Effect of terbutaline and bambuterol on immediate-type allergic skin responses and mediator release in human skin

Background: Beta-2 agonists are potent inhibitors of mast cell degranulation in vitro. Intradermally injected they also inhibit mast cell activation in human skin in vivo. To what extent orally administered ₂-agonists inhibit mast cell degranulation and allergic skin responses in vivo in daily recommended doses remains unclear.Purpose: The main purpose was to study the effects of oral administered terbutaline and bambuterol on allergen- and codeine-induced histamine release and skin responses in intact human skin in vivo. In addition, control studies were carried out with intradermally injected terbutaline.Methods: Ten allergic subjects were randomized to receive bambuterol (10 mg tablets twice daily), terbutaline (7.5 mg controlled release tablets twice daily) and corresponding placebo for 5 days with a washout phase of 3 days between treatments in a double-blind, double-dummy, cross-over trial. The patients were studied at the fifth day of each regimen, i.e. at day 5, 13, and 21. Allergen- and codeine-induced histamine release was measured by microdialysis technique. Wheal and flare reactions to allergen, codeine, and histamine were measured planimetrically. Measurements were performed in the morning on day 5 on each regimen before medication and for additional 5 h after administration of the morning dose. In a separate series of experiments in another 10 allergic patients, 1–1,000 nM (0.05–50 pmoles) of terbutaline was injected intradermally for measurement of histamine release, prostaglandin D2 (PGD2) synthesis and skin responses.Results: Neither orally administered terbutaline nor bambuterol significantly reduced allergen- or codeine-induced histamine release. Flare reactions to allergen, codeine and histamine remained unaffected which was also the case for the majority of the wheal reactions. In comparison, intradermally injected terbutaline significantly reduced allergen-induced histamine release, PGD₂ synthesis, and skin reactions. Codeine-induced histamine release remained unaffected. Terbutaline significantly reduced flare reactions to codeine and histamine with no effect on wheal reactions.Conclusions: Terbutaline, in micromolar concentrations, was a potent inhibitor of immediate allergic skin reactions primarily due to inhibition of mast cell degranulation. However orally administered terbutaline, as the active drug itself or released from its pro-drug bambuterol, did not inhibit mast cell activation or allergic skin responses. Received 28 January 2003; returned for revision 7 March 2003; accepted by M. Parnham 29 April 2003     

Use of the iso-inertial force mass relationship in the prediction of dynamic human performance

The purpose of this investigation was to develop a new test of muscle function, termed the isoinertial force-mass relationship, and to determine its relationship to dynamic physical performance in comparison to an isometric test. A group of 13 trained subjects performed an isometric, and a series of iso-inertial maximal upper body tests, in a bench press movement at loads of 30%, 60%, 100% (concentric) and 100%, 130% and 150% (eccentric) of maximum. Vertical forces exerted throughout the movement were recorded by a force plate. In addition, the subjects performed the following three performance tests: a maximal bench press, a seated shotput, and two drop bench-press throws from a height of 0.25 m, with loads of 10 kg and 30% of maximum. Correlation analysis demonstrated that in each instance the iso-inertial force mass tests were the best predictors of performance (r=0.78–0.88) with both contraction type and mass specific effects apparent. Maximal isometric force and rate of force development were significantly related to some performance variables (r=0.22–0.78). However, for all the performance movements assessed, the iso-inertial test modality recorded the highest relationship to performance. The difference in the relationship between performance and iso-inertial and isometric test modalities was particularly evident in the light load dynamic performance of the seated shotput (r=0.86 vsr=0.38, respectively). These results are explained in part by the neural and mechanical differences between iso-inertial and isometric muscle actions and their respective specificity to dynamic physical performance.     

Combined skin prick and patch testing enhances identification of peanut-allergic patients with atopic dermatitis

BACKGROUND: Food atopy patch tests (APTs) are considered a useful tool for the diagnosis of food allergy. Hypersensitivity to peanuts has not been investigated by means of APTs so far. METHODS: APTs and skin prick tests (SPTs) with peanuts were performed in 136 atopic dermatitis (AD) patients. Relevance of positive and negative responses to these tests was assessed by repeated open challenges with peanuts. RESULTS: Nine percent of our AD patients reacted to the challenge. Positive responses to APTs were recorded in 19% of the patients, whereas in 12% positive SPTs were observed. APTs were more frequently positive in subjects with eczematous responses after challenge with respect to those with urticarial reactions. SPT reactivity proved to be higher in patients above 12 years of age, whereas APT positivity was more frequent in children under 6 years. APT sensitivity proved significantly higher than SPT sensitivity, in particular in children under 12 years of age. On the contrary, SPT specificity and positive predictive value were significantly higher with respect to those of APT in the age group of subjects under 6 years of age. CONCLUSIONS: Our data suggest that APTs with peanuts may represent a useful integration to standard testing modalities employed for the diagnosis of peanut allergy in AD patients.     

High-dose inhaled steroids in the management of asthma A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function

Svendsen UG, Frølund L, Heinig JH, Madsen F, Nielsen NH, Weeke B. High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function.
The efficacy of budesonide (800 μg b.d.) and beclomethasone dipropionate (750 μg b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV₁ FVC, PEF or the histamine PC₂₀. Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study.     

GKT原理的模拟犯罪测试范式实验研究

目的:本实验旨在以实际犯罪较接近的实验场景验证GKT的测谎机制,并探讨其对罪犯以及其他嫌疑人的判定有效性。方法:以72名健康大学生为被试,让被试在模拟犯罪的背景下采用三种包含不同说谎和认知成分的回答方式进行测谎测试,采用Limestone测谎仪测量被试皮肤电反应。结果:回答方式与角色两因子在判定分数上的主效应均显著,交互作用不显著。结论:在模拟犯罪测试范式下,GKT模式中认知与说谎机制是共存的,其中认知成分不占主要地位,说谎成分占主要地位,GKT模式无法兼顾有效地判定"犯罪"和"知情无辜"角色,需进一步改进。     

Gentamicin susceptibility in Escherichia coli related to the genetic background: problems with breakpoints

In total, 120 Escherichia coli isolates positive for one of the gentamicin resistance (GEN(R)) genes aac(3)-II, aac(3)-IV or ant(2')-I were tested for gentamicin susceptibility by the agar dilution method. Isolates positive for aac(3)-IV or ant(2')-I had an MIC distribution of 8-64 mg/L, whereas isolates positive for aac(3)-II had MICs of 32 to >512 mg/L, suggesting a relationship between the distribution of MICs and the specific GEN(R) mechanism. The MIC distribution, regardless of the GEN(R) mechanism, was 8 - >512 mg/L, which supports the clinical breakpoint of MIC >4 mg/L suggested by EUCAST and questions the breakpoint recommended by the CLSI (> or =16 mg/L).     

Isolation of a Trypanosoma cruzi antigen by affinity chromatography with a monoclonal antibody. Preliminary evaluation of its possible applications in serological tests.

By affinity chromatography with a monoclonal antibody (163B6), obtained in our laboratory, we have isolated a T. cruzi antigen which could be useful for differential diagnosis of Chagas' disease from leishmaniasis. This antigen, a 52-kD protein, reacted with all sera from Chagas' disease patients tested but not with sera from patients with leishmania, in ELISA. The 52-kD antigen is widely distributed in the Trypanosoma genus since the 163B6 monoclonal antibody reacts with T. rangeli and 8 strains and a clone of T. cruzi epimastigotes.     

小鼠气道反应性的测定

目的:测量各种小鼠呼吸模型的肺功能，尤其是非离体的动态肺功能，对于呼吸疾病的研究具有重要意义。 方法:主要包括整体测量方法和离体测量方法。而整体法又主要分为有创法（主要为气道阻力、顺应性的测定）和无创法（Penh，enhanced pause的测定）。本篇主要介绍整体的测量方法。 结论:不同的方法各有利弊，适用于不同的实验要求。     

* Immediate allergic reactions to amoxicillin

A large group of patients with suspected allergic reactions to (β-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to β-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to β-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.     

Controlled administration of penicillin to patients with a positive history but negative skin and specific serum IgE tests

BACKGROUND: Although subjects with a positive history of immediate allergy to penicillin and negative skin test are traditionally considered to tolerate penicillin, current evidence indicates that they may develop an immediate reaction despite negative skin and serum specific IgE tests. It is thought that these patients require additional tests to confirm the diagnosis. OBJECTIVE: To assess in a large group of patients with a history of immediate allergy to penicillins but with both skin test and CAP-FEIA-negative to classical and side chain penicillin determinants, the role of controlled administration of betalactams as a diagnostic test. METHODS: A group of 330 patients with a history of immediate allergic reactions to penicillins was studied by two evaluators from the same allergy unit using the following protocol: skin tests with major and minor determinants of benzylpenicillin (benzylpenicilloyl-poly l-lysine and minor determinant mixture), amoxicillin and ampicillin, and determination of specific IgE antibodies to penicillins, by CAP-FEIA, in serum. If both tests proved negative, a controlled administration of the drug was then carried out. RESULTS: A total of 89 (27%) patients were skin test and CAP-FEIA-negative and therefore required controlled administration of the drug. Of these, 49 developed an immediate response and were therefore considered allergic, and the remainder had good tolerance after administration of both benzylpenicillin and amoxicillin. The clinical characteristics of this group were similar to the other allergic patients who were skin test or CAP-FEIA-positive, except that they were younger (P < 0.01). Twenty-two (45%) developed a response to benzylpenicillin and 27 (55%) had a selective response to amoxicillin. Although all reactions appeared within 1 h, a positive correlation was found between the dose inducing the response and the time elapsed from drug administration, for both benzylpenicillin and amoxicillin (P < 0.001). CONCLUSION: These data indicate that an important number of subjects are not correctly identified if only skin tests and/or CAP-FEIA are used and that this is particularly relevant for side chain-specific reactions and younger subjects. This suggests that new diagnostic tests are required so as to limit the use of controlled administration.