(Diagnosis, Diagnostics, Immunodiagnosis, Immunodiagnostics, Pathogenesis, Vaccines & Drugs)



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1132. Birmingham PK.  Suresh S.Latex allergy in children: diagnosis and management.

Indian Journal of Pediatrics.  66(5):717-24, 1999 Sep-Oct.



  Latex allergy is an increasingly common condition, in both children and   health care workers who provide care for them. Subpopulations at   particular risk include children with spina bifida, children undergoing   multiple surgical procedures, and health care workers in the operating   theatre. Chemical additives in latex gloves can cause an irritant or   allergic contact dermatitis. Latex proteins are responsible for most of   the immediate IgE-mediated hypersensitivity allergic reactions. Symptoms   range from rhinitis, conjunctivitis and urticaria to anaphylaxis and   death. A latex-directed history is the primary method of identifying latex   sensitivity, although both skin and serum testing is available and   increasingly accurate. (Latex avoidance should be used in all individuals   with a positive skin or blood test or a positive history). The most   important preventive measure for patients with or at risk for latex   allergy is minimizing direct patient exposure to latex products, most   notably latex gloves. Recent operating room studies indicate simple   preventive measures can dramatically reduce intraoperative reactions.   Preoperative prophylaxis with antihistamines and steroids have not been shown to be necessary or effective. Treatment of an allergic reaction   begins with immediate removal of any identified source of latex in direct   patient contact. Treatment is similar to anaphylaxis from other causes, and may require the use of epinephrine. Everyone caring for the patient at risk for latex allergy must be involved in making their medical environment safe.


1133. Blumenthal MN. Genetics of asthma and allergy. Allergy & Asthma Proceedings.  21(1):55-9, 2000 Jan-Feb.



 Asthma and allergies are complex conditions involving multiple steps and pathways, which are influenced by both genetic and environmental factors.  The genes involved in these processes are just being identified. Most  likely asthma is a result of several genes and their interaction with other genes as well as the environment. Management involves the proper diagnosis, modulating the genetic and environmental factors involved as well as interfering with the activated pathways. Using this approach will lead to a more rational method of managing individuals with allergies and asthma.


1134. No Abstract

1135. Furuichi H.  Yamashita K.  Okada M.  Toyoshima T.  Hata Y.  Suzuki S. Itano T.  Shishibori T.  Tokumitsu H.  Kobayashi R.

Identification of tranilast-binding protein as 36-kDa microfibril-associated glycoprotein by drug affinity chromatography, and its localization in human skin. Biochemical & Biophysical Research Communications.  270(3):1002-8, 2000   Apr 21.



To elucidate the molecular mechanism involved in the suppression of keloids and hypertrophic scars by tranilast, we investigated the target protein of tranilast in bovine skin and aorta. A specific tranilast-binding protein was isolated from both tissues by drug affinity chromatography and was identified as 36-kDa microfibril-associated glycoprotein (36-kDa MAGP). Binding of 36-kDa MAGP to tranilast seemed to be specific since 36-kDa MAGP could be eluted from the drug affinity column by tranilast itself and also binding of 36-kDa MAGP to other  anti-allergy drugs (amlexanox and cromolyn) is significantly weaker than that to tranilast. Light and electron microscopic immunohistochemistry detected the protein at the periphery of elastic fibers in normal human skin. In hypertrophic scar tissue, however, 36-kDa MAGP was located on small bundles of microfibrils. These findings provide support for the concept that elastogenesis occurs in scar tissue and 36-kDa MAGP might be one of the targets for tranilast. Copyright 2000 Academic Press.



1136. Graft DF. Venom immunotherapy: when to start, when to stop.

Allergy & Asthma Proceedings.  21(2):113-6, 2000 Mar-Apr.



Over the past 25 years, major advances have been made in the diagnosis and   treatment of insect sting allergy. Controlled clinical trials have   demonstrated the efficacy of venom immunotherapy (VIT) in the prevention of subsequent systemic reactions in allergic individuals. We have refined our criteria for selection of patients for VIT. Studies on selections of venoms, rush immunotherapy, and interval between VIT injections have been performed. Finally, much work has been done to try to define criteria for the discontinuation of VIT.


1137. Gruchalla RS. Approach to the patient with multiple antibiotic sensitivities.  Allergy & Asthma Proceedings.  21(1):39-44, 2000 Jan-Feb.



Allergists sometimes are asked to evaluate patients who have experienced   multiple adverse drug reactions. By the time the patient reaches the   allergist, the referring physician, as well as the patient, often are   frustrated. Each seeks a quick and simple answer regarding the particular   drugs the patient may safely receive. Unfortunately, however, in most  instances, simple answers cannot be given. Currently we have limited  knowledge of the mechanisms and of the clinically-relevant drug  metabolites responsible for many of the reactions demonstrated and, for  these reasons, we have few valid diagnostic tests that are able to provide  clear-cut answers for our patients who present with multiple drug  "allergies." Despite these limitations, using accurate and complete  historical information along with limited diagnostic testing, logical and   practical management approaches can be devised. In addition, due to new   exciting data that are being generated from basic research studies in drug allergy, the mechanisms underlying the immunopathology of many drug reactions are becoming more clear. Through the acquisition of scientific information of this type, it is hoped that valid diagnostic tools soon will be developed so that definitive answers, desired by both the patient and the referring physician, can be provided.



1138. Jarzab J.  Gawlik R. Immune complexes IgE/IgG in airborne allergy: increase during pollen season. Journal of Investigational Allergology & Clinical Immunology.  10(1):24-9,   2000 Jan-Feb.



In the present study we addressed the question of IgE/IgG immune complex serum level in 92 patients with respiratory allergy in relation to their clinical status. Twenty patients with allergy to insect stings and 22  healthy volunteers were also investigated. IgE/IgG immune complexes and IgG anti-IgE antibodies were estimated using double antibody solid-phase immunoassays in IgG serum fractions isolated by protein A affinity chromatography or in fractions obtained by Sephacryl S-300 gel filtration. Three people (14%) from the control group, two patients (10%) with insect allergy and 41 patients (45%) from the group with airborne allergy exhibited an increased serum level of IgE/IgG immune complexes (chi2, p<0.05). IgG anti-IgE serum level was also significantly higher in the   examined group of patients with airborne allergy than in the control group. None of the factors analyzed, including the kind of allergic disease, the type of inhalant allergen (pollen or house dust antigens), the severity of allergy judged from the frequency and intensity of symptoms for 1 year preceding blood sampling and the symptoms exhibited during blood sampling, showed a statistically significant relation to the level of IgE/IgG immune complexes or IgG anti-IgE, when the whole group of patients with respiratory allergy was analyzed. A distinct difference between patients investigated during and outside of the pollen season was found in patients with isolated pollen allergy. The latter exhibited an increase of IgE/IgG immune complexes (57% vs. 29%) significantly more often, which indicates the possible involvement of IgE/IgG immune complexes in the pathogenesis of pollen allergy.


1139. Jeske AH. COX-2 inhibitors and dental pain control.

Journal of the Greater Houston Dental Society.  71(4):39-40, 1999 Nov.



Celecoxib (CELEBREX) and rofecoxib (VIOXX) appear to offer the following  advantages: reduced incidence of gastric ulceration during long-term  administration; little or no effect on platelet aggregation; longer  clinical duration of action than aspirin, acetaminophen and ibuprofen.  However, in the context of the management of dental pain and inflammation,  the following points and disadvantages should be considered: no greater  effectiveness than conventional NSAIDs (e.g., ibuprofen) for dental pain;  greater cost than conventional NSAIDs (especially those available in generic forms); not available over-the-counter; possible inadequate duration of action for postoperative dental pain (see references 6 and 7); similar contraindications and drug interactions to less expensive, equally effective conventional non-selective NSAIDs. At this time, celebrex and rofecoxib cannot be recommended over conventional, non-selective NSAIDs as first-choice drugs for pain and inflammation in dentistry. Practitioners are cautioned against selecting any new drug based on "clinical trials of one", in which both the dentist and the patient know the drug being prescribed, (as opposed to double-blind studies), usually in the context of considerable "hype" about the drug (based on comments about the fact that the agent being tried is "new") and strong placebo reinforcement based on the dentist's enthusiasm for the new product, which does not usually accompany the prescription of older, routinely prescribed drugs.  Finally, such "clinical trials of one" invariably involve close follow-up about the outcome of the treatment, which is usually not done with more common, older drugs, and which only introduces further bias into the interpretation of the effectiveness of the drug by both the patient and the dentist. Anaglesic drugs should be selected on the basis of controlled, double-blind, randomized clinical trials which utilize a  reasonable, dentally-related pain model. The older NSAIDs, such as  ibuprofen, naproxen, diflunisal and others, remain first-choice drugs for the treatment of mild-to-moderate pain in dentistry in patients lacking the contraindications for such drugs. As proposed by this author several  years ago, the major contraindications to NSAIDs can be remembered by the   "SAAB Rule", an acronym which stands for "Stomach problems", Aspirin Allergy" and "Bleeding problems", in addition to pregnancy and  hepatic/renal disease.




1140. Little SA.  Longbottom JL.  Warner JO. Optimized preparation of Aspergillus fumigatus extracts for allergy diagnosis. Clinical & Experimental Allergy.  23(10):835-42, 1993 Oct.



Extracts of Aspergillus fumigatus are required for the measurement of specific antibodies that are important indices in the diagnosis of allergic bronchopulmonary aspergillosis (ABPA). This study investigated the effect of different culture conditions on the production and release of antigenic and allergenic proteins of A. fumigatus. Increasing the incubation temperature from 25 degrees C to 37 degrees C altered the production of proteins by the mycelium which resulted in the release of a greater number of proteins that reacted with precipitating antibodies. Static sporulating cultures produced a much wider antigenic spectrum than shake cultures although the number of precipitating proteins (5 and 3 respectively) and major IgE binding proteins (5 and 3 respectively) was not greatly altered. The widest range of proteins bound by precipitating antibody or IgE from ABPA serum were released into the culture filtrate during 28 day static incubation at 37 degrees C. The resultant extract  proved useful for screening patients for specific IgE and will provide a  starting material for the identification of individual antigens or  allergens.



1141. Masuda K.  Sakaguchi M.  Fujiwara S.  Kurata K.  Yamashita K.  Odagiri T.  Nakao Y.  Matsuki N.  Ono K.  Watari T.  Hasegawa A.  Tsujimoto H. Positive reactions to common allergens in 42 atopic dogs in Japan. Veterinary Immunology & Immunopathology.  73(2):193-204, 2000 Feb 25.




Clinically important allergens for the diagnosis and treatment of atopic  dermatitis vary geographically. In order to identify the most prevalent  allergens in atopic dogs in Japan, 42 dogs with a clinical diagnosis of  atopy were tested using both in vivo (intradermal skin test (IDST)) and in  vitro (antigen-specific IgE assay) allergy tests. Allergens used for IDST  included 26 allergen extracts from eight allergen groups: trees, weeds, grasses, house dust mites (HDM), molds, foods, epithelia, and arthropods. Immunodot assay was used to measure antigen-specific IgE against 24  allergens from these eight groups and against fish such as cod and sole.  In the 42 dogs, the most common positive allergen reaction was to HDM on both IDST (29/42 dogs or 69%) and in vitro testing (23/42 or 54.8%). The second most frequent positive allergen reaction was to Japanese cedar pollen (21/42 or 50.0% for IDST and 7/42 or 16.7% for in vitro testing). In both tests, less than 20% of dogs had positive reactions to molds or foods. Positive reactions to cat epithelia were frequently found on IDST, but rarely found on in vitro testing. Agreement between the two tests was  found in 26 instances: HDM (21 dogs), Japanese cedar pollen (five dogs) and wheat (one dog). In this study, the two most common allergens involved in atopic dermatitis in dogs in Japan were HDM and Japanese cedar pollen.


1142. Nja F.  Roksund OD.  Svidal B.  Nystad W.  Carlsen KH. Asthma and allergy among schoolchildren in a mountainous, dry, non-polluted area in Norway.Pediatric Allergy & Immunology.  11(1):40-8, 2000 Feb.




The aim of this study was to assess prevalence of asthma and allergy in the non-polluted mountain area of Upper Hallingdal, Norway. All schoolchildren (7-16 years) who in a previous questionnaire survey (n = 1177) reported 'sometime' asthma were enrolled in group I (n = 80), the 59 who reported asthma-like symptoms in the past 12 months formed group II, and 77 of the healthy controls were randomly selected as group III. All 216 children underwent clinical examination, skin prick test, spirometry, bronchial provocation (PD20 metacholine) and treadmill exercise test. Subsequently they were reclassified as (1) healthy, never had asthma or symptoms, (2) symptoms not confirmed as asthma, (3) previous asthma, now healthy, (4) current asthma. Lifetime asthma prevalence was 10.2%. Based upon clinical examination, the specificity and sensitivity of the questionnaire for asthma diagnosis were 88 and 74%, respectively. Forced  vital capacity was significantly higher among the asthmatics (group 4 versus 1), whereas forced expiratory volume in one second (FEV1) and forced expiratory flow at 50% of vital capacity were similar in all groups. More than 10% reduction in FEV1 following treadmill-run was found in 20% of children. Children with current asthma compared to controls had significantly; lower mean values of PD20 (9.1 versus 16.5 micromol), higher eosinophil cationic protein (13.4 versus 7.7 micromol) and more frequent sensitization to animal dander (56% versus 10%). In conclusion, despite a favorable climate, little mite sensitization and low outdoor pollution, asthma prevalence was surprisingly high in Upper Hallingdal.  Sensitization to animal dander was the most important contributing factor for current asthma.


1143. Paramesh H. Practical approach to recurrent respiratory infections. Indian Journal of Pediatrics.  63(2):181-7, 1996 Mar-Apr.



Respiratory diseases are a major cause of morbidity and mortality in developing countries. Recurrent respiratory infections in children pose a great challenge to the pediatrician where he has to exercise his clinical acumen and methodical approach for correct diagnosis and treatment. It is a fact that children should suffer 7 to 8 upper respiratory infections per year until they are 5 years of age when their immune status reaches adult level. In this situation, it is essential to find out whether the frequencies are abnormal. Whenever a child has the following problems, then only it needs to be investigated.--(a) repeated bacterial pneumonias;(b) a child less than 3 months old having repeated respiratory infections;(c) a child of 9 months old without a history of exposure infections; (d) infections complicating into bronchiectasis and; (e) in a child where there is no history of allergy or asthma. Once the problem is established  as a true recurrent respiratory infection, the clinician should pose questions--whether it is chronic, acute or recurrent, to find out the site of pathology, seriousness of the problem, response to previous medications, to establish the possible diagnosis which fall into six categories--congenital anamolies, aspiration syndrome, genital disorders, immunological diseases, immune deficiency disorders and allergic diseases. The author discusses quoting some examples for various categories avoiding non pulmonary causes for recurrent respiratory infections in children.


1144. Pascual CY.  Crespo JF.  Perez PG.  Esteban MM.Food allergy and intolerance in children and adolescents, an update. European Journal of Clinical Nutrition.  54 Suppl 1:S75-8, 2000 Mar.



Epidemiological surveys demonstrate that rapid increase in allergic diseases is a real phenomenon. In developed countries they are about the commonest chronic diseases, reaching between 15% and 30% of the population. Adverse reaction to food can be divided into toxic reaction and non-toxic reactions. The non-toxic reactions are divided into non-immune mediated and immune mediated, these are considered food allergic reactions. We showed our experience in a 4 y survey,  individualized by food allergens during the first two years of life. In Spain egg white protein is the most common allergen followed by cow's milk and peanuts. These three food items represent half of the sensitizations in children under 2 y of age. After 4 y sensitivities to vegetable allergens such as nuts, fruits and legumes are most frequent. The diagnosis of food allergy is still problematic, even in the case of atopy or IgE mediated hypersensitivity. There is a lack of standardized diagnostic procedures; the only test accepted as 'gold standard' for confirmation of food allergy and in general for food intolerance, is a properly performed double blind placebo-controlled oral food challenge.  Negative results should be always followed by an open food challenge. This   test should only be conducted in patients with a good medical condition  and in a clinic or hospital setting, and only if trained personal and equipment for treating systemic anaphylaxis are present. Contraindications to a challenge test are limited to those situations that can be hazardous for the patient in relationship to the studied food. The treatment of food allergy and intolerance is avoiding the implicated food as long as necessary, until tolerance appears. Prevention of food allergy is the first goal of every pediatric allergologist. Controlled trials of food allergy prevention have been performed only in high allergic risk children.


1145. Punnonen J. Molecular breeding of allergy vaccines and antiallergic cytokines.

International Archives of Allergy & Immunology.  121(3):173-82, 2000 Mar.



Molecular breeding, also called DNA shuffling, is a technology that enables the generation of large libraries of novel genes and vectors, from which improved variants can be selected based on functional properties. In a common format, it involves recursive recombination and mutation, performed by random fragmentation of related DNA sequences, followed by reassembly of the fragments in a self-priming polymerase chain reaction. As in natural evolution, the technique takes advantage of crossovers, deletions, insertions, inversions and point mutations of genes to generate large pools of related sequences. Molecular breeding can be used to generate improved variants of proteins used as therapeutics, such as  vaccine antigens, growth factors and immunomodulatory molecules. Moreover, the technology can be applied to evolve entire viruses or vectors, including DNA vaccines. Cytokines downregulating allergic immune responses and allergens are attractive targets for evolution by molecular breeding. This review describes approaches to generate chimeric allergens with T cell epitopes from multiple allergen homologues, while reducing the recognition by preexisting IgE. In addition, the results and applications of molecular breeding in the evolution of improved antiallergic cytokines are discussed. Copyright 2000 S. Karger AG, Basel



1146. Spaite DW.  Karriker KJ.  Seng M.  Conroy C.  Battaglia N. Tibbitts M. Salik RM.

Training paramedics: emergency care for children with special health care   needs. Prehospital Emergency Care.  4(2):178-85, 2000 Apr-Jun.



OBJECTIVE: To enhance knowledge and comfort related to the emergency care  of children with special health care needs (CSHCN) through an innovative  continuing education program for paramedics. METHODS: A self-study program  presenting in-depth information about common problems that affect the  assessment and management of a child's airway, breathing, circulation,  disability, and environment (ABCDEs), regardless of the child's diagnosis,  was developed. This program used a manual, a video, practice mannequins,  and skills evaluations to teach skills to paramedics employed at a  municipal fire department. RESULTS: Pre- and posttraining surveys found  that the paramedics were significantly more comfortable with the  assessment and management of CSHCN after the completion of the self-study  program, with a pretraining average of 2.83 and posttraining average of  4.20 on a five-point Likert-type scale, t(37) = 12.87, p < 0.001. A skills  evaluation showed that skills performance varied widely across 21 skills,  ranging from skills mastery to low skills knowledge. On the posttraining  survey, between 74% and 94% of the paramedics rated each topic (tracheostomies, indwelling central venous catheters, cerebrospinal fluid  shunts, gastrostomies, child abuse, and latex allergy) as applicable to their practices as paramedics. CONCLUSION: Given the growing population of CSHCN, it is important to provide specialized education to increase an EMS provider's preparedness to respond to emergency situations involving children with special health care needs.



1147. Tokunaga T.  Yamamoto T.  Yamamoto S. How BCG led to the discovery of immunostimulatory DNA. Japanese Journal of Infectious Diseases.  52(1):1-11, 1999 Feb.



The concept of immunostimulatory DNA was borne in a long series of studies on BCG-mediated tumor resistance. DNA purified from BCG inhibited the growth of various syngeneic animal tumors, augmented NK cell activity and induced IFN-alpha/beta and -gamma from mouse spleen cells and human PBL. Extending the lines of study, we found two biologically remarkable facts that (i) DNAs from invertebrates, but not from vertebrates and plants, showed the above-mentioned biologic activities, and (ii) the activities were completely dependent on particular base sequences having CpG motifs but in a senseless manner. Details of those early studies carried out mainly in the 1980's have been reviewed in the first part of this paper. In the middle part of this review, the results of toxicity and pharmacology studies and clinical trials of BCG- DNA, performed by other groups in Japan in the late 1980's, were introduced. Since a large amount  of DNA had never been administered repeatedly into experimental animals or  human, those experiences obtained seem to be worthwhile to introduce. Research interests of immunostimulatory DNA were galvanized in 1995 by the report of Krieg et al. showing murine B cell activation with bacterial DNA containing CpG motifs. Within a short period of time, a huge number of papers have been published in this field, and the study has expanded rapidly and largely. Now, it includes a number of research fields, for example, host-defense mechanisms against infection, allergy, autoimmune diseases, cytokine networks, plasmid vaccination, and therapeutic application of certain diseases. This paper reviewed briefly recent advances of immunostimulatory DNA research. The response of higher animals against immunostimulatory DNA must be the most primitive but important mechanism for self-nonself discrimination against foreign DNA. By  utilizing immunostimulatory DNA or controlling this primitive response, it  seems possible to offer many beneficial means to human health. For instance, more potent peptide- or plasmid- vaccines could be developed by the use of immunostimulatory DNA. On the other hand, many study results suggest that immunostimulatory DNA works either beneficially or harmfully for the hosts. We assume that further extensive and careful studies are  required.



1148. Yeang HY. Prevalence of latex allergy may be vastly overestimated when determined by in vitro assays. Annals of Allergy, Asthma, & Immunology.  84(6):628-32, 2000 Jun.



GROUND: The prevalence of latex-specific IgE computed from the results of serologic assays is commonly thought to reflect, to a greater or lesser extent, the prevalence of latex allergy and its implied risk. OBJECTIVE: The study examines how imperfect test specificity of in vitro assays influences the precision of latex allergy prevalence that it estimates. METHODS: Various models encompassing a range of hypothetical test sensitivity and specificity values are investigated to gauge their influence on the estimate of latex allergy prevalence. The models examine these interactions in situations of high or low allergy prevalence. RESULTS: Serologic latex diagnostic assays with test specificity within the range of those of commercially available assays can greatly overestimate prevalence where the true prevalence is low (eg, of the order of one in 100 or one in 1,000). A formula to correct for errors in  prevalence estimates arising from imperfect test sensitivity and specificity of an in vitro assay is presented. CONCLUSION: While serologic assays for latex IgE pose few hazards to the patient and are useful for confirming the diagnosis of latex allergy, the test results may vastly overestimate the true prevalence of latex allergy and its associated risks in situations where latex allergy is actually rare.



1539. Akdis CA.  Blaser K. Regulation of specific immune responses by chemical and structural modifications of allergens. [Review] [103 refs] International Archives of Allergy & Immunology.  121(4):261-9, 2000 Apr.


Specific immunotherapy (SIT) is an efficient treatment of allergic diseases to defined allergens. Despite being used in clinical practice since early in this century, more rational and safer regimens are required, because SIT is faced with the risk of anaphylaxis and standardization problems of allergen-extract-based treatments. A better understanding of the pathogenesis of allergy and of the mechanisms of SIT has led to various approaches to overcome these problems. Knowledge of the influence of IgE-facilitated antigen presentation on allergen-specific Th2 responses increased the efforts to generate non-IgE-binding allergens. The current principal approach to allergen modification is to modify B cell epitopes in order to prevent IgE binding and effector cell cross-linking   while preserving T cell epitopes to retain the capacity of inducing tolerance. In this way, the modified allergen will be directed to T cells by a phagocytosis/pinocytosis-mediated antigen uptake mechanism, bypassing IgE cross-linking and IgE-dependent antigen presentation. Accordingly, a differential regulation of allergen-specific T cell cytokine patterns and IgE:IgG production was demonstrated by modifications of the three-dimensional structure of allergens because of linearity in T cell epitopes and conformation dependence in B cell epitopes. In this context, chemically modified allergen extracts with low IgE-binding capacity have been developed to reduce anaphylactic side effects since the early 1980s. The progress of recombinant techniques for producing allergens and  allergen derivatives has led to a dramatic improvement in the ability of  developing novel vaccines for the treatment of allergy. This has enabled mutation or deletion of decisive amino acids in B cell epitopes and fractionation or oligomerization of allergens by genetic engineering as fruitful approaches to generate hypoallergenic vaccines. Moreover, non-IgE-binding short T cell epitope peptides and single-amino-acid-altered peptide ligands represent potential candidates for future SIT. Copyright 2000 S. Karger AG, Basel


1540. Ballmer-Weber BK.  Vieths S.  Luttkopf D.  Heuschmann P.  Wuthrich B. Celery allergy confirmed by double-blind, placebo-controlled food challenge: a clinical study in 32 subjects with a history of adverse reactions to celery root. Journal of Allergy & Clinical Immunology.  106(2):373-8, 2000 Aug.


  GROUND: Celery root is a frequent cause of food allergy in pollen-sensitized patients. Because of problems in blinding challenges with fresh vegetables and the risk of anaphylactic reactions, no double-blind, placebo-controlled, food challenges (DBPCFCs) with celery have been published so far. OBJECTIVE: The aim of the study was to confirm the clinical relevance of celery as a food allergen by DBPCFCs and to evaluate current diagnostic procedures in patients with true allergy.  METHODS: DBPCFCs were performed in 32 patients with a history of an allergic reaction to celery. The patients underwent skin prick tests (SPTs) with celery extracts, crude celery, and different pollen extracts.   Specific IgE for celery was determined by using the CAP method. RESULTS: Twenty-two of 32 patients had a positive DBPCFC result. Two patients reacted to placebo, and 8 patients did not respond to the challenge. Of the nonresponders, 4 reacted to an open provocation with celery. The sensitivity of CAP determination for specific IgE (> or =0.7 kU/L) to celery in patients with a positive DBPCFC result was 73%, 48% to 86% for  SPTs (> or =3 mm) with commercial extracts, and 96% for prick-to-prick tests with crude celery. The positive predictive value of the SPT and CAP tests was between 87% and 96%, whereas the specificity and negative predictive values were poor. CONCLUSION: This study confirms the importance of celery as a food allergen for use in DBPCFCs. The SPT and CAP methods proved to be reliable for the diagnosis of a relevant allergy to celery in regard to sensitivity and positive predictive value but not to specificity and negative predictive value.


1541. Bischhoff SC.  Mayer JH.  Manns MP Allergy and the gut. [Review] [100 refs] International Archives of Allergy & Immunology.  121(4):270-83, 2000 Apr.


  There have frequently been doubts as to the relevance of food allergy, in   particular as far as the involvement of the intestinal tract is concerned.   Several studies, however, have confirmed the existence of allergic reactions in the gut, with an estimated prevalence of about 1-2% in adults. Clinical symptoms are unspecific and include nausea, vomiting, abdominal pain, cramping and diarrhea. Intestinal mast cells, as well as intestinal eosinophils, have been shown to be involved in the pathogenesis of food-allergy-related enteropathy. In addition to classical IgE-dependent degranulation, further agonists have been demonstrated for mast cell activation, for example IL-4. The methods used to confirm the diagnosis of intestinal allergy are still insufficient. Until now, blinded oral challenge procedures with food antigens have been accepted as the 'gold standard' in diagnosing food allergy, although these tests have practical problems. Therefore, new test systems have been developed, such as endoscopic provocation tests, that may improve diagnostic procedures. Elimination diet still presents the main basis of therapy. Aspects to be focused on in the future are the role fo IgE-independent allergic mechanisms in intestinal allergy, the impact of cross-reactivity with other allergens and the relationship to other inflammatory bowel diseases such as Crohn's disease, ulcerative colitis, celiac disease and irritable bowel syndrome. Copyright 2000 S. Karger AG, Basel [References: 100]


1542. Briassoulis G.  Hatzis T.  Mammi P.  Alikatora A. Persistent anaphylactic reaction after induction with thiopentone and cisatracurium. Paediatric Anaesthesia.  10(4):429-34, 2000.


  A 6-year-old boy presented for surgery for phimosis. The anaesthetic   technique included intravenous induction with thiopentone and  neuromuscular blockade with cisatracurium. Severe persistent bronchospasm and central cyanosis followed the administration of these drugs. A continuous i.v. infusion of epinephrine at 0.2 microg. kg(-1) x min(-1) was necessary to break the severe refractory bronchial hyperresponsiveness. There was no previous exposure to anaesthetic drugs and no definite family history of allergy. Through increased serum eosinophil cationic protein, tryptase and histamine levels and IgE levels  specific to cisatracurium, we demonstrated an IgE-mediated anaphylactic reaction to cisatracurium in the child's first exposure to this new neuromuscular blocking agent. Anaphylactic reactions to new anaesthetic drugs may be challenging to recognize and treat during general anaesthesia in children. The pathogenesis, diagnosis and management of life threatening persistent allergic reactions to intravenous anaesthetics are discussed.


1543. Chapman SW.  Bradsher RW JR.  Campbell GD Jr.  Pappas PG.  Kauffman CA. Practice guidelines for the management of patients with blastomycosis. Infectious diseases society of America. Clinical Infectious Diseases.  30(4):679-83, 2000 Apr.


  Guidelines for the treatment of blastomycosis are presented; these guidelines are the consensus opinion of an expert panel representing the National Institute of Allergy and Infectious Diseases Mycoses Study Group and the Infectious Diseases Society of America. The clinical spectrum of blastomycosis is varied, including asymptomatic infection, acute or chronic pneumonia, and extrapulmonary disease. Most patients with blastomycosis will require therapy. Spontaneous cures may occur in some immunocompetent individuals with acute pulmonary blastomycosis. Thus, in a case of disease limited to the lungs, cure may have occurred before the diagnosis is made and without treatment; such a patient should be followed up closely for evidence of disease progression or dissemination. In contrast, all patients who are immunocompromised, have progressive pulmonary disease, or have extrapulmonary disease must be treated.   Treatment options include amphotericin B, ketoconazole, itraconazole, and fluconazole. Amphotericin B is the treatment of choice for patients who are immunocompromised, have life-threatening or central nervous system (CNS) disease, or for whom azole treatment has failed. In addition, amphotericin B is the only drug approved for treating blastomycosis in pregnant women. The azoles are an equally effective and less toxic alternative to amphotericin B for treating immunocompetent patients with mild to moderate pulmonary or  extrapulmonary disease, excluding CNS disease. Although there are no comparative trials, itraconazole appears more efficacious than either ketoconazole or fluconazole. Thus, itraconazole is the initial treatment of choice for nonlife-threatening  non-CNS blastomycosis.


1544. Fiocchi A.  Restani P.  Riva E. Beef allergy in children. [Review] [26 refs]  Nutrition.  16(6):454-7, 2000 Jun.


  Beef allergy was poorly known before the '90s. Since then, a number of papers appeared elucidating the nature, epidemiology, and symptoms of beef allergy in children allergic to cow's milk and children suffering from atopic dermatitis. It is now clear that beef allergy is not an infrequent occurrence, with an incidence between 3. 28% and 6.52% among children with atopic dermatitis, its incidence may be as much as 0.3% in the general population. A diagnosis of beef allergy must be supported by skin prick tests, RASTs, and challenges. The specificity and sensitivity according to type of test and the type of extract, however, remains to be evaluated. Despite the fact that other allergens can be sensitizing, the major beef allergen is bovine serum albumin (BSA). Beef-sensitive children are also sensitized to ovine serum albumin, as well as to other serum albumins; therefore, the use of alternative meats in beef-allergic children must be carefully evaluated on an individual basis. Because industrial heat processing is more efficient than domestic cooking in reducing reactivity   in beef-sensitive children, freeze-drying and homogenization may support the introduction of processed beef into the diet of beef-allergic children. [References: 26]


1545. Jacquet A.  Haumont M.  Massaer M.  Daminet V.  Garcia L.  Mazzu P. Jacobs P.  Bollen A. Biochemical and immunological characterization of a recombinant precursor form of the house dust mite allergen Der p 1 produced by Drosophila cells. Clinical & Experimental Allergy.  30(5):677-84, 2000 May.


  GROUND: The major house dust mite allergen Der p 1 elicits strong IgE   antibody responses in patients suffering from mite allergy. OBJECTIVE: This study reports the expression and characterization of a recombinant precursor form of Der p 1 secreted as ProDer p 1 from insect cells. METHODS: The cDNA coding for ProDer p 1 was cloned downstream to the gp67 signal peptide, starting from commercial cDNA encoding Der p 1 and PCR-amplified ProDer p 1 genomic fragment. ProDer p 1, expressed in Drosophila cells and purified from culture medium, was compared to Der p 1 isolated from mite culture, in terms of glycosylation, enzymatic activity as well as IgG- and IgE-binding capacity. RESULTS: Sequence analysis of the genomic clone of ProDer p 1 revealed that, besides two introns in the mature Der p 1 coding sequence, two introns were also present in the propeptide coding sequence. ProDer p 1 was purifed to homogeneity by a combination of ion-exchange, hydroxyapatite and gel filtration chromatographies. The precursor form of Der p 1 could be processed in vitro into mature Der p 1 under acidic and reducing conditions. Carbohydrate analysis clearly indicated that ProDer p 1 expressed from insect cells was glycosylated and that glycan structures were located only in the prosequence. ProDer p 1 displayed a similar immunoreactivity towards IgE, monoclonal and polyclonal IgG antibodies compared to natural Der p 1. Specific activity measurements using synthetic substrates clearly indicated that, contrary to natural Der p 1, ProDer p 1 was totally enzymatically inactive. CONCLUSIONS: The expression of an enzymatically inactive and highly antigenic ProDer p 1 zymogen molecule could be a suitable strategy for the development of in vitro diagnosis test as well as for specific immunotherapy.


1546. Kronqvist M.  Johansson E.  Magnusson CG.  Olsson S.  Eriksson TL. Gafvelin G.  van Hage-Hamsten M. Skin prick test and serological analysis with recombinant group 2 allergens of the dust mites L. destructor and T. putrescentiae.  Clinical & Experimental Allergy.  30(5):670-6, 2000 May.


  GROUND: The dust mites Lepidoglyphus destructor and Tyrophagus  putrescentiae are important sources of allergen in farming environments. The major allergens of the dust mites L. destructor and T. putrescentiae have been cloned and expressed as recombinant proteins. OBJECTIVE: To evaluate the use of recombinant group 2 allergens of L. destructor (rLep d 2) and T. putrescentiae (rTyr p 2) in skin prick test (SPT), and serological analysis in sensitized and non-sensitized farmers chronically exposed to dust mites. METHODS: Skin prick test with rLep d 2, rTyr p 2 and the corresponding commercial extracts was performed in 44 farmers sensitized to L. destructor and/or T. putrescentiae, and 38 control farmers. IgE and IgG subclass antibodies to the recombinant allergens were analysed by RAST and ELISA, respectively. RESULTS: Out of the 44 subjects   positive in SPT to L. destructor and/or T. putrescentiae extract, 26 (59%) displayed a positive SPT to one or the other of the recombinant allergens,  whereas 21 (48%) were positive to both. Significant correlations were  registered between the sizes of the weals induced by rLep d 2 and rTyr p 2 and the corresponding RAST values (P < 0.001). A majority of subjects positive in SPT to the recombinant allergens had detectable IgG4 antibodies, and the levels were significantly higher in the dust mite sensitized group than in the controls (P < 0.05). No such differences were found in the IgG1 values (P > 0.05). The results obtained with rLep d 2 and rTyr p 2 correlated relatively well with each other with respect to SPT, RAST and IgG4, suggesting that the allergens have similar or shared IgE epitopes. All the control subjects had a negative SPT and RAST to rLep d 2 and rTyr p 2. CONCLUSION: Recombinant group 2 allergens from the dust mite L. destructor and T. putrescentiae represent useful tools for  diagnosis of dust mite allergy.


1547. Lin RY.  Schwartz LB.  Curry A.  Pesola GR.  Knight RJ.  Lee HS.  Bakalchuk L.  Tenenbaum C.  Westfal RE. Histamine and tryptase levels in patients with acute allergic reactions: An emergency department-based study. Journal of Allergy & Clinical Immunology.  106(1 Pt 1):65-71, 2000 Jul.


  GROUND: Emergency department visits for acute allergic reactions are  common. Although the diagnosis and classification of these allergic reactions is primarily empiric, it is not always clear whether certain signs and symptoms constitute systemic mediator release syndromes, such as anaphylaxis, and thus may warrant more aggressive therapy or follow-up. OBJECTIVE: We sought to determine associations between various clinical signs and symptoms with both plasma histamine levels and serum tryptase levels in adult patients presenting to an emergency department with acute allergic syndromes. The clinical  correlates of raised beta-tryptase levels were also investigated. METHODS: Ninety-seven adult emergency department patients were prospectively studied by using a questionnaire, physical examination, and serum-plasma sampling. Plasma histamine and serum total and beta-tryptase levels were determined. Clinical groupings were compared for mediator levels by using simple and multivariate analysis. RESULTS: Elevated levels of plasma histamine (>10 nmol/L) and serum total tryptase (>15 ng/mL) were observed in 42 and 20 patients, respectively. Detectable beta-tryptase (>/=1 ng/mL) was observed in 23 patients, including 15 of the patients with elevated total tryptase levels. Suspected food allergy  incidences and the duration of reaction were similar in patients with increased histamine levels and in patients with increased tryptase levels. Increased total tryptase levels, histamine levels, or both were observed in some patients who did not have airway, cardiovascular, or abdominal signs. Histamine levels correlated better with clinical signs than tryptase levels. Histamine elevations (>10 nmol/L) were observed more frequently in patients characterized by the following clinical signs in univariate analysis: the presence of urticaria, more extensive erythema, abnormal abdominal findings, and wheezing. Total tryptase increases were observed more frequently only in patients with urticaria. Histamine levels correlated with initial heart rates. In multivariate analysis the extent of urticaria was the best single predictor of plasma histamine levels and of either an elevated histamine or tryptase level. Detectable beta-tryptase levels were observed in some patients who had neither elevated total tryptase nor elevated histamine levels. Unlike patients without detectable beta-tryptase levels, patients who had detectable beta-tryptase levels had a significant correlation between total tryptase and histamine levels (P <.05). CONCLUSIONS: Raised histamine and, less commonly, raised tryptase levels are observed in almost 50% of patients presenting to emergency departments with acute allergic reactions. Some cases associated with systemic mediator release do not have classical features of severe anaphylaxis, such as hypotension or tachycardia. The lack of total tryptase elevations in many patients with elevated plasma  histamine levels suggests basophil involvement. The clinical utility of beta-tryptase determinations in the evaluation of acute allergic reactions needs further study.


1548. Lucarelli S.  Corrado G.  Pelliccia A.  D'Ambrini G.  Cavaliere M. Barbato M. Lendvai D.  Frediani T. Cyclic vomiting syndrome and food allergy/intolerance in seven children: a possible association. European Journal of Pediatrics.   159(5):360-3, 2000 May.


  Cyclic vomiting syndrome (CVS) is characterized by repeated unpredictable,  explosive and unexplained bouts of vomiting. The episodes have a rapid onset, persist over a number of hours or days, and are separated by symptom-free intervals. Despite the recent interest in this disorder, its aetiology, pathogenesis and even its target organ remain unknown. The purpose of this study is to investigate the role played by food allergy in CVS. The report concerns eight children (five male, three female), mean age 8 years (3-13 years), suffering from CVS for 2 years at least. The diagnosis of CVS was based on characteristic history, normal physical examination and negative laboratory, radiographic, neurological and  endoscopic studies. Despite the absence of clinical signs typical of food  allergy, skin prick tests were positive in six of the eight patients (75%). Specific IgE were present in 4/8 (50%) of the patients. Skin tests and specific IgE were positive for cow's milk proteins, egg white and soya. IgE levels were higher than the mean + 2SD in 5/8 (63%) of the  patients. A double blind placebo controlled food challenge (DBPCFC) was carried out on seven of the eight patients who displayed clinical improvement after an elimination diet for cow's milk (and other foodstuffs indicated by positive skin tests). The DBPCFC was positive in all seven children. Clinical follow-up revealed a state of well-being over the 6 months of observation. CONCLUSION: It appears reasonable to suggest that food allergy plays a role in cyclic vomiting syndrome.


1549. Mates JM.  Perez-Gomez C.  Olalla L.  Segura JM.  Blanca M. Allergy to drugs: antioxidant enzymic activities, lipid peroxidation and protein oxidative damage in human blood. Cell Biochemistry & Function.  18(2):77-84, 2000 Jun.


  Reactive oxygen species lead to lipid peroxidation and specific oxidation of some specific enzymes, proteins and other macromolecules, thus affecting many intra- and intercellular systems. Recently, antioxidant functions have been linked to anti-inflammatory properties. Cell defences against toxic oxygen include antioxidant enzymes. We studied the enzymic antioxidant capacity in human blood of both erythrocytes and mononuclear cells from patients suffering from an allergic reaction to different drugs. We determined superoxide dismutases (SODs), glutathione peroxidase (GSHPx) and catalase (CAT) activities in each cell type. We also determined the extent of thiobarbituric acid reactive substances (TBARS) and the oxidative damage to proteins, in order to study the correlation between the cellular enzymic activities, the oxidative status and the  allergic reaction. In mononuclear cells from allergic patients, SODs and  CAT activities were enhanced compared with controls. Conversely, a decrease in GSHPx activity was found. In erythrocytes, higher values for CAT, GSHPx and SODs activities were found in allergic patients. TBARS were also enhanced in both types of cells, and the carbonyl content of serum was equally increased. The respective enzymic imbalances in mononuclear cells and erythrocytes, namely, GSHPx/SOD and CAT/SOD, and their consequences are discussed. To our knowledge, this is the first global study of antioxidant enzyme determinations, including TBARS level and carbonyl content, in patients suffering from allergies to drugs. Copyright 2000 John Wiley & Sons, Ltd.


1550. Motala C.  Kling S.  Gie R.  Potter PC.  Manjra A.  Vermeulen J.  Weinberg  EG.  Green R. Guideline for the management of chronic asthma in children--2000 update. Allergy Society of South Africa Working Group. South African Medical Journal.  90(5 Pt 2):524-8, 530, 532 passim, 2000 May.


  OBJECTIVE: To increase awareness of asthma and diagnose asthma early in   children. To make recommendations regarding management of chronic childhood asthma in a country with diverse cultural, socio-economic and educational characteristics. The guideline should be used by health professionals involved in the treatment of asthma at all levels of care. OPTIONS: Various management options were considered. Ideal treatment includes use of the new generation inhaled corticosteroids (fluticasone, budesonide), housedust mite intervention for asthma control using impermeable covers for pillows and mattresses, and if needed use of inhaled long-acting beta 2 agonists (LABAs) and leukotriene receptor antagonists (LRAs). Alternative therapeutic approaches for situations  where resources are limited include simple housedust mite control measures (e.g. airing mattresses and bedding), avoidance of exposure to passive smoking, use of lower doses of beclomethasone than recommended by other guideline documents and/or sustained-release (SR) theophylline as preventer treatment and use of plastic bottles as cheap spacer devices. OUTCOMES: The main potential outcomes considered were: to reduce morbidity and mortality by correct diagnosis of asthma, to achieve the best quality of life for the child with asthma, to minimise side-effects from medication and to prevent development of permanently abnormal lung function. EVIDENCE: Current international guideline documents for   diagnosis and management of childhood asthma were evaluated. Clinical studies before 1998 pertaining to the various aspects of management of childhood asthma were reviewed, including controlled studies on the use of inhaled  corticosteroids in children with asthma, randomised controlled trials on the use of LRAs and two studies evaluating the efficacy of LABAs. Current data on the anti-inflammatory effects of SR theophylline were also reviewed as well as a randomised controlled trial on the benefits of SR theophylline as adjunct treatment in childhood asthma. The benefit of simple spacer devices, based on well-conducted local studies (published in an international peer-reviewed journal) was also considered. VALUES: The South African Childhood Asthma Working Group (SACAWG) committee members, appointed by the Allergy Society of South Africa (ALLSA), were selected to represent the interests of health professionals  involved in the care of childhood asthma and to co-opt other colleagues with expertise relevant to the guideline. The committee was divided into six task groups headed by a chairperson--each task group had to review critically the previous SACAWG guideline (for deficiencies and obstacles to implementation), review current trends in asthma management (evidence-based where available) and submit proposals and recommendations to their respective chairperson. The hairperson then compiled a report for discussion by the SACAWG executive committee. The executive group convened a meeting to discuss the recommendations and obtain consensus. An editorial board was appointed to compile the final report. Cultural factors, patient preferences, cost, availability and education were considered important. BENEFITS, HARMS AND COSTS: Proper treatment should  enable most children with asthma to lead normal or near-normal lives. The guideline could be implementable at all levels of care. The risk of systemic effects due to inhaled corticosteroids should be minimised in children with mild to moderate persistent asthma (risk of systemic effects is more likely at daily beclomethasone doses exceeding 400 micrograms or the equivalent dose of other inhaled corticosteroids). Promotion of simple environmental control measures and use of inhaled beclomethasone and/or SR theophylline should make treatment more widely available and more affordable and improve adherence to treatment.  Alternative cheap plastic bottle spacer devices will increase availability and assist with overcoming the problem of incorrect inha


1551. Pham TS.  Rudner EJ. Peanut allergy. [Review] [34 refs] Cutis.  65(5):285-9, 2000 May.


  Peanut allergy is acute and severe with symptoms of immediate hypersensitivity. This allergy is very common, affecting 1% of preschoolers. The incidence has increased with succeeding generations, and is possibly due to the increasing exposure of children to peanuts at a young age. Diagnosis is via history, skin prick test, and serum IgE level. The mainstay of therapy is avoidance. Treatment of anaphylaxis includes epinephrine and antihistamines. Children usually will not outgrow this food allergy. Novel treatment with rush immunotherapy and enzyme-potentiated desensitization is not currently acceptable. We describe a 27-month-old Asian boy with a typical presentation of peanut hypersensitivity. A good understanding of the epidemiology of this illness is necessary for treatment and prevention. [References: 34]


1552. Primeau MN.  Kagan R.  Joseph L.  Lim H.  Dufresne C.  Duffy C.  Prhcal D.  Clarke A. The psychological burden of peanut allergy as perceived by adults with  peanut allergy and the parents of peanut-allergic children. Clinical & Experimental Allergy.  30(8):1135-43, 2000 Aug.


  GROUND: Peanut-allergic patients are affected by a condition which forces them and their families to exercise extreme dietary vigilance and experience constant uncertainty throughout their lives. OBJECTIVE: To compare the quality of life and family relations of children and adults with a peanut allergy to that of children and adults with a rheumatological disease. METHODS: Patients with a confirmed diagnosis of peanut allergy or a rheumatological disease completed (for children less than 18 years, by proxy) self-report questionnaires regarding the impact of their condition on their quality of life and family relations. A vertical visual analogue scale and the Impact on Family Questionnaire (IFQ) served as outcome measures. RESULTS: One hundred and fifty-three peanut-allergic children were compared with 69 children with a rheumatological disease while 37 peanut-allergic adults were compared with 42 adults with a rheumatological disease. The parents of peanut-allergic children, compared to the parents of children with a rheumatological disease, reported that their children had significantly more disruption in their daily activities. Furthermore, the parents of peanut-allergic children reported more impairment in the familial-social dimension of the IFQ. Conversely, adults with a chronic rheumatological disease reported more disruption in their family relations than peanut-allergic adults. CONCLUSION: Given the considerable disruption in daily activities and family relations reported by the parents of peanut-allergic children, accurate diagnosis of peanut allergy is essential. Our work should make health care professionals dealing with children with confirmed peanut  allergy more aware of the support that these families may require. Furthermore, we hope to motivate food industries to offer more 'peanut free' products to decrease the dietary restrictions of these patients while minimizing their potential for accidental ingestion.


1553. Rance F.  Dutau G.  Abbal M.  Mustard allergy in children. Allergy.  55(5):496-500, 2000 May.


  GROUND: Mustard allergy is not well known. This study aimed to assess   its clinical features and other associated allergies, and to define skin prick tests (SPT), specific IgE, and dose response by oral food challenge. METHODS: Our study investigated 36 children with positive mustard SPT. The diagnosis of mustard allergy was based on open or single-blind, placebo-controlled food challenge (SBPCFC). We compared the subjects to 22 controls. RESULTS: The initial clinical features were atopic dermatitis (51.8%), and urticaria and/or angioedema (37%). Fifteen children were allergic (positive SBPCFC) and 21 children were nonallergic (negative SBPCFC). Symptoms after mustard ingestion started under 3 years of age in 53.3% of the subjects. There was no significant difference in the food allergies and associated inhalant allergen sensitizations between the two groups. In the allergic group, the mean wheal diameter for mustard SPT was 8.8 mm and the median concentration of mustard serum (s) IgE 14.8 kU/l. The mean cumulative reactive dose were 153 mg. CONCLUSIONS: Allergic  reactions to mustard started early in life. Clinical symptoms were not severe in children. Mustard should be included in screening tests of food allergy in children.


1554. Ryan EJ.  Nilsson L.  Kjellman N.  Gothefors L.  Mills KH. Booster immunization of children with an acellular pertussis vaccine enhances Th2 cytokine production and serum IgE responses against pertussis toxin but not against common allergens. Clinical & Experimental Immunology.  121(2):193-200, 2000 Aug.


  Acellular pertussis vaccines (Pa) protect against severe pertussis in children. However, serum antibody responses decline quickly after immunization. Studies in animal models suggest that cell-mediated immunity also contributes to protection against Bordetella pertussis, and it has already been demonstrated that Pa induce T cells that secrete type-1 and type-2 cytokines in children. In this study we examined the persistence of the T cell response and the effect of booster immunization in 4-6-year-old children. Cell-mediated immunity to B. pertussis antigens was detected in a high proportion of children more than 42 months after their last immunization. Peripheral blood mononuclear cells (PBMC) from the majority  of children secreted interferon-gamma (IFN-gamma) and a smaller proportion  IL-5, in response to specific antigen stimulation in vitro. However, following booster immunization, significantly higher concentrations of  IL-5, but not IFN-gamma, were produced by PBMC in response to B. pertussis antigens. Furthermore, plasma IL-4 and IL-5 concentrations were increased,   whereas IFN-gamma concentrations were reduced following booster immunization. It has been suggested that childhood immunization with Th2-inducing vaccines may predispose some children to atopic disease. Although we found that pertussis toxin (PT)-specific IgE was significantly increased after booster immunization in both atopic and non-atopic children, the levels of IgE to common allergens and the prevalence of positive skin prick test were unaffected by the booster vaccination. Thus, despite the enhancement of type-2 responses to B. pertussis antigens, booster vaccination with Pa does not appear to be a risk factor for   allergy.


1555. Sainte-Laudy J.  Sabbah A.  Drouet M.  Lauret MG.  Loiry M. Diagnosis of venom allergy by flow cytometry. Correlation with clinical history, skin tests, specific IgE, histamine and leukotriene C4 release. Clinical & Experimental Allergy.  30(8):1166-71, 2000 Aug.


  GROUND: Potent allergens such as hymenoptera venoms are capable of  inducing severe and life threatening clinical reactions. Percentage of false negative results obtained by the usual diagnostical methods is comprised between 10 and 25%. OBJECTIVE: Evaluation of the sensitivity and the specificity of cellular tests and particularly evaluation of a new flow cytometric method. METHODS: Forty-five allergic patients having experienced a local, a systemic reaction or an anaphylactic shock and 10 controls having undergone hymenoptera stings without clinical reactions were selected on the basis of the clinical history, skin tests and specific IgE. Three cellular tests were performed on the same cell suspensions and in the presence of 2 ng/mL of rIL3: histamine release  (RIA), leukotriene C4 release (ELISA) and basophil activation test (flow  cytometry after double anti-IgE FITC, anti-CD63 PE labelling). RESULTS: As   compared to the clinical history, sensitivities of skin tests, specific IgE, flow cytometry, histamine release and leukotriene release were, respectively; 85%, 88%, 100%, 89% and 100%. Flow cytometric analysis of basophil activation showed a significant decrease of the mean fluorescence density and number of IgE positive cells and a significant increase of the number of CD63 positive cells. The 10 controls tested by flow cytometry were negative. CONCLUSION: As compared to the clinical history and to the other parameters tested here, flow cytometry showed a high sensitivity and a high specificity. The excellent correlation observed between this method and the other cellular tests such as histamine and leukotriene release are in favour of the specificity of flow cytomery and in favour of the use of this method for venom allergy diagnosis.


1556. van Ree R.  Aalbers M.  Kea O.  Marco De La Calle FM.  Sempere Ortells JM.  Villalba M.  Rodriguez R.  Aalberse RC. A sensitive monoclonal antibody sandwich ELISA for the measurement of the major olive pollen allergen Ole e 1.  International Archives of Allergy & Immunology.  122(3):224-8, 2000 Jul.


  GROUND: Olive pollen is a major cause of inhalant allergy in countries   around the Mediterranean sea. The major allergen of olive pollen is Ole e 1. Measurement of the major allergen content of allergen products for diagnosis and therapy is becoming an essential element of standardization protocols. This study aimed at the development of a monoclonal antibody (mAb) sandwich ELISA for Ole e 1. METHODS: Balb/c mice immunized with Ole e 1 were used for the production of mAbs. Screening of mice and hybridomas was performed in a RIA with radiolabeled purified Ole e 1. Purified mAbs were used as catching and/or (biotinylated) detecting antibodies in sandwich ELISA. RESULTS: Four mAbs (IgG1kappa) directed to nonoverlapping epitopes on Ole e 1 were obtained: 1A12, 5C1, 10A12 and 3H8. Both 1A12 and 10A12 were successfully used for affinity purification of Ole e 1 from olive pollen extract. Two sandwich ELISAs were developed, with 1A12 and 10A12 as catching, and 5C1 and 3H8 as detecting antibodies, respectively. Both catching and detecting antibodies were used in similar concentrations, ranging from 60 to 100 ng/well. For both ELISAs, the  sensitivity was approximately 1 ng/ml of Ole e 1. The measuring range was from 1 to 25 ng/ml. No significant differences were observed, when the performance of both ELISAs in standardization of olive pollen extracts was compared. CONCLUSIONS: Two sensitive sandwich ELISAs for the major olive pollen allergen Ole e 1 were developed. They will prove to be useful tools in allergen standardization protocols. Copyright 2000 S. Karger AG, Basel.


1557. Verma J.  Singh BP.  Gangal SV.  Arora N.  Sridhara S. Purification and partial characterization ofa 67-kD cross-react ive allergen from Imperata cylindrica pollen extract. International Archives of Allergy & Immunology.  122(4):251-6, 2000 Aug.


  GROUND: Grass pollens are known to induce type I allergic reactions in a large number of genetically predisposed individuals. Earlier studies have recognized Imperata cylindrica (Ic) pollen as an important source of  aeroallergen which contained 7 IgE binding proteins in the MW range of 85-16 kD. OBJECTIVES: To isolate, purify and characterize a cross-reactive allergenic protein from Ic pollen extract for diagnosis and therapy of grass pollen allergy. METHODOLOGY: Ic pollen extract was fractionated using DEAE Sephadex A-50, Sephadex G-200 and Mono Q column. Allergenic activity of the fractions was checked by ELISA, skin tests, ELISA inhibition and immunoblot using sera of Ic-sensitive patients. A 67-kD protein was purified to homogeneity from Ic-VIII. The allergenic determinants of this protein were identified by SDS-PAGE and immunoblot after CNBr treatment. RESULTS: Among Ic fractions, Ic-VIII was highly  potent by ELISA, skin tests and showed cross-reactivity with 4 other tropical grasses by immunoblot and ELISA inhibition. The subfraction Ic-VIIIe1 of Ic-VIII showed a band at 67 kD on SDS-PAGE. On CNBr treatment, it gave 7 peptides, 3 of which were found to be allergenic. CONCLUSION: A 67-kD protein (Ic-VIIIe1) was isolated, purified to homogeneity and partially characterized. It showed cross-reactivity with tropical grasses tested and contained at least three allergenic  determinants. Copyright 2000 S. Karger AG, Basel.


1558. Yip L.  Hickey V.  Wagner B.  Liss G.  Slater J.  Breiteneder H.  Sussman G. Beezhold D. Skin prick test reactivity to recombinant latex allergens. International Archives of Allergy & Immunology.  121(4):292-9, 2000 Apr.


  GROUND: Allergy to latex has become a serious and increasingly common   health problem, particularly for healthcare workers and patients who undergo frequent surgical procedures. Testing for latex allergy currently involves in vitro tests and skin prick testing using crude preparations of natural rubber latex (NRL). To date, 10 latex proteins have received designation as allergens (Hev b 1 to Hev b 10) and, except for Hev b 4, have been cloned as recombinant proteins. Our aim was to compare the skin prick test (SPT) reactivity of six recombinant latex allergens with SPT reactivity to natural rubber latex proteins in known latex-allergic individuals. METHODS: Six recombinant proteins were expressed in Escherichia coli, and tested as the intact fusion proteins (Hev b 2, 5, 6,  8) or as purified proteins (Hev b 3 and 7). SPT with the six recombinant latex allergens was performed using 10-fold serial dilutions on 31  latex-allergic subjects to determine the level of reactivity to each recombinant allergen. Latex-specific IgE was determined using the AlaSTAT assay. RESULTS: All six recombinant allergens were reactive by SPT in at least 1 latex-allergic patient but not in any of the control patients. The frequency of sensitization to the various recombinant allergens was similar to previous studies using the native proteins isolated from NRL. The minimal level of protein for a positive skin test was 70 pg/ml for NRL  and 1 ng/ml for one recombinant allergen (Hev b 7). In our patients, the use of a combination of recombinant latex allergens Hev b 5, 6 and 7 diagnosed latex allergy with 93% sensitivity and 100% specificity.  CONCLUSION: Recombinant latex allergens are clinically reactive, can be produced in a standardized manner, and could potentially provide safe, sensitive and specific reagents for the diagnosis of latex allergy. Copyright 2000 S. Karger AG, Basel Date: 27-Feb-2001 Name: absapr Database: Medline <January 2000 to December 2000>

2055. Asero R.  Bottazzi G. Nasal polyposis: a study of its association with airborne allergen hypersensitivity. Annals of Allergy, Asthma, & Immunology.  86(3):283-5, 2001 Mar.


  BACKGROUND: Despite the frequent presence of clinical symptoms such as   sneezing and itching, elevated histamine and IgE in extracellular polyp fluids, tissue eosinophilia, and degranulated mast cells, allergy is not   considered an important cause of nasal polyposis. OBJECTIVE: To   investigate the prevalence of immediate skin reactivity to airborne   allergens in patients with nasal polyposis. METHODS: Sixty-eight patients   with nasal polyposis and 36 controls with chronic sinusitis were submitted   to skin prick tests (SPTs) with a large series of seasonal and perennial   airborne allergens including: grass, mugwort, ragweed, pellitory,   plantain, birch, hazel, olive, cypress, house dust mites, cat and dog   dander, and thirteen molds (Alternaria, Aspergillus, Cladosporium,  Penicillium, Candida, Trichophyton, Fusarium, Curvularia, Botrytis,  Pullularia, Rhizopus, Mucor, Helminthosporium). RESULTS: Forty-three of 68   (63%) patients with nasal polyposis versus 6 of 35 (17%) controls were   positive on SPT with airborne allergens (P < .001). A comparison with   1,128 subjects with respiratory allergy seen from 1996 to 1999 showed a   markedly higher prevalence of sensitivity to Candida albicans (19 of 43   [44%] vs 8 of 1,128 and 2 over black square]; and 2 over black square]; [1  and 2 over black square] and 2 over black square]%]; P < .001) and to  house dust mites (12 of 43 [28%] vs 154 of 1,128 and 2 over black square];  and 2 over black square]; [1 and 2 over black square] and 2 over black   square]4%]; P < .05) among allergic patients with polyps. Altogether, 30   of 43 (70%) patients versus 215 of 1,128 (19%) controls were sensitive to   at least one perennial airborne allergen (ie, mold, mite, or animal   dander) on SPT (P < .001); in contrast, 26 of 43 (60%) patients versus 942   of 1,128 (84%) controls were sensitive to seasonal airborne allergens (P < .005). A review of the clinical histories of SPT-positive patients  revealed the presence of obstructive rhinitis and chronic rhinorrhea only in most cases, whereas acute symptoms, such as sneezing and itching, were   reported only by a minority of subjects. CONCLUSIONS: A clinically slight   respiratory allergy, particularly to perennial airborne allergens, might  play a relevant role in the pathogenesis of nasal polyposis, probably   through the induction of a long-lasting inflammation of the nasal mucosa.


2056. Bengtsson  A.  Lundberg M.  Avila-Carino J.  Jacobsson G.  Holmgren A. Scheynius A. Thiols decrease cytokine levels and down-regulate the expression of CD30 on human allergen-specific T helper (Th) 0 and Th2 cells. Clinical & Experimental Immunology.  123(3):350-60, 2001 Mar.


  The thiol antioxidant N-acetyl- L-cysteine (NAC), known as a precursor of glutathione (GSH), is used in AIDS treatment trials, as a chemoprotectant in cancer chemotherapy and in treatment of chronic bronchitis. In vitro, GSH and NAC are known to enhance T cell proliferation, production of IL-2  and up-regulation of the IL-2 receptor. The 120-kD CD30 surface antigen  belongs to the tumour necrosis factor (TNF) receptor superfamily. It is  expressed by activated T helper (Th) cells and its expression is sustained  in Th2 cells. We have analysed the effect of GSH and NAC on the cytokine  profile and CD30 expression on human allergen-specific T cell clones  (TCC). TCC were stimulated with anti-CD3 antibodies in the presence of  different concentrations of GSH and NAC. Both thiols caused a dose  dependent down-regulation of IL-4, IL-5 and IFN-gamma levels in Th0 and  Th2 clones, with the most pronounced decrease of IL-4. Furthermore, they  down-regulated the surface expression of CD30, and the levels of soluble  CD30 (sCD30) in the culture supernatants were decreased. In contrast, the surface expression of CD28 or CD40 ligand (CD40L) was not significantly changed after treatment with 20 m M NAC. These results indicate that GSH  and NAC favour a Th1 response by a preferential down-regulation of IL-4. In addition, the expression of CD30 was down regulated by GSH and NAC,  suggesting that CD30 expression is dependent on IL-4, or modified by NAC. In the likely event that CD30 and its soluble counterpart prove to contribute to the pathogenesis in Th2 related diseases such as allergy, NAC may be considered as a future therapeutic agent in the treatment of these diseases.


2057. Choquet-Kastylevsky G.  Vial T.  Descotes J. Drug allergy diagnosis in humans: possibilities and pitfalls. [Review] [57 refs] Toxicology.  158(1-2):1-10, 2001 Feb 2.


  Due to the potential hazards of drug allergies, an early and reliable diagnosis is crucial. The use of in vivo tests is not recent but, because of the hazards of skin testing in patients with a history of anaphylaxis, they had been abandoned for a while. Recent reevaluations have shown that for some drugs, e.g. antibiotics-reliable skin tests can ensure the diagnosis of drug allergy in up to 70% of cases. Many in vitro tests based on well-defined mechanisms, e.g. the basophil degranulation test have been used for the diagnosis of totally unrelated allergic mechanisms. It is almost impossible to interpret their validity as diagnosis tools. Nevertheless, other tests, e.g. the lymphocyte transformation test which have been evaluated in well-conducted recent studies, seem to have a good predictive value. Their use is still restricted to clinical trials or research studies. A reliable clinical approach as well as a detailed  examination of the drug intake remains obligatory to diagnose drug allergy. Available in vivo and in vitro tests are sometimes used to confirm the diagnosis. The sensitivity and specificity of these tests is evaluated in clinical studies. Research to improve the existing tests and to develop new diagnostic tools is still of paramount importance. [References: 57]



2061. Larsen GL. Differences between adult and childhood asthma. [Review] [43 refs] Disease-A-Month.  47(1):34-44, 2001 Jan.


  During the last 2 decades, we have gained new insights into the pathogenesis of asthma; consequently, new therapeutic agents and approaches to therapy have emerged. Nevertheless, significant gaps remain in our understanding of this disease. Important new treatment issues affect childhood (the usual time of asthma onset), and researchers have recently described increases in asthma incidence in children. Yet, most clinical studies have been performed with adults, and our knowledge about major determinants of childhood asthma remains incomplete. Major challenges in pediatric asthma include methods of easily assessing lung function and noninvasive methods of assessing asthma's inflammatory nature. Research that addresses the mechanisms responsible for disease onset is also critical to decrease the prevalence of asthma. What we know about adult asthma cannot be used in the treatment of children without further study, but it is now clear that effective treatment should begin during childhood. (J Allergy Clin Immunol 2000;106:S153-7.) [References: 43]


2062. Leff AR. Regulation of leukotrienes in the management of asthma: biology and clinical therapy. [Review] [64 refs] Annual Review of Medicine.  52:1-14, 2001.


  Leukotrienes (LTs) are the ultimate synthetic product resulting from the intracellular hydrolysis of membrane phospholipid at the nuclear envelope in inflammatory cells. Activated cytosolic phospholipase (cPLA2) catalyzes the production of arachidonic acid, which is converted by cyclooxygenases into leukotriene A4 (LTA4) and subsequently into the chemotaxin LTB4, which has no direct bronchoconstrictor activity. In certain inflammatory cells, LTA4 is converted into the cysteinyl leukotriene (cysLT) LTC4, which is converted into LTD4 and finally to LTE4 after extracellular transport. All cysLTs occupy the same receptors and are extremely potent bronchoconstricting agents that are pathogenetic in both asthma and allergy. With the identification of the structure of the cysLT receptor, antileukotriene therapies have been developed that either (a) inhibit synthesis of leukotriene (through 5-lipoxygenase inhibition) or (b) block the cysLT receptor. Preliminary investigations indicate that corticosteroids also may partially block the synthesis of cysLT and that  cysLTs may be chemotactic for other inflammatory cells, e.g. eosinophils, by a mechanism that has not yet been defined. Currently, anti-LT therapies are approved by the US Food and Drug Administration (FDA) only for patients with asthma. These drugs generally are moderately efficacious agents, although they are highly efficacious in aspirin-induced asthma (AIA). In other forms of asthma, inhaled corticosteroid (ICS) therapy has been more effective than anti-LT therapy in improving air flow obstruction. However, anti-LT agents are additive to beta-adrenoceptor and ICS in their effects. Accordingly, anti-LT therapies are used frequently as supplemental treatments in asthmatic patients whose asthma is not optimally controlled by a combination of other drugs, including long-acting beta-adrenoceptor drugs and ICS agents. The growth of leukotriene receptor antagonists (LTRAs) has been extraordinary in the United States. The exceptional safety of these agents and their ease of administration as tablets taken once or twice daily has spurred this  growth. In the past year, the high-affinity cysLT receptor has been cloned. This holds forth the promise of a second generation of LTRA agents of even greater efficacy and possibly greater duration of action. [References: 64]


2063. Lewis SA.  Pavord ID.  Stringer JR.  Knox AJ.  Weiss ST.  Britton JR. The relation between peripheral blood leukocyte counts and respiratory symptoms, atopy, lung function, and airway responsiveness in adults. Chest.  119(1):105-14, 2001 Jan.


  STUDY OBJECTIVES: Eosinophils and neutrophils play major roles, respectively, in the pathogenesis of asthma and COPD, and it is well recognized that levels of these cells in peripheral blood are increased in relation to their pulmonary involvement. However, the relation between peripheral blood cell counts of the other major leukocyte groups and these lung diseases or markers of allergy or airflow obstruction is less clear. We have therefore investigated the association between peripheral blood levels of eosinophils, neutrophils, basophils, monocytes, and lymphocytes and the occurrence of chronic respiratory symptoms, atopy, lung function, and bronchial hyperresponsiveness, and the modifying effect of age, in adults. DESIGN: A cross-sectional general population study. SETTING: Data on > 2,000 British adults, who originally participated in a study of diet and lung health, were analyzed using multiple linear and logistic  regression to adjust for potential confounders, including age, sex, and  smoking history. RESULTS: We found that, like eosinophils, the peripheral basophil count was increased in relation to asthma and associated symptoms, and to airway hyperreactivity and increased total IgE, but differed from eosinophils in that basophils were unrelated to atopy. Monocytes were predominantly associated with symptoms indicative of obstructive airway disease, in similar relation to neutrophils, but both of these leukocyte counts were also increased in asthma patients in older age groups. Lymphocyte counts were unrelated to any objective or subjective marker of disease. CONCLUSIONS: If peripheral blood cell counts reflect pulmonary involvement of these leukocyte groups, basophils and  monocytes may play a distinct role in the pathogenesis of allergic and  nonallergic respiratory disease.


2066. Pichler WJ. Predictive drug allergy testing: an alternative viewpoint. [Review] [40 refs] Toxicology.  158(1-2):31-41, 2001 Feb 2.


  T- and B-cells recognise drugs when bound as haptens to carrier molecules.  Recent studies suggest that drugs might also bind in a non-covalent form to MHC-peptide complexes and T cell receptors, and are thereby able to stimulate T cells. This has, however, only been shown for drug-specific T cell clones. Functional analysis revealed that drug-reactive T cells secrete high amounts of IL-5 and are cytotoxic. Cytotoxicity is mediated by drug-specific CD4(+) and CD8(+) cells and, as revealed by the immunohistochemical analysis of drug-induced exanthems, might be involved in the killing of keratinocytes thus explaining the drug-induced exanthem. Further work is needed to clarify the type and exact location of the rather labile drug binding to MHC and T cell receptors, and to evaluate what drug allergies might be caused by such an unusual presentation and immune stimulation. This new model as well as findings from the analysis of clinical drug allergies may have major implications on how to test and predict the allergenic potential of drugs. A change and expansion of  currently performed test procedures is required to predict the allergenic  potential of drugs. [References: 40]


2067. Sachs B.  Erdmann S.  Al-Masaoudi T.  Merk HF. In vitro drug allergy detection system incorporating human liver microsomes in chlorazepate-induced skin rash: drug-specific proliferation associated with interleukin-5 secretion. British Journal of Dermatology.  144(2):316-20, 2001 Feb.


  BACKGROUND: Chlorazepate is a benzodiazepine often used for pre-operative  anxiolysis. The central metabolite responsible for the pharmacological and  probably for the adverse effects of most benzodiazepines, including  chlorazepate, is N-desmethyldiazepam. We report a woman who developed a  generalized exanthem 1 day after receiving chlorazepate and four other  drugs related to anaesthesia for surgery of the larynx. Patch tests  pointed to chlorazepate as the culprit drug for the skin rash. OBJECTIVES:  The purpose of this study was to detect drug allergy to chlorazepate or a  metabolite in vitro by means of the lymphocyte transformation test (LTT),  and to determine the concentrations of the T-helper (Th) 2-type cytokine  interleukin (IL)-5 and the Th1-type cytokine interferon (IFN) -gamma in  the culture supernatants. METHODS: We performed an LTT with peripheral  blood mononuclear cells from the patient and a control, employing human  liver microsomes containing cytochrome P450 enzymes as a metabolizing  system, in parallel cultures. IL-5 and IFN-gamma concentrations in the  culture supernatants were assessed by enzyme-linked immunosorbent assay.  RESULTS: In the LTT, no T-cell reactivity was observed to the parent  compound chlorazepate, whereas coincubation of the drug with human liver  microsomes yielded proliferative T-cell reactivity, which was associated  with secretion of IL-5 but not of IFN-gamma. CONCLUSIONS: We conclude that  addition of a metabolizing system may be advantageous for in vitro  detection of T-cell reactivity to drug metabolites in the LTT.



2594.  Barnes C.  Tuck J.  Simon S.  Pacheco F.  Hu F.  Portnoy J. Allergenic materials in the house dust of allergy clinic patients. [see comments].  Annals of Allergy, Asthma, & Immunology.  86(5):517-23, 2001 May.


  INTRODUCTION: Environmental agents including animal, fungal, tree, and weed antigens are known to cause allergic rhinitis and asthma. The following study was performed to measure the antigen concentration of several of these in house dust of children seen in an allergy clinic. Comparisons are made between household allergen levels of children seen for asthma and children seen for other reasons. METHODS: Dust samples were solicited from patients in a pediatric allergy specialty clinic and other individuals associated with the clinic. Persons submitting dust were asked to complete a questionnaire describing their house. Samples were extracted, centrifuged, and filtered for sterility. Samples were stored in 50% glycerol at -20 degrees C. Specific antigens for Alternaria, Cladosporium, Aspergillus, Candida, Dermatophagoides farinae, cat, dog, oak, fescue, ragweed, plantain, and cockroach were measured using inhibition assays developed with whole antigen extract. Allergens Der p1, Der f 1, Alt a 1, and Alt a 70 kD were measured using double monoclonal antibody assays. RESULTS: Significant concentrations of whole antigen from cat, dog, oak, Alternaria, and Cladosporium were detected. Between 0.1 and 18 microg of Der f1 and Der p1 per gram of dust were also measured. Alt a 1 and Alt a 70 kD levels varied between 3.0 and 1000 U/g of dust. Significant positive correlations were observed in levels of dust mite and Alternaria allergen for patients with an evaluation of asthma. CONCLUSIONS: We found measurable levels of fungal antigens (Alternaria, Cladosporium), mite antigens, and animal antigens (dog and cat) in the majority of dust samples in this self-selected set of allergy clinic patients. Specific allergens Alt a 1, Alt a 70kD, and Der p 1 were significantly higher in the homes of asthmatic patients when compared with patients seen for reasons other than asthma. These studies support the hypothesis that fungal allergen exposure is an important component in the pathogenesis of the clinical condition known as asthma.

2595. Crimi E.  Milanese M.  Pingfang S.  Brusasco V. Allergic inflammation and airway smooth muscle function. [Review] [13 refs]  Science of the Total Environment.  270(1-3):57-61, 2001 Apr 10.


  It is widely accepted that airway smooth muscle (ASM) contraction plays a key role in asthmatic attacks. Whether abnormalities of contractility or autonomic regulation exist in the asthmatic ASM is still debated. Studies based on isometric contraction failed to show differences in the force-generation capability between asthmatic and normal ASM. Recent studies in vitro have shown that sensitized ASM: (1) shortens more and more rapidly than normal ASM; and (2) develops a myogenic response to stretching. The increased velocity of shortening may compromise in vivo the ability of tidal cycling to reduce airway tone, which would result in an enhanced response to bronchoconstrictor stimuli. The myogenic response may result in a sustained bronchospasm after a deep inhalation, a maneuver that in normal individuals causes bronchodilatation. Although there is no evidence that neural or humoral abnormalities in the autonomic regulation of ASM tone are central to the pathogenesis of bronchial asthma, recent data suggest that ASM receptor dysfunction may develop secondary to airway allergic response. It has been shown that exposure of passively sensitized human bronchi to allergens in vitro causes M2- and beta2-receptor dysfunction. Impairment of pre-junctional M2-autoreceptors may result in an enhancement of neurally mediated bronchoconstrictor responses, whereas beta2-receptor dysfunction may reduce the sensitivity to bronchodilator treatment. Airway inflammation, which is a characteristic feature of bronchial asthma, may alter both the contractile properties and the autonomic regulation of ASM. These changes may contribute to the severity of asthma, as they may cause an, imbalance between factors favoring and opposing airway narrowing. [References: 13]


2596. De Amici M.  Puggioni F.  Casali L.  Alesina R. Variations in serum levels of interleukin (IL)-1beta, IL-2, IL-6, and tumor necrosis factor-alpha during specific immunotherapy.  Annals of Allergy, Asthma, & Immunology.  86(3):311-3, 2001 Mar.


  BACKGROUND: Cytokine production by T helper cells is essential for the induction and maintenance of allergic inflammation in the bronchial mucosa. According to recent views, specific immunotherapy (SIT) favors the differentiation of T lymphocytes into cells of the Th1 rather than those of the Th2 subset. OBJECTIVE: To determine whether or not SIT induces a decrease in the inflammatory reaction by studying eventual variations in the serum levels of IL-1beta, IL-2, IL-6, and TNF-alpha in allergic subjects during SIT. METHODS: Serum levels of IL-1beta, IL-2, IL-6, and TNF-alpha were determined before and after 3, 6, and 9 months of SIT by an immunoradiometric assay (IRMA) in 11 adults with perennial allergic asthma and/or rhinitis caused by house dust mites and in 6 nonatopic healthy volunteers. RESULTS: Median serum IL-1beta and TNF-alpha levels of the patients were significantly higher at baseline than those of the controls and decreased during SIT to values similar to or lower (P < .01) after 6 months of SIT for TNF-alpha than those of the controls. Median serum IL-2, significantly lower at baseline than in the controls, increased during SIT to a level similar to that of the controls. Although the median values of IL-1beta and TNF-alpha in the patients tended to decrease and those of IL-2 to increase during SIT, the differences were not significant; the correlation coefficients (r) of the serum levels of IL-1beta IL-6, and TNF-alpha versus duration of SIT were negative, while that of IL-2 was positive. CONCLUSIONS: Decreases in median serum IL-1beta and TNF-alpha levels during SIT, together with the increases in serum IL-2 and IL-6, compared with those of the controls furnish evidence supporting a reduction in the inflammatory response in the course of SIT.



2597. Dogru H.  Delibas N.  Doner F.  Tuz M.  Uygur K. Free radical damage in nasal polyp tissue. Otolaryngology - Head & Neck Surgery.  124(5):570-2, 2001 May.


  OBJECTIVE: To investigate whether the free radical injury in nasal polyp tissue exists or not. STUDY DESIGN: A prospective study in patients with nasal polyps. METHODS: Polyp specimens were obtained from 19 patients. Control specimens were acquired from 16 patients who underwent partial turbinectomy with concha bullosa free of rhinitis, sinusitis, and allergy, confirmed by endoscopic nasal examination, coronal paranasal sinus CT scan, and prick test. MDA levels of nasal polyps and control specimens were measured by using the method of Knudsen et al. RESULTS: The mean MDA levels of nasal polyps and control specimens were 38.2 +/- 5.1 (33.3-52.2) and 33.9 +/- 1.6 (32.6-37.4), respectively. MDA levels in NP were significantly higher compared with control specimens (P < 0.01). CONCLUSION: High level of MDA in nasal polyp tissue that represents FR increase supports the existence of cell injury in nasal polyp tissue. FRs should be considered in the development and life cycles of NP which is thought to have multifactorial pathogenesis.


2598. Griffiths PD. Getting vaccines into perspective. Reviews in Medical Virology. 11(1):1-2, 2001 Jan-Feb.


2599. Honigman B.  Lee J.  Rothschild J.  Light P.  Pulling RM.  Yu T.  Bates DW. Using computerized data to identify adverse drug events in outpatients.  Journal of the American Medical Informatics Association.  8(3):254-66, 2001 May-Jun.


  OBJECTIVE: To evaluate the use of a computer program to identify adverse drug events (ADEs) in the ambulatory setting and to evaluate the relative contribution of four computer search methods for identifying ADEs, including diagnosis codes, allergy rules, computer event monitoring rules, and text searching. DESIGN: Retrospective analysis of one year of data from an electronic medical record, including records for 23,064 patients with a primary care physician, of whom 15,665 actually came for care. MEASUREMENT: Presence of an ADE; sensitivity and specificity of computer searches for ADE. RESULTS: The computer program identified 25,056 incidents, which were associated with an estimated 864 (95 percent confidence interval [CI], 750-978) ADES. Thus, the ADE rate was 5.5 (CI, 5.2-5.9) per 100 patients coming for care. Furthermore, in 79 (CI, 68-89) ADEs, the patient required hospitalization, resulting in an estimated rate of 3.4 (CI, 2.7-4.3) admissions per 1,000 patients. The sensitivity of the search methods for identifying ADEs was estimated to be 58 (CI, 18-98) percent, and the estimated specificity was 88 (CI, 87-88) percent. The positive predictive value was 7.5 (CI, 6.5-8.5) percent, and the negative predictive value was 99.2 (CI, 95.5-99.98) percent. Compared with age and gender-matched controls with no positive screen, patients with ADEs had twice as many outpatient visits and were taking nearly three times as many drugs. Antihypertensives, ACE-inhibitors, antibiotics, and diuretics were associated with 56 (CI, 47-65) percent of ADES. Among ADEs, 23 (CI, 16-32) percent were life-threatening or serious, and 38 (CI, 29-47) percent were judged preventable. CONCLUSION: Computerized search programs can detect ADEs, and free-text searches were especially useful. Adverse drug events were frequent, and admissions were not rare, although most hospitals today do not identify them. Thus, such detection programs demonstrate "value-added" for the electronic record and may be useful for directing and assessing the impact of quality improvement efforts.


2600. Liu T.  Howard RM.  Mancini AJ.  Weston WL.  Paller AS.  Drolet BA.  Esterly NB.  Pucar F.  Kagan R.  Lim H.  Clarke AE. Peanut challenge: a retrospective study of 140 patients. [see comments]. Clinical & Experimental Allergy.  31(1):40-6, 2001 Jan.

2601. Mari A. Multiple pollen sensitization: a molecular approach to the diagnosis. International Archives of Allergy & Immunology.  125(1):57-65, 2001 May.


2602. Nieters A.  Brems S.  Becker N.  Cross-sectional study on cytokine polymorphisms, cytokine production after T-cell stimulation and clinical parameters in a random sample of a German population. Human Genetics.  108(3):241-8, 2001 Mar.


  We investigated, in a random sample of a German population, the association of polymorphisms in the genes encoding the cytokines interleukin 2 (IL-2), interleukin 4 receptor (IL-4R), interleukin 6 (IL-6), interleukin 10, interferon gamma (IFNG), tumor necrosis factor (TNF) and intercellular adhesion molecule 1 (ICAM-1) with (1) secreted levels of the respective proteins after T-cell stimulation and (2) data on selected diseases obtained from a questionnaire. The scope of this investigation was to further the understanding of the genetic background of allergies and common colds and the observed heterogeneity of many immune responses in the human population. In contrast to previous reports that showed associations of promoter polymorphisms of cytokine genes with the production of the corresponding protein, we did not find associations with protein release after T-cell stimulation in vitro. Among the correlations with the clinical parameters, we observed an increased risk of allergies (odds ratio, OR= 4.1; confidence interval, CI: 1.6-10.4), particularly hay fever (OR=5.6, CI: 1.8-17.1) in individuals homozygous for IFNG 13 CA-repeats. In combination with the TNF wildtype, the risk for hay fever increased to OR=8.4 (CI: 2.7-25.6). Furthermore, individuals with a combination of IL2, IL6 and ICAM-1 polymorphisms tended to have higher frequencies of reported common colds than individuals with the alternate genotypes. As these are results of an explorative investigation, these findings require confirmation in material from a different source. If confirmed, these relationships could contribute to a better characterisation of the genetic component of allergies.

2603. Pryor JP.  Vonfricken K.  Seibel R.  Kauder DR.  Schwab CW.  Anaphylactic shock from a latex allergy in a patient with spinal trauma.  Journal of Trauma-Injury Infection & Critical Care.  50(5):927-30, 2001 May.

2604. Pucar F.  Kagan R.  Lim H.  Clarke AE. Peanut challenge: a retrospective study of 140 patients. [see comments].  Clinical & Experimental Allergy.  31(1):40-6, 2001 Jan.

2605. Salkind AR.  Cuddy PG.  Foxworth JW.  Is this patient allergic to penicillin? An evidence-based analysis of the likelihood of penicillin allergy. [Review] [53 refs] JAMA.  285(19):2498-505, 2001 May 16.

2606. Sampson HA. Utility of food-specific IgE concentrations in predicting symptomatic food allergy. Journal of Allergy & Clinical Immunology.  107(5):891-6, 2001 May.

2607. Settipane RA.  Lieberman P. Update on nonallergic rhinitis. [Review] [93 refs] Annals of Allergy, Asthma, & Immunology.  86(5):494-507; quiz 507-8, 2001 May.


2608. Suzuki N.  Kudo K.  Sano Y.  Ito K.   Can Mycobacterium tuberculosis infection prevent asthma and other allergic disorders?.  International Archives of Allergy & Immunology.  124(1-3):113-6, 2001 Jan-Mar.


  It is generally considered that tuberculosis (TB) is a disease which upregulates Th1 cell function. There is a hypothesis that infection of Mycobacterium tuberculosis may prevent allergic disorders such as bronchial asthma. However, our clinical experience of patients with TB somewhat conflicts this hypothesis. Hence, we investigated Th1/Th2 balance in the peripheral blood of patients with active TB by measuring serum levels of IgE antibody and by intracellular cytokine assay. We found that serum levels of IgE in the patients with active TB were significantly higher than in those with lung cancer or with COPD. In the TB patients, titers of IgE tended to correlate with disease severity. Intracellular cytokine assay demonstrated that IFN-gamma-positive cells were significantly decreased in the patients with active TB compared to normal controls. The ratio of IFN-gamma-positive (Th1-like)/IL-4-positive (Th2-like) cells was remarkably reduced in the TB patients (p < 0.0001). This ratio showed a significant negative correlation with erythrocyte sedimentation rate and with C-reactive protein. Therapy against TB for 2-3 months did not result in significant changes of the Th1/Th2 ratio. These findings suggest that infection of M. tuberculosis does not systematically upregulate Th1 cells in some patients, and is unlikely to prevent allergic disorders like asthma. Copyright 2001 S. Karger AG, Basel


2609. Uchio E.  Matsuura N.  Matsumoto S.  Kadonosono K.  Ohno S. Histamine release test and measurement of antigen-specific IgE antibody in the diagnosis of allergic conjunctival diseases.  Journal of Clinical Laboratory Analysis.  15(2):71-5, 2001.


2610. Veres G.  Helin T.  Arato A.  Farkkila M.  Kantele A.  Suomalainen H.  Savilahti E. Increased expression of intercellular adhesion molecule-1 and mucosal adhesion molecule alpha4beta7 integrin in small intestinal mucosa of adult patients with food allergy. Clinical Immunology.  99(3):353-9, 2001 Jun.


  The mechanisms of adverse reactions to foods in the gastrointestinal tract are poorly understood. Previous studies of other atopic diseases and animal models suggest that adhesion molecules and mucosal lymphocytes may be implicated in the pathogenesis of food allergy (FA). The aim of our study was to investigate the expression of adhesion molecules and mucosal lymphocytes in duodena of patients with food allergies and of controls. Ten patients with FA to cereals (wheat, oats, and rye) or cow's milk and 9 control patients were included in the study. Quantitative analysis and immunohistochemical stainings for two pairs of adhesion molecules (intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-1 (LFA-1), alpha4beta7 integrin, and mucosal addressin cell adhesion molecule (MAdCAM-1) and lymphocyte markers on endoscopic duodenal biopsy specimens were performed. The villous structure and density of LFA-1-positive cells were normal in every biopsy specimen, but the patients had significantly more alpha4beta7+ cells in the intraepithelial space (P = 0.01). The expression of ICAM-1 in the lamina propria of patients with FA was also substantially increased (P = 0.003); however, staining with MAdCAM showed no intergroup difference. Moreover, we found significantly increased CD4+ and HLA-DR+ cells in the lamina propria of patients, in comparison to the controls, P = 0.05 and P = 0.04, respectively. The densities of CD3, CD8, HLA-DP, T cell receptor alphabeta+ and gammadelta+ cells and IgA-, IgA1-, and IgA2-containing cells did not differ in the two groups studied. Our results suggest that the increased expression of ICAM-1 and alpha4beta7 integrin may play an important role in the pathogenesis of food hypersensitivity and with the elevation of CD4- and HLA-DR-positive cells reflect a stage of inflammation in the structurally normal intestines. Copyright 2001 Academic Press.

2611. Walsh GM.  Annunziato L.  Frossard N.  Knol K.  Levander S.  Nicolas JM. Taglialatela M.  Tharp MD.  Tillement JP.  Timmerman H.  New insights into the second generation antihistamines. [Review] [310 refs]  Drugs.  61(2):207-36, 2001.


     Second generation antihistamines are recognised as being highly effective treatments for allergy-based disease and are among the most frequently prescribed and safest drugs in the world. However, consideration of the therapeutic index or the benefit/risk ratio of the H1 receptor antagonists is of paramount importance when prescribing this class of compounds as they are used to treat non-life threatening conditions. There are many second generation antihistamines available and at first examination these appear to be comparable in terms of safety and efficacy. However, the newer antihistamines in fact represent a heterogeneous group of compounds, having markedly differing chemical structures, adverse effects, half-life, tissue distribution and metabolism, spectrum of antihistaminic properties, and varying degrees of anti-inflammatory effects. With regard to the latter, there is growing awareness that some of these compounds might represent useful adjunct medications in asthma therapy. In terms of safety issues, the current second generation grouping includes compounds with proven cardiotoxic effects and others with the potential for adverse drug interactions. Moreover, some of the second generation H1 antagonists have given cause for concern regarding their potential to cause a degree of somnolence in some individuals. It can be argued, therefore, that the present second generation grouping is too large and indistinct since this was based primarily on the concept of separating the first generation sedating compounds from nonsedating H1 antagonists. Although it is too early to talk about a third generation grouping of antihistamines, future membership of such a classification could be based on a low volume of distribution coupled with a lack of sedating effects, drug interactions and cardiotoxicity. [References: 310]


2612. Warner L.  Rochat RW.  Fichtner RR.  Stoll BJ.  Nathan L.  Toomey KE. Missed opportunities for congenital syphilis prevention in an urban southeastern hospital. Sexually Transmitted Diseases.  28(2):92-8, 2001 Feb.


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