Neutrophil-to-Lymphocyte Ratio is a strong predictor of atherosclerotic carotid plaques in older adults.

BACKGROUND AND AIMS: The Neutrophil-to-Lymphocyte Ratio (NLR), an index of systemic inflammation, has been reported to be associated with subclinical atherosclerosis, but its predictive role of the presence of carotid atherosclerotic plaques remains undefined. This study aims to assess this association which gives additional value to this biomarker, with respect to the main risk factors, in the prediction of carotid atherosclerosis in older adults. METHODS AND RESULTS: We recruited 324 patients, aged ≥65 years, without hematopoietic disorders, and/or history of malignancies, evidence of acute infections, chronic inflammatory status, and history of glucocorticoid therapy within the past three months, hospitalized in the Unit of Internal Medicine, University of Catania, Catania, Italy from January 2014 to December 2016. All patients underwent blood sampling for white blood cell, neutrophil, lymphocyte and platelet counts, and for measurements of inflammatory markers, NLR was calculated as the ratio of the absolute neutrophil count to the absolute lymphocyte count. Patients also underwent carotid scan by ultrasonography (US) to evaluate abnormalities of carotid wall. NLR resulted a strong predictor of the presence of carotid plaques. NLR > 2.4 predicted with 80% probability carotid plaques (p < 0.01), while NLR > 3.68 gave 97% probability (p = 0.013). Furthermore, NLR > 2.4 was associated with an average presence of 2.86 carotid plaques (p < 0.001). Fibrinogen and CRP performed well, but with lesser significance, as predictors of the presence of carotid plaques (p = 0.002). CONCLUSION: NLR is a strong predictor of the presence and the number of carotid atherosclerotic plaques. Its use could be useful to identify the risk of harboring carotid plaques.

Inflammation and ventricular-vascular coupling in hypertensive patients with metabolic syndrome.

BACKGROUND AND AIMS: Metabolic syndrome (MetS) is currently considered to raise the risk for type 2 diabetes and cardiovascular events. It has been suggested that part of this risk excess may be due to a cluster of additional factors associated with MetS. We aimed to investigate the role of inflammation on the ventricular-vascular coupling in patients with MetS. METHODS AND RESULTS: We enrolled a total of 227 hypertensive patients (106 with MetS and 121 without MetS) matched for age and gender. Aortic pulse wave velocity (aPWV), intima-media thickness (IMT) and high sensitivity C-reactive protein (CRP) increased according to the number of MetS components. Patients with MetS showed increased aPWV (11.5 ± 3.7 vs. 10.3 ± 2.5 m/s, P = 0.03) compared with controls. In a model adjusted for age, sex, heart rate and mean blood pressure, aPWV resulted increased in patients with CKD (beta 1.29 m/s, 95%CI 0.61-1.96 m/s, P < 0.001) and MetS (beta 0.89 m/s, 95%CI 0.28-1.51 m/s, P = 0.005). After additional adjustment for CRP and IMT, the slope of aPWV was respectively reduced by 16% and 62%, suggesting that inflammation and intima-media thickening could contribute to aortic stiffening in patients with MetS. In these patients, aPWV was also associated with left-ventricular mass index (beta 0.79 g/m2.7, 95%CI 0.05-1.52 g/m2.7, P = 0.05). CONCLUSION: MetS is characterized by an inflammation-dependent acceleration in cardiovascular ageing. This pattern of pathophysiological abnormalities may contribute to amplify the burden of cardiovascular risk in patients with MetS.

B-type natriuretic peptide may predict prognosis in older adults admitted with a diagnosis other than heart failure.

BACKGROUND AND AIMS: The diagnosis of heart failure (HF) in elderly patients is often difficult, due to overlap of typical signs and symptoms with those of comorbidities. B-type Natriuretic Peptide (BNP) predicts diagnosis and prognosis of HF, but little is known on its predictive role of short-term prognosis when admission diagnosis is other than HF. METHODS AND RESULTS: We prospectively recruited 404 consecutive patients (aged≥65 years) hospitalized in the Unit of Internal Medicine, University of Catania, Catania, Italy, with an admission diagnosis other than HF. Clinical examination, laboratory data and BNP were evaluated at the admission. The predictive value of BNP and other variables for in-hospital mortality, thirty-day mortality and three month re-hospitalization was assessed. During hospitalization 48 (12%) patients died; by logistic regression analysis, in-hospital mortality was not predicted by BNP>600 pg/ml (OR = 1.36; CI 95% = 0.60-2.80; p = 0.4), while it was by chronic kidney disease (CKD, p < 0.001), WBC count (p < 0.001), immobilization syndrome (p < 0.008) and age (p = 0.012). After discharge, 54 patients (15%) died within 30 days; in these patients thirty-day mortality was significantly predicted by BNP>600 pg/ml (OR = 2.70; CI 95% = 1.40-5.00; p = 0.001), CKD (p < 0.001), malnutrition (p = 0.029) and age (p = 0.033). Re-hospitalized patients were 97 (32%); three month re-hospitalization was predicted by BNP>600 pg/ml (OR = 12.28; CI 95% = 6.00-24.90; p < 0.001) and anamnestic HF (p = 0.002). CONCLUSIONS: Our study shows that BNP>600 pg/ml, CKD, malnutrition and age predict thirty-day mortality after discharge in elderly patients with an admission diagnosis other than HF, while CKD, WBC count, immobilization syndrome and age predict in-hospital mortality. Three-month re-hospitalization was predicted by BNP>600 pg/ml and anamnestic HF.

Neutrophil-to-lymphocyte ratio and lactate dehydrogenase as biomarkers for urothelial cancer treated with immunotherapy.

PURPOSE: To identify patients with metastatic urothelial cancer (mUC) unlikely to benefit from immune-checkpoint inhibitors (ICIs). METHODS/PATIENTS: We explored the predictive and prognostic values of baseline neutrophil-to-lymphocyte ratio (NLR), with cut-offs ≥ 3 and ≥ 5, and of a urothelial immune prognostic index (UIPI, based on increased NLR and LDH), on 146 patients. RESULTS: NLR and UIPI significantly predicted progressive disease and progression-free survival with both cut-offs (p = 0.0069, p = 0.0034, p = 0.0160, p = 0.0063; p < 0.001, p = 0.021, p = 0.014, p = 0.026; for NLR-3, NLR-5, UIPI-3, UIPI-5, respectively) and overall survival when NLR cut-off was ≥ 5 (p = 0.03 and p = 0.024, for NLR-5 and UIPI-5, respectively). CONCLUSIONS: NLR-5 deserves prospective validation to identify mUC patients with poor prognosis following ICIs.

Endogenous ouabain and cardiomyopathy in dialysis patients.

BACKGROUND AND METHODS: Endogenous ouabain (EO) is markedly raised in patients with chronic renal failure. As high EO induces myocardial cell hypertrophy in vitro and it is associated with left ventricular hypertrophy (LVH) in essential hypertensives and in patients with heart failure we investigated the relationship between plasma EO and LV mass and geometry in 156 end-stage renal disease (ESRD) patients. EO was measured by a specific radioimmunoassay and by mass spectrometry. RESULTS: On univariate analysis, plasma EO was directly related to LV mass (r = 0.26, P = 0.001) and LV end diastolic volume (r = 0.25, P = 0.002) and these relationships held true in multiple linear regression models including a series of potential confounders. Patients with eccentric LVH (n = 41, i.e. 26%) had the highest plasma levels of EO when compared to patients with other patterns of LV geometry (P = 0.001). Furthermore, plasma EO had diagnostic value for eccentric LVH because the area under the corresponding ROC curve (68%) was significantly greater (P = 0.002) than the threshold of diagnostic indifference. In this analysis, the sensitivity was 91% and the specificity was 36%. The positive predictive value was 33% but EO had a remarkably high negative predictive value (92%) for the exclusion of eccentric hypertrophy. CONCLUSIONS: In ESRD patients, plasma EO is independently associated with LV mass, LV volume and eccentric LVH. The results of this study are compatible with the hypothesis that EO is involved in alterations of LV mass in ESRD.

Prediction of left ventricular geometry by clinic, pre-dialysis and 24-h ambulatory BP monitoring in hemodialysis patients: CREED investigators.

OBJECTIVE: Arterial hypertension is an established risk factor for left ventricular hypertrophy (LVH) in the uremic population. However, whether 24-h monitoring is a better predictor of LVH than clinic blood pressure and routine pre-dialysis measurements in these patients is still undefined. METHODS: This problem was studied in 64 nondiabetic hemodialysis patients without heart failure. The echocardiographic study as well as the clinic and 24-h ambulatory blood pressure (BP) measurements were performed during the day off-dialysis. Pre-dialysis arterial pressure was calculated as the average value of the 12 routine recordings taken during the month preceding the study. RESULTS: In multivariate models, including also sex, body mass index, hematocrit and serum cholesterol, pre-dialysis systolic, diastolic and pulse pressures were the only independent BP determinants of heart geometry. Twenty-four hour ambulatory BP monitoring (ABPM) did add significant (but weak) information to the prediction of left ventricular internal dimension, i.e. it increased by 9% (P = 0.01) the variance already explained by pre-dialysis diastolic BP and other significant covariates. However, 24-h ABPM did not add any significant and independent explanatory information to the corresponding pre-dialysis measurements for the posterior wall and interventricular septum measurements, and for left ventricular mass (-0.6 to +3.9%; average +1.1%). CONCLUSIONS: In dialysis patients, pre-dialysis BP is at least as strong a predictor of left ventricular mass as 24-h ambulatory monitoring. Thus, the average of 12 routine pre-dialysis measurements may be used to predict heart geometry in dialysis patients without any loss of information in comparison with 24-h ambulatory monitoring.

Inflammation is associated with carotid atherosclerosis in dialysis patients. Creed Investigators. Cardiovascular Risk Extended Evaluation in Dialysis Patients.

OBJECTIVE: To investigate the relationship between inflammatory processes and atherosclerosis in uraemic patients on chronic dialysis. DESIGN: A cross-sectional study in 138 dialysis patients (92 on haemodialysis and 46 on continuous ambulatory peritoneal dialysis). METHODS: Serum C-reactive protein (CRP), IgG anti-Chlamydia pneumoniae antibodies, lipoprotein (a), fibrinogen and plasma homocysteine as well as the intima-media thickness and the number of atherosclerotic plaques of the carotid arteries (by Echo-Colour-Doppler) were measured in each patient RESULTS: One hundred and eight patients had at least one plaque and 26 had more than six plaques. Serum CRP was above the upper limit of the normal range (5 mg/I) in 85 of 138 patients (62%). IgG anti-Chlamydia pneumoniae antibodies were detectable in 64% of patients (high level in 24%, intermediate in 33% and low in 7%) and undetectable in the remaining 36% of patients. In a multiple regression model age (beta=0.35), serum CRP (beta=0.23), plasma homocysteine (beta=0.19), duration of dialysis (beta=0.19) and pulse pressure (beta=0.18) were independent predictors of intima-media thickness (R=0.54, P < 0.0001). Similarly, age (beta=0.33), serum CRP (beta=0.29), plasma homocysteine (beta=0.20) and serum albumin (beta=-0.18) were independent correlates of the number of atherosclerotic plaques (R = 0.55, P < 0.0001 ). Furthermore, in smokers, the interaction serum CRP-IgG anti-Chlamydia pneumoniae antibodies was the stronger independent predictor (beta=0.43, P=0.0001) of the number of atherosclerotic plaques while no such relationship (P=0.73) was found in non-smokers. CONCLUSIONS: In patients on chronic dialysis treatment CRP is independently associated to carotid atherosclerosis and appears at least in part to be explained by IgG anti-Chlamydia pneumoniae antibodies level. These data lend support to the hypothesis that inflammation plays a role in the pathogenesis of atherosclerosis in these patients.

Hepatocyte growth factor predicts survival and relates to inflammation and intima media thickness in end-stage renal disease.

Hepatocyte growth factor (HGF) is a pleiotropic cytokine involved in tissue protection and repair in the endothelium and various organ systems. The serum concentration of this protein is markedly increased in patients with chronic renal diseases, but the clinical and pathophysiological correlates of this substance in renal failure are scarcely understood. Serum HGF, lipid, albumin, hemoglobin, C-reactive protein (CRP), and immunoglobulin G (IgG) were measured in fasting conditions in a cohort of 244 dialysis patients. In addition, the relationship between HGF and severity of carotid atherosclerosis was studied in a subgroup of 105 patients. The entire cohort was followed up for a median of 31 months (interquartile range, 21 to 34 months). Serum HGF level was directly related to duration of dialysis treatment, CRP level, age, IgG level, and hemoglobin level and inversely related to systolic and diastolic arterial blood pressure. In a multiple regression model, only duration of dialysis treatment (r = 0.38), age (r = 0.26), hemoglobin level (r = 0.17), IgG level (r = 0.15), and CRP level (r = 0.14) were independent correlates of serum HGF level (R = 0.54; P < 0.0001), suggesting that increased levels of serum HGF may be the expression of a chronic inflammatory process. HGF levels were greater in hemodialysis than continuous ambulatory peritoneal dialysis patients, independent of the type of dialysis membrane, and slightly increased in patients seropositive for hepatitis C virus. In the subgroup of patients who underwent echo color Doppler studies, serum HGF level was an independent correlate of intima media thickness (IMT; partial r = 0.23; P = 0.02). In the entire cohort, increased HGF levels predicted shorter survival in a multivariate Cox regression model. These results support the hypothesis that in patients with chronic renal failure, increased serum HGF level is linked to an inflammatory state. The relationships between HGF level and survival and IMT suggest that this cytokine might be a marker of a process that has a major impact in the high mortality and morbidity of the dialysis population.

Circulating natriuretic peptide concentrations in patients with end-stage renal disease: role of brain natriuretic peptide as a biomarker for ventricular remodeling.

OBJECTIVES: To determine levels of natriuretic peptides (NPs) in patients with end-stage renal disease (ESRD) and to examine the relationship of these cardiovascular peptides to left ventricular hypertrophy (LVH) and to cardiac mortality. PATIENTS AND METHODS: One hundred twelve dialysis patients without clinical evidence of congestive heart failure underwent plasma measurement of NP concentrations and echocardiographic investigation for left ventricular mass index (LVMI). RESULTS: Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations correlated positively with LVMI and inversely with left ventricular ejection fraction, whereas C-type NP and Dendroaspis NP levels did not correlate with LVMI. In dialysis patients with LVH (LVMI >125 g/m2), plasma ANP and BNP concentrations were increased compared with those in dialysis patients without LVH (both P<001). In a subset of 15 dialysis patients without LVH or other concomitant diseases, plasma BNP concentrations were not significantly increased compared with those in 35 controls (mean +/- SD, 20.1+/-13.4 vs 13.5+/-9.6 pg/mL; P=.06), demonstrating that the BNP concentration was not increased by renal dysfunction alone. Furthermore, the BNP level was significantly higher in the 16 patients who died from cardiovascular causes compared with survivors (mean +/- SD, 129+/-13 vs 57+/-7 pg/mL; P<.003) and was significantly associated with greater risk of cardiovascular death in Cox regression analysis (P<.001), as was the ANP level (P=.002). CONCLUSIONS: Elevation of the plasma BNP concentration is more specifically related to LVH compared with the other NP levels in patients with ESRD independent of congestive heart failure. Thus, BNP serves as an important plasma biomarker for ventricular hypertrophy in dialysis patients with ESRD.

Urinary adrenomedullin is related to ET-1 and salt intake in patients with mild essential hypertension. Salt Sensitivity Group of Italian Society of Hypertension.

Adrenomedullin (ADM) infusion increases salt excretion in the rat. However, there is no evidence that this substance is related to changes in salt intake in humans. In this study we sought whether the urinary excretion rate of this autacoid is related to salt intake and by the expected changes in arterial pressure in patients with mild essential hypertension. The influence of salt intake on the renal excretion of ADM was investigated in 55 hypertensive patients in a double blind, randomized and crossover study comparing a 2-week 50 mmol/day salt intake period with a 150 mmol/day salt intake period. Twenty-four-hour ADM and endothelin-1 (ET-1) excretion rate were measured by radioimmunoassay on preextracted urinary samples (intraassay confidence variable <8%). The antibodies used in these assays had minimal ADM-ET-1 cross-reactivity (<1%). Twenty-four-hour microalbuminuria was measured by nephelometry. On univariate analysis changes in urinary ADM were significantly related to those in salt excretion (r = 0.33, P = .01) as well as to changes in urinary ET-1 (r = 0.56, P = .0001). Furthermore, changes in urinary albumin excretion were related to those in urinary ET-1 (r = 0.26, P = .05), but were independent of those in urinary ADM (P = .19). In a multiple regression model including age, sex, body mass index, and changes in systolic pressure, plasma renin activity and plasma aldosterone and urine volume, salt excretion resulted as the stronger independent predictor of urinary ADM (r = 0.33, P = .01). However, changes in urinary salt lost prediction power (P = .11) for urinary ADM when urinary ET-1 was introduced into the model. In this model (multiple r = 0.31) urinary ET-1 resulted to be the only independent predictor of urinary ADM (beta = 0.56, P = .0001). This study is the first to show that the renal excretion of ADM is related to changes in salt intake and that it is tightly linked to that of ET-1. The data support the notion that these autacoids play a role in the regulation of sodium metabolism in patients with mild hypertension. The intercorrelations between ET-1, ADM, and microalbuminuria are compatible with the hypothesis that ET-1 is involved in a salt-induced increase in glomerular pressure and suggest that ADM may act as a counterregulatory factor in this situation.

Immunohistochemical modifications of vasoactive neuropeptides and excitatory amino acids in the nervous tissue of the Mongolian gerbil after transient cerebral ischemia.

Modifications in the tissue concentration of vasoactive peptides (Endothelin, Calcitonin Gene Related Peptide, Atrial Natriuretic Peptide) and excitatory amino acids (glutamate, aspartate) were found in the nervous tissue of Mongolian gerbils after transient cerebral ischemia which was induced by unilateral occlusion of the common carotid artery for 30 min 4 h. In fact, immunostaining for these peptides was more intense in the ischemic tissue: the greatest increases of tissue immunoreactivity were observed for Endothelin; smaller differences were found for Calcitonin Gene Related Peptide and Atrial Natriuretic Peptide. Immunostaining for Neuropeptide Y, another vasoactive neuropeptide, was virtually unchanged. Infarct areas, when present, contained numerous Endothelin-immunoreactive cell bodies. On the contrary, the same areas were completely void of glutamate- or aspartate-immunostained neurons, normally present in the correspondent regions of the control tissue. The present results suggest that severe cerebral ischemia is paralleled by an unbalance of local vasoactive factors. The predominance of vasoconstrictor action of Endothelin might play a major role in the irreversible damage, together with the excitotoxic effect of the extracellular accumulation of excitatory amino acids, probably due to a leakage from neuronal cell somata, as suggested by the disappearance of glutamate- or aspartate-immunostained neurons.

The effect of chronic prazosin therapy on the response of the renin-angiotensin system in patients with essential hypertension.

Changes in plasma active and inactive renin and angiotensin II in response to tilt and intravenous frusemide were assessed in ten patients with essential hypertension, before treatment and again during chronic therapy with the alpha 1-adrenoceptor antagonist prazosin. During prazosin treatment blood pressure in the patients fell from mean levels 172/108 mmHg to 149/88 mmHg (P less than 0.05). Both before and during prazosin, tilt and frusemide each led to significant elevation of plasma active renin (P less than 0.001) and angiotensin II (P less than 0.05). Inactive renin tended to fall with tilt, and fell significantly following frusemide (P less than 0.05). Active renin (P less than 0.05) and angiotensin II (P less than 0.01) were lower 15 hours after dosing during chronic prazosin therapy than before treatment, but changes after tilt and frusemide were not attenuated during treatment. Chronic prazosin administration does not appear substantially to affect changes in active renin or angiotensin II in response to two standard stimuli, and may be useful in controlling hypertensive patients pending investigation of their renin-angiotensin system.

Prediction and consistency of blood pressure salt-sensitivity as assessed by a rapid volume expansion and contraction protocol. Salt-Sensitivity Study Group of the Italian Society of Hypertension.

BACKGROUND: This multicenter trial in essential hypertensive patients (n=94) is aimed i) to evaluate the distribution of blood pressure salt-sensitivity by a rapid volume expansion/contraction protocol over three days; ii) to investigate the within-patient reproducibility and to identify predictors of the response to the test; iii) to compare this response with the response to dietary NaCl restriction. METHODS: The study design included: 1) screening for salt-sensitivity by the rapid test; 2) a controlled trial of dietary salt restriction; 3) repetition of the rapid test in a subgroup of patients. RESULTS: The mean BP response to the rapid test fitted a Gaussian curve. In multivariate regression analysis, controlling for the effect of potential confounders, the blood pressure increment during the intravenous saline infusion was the best independent predictor of the response to the test (r=0.713) with minor contributions by the 24-h urinary sodium excretion before the test and by baseline fasting serum insulin. These three variables together explained 61% of the overall variability of the response. The Spearman rank correlation coefficient between the BP response to the rapid test and the response to the dietary protocol was 0.21, p=0.05. Upon repetition of the rapid test, the correlation coefficient between the responses observed on the two occasions was 0.60 (n=19, p<0.01); there were no patients misclassified across the extreme tertiles of the distribution of salt-sensitivity. CONCLUSION: We conclude that the rapid test reproducibly identified patients in the upper and lower parts of the distribution of salt sensitivity. The analysis of possible predictors of the response to the test suggested that the evaluation of the blood pressure response to saline infusion, upon careful standardization of dietary NaCl intake, may represent an alternative to the completion of the whole test for the screening of the salt-sensitivity.

Renal endothelin-1 is linked to changes in urinary salt and volume in essential hypertension. Salt Sensitivity Group of the Italian Society of Hypertension.

METHODS: We investigated the influence of salt intake on urinary and plasma endothelin-1 (ET-1) in 55 patients who entered a two-week double-blind, randomised, crossover study comparing a 50 mMol/day salt intake and 150 mMol/day. Twenty-four-hour ET-1 excretion and plasma ET-1 were measured by RIA on pre-extracted samples. RESULTS: In the whole cohort (n=55), changes in urinary ET-1 were related to salt excretion (r=0.28, P=0.04) and urinary volume (r=0.47, P=0.0001). In a multivariable model, changes in PRA, plasma aldosterone, blood pressure and heart rate did not add any predictive power to salt excretion with regard to urinary ET-1 variations. The relationship between urinary volume and urinary ET-1 was stronger than that of urinary sodium with ET-1 excretion because sodium was excluded from the multivariable model when urinary volume was introduced. Changes in urinary ET-1 were unrelated to mean blood pressure changes (P=0.66). Changes in plasma ET-1 were unaffected by changes in salt intake (P=0.58) but were strongly related to those in PRA (r= -0.45, P=0.01) and plasma aldosterone (r= -0.53, P=0.002). CONCLUSIONS: The renal excretion of ET-1 is influenced by changes in salt intake and appears largely independent of the blood pressure response to salt. Changes in urinary volume which accompany variations in salt excretion play an important role in this response. Since urinary ET-1 reflects its renal synthesis, our data support the notion that renal ET-1 plays a role in the regulation of sodium balance in patients with mild hypertension.

Smoking, blood pressure and serum albumin are major determinants of carotid atherosclerosis in dialysis patients. CREED Investigators. Cardiovascular Risk Extended Evaluation in Dialysis patients.

AIM: To investigate the relationship between carotid atherosclerosis and some major cardiovascular risk factors in uremic patients on chronic dialysis. METHODS: A cross-sectional study was carried out in 119 unselected dialysis patients (89 on hemodialysis and 30 on chronic ambulatory peritoneal dialysis, CAPD). Fasting blood sampling for serum lipids, albumin, hemoglobin, and echo-colour-Doppler evaluation of common carotid arteries were performed in all patients (during the non-dialysis day in hemodialysis patients). In hemodialysis patients BP was measured before and after dialysis; in CAPD patients home BP values were recorded during the month before the study day. RESULTS: Ninety-five patients had at least one plaque and 57 had at least four plaques. Thirty-eight had mild and eleven severe carotid stenosis. In multiple regression models, the mean internal diameter of carotid arteries was explained (R=0.52, P=0.0001) by systolic pressure (r=0.39), serum cholesterol (r=-0.28), age (r=0.27) and smoking (r=0.24) while the degree of carotid stenosis was predicted (R=0.39, P=0.0001) by age (r=0.36) and smoking (r=0.25). The number of atherosclerotic plaques was explained (R=0.51, P=0.0001) by age (r=0.36), smoking (r=0.25) and pulse pressure (r=0.20), serum albumin just failing to reach statistical significance (P = 0.06). However, serum albumin was a significant and independent predictor of the number of atherosclerotic plaques (r=-0.26) in hemodialysis patients (n=89). Sex, diabetes, Kt/V, duration of dialysis treatment, hemoglobin, serum calcium and phosphate did not add any predictive power to the models. CONCLUSIONS: In dialysis patients arterial pressure and smoking are associated with carotid atherosclerosis. Serum albumin appears to serve as an independent predictor of carotid atherosclerosis.

Circulating endothelin-1 levels in patients with "a frigore" vascular acrosyndromes.

The present study was designed to examine the role of endothelin-1 (ET-1), an endothelium-derived potent long-acting vasoconstrictor peptide, in vascular acrosyndromes with hypersensitivity to cold. Plasma ET-1 concentration was measured, before and after cold test, in 12 subjects with "a frigore" vascular acrosyndromes (9 females and 3 males, age range 17-59 years), of whom 6 were with primary Raynaud's phenomenon and 6 with essential acrocyanosis, and in 6 controls (5 females and 1 male, age range 21-37 years). Cold stimulation was performed by immersion of one hand into a water bath at 13 degrees C for 5 minutes. Blood samples were simultaneously drawn from an antecubital vein in the cooled side and in the contralateral arm at baseline, at the stop of cooling, at 10 and 90 minutes from the beginning of the cold challenge. Mean (+/-SD) baseline ET-1 plasma levels, as measured by radioimmunoassay, were higher in patients with "a frigore" vascular acrosyndromes (4.8 +/- 0.3 pmol/l) than in control subjects (1.9 +/- 0.1 pmol/l, p < 0.001). After hand cooling ET-1 rose in patients with "a frigore" vascular disorders to a peak value of 7.0 +/- 0.4 pmol/l, which was much greater than that observed in healthy subjects (2.7 +/- 0.4 pmol/l, p < 0.001). Absolute increase in ET-1 plasma concentrations from baseline to peak value was significantly higher in patients with "a frigore" vascular acrosyndromes than in normal subjects (2.2 +/- 0.3 vs 0.8 +/- 0.2 pmol/l, p < 0.001), being only in the former group the rise in ET-1 still detected 90 minutes after cold test. Plasma levels of ET-1 in the controlateral arm raised in a similar fashion, but absolute values were lower than in cooled arm. Circulating ET-1 levels in patients with primary Raynaud's phenomenon and essential acrocyanosis showed a similar pattern during the study. Our data demonstrate that in patients with "a frigore" vascular acrosyndromes baseline and cold-stimulated plasma ET-1 concentrations are increased. Further, in these vascular disorders, exaggerated ET-1 response to cold is prolonged. These findings suggest that increased ET-1 may contribute to an imbalance between vasoactive mediators in the cutaneous blood vessels contributing to the abnormal vasoconstriction to cold in these disorders. Alternatively, the increment in ET-1 release may represent a marker for endothelial cell damage in "a frigore" vascular acrosyndromes.

Giant paraesophageal hernia in an asymptomatic old man. The case for misdiagnosing.

We describe the case of an asymptomatic 66 year-old man with a giant paraesophageal hernia including colonic migration into the chest, responsible for the appearance of a bilateral anterior mediastinal mass on the chest radiograph. We would like to emphasise that this radiologic pattern could lead to misdiagnosing, due to the bilateral air-fluid level in the chest, close to the heart. Pericardial (effusion, cyst), bronchogenic (cyst), as well as esophageal (diverticula) diseases should be considered in the differential diagnosis, although the paucity of symptoms in our patient makes all of these syndromes unlikely to occur. It should also be emphasised that the esophagram can help differential diagnosis between mediastinic organs responsible for the pattern shown in the chest radiograph.

Plasma endothelin-1 levels in patients with peripheral arterial occlusive disease at different Fontaine's stages.

UNLABELLED: Endothelin-1 (ET-1) is a potent vasoconstrictor and mitogenic peptide produced and secreted by endothelial cells, which can play a potential role in the development of atherosclerosis and in the pathophysiology of extreme vasoconstriction of various diseases. METHODS: To assess plasma endothelin-1 (ET-1) concentrations in patients with peripheral arterial occlusive disease (PAOD) at different Fontaine's stages, we measured plasma ET-1 by radioimmunoassay in 14 stage II PAOD patients (12 men, 2 women; mean age 59.5 +/- 3.4 years) and in 10 stage III-IV PAOD patients (8 men, 2 women, mean age 61.2 +/- 3.3 years). Ten normal subjects (8 men, 2 women, mean age 58.1 +/- 7.2 years) were considered as controls. RESULTS: Mean (+/- SD) plasma ET-1 levels, as measured by radioimmunoassay, were significantly greater in stage II and stage III-IV PAOD patients than in control subjects (4 +/- 0.4 and 5 +/- 0.4 pmol/L vs 2.5 +/- 0.6 pmol/L, respectively, p < 0.001). Furthermore, plasma levels of ET-1 in stage III-IV patients were significantly higher than in stage II patients (p < 0.01). A significant correlation was found between plasma ET-1 levels and number of the arterial obstructive lesions in PAOD patients (r = 0.698; p < 0.0001). No significant correlation was found between plasma ET-1 concentrations and pain-free walking distance (r = -0.279, p = 0.333, in stage II patients; r = 0.137, p = 0.705, in stage III-IV patients), and between plasma ET-1 levels and ankle/arm pressor index (r = 0.032, p = 0.913, in stage II patients; r = 0.149, p = 0.681, in stage III-IV patients) in the PAOD patients. CONCLUSIONS: Raised plasma ET-1 could be a sensible marker both of endothelial damage and disease extension. It could also promote the progression of atherosclerotic plaques and enhance the microvascular resistance in these patients.

Modulation by adenosine of thromboxane A2 receptor-mediated constriction in the human umbilical artery.

The powerful vasoconstrictor autacoid thromboxane A2 (TxA2) has pathological roles in many diseases including pre-eclampsia or pregnancy induced hypertension (PIH). Adenosine and other purines are released by tissues during ischemia as occurs in the utero-placental circulation during PIH. These substances, particularly adenosine, may modulate TxA2 constrictor responses. We therefore characterized TxA2 receptors in the umbilical artery in vitro using the competitive antagonist GR32191. Also examined was the Ca2+ channels' involvement in adenosine-induced inhibition of TxA2 vasoconstriction. Results showed that TxA2 receptors on umbilical arteries are identical to those present in platelets, the placenta and umbilical vein. Adenosine was found to inhibit equally constriction involving either voltage or receptor operated Ca2+ channels.