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Biomedical subjects

K E Andersen

Publications and source records attributed to K E Andersen.

At least 37 records · Page 2Linked to original sources

The fragrance hand immersion study - an experimental model simulating real-life exposure for allergic contact dermatitis on the hands.

Recently, we showed that 10 x 2% of consecutively patch-tested hand eczema patients had a positive patch test to a selection of fragrances containing fragrances relevant to hand exposure. In this study, we used repeated skin exposure to a patch test-positive fragrance allergen in patients previously diagnosed with hand eczema to explore whether immersion of fingers in a solution with or without the patch-test-positive fragrance allergen would cause or exacerbate hand eczema on the exposed finger. The study was double blinded and randomized. All participants had a positive patch test to either hydroxycitronellal or Lyral (hydroxyisohexyl 3-cyclohexene carboxaldehyde). Each participant immersed a finger from each hand, once a day, in a solution containing the fragrance allergen or placebo. During the first 2 weeks, the concentration of fragrance allergen in the solution was low (approximately 10 p.p.m.), whilst during the following 2 weeks, the concentration was relatively high (approximately 250 p.p.m.), imitating real-life exposure to a household product like dishwashing liquid diluted in water and the undiluted product, respectively. Evaluation was made using a clinical scale and laser Doppler flow meter. 3 of 15 hand eczema patients developed eczema on the finger immersed in the fragrance-containing solution, 3 of 15 on the placebo finger and 3 of 15 on both fingers. Using this experimental exposure model simulating real-life exposure, we found no association between immersion of a finger in a solution containing fragrance and development of clinically visible eczema on the finger in 15 participants previously diagnosed with hand eczema and with a positive patch test to the fragrance in question.

Adult↗

Deodorants: an experimental provocation study with cinnamic aldehyde.

BACKGROUND: Axillary dermatitis is common and overrepresented in individuals with contact allergy to fragrances. Many individuals suspect their deodorants to be the incriminating products. OBJECTIVE: Our aim was to investigate the significance of cinnamic aldehyde in deodorants for the development of axillary dermatitis when used by individuals with and without contact allergy to cinnamic aldehyde. METHODS: Patch tests with deodorants and ethanol solutions with cinnamic aldehyde, and repeated open application tests with roll-on deodorants without and with cinnamic aldehyde at different concentrations, were performed in 37 patients with dermatitis, 20 without and 17 with contact allergy to cinnamic aldehyde. RESULTS: A repeated open application test with positive findings was noted only in patients hypersensitive to cinnamic aldehyde (P <.001) and only in the axilla to which the deodorants containing cinnamic aldehyde had been applied (P <.001). CONCLUSION: Deodorants containing cinnamic aldehyde in the concentration range 0.01% to 0.32%, used twice daily on healthy skin, can elicit axillary dermatitis within a few weeks.

Acrolein↗

Citral a fragrance allergen and irritant.

Citral is a well known contact allergen and a contact irritant. Routine patch testing in the past may have been restricted because of possible irritant (IR) patch test responses. 586 consecutive patients, with hand eczema, were patch tested with a selection of fragrances including citral 2% petrolatum and the European standard series. 28 of the patients showed a positive patch test reaction (+ to +++) to citral and 82 at least 1 IR patch test reaction and no positive patch test reaction to citral. A statistically significant association between a positive patch test reaction to citral and positive patch test reactions to other fragrances compared with IR reactions (n = 82) was established. The difference regarding fragrance history found between those with IR and positive reactions to citral was not significant. Citral could be an allergen and/or irritant, worthy of further more extensive studies.

Acyclic Monoterpenes↗

A stronger patch test elicitation reaction to the allergen hydroxycitronellal plus the irritant sodium lauryl sulfate.

Household and cleaning products often contain both allergens and irritants. The aim of this double-blinded, randomized, paired study was to determine whether patch testing with an allergen (hydroxycitronellal) combined with an irritant [sodium lauryl sulfate (SLS)] cause a stronger patch test elicitation reaction than patch testing with the allergen (hydroxycitronellal) alone, in patients previously patch tested positive to hydroxycitronellal. A stronger patch test elicitation reaction was defined as at least 1 day of patch test reading showing more positive patch tests (+, ++ or +++) on the forearm patch tested with 6 concentrations of SLS plus hydroxycitronellal than on the forearm tested with 6 concentrations of hydroxycitronellal alone and no day of patch test readings showing more positive tests on the hydroxycitronellal forearm. 15/20 (75%) had at least 1 day of patch test reading with more positive patch tests on the forearm patch tested with SLS plus hydroxycitronellal and no day of patch test readings with more positive patch tests on the forearm tested with hydroxycitronellal (P = 0.0253). Estimation of the blood flow with laser Doppler supported these findings.

Adult↗

Clinical performance of a new silver dressing, Contreet Foam, for chronic exuding venous leg ulcers.

OBJECTIVE: This study aimed to evaluate the safety and performance of a new sustained silver-releasing dressing, Contreet Foam (Coloplast A/S), in the treatment of moderately to highly exuding chronic venous leg ulcers in which healing is delayed due to the presence of bacteria. METHOD: The clinical performance of Contreet Foam was studied for four weeks in 25 patients with moderately to highly exuding delayed-healing venous leg ulcers. Healing was assessed on a weekly basis with reference to the wound-bed tissue composition, degree of odour and pain, dressing performance and the dressing's effect on the peri-ulcer area. Blood samples were analysed for silver content. RESULTS: Twenty-three out of 25 patients completed the study. One ulcer healed and no wound infections occurred during the study period. A mean 56% reduction in ulcer area (from 15.6 to 6.9 cm2) was recorded during the four weeks, and there was a mean 25% reduction in granulation tissue from dull to healthy after one week. Wound odour reduced significantly after one week. Mean dressing wear time was 3.1 days, and there were only minimal incidences of leakage. Serum silver levels did not exceed reference values. CONCLUSION: Contreet Foam was found to be safe and performed well when used in the treatment of delayed-healing chronic venous leg ulcers, combining effective antibacterial properties with excellent exudate management. DECLARATION OF INTEREST: This study was supported by Coloplast A/S, Humlebaek, Denmark.

Aged↗

Monitoring levels of preservative sensitivity in Europe. A 10-year overview (1991-2000).

A 10-year multicentre analysis of the frequency of sensitivity to common preservatives collected in 16 centres in 11 countries has shown stable but persisting high levels of sensitivity to formaldehyde and 5-chloro-2-methyl-4-isothiazolin-3-one + 2-methyl-4-isothiazolin-3-one (MCI/MI). It has also revealed a significant increase in the level of reactivity to methyldibromoglutaronitrile (MDBGN) from 0.7% in 1991 to 3.5% in 2000. The current high level of sensitivity to MDBGN requires an urgent safety re-evaluation and risk assessment update along with consideration of immediate lowering of use concentrations, especially in leave-on products.

Allergens↗

Do monoterpenes released from feverfew (Tanacetum parthenium) plants cause airborne Compositae dermatitis?

The Compositae plant feverfew (Tanacetum parthenium) is an important sensitizer in Europe and has been suspected of causing airborne Compositae dermatitis. A previous investigation of substances emitted from feverfew plants detected no sesquiterpene lactones, however, but mainly monoterpenes. The aims of this study were to test whether feverfew-allergic patients were also sensitive to some of the above-mentioned monoterpenes and, if so, to study associations between sensitization patterns, relevance of feverfew allergy and clinical features. 17 patients with + +/+ + + reactions to feverfew and parthenolide were tested with 15 selected monoterpenes and 2 sesquiterpenes. Of the 17 persons, 13 had positive and/or doubtful positive reactions to 1 or more monoterpenes. Only 1 person was allergic to several monoterpenes. Her history of gradually worsening Compositae dermatitis culminating in a probable airborne dermatitis, mimicking photosensitivity, and the disappearance of symptoms upon removal of feverfew plants suggest monoterpenes as a possible contributing factor. Similar associations between doubtful positive monoterpene reactions and clinical patterns, fragrance/colophonium allergy and relevance of feverfew allergy were not established with certainty. In conclusion, sensitization to the sesquiterpene lactones of feverfew is not invariably accompanied by sensitization to its volatile monoterpenes. The presence of monoterpene allergy, however, may contribute to airborne Compositae dermatitis.

Adult↗

Further important sensitizers in patients sensitive to fragrances.

In order to find sensitizers additional to the current fragrance mix (FM) a series of fragrance materials (series II) was evaluated in 6 dermatological centres in Europe. 11 of the test materials were essential oils, the remaining 7 being either mixtures of isomers or simple chemicals of frequent usage in the perfume industry. 1606 patients were consecutively tested with series II and 8% FM. Each patient was classified regarding a history of adverse reactions to scented products: certain, probable, questionable, none. Reactions to FM occurred most frequently in 11.4% of the subjects. The 6 materials with the highest reactivity after the FM were ylang-ylang oil (YY) I (2.6%), YY II (2.5%), lemongrass oil (1.6%), narcissus absolute (1.3%), jasmine absolute (1.2%) and sandalwood oil (0.9%). 48 (3.0%) of the patients reacted only to materials of series II and not to FM. 6.0% of 1606 patients gave a history of adverse reactions to fragrances which was classified as certain. This group reacted to FM only in 22.9%, to series II and FM in 15.6% and to series II only in 5.2%. 63.5% of the patients reacting to both FM and 1 of the materials of series II had some type of positive fragrance history, which was higher in comparison to those with isolated reactions to FM (46.2% of 121) or to series II, respectively, (45.8% of 48). However, this difference was not statistically significant. In conclusion, the materials of series II identified a further subset of patients with a fragrance problem, which would have been missed by the current FM as the single screening tool for patch testing.

Dermatitis, Allergic Contact↗

55 cases of allergic reactions to hair dye: a descriptive, consumer complaint-based study.

Severe facial and scalp dermatitis following the use of permanent hair dyes has been reported in several cases. Para-phenylenediamine (PPD) is known as a potent contact allergen, and PPD is allowed in hair dye at a concentration of 6%. Hair dye reactions are usually diagnosed by the patients themselves, and adverse reactions to hair dye may not necessarily be recorded by the health care system, unless the reactions are especially severe. Based on this assumption, we suspected that hair dye dermatitis was occurring more frequently than reported in the literature. Consumer complaint-based data were obtained by advertising for persons with adverse reactions to hair dye. Among those responding to the advertisement, 55 cases of severe, acute allergic contact dermatitis were identified. The main symptoms were severe oedema of the face, scalp and ears, and clinically this was often mistaken for angio-oedema. The 55 cases comprised a total of 75 visits to the health service and 5 admissions to hospital. 18 persons had sick leave, which supports the impression of very severe dermatitis reactions. 60% were treated with antihistamine, while 52% were treated with corticosteroids. 29% of the cases were patch tested and all were found positive to PPD. Our data presented here clearly show that PPD and its derivatives in hair dye at the present concentrations presents a significant health risk for the population. Furthermore, the severe acute allergic skin reactions are often misdiagnosed in the health care system. The frequency of allergic contact dermatitis resulting from hair dye is likely to be underestimated. New methods to survey the frequency of adverse reactions should be considered.

Adolescent↗

Further important sensitizers in patients sensitive to fragrances.

The aim of this study was to determine the frequency of responses to selected fragrance materials in consecutive patients patch tested in 6 dermatological centres in Europe. 1855 patients were evaluated with the 8% fragrance mix (FM) and 14 other frequently used well-defined fragrance chemicals (series I). Each patient was classified regarding a history of adverse reactions to fragrances: certain, probable, questionable, none. Reactions to FM occurred in 11.3% of the subjects. The 6 substances with the highest reactivity following FM were Lyral (2.7%), citral (1.1%), farnesol P (0.5%), citronellol (0.4%), hexyl cinnamic aldehyde (0.3%), and coumarin (0.3%). 41 (2.2%) of the patients reacted only to materials of series I and not to FM. 6.6% of 1855 patients gave a history of adverse reactions to fragrances which was classified as certain. This group reacted to FM only in 41.1%, to series I and FM in 12.0% and to series I only in 7.2%. 74.3% of the 39 patients reacting to both FM and 1 of the materials of series I had any type of positive fragrance history, which was significantly higher in comparison to those with isolated reactions to series I (53.6% of 41), p = 0.04. The study identified further sensitizers relevant for patch testing of patients with contact dermatitis, of which Lyral is the most important single chemical.

Allergens↗

Synthesis of novel gamma-aminobutyric acid (GABA) uptake inhibitors. 5.(1) Preparation and structure-activity studies of tricyclic analogues of known GABA uptake inhibitors.

On the basis of the SAR of a series of known gamma-aminobutyric acid (GABA) uptake inhibitors, including 4 (SKF 89976), new tricyclic analogues have been prepared. These novel compounds are derivatives of nipecotic acid, guvacine, and homo-beta-proline, substituted at the nitrogen of these amino acids by various lipophilic moieties such as (10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)alkoxyalkyl or (10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)alkoxyalkyl. The in vitro values for inhibition of [(3)H]-GABA uptake in rat synaptosomes was determined for each compound in this new series, and it was found that several of the novel compounds showed a high potency comparable with that of the reference compounds 4, 5 (tiagabine), and 6 (CI-966). Several of the novel compounds were also evaluated for their ability in vivo to inhibit clonic seizures induced by a 15 mg/kg (ip) dose of methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM). One compound, (R)-1-(2-(2-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)ethoxy)ethyl)-3-piperidinecarboxylic acid (23), was selected for further biological investigations and showed a protective index comparable to or slightly better than that of the recently launched anticonvulsant product 5 ((R)-1-(4,4-bis(3-methyl-2-thienyl)-3-butenyl)-3-piperidinecarboxylic acid).

Animals↗

The time-dose-response relationship for elicitation of contact dermatitis in isoeugenol allergic individuals.

The elicitation response in allergic contact dermatitis is dose dependent, but the time-concentration relationship for elicitation has not previously been described. In this study 27 isoeugenol-sensitive patients participated in serial dilution patch tests with isoeugenol and a double-blinded Repeated Open Application Test (ROAT) using two concentrations of isoeugenol, 0.2 and 0.05%. Seven controls without isoeugenol allergy were also included. The participants applied 3.72 +/- 1.57 (mean +/- SD) mg/cm(2) of coded isoeugenol solutions twice a day to a 3 x 3 cm(2) area on the volar aspect of the right and left arm, respectively. For each test site the applications continued until a reaction appeared or for a maximum of 28 days. The minimal criteria for a positive reaction regarded as allergic contact dermatitis was persistent erythema at the ROAT test site. All controls were negative and 16/24 (66.7%) of the included isoeugenol-sensitive subjects showed a positive ROAT to the 0.2% solution within the study period (Fisher's test, p = 0.0024). Ten of the positive patients also reacted to the 0.05% solution. The median number of days until a positive reaction to the 0.2% solution was 7 days and was 15 days for the 0.05% solution. There was a highly significant correlation between the patients' patch test threshold and the number of days until a positive ROAT. In conclusion, the time until an isoeugenol allergic individual reacts in a ROAT depends on the individual sensitivity as well as the exposure concentrations; for low concentrations of the allergen or low degree of sensitivity, the allergic contact dermatitis may develop after several weeks of exposure. Therefore, a negative ROAT after 7 days may be a false negative.

Administration, Topical↗

Synthesis of novel GABA uptake inhibitors. Part 6: preparation and evaluation of N-Omega asymmetrically substituted nipecotic acid derivatives.

In a previous series of potent GABA uptake inhibitors published from this laboratory, we noticed that asymmetry in the substitution pattern of the bis-aromatic moiety in known GABA uptake inhibitors such as 4 [1-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylic acid] and 5 [(R)-1-(4,4-bis(3-methyl-2-thienyl)-3-butenyl)-3-piperidinecarboxylic acid] was beneficial for high affinity. This led us to investigate asymmetric analogues of known symmetric GABA uptake inhibitors in which one of the aryl groups has been exchanged with an alkyl, alkylene or cycloalkylene moiety as well as other modifications in the lipophilic part. The in vitro values for inhibition of [(3)H]-GABA uptake in rat synaptosomes was determined for each compound, and it was found that several of the novel compounds inhibit GABA uptake as potently as their known symmetrical reference analogues. Several of the novel compounds were also evaluated for their ability to inhibit clonic seizures induced by a 15 mg/kg (ip) dose of methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) in vivo. Some of the compounds, for example 18 [(R)-1-(2-(((1,2-bis(2-fluorophenyl)ethylidene)amino)oxy)ethyl)-3-piperidinecarboxylic acid], show a high in vivo potency and protective index comparable with that of our recently launched anticonvulsant product, 5 [(R)-1-(4,4-bis(3-methyl-2-thienyl)-3-butenyl)-3-piperidinecarboxylic acid], and may therefore serve as second-generation drug candidates.

Animals↗

Standardization of the TRUE Test imidazolidinyl urea and diazolidinyl urea patches.

The preservatives imidazolidinyl urea (IMID, Germall 115) and diazolidinyl urea (DU, Germall II) are commonly used in cosmetic products and are well-known sensitizers. The aim of the present study was to establish the optimal patch test concentration in hydrophilic dried-in vehicle (TRUE Test) for IMID and DU. 181 patients were included in the study. Of these, 150 were patients referred for patch testing, 12 were patients with known allergy to IMID and 19 were patients with known allergy to DU. 76 consecutive patients and the 12 IMID-allergic patients were patch tested with a dilution series IMID (0 to 600 microg/cm(2)), formaldehyde (180 microg/cm(2)) and DU (200 microg/cm(2)). 74 consecutive patients and the 19 DU-allergic patients were patch tested with a dilution series of DU (0 to 600 microg/cm(2)), formaldehyde (180 microg/cm) and IMID (200 microg/cm(2)). A positive dose-response relationship was found. The number of doubtful reactions decreased with increasing test concentrations. No late reactions were observed. A patch test concentration in hydrophilic dried-in vehicle (TRUE Test) of 600 microg/cm(2) was found to be adequate and safe for both IMID and DU.

Allergens↗

An 8-year experience with routine SL mix patch testing supplemented with Compositae mix in Denmark.

Routine patch testing with sesquiterpene lactone (SL) mix, supplemented with Compositae mix (CM) and other Compositae extracts and allergens where appropriate, was evaluated over an 8-year period. 190 of 4386 patients tested (4.3%) were Compositae-sensitive, 143 females (mean age 51.5 years) and 47 males (mean age 55 years), and 83% of reactions considered clinically relevant. 22% were suspected of occupational sensitization/dermatitis. 62% had a contact allergy to 2 or more compounds, most often to nickel, fragrance and colophonium. SL mix detected 65%, CM 87% of Compositae-allergic patients, and the overall detection rate with both mixes was 93%. Few irritant reactions and no cases of clear-cut active sensitization were recorded with the mixes, but our results emphasize the importance of differentiating late-appearing reactivation reactions from patch test sensitization. The weakly positive CM reactions could reflect some irritancy, but as they were associated with fragrance and/or colophonium allergy to a higher degree than weakly positive SL mix reactions, they probably represented cross-reactions. In conclusion, the detection rate with SL mix was high enough to support its continued use as a screening mix and it was very well and rather safely supplemented by aimed testing with CM.

Adolescent↗

Allergic contact dermatitis from sodium dihydroxycetyl phosphate, a new cosmetic allergen?

Sodium dihydroxycetyl phosphate (trade name Dragophos S 2/918501) was identified as a contact allergen in a herbal moisturizing cream causing severe acute contact dermatitis on the hands and face of a 41-year-old woman. Sodium dihydroxycetyl phosphate is a complex mixture of phosphate esters of dihydroxycetyl alcohol, and subsequent analysis and testing revealed hexadecane-1,2-diol as 1 of the allergenic ingredients. Another possible allergen in the compound appears to be hexadecane-1,2-diol, 2-isopropyl ether.

Adult↗

Tixocortol pivalate contact allergy in the GPMT: frequency and cross-reactivity.

In spite of their intrinsic anti-inflammatory properties, corticosteroids can induce contact allergy. When studying the allergenic properties of corticosteroids it has to be considered that both the allergenic and anti-inflammatory effect may influence the induction phase as well as the elicitation phase and that such effects may be dose-dependent. A multiple dose guinea pig maximization test (GPMT) was therefore used to study the dose-response relationship of tixocortol pivalate. The GPMT was conducted according to OECD guideline #406, using a multiple-dose design and test results were analysed with logistic regression analysis. There was a significant tixocortol pivalate sensitization of the test animals compared to the control group (p<0.05), after both challenge and re-challenge. The challenge with 1% tixocortol pivalate gave more positive reactions than the challenge with 3%. The highest frequency of positive animals was observed when the animals were treated with low to intermediate induction concentrations and intermediate to high challenge concentrations with tixocortol pivalate in the TRUE Test. Cross-reactivity was found between tixocortol pivalate and hydrocortisone, which was expected from their close molecular resemblance, whereas no cross-reactivity was seen between tixocortol pivalate and the 3 other corticosteroids: amcinonide, budesonide, and hydrocortisone-17-butyrate.

Allergens↗

Sensitization and cross-reaction patterns in Danish Compositae-allergic patients.

Results of aimed patch testing with constituents of sesquiterpene lactone (SL) mix, Compositae mix (CM) and other Compositae extracts and allergens in 190 Compositae-allergic patients detected in an 8-year period are presented. Feverfew of CM elicited positive reactions most frequently, followed by tansy, wild chamomile, yarrow and arnica, whereas dehydrocostus lactone of SL was the most frequent elicitor of positive reactions, followed by alantolactone and costunolide. Chrysanthemum (Dendranthema) and marguerite (Argyranthemum frutescens) were the most important suspected sensitizers in both occupationally and nonoccupationally exposed, and cross-reactions between chrysanthemum and feverfew/tansy/chamomile may partly explain the high prevalence of positive reactions to the 3 last mentioned. In the nonoccupationally sensitized group, garden plants such as feverfew, blanket flower (Gaillardia), elecampane (Inula helenium), large yellow ox-eye (Telekia speciosa) and cosmea (Cosmos) were additional important allergenic plants. The 3 last mentioned were picked up by SL mix. Most of the lettuce-sensitized persons were CM-positive. 19% of the occupationally sensitized group were negative to both SL and CM, making very aimed patch testing necessary, notably when suspecting rare sensitizers such as Gerbera and star of the veldt (Osteospermum). The significance of the weeds dandelion, dog fennel and ox-eye daisy as sensitizers is not clarified, but they are probably less important than cultivated plants.

Adult↗