Fibroblast growth factor-23 (FGF-23), a novel regulator of mineral metabolism, is markedly elevated in chronic kidney disease and has been associated with poor long-term outcomes. However, whether FGF-23 has an analogous role in acute kidney injury is unknown. The goal of this study was to measure FGF-23 levels in critically ill patients with acute kidney injury to determine whether FGF-23 levels were elevated, as in chronic kidney disease.Plasma FGF-23 and intact parathyroid hormone (PTH) levels were measured in 12 patients with acute kidney injury and 8 control subjects.p = 0.01). No correlations were observed between FGF-23 and severity of acute kidney injury (defined by the Acute Kidney Injury Network criteria); among patients with acute kidney injury, FGF-23 levels were higher in nonsurvivors than survivors  versus 544 RU/mL . Severe hyperparathyroidism (defined as intact PTH >250 mg/dL) was present in 3 of 12 (25%) of the acute kidney injury subjects versus none of the subjects without acute kidney injury, although this result did not meet statistical significance.FGF-23 levels were significantly higher in acute kidney injury cases than in critically ill subjects without acute kidney injury, with a median FGF-23 level of 1948 RU/mL (interquartile range (IQR), 437-4369) in cases compared with 252 RU/mL  in controls (We provide novel data that demonstrate that FGF-23 levels are elevated in acute kidney injury, suggesting that FGF-23 dysregulation occurs in acute kidney injury as well as chronic kidney disease. Further studies are needed to define the short- and long-term clinical effects of dysregulated mineral metabolism in acute kidney injury patients. Acute kidney injury (AKI) is the most common reason for inpatient nephrology consultation and is associated with in-hospital mortality rates of 45-70% ,2. UntilDysregulated mineral metabolism, including derangements in calcium and phosphate levels, is relatively well characterized in CKD, and correction of hypocalcemia, vitamin D deficiency, and hyperphosphatemia in CKD patients is standard-of-care -13. ThesFGF-23 is a 26-kD protein that is a novel, key regulator of phosphorus excretion and contributes to abnormal bone metabolism in CKD . FGF-23 AKI cases and non-AKI control subjects (controls) were selected from two prospective observational cohort studies conducted at a tertiary care university hospital. Cases were identified from a prospective study of all patients with AKIN Stage I AKI  admittedBaseline creatinine was defined as the lowest creatinine from the 365 days before admission until the episode of AKI for AKI subjects. For control subjects, baseline creatinine were the lowest creatinine from the 365 days before admission until hospital admission. Potential subjects with a baseline creatinine of greater than 1.1 mg/dL were excluded to eliminate subjects with underlying CKD, which would impact FGF-23 and PTH levels. Cause of AKI was determined by two nephrologists  based on chart review. Each nephrologist independently reviewed the medical record to determine the cause of AKI; there was 100% agreement between the two reviewers.Plasma samples obtained from cases and controls were immediately spun at 3000 rpm for 10 minutes and were aliquoted and stored at -80°C until biomarker measurements were made. For AKI cases, samples were obtained at regular intervals during the first week that the patient met criteria for AKI; measurements were made on the sample from the time point closest to the peak serum creatinine. For controls, measurements were made on samples obtained immediately after admission. Intact PTH measurements were made using Immulite 2000 Intact PTH assay . FGF-23 measurements were made using a C-terminal FGF-23 ELISA  according to the manufacturer's instructions. The reported calcium and phosphorus measurements were made as part of routine clinical care; the reported measurements are the closest available relative to the time of biosample collection.2 test. Continuous variables were expressed as mean ± standard deviation or median with interquartile range and were compared using the t test or the Mann-Whitney rank-sum test, where appropriate. Spearman rank correlation coefficients were used to correlate FGF-23 levels with serum phosphorus, calcium, and PTH levels. Linear regression analysis was used to examine the relationship between FGF-23 levels and AKI status, after controlling for age and severity of illness, as measured by Acute Physiology And Chronic Health Evaluation (APACHE) II score [p values < 0.05 were considered significant.Baseline characteristics of cases and controls were first compared. Categorical variables were expressed as proportions, and compared using the χII score ; becausep = 0.05) and had lower APACHE II scores . There was no statistically significant difference for in-hospital mortality rates between the two groups.The baseline demographics and clinical characteristics of the 20 subjects in this study are summarized in Table Subjects with AKI had a baseline serum creatinine of 67 ± 15 μmol/L with a peak inpatient serum creatinine of 217 ± 86 μmol/L compared with a baseline serum creatinine of 69 ± 20 μmol/L and a peak serum creatinine of 81 ± 17 in non-AKI subjects (p < 0.001 for peak levels). As noted earlier, we excluded potential study subjects with a baseline creatinine greater than 97 μmol/L to avoid patients with underlying CKD. No patient had AKI attributable to rhabdomyolysis. Eight patients had acute tubular necrosis, two patients had AKI after orthotopic liver transplantation, one had cardiorenal syndrome, and one had multifactorial AKI. Two patients had Stage I AKI by the AKIN criteria , five pap = 0.41). Serum phosphorus levels were significantly higher in AKI subjects compared with controls . The median intact PTH level was 63 mg/dL (25-75% interquartile range (IQR), 38-213) in AKI subjects and 70 mg/dL  in controls . When severe hyperparathyroidism was defined as an intact PTH >250 mg/dL, a level that has been associated with increased cardiovascular disease risk in prior studies [p = 0.24).Subjects with and without AKI had mean ionized calcium levels of 1.19 ± 0.1 mmol/L and 1.15 ± 0.08, respectively . Although serum phosphorus and FGF-23 levels were both elevated in AKI subjects, no correlation was observed between the two variables, as shown in Figure p = 0.74). There was a correlation between PTH and FGF-23 levels ; when this analysis was restricted to patients with AKI, this correlation only had borderline statistical significance , likely due to the small size of the cohort.FGF-23 levels were significantly higher in critically ill AKI cases compared with critically ill non-AKI subjects, with a median FGF-23 level of 1948 RU/mL  in AKI cases compared with 252 RU/mL  in critically ill controls (In this cross-sectional case series, we report for the first time that critically ill patients with AKI due to causes other than rhabdomyolysis have elevated FGF-23 levels compared with critically ill controls. Among patients with AKI, elevated FGF-23 levels were associated with an increased risk of death. As expected, AKI patients had, on average, higher concentrations of serum phosphorous compared with patients without AKI. In addition, a larger proportion of AKI patients had significant hyperparathyroidism compared with controls, although this result did not meet statistical significance. These results suggest that dysregulated mineral metabolism is common in AKI, analogous to CKD.Interestingly, no correlation was observed between phosphorous and FGF-23 levels in this study. Few reports have analyzed this relationship in AKI patients, although in ESRD a patient's degree of elevation in FGF-23 is often correlated with severity of hyperphosphatemia ,44,45. IElevation of FGF-23 during AKI may have several implications. In ESRD patients undergoing hemodialysis, high FGF-23 concentrations are associated with early mortality, with an increased risk as high as 600% ,38. Our There are several limitations in this study, including small sample size and relatively short follow-up time. Because FGF-23 levels were not measured repeatedly, duration of FGF-23 elevation also was unclear. Nevertheless, this is the first study to report an association between FGF-23 and non-rhabdomyolysis-related AKI, and that among patients with AKI, higher FGF-23 levels are associated with an increased risk of death. Larger and long-term studies should be conducted to clarify the impact of FGF-23 elevation among AKI patients.Dysregulated mineral metabolism is a poorly understood aspect of acute kidney injury. We demonstrated for the first time that FGF-23, a critical regulator of mineral metabolism in chronic kidney disease, is upregulated during acute kidney injury from causes other than rhabdomyolysis. Furthermore, high FGF-23 levels are associated with mortality in patients with AKI.The authors declare that they have no competing interests.MZ and RH were responsible for data analysis and manuscript preparation. CYH was responsible for study design, data analysis, and manuscript preparation. KK, EN, AC, and IA were responsible for the execution of the study, including screening and consenting eligible study subjects, data collection, data analysis, and manuscript preparation. HZ was responsible for database management and data analysis. SB was responsible for FGF-23 measurements. KNK, JS, and CSC were responsible for design of the study and manuscript preparation. KDL was responsible for study design, biomarker measurements, data analysis, and manuscript preparation.


Conclusion. The deeper hypothermia is a safe and feasible, only if it is performed by a well-trained team. DH should only be associated with a clinical trial and prospective randomized trials to validate its use.Whole-body deep hypothermia (DH) could be a new therapeutic strategy for asphyxiated newborn. This retrospective study describes how DH modified the heart rate and arterial blood pressure if compared to mild hypothermia (MH). Fourteen in DH and 17 in MH were cooled within the first six hours of life and for the following 72 hours. Hypothermia criteria were gestational age ≥36 weeks; birth weight ≥1800 g; clinical signs of moderate/severe hypoxic-ischemic encephalopathy. Rewarming was obtained in the following 6–12 hours (0.5°C/h) after cooling. Heart rates were the same between the two groups; there was statistically significant difference at the beginning of hypothermia and during rewarming. Three babies in the DH group and 2 in the MH group showed HR < 80 bpm and QTc > 520 ms. Infant submitted to deep hypothermia had not bradycardia or Qtc elongation before cooling and after rewarming. Blood pressure was significantly lower in DH compared to MH during the cooling, and peculiar was the hypotension during rewarming in DH group.  Hypoxic-ischemic encephalopathy (HIE) is a disease that induces death and severe neurological damage in newborns . HypotheAsphyxiated newborns included in the analysis were those treated with whole-body DH or MH within the first 6 hours of life and if the two following criteria were fulfilled: (1) gestational age ≥36 weeks and birth weight ≥1.800 g, with at least one of the following: (a) Apgar score ≤5 at 10 minutes; (b) endotracheal intubation or mask ventilation for more than 10 minutes after birth; (c) acidosis  within 60 minutes from birth; (2) moderate to severe encephalopathy consisting of altered state of consciousness  and ≥1 of the following signs: (a) hypotonia, (b) abnormal reflexes, including oculomotor or pupillary abnormalities, (c) absent or weak suctioning, and (d) clinical seizures [Patients were cooled by two different cooling blankets, NIG 2  and Blanketrol III . Monitoring was performed by a rectal and esophageal probe. Skin temperature was monitored on the abdominal wall with a skin probe by the radiant warmer thermal sensor or a temperature-monitoring unit . The target of the core temperature was 31°C and 33.5°C for DH and MH, respectively. Cooling was maintained between the stated targets for 72 h, and rewarming to 36.5–37°C was gradually obtained over the following 6–12 h (0.5°C/h).Arterial blood gas, coagulation, and biochemistry were daily checked and temperature corrected. Chest X rays and echocardiography  were performed at the admission. The scans were performed by 2 experienced operators. Respiratory rate, heart rate (HR), blood pressure (BP), and oxygen saturation were continuously monitored during hypothermia and rewarming. BP was measured by using standard oscillometric methods. Invasive blood pressure monitoring was not performed routinely. Only oscillometric blood pressure values were selected for analysis to reduce the bias. Standard electrocardiogram was obtained when bradycardia (HR of <80 bpm) or arrhythmia  was observed. Hypotension, defined as mean arterial blood pressure (MAP) <40 mm Hg, was, firstly, treated with single or repeated normal saline boluses (10–20 mL/kg) and subsequently by dopamine, while dobutamine was infused when the reduction of myocardial contractility was found. Dopamine or dobutamine was started at an initial dose of 5 ug/kg/min and was increased by 5 ug/kg/min up to a maximum dose of 15 ug/kg/min. Fluid intake was started at 60 to 70 mL/kg and increased by 10 to 20 mL/kg each day, based on changes in body weight and serum electrolyte levels. Clinical seizures were treated with phenobarbital . Oral topiramate was administered as neuroprotective drug at starting time of hypothermia, once a day for 3 days , 19. InhBrain magnetic resonance imaging (MRI) was planned within the first week of life. Brain lesions were classified as isolated lesions of white matter, basal ganglia, and thalamus with or without involvement of posterior limb of the internal capsule, cortex, or various combinations of the earlier lesions .t-test, Mann-Whitney test, and ANOVA; categorical variables were analyzed using Fisher exact test or χ2 analyses. A paired t-test was used to determine the effect of a single treatment. P value of ≤0.05 was considered significant.Results were shown as mean ± SD or percentage. Statistical analyses were performed using Student's P = 0.855). Perinatal and basic characteristics of the infants were not significantly different (P < 0.001) from 6 to 72 hours between the two groups (P = 0.326). Newborns did not have bradycardia before cooling and after rewarming. Heart rate decreased significantly by a mean of 11 bpm in DH and nine bpm in MH on cooling  . It is nThe adverse effects of deep cooling may be more severe in asphyxiated newborns with multiorgan dysfunction, or multiorgan dysfunction could be amplified by superimposed cold-injury syndrome , 35. In In conclusion, the present report confirms that patients under DH are also subjected to cardiovascular dysfunction. Indeed, DH patients are subject to an increased risk of hypotension both during and after hypothermia. Small sample size, retrospective data collection, BP recording method, and observational clinical markers of cardiovascular status limit the power of our conclusions. However, deep hypothermia is safe and feasible treatment only if performed by a well-trained team , 17. Whi


The complex mechanism responsible for tinnitus, a symptom highly prevalent in elderly patients, could involve an impaired control of the microcirculation of the inner ear, particularly in patients with poor blood pressure control and impaired left ventricular (LV) function.In order to define the relationship between the presence of tinnitus and the severity and clinical prognosis of mild-to-moderate chronic heart failure (CHF) in a large population of elderly patients (N = 958), a cross-sectional study was conducted with a long-term extension of the clinical follow-up. Blood pressure, echocardiographic parameters, brain natriuretic peptide (BNP), hospitalization, and mortality for CHF were measured. Multivariate logistic regression analysis was used to assess the association between the presence of tinnitus and some of the prognostic determinants of heart failure.P = .027/P = .006), reduced LV ejection fraction , and increased BNP plasma levels  in comparison to patients without symptoms. The distribution of CHF functional class was shifted toward a greater severity of the disease in patients with tinnitus. Combined one-year mortality and hospitalization for CHF (events/year) was 1.43 ± 0.2 in patients with tinnitus and 0.83 ± 0.1 in patients without tinnitus, with an adjusted hazard ratio (HR) of 0.61 : 0.37 to 0.93, P <.002).The presence of tinnitus was ascertained in 233 patients  and was associated with reduced systolic and diastolic blood pressure (123.1 ± 16/67.8 ± 9 vs 125.9 ± 15/69.7 ± 9; Our preliminary data indirectly support the hypothesis that tinnitus is associated with a worse CHF control in elderly patients and can have some important clinical implications for the early identification of patients who deserve a more aggressive management of CHF. Tinnitus is the perception of a sound that cannot be attributed to an external source. It is a nonspecific symptom generally referable to a largely unknown dysfunction of the hearing system. A comprehensive definition has been proposed  to diffeChronic heart failure (CHF) could be an ideal biological model to test the vascular disregulatory hypothesis of tinnitus since it is often associated with a reduced cardiac output, as well as with a reflex activation of vasoconstrictive systems, including the sympathetic nervous system and RAAS . The preThe main objective of the present study is two-fold: To assess the prevalence of tinnitus in a large population of elderly patients with CHF, and to define the relationship between the presence of such an ear disorder and the severity and clinical prognosis of CHFThis is a cross-sectional study with a long-term extension of the clinical follow-up. The researchers evaluated 958 consecutive elderly patients (age > 65 years) with a diagnosis of CHF (New York Heart Association (NYHA) functional class I to III) who were attending the Outpatients Clinic for Congestive Heart Failure of the Department of Medicine at the University of Bologna. CHF was diagnosed by the same two well-trained physicians according to the standard criteria proposed by the European Society of Cardiology .Exclusion criteria were: stage 3 to 5 chronic renal failure, hypoproteinemia, recent increase in diuretic dosage (less than 30 days) or diuretic dosage change during the follow-up, concomitant use of other ototoxic drugs , continuous use of fully dosed non-steroideal antinflammatory drugs (NSAIDs). NSAID use was considered as acceptable if limited to less than one dose per week and with a limited dosage .All patients underwent physical examinations and blood pressure measurements. Blood pressure was measured in the supine position after five minutes of rest, with a mercury sphygmomanometer. The systolic and diastolic blood pressure values were read to the nearest 2 mmHg. Three measurements were taken at two-minute intervals, and the average value was used to define clinical systolic and diastolic blood pressure. The presence of tinnitus was assessed by a standardized questionnaire  for categorical variables. Associations between variables were tested using Pearson's coefficient and correlation in the overall population of patients, as well as in patients with and without tinnitus. Multivariate logistic regression analysis was used to assess the association between the presence of tinnitus and some of the prognostic determinants of heart failure, including LVEF%, levels of BNP, age, and gender and presence of presbyacusis . The statistical analysis was carried out by using a SPSS statistical package .Results are expressed as mean ± standard deviation (SD). Normality of the distribution of the data was examined with the Kolmogorov-Smirnov test. Continuous variables are expressed as mean ± SD or median with interquartile range as appropriate, and categorical variables are expressed as a percentage. Data that were not normally distributed were logarithmically transformed before analysis. Comparisons among groups were made by P <.0001). The correlations between EF% and plasma BNP levels in patients with and without tinnitus are reported in Figure P <.005; patients without tinnitus: R = 0.4060, P <.001). A combination of reduced LVEF (< 45%) and BNP levels above the normal value (100 pg/mL) was observed in 31.3% (73/233) of the patients with tinnitus and in only 18.3% (133/725) of those free from symptoms. The difference achieves statistical significance (P <.003). This suggests a greater degree of systolic dysfunction in patients with tinnitus.Among the 958 patients, 530 (55.3%) were male and 428 (44.7%) female (mean age 73.9 ± 11). The presence of tinnitus was ascertained in 233 patients , while 725 patients  were symptom-free. The baseline clinical, echocardiographic, and neurohumoral characteristics of the population are reported in Table The distribution of NYHA functional class in the population of patients with CHF and tinnitus showed a rightward shift Figure  with a gThe percentages of distribution of concomitant drug treatment in the two populations of patients are reported in Table P <.002) and persisted after adjustment for major confounding prognostic factors  during the 12 months after the enrolment in the study was 1.43 ± 0.2 in patients with tinnitus and 0.83 ± 0.1 in patients without tinnitus, with a Hazard Ratio of 0.61 (95% CI: 0.37 to 0.93). The difference achieved statistical significance (P <.0001) as a consequence of the greater impairment of LV function. This could largely explain the differences in the onset of tinnitus in the different subsets of patients with CHF. The same explanation applies to the correlations between the prevalence of tinnitus and the levels of LVEF% or BNP, suggesting a close relationship between the systemic hemodynamic profile and the response of the inner ear circulation and/or the ear sensorineural pathway. This would reasonably exclude the possibility of an exclusive role of a primary sensorineural derangement in patients with CHF, since if this was the case the prevalence of tinnitus would be largely independent from the extent of LV dysfunction. In fact, the decrease in cardiac output and the associated vasoconstrictive response observed in patients with heart failure can significantly reduce the blood supply to the inner ear. This peripheral hemodynamic response cannot be compensated by a modification of arterial tone because of the peculiar characteristics of the inner ear circulation [P = NS). This reasonably excludes a primary role for depression in the onset or exacerbation of tinnitus, while the importance of such a disease as responsible for these symptoms in the overall population cannot be ruled out. On the other side, the lack of association between tinnitus and auditory thresholds in our patients could be related to the extreme variability in the entity of the hemodynamic derangement that affect the patients with heart failure and that could promote the onset of tinnitus on an ischemic and reversible basis without any major evidence of a concomitant and persistent hearing impairment. Actually, tinnitus is a spontaneous symptom that is immediately perceived without any external stimulation, whereas the perception of hearing impairment needs an external acoustic trigger. This could have increased the sensitivity of our patients toward tinnitus beyond the complaint of any hearing loss. We could also speculate about the possibility that two separate mechanisms of action might contribute to the same symptom, namely one functional (hemodynamic derangement) and the other more structural (hearing disturbance).Tinnitus affects a considerable number of adult patients, and its prevalence increases with age, with a large proportion of the elderly population affected by this common hearing disorder. The results of the present study suggest that in elderly patients with CHF, the presence of tinnitus is associated with a higher prevalence of LV dysfunction. Moreover, a large proportion of patients with tinnitus showed the combination of low levels of EF with elevated plasma levels of BNP as a measure of systolic dysfunction and cardiac overload. The one-year mortality and hospitalization for CHF was significantly increased in patients with tinnitus as an expression of a greater degree of clinical instability of the disease. From a speculative point of view, this suggests the possibility that the onset of tinnitus or the worsening in its severity may be considered as an indirect symptom of poor hemodynamic stability in elderly patients with CHF. Of course, the causal relationship between CHF and tinnitus onset or worsening has to be further investigated with more appropriate studies. In fact, tinnitus could have origins other than or concomitant to circulatory disorders, including localized cochlear disorders , hormonaculation ,12 and wThe clinical relevance of tinnitus is primarily dependent on the degree of LV dysfunction--the major responsibility for signs and symptoms of heart failure. However, the results of the logistic regression analysis support an independent role for the presence of tinnitus after adjustment for the major confounding risk factors, including any measure of LV dysfunction. The present study probably provides the first evidence of the possibility that the hearing system can be involved in the overall assessment of the clinical outcome of patients with CHF in addition to typical prognostic indicators .The use of tinnitus as a measure of severity and stability of heart failure in the elderly population could be complementary to the use of hemodynamic or biochemical markers, since it is easy to assess, does not require any blood sample or instrumental evaluation, and can be perceived by patients when other signs or symptoms of the disease have not yet developed. In particular, the observation of an increase in the relative risk of major cardiovascular events in patients with CHF and tinnitus might support the possibility that the onset of tinnitus can be considered as a useful indicator of a decline in cardiac performance well before the development of the typical manifestations of heart failure. This is supported by the higher proportion of patients treated with NSAIDs among those who complain of tinnitus (see Table As expected, the study has several limitations according to its design and the nature of the observation. First, the study was carried out exclusively in the elderly population and it is unknown if the presence of tinnitus has the same relevance in younger patients with CHF. Nevertheless, since the relationship between tinnitus and CHF appears to be mainly related to the extent of decline in LV function, we should expect a unique causative mechanism regardless of the age of the patients. Second, the enrolment of patients was based on the use of an individual questionnaire without any additional and confirmatory evaluation of the presence of tinnitus. According to the universally accepted definition, tinnitus is a perceived sound that cannot be attributed to an external source. This implies only a categorical estimate based on its presence or absence. In addition, the questionnaire provides a semiquantitative estimate of the presence of tinnitus and has been validated in a large population of patients with a different set of comorbidities where it has been demonstrated to be accurate and reproducible for the diagnosis of tinnitus -19. ThirIn our patients, microcircular dysfunction of the inner ear may generate tinnitus without having an influence on auditory thresholdsTo date, this is the first large, cross-sectional, clinical study supporting an association between tinnitus and CHF control in elderly patients. Data suggest that the onset of tinnitus might be affected by the degree of decline in LV function and is probably the consequence of an insufficient autoregulatory mechanism at the level of the circulation of the inner ear. These data can have some important clinical implications including the possibility that the onset and/or worsening of tinnitus can antedate the destabilization of CHF. This would allow for the early identification of patients who deserve a more aggressive management of heart failure or an adjustment of drug treatment, including a cautious administration of NSAIDs. If confirmed by larger prospective studies, this evidence would indirectly contribute to improve the quality of life of patients with CHF and might reduce the rate of hospitalization, as well as the huge economic burden of the management of CHF.BNP: brain natriuretic peptide; CHF: chronic heart failure (or congestive heart failure; EF: ejection fraction; LV: left ventricular; NSAIDs: non-steroideal antinflammatory drugs; NYHA: New York Heart Association; RAAS: renin-angiotensin-aldosterone system; SD: standard deviationNo author has any direct or indirect conflict of interests in the publication of this article. In particular, the study was observational and has no direct relevance for drug prescription.CB and AP had a main role in study concept and design, moreover they respectively coordinated the internal medicine and the ORL staff. ERC, ERR and MV mainly enrolled the patients and followed-up in regard to heart failure symptomology and therapy. CB and MCR executed the ORL screening. AD and AFGC mainly worked on data analysis and interpretation. All authors read and approved the final article.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/9/80/prepubQuestionnaire sent to asses the presence of tinnitus.Click here for file


To compare the effectiveness of single bolus dose of esmolol or fentanyl in attenuating the hemodynamic responses during laryngoscopy and endotracheal intubation.µg/kg intravenously slowly. Study drug was injected 3 min before induction of anesthesia. Heart rate, systemic arterial pressure and ECG were recorded as baseline and after administration of study drug at intubation and 15 min thereafter.Ninety adult ASA I and ASA II patients were included in the study who underwent elective surgical procedures. Patients were divided into three groups. Group C (control) receiving 10 ml normal saline, group E (esmolol) receiving bolus dose of esmolol 2 mg/kg and group F (fentanyl) receiving bolus dose of fentanyl 2 Reading of heart rate, blood pressure and rate pressure product were compared with baseline and among each group. The rise in heart rate was minimal in esmolol group and was highly significant. Also the rate pressure product at the time of intubation was minimal and was statistically significant rate 15 min thereafter in group E.Esmolol 2 mg/kg as a bolus done proved to be effective in attenuating rises in heart rate following laryngoscopy and intubation while the rise in blood pressure was suppressed but not abolished by bolus dose of esmolol. Stress response under anesthesia has been universally recognized phenomenon which may be in the form of endocrine or autonomic disturbance. The pressure response to laryngoscopy and endotracheal intubation in form of tachycardia, hypertension and arrhythmias may be potentially dangerous. These changes are the maximum at 1 minute after intubation and last for 5-10 min.[There is substantial evidence that, laryngoscopy and intubation is accompanied by a considerable increase in heart rate and arterial blood pressure. These changes are usually of short duration and well-tolerated by patients in the absence of cardiovascular disease or disturbed intracranial pressure homeostasis. In these conditions, an increase in blood pressure may lead to complications, including arrhythmias, myocardial ischemia, increase in intracranial pressure and rupture of cerebral aneurysms.3Various methods of attenuation of response to laryngoscopy and intubation are still in search from the date of its recognition. Several studies have been made in order to attenuate these haemodynamic response to laryngoscopy and intubation. Many drugs also have been used for the same purpose.–10Esmolol is an ultra-short acting β-1 adrenergic blocker. It has predominant effect on β-receptors and possesses no significant membrane stabilizing activity. It has rapid onset and a short duration of action.–12Fentanyl is a phenylpiperidine of the 4-amino piper dine series, structurally related to, but not derived from pethidine.The aim of this study is to do a comparative study of esmolol and fentanyl in attenuating the pressure response during laryngoscopy and intubation.After taking permission from hospital ethics committee and with the patients’ consent, we studied 90 patients of either sex weighing 35-60 kg, aged between 15-55 years were included in the study. All the patients were belonging to ASA grade I and II and were scheduled for elective surgical procedures.Patients with predicted difficult intubation, hypertension, ischemic heart disease, compensatory tachycardia, baseline pulse <60 bpm, baseline systolic B.P. <100 mm Hg, chronic obstructive airway disease, on medicines with cardiovascular effects were and excluded from the study.2, ECG were recorded before as well as after premedication. Pulse, systolic and diastolic blood pressure, oxygen saturation, were monitored continuously and recorded before premedication, after premedication and after intubation at 1, 3, 5, 15, 30, 45, 60, 75, 90 minutes and postoperatively. In group E and group F all these parameters were also recorded after drug i.e., esmolol and fentanyl, respectively.All patients were premedicated with 0.2 mg i.v. injection glycopyrrolate 10 min before surgery. Pulse, bloodpressure, SPOPatients were divided into three groups:2 and 66% N2O. Injection vecuronium was used as a muscle relaxant. Pulse, systolic and diastolic blood pressure, O2 saturation and ECG were monitored continuously and recorded at timely interval. At the end of the surgery all patients were reversed by using injection Neostigmine 0.05 mg/kg and injection glycopyrollate 8 µg/kg intravenously. Patients were then shifted to anesthesia recovery room and monitored for complications like pain, nausea, vomiting, respiratory depression, hypertension, hypotension, bradycardia, drowsiness and rigidity.After preoxygenation and 3 min after the administration of the study drug, induction was done with injection thiopentone sodium 5 mg/kg and injection suxamethonium 1.5 mg/kg. Laryngoscopy and endotracheal intubation was performed 90 second after the administration of succinylcholine. In all the groups intubation was done with Macintosh curve blade with in a period of 15 seconds. Failure to intubate in this period and difficult intubation cases were excluded from this study. After confirming the position of the ET tube and fixing it anesthesia was maintained with 33% Ot’ test was used while for comparison between groups unpaired ‘t’ test was used. Results were considered statistically significant for P values P< 0.05.For statistical analysis of data within the groups, paired Students ‘Cases were selected from different specificity . The demographical data was compared among the three groups. No statistically significant difference between the groups was observed with respect to age, gender or weight.P<0.05). Also, only in the group E, there was no significant rise at any time interval (P<0.001). These changes were significant up to 15 min postintubation [The increase in heart rate at intubation was seen in all the three groups the baseline value. But the rise was minimal in group F and group E as compared to group C, which was statistically significant (tubation .P<0.001) and significant from (P<0.05) in group F while was not significant in group E (P>0.005) [Compared with baseline value, systolic blood pressure, diastolic blood pressure and mean blood pressure were increased in all the three groups after laryngoscopy and intubation and at different time intervals. The increase in mean arterial pressure was least in group E and maximal in group C. The rise was highly significant immediately after intubation in group C (P>0.005) .P<0.001) increase in group C and group F, whereas the increase was insignificant in group E. These changes were highly significant up to 15 min postintubation (P<0.001).The changes in MAP were significant up to 15 min postintubation after which the systolic blood pressure, diastolic blood pressure and mean arterial pressure declined gradually and reached to baseline levels after 15 min of laryngoscopy and intubation in all the three groups. The RPP was calculated as the product of heart rate and systolic arterial pressure. In our study the RPP during intubation revealed a highly significant (P<0.001) increase in RPP in group F at the time of intubation and was statistically significant (P<0.01) at all the instances.While comparing group F to group E these was highly significant (2 consumption) by attenuation effects of increased adrenergic activity. This is particularly derivative in patients with IHD.[The pressure response to laryngoscopy and endotracheal intubation in form of tachycardia and hypertension occurs frequently; even α-adrenoreceptor blockade minimizes increases in heart rate and myocardial contractility (primary determinants of Owith IHD.–13More attention is given to the use of selective β-adrenergic antagonists to prevent the reflex sympathoadrenal discharge-mediated tachycardia and hypertension during procedures of laryngoscopy and endotracheal intubation and these include esmolol.Esmolol has been used in various bolus does or in an infusion form. Esmolol, 2 mg/kg, as a single bolus successfully attenuated the pressure response. There was minimal increase in heart rate than the other group but the blood pressure showed a rise although it was less than other groups after laryngoscopy and endotracheal intubation.et al. who used esmolol infusion to control hemodynamic responses associated with intubation. They found significant decreases in RPP prior to induction and postintubation the increase was 50% less in the esmolol-treated patients compared to the placebo group.[Again our study correlates with the study of Liu Philip bo group.et al. used esmolol 1-2 mg/kg and concluded that the increase in heart rate and blood pressure associated with laryngoscopy and endotracheal intubation were significantly lower in comparison to the control group.[Christopher ol group.et al. used esmolol 1 mg/kg and concluded that esmolol partially attenuated the hemodynamic response but did not abolish it completely. Esmolol in bolus doses 100 mg and 200 mg attenuates tachycardia and hypertension after tracheal intubation.[Sabahat tubation.Esmolol group did not reveal any rhythm abnormality. No ST segment changes were seen in any patients.Narcotics may block afferent nerve impulses resulting from stimulation of the pharynx and larynx during intubationFentanyl has also been used in different doses varying from 2 to 15 µg/kg to blunt haemodynamic responses to laryngoscopy and endotracheal intubation. Low doses of fentanyl, 2 µg / kg were used in our study and the efficacy was compared with esmolol group.It was found that with fentanyl, 2 µg/kg elevation of heart rate and blood pressure after intubation was lower than control group, although not statistically significant.et al. in his study concluded that 2 µg/kg fentanyl suppresses the hemodynamic response to endotracheal intubation more than the response to laryngoscopy.[Yushi ngoscopy.It was shown that supplementation of anesthetic induction with fentanyl 2 µg/kg significantly attenuated the increase in heart rate, arterial pressure and rate pressure product after laryngoscopy and intubation, and fentanyl 6 µg/kg completely abolished pressure responses.et al. who used fentanyl, 8 µg/kg in patients undergoing major vascular surgery.[Doses of fentanyl that are low enough to same little postoperative respiratory depression significantly blunt postintubation hypertension when used as adjoins to thiopental. This was demonstrated in a study conducted by Donald E. Martin  surgery.–21et al. reported apnoeic episodes in four out of seven patients who received 3.2-6.5 µg/kg fentanyl.[Low doses of fentanyl were employed because a large dose was lead to muscular rigidity, bradycardia, nausea and vomiting. Large doses may also cause postoperative respiratory depression; especially in surgery with short duration of less than 1 hour. McClain fentanyl.From the present study it is evident that both esmolol in a bolus dose of 2mg/kg and fentanyl in bolus dose of 2 µg/kg before induction of anesthesia are effective in attenuating the hemodynamic responses to laryngoscopy and endotracheal intubation like heart rate and rate pressure product.But only esmolol provided consistent and reliable protection against increases in both heart rate and systolic blood pressure accompanying laryngoscopy and endotracheal intubation.No evidence of any myocardial insult was seen in any of the patients in any group in our study.It is advisable and safe to use esmolol in patients who are prone to have exaggerated responses of cardiovascular system during laryngoscopy and intubation.


Nonsteroidal anti-inflammatory drugs (NSAIDs) may disrupt control of blood pressure in hypertensive patients and increase their risk of morbidity, mortality, and the costs of care. The objective of this study was to examine the association between incident use of NSAIDs and blood pressure in patients with hypertension.We conducted a retrospective cohort study of adult hypertensive patients to determine the effects of their first prescription for NSAID on systolic blood pressure and antihypertensive drug intensification. Data were collected from an electronic medical record serving an academic general medicine practice in Indianapolis, Indiana, USA. Using propensity scores to minimize bias, we matched a cohort of 1,340 users of NSAIDs with 1,340 users of acetaminophen. Propensity score models included covariates likely to affect blood pressure or the use of NSAIDs. The study outcomes were the mean systolic blood pressure measurement after starting NSAIDs and changes in antihypertensive therapy.Compared to patients using acetaminophen, NSAID users had a 2 mmHg increase in systolic blood pressure . Ibuprofen was associated with a 3 mmHg increase in systolic blood pressure compared to naproxen , and a 5 mmHg increase compared to celecoxib . The systolic blood pressure increase was 3 mmHg in a subgroup of patients concomitantly prescribed angiotensin converting enzyme inhibitors or calcium channel blockers and 6 mmHg among those prescribed a beta-adrenergic blocker. Blood pressure changes in patients prescribed diuretics or multiple antihypertensives were not statistically significant.Compared to acetaminophen, incident use of NSAIDs, particularly ibuprofen, is associated with a small increase in systolic blood pressure in hypertensive patients. Effects in patients prescribed diuretics or multiple antihypertensives are negligible. Cardiovascular diseases are the most common cause of death in the world, and uncThe effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the incidence of hypertension has been previously investigated-8; howevThis retrospective cohort study included adult patients who had received their first prescription for NSAID from the general medicine practice of Wishard Health Services in Indianapolis, Indiana. Wishard is a city-county health center affiliated with the Indiana University School of Medicine. The Regenstrief Medical Record System (RMRS) was used to identify eligible patients within Wishard and to collect data on relevant variables. The RMRS is an electronic medical record system that captures prescriptions, laboratory test results (including electrographic results), and other clinical data.We included incident users in order to prevent under-ascertainment of adverse effects that occur early in treatment. In thisSystolic blood pressure measurements were collected one year before and one year after the date of the first prescription for NSAID or acetaminophen. Information was collected on relevant confounders at baseline. The end date of follow-up was defined as one year after the index date or 30 days after the last dispensed prescription, whichever came first.Propensity score matching was used to prevent selection bias by balancing covariates between comparison groups. Propensity scores estimate the probability of each subject’s exposure to treatment A versus treatment B, based on measured covariates. The score combines all confounding covariates into a single composite factor. Mahalanobis metric matching without replacement was used since it produces a good balance in covariates between comparison groups,29. A caAfter covariate balance, a multiple linear regression model was used to study the effect of NSAIDs on systolic blood pressure and changes in antihypertensive therapy. The primary independent variable was the use of NSAIDs. Covariates unbalanced after propensity score matching were included in the model. Also, the model included the time from index date until blood pressure measurement, since this time occurred after the index date it could not be included in the propensity score matching. Another advantage of using a regression model is that it reduces the standard error and, hence, improves the precision of the estimate.We compared individual commonly used NSAIDs. Non-selective NSAIDs included ibuprofen and naproxen. The effects of naproxen and ibuprofen on blood pressure have not been compared in observational studies of patients using antihypertensive medications. Previous observational studies have not compared the effect of selective COX-2 inhibitors on blood pressure to non-selective NSAIDs. Since celecoxib is the only selective COX-2 inhibitor on the market, it was compared to the non-selective NSAIDs included in this study. We converted the odds ratios and related confidence intervals into relative risks using the conversion formula by Zhang and Yu. We veriBased on previous literature, the models included covariates likely to affect blood pressure or the use of NSAIDs including age, race, gender, and baseline systolic blood pressure. Baseline systolic blood pressure was defined as the last measurement before the index date. The models controlled for the presence of the following diagnoses at the index date: rheumatoid arthritis, osteoarthritis, coronary artery disease or myocardial infarction, stroke (cerebrovascular accident or transient ischemic attack), arrhythmia, asthma or chronic obstructive pulmonary disease, renal insufficiency, cirrhosis with ascites, systemic lupus erythematosus, diabetes mellitus, and congestive heart failure. We controlled for the use of medications known to increase blood pressure including venlafaxine, a high dose of oral glucocorticoids, and the use of oral contraceptives.To minimize bias introduced by variations in the time between baseline systolic blood pressure assessment and the index date and the time between the index date to the first systolic blood pressure, we included in the models indicator variables for these times and the index year. Variations in exposure to NSAID or acetaminophen were controlled by using the medication possession ratio (MPR) and the number of refills per month. The MPR assesses refill adherence and was calculated by dividing the sum of the days between the last refill and the next expected refill (i.e. days’ supply) by the number of days between the last refill and the next actual refill and then multiplied by 100. For each patient, an average MPR was calculated for the index drug. As a proxy for as-needed versus regular NSAID use, the number of refills per month was included in the model.Sensitivity analyses were conducted to assess potential variations in exposure to the index drug. In one analysis, the model included the extent of exposure as the dose-MPR interaction. In the other, the analysis was restricted to only those patients who had a blood pressure measurement within 30 days of the index date. These results did not change our conclusions. Furthermore, we examined the dose effect of NSAIDs by stratifying patients into low and high dose groups. Patients who were prescribed less than 75% of the maximum daily dose listed in Facts and Comparisons were incBaseline use of antihypertensive medications was included as covariates in the models. Five groups of antihypertensive medications were formed: beta-adrenergic antagonists, calcium channel blockers (CCBs), diuretics, angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor antagonists, and other antihypertensive medications. The MPR was used to control for adherence with antihypertensive medications.The outcomes of the study were the first and average systolic blood pressure measurements after starting NSAIDs, included as a continuous variable, and changes in antihypertensive therapy. Systolic blood pressure was assessed because it is associated with morbidity and mortality more so than diastolic blood pressure and is targeted in the treatment of hypertension. The firChanges in antihypertensive therapy post-index were considered as intensified when: (1) the dose of any currently prescribed antihypertensive medication was increased; or (2) the patient was started on a new antihypertensive medication from another class.A total of 3,928 patients prescribed NSAIDs n=2,181) or acetaminophen  met the inclusion criteria. Before matching on propensity score, many relevant baseline characteristics differed between the NSAID and acetaminophen cohorts , and ibuprofen was associated with a clinically important increase in systolic blood pressure as defined above . The absolute risk of clinically important blood pressure increase in the ibuprofen group was 20.6% and in the naproxen group it was 14.6% and the calculated number needed to harm was twelve patients.Ibuprofen was associated with a 5.9 mmHg increase in average systolic blood pressure in patients who were prescribed a beta-adrenergic blocker  compared to naproxen  and a high dose of naproxen slightly decreased in systolic blood pressure by – 3.3 mmHg .Based on their propensity scores, 113 patients prescribed celecoxib were matched to 113 patients from the ibuprofen group. A prescription for ibuprofen was associated with a 5.2 mmHg increase in the mean systolic blood pressure compared to celecoxib  .In the current study, patients receiving NSAIDs showed a 2 mmHg increase in systolic blood pressure compared to acetaminophen recipients. The systolic blood pressure increase was 3 mmHg in a sub-sample of those who were concomitantly prescribed ACE-I or CCB and 6 mmHg in those prescribed a beta-adrenergic blocker. Ibuprofen was associated with a systolic blood pressure increase, compared to both naproxen and celecoxib, of 3 and 5 mmHg, respectively. Despite these effects we did not detect significant changes in antihypertensive therapy in the NSAIDs users suggesting clinicians were not noticing these blood pressure changes that were admittedly subtle though sufficient to increase risk.Similar to the current results, previous studies reported an up to 7 mmHg increase in blood pressure in patients who were stable on beta-adrenergic antagonists and had started NSAID therapy,35. InteThe blood pressure increase we observed with NSAIDs in ACE-I users agrees with previous studies that reported a 5 to 10 mmHg increase in systolic blood pressure,18,19,23No statistically significant changes in systolic blood pressure were associated with a prescription for NSAID in patients who were prescribed multiple antihypertensive medications. This can be explained by small sample size in some of these combinations. Because some of the combinations with beta-adrenergic blockers involved only small number of patients, it is possible that this study was not powered to detect small effects.Similar to previous studies,11, the The results of the current study may have some clinical implications. Blood pressure is often poorly controlled in hypertensive patients, Our resThis study has limitations that should be considered when interpreting the results. Patients included in this study came from a single health system and may not be representative of other practices. Hence, this study should be replicated in other clinical settings. Although propensity score matching balances many covariates at baseline, unobserved covariates could still differ between the groups. Bias is a threat to the validity of these results especially when comparing NSAID and acetaminophen groups. Acetaminophen has mild pressor effects that may have dampened the relative effects of NSAID. NonetheIn conclusion, compared to acetaminophen, incident use of NSAIDs (particularly ibuprofen) is associated with a small increase in systolic blood pressure in hypertensive patients. Effects in patients prescribed diuretics or multiple antihypertensives are negligible.The author(s) declare that they have no competing interests.All authors contributed to the study idea, design, and methods. HA carried out the statistical analyses and drafted the manuscript. All authors contributed to the manuscript writing. All authors reviewed and edited the final version of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/12/93/prepub


No significant differences in pulmonary function were observed between DSGA and ESGA. The genotypic frequency of ACE I/D polymorphism was found to differ slightly between DSGA and ESGA (P = .0495). However, there were no significant differences in allelic frequency observed between DSGA and ESGA . Interestingly, the allelic  and genotypic (P = .0126) frequencies of the ACE I/D polymorphism in female patients differed significantly between DSGA and ESGA. Taken together, the results presented here indicate that the symptomatic classification of DSGA and ESGA by differentiation-syndrome in Korean asthma patients could be useful in evaluation of the pathogenesis of bronchial asthma.In this study, genetic analysis was conducted to investigate the association of angiotensin I converting enzyme (ACE) gene polymorphism with clinical phenotype based on differentiation-syndrome of bronchial asthma patients. Differentiation-syndrome is a traditional Korean medicine (TKM) theory in which patients are classified into a Deficiency Syndrome Group (DSG) and an Excess Syndrome Group (ESG) according to their symptomatic classification. For this study, 110 participants were evaluated by pulmonary function test. Among them, 39 patients were excluded because they refused genotyping. Of the remaining patients, 52 with DSG of asthma (DSGA) and 29 with ESG of asthma (ESGA), as determined by the differentiation-syndrome techniques were assessed by genetic analysis. ACE insertion/deletion (I/D) polymorphism analysis was conducted using polymerase chain reaction (PCR). Student's  Asthma is a chronic inflammatory disease characterized by airway inflammation, increased mucus production, intermittent airway obstruction, and increased responsiveness –4. The aThe ACE gene is located in the chromosome 17q23 region. Individual variability in the plasma ACE is associated with an insertion/deletion (I/D) polymorphism involving a 250-bp region situated in intron 16 of the ACE gene, which is known as the ACE I/D polymorphism . ConversTraditional Korean medicine (TKM) uses a unique diagnostic technique known as differentiation-syndrome to analyze signs and symptoms of patients. In TKM, it is possible to have various treatments for the same disease because differentiation-syndromes are based on the overall analysis of symptoms and signs, causes, nature and the location of the illness. Wu and Guo  reportedUsing differentiation-syndrome, asthma patients can be divided into two groups, the Deficiency Syndrome Group of Asthma (DSGA) and an Excess Syndrome Group of Asthma (ESGA). Deficiency refers to a deficiency of genuine Qi, lowered body resistance and declining function, including Yin and Yang-deficiency. Excess is characterized by the presence of excessive pathogenic factors that lead to an intense body reaction, or by the presence of pathological products due to the dysfunction of internal organs, such as stagnant Qi and blood, excessive fluid, retained phlegm and undigested food.This study was conducted to determine if ACE I/D polymorphism was associated with a clinical phenotype of DSGA or ESGA in asthma patients. To accomplish this, we classified asthma patients into DSGA or ESGA categories and then analyzed the patients for the presence of ACE I/D polymorphism using polymerase chain reaction (PCR).1) spontaneously or after treatment with a nebulized β2-agonist. Written informed consent was obtained from each subject and all experiments were conducted under protocols approved by the ethics review committee of the Oriental Medical Research Institute at the Kyung Hee University Medical Center.One hundred and ten asthma patients participated in this study. All patients were diagnosed between December 2001 and September 2004 at the Kyung Hee University Oriental Medical Center. The diagnosis of asthma was confirmed based on a clinical history with current clinical symptoms such as episodic wheezing, chest tightness, dyspnea, and 15% or greater reversibility of forced expiratory volume at one second (FEV1 and peak expiratory flow rate (PEF). Results are given as the percentage of the predicted values by Polgar and Morris.Pulmonary function was tested using a Vmax 22 D Sensormedix  to measure the forced vital capacity (FVC), FEVAll patients were diagnosed by TKM and then categorized into the DSGA or the ESGA. Patients were asked whether they had any of 37 symptoms relevant to the TKM diagnosis for asthma. These 37 symptoms were then arranged into seven categories of TKM patterns that each consisted of seven symptoms, with some symptoms being assigned to more than one category  13]. Ea. Ea13]. Peripheral blood samples were obtained from 81 subjects and collected in tubes containing ethylenediaminetetraacetic acid (EDTA). Genomic DNA was extracted using a DNA isolation kit for mammalian blood . The sense oligonucleotide primer used for PCR was 5′-CTG GAG ACC ACT CCC ATC CTT TCT-3′, and the antisense primer was 5′-GAT GTG GCC ATC ACA TTC GTC AGA T-3′ . Brieflyt-test, while genotypic and allelic frequencies were compared using a chi-squared test. Chi-squared and Fisher tests were also used to determine if the observed genotype frequency was in Hardy-Weinberg equilibrium. A P-value of less than .05 was considered statistically significant for all analyses.All numerical variables are reported as the mean ± standard deviation. Analyses were conducted using SAS . The differences in the asthma patient's ages and pulmonary functions were compared using a Student's All 110 patients had participated in this study. They had signed the informed consent form, tested pulmonary functions, and asked whether they had any of 37 symptoms relevant to TKM diagnosis for asthma. Of those 39 patients had refused genotyping analysis, therefore 81 patients were analyzed completely .The characteristics of the 110 patients who were participated the pulmonary function test are presented in 1 levels were 77.5 ± 24.2, 76.0 ± 23.0, and 78.3 ± 26.5 for the entire group, DSGA patients and ESGA patients, respectively. The mean PEF values were 78.3 ± 28.8, 73.7 ± 25.4, and 79.1 ± 30.6 for all asthma patients, DSGA patients and ESGA patients, respectively. None of these values differed significantly between the DSGA and ESGA patients . However, the genotypic frequency of ACE differed significantly between the ESGA and DSGA groups (P = .0445) . In addition, there were no significant differences in the allelic and genotypic frequencies of ACE of males in the ESGA and DSGA groups . However, the allelic and the genotypic frequencies of the ACE I/D polymorphism differed significantly between DSGA and ESGA females   . The all, resp.) .Bronchial asthma is influenced by many environmental and genetic factors . One of DSGA and ESGA have been extensively studied in Korea. Choi et al.  analyzedIn the present study, the clinical phenotypes of DSGA and ESGA were not associated with the pulmonary function test. Furthermore, no differences between DSGA and ESGA patients were observed when the asthmatic patients were categorized according to their distribution of ACE allelic frequencies. Consequently, based on the results of the current study, DSGA and ESGA do not appear to be related to the degree of airway obstruction. A high prevalence of ACE deletion polymorphisms were found in DSGA patients  . In addiMany other researchers and practitioners of complementary and alternative medicine including TKM doctors understand that all-inclusive diagnostic approach is essential for new perspectives and ideas to this developmental endeavor .In conclusion, the results of this study suggest that DSGA and ESGA are significant clinical phenotypes associated with the ACE polymorphisms in Korean asthma patients. In addition, these findings may provide a new approach to investigation of the etiology of asthma.


Increasing childhood obesity has become a major health threat. This cross-sectional study reports associations between schoolchildren's waist circumference (WC) and risk of elevated blood pressure.We measured height, weight, neck and waist circumference, and blood pressure in regular health examinations among children in grade 1 (ages 6-7 years) at six elementary schools in Taipei County, Taiwan. Elevated blood pressure was defined in children found to have mean systolic or diastolic blood pressure greater than or equal to the gender-, age-, and height-percentile-specific 95th-percentile blood pressure value.All 2,334 schoolchildren were examined (response rate was 100% in the six schools). The mean of systolic and diastolic blood pressure increased as WC quartiles increased (p < 0.0001). The prevalence of elevated blood pressure for boys and girls within the fourth quartile of waist circumference was 38.9% and 26.8%, respectively. In the multivariate logistic regression analyses, the adjusted odds ratios of elevated blood pressure were 1.78 , 2.45 (95% CI = 1.56-3.85), and 6.03 (95% CI = 3.59-10.1) for children in the second, third, and fourth waist circumference quartiles compared with the first quartile. The odds ratios for per-unit increase and per increase of standard deviation associated with elevated blood pressure were 1.14 (95% CI = 1.10-1.18) and 2.22 (95% CI = 1.76-2.78), respectively.Elevated blood pressure in children was associated with waist circumference. Not only is waist circumference easier to measure than blood pressure, but it also provides important information on metabolic risk. Further research is needed on effective interventions to identify and monitor children with increased waist circumference to reduce metabolic and blood pressure risks. Recent studies have shown significant increases in obesity among Asian and Caucasian children over the past 20 years -3. In TaPediatric hypertension is increasing along with the pediatric obesity epidemic. Blood pressure measurement has not been included in elementary schoolchildren's health examinations, nor have blood pressure checks been required during pediatric medical visits in Taiwan. This has led to underdiagnosis of pediatric hypertension in clinical settings .Body mass index is a common measure used to identify obesity. However, compared with body mass index, waist circumference (WC) is a better index for investigating metabolic abnormalities such as hypertension and impaired fasting glucose -7,16-24.We conducted health examinations among 7-year-old first-grade children at six public elementary schools in Taipei County, Taiwan. In 2007, 12 of 211 (5.7%) public elementary schools (enrolling 5142 students) in Taipei County cooperated with Taipei Medical University Hospital for regular health examinations. More than 95% of Taiwan's children study at public elementary schools. These 12 public elementary schools were of medium size and located in moderately urbanized areas of mixed socioeconomic status. We randomly chose six of these schools  to collected data for this study. The age and sex distribution of children in the six schools was similar to the other six schools. The gender distribution in our study (the proportion of boys was 52.16%) was similar to other studies (52.57%) conducted in Taiwan among children aged 6-7 years ,29. RecrThe numbers of first-grade children at schools A, B, C, D, E and F were 329, 642, 300, 368, 634, and 174. Teams consisting of six physicians, two dentists, nine registered nurses and three research assistants conducted these health examinations. About 103 children were excluded from analysis because their values were considered to be incorrect due to data registry error and/or incomplete anthropometric information. There were no significant differences in age or sex between children included (n = 2447) and those not included (n = 2695). This study was approved by the Research Ethics Committee of Taipei Medical University Hospital. Oral informed consent was obtained from parents of examinees.2) to calculate body mass index. The instruments  were calibrated according to standard operating prodedures before measuring for anthropometries and blood pressure.Children wearing lightweight clothing without shoes were measured for standing height  and weight  ,31. The The blood pressure measurement followed the recommendation of the Fourth Report on the Diagnosis, Evaluation and Treatment of High Blood Pressure in Children and Adolescents . In the Kruskal-Wallis tests were used to compare the means of height, weight, body mass index, neck circumference, WC, hip circumference, and blood pressure between quartiles of WC by sex. We used Chi-square tests to compare the proportion of elevated systolic blood pressure, elevated diastolic blood pressure, and elevated blood pressure between quartiles of WC circumference. Pearson's correlation coefficients were used to investigate the correlations between WC and height, neck circumference, hip circumference, body mass index, and blood pressure. Sex-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for elevated blood pressure in association with WC and hip circumference were calculated in multivariate logistic regression analysis adjusted for age, sex, operator, height, and body mass index. For further analysis, we used per-unit increase and per-standard deviation (SD) increase in hip circumference, waist-to-height ratio and body mass index to predict elevated blood pressure in the multivariate logistic regression analysis, and calculated corresponding ORs and 95% CIs. We also estimated the sex-specific sensitivity specificity, positive predictive value and negative predictive value of WC for predicting elevated blood pressure. All analyses were performed with SAS software, version 8.0 . Two-sided probability value < 0.05 was considered statistically significant.All anthropometric measurements, including height, weight, body mass index, neck circumference and hip circumference, and all measures of blood pressure, including systolic blood pressure, diastolic blood pressure, and elevated blood pressure, increased with increasing waist circumference Table .As shown in Figure In the multivariate logistic regression, elevated blood pressure was associated with quartiles, per-unit increase, and per-SD increase of WC both in girls and boys Table . The corThe best cutoff points for WC to predict elevated blood pressure for boys and girls were 59 cm  and 57 cm , respectively (not shown in the tables).This study meticulously investigated the relationship between WC and elevated blood pressure among children aged 6-7 years after adjustment for age, sex, operator, height, and body mass index. Children with elevated blood pressure had higher mean WC than those with normal blood pressure. Over a quarter of the children (26.8%) in the highest WC quartile had elevated blood pressure, revealing that high WC is a risk factor for elevated blood pressure in children aged 6-7 years.Associations between elevated blood pressure and WC have been documented among children in Mexico, Greece and the United States ,36,37. Sper se may be a useful parameter to predict elevated blood pressure independently of body mass index. Although body mass index and WC have a very high correlation coefficient and may be used interchangeably, our study found a significant association between large WC and elevated BP after adjusting for body mass index. Body mass index represented whole-body obese status, while WC was considered an indicator of central obesity or abdominal obesity. Compared with body mass index it is likely that WC is more important, because it has a greater association with metabolic syndrome and cardiovascular diseases [In contrast with another study , we foundiseases .The relation between childhood cardiovascular risk factors and metabolic syndrome is undeniable . Among cSimple anthropometric measurements are the most commonly used and practical tools for assessing body composition . WC is aIn addition, waist-to-height ratio is another index to measure abdominal obesity. Much evidence suggests waist-to-height ratio is associated with elevated blood pressure ,23,33. ICompared to WC, the association between hip circumference and elevated blood pressure was poorly understood. Previous studies associated larger hip circumference with reduced risk of elevated blood pressure in adults -27, but We have no information on family history of cardiovascular diseases, intake of sugar-added beverages, or nutritional status and lifestyle in these elementary school children. These factors are associated with childhood hypertension -44. AnotThis study showed that elevated blood pressure in children was associated with waist circumference, which is both easier to measure than blood pressure and provides important information on metabolic risk. We also found that hip circumference is as good as WC in predicting elevated blood pressure in children. This suggests the need to monitor elevated blood pressure in childhood by taking regular WC and blood pressure measurements during school health examinations. Further research is needed into the effectiveness of interventions to monitor waist circumference to reduce BP and metabolic risks in children.CI: confidence interval; OR: odds ratio; SD: standard deviation; WC: waist circumferenceThe authors declare that they have no competing interests.CSC participated in data management and interpretation, drafting the manuscript, and substantial revision of the article. WYC participated in study design, data analysis, data management and interpretation, and substantial revisions. TLC participated in the literature review, drafting the manuscript, data management, interpretation of the data, and substantial revisions. CCS participated in study design, data analysis, data management, interpretation of the data, and substantial revisions. WLC participated in study design, data analysis, data management, interpretation of the data, and substantial revisions. CCL participated in literature review, study design, data management, data analysis, interpretation of the data, drafting the manuscript and substantial revisions. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/11/613/prepub


We sought to determine if functional measures of cardiovascular reserve, in particular the anaerobic threshold , echocardiography and arterial applanation tonometry were performed.2AT) was the most significant predictor, independently  and in the multivariate logistic regression analysis . The area under the receiver-operating-characteristic curve was 0.93, based on a risk prediction model that incorporated VO2AT, body mass index and desensitization status. Neither echocardiographic nor measures of aortic compliance were significantly associated with CCU admission.There were 70 participants . 14 patients (20%) required escalation of care from the ward to CCU following transplantation. Reduced anaerobic threshold (VO2AT has the potential to predict perioperative morbidity in kidney transplant recipients.To our knowledge, this is the first prospective observational study to demonstrate the usefulness of CPET as a preoperative risk stratification tool for patients undergoing kidney transplantation. The study suggests that VO A successful kidney transplant reduces the cardiovascular mortality risk when compared with maintenance dialysis therapy and relies on survival beyond the perioperative period The main novelty of cardiopulmonary exercise testing (CPET) lies in its ability objectively to measure cardiovascular functional reserve, in contrast to other tools frequently used to assess cardiac function such as echocardiography or cardiac magnetic resonance (CMR) which focus mainly on left ventricular (LV) morphology 2AT) provide a reliable predictor of perioperative complications and mortality following major intra-abdominal surgery Several studies have demonstrated that non-invasive CPET derived measures of cardiovascular reserve, especially the anaerobic threshold (VOThe study protocol was approved by the Black Country Research Ethics Committee (REC reference number: 09/H1202/113).All patients aged 18 or over undergoing kidney transplantation at the University Hospitals Coventry and Warwickshire NHS Trust (United Kingdom) were invited to participate within 4 weeks prior to the surgery between April 2010 and June 2012. These patients had previously undergone standard kidney transplant work-up according to our center’s protocol that included clinical evaluation, chest X-ray, electrocardiogram and echocardiography. Each prospective transplant recipient was evaluated by a transplant physician and a transplant surgeon. Thallium myocardial perfusion imaging, exercise tolerance test, coronary angiography, pulmonary function test and imaging of the iliac vessels were performed selectively as determined by the clinical assessment during the work-up period. All transplant recipients were reviewed by the anesthetist 6–36 hours prior to surgery.For the purpose of this study, all recruited patients underwent the additional CPET, arterial applanation tonometry and a study-specified echocardiography within 4 weeks prior to transplantation. CPET data were not used to determine the inclusion or exclusion of prospective kidney transplant recipients. All assessments at study entry were carried out on the first non-dialysis day for living donor kidney transplant recipients who were hemodialysis dependent and prior to first antibody removal therapy with double filtration plasmapheresis (desensitization) for those who had donor kidney directed antibodies The main outcome of interest was unplanned admission to CCU due to post-operative requirement for invasive or intensive central hemodynamic monitoring allowing for accurate infusion of volume expanders or circulatory support with vasoactive drugs. Indications for this were persisting hemodynamic instability alone or hemodynamic instability in patient with sepsis. Hemodynamic instability was defined as persistently low systolic arterial blood pressure (≤85 mmHg) despite adequate blood volume expansion targeted to a central venous pressure of 10–12 mmHg and as determined by clinicians in the ward. In addition, an observation based modified early warning scoring system (MEWS) (1) A previous coronary artery disease event , (2) cerebrovascular disease (CVD: transient ischemic attack or stroke), (3) diabetes , (4) dyslipidemia (use of lipid-lowering therapy), (5) hypertension (use of antihypertensives), and (6) smoking status (ever or never). Serial 12-lead electrocardiograms were performed at study entry, during hospital admission for surgery  and at clinic visit, 60 days following transplantation. All kidney transplant recipients who were admitted to CCU were identified. Length of stay in the CCU and hospital were recorded.Baseline clinical and demographic data were recorded including weight, height, body mass index (BMI), duration of CKD and dialysis vintage. Assessment of traditional cardiovascular risk factors included a history of any of the following: 1) and full vital capacity (FVC) of the lungs were measured. Exercise testing to maximal exhaustion using cycle ergometer ramping protocol, incorporating an individualized work rate was performed. Minute ventilation (VE), oxygen consumption (VO2), carbon dioxide production (VCO2) and other associated parameters were acquired via breath-by-breath analysis . The metabolic cart was recalibrated for consecutive patients. A 12-lead electrocardiogram was recorded continuously throughout testing and during recovery. Test was terminated at maximal exhaustion, accompanied by attainment of a respiratory exchange ratio  of a value ≥1.15. VO2peak was measured as the highest VO2 achieved during the final 30 sec of peak exercise. VO2AT was determined by the V-slope method in conjunction with analyses of the ventilatory equivalents (VE/VO2 and VE/VCO2) and end-tidal gas tensions (PETO2 and PETCO2) plots Prior to exercise testing, forced expiratory volume in 1 sec  was used to evaluate arterial compliance. Aortic pulse wave-form, augmentation pressure, and augmentation index were derived by tonometric applanation of the radial artery. Using similar technique, carotid-femoral pulse wave velocity (PWV) was determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. A minimum of 3 readings were obtained for all parameters.2AT ‘cut-off’ values to predict CCU admission, ordinary and cross validated receiver operating characteristic (ROC) curves and area under curve (AUC) estimates were calculated. The optimal cut-off is estimated based on the Youden index criterion Results are expressed as mean, median or frequencies with corresponding confidence interval (CI) estimates depending on the distribution and type of the variable. Logistic regression was utilized to calculate odds ratios (ORs) with 95% CI limits for risk factors of CCU admission. Multiple (binary) logistic regression models were fitted to identify a prediction model for CCU admission. For this, risk factors which were significant in the univariate modeling (plus known confounders) were considered for the model allowing multiple predictor variables. Three different effect selection methods  were used for the multiple logistic regression modeling to evaluate the consistency of results. A p-value <0.05 was required for effect inclusion in the multivariate modeling and an effect elimination criterion of p<0.10 was chosen. To evaluate the accuracy of different VOEighty-one patients were screened for inclusion into the study and seventy individuals were included after the exclusions of eleven . Analysis of unplanned CCU admitted patients included the fourteen patients who fulfilled the study-defined indications for CCU admission. One patient who was admitted to CCU electively from theatre for a non-study indication (telemetry monitoring due to prior history of ischemic cardiomyopathy) was grouped as ‘non-CCU’.Baseline characteristics of seventy CKD patients are shown in Admission to CCU within 24 hours following transplantation was documented in twelve patients whilst two patients had escalation of care to CCU more than a week following transplantation (day 10 and day 12 respectively). Hemodynamic instability  accounted for all CCU admissions including two patients who also had sepsis (Gram negative bacteremia). 71.4% of CCU admitted patients received intravenous vasopressors whilst four patients had intra-arterial blood pressure and central venous pressure measurements to guide volume expansion without the eventual need for vasoactive drugs. There were no ischemic or arrhythmic ECG changes during the peri- and post-operative period; and at 60 days follow-up in all patients. The average duration of stay for those admitted to CCU was 3 days and this group had a longer hospital stay following transplantation  versus those that were not admitted to CCU . No major cardiovascular events  were recorded at 60 days post transplantation.). Univariate logistic regression modeling did not yield a significant association between preoperative LVEF, LV mass, LV filling pressure (diastolic compliance) or LA volume with the risk of CCU admission , oxygen pulse  and maximum work rate  (2AT was significantly lower in the CCU admitted compared to non CCU patients (p<0.001)  Table 3.2AT and CCU admission. Therefore, and because of its high reproducibility 2max, oxygen pulse and maximal work rate . 2AT, BMI and desensitization status; model-building strategies forward selection, backwards elimination and stepwise variable selection resulted in the same model. The Hosmer-Lemeshow test is not significant, indicating that there is no evidence for lack of fit in the final multiple logistic regression model . The area under the ROC curve is 0.93, indicating a very high probability of correctly classifying a randomly chosen pair consisting of a patient who requires CCU admission and a patient who does not +(−0.334×BMI)+(−2.342× Desensitization status)]. The measured values are entered for the risk variables VO2AT and BMI, whilst desensitization status is coded as either 1 (yes) or 0 (no). The predicted risk (probability) of CCU admission following kidney transplantation is calculated as odds/1+ odds.The odds of admission to CCU following kidney transplantation is calculated as 2AT univariately as a predictor yields an optimal cut-off of VO2AT = 11.31 ml/min/kg for distinguishing between the CCU admitted and non-admitted populations (Youden index J = 0.68). This translates into a sensitivity of 92.9% and a specificity of 75.0% at this cut-off point.Considering the variable VO2AT, measured preoperatively and CCU admission following kidney transplantation. In the preoperative assessment setting of major intra-abdominal surgery , three physiological CPET variables have been shown effectively to identify high risk patients: VO2AT 2peak 2) 2peak and VO2AT, with the additional measures of oxygen pulse and maximal work rate as markers of high perioperative risks  carries the strongest risk predicting strength independently  and remains significant after adjusting for age and gender  who underwent surgery had an VO2AT of less than 11 ml/min/kg in this study compared with previous studies, such as 29% in the one by Older and colleagues 2AT in other major intra-abdominal studies may not be transferable to kidney transplantation. The study also shows no associations between the static measures of cardiac function (echocardiography) or aortic compliance and perioperative risk among CKD patients. Additionally, there were no events of cardiac ischemia during the perioperative period to 60 days following surgery. The relevance of these is in keeping with the findings of a recent preoperative (kidney transplant) cardiac assessment study that demonstrated not only the low incidence of cardiac ischemia perioperatively among high cardiac risk cohort but also the lack of prognostic abilities of tools such as myocardial scintigraphy, dobutamine stress echocardiography or coronary angiogram (with subsequent revascularization if positive stress test) in reducing perioperative cardiac events In contrast with other studies In antibody incompatible transplantations, patients receive more cumulative immunosuppression treatment, including plasmapharesis and anti-thymocyte globulin ). This could be due to the fact that PWV provides information on the stiffness of the local vessels being studied rather than the systemic arterial stiffness PWV was found to be insignificant in predicting perioperative morbidity in this study Table 42 are suspended from transplantation. However, it is important to note that this study has shown that lower BMI is associated with significant perioperative morbidity after adjusting for important covariates as shown in 2peak in hemodialysis patients Many nephrologists and transplant surgeons have concerns about the higher rates of postoperative complications in overweight patients with their possible effects on survival outcomes and hence patients with BMI greater than 35 kg/m2AT is demonstrated in the risk-prediction model that included both the BMI and desensitization status  with a subsequent reduction in the perioperative risk associated with kidney transplantation or if the measure of VO2AT could improve the transplant work-up process and increase the inclusion of patients into the transplant programme, who are otherwise excluded based on current clinical criterions.Even though the design of this study was prospective, the limitation was the relatively small sample size. The study was also not powered for mortality. However, there were no deaths despite the lowest measured VO2AT, have the potential to predict perioperative morbidity in kidney transplant recipients. A further study of larger sample is required to validate the findings.This is the first prospective study to demonstrate the usefulness of CPET as a preoperative risk stratification tool for patients undergoing kidney transplantation. The study suggests that objective measures of functional cardiovascular reserve, in particular the VO