Skin testing for immediate hypersensitivity to betalactams: comparison between two commercial kits.

INTRODUCTION: Skin testing with major and minor determinants of benzylpenicillin is the recommended standard practice to evaluate subjects with immediate hypersensitivity to betalactams. The withdrawal of these products from the market has set us back to the early days, before the introduction of reagents for in vivo testing. OBJECTIVES: To compare a recently released kit of benzylpenicillin conjugated to poly-l-lysine (PPL) and minor determinants mixture (MDM) with the previously existing kit in a positive control group of subjects sensitized to major and/or minor determinants of benzylpenicillin. METHODS: Skin tests with both kits were made in a group of positive subjects previously diagnosed with immediate hypersensitivity to penicillins and with positive results to PPL and/or MDM and in a negative control group. Radioallergosorbent test (RAST) inhibition assays with a pool of sera and individual samples were carried out to compare the inhibition capacity of PPL and MDM of both kits. RESULTS: Of 22 cases selected from our historical group, 14 were positive: eight to PPL, three to MDM and three to both. These results were equivalent for both kits. RAST inhibition studies showed similar potencies in the inhibition of PPL and MDM. CONCLUSIONS: Both tests show similar results in terms of RAST inhibition assays and skin tests sensitivity and specificity in the groups selected. The new assay can be used for the same purpose and indications as the previous test.

Identification and quantification of isoquinoline alkaloids in the genus Sarcocapnos by GC-MS.

Six cularine alkaloids, cularicine, O-methylcularicine, celtisine, cularidine, cularine and celtine, three isocularine alkaloids, sarcophylline, sarcocapnine and sarcocapnidine, and five non-cularine alkaloids, glaucine, protopine, ribasine, dihydrosanguinarine and chelidonine, were identified and quantified by GC-MS in nine taxa of the genus Sarcocapnos (Fumariaceae). The chemotaxonomic significance of the results is discussed.

Direct determination of alkaloid contents in Fumaria species by GC-MS.

The isoquinoline alkaloids protopine, cryptopine, sinactine, stylopine, bicuculline, adlumine, parfumine, fumariline, fumarophycine, fumaritine, dihydrofumariline, parfumidine and dihydrosanguinarine have been determined and identified by gas chromatography-mass spectrometry in Fumaria agraria, F. bastardii, F. capreolata, F. sepium, F. densiflora, F. faurei, F. officinalis subsp. officinalis, F. parviflora, F. petteri subsp. calcarata and F. macrosepala. The chemotaxonomic significance of the results is discussed.

Immediate allergic reactions to cephalosporins: cross-reactivity and selective responses.

BACKGROUND: After penicillins, cephalosporins are the most important beta-lactams inducing IgE-mediated reactions. Responses may be selective or cross-reactive with common beta-lactam determinants. Unlike determinants derived from benzylpenicillin, cephalosporin allergenic determinants have not been properly identified, even though a wide variety of these beta-lactams is currently used. OBJECTIVE: We sought to evaluate the IgE response in subjects with immediate allergic reactions to injectable cephalosporins and to assess their reactivity to different penicillins and cephalosporins. METHODS: We studied 30 subjects with immediate reactions to one or more of the following cephalosporins: ceftriaxone, cefotaxime, ceftazidime, and cefuroxime. Skin tests and in vitro-specific IgE antibody assays were performed for major and minor determinants of penicillin G, amoxicillin, and ampicillin, as well as for the culprit cephalosporins. Responses to cephalosporins other than the culprit ones were also studied by using skin testing. RESULTS: Twenty-six patients (group A, 86.7%) displayed skin test and RAST negativity to penicillin determinants and skin test positivity to cephalosporins, with RAST confirmation in 9 patients. Four subjects (group B, 13.3%) had a positive response to penicillin determinants. In group A two patterns of reactivity were observed: one characterized by a response only to the culprit cephalosporin (n = 15, 57.7%) and the other by positive responses to different cephalosporins, including the responsible cephalosporins (n = 11, 42. 3%). CONCLUSION: Most patients with a history of immediate reactions to cephalosporins are sensitized to determinants generated only by cephalosporins (group A), although a small percentage react to penicillin determinants (group B). Some patients from group A responded only to the culprit cephalosporin, but others reacted to different cephalosporins. These findings can be explained in terms of either selective response to unique determinants or cross-reactivity.

Omeprazole and ranitidine in long-term treatment of duodenal ulcer: a double-blind comparison of length of time in remission.

In most patients duodenal ulcer is a chronic relapsing disease. If no active maintenance treatment or eradication therapy is given after healing, around 70-100% of patients have a relapse during the first year. We conducted a double-blind multicenter study in 472 patients with duodenal ulcer. They were treated with omeprazole 20 mg every morning for four or eight weeks and when healed were randomly allocated to maintenance treatment with either omeprazole 20 mg every morning or ranitidine 150 mg at bedtime for up to six months. The patients were assessed by endoscopy at monthly intervals until healing occurred. Thereafter scheduled endoscopy was carried out after 1, 3, and 6 months of maintenance treatment or immediately in the event of a suspected relapse. Healing status (intention to treat approach) was 87% at four weeks and 93% at eight weeks. At six months the estimated remission rate was 90% for omeprazole and 82% for ranitidine (P = 0.03, 95% CI 1-15%). The incidence of adverse events was similar during the two maintenance treatments. Treatment with omeprazole 20 mg every morning maintained significantly more patients in remission than treatment with ranitidine 150 mg at bedtime.

Studies of the specificities of IgE antibodies found in sera from subjects with allergic reactions to penicillins.

Penicillins are immunogenic when administered to humans and in some instances they can also be allergenic, inducing specific IgE antibodies. Whilst the major haptenic group, the penicilloyl, is well characterised, less is known about the relative importance of the different parts of the structure for antibody binding and how this can influence the specificity of patients response. In order to investigate this further, sera from subjects who had suffered an IgE-mediated reaction to penicillins were studied using the radioallergosorbent test (RAST) and RAST inhibition. The assays employed reagents related to the penicillins causing the reaction. Using 173 sera, positive RAST results were only found with reagents based on benzyl penicillin (BP) and amoxicillin (AX). Fifty-three positive sera were selected for further studies and categorized into three groups: (A) sera only RAST positive to AX, (B) sera only positive to BP and (C) sera positive to both penicillins. RAST inhibition studies were then carried out using monomeric penicilloyl conjugates and compounds representing parts of the penicilloyl structures of BP and AX. For all three groups, monomeric penicilloyl conjugates were the most efficient inhibitors but there were differences for the other compounds. Group A sera were also inhibited by the side chain amoxicillin, whereas group B sera were poorly inhibited by all other inhibitors. Group C sera showed two patterns of inhibition, both consistent with their more cross-reactive profile.

Determination of IgE antibodies to the benzyl penicilloyl determinant. A comparison between poly-L-lysine and human serum albumin as carriers.

The influence of two different carriers, poly-L-lysine (PLL) and human serum albumin (HSA) in the binding of specific IgE antibodies to the benzyl penicilloyl hapten (BPO) was determined in a solid-phase assay. Serum samples from patients with a history of immediate reaction to penicillin and which had shown the presence of IgE antibodies to BPO were used. Benzyl penicilloyl derivatized cellulose discs were prepared using PLL of different molecular weight and HSA as carriers. These were treated with different molar ratios of benzyl penicillin. These reagents were compared for uptake of BPO-specific IgE using a pool of sera in a radioallergosorbent test (RAST) type assay. Two PLL systems and two HSA systems were finally compared using 26 individual sera. RAST values were compared by Kruskal-Wallis and Wilcoxon tests. The relationships between the four different assays were evaluated by determining Pearson correlation coefficients and the concordance by determining intraclass correlation coefficients (ICC). Analysis of means by the Wilcoxon test revealed significant differences (P less than 0.01) only when the different carrier assays were compared. The correlation coefficients between all the assays were significant (P less than 0.0001), but the ICC was low when the different carrier assays were compared. These results indicate that the nature of the carriers studied (PLL and HSA) influences the capacity for binding IgE antibodies in the RAST procedure. The differences observed indicate that one conjugate cannot be substituted for the other in the determination of IgE antibodies to BPO and that BPO-PLL is preferable.

Differences in serum IgE antibody activity to benzylpenicillin and amoxicillin measured by RAST in a group of penicillin allergic patients.

To determine the influence of the acyl side chain on the IgE antibody specificity of the two most common penicillins inducing allergic reactions in our community, benzylpenicillin (BP) and amoxicillin (AX), IgE positive sera from a group of 24 patients allergic to penicillin were studied. RAST was determined in parallel to benzyl penicilloyl-polylysine (BPO-PLL) and amoxicilloyl-polylysine (AX-PLL) in each serum, and values greater than an established coefficient of variation of 15% were considered as different for either of the haptens used (BP and AX). 16 sera proved to be more positive to BP (Group A), six to AX (Group B) and in two IgE was positive to both haptens with a similar value (Group C). RAST titration concentration effect curves and RAST inhibition studies with a pool of sera from each group (A, B, C) and individual sera showed that most of them were more specific for either BPO or AX, a minority being of similar value to both. These findings indicate that the side chain structure of penicillins is relevant in the constitution of the antigenic determinant, although in some instances the common chemical structure of betalactam is recognised mainly by the IgE antibodies. The clinical relevance of these data needs to be established.

Angioedema and IgE antibodies to aspirin: a case report.

We present a case of a patient who developed two episodes of angioedema after taking acetylsalicylic acid orally. Specific IgE antibodies to acetylsalicylic human serum albumin (ASA-HSA) were found. A control group of 37 patients with aspirin intolerance was studied and evidence of specific IgE antibodies was not found. The follow-up of this case shows that in a short period of time the level of specific IgE antibody decreases to undetectable levels similar to the negative control population.

Cross-reactivity between penicillins and cephalosporins: clinical and immunologic studies.

Nineteen well-characterized penicillin-allergic patients were investigated for their sensitivity to cephalosporins containing potentially cross-reactive side chains. All patients were administered cephamandole parenterally and, if this was tolerated, a course of oral cephaloridine was administered. Only two patients responded to the cephamandole; none of the remaining patients reacted to cephaloridine. Benzylpenicilloyl RAST-inhibition studies with sera from three subjects who had not reacted to the cephalosporins demonstrated that cephamandole linked to proteins was capable of recognizing benzylpenicilloyl-specific IgE antibody. It is concluded that consideration of side chain structures can help to predict possible cross-reactions between penicillins and cephalosporins, but carefully controlled challenge tests are advisable before penicillin-allergic patients are treated with cephalosporins. In relation to cross-reacting potential, in vitro experimental studies are difficult to interpret and may in some circumstances overestimate the risk.

Anaphylaxis to amoxycillin but good tolerance for benzyl penicillin. In vivo and in vitro studies of specific IgE antibodies.

Three patients are reported on who suffered anaphylactic reactions after amoxycillin (AX) treatment and challenge but tolerated benzylpenicillin (BP) parenterally and orally. Two of the three patients had positive skin tests and RAST to AX reagents but negative responses to benzyl penicilloyl (BPO) specific skin tests and RAST and the minor determinant mixture (MDM) skin test reagent. The third case was negative to all skin tests and RAST. RAST and RAST inhibition on the two positive sera suggest that the response is related to the acyl side chain of AX.

[Scleroderma and Rendu-Osler disease. A casual association? (author's transl)]. / Esclerodermia y enfermedad de Rendu-Osler: una asociación casual?

An uncommon association of scleroderma and Rendu-Osler disease in the same patient is reported. The authors have not found similar descriptions after an extense bibliographic review. A possible relationship is suggested on the basis of the etiopathogenesis of both disorders; Rendu-Osler syndrome is an hereditary disease of unknown etiology with mesoblastic involvement (embryonic tissue which gives origin to the connective tissue), and scleroderma is an immune disease characterized by diffuse sclerosis of the connective tissue. Rendu-Osler disease was diagnosed because of the presence of angiomatous telangiectasias since childhood, recurrent mucosal hemorrhages, and the possible existence of the syndrome in a familial member. The diagnosis of scleroderma was supported by the demonstration of: 1) cutaneous infiltration, 2) Raynaud's phenomenon, 3) functional esophageal alterations with clinical dysphagia, 4) resorption of the distal phalanges, and 5) conclusive skin biopsy.