Suspected allergy to local anaesthetics: follow-up in 135 cases.

BACKGROUND: Local anaesthetics (LA) are generally considered safe with respect to allergy. However, various clinical reactions steadily occur. Even though most reactions are manifestations of reflexes to perceptive stimuli, uncertainty often remains regarding a possible allergic mechanism. This uncertainty later leads to an avoidance of local anaesthesia and unnecessarily painful interventions, resource-consuming general anaesthesia or even the risk of re-exposure to other yet unidentified allergens. In the present study, follow-up procedures at an allergy clinic were analysed to examine the frequency of identified causative agents and pathogenetic mechanisms and evaluate the strength of the diagnostic conclusions. METHOD: The medical records of 135 cases with alleged allergic reactions to LA were reviewed. Diagnoses were based on case histories, skin tests, subcutaneous challenge tests and in vitro IgE analyses. RESULTS: Two events (1.5%) were diagnosed as hypersensitivity to LA, articaine-adrenaline and tetracaine-adrenaline, respectively. Ten reactions (7%) were diagnosed as IgE-mediated allergy to other substances including chlorhexidine, latex, triamcinolone and possibly hexaminolevulinate. As challenge testing was not consistently performed with the culprit LA compound, follow-ups were short of definitely refuting hypersensitivity in 61% of the cases. The reported clinical manifestations were in general diagnostically unspecific, but itch and generalised urticaria were most frequent in test-positive cases. CONCLUSION: Reactions during local anaesthesia are rarely found to be an IgE-mediated LA allergy. Whenever the clinical picture is compatible with allergy, other allergens should also be tested.

National pholcodine consumption and prevalence of IgE-sensitization: a multicentre study.

BACKGROUND: The aim of this study was to test, on a multinational level, the pholcodine (PHO) hypothesis, i.e. that the consumption of PHO-containing cough mixtures could cause higher prevalence of IgE antibodies to PHO, morphine (MOR) and suxamethonium (SUX). As a consequence the risk of anaphylaxis to neuromuscular blocking agents (NMBA) will be increased. METHODS: National PHO consumptions were derived from the United Nations International Narcotics Control Board (INCB) database. IgE and IgE antibodies to PHO, MOR, SUX and P-aminophenyl-phosphoryl choline (PAPPC) were measured in sera from atopic individuals, defined by a positive Phadiatop test (>0.35 kU(A)/l), collected in nine countries representing high and low PHO-consuming nations. RESULTS: There was a significant positive association between PHO consumption and prevalences of IgE-sensitization to PHO and MOR, but not to SUX and PAPPC, as calculated both by exposure group comparisons and linear regression analysis. The Netherlands and the USA, did not have PHO-containing drugs on the markets, although the former had a considerable PHO consumption. Both countries had high figures of IgE-sensitization. CONCLUSION: This international prevalence study lends additional support to the PHO hypothesis and, consequently, that continued use of drugs containing this substance should be seriously questioned. The results also indicate that other, yet unknown, substances may lead to IgE-sensitization towards NMBAs.

Prevalence of IgE antibodies to morphine. Relation to the high and low incidences of NMBA anaphylaxis in Norway and Sweden, respectively.

BACKGROUND: Anaphylactic reactions to a neuromuscular blocking agent (NMBA) is more than six times as common in Norway as in Sweden, probably due to differences in preoperative sensitization. The prevalence of IgE-sensitization to morphine (MOR) and suxamethonium (SUX) in comparable populations in Bergen, Norway, and Stockholm, Sweden, was studied and related to possible sensitizing agents. METHODS: Three hundred sera of 'allergics' and 500 blood donors in Bergen and Stockholm were tested for IgE antibodies to MOR and SUX using Pharmacia Diagnostics ImmunoCAP(Uppsala, Sweden) assay and the results compared to those of 65 patients from Bergen with documented anaphylaxis to NMBA. In addition, 84 different household chemicals were tested, by IgE antibody inhibition, for SUX and MOR. RESULTS: In Norway 0.4% of blood donors, 3.7% of allergics and 38.5% of anaphylactics were IgE-sensitized to SUX, and 5.0, 10.0 and 66.7%, respectively, to MOR. No serum from Sweden was positive. The majority of those sensitized (69%) were women. Several household chemicals contained SUX and/or MOR activity, but the only difference between Norway and Sweden was cough mixtures containing pholcodine (PHO). IgE antibodies to PHO were present in 6.0% of blood donors from Norway and in no serum from Sweden. Of the anaphylactics, 65-68% were sensitized to MOR or PHO but only 39% to SUX. CONCLUSIONS: IgE-sensitization to SUX, MOR and PHO was detected in Norway but not in Sweden. One possible explanation is the unrestricted use of cough mixtures containing MOR derivatives in Norway.

Screening for mast cell tryptase and serum IgE antibodies in 18 patients with anaphylactic shock during general anaesthesia.

BACKGROUND: In the perioperative setting multiple agents can cause anaphylaxis. Often the reactions are dramatic, and due to their lifethreatening potential it is crucial that the responsible agent is identified in order to avoid future adverse reactions. The aim of the present study was to measure the concentration of serum mast cell tryptase (MCT), to investigate the prevalence of serum IgE antibodies against ammonium groups, choline, morphine, suxamethonium, thiopentone and latex and to perform skin prick tests (SPTs) in 18 patients experiencing an anaphylactic reaction during induction of general anaesthesia. METHODS: Serum samples from 18 patients with an anaphylactic reaction during general anaesthesia were analyzed for MCT and specific IgE against ammonium groups, choline, morphine, suxamethonium, thiopentone and latex. Skin prick tests were performed in 11 out of 18 patients. RESULTS: Ten patients had elevated MCT levels and specific IgE against ammonium ion, morphine and (with the exception of patient nos 3, 9 and 10) suxamethonium. Seven of these patients had positive SPTs to suxamethonium. One of the patients tested positive to latex in addition to suxamethonium. Two patients showed elevated MCT, while specific IgE against the drugs tested was not detected. Three patients tested positive to ammonium ion, morphine and suxamethonium, but negative to MCT. Three patients tested negative to both MCT and specific IgE. CONCLUSIONS: Fifteen out of 18 sera tested positive for MCT and/or specific IgE against neuromuscular blocking drugs (NMBDs). Ten of the 18 patients experienced an IgE-mediated anaphylactic reaction to NMBDs during anaesthesia, verified by detection of specific IgE and elevated levels of MCT.

[What do health professionals ask RELIS Vest service and how satisfied are they with the answers?]. / Hva spør helsepersonell RELIS Vest om og hvor fornøyde er de med svarene?

RELIS Vest provides drug information by answering questions from mainly physicians and pharmacists. In the present paper we evaluated this service. All questions to RELIS Vest during the 1995-98 period were systematically categorized and analysed. The quality of the service was assessed by evaluation forms. Of a total of 875 queries, 393 came from physicians and 370 from pharmacists. 42% were about psychoactive drugs; the most frequent types of queries concerned documentation and adverse effects. Analysis of 180 evaluation forms showed that 79% of the physicians and 56% of the pharmacists found the answers fast enough, relevant, adequately comprehensive and with valuable references while 16% of the physicians and 29% of the pharmacists found that the answers satisfied three of these four criteria. We conclude that problem-oriented drug information based on actual cases of prescribing is highly appreciated.

Allergen content in dust from homes and schools in northern Norway in relation to sensitization and allergy symptoms in schoolchildren.

BACKGROUND: Previous studies have shown a high prevalence of atopic diseases among school children in the community of Sør-Varanger. Moreover, animal dander followed by pollen and house dust mite, were the most common allergens in skin prick tests. OBJECTIVE: To assess the allergen content in homes (living-rooms and mattresses) and classrooms of children living in an arctic area at 70 degrees. The presence of allergens in homes and schools and their relationship to atopy was of particular interest. METHODS: Dust samples from 38 homes and seven schools in northern Norway were collected by vacuum cleaning. The presence of allergens of dog, birch, timothy, Cladosporium herbarum, codfish and hen egg-white was investigated by radio-allergosorbent test (RAST) inhibition and the presence of major allergens of cat Felis domesticus (Fel d I) and house dust mites (HDM) Dermatophagoides pteronyssinus (Der p I) and Dermatophagoides farinae (Der f I) by enzyme-linked immunosorbent assay (ELISA). RESULTS: Mattresses contained significantly more dust per unit area than living-rooms and classrooms. No statistically significant differences in allergen content for dog, birch, timothy. Cladosporium, codfish and hen egg-white were seen between HDM-sensitized and non-atopic children. Most dust samples contained dog allergens with the highest allergenic activity found in living-rooms of those keeping dogs. An increased level of Fel d I was detected in only one of 38 samples from living-rooms (this family kept a cat) and in 25 of 38 samples from mattresses with ranges from 24 to 84 ng/m2. The highest concentrations were found in mattresses of children keeping cats. Increased levels (> or = 25 ng/m2) of Der p I were found only in homes and virtually only in mattresses of HDM-sensitized children. An increased level of Der f I was found in only one case, i.e. in the mattress of an HDM-sensitized child where additionally Der p I and HDMs were demonstrated microscopically. When relating Der p I to HDM-sensitization an odds ratio of more than 16 (95% CI: 1.6-394.3) was found. All extracts from living-rooms included codfish allergens. Low RAST inhibition values were detected for hen egg-white. Cladosporium, birch and timothy pollen in most samples. Furthermore, the study demonstrated that dust from schools was relatively free of allergens. CONCLUSION: Previous findings indicating that the main allergen exposure problem in this geographical area is that of pet allergens were confirmed.

Dust from carpeted and smooth floors. VI. Allergens in homes compared with those in schools in Norway.

The amounts of dust, protein, and allergens in vacuumed floor covering samples taken from both schools and homes in Norway have been investigated. Classrooms contained significantly more crude dust per unit area than homes, while the mean protein content per unit area was somewhat higher in homes. The main allergen exposure problem in classrooms was that of pet allergens; the contents of dog allergens and the major cat (Felis domesticus) allergen Fel d I per unit area were significantly higher in school classrooms than in homes of families who do not keep pets. The mite and food allergens, on the contrary, were more prevalent in homes. Carpeted floors in schools and homes contained significantly more dust, proteins, and allergens than smooth floors (P < 0.05). Fel d I was detected in the vacuum cleaners' filter system in concentrations from < 1 ng to 1080 ng, confirming that this allergen can pass through the dust bag during vacuuming.

[Indoor climate and allergy. The prevalence of allergens in Norwegian primary schools]. / Inneklima og allergi. Forekomsten av allergener i norske barneskoler.

We have investigated the prevalence of allergens from cat, dog, house dust mite, pollen, mould and food in dust samples from schools and homes in Norway. Occurrence of cat and dog allergens in schools was surprisingly high, especially in classrooms with carpeted floors. Cat and dog-derived allergens are brought into schools through the pupils' outside contact with pets. Children who are in contact with pets at home or in their surroundings carry animal hair and dander into the classrooms on their clothes, shoes and bags. The schools seemed to be a protective environment against mite infestation, as verified by very low content of mites in both carpeted and smooth floors. Furthermore, while cat and dog allergens were more prevalent in schools than in homes without pets, mite and food allergens were more dominant in homes. Frequent cleaning is important in schools, to prevent accumulation of animal hair and dander in the classrooms. We emphasize the obvious advantages of linoleum floors over carpets in decreasing the pupils' level of exposure to indoor allergens and dust.

Dust from carpeted and smooth floors. V. Cat (Fel d I) and mite (Der p I and Der f I) allergen levels in school dust. Demonstration of the basophil histamine release induced by dust from classrooms.

Sixty dust samples from schools in Norway were analysed for major allergens from cat and mite after sampling with the regularly used vacuum cleaners for 5 days and with a new model vacuum cleaner for 10 days, respectively. The major feline allergen Felis domesticus allergen I (Fel d I) was detected in all the classrooms, with ranges from 12 to 16,840 ng/m2 floor area. The mean Fel d I concentration was about 11 times higher per unit area carpeted floors as compared with smooth floors after the 10 days sampling period. Mite allergens Dermatophagoides pteronyssinus allergen I (Der p I) and Dermatophagoides farinae allergen I (Der f I) were detected in very low concentrations, with ranges from < 1 ng to 104 ng/m2 floor area. These findings suggest that the school is a protective environment against mite infestation, while the prevalence of cat allergens in classrooms seems higher than previously assumed. Basophil histamine release was measured after provocation with 20 dust extracts from 10 different schools. In nine of the 10 schools examined, the basophil histamine release caused by challenge with carpet dust was higher than the corresponding release with smooth floor dust. The calculated floor areas in each school in which dust led to 15% histamine release were from 2 to 55 times larger for smooth floors compared with carpeted floors. These results emphasize previous findings regarding higher allergen concentrations in classrooms with carpeted floors.

Dust from carpeted and smooth floors. IV. Solid material, proteins and allergens collected in the different filter stages of vacuum cleaners after ten days of use in schools.

The accumulation of dust, proteins and allergens from alder, birch, timothy, cat, dog, mite, hen egg white, codfish and mould in schools was investigated by analysing the content of vacuum cleaners after 10 days of use. The main goals were to compare the dust accumulation on carpeted and smooth floors and to estimate to what degree the three vacuum cleaner filter stages (i.e. the disposable bag, the main filter and the microfilter) collected dust, proteins and allergens. Carpeted floors accumulated more dust, proteins and allergens per unit area than smooth floors. Histamine release studies of some of the dust extracts showed that the dust from carpeted floors released histamine from passively sensitized basophils at concentrations for which dust from smooth floors gave low or no histamine release. The analyses showed that most of the dust, proteins and allergens were retained in the dust bags. Less than 1% of the vacuumed material had accumulated in the main filters, which, according to the manufacturer, detain 99.5% of particles greater than 2 microns. By the use of a scanning electron microscope (SEM), particle deposits were observed in the microfilters. These deposits, which represented less than 0.1% of the total mass, showed no significant allergenic activity. Thus, for the field conditions of this study, the microfilters were not needed for cleaning the exit air of allergens, although they were useful for removing fine (less than 2 microns) particles.

The structural requirements of epitopes with IgE binding capacity demonstrated by three major allergens from fish, egg and tree pollen.

Three major allergens from cod fish, egg white and tree pollen, were characterized by studies on their allergenic and antigenic structures. The major allergen of cod fish, Allergen M "parvalbumins pI 4.75", is composed of 113 amino acid residues with a molecular weight of 12,328 daltons. It comprised three domains, AB, CD and EF, consisting of 3 helices interspaced by one loop. Each of the loops of the CD and EF domains each coordinates one Ca2+. The antigenicity and allergenicity of Allergen M was deduced from studying the modified protein and some particular synthetic peptides. Three sites were encompassing IgE binding epitopes namely peptides 33-44, 65-74 and 88-96. A novel peptide (49-64), of the CD-domain, was demonstrated to be allergenically/antigenically active and cross reactive with birch pollen allergen, which incidentally was used as a negative control. This site encompassed two repetitive sequences (D-E-D-K) and (D-E-L-K), suggested to be mutually critical for the specificity of antibody binding. This hypothesis was reconfirmed by SPPS of several analogous peptides of region 39-64. Furthermore, peptide 88-103 of the EF-domain was similarly synthesized; it functioned as a monovalent hapten, blocking and not eliciting allergic reaction. Moreover, peptide 13-32 of domain AB, the non-calcium binding domain, was thoroughly tested. The results of PK inhibition showed clear activity and the peptide was found to function at the level of a divalent determinant. Ovalbumin (OA) is the most dominant of five major allergens of egg white and universally used as model protein. OA allergenic epitopes were shown to be mainly determined by the primary structure and depend on certain peptide chain length. The N-terminal decapeptide (OA 1-10) was shown to react with reaginic IgE. Direct skin test on egg allergic patients, showed no activity and the site was therefore concluded to encompasses one single Ig binding haptenic epitope. Peptide OA 323-339, was demonstrated to be valuable in studies of T-cell recognition of protein antigens. Three analogous peptides of this region were prepared and clearly shown to be immunogenic in rabbits and to bind specific IgE from patients allergic to egg. OA 323-339 was concluded to encompass an allergenic and antigenic epitope which was recognized by human and rabbit B-lymphocytes. Eight peptides in the region 11-122 were similarly synthesized. A test battery was performed to study this region using rabbit polyclonal antibodies and human specific IgE. Some of these sites were involved in binding of particular Ig paratopes. Five immunogenic peptides from the major allergens of tree pollen extracts (segment 23-38), were synthesized. The selection of those peptides was setteled using two algorithms for providing the optimal hydrophobicity.(ABSTRACT TRUNCATED AT 400 WORDS)

Dust from carpeted and smooth floors--III. Trials on denaturation of allergenic proteins by household cleaning solutions and chemical detergents.

The effects of detergents on antigens and allergens of birch and timothy grass pollen extracts, codfish, hen egg-white, cat dander and house dust mite were investigated by crossed immunoelectrophoresis (CIE), crossed radio-immunoelectrophoresis (CRIE), radio-allergosorbent test (RAST) inhibition and quantitative precipitation test using laser nephelometry. Nine household cleaning solutions and five chemical detergents were tested. Higher concentrations than recommended for regular cleaning purposes were used as no influence on the antigenic and allergenic activities could be detected using the usual concentrations. Soft soap, guanidine hydrochloride and sodium lauryl sulphate induced most modifications of the antigens and allergens tested. None of the detergents totally destroyed the antigenic and allergenic activities of the selected material, even when used in concentrations up to 10 times that recommended. The materials used for carpet cleaning would not be able to impose any denaturing effects on allergens left on carpets after cleaning.

Dust from carpeted and smooth floors. II. Antigenic and allergenic content of dust vacuumed from carpeted and smooth floors in schools under routine cleaning schedules.

Dust samples were collected twice from smooth and carpeted floors in 10 Norwegian schools. The content of antigens and allergens of alder (Alnus incana), birch (Betula verrucosa), timothy (Phleum pratense), cat and dog dander, house dust mite (Dermatophagoides farinae), mould (Cladosporium herbarum), hen egg white and codfish (DIII) were investigated by crossed immunoelectrophoresis (CIE), crossed radio immunoelectrophoresis (CRIE), radio allergosorbent test (RAST) inhibition and quantitative precipitation inhibition analysis by laser nephelometry. Antigens and allergens of cat and dog dander and hen egg white were most prevalent in the dust samples investigated. With the exception of hen egg white and codfish allergens, no statistically significant differences in mean allergen content were shown in identical quantities of freeze-dried dust extracts from carpeted and smooth floors. RAST-inhibition analyses of identical amounts of dust from either floors showed higher content of allergens of cat, dog, hen egg white, codfish, mould and timothy pollen in classrooms with carpets.

Dust from carpeted and smooth floors. I. Comparative measurements of antigenic and allergenic proteins in dust vacuumed from carpeted and non-carpeted classrooms in Norwegian schools.

Dust samples from fitted-carpets and linoleum floors in 12 schools in Norway were collected by vacuum cleaning. The presence of antigens and allergens of alder (Alnus incana), birch (Betula verrucosa), timothy (Phleum pratense), mould (Cladosporium herbarum), house dust mite (Dermatophagoides farinae), cat and dog dander, codfish, hen egg white and human dander were investigated by crossed immunoelectrophoresis (CIE), crossed radio-immunoelectrophoresis (CRIE) and radio-allergosorbent test (RAST) inhibition. No qualitative differences in allergen contents of dust from both types of floor tested were noted. Similarly, no relationship could be demonstrated between floor-type and allergen concentration under identical experimental conditions. Antigens and allergens of both cat and dog were frequently demonstrated in dust extracts. All extracts included human dander and mould allergens. In addition, most dust samples from both carpeted and smooth floors contained hen egg white and codfish allergens. Furthermore, the study demonstrated that dust from smooth floors and fitted-carpets was relatively free of mite and pollen from alder, birch and timothy.

Reestimations of the protein concentrations of birch pollen allergen extracts selected as candidates for the international standard (IS) preparation.

The total protein concentrations of six selected candidates for an international standard (IS) of birch pollen were previously estimated (Ann Allergy 1987;58:71-77). The results of analyses showed large variations depending both on the method and the reference protein used. More than 2-fold variations in the protein content were obtained using Bradford's protein binding method. In the present communication the protein contents of these birch IS-candidates were reestimated by Lowry, a modified Lowry technique, Bradford's protein-dye binding, bicinchoninic acid reagent and amino acid compositions. Great variations were obtained for the protein contents, depending on the technique employed, emphasizing the difficulties of choosing a proper method of protein analyses of pollen allergens. The Lowry and the bicinchoninic acid reagent methods gave the highest obtained protein estimates, while the modified Lowry and Bradford's protein-dye binding methods showed the lowest values. The amino acid analysis gave concentrations similar to those obtained by Lowry and bicinchoninic acid reagent methods. The Lowry method seemed to be adequate for the analysis of plant proteins. The amino acid analysis is currently the most precise method for estimation of the protein concentration irrespective of additional prosthetic groups. A serious shortcoming of the method is that it requires an amino acid analyser or other liquid chromatrographic systems, which are not commonly in laboratory use.

Synthetic allergenic epitopes from the amino-terminal regions of the major allergens of hazel and birch pollen.

Five immunogenic peptides from the major allergens of tree pollen extracts (residues 23-38) were synthesized by Merrifield solid-phase peptide synthesis. The primary structures of these peptides were deduced from the known N-terminal amino acid sequence of the major allergen of hazel, HIa, and birch, Bet v I. In a segment of 16 amino acids (23-38), 2 residues were the difference between birch and hazel. The selection of the peptides was on the basis of optimal hydropathicity. The segment 29-34 of these peptides was predicted to prefer a helical rather than beta-sheet conformational state. The insertion of amino acid residues during the synthesis was confirmed by the analysis of amino acid composition prior to coupling the preceding residue. The linearities of the synthetic chains were assigned by the primary structure analysis of the entire chain by automatic Edman degradation. The synthetic peptides were purified by gel filtration chromatography and reversed-phase high-performance liquid chromatography, resulting in satisfactory homogeneity of the preparations. The immunogenicity of the peptides was tested in rabbits using conjugated peptide-bovine serum albumin through a carbodiimide spacer arm. The results indicated that all constituents of the conjugate could elicit an immune response. The peptides gave precipitation lines in crossed immunoelectrophoresis when using rabbit antibodies against the conjugated preparation. All the synthetic peptides and analogues from region 23-38 could inhibit, in dose-response patterns, the binding of specific IgE to the intact molecules. Similar results were shown for the shorter segment 25-34, suggesting that the C-terminal tetrapeptide did not contribute to the activity.(ABSTRACT TRUNCATED AT 250 WORDS)