Relationship of late arteriovenous fistula stenosis with soluble E-selectin and soluble EPCR in chronic hemodialysis patients with arteriovenous fistula.

BACKGROUND/AIMS: Vascular access dysfunction caused by stenosis is a major complication for hemodialysis (HD) patients. However, physiopathology of late arteriovenous fistula (AVF) stenosis is still under investigation. The aim of the present study was to evaluate the association between plasma soluble EPCR (sEPCR) with serum soluble E-selectin (sE-selectin) concentration and late AVF stenosis in HD patients. METHODS: Plasma sEPCR and serum sE-selectin concentrations were measured in 94 HD patients. Using these data, we studied the association of sEPCR and sE-selectin with the presence and degree of AVF stenosis using ultrasonography and fistulogram. RESULTS: Fifty-one patients have AVF stenosis, and the others (n = 43) have patent AVF. The degree of AVF stenosis was correlated with serum sE-selectin levels (r = 0.351, p = 0.01), but not sEPCR (r = 0.075, p = 0.702). The median level of sE-selectin was statistically higher in the group of AVF stenosis than in the group of patent AVF [463.2 pg/ml (275.4-671.4) vs. 162.5 pg/ml (96.7-285.3), p = 0.001]. Increased sE-selectin levels [OR (OR) = 6.356, p = 0.015] and high levels of LDL (OR = 4.321, p = 0.044) were independent predictors of late AVF stenosis in the multivariate model. CONCLUSIONS: sE-selectin and the LDL were the most important predictors of late AVF stenosis. In addition, sE-selectin correlated with the degree of AVF stenosis. We suggested that atherosclerosis might be contributing factor for development of late AVF stenosis.

Galectin-3 as a new biomarker of diastolic dysfunction in hemodialysis patients.

BACKGROUND: Galectin-3 (gal-3) is an emerging prognostic biomarker in heart failure (HF). Clinical and experimental studies suggest that gal-3 is an important mediator of HF. Here we aimed to examine the relationship between gal-3 and diastolic dysfunction in patients undergoing maintenance hemodialysis (HD). METHODS: We examined the relationship between plasma gal-3 levels and left ventricular diastolic function. Plasma gal-3 was measured in 87 subjects with chronic HD and in 45 healthy controls using biochemical evaluations. Conventional echocardiography and pulsed tissue Doppler assessment were performed in all patients. Left ventricular diastolic dysfunction (LVDD) was defined as E' < 8 cm/s. The E/E' ratio was used as the main determinant of LVDD grade. RESULTS: The mean gal-3 concentrations were: 16.05 ng/ml (13.89-19.75) in healthy controls; 14.54 ng/ml (10.85-17.65) in HD patients with normal diastolic function; and 23.30 ng/ml (20.12-26.87) in HD patients with LVDD (p < 0.01). Plasma gal-3 levels correlated with E/E' (r = 0.933, p < 0.01), left atrial volume index (r = 0.713, p < 0.01), and E' (r = -0.685, p < 0.01). ROC analysis showed that the best gal-3 cut-off point for the diagnosis of LVDD was 20.12 ng/ml with a sensitivity of 67.6 % and specificity of 84.6 % (AUC = 0.803). CONCLUSION: We suggest that gal-3 may be a promising biomarker for the detection of LVDD in HD patients.

Association of ambulatory arterial stiffness index with sEPCR in newly diagnosed hypertensive patients.

AIM: Increased arterial stiffness is strongly associated with cardiovascular diseases, while thrombotic events are more common than hemorrhagic events in hypertensive patients. Markers of a hypercoagulable state may also predict future cardiovascular events in hypertensive patients. Here, we speculated that increased arterial stiffness might lead to the development of a hypercoagulable state that can play a role in the thrombotic complications of hypertension. Soluble endothelial protein C receptor (sEPCR) is one such marker of hypercoagulation. The ambulatory arterial stiffness index (AASI) could be accepted as a non-invasive measure of arterial stiffness. The aim of this study was to investigate association of AASI with levels of sEPCR in newly diagnosed hypertensive patients. MATERIALS AND METHODS: The study included 263 newly diagnosed essential hypertensive patients and 55 healthy normotensive controls. All subjects underwent 24 h ambulatory blood pressure monitoring (ABPM); the AASI was derived from ABPM tracings. Plasma sEPCR was measured by ELISA. RESULTS: Hypertensive patients (n = 263) had higher AASI, C-reactive protein (CRP) and sEPCR versus the normotensive healthy group (n = 55). Univariate analysis showed that AASI was positively associated with age (r = 0.212, p < 0.001) body mass index (r = 0.412, p < 0.001), pulse pressure (r = 0.350, p < 0.001), plasma sEPCR (r = 0.894, p < 0.001), 24-h heart rate (r = 0.176, p = 0.001) and inversely related to high-density lipoprotein (HDL) (r = -0.293, p < 0.001). Multivariate analyses revealed that sEPCR and HDL are independently correlated to AASI. CONCLUSION: We suggest that increased AASI is associated with elevated sEPCR. It might be responsible for subsequent thrombotic events in newly diagnosed hypertensive patients.

Relationship between late arteriovenous fistula (AVF) stenosis and neutrophil-lymphocyte ratio (NLR) in chronic hemodialysis patients.

OBJECTIVES: Primary cause of late arteriovenous fistula (AVF) dysfunction is venous stenosis as result of neointimal hyperplasia. The mechanism of AVF stenosis is not exactly understood. But inflammation is a contributing factor for development of AVF stenosis. Neutrophil-lymphocyte ratio (NLR) reflects systemic inflammation, and it was investigated in many diseases. The aim of this study was to investigate the relationship between NLR and AVF stenosis in chronic hemodialysis patients. MATERIALS AND METHODS: Of 593 patients applied to the department of interventional radiology between January 2011 and November 2012, a total of 108 patients meeting the appropriate criteria were included in this study. All patients were assessed with Color Doppler ultrasonography and then digital subtraction angiography was used for the patients with abnormal results. Sixty-four patients were classified as patients with AVF stenosis (group 1) and 44 patients without AVF stenosis (group 2). Routine biochemical and complete blood count values measured six months ago were recorded for all patients. RESULTS: Mean NLR (3.47 ± 0.46 vs. 2.27 ± 0.22; p < 0.001) was higher in group 1 compared to group 2, whereas high-density lipoprotein (HDL; 31.8 ± 12.6 mg/dL vs. 51.5 ± 11.9 mg/dL; p < 0.001) was lower in group 1. NLR level was correlated with degree of AVF stenosis (r = 0.625; p < 0.01). Receiver operating characteristic curve analysis showed that NLR (optimal-cut-off = 2.70) was a useful parameter in prediction of AVF stenosis (AUC = 0.893, sensitivity = 98.4% and specificity = 75%; p < 0.001). NLR level and HDL < 30 mg/dL in logistic regression analysis are independent predictors of AVF stenosis. CONCLUSIONS: For hemodialysis patients with increased level of NLR and decreased level of HDL, regular monitoring with regard to the development of AVF stenosis may be beneficial. Our study suggests that the mechanism of AVF stenosis might have similarities to that of atherosclerosis.

Correlation between iron stores and QTc dispersion in chronic ambulatory peritoneal dialysis patients.

AIM: We aimed to investigate the QT dispersion and corrected QT (QTc) dispersion which are suggested as the signals of ventricular arrhythmias, in patients on maintenance CAPD and to evaluate the correlation between iron stores and these electrocardiographic parameters. MATERIALS AND METHOD: Fifty-eight patients on maintenance CAPD and 19 healthy age- and sex-matched adults without cardiac disease were included. The PD patients were divided into two groups according to whether their computerized measurements of QTc dispersion were longer than 65 ms. RESULTS: Although QT interval was statistically significantly shorter in control group (34 ± 28 vs. 43 ± 34 ms; p < 0.05), there was no significant difference in regards to the QTc, QT dispersion and QTc dispersion between two groups. PD patients with QTc dispersion longer than 65 ms had higher levels of serum ferritin (p = 0.038) and transferrin saturation (TSAT; p = 0.022) than the others. QTc dispersion were positively correlated with ferritin (r = 0.469, p < 0.01) and TSAT (r = 0.430, p < 0.01) in CAPD patients. CONCLUSION: Although prolonged QTc, QT dispersion and QTc dispersion were suggested as the markers of ventricular arrhythmias we did not find any significant difference in regards to these parameters between control patients and CAPD patients. But the high body iron stores in these patients increase the risk of increased QT dispersion. The concern over iron overload in dialysis patients is not only because of its oxidative toxicity, but also its precipitation of arrhythmias, which may be measured by the surrogate marker of QTc dispersion.

Higher thrombin activatable fibrinolysis inhibitor levels are associated with inflammation in attack-free familial Mediterranean fever patients.

BACKGROUND: Coagulation abnormalities have been reported in familial Mediterranean fever (FMF) patients with amyloidosis and nephrotic syndrome; but there is not enough data about the continuity of the thrombogenic activity in FMF patients in clinical remission. The purpose of this study was to assess thrombin activatable fibrinolysis inhibitor (TAFI) levels and its relationship with fibrinolytic activity and also evaluate relationships between mutations and clinical signs in attack-free patients without amyloidosis. METHODS: Seventy-nine FMF patients and 40 healthy adults were included. The study group was divided into five groups as follows: first group, homozygote M694V; second group, homozygote M680I; third group, M694V in one allele, the other allele have other mutations or not; fourth group, other mutations; and fifth group, no mutation. RESULTS: Serum TAFI levels were significantly increased in patients compared with healthy individuals (116.64 ± 21.8 vs. 78.48 ± 19.7 µg/mL, p < 0.001) and a positive correlation was detected between TAFI antigen level and erythrocyte sedimentation rate and C-reactive protein levels (r = 0.247, p = 0.029 and r = 0.252, p = 0.032, respectively). Mean fibrinogen and TAFI levels were significantly higher in Group 1 than the other groups (p = 0.04 and p = 0.001, respectively) and in Group 3 it was higher than Groups 2, 4 and 5 (p = 0.04 and p = 0.001, respectively). CONCLUSIONS: High level of TAFI antigen in attack-free period of FMF disease shows ongoing subclinical inflammation and hypercoagulability. Clinicians should be careful about thrombosis even in patients at clinical remission. Also, genetic tests must be considered to predict clinical outcome and to reduce complications of FMF disease.

CA 125 levels and left ventricular function in patients with end-stage renal disease on maintenance hemodialysis.

PURPOSE: The aim of this study was to analyze associations between serum cancer antigen 125 (CA 125) levels and left ventricular (LV) function in patients with end-stage renal disease on maintenance hemodialysis (HD). METHODS: CA 125 levels, pro-brain natriuretic peptide (pro-BNP) and biochemical parameters were measured, and echocardiography was performed for 110 patients and 47 healthy controls. RESULTS: The mean CA 125 level in patients, 38.78 ± 35.48 U/mL, was significantly higher than that found in healthy controls (9.20 ± 4.55 U/mL; p = 0.003). Patients with elevated CA 125 levels (n = 40) had significantly lower levels of albumin and reduced relative wall thickness, LV ejection fraction (EF) and fractional shortening but significantly higher levels of pro-BNP and a greater left ventricular end-diastolic diameter (LVEDd) and -systolic diameter (LVESd). CA 125 levels were positively correlated with pro-BNP (r = 0.596, p < 0.05) and C-reactive protein (CRP) levels (r = 0.439, p < 0.05), as well as LVEDd (r = 0.599, p < 0.001), LVESd (r = 0.750, p < 0.001) and LV mass index (r = 0.378, p < 0.05). In contrast, serum CA 125 levels were negatively correlated with albumin (r = -0.513, p < 0.05) and hemoglobin (r = -0.475, p < 0.05) as well as the EF (r = -0.878, p < 0.0001). A depressed EF (ß = -1.121, p < 0.0001) and increased CRP levels (ß = 0.247, p = 0.035) were independent predictors of high CA 125 levels in the whole group in the multivariate-model. CONCLUSIONS: Our study is the first to demonstrate an association between serum CA 125 levels and LV systolic dysfunction via inflammation in patients on maintenance HD.

Effect of dialysis type on orbital vascular flow in patients with end-stage renal disease.

PURPOSE: To evaluate ocular blood flow dynamics by color Doppler ultrasonography (CDU) in patients with end-stage renal disease (ESRD). Additionally, to investigate the effect of dialysis type on ocular blood flow by comparing the findings of peritoneal dialysis (PD) subjects, hemodialysis (HD) subjects, and healthy controls. MATERIAL AND METHODS: Forty patients (21 HD and 19 PD) and 40 controls were included in the study. CDU and spectral analysis of temporal posterior ciliary artery (TPCA) and central retinal artery (CRA) were performed to evaluate peak systolic flow velocity (PSV), end diastolic flow velocity (EDV), and resistive indices (RIs). Ocular blood flows were examined before and after HD. Post-HD findings were compared with those in PD subjects and healthy controls. RESULTS: PSV and EDV values in CRA and TPCA after HD sessions were found to be significantly decreased when compared with pre-dialysis values. There was no statistically significant difference between the pre-dialysis and post-dialysis RI values of both arteries. Systolic and diastolic blood flows in CRA and TPCA were higher and RI values were lower in PD subjects than in HD and controls. No significant difference was seen between HD subjects and controls. CONCLUSION: After a single HD session, ocular blood flows of patients with ESRD were normalized. But PD subjects show higher systolic and diastolic ocular blood flows than healthy controls, suggesting that HD is more effective than PD for achieving normal ocular blood flow.

Validation of the Oxford classification of IgA nephropathy.

The Oxford classification of IgA nephropathy (IgAN) identified four pathological elements that were of prognostic value and additive to known clinical and laboratory variables in predicting patient outcome. These features are segmental glomerulosclerosis/adhesion, mesangial hypercellularity, endocapillary proliferation, and tubular atrophy/interstitial fibrosis. Here, we tested the Oxford results using an independent cohort of 187 adults and children with IgAN from 4 centers in North America by comparing the performance of the logistic regression model and the predictive value of each of the four lesions in both data sets. The cohorts had similar clinical and histological findings, presentations, and clinicopathological correlations. During follow-up, however, the North American cohort received more immunosuppressive and antihypertensive therapies. Identifying patients with a rapid decline in the rate of renal function using the logistic model from the original study in the validation data set was good (c-statistic 0.75), although less precise than in the original study (0.82). Individually, each pathological variable offered the same predictive value in both cohorts except mesangial hypercellularity, which was a weaker predictor. Thus, this North American cohort validated the Oxford IgAN classification and supports its utilization. Further studies are needed to determine the relationship to the impact of treatment and to define the value of the mesangial hypercellularity score.

The effects of L-carnitine therapy on respiratory function tests in chronic hemodialysis patients.

BACKGROUND: Respiratory functions are affected during hemodialysis. The strength of respiratory muscles, ultrafiltration rate, and acid-base balance have been suggested as important factors. L-carnitine is crucial for energy producing, utilization of fatty acid, and possible amino acids. A lack of carnitine in hemodialysis patients is caused by insufficient carnitine synthesis and especially by its loss during dialysis. This study was performed to investigate the chronic effects of L-carnitine treatment on respiratory functions in adults receiving chronic hemodialysis therapy. METHODS: A total of 20 hemodialysis patients were scheduled to take L-carnitine supplementation (20 mg/kg three times/week) (group 1), and the rest of 20 hemodialysis patients served as the control group and were observed without supplementation with L-carnitine (group 2). Pre- and post-dialytic L-carnitine levels and post-dialytic respiratory functions tests were performed in both groups at baseline and after six months. RESULTS: The average concentration of free and total carnitine levels increased significantly after six months of supplementation (p < 0.01). While a statistically significant increase between postdialytic forced expiratory volume in one second/forced vital capacity values after treatment period (77.10 +/- 12.15 and 83.00 +/- 14.49, before and after treatment, respectively, p < 0.05) was observed, the increase of vital capacity, forced expiratory volume in one second, and forced expiratory flow between 25-75% of expired vital capacity were not significant in the treatment group (p > 0.05). CONCLUSION: Intravenous L-carnitine supplementation could contribute to the management of respiratory dysfunction in chronic hemodialysis patients by improving FEV1/FVC. The mechanism by which LC causes these effects merits further investigation.

Association of visceral fat accumulation and adiponectin levels with colorectal neoplasia.

PURPOSE: There are few studies addressing the association between measured values of visceral fat accumulation (VFA), adiponectin, and colorectal neoplasia. Our purpose is to investigate the association of VFA and serum adiponectin levels with colorectal adenoma and carcinoma patients. For this purpose, 54 patients with colorectal adenoma and carcinoma, diagnosed by colonoscopic evaluation, and 50 healthy control subjects were included. Patients were subjected to measurement of VFA and adiponectin level and calculation of insulin resistance. RESULTS: Patients with colorectal carcinoma had lower plasma adiponectin levels compared with controls. VFA level did not differ between patients and controls. Adiponectin level was found to be uncorrelated with VFA in the colorectal cancer and adenoma group. No correlation was found between insulin resistance and plasma adiponectin level and VFA. CONCLUSION: Our findings suggest that decreased plasma adiponectin level may be a factor involved in the development of colon cancer or a secondary effect of the metabolic derangements in colorectal cancer.

Prevalence of proximal neoplasms among asymptomatic patients according to distal colorectal findings.

Colorectal cancer has been described in association with hyperplastic polyposis. Only half of proximal colon cancers are associated with distal adenomas. To compare the prevalence of proximal and advanced neoplasia between patients with distal hyperplastic polyps only; with distal adenomas with or without hyperplastic polyps; and with no distal polyps, we retrospectively analyzed data of 1,064 adults who underwent colonoscopy. Of these patients, 3% had neoplasia. Proximal neoplasia occurred in 0.8% of 945 patients with no distal polyps, compared to none of 19 with distal hyperplastic polyps (P > 0.05) and 6% with distal adenomas (P > 0.05). Proximal advanced neoplasia occurred in 0.6% patients with no distal polyps, compared with none with distal hyperplastic polyps (P > 0.05) and 6% with distal adenomas (P > 0.05). In conclusion, patients with distal hyperplastic polyps, unlike those with distal adenomas, do not exhibit an increased risk for proximal neoplasia or proximal advanced neoplasia compared to those with no distal polyps.

Nigella sativa oil for prevention of chronic cyclosporine nephrotoxicity: an experimental model.

Nephrotoxicity is the main secondary effect of cyclosporine A (CsA) treatment. The antioxidant action of Nigella sativa oil (NSO) may explain the protective effect of these agents against various hepatotoxic and nephrotoxic models in vivo and in vitro. This study was designed to investigate the possible protective effects of NSO, in prevention of chronic CsA-induced nephrotoxicity in rats. Animals were randomly divided into four experimental groups: the control group received sunflower oil, the other groups were treated with CsA (25 mg/kg/day b.w. orally) or NSO (2 ml/kg orally) or CsA + NSO, respectively. Urine and serum creatinine levels, tissue superoxide dismutase, glutathione peroxidase and catalase enzyme activities, and nitric oxide and malondialdehyde levels were measured, and histological examination was performed. In our study, CsA caused a significant deterioration in the renal function, morphology and gave rise to severe oxidative stress in the kidney. NSO significantly improved the functional and histological parameters and attenuated the oxidative stress induced by CsA. In conclusion, our study demonstrated for the first time that NSO protects kidney tissue against oxygen free radicals, preventing renal dysfunction and morphological abnormalities associated with chronic CsA administration.

Nigella sativa protects against ischaemia/reperfusion injury in rat kidneys.

BACKGROUND: Renal ischaemia followed by reperfusion leads to acute renal failure in both native kidneys and renal allografts, which is a complex pathophysiologic process involving hypoxia and free radical (FR) damage. The oil of Nigella sativa (NSO) has been subjected to considerable pharmacological investigations that have revealed its antioxidant activity in different conditions. But there is no previously reported study about its effect on ischaemia/reperfusion (I/R) injury of kidneys. The aim of this study was to investigate the possible effects of NSO in I/R-induced renal injury in rats. METHODS: Thirty healthy male Wistar albino rats were randomly assigned to one of the following groups: control, sham, I/R, NSO+I/R, I/R+NSO and NSO. I/R, NSO+I/R and I/R+NSO rats were subjected to bilateral renal ischaemia followed by reperfusion and then all the rats were killed and kidney function tests, serum and tissue oxidants and antioxidants were determined and histopathological examinations were performed. RESULTS: Pre- and post-treatment with NSO produced reduction in serum levels of blood urea nitrogen (BUN) and creatinine caused by I/R and significantly improved serum enzymatic activities of superoxide dismutase (SOD) and glutathion peroxidase (GSH-Px) and also tissue enzymatic activities of catalase (CAT), SOD and GSH-Px. NSO treatment resulted in lower total oxidant status (TOS) and higher total antioxidant capacity (TAC) levels and also significant reduction in serum and tissue malondialdehyde (MDA), nitric oxide (NO) and protein carbonyl content (PCC) that were increased by renal I/R injury. The kidneys of untreated ischaemic rats had a higher histopathological score, while treatment with NSO nearly preserved the normal morphology of the kidney. CONCLUSIONS: In view of previous observations and our data, with the potent FR scavenger and antioxidant properties, NSO seems to be a highly promising agent for protecting tissues from oxidative damage and preventing organ damage due to renal I/R.

Association of obesity with inflammation in occult chronic kidney disease.

BACKGROUND: There are few studies concerning the development of chronic kidney disease (CKD) in obese patients independent of its relation with other risk factors. Also, the role of inflammation in this relationship is unclear. In this study we aimed to test the hypothesis that obesity is associated with risk for CKD and whether this risk is associated with serum C-reactive protein (CRP) levels in an apparently healthy obese population. METHODS: Biochemical parameters and urinary protein excretion were determined in 110 patients with body mass index (BMI) >30.0 (calculated as kg/m2) and 50 age-matched healthy controls. Glomerular filtration rate was estimated by calculation of creatinine clearance. RESULTS: Of the patients, 17.3% had CKD. They had higher CRP levels than controls (6.52 +/- 0.58 mg/L and 4.48 +/- 1.26 mg/L, respectively, p=0.001). Furthermore, CRP levels were positively correlated with BMI, waist circumference, waist to hip ratio and proteinuria, and negatively correlated with glomerular filtration rate (GFR). When GFR was considered as the dependent variable in a multiple regression analysis, CRP maintained its significant correlation with GFR. CONCLUSION: Our study of apparently healthy obese individuals, has shown a significant association between BMI and CKD independent of other potential mediators. Furthermore, our findings suggest that inflammation may be the pathogenic mechanism of obesity-related CKD.

Increased thrombin-activatable fibrinolysis inhibitor antigen levels as a clue for prothrombotic state in polycystic ovary syndrome.

OBJECTIVES: Our study was undertaken to evaluate the levels of thrombin-activatable fibrinolysis inhibitor (TAFI) antigen and also its relationship with other hemostasis markers in a group of patients affected with polycystic ovary syndrome (PCOS)-under Diane-35 (ethinyl estradiol 0.035 mg/cyproterone acetate 2 mg) treatment or not-as compared with a group of healthy controls. METHODS: Forty-two women with PCOS and 30 age-matched healthy controls were involved in the study. Group A were on Diane-35 for at least 6 months; group B did not take any drug; group C served as a control group. RESULTS: TAFI antigen levels of groups A and B were significantly higher than in controls, but no difference was observed between them. All of the other coagulation and fibrinolysis parameters (including prothrombin time, activated partial thromboplastin time, fibrinogen and D-dimer) were comparable between the three groups. CONCLUSION: The evidence presented herein suggests that women with PCOS have impaired fibrinolysis, as reflected by increased TAFI. This impairment can contribute to the risk of cardiovascular disease in PCOS. Elucidation of the modifiable mechanisms in PCOS can represent an opportunity for preventive therapy of the cardiovascular risks associated with PCOS.

Multifactorial thrombophilia in a pregnancy: a case report.

Thrombophilias are inherited or acquired conditions that predispose individuals to thromboembolism. Thrombophilic disorders increase obstetric complications, such as early pregnancy loss, fetal growth retardation, placental abruption, and preeclampsia. Recurrent pregnancy loss affects 1% to 3% of women of reproductive age, and a large proportion of these losses remain unexplained. Thrombophilic defects were found in 49% to 65% of women with pregnancy complications compared with 18% to 22% of women with normal pregnancies, suggesting a 3- to 8-fold increase in risk. We report a case of a pregnant woman who had a history of recurrent pregnancy losses that was complicated with protein S deficiency, factor V Leiden mutation, methylene tetrahydrofolate reductase mutation, and antiphospholipid syndrome in her pregnancy.

Comparison of the clinical efficacy of flutamide and spironolactone plus ethinyloestradiol/cyproterone acetate in the treatment of hirsutism: a randomised controlled study.

INTRODUCTION: Hirsutism is commonly a consequence of ovarian androgen over-production. Polycystic ovary syndrome (PCOS) or peripheral hypersensitivity to normal androgen circulating levels (idiopathic hirsutism) can be the underlying cause. Several drugs with anti-androgenic properties, such as cyproterone acetate (CPA), spironolactone and flutamide have been used to treat hirsutism, but the efficacy of these drugs has yet to be fully elucidated. The objective of this study was to compare the effectiveness of flutamide, and spironolactone plus a combination tablet of 2 mg CPA/35 microg ethinyloestradiol (EE) in the treatment of hirsutism. METHODS: A prospective randomised clinical study was conducted in a tertiary care hospital setting. Twenty-nine women with hirsutism as a consequence of PCOS or idiopathic hirsutism were randomly assigned to receive 250 mg/day flutamide alone or 100 mg/day spironolactone plus a combination tablet of 2 mg CPA/35 microg EE, for 6 months. Patients' hormonal and lipid profiles were evaluated. Hirsutism was graded according to the modified Ferriman-Gallwey (mF-G) score, and side effects were monitored. RESULTS: A significant decrease in mF-G scores was observed in the flutamide (from 11.2+/-3.3 to 7.6+/-4.0) and spironolactone plus CPA/EE (from 9.9+/-1.9 to 7.1+/-2.0) groups. However, there was no statistically significant difference between the two groups. After flutamide therapy, total cholesterol levels decreased significantly but no significant change was observed in any other lipid parameters or in the patients' hormone profiles. After spironolactone plus CPA/EE therapy, levels of luteinising hormone, total testosterone and free testosterone significantly decreased and triglyceride levels increased. No patients were found to have abnormal liver function test results. CONCLUSION: Flutamide and spironolactone plus CPA/EE are effective drugs in the treatment of hirsutism.

Relation between serum calcium, phosphate, parathyroid hormone and 'nondipper' circadian blood pressure variability profile in patients with normal renal function.

BACKGROUND AND AIMS: In patients with renal disease, an association between abnormal circadian blood pressure profile and abnormalities in bone and mineral metabolism, including vascular calcifications, is well known. However, such a link has not yet been reported in hypertensive patients with normal renal function. We aimed to evaluate if higher serum phosphate, calcium, parathyroid hormone (PTH) level and the calcium x phosphate (Ca x P) product would be associated with a nondipper hypertension, in patients with normal renal function and without any PTH disorder. METHODS: 190 hypertensive subjects with the following inclusion criteria were enrolled: (1) normal phosphate and PTH levels; (2) glomerular filtration rate (GFR) >60 ml/min, and (3) no history of calcium, phosphate, vitamin D medication and hyperparathyroidism. RESULTS: Of the total population, 76 patients (40%) were classified as dippers and 114 (60%) as nondippers. Nondipper patients had higher levels of phosphate (3.70 +/- 0.61 vs. 3.35 +/- 0.44 mg/dl, p = 0.001), Ca x P product (35.4 +/- 6.5 vs. 31.5 +/- 5.0, p = 0.001) and PTH (75.7 +/- 28.8 vs. 46.6 +/- 17.1 pg/ml, p = 0.000) compared to dipper patients. Independent predictors (multiple regression) for nondipper hypertension were PTH (beta = 0.43, p = 0.001) and phosphate (beta = 0.9, p = 0.03). CONCLUSION: We demonstrate a graded independent relation between higher levels of phosphate, PTH, Ca x P product and the risk of nondipping in hypertensive patients with an estimated GFR of >60 ml/min and normal mineral metabolism.

Hemostasis and global fibrinolytic capacity in chronic liver disease.

Accelerated fibrinolysis associated with liver disease can be demonstrated by various tests that are either nonspecific in liver disease or that demonstrate only an extrinsic pathway. In the present study we used a new method to assess the global fibrinolytic capacity (GFC) of both the intrinsic and extrinsic pathways in patients with chronic liver disease. Forty patients with the diagnosis of chronic liver disease were included in the study. Seventeen age-matched and gender-matched healthy control individuals were enrolled as a control group. The GFC was studied with semiquantitative macrolatex agglutination. The study population consisted of 40 patients with chronic liver disease (group 1, patients with chronic hepatitis; group 2, patients with cirrhosis; group 3, patients with hepatocellular carcinoma), mean age 53.3 +/- 13 years, and a control group (group 4) consisting of 17 healthy individuals (mean age 55 +/- 12.2 years). The GFC was significantly higher in patients than in control individuals (13.8 +/- 9 microg/ml, 13.6 +/- 11 microg/ml, 14.1 +/- 14 microg/ml, 1.9 +/- 2.2 microg/ml, respectively; P < 0.05). There was no difference between the patient groups (P > 0.05). There was a significant positive relationship between the GFC and the prothrombin time and activated partial thromboplastin time values (P < 0.05). A negative correlation was also observed between the GFC and thrombocyte counts (P < 0.05). In conclusion, our results suggest that patients with chronic liver disease have hyperfibrinolysis, as reflected by the increased GFC. Elucidation of the GFC in chronic liver disease can reflect the net fibrinolytic capacity of those patients who are prone to hyperfibrinolysis resulting in bleeding tendencies and hemorrhages.