Intraocular pressure (IOP) is the major known risk factor in glaucoma and the primer mover of the functional damage in glaucomatous patients but it is not a unique determinant of glaucomatous damage. Clinical assessment of glaucoma patients may not be a true reflection of overall IOP control. Evaluation of the effect of glaucoma medication is restricted by measurement of IOP as a dynamic physiological parameter.To compare IOP fluctuations over time using Goldmann applanation tonometry (IOPGAT) and pulsatile ocular blood flow analyzer (IOP-POBFA) under the Dorzolamide/timolol or latanoprost treatment regimes.Prospective 1 year follow-up study.30 randomly chosen controlled open angle glaucoma patients (60 eyes): 16 patients (32 eyes) receiving Dorzolamide/timolol fixed combination (D/T) and 14 (28 eyes) latanoprost 0.005% treatment. Main outcome measures: Changes in IOP and perfusion pressure dynamics.p=0.314). Both treatment regimes were tolerated and patients were adherent to treatment. Determined a strong positive correlation between IOP-GAT and IOP-POBFA; verified over time period under particular treatment regime. After 1 year follow-up D/T and latanoprost results referred to statistically significant tachyphylaxis effect, i.e. IOP-GAT increased in 2.31mmHg with D/T (p=0.007) and 2.72 mmHg (p=0.004) with latanoprost and IOP-POBFA increased in 1.74 mmHg (p=0.026) and 3.13 mmHg (p=0.007) respectively. Multiple regression analysis revealed no important blood flow factors as predictors in the increase of IOP.There was no statistically significant difference in baseline IOP parameters between study groups: 15.69 ± 2.02 mmHg with D/T and 16.71 ± 2.84 mmHg with latanoprost (Strong positive correlation was revealed between IOP-POBFA and IOP-GAT over a time period. Observed tachyphylaxis effects after 1 year under both treatment regimes should be assessed with respect to patient compliance and persistence to treatment. Treatment regime was defined referring to European terminology and Guidelines for Glaucoma (2003), i.e. target therapeutic response with minimal amount of side effects. All subjects read and signed an informed consent, and the study was approved by an institutional review board and was conducted within the tenets of the Helsinki Agreement.The study groups comprised of individuals with no current or past history of other eye disease or suspicion of eye disease that could not be accounted for by refractive error. Patients had no history of orbital or ocular traumas, respiratory or other obstructive pulmonary disease, significant heart failure, sinus bradycardia, 2°or 3° AV block or cardiogenic shock and no history of allergy to any of the components. Patients younger than 18 years of age, pregnant or nursing women, patients with corrected visual acuity less than 20/40, with a mean deviation in Humphrey Visual Fields central 30-2 greater than or equal to 20DB, or having a cup disc ratio of 0.9 or greater, were not included in the study. Subjects were instructed to avoid caffeine and alcohol intake, smoking, and exercise for three hours prior to each study visit. All study visits were scheduled at the same time of day ± 1 hour in order to avoid diurnal fluctuations in IOP.The following procedures were carried out at baseline and after 1 year: subjective anamnesis and adverse events check, visual acuity, biomicroscopy, fundus examination, visual field (Humphrey 30-2 SITA Fast). Brachial artery pressure and radial pulse were obtained in a sitting position after 5 minutes of rest. Ocular perfusion and diastolic perfusion pressures were calculated.Goldmann applanation tonometry was used for IOP determination (IOP-GAT). The average of two consecutive measurements (in mmHg) was taken for the analysis. The pulsatile ocular blood flow analyzer (POBFA)  was used to measure pulsatile IOP (IOP-POBFA). Pulsatile waves acquiring approximately 200 measurements per second and pulsatile IOP waves during the cardiac cycle exhibits a nearly sinusoidal pattern within a range of 2 mmHg. The amplitudes of the IOP pulse waves are used to calculate the change in ocular blood volume and the pulsatile component of total ocular blood flow. Clinically, the pulsatile component of this value is reasonably well correlated to the quality of the blood supplied to the orbital portion of the nerve as measured in microlitres per second (ul/sec). Technique produces a detailed report, which provides the time, date, and a graphic representation of the patient’s test results Fig. . The pulStatistical Analysis was performed using SPSS for Windows version 10.1. A mixed-effects analysis of variance (ANOVA) applying Fisher’s and Bonferonni models to control for overall type I error with p = 0.05 was used. In this ANOVA model we tested for the effects of treatment, period and sequence on mean IOP-GAT, IOP-POBFA and perfusion pressure changes. In the event that significance was achieved by repeated measures ANOVA, changes in individual parameters were examined by paired student’s t-test. To test the hypothesis that the mean difference between two measurements is zero, Wilcoxon signed ranks test was used. Changes in IOP-GAT and IOP-POBFA parameters were analyzed by Pearson’s correlation analysis. Multiple regression analysis with final IOP-GAT and IOP-POBFA as dependent variables; initial and final pulse volumes, systolic and diastolic arterial blood pressures, perfusion pressures as predictors was constructed. The level of significance was 5% - and all values of p<0.05 were considered statistically significant.p=0.314). Following 1 year of treatment we observed IOP shift in both treatment groups: with D/T IOP increased by 2.31 mmHg (p=0.007) and with latanoprost increased in 2.72 mmHg (p=0.004). IOP after 1 year treatment was statistically significantly higher with latanoprost than D/T (p=0.042).Clinical characteristics of 16 patients treated and observed for 1 year period using fixed D/T combination and latanoprost regime are presented in Table p=0.804). We observed an increase of IOP-POBFA values after 1 year: 1.74 mmHg (p=0.026) with D/T and 3.13 mmHg (p=0.007) with latanoprost. The difference between IOP-POBFA after 1 year with D/T and latanoprost treatment was significant (p=0.0415).We found no initial differences in IOP-POBFA and IOP-GAT values (p=0.000) or final  IOP measurements; in the latanoprost group in initial  and final  IOP measurements as well. The coefficients distribution limits depended on particular patients’ characteristics carried out over time period under particular treatment regime.Determined a strong positive correlation between IOP-GAT and IOP-POBFA measurements is presented in Fig. We observed an increase in IOP measurements in both treatment regimens and both IOP measuring techniques. Analysing tachyphilaxis for patients we found no statistically significant differences of age and axial length, either in systemic blood flow parameters or visual field mean indices between the groups Table .Patient anamnesis data revealed no subjective discomfort or adverse effects that might cause discontinuation of prescribed treatment regime or influence non compliance.Multiple regression analysis with the final visit IOP as a dependant variable and initial and final perfusion pressures, pulse volumes as independent variables indicate no significant association and no important predictors for both groups.The D/T group showed an increase in perfusion pressure and diastolic perfusion pressure after 1 year in 6%. The latanoprost group showed a decrease in perfusion pressure by 2% and 0.5% decrease in diastolic perfusion pressure. However, the differences were not statistically significant, thaw it should be analysed for a large sample to accept in daily clinical practice.p=0.047). The initial difference in amount was 16% in favor of D/T. The difference in ocular pulse volume after 1 year remained at 1.17 μl or 13% higher in the D/T group as compared to latanoprost.Initial results in ocular pulse volume were significantly better in the D/T group by 1.51 μl (Apoptosis of retinal ganglion cells is considered to be the most plausible pathogenic mechanism of glaucomatous damage. Among the potential glaucoma treatment options reduction of IOP, improvement of ocular blood flow and direct neuroprotection have been identified , 13. Thuet al also found that IOP measurements with ocular blood flow tonograph correlated with Goldmann readings over a wide range of pressures (et al suggested that in normal subjects the POBF and choroidal blood flow decreases as axial length increases (We compared IOP-GAT and IOP-POBFA under different OAG treatment regimes. We found strong IOP correlations between the techniques over the time period. Yang ressures . Over a ressures . Data frressures  and lataressures  showed tncreases .et al reported that POAG patients showed higher IOP and lower mean perfusion pressure compared with healthy subjects, when ocular perfusion pressure is low, ocular resistance to blood flow is high (Evidence shows that despite a wide range of glaucoma therapy options in some cases it is still difficult to control slowly progressing of optic neuropathy while controlling only to IOP factor. The contribution of diminished blood flow resulting in ischemia of the optic nerve is debated. We evaluated POBFA parameters and found that ocular pulse volume was higher with D/T than with latanoprost both at baseline and after 1 year. Analyzing ocular perfusion parameters over a period of 1 year we found 6% increase in both perfusion pressure and diastolic perfusion pressure with D/T and small decrease in perfusion pressure measurements with latanoprost. Though differences were not very significant we tried to find possible explanation for observed tachyphylaxis effect. Findings from Ocular Hypertension Treatment study suggest that blood pressure, heart disease were not statistically significant in multivariate risk model, but may become statistically significant with larger sample size . Gherhge is high -24. TakiRecent reports by Quigley H.A. indicate that as few as 10% of patients prescribed a new glaucoma drug are still taking that drug in an effective way at the end of one year. Data from Harvard School of medicine medical database showed that patients actually had their drugs available for use only 70% of days. The evidence based review of non compliance in glaucoma patients revealed that the proportions of patients who deviate from their prescribed medication regiment ranged from 5% to 80% . Tachyph


Obesity exhibits a wide variety of electrocardiogram (ECG) abnormalities in adults, which often lead to cardiovascular events. However, there is currently no evidence of an association between obesity and ECG variables in children and adolescents. The present study aimed to explore the associations between obesity and ECG intervals and axes in children and adolescents. A cross-sectional observational study of 5,556 students aged 5–18 years was performed. Anthropometric data, blood pressure and standard 12-lead ECGs were collected for each participant. ECG variables were measured manually based on the temporal alignment of simultaneous 12 leads using a CV200 ECG Work Station. Overweight and obese groups demonstrated significantly longer PR intervals, wider QRS durations and leftward shifts of frontal P-wave, QRS and T-wave axes, while the obese group also demonstrated significantly higher heart rates, compared with normal weight groups within normotensive or hypertensive subjects (P<0.05). Abdominal obesity was also associated with longer PR intervals, wider QRS duration and a leftward shift of frontal ECG axes compared with normal waist circumference (WC) within normotensive or hypertensive subjects (P<0.05). Gender was a possible factor affecting the ECG variables. Furthermore, the ECG variables, including PR interval, QRS duration and frontal P-wave, QRS and T-wave axes, were significantly linearly correlated with body mass index, WC and waist-to-height ratio adjusted for age, gender, ethnicity and blood pressure. However, there was no significant association between obesity and the corrected QT interval (P>0.05). The results of the current study indicate that in children and adolescents, general and abdominal obesity is associated with longer PR intervals, wider QRS duration and a leftward shift of frontal P-wave, QRS and T-wave axes, independent of age, gender, ethnicity and blood pressure. Electrocardiogram (ECG) abnormalities are associated with an increased risk of adverse cardiovascular outcomes, including high resting heart rate (HR), prolonged PR interval, QRS duration and QT interval and abnormal shift in electrocardiographic axes . A prospObesity is a strong independent risk factor for cardiovascular disease mortality and it predisposes patients to numerous cardiac complications, including hypertension, coronary heart disease, HF, stroke and sudden death ,16. The Numerous studies have reported a correlation between obesity and QTc interval prolongation ,21; howeTherefore, in this study, the differences in electrocardiographic intervals and axes associated with various degrees of obesity in normotensive and hypertensive children and adolescents were examined in a large-scale population. The final aims were to determine the effect of obesity on electrocardiographic variables besides the aforementioned possible risk factors and identify the possible association with body fat distribution in children and adolescents.The study protocol and the procedures were approved by the Ethics Committee of China Medical University  and fully informed consent was obtained from the parents or legal guardians of all subjects.A total of 5,556 Chinese elementary and secondary school students aged 5–18 years were recruited from 12 rural public schools using multistage cluster sampling in this cross-sectional study between July 2010 and January 2011 in Shenyang (China). The following exclusion criteria and processes were enforced: i) 28 students who had any history of heart diseases, diabetes mellitus, chronic renal diseases or thyroid diseases were excluded; ii) 91 students who had abnormal ECGs, including atrial rhythm, premature beat, ventricular tachycardia, pre-excitation wave, right bundle branch block or apparent first degree atrioventricular block, were excluded. Therefore, the final study group consisted of 5,437 students . Clinical data  and standard 12-lead ECG was collected for each participant in this study.2 (m2). Overweight and obesity were defined by the recommended BMI cutoff values (through BMI of 25 and 30 kg/m2 at 18 years of age) by the International Obesity Task Force, according to age and gender  using the standard protocols. Body weight and height were measured while the participants were barefoot and in light underclothes, to the nearest 0.1 kg and 0.5 cm, respectively. WC was measured to the nearest 0.5 cm at umbilicus level following a normal expiration using a non-elastic tape . BMI wasd gender .Blood pressure was measured in all subjects in this study by well-trained personnel using a mercury sphygmomanometer and appropriate size cuffs. The subjects were advised to avoid coffee, tea and exercise for ≥30 min and had rested for ≥5 min prior to the measurement. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured twice in the right arm in the supine position with the arm level with the heart. The average of the two blood pressure measurements, SBP and DBP, was used in the analysis. According to the Fourth Report on the Diagnosis, Evaluation and Treatment of High Blood Pressure in Children and Adolescents, hypertension was defined as having SBP and/or DBP levels above the 95th percentile for gender, age and height .1/2.Standard simultaneous 12-lead resting ECGs were recorded for participants in a supine position at a 1,000-Hz sampling rate with the use of a PC-based acquisition and analysis system  and stored in a personal computer as separate files for subsequent processing. All recordings were performed by well-trained technicians and all digital ECGs were measured and interpreted on the computer by the same well-trained cardiologist. Cases with apparent disturbances or lack of one or more leads were excluded from the study population. In the CV200 ECG Work Station, temporally aligned superimposed ECG leads, at a magnification of five-fold for paper speed (125 mm/sec) and four-fold for amplitude (40 mm/mV), were made available in order to facilitate the measurement of variables and to validate the onset and end points of the intervals, in accordance with the American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACCF/HRS) recommendations . The key2 test. Pearson’s correlation coefficients were used to explore the correlation between ECG variables and obesity-associated measurements, including BMI, WC and WHtR. The linear associations between variables were further examined using the multivariate linear regression analysis. All tests of statistical significance were two-sided and P<0.05 was considered to indicate a statistically significant difference. The statistical analyses were conducted with SPSS 17.0 .Continuous variables are expressed as mean ± standard deviation (SD). Categorical data are presented as frequencies and percentages. Differences between the groups were compared using the two-tailed, non-paired Student’s t-test or one-way analysis of variance for continuous variables, where appropriate. Comparisons of categorical variables between groups were performed using the χThe final study sample consisted of 5,437 participants  with a mean age of 10.9±2.7 years. Of the study population, 16.8% were presented as overweight  and 7.3% as obese . Abdominal obesity was found in 502 males (17.0%) and 339 females (13.6%) with an overall prevalence of 15.5%. The prevalence of abdominal obesity increased significantly with BMI categories .The baseline characteristics of the participants enrolled in this study according to BMI category are presented in The differences in electrocardiographic intervals and axes among normal weight, overweight and obese groups are listed in Furthermore, detailed differences of electrocardiographic intervals and axes among normal weight, overweight and obese groups stratified by gender are presented in The differences in electrocardiographic intervals and axes between abdominal obesity and normal WC, stratified by blood pressure, are listed in Pearson correlation coefficients between ECG variables and measures of obesity are presented in Considering differences in baseline characteristics among various weight groups may have possible impacts on the study results, multivariate linear regression analysis was performed to explore the linear association between ECG variables and obesity. Multivariate linear regression data are listed in The prevalence of overweight and obese children is a growing global health concern according to the World Health Organization . A previet al in a healthy young population (Obesity in adults is closely associated with a wide variety of ECG changes, including high resting HR, prolongation of PR interval and QRS duration and leftward shifts of electrocardiographic axes. However, the effect of obesity on QTc intervals is controversial in children and adults. Significant positive associations between BMI and ECG intervals, including PR interval and QRS duration, were reported in this cross-sectional study. Furthermore, these associations were linear and independent of age, gender, ethnicity and blood pressure . Signifipulation .Abdominal obesity is an independent cardiovascular risk factor; however, the association between abdominal obesity and ECG variables has not been examined previously in large-scale populations. Differences in ECG intervals and axes between normal WC and abdominal obesity in rural Chinese children and adolescents were explored in this study. Abdominal obesity was associated with longer PR intervals, wider QRS duration and leftward shifts in frontal P-wave and QRS axes compared with the normal WC. Leftward shift of frontal T-wave axis was also apparent, although the difference within hypertensive participants was not significant. The ECG variables, including PR interval, QRS duration, frontal P-wave axis, QRS axis and T-wave axis, correlated with WC and WHtR following adjustment. Furthermore, these associations were linear and independent of age, gender, ethnicity and blood pressure. In general, the effects of abdominal obesity on ECG were in agreement with general obesity.In measuring ECG values, this study differed in two ways from the others. Firstly, a combination of manual locations and computer-based calculations was used in the evaluation of the ECG variables, as described previously, while the majority of previous studies used computer-generated calculations. Manual operation may reduce mistakes in measurements made by the computer . SecondlThere were certain limitations to the present study. As a cross-sectional study, the associations between obesity and ECG intervals and axes were explored; however, the long-term interaction between obesity and ECG variables was not elucidated. Furthermore, the electrocardiographic changes were relatively small and all within normal limits. Therefore, whether these differences had clinical significance was unclear. These issues require more investigation and further follow-up studies.In conclusion, ECG variables were examined and a novel result was reported from a large-scale cross-sectional study among children and adolescents in rural Liaoning in Northeast China. In addition, general and abdominal obesity in children and adolescents was revealed to be associated with longer PR intervals, wider QRS duration and leftward shifts in frontal P-wave, QRS and T-wave axes. Gender itself was a possible factor affecting the ECG variables. In addition, these associations with BMI, WC and WHtR were linear and independent of age, gender, ethnicity and blood pressure.


The treatment did not affect the values of ankle-brachial index (ABI), body weight, and body mass index (BMI).Parameters reflecting cardiovascular health and inflammation were studied in a pilot clinical trial conducted on 40 patients with prehypertension. The patients were treated with a new proprietary formulation of a whey protein (WP) isolate embedded into lycopene micelles (WPL) during a 1-month period. Control groups received lycopene or WP as a singular formulation or placebo pills for the same period of time. Combined WPL formulation of whey protein and lycopene has caused multiple favorable changes in the cardiovascular function (including a tendency to the reduced systemic blood pressure), the plasma lipid profile, and the inflammatory status of patients with prehypertension, whereas singular formulations of the compounds and placebo did not have such an effect. The reduction of plasma triglycerides and cholesterol fractions and almost two-fold decline in C-reactive protein (CRP) and inflammatory oxidative damage (IOD) levels as well as an increase in nitric oxide (NO), tissue oxygenation (StO Whey proteins and whey-related peptides represent a newly emerging class of biological substances with as yet poorly understood potential benefits for human health. For decades whey has been considered as a fairly useless liquid byproduct from the production of cheese. However, modern methods for the fractionation of whey allow the isolation of a variety of substances with an enormously wide spectrum of biological activity . Undenatin vitro systems is comparable to that of well-known pharmacological agents. As an example, three newly identified peptides derived from  α-lactalbumin ,  α-lactalbumin , and β-lactoglobulin  have been shown to have a remarkable inhibitory effect against angiotensin-converting enzyme, ACE [μmol [Moreover, there is a growing number of whey-derived peptides whose pharmacological activity yme, ACE . In anotyme, ACE . The mosCE [μmol .Despite their high inhibitory potency, whey-derived proteins and peptides are highly susceptible to gastrointestinal enzymes which undermine their oral use in treatment of hypertension. This is the main reason why most clinical trials on whey proteins or their derivatives require a significant quantity to be consumed daily. Indeed, susceptibility of whey protein and its derivates to the intestinal enzymes is a major problem complicating their therapeutic use. It explains variations in individual responses to whey protein administration among patients and dictates the necessity for the development of new whey protein formulations development providing a degree of protection for the whey protein and its peptides from the intestinal environment. This would consequently increase their bioavailability and, as result, of this their efficacy.In the present paper, we report the results of a pilot clinical trial with a new proprietary formulation of a whey protein (WP) isolate embedded into lycopene micelles . LycopenThe study was conducted at the Institute of Cardiology, the Ministry of Health of the Russian Federation , during 2010-2011. The protocol was approved by the local ethics committee. All patients were informed about the purpose of the study and have given written consent regarding their participation in the study. The study was part of a larger multiarm trial for which 107 patients with prehypertension fulfilling clinical inclusion criteria were selected. Prehypertension was defined according to the USA Joint National Committee, JNC 7 , as a stInclusion CriteriaCaucasian male or female subjects 45–73 years old.Signed informed consent. Non- or light-to-moderate smokers (≤10 cigarettes daily).Sustained resting systolic blood pressure 120–139 mm Hg.Sustained resting diastolic blood pressure 80–89 mm Hg.3 ≥ 400 and CRP ≥ 6 μg/mL.Serum markers for inflammation Chl.pn-IgG ELISA × 103 ≥ 250 and IOD ≥ 40 μM/mL.Serum markers for oxidative stress LDL-Px ELISA × 10No antihypertensive, lipid-lowering or any other cardiovascular drugs.Willingness and ability to comply with the protocol for the duration of the study.Exclusion CriteriaUnwillingness to sign informed consent.Unable to comply with the protocol for the duration of the study.History of MI in the 3 months preceding the study.Ejection fraction (EF) < 45%.Significant medical condition that would impact safety considerations , pancreatitis, respiratory diseases, epilepsy, etc.). Compulsive alcohol abuse (>10 drinks weekly), or regular exposure to other substances of abuse.Participation in other nutritional or pharmaceutical studies.Resting heart rate of >100 beats per minute or <45 beats per minute.Positive test for tuberculosis, HIV, or hepatitis B.Did not tolerate phlebotomy.On a special diet in the 4 weeks prior to the study .Tomato or milk intolerance.The first product was whey protein isolate (WP), Prolacta . The daily dose was given as 1 capsule containing 70 mg of WP. The second control product was lycopene . The daily dose was 1 capsule containing 7 mg of lycopene. The third product was a complex of WP embedded into protective lycopene matrix, whey protein lycosome  . The dai2. Pulse rate, systolic and diastolic blood pressure, SBP, and DBP were measured three times in the left arm of the seated patient after 15 min of rest. The time between measurements was no less than 2 minutes. The mean number for each parameter was calculated.To measure body mass index, BMI, body mass of the patients, and their height were measured in the morning and BMI was calculated in kg/mAll body and vascular parameters were measured in the morning between 8 and 10 am. Endothelium-dependent flow mediated vasodilatation was measured in accordance with traditional guidelines accepted in the last 10 years , 19. PatHigh resolution ultrasound was used at the same anatomical landmark of a section of the brachial artery for a period of 30 sec before and during the peak of reactive hyperaemia. It was applied prior to sphygmomanometer cuff occlusion and 1 min after its deflation. The level of inflation was 50 mm Hg above the patient's systolic blood pressure and it lasted for 5 minutes. Arterial diameter was imaged above the antecubital fossa in a longitudinal scan by duplex ultrasound with linear phase-array transducer. FMD was calculated as a change in poststimulus diameter as a percentage of the baseline diameter . Between left and right brachial arteries, the one with the highest SBP, and between left and right tibial arteries, the one with the highest SBP were chosen for the assessment of ABI. For this purpose, a continuous-wave Doppler probe was used after patients had been in a supine position for at least 15 min of rest , 22. 2, or combined level of oxygenated haemoglobin and myoglobin, we used the the Nar eminence and forearm muscles of the patients. StO2 was analysed by continuous wavelength near-infrared spectroscopy, NIRS, with wide-gap second-derivative . The measurements were made at different time points. The recording was started after 15 min of rest in a supine position before occlusion of the brachial artery. It was then continued during stagnant ischemia induced by rapidly inflating the cuff to 50 mm Hg above systolic BP. The ischemia lasted for 3 min, and the recording period lasted for another 5 min after that until StO2 was stabilized [As a tissue target for the assessment of oxygen saturation, StOabilized , 24. 2/minute [Then the area under the hyperaemic curve, AUC, of the recorded signal for the settling time in the postocclusion period was calculated as described earlier in % O2/minute , 26.Blood was collected in the morning after night fast from arm veins of the patients. The plasma was separated from the rest of the clotted mass by centrifugation, then aliquots were stored at −80°C prior to analysis. Chlamydia pneumoniae IgG (Chl.pn-IgG), and NOx were measured using commercially available analytical kits according to the manufacturers' recommendations .Glucose, total cholesterol, TC, triglycerides, TG, high density cholesterol, HDL, low density cholesterol, LDL, C-reactive protein, CRP, Plasma samples were incubated overnight in 0.05 M PBS acetate buffer (pH 5.6) which would imitate the type of oxidative damage which occurs during the release of lycosomes following neutrophil degranulation. The following morning, the reaction was terminated using trichloroacetic acid. The concentration of the end products such as malonic dialdehyde (MDA), and other possible thiobarbituric acid reactive substances, TBARS, was then measured by colorimetric methods  using reActivity of serum LDL peroxidase proteins, which include IgG with superoxide dismutase activity , was meat-test was then applied both for paired and unpaired samples. In cases where parameters were not normally distributed Mann-Whitney  U  test and Kruskal-Wallis test were used. ANOVA and ANCOVA were used with post hoc analysis . Statistical significance between two-tailed parameters was considered to be  P < 0.05.For the assessment of normally distributed parameters, the Shapiro-Wilk method was used. Student's  As can be seen from C. pneumoniae-specific IgG. In addition, there was a measurable increase in plasma NOx levels validated by statistical analysis in patients treated with the combined formulation of WP and lycopene. No changes in the parameters of inflammation and oxidative stress were seen in the placebo group. As shown in 2 values. The latter increase exceeded control level by 43.8%. Moreover, treatment with WP embedded into lycopene gave some decrease in the values of systemic blood pressure as revealed by statistical trend analysis. The monoformulations and placebo treatment did not show significant changes in the cardiovascular parameters.None of the treatments affected values for pulse rate and ABI . HoweverPrehypertension is a progressive human disease which often develops without any specific identifiable cause and involves multiple functional changes in microcirculation, inflammatory response, and plasma lipid profile . Althougx, StO2 and flow-mediated dilation values constitute the most significant benefit/outcome of treatment with the combined formulation of whey protein and lycopene. Pleiotropy as well as synergetic and antagonistic interactions between different nutrients represents keystone features governing the physiological response to dietary interventions. Therefore, any given mixture of nutrients may lead to a physiological response not independently obtainable from each individual constituent. Indeed, multiple favorable changes in the cardiovascular system achieved by treatment with a combination of WP and lycopene were not seen in our study in the groups of patients treated with WP or lycopene alone. It is worth mentioning that WP derivates and lycopene have remarkably distinctive patterns of physiological and pharmacological activity. Multiple in vitro and in vivo studies indicate that WP derivates have various effects on microcirculation, vascular tone and blood pressure [The major finding of the clinical trial reported above is that a combined WPL formulation of whey protein and lycopene causes multiple favorable changes in cardiovascular function (including tendency to the reduction of the systemic blood pressure), plasma lipid profile, and inflammatory status of patients with prehypertension, whereas singular formulations of the compounds do not have such an effect. The reduction of plasma triglycerides and cholesterol fractions and almost two-fold decline in CRP and IOD levels as well as an increase in NOpressure –14 as opThese changes in inflammatory activity were accompanied by a reduction in the level of oxidative stress. We cannot claim that they were the consequence of anti-inflammatory activity of WPL or that the whey protein that isolates itself contained antioxidant components which were able to take effect when they were delivered in the lycosome format. Level of NO production, flow mediated dilation, and tissue oxygenation are inversely correlated to markers of inflammation and oxidative stress. Therefore, we again cannot be certain here whether the improvement of these parameters is a result of anti-inflammatory and anti-oxidant activity of WPL or a result of intrinsic vasoactive molecules in the protein isolates itself. Or perhaps it was a combination of both possibilities.In conclusion, it is possible to say that the improved protection of whey protein product by lycosome could allow people to improve their metabolic parameters, vascular function, and antiageing microcirculation. Perhaps this resembles the similar practice of embedding cheese and whey products into lycopene-rich tomato sauce which is one of the factors behind the longevity and cardiovascular health provided by the Mediterranean diet.Although additional studies are required to confirm and extend our results, the results presented above represent a significant step forward in the management of hypertension and cardiovascular disease.


Liver enzymes elevations (LEE) can be observed after kidney transplantation due to multifactorial causes.We performed a retrospective study on 1589 kidney transplants, 971 male and 618 female, who were hepatitis B surface antigen (HBsAg) and hepatitis C virus-antibody (HCV Ab) negative, and had no other liver diseases, to detect the prevalence of LEE and its risk factors in these patients between May 2008 and May 2010.Liver enzymes and other biochemical parameters were measured in all recipients. Patients were divided into three groups, according to laboratory test time since transplantation: Group I, less than 3 months, Group II, 4 - 12 months after transplantation, and Group III, more than one year post-transplantation.The highest LEE was more frequent in older patients (P < 0.001) and male individuals (P < 0.001). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were higher in patients who received kidneys from deceased donors  as compared to living donor transplants  (P < 0.001). The elevation of ALT was the liver enzyme abnormality after kidney transplantation with the highest prevalence (34.3%). The levels of ALT and AST were significantly elevated within the first 3 months after transplantation, followed by the 4-12 months period (P < 0.001). There was a reverse correlation between liver enzyme levels and renal allograft function in both univariate and linear regression analyses. This correlation increased over time. There was also a significant relation between cyclosporine blood levels and liver enzyme values in the univariate analysis. However, this relationship was attenuated over time. Elevated liver enzymes also correlated with anemia.The LEE is a common finding among kidney transplant recipients. Serial monitoring of aminotransferases, particularly ALT, should be performed in all patients after kidney transplantation. Chronic liver disease, usually caused by hepatitis B virus (HBV) and hepatitis C virus (HCV), is an important threatening complication after kidney transplantation , 2. The Liver enzymes elevations (LEE), including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), are indicators of hepatocellular injury . PatientThis retrospective study was performed a on a reasonable number of kidney transplants to detect the prevalence of LEE and its risk factors in these patients, between May 2008 and May 2010.We enrolled 1589 renal transplant recipients (RTRs) who were negative for hepatitis B surface antigen (HBsAg) and hepatitis C virus-antibody (HCV Ab), and had no other liver diseases. Blood samples were taken from all cases (7632 samples) for the measurements of routine parameters such as liver enzymes, serum creatinine (SCr), cyclosporine (CsA) through level (C0) and 2-hour post-dose level of CsA (C2).Patients were divided into three groups, according to laboratory test time since transplantation: Group I, less than 3 months, Group II, 4-12 months after transplantation, and Group III, more than 1 year post-transplantation.Demographic variables and other biochemical measurements were gender of recipient and donor, age of recipient and donor, donor sources (living and deceased), blood urea, lipid profiles, fasting blood sugar (FBS), uric acid and hemoglobin (Hb). All recipients were followed for at least 6 months. The study was approved by the local research center ethics committee.Immunosuppression maintenance in all recipients was primarily based on cyclosporine (CsA). The majority of patients also received mycophenolate mofetil/azathioprine and prednisolone. Induction therapy with anti-thymocyte globulin was routinely administered in highly sensitized cases, such as patients with high panel reactive antibody and second or third transplantation. All patients were clinically examined and a blood sample was taken for routine laboratory test at a weekly interval until 1 month, then at two weeks period up to 3 months, followed by monthly test for 1 year and every 1-2 months subsequently.We considered the upper limit of normal for aminotransferases (ALT and AST) at 40 IU/L and ALP to 316 IU/L. Patients with renal allograft dysfunction (SCr > 2 mg/dl) were considered to have high ALT levels if the ALT level was > 27 IU/l. It has been shown that 27-IU/l is the upper limit of ALT for dialysis patients without liver disease .Data were analyzed using SPSS for Windows version 17.0  and the quantitative results were presented as mean ± SD, while qualitative variables were expressed by number and percentage. The Kolmogorov-Smirnov test (K-S test) showed that AST and ALT levels were not distributed normally. Consequently, Spearman's correlation analysis was used to assess the correlations between liver enzymes levels with numeric variables. Chi square test was used to compare qualitative data. Comparisons of variables, such as AST, ALT and ALP, between male and female recipients, were performed using the Mann-Whitney U-test. Multiple logistic regression was also performed for abnormal ALT, considered as a categorical factor. A result was considered statistically significant when P < 0.05.A total of 1589 RTRs, 971 males and 618 females, were included in this study. Elevated liver enzymes were correlated with anemia . The conIn recipients with serum SCr > 2 mg/dL, we considered an ALT level > 27 IU/L as abnormal. Consequently, at multivariate logistic regression, renal impairment was an independent risk factor for abnormal ALT in patients with SCr > 2 mg/dL (Exp(B) = 0.48, 95% CI: 0.32-0.73, P = 0.001).Elevation of hepatic aminotransferases, ALT and AST, is suggestive of hepatocellular injury. Despite the importance and high prevalence of LEE after kidney transplantation, there are surprisingly few studies on the evaluation of liver enzyme levels among kidney transplant patients and risk factors of their abnormalities after kidney transplantation. In addition, to our knowledge, recent published data in literature on prevalence of liver enzymes abnormalities after kidney transplantation are scarce. The current study shows that, in a quite large sample of kidney transplant patients, liver enzymes are significantly higher in these patients, accounting around 34% for ALT. Liver dysfunction is reported in 7-67% of kidney transplant patients in various studies -14. It sChronic liver disease, which is a frequent complication after renal transplantation, represents the fourth highest cause of death in most series . PatientThe source of allograft is important in estimating the incidence of liver enzymes elevation. In deceased transplants, this incidence is higher than in living donors -20. SimiLorber et al. in 1987, mentioned that 49% of their renal allograft patients had post-transplant hepatotoxicity with CsA, including hyperbilirubinemia (48% of patients), elevated AST (47%), ALT (73%), LDH (84%), and ALP (59%). Abnormal liver enzymes usually were self-limited in 82% of the cases and generally occurred very soon after transplantation (76%). The serum CsA was relatively high in these patients (225 +/- 17 ng/mL) . Their fThe main limitations of this study include its retrospective nature, exclusion of non-alcoholic fatty liver disease, as the most common cause of chronic liver disease worldwide, and hepatitis E virus infection, which we did not check in patients with elevated liver enzymes. In addition, liver biopsy and molecular tests were not performed in all kidney transplants with abnormal ALT. It should be noted that liver biopsy is considered as the gold standard of diagnosis of hepatic injury. However, it is invasive, expensive, and may bear potential risks. In addition, the data for the status of opportunistic infections after kidney transplant, ischemia time, ALP bone isoenzyme, medications affecting the liver enzymes such as statins, and body mass index were not available in this study and we could not estimate the impact of these factors on liver enzyme levels after kidney transplantation. The majority of patients also received mycophenolate mofetil and prednisolone. Azathioprine was only used in a small number of patients and we did not investigate the impact of azathioprine on the liver enzymes.The abnormal liver enzymes are a common finding among kidney transplant patients. The LEE was correlated with age, gender, source of donors, renal allograft function, anemia and CsA blood levels. Serial monitoring of aminotransferases, particularly ALT, should be performed in all patients after kidney transplantation.


The present study evaluated the predictive value of renal resistive index (RI) for renal function and blood pressure (BP) outcome in hypertensive patients with unilateral atherosclerotic renal artery stenosis submitted to successful revascularization.In 158 hypertensive patients with atherosclerotic renal artery stenosis RI was acquired. Twelve months after revascularization, they were classified on the basis of renal function and BP outcome as benefit , or failure.Regarding renal function outcome, RI in the stenotic and in the contralateral kidney were significantly higher in patients with failure (n = 20) than in those with benefit . Among different cutpoints generated, RI in the contralateral kidney >0.73 provided the largest area under the curve (0.77), and the highest sensitivity (80%) and specificity (72%). In the multivariate logistic regression analysis, RI in the contralateral kidney >0.73 was an independent predictor of a failure in renal function outcome.Regarding BP outcome, patients with no benefit from revascularization (n = 60) had similar RI in the stenotic and contralateral kidney (p = ns), but presented higher pulse pressure, albuminuria and hypertension duration in comparison to patients with improved BP control.RI in the contralateral kidney is an independent predictor of renal function outcome after successful revascularization in hypertensive patients with unilateral atherosclerotic renal artery stenosis, whereas it is not able to predict blood pressure outcome. In the last decades the prevalence of atherosclerotic renal artery stenosis (ARAS), possible cause of secondary hypertension and ischemic nephropathy, has progressively increased in Western countries, due both to the aging of the population and to improved technical capability of detecting it. The debThe renal resistive index (RI), measured by duplex ultrasound, has been suggested to be a useful prognostic tool, that enables to identify patients who will not benefit from revascularization in terms of renal function or blood pressure (BP) improvement-11. In pTherefore, the aim of the present study was to evaluate the prognostic value of baseline RI in the stenotic and controlateral kidney in predicting the outcome (12-month follow up) of BP and renal function in hypertensive patients with unilateral ARAS submitted to successful revascularization.One hundred and sixty eight patients  were enrolled from 1990 to 2008. Inclusion criteria were:Unilateral atherosclerotic renal artery stenosis >60% defined by a renal to aortic ratio greater than 3.5 at duplex ultrasound examination, confirmDiagnosis of arterial hypertension according to current Guidelines, with orPatient’s informed consent;Exclusion criteria were: fibromuscolar dysplasia; bilateral renal artery stenosis; age > 80 years; KDOQI stage 5 chronic kidney disease ; history of severe adverse reaction to iodinated contrast; technical limitations to revascularization procedure; severe comorbidities that contraindicated the intervention according to clinical judgment.The study was approved by the ethical committee of the Azienda Ospedaliero-Universitaria Pisana and conformed the Declaration of Helsinki. In accordance with institutional guidelines, all patients were aware of the investigational nature of the study and gave written consent to it.All the patients underwent abdominal duplex ultrasonography  in the month before revascularization after fasting 6–8 hours. The study was performed by the same operators (R.M.B and M.S.) using a high resolution multifrequency (2.5 - 4.5 MHz) Convex probe. Three velocimetric measurements of the interlobar renal arteries adjacent to medullary pyramids were obtained by a translumbar and/or anterior approach and RI was calculated according to the formula: RI = (systolic peak velocity – end diastolic velocity)/systolic peak velocity, as already reported in previous studies.Office BP  was measured by a trained physician. Office BP was measured in both arms at the first visit in our center and then measured in subsequent visits in the arm in which resulted to be higher. Blood samples were collected in all patients to measure serum creatinine and other routine parameters, by standard technique. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease (MDRD) formula.Angioplasty was performed following Tegtmeyer technique, by usin•“Benefit” if: diastolic blood pressure < 90 mm Hg and/or systolic blood pressure < 140 mm Hg without pharmacological treatment or on the same or reduced number of medications (or reduced number of defined daily doses); reduction in diastolic blood pressure by at least 15 mm Hg on the same or reduced number of medications;•“Failure” if the abovementioned criteria were not met.Twelve months after revascularization, patients were also classified in two categories, according to renal outcome:•“benefit” if there was an increase in eGFR ≥20% compared to pretreatment values or a value of eGRF within ±20% of pretreatment values;•“failure” if there was a deterioration in eGFR ≥20% after treatment,26.Statistical analysis was performed by means of NCSS 2004 software . Results are expressed as mean ± SD. Differences between two means were compared by the Student’s t test for paired or unpaired observations, as appropriate, while categorical variables were compared using the chi-square test. Differences were considered to be statistically significant when p was <0.05.Receiver operating characteristic (ROC) analysis was performed to calculate the best threshold value of RI associated with a benefit of revascularization in terms of BP and renal function outcome, both defined as dichotomous variables as explained above. Cut-points selected were those that yielded the greatest sum of sensitivity and specificity. Logistic regression analysis was used to identify independent predictors of clinical outcome, according to clinical and ultrasonographic parameters.Baseline characteristics of the study population are summarized in Table All the patients underwent angioplasty with (n = 104) or without stent (n = 64). Before 1995, angioplasty without stenting was the only kind of intervention performed (n = 25); from 1995 to 2003, angioplasty with stent placement was performed mainly in ostial stenosis (n = 51 out of 85); from 2003 to 2008, stent placement was performed in all but 5 cases in which was technically not feasible. The rate of procedure-related major clinical adverse events was 2.4% , whereas a residual stenosis was demonstrated soon after the revascularization procedure in 1 patient. Two cases of retroperitoneal bleeding/hematoma and 3 cases of partial renal ischemia, not requiring medical or surgical intervention and without any clinical sequelae, also occurred. During 12-month follow-up, 24 restenosis in the site of the intervention occurred, 9 patients developed contralateral renal artery stenosis, 1 patient died for a cardiovascular event and 1 patient started dialysis. In total 10 patients were excluded , thus the following analysis were performed on 158 patients.Clinical and ultrasonographic characteristics, BP and renal outcome and restenosis rate were analyzed according to the type of intervention: percutaneous angioplasty with stent placement (n = 97) versus angioplasty only (n = 61). At baseline the two groups resulted to be substantially similar for clinical and ultrasonographic characteristics, except for a greater diastolic BP in the angioplasty-only group and a greater use of antithrombotic and lipid-lowering drugs in the stenting group, the latter probably due to change in guidelines recommendations over years (data not shown). No significant difference in terms of restenosis rate  and BP outcome failure  was encountered between patients undergoing angioplasty with or without stenting. Renal outcome failure tended to be more frequent in subjects receiving only angioplasty .After 12-month follow-up, a failure in renal function outcome was demonstrated in 20 patients, while in 138 patients glomerular filtration rate was unchanged (n = 101) or improved (n = 36). Patients with worsened renal function were older, were more frequently males, had a higher body mass index, higher systolic and pulse pressure values in comparison to the group who showed benefit from revascularization  Figure .At one year follow up, clinical characteristics of patients classified according renal function outcome were also analyzed. Patients in the failure group presented a significantly higher serum creatinine  and lower glomerular filtration rate  in comparison to their counterparts. Despite similar systolic and diastolic BP were observed , pulse pressure  and the number of hypertensive drugs  were significantly greater in the failure group.On the basis of BP outcome, 98 patients were classified in the benefit category and 60 in the failure category. Since a higher restenosis rate was encountered in the failure group , statistical analysis was performed with the exclusion of the patients who experienced restenosis Table . Among cThe present study demonstrated that RI in the contralateral kidney is an independent predictor of renal function outcome after successful revascularization in hypertensive patients with unilateral atherosclerotic renal artery stenosis, whereas it is not able to predict blood pressure outcome.Past and ongoing trials-6 have bRenal RI has been demonstrated to be useful as a negative prognostic index for renal function outcome by Radermacher and colleagues,10, showThe present study showed a 13% of patients who had worsened renal function, defined as a GFR decline of at least 20%, one year after revascularization. RI in the stenotic as well as in the contralateral kidney were both significantly higher in patients with no benefit in terms of renal function in comparison to their counterparts; this is in line with the previous report by Radermacher and coauthors, suggesting an high RI as a significant negative prognostic factor. We consIt is interesting to note that in a relevant percentage of patients the contralateral kidney was characterized by nephrosclerosis, identified by a RI > 0.70. Indeed,The present study confirmed previous results that shoIn terms of BP outcome, the results of the present study, showing a 64% of cured/improved and a 32% of patients with no benefit at one year follow up after revascularization, are consistent with those of previous studies. This hyThese data indicate that duplex ultrasound evaluation of RI in the contralateral kidney is an independent predictor of renal function outcome after successful revascularization in hypertensive patients with unilateral atherosclerotic renal artery stenosis, whereas it is not able to predict blood pressure outcome.The results of the present study suggest that RI evaluation could contribute, at least in part, to better identify patients that could benefit from revascularization. At the moment, renal artery revascularization has not been demonstrated to be superior to medical therapy in hypertensive patients with RAS, possibly due to inadequate patient selection. Thus it is desirable to design further studies with the aim of identify non-invasive, highly predictive diagnostic tests in order to limit renal revascularization to patients who will really benefit from it.ARAS: Atherosclerotic renal artery stenosis; AUC: Area under the curve; BP: Blood pressure; KDOQI: Kidney Disease Outcomes Quality Initiative; RI: Renal resistive index; MDRD: Modification of Diet in Renal Disease; eGFR: Estimated glomerular filtration rate; ROC: Receiver operating characteristic.The authors declare that they have no competing interests.RMB and ED and performed statistical analysis and drafted the manuscript; ST, SP, LG, conceived the study and participated in its design; MS performed ultrasound exams; MS, LV, CR, IDP, ED collected data and were involved in the clinical follow-up; DV, SP and LOL participated in design and coordination of the study and critically revised the manuscript. All authors read and approved the final manuscript.


P = 0.031). This increase in uNGAL was minor compared to ICU patients with acute renal failure (2.05 × 106 ng/g). Patients with repeated findings of ATI or severe ATI did not have higher urinary NGAL levels compared to those with only one ATI finding or moderate ATI. Female recipient gender and urinary tract infection were identified as potential confounders. uNGAL has a relation with histological signs of acute tubular injury. The usability of this biomarker in renal allograft recipients is limited because of the low sensitivity.Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is known to predict the prolonged delayed graft function after kidney transplantation. We examined the relation of uNGAL with histological findings of acute tubular injury (ATI). Analyses were made in biopsies taken at 6 weeks, 3 months, and 6 months after kidney transplantation. uNGAL was measured in the spot urines, normalized to urinary creatinine excretion, and correlated to biopsy findings and clinical, laboratory, and demographic variables. Controls included healthy individuals, individuals after kidney donation and ICU patients with acute kidney failure. Renal transplant recipients without ATI did not display elevated uNGAL levels compared to the healthy controls. Transplant patients with ATI had a higher uNGAL excretion at 6 weeks than patients without ATI (27,435 versus 13,605 ng/g;  Acute kidney injury early after transplantation may arise from the donor's condition, prolonged cold ischemia time, and early posttransplant injuries like rejection and drug toxicity. Immediate clinical correlates of this injury may be delayed graft function or a less-than-optimal glomerular filtration rate. However, acute kidney injury carries adverse long-term consequences as patients with acute tubular injury early posttransplantation have an inferior long-term allograft function . TherefoTraditionally, serum parameters as creatinine and urine output are used to monitor kidney function in transplanted patients. However, a rise in serum creatinine already implies a significant amount of kidney damage, which limits its ability to detect impaired graft function at early stages. Recently, novel biomarkers such as Kim-1, IL-18, and neutrophil gelatinase-associated lipocalin (NGAL) have been proven useful in detecting nontransplant acute kidney damage . NGAL, aAcute kidney injury primarily affects renal tubules and NGAL is produced in injured tubular epithelial cells. Therefore, we addressed the question whether urinary NGAL correlates with histologically confirmed acute tubular injury using protocol biopsies taken within the first six months after transplantation. n = 35 patients who never had any signs of ATI and n = 105 patients with at least one finding of ATI during the protocol biopsy program). Controls included 9 healthy individuals (2-kidney controls), 13 individuals after kidney donation (1-kidney control), and 5 ICU patients with acute kidney failure. Renal protocol biopsies are regularly performed 6 weeks and 3 and 6 months after kidney transplantation in the transplant center of the Medical School of Hannover since 2001. All patients are eligible for the protocol biopsies unless certain medical conditions like bleeding disorders and other comorbidities advice against a biopsy. In addition to these regular protocol biopsies, biopsies for cause are performed in case of unclear allograft impairment. Only data of patients undergoing regular protocol biopsies were included in this study. Demographic and clinical data of patients participating in this program were collected prior to and at the time of transplantation. The demographics for patients with and without ATI are depicted in n = 23 samples were taken at 6 weeks, n = 17 at 3 months, and n = 16 at 6 months after transplantation. For patients with signs of ATI n = 44 samples were taken at 6 weeks, n = 3 samples at 3 months, and n = 55 samples at 6 months. After transplantation, clinical data and routine laboratory results were collected corresponding to the time points of the three protocol biopsies. Spot urine was frozen in −80°C at time of the biopsy. Biopsies were evaluated according to the updated Banff classification [The study population consisted of 140 adult kidney transplant recipients randomly chosen from our protocol biopsy archive , according to the manufacturer's protocol. Urinary NGAL excretion was normalized to urinary creatinine excretion to correct for differences in NGAL due to urine dilution. Urinary NGAL excretion is presented as the amount of urinary NGAL in ng per g of urine creatinine.P < 0.05. Note that for better visualisation the logarithm to base 10 was used in all figures with NGAL results, because these values were highly variable and not normally distributed.Descriptive data were reported as medians with ranges. Comparisons of categorical data between groups were performed with Fisher's exact test and the chi-square test for two or more samples. Numerical data were compared with the Kruskal-Wallis test and the Mann-Whitney test. Linear regression analyses were performed with log transformed NGAL values as the dependent variable and the demographical, clinical, and laboratory factors that had been significantly different in univariate analyses. Variables from the univariate analyses were separately examined for the samples at 6 weeks and 6 months using the backward selection. SPSS statistical software package version 18.0  was used for statistical analysis. Statistical significance was assumed for P < 0.001). Subsequent analyses represent a cross-sectional study of samples where not all patients provided urine samples at every time point, showing no time-associated differences in samples taken at 6 weeks, 3 months, and 6 months after transplantation  and healthy individuals with 2 kidneys . In nontantation .  FigureNext, we tested the sensitivity of urinary NGAL as a biomarker to indicate ATI in transplanted patients. At six weeks, patients with ATI had urinary NGAL values that were two-fold higher than the values from patients without ATI in the biopsies, yet there was a considerable overlap of values between the two groups. At 6 months, no differences between patients with and without ATI were apparent .  Figurer2 ≤ 0.1; data not shown).In an explorative analysis, we correlated NGAL levels to allograft damage  and to additional clinical, laboratory, and demographic variables . The main findings of the univariate analysis are depicted in Isometric vacuolization and prevalence of chronic graft changes (cGrade>0) according to the current BANFF classification at 6 weeks after transplantation were associated with significantly higher uNGAL levels. However, after 6 months, uNGAL ratios were lower in patients with isometric vacuolization. In addition, patients with urinary tract infection at the time of sampling had significantly higher uNGAL ratios at 6 weeks as well as 6 months .r2 = 0.296; unadjusted R Square of model fit). Recipient gender was not a significant factor in the regression model at 6 weeks . In the 6-month samples (r2 = 0.357). Next, linear regression analyses were performed with log transformed NGAL values to determine the contribution of the identified variables of the explorative univariate analysis to the observed NGAL levels. Significant variables from the univariate analyses were separately examined for the samples at 6 weeks and 6 months using the backward selection. For the 6-week samples , presenc samples , urinaryP = 0.20). Since the univariate analysis indicated a relation between donor and recipient gender and NGAL levels, the possible gender combinations are additionally presented . SignifiAcute tubular injury (ATI) is a frequent finding in biopsies of renal allograft recipients and is linked to an inferior long-term allograft function . In thisNGAL can be produced locally in the kidney by injured tubular cells and can be secreted by activated neutrophils/macrophages or inflamed vasculature . In a reWe established the baseline uNGAL excretion in our transplanted patient cohort without findings of ATI. uNGAL levels in this group were comparable to healthy controls and remained stable 6 weeks, 3 months, and 6 months after transplantation. As proper controls for patients with a renal allograft, we collected sample material from healthy individuals with one kidney , in addition to healthy controls with 2 kidneys. Our observation of a tendency towards a higher NGAL excretion in healthy individuals with 2 kidneys versus 1 kidney may point to a confounding effect by the kidney mass. This finding should be confirmed with a larger cohort. In patients with ATI, median uNGAL ratios were significantly higher at 6 weeks after transplantation than in patients without signs of ATI. While these findings may indicate a correlation of uNGAL excretion to ATI in patients early after transplantation, we could not demonstrate increased uNGAL levels in patients with ATI at 6 months after transplantation. On the contrary, median uNGAL levels in patients with ATI were even lower at 6 months compared to the controls without ATI. Further analyses showed no differences of NGAL excretion depending on the frequency of ATI or the distinction between diffuse versus focal ATI. NGAL levels were weakly inversely correlated to the eGFR; however, no link could be established between uNGAL levels and acute rises in serum creatinine at the time of ATI diagnosis. Urinary NGAL levels have been shown to correlate with histopathological alterations in IgAN patients . TubuloiPlasma NGAL measurements can be influenced by numerous clinical variables, such as hypertension , systemiThe limitations to our study are that we present a single-centre study and that urine samples were stored at −80°C for more than a year and some protein degradation may have occurred during the freeze-thaw cycle thus, this study should be confirmed with immediate uNGAL measurements in fresh urine samples. In addition we do not have information about the uNGAL levels in our patients prior to transplantation or in the donors and some patients did not provide urine samples at all time points when protocol biopsies were taken. Thus, further studies are necessary to evaluate the diagnostic value of uNGAL measurements in patients after kidney transplantation.In conclusion, even though NGAL may be useful in classifying patients with established AKI or glomerulonephritis in native kidneys or may be a predictor for delayed graft function and recovery early after kidney transplantation –16, 23, Variables without statistical significance after correlation to urinary NGAL ratios in an explorative analysis.Click here for additional data file.


The aim of the study was to assess the effect of three different types of anaesthesia on perioperative bleeding control and to analyse the mean arterial blood pressure and heart rate in patients undergoing endoscopic paranasal sinus surgery. Ninety patients  scheduled to undergo functional endoscopic sinus surgery in the years 2008–2010 were identified as candidates for inclusion in the study. Patients were randomly assigned to one of three groups (30 patients each) according to the type of general anaesthesia to be administered. Groups I and II both received inhalation anaesthesia (sevoflurane for sedation) and intravenous anaesthesia . Anaesthesia was delivered solely via intravenous route (TIVA) in group III, with propofol used for sedation and remifentanil for analgesia. Blood pressure and heart rate were monitored during surgery and post-surgically for 4 h. Mean anaesthesia duration in groups I, II and III was 108.7 ± 20.8, 112.6 ± 22.2 and 103.7 ± 17.5 min and the surgery duration was 71.3 ± 16.7, 78.8 ± 24.2 and 66.5 ± 15.5 min, respectively. Mean blood loss during surgery was 365.0 ± 176.2, 340.0 ± 150.5 and 225.0 ± 91.7 ml, with a mean blood loss rate of 5.1 ± 2.4, 4.5 ± 2.2 and 3.4 ± 1.1 ml/min in groups I, II and III, respectively. Technologically advanced control of the drug dose with the TIVA technique allows for better control of perioperative bleeding. Excessive bleeding during extensive endoscopic surgery of the paranasal sinuses can compromise the safety and efficiency of the surgical procedure. To ensure hemodynamic balance and patient safety, it is essential to monitor and control perioperative bleeding. Fortunately, the amount of blood lost during surgery can be easily determined by measuring the total quantity of blood suctioned from the operative field.Good surgical field visibility is one of the basic prerequisites for a precise and safe otolaryngological operation, and the main obstacle to good visibility is excessive perioperative bleeding. Several factors, including arterial blood pressure, heart rate and coagulation disorders, have a large impact on perioperative bleeding. For this reason, every effort should be made to maintain these cardiovascular parameters at low levels.One of the main methods of reducing perioperative bleeding during functional endoscopic sinus surgery (FESS) is the use of controlled hypotension. However, poorly controlled hypotension can lead to lower blood flow to organs that are sensitive to fluctuations in perfusion pressure. The use of precisely dosed modern anaesthetic agents, together with proper patient positioning, allows us to manage haemodynamic parameters during surgery  and thusThe aim of the present study was to compare TIVA to two other types of conventional anaesthesia delivery in order to assess the impact on perioperative bleeding control and on mean arterial pressure and heart rate in patients before, during and after endoscopic paranasal sinus surgery.In the 2-year period from 2008 to 2010, 502 patients (209 women 41.6 %] and 293 men [58.4 %]), aged 18–85 years underwent FESS at the Department of Otolaryngology of the Military Medical Academy in Lodz. Of these 502 patients, 90 (30 women and 60 men) were randomly selected to participate in this randomized, prospective study. The women ranged in age from 18 to 75 years (mean 46.6 ± 11.12) and the men from 20 to 85 years (mean 54.4 ± 13.29). The inclusion criteria were based on the American Society of Anesthesiologists (ASA) Physical Status Scale Ratings [ % and 29The patients were allocated to one of three groups (30 patients each) based on the intended general anaesthesia approach . Both inhalation anaesthesia (sevoflurane for sedation) and intravenous anaesthesia were used for patients in groups I and II. The only difference between groups I and II was in the intravenous anaesthetic agent used . Sevoflurane concentration was regulated by an evaporator and monitored in expired gases. The third group (group III) received anaesthesia administered solely via the intravenous route (TIVA), with propofol used for sedation and remifentanil for analgesia.Target-controlled infusion (TCI) was used to deliver the anaesthetics in group III, with the infusion pump programmed in the usual manner. Briefly, this is done by entering the value of the target plasma drug level along with the patient’s age and weight. The device contains the appropriate pharmacokinetic profile and, using these input data, calculates and adjusts  the correct speed for intravenous drug delivery to achieve the targeted plasma level. The pharmacokinetic profile programmed in the pump is specific for each company and development of this profile is based on several thousand studies of plasma drug concentration during anaesthesia in patients of various ages and weights , 7.For intubation, the same muscle relaxant was used in all three groups. Controlled hypotension was applied to maintain the systolic blood pressure below 100 mm Hg, with analgesic and sedative doses administered accordingly.The following parameters were assessed: duration of anaesthesia, duration of surgery, total perioperative blood loss and perioperative blood loss rate (ml/min). Patients who met the criteria for surgery were randomly allocated to one of the three groups. All patients were ASA class one and two for general anaesthesia risk. Surgery was performed in the reverse Trendelenburg position, at a 15°–20° angle, without use of a shaver.Inclusion criteria for surgery were as follows: arterial blood pressure ≤140/90 mm Hg and general anaesthesia risk ≤class 2 on the ASA scale. Patients took antihypertensive agents up to the day of the surgery to ensure a stable blood pressure during the perioperative period .On hospital admission, blood pressure was measured and a clinical examination was performed to assess cardiovascular status and the possible need for additional treatment. In addition, the following laboratory tests were performed: blood cell counts, coagulogram, ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein). All patients underwent a CT scan of the paranasal sinuses and, depending on comorbidities and blood type, additional tests were performed as necessary.All patients received premedication (benzodiazepine) to minimize the impact of the sympathetic nervous system on the cardiovascular system. All surgical interventions were conducted under thermally induced voltage alterations with remifentanil and propofol (anaesthesia induction). Arterial blood pressure and heart rate were monitored continuously during surgery. Patients remained under nursing care during the postoperative period. Cardiovascular system parameters were monitored every 15 min for at least 4 h following surgery. The mean arterial blood pressure (MAP) and heart rate (HR) values, as well as standard deviations, were calculated.p < 0.05. The Student’s t test was used for inter-group comparisons. Tukey’s HSD post hoc test was used to compare more than one group. Pearson’s correlation coefficient was used to assess the strength of linear relationship between the variables.Results were analysed with Chi-squared tests, with a significance level of A total of 30 women and 60 men were included in the study. Group I consisted of 8 (26.7 %) women and 22 (36.7 %) men; group II 9 (30.0 %) women and 21 (35.0 %) men; and group III 13 (43.3 %) women and 17 (28.3 %) men. The statistical analysis showed no significant differences between men and women in total blood loss or blood loss rate. At baseline, 55 of the 90 patients (61.1 %) had normal arterial blood pressure, 25 (27.8 %) were receiving treatment for hypertension and 10 (11.1 %) had untreated hypertension.p < 0.05; coefficient of determination, R2 = 6.7 %). No significant differences were observed in surgical time between groups I and II.The mean duration of anaesthesia was as follows Fig. : group Ip < 0.00; coefficient of determination, R2 = 15.7 %); no significant differences between groups I and II were observed for this variable. Mean blood loss rates were as follows: group I, 5.1 ± 2.4 ml/min; group II, 4.5 ± 2.2 ml/min; and group III, 3.4 ± 1.1 ml/min .Mean blood loss during surgery was as follows Fig. : group Ip > 0.05). In patients with treated hypertension, blood pressure decreased (in both men and women) during surgery, although these values returned to pre-surgical levels after surgery. Notwithstanding these changes, the observed differences in MAP were not statistically significant (p > 0.05). In patients with untreated hypertension, blood pressure normalized (i.e. became non-hypertensive) during surgery in both men and women, but returned to pre-surgical levels after surgery; however, this variation in blood pressure was not significant (p > 0.05).MAP values before, during and after surgery are shown in Table p > 0.05). The greatest differences in MAP values occurred in patients with treated and untreated hypertension , or when topographical identification of the surgical field is impeded. Local bleeding, which is difficult to control due to anatomical and pathological characteristics, affects the visibility of the surgical field during FESS. Excessive bleeding—which can be evaluated by the quantity of blood suctioned from the surgical field—is often a signal to interrupt surgery . TherefoAccording to the United States National Library of Medicine, controlled hypotension is defined as a pharmacologically induced reduction of the systolic blood pressure to 80–90 mm Hg, a reduction of MAP to 50–65 mmHg or a 30 % reduction in baseline MAP. Controlled hypotension can be induced by patient-controlled epidural anaesthesia and a number of different hypotensive drugs. Of the various hypotensive medications available, vasoactive drugs  and clonidine and ACE inhibitors have proven to be the most effective. However, controlled hypotension is best achieved with precisely dosed, modern anaesthetic drugs, which have an immediate impact on hemodynamic parameters –12. The A major limitation of the conventional administration of intravenous drugs is that even though the total drug dose administered is determined by the anaesthetist, its concentration in the brain depends on the volume and rate of distribution, the drug’s affinity for brain tissue and the speed of drug elimination from the body. Moreover, it is difficult to determine the appropriate drug infusion rate to ensure the appropriate level of sedation , 17.Due to the disadvantages associated with the conventional intravenous techniques described above, TIVA and similar techniques have become popular in recent times and offer a viable alternative to inhalational anaesthesia. The emergence and feasibility of TIVA is due to advances in the pharmacokinetic and pharmacodynamic properties of newer drugs such as propofol. These properties make these drugs ideal for delivery via continuous infusion. Similarly, new computer technology has allowed for the development of sophisticated delivery systems (target-controlled infusion) that enable anaesthetists to easily control intravenous delivery.Advances in the field of anaesthesiology have led to greater patient safety. Control and modification of cardiovascular system parameters ensure that arterial blood pressure and heart rate remain stable, thus facilitating good visibility of the surgical field, which in turn enables surgeons to work with greater confidence during surgery. In Poland, nearly all laryngological centres perform surgery under general anaesthesia, and use of this type of general anaesthesia has become so widespread that it can now be considered the standard in laryngological surgery.Sieśkiewicz et al.  evaluateIn that same study , SieśkieA postoperative increase in arterial blood pressure, as occurred in our study, is usually associated with pain and for this reason analgesic treatment should be implemented in the intensive care unit (ICU). In our case, we did this by devising an algorithm to administer postoperative analgesics according to pain intensity levels. Using a visual analogue scale (VAS) ranging from 0 (no pain) to 10 scores (very severe pain), the intensity of the postoperative pain was divided into four categories, as follows: I—slight pain (VAS < 4); II—moderate pain ; III—severe pain ; and IV—very severe pain (VAS > 6). Depending on the patient’s medical history , we first administer non-opioid drugs, followed by opioids if the pain is long lasting.The use of technologically advanced dosing techniques (TCI) during entirely intravenous general anaesthesia in group III provides better control of hypotension, leading to less bleeding in the operative field, and a shorter operating time. Blood pressure in patients with hypertension (whether treated or not) should be pharmacologically normalized by an anaesthetist during the operation. However, this is often not possible and in such cases intensive bleeding will likely hamper the operation.


Our previous study has shown that visually evoked cerebral blood flow velocity response (VEFR) is increased during cold pressor test (CPT) in healthy human subjects . Our resIn the present study, we investigated the hypothesis that the effect of tonic pain stimulus on NVC is altered in patients with migraine.23 healthy subjects  and 29 patients with migraine  participated in the study. Arterial blood pressure, heart rate, end-tidal carbon dioxide partial pressure and blood flow velocities in the right posterior and the left middle cerebral artery were continuously measured. VEFR was calculated as relative increase in blood flow velocity in the posterior cerebral artery from average values during last 5 seconds of stimulus OFF period to average values during last 10 seconds of following stimulus ON period. Three consecutive experimental phases were compared: basal, CPT and recovery.In healthy subjects, during CPT, end-diastolic VEFR increased from 20.2 to 23.6% (p<0.05) and subsequently decreased to 17.7% in recovery phase (p<0.05). In patients with migraine, no statistically significant change in end-diastolic VEFR was observed between phases (p>0.05). Additionaly, the differences in end-diastolic VEFR between the basal phase and the CPT phase and between the CPT phase and the recovery phase were statistically significantly higher in healthy subjects than in patients with migraine (p<0.05).Our results are consistent with the assumption that there is a lack of effect of tonic pain on the activity of NVC due to dysfunction of modulatory subcortical pain structures in patients with migraine.


During ultrasound examination, tricuspid regurgitation may be absent or gives a signal that is not reliable for the estimation of systolic pulmonary pressure. The aim of this study was to evaluate the usefulness of acceleration time (AT) from the right ventricular outflow tract (RVOT) as an estimation of the trans-tricuspid valve gradient (TTVG) and to investigate the correlation between estimated and invasive pulmonary vascular resistance (PVR).The AT was correlated to the TTVG measured with routine standard echocardiography in 121 patients. In a subgroup of 29 patients, systolic pulmonary pressure (SPAP) and mean pulmonary arterial pressure (MPAP) were obtained from recent right heart catheterization (RHC).RVOT ) had a strong linear relation.We found no significant correlation between the estimation of right atrial pressure (RAP) by echocardiography and the RAP obtained by RHC. Estimated SPAP (TTGV + RAP mean from RHC) showed a good linear relation to invasively measured SPAP. TTVG and AT showed a non-linear relation, similar to SPAP and MPAP measured by catheterization and AT. For detection of SPAP above 38 mmHg a cut-off for AT of 100 ms resulted in a sensitivity of 89% and a specificity of 84%. For detection of MPAP above 25 mmHg a cut-off for AT of 100 ms resulted in similar sensitivity and specificity. Invasive PVR and the ratio of TTVG and the time velocity integral of the RVOT (TVI RVOT.Our study confirms that AT appears to be useful for the evaluation of pulmonary hypertension. In high risk patients, an AT of less than 100 ms indicates a high probability of pulmonary hypertension. Furthermore, PVR estimation by ultrasound seems preferably be done by using the ratio of TTVG and TVI  Furthermore, alternative ways of estimating echocardiographic PVR either with heart rate in the formula as suggested by Haddad et al.[Right ventricular (RV) pressure is routinely estimated by analysing the tricuspid regurgitation (TR) Doppler signal. This is especially important when screening for pulmonary hypertension (PH) in high risk patients for example with systemic sclerosis (SSc)  or HIV . Often tn of PVR  was usedn of PVR . In the ad et al., or withBetween June 2010 and December 2011, echocardiographic data that could be further analysed for both AT and TTVG was obtained from 121 patients at Uppsala University Hospital and retrospectively analysed. To be included in the study the Doppler signals had to be of adequate quality for measurements. RHC was performed in 29 of these patients within two days from echocardiography and data from the two methods were compared in this subgroup. In Uppsala University Hospital the Department of Cardiology is a referral centre for pulmonary arterial hypertension (PAH) which provides the echocardiographic laboratory with a large group of patients with suspected pulmonary hypertension (PH) defined as SPAP above 38 mmHg. This level of SPAP corresponds to mean pulmonary arterial pressure (MPAP) of above 25 mmHg. This level of estimated SPAP has been suggested for further investigation for PH [,s IE 33 , and in a minority General Electric,s Vivid e9 . Patients were retrospectively included when the quality of both TTVG and AT was satisfactory for evaluation. Systolic right ventricular (RV) pressure was estimated from the velocity of the TR. The forward velocity profile, obtained by pulsed Doppler in the RVOT close to the pulmonary valve, was used to obtain AT and TVI RVOT. The AT was measured in accordance with previous studies [RVOT · 10 + 0.16. Alternative ways of estimating PVR from TTVG and TVI RVOT were evaluated, either with heart rate taken into account (TTVG/ (TVI RVOT · heart rate)) or not (TTVG/ TVI RVOT) [Ultrasound examination was performed mainly using Philip studies ,9,11, de studies , PVR = TVI RVOT) ,9. NoninIn a subgroup of 29 patients, both RHC data and echocardiographic data were available.,s method in which oxygen consumption was calculated. PVR is presented in Wood units (WU) from the following equation: (MPAP-PCW)/ CO. Pressures were registered with a Cathcor system 3.3 .All catheterizations were clinical routine examinations that involved an echocardiography within two days and the study included all patients referred to catheterization laboratory without atrial fibrillation and congenital heart disease with echocardiographic data including AT and TR available within the study period. Catheterization was performed by an experienced invasive cardiologist using conventional catheterization technique. A balloon catheter  was inserted through the right internal jugular vein or right brachial vein. RAP, SPAP, mean pulmonary arterial pressure (MPAP) and the pulmonary capillary wedge pressure (PCW) were measured as well as saturations. Cardiac output (CO) was calculated using thermodilution or FickThe study was performed with permission from the ethical committee for clinical studies at Uppsala University.Linear and non-linear regression analyses were performed. Both the 95% confidential intervals for the line and for the population are shown in the figures which also include the r-values. Linear relations with a p-value of < 0.05 were considered significant. Specificity and sensitivity are presented where appropriate. All statistical analyses were performed using Graph Pad Prism software . Absolute values are presented as means ± SD.In the total group 56% (68 patients) had SPAP above 38 mmHg estimated from echocardiography and the average SPAP was 46 ± 23 mmHg. All patients had a sinus rhythm between 50 and 100 beats/min. None of the included patients had atrial fibrillation, pulmonary stenosis or any other congenital heart disease. In the whole population the average age was 61 years (range 16–89 years) with 67 males and 54 females. For the subgroup of 29 patients with RHC data a more detailed characterization is presented in Table -0.0313·AT + 16.5 (with AT in ms and TTVG in mmHg). In the subgroup of patients (n = 29) with data from RHC, a similar nonlinear relationship between SPAP and AT was found . Therefore trans-tricuspid valve gradient (TTVG) alone or an estimation of systolic pulmonary pressure (SPAP) by adding 8 mmHg to the TTVG in the RHC-subgroup was used (8 mmHg was the mean RA pressure measured by RHC in the subgroup). In the whole group  was also significant  but weaker between PVRRHC and the estimated PVR when adding heart rate to the equation (TTVG/TVI RVOT · heart rate) as suggested by Haddad et al.[In the PVR analysis, four patients were excluded due to a very high PVR (>10 WU) found at RHC representing outliers with low cardiac output regarded as end-stage disease and clearly outside the linear relation between the methods  in both the whole population and the RHC subgroup in the present study has important implications for patients without a measurable TR. An AT of less than 100 ms would detect most patients with PH  with an acceptable specificity as well. Furthermore, almost all patients with severe PH (SPAP >58 mmHg) could be identified using this cut-off for AT but at the price of lower specificity. However, when screening a high-risk population for PAH, the most important quality would be to have a high sensitivity for selecting patients for further evaluation with RHC. In other clinical scenarios, another cut-off level might be more appropriate. Although some early reports suggested that AT would have a good correlation to MPAP ,12, the et al. emphasizEchocardiographic estimation of SPAP has shown a good correlation to RHC in previous studies ,17 as weRVOT had a better correlation than PVR estimated by the formula of Abbas. Estimating PVR by echocardiography provides additional noninvasive hemodyanamic information. Invasive measurements are essential for exact values for example pretransplantation. Being able to estimate increased PVR noninvasively could have additional value when following patients and changes of treatments. It could be more accurate to use a pressure estimate rather than velocity estimate as in the formula of Abbas when calculating resistance. Different methods could be applied to make the PVR and in our study design it seems more useful to apply the TTVG and TVI RVOT ratio. Regardless of how the PVR estimation is performed the four patients with PVR > 10 WU in the RHC-population were outliers. One reason for this might be that these four patients had poor CO on RHC (CI < 2.0). To detect this noninvasively, the tracing of the pulmonary flow might not be sensitive enough. This agrees with the findings reported by Rajagopalan [Our estimation of PVR using TTVG and TVI agopalan  who showagopalan  was not Despite the clear and interesting findings the retrospective design introduces some limitations. The accuracy when evaluating AT could likely be improved if it was a standard procedure in clinical practise and performed routinely in most patients. Furthermore, even if there was a short time between RHC and echocardiography, the examinations were not simultaneous which might influence data. The number of patients without measurable AT is not available and could reflect some bias. However, it has been shown that the AT measurement is possible to measure in 99% of patients  when decRVOT .We suggest that an increased use in clinical practise of AT is justified by its acceptable discriminatory capacity between healthy subjects and patients with pulmonary hypertension. Furthermore, our findings confirm that estimation of SPAP by echocardiography correspond well to the SPAP measured by RHC. Moreover, we found that the PVR from RHC could be estimated by the ratio TTVG/ TVI AT: Acceleration time; CO: Cardiac output; CI: Cardiac index; ICV: Inferior vena cava; MPAP: Mean pulmonary arterial pressure; PAH: Pulmonary arterial hypertension; PCW: Pulmonary capillary wedge pressure; PH: Pulmonary hypertension; PR: Pulmonary regurgitation; PVR: Pulmonary vascular resistance; RAP: Right atrial pressure; RHC: Right heart catheterization;RVOT: Right ventricular outflow tract; SPAP: Systolic pulmonary pressure; SSc: Systemic sclerosis; TR: Tricuspid regurgitation; TTVG: Trans-tricuspid valve gradient; TVIRVOT: Time velocity integral of the RVOT; WHO: World Health Organization; WU: Wood unitsWe declare that we have no competing interest. GV has received lecture fees from Actelion Pharmaceuticals and Pfizer. SOG has received a consultant fee 2010 from Actelion Pharmaceuticals, however not associated with findings in this study. No support has influenced this study or has had any influence on the study design.SOG, MWR and EB planned the study. SOG and MWR made the echocardiographic evaluation and EB and GV the RHC evaluation. MWR and SOG evaluated the statistical analyses and Figure presentations. All took major part in the writing of the article and have read and approved the final form.