Basophil Activation Test Is Inferior to Provocation Test in Diagnosing Aspirin Hypersensitivity.

INTRODUCTION: Diagnostic of aspirin (ASA) hypersensitivity is largely based on provocation tests. However, they have significant limitations including influence of medications, necessity of hospitalization, and safety issues. Basophil activation test (BAT) seems to be a promising in vitro alternative. It has already proven to be a useful tool for diagnosing IgE-mediated allergy to certain food and airborne allergens as well as insects venoms. The aim of the study was to assess performance of BAT in diagnosing aspirin hypersensitivity in comparison with current golden standard (oral provocation test, OPT). METHODS: The study group comprised 148 adult patients with suspicion of aspirin hypersensitivity, including 51 (36%) with chronic urticaria, 73 (51%) with asthma, and 55 (39%) with chronic sinusitis. The control group was 10 healthy adult patients who used NSAIDs during preceding year with good tolerance. BAT with ASA was conducted in all the participants. Additionally, in the study group, OPT was performed with cumulative dose of 1,000 mg of ASA. RESULTS: Out of 148 study group participants, 114 underwent BAT and ASA provocation with conclusive results acquired in both tests. In this group, the threshold for positive BAT was 4.9%. Sensitivity and specificity of BAT were found to be 55.9% and 75%, respectively, with a positive predictive value of 77% and a negative predictive value of 54%. The highest sensitivity (78%) was found in subgroup patients with chronic urticaria, while specificity was highest in the subgroup with chronic respiratory diseases (87%). CONCLUSION: Despite significant advantages of BAT such as safety, no influence of drugs, and objectivity, its performance makes it inferior to current standard in ASA hypersensitivity.

Venom Immunotherapy Does Not Affect Survival of Patients with Malignant Tumor in Poland.

Background: Allergen immunotherapy (AIT) is a well-established and efficient method of causative treatment for allergic rhinitis, asthma and insect venom allergy. Traditionally, a recent history of malignant neoplasm is regarded as a contraindication to AIT due to concerns that AIT might stimulate tumor growth. However, there are no data confirming that the silencing of the Th2 response affects prognosis in cancer. Objectives: The aim of this study was to investigate frequency of malignant tumors in patients undergoing AIT and the association between AIT and cancer-related mortality. Patients and Methods: A group of 2577 patients with insect venom allergy undergoing AIT in 10 Polish allergology centers was screened in the Polish National Cancer Registry. Data on cancer type, diagnosis time and patients' survival were collected and compared with the general population. Results: In the study group, 86 cases of malignancies were found in 85 patients (3.3% of the group). The most common were breast (19 cases), lung (9 cases), skin (8 cases), colon and prostate cancers (5 cases each). There were 21 cases diagnosed before AIT, 38 during and 27 after completing AIT. Laplace's crude incidence rate was 159.5/100,000/year (general population rate: 260/100,000/year). During follow-up, 13 deaths related to cancer were revealed (15% of patients with cancer). Laplace's cancer mortality rate was 37.3/100,000/year (general population rate: 136.8/100,000/year). Conclusions: Malignancy was found in patients undergoing immunotherapy less often than in the general population. Patients with cancer diagnosed during or after AIT did not show a lower survival rate, which suggests that AIT does not affect the prognosis.

YKL-40 as a possible marker of neutrophilic asthma.

Asthma is a heterogeneous chronic disorder of the airways, with inflammation and bronchial hyperresponsiveness as its major underlying phenomena. Asthmatics vary in terms of inflammation pattern, concomitant pathologies, and factors aggravating the course of the disease. As a result, there is a need for sensitive and specific biomarkers that could facilitate diagnosing asthma as well as phenotyping in everyday practice. Chitinases and chitinase-like proteins (CLPs) seem promising in this field. Chitinases are evolutionarily conserved hydrolases that degrade chitin. In contrast, CLPs bind chitin but do not have degrading activity. Mammalian chitinases and CLPs are produced by neutrophils, monocytes, and macrophages in response to parasitic or fungal infections. Recently, several questions have been raised about their role in chronic airway inflammation. Several studies demonstrated that overexpression of CLP YKL-40 was associated with asthma. Moreover, it correlated with exacerbation rate, therapy resistance, poor control of symptoms, and, inversely, with FEV1. YKL-40 facilitated allergen sensitization and IgE production. Its concentration was elevated in bronchoalveolar lavage fluid after an allergen challenge. It was also found to promote the proliferation of bronchial smooth muscle cells and correlate with subepithelial membrane thickness. Thus, it may be involved in bronchial remodeling. Associations between YKL-40 and particular asthma phenotypes remain unclear. Some studies showed that YKL-40 correlates with blood eosinophilia and FeNO, suggesting a role in T2-high inflammation. Quite the opposite, cluster analyses revealed the highest upregulation in severe neutrophilic asthma and obesity-associated asthma. The main limitation in the practical application of YKL-40 as a biomarker is its low specificity. High serum levels of YKL-40 were also found in COPD and several malignancies, in addition to infectious and autoimmune diseases. To conclude, the level of YKL-40 correlates with asthma and some clinical features in the whole asthmatic population. The highest levels are found in neutrophilic and obesity-related phenotypes. However, due to its low specificity, the practical application of YKL-40 remains uncertain but could be useful in phenotyping, especially when combined with other biomarkers.

miRNA profiles change during grass pollen immunotherapy irrespective of clinical outcome.

Background: Subcutaneous immunotherapy (SCIT) is widely used in the treatment of allergic rhinitis (AR). This study aimed to determine the expression of 48 miRNAs in patients with AR undergoing grass pollen SCIT and investigate relations with clinical outcomes. Methodology: Expression of selected miRNAs was determined using RT-PCR in the full blood of 16 patients with AR and seven healthy controls. Results: miR-136, miR-208 and miR-190 were upregulated in the AR group. After 6 months of SCIT, significant downregulation of some proinflammatory miRNAs and upregulation of several miRNAs regulating Th1/Th2 balance were found. No differences were found between good and poor responders. Conclusion: miRNAs may play a regulatory role in SCIT, leading to tolerance induction.

Background: Subcutaneous immunotherapy is widely used in the treatment of allergic rhinitis (AR). MicroRNAs (miRNAs) are small molecules controlling gene expression. Their role in the process of immunotherapy is not yet well understood. This study aimed to investigate the expression of 48 miRNAs in patients with AR undergoing grass pollen immunotherapy and relations between miRNAs and clinical outcomes. Methodology: The expression of selected miRNAs was determined in the blood of 16 patients with AR and seven healthy people. Results: Three miRNAs were found to be overproduced in allergic patients. During immunotherapy, the production of several proinflammatory miRNAs was reduced while those responsible for allergen tolerance were produced in larger amounts. Conclusion: miRNAs may play an important role in immunotherapy, leading to better tolerance of allergens.

IFNG, FCER1A, PCDHB10 expression as a new potential marker of efficacy in grass pollen allergen-specific immunotherapy.

INTRODUCTION: Allergen-specific immunotherapy (AIT) is the core treatment in allergic rhinitis and asthma. Although widely used, some patients do not benefit from treatment and there is no efficacy objective marker. AIM: To define the profile of gene transcripts during the build-up phase of AIT and their comparison to the control group and then search for a viable efficacy marker in relation to patient symptoms. MATERIAL AND METHODS: AIT was administered in 22 patients allergic to grass pollen. Analysis of 15 selected transcript expression was performed in whole blood samples taken before AIT (sample A) and after reaching the maintenance dose (sample B). The control group included 25 healthy volunteers (sample C). The primary endpoint was Relative Quantification. The gene expression analysis was followed by clinical evaluation with the use of Allergy Control Score (ACS). RESULTS: Comparison between samples A and B of gene expression showed a significant increase in IFNG expression (p = 0.03). In relation to the control group, pretreatment samples from patients showed higher levels of AFAP1L1 (p = 0.006), COMMD8 (p = 0.001), PIK3CD (p = 0.027) and TWIST2 (p = 0.0003) in univariate analysis. A generalized linear regression model was built according to the Bayesian Information Criterion based on the IFNG, FCER1A and PCDHB10 expression pattern for prediction of the AIT outcome. The model showed a correlation in predicted and observed changes in ACS. CONCLUSIONS: There is a significant change in the expression of IFNG during the build-up phase of AIT. The authors propose an in vitro model of AIT efficacy prediction for further validation.

Oral premedication in patients with a history suggesting hypersensitivity to iodinated contrast media.

INTRODUCTION: Iodinated contrast media (ICM) are pharmaceuticals widely used in diagnostic procedures. Adverse effects associated with their administration are quite frequent and mostly mild. However, they raise concerns in patients and doctors in the context of their future use. AIM: To determine efficacy of premedication before medical procedures with the use of iodinated contrast media in patients with a history suggesting a hypersensitivity reaction after their past use. MATERIAL AND METHODS: Out of 152 patients consulted due to adverse reactions after ICM (85 women and 67 men, aged 43-90), 101 were selected with the history suggesting a mild hypersensitivity reaction (urticaria, itching, skin redness, malaise etc.). All the patients had health problems requiring a procedure with ICMadministration in the near future. The premedication was given with cetirizine (10 mg) and prednisone (20 mg or 50 mg, randomly assigned) 13, 7 and 1 h before the ICM administration. Presence of adverse events was compared between the subgroups with χ 2 test and efficacy of premedication - with Wilcoxon test. RESULTS: Seventy-six patients underwent the radiologic procedure with premedication with antihistamine and a lower (40 patients) or higher dose (36 patients) of prednisone. Four of them reported a cutaneous hypersensitivity reaction (urticaria, itching, redness) and one - dyspnoea. There was no statistically significant difference in relation to the premedication protocol (p = 0.1306). CONCLUSIONS: Premedication with cetirizine and prednisone before radiologic procedures proved to be efficient in patients with a history suggesting hypersensitivity to iodinated contrast media. There was no significant difference in efficacy related to the dose of prednisone (20 mg vs. 50 mg).

MicroRNAs: future biomarkers and targets of therapy in asthma?

PURPOSE OF REVIEW: MicroRNAs (miRNAs) are small noncoding RNA molecules that are considered one of the fundamental regulatory mechanisms of gene expression. They are involved in many biologic processes, such as signal transduction, cell proliferation and differentiation, apoptosis and stress responses. The purpose of this review is to present recent knowledge about the role of miRNAs in asthma and outline possible applications of miRNAs. RECENT FINDINGS: A core set of miRNAs involved in asthma includes downregulated let-7 family, miR-193b, miR-375 as well as upregulated miR-21, miR-223, miR-146a, miR-142-5p, miR-142-3p, miR-146b and miR-155. Recently it has been shown that most of the involved miRNAs increase secretion of Th2 cytokines, decrease secretion of Th1 cytokines, promote differentiation of T cells towards Th2 or play a role in hyperplasia and hypertrophy of bronchial smooth muscle cells. The profiles of miRNAs correlate with clinical characteristics, including lung function, phenotype and severity of asthma. SUMMARY: Recent publications confirmed crucial regulatory role of miRNAs in the pathomechanism of asthma. Some single miRNAs or their sets hold the promise for their use as asthma biomarkers facilitating diagnosis or prediction of treatment outcomes. They are also possible target of future therapies. The studies in this field are lacking though.

Histoplasmosis in an elderly polish tourist - a case report.

BACKGROUND: Histoplasmosis is a mycosis caused by soil-based fungus Histoplasma capsulatum endemic in the USA, Latin America, Africa and South-East Asia. The disease is usually self-resolving, but exposure to a large inoculum or accompanying immune deficiencies may result in severe illness. Symptoms are unspecific with fever, cough and malaise as the most common. Thus, this is a case of disease which is difficult to diagnose and very rare in Europe. As a result, it is usually not suspected in elderly patients with cough and dyspnea. CASE PRESENTATION: This is a case of a 78-year-old patient, admitted to our department due to respiratory failure, cough, shortness of breath, fever and weight loss with no response to antibiotics administered before the admission. Chest CT revealed numerous reticular and nodular infiltrations with distribution in all lobes. The cytopathology of BAL showed small parts of mycelium and numerous oval spores. Considering clinical presentation and history of travel to Mexico before onset of disease, pulmonary histoplasmosis was diagnosed. After introduction of antifungal treatment rapid improvement was achieved in terms of both clinical picture and respiratory function. CONCLUSIONS: Since the risk of Histoplasma exposure in Europe is minimal, patients, who present with dyspnea, fever and malaise are not primarily considered for diagnosis of histoplasmosis. However, taking into account increasing popularity of travelling, also by elderly or patients with impaired immunity, histoplasmosis should be included into differential diagnosis.

Changing microRNA Expression during Three-Month Wasp Venom Immunotherapy.

MicroRNAs are small non-coding molecules playing a significant regulatory role in several allergic diseases. However their role in tolerance induction remains unclear. The aim of this study was to determine the expression of selected microRNAs during the first three months of wasp venom immunotherapy (VIT). 5 adult patients with a history of severe systemic reactions after stinging by wasps and confirmed sensitization were included. Venous blood samples were collected before VIT, 24 hours after completing its initial phase and after 3 months of the maintenance therapy. A control group was comprised of 5 healthy individuals with no history of allergy. In the blood samples expression of 96 microRNAs was determined with the use of microfluidic cards. In a statistical analysis the expression was compared between the study groups as well as between the pre- and post-VIT samples. Significant differences were found between the patients with wasp venom allergy and the healthy controls in the expression of miR-601 and miR-1201 upregulated in allergic patients at every time point (p = 0.04; p = 0.015, respectively). During VIT profile of microRNA was changing with lower expression of 6 microRNAs (including miR-182, miR-342, miR-375) and higher of 11 microRNAs (including let-7d, miR-34b, miR-143). To conclude, VIT has led to some changes in the expression of microRNA associated with Th2-type inflammation and tolerance induction.

MicroRNAs: Potential Biomarkers and Targets of Therapy in Allergic Diseases?

MicroRNAs (miRNAs) are small non-coding RNA molecules that are 18-22 nucleotides long and highly conserved throughout evolution. Currently, they are considered one of the fundamental regulatory mechanisms of genes expression. It has been demonstrated that miRNAs are involved in many biologic processes, such as signal transduction, cell proliferation and differentiation, apoptosis and stress responses. More recently, the role of miRNA has also been revealed in numerous immunological and inflammatory disorders, including allergic inflammation. Specific miRNA profiles were demonstrated in asthma, allergic rhinitis and atopic dermatitis. A core set of miRNAs involved in atopic diseases include upregulated miR-21, miR-223, miR-146a, miR-142-5p, miR-142-3p, miR-146b, miR-155 and downregulated let-7 family, miR-193b and miR-375. Most of the involved miRNAs increase secretion of Th2 cytokines (miR-1248, miR-146b), decrease secretion of Th1 cytokines (miR-513-5p, miR-625-5p) or promote differentiation of T cells towards Th2 (miR-21, miR-19a). In asthma miR-140-3p, miR-708 and miR-142-3p play a role in hyperplasia and hypertrophy of bronchial smooth muscle cells. Some single miRNAs or, more probably, their sets hold the promise for their use as biomarkers of atopic diseases. They are also promising target of future therapies.

Smoking history is negatively associated with allergen specific immunotherapy efficacy: a retrospective analysis.

INTRODUCTION: Allergen specific immunotherapy (AIT) is the only treatment modifying the course of the disease in patients allergic to airborne allergens. It has been proven to be effective in allergic populations, however individual patients vary in terms of response to the therapy. AIM: To assess the factors that might affect the efficacy of AIT. MATERIAL AND METHODS: Patients treated with AIT for grass pollen or house dust mites were included. The efficacy of AIT was assessed with the use of Allergy Control Score (ACS), performed before and at least 1 year after AIT. The following variables were assessed as potential risk factors for a worse response to AIT: age, gender, type of allergy, type of allergen, type of vaccine, type of AIT and smoking history. RESULTS: The study group consisted of 145 subjects.AIT was effective in the entire group; the mean ACS results decreased from 21.14 to 14.41 points (p< 0.0001). No differences in efficacy in terms of assessed risk factors were found, except for smoking history (ACS change in the smoking group was smaller: from 21.8 to 18.1 points; p = 0.09, OR = 0.323; 95% CI: 0.11-0.88; p = 0.02). CONCLUSIONS: Smoking history may affect AIT outcomes.

Changes in the Expression of MicroRNA in the Buildup Phase of Wasp Venom Immunotherapy: A Pilot Study.

BACKGROUND: Allergen-specific immunotherapy is the most effective method of treatment in allergy to wasp venom. However, its mechanism of action is still not fully understood. The aim of this study is to describe changes in microRNA (miRNA) expression in patients undergoing the buildup phase of venom immunotherapy. METHODS: The study group comprised 7 adult patients with a history of severe systemic reactions after stinging by a wasp. In all patients, sensitization to wasp venom had been confirmed by skin tests and serum IgE. The buildup phase of wasp venom immunotherapy (VIT) was conducted according to an ultrarush protocol. In blood samples collected before and 24 h after completing the VIT buildup phase, 740 miRNAs were assessed. RESULTS: Of the 740 miRNAs, 440 were detected in the study group, and in 5 expression was significantly changed after the buildup phase of VIT: miR-370, miR-539, miR-502-3p, miR-299, and miR-29c. Another 62 miRNAs changed 2-fold in some patients (nonsignificant), including increases in miR-143 (stimulating FOXp3 expression) and let-7d (reducing expression of IL-13, IL-6, and TLR4), and decreases in proinflammatory miR-301, miR-146b, miR-106, and miR-485. CONCLUSIONS: Several changes in miRNA expression have been found as a result of the buildup phase of wasp VIT, with lower expression of some miRNAs involved in allergic inflammation and higher expression of those possibly involved in tolerance induction. However, the role of the most significant changes is uncertain.

Differentiating of cross-reactions in patients with latex allergy with the use of ISAC test.

INTRODUCTION: Differentiating between cross-reactivity and double sensitization is still a challenging issue in allergology. AIM: To differentiate cross-reactions accompanying latex allergy with the use of the ISAC test. MATERIAL AND METHODS: Thirty-nine patients reporting immediate allergic reactions to latex were enrolled into the study (group A). The control group was comprised of 41 patients with allergic diseases not associated with latex (group B) and 20 healthy individuals (group C). Their history was recorded and skin prick tests were performed with latex, airborne and food allergens. Specific IgE against food allergens, latex (k82) and recombined latex allergens were determined. ImmunoCAP ISAC test was performed with 103 molecules. RESULTS: Sensitization to latex was found by means of skin tests in 16 cases and sIgE against latex was revealed in 12 cases (including 10 positive in both SPT and sIgE). In the ISAC test antibodies against recombined latex allergens were found in 8 patients with rHev b 6 as the most common. All the patients positive for rHev b 1, 5, 6, 8 had allergy or asymptomatic sensitization to food allergens cross-reacting with latex. Some reactions could not have been differentiated due to the lack of allergens in the ISAC test. Others, not related to latex-fruits syndrome were explained by cross-reactivity with other profilins or PR-10 proteins. CONCLUSIONS: ImmunoCAP ISAC test could be useful in differentiating between cross-reactions and double sensitizations. However, in the case of latex its advantages are limited due to a small panel of allergens.

Typing safe antibiotics in amoxicillin hypersensitive patients--development of a stepwise protocol.

INTRODUCTION: A history of an adverse reaction to amoxicillin, irrespective of the mechanism involved, significantly elevates patients' anxiety and affects therapeutic decisions in the future, leading to unnecessary avoidance of antibiotics. As a consequence, it would be useful to find a safe and reliable protocol for typing safe alternative antibiotics. The aim of the study was to determine negative predictive value of typing safe antibiotic in patients with a history of hypersensitivity reaction to amoxicillin. MATERIAL AND METHODS: 71 patients, aged 20-83, with a history of an adverse reaction to amoxicillin were retrospectively analysed. On the basis of the reaction type they were divided into three groups: A - symptoms not typical for hypersensitivity reactions, B - allergy manifested by urticaria and/or angioedema, C - anaphylaxis. In group A amoxicillin was tested, in group B - cefuroxime, and in group C - macrolide: azithromycin or clarithromycin. Telephone follow-up visits were performed twice: 6-12 months and 3-5 years after the clinical assessment to evaluate tolerance of antibiotics. On the basis of the follow-up results, the negative predictive value (NPV) of the protocol was calculated. RESULTS: The full diagnostic protocol was applied in 62 participants. Amoxicillin was found safe in 22, cefuroxime - in 21 and macrolide - in 19 patients. No anaphylactic reactions were observed during the tests. On the basis of the telephone follow-up, the NPV of the protocol was 96% in the first follow-up and 97% in the second one. CONCLUSION: A stepwise approach including SPTs, ICTs and provocations with amoxicillin / cefuroxime/macrolide - depending on a patient's history - is safe and allows typing an antibiotic in the vast majority of patients.

In Vitro Evaluation of the Allergic Potential of Antibacterial Peptides: Camel and Citropin.

Peptide-based drugs are promising group of compounds which are characterized by specificity to their in vivo targets and high potency of action (antineoplastic, immunoregulatory, antibacterial). The peptides, however, involve a relatively high risk of allergic reactions that are not predictable on the basis of their sequence and chemical properties. In this study, peripheral blood was obtained from 53 patients including 38 hypersensitive patients and 15 control patients. Basophil activation stimulated by two antibacterial peptides (camel, citropin 1.1), and acetylsalicylic acid was assessed by means of BAT (basophil activation test). Basophil activation stimulated by camel occurred in 7 of 38 patients with hypersensitivity (18.42%) as well as in 2 of 15 control patients (13.33%). Basophils were activated by citropin 1.1 in 7 of 38 hypersensitive patients (18.42%) and in none of the control patients. Using the Structural Database of Allergenic Proteins, we confirmed that the examined peptides share some structural similarities with common environmental allergens. Therefore, the cross-reactivity between potentially present anti-allergen IgE with examined peptides cannot be excluded. Our study proved that BAT, together with other biological tests and specific databases of allergenic compounds, may serve as an initial selection of new active peptides and proteins.

YKL-40 protein correlates with the phenotype of asthma.

PURPOSE: YKL-40 is a chitinase-like protein found to correlate with asthma as well as numerous infectious and autoimmune diseases or cancer. The aim of the present study was to investigate the role of YKL-40 as a possible marker of asthma and its associations with factors differentiating phenotypes of asthma. METHODS: The study group comprised 167 patients, including 116 women and 51 men aged 18-88 years with chronic asthma. The control group comprised 81 healthy individuals, including 50 women and 31 men aged 19-86 years. In every participant, medical history was taken; spirometry and skin prick tests were performed. YKL-40 was determined in sera by means of ELISA test. RESULTS: Mean serum YKL-40 level was 59.7 ng/ml (53.6-65.7 ng/ml; 95% CI) with significant difference between asthmatics and healthy controls (mean values: 66.8 ± 53.8 vs. 44.9 ± 29.4 ng/ml; p < 0.001). In asthmatics, the level was significantly higher in subgroup with poor control of symptoms and exacerbations (91.8 ± 57.1 ng/ml) compared to stable asthmatics (59.6 ± 50.8 ng/ml; p < 0.001) as well as in atopic compared to non-atopic asthmatics (77.2 ± 53.9 vs. 61.1 ± 57.8 ng/ml; p < 0.001). Mean YKL-40 level in obese asthmatics was 135.6 ng/ml compared to 50.0 ng/ml in non-obese (p < 0.001). When phenotypes of early-onset atopic, late-onset non-atopic, and obesity-related asthma were compared, YKL-40 levels were 80.62 ± 46.9, 51.5 ± 24.9, and 168.1 ± 71.5 ng/ml, respectively (p < 0.05). CONCLUSION: Although YKL-40 is not a specific marker for asthma, it correlates with some clinical features such as exacerbation, level of control, atopy, and obesity.

[Application of basophil activation test in diagnosing aspirin hypersensitivity]. / Zastosowanie testu aktywacji bazofilów w diagnostyce nadwrazliwosci na kwas acetylosalicylowy.

In the face of increasing prevalence of hypersensitivity reactions, introduction of effective, reliable and safe methods plays a crucial role in their diagnosing. Among the currently available laboratory (in vitro) methods is basophil activation test (BAT). It is a flow- cytometry based assay that allows to identificate in the blood sample basophils and additionally to asses the degree of cell activation after exposure to an antigen. The most common superficial identification markers are CD63 and CD203c, which increase in number after activation. Basophil actvation test can be applied to confirm diagnosis of allergy to Hymenoptera venoms, food, pollens and hypersensitivity to drugs. The aim of present paper is to present theoretical methods of this test as well as its pros and cons. We focus also on presentation of clinical case where BAT seemed to be a necessary addition to a routine diagnostic pathway. We present a case of identification of the culprit drug which caused an anaphylactic reaction.

The negative predictive value of typing safe local anesthetics.

BACKGROUND: Although allergy to local anesthetics (LA) is rare, patients often report unwanted reactions after their administration. A history of anaphylaxis or an atypical reaction related to LA is an indication for typing a safe anesthetic for future surgical or dental procedures. AIM: The aim of the study was to determine the negative predictive value (NPV) of typing safe LA. METHODS: A total of 154 patients with a history of an unwanted reaction to LA were enrolled into the study. Stepwise typing of a safe anesthetic included skin prick tests (SPT) and intracutaneous tests (ICT) with two or three of the following LA: lidocaine, bupivacaine, mepivacaine, and articaine. Skin tests were followed by provocations with one or two LA. Telephone follow-up visits were performed 4-12 months after drug typing. On the basis of follow-up questionnaire results, the NPV of the protocol was calculated. RESULTS: The full protocol was performed in 148 patients. Positive results of SPT were observed in 2, of ICT in 19 and of provocations in 11 cases. Lidocaine was found safe in 44, bupivacaine in 14, mepivacaine in 34 and articaine in 61 patients. The drug typed at the clinical visit was administered in 78 patients, and 76 reported no reactions (NPV = 97%). CONCLUSION: Stepwise approach including SPT, ICT and provocations is safe and allows typing a safe anesthetic in a vast majority of patients.

Intima-media thickness in patients with obstructive sleep apnea without comorbidities.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with elevated risk of cardiovascular events. The early stages of vascular complications can be visualized by means of ultrasound. Intima-media thickness (IMT) correlates with the presence of risk factors of cardiovascular diseases such as hypertension, diabetes, tobacco smoking, or hyperlipidemia. However, little is known whether OSA itself may be the cause of IMT thickening. METHODS: The study group was composed of 28 patients (6 women, 22 men; mean age = 53.8 years, mean BMI = 27.1 kg/m(2), mean AHI = 22.4/h) with OSA who had no comorbidities. The control group consisted of 28 healthy subjects (6 women, 22 men; mean age = 53.9 years; mean BMI = 27.5 kg/m(2)). In both groups IMT was assessed in common carotid arteries with the use of ultrasonography. Additionally, in patients with OSA, pulse wave velocity, echocardiography, 24-h automated blood pressure monitoring, clinical signs and symptoms, and blood tests were performed to investigate possible correlations with IMT. RESULTS: Median IMT was 0.41 mm in OSA patients and 0.46 mm in the control group (p = 0.087). Echocardiography revealed left ventricle hypertrophy in 21%, systolic disorders in 8%, and diastolic disorders in 57% of the patients. In a large majority of patients, pulse wave velocity was found to be normal. IMT correlated with age (r = 0.446, p = 0.017), total cholesterol (r = 0.518, p = 0.005), daytime systolic blood pressure (r = 0.422, p = 0.025), pulse pressure 24 h and daytime (r = 0.424, p = 0.027 and r = 0.449, p = 0.019), early mitral flow/atrial mitral flow (E/A) (r = -0.429, p = 0.023), and posterior wall diameter (PWD) (r = 0.417, p = 0.270). CONCLUSION: In a relatively nonobese group of patients, no significant differences were found in the intima-media thickness between OSA patients without concomitant cardiovascular diseases and healthy controls. This may lead to the conclusion that IMT does not reflect increased risk of cardiovascular events in patients with isolated OSA.

The osteocalcin gene rs1800247 polymorphism in Kashubian population.

Osteocalcin is the most important noncollagenous protein component of the bone. Polymorphisms of osteocalcin gene were reported to be associated with bone mineral density. However, this relation was only confirmed in some populations. In this study presence of C/T polymorphism in osteocalcin gene (rs1800247) was determined in Kashubian population (northern Poland). The frequencies of variants were CC 9 %, TC 31 %, and TT 60 %, with no significant differences between genders. The genotypes were in Hardy-Weinberg equilibrium.