Association Between CHRNA3 and CHRNA5 Nicotine Receptor Subunit Gene Variants and Nicotine Dependence in an Isolated Populationof Kashubians in Poland.

BACKGROUND Genome-wide and allelic association studies have shown the contribution of CHRNA5-A3-B4 nicotinic receptor subunit gene cluster within chromosome 15 to nicotine dependence (ND). While an association between several single-nucleotide polymorphisms (SNPs) at that locus and smoking quantity (cigarettes per day; CPD) has been well recognized, there are some inconsistencies in demonstrating the influence of these SNPs on other ND phenotypes. This uncertainty motivated us to examine the association of 3 selected SNPs (CHRNA3 rs1051730, rs6495308, and CHRNA5 rs55853898) with ND in an isolated population of Kashubians from Poland. MATERIAL AND METHODS The study sample consisted of 788 current daily smokers. ND was assessed by CPD, the Fagerstrom Test for Nicotine Dependence (FTND), its brief version - Heavy Smoking Index (HSI), and time to first cigarette after waking (TTF). The correlation between studied SNPs and dichotomized values of ND measures was assessed in the regression analysis. Bonferroni corrected p-value of 0.017 was set for a type 1 error. RESULTS We found a robust association between risk allele A of rs1051730 and CPD >10 (odds ratio (OR)=1.77, 95% confidence interval (CI): 1.20-2.59, p=0.004), and a weak association, which did not survive correction for multiple testing, with FTND ³4. No associations between studied SNPs and HSI or TTF were demonstrated. CONCLUSIONS Our findings confirm that rs1051730 influences ND phenotype, as defined by CPD.

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.

Nicotine dependence in an isolated population of Kashubians from North Poland: a population survey.

BACKGROUND: Tobacco use is a complex, multistage behaviour. The particular stages of this behaviour, including nicotine dependence (ND), are influenced by both genetics and the environment. Surveys on factors influencing tobacco use and ND, conducted in ethnically homogenous populations, can provide results less influenced by genetic and cultural heterogeneity. We aimed to assess ND in a sample of current smokers, derived from the geographically and culturally isolated population of Kashubians from North Poland, and evaluate its potential association with age, sex, and self-reported comorbidities. In addition, we attempted to replicate - for the first time in this population - previous findings on the association between ND and several variants within the CHRNA5A3-A5-B4 nicotine receptor subunit gene cluster. METHODS: The study sample consisted of 969 unrelated subjects who were all current smokers. ND was evaluated using four measures: the Fagerstrom Test for Nicotine Dependence (FTND), the Heavy Smoking Index (HSI), the number of cigarettes per day (CPD) and the time to first cigarette after waking (TTF). All subjects underwent genotyping for CHRNA5 rs16969968, CHRNA3 rs578776, and CHRNB4 rs12914008 variants. Multivariate regression analysis was used for the assessment of the studied correlations. A significance level of 0.05 with the Bonferroni correction for multiple testing was set for a type 1 error in the analyses. RESULTS: The mean CPD, FTND and HSI scores in the study sample were 17.3 ± 7.7, 3.9 ± 2.3 and 2.6 ± 1.5, respectively. No association between ND defined by FTND, HSI or TTF and age was found. In turn, heavy smoking was significantly associated with older age (odds ratio (OR) = 1.72, 95% confidence interval (CI): 1.14-2.59, p = 0.009), and men were more likely than women to be heavy smokers (OR = 1.70, 95% CI: 1.09-2.65, p = 0.018). Chronic comorbidity did not significantly influence ND. An analysis of association of studied polymorphisms with ND showed a borderline association of rs16969968 with CPD (OR = 1.63, 95% CI: 1.09-2.45, p = 0.017). CONCLUSION: Our study showed a low to moderate level of ND in the Kashubians, influenced by age, sex, as well as the CHRNA5 rs16969968 variant.

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.

[Coexistence of sarcoidosis with seminoma--a case report]. / Wspólistnienie sarkoidozy i nasieniaka jadra ­ opis przypadku.

A 30-year-old patient, with diagnosis of seminoma (T1 Nx Mx) was treated radically with orchidectomy. In chest CT performed postoperatively numerous diffuse nodules were revealed in both lungs. Lesions were situated particularly in the upper and middle pulmonary zones. In order to verify the nature of pulmonary abnormalities videothoracoscopy of the right pleural cavity was performed with specimen collection. Histopathological examination excluded the possibility of cancer metastases to pulmonary parenchyma and revealed the presence of sarcoid-like granulomas. Coexistence of seminoma and diffuse sarcoid-like abnormalities is only sporadically described. Up till now it has not been unequivocally explained whether the pulmonary abnormalities develop in the course of idiopathic sarcoidosis or only reflect a sarcoid-like reaction to cancer antigens.