Compound Heterozygosity for Silent Cap +1570 (T>C) (HBB: c*96T>C), Codon 39 (C>T) (HBB: c.118C>T) and the Presence of αααanti–3.7/αα in Greece. A Case Presentation

Abstract

The rare point mutation Cap +1570 (T>C) (HBB: c*96T>C) has been reported in families of Czech, Greek, Turkish and Italian origin. The mutation contributes to a reduction of the β-globin chain synthesis, and in heterozygous carriers, it causes a silent phenotype, while in compound heterozygosity with severe β-thalassemia (β-thal) mutations, it leads to a non transfusion dependent β-thal intermedia (β-TI) state. We report a case of compound heterozygosity for codon 39 (C>T) (HBB: c.118C>T) and Cap +1570, in addition to the presence of ααα^anti–3.7/αα.     

Genetic modifiers of the severity of sickle cell anemia identified through a genome‐wide association study

We conducted a genome‐wide association study (GWAS) to discover single nucleotide polymorphisms (SNPs) associated with the severity of sickle cell anemia in 1,265 patients with either “severe” or “mild” disease based on a network model of disease severity. We analyzed data using single SNP analysis and a novel SNP set enrichment analysis (SSEA) developed to discover clusters of associated SNPs. Single SNP analysis discovered 40 SNPs that were strongly associated with sickle cell severity (odds for association >1,000); of the 32 that we could analyze in an independent set of 163 patients, five replicated, eight showed consistent effects although failed to reach statistical significance, whereas 19 did not show any convincing association. Among the replicated associations are SNPs in KCNK6 a K⁺ channel gene. SSEA identified 27 genes with a strong enrichment of significant SNPs (P < 10^?6); 20 were replicated with varying degrees of confidence. Among the novel findings identified by SSEA is the telomere length regulator gene TNKS. These studies are the first to use GWAS to understand the genetic diversity that accounts the phenotypic heterogeneity sickle cell anemia as estimated by an integrated model of severity. Additional validation, resequencing, and functional studies to understand the biology and reveal mechanisms by which candidate genes might have their effects are the future goals of this work. Am. J. Hematol., 2010. © 2009 Wiley‐Liss, Inc.     

In a flexible antagonist protocol, earlier, criteria-based initiation of GnRH antagonist is associated with increased pregnancy rates in IVF

BACKGROUND: The purpose of the study was to assess ongoing pregnancy rates across groups of patients treated by IVF, which were defined according to criteria aimed at the prevention of premature LH surge and used for initiating GnRH antagonist. METHODS: This is a prospective observational cohort study. During the last 3 years, in IVF-ICSI patients undergoing controlled ovarian stimulation (COS) with the antagonist protocol, the antagonist administration was initiated according to at least one of the following patient-specific criteria: (i) at least one follicle measuring >14 mm; (ii) estradiol levels >600 pg/ml; and (iii) LH levels >10 IU/l. Based upon these criteria, 208 cases of normal responders were analysed and categorized into three groups according to the starting day of the regimen: group D4 (n = 40) for day 4, group D5 (n = 98) for day 5 and group D6 (n = 70) for day 6. The main outcome measure was the ongoing pregnancy rate per started cycle. RESULTS: The total number of patients in the D4 and D5 groups (138 out of 208), who received the antagonist earlier, was considerably larger compared with that of D6 (70 out of 208). Ongoing pregnancy rates were 37.5, 34.7 and 18.6% for groups D4, D5 and D6, respectively. Patients who initiated the GnRH antagonist on days 4 and 5 had statistically significant higher pregnancy rates compared with day 6. Rapid response, causing earlier antagonist administration initiation, according to the proposed criteria for the prevention of premature LH surges, and the absence of premature luteinization, as evidenced by normal progesterone levels on HCG day, were found to be independent positive predictive factors for favourable IVF outcome. CONCLUSIONS: The employment of an algorithm of criteria, aimed at the prevention of premature LH surges in a flexible antagonist protocol, resulted in antagonist initiation earlier than on stimulation day 6 in a significant proportion of patients. In those patients, a higher pregnancy rate was observed.     

Osseous metaplasia: case report and review

OBJECTIVE: To discuss, through the experience of a case report and extensive literature review, the best practices for the diagnosis and treatment of osseous metaplasia, which is the cause of secondary infertility. DESIGN: Case report. SETTING: In vitro fertilization unit in Athens. PATIENT(S): A 40-year-old woman with a 10-year history of secondary infertility. INTERVENTION(S): Hysteroscopic diagnosis and removal of the bony fragment. MAIN OUTCOME MEASURE(S): Elimination of secondary infertility caused by osseous metaplasia. RESULT(S): After treatment, the woman underwent an IVF program and a healthy neonate was born with cesarean section. CONCLUSION(S): Hysteroscopy remains the best practice for the diagnosis and removal of endometrial ossifications, causing secondary infertility.     

Determination of mineral content of active dry yeast used in pharmaceutical formulations

The efficiency of seven common methods of digestion of active dry yeast (ADY), which is used in anticariogenic dental formulations, was evaluated for the analytical determination of Fe, Zn, Ca, Mg, Na and K. Four wet-acid digestion and three dry ashing methods are compared in consideration of their estimated reproducibility and metal concentrations obtained. HNO(3), HNO(3)+HCl, HNO(3)+H(2)SO(4) and HNO(3)+HClO(4) were applied for wet digestion of the samples in medium temperatures, while dry ashing at higher temperature with Mg(NO(3))(2) or SrCl(2) as ashing aid agents, were the alternative methods. The final solutions were subsequently analyzed for Fe, Zn, Ca and Mg by flame atomic absorption spectroscopy (FAAS) and for Na and K by atomic emission spectroscopy (AES). Two multivariate statistical methodologies, Analysis of variance (ANOVA) and the Kruskal-Wallis test were applied for the interpretation of the results. Seven additional statistical tests (least-significant difference, Bonferoni, Duncan multiple range, Student-Newman-Keuls, Tuckey significant difference, Tuckey b and Scheffe) were used and proved useful to estimate which of the decomposition methods are outliers. The ideographic approach enabled the comparison of the methods in terms of complexity and difficulty of their steps. Zn and Mg could be reliably determined by any one of the tested methods, while for the other elements, the most powerful method was found and the obtained recoveries were found (>95%).     

Pharmacokinetics of fusidic acid and cefepime in heart tissues: implications for a role in surgical prophylaxis

The pharmacokinetic profiles of fusidic acid and cefepime in heart tissues were assessed in 30 patients undergoing elective valve replacement and cardiopulmonary bypass. Single doses of 1 g of fusidic acid and 2 g of cefepime were administered intravenously to two groups of 15 and 15 patients respectively upon initiation of anesthesia. Samples of serum, heart valves, myocardium, pericardium, mediastinal fat and sternum were collected within <1 hour, 1-2 h and 2-4 h after the end of drug infusion. Drug concentrations were estimated by a microbiological assay. It was found that concentrations of fusidic acid in all specimens were 20-fold higher than the MIC90s of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, being at such levels throughout all period of sampling. Cefepime concentrations in heart valves collected 1-2 h after drug infusion were higher than the MIC90s of multidrug-resistant Enterobacteriaceae. It is concluded that both fusidic acid and cefepime penetrated heart tissues adequately; however only fusidic acid could also accumulate in the mediastinum. These data suggest that both antibiotics may be a good alternative for prophylaxis in open heart surgery.     

The iMPROVE Study; Design,Dietary Patterns,and Development of a Lifestyle Index in Overweight and Obese Greek Adults

Background: Dietary and lifestyle habits constitute a significant contributing factor in the formation of anthropometric and biochemical characteristics of overweight and obese populations. The iMPROVE study recruited overweight and obese Greek adults and investigated the effect of gene–diet interactions on weight management when adhering to a six-month, randomized nutritional trial including two hypocaloric diets of different macronutrient content. The present paper displays the design of the intervention and the baseline findings of the participants’ dietary habits and their baseline anthropometric and biochemical characteristics. Methods: Baseline available data for 202 participants were analyzed and patterns were extracted via principal component analysis (PCA) on 69-item Food-Frequency Questionnaires (FFQ). Relationships with indices at baseline were investigated by multivariate linear regressions. A Lifestyle Index of five variables was further constructed. Results: PCA provided 5 dietary patterns. The “Mixed” pattern displayed positive associations with logBMI and logVisceral fat, whereas the “Traditional, vegetarian-alike” pattern was nominally, negatively associated with body and visceral fat, but positively associated with HDL levels. The Lifestyle Index displayed protective effects in the formation of logBMI and logGlucose levels. Conclusions: Dietary patterns and a Lifestyle Index in overweight and obese, Greek adults highlighted associations between diet, lifestyle, and anthropometric and biochemical indices.