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Biomedical subjects

K E Andersen

Publications and source records attributed to K E Andersen.

At least 55 records · Page 3Linked to original sources
PubMed2001

Prevalence of atopic dermatitis, asthma, allergic rhinitis, and hand and contact dermatitis in adolescents. The Odense Adolescence Cohort Study on Atopic Diseases and Dermatitis.

BACKGROUND: Atopic diseases are common in children and adolescents. However, epidemiological knowledge is sparse for hand eczema and allergic contact dermatitis in this age group. Furthermore, no population-based studies have evaluated the prevalence of atopic diseases and hand and contact dermatitis in the same group of adolescents. OBJECTIVES: To assess prevalence measures of atopic dermatitis (AD), asthma, allergic rhinitis and hand and contact dermatitis in adolescents in Odense municipality, Denmark. METHODS: The study was carried out as a cross-sectional study among 1501 eighth grade school children (age 12-16 years) and included questionnaire, interview, clinical examination and patch testing. RESULTS: The lifetime prevalence of AD was 21.3% (girls 25.7% vs. boys 17.0%, P < 0.001) using predefined questionnaire criteria. The 1-year period prevalence of AD was 6.7% and the point prevalence 3.6% (Hanifin and Rajka criteria). In the interview the lifetime prevalence of inhalant allergy was estimated as 17.7% (6.9% allergic asthma, 15.7% allergic rhinitis). The lifetime prevalence of hand eczema based on the questionnaire was 9.2%, the 1-year period prevalence was 7.3% and the point prevalence 3.2%, with a significant predominance in girls. A significant association was found both between AD and inhalant allergy, and between AD and hand eczema using lifetime prevalence measures. The point prevalence of contact allergy was 15.2% (girls 19.4% vs. boys 10.3%, P < 0.001), and present or past allergic contact dermatitis was found in 7.2% (girls 11.3% vs. boys 2.5%). Contact allergy was most common to nickel (8.6%) and fragrance mix (1.8%). CONCLUSIONS: High prevalence figures were found for atopic diseases, hand eczema and allergic contact dermatitis, and the diseases were closely associated. A considerable number of adolescents still suffers from AD, and a considerable sex difference was noted for hand eczema and allergic contact dermatitis. Nickel allergy and perfume allergy were the major contact allergies. In the future this cohort of eighth grade school children will be followed up with regard to the course and development of atopic diseases, hand eczema and contact dermatitis.

Adolescent↗
PubMed2000

Patch testing with corticosteroid mixes in Europe. A multicentre study of the EECDRG.

This study investigated whether a corticosteroid mix containing tixocortol pivalate, budesonide, and hydrocortisone-17-butyrate could detect contact allergy to corticosteroids. 2 corticosteroid mixes, 1 with a high (mix I) and 1 with a low (mix II) concentration and the 3 individual constituents, each at 2 concentrations, were inserted into the standard series of 16 participating clinics. Tests were read on day (D) 3 or 4. 5432 patients were tested, and 110 (2.0%) had positive reactions to at least 1 of the 8 test preparations. Of the 8 preparations, mix I identified most allergic patients, followed by mix II, budesonide 0.10%, budesonide 0.002%, and tixocortol pivalate, both concentrations (1.0 and 0.10%) tracing the same number. With the mixes, 53.2-59.6% of tixocortol pivalate allergy was missed. 47 patients were allergic to either concentration of tixocortol pivalate, 25% of these only to 1.0% and another 25% only to 0.10%. Testing with mix I and tixocortol pivalate 0.10% picked up 98/110, testing with tixocortol pivalate 1.0% and 0.10% and budesonide 0.10% picked up 105/110. 3379 patients were read on both D3 or D4 as well as on D7. Without a late reading (D7), up to 30% of contact allergy to corticosteroid markers was missed.

Administration, Topical↗
PubMed2000

Identification of Lilial as a fragrance sensitizer in a perfume by bioassay-guided chemical fractionation and structure-activity relationships.

Fragrance materials are among the most common causes of allergic contact dermatitis. The aim of this study was to identify in a perfume fragrance allergens not included in the fragrance mix, by use of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships (SARs). The basis for the investigation was a 45-year-old woman allergic to her own perfume. She had a negative patch test to the fragrance mix and agreed to participate in the study. Chemical fractionation of the perfume concentrate was used for repeated patch testing and/or repeated open application test on the pre-sensitized patient. The chemical composition of the fractions giving a positive patch-test response and repeated open application test reactions was obtained by gas chromatography-mass spectrometry. From the compounds identified, those that contained a "structural alert" in their chemical structure, indicating an ability to modify skin proteins and thus behave as a skin sensitizer, were tested on the patient. The patient reacted positively to the synthetic fragrance p-t-butyl-alpha-methylhydrocinnamic aldehyde (Lilial), a widely used fragrance compound not present in the fragrance mix. The combination of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships seems to be a valuable tool for the investigation of contact allergy to fragrance materials.

Aldehydes↗
PubMed1999

Synthesis of novel GABA uptake inhibitors. 4. Bioisosteric transformation and successive optimization of known GABA uptake inhibitors leading to a series of potent anticonvulsant drug candidates.

By bioisosteric transformations and successive optimization of known GABA uptake inhibitors, several series of novel GABA uptake inhibitors have been prepared by different synthetic approaches. These compounds are derivatives of nipecotic acid and guvacine, substituted at the nitrogen of these amino acids by various lipophilic moieties such as diarylaminoalkoxyalkyl or diarylalkoxyalkyl. The in vitro values for inhibition of [(3)H]GABA uptake in rat synaptosomes was determined for each compound, and it was found that the most potent compound from this series, (R)-1-(2-(3,3-diphenyl-1-propyloxy)ethyl)-3-piperidinecarboxyli c acid hydrochloride (29), is so far the most potent parent compound inhibiting GABA uptake into synaptosomes. Structure-activity results confirm our earlier observations, that an electronegative center in the chain connecting the amino acid and diaryl moiety is very critical in order to obtain high in vitro potency. 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). Some of the compounds tested show a high in vivo potency comparable with that of the recently launched anticonvulsant product 6 ((R)-1-(4, 4-bis(3-methyl-2-thienyl)-3-butenyl)-3-piperidinecarboxylic acid).

Animals↗
PubMed1999

Synthesis of novel GABA uptake inhibitors. 3. Diaryloxime and diarylvinyl ether derivatives of nipecotic acid and guvacine as anticonvulsant agents.

(3R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid 1 (tiagabine, Gabitril) is a potent and selective gamma-aminobutyric acid (GABA) uptake inhibitor with proven anticonvulsant efficacy in humans. This drug, which has a unique mechanism of action among marketed anticonvulsant agents, has been launched for add-on treatment of partial seizures with or without secondary generalization in patients >12 years of age. Using this new agent as a benchmark, we have designed two series of novel GABA uptake inhibitors of remarkable potency, using a putative new model of ligand interaction at the GABA transporter type 1 (GAT-1) uptake site. This model involves the postulated interaction of an electronegative region in the GABA uptake inhibitor with a positively charged domain in the protein structure of the GAT-1 site. These two novel series of anticonvulsant agents contain diaryloxime or diarylvinyl ether functionalities linked to cyclic amino acid moieties and were derived utilizing the new model, via a series of design steps from the known 4,4-diarylbutenyl GABA uptake inhibitors. The new compounds are potent inhibitors of [(3)H]-GABA uptake in rat brain synaptosomes in vitro, and their antiepileptic potential was demonstrated in vivo by their ability to protect against seizures induced by the benzodiazepine receptor inverse agonist methyl 4-ethyl-6,7-dimethoxy-beta-carboline-3-carboxylate (DMCM) in mice. From structure-activity studies of these new GABA uptake inhibitors, we have shown that insertion of an ether oxygen in conjugation with the double bond in tiagabine (K(i) = 67 nM) improves in vitro potency by 5-fold to 14 nM.

Animals↗
PubMed1999

Absorption and retention of nickel from drinking water in relation to food intake and nickel sensitivity.

Two studies were performed to examine the influence of fasting and food intake on the absorption and retention of nickel added to drinking water and to determine if nickel sensitization played any role in this regard. First, eight nonallergic male volunteers fasted overnight before being given nickel in drinking water (12 micrograms Ni/kg) and, at different time intervals, standardized 1400-kJ portions of scrambled eggs. When nickel was ingested in water 30 min or 1 h prior to the meal, peak nickel concentrations in serum occurred 1 h after the water intake, and the peak was 13-fold higher than the one seen 1 h after simultaneous intake of nickel-containing water and scrambled eggs. In the latter case, a smaller, delayed peak occurred 3 h after the meal. Median urinary nickel excretion half-times varied between 19.9 and 26.7 h. Within 3 days, the amount of nickel excreted corresponded to 2.5% of the nickel ingested when it was mixed into the scrambled eggs. Increasing amounts were excreted as the interval between the water and the meal increased, with 25.8% of the administered dose being excreted when the eggs were served 4 h prior to the nickel-containing drinking water. In the second experiment, a stable nickel isotope, 61Ni, was given in drinking water to 20 nickel-sensitized women and 20 age-matched controls, both groups having vesicular hand eczema of the pompholyx type. Nine of 20 nickel allergic eczema patients experienced aggravation of hand eczema after nickel administration, and three also developed a maculopapular exanthema. No exacerbation was seen in the control group. The course of nickel absorption and excretion in the allergic groups did not differ and was similar to the pattern seen in the first study, although the absorption in the women was less. A sex-related difference in gastric emptying rates may play a role. Thus, food intake and gastric emptying are of substantial significance for the bioavailability of nickel from aqueous solutions.

Absorption↗
PubMed1999

Immediate allergic and nonallergic reactions to Christmas and Easter cacti.

BACKGROUND: Occupational exposure to Christmas cacti has been reported as a cause of type I allergy. Therefore, the prevalence of immediate-type mucosal and skin reactions related to cactus exposure was studied in 103 employees in a cactus nursery. METHODS: The study was based on a questionnaire followed by clinical examination, skin prick tests (SPT) with standard inhalant allergens and cacti, and a histamine-release test (HRT/Refix) using fresh cactus extracts as elicitor. RESULTS: The questionnaire was answered by 84 (82%) of the nursery employees, and 63 (61%) were interviewed and skin prick tested; 58 of these were tested with HRT/Refix. Furthermore, 22 healthy controls were included and tested in vivo and in vitro. Cactus-related contact urticaria and/or rhinoconjunctivitis were reported by 37% of the cactus workers. Based on a combination of positive history, positive SPT, and positive HRT/ Refix to cactus, 8% of the cactus workers were allergic to cacti. No noncactus workers or controls were allergic to cacti by these criteria. Testing with fresh cactus material elicited positive SPT and negative HRT/Refix in 27 nursery workers and controls, of whom 12 had immediate-type skin and mucosal symptoms. CONCLUSIONS: Christmas and Easter cacti seemed to be able to induce contact urticaria and rhinoconjunctivitis on both an immunologic and a nonimmunologic basis. Personal atopy was associated with positive reactions to cacti.

Allergens↗
PubMed1999

Lyral is an important sensitizer in patients sensitive to fragrances.

Contact allergy to fragrances is a common problem world-wide. The currently used fragrance mix (FM) for patch testing has only eight constituents and does not identify all fragrance-allergic patients. As perfumes may contain 100 or more substances, the search for markers for allergy continues. The synthetic fragrance 4-(4-hydroxy-4-methylpentyl)-3-cyclohexene carboxaldehyde (Lyral) was tested together with the FM and 11 other fragrance substances on consecutive patients in six European departments of dermatology. All patients were carefully questioned regarding a history of reactions to scented products in the past and were grouped into four categories: 'certain', 'probable', 'questionable' and 'none'. Lyral (5% in petrolatum) gave a positive reaction in 2.7% of 1855 patients (range 1.2-17%) and ranked next to 11.3% with FM allergy. Twenty-four patients reacted to both Lyral and FM, but 21 (1.1%) reacted positively only to Lyral. Of 124 patients with a 'certain' history, 53.2% reacted to the FM and a further 7.2% to Lyral only. If any kind of history of fragrance intolerance was given, 80% (40 of 50) of Lyral positive patients had a 'positive' history while only 58.6% (123 of 210) of FM positive patients had such a history; this difference was significant at P < 0.01. Lyral was identified by gas chromatography-mass spectrometry in some products which had caused an allergic contact dermatitis in four typical patients who showed a patch test positive to Lyral and negative or doubtful to FM. In conclusion, we recommend the testing of 5% Lyral (in petrolatum) in patients suspected of contact dermatitis.

Adult↗
PubMed1999

Routine patch testing with the sesquiterpene lactone mix in Europe: a 2-year experience. A multicentre study of the EECDRG.

To test the screening value of the sesquiterpene lactone (SL) mix in Europe today and describe epidemiological and clinical features of Compositae-sensitive patients, the SL mix 0.1% pet. was included in the standard patch test series in 11 European clinics. 10,695 patients were tested, and 106 (1%) had positive reactions, 74% of which were of current or old relevance. The prevalence of positive reactions varied between 0.1 and 2.7% in different centres. The median age of the 66 females was 51.5 years, and 55.2 in the 40 males. The 20 occupationally sensitized had a higher % of males and a median age of 43 years, whereas 7 UV-sensitive patients had a median age of 72 years. Garden plants were the major suspected sensitizers and the clinical patterns were partly, in accordance with plant dermatoses in general, involving hands, forearms and face, and partly widespread eczema in a large proportion of the patients. More than 1/3 were positive to perfume and/or colophony, possibly reflecting cross-reactivity. With only 1 case of active sensitization and no irritant reactions, the SL mix is a safe allergen and the overall prevalence of positive reactions supports its continued use in the standard patch test series.

Adult↗
PubMed1999

Identification of coumarin as the sensitizer in a patient sensitive to her own perfume but negative to the fragrance mix.

The aim of this study was to identify the chemicals responsible for the sensitivity of a 44-year-old woman to her own perfume, but showing negative patch test results to the fragrance mix. For this purpose, the perfume concentrate from the eau de toilette was chemically fractionated. Each fraction obtained was afterwards tested on the patient using a ROAT and/or a patch test. Only 1 fraction gave a positive ROAT result. This fraction was analyzed and found to contain coumarin and ethyl vanillin. Coumarin, one of the most widely used fragrance compounds that is not present in the fragrance mix, was confirmed as being the sensitizer.

Adult↗
PubMed1999

Gold--a controversial sensitizer. European Environmental and Contact Dermatitis Research Group.

Until recently, gold allergy was considered to be extremely rare. Gold has been used and worshipped for thousands of years without any obvious complaints of skin problems, either in those participating in mining and other ways of prospecting, or in those wearing jewellery. When studies on contact allergy to gold sodium thiosulfate were published at the beginning of the 1990s, the allergic nature of the reported positive patch test reactions to gold was questioned. The major argument for such questioning was the lack of demonstrable clinical relevance in most positive reactors. A major reason for the questioning may have been confusion in differentiating between contact allergy and allergic contact dermatitis. To arrive at a diagnosis of allergic contact dermatitis, 3 steps have, in principle, to be fulfilled: (i) establishment of contact allergy; (ii) demonstration of present exposure; (iii) assessment of clinical relevance, i.e., causing or aggravating a contact dermatitis. In this paper, these steps are discussed with regard to gold. With our present knowledge of contact allergy-allergic contact dermatitis, we do not recommend including gold sodium thiosulfate in the standard series. It should be applied for scientific purposes and when allergic contact dermatitis from gold is suspected.

Dermatitis, Allergic Contact↗
PubMed1999

Allergic contact dermatitis in children and adolescents.

From a clinical point of view, the prevalence of allergic contact dermatitis (ACD) among children and adolescents seems to be low. However, many children have dermatitis, most often atopic dermatitis. In selected cases, ACD is suspected, and the child is tested. The question remains, whether the prevalence of ACD in children really is low or whether the possibility of ACD is not sufficiently considered. During the last decade, reports have appeared on series of children and adolescents with contact allergy and ACD. Few cases have been reported in infants, but the development of contact allergy and ACD increases with age. Most studies include selected groups of children and adolescents with suspected ACD. Few studies have examined unselected populations, and most consider only the prevalence of contact allergy without evaluating the clinical relevance, e.g., the prevalence of ACD. Furthermore, no follow-up studies exist. Therefore, the incidence and prevalence of contact allergy and ACD in children and adolescents is largely unknown.

Adolescent↗
PubMed1999

Histological distinction between early allergic and irritant patch test reactions: follicular spongiosis may be characteristic of early allergic contact dermatitis.

Comparative light microscopic studies have revealed subtle differences between allergic and irritant reactions in the skin. In the search for specific differences, we focussed on the early inflammatory response. This pilot study was conducted to test the hypothesis that follicular spongiosis can differentiate between early allergic and irritant patch test reactions. 8 patients with known contact allergy to either colophony or quarternium-15 participated in the study. In each patient, allergic and irritant patch tests reactions were elicited, and 4-mm punch biopsies were taken after 6 8 h from clinically equipotent reactions. Paired sets of slides were assessed blindly by 2 pathologists. 1 patient showing a pityrosporum folliculitis was excluded from the study. All biopsies from allergic patch tests were characterized by follicular spongiosis, while biopsies from irritant patch tests showed no recognizable changes except a slight follicular spongiosis in 1 patient. The 2 pathologists agreed independently on the correct classification in 6 out of 7 cases (p=0.0156). We tested an optimized model, selecting non-irritant allergens and a well-known irritant. Further investigations are needed to elucidate the diagnostic significance of the histological classification of allergic and irritant cutaneous reactions in punch biopsies.

Adult↗