Concomitant evaluation of flow-mediated vasodilation and epicardial fat thickness in idiopathic deep venous thrombosis

Flow mediated vasodilation (FMD) evaluates the endothelium-dependent vasodilation, is a reliable marker of arterial endothelial dysfunction and is related to coronary artery disease. Visceral fat predicts an unfavorable cardiovascular and metabolic risk profile in humans and echocardiographic assessment of epicardial fat (EF) is a reliable marker of visceral adiposity. We measured the FMD and EF thickness in 77 subjects, 38 without idiopathic deep vein thrombosis (DVT) (mean age 65.95 ± 16.29 years) and 39 with idiopathic DVT (mean age 65.49 ± 17.22 years). The purpose of this work is to investigate the presence of statistical association between FMD and DVT and between EF thickness and DVT. Furthermore, to account for possible atherosclerosis risk factor unbalances, comparison between FMD and DVT (and between EF and DVT) was assessed using a multivariate logistic regression model which included the following covariates: FMD, EF, age, sex, smoking and the presence of obesity. Subjects without DVT showed significant lower values of EF thickness (9.07 ± 1.89 mm vs 12.32 ± 1.73 mm, p=0.005) and borderline-significant greater values of FMD (9.01 ± 2.77 percent vs 7.47 ± 5.37 percent, p=0.058) as compared to those with DVT. In conclusion, the data presented indicate that subjects affected by spontaneous deep vein thrombosis may have an impaired endothelium-dependent vasodilation, a marker of arterial endothelial dysfunction related to coronary artery disease, and an increased epicardial adipose tissue, a marker of cardiometabolic risk.     

Structural analysis of human placental stem and terminal villi from normal and idiopathic growth restricted pregnancies

Studying in detail different histomorphological and pathological findings in placental stem and terminal villi of appropriate for gestational age (AGA) and idiopathic intrauterine growth restricted (IUGR) fetuses, then analyzing their correlation to the neonatal birth weight and to the some morphological features of the placenta. Fifty full-term human placentae of idiopathic IUGR and 25 of AGA pregnancies were processed for haematoxylin and eosin staining and evaluated by light microscope aided with Image Analyzer. The mean number of stem villous arteries, and the mean number of terminal villous capillaries per field are significantly lower in idiopathic IUGR group (4.63 ± 0.46, 47.09 ± 4.44, respectively) than in AGA group (12.36 ± 0.61, 73.35 ± 5.13, respectively) (p = 0.001). Both AGA and idiopathic IUGR placentae share the presence of many pathological features: (1) narrowing of stem villous arteries appears in 38 (76 %) of IUGR cases and in 9 (36 %) of AGA cases with significant difference between groups (p = 0.001); (2) cellular infiltration (villitis) of the stem villi is significantly higher in IUGR cases [24 (48 %)] than in AGA cases [2 (8 %)] (p = 0.001). The study shows significant correlation between the birth weight and different pathologic features in the stem villi as arterial number (r = 0.494; p = 0.000), arterial narrowing (r = 0.283, p = 0.004), degenerative changes (r = 0.331, p = 0.001) and villitis (r = 0.275, p = 0.005). There is also significant correlation between neonatal birth weight and terminal villous capillary number (r = 0.281, p = 0.001) but no significant correlation is found between the birth weight and terminal villous fibrotic changes (r = -0.098, p = 0.318). Histomorphological and pathological changes in the stem villi could explore the cause of idiopathic IUGR. Stem villous arterial number, arterial narrowing, degeneration and villitis could be underlying mechanisms. Further researches on the hormonal and cytokine level should be undertaken to demonstrate the precipitating factors of these changes and the possible preventing measures.     

Resistance and aerobic exercise protects against acute endothelial impairment induced by a single exposure to hypertension during exertion

Resistance and aerobic exercise is recommended for cardiovascular health and disease prevention. However, the accompanying increase in arterial pressure during resistance exercise may be detrimental to vascular health. This study tests the vascular benefits of aerobic compared with resistance exercise on preventing impaired vascular function induced by a single weight lifting session that is associated with acute hypertension. Healthy, lean sedentary (SED) subjects, weight lifters, runners (>15 miles/wk), and cross trainers (chronic aerobic and resistance exercisers), underwent a single progressive leg press weight lifting session with blood pressure measurements. Brachial artery flow-mediated vasodilation (FMD; an index of arterial endothelial function) was determined using ultrasonography immediately before and after weight lifting. Sublingual nitroglycerin (0.4 mg) was used to determine endothelium-independent dilation after weight lifting. All subjects were normotensive with similar blood pressure responses during exercise. Baseline FMD was lower in runners (5.4 ± 0.5%; n = 13) and cross trainers (4.44 ± 0.3%; n = 13) vs. SED (8.5 ± 0.8%; n = 13; P = 0.037). Brachial FMD improved in conditioned weight lifters (to 8.8 ± 0.9%; P = 0.007) and runners (to 7.6 ± 0.6%; P < 0.001) but not cross trainers (to 5.3 ± 0.6%; P = NS) after acute hypertension. FMD was decreased in SED (to 5.7 ± 0.4%; P = 0.019). Dilation to nitroglycerin was similar among groups. These data suggest that endothelial responses are maintained after exposure to a single bout of weight lifting in resistance and aerobic athletes. Resistance and aerobic exercise may confer similar protection against acute vascular insults such as exertional hypertension.     

A prospective randomized controlled trial of the effects of vitamin D supplementation on cardiovascular disease risk

Vitamin D (VitD) supplementation has been advocated for cardiovascular risk reduction; however, supporting data are sparse. The objective of this study was to determine whether VitD supplementation reduces cardiovascular risk. Subjects in this prospective, randomized, double-blind, placebo-controlled trial of post-menopausal women with serum 25-hydroxyvitamin D concentrations >10 and <60 ng/mL were randomized to Vitamin D3 2500 IU or placebo, daily for 4 months. Primary endpoints were changes in brachial artery flow-mediated vasodilation (FMD), carotid-femoral pulse wave velocity (PWV), and aortic augmentation index (AIx). The 114 subjects were mean (standard deviation) 63.9 (3.0) years old with a 25-hydroxyvitamin D level of 31.3 (10.6) ng/mL. Low VitD (<30 ng/mL) was present in 47% and was associated with higher body-mass index, systolic blood pressure, glucose, CRP, and lower FMD (all p<0.05). After 4 months, 25-hydroxyvitamin D levels increased by 15.7 (9.3) ng/mL on vitamin D3 vs. -0.2 (6.1) ng/mL on placebo (p<0.001). There were no significant differences between groups in changes in FMD (0.3 [3.4] vs. 0.3 [2.6] %, p = 0.77), PWV (0.00 [1.06] vs. 0.05 [0.92] m/s, p = 0.65), AIx (2.7 [6.3] vs. 0.9 [5.6] %, p = 0.10), or CRP (0.3 [1.9] vs. 0.3 [4.2] mg/L, p = 0.97). Multivariable models showed no significant interactions between treatment group and low VitD status (<30 ng/mL) for changes in FMD (p = 0.65), PWV (p = 0.93), AIx (p = 0.97), or CRP (p = 0.26). In conclusion, VitD supplementation did not improve endothelial function, arterial stiffness, or inflammation. These observations do not support use of VitD supplementation to reduce cardiovascular disease risk.     

Oxidative stress-mediated arterial dysfunction in patients with metabolic syndrome: Effect of ascorbic acid

Arterial dysfunction is a hallmark of early atherosclerosis; however, its behavior in patients with metabolic syndrome (MS) is still unclear. We investigated the role of oxidative stress on ischemia-induced flow-mediated dilatation (FMD) in patients with MS. FMD and oxidative stress, as assessed by serum levels of 8-hydroxy-2-deoxy-2-deoxyguanosine (8-OHdG), were studied in 18 MS and 30 control subjects. Thereafter, in the 18 MS patients, FMD was assessed after iv infusion of 1 g vitamin C or placebo in a randomized, double-blind, crossover design; serial blood samples were taken in peripheral circulation before and after FMD to analyze 8-OHdG. Compared to controls, MS patients had higher 8-OHdG (p<0.001) and lower FMD (p<0.001); 8-OHdG and FMD were inversely correlated (R=-0.74; p<0.01). In MS patients, placebo administration did not change FMD, whereas vitamin C significantly enhanced it (p<0.001). After placebo, ischemia-induced FMD was associated with a significant increase in 8-OHdG (p<0.001), an effect that was counteracted by vitamin C. Vitamin C infusion was associated with an inverse correlation between the changes in FMD and oxidative stress (R=-0.67; p<0.01). The present study shows that arterial dilatation is impaired and that enhanced oxidative stress may play a key role in patients with MS.     

Effects of inhaled nitric oxide at rest and during exercise in idiopathic pulmonary fibrosis

Patients with idiopathic pulmonary fibrosis (IPF) usually develop hypoxemia and pulmonary hypertension when exercising. To what extent endothelium-derived vasodilating agents modify these changes is unknown. The study was aimed to investigate in patients with IPF whether exercise induces changes in plasma levels of endothelium-derived signaling mediators, and to assess the acute effects of inhaled nitric oxide (NO) on pulmonary hemodynamics and gas exchange, at rest and during exercise. We evaluated seven patients with IPF (6 men/1 woman; 57 ± 11 yr; forced vital capacity, 60 ± 13% predicted; carbon monoxide diffusing capacity, 52 ± 10% predicted). Levels of endothelin, 6-keto-prostaglandin-F(1α), thromboxane B(2), and nitrates were measured at rest and during submaximal exercise. Pulmonary hemodynamics and gas exchange, including ventilation-perfusion relationships, were assessed breathing ambient air and 40 ppm NO, both at rest and during submaximal exercise. The concentration of thromboxane B(2) increased during exercise (P = 0.046), whereas levels of other mediators did not change. The change in 6-keto-prostaglandin-F(1α) correlated with that of mean pulmonary arterial pressure (r = 0.94; P < 0.005). Inhaled NO reduced mean pulmonary arterial pressure at rest (-4.6 ± 2.1 mmHg) and during exercise (-11.7 ± 7.1 mmHg) (P = 0.001 and P = 0.004, respectively), without altering arterial oxygenation or ventilation-perfusion distributions in any of the study conditions. Alveolar-to-capillary oxygen diffusion limitation, which accounted for the decrease of arterial Po(2) during exercise, was not modified by NO administration. We conclude that, in IPF, some endothelium-derived signaling molecules may modulate the development of pulmonary hypertension during exercise, and that the administration of inhaled NO reduces pulmonary vascular resistance without disturbing gas exchange.     

Thrombus size is associated with etiology of deep venous thrombosis--a cross-sectional study

The aim of this study was to evaluate the impact of risk factors for deep vein thrombosis (DVT) on thrombus sizes in lower extremities. The size and extent of thrombus was scored according to International Consensus Committee for venous disease classification. After the diagnosis of DVT was established and its size scored, predominant risk factors for DVT in each patient were identified (malignant disease, thrombophilia, postoperative state, hormonal therapy, heredity, limb trauma, immobilization, others and unknown risk factors). The average thrombus score was 6 (95% CI 5.47-6.53). The analysis of thrombus size indicated that the largest thrombi were found in patients with malignancy. Their average score was 8.5 (95% CI 7-10) and was significantly higher than in patients with other risk factors for deep vein thrombosis. There was no significant correlation between numbers of days from the onset of symptoms to the moment of DVT diagnosis and thrombus score (r = -0.08, p = 0.38). Age was very slightly correlated to thrombus size (r = 0.19; p = 0.046), while the gender did not have significant impact on thrombus score (p = 0.074). The conclusion of our study was that etiology of thrombosis and particularly malignant diseases has the largest impact on venous thrombus size.     

Abnormal systolic blood pressure during treadmill test and brachial artery flow-mediated vasodilatation impairment

The aim of the study was to assess the relationship between systolic blood pressure during maximal treadmill test (SBP9mtt)) and flow-mediated vasodilation (FMD). Abnormal rise of SBP(mtt) is the phenomenon more frequent in hypertensive persons but it could be found in normotensive subjects too. 199 subjects referred to treadmill test were enrolled in the study. Four groups were formed: hypertensives with abnormal SBP(mtt) (group A), hypertensives with normal SBP(mtt) (group B), normotensives with abnormal SBP(mtt) (group C) and normotensives with normal SBP(mtt) (group D). Rise of SBP(mtt) above 200 mmHg was considered abnormal reaction. Simple linear regression analysis showed significant inverse relationship between SBP(mtt) and FMD (F = 20.2036, p < 0.001, R2 = 0.0956). Mean FMD index was worst in hypertensive subjects with abnormal SBP(mtt) (group A), followed by normotensives with abnormal SBP(mtt) (group C), hypertensives with normal SBP(mtt) (group B) and the best was in normotensives with normal SBP(mtt) (3.56 +/- 5.17, 4.19 +/- 5.14, 6.81 +/- 8.43 and 10.92 +/- 7.48%, respectively). In multivariate regression analysis FMD showed significant association with abnormal SBP(mtt) (p < 0.001) along with brachial artery diameter (p < 0.001), male gender (p < 0.001), but not with hypertension (p = 0.073), BMI (p = 0.137) and total cholesterol (p = 0.23) (coefficients: -0.26, -0.40, -0.27, -0.13, -0.11 and -0.07, respectively). There was a significant inverse relationship between SBP(mtt) and FMD. An impairment of FMD exists in normotensive subjects with abnormal SBP(mtt). In hypertensives with abnormal SBP(mtt) an additional impairment of FMD exists when compared to hypertensives with normal SBP(mtt). Abnormal SBP(mtt) should be taken into account in global cardiovascular risk assessment.     

The optimization of the diagnostic work-up in patients with suspected obstructive lung disease

Background

Liver dysfunction reflects the status of heart failure, with congestion and low perfusion of the liver serving as causative mechanisms. Previous studies demonstrated relationship between the results of liver function test and the prognosis in patients with heart failure. However, few studies have examined this relationship in patients with pulmonary arterial hypertension (PAH).

Methods

The subjects were 37 patients with PAH (8 men and 29 women; 18 with idiopathic PAH and 19 with connective tissue disease-associated PAH). A blood test was performed after a 3-month period free from hospitalization and without changes in functional class, treatment, heart sounds, body weight, or heart rate.

Results

In a mean follow-up period of 635 ± 510 days, 12 patients died due to heart failure, 2 died due to pulmonary hemorrhage, and 23 patients survived. Cox proportional hazard analyses identified functional class (p < 0.001), plasma concentration of brain natriuretic peptide (BNP) (p = 0.001), and hyperbilirubinemia (serum total bilirubin > 1.2 mg/dL; p < 0.001; hazard ratio = 13.31) as predictors of mortality. Patients with hyperbilirubinemia had a worse functional class (P = 0.003), a higher right atrial pressure (p < 0.001), a higher plasma concentration of BNP (p = 0.004), and a larger Doppler right ventricular index of the right ventricle (p = 0.041).

Conclusion

Elevated serum bilirubin is a risk factor for death in patients with PAH.     

Tetrahydrobiopterin improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women

The mechanisms mediating arterial stiffening with aging and menopause are not completely understood. We determined whether administration of tetrahydrobiopterin (BH(4)), a critical cofactor for endothelial nitric oxide synthase to produce nitric oxide, would increase vascular endothelial-dependent vasodilatory tone and decrease arterial stiffness in estrogen-deficient postmenopausal women. Additionally, we examined whether the beneficial effects of estrogen on vascular function were possibly related to BH(4). Arterial stiffness (carotid artery compliance) and endothelial-dependent vasodilation [brachial artery flow-mediated dilation (FMD)] were measured in postmenopausal (n = 24; 57 ± 1 yr, mean ± SE) and eumenorrheic premenopausal (n = 9; 33 ± 2 yr) women before and 3 h after the oral administration of BH(4). Subsequently, in postmenopausal women, vascular testing (before and after BH(4)) was repeated following randomization to either 2 days of transdermal estradiol or placebo. Baseline carotid artery compliance and brachial artery FMD were lower in postmenopausal than in premenopausal women (P < 0.0001). BH(4) administration increased carotid artery compliance (0.61 ± 0.05 to 0.73 ± 0.04 mm(2)·mmHg(-1)·10(-1) vs. baseline, P < 0.0001) and brachial artery FMD (P < 0.001) in postmenopausal women but had no effect in premenopausal women (P = 0.62). Carotid artery compliance (0.59 ± 0.05 to 0.78 ± 0.06 mm(2)·mmHg(-1)·10(-1), P < 0.001) and FMD increased in postmenopausal women in response to estradiol (P = 0.02) but were not further improved with the coadministration of BH(4), possibly because estrogen increased BH(4) bioavailability. Carotid artery compliance and FMD increased with BH(4) in the placebo group (P = 0.02). Although speculative, these results suggest that reduced vascular BH(4) may be an important contributor to arterial stiffening in estrogen-deficient postmenopausal women, related in part to reduced endothelial-dependent vasodilatory tone.     

Effects of refrigeration and freezing on the electromechanical and biomechanical properties of articular cartilage

In vitro electromechanical and biomechanical testing of articular cartilage provide critical information about the structure and function of this tissue. Difficulties obtaining fresh tissue and lengthy experimental testing procedures often necessitate a storage protocol, which may adversely affect the functional properties of cartilage. The effects of storage at either 4°C for periods of 6 days and 12 days, or during a single freeze-thaw cycle at -20°C were examined in young bovine cartilage. Non-destructive electromechanical measurements and unconfined compression testing on 3 mm diameter disks were used to assess cartilage properties, including the streaming potential integral (SPI), fibril modulus (Ef), matrix modulus (Em), and permeability (k). Cartilage disks were also examined histologically. Compared with controls, significant decreases in SPI (to 32.3±5.5% of control values, p<0.001), Ef (to 31.3±41.3% [corrected] of control values, p=0.046), Em (to 6.4±8.5% of control values, p<0.0001), and an increase in k (to 2676.7±2562.0% of control values, p=0.004) were observed at day 12 of refrigeration at 4°C, but no significant changes were detected at day 6. A trend toward detecting a decrease in SPI (to 94.2±6.2% of control values, p=0.083) was identified following a single freeze-thaw cycle, but no detectable changes were observed for any biomechanical parameters. All numbers are mean±95% confidence interval. These results indicate that fresh cartilage can be stored in a humid chamber at 4°C for a maximum of 6 days with no detrimental effects to cartilage electromechanical and biomechanical properties, while one freeze-thaw cycle produces minimal deterioration of biomechanical and electromechanical properties. A comparison to literature suggested that particular attention should be paid to the manner in which specimens are thawed after freezing, specifically by minimizing thawing time at higher temperatures.     

Anthropometric parameters as predictors for iliopsoas muscle strength in healthy girls and in girls with adolescent idiopathic scoliosis

In this study iliopsoas muscle strength was measured by portable dynamometer and it was explored to what extent independent predictors (age, body weight, body height and body mass index) affect iliopsoas strength in healthy subjects and in subjects with adolescent idiopathic scoliosis. The study population was consisted of 183 girls (90 healthy girls and 93 girls with adolescent idiopathic scoliosis). Student t test analysis showed no differences in maximal voluntary isometric contraction between healthy girls and girls with scoliosis. Independent variables predicted significantly iliopsoas strength in healthy group (r=0.96, p<0.01) and in scoliosis group (r=0.94, p<0.001). Separate analysis with respect to types of scoliosis demonstrated that independent variables significantly predict iliopsoas strength in right thoracic (r=0.97, p<0.01), left thoracic (r=0.98, p=0.004), right thoracic lumbar (r=0.97, p<0.01) and left lumbar (r=0.96, p<0.01) scoliosis subgroups. In healthy girls iliopsoas strength was mostly predicted by body weight, followed by body height and body mass index. In girls with scoliosis body weigth was the strongest predictor of iliopsoas strength and was followed by curvature angle degree.     

Seasonal variation in occurrence of pulmonary embolism: analysis of the database of the Emilia-Romagna region, Italy

Seasonal variation in the occurrence of cardiovascular and cerebrovascular events, including pulmonary embolism (PE), has been reported; however, recent large-scale, population-based studies conducted in the United States did not confirm such seasonality. The aim of this large-scale population study was to determine whether a temporal pattern in the occurrence of PE exists. The analysis considered all consecutive cases of PE in the database of all hospital admissions of the Emilia Romagna region in Italy at the Center for Health Statistics between January 1998 and December 2005. PE cases were first grouped according to season of occurrence, and the data were analyzed by the chi(2) test for goodness of fit. Then, inferential chronobiologic (cosinor and partial Fourier) analysis was applied to monthly data, and the best-fitting curve for the annual variation was derived. The total sample consisted of 19,245 patients (8,143 male, mean age 71.6+/-14.1 yrs; 11,102 female, mean age 76.1+/-13.7 yrs). Of these, 2,484 were <65 yrs, 5,443 were between 65 and 74, and 11,318 were > or = 75 yrs. There were 4,486 (23.3%) fatal-case outcomes. PE occurred least frequently in spring (n=4,442 or 23.1%) and most frequent in winter (n=5,236 or 27.2%, goodness of fit chi(2)=75.75, p<0.001). Similar results were obtained for subgroups formed by gender, age, fatal/non-fatal outcome, presence/absence of major underlying co-morbid conditions, and specific risk factors. Inferential chronobiological analysis identified a significant annual pattern in PE, with the peak between November and December for the total sample of cases (p<0.001), males (p<0.001), females (p=0.002), fatal and non-fatal cases (p<0.001 for both), and subgroups formed by age (<65 yrs, p=0.012; 65-74 yrs, p<0.001; > or = 75 yrs, p=0.012). This pattern was independent of the presence/absence of hypertension (p=0.003 and p<0.001, respectively), pulmonary disease (p<0.001 and p<0.001, respectively), stroke (p<0.001 and p=0.004, respectively), neoplasms (p=0.005 and p=0.001, respectively), heart failure (p=0.022 and p<0.001, respectively), and deep vein thrombosis (p=0.002 and p<0.001, respectively). However, only a non-statistically significant trend was found for subgroups formed by cases of diabetes mellitus, infections, renal failure, and trauma.     

Exertional dyspnea in mitochondrial myopathy: clinical features and physiological mechanisms

Exertional dyspnea limits exercise in some mitochondrial myopathy (MM) patients, but the clinical features of this syndrome are poorly defined, and its underlying mechanism is unknown. We evaluated ventilation and arterial blood gases during cycle exercise and recovery in five MM patients with exertional dyspnea and genetically defined mitochondrial defects, and in four control subjects (C). Patient ventilation was normal at rest. During exercise, MM patients had low Vo(2peak) (28 ± 9% of predicted) and exaggerated systemic O(2) delivery relative to O(2) utilization (i.e., a hyperkinetic circulation). High perceived breathing effort in patients was associated with exaggerated ventilation relative to metabolic rate with high VE/VO(2peak), (MM = 104 ± 18; C = 42 ± 8, P ≤ 0.001), and Ve/VCO(2peak)(,) (MM = 54 ± 9; C = 34 ± 7, P ≤ 0.01); a steeper slope of increase in ΔVE/ΔVCO(2) (MM = 50.0 ± 6.9; C = 32.2 ± 6.6, P ≤ 0.01); and elevated peak respiratory exchange ratio (RER), (MM = 1.95 ± 0.31, C = 1.25 ± 0.03, P ≤ 0.01). Arterial lactate was higher in MM patients, and evidence for ventilatory compensation to metabolic acidosis included lower Pa(CO(2)) and standard bicarbonate. However, during 5 min of recovery, despite a further fall in arterial pH and lactate elevation, ventilation in MM rapidly normalized. These data indicate that exertional dyspnea in MM is attributable to mitochondrial defects that severely impair muscle oxidative phosphorylation and result in a hyperkinetic circulation in exercise. Exaggerated exercise ventilation is indicated by markedly elevated VE/VO(2), VE/VCO(2), and RER. While lactic acidosis likely contributes to exercise hyperventilation, the fact that ventilation normalizes during recovery from exercise despite increasing metabolic acidosis strongly indicates that additional, exercise-specific mechanisms are responsible for this distinctive pattern of exercise ventilation.     

Comparison of postsurgical and community acquired bacterial meningitis--analysis of 372 cases within a nationwide survey

The aim of this study was to assess if differences in etiology and risk factors among 372 cases of bacterial meningitis acquired after surgery (PM) or in community (CBM) have impact on outcome of infected patients. Among 372 cases of bacterial meningitis within last 17 years from 10 major Slovak hospitals, 171 were PM and 201 CBM. Etiology, risk factors such as underlying disease, cancer, diabetes alcoholism, surgery, VLBW, ENT infections, trauma, sepsis were recorded and mortality, survival with sequellae, therapy failure were compared in both groups. Significant differences in etiology and risk factors between both groups were reported. Those after neurosurgery had more frequently Coagulase negative staphylococci (p<0.001), Enterobacteriaceae (p=0.01) and Acinetobacter baumannii (p=0.0008) isolated from CSF and vice versa Streptococcus pneumoniae (p<0.001), Neisseria meningitis (p<0.001) and Haemophillus influenza (p=0.0009) were more commonly isolated from CSF in CBM. Neurosurgery (p<0.001), sepsis (p=0.006), VLBW neonates (p=0.00002) and cancer (p=0.0007) were more common in PM and alcohol abuse (p<0.001) as well as otitis/sinusitis (p<0.001) and Roma ethnic group (p=0.001) in CAM. Initial treatment success was significantly more frequently observed among CAM (p<0.001) but cure after modification was more common in PM (p=0.002). Therefore outcome in both groups was similar (14.6% vs. 12.4%, p=NS).     

Plasma nitrite concentrations reflect the degree of endothelial dysfunction in humans

A reduced nitric oxide availability is a hallmark of endothelial dysfunction occurring early in atherosclerosis. Recently, we have shown that plasma nitrite mirrors acute changes in endothelial nitric oxide synthase activity in various mammals, including humans. Here, we examined the hypothesis that plasma nitrite levels are reduced in humans with endothelial dysfunction and the decrease is correlated with increasing numbers of cardiovascular risk factors (RF). Plasma nitrite concentrations were quantified by flow-injection analysis. The coefficient of variation for repeated measurements of plasma nitrite was <8%, and heart rate and blood pressure at the time of blood sampling had no significant effect on nitrite values measured (n=10). Baseline levels of plasma nitrite followed a normal distribution in each group studied and decreased progressively with increasing numbers of cardiovascular risk factors (n=351, p<0.001): 351+/-13 (0 RF), 261+/-10 (1 RF), 253+/-11 (2 RF), 222+/-18 (3 RF), and 171+/-29 nmol/L (4 RF). Intima media thickness (IMT) and flow-mediated dilation (FMD) were determined via ultrasound. Plasma nitrite and FMD levels were lower, whereas IMT was greater in individuals with endothelial dysfunction (n=12) compared to healthy volunteers (n=12). Nitrite correlated significantly with FMD (r=0.56, p<0.001) and inversely with IMT (r= -0.49, p<0.01). Plasma nitrite levels are reliably measurable in humans, indicate endothelial dysfunction, and correlate with cardiovascular risk factors. Future studies are necessary to identify the prognostic relevance of plasma nitrite determination in patients suffering from cardiovascular disease.     

Time course of endothelial adaptation after acute and chronic exercise in patients with metabolic syndrome

Clustering of cardiovascular risk factors may lead to endothelial dysfunction. Physical exercise is an important factor in prevention and treatment of endothelial dysfunction. We wanted to determine the time course of adaptation to a single bout of exercise at either high or moderate intensity upon endothelial function both before and after a 16-week fitness program in patients with metabolic syndrome. Twenty-eight patients with metabolic syndrome participated in the study and were randomized and stratified (according to age and sex) into an aerobic interval exercise training group (AIT, n = 11), a continuously moderate-intensity exercise training group (CME, n = 8) or to a control group (n = 9). Flow-mediated dilatation (FMD) was determined at baseline, immediately, 24, 48, and 72 hours after 1 bout of exercise and repeated after 16 weeks of exercise. In the untrained state, FMD improved from 5 to 11% (p = 0.003) immediately after a single bout of aerobic interval training (AIT), an effect lasting 72 hours postexercise. In comparison, continuous moderate exercise (CME) improved FMD immediately after a single bout of exercise from 5 to 8% (p = 0.02), an effect lasting 24 hours postexercise (group difference, p < 0.001). In the trained state, a single bout of AIT resulted in a 2% (p = 0.007) acute increase of FMD lasting 48 hours postexercise. The CME increased FMD by 3% (p < 0.01), an effect lasting 24 hours postexercise (group difference p = 0.0012). Blood glucose level decreased after 1 single bout of AIT in the untrained state (p < 0.05), and the effect lasted at least 72 hours postexercise (p < 0.01). Acute CME decreased blood glucose with normalization of the values 24 hours postexercise (p < 0.01). A single bout of exercise in the trained state reduced fasting blood glucose by 10% (p < 0.05) after both AIT and CME. Exercise training, especially high intensity, thus appears to be highly beneficial in reducing blood glucose and improving endothelial function.     

High serum fasting peptide YY (3-36) is associated with obesity-associated insulin resistance and type 2 diabetes

We studied whether serum fasting levels of active form of peptide YY (PYY), PYY(3-36), are associated with obesity and related phenotypes. The study population consisted of 428 patients with coronary artery disease and diagnosed type 2 diabetes and 440 patients with coronary artery disease but without evidence of diabetes from the ARTEMIS study. The patients were recruited from the consecutive series of patients undergoing coronary angiography in the Oulu University Hospital. The patients without diabetes underwent a 2-hour oral glucose tolerance test. PYY(3-36) levels were analyzed by human PYY(3-36) specific radioimmunoassay. Result suggested that when PYY(3-36) tertiles were considered, high serum fasting PYY(3-36) concentration was associated with high body mass index, waist circumference, hemoglobin A1c, fasting blood glucose, leptin, triglyceride (p for all p ≤ 0.001), serum insulin (p=0.013) and with a low high-density lipoprotein cholesterol (p=0.004) concentrations in the analyses adjusted for age, sex and study group. The link high PYY(3-36)-high insulin level was evident in subjects with normal glucose tolerance (p<0.05). The prevalence of diabetes was 72%, 46% and 30% in the highest, medium and lowest PYY(3-36) tertile (p<0.001). The PYY(3-36) concentrations (after adjustment for age, sex and body mass index) were higher in type 2 diabetics compared to subjects with impaired fasting glucose, impaired glucose tolerance and normal glucose tolerance (p<0.001 for trend). In conclusion, fasting PYY(3-36) concentrations in type 2 diabetic subjects are high. Although high PYY(3-36) is strongly linked to obesity and associated insulin resistance, the relation between PYY(3-36) and type 2 diabetes is independent of body fatness.     

Prognostic value of carcinoma-associated antigen MK-1 in urinary bladder carcinoma

BACKGROUND: The present study has been performed to evaluate the expression of MK-1 in schistosomiasis-associated squamous cell carcinoma of the urinary bladder and to correlate this new marker with the conventional histopathological parameters. PATIENTS AND METHODS: Paraffin sections of 5-microm thickness from 81 cases were prepared for hematoxylin and eosin staining and immunohistochemical analysis of MK-1 expression was carried out. RESULTS: Forty-six cases (56.8%) were positive for MK-1 protein expression. Significant correlations between MK-1 expression and tumor grade (p=0.004), schistosoma (p=0.031), DNA ploidy (p=0.001), and tumor recurrence (p<0.001) were observed. MK-1, sex, tumor grade, stage, schistosoma, DNA ploidy, and recurrence were evaluated in relation to outcome. Univariate and multivariate analysis of survival were performed. The overall 5-year survival was 51.85%. In univariate analysis, MK-1 expression, tumor grade, DNA ploidy, and recurrence had a significant impact on the survival of these patients. In a Cox proportional hazards model, recurrence maintained its significant impact on survival. CONCLUSIONS: These findings suggest that MK-1 is a prognostic marker for recurrence: 34 (87.2%) of 39 recurrent cases were positive for MK-1 expression. However, only recurrence was an independent prognostic factor in patients with schistosomiasis- associated squamous cell carcinoma of the bladder.     

Short-term oral progesterone administration antagonizes the effect of transdermal estradiol on endothelium-dependent vasodilation in young healthy women

Very few studies have explored the cardiovascular effects of progesterone in premenopausal women. This study aimed to examine the short-term effects of oral progesterone alone, transdermal estrogen alone, and progesterone and estrogen combined on flow-mediated dilation (FMD) in healthy reproductive-aged women. We suppressed endogenous estrogens and progesterone in 17 premenopausal women for 10-12 days using a gonadotropin-releasing hormone antagonist. On day 4 (hormone suppression condition), subjects were tested (n = 17) and were then supplemented with either 200 mg micronized progesterone (n = 8) orally or 0.1 mg estradiol (n = 9) transdermally per day. On day 7 (progesterone-first or estradiol-first condition), subjects were tested and began supplementation with both hormones (n = 17) and were tested again on day 10 (combined hormone condition). FMD of the brachial artery was assessed using B-mode arterial ultrasound, combined with synchronized Doppler analysis. As a result, significant differences in FMD were observed between hormone suppression (7.85 ± 1.06%) and estrogen-first conditions (10.14 ± 1.40%; P < 0.05). The estradiol-induced increase was abolished when oral progesterone was also supplemented (6.27 ± 0.96%). In contrast, we observed a trend toward a decrease in FMD with unopposed progesterone administration, but no statistically significant differences were found between the progesterone-first (6.66 ± 1.23%), hormone suppression (7.80 ± 1.23%), and combined hormone conditions (7.40 ± 1.29%). In conclusion, these data suggest that short-term oral micronized progesterone administration antagonizes the beneficial effect of transdermal estradiol on FMD.