Favorable Prognosis of Wheat Allergy in Adults.

BACKGROUND AND OBJECTIVE: Wheat ingestion can lead to disorders such as IgE-mediated food allergy and wheat-dependent exercise-induced anaphylaxis (WDEIA), both of which are associated with impaired quality of life and significant morbidity. Allergy to wheat is relatively benign in children, although its natural history in adults is still unknown. Objective: We used placebo-controlled challenge to evaluate the natural history of wheat hypersensitivity in atopic patients with adultonset wheat allergy. METHODS: We enrolled 13 patients from an initial cohort of adult patients with IgE-mediated wheat allergy (mean age, 40 years). After diagnosis, the patients observed a wheat-free diet and were followed as outpatients for 5 years to evaluate wheat exposure. Wheat-IgEtiters were determined at the end of follow-up, and a second wheat-challenge was performed. RESULTS: Ten out of 13 patients took part in the study. The mean period of wheat avoidance was 4.2 years. Three patients had spontaneously reintroduced wheat before the second evaluation, after a mean (IQR) of 28 (18-36) months, with only mild gastrointestinal discomfort at reintroduction. At the end of follow-up, 9 of the 10 patients were wheat-tolerant. Two patients had a history of WDEIA. We observed a reduction in IgE levels, with median (IQR) IgE falling from 2.77 (0.35-100) kU/L at diagnosis to 0.88 (0.1-20.8) kU/L. The association between IgE and a negative challenge result was not statistically significant. CONCLUSION: IgE-mediated wheat allergy in adults is benign and represents a temporary break in gastrointestinal tolerance. Future studies may improve our knowledge of wheat allergens, routes of and factors leading to sensitization, and prognostic biomarkers.

Favorable prognosis of wheat allergy in adults

Background: Wheat ingestion can lead to disorders such as IgE-mediated food allergy and wheat-dependent exercise-induced anaphylaxis (WDEIA), both of which are associated with impaired quality of life and significant morbidity. Allergy to wheat is relatively benign in children, although its natural history in adults is still unknown. Objective: We used placebo-controlled challenge to evaluate the natural history of wheat hypersensitivity in atopic patients with adult-onset wheat allergy. Methods: We enrolled 13 patients from an initial cohort of adult patients with IgE-mediated wheat allergy (mean age, 40 years). After diagnosis, the patients observed a wheat-free diet and were followed as outpatients for 5 years to evaluate wheat exposure. Wheat-IgE titers were determined at the end of follow-up, and a second wheat-challenge was performed. Results: Ten out of 13 patients took part in the study. The mean period of wheat avoidance was 4.2 years. Three patients had spontaneously reintroduced wheat before the second evaluation, after a mean (IQR) of 28 (18-36) months, with only mild gastrointestinal discomfort at reintroduction. At the end of follow-up, 9 of the 10 patients were wheat-tolerant. Two patients had a history of WDEIA. We observed a reduction in IgE levels, with median (IQR) IgE falling from 2.77 (0.35-100) kU/L at diagnosis to 0.88 (0.1-20.8) kU/L. The association between IgE and a negative challenge result was not statistically significant.Conclusion: IgE-mediated wheat allergy in adults is benign and represents a temporary break in gastrointestinal tolerance. Future studies may improve our knowledge of wheat allergens, routes of and factors leading to sensitization, and prognostic biomarkers

Introducción: La ingesta de trigo puede originar varias patologías como alergia alimentaria mediada por IgE y la anafilaxia inducida por ejercicio previa ingesta de trigo. Todas ellas originan un descenso en la calidad de vida y una importante morbilidad. La alergia a trigo es relativamente benigna en niños, sin embargo, su historia natural en adultos es aún desconocida. Objetivo: Evaluamos la historia natural de la hipersensibilidad al trigo de inicio en la edad adulta en pacientes atópicos confirmado mediante pruebas de exposición oral. Métodos: Se incluyeron 13 pacientes de una cohorte de pacientes adultos (edad media 40 años) con alergia a trigo mediada por IgE. Tras el diagnóstico los pacientes siguieron una dieta exenta de trigo y fueron seguidos durante 5 años para valorar su tolerancia tras la exposición al trigo. Al final del seguimiento se determinaron los valores de IgE específica a trigo y se realizó una segunda provocación oral con trigo. Resultados: 10 de los 13 pacientes tomaron parte en el estudio. La duración media del periodo de no ingesta de trigo fue de 4,2 años. 3 pacientes reintrodujeron por iniciativa propia la ingesta de trigo antes de la segunda evaluación, después de un periodo medio de 28 meses (RIQ 18-36 meses), presentando solo leves síntomas gastrointestinales. Al final del seguimiento, 9/10 pacientes toleraron la ingesta de trigo. 2 pacientes tenían historia de anafilaxia inducida por ejercicio. Se observó una disminución de los valores de IgE específica desde una mediana de 2,77 kU/l (RIQ 0,35-100 kU/L) en el momento del diagnóstico hasta 0,88 kU/l (RIQ 0,1-20,8 Ku/L) al final del seguimiento. No se observó correlación entre los valores de IgE específica y los resultados de la tolerancia final. Conclusión: La alergia a trigo mediada por IgE en adultos es una patología benigna y representa una interrupción temporal de la tolerancia gastrointestinal. Futuros estudios podrían mejorar nuestro conocimiento sobre los alérgenos del trigo, rutas y factores que llevan a la sensibilización, y biomarcadores de pronóstico

Basal Tryptase Levels Can Predict Clinical Severity in Hymenoptera Venom Anaphylaxis and Ischemic Cardiovascular Disorders

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Hypersensitivity to Tomato (Lycopersicon esculentum) in Peach-Allergic Patients: rPrup 3 and rPrup 1 Are Predictive of Symptom Severity.

UNLABELLED: Background: The role of allergens in the severity of tomato allergy symptoms has not yet been studied. OBJECTIVES: To evaluate the relationship between severe allergic reactions to peach and tomato and between tomato allergy symptoms and the pattern of IgE positivity for rPru p 1, rPru p 3, rPru p 4, rBetv 1, rBetv 2, rBetv4, rPhl p 1, and rPhl p 12 in order to identify the role of recombinant allergens in the severity of reactions to tomato. METHODS: We studied peach-allergic patients with clinical reactions to tomato by performing an open food challenge, skin prick test, and determination of serum specific IgE to tomato and to recombinant peach, birch, and grass allergens. Statistical analysis was carried out to evaluate the relationship between the severity of tomato symptoms and IgE positivity to the different allergens and to peach-induced symptoms. RESULTS: We found a significant association between severe reactions to tomato and severe reactions to peach (P = .01 7) and levels of IgE to rPru p3 (P = .029) and between mild tomato allergy symptoms and levels of IgE to rPru p1 (P = .047), anti-rBetv 1 (P = .0414), anti-rBetv 2 (P = .0457), and Phleum pratense (P = .0022). CONCLUSION: We observed a significant relationship between peach and symptoms of tomato allergy. IgE positivity for rPru p3 seems to be a surrogate biochemical marker for severe tomato allergy, whereas the presence of anti-rPru p 1 IgE may be an indicator of mild tomato allergy.

Two cases of elevated tryptase in abdominal aortic aneurysm.

INTRODUCTION: From the literature, patients with a history of anaphylaxis to hymenoptera venom and positive specific IgE have shown a correlation between elevated tryptase levels and two clinical situations: systemic mastocytosis and an increased risk of reactions to venom immunotherapy or hymenoptera sting. Other clinical scenarios could explain elevated tryptase levels. MATERIAL AND METHODS: A 67 year old male (P1) and a 77 year old male (P2) were evaluated for previous severe anaphylaxis to hymenoptera sting. They underwent standard diagnostic work-up for hymenoptera venom allergy. Having found elevated tryptase levels, these were followed by a bone marrow biopsy to rule out systemic mastocytosis. RESULTS: P1: specific IgE and skin tests were positive for Vespula species; tryptase 52.8 ng/ml; P2: specific IgE and skin tests were positive for Vespa cabro and tryptase 153 ng/ml. Bone marrow biopsy results were negative for mastocytosis. We carried out magnetic resonance imaging, in P1 to better characterize the severe osteoporosis and in P2 because during physical examination a pulsating mass had been identified in the mesogastrium, and an aneurysm of the abdominal aorta which required surgical intervention in both patients was detected. Eight months after surgery, tryptase levels had diminished significantly (P1: 11.6 ng/ml and P2: 14.5 ng/ml). DISCUSSION: The elevated tryptase levels were correlated to abdominal aneurysm in both patients. In fact, post-surgery tryptase levels dramatically decreased. These two cases demonstrate that high tryptase levels in subjects with a history of hymenoptera venom anaphylaxis can be associated to undiagnosed aneurysmatic disease.

Hypersensitivity to tomato (Lycopersicon esculentum) in peach-allergic patients: rPrup3 and rPrup1 are predictive of symptom severity

Antecedentes: La relevancia de los diferentes alérgenos del tomate, en relación a la severidad de los síntomas producidos tras su ingesta, no ha sido aún establecida. Objetivos: Evaluar la relación entre las reacciones alérgicas graves inducidas por melocotón y tomate y entre los síntomas presentados tras ingesta de tomate, y el patrón de sensibilizaciones IgE mediadas frente a rPru p1, rPrup3, rPrup4, rBetv1, rBetv2, rBetv4, rPhlp1 y rPhlp12 con el fin de concretar la responsabilidad de cada uno de los alérgenos en la gravedad de las reacciones producidas por el tomate. Métodos: Dentro de una población de pacientes alérgicos a melocotón seleccionamos aquellos pacientes con antecedentes de reacciones a tomate mediante una provocación oral abierta (OFC), pruebas cutáneas (SPT) e IgE específica a tomate, a alérgenos recombinantes de melocotón y gramíneas. La gravedad de los síntomas producidos por el tomate estaba relacionada con la presencia de IgE frente a los diferentes alérgenos así como a los síntomas causados por la ingesta de melocotón. Resultados: Se halló una asociación significativa entre las reacciones alérgicas graves a tomate con las reacciones graves a melocotón (p = 0,017) así como con los valores de IgE específica a rPrup3 (p = 0,029), en tanto que los valores de IgE específica a rPrup1, rBetv1, rBetv2 y Phleum pratense se relacionaban con síntomas leves tras ingesta de tomate (p = 0,047, p = 0,0414, p = 0,0457, p = 0,0022 respectivamente). Conclusión: Existe una relación significativa entre los síntomas producidos por el melocotón y el tomate. La presencia de IgE específica frente a rPrup3 parece ser un marcador de síntomas graves por alergia a tomate, en tanto que la presencia de IgE específica anti rPrup1 parece ser un marcador de síntomas leves en los pacientes alérgicos a tomate (AU)

Background: The role of allergens in the severity of tomato allergy symptoms has not yet been studied. Objectives: To evaluate the relationship between severe allergic reactions to peach and tomato and between tomato allergy symptoms and the pattern of IgE positivity for rPrup1, rPrup3, rPrup4, rBetv1, rBetv2, rBetv4, rPhlp1, and rPhlp12 in order to identify the role of recombinant allergens in the severity of reactions to tomato. Methods: We studied peach-allergic patients with clinical reactions to tomato by performing an open food challenge, skin prick test, and determination of serum specific IgE to tomato and to recombinant peach, birch, and grass allergens. Statistical analysis was carried out to evaluate the relationship between the severity of tomato symptoms and IgE positivity to the different allergens and to peach-induced symptoms. Results: We found a significant association between severe reactions to tomato and severe reactions to peach (P=.017) and levels of IgE to rPrup3 (P=.029) and between mild tomato allergy symptoms and levels of IgE to rPrup1 (P=.047), anti-rBetv1 (P=.0414), anti-rBetv2 (P=.0457), and Phleum pratense (P=.0022). Conclusion: We observed a significant relationship between peach and symptoms of tomato allergy. IgE positivity for rPrup3 seems to be a surrogate biochemical marker for severe tomato allergy, whereas the presence of anti-rPrup1 IgE may be an indicator of mild tomato allergy (AU)

Characterization of the T-cell epitopes of the major peach allergen Pru p 3.

BACKGROUND: Pru p 3 is the major peach allergen recognized by more than 90% of peach-allergic individuals of the Mediterranean area. Identification of the dominant Pru p 3 T-cell epitopes can improve our understanding of the immune responses against this protein and could be helpful in the development of hypoallergenic immunotherapy. For this purpose, we examined the phenotypes, specificities and cytokine secretion profiles of proliferating T cells in response to Pru p 3 in peach-allergic individuals. METHODS: Peripheral blood mononuclear cells from 15 peach-allergic patients were incubated with Pru p 3. The proliferation of antigen-specific T-cell lines (TCLs) was assessed by tritiated methylthymidine incorporation. T-cell epitopes were identified by analyzing the reactivity of TCLs against 8 overlapping peptides spanning the entire length of Pru p 3. We characterized the phenotype of Pru-p-3-specific TCLs by flow cytometry and analyzed their production of interleukin (IL) 4 and gamma-interferon (IFN-gamma) by ELISA. RESULTS: Ninety-two Pru-p-3-specific TCLs were isolated (stimulation index > or =5). These TCLs proliferated mainly in response to Pru p 3(12-27) and Pru p 3(57-72). Pru-p-3-specific TCLs were mainly CD4+ (81%) and expressed cell surface CD30. In addition, TCLs produced high levels of IL-4 and low levels of IFN-gamma, indicating a Th2 phenotype. CONCLUSIONS: Two immunodominant T-cell-reactive regions of Pru p 3 were identified: Pru p 3(12-27) and Pru p 3(57-72). These peptides showed a differential ability to elicit a Th2 response. Taken together, our results provide a better understanding of the immunological T-cell reactivity against Pru p 3.

Maize food allergy: a double-blind placebo-controlled study.

BACKGROUND: Maize allergy is not very common especially in Europe. The number of studies that address IgE mediated maize allergy is all too few. OBJECTIVE: Evaluate subjects with a history of maize allergy by double-blind, placebo-controlled food challenge; identify the spectrum of symptoms manifested during challenge; determine the lowest provocation dose (PD) during challenge; determine the performance characteristics of maize skin prick test and specific IgE. METHODS: Twenty-seven patients with a history of maize allergy were enrolled to be evaluated by skin test, specific IgE and double-blind placebo-controlled maize challenge. RESULTS: Forty-eight percent of the patients were challenge positive. PD range was 0.1-25 g. Fifty-four percent of the maize allergic subjects had a PD that was < or = 2.5 g; two subjects reacted to 100 mg of maize. Comparison of maize specific IgE levels and skin test results to the challenge results revealed the following (specific IgE level/skin testing): sensitivity 1.00/0.846, specificity 0.077/0.384, positive predictive value 0.520/0.579, and negative predictive value 1.00/0.714. CONCLUSION: Maize is a cause of IgE-mediated allergic reactions to foods in adults and children. Nearly half of the subjects recruited were confirmed by challenge to be allergic to maize. Twenty-three percent of the positive challenge patients manifested symptoms that involved two organ systems, thus fulfilling the criteria for maize induced anaphylaxis. Maize is allergenic and can pose a risk for symptomatic food allergy at a dose of 100 mg.

Screening the allergenic repertoires of wheat and maize with sera from double-blind, placebo-controlled food challenge positive patients.

BACKGROUND: Food allergy to wheat and maize is an increasing factor of deterioration of life quality, especially childhood and can, in rare cases, even induce anaphylaxis. Although omega-5 gliadin from wheat and maize lipid transfer protein have been characterized as major cereal allergens on the molecular level, the list of food allergens is far to be complete. METHODS: To identify the IgE-binding repertoires of wheat and maize we screened respective cDNA libraries displayed on phage surface with sera from patients with a confirmed food allergy. The study included six patients with a positive double-blind, placebo-controlled food challenge (DBPCFC) to wheat, nine patients with a positive DBPCFC to maize, and six patients with anaphylactic reactions after ingestion of wheat. RESULTS: The enriched sequences encoding IgE-binding proteins showed heterogeneous repertoires for both, wheat and maize. The selected wheat repertoire yielded 12, the maize repertoire 11 open reading frames. Among these we identified allergens belonging to already characterized allergens families, such as gliadin, profilin and beta-expansin. Besides, we found novel proteins with high cross-reactive potential, such as thioredoxins, as well as sequences that had so far not been related to cereal allergy at all. The IgE-binding capacity of some selected proteins was evaluated in vitro and cross-reactivity was demonstrated by competition ELISA. CONCLUSION: With regard to the heterogeneity of the characterized sequences as well as to the biochemical nature of the new allergens detected we conclude that wheat and maize-related food allergy is more complex than so far anticipated.

Introducing chemists to food allergy.

Adverse reactions to food may be toxic or non toxic, depending on the susceptibility to a certain food; non toxic reactions that involve immune mechanisms are termed allergy if they are IgE-mediated. If no immunological mechanism is responsible, it is termed intolerance. The following disorders are considered a consequence of food allergy: gastrointestinal reactions (oral allergy syndrome, vomiting, diarrhea, protein-induced enterocolitic syndrome, eosinophilic gastroenteritis); respiratory reactions (rhinitis, asthma, laryngeal edema); cutaneous reactions (urticaria-angioedema, atopic dermatitis); anaphylaxis. There is much recent evidence to consider celiac disease an immunological disorder. Food allergy diagnosis is based on history, SPT, specific IgE, food challenges. DBPCFC is fundamental for diagnosing true food allergy; patients who have had anaphylaxis to food must not undergo DBPCFC. Rapidly progressive respiratory reactions and anaphylactic shock are life-threatening reactions that can be caused by food allergy. The doses of food inducing anaphylaxis can be very low, therefore commercial cross-contamination with an unsuspected food during food processing can be risky for the food allergic patient. The prevention of severe anaphylactic food reactions may lie in interdisciplinary collaboration among allergologists, chemists, food technologists, and experts in food industry research.

Corneal foreign bodies--first aid, treatment, and outcomes. Skills review for an occupational health setting.

Eye injuries from foreign body incidents remain prevalent in the workplace setting. Often the professional nurse provides the first line of treatment. The informal class presented at the authors' facility offered a comprehensive, organized presentation of a common injury encountered in the practice of occupational health nursing. Strenghts of the presentation included handouts demonstrating eye eversion technique and a flip chart summarizing the content to be placed in each medical station as quick reference. One challenge involved presenting the information to all nurses. The site encompasses four locations and some nurses function as the only staff in the plant for a given shift. With the support of administration and some creative scheduling, 10 of 17 nurses attended one of three classes offered in one morning, and the remaining 7 were able to view the class on videotape. Videotaping the presentation also provided material for future orientation, as well as an opportunity for review. Overall analysis found this a worthwhile offering relevant to practice. A brief formal written evaluation indicated the objectives for the class were achieved and elicited subjects for future topics. Informal chart reviews to check for documentation of visual acuity testing and eversion of the upper lid for foreign body injuries is another outcome measure currently in progress. In addition, a performance improvement project could be accomplished easily by retrospective chart review of assessment and treatment documentation, and tracking of revisits and referrals. Knowledge of current standards in the assessment, first aid, and treatment of eye injuries is every occupational health nurse's responsibility. However, prevention of foreign body injuries is far superior to any treatment modality available. As highly visible leaders within the occupational setting, nurses can be advocates and role models for safe work practices. Occupational health nurses may promote safe eye practices by actively seeking collaboration with safety departments to continuously monitor and improve eye injury and outcome statistics and use of protective eye-wear. By consistently wearing proper safety eyewear, such as approved goggles or prescription safety glasses with side sheilds, during each and every venture into the work area, occupational health nurses provide a strong role model and have the opportunity to educate employees and encourage safe work practices. It is important to encourage shared responsibility and awareness between workers and management for prevention of foreign body incidents and prompt, accurate treatment when necessary to promote optimal outcome.

Hazelnut allergy: a double-blind, placebo-controlled food challenge multicenter study.

BACKGROUND: Tree nuts are a common cause of food allergy in Europe. However, few studies deal with real food allergy to hazelnuts in subjects believed to be allergic to this food. OBJECTIVE: We sought to select subjects with a history of allergic reactions on ingestion of hazelnut and determine how many of these have true allergy by means of the double-blind, placebo-controlled food challenge (DBPCFC). METHODS: Eighty-six subjects with a history of symptoms after hazelnut ingestion were recruited from 3 allergy centers (Milan, Zurich, and Copenhagen). All subjects underwent skin prick tests (SPTs) with aeroallergens and hazelnut, as well as having their specific hazelnut IgE levels determined. Diagnosis of clinical relevant food allergy was made on the basis of the DBPCFC. RESULTS: Sixty-seven (77.9%) of 86 subjects had a positive DBPCFC result; 8 were placebo responders, and 11 were nonresponders. Of the 11 nonresponders, 4 had positive open-challenge test results. Of the DBPCFC-positive subjects, 87% also had positive skin test responses to birch pollen extract. Specific IgE determination for hazelnut (positive CAP response >/=0.7 kU/L [ie, class 2]) showed a sensitivity of 0.75, a positive predictive value (PPV) of 0.92, a specificity of 0.16, and a negative predictive value (NPV) of 0.05. Skin tests with commercial hazelnut extract produced a sensitivity of 0.89, a PPV of 0.92, a specificity of 0.05, and an NPV of 0.05. Skin tests with natural food produced a sensitivity of 0.88, a PPV of 0.94, a specificity of 0.27, and an NPV of 0.15. CONCLUSION: This study shows that hazelnut is an allergenic source that can cause real food allergy, as confirmed by DBPCFC. Skin and IgE tests demonstrated reasonable sensitivity and PPV but a very low specificity and NPV, thus implying that these should not be used to validate the diagnosis of food allergy to hazelnut.

Occupational asthma and rhinitis caused by 1,2-benzisothiazolin-3-one in a chemical worker.

We report a case of occupational asthma and rhinitis caused by inhalation of 1,2-benzisothiazolin-3-one, an additive used as a microbicidal in detergent production, in a 26-year-old man employed in a chemical factory producing detergents. The subject's task consisted of pouring raw materials into the recipient of a machine which mixed the substances. Two months after the beginning of this job the patient complained of rhinitis and asthma at the workplace. The specific challenge test with 1,2-benzisothiazolin-3-one, one of the raw materials to which the subject was exposed, provoked an immediate prolonged asthmatic response and nasal symptoms, whereas exposure to other agents (e.g., alpha-amylase, alcalase or bezalkonium chloride) to which the patient was also exposed at work did not. To our knowledge this is the first case of occupational asthma and rhinitis caused by this compound.

Bronchial responsiveness to ultrasonic "fog" in occupational asthma due to low molecular weight chemicals.

BACKGROUND: In a previous work we have demonstrated that the use of an indirect stimulus such as ultrasonically nebulized distilled water (UNDW, "fog") challenge, in addition to methacholine, in the assessment of occupational asthma due to TDI improves our ability in detecting sensitized subjects. OBJECTIVE: In the present study we aimed to determine the validity of "fog" in the assessment of occupational asthma induced by various low molecular weight substances. METHODS: Fourty subjects exposed to low molecular weight substances with work-related respiratory symptoms underwent methacholine, UNDW and specific bronchial challenge tests. Diagnosis of occupational asthma was made in 20 of 40 patients who developed bronchoconstrictive responses to the specific challenges (reactors). Sensitivity and specificity of UNDW alone, of methacholine alone, and of the combination of the two tests were determined at two different cutpoints of PD20FEV1 of methacholine, with the results of the specific challenge as the "gold standard". RESULTS: Frequency and severity of bronchial hyperresponsiveness both to UNDW and to methacholine were significantly higher in reactors than in nonreactors. Ultrasonically nebulized distilled water had higher specificity (80% versus 60%) but lower sensitivity (65% versus 75% to 90%) than methacholine. As compared with methacholine alone, the combination in series of the two challenges (both challenges positive) substantially improved specificity (85% versus 60%). CONCLUSIONS: In conclusion, in the assessment of low molecular weight chemical-induced asthma diagnosed with the specific challenge as the "gold standard," UNDW challenge proves more specific than methacholine for occupational asthma, but it is considerably less sensitive. The combination of the two challenges results in very high sensitivity and high specificity for occupational asthma, therefore, although further investigations are required for the definitive diagnosis, it should be regarded as a useful means to confirm objectively a suggestive history.

Comparative prognostic value of Ki-67 and MIB-1 proliferation indices in breast cancer.

BACKGROUND: Tumor proliferation index was evaluated in 246 samples of breast carcinoma using Ki-67 and MIB-1 monoclonal antibodies on frozen and paraffin sections, respectively, with the purpose to compare the two proliferation indices from both a quantitative and prognostic point of view. MATERIALS AND METHODS: All determinations were performed with the same immunohistochemical procedure (Avidin-Biotin Complexes). The prognostic relevance of tumor proliferation index, defined by both the antibodies, was investigated in 127 patients. Ki-67 and MIB-1 median values were used to obtain two groups of patients at different risk and life-table analysis (Mantel-Cox) was performed to assess the probabilities of overall survival (OS) and relapse-free survival (RFS). The median time of observation was 61 months. RESULTS: Ki-67 and MIB-1 values were exponentially distributed with overlapping ranges varying from 2% to 90%. Ki-67 mean and median values were 16.7% and 14.0%, respectively, compared to 22.5% and 20% for MIB-1. Ki-67 and MIB-1 mean values were statistically different (t = -4.396; p < 0.001), while no difference was observed for MIB-1 mean values on frozen and paraffin sections (t = 1.35; p = n.s.). Ki-67 and MIB-1 values were statistically correlated (Spearman's coefficient = 0.75; p < 0.0001) and directly associated (agreement rate = 79.3%; p < 0.0001). Patients with tumors having a high proportion of MIB-1 positive cells showed a higher 5-year probability of relapse of disease (43.7% versus 27.6%; p = 0.02) and death (35.4% versus 15.8%; p = 0.007) than those with a low one. In parallels Ki-67 was found to be prognostically relevant for OS (32.2% versus 16.2%; p = 0.02) but not for RFS (40.7% versus 27.9%; p = 0.10). CONCLUSIONS: Such results indicate that the detection of proliferative activity on paraffin sections with MIB-1 monoclonal antibody provides in formation analogous to or even better than that obtained with Ki-67 antibody on frozen ones. Moreover, it represents a valuable tool to obtain kinetic data on "routine" histological samples and, above all, to give prognostic evaluations on the clinical outcome of breast cancer patients.

Occupational asthma, rhinitis and urticaria due to piperacillin sodium in a pharmaceutical worker.

A 28 year old man with no history of atopy was referred to our hospital for possible work-related asthma. He had been employed in the production section of a pharmaceutical company for 2 yrs, and in the last 2 months he had complained of dyspnoea, wheezing, chest tightness, symptoms of rhinitis and a cutaneous rash when exposed to powdered antibiotics. Symptoms disappeared after being transferred to the packaging section. When the subject was admitted to our department he was asymptomatic. Basal lung function tests were in the normal range. Bronchial challenges with methacholine and with ultrasonically-nebulized distilled water were negative. Skin-prick test with piperacillin sodium gave a strong positive response at a very low concentration. Specific inhalation challenge with piperacillin sodium resulted in an immediate asthmatic reaction, and also reproduced rhinitis symptoms and the cutaneous rash. A control challenge with lactose, and the specific challenge test with cefuroxime sodium (another antibiotic to which the patient was exposed at the workplace) were negative. We conclude that piperacillin sodium is an agent that can cause occupational asthma.

Effects of nedocromil sodium on bronchospasm and HS-NCA release induced by allergen inhalation in asthmatic patients.

The aim of this study was to assess the ability of nedocromil sodium (NS) to prevent the immediate asthmatic reaction and the increase in the serum level of heat stable neutrophil chemotactic activity (HS-NCA) induced by antigen inhalation. In a double-blind, cross-over study, 13 atopic subjects affected with seasonal asthma underwent a bronchial provocation test with a preselected dose of grass pollen allergen (enough to cause a decrease of > or = 20% in FEV1:FEV1 PD20) after pre-treatment with 4 mg NS or placebo. Serum samples were withdrawn from 11 subjects for HS-NCA determination. After NS administration the decrease in FEV1 was significantly less than after placebo administration at all time points after challenge (2 min P = 0.0004; 7 min, P = 0.0005; 17 min P = 0.0002 and 27 min P = 0.0005). The percentage increase in HS-NCA was significantly higher after placebo than after NS inhalation, both 10 (P = 0.0048) and 20 (P = 0.0068) min after challenge. Our study confirms previous investigations, showing that NS inhibits the immediate asthmatic response to allergen inhalation in atopic, asthmatic subjects and moreover it shows that this drug prevents in vivo the increase of the serum HS-NCA. This last finding has not been previously reported.