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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/S0140-6736(10)61151-8 Byline: Prabath WB Nanayakkara (a), Martina Meijboom (a), Mark HH Kramer (a), Ron A Wevers (b), Cornelis Jakobs (c) Author Affiliation: (a) Department of Internal Medicine, VU University Medical Centre, Amsterdam, The Netherlands (b) Laboratory of Metabolic Endocrine and Genetic Diseases, Department of Laboratory Medicine, Radboud University Medical Centre Nijmegen, The Netherlands (c) Metabolic Unit, Department of Clinical Chemistry, VU University Medical Centre, Amsterdam, The Netherlands

Background: Systemic hemodynamic characteristics of patients with suspected acute ischemic stroke are poorly described. The objective of this study was to identify baseline hemodynamic characteristics of emergency department (ED) patients with suspected acute stroke.Methods: This was a planned analysis of the stroke cohort from a multicenter registry of hemodynamic profiling of ED patients. The registry prospectively collected non-invasive hemodynamic measurements of patients with suspicion for acute stroke within 12h of symptom onset. K-means cluster analysis identified hemodynamic phenotypes of all suspected stroke patients, and we performed univariate hemodynamic comparisons based on final diagnoses.Results: There were 72 patients with suspected acute stroke, of whom 38 (53%) had a final diagnosis of ischemic stroke, 10 (14%) had hemorrhagic stroke, and 24 (33%) had transient ischemic attack (TIA). Analysis defined three phenotypic clusters based on low or normal cardiac index (CI) and normal or high systemic vascular resistance index (SVRI). Patients with TIA had lower mean CI (2.3L/min/m2) compared to hemorrhagic or ischemic stroke patients (p<0.01).Conclusions: The study demonstrates the feasibility of defining hemodynamic phenotypes of ED patients with suspected stroke. [ABSTRACT FROM AUTHOR]

Background: There is little known about the baseline hemodynamic (HD) profiles (beyond pulse/blood pressure) of patients presenting to the Emergency department (ED) with acute heart failure (AHF). Assessing these baseline parameters could help differentiate underlying HD phenotypes which could be used to develop specific phenotypic specific approaches to patient care.Methods: Patients with suspected AHF were enrolled in the PREMIUM (Prognostic Hemodynamic Profiling in the Acutely Ill Emergency Department Patient) multinational registry and continuous HD monitoring was initiated on ED presentation using noninvasive finger cuff technology (Nexfin, BMEYE, Edwards Lifesciences, Irvine, California). Individuals with clinically suspected and later confirmed AHF were included in this analysis and initial 15minute averages for available HD parameters were calculated. K-means clustering was performed to identify out of 23 HD variables a set that provided the greatest level of inter-cluster discrimination and intra-cluster cohesions.Results: A total of 127 patients had confirmed AHF. The final model, using mean normalized patient baseline HD values was able to differentiate these individuals into 3 distinct phenotypes. Cluster 1: normal cardiac index (CCI) and systemic vascular resistance index (SVRI); cluster 2: very low CI and markedly increased SVRI: and cluster 3: low CI and an elevated SVRI. These clusters were not differentiated using clinically available ED information.Conclusions: Three distinct clusters were defined using novel noninvasive presenting HD monitoring technology in this cohort of ED AHF patients. Further studies are needed to determine whether phenotypic specific therapies based on these clusters can improve outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To derive distinct clusters of septic emergency department (ED) patients based on their presenting noninvasive hemodynamic (HD) measurements and to determine if any clinical parameters could identify these groups.Methods: Prospective, observational, convenience study of individuals with confirmed systemic infection. Presenting, pretreatment noninvasive HD parameters were compiled using Nexfin (Bmeye/Edwards LifeSciences) from 127 cases. Based on normalized parameters, k-means clustering was performed to identify a set of variables providing the greatest level of intercluster discrimination and intracluster cohesion.Results: Our best HD clustering model used 2 parameters: the cardiac index (CI [L/min per square meter]) and systemic vascular resistance index (SVRI [dynes·s/cm5 per square meter]). Using this model, 3 different patient clusters were identified. Cluster 1 had high CI with normal SVRI (CI, 4.03 ± 0.61; SVRI, 1655.20 ± 348.08); cluster 2 low CI with increased vascular tone (CI, 2.50 ± 0.50; SVRI, 2600.83 ± 576.81); and cluster 3 very low CI with markedly elevated SVRI (CI, 1.37 ± 0.81; SVRI, 5951.49 ± 1480.16). Cluster 1 patients had the lowest 30-day overall mortality. Among clinically relevant variables available during the initial patient evaluation in the ED age, heart rate and temperature were significantly different across the 3 clusters.Conclusions: Emergency department patients with confirmed sepsis had 3 distinct cluster groupings based on their presenting noninvasively derived CI and SVRI. Further clinical studies evaluating the effect of early cluster-specific therapeutic interventions are needed to determine if there are outcome benefits of ED HD phenotyping in these patients. [ABSTRACT FROM AUTHOR]

Background: Low serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with insulin resistance, the metabolic syndrome, and type 2 diabetes. Because many non-Western immigrants in the Netherlands are vitamin D deficient, obese, and at high risk of diabetes, vitamin D supplementation may contribute to prevent diabetes and insulin resistance. Objective: We examined the effect of vitamin D supplementation on insulin sensitivity and β cell function in overweight, vitamin D-deficient, non-Western immigrants at high risk of diabetes. Design: The study was a 16-wk, randomized, placebo-controlled trial. A total of 130 non-Western immigrants with prediabetes (fasting glucose concentration >5.5 mmol/L or random glucose concentration from 7.8 to 11.1 mmol/L) and vitamin D deficiency (serum 25[OH]D concentration <50 nmol/L) were randomly assigned after stratification by sex to receive either cholecalciferol (1200 IU/d) or a placebo for 16 wk. All participants received 500 mg Ca/d as calcium carbonate. The primary outcome was the difference in the area under the curve of insulin and glucose after a 75-g oral-glucose-tolerance test after 4 mo of treatment. Secondary outcomes were insulin-sensitivity variables, β cell-function variables, and metabolic syndrome. Results: Mean serum 25(OH)D concentrations increased significantly in the vitamin D compared with placebo groups. After 4 mo of therapy, the mean between-group difference was 38 nmol/L (95% CI: 32.1, 43.9 nmol/L; P < 0.001). There was no significant effect on insulin sensitivity and β cell function. In a post hoc analysis, when patients with diabetes at baseline were excluded, a significant increase in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L (P = 0.040). Conclusions: Vitamin D supplementation in non-Western vitamin D-deficient immigrants with prediabetes did not improve insulin sensitivity or β cell function or change the incidence of metabolic syndrome. However, after the exclusion of diabetic subjects, an improvement in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L. [ABSTRACT FROM AUTHOR]

Abstract: The Active Straight Leg Raise (ASLR) is an important test in diagnosing pelvic girdle pain (PGP). It is difficult to understand what happens normally during the ASLR, let alone why it would be impaired in PGP. In the present study, healthy subjects performed the ASLR under normal conditions, with weight added above the ankle, and while wearing a pelvic belt. Activity of the abdominal muscles, rectus femoris (RF), and biceps femoris (BF) was recorded with surface electromyography (EMG), and transversus abdominis (TA) with fine wire EMG. RF was ipsilaterally active, BF contralaterally, and the abdominal muscles bilaterally. All muscle activity was higher with weight, and abdominal muscle activity was lower with the pelvic belt. In both these conditions, TA and obliquus abdominis internus (OI) were more asymmetrically active than obliquus externus. The abdominal muscles engage in multitasking, combining symmetric and asymmetric task components. Hip flexion causes an unwanted forward pull on the ipsilateral ilium, which is counteracted by contralateral BF activity. To transfer this contralateral force toward ipsilateral, the lateral abdominal muscles press the ilia against the sacrum (“force closure”). Thus, problems with the ASLR may derive from problems with force closure. Also abdominal wall activity counteracts forward rotation of the ilium. Moreover, contralateral BF activity causes transverse plane rotation of the pelvis, often visible as an upward movement of the contralateral anterior superior iliac spine. Such transverse plane rotation is countered by ipsilateral TA and OI. The present study facilitates the understanding of what normally happens during the ASLR. [Copyright &y& Elsevier]

Background: Chronic kidney disease (CKD) is associated with an increased incidence of cardiovascular disease (CVD). The Anti-oxidant Therapy In Chronic Renal Insufficiency (ATIC) Study showed that a multistep treatment strategy improved carotid intima-media thickness, endothelial function, and microalbuminuria in patients with stages 2 to 4 CKD. Increased plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been linked to greater CVD risk in patients with CKD. The aim of this study is to assess effects of the multistep intervention on plasma ADMA concentrations in the ATIC Study.Study Design: Secondary analysis of a randomized double-blind placebo-controlled trial.Setting& Participants: 93 patients with creatinine clearance of 15 to 70 mL/min/1.73 m(2) (according to the Cockcroft-Gault equation) from 7 outpatient clinics in Amsterdam, The Netherlands.Intervention: The treatment group received sequential treatment consisting of pravastatin, 40 mg/d. After 6 months, vitamin E, 300 mg/d, was added, and after another 6 months, homocysteine-lowering therapy (folic acid, 5 mg/d; pyridoxine, 100 mg/d; and vitamin B(12), 1 mg/d, all in 1 tablet) were added and continued for another year. The control group received matching placebos.Outcome& Measures: Plasma ADMA levels.Results: 36 participants (77%) in the treatment group and 38 (83%) in the placebo group completed the study. Mean ADMA and symmetric dimethylarginine concentrations in the total study population were 0.53 +/- 0.07 (SD) and 1.14 +/- 0.46 mumol/L, respectively. After 24 months, there was no overall effect of the treatment strategy on ADMA concentrations (beta = -0.006; P = 0.27). Analysis of separate treatment effects suggested that vitamin E significantly decreased ADMA levels by 4% in the treatment group compared with the placebo group (multiple adjusted P = 0.02).Limitations: The study was a secondary analysis, power calculation was based on the primary end point of carotid intima-media thickness, mean plasma ADMA levels were relatively low.Conclusion: Overall, a multistep treatment strategy consisting of pravastatin, vitamin E, and B vitamins had no effect on plasma ADMA levels in a stage 2 to 4 CKD population. This suggests that the beneficial effects of the intervention were not mediated by changes in ADMA levels. Possible ADMA-lowering effects of vitamin E deserve further attention. [ABSTRACT FROM AUTHOR]

Background: Patients with renal insufficiency have an increased risk of cardiovascular disease that is not fully explained by the presence of known cardiovascular risk factors. In patients with end-stage renal disease, increased serum concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), has been linked to excess cardiovascular morbidity. We investigated, in patients with mild-to-moderate renal failure, the relationship between plasma ADMA and three surrogate markers of atherosclerosis that have been shown to have prognostic value, namely carotid intima-media thickness (IMT), plasma soluble vascular cell adhesion molecule-1 (sVCAM-1), and plasma C-reactive protein (CRP). Methods: We used baseline data of an ongoing randomized trial in which the effects of oxidative stress-lowering treatment on vascular function and structure are studied in patients with chronic nondiabetic renal failure without clinical evidence of atherosclerosis (GFR 15 to 70 mL/min/per 1.73 m(2) according to the Cockcroft-Gault equation; ATIC study). Results: Data from 93 patients were used. Creatinine clearance was inversely related to plasma ADMA concentration (standardized beta after adjustment = -0.342, P = 0.023). Plasma ADMA was strongly related to carotid IMT in univariate (beta = 0.459, P < 0.0001) and multivariate analysis (beta= 0.444, P < 0.0001). Plasma ADMA was also significantly related with plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) in univariate (beta = 0.260, P = 0.010) and multivariate (beta = 0.242, P = 0.022) analysis. Plasma ADMA was not significantly related to C-reactive protein (beta = -0.134, P = 0.204). Conclusion: In patients with mild-to-moderate renal failure, renal function is inversely associated with plasma ADMA, which, in turn, is positively associated with carotid IMT and plasma sVCAM-1 concentration. Increased plasma ADMA may be a link between renal function and cardiovascular disease in patients with mild-to-moderate renal failure. [ABSTRACT FROM AUTHOR]

Abstract: Women with pregnancy-related pelvic girdle pain (PPP), or athletes with groin pain, may have trouble with the active straight leg raise (ASLR), for which a pelvic belt can be beneficial. How the problems emerge, or how the belt works, remains insufficiently understood. We assessed muscle activity during ASLR, and how it changes with a pelvic belt. Healthy nulligravidae (N=17) performed the ASLR, and walked on a treadmill at increasing speeds, without and with a belt. Fine-wire electromyography (EMG) was used to record activity of the mm. psoas, iliacus and transversus abdominis, while other hip and trunk muscles were recorded with surface EMG. In ASLR, all muscles were active. In both tasks, transverse and oblique abdominal muscles were less active with the belt. In ASLR, there was more activity of the contralateral m. biceps femoris, and in treadmill walking of the m. gluteus maximus in conditions with a belt. For our interpretation, we take our starting point in the fact that hip flexors exert a forward rotating torque on the ilium. Apparently, the abdominal wall was active to prevent such forward rotation. If transverse and oblique abdominal muscles press the ilia against the sacrum (Snijders’ “force closure”), the pelvis may move as one unit in the sagittal plane, and also contralateral hip extensor activity will stabilize the ipsilateral ilium. The fact that transverse and oblique abdominal muscles were less active in conditions with a pelvic belt suggests that the belt provides such “force closure”, thus confirming Snijders’ theory. [Copyright &y& Elsevier]

This randomised double-blind, placebo-controlled, clinical trial investigated the effect of 3 months of treatment with calcium dobesilate on endothelium-dependent vasodilation, markers of endothelial function, blood pressure, and markers of oxidation in obese, male smokers. Vascular effects may depend on the type of vessel and we, therefore, investigated both smaller arteries, i.e. resistance arteries and small arterioles, and large conduit arteries. Vascular function was measured by acetylcholine- and sodium-nitroprusside-mediated vasodilation, and capillary recruitment, in the skin microcirculation; by forearm blood flow (FBF) responses to several agonists and to N-G-monomethyl l-arginine (l-NMMA) in the forearm vascular bed; by flow-mediated vasodilation in the brachial artery; and by determination of soluble levels of vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1) and E-selectin. Twenty-eight individuals received dobesilate and 24 placebo. No effect of calcium dobesilate on endothelial function, blood pressure or markers of oxidation was observed compared with placebo. The difference in acetylcholine-mediated vasodilation in the microcirculation was −52.1%-point (95% confidence interval −132.8 to 28.1); in sodium-nitroprusside-mediated vasodilation in the microcirculation, 2.6%-point (−95.1 to 100.2); in capillary recruitment, 2.5%-point (−6.8 to 11.7); in acetylcholine-induced increases in FBF (n=28), 23%-point (−173 to 126); in l-NMMA-induced reduction of basal FBF, −2.8%-point (−29.3 to 23.8); in flow-mediated vasodilation of the brachial artery, 0.3%-points (−2.7 to 3.3); in 24-h systolic blood pressure, 2.1 mmHg (−1.3 to 5.5); in soluble VCAM-1, 54 ng/ml (−8 to 115); in soluble ICAM-1, 9 ng/ml (−49 to 67); in sE-selectin, −17 ng/ml (−44 to 11); in ketocholesterol 5 nM (−17 to 26); and in oxidised LDL −1.6 U/l (−6.7 to 3.5). We have shown that endothelial function, blood pressure, and markers of oxidation were not affected by 3 months of treatment with calcium dobesilate in mildly obese, smoking men. Thus, our data provide no evidence of an effect on vascular function of calcium dobesilate in humans. [Copyright &y& Elsevier]