology of ROAT on arm, neck and face in formaldehyde and diazolidinyl urea sensitive individuals.

The morphology of early allergic contact dermatitis reactions was studied in formaldehyde allergic individuals exposed to a cream product preserved with 4 different concentrations of diazolidinyl urea. The study was made using a dose-escalating design in 3 different anatomical regions, the upper arm, neck and face. On the arm and neck, the dominant initial morphology was an eczematous papular eruption. In the face, the initial skin changes were more homogeneous and infiltrated erythema.

Adolescent↗

Severe allergic hair dye reactions in 8 children.

Serious adverse skin reactions to permanent hair dyes and temporary black tattoos have been reported. As temporary tattoos have become fashionable among adolescents, the risk profile for p-phenylenediamine (PPD) sensitization of the population has changed simultaneously with an increasing use of hair dyes in this age group. This investigation reports PPD sensitization in children with regard to cause of sensitization, clinical presentation and consequences. Clinical history and patch test results for consecutive children below 16 years of age with suspected hair dye allergic reactions and positive patch tests to PPD were collected over 2 years in 2 Danish dermatology clinics. 8 children aged 12-15 years were collected, and they all reacted to several hair dye ingredients. 5 of the patients were hospitalized, 1 in the intensive care unit. 6 of the patients gave a history of prior reaction to temporary black tattoos. These children showed simultaneous positive patch reactions to N-isopropyl-N-phenyl-p-phenylenediamine and local anaesthetics, while such reaction patterns were not seen in children with hair dye reactions only. The clinical consequences of these reactions are unknown. A re-evaluation of the risk assessment/risk management for hair dyes is required.

Adolescent↗

Systemic contact dermatitis after oral exposure to nickel: a review with a modified meta-analysis.

Systemic contact dermatitis can be elicited experimentally in nickel-sensitive individuals by oral nickel exposure. A crucial point interpreting such experiments has been the relevance of nickel exposure from drinking water and diet. The aim of this meta-analysis study on former nickel-exposure investigations was to provide the best possible estimation of threshold values of nickel doses that may cause systemic contact dermatitis in nickel-sensitive patients. 17 relevant investigations were identified, and statistical analyses were performed in a stepwise procedure. 9 studies were included in the final dose-response analysis, which divided the studies into a homogenous middle group of 5 studies and 2 groups of 2 studies with a higher and lower response frequency, respectively, described by logistic dose-response curves shifted in parallel. On the basis of these curves, calculations were made of the doses that, theoretically, would cause systemic contact dermatitis in exposed nickel-sensitive patients. The results from the 2 most sensitive groups show that 1% of these individuals may react with systemic contact dermatitis at normal daily nickel exposure from drinking water and diet, i.e. 0.22-0.35 mg nickel.

Administration, Oral↗

Cross-reactivity between thiurams.

Retesting with an allergen at a site with previous allergic contact dermatitis has been shown to enhance reactivity. It has been suggested that retesting with a cross-reactive allergen will also induce hyperreactivity. Concurrent sensitization to more than 1 thiuram is common, but whether this is due to concomitant primary sensitization or cross-reactivity is uncertain. The aim of this study was to investigate the use of retesting to distinguish between concomitant sensitization and cross-reactivity in the rubber chemicals tetraethylthiuram disulphide (TETD) and tetramethylthiuram disulphide (TMTD). There was a non-significant trend towards enhanced reactivity for both TETD and TMTD when testing in an area with previous allergic contact dermatitis due to TETD. Cross-reactivity between the 2 chemicals is likely, but a definite conclusion from this pilot study is not possible.

Adult↗

Cr(III) reactivity and foot dermatitis in Cr(VI) positive patients.

Chromium allergy has become synonymous with Cr(VI) allergy. However, real exposure to chromium from leather products may include both Cr(III) and Cr(VI). In this study, we investigate the reactivity to both Cr(VI) and Cr(III) in consecutive patients to analyse the relation between foot eczema/leather exposure and reactivity to Cr(III). From March 2002 to December 2004, 2211 consecutive patients with suspected allergic contact dermatitis were patch tested with 0.5% potassium dichromate (Cr(VI)) and 13% chromium trichloride (Cr(III)). A total of 71 (3.2%) patients had a positive reaction to Cr(VI), of which 31 also had a positive Cr(III) reaction. No Cr(VI) negative patients had a positive reaction to Cr(III). An increased risk of foot dermatitis was found in Cr(VI) positive patients with a concomitant positive or doubtful reaction to Cr(III) compared with Cr(VI) positive patients with no reactions to Cr(III). The increased risk was not due to a higher degree of sensitivity to Cr(VI). Leather was reported most frequently as the suspected cause of chromium dermatitis (54%). However, Cr(VI) allergics having foot eczema and positive or doubtful Cr(III) reactions often had positive reactions to other shoe allergens. Thus, Cr(III) allergy is part of a multiple shoe allergy pattern.

Allergens↗

Patch test dose-response study of p-phenylenediamine: thresholds and anatomical regional differences.

The elicitation response in allergic contact dermatitis for the hair dye substance p-phenylenediamine (PPD) is dose dependent, but threshold concentrations have not previously been investigated. 15 PPD-sensitive patients participated in a serial dilution 48-hr patch test with PPD using 8 concentrations of PPD ranging from 1 to 10 000 on the upper back. Petrolatum was applied as control. Three concentrations (50, 100 and 500 p.p.m. PPD) were also applied to the retroauricular area and on the lateral aspects of the upper arms. 14 of the 15 participants reacted to one or more of the test samples. The threshold value for 10% of the tested persons (ED10) based on+or stronger reactions for PPD on the back was 38 p.p.m. (CI: 4.3-100). There were no statistically significant differences in the sensitivity of the three anatomical regions. The upper back is a suitable region for patch testing patients with hair dye dermatitis.

Adult↗

Mercaptobenzothiazole or the mercapto-mix: which should be in the standard series?

Mercaptobenzothiazole (MBT) compounds are well known contact allergens. To detect rubber allergic patients we use both MBT (2% in petrolatum) and a mercapto-mix with 4 constituents of 0.5% each in our standard series. In this article the EECDRG presents data of in total 32,475 consecutive tested patients attending the respective contact dermatitis clinics from 11 centres in Europe to determine if the mix and MBT detected the same allergic patients. We found 327 patients positive to the mix or MBT, or to both. 261 were positive to the mix and 254 to MBT. MBT was negative in 73 patients who were positive to the mix. If the mix had not been in the standard series, on average 22% of patients allergic to a mercapto-compound would have been missed, for MBT this would have been on average 20%. All clinics would have missed a significant number of positive reactions if both compounds had not been tested. We conclude, that both the mercapto mix and MBT are required in the standard series.

Benzothiazoles↗

Unconsumed precursors and couplers after formation of oxidative hair dyes.

Contact allergy to hair dye ingredients, especially precursors and couplers, is a well-known entity among consumers having hair colouring done at home or at a hairdresser. The aim of the present investigation was to estimate consumer exposure to some selected precursors (p-phenylenediamine, toluene-2,5-diamine) and couplers (3-aminophenol, 4-aminophenol, resorcinol) of oxidative hair dyes during and after hair dyeing. Concentrations of unconsumed precursors and couplers in 8 hair dye formulations for non-professional use were investigated, under the conditions reflecting hair dyeing. Oxidative hair dye formation in the absence of hair was investigated using 6 products, and 2 products were used for experimental hair dyeing. In both presence and absence of hair, significant amounts of unconsumed precursors and couplers remained in the hair dye formulations after final colour development. Thus, up to 1.1% p-phenylenediamine (PPD), 0.04% toluene-2,5-diamine, 0.02% 3-aminophenol and 0.02% resorcinol were found in the hair dye formulation after the required colour was developed. The consumers are thus exposed to precursors and couplers of oxidative hair dyes, both during and after hair dyeing, when the hair is washed. Furthermore, the consumers are also expected to be exposed to intermediates of oxidative hair dyes. The allergenic potential of oxidative hair dyes as well as the intermediates of these remains unknown.

Adult↗

An evaluation of dose/unit area and time as key factors influencing the elicitation capacity of methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) in MCI/MI-allergic patients.

Methylchloroisothiazolinone and methylisothiazolinone (MCI/MI) contact allergy affects 1-3% of patch-tested patients in European centres. The aim of the present study was to evaluate the importance of the factors--time and concentration (dose/per unit area)--in the elicitation capacity by means of a repeated open application test (ROAT) experimental design. The study was designed as a double-blind, placebo-controlled, dose-response ROAT preceded by a diagnostic patch testing. 25 subjects with confirmed MCI/MI allergy and 10 healthy, non-MCI/MI allergic control subjects were exposed to 0.025 microg/cm2 (2 p.p.m.) of MCI/MI/unit area of the skin for 4 weeks. After a wash-out period of at least 4 weeks, the subjects were exposed to 0.094 microg/cm2 (7.5 p.p.m.) of MCI/MI/unit area of the skin for 4 weeks. The study showed the importance of both time and exposure in the elicitation process. It demonstrated that the elicitation threshold for MCI/MI is expected to be in the proximity of 0.025 microg/cm2 although it was not possible to establish a definitive elicitation threshold for MCI/MI in this study.

Adolescent↗

Increased retest reactivity by both patch and use test with methyldibromoglutaronitrile in sensitized individuals.

Hyperreactivity on re-exposure of previous allergic contact dermatitis skin areas has been previously demonstrated. This study aimed to investigate in methyldibromoglutaronitrile (MDBGN) allergic patients whether skin with previous allergic dermatitis from MDBGN showed an augmented response on re-exposure by both a patch test challenge and a use test with a liquid soap preserved with MDBGN. MDBGN dermatitis was elicited on the back and arms of sensitized individuals. One month later the previously eczematous areas were challenged with MDBGN. On the back, the test sites were patch-tested with a serial dilution of MDBGN and a use test was performed on the arms with an MDBGN-containing soap. A statistically significant increased response was seen on the areas with previous dermatitis on the back. Eight of the nine patients who developed dermatitis on the arms from the MDBGN-containing soap had an augmented response on areas with prior allergic contact dermatitis. Even though the allergic dermatitis appeared to be healed, an increased reactivity to allergen re-exposure was demonstrated both by patch test and use test challenge.

Adult↗

Experimental nickel elicitation thresholds--a review focusing on occluded nickel exposure.

Nickel (Ni) is the most frequent cause of contact allergy among the female population. This makes it interesting to examine thresholds for elicitation under different conditions. Even though Ni exposure may be open, occluded, penetrating or oral, most dose-response studies in the literature concern single occluded application. The aims of this study were to assess thresholds of response by making a statistical analysis of available dose-response studies with single occluded exposure and comparing the results to thresholds from other modes of exposure. 8 occluded Ni dose-response studies were selected based on statistical considerations. The statistical analysis showed that 5% of a sensitized population react to 0.44 microg Ni/cm2 and 10% react to 1.04 microg Ni/cm2. In another study with a single open application, 7.8% of sensitized persons responded to a dose x6 higher than the dose to which 10% reacted in occluded exposure. When combining the exposure to Ni with an irritant, divagating results were found, although the literature shows evidence of an augmented response when combining exposure to an allergen and an irritant. The thresholds of penetrating exposure were found to be lower than the thresholds of single occluded exposure. Comparisons of different kind of exposures across studies are difficult, because of differences in the studies, although a comparison could be made by a study that compares the different exposures within the same individuals at the same time.

Allergens↗

Patch testing with a new fragrance mix detects additional patients sensitive to perfumes and missed by the current fragrance mix.

The currently used 8% fragrance mix (FM I) does not identify all patients with a positive history of adverse reactions to fragrances. A new FM II with 6 frequently used chemicals was evaluated in 1701 consecutive patients patch tested in 6 dermatological centres in Europe. FM II was tested in 3 concentrations - 28% FM II contained 5% hydroxyisohexyl 3-cyclohexene carboxaldehyde (Lyral), 2% citral, 5% farnesol, 5% coumarin, 1% citronellol and 10%alpha-hexyl-cinnamic aldehyde; in 14% FM II, the single constituents' concentration was lowered to 50% and in 2.8% FM II to 10%. Each patient was classified regarding a history of adverse reactions to fragrances: certain, probable, questionable, none. Positive reactions to FM I occurred in 6.5% of the patients. Positive reactions to FM II were dose-dependent and increased from 1.3% (2.8% FM II), through 2.9% (14% FM II) to 4.1% (28% FM II). Reactions classified as doubtful or irritant varied considerably between the 6 centres, with a mean value of 7.2% for FM I and means ranging from 1.8% to 10.6% for FM II. 8.7% of the tested patients had a certain fragrance history. Of these, 25.2% were positive to FM I; reactivity to FM II was again dose-dependent and ranged from 8.1% to 17.6% in this subgroup. Comparing 2 groups of history - certain and none - values for sensitivity and specificity were calculated: sensitivity: FM I, 25.2%; 2.8% FM II, 8.1%; 14% FM II, 13.5%; 28% FM II, 17.6%; specificity: FM I, 96.5%; 2.8% FM II, 99.5%; 14% FM II, 98.8%; 28% FM II, 98.1%. 31/70 patients (44.3%) positive to 28% FM II were negative to FM I, with 14% FM II this proportion being 16/50 (32%). In the group of patients with a certain history, a total of 7 patients were found reacting to FM II only. Conversely, in the group of patients without any fragrance history, there were significantly more positive reactions to FM I than to any concentration of FM II. In conclusion, the new FM II detects additional patients sensitive to fragrances missed by FM I; the number of false-positive reactions is lower with FM II than with FM I. Considering sensitivity, specificity and the frequency of doubtful reactions, the medium concentration, 14% FM II, seems to be the most appropriate diagnostic screening tool.

Acrolein↗

Deodorants: an experimental provocation study with isoeugenol.

Axillary dermatitis is common and overrepresented in people with contact allergy to fragrances. Many people suspect their deodorants to be the incriminating products. In order to investigate the significance of isoeugenol in deodorants for the development of axillary dermatitis when used by people with and without contact allergy to isoeugenol, patch tests with deodorants and ethanol solutions with isoeugenol, as well as repeated open application tests (ROAT) with roll-on deodorants with and without isoeugenol at various concentrations, were performed in 35 dermatitis patients, 10 without and 25 with contact allergy to isoeugenol. A positive ROAT was observed only in patients hypersensitive to isoeugenol (P<0.001) and only in the axilla to which the deodorants containing isoeugenol had been applied (P<0.001). Deodorants containing isoeugenol in the concentration range of 0.0063-0.2% used 2 times daily on healthy skin can thus elicit axillary dermatitis within a few weeks in people with contact allergy to isoeugenol.

Adult↗

Allergy to 3-nitro-p-hydroxyethylaminophenol and 4-amino-3-nitrophenol in a hair dye.

Contact allergy to 3-nitro-p-hydroxyethylaminophenol in a hair dye is described for the first time. p-Phenylenediamine is the most common screening allergen when allergic contact dermatitis is suspected, but sometimes the allergen is not sufficient for diagnosing allergic contact dermatitis to hair dyes. A 50-year-old woman developed a severe scalp dermatitis and developed vesicular hand eczema for the first time in her life. Patch testing was performed with the European Standard Series. The patch testing was supplemented with a local series of cosmetic allergens and the hairdresser's series. At the initial patch testing, there was a + reaction to nickel and a +? to PPD at days 3 and 7. Further, she reacted with a +? to her own hair collected at day 3 after the hair dying which elicited the dermatitis reaction. Open exposure to the product, which had initiated the dermatitis, was negative both before and after the allergic reaction to the product. None of the screening chemicals in the hairdresser's series gave a definite positive reaction. Only by patch testing with the individual hair dye product ingredients, the patient's reactions were explained. The patient gave a positive patch test to 4-amino-3-nitrophenol and 3-nitro-p-hydroxyethylaminophenol at days 3-4 reading.

Allergens↗