Pharmacokinetic interaction between methotrexate and piperacillin/tazobactam resulting in prolonged toxic concentrations of methotrexate.
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Anti-Bacterial Agents↗
Biomedical subjects
R Ariano
Publications and source records attributed to R Ariano.
Randomized double-blind controlled study with sublingual carbamylated allergoid immunotherapy in mild rhinitis due to mites.
BACKGROUND: The clinical efficacy of sublingual immunotherapy (SLIT) in mite allergy and in mild disease is still a matter of debate, thus we performed a long-term clinical trial. METHODS: The study was randomized, double-blind and placebo-controlled. After a 1-year assessment, 68 patients with mild rhinitis with/without asthma due to mites were randomized to drugs + placebo or drugs + SLIT for 2 years. Sublingual immunotherapy was given as soluble tablets of monomeric carbamylated allergoid. Clinical scores for asthma and rhinitis (0, absent to 3, severe) and drug consumption were assessed by diary card in the period November-February. Quality of life was assessed before and after each observation period and pharmaco-economy data were evaluated as well. RESULTS: Fifty-six patients completed the study. The rate of dropouts was similar in the two groups. No relevant side effect was reported. There was a significant reduction of total clinical scores (P < 0.05) in the active group vs placebo at the first year, but not at the second whereas nasal obstruction significantly improved in both years (P < 0.05). The reduction of drug intake score was significant only at the first year. No change was observed concerning most of the Short Form-36 items, because at baseline all patients displayed a normal profile. A significant change in SLIT group was seen for the item 'change in health status'. The need for extra visits was significantly lower in the active group (25%vs 43%). CONCLUSIONS: Sublingual immunotherapy was clinically effective and safe in mite-induced mild disease.
Administration, Sublingual↗
Practice parameters for sublingual immunotherapy.
The efficacy and safety of sublingual immunotherapy (SLIT) are currently supported by clinical trials, meta-analysis and post-marketing surveys. Practice parameters for clinical use of SLIT are proposed here by a panel of Italian specialists, with reference to evidence based criteria. Indications to SLIT include allergic rhinoconjunctivitis, asthma, and isolated conjunctivitis (strength of recommendation: grade A). As to severity of the disease, SLIT is indicated in moderate/severe intermittent rhinitis, persistent rhinitis and mild to moderate asthma (grade D). SLIT may be safely prescribed also in children aged three to five years (grade B), and its use in subjects aged more than 60 years is not prevented when the indications and contraindication are ascertained (grade D). The choice of the allergen to be employed for SLIT should be made in accordance with the combination of clinical history and results of skin prick tests (grade D). Polysensitisation, i.e. the occurrence of multiple positive response does not exclude SLIT, which may be done with the clinically most important allergens (grade D). As to practical administration, co-seasonal, pre co-seasonal, and continuous schedules are available, being the latter recommended for perennial allergens or for pollens with particularly prolonged pollination, such as Parietaria (grade D). For pollens with relatively short pollination, such as grasses and trees (cypress, birch, alder, hazelnut, olive) the pre co-seasonal and perennial schedules are preferred (grade C). The build-up phases suggested by manufacturers can be safely used (grade A), but they can be modified according to the patient's tolerance (grade C). A duration of SLIT of 3-5 years is recommended to ensure a long-lasting clinical effect after the treatment has been terminated (grade C).
Administration, Sublingual↗
Occupational respiratory allergy to cyclamen pollen: a case report.
A case of cyclamen (Cyclamen persicum) pollen allergy is described on a flower cultivator. The diagnosis was assessed by skin test, methacoline test, nasal provocation test and RAST. SDS-PAGE and immunoblotting have shown an intense response against a 18 kDa component and a weaker one at 100 Kda. A RAST inhibition against Cupressus sempervirens and Acacia floribundia showed no identity with cyclamen. This case confirm the cyclamen allergenity, in professional exposure. The nasal challenge prove to be very useful to confirm allergic sensitizations an we emphasize the necessity of preventive measures of protection for those florists who cultivate cyclamen plants.
Agricultural Workers' Diseases↗
In vitro and in vivo biological activities of old and fresh Cupressus arizonica pollen.
BACKGROUND: Respiratory allergy to the pollen of Cupressaceae is becoming more and more common every year in the Mediterranean area. OBJECTIVE: The purpose of this study was to see whether the allergenic potency of Cupressus arizonica pollen diminished after a 6-year period (1994-2000). MATERIALS AND METHODS: Among the Cupressaceae, we selected the pollen of C arizonica. The mode of sampling in 1994 and in 2000 was the same and the pollen was collected on the same tree and stored at room temperature. To compare its biological and allergenic activities data was collected with the following methods: cytohistology of Alexander, 2,3,5-triphenyltetrazolium chloride enzyme staining, skin testing, nasal provocation test, radioallergosorbent test (RAST), RAST inhibition, sodium dodecyl sulfate polyacrylamide gel electrophoresis, and immunoblotting to detect protein content. Thirty-eight patients with respiratory allergy to Cupressaceae were selected. RESULTS: We found no decrease in the allergenic potency of the pollen, but did find that viability and germinating power had disappeared completely after 30 to 40 days. Moreover, the amount of protein in the old pollen was half the amount found in the fresh one. Skin prick testing showed identical results with the old and the fresh pollens. CONCLUSIONS: The allergenic in vivo and in vitro activity of cypress pollen is retained for years after its collection. This activity seems to be independent of the viability of pollen grains and of the total protein content. This may explain the presence of clinical symptoms in patients out of the pollen season.
Adult↗
Evaluation of cross-reactivity between Holoptelea integrifolia and Parietaria judaica.
BACKGROUND: Holoptelea integrifolia and Parietaria judaica belong to the family Urticaceae, but are geographically distantly located. H. integrifolia is an important pollen allergen of India and sensitizes almost 10% of the atopic population in Delhi. P. judaica, on the other hand, is a very dominant pollen allergen of the Mediterranean region, sensitizing almost 80% of the allergic population. Since both these important pollen allergens belong to the family Urticaceae, the objective of the present study was to assess cross-reactivity between these two pollen allergens from different geographical regions. METHODS: Cross-reactivity between these two pollen allergens was assessed on the basis of skin prick tests and ELISA, ELISA inhibition and immunoblot inhibition studies. RESULTS: Out of 44 atopic Indian patients skin prick tested with H. integrifolia extract, 34% were found to be sensitized. All the patients sensitized to H. integrifolia also showed varying degrees of skin positivity to P. judaica pollen extract. ELISA and ELISA inhibition studies suggested strong cross-reactivity between H. integrifolia and P. judaica pollen. Immunoblot inhibition studies revealed that 14-, 16-, 28-, 38-, 42- and 46-kDa proteins are the cross-reactive proteins in H. integrifolia and P. judaica. However, Par j 1, the major allergen of P. judaica, is absent in H. integrifolia pollen. CONCLUSION: H. integrifolia and P. judaica pollens share cross-reactive as well as unique epitopes. The major allergen of P. judaica, Par j 1, seems to be absent in H. integrifolia pollen allergen.
Allergens↗
Immunological characterization of a recombinant tropomyosin from a new indoor source, Lepisma saccharina.
BACKGROUND: The presence of specific IgE antibodies to invertebrates is common among patients with rhinitis and asthma. Tropomyosin has been described as an invertebrate cross-reactive allergen. We have recently characterized an allergenic extract from silverfish (Lepisma saccharina). Since this insect could be a new source of tropomyosin in the indoor environment, we have thought important to clone and characterize the tropomyosin from it. METHODS: Recombinant tropomyosin was cloned and characterized by means of immunoblotting with tropomyosin-specific monoclonal antibodies, rabbit polyclonal antibodies and IgE from allergic patients. Its allergenic activity was investigated in histamine release assays. Immunoblotting and ELISA inhibition were carried out to identify the natural tropomyosin in the silverfish extract and to study the cross-reactivity among other arthropod tropomyosins. RESULTS: Tropomyosin-specific antibodies recognized in immunoblotting the natural tropomyosin in the insoluble fraction of silverfish extract. The silverfish tropomyosin (Lep s 1) was cloned and fully expressed. It shared high homology with other arthropod tropomyosins. rLep s 1 was recognized by tropomyosin-specific monoclonal and polyclonal antibodies and by IgE of allergic patients. It was able to inhibit the IgE binding to the insoluble fraction of silverfish extract, and to induce histamine release by an arthropod-allergic serum. Inhibition experiments revealed IgE cross-reactivity between rLep s 1 and other arthropod tropomyosins. CONCLUSION: rLep s 1 is the first allergen cloned and characterized from silverfish extract. It enabled us to identify the natural counterpart in the insoluble fraction of silverfish extract, suggesting that the tropomyosin is not readily extractable with a classic aqueous extraction procedure. rLep s 1 displayed biological activity, suggesting that it could be regarded as a useful tool to study the role of silverfish tropomyosin in the sensitization to invertebrate allergic sources.
Allergens↗
Efficacy of sublingual coseasonal immunotherapy with a monomeric allergoid in Cupressaceae pollen allergy--preliminary data.
BACKGROUND: Respiratory allergy to conifers pollens is a growing phenomenon all over the world (Mediterranean area, USA, Japan). In France and Italy Cupressus sempervirens is the commonest offender. OBJECTIVE: To check the efficacy of specific immunotherapy by the sublingual route using a monomeric allergoid of Cupressus Arizonica pollen. MATERIAL AND METHODS: 20 patients and 10 controls were randomly selected. The diagnosis was assessed on a clinical hivernal symptomatology of allergic rhinitis, and/or asthma, positive skin test and RAST, and nasal provocation test to Cupressus arizonica. The extract was a monomeric allergoid titrated in allergenic units (AU). The treatment was coseasonal from the beginning of december to the end of march. It was not conducted double blind. RESULTS: The evaluation of the allergenic potency of native and modified Cupressus arizonica extracts have shown that the modified extract has a decreased skin test IgE binding capacity. According to symptom, drug consumption scores and nasal provocation test, there was a statistical improvement in the active group (compared to the control group) without any side effect. DISCUSSION: The use of a modified Cupressus arizonica extract, which is easier to prepare than Cupressus sempervirens and which is a monomeric allergoid, has shown that by the sublingual route, this therapeutic approach is safe and that the first results were satisfactory without any side effect. This good tolerance was anticipated by the fact that, checked on 16 volunteers by skin test, the allergoid gave a less important local reaction on skin testing than the native extract. CONCLUSION: This study has shown that: The KCNO modified Cupressus arizonica extract has a reduced IgE binding capacity; This monomeric allergoid is safe and effective administrated by the oromucosal route in clinical respiratory allergy to Cupressaceae and devoid of any side effect.
Administration, Sublingual↗
Where do we stand: the basic treatment of asthma and atopy: are we making backward progresses?
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Allergens↗
Efficacy and safety of specific immunotherapy to mosquito bites.
BACKGROUND: Adverse effects of mosquito bites are often very unpleasant and need a treatment. OBJECTIVE: To evaluate the efficacy of specific immunotherapy (S.I.T) with an extract of the whole body of the mosquito Aedes communis. METHOD: Twenty patients having strong local immediate and delayed reactions with in many cases also an allergic rhinitis, were selected. A similar control group was included. In all these patients skin tests, RASTs and nasal provocation tests were carried out with an extract of Aedes communis and a battery of the commonest allergens in our area including two insects : Blatella germanica (german cockroach) and Gasterophilus intestinalis (horse fly). The specific immunotherapy was carried out by the conventionnal subcutaneous route. RESULTS: After 18 months of S.I.T all the patients reported the disappearance of local reactions and symptoms of allergic rhinitis, which was correlated with a statistically improvement of symptom and drug consumption scores and a decrease of allergenic reactivity by the nasal provocation test. CONCLUSIONS: S.I.T with an extract of Aedes communis produced after 18 months of treatment a significant improvement of allergic symptoms, a decrease of symptom and drug consumption scores and of allergen specific nasal reactivity. S.I.T in mosquito bite allergy appears to be effective and safe in the treatment of both cutaneous and respiratory symptoms.
Adolescent↗
An underestimated cause of respiratory allergy: inhalant arthropods and invertebrates allergy (with the exclusion of mites).
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Air↗
Comparison between the native glycosylated and the recombinant Cup a1 allergen: role of carbohydrates in the histamine release from basophils.
BACKGROUND: Cypress pollinosis is an important cause of respiratory allergies. Recently, the Cupressus arizonica major allergen, Cup a1, has been cloned and expressed. The native counterpart of this allergen has been purified and characterized by our group. It has been suggested that sugar moieties play a role in the in vitro IgE binding on Cupressus arizonica pollen extract. OBJECTIVE: To characterize the immunoreactivity of the recombinant major allergen in comparison with its native counterpart. To evaluate the role of carbohydrate moieties in the IgE-mediated in vitro histamine release from basophils by using the native glycosylated Cup a1 as compared with the recombinant one. METHODS: Recombinant Cup a1 was expressed in E. coli. IgE reactivity of Cupressaceae-allergic patients on the native as well as the recombinant molecule was investigated by immunoblotting, ELISA experiments and histamine release test from passively sensitized basophils. RESULTS: Fourteen out of 17 Cup a1-positive sera had IgE antibodies reactive with the native molecule only and lost their reactivity-after periodate deglycosylation of the allergen. Moreover, only native molecule was capable of inducing histamine release by this group of sera. Both the recombinant and the native molecules were recognized by three out of the 17 sera and were equally capable of triggering degranulation. CONCLUSION: A large number of sera reactive with the major allergen recognize carbohydrate epitopes only. IgE from these sera are able to induce histamine release from basophils and they might play a functional role in the clinical symptoms of allergy.
Allergens↗
Preparation and characterization of silverfish (Lepisma saccharina) extract and identification of allergenic components.
BACKGROUND: Airborne insect antigens represent important aeroallergens which have been widely investigated. Although it has been demonstrated that house dust contains significant silverfish (Lepisma saccharina) levels, none of the extracts obtained so far has been extensively characterized. Thus, we have prepared and characterized a silverfish extract and investigated its IgE-reactive components by testing the reactivity of sera from patients allergic to inhalant insect allergens. METHODS: The extract from silverfish insect bodies was prepared by homogenizing frozen silverfish in Tris-HCl buffer. The soluble material (Sup) was filtered and the insoluble material (Ppt) was resuspended in 100 mM Tris pH 10.6. The two fractions were characterized by biochemical and immunochemical methods. IgE reactivity was investigated on both fractions before and after periodate treatment. RESULTS: Protein content and total carbohydrates was 2 and 3% w/w for Sup and 1 and 0.3% w/w for Ppt. The SDS-PAGE profile of the two fractions showed a different pattern in the MW range of 5-175 kD. Sup and Ppt, probed with allergic sera, showed a complex pattern of IgE reactivity. When periodate-treated fractions were tested, IgE reactivity was either completely abrogated, reduced or not affected, depending on the allergic serum employed. CONCLUSIONS: The results obtained indicate that the classic aqueous-extraction procedures that have been used up to now for other insects might not be completely satisfactory, since several allergenic components are not soluble at the normally used pH. We developed a dedicated extraction procedure allowing the detection of a certain degree of reactivity in sera negative to allergens extracted following classic procedures.
Allergens↗
Allergenic relevance of Cupressus arizonica pollen extract and biological characterization of the allergoid.
BACKGROUND: Cupressaceae (cypress) pollens can cause pollinosis in winter. However, the lack of specific commercial extracts combined with the early pollination period of cypress trees make a precise diagnosis difficult. The need for a reliable and effective cypress extract for diagnostic and therapeutic purposes is increasingly felt. METHODS: Mixed or single Cupressus arizonica, lusitanica and sempervirens pollen extracts precipitated with ammonium sulfate (PPT) were compared by direct RAST, RAST inhibition and SDS-PAGE techniques. The major allergen of C. arizonica (Cup a 1), purified by anion exchange chromatography, was checked by immunoblotting experiments before chemical modification, in parallel with a C. arizonica extract, with potassium cyanate (KCNO) to obtain a monomeric allergoid. The allergoid extract was characterized for its biological, chemico-physical and immunological features by RAST inhibition, SDS-PAGE and ELISA assays. RESULTS: Direct RAST, RAST inhibition, and SDS-PAGE data indicated that the PPT C. arizonica pollen extract showed the most allergenic potential, and it can be considered representative of the Cupressus spp. Immunoblotting data confirmed Cup a 1 as a major allergen. RAST inhibition and ELISA showed that modified PPT C. arizonica extract had less IgE reactivity than the native, non-modified extract, while preserving the immunogenic capacity typical for an allergoid. Finally, the SDS-PAGE profile of Cup a 1 allergoid was similar to native Cup a 1 allergen, suggesting the modified C. arizonica extract shows the characteristics of a monomeric allergoid. CONCLUSIONS: The PPT C. arizonica pollen extract shows good in vitro diagnostic potential and its chemically modified form offers the features of a monomeric allergoid. It might therefore lend itself to the development of a product to be administered by the sublingual or oromucosal route for immunotherapy of individuals with cypress pollinosis.
Allergens↗
Rapid isolation, characterization, and glycan analysis of Cup a 1, the major allergen of Arizona cypress (Cupressus arizonica) pollen.
BACKGROUND: A rapid method for the purification of the major 43-kDa allergen of Cupressus arizonica pollen, Cup a 1, was developed. METHODS: The salient feature was a wash of the pollen in acidic buffer, followed by an extraction of the proteins and their purification by chromatography. Immunoblotting, ELISA, and lectin binding were tested on both the crude extract and the purified Cup a 1. Biochemical analyses were performed to assess the Cup a 1 isoelectric point, its partial amino-acid sequence, and its glycan composition. RESULTS: Immunochemical analysis of Cup a 1 confirmed that the allergenic reactivity is maintained after the purification process. Partial amino-acid sequencing indicated a high degree of homology between Cup a 1 and allergenic proteins from the Cupressaceae and Taxodiaceae families displaying a similar molecular mass. The purified protein shows one band with an isoelectric point of 5.2. Nineteen out of 33 sera (57%) from patients allergic to cypress demonstrated significant reactivity to purified Cup a 1. MALDI-TOF mass spectrometry indicated the presence of three N-linked oligosaccharide structures: GnGnXF(3) (i.e., a horseradish peroxidase-type oligosaccharide substituted with two nonreducing N-acetylglucosamine residues), GGnXF(3)/GnGXF(3) (i.e., GnGnXF with one nonreducing galactose residue), and (GF)GnXF(3)/Gn(GF)XF(3) (with a Lewisa epitope on one arm) in the molar ratio 67:8:23. CONCLUSION: The rapid purification process of Cup a 1 allowed some fine studies on its properties and structure, as well as the evaluation of its IgE reactivity in native conditions. The similarities of amino-acid sequences and some complex glycan stuctures could explain the high degree of cross-reactivity among the Cupressaceae and Taxodiaceae families.
Allergens↗
Arthropods and invertebrates allergy (with the exclusion of mites): the concept of panallergy.
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Allergens↗
Analysis of microbiological trends in peritoneal dialysis-related peritonitis from 1991 to 1998.
The microbial cause of peritoneal dialysis-related peritonitis is an important determinant of clinical outcome and the basis of widely used treatment guidelines. Five hundred forty-six cases of peritonitis in 374 patients from 1991 to 1998 were analyzed. The rate of peritonitis declined significantly from 1.37 episodes/patient-year in 1991 to 0.55 episode/patient-year in 1998 (P = 0.02). The rate of Gram-positive peritonitis decreased significantly from 0.75 to 0.28 episode/patient-year during the same period (P = 0.02). Conversely, the occurrence of Gram-negative peritonitis remained constant at approximately 0.16 episode/patient-year (P = 0.28). Staphylococcus epidermidis and Staphylococcus aureus were the most common causes of peritonitis, isolated in 27.8% and 19.3% of the culture-positive cases, respectively. A distinct decrease in peritonitis caused by S epidermidis was observed, with 0.40 episode/patient-year in 1991 compared with 0.11 to 0.20 episode/patient-year during subsequent years. The rate of infections caused by S aureus decreased significantly over time from a high of 0.21 episode/patient-year in 1992 to a low of 0.04 episode/patient-year in 1998 (P = 0.01). Pseudomonas aeruginosa, Escherichia coli, and KLEBSIELLA: species were the most common causes of Gram-negative peritonitis, identified in 7.1%, 6.8%, and 5.2% of culture-positive cases, respectively. The most dramatic increase in antibiotic resistance was seen among S epidermidis. From 1991 and 1992 to 1997 and 1998, resistance to ciprofloxacin increased from 5.4% to 47.8% (P = 0.003), and resistance to methicillin increased from 18.9% to 73.9% (P = 0.03). Our study showed significant trends in the causative pathogens of peritoneal dialysis-related peritonitis and dramatic increases in antibiotic resistance. These data support further study and warrant reevaluation of current treatment practices.
Case-Control Studies↗