The aim of the study was to explore the impact of oxidative stress on frozen seminal plasma in fertile and infertile men by examining the total antioxidant capacity. Patients: Infertile patients from male infertility clinic with various diagnoses and fertile men. Design: Seminal plasma from proven fertile men [n=50] and infertile patients [n=50] were examined for total antioxidant capacity (TAC) level, semen parameters such as morphology, motility and concentration, and DNA integrity test. Interventions: Seminal plasma TAC measurement by luminometric assay using the TAC assay kit, semen analysis parameters, DNA integrity test. Fertile men showed higher TAC values (median and SD): 1201µM (SD±548), as compared with the infertile patients: 831μM (SD±343). The result from sperm morphology of fertile patients showed a mean percentage of 4.8 % (SD±1.68) whereas the percentage in the infertile group was 2.68% (SD ±1.68). The same group of samples, analyzed for DNA damage showed a mean of DFI 10.38% (SD±5.17%) in fertile men and a mean of DFI 17.22% (SD±7.22%) in infertile men. Total antioxidant capacity of the seminal plasma as measured by the luminоmetric assay is a reliable and simple test for diagnosing and management of male infertility.
Pulmonary embolism (PE) is a relatively common cardiovascular emergency, though its exact incidence is difficult to assess. Accurate diagnosis is critical because of the high 30-day mortality in patients in whom the diagnosis is missed on admission. Doubt for PE is often raised by the presence of risk factors for venous thromboembolism (VTE), which are categorized into inherited and acquired. Among these, the importance of inherited/genetic thrombophilic factors is increasingly recognized. The most frequent markers of inherited thrombophilia are Factor V Leiden (FVL) and G2021OA prothrombin gene mutation. Among the inherited factors causal to thrombophilia, the C677T variant in methylentetrahydrofolate reductase (MTHFR) gene as well as factors like P1A1/P1A2 polymorphism in platelet glycoprotein Ilb/IIIa (P1A2) and hypofibrinolytic polymorphism 4G/4G in PAI-1 gene are discussed with controversial results. In our study, thrombophilic and hypofibrinolytic genetic variants were identified in 54.2% of 115 patients with PE. The most common significant genetic defects were FVL- 16.5% in patients versus 6.2% in controls (OR=3.102; p=0.05), G20210A PT 5.7% versus 2.1% (OR=2.983; p>0.05). P1A2 was found in 27.3% patients versus 19.9% in controls (OR= 1.523, p>0.05) and PAM 27.8% versus 22.6% (OR =1.501 p>0.05). MTHFR C677T carriage was inverse: 6.7% in patients versus 13.4% in controls. (OR=0.461 p=0.05). Of all the patients studied, 15.65% had a history of recurrent embolic incidents. The risk of recurrence was higher for the carriers of FVL and G20210A prothrombin gene mutation. The association between carriage of thrombophilic genetic factor and the early onset of the first embolic episode was found in the patients with PE. The awareness of risk factors and risk stratification is a critical issue in treatment and prevention policy. Preventive measures should be taken in particular medical conditions.
The present study aimed to evaluate the impact of factor V Leiden (FVL) polymorphism within the reproductive problems encountered by patients with polycystic ovary syndrome (PCOS). A total of 92 female patients with PCOS and 101 healthy controls were included in the study. Clinical and laboratory parameters were examined. The full history of each patient was taken. Single nucleotide polymorphism rs6025 in F5 was genotyped in PCOS patients and compared to the genotype frequency of the healthy controls. The data were analysed for correlation with infertility and pregnancy loss in PCOS patients. The prevalence of FVL polymorphism was higher, however not significantly, in PCOS patients compared to that of the control group (respectively OR=2.238, 95 % CI 0.777±6.449, p=0.104). The carriers of FVL polymorphism showed a higher rate of primary infertility (30.0% versus 12.5%, OR=3.143, 9 % CI 0.686±14.388, p=0.047) and their total reproductive failure rate was higher (60.5% versus 47.2%, OR=1.819, 95% CI 0.632±9.259, p=0.117). Carriage of FVL polymorphism in PCOS patients is associated with primary infertility and a presumed cause of the further investigations needed to understand the impact of FVL on PCOS. Carriage of FVL polymorphism in PCOS patients is associated with a higher rate of primary infertility, which draws attention to the role of this factor in the aetiology of the PCOS-related subfertility. Further investigations are needed to understand the impact of FVL on PCOS.
Detection of mutations in breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) gene is an effective method of early diagnosis and prevention of breast cancer (BC). The mutational spectrum of both genes in Bulgarian population has not been studied in depth. The aim of this study was to investigate the prevalence of five deleterious BRCA1/2 point mutations in high-risk BC women, selected according to the National Comprehensive Cancer Network (NCCN) Guidelines including early age of onset, triple-negative BC and family history of breast or ovarian cancer. The prevalence of two BRCA1 mutations (C61G and 5382insC) and three BRCA2 mutations (6079del4, 9326insA and 9908delA) was evaluated in 80 females with BC, obtained from the Cancer Registry of University Hospital - Pleven. Genetic testing was performed by direct DNA sequencing. One deleterious mutation (5382insC in exon20 in BRCA1) was been found in two patients (2.5%). Both women were diagnosed with BC before age 45. The prevalence of BRCA mutations established in our study was lower than the one found in another preliminary study on Bulgarian population. We concluded that this discrepancy was due to the genetic heterogeneity of the population and the specific mutational spectrum of the BC patients from the Pleven region.
The incidence of deep venous thrombosis (DVT) depends on the specific genotype, inheritance of prothrombotic polymorphisms and the influence of environmental risk factors. Rs1799889(-) polymorphism in the promotor of PAI-1 gene has been described as a risk factor for hypercoagulable state. Objective: To evaluate the contribution of thrombophilic rs1799889 (-) in the promotor of PAI-1 gene on the incidence of DVT in women and men in groups below and above 45 years of age. Тhere was significantly higher rs1799889 (-) polymorphism carriage among female patients with DVT vs controls (Chi squared =5.506, OR=2.170, p=0.021) but not in male patients (Chi squared =0.090 OR=1.147, p=0.825). A significant contribution of rs1799889 (-) polymorphism to early onset of the disease was found in female patients aged 45+ and carriers of the polymorphism (Chi squared =7.476, p=0.006), but not in young women.
Genetic testing for BRCA 1/2 mutation is a well recognized medical management tool. Identification of healthy carriers of such mutations allows effective risk reduction procedures to be performed. There is no data reported on the founder mutations in the Bulgarian population. To evaluate the contribution of genetic factors to breast cancer (BC), we investigated the carrier state of Bulgarian women with BC for five common (according to BIC database) deleterious BRCA1/2 mutations. The list of patients diagnosed with BC between January 2011 and April 2012 was obtained from the Cancer Registry of University Hospital, Pleven. Eighty-two women with BC were interviewed and a pedigree was constructed of each of them. The patients were classified into seven categories, according to personal, disease and family history. Based on the preliminary prepared selection criteria and the personal family history, we defined a target group of 33 Bulgarian women with BC. They were screened for five deleterious mutations: 5382insC in BRCA1 and 6174delT, 6079del4, 8138del5, 5946delCT in BRCA2, by DNA sequencing. The genetic analysis detected none of the tested mutations. Two polymorphic variants were found in BRCA2 gene: c.5744C>T (rs4987117, SNP database) in exonl 1E in one patient and c.7806-14T>C (rs9534262, SNP database) in exonl7 in 22 patients. In conclusion, without basic information on the founder mutations in the population, the genetic screening for the specific mutations in a small group of tested patients is ineffective.
Colorectal cancer in pregnant women is rare and represents a diagnostic and therapeutic challenge for clinicians. We present a case of a 38-year-old pregnant woman, diagnosed with colorectal cancer and liver metastases during the 29th week of gestation. After clinical evaluation and making the diagnosis, the patient underwent an emergency cesarean section (C-section) and bypass anastomosis between the transverse colon and sigmoid colon. The babies were born healthy without any complications. After recovery, the mother started treatment with chemotherapy, but two months later she died due to the spread of the disease. Cancer during pregnancy is always a challenge for diagnosis and treatment.
Myeloproliferative neoplasms (MPN) are haematological diseases, characterized by clonal hematopoiesis. Hemostasis abnormalities are among the most critical and frequent complications, affecting the quality of life and a possible reason for death. Thrombotic complications are common and multifactorial. Our aim was to study some genetic thrombophilia factors – Factor V Leiden (FVL), G20210A mutation in prothrombin gene (PR G20210A) and PLA2 allele polymorphism of glycoprotein IIIa gene (GPIIIa gene), and their frequency and association with thrombotic risk in both Philadelphia-positive and Philadelphia-negative MPN – chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary and secondary myelofibrosis (MF). In our patient population, PLA2 allele polymorphism of GPIIIa gene proved to be the most common and significantly associated with thrombotic complications – 26.85% of our patients were carriers, and 24.14% of them reported thrombotic complications.
Breast cancer is the most common cancer in women worldwide. The standard for detecting it includes clinical exam, mammography and fine-needle aspiration cytology. Our aim was to establish the role of the tru-cut biopsy in the diagnosis of malignant breast lesions. We provideatwo-year retrospective clinical study defining 98.67%sensitivity, 100%specificity, 100%positive predictive value, 80%negative predictive value and an overall diagnostic accuracy of 98.73%. In 89.1%of the malignant lesions, the sample was adequate to define the receptor status. Therefore, tru-cut biopsy is an easy, cheap, safe and accurate alternative to fine-needle aspiration cytology in the diagnosis of breast lesions.
The study aimed to assess the inhalation technique of patients with bronchial asthma/chronic obstructive pulmonary disease (COPD) via an objective method and to evaluate the effect of training in patients with incorrect technique. Тhe inhalation technique of 120 patients with obstructive pulmonary disease was tested. The patients were divided into two groups: using metered dose inhalers (MDI) - 34 patients (28%) and dry powered inhalers (DPI) - 86 patients (72%). The most frequent mistakes in the MDIgroup were short duration of the inhalation (55.88%) and bad synchronization between activating the canister and the inhalation (29.41%). For the DPIgroup, the inhalation was not forceful enough (48.84%) and the short duration of the inhalation (12.79%). Patients claiming to have good inhalation technique accounted for 97%of those in the MDIgroup, and 96.5%of those in the DPIgroup. There were two patients (5.88%) with correct inhalation technique in the MDIgroup at their first attempt, and 31 patients (36.05%) in the DPIgroup. We found that in the MDIgroup there wasasignificant reduction in the number of mistakes (p<0.001). In the DPIgroup, such correlation was not found but during visit 2 there were no patients with more than 1 mistake. Correcting poor inhalation technique led to reduction of the number of mistakes during inhalation.