Positive Cutaneous Reactions Research Articles

Physico-chemical and clinico-immunologic studies on the allergenic significance of Aspergillus tamarii, a common airborne fungus

Aspergillus-derived inhalant allergens play an important role in the etiology of allergic respiratory diseases. In the present study, we investigated the allergenic potential of Aspergillus tamarii, quantified its airborne content, identified its major/minor allergens, evaluated heterogeneity of patients’ IgE response to its allergens and cross-reactivity of its allergens with other Aspergillus allergens. Skin prick tests with A tamarii extract were performed on 300 patients of bronchial asthma/allergic rhinitis and 20 healthy volunteers. Sixty-six patients (22%) elicited positive cutaneous reactions to A tamarii extract. Only one of the 20 non-allergic healthy volunteer showed a mild positive cutaneous reaction. Allergen-specific IgE levels increased with increase in patients’ cutaneous response (0% in negative to 100% in 3+/4+). The skin positivity and allergen-specific IgE levels were significantly higher in patients compared to healthy volunteers ( P > 0.05). However, no differences were found for these two parameters among patients of bronchial asthma, allergic rhinitis and bronchial asthma with allergic rhinitis. The airborne A tamarii allergen content was highest in February and October. A tamarii extract revealed at least 22 proteins (13.3–120 kDa). Seventeen of these proteins bound patients’ IgE with six being major allergens (13.3, 23, 25, 34, 39.5, 43 kDa). Three major allergens (13.3, 34, 43 kDa) were found to cross-react with A flavus and one (34 kDa) with A niger. Our results revealed that A tamarii allergen(s) are present in the air, which might serve as important inhalant allergens in IgE-mediated allergic respiratory diseases.

Progesterone sensitive Interferon-? producing cells detected by ELISpot assay in autoimmune progesterone dermatitis

Autoimmune progesterone dermatitis (APD) is a rare cutaneous disorder, characterized by recurrent polymorphous cutaneous and mucosal manifestations. It is considered to be caused by a hypersensitive reaction to endogenous progesterone. However, in vitro T-cell activity to this hormone has been described in few patients. Here we report the case of a 30-year-old woman with recurrent pruritic erythematous, and erythema multiforme-like eruptions localized to the genital area. Positive cutaneous reaction to intradermal progesterone injection suggested the diagnosis of APD. The analysis of cellular immune response to progesterone, investigated by the ELISpot assay, showed a significantly higher level of Interferon-gamma (IFN-gamma) producing cells in this patient compared with a control group comprising five asymptomatic women in the luteal phase of the menstrual cycle. Our results suggest that the ELISpot technique, together with clinical evaluations and assessment of allergies, could be useful in the diagnosis of APD.

Induction of protective immunity by Legionella pneumophila flagellum in an A/J mouse model

The capacity of a purified preparation of Legionella pneumophila flagella (FLA) to induce protective immune responses was studied in an A/J mouse model. Animals immunized with FLA promptly mounted an anti-FLA antibody response and also developed a strong activation of both innate and adaptive cell-mediated immunity, as shown by an early release of pro-inflammatory cytokines in the peritoneal cavity, and by a positive cutaneous delayed-type hypersensitivity reaction and in vitro splenic lymphocyte proliferation in response to FLA antigens. Mice treated with FLA either i.v. or i.p. also survived (100% rate) a lethal i.p. challenge with L. pneumophila. Protection induced by FLA lasted for at least 30 days after treatment, but less than 60, and was effective against the challenge with different serogroups of L. pneumophila. Resistance conferred by FLA immunization could be partially transferred to naïve animals by the adoptive transfer of immune splenocytes but not by passive immunization with anti-FLA iperimmune sera. The capacity to induce protective immunity was specifically attributable to flagellar components, as demonstrated by the lack of protection in mice immunized with a sham flagella preparation from a non-flagellated bacterial strain or with protease-digested FLA. In addition, heat-denatured FLA was inactive, suggesting loss of immunogenicity following denaturation. The present study provides evidence that L. pneumophila flagellum is strongly immunogenic and capable to stimulate, without adjuvants, early natural and acquired, T-cell-mediated immune responses and to induce significant protection against a lethal bacterial challenge in A/J mice. Antigenic characterization of this bacterial organelle and elucidation of mechanisms underlying flagella-induced protection would be of great value in understanding the immunopathogenesis of the disease and in developing possible therapeutic strategies for human legionellosis.

Peripheral anergy and local immune hyperactivation in sarcoidosis: a paradox or birds of a feather

Sarcoidosis is a multisystem non-caseating granulomatous disorder, which is frequently self-limiting. Not only does its aetiology remain an enigma, but equally curious is its immunological background, which appears to be pathognomonic for this disease. Studies have shown aberrant cell-mediated active, if not overactive, immune responses at sites of inflammation [1] in the presence of hypergammaglobulinaemia [2] and cutaneous anergy to particular antigens, including tuberculoprotein but not Kveim antigen [3]. This apparent paradox in peripheral and local cellular immune responses, with preferential activation at the organ level, has provoked a great deal of interest over the years, and begged the question of whether the proposed depression in peripheral cellmediated immunity in sarcoidosis is in fact real or apparent. The accumulation of activated oligoclonal CD4 T lymphocytes [4] and specific subpopulations of macrophages [5,6], together with a release of various proinflammatory cytokines [7], determine the immune phenomena as well as the development and fate of granulomata at the sites of sarcoid inflammation. The recruitment of CD4 T lymphocytes around granulomata is more prominent within fresh active lesions, and tends to diminish as the granulomata mature [8]. Indeed, as lesions become less active, these cell types decrease, and T cells expressing CD8 surface antigens predominate [8]. A similar switch in immunoregulatory T cells has also been observed in animal models of granulomatous lung disease [9,10]. In patients with active sarcoidosis, the increase in activated T cell numbers at sites of granulomatous inflammation is simultaneously accompanied by an absolute decrease in the number of circulating T cells in autologous peripheral blood. One of the earliest immunological abnormalities to be observed in active sarcoidosis is a partial to complete anergy to tuberculin purified protein derivative (PPD). Such skin anergy also extends to certain antigens, e.g. Trichophyton, mumps virus, streptokinase/ streptodornase, Candida, as well as dinitrochlorobenzene. The incidence of anergy to tuberculoprotein and other antigens in sarcoid patients varies from 30% to 70%, depending on the number of antigens used [3,11,12]. This anergy appears to parallel disease severity, being especially marked when the sarcoidosis is clinically active, and disappearing months to years after resolution of the disease. Usually such cutaneous anergy is associated with depressed cellular immunity. The partial cutaneous anergy observed in sarcoidosis is frequently attributed to a reduction in the number and function of circulating T lymphocytes [13]. It has been suggested that the reduction of delayed-type skin test reactivity could reflect a depletion of the population of immunoreactive cells being sampled from the skin. It is recognized that in granulomatous disease there is an altered circulating pattern for T lymphocytes with the onset of inflammation. In particular, CD4 T cells become sequestrated in central lymphoid organs and sites of inflammation, leaving proportionately increased numbers of CD8 T cells in the peripheral blood [14]. In sarcoid patients, the ratio of CD4 to CD8 T cells in the blood may be normal or slightly decreased, with corresponding T cell ratio in the lung being 4–10 times greater than normal [15]. At the height of inflammation, the compartmentalized CD4 T cells have been shown to express IL-2R, very late activation Ag1, and DR class II MHC molecules: the hallmarks of antigenstimulated T cells [16,17]. In addition, it appears that these CD4 T lymphocytes are oligoclonal, consistent with a conventional antigen-driven process [18,19] (albeit the nature of the antigenic stimulus in sarcoidosis remains unclear). However, whilst T cells obtained from inflamed sites appear to be activated both morphologically and functionally, with augmented responses to external stimuli such as lectins and antigens, the functional response of autologous peripheral blood lymphocytes to mitogen and recall antigen is impaired, with consequent depression of B cell function in vitro. In addition, inhibitory factors, partly derived from monocytes, have been isolated from the blood of active sarcoid patients, and shown to inhibit the in vitro response of normal lymphocytes to mitogens and antigens [13,20,21]. Such findings in the peripheral blood have been related to the observed depression in certain cutaneous delayed hypersensitivity responses [13,22]. Despite this apparent cutaneous anergy, patients with sarcoidosis are uniquely capable of mounting a positive cutaneous reaction to a Kveim antigen. The mechanisms of this Kveim response are not entirely clear. Although Kveim test lesions exhibit histopathologic similarities to sarcoid granulomata, there are marked differences between the Kveim reaction and the classic DTH skin response. The most obvious difference is in the kinetics of the two reactions. DTH reaction begins at 8 h, peaks at 24–48 h, and resolves by 96–120 h. By contrast, the Kveim reaction takes 4–6 weeks to develop. Furthermore, no specific antigen in the Kveim preparation has been identified as the inducing agent in this response, and no convincing data have been generated to show reproducibly that sarcoid lymphocytes are actively sensitized to the Clin Exp Immunol 1997; 110:1–3

Intradermal skin testing in Icelandic horses in Austria.

Icelandic horses in Austria are commonly affected by an allergic inflammatory skin disease recurring during the summer seasons, which shares characteristic features with Culicoides hypersensitivity. However, the causative agents have not yet been identified. Therefore, intradermal skin testing (IDST) with a standardised extract of Culicoides variipennis and 21 other allergens relevant within Austria was performed in 81 Icelandic horses. All horses included into the study were treated regularly with ivermectin and had no history of administration of anti-inflammatory drugs. Forty-three of these horses were affected by summer seasonal recurrent dermatitis (SSRD). No history or signs of any other disease were evident in any horse. Pruritic dermatitis due to ectoparasites, bacteria and dermatophytes were ruled out by means of fungal culture, skin scraping and biopsy. Culicoides variipennis antigens evoked a positive cutaneous reaction in 1 of 38 normal and 3 of 43 SSRD horses at the proposed dilution of 1:50,000 or 1:25,000, and in 24 of 38 normal and 13 of 43 SSRD horses at a dilution of 1:10,000. Furthermore, no significant differences in onset or intensity of skin reactions to the 21 other allergens, including pollens, moulds, mites and insects, except deerfly and horsefly, were obvious between the 2 groups. Efficiency (percentage of correct results) for the used antigens in the skin test was 0.47-0.60. Maximal sensitivity was 0.51. Altogether, 38 of 43 SSRD horses and 28 of 38 normal horses were positive 4 h after allergen administration. The divergence between IDST results and manifestation of clinical signs found in this study underlines the difficulties associated with establishing a skin test protocol in horses within a geographic area. Whether the outcome of this study would have been influenced significantly by using Culicoides spp. present in Austria has to be clarified in future research.

Bacterial infections and atopic dermatitis.

Bacterial infections and atopic dermatitis.

Tuberculous Neuroretinitis

To describe a patient with tuberculous neuroretinitis. Retrospective case report. We describe a 43-year-old otherwise asymptomatic woman with a known exposure to tuberculosis who had unilateral optic disc edema and a partial macular star (neuroretinitis). This was followed approximately 1 year later by the development of an exudative retinal detachment in the setting of bilateral multifocal choroiditis. Laboratory testing revealed a marked positive cutaneous reaction to purified protein derivative (PPD). Treatment with antituberculosis medicine alone resulted in prompt resolution of the choroidal infiltrates and complete flattening of the exudative detachment. Tuberculosis should be considered in the differential diagnosis for patients with neuroretinitis.

Inhibitory effect of heparin on skin reactivity to autologous serum in chronic idiopathic urticaria

Background: Most patients with chronic idiopathic urticaria (CIU) show cutaneous reactivity to intradermal injection of autologous serum. In some cases this reactivity is associated with the presence of autoantibodies directed against IgE or IgE receptors expressed on mast cells, whereas in others no autoimmune mechanisms can be documented. Objectives: The aims of this study were to compare the cutaneous reactivity to serum and plasma samples in a series of patients with active CIU and to address the mechanisms of the inhibitory effect exerted by heparin on the cutaneous responsiveness to the histamine-releasing factors (HRFs) present in CIU serum. Methods: Fourteen patients with CIU were injected intradermally with autologous serum, plasma (anticoagulated by either heparin or EDTA), or serum samples to which heparin had been added. The effects of heparin injection on cutaneous responsiveness to allergens was tested in 5 atopic patients. Moreover, in a set of experiments sera were also adsorbed with Sepharose-conjugated heparin. Results: All the patients had positive cutaneous reactions to autologous serum injection. When heparinized plasma was injected, negative reactions were observed in 12 of 14 patients, and a sizable reduction in the wheal-and-flare reactions was recorded in the remaining 2. Compared with results obtained with serum, no substantial change was observed in 6 of 8 patients injected with EDTA-anticoagulated plasma. When heparin was added to serum, abrogation of skin reactivity was seen; nonetheless, no change in the cutaneous response to allergens was associated with locally administered heparin in 5 atopic patients with no history of CIU. Finally, adsorption of CIU sera with solid-phase heparin abrogated the ability to induce cutaneous reactions in 5 of 7 patients, whereas in the remaining 2 a sizable reduction was observed. Conclusions: These data indicate that heparin is able to profoundly inhibit the cutaneous response to HRFs present in the sera of patients with CIU. Although the precise level of action of this heparin-mediated effect is unclear from present data, preliminary evidence seems to indicate that heparin could directly interfere with HRFs present in CIU sera. (J Allergy Clin Immunol 1999;103:1143-7.)

Anaphylactoid reaction induced by pancuronium during general anaesthesia

Sir: Anaesthetists should be alert to the possibility of serious adverse reactions when using muscle relaxants. Life-threatening allergic reactions during anaesthesia occur in approximately 1 in 3500 to 10 000 and contribute to higher mortality and morbidity [1]. We report an adverse reaction in a healthy man scheduled for a septorhinoplasty. The patient was a 73-year-old man weighing 86 kg and 174 cm tall. He was an ASA I, non-smoker, non-drinker, who had no history of atopy and had not been previously exposed to general anaesthesia. On arrival in the operating theatre, the patient received midazolam 2.5 mg. Anaesthesia was induced with thiopentone 350 mg, fentanyl 350 μg and lignocaine 125 mg by slow bolus. One minute later pancuronium 8.6 mg was administered by rapid bolus to facilitate tracheal intubation. Ventilation was assisted using 100% oxygen for 4 min before tracheal intubation. Before laryngoscopy, thiopentone 50 mg was administered. After intubation (5 min after pancuronium), he developed bronchospasm, severe hypotension, diffuse erythema and tachycardia, which were treated successfully with adrenaline, theophylline, corticosteroids and antihistamines. Surgery was postponed. Because several drugs had been used simultaneously during induction of anaesthesia, it was impossible to establish with certainty which drug and mechanism were involved without performing immunological investigations. Venous blood samples were taken within 30 min of reaction and subsequent samples at 3, 6, 12 and 24 h and 5 days later for measuring IgE and complement C3 and C4. We did not observe any significant changes in total IgE levels or complement consumption. Serum tryptase levels, measured by radioimmunoassay, were undetectable (<2 IU L−1). The patient was further investigated 6 weeks after the incident. Prick and intradermal skin tests were carried out with latex, suxamethonium, atropine, midazolam, propofol, thiopentone, fentanyl, pancuronium and atracurium [2]. A negative result was found for all, except for pancuronium and atracurium, which showed positive intradermal tests (0.2 and 0.001 mg mL−1 respectively). Ten atopic patients used as a control exhibited negative intradermal tests with pancuronium and atracurium at the same concentrations. Specific IgE serum levels could not be detected by radioimmunoassay. Most commonly, life-threatening adverse events that occur during anaesthesia happen during induction (80%) [3]. During this period, many intravenous drugs (including antibiotics, sedatives, hypnotics, muscle relaxants, etc.) may be given in rapid succession. Muscle relaxants are by far the most frequently involved in inducing allergic reactions (51%) [4]. A direct release of histamine from mast cells and basophils following quaternary ammonium compounds has been shown to occur both systematically and cutaneously with almost all muscle relaxants currently in use. Several authors [5,6] have reported cross-reactivity between muscle relaxants. Such cross-reactivity is caused by the presence in the molecules of quaternary ammonium ions [7], which are involved in a number of mechanisms mediating allergic and pseudoallergic reactions. Although a true allergic reaction has been excluded by the absence of specific antibodies to the drug and undetectable tryptase levels, the intradermal skin tests with both muscle relaxants at the maximal recommended concentration elicited a positive cutaneous reaction. This, together with the fact that this patient had not received prior general anaesthesia, suggests that pancuronium, which is rarely implicated in this type of reaction, was the culprit. I. M. SÁNCHEZ-GUERRERO J. A. TORTOSA* J. HERNÁNDEZ-PALAZÓN* A. I. ESCUDERO Department of Allergy, 'Rafael Mendez' Hospital, Lorca, Murcia, Spain *Department of Anaesthesia, 'Virgen de la Arrixaca' University Hospital, Murcia, Spain

Allergic contact dermatitis from latex rubber

Previously we have found occasional patients with delayed hypersensitivity to latex (in rubber gloves) in the absence of allergy to any chemicals in the rubber chemical screen. There are many reports of contact urticaria to latex and isolated reports of delayed hypersensitivity to latex, usually in the presence of contact urticaria. To establish if latex ruber is a more common cause of delayed hypersensitivity than is currently recognized, we patch tested all patients attending our contact dermatitis clinic, over a 6-month period, with latex. Of 822 patients, 16 (1.9%) demonstrated positive cutaneous reactions to latex. Six exhibited contact urticaria to latex, five contact urticaria and allergic contact dermatitis, and five allergic contact dermatitis alone. Of the five with delayed hypersensitivity to latex in the absence of contact urticaria, only one was atopic and the sensitivity was thought to be relevant or possibly relevant in four. Of our patients, 1.2% exhibited positive patch-test reactions to latex. Patch testing with latex should be considered where contact dermatitis to a latex rubber-containing product is suspected, e.g. gloves and footwear.

Reactivity of Mast-Cell-Bound IgE Idiotypes with Anti-Idiotypic Antibody: Mediator Release or Inhibition of Antigen-Induced Mediator Release?

When anti-idiotypic antibodies specific for idiotopes on IgE antibodies react with mast-cell-bound IgE antibody, the reaction may be expected to lead either to mediator release or to inhibition of allergen-induced release. This study was carried out to determine which would occur. Anti-idiotype antiserum (anti-Ids) was raised in syngeneic mice by immunisation with affinity-purified DNP-specific mouse monoclonal IgE. Sera from these immunised mice and from a similarly immunised rabbit inhibited the binding of the monoclonal IgE to radio-iodinated dinitrophenylated (DNP) ovalbumin, whereas a high concentration of affinity-purified rabbit antimouse epsilon-chain-specific antibody was unable to inhibit even though it was shown to bind to the monoclonal IgE. The mouse anti-Ids did not give a positive passive cutaneous anaphylactic reaction in rats sensitised with high-titre grass-pollen-specific IgE-containing antiserum, whereas it gave a positive result in rats sensitised with the DNP-specific monoclonal IgE. Rabbit antimonoclonal antiserum and rabbit anti-epsilon-chain antibody both gave positive results in these two assays. The results indicated that anti-idiotypic antibodies specific for idiotopes on IgE antibody can react and release mediators from IgE-sensitised mast cells. The significance of this in view of the increased levels of anti-idiotypes that can occur during immunotherapy is discussed.

Shared and specific allergenic and antigenic components in the two sexes of American cockroach—Periplaneta americana

The whole body extracts (WBEs) of female and male cockroaches (Periplaneta americana; Pa) were prepared separately to study the specific and/or shared allergenic and antigenic components in the two sexes. These two extracts were skin-tested on 170 respiratory allergy patients and 52 (30.6%) of them elicited a markedly positive cutaneous reaction (2+ to 4+) to any one or both the WBEs. Of these 52 patients, 32 (61.5%) produced a 2+ to 4+ response to only one, and the remaining 20 (38.5%) to both the extracts. In female and male RASTs to Pa both the extracts produced dose-related inhibition. Using rabbit anti-Pa female serum: (1) immuno-diffusion experiments resulted in lines of identity with the two extracts, and (2) the two-dimensional immunoelectrophoresis of Pa female and Pa male WBEs elicited 12 and nine precipitin peaks, respectively. In partial purification studies, only fraction Pa(F)III (approximately 50 kD) of Pa female WBE and Pa(M)I (greater than or equal to 600 kD) and Pa(M)III (approximately 50 kD) fractions of Pa male WBE revealed significant allergen activity both on skin testing and also in RAST inhibition studies. These results provide evidence for the presence of shared as well as specific allergenic and antigenic components in the two sexes of American cockroach.

Biological and Cellular Responses to Grass Pollen in Sensitive Patients

Using a noninvasive skin chamber technique, we studied the in vivo development of anaphylactic reactions in 8 pollen-sensitive patients suffering from seasonal allergic rhinitis/conjunctivitis/asthma and showing positive cutaneous reactions after intradermal allergen challenge. As agonists, histamine and pollen were introduced into the skin chambers and left in contact with superficial dermis during 6 h. The release of mediators (histamine and prostaglandin [PG] D2) and the modifications in protein diffusion occurring during the immediate (30 min) and the late (6 and 24 h) cutaneous reaction phases were quantitatively analyzed. 24 h after agonist introduction, the recruitment of inflammatory cells on the superficial dermis was studied by use of Rebuck's windows. Histamine release in pollen-containing skin chambers was immediate and persisted until the 24th h despite replacement of the agonists by control medium at the 6th h. An intense PGD2 release occurred as soon as the first 30 min in chambers containing either exogenous histamine or pollen and was maintained until the 24th h. Protein diffusion induced by histamine and pollen was similar to the control one at 30 min but was intensely enhanced at the 6th h. At the 24th h, pollen-induced protein diffusion was still intense whereas that induced by histamine was analogous to the control one. 24 h after pollen challenge, numerous eosinophils were recruited on the superficial dermis but almost none were observed after control medium or histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma due to the complex salts of platinum—a cross‐sectional survey of workers in a platinum refinery

Anamnestic and immunological data of workers of a platinum refinery (group A: workers with work-related symptoms, n = 8; group B: workers with symptoms not clearly work-related, n = 9; group C: asymptomatic workers, n = 13) and controls (group D: atopics, n = 10; group E: non-atopics, n = 16) were compared. Exposure to platinum salt was higher in group A than in groups B or C. In group A, symptoms developed 4 months (median) after the onset of exposure. All subjects of group A and three workers of group B, but none of the workers of the other groups, showed a positive cutaneous reaction to (PtCl6)2-. Total serum IgE was higher in groups A and D than in groups B, C or E. (PtCl6)2(-)-specific IgE was higher in group A, but there was non-specific binding of (PtCl6)2- to IgE. Histamine release with (PtCl6)2- was found in all groups and was highest in atopic controls. Histamine release with (PtCl6)2- and histamine release with anti-IgE showed an excellent correlation, suggesting a similar release mechanism of (PtCl6)2- and anti-IgE. In skin-test positive subjects, high cutaneous (PtCl6)2(-)-sensitivity is linked to high histamine release with (PtCl6)2- or anti-IgE, supporting the concept of a role of cell surface IgE or IgE-Fc-receptor in the release process with platinum salts. However, high specificity of cutaneous reactions contrasts with low specificity of in-vitro tests with (PtCl6)2-. A different reaction of basophils and mast cells, when challenged with free platinum salts, is hypothesized. We conclude that neither histamine release from basophils with (PtCl6)2- nor RAST for the detection of (PtCl6)2- -specific IgE are helpful in the diagnosis of platinum salt allergy.

Tuberculous Pleural Effusions

While a number of recent reports have documented the changing clinical and radiographic spectrum of parenchymal tuberculosis, relatively little attention has been paid to changes in the patterns of pleural tuberculosis. We therefore reviewed the clinical, laboratory, and radiographic characteristics of 26 adult patients with tuberculous pleural effusions. We found that pleural tuberculosis has become a disease of older adults (median age, 56 years) and that 19 percent (5/26) of the cases were due to postprimary (reactivation) disease. This shift in age led to problems in diagnosis, since many of these older patients had underlying or coexisting disease that could have caused a pleural effusion. Both specimens of pleural fluid and pleural biopsy were useful in establishing the diagnosis. Examination of sputum was less helpful. All patients who were not anergic had positive cutaneous reactions to first-strength purified protein derivative of tuberculin. Lymphocytosis of the pleural fluid was not a uniform finding; only 62 percent of our patients had greater than 50 percent lymphocytes on their initial examinations of pleural fluid, and four patients had greater than 90 percent polymorphonuclear cells. All of the effusions were exudates, and four had glucose levels in the pleural fluid that were less than 30 mg/dl. Pleural tuberculosis is an important diagnostic consideration in adult or elderly patients with exudative pleural effusions.

Allergy induced by Parietaria officinalis pollen in southern Croatia.

Pollen of Parietaria officinalis causes season-associated respiratory symptoms. In Southern Croatia (Yugoslavia) we found 65% patients with rhinitis and/or asthma to be allergic to this pollen. They showed positive cutaneous reactions and had specific IgE antibodies to the respective isolated allergen. The finding represents the first report on Parietaria officinalis-induced allergy on the east Adriatic coast.

Ciliary responsiveness in allergic and nonallergic airways

Allergic asthma is associated with airway (smooth muscle) hyperresponsiveness to several chemical mediators of anaphylaxis; however, it is not known whether this is accompanied by mucociliary hyperresponsiveness. The purpose of this study was therefore to determine if airway ciliary activity, a component function of mucociliary clearance, exhibits exaggerated responses to prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), and leukotriene D4 (LTD4) in allergic sheep when compared with nonallergic sheep, and the effects of LTD4 are direct or involve the generation of cyclooxygenase products of arachidonate metabolism. Ciliary beat frequency (CBF) was measured in a perfusion chamber with a microscopic technique using tracheal epithelial cells obtained from brushing of "allergic" (positive cutaneous reaction and previous bronchospastic response to inhaled specific antigen) and "nonallergic" (negative cutaneous reaction, no previous inhalation challenge with antigen) sheep. Mean base-line CBF was not different among the groups; PGE1, PGE2, and LTD4 induced dose-dependent increases in CBF, and these increases were not different in allergic and nonallergic sheep. At the highest agonist concentration the mean increase in CBF from base line varied between 13 and 16% (P less than 0.05). The ciliostimulatory effect of LTD4 was significantly blunted by both the sulfidopeptide leukotriene antagonist FPL-55712 and the cyclooxygenase inhibitor indomethacin. These results suggest that allergic sheep fail to exhibit ciliary hyperresponsiveness to selected chemical mediators of anaphylaxis and the ciliostimulatory effect of LTD4 depends on the activation of cyclooxygenase and possibly the generation of prostaglandins.

Histaminoid responses to atracurium, vecuronium and tubocurarine

Sixty patients scheduled for elective surgery underwent intradermal testing with 0.1 ml of the following solutions diluted in 0.9% saline : vecuronium and tubocurarine (1 in 1,000), atracurium (1 in 1,000 and 1 in 10,000), thiopentone (1 in 100) and also a 0.9% saline control. Thirty minutes later, an area of erythema of greater than 1.5 cm, or a wheal exceeding 1.0 cm in diameter, was recorded as a positive reaction. The patients then randomly received equipotent doses of atracurium, vecuronium or tubocurarine during a standardized anaesthetic induction. Any cutaneous reaction and the percentage fall in systolic pressure three minutes after administration of the relaxant were recorded. In 51 patients plasma IgE levels were measured. The incidence of positive cutaneous reactions to intradermal and intravenous relaxants was significantly different with each agent (p <0.01). The percentage fall in systolic pressure after tubocurarine was significantly different relative to the other two agents (p <0.01). This was regarded as reflecting potency in releasing histamine and placed the relaxants in the same order : tubocurarine, atracurium and vecuronium. The response to intradermal administration was no guide to the subsequent response after intravenous administration of the three relaxants. IgE levels below 15 IU · ml −1 occurred significantly more often in females and were associated with a significantly higher incidence of cutaneous reactions after intradermal atracurium (1 in 1,000 and 1 in 10,000) (p <0.05 and 0.001 respectively) and tubocurarine (1 in 1,000). With these two agents, generalized flushing after intravenous administration was also more common in this group, relative to the normal/high IgE group.

Biologic and immunologic characterization of the soluble skin-test antigen of varicella-zoster virus.

A sensitive method for assay of the potency of the skin-test antigen of varicella-zoster virus was established. Potency was determined by a reverse passive hemagglutination test, and the results correlated well with the cutaneous reaction of sensitized guinea pigs and an immune human adult to the antigen. Cutaneous reactivity was not induced by repeated inoculation of the antigen, but humoral neutralizing antibody was detected in most guinea pigs when a large amount of antigen was used. No cutaneous cross-reactivity between varicella-zoster virus and herpes simplex virus was noted; however, positive cutaneous reactions and neutralizing antibody responses to homologous virus were detected in infected guinea pigs. These results suggest that both skin tests are specific and support the clinical usefulness of the varicella-zoster skin test.

Deposition of ragweed pollen and extract on nasal mucosa of patients with allergic rhinitis: Effect on nasal airflow resistance and nasal mucus velocity

This study was undertaken to ascertain whether nasal mucus velocity (NMV) could be altered by short-term exposure to antigen. Asymptomatic patients with a history of allergic rhinitis who had a positive cutaneous reaction to ragweed extract were investigated. The plan was to achieve approximately a fourfold elevation of nasal airflow resistance (NAR) with antigen challenge and then obtain serial measurements of NAR and NMV. NMV was not significantly altered when the antigen was introduced by nasal inhalation of (1) ragweed pollen grains, (2) nebulized ragweed extract for 10 breaths, and (3) nebulized ragweed extract for 30 min on each of 3 successive days. When ragweed extract was introduced by direct instillation of the solution into the nose, NMV fell below baseline values at either 0.5 or 1.5 hr, or at both times after administration. Persistence of impairment of mucociliary transport at a time when nasal airway constrictor response had dissipated suggested that a chemical mediator might have been responsible for the alteration of clearance. The failure to demonstrate depression of mucus transport with the inhalation studies might have been due to insensitivity of the radiopaque Teflon disk method or to a qualitatively different allergic reaction to direct instillation of antigen solution.