5-aminolaevulinic acid nanoemulsion is more effective than methyl-5-aminolaevulinate in daylight photodynamic therapy for actinic keratosis: a nonsponsored randomized double-blind multicentre trial.

BACKGROUND: Daylight photodynamic therapy (DL-PDT) with methyl-5-aminolaevulinate (MAL) is an effective treatment for mild and moderate actinic keratosis (AK). OBJECTIVES: To assess the clinical efficacy, tolerability and cost-effectiveness of 5-aminolaevulinic acid nanoemulsion (BF-200 ALA) compared with MAL in DL-PDT for grade I-II AKs. METHODS: This nonsponsored, prospective randomized double-blind multicentre trial included 69 patients with 767 grade I-II AKs located symmetrically on the face or scalp. A single DL-PDT was given in a randomized split-face design. The primary outcome was clearance of the AKs at 12 months as assessed by a blinded observer. The secondary outcomes were pain, treatment reactions, cosmetic outcome and the cost-effectiveness of the therapy. RESULTS: In the per-patient (half-face) analysis, clearance was better for the BF-200 ALA sides than for those treated with MAL (P = 0·008). In total, BF-200 ALA cleared 299/375 AKs (79·7%) and MAL 288/392 (73·5%) (P = 0·041). The treatment was practically painless with both photosensitizers, the mean pain visual analogue scale being 1·51 for BF-200 ALA and 1·35 for MAL (P = 0·061). Twenty-six patients had a stronger skin reaction on the BF-200 ALA side, seven on the MAL side and 23 displayed no difference (P = 0·001). The cosmetic outcome was excellent or good in > 90% of cases with both photosensitizers (P = 1·000). The cost-effectiveness plane showed that the costs of DL-PDT were similar for both photosensitizers, but the effectiveness was slightly higher for BF-200 ALA. CONCLUSIONS: Our results indicate that BF-200 ALA is more effective than MAL in DL-PDT for grade I-II AKs. BF-200 ALA provides slightly better value for money than MAL.

Natural rubber latex allergy in children: a follow-up study.

BACKGROUND: Natural rubber latex (NRL) allergy occurs frequently in children with spina bifida and other children with disorders requiring multiple operations. Also atopic children who have not undergone surgery can be sensitized to NRL, but the outcome of these children has not been studied. OBJECTIVE: To study how NRL-allergic children manage at home and whether their skin prick test (SPT) reactivity, latex RAST or IgE antibody levels to NRL allergens change during the follow-up. METHODS: Twenty-four NRL-allergic children who had not undergone surgery and eight children with histories of multiple operations were followed up for a mean of 2.8 years. Clinical symptoms were recorded and all children were re-examined with SPT, latex RAST and ELISA for IgE antibodies to prohevein (Hev b 6.01), hevein (Hev b 6.02) and rubber elongation factor (REF, Hev b 1). RESULTS: Nineteen of the 24 NRL-allergic children (79%) who had not undergone surgery had occasionally contacts to balloons and other NRL products at home, and 10 of them experienced symptoms ranging from contact urticaria to systemic reactions. Three of the eight NRL-allergic children with a history of multiple operations had contacts to rubber balloons without any symptoms, and five children underwent 1-8 uneventful operations in a latex-free environment. SPT reactivity to NRL allergens, latex-RAST or IgE antibody levels to prohevein or hevein did not change in either group of NRL-allergic children during the follow-up. CONCLUSIONS: Occurrence of clinical symptoms and no decrease in SPT reactivity or IgE levels to NRL allergens in the course of the present follow-up study imply that more attention should be paid to the protection of NRL-allergic children from rubber contacts in the home environment.

IgE reactivity to patatin-like latex allergen, Hev b 7, and to patatin of potato tuber, Sol t 1, in adults and children allergic to natural rubber latex.

BACKGROUND: Patients allergic to natural rubber latex (NRL) frequently show positive skin prick tests (SPT) and hypersensitivity reactions to various fruits, such as avocado, banana, and kiwi, as well as to vegetables such as potato. METHODS: Hev b 7 was purified from NRL "C-serum" and Sol t 1 from potato extract, and they were detected by immunoblotting. IgE antibodies to Hev b 7 and Sol t 1 were measured with ELISA in sera from 35 adults and 35 children allergic to NRL. ELISA inhibition and immunoblotting were used to study allergen cross-reactivity. The in vivo reactivity of Hev b 7 and Sol t 1 were demonstrated in the SPT. RESULTS: Seventeen (49%) of the 35 NRL-allergic adults had IgE antibodies to Hev b 7, in contrast to only one of the 35 NRL-allergic children. Fifteen (43%) of the NRL-allergic adults and 29 (83%) of the NRL-allergic children had IgE antibodies to Sol t 1. Ten (29%) of the adult sera showed IgE binding to both Sol t 1 and Hev b 7, and crosswise inhibition tests with pooled sera revealed marked cross-reactivity. In the SPT, both natural Hev b 7 and Sol t 1 were able to produce a wheal and flare reaction. CONCLUSIONS: One-half of the NRL-allergic adults, but only one of the NRL-allergic children, had IgE antibodies to natural Hev b 7. These results suggest that Hev b 7 is an important NRL allergen for adults, but not for children. Elucidation of the clinical importance of the observed cross-reactivity between Hev b 7 and Sol t 1 requires further studies.

Cow's milk casein, a hidden allergen in natural rubber latex gloves.

BACKGROUND: We have previously noted that one natural rubber latex (NRL) glove brand used for skin prick testing in the diagnosis of NRL allergy contained cow's milk casein. OBJECTIVE: We sought to examine whether other commonly marketed NRL glove brands contain cow's milk casein. METHODS: The casein content of 30 NRL glove extracts (1:5 wt/vol) was measured by RAST inhibition and by rocket immunoelectrophoresis and rocket radioimmunoelectrophoresis by using casein-specific rabbit antiserum, a serum pool from patients with cow's milk allergy, and radiolabeled anti-human IgE. The NRL allergen content was measured by ELISA inhibition. RESULTS: The casein content of the glove used in NRL allergy screening (Triflex, Baxter) was rather high (ie, about 400 microgram/g of glove). Its total protein content was 1000 microgram/g of glove. Rocket radioimmunoelectrophoresis detected distinct amounts of casein in 8, minimal amounts in 7, and no casein in the remaining 15 NRL glove brands. CONCLUSIONS: Several brands of NRL gloves were found to contain casein, implying that extracts prepared from such gloves can cause false-positive skin prick test reactions when diagnosing NRL allergy. The use of casein as a stabilizer in glove manufacture without appropriate labeling should be stopped because it can also cause contact urticaria syndrome in individuals with cow's milk allergy.

Increased allergen production in turnip (Brassica rapa) by treatments activating defense mechanisms.

BACKGROUND: Practical applications to enhance the productivity of agriculture by using plants with improved resistance to pathogens are expected to increase in the near future. Defense proteins play an important role in pathogen resistance, and some defense-related proteins are significant cross-reacting allergens. For example, cross-allergies are common among patients allergic to natural rubber latex (NRL), which contains many defense-related proteins. OBJECTIVE: Using a model plant (ie, turnip), we studied whether allergen contents increase after treatments activating defense mechanisms of the plants. METHODS: Whole or wounded turnips treated with salicylic acid, ethephon, or water were incubated for 2, 4, or 8 days. Allergen content was investigated by IgE immunoblotting with sera from patients allergic to NRL. An induced protein that bound IgE most intensively was purified and further characterized by mass analysis, amino acid sequencing, IgE-ELISA, and skin prick tests. RESULTS: In immunoblotting, clear IgE-binding bands were discernible only in samples from chemically treated plants. IgE was bound most intensively to a protein with an apparent molecular weight of 25 kd in SDS-PAGE and with a determined molecular weight of 18.7 kd. Sequenced peptides of the 18.7-kd protein showed over 70% homology to prohevein, a major allergen of NRL, and to many other prohevein-like defense proteins. In ELISA, sera from 30 of 34 (88%) adults and 21 of 26 (81%) children previously shown to have IgE against prohevein bound to the purified protein. In skin prick testing with the protein, 4 of 6 patients allergic to NRL had positive reactions. CONCLUSION: These results demonstrate that activating defense mechanisms of plants may considerably increase their allergen content.

IgE antibodies to prohevein, hevein, and rubber elongation factor in children with latex allergy.

BACKGROUND: Prohevein (Hev b 6.01) and hevein (Hev b 6.02) have been shown to be major IgE-binding allergens in health care workers and other adult patients allergic to natural rubber latex (NRL). Rubber elongation factor (REF; Hev b 1) and the 23/27 kd NRL allergen (Hev b 3) are characteristic of children with latex allergy who have spina bifida and other children requiring multiple operations at an early age. In addition, there are children with latex allergy and no history of multiple operations in whom sensitizing allergens are not known. OBJECTIVES: We studied IgE antibodies to NRL allergens in children with latex allergy who had not undergone surgery and compared the findings with those in children with latex allergy and a history of multiple operations. METHODS: Sera from 30 children with latex allergy who had not undergone surgery, 12 children with latex allergy with a history of multiple operations, and 19 control children without evidence of NRL allergy were examined. Immunoblotting was used to study IgE binding to NRL proteins, and purified prohevein, hevein, and REF were used in ELISA to measure specific IgE antibodies. RESULTS: In immunoblotting, sera from 21 (70%) children who had not undergone surgery and from 4 (33%) children with a history of multiple operations showed IgE binding to a 20-kd protein band (known to contain prohevein), and 9 (30%) and 8 (67%) sera, respectively, to a 14-kd protein band (known to contain REF). In ELISA, sera from 26 (86%) children who had not undergone surgery and from 7 (58%) children with a history of multiple operations had IgE antibodies to prohevein and 19 (63%) and 7 (58%) sera, respectively, to hevein. Eight (27%) sera from the children who had not undergone surgery had IgE antibodies to REF in contrast to 8 (67%) sera from children with a history of multiple operations. CONCLUSIONS: The IgE antibody pattern differs between children with latex allergy who had not undergone surgery and those with a history of multiple operations. The major allergens in children with no history of surgery appear to be prohevein and hevein and not REF, a finding that agrees well with that reported for health care workers with allergy to latex.

Natural rubber latex allergy in children who had not undergone surgery and children who had undergone multiple operations.

BACKGROUND: Children with spina bifida and other children requiring multiple surgical procedures represent a well-known risk group for natural rubber latex allergy. Children not undergoing surgery can also be sensitized, but findings in this group of children with latex allergy have not been thoroughly examined. OBJECTIVES: We sought to examine the frequency of latex allergy in a large group of children admitted for inhalant or food allergy testing for the purpose of collecting information on a series of children with latex allergy and comparing the symptoms and findings between those not undergoing surgery and those undergoing multiple operations. METHODS: Children admitted to the allergy laboratory of Tampere University Hospital were screened by skin prick tests (SPTs) with latex glove extract. All children with allergy as determined by the screening or admitted because of suspected latex allergy were reexamined from 1995 to 1996. For a definite diagnosis of latex allergy, positive SPT, latex RAST, and latex glove use test results were required. RESULTS: From 1992 to 1995, a total of 3269 children were skin prick tested with latex glove extract, and 55 (1.7%) had a positive response. On reexamination, 37 (1.1%) children had positive responses to SPTs, and 33 (1.0%) were confirmed to have latex allergy by means of RASTs and latex glove use tests. Since 1988, we have identified a total of 30 children with latex allergy who had not undergone surgery and 12 who underwent multiple operations. The clinical histories were similar in both groups; the mean ages at diagnosis were 5.7 and 8.1 years, and the frequency of atopy was 97% and 83%, respectively. Symptoms had occurred in 63% of the children who had not undergone surgery and in 75% of the children who underwent multiple operations. Contact urticaria was the most frequent symptom, and only one child had intraoperative anaphylaxis. Balloons, followed by gloves, were the most common latex products causing symptoms. The children with latex allergy who had not undergone surgery and those who underwent multiple operations showed no significant differences in SPT responses to commercial latex allergen extract or in specific IgE levels. CONCLUSIONS: The prevalence of latex allergy among children admitted for inhalant or food allergy testing was 1%. Although multiple operations at an early age are a well-known risk factor for latex allergy, the majority of children with latex allergy identified at screening or admitted because of suspicion of latex allergy belonged to the group of children who had not undergone surgery. One third of all the children studied were free of symptoms, indicating that screening with SPTs can be a valuable tool for detecting occult latex allergy in children.

Reactivity of tixocortol pivalate-positive patients in intradermal and oral provocation tests.

Pivalone/tixocortol pivalate commonly yields positive reactions in the patch test series. The clinical relevance of these positive reactions was investigated in more detail. In the standard patch test series 5.6% (73 of 1306) of the patients were positive to corticosteroids, 5.2% to 0.1% tixocortol pivalate in ethanol (Pivalone nasal spray diluted 1:10) and 2.3% to 1% hydrocortisone butyrate in ethanol. Some of the patients were tested in parallel with Pivalone and 1% tixocortol pivalate in petrolatum. The former test reagent yielded some false-positive reactions, whereas with the latter, some allergic responses were missed. Intradermal tests with the succinate esters of hydrocortisone, methylprednisolone and prednisolone were performed with 52 patients positive to Pivalone. Of these 76.9% (40 of 52) were positive in the intradermal tests; 38 to hydrocortisone, 35 to methylprednisolone and 30 to prednisolone. Twelve patients who had been positive in the intradermal tests were challenged orally with corticosteroids and they all showed positive reactions to hydrocortisone, methylprednisolone or prednisolone. The patients developed localized reactions at the sites of previous eczema or positive skin tests or diffuse erythema or exanthema. The oral doses of hydrocortisone eliciting positive delayed skin reactions ranged from 20 to 200 mg. Reactivity to tixocortol pivalate is closely related to sensitivity to hydrocortisone, methylprednisolone and prednisolone, but high oral doses of these corticosteroids may be required to produce allergic symptoms.

Serum levels and urinary excretion of mequitazine after a single oral dose.

Pharmacokinetics of mequitazine, a recently introduced peripheral H1-histamine receptor antagonist of phenothiazine type, was followed up to 72 h after the single oral dose of 5 mg of the drug to eight fasted healthy volunteers. Each subject was treated thrice with a dosing interval of 15 days or more. Thus all the results were triplicated. Serum mequitazine was measured by mass fragmentography using a gas-liquid chromatograph/mass spectrometer set in the electron impact mode. Urine phenothiazines were determined fluorometrically before and after cleaving phenothiazines from their glucuronide conjugates. Peak concentration of mequitazine in serum was 3.19 +/- 1.70 (s.d.) ng.ml-1, time to peak concentration 5.67 +/- 1.68 h, elimination half-life 45 +/- 26 h, and elimination rate constant 0.018 +/- 0.007 h-1. Only 10.9 +/- 3.3% of the dose appeared in urine in unconjugated plus the glucuronidated form during the first 72 h. About 46% of the urinary phenothiazines were glucuronide conjugates. The results suggested that after the oral administration only low mequitazine concentrations appeared in serum, most of the drug seemed to be deactivated by the extrarenal route, and the kinetic properties of the drug resembled those of several phenothiazines used for psychiatric therapy.