Family members of patients with end stage renal disease were reported to have an increased prevalence of chronic kidney disease (CKD). However, studies differentiated genetic and non-genetic family members are limited. We sought to investigate the prevalence of CKD among fist-degree relatives and spouses of dialysis patients in China.2) or albuminuria.Seventeen dialysis facilities from 4 cities of China including 1062 first-degree relatives and 450 spouses of dialysis patients were enrolled. Sex- and age- matched controls were randomly selected from a representative sample of general population in Beijing. CKD was defined as decreased estimated glomerular , 16.8% vs. 14.6% (P = 0.29) and 18.4% vs. 19.8% (P = 0.61), respectively. The prevalence of eGFR less than 60 mL/min/1.73 m2, albuminuria and the overall prevalence of CKD in dialysis relatives were also compared with their counterpart controls, which was 1.5% vs. 2.4% (P = 0.12), 14.4% vs. 8.4% (P < 0.01) and 14.6% vs. 10.5% (P < 0.01), respectively. Multivariable Logistic regression analysis indicated that being spouses of dialysis patients is negatively associated with presence of low eGFR, and being relatives of dialysis patients is positively associated with presence of albuminuria.The prevalence of eGFR less than 60 mL/min/1.73 mThe association between being family members of dialysis patients and presence of CKD is different between first-degree relatives and spouses. The underlying mechanisms deserve further investigation. Chronic kidney disease (CKD) is a global public health problem ,2, and iRecent studies revealed that family members of patients with end stage renal disease (ESRD) have an increased prevalence of CKD -12. DiffSeventeen dialysis facilities from 4 cities of China were enrolled . ESRD Patients with inherited kidney disease, such as autosomal dominant polycystic kidney disease or Alport’s syndrome were excluded for this study. All family members, including first-degree relatives  and spouses of these patients were invited to participate in the study from October 2006 to August 2007. Altogether 1642 family members of ESRD patients participated in this study on a voluntary basis. Among them, 130 members who didn’t have either complete questionnaire or complete lab results were excluded. Finally, 1062 relatives and 450 spouses from 715 hemodialysis and 127 peritoneal dialysis families were eligible for present analysis. The ethics committee of Peking University First Hospital approved the study, which covers all participating institutions. All participants gave written informed consent before data collection.Controls were selected from a representative sample of the general population of adults in Beijing, which is described in details elsewhere .Data were collected in examination centers at local health stations. All subjects completed a questionnaire documenting their sociodemographic status , health status , history of nephrotoxic medications , lifestyle behaviors , and the primary causes of renal failure of dialysis patients .Anthropometric measurements were obtained. Indicators of kidney damage and possible risk factors then were examined. All blood samples and urinary samples were tested in the central laboratory of Beijing University First Hospital.Albumin and creatinine were measured from a fresh morning spot urine sample or morning urine sample stored at 4°C for less than 1 week. Albuminuria was measured using immunoturbidimetic methods . Urinary creatinine was measured by means of Jaffe’s kinetic method on a Hitachi 7170 autoanalyzer . Urinary albumin-creatinine ratio  was calculated. Patients with ACR determinations that ranged from 17 to 250 mg/g (1.9 to 28.3 mg/mmol) for males and 25 to 355 mg/g (2.8 to 40.2 mg/mmol) for females were classified as having microalbuminuria, and participants with ACR values greater than the microalbuminuria range were classified as having macroalbuminuria. Albuminuria was defined as the presence of either microalbuminuria or macroalbuminuria. Women during menstruation were excluded from analyses for albuminuria.2 (1.00 ml/s/1.73 m2):Blood was collected by venipuncture after an overnight fast of at least 10 hours. Serum creatinine was measured by the same methods as was urinary creatinine. eGFR was calculated with an equation developed by modifying the Modification of Diet in Renal Disease (MDRD) equation based on data from Chinese CKD patients . And decwhere Scr is serum creatinine concentration (in mg/dL) and age in years.The CKD was defined as decreased kidney function or albuminuria based on the classification system established by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) .Blood pressure was measured by sphygmomanometer, three times at 1 minute intervals. The mean of the three readings was calculated, unless the difference between readings was greater than 10 mmHg, in which case the mean of the two closet of the three measurements was used. Hypertension was defined as systolic blood pressure of 140 mmHg or greater or diastolic blood pressure of 90 mmHg or greater or use of antihypertensive medications in past 2 weeks irrespective of blood pressure, or any self-reported history of hypertension. Fasting blood glucose was measured enzymatically by means of a glucose oxidase method using the Hitachi 7170 autoanalyzer. Diabetes was defined as fasting plasma glucose of 7.0 mmol/L or more, by hypoglycaemic agents despite fasting plasma glucose, or any self-reported history of diabetes.Serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides and uric acid were measured with commercially available reagents using a Hitachi 7170 autoanalyzer.2. BMI = weight (kg)/height (m2) × 100%. Dyslipidemia was defined as present if total cholesterol was ≥ 5.72 mmol/L (220 mg/dL), or if low density lipoprotein (LDL) was ≥ 3.64 mmol/L (140 mg/dL), or triglyceride was ≥ 1.70 mmol/L (150 mg/dL) or high density lipoprotein (HDL) was < 0.91 mmol/L (35 mg/dL). Hyperuricaemia was defined as serum uric acid > 422 μmol/L for males and > 363 μmol/L for females.The body mass index (BMI) was calculated as weight (in kilograms) divided by height squared (in meters squared). Overweight is defined as BMI greater than 24 kg/mAll analyses and calculations were performed by SPSS statistical package, version 16.0 . Controls were selected from the cross-sectional survey of CKD in a representative sample of the general adults in Beijing [t-test for continuous variables. The unadjusted odds ratios (OR) between family members of dialysis patients and indicators of kidney damage were determined by univariate Logistic regression analysis. McNemar’s test was used to test univariate associations. A multivariate Logistic regression analysis was then performed to adjust for confoundings including age, gender, diabetes, hypertension, nephrotoxic medications, dyslipidemia, overweight, and chronic respiratory tract infection. Odds ratio (OR) was calculated and 95% confidence interval (CI) was provided. A P value of 0.05 or less was considered to be statistically significant.Data were presented as the mean ± standard deviation for continuous variables and as proportions for categorical variables. Descriptive analysis were used to characterize the participant population by sociodemographic data  and health status (eg. hypertension and diabetes). Differences in variables between the two groups were analyzed using chi-square statistics for categorical variables or independent 2, P < 0.01). A significantly lower prevalence of low eGFR was found in dialysis spouses compared with controls . There were no differences in the prevalence of albuminuria  and CKD  between these two groups.Characteristics of spouses and matched controls are listed in Table Among spouses, the prevalence of nephrotoxic medications use was higher and the prevalence of hypertension was lower compared with that of controls. There were no differences in prevalence of diabetes and overweight between these two groups. After adjusting for potential confounders, being spouses of dialysis patients was negatively associated with presence of decreased eGFR, with an OR of 0.50  [The high prevalence of CKD among first-degree relatives of dialysis patients in our study is consistent with previous studies ,20. Comp – 7.4%) ,23. One  – 7.4%) ,24. Envi – 7.4%) ,26. HoweGenetic traits may contribute to the development of CKD in relatives of dialysis patients. It is well known that familial focal segmental glomerulosclerosis (FSGS) is a significant and growing cause of CKD. Given the progress in understanding the biology and pathology of podocyte, mutation of associated genes, such as ACTN4, TRPC6 and NPHS2, contribute to the damage of podocyte and podocyte dysfunction ,28. The Spouses of patients with ESRD were considered to be nongenetic controls for studying the family clustering of CKD . SpousalOur study has limitations that deserve mention. Firstly, it was implemented on a voluntary bias within the dialysis units. Additionally, ESRD patients who didn’t start dialysis treatment were not included in present study. There were kinds of selecting bias in the study which limited the extension of the results from this study. Secondly, urine and blood results were based on a single measurement. It should be noticed that it might overestimate the prevalence of albuminuria based on one measurement. Finally, a cross-sectional study design has several inherent weaknesses, such as lack of long-term observation for outcome and difficulty interpreting the association of exposure with outcome.In conclusion, the association between being family members of dialysis patients and presence of CKD is different between first-degree relatives and spouses. Genetic susceptibility may account for the phenomenon of family clustering of CKD. However, non-genetic environmental factors also should be considered as potential contributing for CKD. The underlying mechanisms deserve further investigation. Strategies aimed at intervention of hypertension and other metabolic disorders might prove effective in controlling the pandemic of CKD in family members of dialysis patients.The authors declare that they have no competing interests.KX and ZL participated in the study, analyzed the data, interpreted the results, and drafted the manuscript. LL, ZL, YP, LZ, LW, CM, CX, JA, LG, XJ, LH, WS, HW, WY, GY, CP, WH and JQ participated in the survey and study design and collected the data. ZL and WM formed the study concept, interpreted the results, and revised the manuscript. WH revised the manuscript for important intellectual content. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/14/19/prepub


According to the National Heart, Lung, and Blood Institute of the National Institute of Health, hypotension refers to an abnormally low blood pressure (BP). In childhood, hypotension can be determined according to two different definitions: BP below the 5th percentile or below two standard deviations (SDs) of the mean for age and gender . A graphWe used a computerized calculation method to develop high-resolution graphics containing curves with 5,841 points each, to depict the main percentiles associated with low BP for boys from 1 to 17 years old in the 50th percentile of height. Each point represents the calculation of the polynomial equation that includes the statistical processing of the last Report on Blood Pressure . We alsoFive monotonic curves of systolic BP for boys representing the 50th, 25th, 10th, 5th, and 2.275th (-2SD) percentiles were built (Figure The adjustment of systolic BP for height is of little significance, and the updated graphic can be used to diagnose low systolic BP for boys. Clinical studies are necessary to determine the systolic BP percentile that better represents clinically significant hypotension.


Various diagnostic methods have been used to evaluate hypertensive patients under physical and pharmacological stress. Several studies have shown that exercise hypertension has an independent, adverse impact on outcome; however, other prognostic studies have shown that exercise hypertension is a favorable prognostic indicator and associated with good outcome. Exercise hypertension may be encountered as a warning signal of hypertension at rest and future hypertensive left ventricular hypertrophy. The results of diagnostic stress tests support that hypertensive response to exercise is frequently associated with high rate-pressure product in hypertensives. In addition to the observations on high rate-pressure product and enhanced ventricular contractility in patients with hypertension, evaluation of myocardial contractility by Doppler tissue imaging has shown hyperdynamic myocardial function under pharmacological stress. These recent quantitative data in hypertensives suggest that hyperdynamic myocardial function and high rate-pressure product response to stress may be related to exaggerated hypertension, which may have more importance than that it has been already given in clinical practice. Measurement of blood pressure at rest has been usually used in epidemiological studies . Some otIt is well documented in large prospective epidemiological trials that high blood pressure at rest results in fatal and nonfatal cardiovascular events . There aAlthough some studies suggested that systolic blood pressure rises with dynamic exercise, while diastolic blood pressure does not change or falls slightly at submaximal exercise , in anotA finding of another study was a high prevalence of masked hypertension in apparently healthy patients presenting with normal office blood pressure but high blood pressure during a clinically indicated exercise stress test . The preThe findings that an individual's risk of developing hypertension in those with high-normal blood pressure was greatly increased if they exhibit an exaggerated blood pressure response to exercise confirms an incremental contribution of exercise blood pressure response above resting blood pressure in predicting future hypertension. Therefore, exercise testing in populations at high risk for hypertension could provide important additional information concerning hypertension risk .A hypertensive response to exercise is associated with subtle systolic dysfunction, even in the absence of resting hypertension. These changes occur before the development of left ventricular hypertrophy or detectable diastolic dysfunction and likely represent early hypertensive heart disease .An exaggerated increase in systolic blood pressure prolongs myocardial relaxation and increases left ventricular chamber stiffness, resulting in an increase in left ventricular filling pressure. Left ventricular filling pressures can be estimated reliably by combining mitral inflow early diastolic velocity (E) and annulus velocity (E'). An increased E/E' ratio reflects elevated filling pressures and may be useful in assessing an abnormal increase in filling pressures for patients with diastolic dysfunction. In a study to evaluate left ventricular diastolic dysfunction leading to exercise intolerance, even in the absence of resting hypertension, (129 subjects with a preserved ejection fraction and a negative stress test) hypertensive response to exercise was evaluated at the end of a 6-min exercise test using the modified Bruce protocol. It is shown that early diastolic mitral annular velocity (E') by tissue Doppler imaging was significantly lower and the ratio of early diastolic mitral inflow velocity (E) to E' (E/E') was significantly higher in patients of the hypertensive response to exercise. Irrespective of the presence of resting hypertension, patients with hypertensive response to exercise had impaired left ventricular longitudinal diastolic function and exercise intolerance . DiastolVarious diagnostic methods have been used to evaluate hypertensive patients and there have been conflicting data relating the effectiveness of the diagnostic methods. Exercise electrocardiography has low specificity especially in patients who have electrocardiographic abnormalities at rest . DobutamFactors related to false-positive results of exercise echocardiography to diagnose coronary disease have been extensively studied and it has been suggested that the factors predictive of false-positive results during exercise echocardiography to diagnose coronary disease were female sex, higher blood pressure at peak exercise, lower risk by Duke score and lower number of abnormal segments and wall motion score index after peak exercise. Women appear to be susceptible to wall motion abnormalities caused by elevated exercise blood pressure .We have recently documented increased regional myocardial contractility of left ventricular base using exercise stress echocardiography tissue Doppler imaging in hypertensives with left ventricular hypertrophy and relation between stress-related regional tissue dynamics and left ventricular outflow tract blood flow Figure  28]. In. In28]. We have observed that peak pharmacologic stress causes high systolic velocities on basal septal tissue in the hypertensive patients with basal septal hypertrophy suggesting stress may produce an enhanced left ventricular contractility Figure  30]. It. It30]. Left ventricular end-systolic pressure-volume relationship provides a robust, relatively load-insensitive evaluation of contractility and can be assessed non-invasively during stress echocardiography. This index of global contractility is reasonably simple, does not affect the imaging time, and only minimally prolongs the off-line analysis time. It allows unmasking quite different, and heterogeneous, contractility reserve patterns underlying a given ejection fraction at rest . RecentlExaggerated hypertension is well tolerated and associated with only minor symptoms in most of the patients for the evaluation of hypertensives with chest pain . In thesSystemic hypertension and an exaggerated blood pressure response with exercise have been associated with 'false-positive' findings on stress electrocardiography and echocardiography . In a coIt has been reported that hypertensive patients who have well controlled blood pressure at rest may give exaggerated blood pressure response to exercise . HyperteIt has been suggested that exaggerated blood pressure response during exercise testing may provide a foresight for the future of sustained hypertension development . It is kIt has been documented that the patients with exercise hypertension presented significantly greater posterior wall thickness and Doppler functional data showed significant increase in the late to early flow velocity ratio. Even in the absence of hypertension, exaggerated blood pressure reactivity to physical exercise suggests greater blood pressure elevation during daily activity as well as enhanced sympathetic nervous tonus, which may be considered a risk factor promoting hypertension and these hemodynamic and neurohumoral behaviors are associated with a tendency to develop target organ abnormalities in the heart .Although the mechanism responsible for the exaggerated blood pressure response to exercise has not been revealed, there are some plausible mechanisms linking with underlying structural abnormalities in the cardiovascular system. Wilson et al.  found thLauer et al.  have detAl-Nasser et al.  have shoSome results indicate that an angiotensin converting enzyme inhibitor provides a sustained 24 h blood pressure reduction associated with blood pressure reduction during physical exercise. These effects have been obtained without altering diurnal blood pressure profile, without excessive hypotension at the time of maximal antihypertensive effect and with a slight improvement of exercise tolerance . It has Franz et al.  examinedRecent quantitative data support that exercise hypertension in hypertensive patients may be related to enhanced ventricular contractility and excessive rate-pressure product response to stress and this finding may have more importance than that it has been already given in clinical practice.The authors declare that they have no competing interests.All authors contributed to the paper and meet the criteria for authorship. All authors read and approved the final manuscript.


One of the long-term complications of diabetes mellitus type 1 (DM type 1) in children is diabetic nephropathy. Diabetes longstanding suffered and pubertal status are the influencing factors which make the complications come up to the surface. Diabetic nephropathy case will be accompanied by increasing of blood pressure symptoms.To detect the illustration of childrens blood pressure in DM type 1 base on their age, sex, longstanding suffered, and the latest level of HbA1c.A retrospective observational studies on national registered of DM type 1 at pediatric endocrinology chapter to 2010. Age, sex, longstanding suffered, the latest level of HbA1c, systolic blood pressure (SBP) and dyastolic (DBP) are variables which has been researched.Starting at 177 children suffered by DM type 1, 118 (66.7%) are girls and 59 (33.3%) are boys. The average age when they got diagnose for the first time is 11,8 years old. Only one girl (0.6%) who suffered DM type 1 more than 5 years, has SBP and DBP > percentile 95, There is no any significant correlation with the others.Most of the childrens blood pressure in DM type 1 are still normal. In this research, a girl who being suffered in DM type 1 with hypertension (> 95th percentile) has been being suffered more than 5 years. It needs doing blood pressure measurement regularly, for screening the diabetic nephropathy, if s microalbumin examination has not been done yet.


The diagnostic approach to dizzy, older patients is not straightforward as many organ systems can be involved and evidence for diagnostic strategies is lacking. A first differentiation in diagnostic subtypes or profiles may guide the diagnostic process of dizziness and can serve as a classification system in future research. In the literature this has been done, but based on pathophysiological reasoning only.To establish a classification of diagnostic profiles of dizziness based on empirical data.Cross-sectional study.417 consecutive patients of 65 years and older presenting with dizziness to 45 primary care physicians in the Netherlands from July 2006 to January 2008.We performed tests, including patient history, and physical and additional examination, previously selected by an international expert panel and based on an earlier systematic review. We used the results of these tests in a principal component analysis for exploration, data-reduction and finally differentiation into diagnostic dizziness profiles.Demographic data and the results of the tests yielded 221 variables, of which 49 contributed to the classification of dizziness into six diagnostic profiles, that may be named as follows: “frailty”, “psychological”, “cardiovascular”, “presyncope”, “non-specific dizziness” and “ENT”. These explained 32% of the variance.Empirically identified components classify dizziness into six profiles. This classification takes into account the heterogeneity and multicausality of dizziness and may serve as starting point for research on diagnostic strategies and can be a first step in an evidence based diagnostic approach of dizzy older patients. Dizziness is a common symptom, especially in older patients. The prevalence of dizziness in the community ranges from 2% in young adults to over 30% in older people. Annual consultation rates in primary care increase from 3% for patients aged 25 to 44 years, to 8% in patients over 65 years of age, and to 18% for the oldest elderly The diagnostic approach to dizziness is often difficult for clinicians: dizziness is self-reported by definition, refers to various abnormal sensations of body orientation in space, and may be caused by a wide range of benign and serious conditions that may or may not co-exist in one patient The objective of our study was to establish an empirical classification of diagnostic profiles of dizziness in older patients, using information readily obtainable in a primary care setting in order to establish a starting point for a more specific diagnostic approach.Participants were recruited among consecutive patients seen by 45 PCPs in 24 Dutch primary care practices from July 2006 to January 2008. Patients of 65 years or older consulting their PCP for dizziness were invited to participate. Additionally, each month the electronic databases of all practices were searched retrospectively for dizzy patients the PCPs had failed to invite. These patients received, after approval of their PCP, a written invitation to participate in the study. Our definition of dizziness included patients describing a giddy or rotational sensation, a feeling of imbalance, lightheadedness, and a sensation of impending faint. The complaints had to be present at inclusion and dizziness had to be the main reason for consultation. We included patients irrespective of prior consultations concerning the same symptoms. Criteria for exclusion were the inability to speak Dutch or English, severe cognitive impairment, severe visual impairment , severe hearing impairment , or wheelchair dependency.The study was approved by the medical ethics committees of both involved academic medical centers  and Medical Ethics Committee VU Medical Center (METc VUmc)). All patients gave written informed consent.All patients were assessed by one of the authors (JD or OM) or one of three well-trained research assistants with a medical degree using a predefined protocol. The creation of the protocol is described elsewhere in more detail Data were entered real-time in a database.The full diagnostic test battery, including demographic data, consisted of 221 variables. We organized the dataset by merging and recoding (multi)nominal and ordinal variables into dichotomous variables . We left continuous variables continuous , and dichotomous variables dichotomous (e.g. gender) (see supporting information). This process reduced the number of variables to 91. Next, we discarded variables that scored positive in less than 5% or in more than 95% of the patients and in addition were not indicative of acute (serious) conditions. Four variables were dropped: “epilepsy in history”, “urologic drugs increasing blood pressure”, “alcohol problem based on the PHQ”, and “abnormal non-fasting blood glucose”. All were dropped because of a very low prevalence, respectively 1.4%, 4.3%, 2.4%, and 1.4%.We imputed missing data using the iterative chained equations method (ICE) in STATA/SE 10.0 . Briefly, for each variable in turn missing values are filled in with random predicted values based on observed values. Then “filled-in” values in the first variable are removed, leaving the original missing values for this variable. These missing values are then imputed using regression imputation on all other variables . This process is repeated for each variable with missing values until one ‘cycle’ is completed. We continued this process for 5 cycles We used principal component analysis (PCA). PCA is a technique that can be used to summarize a large number of variables by a small number of components, wherein associated variables form a distinct pattern or profile. We performed PCA in a two-stepped procedure to mimic the diagnostic approach in daily practice. In the first step we used PCA to explore the inter-relationships of the demographic data and information from history taking. Variables with high loadings (≥+.35 or ≤−.35) The aim was to obtain as few components as possible whilst each variable loaded with a high value (≥+.35 or ≤−.35) onto one component and low values (−.34 to +.34) After completion of the PCA we calculated so-called “profile-scores” by summing, for each component, all variables associated with that component. These profile scores were standardised for each component to a score ranging from 0 to 100.U test was used to test statistical differences in the distribution of the dizziness profiles by gender and age. Values of p<0.05 were considered statistically significant.Internal consistency was estimated by calculating the Cronbach's alpha for each profile. Spearman correlation coefficients were calculated between profile-scores. Descriptive statistics were used to examine the distribution of the profile-scores in our population. Finally, profile-scores were dichotomized at a value of 67% in order to identify patients scoring high on specific components. The Mann-Whitney Data were available from 417 older patients with dizziness  [30]. ThIn the second step we added 30 variables providing information on physical examination and additional diagnostic tests. Based on inspection of the scree plot  and comp“frailty”: (older) age, living in nursing home, living alone, using hearing and walking aid, impaired stability in rest, impaired walking , impaired mobility of knee joint(s), abnormal tandem gait, abnormal functional mobility (performance of the timed ‘up and go’ test ≥20 seconds), corrected visual acuity ≤0.5, impaired hearing (Fletcher index ≥35 dB).“psychological”: female, history of anxiety and/or depressive disorder, use of psychotropic drugs; presence of somatoform disorder, major depressive disorder, and anxiety disorder ; high total score and high scores on emotional, functional and physical scales of DHI, indicating severe disability.“cardiovascular”: history of cardiovascular disease, hypertension, history of arrhythmia, polypharmacy, use of cardiovascular drugs, use of fall risk increasing drugs (FRID).“presyncope”: lightheadedness as subtype description of dizziness by patient, duration of dizziness >60 seconds, associated symptoms: tinnitus/decay in hearing; nausea; sweaty, pale or clammy; palpitations; chest pain; dyspnoea; trouble with walking; falling/almost falling; other symptoms.“non-specific dizziness”: not frequently dizzy, absence of the following provoking circumstances: turning head, bending forward, looking up, getting up from lying or sitting position; negative Dix-Hallpike test; low total score and low score on physical scale of DHI.“ENT”: ENT-disorders and/or ENT-surgery in history; use of antivertiginous drugs; using hearing aid; duration of dizziness 1 hour to days; nausea as associated symptom; impaired hearing (Fletcher index ≥35 dB).“Frailty” accounted for 11.2% of the total variance, “psychological” for 5.7%, “cardiovascular” for 4.5%, “presyncope” for 4.0%, “non-specific dizziness” for 3.6%, and “ENT” for 3.0%.Cross loading did not occur in the first step . In the Cronbach's alpha for each component was respectively .82 for “frailty”, .77 for “psychological”, .77 for “cardiovascular’, .69 for “presyncope”, .71 for “non-specific dizziness”, and .56 for “ENT”. This is satisfactory for most components , meaning that contributive variables in the different dizziness profiles are measuring the same underlying construct.p<0.05), but not very strong for most components, confirming that the components represent different distinct presentations of dizziness. Higher correlations were found between the “psychological” and ”non-specific dizziness” profiles, and between the “psychological” and “ENT” profiles (correlation coefficients >0.50). Some higher correlation coefficients are inflated due to variables loading on more than one component .We classified the participating patients according to the identified profiles. For each of the dizziness profiles Based on findings from history, physical examination and diagnostic tests, that can be performed in a primary care setting, we found six dizziness profiles: “frailty”, “psychological”, “cardiovascular”, “presyncope”, “non-specific dizziness”, and “ENT”. The vast majority of patients (in this study 88%) could be classified in one of six profiles.The components identified by the first PCA step, based on demographic data and patient history were quite similar to the components of the second step, in which we added physical examination and diagnostic tests. Additional information on physical examination and diagnostic tests seems to be redundant and only confirmed the diagnostic information provided by demographic data and patient history. This means that a thorough history taking seems to be sufficient for the initial classification of dizziness. This fact does not mean that additional tests should be abandoned, as these tests might be useful within a profile for diagnosing or ruling out a specific disease The existing pathophysiological classification of dizziness used four subtypes: vertigo, disequilibrium, presyncope, and atypical dizziness. This classification shows resemblance with our results: “ENT” combined with the absence of “non-specific dizziness” resemble vertigo. “Frailty”, although much broader, resembles disequilibrium, “cardiovascular” and “presyncope” together resemble presyncope, and “psychological”, although more specific, resembles atypical dizziness. The empirically established profiles thus provide a more in depth addition to the existing theoretical classification.To our knowledge this is the first study that used empirical data to define profiles of dizziness in an unselected older primary care population presenting with dizziness The explained variance of the identified profiles of 32% is only moderate. This percentage is to be expected within the broad, heterogeneous spectrum of patients with dizziness in our dataset We did find cross loading. We retained all cross loaders, however, as all these variables showed sufficiently high factor loadings and add relevant information to the profiles. The use of hearing aids and impaired hearing, for instance, can be expected in both “frailty” and “ENT”, as older patients often have sensory deficits, and patients with (a history of) ENT problems may both have impaired hearing and use hearing aids. This is similar for nausea, which can be an associated symptom in vertigo (associated with “ENT”) as well as in presyncope. Furthermore, high total scores on the self-perceived Dizziness Handicap Inventory are to be expected in the “psychological” dizziness profile and the opposite (negative cross loading) in the relatively healthy “non-specific dizziness” group.We performed the study in an older primary care population suffering from dizziness for at least two weeks, often for a long time. Our results therefore may not be applicable to other populations, like younger patients with acute onset of dizziness. In acute dizziness, however, diagnostic problems are less extensive.From our study emerged six dizziness profiles that might provide clinical guidance in the diagnostic approach of dizzy older primary care patients. We were able to classify 88% of the patients, mostly in more than one profile. The fact that most patients scored positive on more than one profile could be expected as dizziness in the elderly is often a multifactorial problem. These profiles, based on readily available information during a consultation, might however guide the diagnostic process, thereby limiting the number of diagnostic tests which are needed to reach a more precise diagnosis. Instead of performing a complete diagnostic work-up for dizziness, PCP's might be able to taper the diagnostic process, using these dizziness profiles.Before implementing this classification of dizziness profiles, external validation in another older primary care patient population with dizziness is mandatory. An empirical classification of dizziness profiles might serve as starting point for further research on diagnostic strategies, diagnostic test accuracy or prediction models within a more homogeneous group of patients presenting with dizziness. Then, within these profiles, an attending doctor can explore diagnostic options with uncomplicated and inexpensive testing and look for treatable conditions, etiologic or contributory.Table S1Principal component analysis of demographic data, and patient history (first step). Principal component analysis with OBLIMIN rotation and Kaiser normalisation. All component loadings are rounded to two decimals. Component loadings of ≥+.350 or ≤−.350 are deemed contributive and highlighted in bold. Empty cells represent component loadings of −.004 to +.004. *Continuous variables, all other variables are binary. We performed principal component analysis (PCA) in a two-stepped procedure to mimic the diagnostic approach in daily practice. In the first step we used PCA to explore the inter-relationships of the demographic data and information from history taking (57 variables). This analysis identified 6 components which explained 29.4% of the variance. A total of 38 variables with component loading values ≥+.35 or ≤−.35 were considered contributively and were retained for the second step. The results of this first analytic step with PCA resemble the results of the second step which also included physical examination and additional testing, with the component “healthy” being the opposite of the component “frailty”, and the component “vestibular” the opposite of the component “non-specific dizziness” (table S1 and (DOC)Click here for additional data file.Table S2Principal component analysis of contributing demographic data and patient history, and physical examination, and additional information (second step). Principal component analysis with OBLIMIN rotation and Kaiser normalisation. All component loadings are rounded to two decimals. Component loadings of ≥+.350 or ≤−.350 are deemed contributive and highlighted in bold. Empty cells represent component loadings of −.004 to +.004. *Continuous variables, all other variables are binary.(DOC)Click here for additional data file.


Tizanidine is αThis study evaluates the effects of oral Tizanidine on hemodynamic responses during operations and aims to determine the appropriate Propofol dosage to maintain anesthesia under BIS monitoring.A double-blind clinical trial has been performed on 70 candidates for elective abdominal surgery undergoing general anesthesia in Educational Hospital of Ghaem, Mashhad, Iran. 35 randomly selected patients (the case group) were given 4 mg of oral Tizanidine 90 minutes before the induction of anesthesia whereas the remaining subjects (the control group) were given placebo. Blood pressure and heart rate before and after induction of anesthesia, and after intubation and extubation, existence of postoperative shivering, and the needed Propofol dosage were measured and recorded. Data analysis was done with T-test and Chi-squared test, using SPSS software version 16.Variations of blood pressure and heart rate after anesthesia induction, intubation and extubation were less in Tizanidine group generally. Postoperative shivering was reported in 28.6% and 11.4% of patients in control and case group respectively. Average propofol needed dose for anesthesia maintenance in case group was 25% less than the needed amount in the control group.Using oral Tizanidine as a premedication, yielded stability in blood pressure and heart rate during surgery and decreased required Propofol. Considering its short duration of action, Tizanidine use as a premedication is recommended for sedation and stabilization of hemodynamic responses during the operations. Mild diminution in heart rate preserves the oxygen supply to demand ratio in an appropriate range. Hemodynamic stabilization, during and after the operations, is the most important mechanism by which the α2-receptor agonists reduce peri-operative ischemia  class 1 and 2 candidates for elective abdominal surgery undergoing general anesthesia at Ghaem Educational, Research and Treatment Center of Mashhad University of Medical Sciences (MUMS). Prior to the surgery all the patients were informed about the investigation and the testimonials were obtained. The patients with positive history of hypertension, Diabetes Mellitus, cardiac disease, renal failure, cirrhosis, neurological disease, or recent consumption of drugs were omitted from the study, as well as the smokers, opiate addicts and the patients with bradycardia (heart rates below 60 beats/min). The study was finally approved in session of 28th may 2011 regional ethics committee, Mashhad University of medical sciences, with code of 89869.®) was prescribed to case group, while the other group was treated with placebo. All of the patients underwent basic monitoring including noninvasive observation of blood pressure, electrocardiography, arterial saturation of oxygen (SaO2), heart rate, and bispectral index (BIS) monitoring as they entered the operating room.Randomly, the patients were divided into two groups. 90 minutes before the surgery one 4 mg Tizanidine tablet  increase and decrease in blood pressure either 5-50 mcg/min of nitroglycerin and 5 mg of ephedrine or 500 cc of Ringer solution was infused respectively. Also, 0.5 mg of Atropine was prescribed for cases with heart rates below 40 beats/min.Initially, 0.04 mg/kg of Midazolam and 3-4 mcg/kg of Fentanyl were administered as premedication to all patients. Anesthesia induction was performed with 2mg/kg Propofol and 0.6 mg/kg Atracurium. The anesthetics used for maintenance for all patients were 50-150 mcg/kg/h Propofol (which was infused by the pump) alongside with the composition of CO2 (ET CO2) was sustained in a limit of 30-40 mmHg. The patient’s blood pressure and heart rate were monitored and recorded before induction of anesthesia, at two minutes after anesthesia, at one and five minutes after intubation, and after extubation of the airways. Eventually, at the end of the surgery, relaxing effect of anesthetics on skeletal muscles was neutralized using 0.04 mg/kg of Neostigmine and 0.02 mg/kg of Atropine. The amount of consumed Propofol, duration of anesthesia from induction of anesthesia to extubation of the airways, the postoperative shivering presence from patients’ extubation to his/her discharge from the recovery was recorded in a specifically designed checklist. All the observations and measurements were done by one of the authors or under supervision of her. She was completely trained for instruments usage. We used automatic blood pressure device (non-invasive blood pressure) for measuring Blood pressure (mmHg) and pulse oximetry monitor for heart rate (beats/min). We also used biseptical index monitor for anesthesia depth (0-100). All the instruments were calibrated.All of the patients underwent ventilation with tidal volume (TV) and Flow (F) values of 8-10 cc/kg and 10-12/min, respectively. End tidal Statistical analysis of data was performed by student’s T-test and Chi-squared test via SPSS (Version 16.0). This study aimed to compare instability seen in hemodynamic properties between tizanidine received (case) and non-tizanidine received (control) patients. Regarding the fact that some of the patients would show increase and some other would manifest with decrease in the aforementioned variables, using the Mean in whole sample size do not seem to be appropriate for comparison. So we separated the patients into two groups for statistical analysis: 1- Group with variable reduction and 2- Group with variable increase.70 patients  with the mean age of 36.77 ± 11.13 years were enrolled the study in case  and control  groups. The mean age of the patients was reported 36.57 ± 11.31 years in cases and 36.97 ± 11.11 years in controls. The difference between the two groups was not significant. (P = 0.882) Most of the participants were in ASA class I. Only 9 patients (13%) belonged to class II. . The mean duration of anesthesia was 110.64 ± 44.63 min (35 to 240) in all the patients. Cases (113.57 ± 48.83) and controls (107.71 ± 40.52) were similar in terms of anesthesia duration (P = 0.587).As demonstrated in The findings are summarized with details in In patients with increased mean arterial blood pressure, the changes were more severe in controls (15.17 ± 16.22 mmHg) in comparison to cases following a 5 minute interval after intubation (2.76 ± 2.68 mmHg). The difference was significant. (P = 0.038) In the patients with decrease in hemodynamic properties, the mean arterial blood pressure was found to have -18.06 ± 11.69 mmHg decreases in controls which is obviously more severe than the measured -16.05 ± 7.40 seen in cases. When if the difference was not statistically significant. (P = 0.458) The conditions were similar for systolic, diastolic blood pressure, and heart rate . In a 1 Study of Takenaka et al. suggested that Clonidine can decreases severe alterations in blood pressure and heart rate during the surgeries . The ideAlthough the prescription of Clonidine was associated with severe decrease of blood pressure in cardiothoracic and non-cardiothoracic surgeries in several studies , in our Incident of postoperative shivering did not show any statistically significant difference between the two groups (P = 0.073); however, we did not find any synonymous studies that evaluated the effect of Tizanidine on postoperative shivering. Pier et al. investigation to compare the effect of Clonidine with Nefopam in preventing postoperative shivering proved that both Clonidine and Nefopam decrease the incidence and severity of postoperative shivering considerably in comparison to placebo, but the recovery time in Clonidine group was significantly more prolonged . ButorphGiven that cardiovascular status alteration in patients with coronary artery disease (CAD) can lead to dangerous and fatal consequences, we recommend more investigations be carried out to evaluate the effects of Tizanidine in these patients such as the effects of Tizanidine on patients’ recovery time. It is also suggested further studies be performed on effects of various doses of Tizanidine, regarding the effectiveness and cost-effective issues, in comparison with other drugs used to stabilize hemodynamic responses in stressful conditions of the operations (e.g. intubation and extubation of the airways). Prescription of oral Tizanidine as a premedication prior to the operations, in addition to sedative effects, causes stability in blood pressure and heart rate during the operations via decreasing central sympathetic activity. Regarding Tizanidine short duration of action, administration of this drug is recommended for sedating, stabilizing hemodynamic responses during the operations, and for reducing the required dose of anesthetic.


The aim of this study was to evaluate the effect of MetS on arterial stiffness in a longitudinal study.Brachial-ankle pulse wave velocity (baPWV), a measurement interpreted as arterial stiffness, was measured in 1518 community-dwelling persons at baseline and re-examined within a mean follow-up period of 3 years. Multivariate linear regression with generalized estimating equations (GEE) were used to examine the longitudinal relationship between MetS and its individual components and baPWV, while multivariate logistic regression with GEE was used to examine the longitudinal relationship between MetS and its individual components and the high risk group with arterial stiffness.Subjects with MetS showed significantly greater baPWV at the end point than those without MetS, after adjusting for age, gender, education, hypertension medication and mean arterial pressure (MAP). MetS was associated with the top quartile of baPWV , and a significant linear trend of risk for the number of components of MetS was found (p for trend < 0.05). In further considering the individual MetS component, elevated blood pressure and fasting glucose significantly predicted a high risk of arterial stiffness .MetS affects the subject's progression to arterial stiffness. Arterial stiffness increased as the number of MetS components increased. Management of MetS is important for preventing the progression to advanced arterial stiffness. Metabolic syndrome (MetS), defined as a cluster of features such as visceral obesity, impaired glucose tolerance, dyslipidemia, hypergtriglyceridemia, and elevated blood pressure ,2, is hiThe association of MetS with arterial stiffness has been investigated in many studies -31; howeThis was a population-based follow-up study. The design and selection criteria of the Taichung Community Health Study (TCHS) have been described previously . BrieflyAll study subjects underwent a physical examination measuring height, waist circumference (WC), and blood pressure by trained staff at baseline, as well as at the endpoint. MAP was calculated as (2 ×diastolic blood pressure + systolic blood pressure) ÷ 3. Blood was drawn with minimal trauma from an antecubital vein in the morning, after a 12-hour overnight fasting, and was sent for analysis within four hours of collection. Biochemical markers such as HDL cholesterol, triglyceride, and fasting glucose were analyzed by a biochemical autoanalyzer  at the Clinical Laboratory Department of China Medical University Hospital.Data on sociodemographic factors , lifestyle factors, and medical history were collected by self-administered questionnaires. Lifestyle factors, such as smoking and alcohol drinking history, were categorized as never and former/current. We collected self-reported personal medical histories, including diabetes and hypertension medication at the baseline and follow-up examination.380 cm in women), (2) high triglycerides level (31.7 mmol/L or on drug treatment for elevated triglycerides), (3) low HDL-C level (< 1.03 mmol/L in men and < 1.30 mmol/L in women or on drug treatment for reduced HDL-C), (4) high blood pressure (systolic BP 3130 mmHg or diastolic BP 385 mmHg or under anti-hypertensive drug treatment in a patient with a history of hypertension), and (5) high fasting plasma glucose concentration (35.5 mmol/L or on drug treatment for elevated glucose). Diabetes was defined as fasting plasma glucose concentration 37.0 mmol/L or on drug treatment for diabetes. Hypertension was defined as systolic BP 3140 mmHg or diastolic BP 390 mmHg or on drug treatment for hypertension.MetS was defined clinically, based on the presence of three or more of the following American Heart Association and the National Heart Lung Blood Institute(AHA/NHLBI) MetS criteria : (1) cenBaPWV, presenting for arterial stiffness, was measured non-invasively with subjects in the supine position and with a VP-1000 automated PWV/ABI analyzer  attached to the four limbs . For evep values were those of the two-sided tests; statistical significance was set at p < 0.05. All analyses were performed using SAS version 9.1 .Continuous variables were reported as mean ± standard deviation (SD) and categorical variables were reported as percentage . The variables that predicted the baPWV change were evaluated by analysis of covariate with baPWV at baseline as covariate due to its high impact on the baPWV change. Moreover, to explore the effect of MetS and its components on baPWV, three multivariate models were used. First, the longitudinal effect of MetS and the number of components on the change baPWV at follow-up were examined using multivariate linear regression with the generalized estimating equations (GEE) method. Second, we further evaluated how the longitudinal effect of individual MetS components on baPWV was affected by the other components being considered sequentially, using hierarchical linear regression analysis with the GEE approach. The order of entering the variables was elevated blood pressure, fasting glucose, WC, triglyceride, and low HDL cholesterol after adjustment. Last, the top quartile of baseline baPWV was used as the cutoff point to classify the high risk group with arterial stiffness. Multivariate logistic regression with the GEE approach was used to analyze the longitudinal effect of MetS and its components on arterial stiffness. We treated the number of MetS components as continuous variables to examine the linear trend on the risk of arterial stiffness. All reported Compared with individuals without MetS, a higher proportion of individuals with MetS were older, male, with ≤ 9 years of educational attainment, former or current smokers, former or current drinkers, and users of hypertension, hyperlipidemia, and diabetes medication Table .p < 0.05). The changes were not significantly different in terms of marital status and health factors at baseline, such as smoking and drinking.The baseline baPWV and changes in baPWV during the follow-up period, according to the various groups of sociodemographic factors, health factors, and medication after adjusting for baPWV at baseline, are illustrated in Table p for trend < 0.001).Subjects with MetS had a higher mean value of baPWV at baseline. Compared to subjects without MetS, subjects with MetS had a significantly greater 3-year mean change of baPWV  (Table p < 0.001) after adjusting for age, gender, education, smoke status, time-dependent hypertension medication, and time-dependent MAP   and fasting glucose  had an independent effect on longitudinal baPWV . The adjusted ORs of the high-risk group with arterial stiffness were 3.72  and 1.35  in individuals with elevated blood pressure and fasting glucose (both p < 0.05) . The adjusted odds ratios (ORs) of the high-risk group with arterial stiffness were 3.31 , 4.21 , and 5.24  in subjects with 1, 2, and ≥ 3 MetS components after multivariate adjustment. A significant linear relationship between the adjusted OR and the number of components of MetS was found (In this 3-year community-based prospective study, we found that MetS and the MetS components independently predicted the future progression or incidence of arterial stiffness. Regarding the influence of individual components of MetS on arterial stiffness, we found that blood pressure and fasting glucose were independent determinants of longitudinal arterial stiffness progression in this general population. Moreover, they were independent risk factors for predicting the 3-year incidence of the higher risk of developing arterial stiffness.The existence of a strong association between the presence of MetS and arterial stiffness has been shown in many cross-sectional studies -29. HoweIn the present study, only elevated blood pressure and fasting glucose were independent predictors of progressive arterial stiffness. Tomiyama et al. , in theiThe possible mechanism that can explain the effect of elevated blood pressure on progressive arterial stiffness is its direct effect on arterial walls. Elevated blood pressure may accelerate arterial stiffening because it forces endothelial cells and arterial smooth muscle cells to be exposed to the increase arterial wall dispensability chronically, which reflects arterial stiffening . ElevateThis study has several strengths. First, this was a prospective study; therefore, the temporal relationship between metabolic risk factors and arterial stiffness could be clearly ascertained. Second, this was a community-based cohort which could be representative of the general population. And lastly, our study evaluated arterial stiffness using non-invasive and simple baPWV measurement, and statistical corrections were made to prevent the influence of blood pressure. However, there are two limitations to our study. One is that our findings could not be generalized to young adults because we recruited participants aged 40 and over. The other is that the findings of our study may not be generalized to adults living in areas of less urbanization, because our sample was randomly selected from a population in a metropolitan area.We found that MetS and its components of fasting glucose and blood pressure are independent predictors of the longitudinal increase in arterial stiffness. Since these predictors are associated with significant cardiovascular morbidity and mortality, our findings suggest that management of MetS to prevent progression to advanced arterial vascular disease is important.The authors declare that they have no competing interests.CCL and TCL conceived and designed the experiments. CIL, TCL and CSL analyzed the data. WYL, CHL, YDL, and CCL participated in coordination and evaluation of data. SLK and FCS contributed to the study with their knowledge on field study. CCL, TCL and CCL wrote the paper. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/11/808/prepub


Background. Hypertension and excess body weight are important risk factors for endothelial dysfunction. Recent evidence suggests that high-polyphenol dark chocolate improves endothelial function and lowers blood pressure. This study aimed to evaluate the association of chocolate 70% cocoa intake with metabolic profile, oxidative stress, inflammation, blood pressure, and endothelial function in stage 1 hypertensives with excess body weight. Methods. Intervention clinical trial includes 22 stage 1 hypertensives without previous antihypertensive treatment, aged 18 to 60 years and presents a body mass index between 25.0 and 34.9 kg/m2. All participants were instructed to consume 50 g of chocolate 70% cocoa/day (2135 mg polyphenols) for 4 weeks. Endothelial function was evaluated by peripheral artery tonometry using Endo-PAT 2000 . Results. Twenty participants (10 men) completed the study. Comparison of pre-post intervention revealed that (1) there were no significant changes in anthropometric parameters, percentage body fat, glucose metabolism, lipid profile, biomarkers of inflammation, adhesion molecules, oxidized LDL, and blood pressure; (2) the assessment of endothelial function through the reactive hyperemia index showed a significant increase: 1.94 ± 0.18 to 2.22 ± 0.08, P = 0.01. Conclusion.In individuals with stage 1 hypertension and excess body weight, high-polyphenol dark chocolate improves endothelial function. Alterations in endothelial-cell function can precede the development of atherosclerotic changes and the progression of cardiovascular diseases . Hypertefunction . Accordifunction  high blofunction . Lifestyle interventions, including diet, may affect endothelial function: high-fat diets impair endothelial function, and diets such as the Mediterranean diet are associated with improved endothelial function . RecentlThere are several plausible mechanisms by which polyphenols may improve endothelial function and lower blood pressure. In addition to their antioxidant effects which are assumed to increase the biodisponibility of nitric oxide (NO), polyphenols have been shown to increase the formation of NO by endothelial NO synthase via increased calcium level and redox-sensitive activation of the phosphoinositide 3 (PI3)-kinase/Akt pathway. Polyphenols also (1) enhance the production of endothelium-derived hyperpolarizing factor (EDHF) and prostacyclin and (2) inhibit the synthesis of vasoconstrictors such as endothelin-1 and the angiotensin-converting enzyme , 17.Recent studies have also demonstrated beneficial effects of dark chocolate or cocoa on insulin resistance , 18–20, The effects of dark chocolate or cocoa have already being evaluated in hypertensive individuals , 10, 19.This pre-post trial was conducted at the Laboratory of Clinical and Experimental Pathophysiology, CLINEX, located at Pedro Ernesto University Hospital, of Rio de Janeiro State University. Written informed consent was obtained from all the enrolled patients. The study protocol was approved by the Human Ethics Committee of Pedro Ernesto University Hospital. The procedures followed in this study were in accordance with institutional guidelines.2 and diagnosis of stage 1 hypertension (without previous antihypertensive treatment) [Potential participants were recruited at the Department of Plastic Surgery, among the candidates for lipoplasty. Candidates for the study, underwent eligibility screening by registered dietitians. Subjects were screened according to the following criteria: age between 18 and 60 years, BMI from 25.0 to 34.9 kg/meatment) . The excOf the 550 individuals initially screened, 28 entered the run-in period. During the 2-week run-in period all cocoa foods were excluded, and potential participants were submitted to clinical, dietary, anthropometric, and biochemical evaluation. Six subjects failed to complete the run-in period, four individuals because their levels of blood pressure were not in the range of stage 1 hypertension and two because of lost of interest. So after completing the run-in period, 22 participants were included in the study and 20 completed the follow-up period (4 weeks), being included in the final analysis . The nonDuring the intervention phase (4 weeks), participants were submitted to clinical and nutritional assessment at baseline (week 0) and weeks 1, 2, 3, and 4. All participants were instructed to consume 50 g of chocolate 70% cocoa/day (containing 2135 mg polyphenols) for 4 weeks . They reα), biomarker of oxidative stress (oxidized LDL), and biomarkers of endothelial dysfunction (intracelluar adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin). Body weight, waist circumference, hip circumference were measured at baseline and at weeks 1, 2, 3, and 4. At baseline and at week 4 participants were also submitted to ambulatory blood pressure monitoring (ABPM) and evaluation of endothelial function; body composition and fasting plasma levels of circulating insulin, glucose, leptin, lipid profile  cholesterol, and low density lipoprotein (LDL) cholesterol), biomarkers of inflammation . During the intervention phase, the food records were reviewed and clarified in an interview with a nutritionist every week to assess dietary adherence. Nutrient analysis of the 3-day food record was performed using the software NutWin . Reported total energy, percent of energy from protein, fat and carbohydrate, and fiber content at the run-in phase were similar to that of the last week of the study. Subjects were carefully instructed to refrain from flavonoid-rich foods and beverages, including tea and wine; a list of these foods and beverages was given to each participant. All participants were encouraged to continue their usual physical activity throughout the study period.Height, weight, and waist and hip circumferences were measured from 08:00 to 10:00 h after a 12 h fast. Height was measured using a stadiometer accurate to ±0.5 cm, and weight was obtained with a calibrated scale, accurate to ±0.1 kg , with participants wearing light clothing and no shoes. BMI was calculated using the standard equation (kilograms per meters squared). Waist circumference was measured in the standing position, midway between the lower margin of the last rib and the iliac crest. The measurements were taken at midexhalation. Hip circumference was measured at the widest point of the hip/buttocks area with the measuring tape parallel to the floor. Waist-to-hip ratio was determined by dividing waist circumference by hip circumference. Anthropometric measurements were taken twice, and mean values were used in all analyses. Percentage of body fat was estimated by electrical bioimpedance using a Biodynamics BIA-450 body fat analyzer .μU/mL) × plasma glucose (mmol/L)/22.5 [α and IL-6 were determined by enzymatic immunometric method (TiterZyme EIA) using commercial kits . Highly sensitive CRP (hs-CRP) was determined by turbidimetry, using commercial kit . Blood samples were collected after a 12 h fasting period and were stored at −80°C. Total cholesterol, HDL cholesterol, and triglyceride concentrations were assessed by using an automated analyzer. LDL cholesterol was calculated using the Friedewald formula  when tri/L)/22.5 . The val Endothelial function was evaluated by peripheral artery tonometry (PAT) using Endo-PAT 2000 , a finger plethysmographic device that allows the isolated detection of pulsatile arterial volume changes . Endo-PAEndo-PAT consists of two finger-mounted probes, which include a system of inflatable latex air cushions within a rigid external case. The probe design allows the application of a constant and evenly distributed near-diastolic counterpressure within the entire probe, which increases sensitivity by unloading arterial wall tension and prevents venous blood pooling to avoid venoarteriolar reflex vasoconstriction. Pulsatile volume changes of the fingertip are sensed by a pressure transducer and transferred to a personal computer where the signal is band pass filtered (0.3 to 30 Hz), amplified, displayed, and stored . The EndDuring the run-in phase blood pressure was recorded by using a calibrated Dinamap 1846 Critikon automated sphygmomanometer  after a resting period of at least 10 min in the sitting position. An appropriate arm cuff was used. Arm position was adjusted so that the cuff was at the level of the right atrium. Blood pressure was measured on the nondominant arm every 3 min for 15 minutes. The first value was discarded, and the mean of the last five readings was used in the analysis. Patients were considered to have stage 1 hypertension if their systolic blood pressure levels were between 140–159 mmHg and/or diastolic blood pressure between 90–99 mmHg .At baseline (week 0) and at the end of the study (week 4) blood pressure was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) to improve the estimate of “true” blood pressure. Ambulatory blood pressure was recorded using the SpaceLabs 90207 oscillometric blood pressure monitors  calibrated against a mercury sphygmomanometer before use on each patient. Monitors were programmed to read blood pressure and heart rate every 20 min from 6:00 to 18:00 h. and every 30 min from 18:00 to 6:00 h. Mean daytime (6:00 to 18:00 h), and nighttime (18:00 to 6:00 h) blood pressure and heart rate were calculated.t-test was used when variables had normal distribution and Wilcoxon test was used for variables without normal distribution. Means ± standard errors were used to summarize continuous variables. To test the possible association of chocolate 70% cocoa intake with nutritional parameters, biochemical variables, endothelial function, and blood pressure, we compared data obtained at baseline (week 0) with data obtained at the end of the study (week 4). Paired Student's Correlation tests were conducted to determine the relationship between RHI and variables of interest. Partial correlations controlled for different confounders were also used.P < 0.05 was considered statistically significant. On the basis of a previous study , this tr2. During the run-in phase, systolic and diastolic blood pressure levels were 146.50 ± 1.28 and 93.20 ± 0.74 mmHg, respectively.  Twenty participants (10 men and 10 women) completed the study and were included in the final analysis. The average age of these patients was 44.00 ± 2.87 years, and their BMI was 31.29 ± 1.16 kg/mAs expected from the experimental design, all anthropometric parameters and the percentage of body fat remained almost unchanged after the 4 weeks of chocolate supplementation . As presThe comparative analysis of the values obtained with ABPM between week 0 and week 4 revealed no significant modifications. However, there was a small decrease in both systolic and diastolic blood pressure at 24 h, daytime and nighttime .After 4 weeks of chocolate supplementation there was a significant increase in RHI . Serum lr = −0.60; P = 0.02). Even after adjusting for confounders, this association remained significant . The confounding factors included in this analysis were age and changes during the study period in BMI, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, hs-CRP, and HOMA.An inverse and a significant association was observed between the RHI at baseline and the modification in this index during the study period  after adjusting for age and changes in BMI, HOMA, and hs-CRP. Modifications in nocturnal and 24 h blood pressure did not present significant associations with changes in RHI. The changes in RHI during the study presented a negative and significant association with the modifications in diurnal systolic and diastolic blood pressure  improved endothelial function. An improvement in endothelial function after high-polyphenol cocoa and/or dark chocolate intake was observed in several studies , 32–37. The duration of the studies varies widely: there are trials that observe acute effects  , 33–36, The participants of the clinical trials that observed improvements in endothelial function with cocoa supplementation included health individuals , 12, 37,The participants of this study presented a decrease in blood pressure levels, although without reaching statistical significance. This finding contrasts with some studies that also evaluated the effects of cocoa and/or cocoa rich chocolate in hypertensive individuals –10, 19. Desch et al. (2010)  performePossible explanations for the lack of significant reduction in blood pressure in the present study are (1) baseline levels of blood pressure, evaluated by ABPM, in our patients were lower than the levels found in others studies and (2) dose of dark chocolate was also lower , 19. RieIn the present study, the lipid profile had no significant modifications. However, some studies observed significant reductions on total and/or LDL cholesterol after the intake of dark chocolate or cocoa , 21, 22.The content of lipids in dark chocolate is high. As seen in 2). As weight loss improves endothelial function and decreases blood pressure, while weight gain has the opposite effect [All participants included in the present study had excess body weight (BMI from 25.0 to 34.9 kg/me effect –48; an iThere are several limitations in our study. One of them is the lack of a control group, which was not planned in the initial design of the study. However, the eligibility criteria of the present study were to rigorously to try to avoid confounding factors, so as seen in The findings of the present study suggest that, in individuals with stage 1 hypertension and excess body weight, the consumption of high-polyphenol dark chocolate is associated with improvements in endothelial function.


Asthma is considered a global public health issue requiring a significant medical expenditure as a result of its high prevalence and the low rate of disease control.This is the first nationwide survey of severe asthma patients carried out in Israel. In this study we aimed to assess health resources utilization, compliance with treatment and disease-control in a subgroup of patients with severe asthma in Israel.One hundred and twenty-three patients with a diagnosis of asthma for more then one year, as well as a hospitalization during the last 12 months due to asthma exacerbation or maintenance systemic steroids therapy, were included in this non-interventional observational study.Asthma was uncontrolled in 43.9%, partly controlled in 50.4% and well controlled in only 5.7%. The majority of the patients (83%) were compliant with drug treatment.The fact that 83% of the asthma patients included in this study were compliant with their asthma therapy was not manifested in asthma control. Therefore concrete tools are required for achieving and maintaining asthma control, especially in the treatment of the most severe asthmatic patients. Asthma represents a major public health concern, with increasing incidence and prevalence worldwide . Asthma Various studies indicate that the burden of illness is not necessarily associated with asthma itself but with the lack of asthma control . The unfThe aim of this survey was to assess health resources utilization, compliance with treatment and disease-control in a subgroup of patients with severe asthma in Israel.This is a non-interventional observational study based on a single patient visit conducted in 12 Israeli centers by pulmonologists, all members of the Israeli Pulmonary Society. The patients completed Hebrew-translated standard, international used questionnaires regarding asthma control, therapy compliance and quality of life, and the pulmonologists completed questionnaires with regard to severity, disease-control, comorbidities and treatment. More specifically, questionnaires were divided into five parts: 1) demographics 2) health resource utilization 3) compliance to treatment based on the standard Asthma Compliance Test , 4) levePatients above the age of 18 were included in this study after signing informed consent. Inclusion criteria were a diagnosis of asthma (based on the ATS and GINA guidelines) for more then one year together with either a hospitalization during the last 12 months due to asthma exacerbation, or maintenance systemic steroids therapy for at least 50% of the year. Total IgE level from up to 12 months before visit 1 until one month after visit 1 was obtained. All patients fulfilling inclusion criteria were asked to participate in this survey, during a 12 month period of time. Asthmatic patients who were hospitalized for reasons other than asthma, or patients with a diagnosis of COPD, were excluded from this survey. Asthma-control was assessed for every patient according to the Global Initiative for Asthma (GINA) update of 2006 ,11.This observational survey was performed according to the principles of Good Clinical Practice, the Helsinki Declaration, and national laws and regulations for clinical studies. This survey received extraordinary approval from the Israeli Ministry of Health which authorized the participation of all affiliated pulmonologists in this study based upon the approval of the Independent Ethics Committee of Kaplan Medical Center (Rehovot) and receipt of the patients’ written informed consent.Results are presented in Table Asthma-related information is presented in Table Ninety percent of the patients were treated with short-acting beta-2-agonists , 19.2% with long-acting beta-2-agonists (LABA) (formoterol preferred among other LABA), 15% inhaled corticosteroids (budesonide preferred), and 83.7% inhaled combination therapy . Other drugs included montelukast , theophylline , and omalizumab . No patient received LABA alone. The majority (68%) of the patients receiving LABA did so on-top of inhaled combination therapy while the rest (32%) were treated with separate LABA and inhaled corticosteroids. Amongst patients treated with inhaled combination therapy 87% received the maximal dose  as a maintenance therapy. The most common treatment-associated adverse events included osteoporosis, obesity, and hypertension.Visits to the emergency room, number of hospitalizations and the average hospital-stay is shown in Table This is the first nationwide survey undertaken in Israel concerning severe asthma patients. In this study we found that the majority of the patients (83%) were compliant with drug treatment. However this high self-declared compliance did not translate into asthma control. According to 2006 GINA assessment, 94.3% of patients had partially-controlled or uncontrolled asthma in this study. The median number of exacerbations within the last year was four. The results of this survey are based on questionnaires filled in by patients and physicians, and differ somewhat from the results of the telephone survey performed by Chapman et al.  in CanadThe limitations of this survey are firstly the small size of the study group. The relatively small size of the group can be explained by the restrictive inclusion criteria. It is not a general survey of asthma control in Israel but a survey of a severe asthmatic population. Moreover, as participation to this national survey was on a volunteer basis, not all the hospitals and pulmonologists, took an active part in this survey. Nevertheless we do think that this is a representative sample of the sub-population of patients with severe asthma. It should also be stressed that since there is no uniform definition of severe asthma, the results of this study are limited to the recruited population and not to all severe asthmatics. Secondly, we did not analyze the association of asthma control with other diseases, health attitudes  or treatments. The third limitation is the use of the questionnaire to assess compliance with asthma medication. The patients' questionnaires were self-administered and completed. There are more objective methods to assess compliance but as this was a non-interventional survey we used validated questionnaires. Finally it might be argued that surveying patients in hospital facilities would be biased towards including mostly uncontrolled asthma patients since such patients are more likely to require care in a hospital setting.In this survey, asthma impaired quality of life and was a major cause of hospitalizations, emergency room visits and absence from work/school. Although most patients surveyed in this study (83%) declared full treatment compliance, this overwhelming number did not translate into satisfactory disease control, as only 5.7 - 8.3% of the patients , claimed well controlled asthma. Several studies, including this survey, show that the illness burden is not only associated with the severity of the disease but mostly with the lack of asthma control. More concerted efforts in achieving and maintaining control are needed. Other treatment options for severe asthmatic patients should be considered since most of the severe patients were not well controlled.List of centers participating in this trial who recruited more then 5 patients, Name of PI (and number of patients they recruited).• Kaplan Medical Center, Rehovot, Dr. G. Fink, (30).• Shaare Zedek Medical Center, Jerusalem, Dr. G. Izbicki (15)• Barzilai Medical Center, Ashkelon, Dr. Z. Weiler (11)• Macabi and Meuhedet Sick funds, Jerusalem, Dr. A. Grossman (11)• Sheba Medical Center, Tel-Hashomer, Prof. Y. Ben-Dov (10)• Hadassah Medical Center, Jerusalem, Prof. R. Breuer (10)• Assaf Harofeh Medical Center, Zrifin, Dr. D. Stav (8)• Hillel Yaffe Medical Center, Hadera, Dr. M. Bekerman (7)• Haemek Medical Center, Afula, Dr. M. Yunis (7)• Poria Medical Center, Tiberias, Dr. C. Sismolo (5)• Three other centers recruited a total of nine patients together.The authors report no competing interests. The authors alone are responsible for the content and writing of this paper.GI and GF contributed to Conception and design of the study, acquisition, analysis and interpretation of data, drafting the manuscript and final approval. They were also involved in acquisition of funding, collecting data and general supervision. AG, ZW, TS and UL were involved in Acquisition of data, analysis and interpretation of data, significant revision of the manuscript and final approval. All authors read and approved the final manuscript.For the list of all centers participating in this survey and PI of each center see Appendix 1.The abstract was presented at the annual scientific meeting of the Israel Pulmonary Society in 2011.


Aims. The purpose of the study was to investigate the differences of adenosine, adenine, inosine, xanthine, hypoxanthine, and uric acid concentrations in patients with type 2 diabetes mellitus and diabetic retinopathy and assess the relationship between purine metabolites and disease. Materials and Methods. The study group consisted of 114 subjects which were divided into three groups: control (n = 40), type 2 diabetes without retinopathy (n = 35), and type 2 diabetes with retinopathy (n = 39). Levels of metabolites were measured in plasma of all participants. Results. There is a significant increase of levels of adenosine , inosine , xanthine , and uric acid  with diabetic retinopathy compared to diabetes mellitus. The levels of adenine, hypoxanthine, and xanthine oxidase did not change. Uric acid, xanthine, inosine, and adenosine correlated positively with systolic blood pressure and urea nitrogen. Conclusions. The levels of adenosine, inosine, uric acid, and xanthine may be useful for monitoring the progression of diabetic retinopathy and evaluating the treatment. As shown by epidemiological studies, the prevalence of type 2 diabetes has a significant rise worldwide, which resulted in an increased burden on individuals and health care systems . For diaIt is well known that purine metabolic pathway may be strongly associated with the development of diabetic microvascular complication. Adenosine is reported to play an important role in water-electrolyte metabolism, such as retinal blood flow , 12, becIn this paper, we measured six purine metabolites including adenosine, adenine, inosine, xanthine, hypoxanthine, uric acid, and xanthine oxidase (reflected by the uric acid : xanthine) in the plasma of patients with DM and DR. We also observed the relationship between the related metabolites and clinical parameters.The current study included 74 type 2 diabetes patients  in Beijing, China. Type 2 diabetes was defined in accordance with the criteria of the American Diabetes Association. Their plasma samples were collected as cases. And 40 plasma samples of healthy people  in the same area were collected as controls. Among these patients, 39 patients had a diagnosis of nonproliferative DR according to International Clinical Diabetic Macular Edema Disease Severity Scale. The DR was determined by ophthalmoscopy and fluorescein angiography through dilated pupils by a retinal specialist prior to the examination of the blood samples, and the patients were classified according to the presence or absence of DR, regardless of its degrees of severity. The other 35 patients were diagnosed to be having type II diabetes without retinopathy by clinician. And the diabetic patients with and without DR were not diagnosed to have nephropathy, neuropathy, or other microvascular or macrovascular complications.All study participants had given their informed consent, and the Institutional Ethics Committee approved the study. A complete clinical examination was conducted for all subjects. And the related information such as age and duration of diabetes and other details of diabetic therapy were recorded.2); that is, BMI = W/(H2). Blood pressure was taken in the seated position using standardized sphygmomanometers. The clinical and biochemical analyses of all the cases were carried out in 2007 and 2008. Fasting glucose was measured using hexokinase enzymatic reference method. urea nitrogen were measured using diacetyl monoxime method. Hemoglobin A1c (HbA1c), and lipid levels were measured using an automatic biochemical analyzer .The clinical and biochemical parameters of 74 patients were reviewed and approved by the Clinical Medicinal Research Institute, Sino-Japanese Friendship Hospital, Beijing, China. The diabetic duration was defined as the duration from the first diagnosis of type 2 DM to the time of blood sampling. The dates of first diagnosis of DM2 were obtained from the patients' medical records. Exclusion criteria included acute myocardial infarction, pregnancy, liver disease, stroke, current use of cholesterol lowering agents, and uncertained diabetic duration. Body mass index (BMI) was defined as weight (kg) divided by squared height  and stored at 4°C before analysis.Blood samples were collected into EDTA from 6 to 9 o'clock after an overnight fast. All blood samples were centrifuged to obtain plasma in the hospital and sent to our laboratory, where they were stored at −80°C until sample preparation. Before analysis, 800 18 column with an Alltech guard column. The column temperature was maintained at 25°C, the UV detector was set at 254 nm, and the injection volume was 20 μL. The method has been validated according to the requirement of analytical chemistry [Using high-performance liquid chromatography coupled to ultraviolet and tandem mass spectrometry method (HPLC-MS/MS), plasma concentrations of adenosine, adenine, inosine, xanthine, hypoxanthine, and uric acid were simultaneously measured. The HPLC-MS/MS includes an Applied Biosystems  API 3000 triple quadrupole tandem mass spectrometer equipped with a Turbo Ionspray interface for determination and an Agilent 1100 binary HPLC system for separation. Samples were separated on an Agilent TC-Chemistry , 20.r2 > 0.999) with limits of detection (LOD) from 10 to 50 ng/mL. The recovery for every metabolite is from 79.1% to 102.0% with the relative standard deviation (RSD) less than 10%. Intraday and interday RSD were both lower than 10%. Calibration curves suitable for the analysis of plasma were linear  of DM and BMI. The Spearman or the Pearson correlations were also examined for the research on correlations between metabolites and clinical parameters. In this study, a value of P < 0.05 was considered statistically significant. The metabolites, the levels of which have statistically significant differences between two groups of the three groups , were defined as potential biomarkers. Receiver Operating Characteristics (ROC) graph was performed.All statistical analyses were performed with SPSS statistical package . The P = 0.034) longer duration of the disease compared to DM patients without retinopathy (DM patients), (13.63 ± 2.08 years versus 10.47 ± 1.48 years). For age, BMI, fasting blood glucose, and HbA1c, the differences between the DM patients and DR patients were not statistically significant . And Lipid profiles such as total cholesterol, triglyceride, high density lipoprotein (HDL), and low density lipoprotein (LDL) of DM patients are not significantly changed compared to DR patients. For blood pressure, systolic blood pressure is significantly (P = 0.011) increased in DR patients compared with DM patients (143.07 ± 6.44 mm Hg versus 131.87 ± 4.21 mm Hg) whereas diastolic blood pressure is not changed. In addition, urea nitrogen is significantly (P < 0.001) increased in DR patients compared with DM patients (14.71 ± 3.33 mmol/L versus 8.23 ± 1.77 mmol/L).A total of 74 patients were enrolled in this study. P < 0.001; 1.01 ± 0.21 versus 0.54 ± 0.05, P = 0.009) and control group . Additionally, also, group of DM had significantly higher level of uric acid as compared to the healthy subjects . For level of uric acid : xanthine, no statistically significant differences between the groups were observed  and control group . But no statistically significant differences of levels of inosine and adenosine between the group of control and DM were observed. The concentrations of the metabolites with significant changes were shown in The levels of related purine metabolites in plasma were checked. The levels of uric acid and xanthine in the group of DR were significantly higher as compared with DM . This means that the plasma adenosine level could serve as a potential diagnostic marker for DM to DR. Plasma uric acid yielded an AUC of 0.832 with 71.3% sensitivity and 97.2% specificity in discriminating DR. Plasma xanthine yielded AUC of 0.751 with 68.2% sensitivity and 81.3% specificity in discriminating DR. Plasma inosine yielded an AUC of 0.824 with 63.7% sensitivity and 100% specificity in discriminating DR. To find an optimal cutoff point to discriminate dichotomize “diseased” or “healthy”, Youden's index was used in this study. According to Youden's index, the optimal operating point of adenosine was 0.32 mg/L. At this cutoff point, the sensitivity was 94.7% and specificity was 100%. Adenosine = 0.32 mg/L was the optimal numerical value for predicting the risk of DR in patients with type 2 diabetes.ROC curve analysis  was used to estimate the optimal numerical value of related metabolites to predict the risk of DR in patients with type 2 diabetes . As a reAt present, DR remains a major cause of blindness in the world. Many related researches have been carried out worldwide. And the researchers have reported that both genetic and environmental factors determine the susceptibility for the development of DR , 22. It P = 0.011). It demonstrated that the high level of uric acid might be a cause of microvascular complications. In addition, we found that the level of plasma uric acid correlated positively with urea nitrogen  and SBP . There was also a statistically significant difference of the level of plasma uric acid between the group of control and DR (P < 0.001), as well as the group of DM and DR (P < 0.001). The results demonstrated that uric acid might be a risk factor for DR. In addition, several lines of evidence suggest that increased plasma uric acid may be a significant risk factor of vascular disease. Ioachimescu believes that uric acid may causally/mechanistically contribute to vascular disease [As reported, serum uric acid concentration was found to be independently correlated with insulin resistance , 25. And disease . Fukui e disease . The evi disease  and incr disease . Hence, P value below 0.001. In addition, adenosine correlated positively with urea nitrogen (r = 0.568) and SBP (r = 0.336). Therefore, adenosine was supposed to be a potential biomarker for the prediction and diagnosis of diabetic retinopathy, for the guidance and evaluation of treatment. Adenosine plays an important role in water-electrolyte metabolism, such as retinal blood flow and renin release, which make the patients with diabetes be susceptible to retinopathy. For the produce of adenosine, there are two kinds of important enzymes, S-adenosylhomocysteine hydrolase and 5′-nucleotidase. The extracellular metabolism of adenosine is mediated by two mechanisms. First, via an equilibrative facilitated diffusion system, adenosine is taken up quickly and efficiently by red blood cells [In this study, compared to DM and normal group, the concentration of adenosine in the group of DR was significantly higher with od cells . Second,od cells  and intrBP r = 0.6. Therefod cells . It is sod cells .P < 0.001), as well as the group of DM and DR (P < 0.001), was presented. Therefore, xanthine may be a potential marker for monitoring the progression of DR. Xanthine acts as a substrate for xanthine oxidase and enhances superoxide generation. When xanthine oxidase converts hypoxanthine to xanthine in the presence of molecular oxygen, superoxide radicals (O2−) are released. Thereby, reactive oxygen species (ROS) is generated, which play a major role in microvascular dysfunction and exert direct tissue damage, leading to lipid peroxidation, denaturation of proteins, and oxidation of DNA [In this study, the significant difference of xanthine between the group of control and DR (n of DNA . In addin of DNA . Anothern of DNA . In thisIn summary, plasma adenosine, inosine, uric acid, and xanthine were higher in subjects with DR. Plasma levels of adenosine, inosine, uric acid, and xanthine were also significantly correlated with the urea nitrogen and SBP. The levels of these four metabolites, especially the level of adenosine, may be useful for monitoring the progression of diabetic retinopathy and evaluating the treatment.