Several studies have shown that blood pressure can be lowered by the use of drugs that are not traditional antihypertensive drugs. This might be of clinical importance when many risk patients are treated by combination drug therapy in order to prevent cardiovascular disease by way of improving the cardiovascular risk factor profile. Examples of such drugs include not only lipid-lowering drugs (statins), anti-diabetic drugs , and weight-reducing drugs (orlistat), but also drugs with temporary effects such as nitrates used as anti-anginal drugs in coronary heart disease. It is useful to know about these effects even if they often seem to be much less pronounced as compared to the effect of the registered and recognised antihypertensive drugs that are discussed in current guidelines for evaluation and treatment of the hypertensive patient ,5. Even 2.2.1.in vitro model [It has been documented that statin therapy is associated with a few mmHg blood pressure reduction, based on systematic reviews of several intervention trials ,7. This ro model . If thisro model . Further2.2.The aim of using anti-diabetic drugs is foremost to normalize glucose metabolism and to decrease the risk of micro- as well as macrovascular events in patients with either type 1 or type 2 diabetes. Based on intervention studies, this approach has been documented to be successful in both forms of diabetes, even if the therapeutic goal for glycaemic control is still debated. Systematic reviews have recently shown that coronary events, but not stroke events, can be reduced by intensive glycaemic control in patients with type 2 diabetes without a concomitant risk of increasing total mortality rates . One parOn the contrary, it has also been shown that an older type of sulphonylurea drug, chlorpropamide, as used in the UKPDS trial , could e2.3.As there exists a linear relationship between increase in body weight and increase of mean blood pressure levels in most subjects , as a reFinally, it should be mentioned that bariatric surgery has been documented to lower blood pressure in the short run (2 years), secondary to weight loss, but with no difference compared to a control group after longer time (8 years) of follow-up, as shown in the Swedish Obese Subject trial . The exp3.It has been repeatedly shown that some drugs used for indications other than hypertension are able to affect blood pressure levels, sometimes to a marked degree, but most often just marginally. As cardiovascular risk patients of today are treated more vigorously than previously, the effect of drugs other than conventional antihypertensives on reduction of blood pressure levels could improve blood pressure control. Besides this, the haemodynamic effects shown by some classes of drugs should be further explored in experimental studies to learn more about the potential mechanisms involved. This will benefit the overall understanding of the complexities of blood pressure regulation.


Critically ill patients and patients undergoing high-risk and major surgery, are instrumented with intra-arterial catheters and invasive blood pressure is considered the “gold standard” for arterial pressure monitoring. Nonetheless, artifacts due to inappropriate dynamic response of the fluid-filled monitoring systems may lead to clinically relevant differences between actual and displayed pressure values. We sought to analyze the incidence and causes of resonance/underdamping phenomena in patients undergoing major vascular and cardiac surgery.Arterial pressures were measured invasively and, according to the fast-flush Gardner’s test, each patient was attributed to one of two groups depending on the presence (R-group) or absence (NR-group) of resonance/underdamping. Invasive pressure values were then compared with the non-invasive ones.P <0.0001) while in the NR-group the overestimation was 4.1(5.3) mmHg (P <0.0001). The mean IBP-NIBP difference in diastolic pressure in the R-group was −2.2 (10.6) mmHg and, in the NR-group −1.1 (5.8) mmHg. The mean arterial pressure difference was 7.4 (11.2) mmHg in the R-group and 2.3 (6.4) mmHg in the NR-group. A multivariate logistic regression identified five parameters independently associated with underdamping/resonance: polydistrectual arteriopathy , history of arterial hypertension , chronic obstructive pulmonary disease , arterial catheter diameter (20 vs. 18 gauge)  and sedation . The ROC curve for the maximal pressure–time ratio, showed an optimum selected cut-off point of 1.67 mmHg/msec with a specificity of 97% (95% CI: 95.13 to 99.47%) and a sensitivity of 77% (95% CI: 67.25 to 85.28%) and an area under the ROC curve by extended trapezoidal rule of 0.88.A total of 11,610 pulses and 1,200 non-invasive blood pressure measurements were analyzed in 300 patients. Ninety-two out of 300 (30.7%) underdamping/resonance arterial signals were found. In these cases (R-group) systolic invasive blood pressure (IBP) average overestimation of non-invasive blood pressure (NIBP) was 28.5 (15.9) mmHg (Physicians should be aware of the possibility that IBP can be inaccurate in a consistent number of patients due to underdamping/resonance phenomena. NIBP measurement may help to confirm/exclude the presence of this artifact avoiding inappropriate treatments. MAX) possibly suggesting underdamping/resonance of the arterial pressure signal.Arterial pressure measurement represents a mandatory step in the evaluation of patients’ hemodynamics because it gives primary information about the performance of the cardiovascular system and tissue perfusion . In ever2, any type of arrhythmia or hemodynamic instability (>5 mmHg variation in mean blood pressure) during the period of data collection, presence of tissue edema, an artery line different to the left or right radial artery, overdamped arterial signals (according to a fast-flush test), and the inability to measure NIBP in the same arm as that in which the arterial line was placed. Data acquisition has been performed by the investigators prior to anesthesia induction, during surgery, in the ICU, with or without sedation. None of the investigators was involved in the clinical management of the patients.A prospective observational cohort study was conducted. The study was approved by the hospital ethics committee of the Azienda Ospedaliero-Universitaria Careggi - University of Florence, and informed consent was obtained by all participants. All consecutive patients with indwelling radial arterial catheter as standard practice in vascular surgery and cardiac surgery operating theatres and cardiac surgery ICU were enrolled in the study. The exclusion criteria were: age <18 years, body mass index ≥30 Kg/mMAX. This ratio represents the maximal rate of pressure change over time between two consecutive points during the systolic upstroke recorded at 1000 Hz: in a previous study [A standard procedure was used for all measurement collection. First, the arterial pressure transducer was leveled and zeroed to the intersection of the anterior axillary line and the fifth intercostal space. The investigators then purged the system of any air bubble with a dedicated inflated flush system set at 300 mmHg. Second, invasive systolic blood pressure (Sys-IBP), diastolic blood pressure (Dia-IBP), and mean blood pressure (Mean-IBP) were measured by means of a radial artery catheter , connected to a disposable pressure transducer  and measured with a Philips MP60 IntelliVue monitor . The signal was then directed via the analogic output to a MostCare® pulse contour hemodynamic monitoring system  in order to measure the dP/dtus study  -NIBP, diastolic (Dia)-NIBP, Mean-NIBP values were measured and recorded (an average of four)  immediatEach patient was then assigned to one of two groups depending on the presence (R-group) or absence (NR-group) of resonance/underdamping identified by the fast-flush test . In addit-test in both the R-group and NR-group. Pairwise comparison was performed using the regression-based Bland-Altman technique, which models the mean and SD of the blood pressure differences as a function of the averaged measurements obtaining the bias (mean difference between methods) and limits of agreement (LoA)  [t-test was used for the identification of differences in norepinephrine infusion between the R- and NR-groups. A two-sided P-value <0.05 was considered to be statistically significant.All data were analyzed using Stats Direct  and GraphPad . The single-sample Kolmogorov-Smirnov test was used to test all data for normality. Continuous variables were expressed as mean (SD) or median with interquartile range where applicable. For dichotomous data, percentages were calculated. IBP and NIBP values were compared using the two-sided paired erences) . The unpP-value was <0.1) with underdamping/resonance as the dependent variable. Co-linearity between variables was excluded before modeling and none of the covariates was co-linear. The Hosmer and Lemeshow goodness-of-fit test was performed and the odds ratio (OR) and 95% CI was computed.In order to define the possible clinical/pharmacological or technical factors associated with the resonance phenomenon, we performed multivariable logistic regression analysis (backward selection) , body mass index ≥30 Kg/m2 (10 patients), any type of arrhythmia or hemodynamic instability , or artery line other than left or right radial (4 patients). No patient was excluded for overdamping. Three hundred patients were definitively enrolled in the study. They were divided as follows: 1) patients undergoing vascular surgery for arterial disease  ; 2) patients undergoing cardiac surgery  ; 3) patients admitted to cardiac surgery ICU (different from the previous group of patients)  (Table  patientsP <0.05)  with a rather homogeneous distribution among the different settings . Fast-flush test for these patients resulted in an Fn of 15.9 (6.12) Hz with an AR of 0.39 (0.07) and β of 0.29 (0.05). In both the R-group and the NR-group, Sys-, Dia-, and Mean-BP measured by IBP were significantly different from NIBP values (5) Table  showed aP = 0.066). No statistically significant differences were found in epinephrine dose (P = 0.15), arginine-vasopressin dose (P = 0.56), heart rate (P = 0.62) or ejection fraction of the left ventricle (preoperative measurement during routine risk stratification) (P = 0.19) when comparing the two groups. The multivariate logistic regression included a total of 18 parameters  (Table P = 0.0023), history of arterial hypertension (P = 0.0214), chronic obstructive pulmonary disease (P = 0.0198), arterial catheter diameter (20- versus 18-gauge) (P <0.0001), and sedation (P = 0.0131). Heart rate (HR) was not correlated with underdamping/resonance even after division into three terciles . According to the OR, three of these parameters resulted from a predisposition to underdamping/resonance: polydistrectual arteriopathy (OR = 2.82), chronic obstructive pulmonary disease (OR = 2.61), and arterial hypertension (under drug therapy) (OR = 2.09). Two of them were protective: arterial catheter diameter (20- versus 18-gauge) (OR = 0.35) and sedation (OR = 0.5). Finally, the receiver operating characteristic (ROC) curve for the maximal pressure-time ratio (dP/dtMAX), showed an optimum selected cutoff point of 1.67 mmHg/msec with a specificity of 97% (95% CI: 95.13 to 99.47%), a sensitivity of 77% (95% CI: 67.25 to 85.28%), and an area under the ROC curve by extended trapezoidal rule of 0.88  received a continuous infusion of norepinephrine at a dose of 0.019 (0.043) μg/Kg/minute. The R-group received a lower norepinephrine dosage (0.01 (0.03) μg/Kg/minute;) than the NR-group (0.02 (0.04) μg/Kg/minute)  ,16. As fP = 0.0023) and 2.09 (P = 0.021) respectively. COPD has been found to be correlated with underdamping/resonance . This association may be explained with the hypothesis that arterial hypertension and atherosclerosis, both associated with underdamping/resonance and frequently affecting COPD patients [P = 0.013), as the reduction in vascular tone caused by a direct effect on the vessels’ smooth muscles and attenuation of the sympathetic nervous system limits the development of high frequency harmonics [In our cohort of patients, the multivariate analysis identified five conditions independently correlated with underdamping/resonance: three clinical conditions ), one pharmacological state (sedation), and a technical parameter . We found that hypertensive arteriopathy is a predisposing factor for underdamping/resonance: this result confirms the findings of our previous work in vascular surgery patients . It is carmonics ,20. Fina9 P = 0.0 respectiHere, β is the damping coefficient (entity of friction forces), μ is the viscosity of the fluid, r is the internal radius of the catheter, ρ is the density of the fluid, L is the length of the catheter, and E is the elasticity of the system. By increasing the internal radius (r) of the catheter , the damping coefficient (β) decreases significantly as it varies inversely to the cube of the radius. Similarly, by increasing the length of the catheter (L), β also increases. Moreover, as the physical properties of the catheter-tubing-manometer system determine the Fn according to the following formula :\documenk is the elasticity and m is the mass), by changing the length and the diameter of the arterial cannula, the Fn changes as well.(where P <0.0001). When an arterial line is put in place, this fact should certainly be taken into consideration. Equally, eventual fibrin deposition may, with time, increase β. Lambermont et al. developed, in an experimental setting, a mathematical transfer function that, by adjusting the natural frequency and the damping coefficient of the fluid-filled catheter system, may reconstruct the pressure waveform free of artifacts [MAX as an indicator of myocardial contractility [MAX in arterial signal affected by underdamping/resonance was significantly higher than in artifact-free waveforms [MAX greater than 1.67 may be helpful in identifying suspected underdamped/resonant signals prior to the performance of a fast-flush test. Moreover, in light of our results, the comparison of Sys-IBP and Sys-NIBP may have a strong predictive value for the identification of resonance-affected waveforms.Our data show a strong relationship between catheter diameter and length and underdamping/resonance, with smaller catheters demonstrating a highly protective effect . Finally, it is likely that low-dose norepinephrine may have played a minor role in the development of underdamping/resonance. It is reasonable to speculate that higher doses , may lead to different effects.Finally, we acknowledge several weaknesses. First, the oscillometric method for NIBP measurement is not standardized. Algorithms for systolic and diastolic pressure estimation may differ from manufacturer to manufacturer, and even from device to device . We usedIn conclusion, IBP remains the gold standard for arterial pressure monitoring in critically ill patients. However, as faithful representation of arterial waveform and blood pressure values are the foremost prerequisites in intensive care, anesthesia, and modern medicine, the physician should be aware of the possibility that IBP can be overestimated in a consistent number of patients. NIBP may help to confirm/exclude the presence of underdamping phenomena and avoid inopportune treatments.Invasive blood pressure monitoring, free of artifacts, is the gold standard for arterial pressure measurement in critically ill patientsUnderdamping/resonance artifacts may alter blood pressure values in about one third of critically ill patientsPhysicians should always test arterial pressure waveform for underdamping/resonance artifactsMAX greater than 1.67 mmHg/msec) may help to identify the presence of underdamping phenomenaThe presence of a systolic invasive arterial pressure greater than 15 to 20 mmHg in respect of the non-invasive technique (or a dP/dt


We evaluated whether Gly16Arg beta2-receptor genotype relates to impulse oscillometry (IOS) in a real-life clinic setting.Patients with persistent asthma taking inhaled corticosteroid ± long-acting beta-agonist (ICS ± LABA) were evaluated. We compared genotype groups comprising either no Arg copies (i.e. GlyGly) versus one or two Arg copies (i.e. ArgArg or ArgGly). IOS outcomes included total airway resistance at 5 Hz (R5), central airway resistance at 20 Hz (R20), peripheral airway resistance (R5–R20), reactance at 5 Hz, area under reactance curve (AX) and resonant frequency (RF). In addition, we recorded ACQ-5 and salbutamol use.One hundred and twelve ICS-treated asthmatic patients (mean ICS dose 1238 µg/day), mean age 43 years, ACQ 2.34, FEV1 82 %, R5 177 % were identified—89 were also taking LABA. 61 patients were GlyGly, while 14 were ArgArg and 37 were ArgGly. There were no significant differences in IOS outcomes, ACQ or salbutamol use between the genotypes. The allelic risk (as odds ratio) for less well-controlled asthma (as ACQ > 1.5) was 1.1 (95 % CI 0.72–1.68) in relation to each Arg copy with a corresponding odds ratio for abnormal R5–R20 > 0.07kPA/l.s being 0.91 (95 % CI 0.57–1.44). 71 % of patients had an ACQ > 1.5 in the GlyGly group, versus 67 % in GlyArg/ArgArg group, with corresponding figures for abnormal R5–R20 > 0.07 kPa/l.s being 69 versus 73 %.In a real-life clinic setting for patients with poorly controlled persistent asthma taking ICS ± LABA, we found no evidence of any relationship of Gly16Arg to IOS, ACQ or salbutamol use. Beta-2 adrenoceptor (β2ADR) allelic polymorphisms at position 16 (Gly16Arg) may have a clinically important effect on individual asthmatic patient’s response to beta-agonist therapy –5. For eOther studies have reported no link between Gly16Arg and pulmonary function outcomes using spirometry or airway hyper-responsiveness in adult asthmatic patients taking ICS/LABA –10. HoweTo the best of our knowledge, no study has yet looked at the putative effect of Gly16Arg on IOS in asthmatic patients taking ICS/LABA. As a pilot study, we have therefore performed a retrospective analysis in a real-life asthma clinic setting where we performed both IOS measurements and Gly16Arg genotyping as part of routine care. In addition, we also assessed the potential impact of Gly16Arg upon asthma control using the Juniper asthma control questionnaire (ACQ) .n = 112 consecutive ICS-treated non-smoking asthma patients attending our hospital clinic in order to analyse their IOS and ACQ score. Patients were divided into two genotype groups, namely those that do not possess the Arg polymorphism (n = 61:GlyGly) and those that possess either one or two Arg copies (n = 14: ArgArg or n = 37 ArgGly). As part of their routine workup, all patients had IOS and spirometry performed. Patient demographics and medications were recorded, as was asthma control, based on the ACQ questionnaire. Salbutamol use was recorded over the previous week. We routinely perform Gly16Arg genotyping in our clinic to help guide asthma management; hence, this audit of routine clinical care did not require internal review board ethical approval, although Caldicott guardian approval was obtained for access to the data. Lung function was measured on the morning of clinic between 9am and 11am. The patients had already taken their morning asthma medications in the usual fashion. The patients all had IOS first, followed by spirometry.We evaluated IOS  was performed as previously described  in triplt test or analysis of variance was used to compare normally distributed continuous variables, whereas the Mann–Whitney or Kruskal–Wallis test was used for non-normally distributed continuous variables. We compared two genotype groups comprising either no Arg copies (GlyGly) versus one or two copies (GlyArg or ArgArg). Binary logistic regression was used to calculate odds ratios for asthma that was not well controlled (i.e. ACQ > 1.5) as well as abnormal peripheral airway resistance as R5–R20 > 0.07 kPa/l.s [P < 0.05 (2-tailed). SPSS statistical software, version 21  was used for all analyses.Unpaired students  kPa/l.s , in relaP < 0.0001). Genotype frequencies were as follows: GlyGly 54.5 %, ArgGly 33 %, ArgArg 12.5 %.A total of 112 ICS-treated persistent asthmatic patients were analysed. The mean age of patients was 43 years and most of our patients (99 %) were Caucasian. Mean FEV1 was 82 % predicted, mean R5 177 % predicted, mean ACQ was 2.34, mean ICS dose was 1238 µg , 80 % of patients were on a LABA and 36 % were on LTRA. The mean ICS dose was 1353 and 786 ug, respectively, for patients taking ICS/LABA and ICS alone (P = 0.04). Despite the lower ICS dose in the GlyGly patients, there were no significant differences in any IOS outcomes, ACQ or salbutamol use between the two groups  was 1.1 (95 % CI 0.72–1.68) and for abnormal R5–R20 > 0.07 kPa/l.s was 0.91 (95 % CI 0.57–1.44). 71 % of patients had an ACQ > 1.5 in the GlyGly group, versus 67 % in GlyArg/ArgArg group, with corresponding figures for abnormal R5–R20 > 0.07 kPa/l.s being 69 versus 73 %  were 1136 and 1358 µg for GlyGly and ArgArg/ArgGly respectively (n = 89/112), there were also no significant differences in any outcomes when comparing ArgArg/ArgGly (n = 42) versus GlyGly (n = 47) groups: R5 0.56 versus 0.57 kPa/l.s P = 0.91, R20 0.42 versus 0.43 kPa/l.s P = 0.87, R5–R20 0.14 versus 0.15 kPa/l.s P = 0.16, AX 1.35 versus 1.50 kPa/l P = 0.45, ACQ 2.25 versus 2.37 P = 0.67 and salbutamol use 6.1 versus 6.5 puffs/day P = 0.73. However, for the R5–R20 those taking ICS/LABA had lower value compared to ICS alone: 0.15 versus 0.23 kPa/l.s P = 0.03. Spirometry variables were non-significant comparing ICS/LABA versus ICS alone; FEV1 % predicted 82 versus 80 % P = 0.65, FEF25-75 % predicted 51.6 versus 47.9 % P = 0.6. For homozygous genotypes in ICS/LABA users (ArgArg n = 11 vs. GlyGly n = 47), there were also no significant differences: R5 0.57 versus 0.60 kPa/l.s P = 0.70, R20 0.41 versus 0.43 kPa/l.s P = 0.73, AX 1.39 versus 1.56 kPa/l P = 0.75, ACQ 2.87 versus 2.34 P = 0.16 and salbutamol use 8.54 versus 6.52 puffs/day P = 0.16. The odds ratio per Arg copy for ACQ > 1.5 among ICS/LABA users was 1.34 (95 % CI 0.87–2.06) and for abnormal R5–20 > 0.07 kPa/l.s was 1.1 (0.70–1.75 95 % CI).When the data were filtered for LABA users  of 177 % as well as a high peripheral airway resistance (R5–R20) of 0.16 kPa/l.s. This along with a mean ICS dose of 1238 µg/day with most patients taking ICS/LABA and at least 6 puffs/day of reliever use would indicate that our cohort had moderate to severe persistent asthma in keeping with a secondary care setting.The ACQ7 score includes input for both reliever use as well as FEV to ACQ7 . The min to ACQ7 . The mea to ACQ7  with 69 n = 14 vs. n = 61). Nonetheless, when we analysed the data among all patients looking at the attributable risk of each Arg copy according to poor asthma control (ACQ > 1.5), we found an odds ratio of 1.1 (95 % CI 0.72–1.68) and for abnormal R5–R20 > 0.07kPA/l.s an odds ratio 0.91 (0.57–1.44).As this was a pilot study, we only captured cross-sectional data from one clinic visit, and did not assess variability over time, which is the hallmark of patients with persistent asthma. Moreover, we did not evaluate treatment compliance and so we can only assume that patients were taking what was recorded in the notes at the time of the clinic visit. We appreciate the small number of individuals possessing the homozygote Arg genotype which limited our analysis when comparing homozygous genotypes (Studies have shown corticosteroids may reverse β2ADR down-regulation and associated subsensitivity of response in asthmatics taking regular LABA , 20. ConIn conclusion, our real-world pilot study demonstrated no significant impact of Gly16Arg upon IOS outcomes, salbutamol use or asthma control, in adults with persistent asthma. Further large-scale studies are required to evaluate the impact of Gly16Arg genotype on serial IOS measurements over time, perhaps comparing cohorts with and without LABA therapy.


Objective: This study aims to observe the risk factors of cardiovascular disease in patients after kidney transplantation.Methods: Total 102 patients after renal transplantation (group A) and 96 clinic examination cases (group B) were recruited. Blood pressure, blood urea nitrogen (BUN) and creatinine (Cr), blood glucose (GLU), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and apolipoprotein A-I ( apoA-I ) of the subjects were tested. These indexes were tested 3 times in group A in the 1, 2, and 3 month after kidney transplantation surgery. Electrocardiogram examination was done in the third month after kidney transplantation surgery.Results: There were significant differences in the incidence of hypertension, hyperglycemia and dyslipidemia between the two groups. After operation, the levels of BUN and Cr decreased significantly in 57 cases of group A without taking antihypertensive drugs (P<0.01). However, there was no significant difference in the blood pressure regardless of the systolic blood pressure (SBP) and diastolic blood pressure (DBP) before and after operation. In group A, the abnormal rate of ECG was 65%, the incidence of ST-T changes, prolongation of QT interval, left ventricular hypertrophy and left ventricular high voltage increased significantly (P<0.01).Conclusion: The incidence of coronary heart disease risk factors such as hypertension and hyperglycemia are high in patients after renal transplantation. These risk factors accumulated in patients after renal transplantation. This study aims to observe the traditional cardiovascular risk factors among renal transplant recipients, which can provide clues for treatments of patients with end stage renal disease to increase their survival rate.The morbidity of cardiovascular complications is very high in patients with chronic renal failure and uremia. The 5 years survival rate of uremia patients has increased in recent years along with the improving dialysis technology, but it does not reduce the cardiovascular complications. Cardiovascular disease is still a major cause of morbidity and mortality in patients with end stage renal diseaseData for this study was obtained from the general hospital of Jinan military region. The ethics committee of the General Hospital of Jinan Military Command approved the study protocols and all patients gave informed consent. A total of 102 patients  diagnosed with chronic glomerular nephritis uremia who underwent renal transplantation, as well as 96 healthy controls  were recruited from July 2010 to September 2012. The patients were on regular dialysis before renal transplantation with 2 ~ 3 times a week. Their durations of illness were 38 months. There was no significant difference between two groups in gender, age and body weight. st 2nd and 3rd month after transplantation, BUN and Cr of all patients were measured two times and their average values were the BUN and Cr values of that month, blood pressure were measured at least 3 times daily and their average values were the blood pressure values of that month. 12 lead ECG was done for all the patients and three 3 months. Glucose (GLU), total cholesterol (TC), three triacylglycerol (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and apolipoprotein A - I (apoA- I) were collected.The daily morning resting blood pressure, blood urea nitrogen (BUN) and creatinine (Cr) of all patients were measured one week before the operation and for 3 consecutive times. Their average values were the preoperative mean preoperative blood pressure, BUN and Cr respectively. At the last week of 1Transplant operation mode was conventional right abdominal incision, cadaveric kidney were used, donor renal vein and external iliac vein were end-to-side anastomosis, donor renal artery and internal iliac artery were also end to side anastomosis. Pathogenic kidney was not resected.In 102 cases of renal transplantation, 57 patients had no antihypertensive therapy in 10 days before operation and the observation period of after operation. Diagnostic criteria of hypertension used was the new diagnostic criteria of WHO and the international society of hypertension. Glucose was determined with venous plasma. It was thought to be high when it was greater than 5.6 mmol / L.Statistical Analysis: Differences in patient characteristics and clinical variables were analysed using the 2 test and ANOVA. Data analyses were performed with commercially available statistical software .The morbidity of high blood glucose and blood lipid abnormality in patients after renal transplantation was significantly higher than that of the control group . A totalP<0.01).The abnormal rate of electrocardiogram (ECG) in group A was 65%. The incidence of ST-T changes, prolongation of the QT interval, left ventricular hypertrophy and with high voltage was higher in group A than that in control group significantly (5,6 Our investigation found that the morbidity of hypertension, hyperglycemia and dyslipidemia among renal transplant recipients was very high, which confirmed that the risk factors of cardiovascular disease still exist in transplant patients.Renal transplantation is one of the most effective treatments for most patients with end-stage renal disease. The survival rate of patients undergoing renal transplantation has improved considerably over the past decades. Patients with end-stage renal disease often suffer from complications with cardiovascular disease, which is much more common in transplant patients. Its contribution to post-transplant mortality to some extent reflects the incidence of cardiac disease in the general population.7,8 We observed that the incidence of hypertension was as high as 93% after renal transplantation for 3 months. There was no reduction in blood pressure although their BUN and Cr decreased and urine volume increased significantly. Hypertension in the renal transplant patients represents a greater risk for cardiovascular outcome and renal survival than it does in the common population and it plays a major role in the causation of chronic graft dysfunction, morbidity and deaths from cardiovascular disease.9 Many causes for post transplant hypertension such as the interaction between recipient and donor, hypercalcemia and recurrence of glomerular nephritis are well-documented in the literature.8-11 Persistent hypertension after renal transplantation has serious harm to the function of heart, brain and kidney function of transplant patient. We found that the abnormal ECG rate was as high as 65% in transplant patients, which was related with persistent hypertension undoubtedly. The incidence of hypertension in patients after renal transplantation was more than 40%.12 had a high prevalence of glucose metabolism disorders13 and had atherosclerosis.14 We found that the incidence of hyperlipidemia especially high cholesterol and high triglycerides was significantly higher in patients after renal transplantation than that in the general population. Our data also showed that the morbidity of hyperglycemia in the renal transplantation patients was higher than that of control group. These may promote the occurrence and development of coronary heart disease. Previous studies have found that renal transplantation patients had complications of hyperlipidemia,In summary, we observed the traditional cardiovascular risk factors among renal transplant recipients in this study. We found that the incidence of cardiovascular disease continues to be high after renal transplantation. Therefore, treatment of risk factors must be effective and introduced early in the course of renal failure and continued following transplant to increase their survival rate.


Kidney diseases are a growing worldwide problem and one of the major public health threats. We analyzed the spectrum of kidney diseases seen over a five-year period in the nephrology in-patient unit of the Yaounde general hospital.This was a retrospective analysis of 225 medical records of patients admitted from January 2005 to December 2009 in the unit with a discharge diagnosis of kidney and urinary tract diseases. The first hospitalization was considered for patients admitted several times for the same disease. Socio-demographic and clinical patient data were recorded.The patients mean age was 44.8±16 years with 135 (60%) males and 211 (93.8%) emergency admissions. All 139 (61.8%) patients with chronic kidney disease (CKD) had chronic renal failure. Acute kidney injury (AKI) (28%), nephrotic syndrome (7.6%), renal colic (1.3%) and acute pyelonephritis (1.3%) were other patterns observed. Chronic glomerulonephritis (25.9%), hypertension (22.3%) and diabetes (20.1%) were the main etiological factors of CKD. All AKI patients were in stage RIFLE-F. AKI was secondary to parenchymal (58.7%), functional (25.4%) and obstructive (15.9%) etiologies. Black water fever (36.4%), sepsis (22.7%), drugs (18.2%), eclampsia (13.6%) and herbal concoctions (9.1%) were the etiologies of acute tubular necrosis while enterocolitis (56.2%), heart failure (31.3%) and digestive hemorrhage (12.5%) were the etiologies of functional AKI.The clinical pattern of renal diseases is dominated by advanced CKD and AKI secondary to preventable causes. This study suggests a need for an array of actions including sensitization, continuous medical education and strengthening of the health system. Kidney diseases are a growing worldwide problem and constitute one of the major public health threats . WhetherThis was a retrospective analysis of medical records of patients admitted from January 2005 to December 2009 in the nephrology-cardiology-psychiatry unit of the Yaoundé General Hospital (YGH); the main tertiary hospital in the Cameroon capital city. This unit of 25 beds is part of the internal medicine department and constitutes the main national referral nephrology unit. The staff comprised three nephrologists taking care of patients mainly from the center region and neighborhood but also from other parts of the country. This study received administrative authorization from the YGH and was approved by the Ethic Committee of the Faculty of Medicine and Biomedical Sciences (FMSB) of Yaoundé 1 University, Cameroon.During the study period, we used the in-patient register of the unit to identify all patients with a discharge diagnosis of diseases of the kidney and urinary tract. This list was then used to retrieve the individual medical records from the hospital archives department. We considered only the first hospitalization for patients admitted several times for the same disease. For those with several diagnoses, each diagnosis was counted separately. We excluded files with missing data and patients hospitalized for hemodialysis-related complications. Patient information recorded included age, gender, type of admission , kidney and urinary tract disorder, comorbidities, type and etiological factors of AKI, as well as stage and etiological factors of CKD.Acute kidney disease (AKD) referred to any kidney disease of less than three months duration including AKI. AKI was defined as sudden loss of kidney function with recovering within three months. AKI was then classified into functional, parenchymal and obstructive. The RIFLE classification was used to stage AKI severity . CKD ref® 9 software for Windows . We have reported results as mean (standard deviation) and count (percentages).Statistical analysis were performed using the SPSSDuring the study period, 358 patients were hospitalized for kidney and urinary tract disorder among which 256 (71.5%) fulfilled the study criteria. Only 225 (87.9%) files were available for analysis divided into 139 (61.8%) CKD and 86 (38.2%) AKD. As presented in All CKD patients had chronic renal failure. According to KDOQI classification, 4 (2.9%), 19 (13.7%) and 116 (83.4%) patients were respectively classified in stage 3, 4 and 5. Chronic glomerulonephritis (25.9%), hypertension (22.3%) and diabetes (20.1%) were the main etiological factors of CKD as presented in All AKI patients were in RIFLE-F; with the suspected mechanism of injury being parenchymal, functional and obstructive in 37 (58.7%), 16 (25.4%) and 10 (15.9%) patients respectively. As presented in Among 17 patients with kidney biopsy for nephrotic syndrome, 10 (58.8%) cases were identified as primary including focal and segmental glomerulosclerosis  and minimal change disease  lesions on kidney biopsy. The remaining cases were identified secondary to systemic lupus erythematosus , HIV-associated nephropathy , hepatitis B virus , filariasis  and non-steroidal anti-inflammatory drugs .In a context marked by a scarcity of kidney specialists and units dedicated to renal care, we found that the clinical spectrum of diseases of the kidney and urinary tract observed in an in-patient medical ward were diverse and included CKD, AKI, nephrotic syndrome, renal colic and acute pyelonephritis. They affect mostly young males who frequently are admitted as emergency. This study revealed that kidney diseases dominated by CRF affect young individuals in their economically productive years and who are usually diagnosed late already in end stage as previously reported in similar settings; thus contrasting with the advanced age of patients in developed countries , 9–16. TAcute kidney injury was the second most frequent presentation of kidney disease in our setting with unsurprisingly all patients in RIFLE-F. AKI was mainly from renal parenchymal disease dominated by acute tubular necrosis with etiologies similar to previous reports in developing countries , 18. TheThis study revealed that patients admitted in a specialized nephrology unit for kidney and urinary tract diseases in Cameroon are mainly young adults in their economically productive years. The clinical pattern of disease is dominated by advanced CKD and AKI secondary to preventable causes. This study suggests a need for an array of actions including sensitization, continuous medical education and strengthening of the health system to improve the management of patients with kidney disease, and the implementation of a national program to prevent and control risk factors for kidney diseases.


OSA females showed greater differences from males in response magnitude and pattern, relative to healthy counterparts. Cold pressor BOLD signal increases (mean ± adjusted standard error) at the 8 s peak were: OSA 0.14±0.08% vs. Control 0.31±0.06%, and hand grip at 6 s were: OSA 0.08±0.03% vs. Control at 0.30±0.02%. These findings, indicative of reduced cerebral blood flow changes to autonomic challenges in OSA, complement earlier reports of altered resting blood flow and reduced cerebral artery responsiveness. Females are more affected than males, an outcome which may contribute to the sex-specific brain injury in the syndrome.Obstructive sleep apnea (OSA) is accompanied by brain injury, perhaps resulting from apnea-related hypoxia or periods of impaired cerebral perfusion. Perfusion changes can be determined indirectly by evaluation of cerebral blood volume and oxygenation alterations, which can be measured rapidly and non-invasively with the global blood oxygen level dependent (BOLD) signal, a magnetic resonance imaging procedure. We assessed acute BOLD responses in OSA subjects to pressor challenges that elicit cerebral blood flow changes, using a two-group comparative design with healthy subjects as a reference. We separately assessed female and male patterns, since OSA characteristics and brain injury differ between sexes. We studied 94 subjects, 37 with newly-diagnosed, untreated OSA , and 20 female (age 50.5±8.1 yrs) and 37 male (age 45.6±9.2 yrs) healthy control subjects. We measured brain BOLD responses every 2 s while subjects underwent cold pressor, hand grip, and Valsalva maneuver challenges. The global BOLD signal rapidly changed after the first 2 s of each challenge, and differed in magnitude between groups to two challenges , but not to the Valsalva maneuver (repeated measures ANOVA,  Obstructive sleep apnea (OSA) is present in approximately 10% of the adult population, and is accompanied by symptoms related to central nervous system dysfunction, including excessive daytime sleepiness, high levels of depression and anxiety, elevated sympathetic tone, and memory deficits Rapid changes in CBF occur in response to blood pressure alterations. However, in subjects with OSA, the heart rate responses to blood pressure changes are time-lagged and weaker than in their healthy counterparts. In a companion paper, we showed that peripheral vascular responses to typical autonomic challenges  are impaired 2), and cerebral blood volume (CBV) 2, and CBV occur due to metabolic demands of neural activation, and can result in localized BOLD signal changes Rapid and non-invasive measures sensitive to changes in cerebral blood volume and oxygenation are available. Arterial spin labeling is a non-invasive magnetic resonance imaging (MRI) technique that enables absolute blood flow quantification, but at an effective time resolution of a minute or longer To address the question of whether cerebral blood volume and oxygenation responses within brain tissue in OSA were impaired, we described whole-brain changes in global BOLD signal to transient blood pressure increases that normally elicit changes in cerebral blood flow and volume. The intention was not to mimic apneic stimuli, but to identify potential waking state impairments. We selected three autonomic stimuli that mimic daily challenges eliciting pressor responses, the cold pressor (cold temperature and pain or discomfort), the hand grip (muscle contraction), and the Valsalva maneuver, a forced expiratory effort that raises thoracic pressure . These standard challenges elicit cerebral autoregulatory responses in healthy people We recruited OSA patients from the UCLA Sleep Laboratory, and control subjects from the local community. No OSA subjects had started treatment for the sleep disorder, and all were recently-diagnosed. OSA patients were classified as either moderate based on an apnea/hypopnea index (AHI) between 15 and 29 events/hour, or severe based on an AHI>30 events/hour. No subjects were using psychotropic or cardiovascular medications, and none had a history of psychiatric disorders, cardiovascular disease, stroke, or other major illness. In particular, no subjects had a diagnosis of hypertension or atherosclerosis. Diabetes mellitus type 2 was confirmed in four patients and suspected in one. Scanner limitations precluded patients with metallic implants or weight over 125 kg. Subjects were classified as female or male according to their self-identified response on a screening questionnaire. All procedures were in accordance with the Declaration of Helsinki and approved by the UCLA Office of the Human Research Protection Program Medical Institutional Review Board 3, and subjects provided written, informed consent. These subjects overlap samples from other papers Subjects were asked to refrain from coffee and other substances with stimulants for the 24 hours prior to the study. After completion of screening and enrollment, subjects practiced the Valsalva maneuver and the hand grip challenges. The sequence of challenges was hand grip, Valsalva maneuver, and cold pressor. For the hand grip challenge, subjects were instructed to squeeze an inflated bag with the right hand. They were initially directed to briefly squeeze at maximum effort as a reference. The challenge consisted of a 16 s strain period (indicated by a blue light) at a subjective 80% of maximum. Subjects practiced this task outside, then inside the scanner. For the Valsalva maneuver, subjects were instructed to wait for a visual signal (blue light), then take a deep breath and expire from their chest  until they achieved a pressure of 30 mmHg (indicated by a green light). Subjects were to maintain this pressure until the end of the 18 s challenge period (indicated by blue light being turned off), at which point they would breathe normally. Once subjects could perform the task, they were moved into the scanner, where they further practiced the challenge.After practice, subjects were scanned with anatomical protocols, which allowed their physiologic functions to return to a baseline state. Following a minimum of 30 minutes of such scanning, the BOLD protocols were started, consisting of 436 s scans, including a 1 minute baseline, followed by four Valsalva challenges 1 minute apart, and a final 1 minute recovery. A similar pattern was followed for the hand grip challenge. The cold pressor challenge consisted of a 108 s baseline, 60 s foot immersion to approximately ankle height in cold water , and a 60 s recovery. Two investigators held the foot throughout the protocol, and lifted the foot into and out of the water at the appropriate times.We collected BOLD and anatomical scans with a 3.0 Tesla MRI scanner . The BOLD scans were collected with an echo-planar sequence in the axial plane . Two high-resolution, three-dimensional T1-weighted anatomical scans were collected sequentially using a magnetization-prepared-rapid-acquisition-gradient-echo pulse sequence .Physiological signals were recorded on a laptop with an a/d converter synchronized with the scanning signal. The expiratory pressure for the Valsalva maneuver was measured with a pressure sensor outside the scanner room, connected via a low-compliance tube into which a subject created expiratory pressure. Change in hand grip pressure was measured with a pressure sensor connected to a compressible bag which the subjects’ squeezed. This signal was not absolute; thus, only the presence or absence of pressure could be identified.The scans were checked for non-physiologic changes in signal intensity by plotting the global BOLD signal, and excluding series with step changes in intensity of more than 0.5%. Motion between scans of more than 4 mm in any direction, as calculated using the “Realign” procedure in SPM8 Performance of each autonomic task was verified by inspecting the physiologic signals. For the Valsalva maneuver, subjects who did not achieve a sustained 30 mmHg pressure for the duration of each of the four challenges were excluded. The signals were checked to ensure all subjects exerted force during the four hand grip periods. Since the cold pressor was a passive challenge, no series were excluded based on performance.Preprocessing of the MRI images was performed using SPM8 and custom MATLAB software. Each subject’s two T1 anatomical scans were realigned and averaged, resulting in a higher signal-to-noise ratio relative to a single scan. Any series with motion greater than 4 mm in any direction, as identified by the SPM realignment procedure, was excluded. A brain mask was generated based on segmentation of the T1 image using the SPM procedures “unified segmentation” and “DARTEL” normalization We used repeated measures ANOVA to assess global BOLD time trends in a mixed linear model implemented in SAS software (“proc mixed”) 2 nadir was significantly different.Detailed characteristics of the subjects are shown in Time trends and time points of within- and between-group differences are shown for OSA and control groups in Large signal changes, considered artifacts due to foot movement in and out of the cold water, were apparent in all subjects at the onset and termination of the challenge period , 2. The The global BOLD signal showed a rapid increase in both groups to a peak at 8 s , but theThe global BOLD signal showed a slightly earlier and lower peak in female OSA than control subjects , as mimicked by the standard tests used in this study. Presumably, the blood volume and oxygenation impairments would also be present during sleep, especially during obstructive apneas, which are accompanied by large, acute blood pressure changes The lack of a delay in the global BOLD responses in OSA relative to control subjects was surprising, given the timing differences in heart rate changes to the same challenges The brain global BOLD responses were lower to the foot cold pressor and hand grip challenges in OSA, relative to control subjects, but did not differ between groups to the Valsalva maneuver. The signal changes to the challenges principally reflect alterations in the volume of blood in the brain, with only modest influence of changes in blood oxygenation levels If cerebral autoregulation operates similarly in all challenges, and the BOLD signal response is driven by blood pressure changes, the question that arises is whether the pressure changes in OSA were lower to the hand grip and cold pressor, but similar to the Valsalva maneuver, relative to the control group. Given the weaker heart rate changes in OSA to the hand grip and cold pressor, it is possible that blood pressure in the patient group does not increase as much 2 levels typical in the sleep condition would be associated with vasodilation, and hence, larger vessel volume in OSA vs controls, but there is no evidence of such differences. On the other hand, OSA patients show lower resting CBF in several brain regions One possible explanation for the muted responses in OSA is a ceiling effect, whereby a high resting cerebral blood volume in the patient group would limit the capacity for further transient increases. In theory, the higher blood gas COThe most notable difference in the global BOLD signal between sexes appeared in the cold pressor challenge, which was also reflected in very different heart rate responses in female vs. male OSA patients Cerebral blood flow, measured indirectly here with the global BOLD signal, is a function of blood pressure and cerebral vascular resistance, factors regulated by chemical, hormonal, mechanical, and neural factors Whether physiology during these awake challenges parallels the cerebrovascular patterns during obstructive events in sleep is unknown, given the state-dependence of cerebral hemodynamics Impaired perfusion may contribute to the structural brain injury found in OSA, especially during the large blood pressure changes associated with obstructive events. Cerebral blood volume dips after obstructive events The hand grip was a subjective, non-isometric challenge, whereas ideally, the protocol would involve sustaining a grip pressure at a predetermined, quantified percentage of measured, as opposed to perceived, maximum. Thus, unlike the Valsalva and cold pressor challenges, the hand grip effort may not be considered a strictly equivalent challenge across subjects or groups. However, the timing and pattern of physiologic responses were consistent across subjects within groups. The generalizability of the sex-specific findings is limited, since the female OSA group had only six subjects. No delay was found in the BOLD responses in OSA to any challenge, in contrast with the slowed heart rate changes (1–2 s late); however, the time resolution for the BOLD signal was 2 s, whereas the heart rate was 1 s, so it is possible that short delays (<2 s) were also present in the cerebral responses. The BOLD signal is an average of signals over the whole brain, but regional variations may exist. Thus, for example, the absence of differences between OSA and control subjects to the Valsalva maneuver could potentially result from masking by increases in some regions canceling declines in others. The confounding effects of changes in oxygen consumption due to neural activation (or deactivation) are likely modest, since neural effects are local, whereas the global BOLD signal is measured across all brain tissue. Caution should be used when interpreting a lower global BOLD signal as reflecting lower oxygen delivery or consumption, since changes in CBF and perfusion are possible without changes in metabolism due to compensatory changes in oxygen extraction.Possible subject classification confounds include the presence of diabetes in four (likely five) OSA patients, as well as the potential for undiagnosed hypertension, with both conditions associated with neural deficits Whole brain blood volume and oxygenation responses to hand grip and cold pressor autonomic challenges are blunted in OSA patients; these differences are exacerbated in female subjects. The brain vascular responses, likely reflecting changes in CBF to various stimuli, are less affected in OSA by the stimuli associated with the Valsalva maneuver than by cold and hand grip challenges. The exacerbation of impairments in female vs. male OSA may contribute to the additional brain injury found in female patients.File S1Cold pressor global BOLD raw data, in Excel format. Individual subject values are in worksheets specific to sleep status and sex , and group means (Y) and standard deviations (STDEV(Y)) are in the “Group Means” worksheet. Values are recorded every 2 s (“X” column in “Group Means” worksheet).(XLSX)Click here for additional data file.File S2Hand grip global BOLD raw data, in Excel format. Individual subject values are in worksheets specific to sleep status and sex , and group means (Y) and standard deviations (STDEV(Y)) are in the “Group Means” worksheet. Values are recorded every 2 s (“X” column in “Group Means” worksheet).(XLSX)Click here for additional data file.File S3Valsalva global BOLD raw data, in Excel format. Individual subject values are in worksheets specific to sleep status and sex , and group means (Y) and standard deviations (STDEV(Y)) are in the “Group Means” worksheet. Values are recorded every 2 s (“X” column in “Group Means” worksheet).(XLSX)Click here for additional data file.


The relationship between asthma and ankylosing spondylitis (AS) is controversial. We examined the risk of asthma among AS patients in a nationwide population.We conducted a retrospective cohort study using data from the National Health Insurance (NHI) system of Taiwan. The cohort included 5,974 patients newly diagnosed with AS from 2000 to 2010. The date of diagnosis was defined as the index date. A 4-fold of general population without AS was randomly selected frequency matched by age, gender and the index year. The occurrence and hazard ratio (HR) of asthma were estimated by the end of 2011.The overall incidence of asthma was 1.74 folds greater in the AS cohort than in the non-AS cohort (8.26 versus 4.74 per 1000 person-years) with a multivariable Cox method measured adjusted HR of 1.54 , 1.34–1.76). The adjusted HR of asthma associated with AS was higher in women , those aged 50–64 years , or those without comorbidities .Patients with AS are at a higher risk of developing asthma than the general population, regardless of gender and age. The pathophysiology needs further investigation. Spondyloarthropathies (SpAs) are a group of interrelated diseases characterized by joint inflammation and extra-articular involvement, including mainly the axial and peripheral type and extra-articular type –3. Ankylet al have reported that the prevalence rates of atopic disorders were 61/248 (24.6%) in AS patients and 111/536 (20.7%) in the control population, while the prevalence rates of asthma were 18/248 (7.3%) in AS patients and 35/536 (6.5%) in the control population. They concluded that there was a slight but insignificant increase in atopic disorders in AS patients [Asthma is a chronic inflammatory disorder of the airways and it is a representative disease of atopic disorders. Rudwaleit patients . Howeverpatients –17. AS iAutoimmune diseases (ADs) are caused by the loss of immune tolerance and are characterized by T- or B-cell activation leading to tissue damage. Patients with AD can be defined by a direct and indirect circumstantial evidence. Because of lack of the direct proof, patients with AS have limited features of AD . HoweverThis study attempts to determine whether patients with AS are at an elevated risk of developing asthma. We conducted a retrospective cohort study using nationwide population-based data, the National Health Insurance Research Database (NHIRD) of Taiwan.http://www.nhi.gov.tw/english/index.aspx). The NHIRD, established by the Bureau of National Health Insurance (BNHI) and the National Health Research Institutes (NHRI), is one of the large administrative health care databases in the world and is available to scientists for research purposes. All identification numbers of insured people and healthcare facilities in this database are encrypted for privacy protection. The encrypted identification numbers are unique, enabling record linking. The present study used the electronic data of the Longitudinal Health Insurance Database (LHID) obtained from NHRI, consisting of claims data of 1,000,000 individuals randomly sampled from all population. The data can be retrospectively traced from 1996 onwards and followed up to the end of 2011. The NHRI reported no statistically significant differences in gender, age, and health care cost distribution between these subjects and whole insured population. This study was exempted from full ethical review by the China Medical University and Hospital Research Ethics Committee (IRB permit number: CMU-REC-101-012). The diagnostic code is in the format of the International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM).The National Health Insurance (NHI) program in Taiwan was launched in 1995 to provide comprehensive medical care for over 99% of the 23.74 million people residing in Taiwan (We identified a cohort of patients newly diagnosed with AS (ICD-9-CM code: 720 and 720.0)  between Each subject was monitored from the index date until a new diagnosis of asthma was reached or until the subject was eliminated because of failure of follow-up, death, withdrawal from the insurance system, or the end of follow-up on December 31, 2011. The baseline history of comorbidity and medication for each subject was determined from the claims data, including rhinitis (ICD-9-CM codes: 472.0 and 477), chronic sinusitis (ICD-9-CM code: 473), gastroesophageal reflux disease , obstructive sleep apnea , chronic obstructive pulmonary disease  and usage of aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) , 23.t-test for continuous variables. The incidence density rates by gender, age, and comorbidity for each cohort were estimated by follow-up time (in person-years). The AS cohort to non-AS cohort incidence rate ratio (IRR) with 95% confidence intervals (CI) was determined using the Poisson regression model. The multivariable Cox proportional hazards regression model was used to assess the risk of asthma associated with AS, comparing with the non-AS cohort and adjusted for demographic factors, comorbidities of rhinitis, chronic sinusitis, GERD, OSA, COPD, and usage of aspirin and NSAIDs. We also used the Kaplan–Meier method to estimate the cumulative asthma incidence for the two cohorts in the follow-up period and examined the difference using the log-rank test. All analyses were performed using the SAS statistical package , with the statistical level of significance being 0.05.Distributions of categorical demographic factors including gender and age  and comorbidities including rhinitis, chronic sinusitis, GERD, OSA, COPD, and usage of aspirin and NSAIDs, were compared between the AS and non-AS cohorts. Differences were examined using the Chi-square test for categorical variables and the The study cohorts consisted of 5,974 AS patients and 23,896 non-AS control subjects. The age and gender distributions were similar in both cohorts . Most suTo the best of our knowledge, this is the first nationwide population-based study evaluating the relationship between AS and subsequent risk of asthma. We identified a significant risk of asthma among AS patients compared to the general population. Sex-specific analysis shows the highest asthmatic risk for females with AS patients. In addition, we found AS patients without comorbidities had a near 2-fold higher asthmatic risk than controls without comorbidities. Our data suggest that AS may play an independent role in the development of asthma.The incidence of asthma increased with age in both cohorts. However, the crude AS patients to controls HR was the highest in the 30–49 years. The possible explanation for this might be that older subjects in both cohorts tend to be more prevalent with comorbidities, which may account for late-onset asthma. Risk factors may also include occupational exposure to irritants, environmental pollutants, female sex hormones, upper airway diseases, medications, respiratory infections, obesity, and stressful life events . The cruet al. reported the prevalence of asthma to be 7.3% in AS patients and 6.5% in a control population [Few studies have discussed the relationship between AS and risk of asthma. Rudwaleit pulation . They uspulation . TherefoSeveral studies have shown a decreased risk of atopic diseases in patients with autoimmune diseases such as RA , 26–27. There are a number of factors that influence the risk of developing asthma. Although asthma is a representative atopic disorder, the pathophysiological mechanisms are very complex. Development of asthma can be attributed to host factors such as genetics, obesity, and gender and environmental factors such as allergens, infections, occupational exposure, tobacco smoke, air pollution, and diet. Additionally, racial and ethnic differences, lifestyle, socioeconomic status, and the efficacy of the public health system have been linked to the prevalence of asthma . In the A major strength of our study is that it was performed using population-based data that are highly representative of the general population. However, certain limitations should be considered. First, this study used the ICD-9-CM algorithm to define AS, asthma and comorbidities. The diagnosis depends on the performance of clinical physicians. An ad hoc committee established by the insurance authority was in charge of evaluating the claims data to prevent errors and violation. In addition, we selected only diagnosis appeared at least twice within a year to increase the validity and accuracy of diagnosis. Second, information on smoking, diet, occupational exposure, and family disease history was not available in the data analysis for adjusting the association between AS and asthma. Third, relevant clinical data such as pulmonary function tests, laboratory data on urinary and blood tests, imaging results, and pathology findings of the subjects were also unavailable in our study. Therefore, the statistical quality in a retrospective cohort study may be weaker.Our data suggest that patients with AS have a significantly higher risk of developing asthma than the general population regardless of gender and age. Although, the pathophysiology association between AS and asthma needs further investigation.


Cerebral perfusion pressure (CPP) can adversely impact cerebrovascular hemodynamics but cannot be practically measured in most clinical settings. Here, we aimed to establish a representative mathematical model for CPP in geriatric patients with suspected cerebrovascular disease.A total of 100 patients  with suspected cerebrovascular disease and no obvious cerebrovascular stenosis were selected for invasive CPP monitoring via catheterization of the middle segment of the common carotid arteries and openings of the vertebral arteries bilaterally. Curves were function-fitted using MATLAB 7.0, and data was statistically processed by SPSS 20.0.MATLAB 7.0 constructed eighth-order Fourier functions that fit all recorded CPP curves. Since the coefficients of the 100 functions were significantly different, all functions were standardized to derive one representative function. By manipulating the heart rate and maximum/minimum CPP of the representative function, estimated CPP curves can be constructed for patients with differing heart rates, intracranial pressures (ICPs) and blood pressures.CPP can be well-modeled through an eighth-order Fourier function that can be constructed from a patient’s brachial artery blood pressure (BABP), ICP and heart rate. This function is representative of geriatric patients with cerebrovascular disease and can be used in the future study of cerebral hemodynamics. The incidence of cerebrovascular disease has been steadily increasing year-by-year and has become a serious public health problem,2. PreviHowever, CPP cannot be practically measured in most clinical settings, making CPP an inconvenient measure for the study of cerebrovascular hemodynamics,6. In 19max /CPPmin range was 80–180/50–110 mm Hg, the intracranial pressure (ICP) range was 5.88–13.24 mm Hg and the heart rate range was 60–100 beats/min. Patients were excluded from the study if they had severe steno-occlusive disease of the carotid and vertebrobasilar artery. Patients with recent onset moderate to severe stroke which is defined as NIHSS score>4 points were excluded from the study. Patients with Arrhythmia were excluded from the study.All subjects gave their written informed consent after a detailed introduction to the study. The study was approved by the Ethics Committee of Chongqing Medical University  and was performed according to the Helsinki Declaration.We have included patients with suspected cerebrovascular disease who underwent CPP monitoring and digital subtraction angiography (DSA) in our institution between January 2011 and August 2013. The inclusion criteria was as follows: 1) patients had signs and symptoms suggestive of cerebrovascular disease. 2) patients had to complete DSA examination for visualization of cerebral vasculatures. 3) patients had to complete CPP monitoring for inclusion. 4) in the included patients, the CPPAfter completing the DSA, a total of four CPP monitoring curves were bilaterally recorded for each patient: two from the (left and right) common carotid arteries and two from the openings of the (left and right) vertebral arteries were obtained. Briefly, angiographic catheters were inserted into the middle segments of the common carotid arteries bilaterally and openings of the vertebral arteries  bilaterally, then the carotid and vertebral artery pressure (CVAP) was monitored. The intracranial pressure(ICP) was monitored by using non-invasive methods. First, the pulsatility index (PI) of the middle cerebral artery was detected by using Transcranial Doppler (TCD) in each patient. The mean value of the PI was calculated by using the two PI on both sides. The ICP was calculated by using the equation“ICP = 10.927* PI—1.284” –[8.731cos(2*7.85t)– 0.6382sin(2*7.85t)]–[0.9819cos(3*7.85t)+2.315sin(3*7.85t)]–[1.086cos(4*7.85t)– 0.3577sin(4*7.85t)]–[1.098cos(5*7.85t)+1.342sin(5*7.85t)] + [0.3895cos(6*7.85t)– 0.4227sin(6*7.85t)]–[0.4628cos(7*7.85t)– 0.02835sin(7*7.85t)] + [0.04679cos(8*7.85t)– 0.7078sin(8*7.85t)]. As shown in f0(t) curve closely approximates the underlying data points (four representative data series of 100 new fitted functions) with a cycle of CPPmin = 90 mm Hg, CPPmax = 140 mm Hg.Based on the standardized coefficients in f0(t) displays a pendulum-like periodic motion around a0 (112.3 mm Hg) with its positive amplitude (27.7 mm Hg) slightly greater than its negative amplitude (23.3 mm Hg)  and the heart rate as C (beats/min), yielding a cycle of X's CPP function fx(t) should satisfy the following relationship:3 mm Hg) . By manifx(t) has an average value of (1/50)(22.3A + 27.7B) (mm Hg), an ordinate range from A to B, and a cycle of 60/C (s)(fx(t) curve simply involves the lengthening and/or shortening of f0(t) in the longitudinal and transverse directions, the fx(t) function can be manipulated to fit the CPP curves for differing blood pressures,ICPs and heart rates. However, if a particular patient X’s blood pressure, ICP and/or the heart rate is too high or low, it will produce extreme variations in the CPP curve that may not be suitable for fitting using fx(t).Based on this formula,  60/C (s). As the Série de Fourier)[The French mathematician Fourier discovered that any periodic function can be expressed via an arithmetic sum of constituent sine and cosine functions. This concept is now commonly known as the Fourier series (French:  Fourier). In the  Fourier),13. The max /CPPmin to 140/90 mm Hg when calculating f0(x). Here, the authors invasively monitored the CPP(CPP = CVAP-ICP) of 100 patients; thus, the CPP curves accurately reflected the dynamic CPP changes in each patient.Normal ICP range is 5.88–13.24 mm Hg and is not easily affected by the heart rate. Under normal conditions it fluctuates between 2–4mmHg. In sharp contrast to the fluctuation of CVAP and CPP, the ICP curve could be regarded as a nearly straight line. In order to simplify calculations, we used ICP curve as a straight line. So CPP curve is like a downward shift of the CVAP curve. We have used non-invasvie methods for detection of ICP, which is expressed as a mean value. Although it might be less accurate than invasive measurement, the bias error is too small to affect our results because we have standardized all CPPCPP  are periodic, continuous, and smooth with no obvious breakpoints and buckling, generally conforming to a complex sinusoidal function. Moreover, the common carotid and cerebral arterial trees are unique anatomical structures; they are not simple cylindrical tubes attached to the aortic arch. Due to these underlying complexities in peripheral arterial blood flow and anatomical architecture, the CPP is an irregular sinusoidal curve that requires an eighth-order Fourier function for effective fitting,14.fx(t) function requires three variables: the patient's heart rate, the maximal CPP, and the minimal CPP. The heart rate can be easily assessed; however, this study used an invasive method to check the CPP that was only incidentally performed after DSA, which is not clinically feasible and thus not worth promoting as the basis of a practical diagnostic modality. Thus, the maximal and minimal CPP values can only be estimated through the patient’s non-invasive BABP and ICP, or non-invasive ATCAP and ICP. the accuracy of which depends on the measurement errors of BABP, ATCAP and/or ICP and the conditions of the patient's vasculature.This study found no significant differences among CPPs of the common carotid arteries and vertebral arteries in each patient on account of their shared source (the aortic arch) and close proximity. The fx(t) function obtained here is only applicable in this patient population. However, the majority of patients with cerebrovascular disease are in this age group, and most of them experience hypertension[fx(t) function derived here is of applicable value to cerebrovascular hemodynamic investigations in cerebrovascular disease patients. Further studies should apply the fx(t) to investigating CPP changes in patients with cardiovascular disease and the role of CPP changes in the pathogenesis of cerebrovascular disease.Patients involved in this research were between 60–80 years old, some of which suffered from hypertension. Therefore, in theory, the ertension–17. Therfx(t) obtained here is widely representative of geriatric patients with cerebrovascular disease and can be used in the future study of cerebral hemodynamics. It also serves as a useful reference for further investigations on cerebrovascular disease.CPP can be well-modeled through an eighth-order Fourier function using MATLAB 7.0. This function can be roughly estimated through non-invasively collecting the patient's BABP, ICP and heart rate. The Fourier function


Background:Acute kidney injury (AKI) is a life threatening condition. Despite intensive care treatment the occurrence cannot be predicted as very little indicators exist for direct measurement when tubular epithelial cell injury takes place. We therefore searched for novel peptide indicators expressed at intracellular level at the proximal kidney tubule for its appearance in urine samples.Objectives: Establishing a test for urinary C20orf116 protein measurement.Patients and Methods: Generation of immunoreagents against C20orf116 also named DDRGK1. These were used to measure its presence in urine collected at 8-24 hours interval in a prospective study from 99 ICU patients at 4-6 time points. These patients received therapy because of serious infection and were categorized into 4 groups.Results: 1) Ten tested highly for C20orf116 undergoing AKI graded Failure or Loss (3210 ± 4268 ng/mL) according to RIFLE criteria, all requiring renal replacement therapy (RRT) out of them 9 died. 2) Six patients with pre-existing kidney disease developed AKI and required RRT but had much lower C20orf116 levels of (33 ± 19), two of them died. 3) In contrast, out of 11 patients undergoing AKI grade Risk or Injury, four tested positive for C20orf116 but to much lower extent (66 ± 43) who recovered fully. 4) Out of 72 patients 25 tested positive (18 ± 12 ng/mL) not fulfilling criteria of AKI but with serum creatinine (sCr) rises of 1.2-1.4 (n = 52). Healthy donors (n = 48) showed no detectable C20orf116 at any time point.Conclusions: C20orf116 excretion was detectable more than 24 hours before sCr rise could be measured; high level seemed to indicate severity of organ failure. Protein biomarker testing in urine for patients presenting with morbidities associated with high risk to undergo acute kidney injury (AKI) is a new option for early diagnosis of kidney stress und would therefore be helpful to mitigate injuries by early intervention strategies.Disease specific biomarker profiles have been established for various clinical conditions. This has enabled emergency departments and critical care units to rapidly respond by therapeutic strategies. Not only acute diagnosis of diseases but also monitoring of treatment response and disease progression has increasingly become a domain of biomarker follow up. Only few kidney specific biomarkers have been characterized up till now -7. Due tThe detection of AKI is based on serum creatinine (sCr) rise and reduction of urine output. However, this marker has limitations as a marker of glomerular filtration rate (GFR) because substantial kidney injury may have already occurred by the time sCr increases  and urinRecently, we have cloned a novel protein, encoded by open reading frame 116 at chromosome 20 , and demonstrated its abundant expression in the kidney and in the proximal tubular cells . In addiEarly diagnosis of kidney cell damage is of importance in medical care therefore we searched for novel urinary biomarkers indicative for tubular cell injury.Catheter urine or clean catch urine samples were centrifuged (3000 rpm at 4°C for 10 minutes) to remove cell components and stored at -20°C for further use. The study design suggested urine sampling at admission/diagnosis and at 8-12, 24, 48, 72 and 96 hours following ICU treatment. All ICU patients were diagnosed with septicemia or severe infections (pneumonia). ICU patients were categorized according to RIFLE staging  into four groups 1) developing AKI grade F and L and requiring renal replacement therapy , 2) AKI grade I upon preexistent kidney disease with sCr >2.5 m/dl (n=6), 3) AKI grade R or I (n=11) and group 4) all remnants (n=72) not fulfilling AKI according to RIFLE criteria but with sCr rise 1.2-1.4 fold (n=52). Healthy individuals (n=48) collected 4 individual urine samples by clean catch over a period of at least 48 hours. The four time points of measurement were chosen in a way that from each urine donor a morning urine sample had been collected and the urine collection time interval was spread over a period of at least 48 hours.The full coding sequence of C20orf116 was cloned into the pMSCV plasmid and lentivirus particles were generated essentially as described earlier . The celHigh binding E.I.A/R.I.A plates were coated over night at 4°C with 100 µl recombinant C20orf116 (12.5 ng/mL in PBS) generated as a His-tag fusion protein in Sf9 insect cells as described earlier . After wUrine samples (30 µl) were loaded after denaturation in SDS sample buffer onto 10% SDS-PAGE gel. After electrophoresis, the proteins were electrotransferred onto a nitrocellulose using a semidry blotting device. Following the blocking step, the blotted membrane was consecutively exposed to the primary Ab  and to the secondary Ab . Between each incubation step, the blotted membrane was washed in PBS containing 0.1% Tween 20. Antigen visualisation was performed by chemiluminescence using lumi-imager F1 (Roche).®, La Jolla, CA, USA) (1/5000 in 0.5x blocking solution) was added and incubated at RT for 45 minutes. Wells were washed with PBS (4 times with 300 µl PBS) and developed with two component TMB substrate  for 15 minutes at RT in the dark. The reaction was stopped by adding 100 µl 1M H3PO4 and read at 450 nm with the ELISA reader  at 450 nm. The concentrations were then calculated according to the standard curve. All samples were analyzed in duplicate. In total 1280 samples had been available for testing.High binding E.I.A/R.I.A plates  were coated with purified anti-C20orf116 IgG for 4 hours at RT or overnight at 4°C. After a brief wash, 50 µl urine was dispensed into the 50 µl of blocking solution (KPL) pre-applied onto the multi-well dish. The plate was then incubated at RT for 2 hours under constant shaking including a standard series at each plate. After a brief wash with PBS, biotinylated rabbit anti-C20orf116 IgG and biotinylated mAb A2 was applied (dilution 1:2000 in PBS/rabbit serum) and incubated for 1 hour at 37°C. Following a second washing step (4 washes with 300 µl PBS) NeutrAvidin .Protein G-Sepharose eluted rabbit IgG or mAb A2 was dialyzed against PBS for 3 days at 4°C and at least three changes of dialysis fluid. D-Biotinoyl-ε-Aminocaproic Acid N-Hydroxysuccinimide Ester  was dissolved in DMSO (30 mg/ml) and biotin was added to the antibody solution under constant stirring in 15 fold molar excess. The biotinylation was carried out at RT over 2 hours and free biotin was removed from the antibody by gel filtration chromatography using SephadexThe research followed the tenets of the Declaration of Helsinki. Informed consents were obtained. All patients took part in this study voluntary. Sample analysis was carried out by blinded investigators each in duplicate. The research was approved by the ethical committee of the Medical University of Vienna (ethic code: 721/2007).P<0.05. The graphic representation was performed using GraphPad Prism .The 5th to 95th percentile of C20orf116 values are demonstrated in Whiskers blots. Differences between multiple groups were calculated with SPSS using analysis of variance (ANOVA) with correction for post hoc analysis. Statistical significance was defined when High throughput gene expression analysis has generated extensive data sets on uncharacterized gene transcripts in various tissue types and disease processes. In order to obtain further information on till now undefined protein function we generated immunoreagents and established quantitative methods for mRNA and protein expression of C20orf116 also named Dashurin and DDRGK1. The presence of the protein was observed in kidney tubules in tissue sections. This has been established by immunofluorescence analysis of kidney cryosections . C20orf1Motivated by a striking kidney tubule expression pattern as mentioned above we established a urinary ELISA method to measure C20orf116 in urine samples collected at 4-6 time points from intensive care patients (n=99) and we compared these with healthy donor urine which were collected at four different time points. Equivocally, all 48 healthy donors had no detectable level by our ELISA method. In the control group only healthy donors fully active in various professional backgrounds with sCr levels within the normal range were included.In contrast to healthy controls 10 ICU patients tested high (3210±1350 ng/mL) for C20orf116  at leastP<0.001). The post hoc test revealed again a statistically significant higher concentration of C20orf116 product in the group graded AKI, F or L when compared with other ICU groups and healthy controls .Eleven patients developed AKI grade R with C20orf116 (66±43 ng/ml)  and onlyOne of the patients in the group who did not reach AKI criteria showed high levels due to a non-explainable reason undergoing a sCr rise of 1.3 fold which was entirely reversible under intensive care treatment. She did not recover from infectious episodes for more than 5 months but was discharged from ICU after 1 month. Her kidney function tests stayed within the normal range.Most importantly, in patients with previously intact kidney function high urinary levels of C20orf116 were detected 24-48 hours earlier before a rise in sCr could be observed . Urine C20orf116 testing was carried out at 4-6 time points following diagnosis or admission to ICU as depicted in the methods section. As sample analysis was carried out in retrospect no further samples were available for testing at the time-point of C20orf116 measurement. SCr values were taken from the hospital routine data and used together with fluid output and disease records to evaluate grading and course of AKI.Levels of C20orf116 in urine seemed to predict severity of kidney injury  and precEarlier work has demonstrated that the DDRGK1 protein migrates at the SDS-PAGE at about 40 kDa ,23 whichAlthough all data pointed towards detectability of the protein upon cellular breakdown we intended to assure that C20orf116 would not be a secretion product. Therefore we generated an over-expressing cell line as indicated in the methods section and tested whether the protein was detectable in tissue culture supernatant or not. Secretion of detectable amount could be excluded whereas intracellular protein was abundant which confirms data obtained by another group .http://www.proteinatlas.org), the predilection site of tubular injury in AKI, has highest C20orf116 expression levels within this organ. It has been demonstrated recently that this protein forms complexes with the cell cycle check point kinase Cdk5rap3 and resides at the ER with its N-terminal hydrophobic signal peptide like structure  against this protein. Using the newly established ELISA technique with these antibodies, we demonstrate that patients develop C20orf116-uria days or hours before sCr starts rising and oliguria develops. The idea to test C20orf116 in ICU patients was created following the observation that C20orf116 can be visualized in the lumen of kidney tubules by immunolocalization in tissue sections. Furthermore, it had been striking that especially the proximal kidney tubular cells . However, these antibodies did not prove usable in sandwich capture ELISA but together with the polyclonal antibody these might provide greater sensitivity in further experiments. Therefore polyclonal rabbit antibodies had to be produced for clinical specimen testing. These detected various fragments which originate from degradation during cell fragmentation and urine flow. Contamination with cells can be excluded due to the fact that each urine sample had been centrifuged as indicated in the methods section prior to freezing.The observation that a subgroup of ICU patients with minor changes in sCr not fulfilling criteria of overt AKI show C20orf116 secretion in urine might indicate that tubular cell injury might occur silently not detectable by routine clinical parameters. In this direction observations by others showed that even minor changes in sCr while under ICU treatment will be of relevance for the further life span and patient outcome .In conclusion we demonstrate that this novel protein expressed highly at the proximal kidney tubule might be promising to detect kidney damage which might be induced by potential nephrotoxic agents such as antibiotics and contrast agents and endogenous conditions at serious infections. However, most likely it will have to be combined with other novel markers such as Timp 2 and IGFBP 7 , KIM-1, . Comparison with other available biomarkers was beyond the borders of this study.Antibodies which are necessary for such measurement are not commercially available, furthermore the protein might be a too sensitive marker as a certain patient group presented with detectable levels without manifestation of any AKI stageHeinz Regele provided normal kidney tissue from tumor nephrectomy. D. Neziri received a scholarship from Astute Medical. We thank Panagiota Patsiou who helped to revise the manuscript.DN was responsible for antibody generation and purification as well as sample analysis, SP helped in sample analysis and manuscript preparation and data recording, AR helped in laboratory work, AI performed statistical analysis, GH generated virus particles, MW was responsible for ICU patient care and sample collection, CZ supported the work as chief of the ICU and helped to enroll patient in the study, LW guided the study helped in ELISA development sample analysis and manuscript writing.The authors declared no competing interests.This study was in part the doctoral thesis of Dashurie Neziri. She was supported by a scholarship from Astute Medical. The department’s research budget paid for all chemicals and plastic ware used in the study.


Hypertension is a globally prevalent condition, with a heavy clinical and economic burden. It is the predominant risk factor for premature cardiovascular and cerebrovascular disease, and is associated with a variety of clinical disorders including stroke, congestive cardiac failure, ischaemic heart disease, chronic renal failure, and peripheral arterial disease. A significant subset of hypertensive patients have resistant hypertensive disease. In this group of patients, catheter-based renal artery denervation has emerged as a potential therapy, with favourable clinical efficacy and safety in early trials. Additional benefits of this therapy are also being identified and include effects on left ventricular remodeling, cardiac performance, and symptom status in congestive cardiac failure. Utility of renal denervation for the management of resistant hypertension, however, has become controversial since the release of the Symplicity HTN-3 trial, the first large-scale blinded randomised study investigating the efficacy and safety of renal artery denervation. The aim of this paper is to evaluate the history, utility, and clinical efficacy of renal artery denervation technology, including an in-depth appraisal of the current literature and principal trials. Hypertension is a clinical disorder that is defined as an aberrancy of blood pressure, with systolic blood pressure (SBP) equal to or greater than 140 mmHg and/or diastolic blood pressure (DBP) equal to or greater than 90 mmHg , 3.As blood pressure is a continuous variable, hypertension can be categorized into separate classes or stages, with current clinical classification systems encompassing Stages 1 (SBP 140–159 mmHg and/or DBP 90–99 mmHg), 2 (SBP 160–179 mmHg and/or DBP 100–109 mmHg), and 3 (SBP ≥ 180 mmHg and/or DBP ≥ 110 mmHg) , multiple [n = 2], or highly tortuous renal arteries [n = 0] were excluded from the procedure as were those with significant (>30%) renal artery stenosis [n = 4] [Recruitment in this study included patients in varying age brackets (18–80 years of age) who were selected by referral from primary healthcare providers or specialists across four participating centres. Enrolled subjects were required to have a clinic-based SBP measurement of ≥160 mmHg (≥150 mmHg for diabetics) despite prolonged use of at least three antihypertensives (including a diuretic) and suitable renal artery anatomy assessed via renal artery angiography. Participants with small  [ [n = 4] . All eli [n = 4] .Renal artery denervation procedure was performed under conscious sedation and local anaesthesia . A minimp < 0.0001) were observed, respectively. The blood pressure reductions were sustained to the 18-month period, whereby an average SBP reduction of 24 mmHg was noted, with the majority (77%) of studied participants having a clinically significant response to therapy. In terms of safety, no serious adverse events were noted in the cohort. A nonclinically significant reduction in eGFR was reported at 6 months . At 18 months however, no clinically significant changes to renal function were noted  relative to the control group [mean LVEF 26% at baseline to 28% at twelve months (p = 0.36)]. Other markers of left ventricular impairment  were similarly improved. In addition to the improvements in left ventricular function, there was a trend towards lower rehospitalisations for heart failure (8 versus 18) in the intervention arm (p < 0.001). Two complications, however, were registered in the intervention arm; one patient developed a femoral fistula formation and the second had formation of postoperative thrombus [Overall, the intervention group saw a modest improvement in left ventricular ejection fraction (LVEF) [mean LVEF 25% at baseline to 31% at twelve months  or control arm (n = 18). Patients over the age of 18 with a clinic-recorded SBP ≥160 mmHg despite management with three antihypertensives (including a diuretic) were included into the study. These subjects were followed over a 6-month period, with transthoracic echocardiography performed at baseline, 1 and 6 months [Another study, published in early 2012, investigated the effect of renal artery denervation therapy on left ventricular parameters, including echocardiographic indices of systolic and diastolic function. This study employed 64 participants, which were either placed into the treatment arm (6 months .p < 0.001), a significant reduction in markers of diastolic impairment  was appreciated in the treatment group. Additionally, a statistically significant improvement in LVEF was noted  [Echocardiographic endpoints included LVEF, left ventricular mass index (a marker of left ventricular hypertrophy), mean interventricular septal thickness, and mitral inflow parameters  measured via Doppler echocardiography. Besides a sustained reduction in office-based blood pressure  .Interestingly, although regression of parameters of left ventricular diastolic dysfunction was incremental with SBP reduction, “nonresponders”  still demonstrated a marked reduction in these indices . This fiThis improvement in cardiac function has been shown to translate to a symptomatic benefit in a recent trial by Davies et al. (2013), which assessed seven patients with chronic heart failure with reduced LVEF receiving renal artery denervation therapy over a six-month period. Of interest, the mean blood pressure on referral was 112/65 mmHg (normotensive range), significantly lower than that employed in the majority of trials .p = 0.35; DBP −0.6 ± 4.0 mmHg, p = 0.88) at 6 months, with no hypotensive events noted. Renal function was unaffected. All seven patients reported a significant symptomatic improvement, with significant quantitative improvement in six-minute walk distance at 6 months . No procedural or postprocedural complications were noted [Following denervation, a nonsignificant trend towards blood pressure reduction was found  [In addition to the previously mentioned effects on left ventricular remodeling, cardiac performance, and symptom status in congestive cardiac failure, studies have also demonstrated the efficacy of renal denervation in patients with impairment of the baroreflex sensitivity. In a study by Zuern et al. (2013), 50 patients with resistant hypertension and a mean ambulatory SBP of 157 ± 22 mmHg were enrolled in the prospective cohort study and underwent renal denervation therapy. At six-month follow-up subsequent to procedure, 26 patients (52%) achieved a drop in mean ambulatory SBP of ≥10 mmHg. Upon review, impaired baroreflex sensitivity was strongly associated with response to renal denervation (< 0.001) .The Symplicity HTN-3 study was a multicentre, prospective, double-blinded, randomised study investigating the efficacy and safety of renal arterial denervation using the Symplicity catheter system in patients with medically refractory hypertension. Like the previous Symplicity HTN trials, the primary efficacy endpoint of the study looked at the change in office SBP measurements at 6 months. Secondary efficacy endpoints of the trial differed, looking at the change in mean 24-hour ambulatory SBP. The primary safety endpoint was a composite of major adverse events  .Inclusionary criteria were that of resistant hypertension (SBP ≥ 160 mmHg) despite three or more maximally tolerated antihypertensive medications (including a diuretic) in the absence of haemodynamically significant valvular disease or renovascular abnormalities determined via angiographic assessment. All recruited patients underwent a confirmatory screening visit beforehand to confirm SBP of >160 mmHg and adherence to medications. Once included, patients were then randomised in 2 : 1 fashion to treatment arm and control arm, respectively. Those in the control group underwent renal angiography only (sham control). Patients in the interventional arm underwent the renal denervation procedure which was performed with the Medtronic Symplicity Catheter .A total of 535 patients  were included into the study, 364 of whom were allocated to the interventional cohort and 171 to the control cohort. Procedural technique and periprocedural pharmacotherapy of the interventional arm were unchanged from the previous Symplicity trials. Regardless of group, all blood pressure assessors were unaware of study group assignments and a blinding index was utilised to verify the effectiveness of blinding at hospital discharge and at 6 months. Patients were subsequently followed up at 6-month intervals after randomisation (with an aim follow-up up to 5 years). Changes to baseline doses of antihypertensive therapy were not encouraged unless deemed medically necessary .p = 0.67). No significant changes in renal function were observed between both groups [In terms of safety, no significant difference was noted in terms of overall composite adverse events between denervation and control groups. The rate of major adverse events in the denervation group was 1.4% compared to 0.6% in the control group (h groups .p = 0.26 with a superiority margin of 5 mmHg) [p = 0.98 with a superiority margin of 2 mmHg). There was also no significant between-group difference in terms of change in heart rate from baseline to 6 months  [With regard to efficacy endpoints however, investigators surprisingly found no clinically significant changes in baseline SBP between both groups. At 6 months, an average office blood pressure reduction of −14.3 ± 23.93 mmHg was noted in the intervention arm compared to −11.74 ± 25.94 mmHg in the control group with a between-group difference of −2.39 mmHg  . Ambulat = 0.30) .Though the trial essentially confirmed the safety of the procedure, the negative findings in terms of efficacy were sobering and essentially contradicted the findings of the other Symplicity HTN and denervation trials.Investigators and stakeholders raise several possibilities to explain the discrepancy of the findings. Of note was the difference in population studied. Whilst there were no significant differences in terms of baseline characteristics between the two arms in the Symplicity HTN-3 trial, the trial included a significant number of African Americans , a demographic that was not present in the previous Symplicity trials. Subgroup analysis of this demographic showed a paradoxical effect of denervation therapy, with preferential  blood pressure lowering effects in the control arm as opposed to the Caucasian cohort , 42.Patient characteristics and medication profiles between the Symplicity HTN-2 and Symplicity HTN-3 trials likewise differed, with a higher proportion of obese patients, patients with increased cardiovascular risk factors, and patients with greater use of diuretics and aldosterone antagonists as part of their antihypertensive regimen included into the Symplicity HTN-3 trial. In addition, participants included in the trial only received maximal antihypertensive therapy for two weeks prior to evaluation of efficacy, whilst a recommendation for at least two months is endorsed by current guidelines on hypertension, raising the possibility that patients with an incorrect diagnosis of resistant hypertension were included into the trial .From a procedural and technical perspective, a large proportion of operators in the Symplicity HTN-3 trial had no previous experience with the procedure and as such may have been less experienced compared to the site-specific trained Symplicity HTN-1 and -2 operators. Moreover, whilst indirect electrical impedence was utilised to discern contact with the arterial wall and thus guide the positioning of the catheters, there were unfortunately no objective measures of procedural success. As such, inadequate thermoablation was possible, regardless of the experience of the operator , 44.Finally, in the Symplicity HTN-3 trial, there were tighter entry control criteria with regard to ambulatory blood pressure. As part of the inclusionary criteria, ambulatory blood pressure monitoring was performed with the aim of excluding patients with pseudo- or white-coat hypertension. The same did not hold true for the Symplicity HTN-2 trial. This may have led to overestimation of initial blood pressure measurements in the earlier Symplicity trials and thus led to lower follow-up blood pressure results.Given the heavy clinical and economic burdens of hypertensive disease, new treatment methodologies are currently being explored. Catheter-based renal artery denervation technology is one of the novel treatments in the management of resistant hypertension. Based on the concept of sympathetic nerve modulation, many were initially in favor of the technology given the promising results of the early trials. In view of the disheartening results of the Symplicity HTN-3 trial however, widespread utilisation of the procedure has now become controversial.Skeptics allude to the lack of compelling evidence regarding efficacy in the trials and the significant profit driven goals with the technology. Advocates on the other hand argue that further vigorous randomised trials are required before complete disbanding of the technology and state that while the use of renal artery denervation in blood pressure reduction may be contentious, the efficacy of the technology in other areas is yet unproven and potentially beneficial.As smaller studies have shown benefit in left ventricular remodeling, cardiac performance, and symptom status in patients with cardiac failure when utilized as an accessory tool to medical therapy, larger trials are recommended to assess the effect of this modality in this group. Additional double-blinded trials would also be recommended in patients with impaired baroreceptor sensitivity, as this represents a potentially vulnerable group of sympathetic hypertensive diseases which may be amenable to percutaneous catheter renal denervation therapy.