Chemotherapy-Associated Thrombocytopenia

Chemotherapy-related thrombocytopenia, although less frequent than granulocytopenia, may represent a life-threatening and less easily controlled event. It is usually the consequence of hypoplasia or aplasia of the megakaryocytic series in the bone marrow, although some cytotoxic and biologic agents are known to induce immune thrombocytopenias and thrombocytopenia associated with thrombopathic microangiopathy. The differential diagnoses should include the idiopathic thrombocytopenic purpura-like syndrome, progressive cancer involving bone marrow, and disseminated intravascular coagulation with thrombocytopenia caused by Gram-negative sepsis, tumor lysis syndrome and widespread metastatic cancer. Patients at risk of spontaneous bleeding are those with National Cancer Institute (NCI) grade 4 thrombocytopenia (i.e. those with a platelet count below 10×10⁹/L); even patients with a higher platelet count may spontaneously bleed if there is an associated vascular disorder or coagulopathy. Chemotherapy-related thrombocytopenia is usually acute and requires urgent therapeutic decisions. Recently, several pleiotropic hematopoietic growth factors with thrombopoietic activity have been developed for prospective therapeutic use; they include interleukins, especially IL-3, thrombopoietin, pegacaristim, promegapoietin and peptide agonists capable of binding and activating the thrombopoietin receptor. Some of these molecules (oprelvekin) have been approved for treatment of chemotherapy-induced thrombocytopenia. The main disadvantage of these drags is an overall long time lapse before peak platelet response. At present, platelet transfusions remain the only secure means to acutely increase the platelet count in patients with imminent or actual bleeding due to thrombocytopenia caused by chemotherapy. Most patients with NCI grade 4 thrombocytopenia need platelet transfusions and those with platelet counts within the range for grade 3 thrombocytopenia need their coagulation status determined. ‘Preventive’ platelet transfusions are not recommended and may increase the risk of alloimmunization and transfusion-transmitted disease.     

Exogenous modulation of intrinsic optic nerve neuroprotective activity

Background  

To characterize the molecular and functional status of the rat retina and optic nerve after acute elevation of intraocular pressure (IOP).     

Quantitative evaluation of collateral circulation in patients with previous myocardial infarction: relation to myocardial ischemia, angiographic appearance and functional improvement of myocardium

Evaluation of coronary pressures during angioplasty may functionally quantify collateral circulation. The aim of the study was to evaluate the relation between the amount of collateral circulation and development of myocardial ischemia during balloon occlusion, anatomic degree of collaterals, and functional improvement of myocardium. Study population consisted of 31 pts (mean age 53 ± 7 years; 25 male) with previous myocardial infarction and significant one-vessel stenosis undergoing angioplasty. Collateral circulation was calculated as the ratio between distal coronary pressure during balloon occlusion (P _w) and aortic pressure (P _a). Angiographic appearance of collaterals was evaluated by Rentrop classification. Patients were evaluated by echo for functional improvement of myocardium in the follow-up period. Mean P _w/P _a was 0.24 ± 0.10 (range of 0.07–0.51). Rentrop grade 0 of collaterals was present in 16 patients (52%), grade 1 in11 patients (35%), and grade 2 in 4 patients (13%). A mild correlation between angio and hemodynamic evaluation of collaterals was observed (r = 0.38, P = 0.035). In patients without ECG changes during angioplasty (21 pts, 68%), P _w/P _a was significantly higher in comparison to patients with ECG changes (0.28 ± 0.09 vs. 0.15 ± 0.06, P < 0.001; area under the curve 0.93). In patients with myocardial functional improvement during follow-up (21 pts, 68%), P _w/P _a was significantly higher than in the patients without echo improvement (0.26 ± 0.10 vs. 0.18 ± 0.08, P = 0.035). The amount of recruitable collaterals is not negligible even in the patients with no angio visible collaterals. Low values of P _w/P _a are associated with ECG changes during balloon occlusion. Higher P _w/P _a was associated with better functional improvement of myocardium.     

Molecular and Antimicrobial Susceptibility Analyses Distinguish Clinical from Bovine Escherichia coli O157 Strains

A population-based study combining (i) antimicrobial, (ii) genetic, and (iii) virulence analyses with molecular evolutionary analyses revealed segregative characteristics distinguishing human clinical and bovine Escherichia coli O157 strains from western Canada. Human (n = 50) and bovine (n = 50) strains of E. coli O157 were collected from Saskatchewan and Manitoba in 2006 and were analyzed by using the six-marker lineage-specific polymorphism assay (LSPA6), antimicrobial susceptibility analysis, the colicin assay, plasmid and virulence profiling including the eae, ehxA, espA, iha, stx₁, stx₂, stx_2c, stx_2d, stx_{2d-activatable}, stx_2e, and stx_2f virulence-associated genes, and structure analyses. Multivariate logistic regression and Fisher''s exact test strongly suggested that antimicrobial susceptibility was the most distinctive characteristic (P = 0.00487) associated with human strains. Among all genetic, virulence, and antimicrobial determinants, resistance to tetracycline (P < 0.000) and to sulfisoxazole (P < 0.009) were the most strongly associated segregative characteristics of bovine E. coli O157 strains. Among 11 virulence-associated genes, stx_2c showed the strongest association with E. coli O157 strains of bovine origin. LSPA6 genotyping showed the dominance of the lineage I genotype among clinical (90%) and bovine (70%) strains, indicating the importance of lineage I in O157 epidemiology and ecology. Population structure analysis revealed that the more-diverse bovine strains came from a unique group of strains characterized by a high degree of antimicrobial resistance and high frequencies of lineage II genotypes and stx_2c variants. These findings imply that antimicrobial resistance generated among bovine strains of E. coli O157 has a large impact on the population of this human pathogen.     

Association of TP53 codon 72 polymorphism with susceptibility to ovarian carcinomas in Serbian women

Objectives

Finding a potential genetic factor associated with a deadly disease, such as ovarian carcinoma, is of particular importance. The aim of this study was to examine the role of the TP53 codon 72 polymorphism in ovarian carcinoma development in Serbian women.

Study design

47 wild-type TP53 gene ovarian carcinoma samples and 70 cervical smears from gynecologically healthy women were analyzed. DNA was extracted by a salting-out procedure. Codon 72 polymorphism was assessed by PCR-RFLP method. χ², Fisher exact test and odds ratio were used for statistical analysis.

Results

The distribution of Arg/Arg, Arg/Pro and Pro/Pro genotypes of codon 72 of the TP53 gene was: 46.8%, 46.8% and 6.4%, respectively in the ovarian carcinomas and 64.3%, 31.4% and 4.3%, respectively in the control group. We observed an increased risk for the development of ovarian carcinoma for Pro homozygotes in relation to heterozygotes plus Arg homozygotes (OR = 1.52; 95% CI 0.29–7.89) and a higher one for Pro/Pro plus Arg/Pro genotype in relation to Arg homozygotes (OR = 2.04; 95% CI 0.96–4.34).

Conclusion

The results showed no association between codon 72 TP53 gene polymorphism and risk for development of ovarian carcinoma in Serbian women. However, this observation requires further analysis of a larger case–control study group.     

The Serbian version of the Epworth Sleepiness Scale

Purpose  

The Epworth Sleepiness Scale (ESS) is extensively used for evaluating daytime sleepiness in patients with sleep apnea–hypopnea syndrome (SAHS). The aim of this study was to translate and validate the ESS in the Serbian language.