Assessment of Platelet Reactivity and Inflammatory Markers in Coronary Artery Bypass Graft Patients Treated with Acetylsalicylic Acid with Flavonoid Supplementation.

The recommended pharmacological therapy for patients with coronary artery disease (CAD) treated by coronary artery bypass grafting (CABG) is acetylsalicylic acid (ASA). To improve the antiplatelet effect, supplementation with flavonoids is also recommended. The aim of this study was to estimate anti-aggregation properties of diosmin, in combination with ASA, pre- and postoperatively and assess the relationship of this therapy with inflammatory processes in CAD patients undergoing CABG. The study patients (n = 26) took diosmin (1000 mg/day); the control patients (n = 27) took a placebo. The therapeutic period for taking diosmin was from at least 30 days before to 30 days after CABG. All patients also took 75 mg/day ASA. Platelet aggregation and IL-6, CRP, and fibrinogen concentrations were determined before and 30 days after surgery. Results showed that diosmin did not enhance the anti-aggregation effect of ASA at any assessment time. However, there was a stronger anti-aggregation effect 30 days after surgery that was diosmin independent and was associated with acute-phase markers in the postoperative period. Increased levels of inflammatory markers in the late phase of the postoperative period may provide an unfavorable prognostic factor in long-term follow-up, which should prompt the use of stronger antiplatelet therapy in patients after CABG.

Atypical Pupil Reactions in Brain Dead Patients.

BACKGROUND: During routine diagnosis of brain death, changes in pupil diameter in response to the stimulation of peripheral nerves are sometimes observed. For example, pupillary dilation after diagnosed brain death is described in the literature as the ciliospinal reflex. However, pupil constriction creates diagnostic doubts. OBJECTIVE: The pupillometric analysis of pupil response to stimulation of the cervicothoracic spinal cord in patients with diagnosed brain death. METHODS: Instrumental tests to confirm the arrest of cerebral circulation were performed in 30 adult subjects (mean age 53.5 years, range 26-75 years) with diagnosed brain death. In addition, a pupillometer was used to measure the change in pupil diameter in response to neck flexion. INTERVENTION: Flexion of the neck and measuring the response in change of the pupil with the use of the pupillometer. RESULTS: The change in the pupil was observed in the examined group of patients. Difference in pupil size ≥ 0.2 mm was observed in 14 cases (46%). In five cases (17%), pupil constriction was found (from 0.2 to 0.7 mm). Measurement error was +/- 0.1 mm. CONCLUSIONS: Both pupillary constriction and dilatation may occur due to a ciliospinal reflex in patients with brain death. This phenomenon needs further research in order to establish its pathophysiology.

Reference Values of D-Dimers and Fibrinogen in the Course of Physiological Pregnancy: the Potential Impact of Selected Risk Factors-A Pilot Study.

Pregnancy predisposes to thrombotic hemostasis, reflected in the laboratory as, e.g., increased levels of D-Dimers and fibrinogen, but in physiological pregnancy, the risk of venous thrombosis does not increase. Risk may increase if gestational diabetes mellitus (GDM) or nicotinism coexists. Study aims were to determine reference values for D-Dimers and fibrinogen concentrations in each trimester of pregnancy, corrected for GDM and nicotinism. Subjects and Methods. The study involved 71 pregnant women aged 25-44 y. Venous blood was collected three times: in the first (11-14 weeks), second (20-22 weeks), and third (30-31 weeks) trimesters. D-Dimer concentrations were determined by an enzyme-linked fluorescence assay, fibrinogen concentrations by a coagulation method according to Clauss. Results. Significant increases in D-Dimers and fibrinogen concentrations were observed, increasing with successive trimesters (p ANOVA < 0.0001). Furthermore, a positive correlation between D-Dimers and fibrinogen was detected in the second trimester of pregnancy (r = 0.475; p < 0.0001). In addition, a significantly higher fibrinogen concentration was found in women with GDM compared to without GDM (p = 0.0449). Reference ranges for D-Dimers were established, in trimester order, as follows: 167-721 ng/mL, 298-1653 ng/mL, and 483-2256 ng/mL. After adjusting for risk factors, significantly higher D-Dimer values (mainly second and third trimesters) were obtained: 165-638 ng/mL, 282-3474 ng/mL, and 483-4486 ng/mL, respectively. Reference ranges for fibrinogen were, in trimester order, 2.60-6.56 g/L, 3.40-8.53 g/L, and 3.63-9.14 g/L and, after adjustment for risk factors, 3.34-6.73 g/L, 3.40-8.84 g/L, and 3.12-9.91 g/L. Conclusions. We conclude that the increase in D-Dimers and fibrinogen levels in women with physiological pregnancy was compounded by gestational diabetes (GDM) and nicotinism. Therefore, D-Dimers and fibrinogen pregnancy reference values require correction for these risk factors.

Diagnostic value of non-enhanced computed tomography in identifying location of ruptured cerebral aneurysm in patients with aneurysmal subarachnoid haemorrhage.

BACKGROUND: In patients with SAH and multiple aneurysms, the ruptured lesion must be identified to prevent recurrent bleeding. AIM OF THE STUDY: To assess the diagnostic value of non-enhanced computed tomography (NECT) in identifying the rupture site in patients with subarachnoid haemorrhage (SAH) and multiple aneurysms. MATERIAL AND METHODS: We included patients with SAH revealed by NECT and multiple aneurysms detected on computed tomography angiography (CTA) in whom a ruptured aneurysm was identified during neurosurgery. Two radiologists predicted the location of the ruptured aneurysm based on the distribution of the SAH and location of intracerebral haematoma (ICH) by NECT. RESULTS: Eighty-three patients with a mean age of 55.7 ± 14.4 years were included. Ruptured aneurysms were significantly larger (mean size 7.7 ± 4.7 mm) than unruptured aneurysms (mean size 5.9 ± 4.5 mm; p = 0.014). Interobserver agreement was 0.86 (p < 0.001). Overall sensitivity and specificity of radiological prediction were 78.3% (95% CI, 68.6%-87.1%) and 96.4% (95% CI, 94.3%-97.8%) respectively. Overall PPV and NPV were 78.3% (95% CI, 67.6%-86.3%) and 96.8% (95% CI, 94.8%-98.1%) respectively. The sensitivity and PPV for aneurysms in the anterior communicating, anterior, and middle cerebral arteries appeared to be significantly higher than in other locations (p = 0.015 and 0.019 respectively). Analysis of independent predictive factors of correct radiological location revealed that ICH predisposes to a correct radiological diagnosis with an odds ratio of 8.57 (95% CI, 1.07-68.99; p = 0.03). CONCLUSIONS: NECT has a high diagnostic value in identifying the source of bleeding in patients with multiple aneurysms for anterior circulation aneurysms, especially with coexisting ICH. For other locations, NECT is not reliable enough to base treatment decisions upon.

Association between the Urinary Bladder Volume and the Incidence of "De Novo" Overactive Bladder in Patients with Stress Urinary Incontinence Subjected to Sling Surgeries or Burch Procedure.

Aim. The aim of the study was to compare the incidence of "de novo" overactive bladder (OAB) after sling surgeries and Burch procedure and to analyze the effect of the preoperative bladder volume on the incidence of this condition. Methods. This prospective trial included 290 female patients with stress urinary incontinence (SUI) who were subjected to sling surgeries (TOT or TVT, n=170) or Burch procedure (n=120). Urodynamic testing was performed prior to the surgery and 6 months thereafter. The presence of OAB was diagnosed on the basis of subjective symptoms and urodynamic parameters. Results. The incidence of OAB 3 at 6 months postsurgery was the highest in patients who were subjected to the Burch procedure (14.2% and 17.5%, respectively). The incidence of OAB at 6 months turned out to be significantly higher in patients subjected to the Burch procedure with preoperative bladder volumes greater than 353 ml. We observed the significant postoperative decrease in the bladder volume of women who developed this complication following the Burch procedure. Conclusions. Among surgeries for stress urinary incontinence, Burch procedure is associated with the greatest risk of overactive bladder development. Probably, one reason for the higher incidence of overactive bladder after Burch procedure is the intraoperative reduction of the urinary bladder volume.

Comparison of Two Apnea Test Methods, Oxygen Insufflation and Continuous Positive Airway Pressure During Diagnosis of Brain Death: Final Report.

INTRODUCTION: Deterioration of the pulmonary function after the apnea test (AT) conducted with the classic oxygen insufflation AT (I-AT) is often observed during the brain death (BD) diagnosis procedure. In the present study, two AT methods were compared before a method is recommended for the currently revised Polish BD criteria. METHODS: Classic I-AT and continuous positive airway pressure AT (CPAP-AT) were performed in 60 intensive care unit patients. I-AT was performed at the end of two series of clinical tests, and approximately 1-1.5 h later, after BD was confirmed, a different method, CPAP-AT with 100% FiO2 and CPAP value of 10 cm H2O provided by a ventilator in CPAP mode was performed. The patients in I-AT and CPAP-AT groups were further divided into two subgroups: non-hypoxemic (NH) with good lung function before AT (PaO2/FiO2 index ≥ 200 mmHg) and hypoxemic (H) with poor lung function (PaO2/FiO2 index < 200 mmHg). PaO2 and PaCO2 were recorded prior to I-AT and CPAP-AT at time-point one (T1), 5 min after each test at time-point two (T2), and after 10 min prior to the end of tests at time-point three (T3). The I-AT NH subgroup consisted of 50 patients, and CPAP-AT NH subgroup 43 patients. The I-AT H subgroup consisted of 10 patients, and the CPAP-AT H subgroup 17 patients. RESULTS: In the I-AT NH subgroup, a gradual decrease in PaO2/FiO2 was observed throughout the AT but not in the CPAP-AT NH subgroup. The PaO2/FiO2 ratio during the AT in the CPAP-AT H group was stable with a slight tendency to increase but not in the I-AT H group. During the first 5 min of the AT, the mean increase in CO2 was approximately 5 mmHg/min. Most patients in all groups met the AT criteria after 5 min of the test. CONCLUSIONS: The results from the study show that I-AT may compromise pulmonary function in some cases and is one of the reasons for the recommendation of a safer option, CPAP-AT, in the currently revised Polish BD criteria. During AT, the mean CO2 increase rate was 5 mmHg/min, which, in most patients, would allow the test to be completed after just 5 min.

Vitamin D as a follicular marker of human oocyte quality and a serum marker of in vitro fertilization outcome.

PURPOSE: This study investigated the relationship between the vitamin D [25(OH)D] level in individual follicles and oocyte developmental competence. METHODS: A prospective cohort study in a private infertility center. Infertile women (N = 198) scheduled for intracytoplasmic sperm injection (ICSI) and a single embryo transfer (SET) provided serum samples and 322 follicular fluid (FF) specimens, each from a single follicle on the day of oocyte retrieval. RESULTS: FFs corresponding to successfully fertilized oocytes (following ICSI) contained significantly lower 25(OH)D level compared with those that were not fertilized (28.4 vs. 34.0 ng/ml, P = 0.001). Top quality embryos on the third day after fertilization, when compared to other available embryos, developed from oocytes collected from follicles containing significantly lower 25(OH)D levels (24.56 vs. 29.59 ng/ml, P = 0.007). Positive hCG, clinical pregnancy, and live birth rates were achieved from embryos derived from oocytes that grew in FF with significantly lower 25(OH)D levels than in follicles not associated with subsequent pregnancy. The concentration of 25(OH)D in FF in women with negative hCG was 32.23 ± 20.21 ng/ml, positive hCG 23.62 ± 6.09 ng/ml, clinical pregnancy 23.13 ± 6.09 ng/ml, and live birth 23.45 ± 6.11 ng/ml (P < 0.001). Women with serum 25(OH)D < 20 ng/ml had not only a higher fertilization rate (71 vs. 61.6%, P = 0.026) and a higher clinical pregnancy rate (48.2 vs. 25%, P = 0.001), but also higher miscarriage rate (14.5 vs. 3.8%, P = 0.013) compared with those with levels ≥ 20 ng/ml. CONCLUSION: This study reveals that the level of 25(OH)D in FF correlates negatively with the oocytes' ability to undergo fertilization and subsequent preimplantation embryo development. Oocytes matured in FF with low 25(OH)D concentration are more likely to produce top quality embryos and are associated with higher pregnancy and delivery rates. On the other hand, low serum vitamin D concentration is associated with higher miscarriage rates.

Alcohol Drinking Pattern Is Associated with Demographic Features of Primary Health Care Patients in Poland: A Cross-Sectional Study.

BACKGROUND The Optimizing Delivery of Health Care Interventions (ODHIN) project focused on the implementation of screening and brief intervention for hazardous and harmful alcohol consumption in primary health care. The aim of the present study was to investigate whether alcohol drinking pattern is associated with demographic features of primary health care patients in Poland and if it is possible to identify groups at highest risk for hazardous and harmful drinking. MATERIAL AND METHODS The study enrolled 8805 adult (mean age 54.98±16.94, M/F - 3581/5224) patients reporting to 30 general practitioners working in 10 primary health care units located in urban and partially rural areas in Poland. The shortened, 3-item version of the Alcohol Use Disorders Identification Test (AUDIT-C) was the screening tool used. RESULTS Place of residence was significantly associated with higher odds of hazardous and harmful drinking diagnosis, referred to as AUDIT-C (+). Age and sex were significantly associated with AUDIT-C (+) and suspicion of alcohol dependence, referred to as AUDIT-C ³8 scores. Logistic regression revealed that males had 5-fold higher odds for hazardous and harmful drinking diagnosis and almost 28-fold higher odds for suspected alcohol dependence compared to females. CONCLUSIONS Demographic features are associated with drinking pattern of primary health patients in Poland. Young males and those inhabiting rural areas are at highest risk of being hazardous or harmful drinkers and of being alcohol dependent. There is a growing need for development of national guidelines to address the prevention of alcohol-related health problems by general practitioners.

Apnea testing using the oxygen insufflation method for diagnosis of brain death may compromise pulmonary function.

INTRODUCTION: The aim of our study was to compare the reliability and safety of the classical I-AT with the continuous positive airway pressure apnea test (CPAP-AT). MATERIAL AND METHODS: In the group of 48 patients (group O), an I-AT was performed at the end of BD diagnostic procedures, and approximately 1-1.5h later CPAP-AT with 100% FiO2 and CPAP of 10cm H2O, provided by ventilator in CPAP mode. After pre­oxygenation with 100% FiO2 for 10min, the PaO2/FiO2 ratio was recorded prior to I-AT at time-point one (T1) and prior to CPAP-AT at time-point two (T2). Group O was categorized into subgroup N-H (non-hypoxemic), consisting of 41 patients with good lung function, and subgroup H (hypoxemic) consisting of 7 patients with poor lung function. Within each subgroup PaO2/FiO2 at T1 and T2 were compared. RESULTS: In Group O, PaO2/FiO2 decreased from 321±128mmHg at T1 to 291±119mmHg at T2 (p=0.004). In subgroup N-H, PaO2/FiO2 declined from 355±103 to 321±100mmHg (p=0.008), and in subgroup H, PaO2/FiO2 remained almost unchanged. Additionally, in 4 patients from subgroup N-H, PaO2/FiO2 decreased below 200mmHg at T2. CONCLUSIONS: Our study indicates that I-AT may compromise pulmonary function and this may support the recommendation of safer CPAP-AT alternative.

Homocysteine-Enhanced Proteolytic and Fibrinolytic Processes in Thin Intraluminal Thrombus and Adjacent Wall of Abdominal Aortic Aneurysm: Study In Vitro.

Homocysteine (Hcy) may affect the pathogenesis of abdominal aortic aneurysms (AAAs) through enhancement of proteolysis and an impaired coagulation/fibrinolysis system. Intensified haemostatic capacity may promote local proteolytic degradation of the aortic wall. This study aimed to examine the effects of Hcy on haemostatic and proteolytic processes in samples of thick and thin fragments of the ILT and underlying walls. Subjects and Methods. Thirty-six patients who underwent AAA surgery were enrolled. Aneurysm tissue sections were incubated with DL-Hcy (100 and 500 µmol/L) in a series of experiments and analyzed for concentration/activity of proteolytic and haemostatic markers by enzyme-linked immunosorbent assay. Results. Incubation of wall underlying thin ILT segments (B) with DL-Hcy resulted in an increase of active MMP-2 levels compared to control tissue (9.54 ± 5.88 versus 7.44 ± 4.48, p=0.011). DL-Hcy also induced t-PA and plasminogen concentration increases in thin thrombus sections (B1) compared to control tissue (respectively: 1.39 ± 1.65 versus 0.84 ± 0.74, p=0.024; 11.64 ± 5.05 versus 10.34 ± 5.52, p=0.018). In contrast, wall adjacent to thick thrombus segments (A) showed decreases in MMP-2 and TF activities compared to control (respectively, 5.89 ± 3.39 versus 7.26 ± 5.49, p=0.046; 67.13 ± 72.59 versus 114.46 ± 106.29, p=0.007). In thick ILT sections (A1), DL-Hcy decreased MMP-2 activity and t-PA and plasminogen concentrations compared to control tissue (respectively, 2.53 ± 2.02 versus 3.28 ± 2.65, p=0.006; 0.67 ± 0.57 versus 0.96 ± 0.91, p=0.021; 9.25 ± 4.59 versus 12.63 ± 9.56, p=0.017). In addition, analysis revealed positive correlations at all sites between activities/concentrations of MMP-2, TF, and PAI-1 measured in control tissues and after incubation with DL-Hcy. Conclusions. These data indicate the potential for excess Hcy to enhance damage of arterial wall in thinner AAA segments as a result of the increased activity of MMP-2 and fibrinolytic factors.

The Influence of Cigarette Smoke Exposure on the Copper Concentration in the Serum Depending on the Use of Menopausal Hormone Therapy.

This study evaluated the effect of menopausal hormone therapy (MHT) on serum concentration of copper in postmenopausal women depending on passive or active exposure to tobacco smoke or lack thereof. The study included healthy postmenopausal women aged 42-69 years, who used (n = 76) or did not use (n = 76) MHT. Salivary cotinine and serum copper concentrations were determined in all the study subjects. Salivary cotinine exceeded 14 ng/ml in 14 women from the MHT group (18.5%) and in 16 controls (21.1%). Up to 41 (27%) study subjects had serum copper above the upper normal limit (1.17 mg/l). No correlation was found between salivary cotinine and serum copper in women with cotinine concentrations <14 ng/ml, and these two parameters correlated weakly in subjects with cotinine >14 ng/ml. Salivary concentration of cotinine increased with serum copper level in the MHT group, but not in the controls; smokers using MHT presented with significantly higher serum copper than nonsmokers. These findings imply that MHT does not affect serum concentration of copper in women who are not exposed to tobacco smoke. However, MHT seems to contribute to unfavorable increase in serum copper in passive and active smokers.

Factors influencing multiplate whole blood impedance platelet aggregometry measurements, during aspirin treatment in acute ischemic stroke: a pilot study.

Among patients with stroke, the phenomenon of resistance to treatment with low-dose aspirin acetylsalicylic acid (ASA) is quite common. The study included 133 patients hospitalized with acute ischemic stroke. Impedance platelet aggregometry (IPA) and levels of vWF and thromboxane (TXB2) were assessed - with the efficacy of aspirin in daily clinical investigation. Responses to treatment with doses of 150 and 300 mg/day were measured. In addition, we analyzed the response of proinflammatory factors [fibrinogen, C-reactive protein (CRP), white blood corpuscles (WBC)], lipids and hemoglobin A1c, which may alter platelet aggregation response to treatment. After a week of treatment at 150 mg/day, ASA patients were classified as laboratory resistant (42%) or sensitive (58%). Values of IPA in the resistant group were significantly higher (472 ±â€Š150 vs. 222 ±â€Š59 AUC, P < 0.0001). In resistant patients were also found higher levels of fibrinogen (3.90 ±â€Š0.89 vs. 3.46 ±â€Š0.74 g/l, P = 0.0046), CRP (6.97 ±â€Š5.66 vs. 4.17 ±â€Š4.03 mg/l, P = 0.0011), WBC (9.2 ±â€Š2.4 vs. 8.3 ±â€Š2.2 × 10/l, P = 0.0207) and lower HDL cholesterol (46 ±â€Š12 vs. 52 ±â€Š15 mg/dl, P = 0.016). This research shows that aspirin resistance assessment by IPA well reflects the clinical status of patients and should be used routinely. Resistance generally fails to 'break' at higher doses, hence our suggestion that patients resistant to low doses of the drug immediately switch to a thienopyridine class antiplatelet agent, for example, clopidogrel.

Association between low-dose folic acid supplementation and blood lipids concentrations in male and female subjects with atherosclerosis risk factors.

BACKGROUND: Folic acid (FA) is one of the B complex vitamins. It is thought that FA deficiency promotes atherosclerosis formation in arterial endothelium. FA, acting through reducing homocysteine (Hcy) levels, may contribute to decreased cholesterol (Ch) synthesis. The aim of this study was to analyze the association of low-dose folic acid supplementation with blood lipids concentrations in subjects with atherosclerosis risk factors. MATERIAL/METHODS: The study enrolled 124 Caucasian individuals (60 M, ages 20-39; and 64 F, ages 19-39) with atherosclerosis risk factors (family history of premature ischemic stroke, arterial hypertension, dyslipidemia, overweight and obesity, cigarette smoking, and low level of physical activity). The participants were asked to take FA at a low dose of 0.4 mg/24 h for 12 weeks. RESULTS: FA levels increased in females (6.3 vs. 12.5 ng/dL; p=0.001) and males (6.4 vs. 11.4 ng/dL; p=0.001) and Hcy levels decreased (10.6 vs. 8.3 µmol/L; p=0.001 and 11.5 vs. 9.3; p=0.001, respectively). A significant reduction in mean concentration of total cholesterol in females (203.4 vs. 193.1 mg/dL; p=0.001) and in males (209.5 vs. 201.9; p=0.002) was observed. The low-density lipoprotein cholesterol (LDL-C) levels decreased in females and in males (107.4 vs. 99.9 mg/dL; p=0.001 and 121.5 vs. 115.1; p=0.002, respectively). The apoAI concentrations increased in smoking women and in men with BMI≥25 kg/m2 (p=0.032 and p=0.024, respectively). CONCLUSIONS: Low-dose FA supplementation has a beneficial effect on blood lipids through decreasing concentrations of total cholesterol and LDL-C and increasing concentrations of apoAI.

Homocysteine and metabolic risk factors in individuals with family history of premature ischemic stroke.

INTRODUCTION: Family history of stroke is an independent risk factor for cardiovascular disease (CVD). OBJECTIVES: The aim of this study was to evaluate selected metabolic risk factors and an association between the interaction of family history of premature ischemic stroke (PIS) and homocysteine (Hcy) levels with other risk factors in individuals with family histo ry of PIS. PATIENTS AND METHODS: The study involved 344 healthy individuals, including 143 with family history of PIS and 201 without family history of PIS (control group). RESULTS: In the group with family history of PIS, a significantly higher mean body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), ApoB/ apolipoprotein A-I (ApoA-I), and glucose values were observed in women, while in men, significantly higher mean values of BMI, SBP and DBP, total cholesterol (TC), LDL-C, ApoB/ApoA-I, and lower ApoA-I. There was a significant interaction of family history of PIS × Hcy for TC/high-density lipoprotein cholesterol (HDL-C), HDL-C, and triglycerides (TG) in women, and for TC/HDL-C, TC, and TG in men. Higher Hcy levels were associated with significantly higher values of TC/HDL-C and TG both in men and women, and with lower HDL -C levels in women and higher T C and LDL-C levels in men. CONCLUSIONS: Men and women with family history of PIS are characterized by an unfavorable shift in the risk factor profile. This effect is additionally enhanced by higher Hcy levels, which might be an indication for primary prevention in these individuals.

PvuII and XbaI polymorphisms of estrogen receptor-α and the results of estroprogestagen therapy in girls with functional hypothalamic amenorrhea - preliminary study.

INTRODUCTION: The aim of this study was the long-term prospective evaluation of the effects of estroprogestagen (EP) therapy on the bone mineral density (BMD) of girls with functional hypothalamic amenorrhea (FHA) carrying various PvuII and XbaI polymorphisms of ER-α. MATERIAL AND METHODS: Prospective observation included 84 FHA girls and 50 controls. The FHA patients were subjected to 4-year sequential therapy with 17ß estradiol (2 mg from the 2(nd) to 25(th) day of the menstrual cycle) and dydrogesterone (10 mg from the 16(th) to the 25(th) day). Hormonal parameters, serum concentration of the bone fraction of alkaline phosphatase (BALP), urine concentration of cross-linked n-telopeptide of type I collagen (Ntx) and BMD were determined before and after the treatment. RESULTS: Six-month treatment resulted in a marked increase in estradiol (p = 0.001), testosterone and prolactin levels (p = 0.01 both) and a significant decrease in BALP and Ntx (p = 0.001 both). Patients with the PP polymorphism had significantly lower baseline BMD compared to carriers of other polymorphic variants of PvuII (p = 0.003). A significant increase in BMD was observed throughout the entire therapy period, with no significant differences in the yearly dynamics of BMD changes observed amongst various polymorphic variants and haplotypes of ER-α. CONCLUSIONS: The EP therapy is effective in the treatment of BMD disorders associated with FHA, and treatment results do not depend on PvuII and XbaI polymorphisms of ER-α.

Is there an effect of folic acid supplementation on the coagulation factors and C-reactive protein concentrations in subjects with atherosclerosis risk factors?

INTRODUCTION: Folic acid (FA) may delay the formation of atherosclerotic lesions. Increased plasma levels of von Willebrand factor (VWF) are observed in cardiovascular disease, which leads to higher risk of thrombosis. Fibrinogen (Fb) is a well-documented risk factor of cardiovascular disease. The aim of this study was to analyze the effect of FA supplementation on the Fb, VWF and C-reactive protein (CRP) plasma concentrations in subjects with atherosclerosis risk factors. MATERIAL/METHODS: The study enrolled 124 Caucasian individuals (60 M, 64 F) with atherosclerosis risk factors--family history of premature ischaemic stroke, arterial hypertension, dyslipidaemia, overweight and obesity, cigarette smoking and low physical activity. The participants were asked to take FA in the low dose of 0.4 mg/24 h for three months. RESULTS: After FA supplementation a significant reduction of the VWF concentrations in females (76.6 vs 72.3%; p=0.028) and in males (75.5 vs 66.9%; p=0.001) was observed. Among women and men with dyslipidaemia concentrations of VWF decreased after FA supplementation (76.8% vs 69.6%; p=0.003 and 76.7% vs 67.8%; p=0.001 respectively). Among females and males with BMI ≥25 kg/m² concentrations of VWF decreased only in men (77.6% vs 66.5%; p=0.001). In female and male smokers supplementation of FA decreased VWF concentrations (82.5% vs 74.4%; p=0.012 and 76.6% vs 69.5%; p=0.036 respectively). DISCUSSION: The results of our study suggest that there is an effect of FA supplementation on VWF concentrations in subjects with atherosclerosis risk factors.

Genetic predispositions and the short- and long-term effects of hormonal therapy on bone mineral density in girls with functional hypothalamic amenorrhoea.

INTRODUCTION: The aim of this study was to verify if genetic factors influence the short- and long-term therapeutic responses to oestroprogestagen (OP) therapy, implemented in girls with functional hypothalamic amenorrhoea (FHA) in order to improve their bone mineral density (BMD). MATERIAL AND METHODS: The study included 78 FHA girls who underwent a four-year sequential OP therapy with 17-beta oestradiol and didrogesterone. Changes in the lumbar spine BMD were determined at the end of the therapy and six years after its discontinuation, and analysed in regards to PvuII and XbaI polymorphisms of oestrogen receptor-alpha gene, BsmI polymorphism of vitamin D3 receptor gene, and Sp1 polymorphism of the type-1 collagen gene. RESULTS: After four years of OP therapy, a significant increase in BMD was documented in the studied group. Follow-up densitometry performed six years after completing the therapy revealed a significant decrease in BMD level; nonetheless, the values of this parameter were still significantly higher compared to pretreatment level. Neither the particular polymorphisms nor their combinations influenced the relative change in BMD at the end of the therapy and after a six-year follow-up. CONCLUSIONS: Variability of genes involved in oestrogen, vitamin D3 and collagen metabolism does not influence the short- and long-term results of OP therapy in girls with FHA.

The character of haemostatic disorders and level of protein S-100 in acute ischaemic stroke can affect survival in the first week of follow-up: a pilot study.

Disorders of haemostasis which result in ischaemic stroke usually appear as thromboembolism in peripheral veins and the pulmonary circulation, and to a lesser extent as coagulopathy. The S-100 protein, a marker of stroke, correlates positively with the neurological deficit National Institutes of Health Stroke Scale (NIHSS). We adopted the hypothesis that early death of patients with acute ischaemic stroke can be explained by changes in blood coagulation and fibrinolysis. The study included 84 patients hospitalized with acute ischaemic stroke. Three groups were created: I (death between 1 and 2 days), II (death between 5 and 7 days) and III (with no deaths in hospital). We measured levels of fibrinogen, antithrombin, D-dimers, plasmin-antiplasmin complexes, plasminogen and clotting times (prothrombin time and activated partial thromboplastin time), platelet number, euglobulin clot lysis time (ECLTindex) and S-100 protein, C-reactive protein and white blood cells (WBCs). Group I had lower concentrations of fibrinogen compared to groups II (3.13 vs. 4.18, P<0.01) and III (3.13 vs. 3.77, P<0.02) and higher levels of D-dimers (3643 vs. 2278, P<0.05), higher concentrations of plasmin-antiplasmin complexes (1410 vs. 882, P=0.03) and a lower ECLTindex (152 vs. 219, P<0.02) when compared with group III. Group I also had higher concentrations of protein S-100 (2.09 vs. 0.61, P<0.001), higher NIHSS (18.0 vs. 13.2, P=0.073) and number of WBC (14.1 vs. 11.1, P<0.02) than in group III. The observed abnormalities in haemostasis, either found systemically or locally as cerebral microvascular thrombosis, may be factors potentially associated with death of patients with the shortest survival time.

Bone mineral density in girls with functional hypothalamic amenorrhea subjected to estroprogestagen treatment--a 4-year prospective study.

The aim of this study was to evaluate the effects of 4-year estroprogestagen therapy (EP) on the bone mineral density (BMD) of 16- to 17-year-old girls with functional hypothalamic amenorrhea (FHA, n = 78). Baseline values of hormonal parameters, bone fraction of alkaline phosphatase (BALP), and cross-linked n-telopeptide of type I collagen (Ntx) were taken along with BMD measurements. Follow-up measurements of laboratory parameters were performed after 6 months of EP treatment. BMD was measured on a yearly basis. Six-month treatment resulted in a marked increase in estradiol levels and a significant decrease in BALP and Ntx. The relative increase in BMD was highest after the second year of treatment. Based on the dynamics of BMD changes during the first year of treatment, we identified a subgroup with no or insignificant reactions to the treatment. It was characterized by significantly higher baseline BMD and markedly lower baseline Ntx compared to the patients who responded to 1-year therapy well or extremely well. Further follow-up proved, however, that this subgroup did not differ significantly in terms of the long-term prognosis for BMD normalization. In conclusion, this study showed that EP therapy is effective in the treatment of BMD disorders associated with FHA.

Association between ER-α polymorphisms and bone mineral density in patients with Turner syndrome subjected to estroprogestagen treatment--a pilot study.

Reduced bone mineral density (BMD) is present in many women with Turner syndrome (TS), and hypo-estrogenism is known to play a vital role in bone mineralization disturbances. It has been suggested that genetic factors play an important role in the regulation of BMD. The aim of this study was to analyze the association between Pvu II and XbaI ER-α polymorphisms and BMD in TS patients subjected to estroprogestagen (EP) treatment. Thirty-two TS patients aged 17-38 (mean age 22.7 ± 8.2) along with 82 healthy controls were the subjects for this study. Baseline values of hormonal parameters, BMD and bone density markers were measured in the subjects. Subsequently, TS patients underwent 4 years of EP therapy. The results of laboratory parameters and BMD were analyzed in regard to PvuII and XbaI polymorphic variants of the ER-α gene. The increase in BMD of TS subjects was the highest in the 1st (7.5%, p = 0.013) and 2nd (6.6%, p = 0.008) years of treatment. Four years of EP therapy was reflected by a significant increase in BMD z-scores in patients with xx and Xx genotypes of the XbaI gene and in those with with the pp and Pp genotypes of PvuII. In patients with haplotypes other than XXPP, BMD z-scores were significantly higher compared to their baseline after 2 (p = 0.002), 3 (p < 0.001) and 4 (p < 0.001) years of treatment. In conclusion, genotypes xx and pp were shown to be prognostic markers of a good response to EP treatment, whereas the XXPP haplotype carriers were revealed to have the risk factors for insufficient responsiveness against EP treatment in BMD control.