bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indexed glomerular filtration rate as a function of age and body size
Authors: PETERS A. M. , HENDERSON B. L. , LUI D. 
Published: August 2015

The conventional way in which to scale or index a measurement of glomerular filtration rate (GFR) is to express it in relation to body surface area (BSA). However, BSA may not be appropriate for infants and children because, as individuals increase in size, their relative BSA decreases. Several other whole-body variables have been suggested as alternatives, including extracellular fluid volume (vECF). The purpose of the present study was to compare BSA and vECF as variables against which to index GFR, and in particular to look at this comparison in children versus adults. A total of 130 patients (age range 1–80 years; 40 patients < 12 years) undergoing clinically indicated routine measurement of GFR using the bolus-injection single-compartment technique were included in the study. GFR was measured as the plasma clearance of [51Cr]EDTA as assessed from three peripheral venous blood samples taken between 2 and 4 h after injection of [51Cr]EDTA. Volume of distribution (Vd) was obtained by extrapolation of the clearance curve to zero time. GFR was scaled to a BSA of 1.73 m2. GFR and GFR/1.73 m2 were corrected to account for the assumption of a single compartment. The rate constant of the exponential between 2 and 4 h was also corrected to give GFR/litre ECF. GFR and GFR/1.73 m2 were both divided by GFR/litre ECF, to give vECF and vECF/1.73 m2 respectively. Weight per unit BSA increases as a linear function of BSA. vECF is always less than Vd, on average by about 30%. vECF increased as an exponential function of BSA and as a linear function of body weight. vECF/70 kg body weight was higher in children (16.2±3 litres) than adults (13.4±2.3 litres), but vECF/1.73 m2 was lower in children (9.7±1.7 litres) compared with adults (12.4±2 litres). vECV/1.73 m2 increased as a function of both age and BSA, but vECF/kg decreased. GFR/12.5 litres vECF was higher than GFR/1.73 m2 in children, but these values were similar in adults, with the ratio of these two forms of indexed GFR falling significantly with both age and BSA. Although this was not a normal population, but one with a wide range of renal function, GFR/vECF showed a strong inverse association with age, whereas for GFR/BSA the association was weak. In conclusion, these data provide further evidence that vECF is more valid physiologically for indexing GFR than is BSA, especially in children. Nevertheless, a GFR measurement in a child should ideally be expressed as a percentage of normal for that child's age. However, such normal values are not yet available.
Non-invasive measurement of stroke volume during exercise in heart failure patients
Authors: AGOSTONI Pier Giuseppe , WASSERMAN Karlman , PEREGO Giovanni B. , GUAZZI Marco , CATTADORI Gaia , PALERMO Pietro , LAURI Gianfranco , MARENZI Giancarlo 
Published: August 2015

The objective of the present study was to determine the variability of the arterio–venous O2 concentration difference [C(a–v)O2] at anaerobic threshold and at peak oxygen uptake (VO2) during a progressively increasing cycle ergometer exercise test, with the purpose of assessing the possible error in estimating stroke volume from measurements of VO2 alone. We sampled mixed venous and systemic arterial blood every 1 min during a progressively increasing cycle ergometer exercise test and measured, in each blood sample, haemoglobin concentration and blood gas data. Ventilation, VO2 and CO2 uptake were also measured continuously. We studied 40 patients with normal haemoglobin concentrations and with stable heart failure due to ischaemic or idiopathic cardiomyopathy. Mean values (±S.D.) for C(a–v)O2 were 7.8±2.6, 13.0±2.4 and 15.0±2.7 ml/100 ml at rest, anaerobic threshold and peak VO2 respectively. The patients with heart failure were divided into classes according to their peak VO2. Classes A, B and C contained patients with peak VO2 values of > 20, 15–20 and 10–15 ml·min-1·kg-1 respectively. At anaerobic threshold, C(a–v)O2 was 12.3±1.3, 13.1±2.7 and 13.5±2.6 ml/100 ml for classes A, B and C respectively (class A significantly different from classes B and C; P < 0.05). At peak exercise C(a–v)O2 was 13.6±1.4, 15.6±2.5 and 15.4±3.2 ml/100 ml for classes A, B and C respectively (class A significantly different from classes B and C; P < 0.05). Stroke volume was estimated for each subject using the mean values of the measured C(a–v)O2 in each functional class and individual values of VO2 and heart rate using the Fick formulation. The average difference between the stroke volume estimated from mean C(a–v)O2 and that obtained using the patient's actual C(a–v)O2 value was 9.2±9.7, 1.0±8.8 and -0.2±6.1 ml at anaerobic threshold, and -1.9±11.3, 0.9±10.0 and -2.3±8.5 ml at peak exercise, in classes A, B and C respectively. Among the various classes, the most precise estimation of stroke volume was observed for class C patients. We conclude that stroke volume during exercise can be estimated with the accuracy needed for most purposes from measurement of VO2 at the anaerobic threshold and at peak exercise, and from population-estimated mean values for C(a–v)O2 in heart failure patients.
Haemodynamic and renal evolution of the bile duct-ligated rat
Authors: MARTÍNEZ-PRIETO Concepción , ORTÍZ M. Clara , FORTEPIANI Lourdes A. , RUIZ-MACIÁ Jose Antonio , ATUCHA Noemí M. , GARCÍA-ESTAÑ Joaquín 
Published: August 2015

In the present study we have characterized the evolution of changes in systemic haemodynamics (thermodilution in conscious animals) and sodium balance (metabolic cages) in a model of liver cirrhosis induced by chronic bile duct ligation (BDL). Mean arterial pressure (BDL, 111.5±4.7 mmHg; sham-operated, 122.9±3.0 mmHg) and peripheral vascular resistance (BDL, 2.63±0.08 units; sham-operated, 2.93±0.09 units) were lower in BDL rats from day 12 after surgery and decreased progressively throughout the following days. Portal hypertension was evident earlier in BDL rats and was maintained throughout the study period. Cardiac index (BDL, 58.8±3.9 ml·min-1·100 g-1; sham-operated, 43.9±1.5 ml·min-1·100 g-1) and stroke volume (BDL, 147.2±12.7 ml·beat-1·100 g-1; sham-operated, 109.0±4.2 ml·beat-1·100 g-1) were significantly elevated in the BDL rats only from day 18 after surgery. There were no significant differences in sodium balance between the groups until day 16 after surgery, at which time BDL animals started to retain significantly more sodium than the controls. Sodium retention increased progressively, and at day 20 BDL rats had retained 0.7 mmol/100 g more than the control animals (accumulated retention: BDL, 2.2±0.2 mmol/100 g; sham-operated, 1.5±0.2 mmol/100 g). Plasma renin activity and aldosterone concentration were not elevated in the BDL animals at days 12, 16 or 20 after surgery. These data indicate that the BDL rat model shows early portal hypertension, peripheral vasodilation and arterial hypotension, several days before sodium retention is detectable, and in the absence of changes in plasma levels of renin and aldosterone. Overall, these data suggest that, in the BDL rat model, sodium retention is secondary to portal hypertension and peripheral vasodilation.
Comparison of two indices for forearm noradrenaline release in humans
Authors: RONGEN Gerard A. , LENDERS Jacques W. M. , SMITS Paul , FLORAS John S. 
Published: August 2015

Although there is as yet no method which measures directly the neuronal release of noradrenaline in humans in vivo, the isotope dilution technique with [3H]noradrenaline has been applied to estimate forearm neuronal noradrenaline release into plasma. Two different equations have been developed for this purpose: one to estimate the spillover of noradrenaline into the venous effluent, and a modified formula (often referred to as the appearance rate) which may reflect more closely changes in the neuronal release of noradrenaline into the synaptic cleft, particularly during interventions that alter forearm blood flow. The present study was performed to compare the effects of two interventions known to exert contrasting actions on neuronal forearm noradrenaline release and forearm blood flow. Intra-arterial infusion of sodium nitroprusside at doses without systemic effect increases forearm blood flow, but not neuronal noradrenaline release. In contrast, lower-body negative pressure at -25 mmHg causes forearm vasoconstriction by stimulating neuronal noradrenaline release. During sodium nitroprusside infusion, forearm noradrenaline spillover increased from 1.1±0.3 to 2.2±1.0 pmol·min-1·100 ml-1 (P < 0.05), whereas the forearm noradrenaline appearance rate was unchanged. Lower-body negative pressure did not affect the forearm noradrenaline spillover rate, but increased the forearm noradrenaline appearance rate from 3.4±0.4 pmol·min-1·100 ml-1 at baseline to 5.0±0.9 pmol·min-1·100 ml-1 (P < 0.05). These results indicate that the noradrenaline appearance rate provides the better approximation of changes in forearm neuronal noradrenaline release in response to stimuli which alter local blood flow.
Vasodilator prostanoids, but not nitric oxide, may account for skeletal muscle hyperaemia in Type I diabetes mellitus
Authors: SKYRME-JONES R. Andrew P. , O'BRIEN Richard C. , MEREDITH Ian T. 
Published: August 2015

We and others have previously documented increased resting and exercise-induced skeletal muscle blood flow in young subjects with Type I (insulin-dependent) diabetes mellitus compared with healthy controls. Both NO and prostanoids are important regulators of vascular tone and may therefore contribute to this hyperaemia. The aim of the present study was to determine the contribution of NO and vasodilator prostanoids to this skeletal muscle hyperaemia in diabetes. We assessed the effects of infusion into the intrabrachial artery of the cyclo-oxygenase inhibitor acetylsalicylic acid (ASA; aspirin) and of the L-arginine analogue NG-monomethyl-L-arginine (L-NMMA) on skeletal muscle blood flow in subjects with Type I diabetes mellitus (DM subjects) and control subjects. Blood flow was measured by venous occlusion plethysmography. Isotonic forearm exercise involved 2 min of wrist flexion and extension. Resting flow (forearm blood flow; FBF) was augmented in DM subjects, as was peak exercise-related blood flow (PFBF) and the volume repaid to the forearm 5 min after exercise (AUC 5, where AUC is area under the flow–time curve) (P < 0.05), even when accounting for differences in basal flow. Infusion of L-NMMA reduced resting flow by 48% in controls (P < 0.005) and by 12% in DM subjects (not significant). L-NMMA reduced PFBF and AUC 5 by 29% (P < 0.05) and 39% (P < 0.0005) respectively in controls, but had no significant effect on these parameters in DM subjects. Infusion of ASA reduced FBF, PFBF and AUC 5 in both DM (P < 0.05) and control (P < 0.05) subjects, but the magnitude of this reduction was greater in DM than in control subjects (ANOVA, P < 0.05), even when differences in resting FBF were accounted for. Indeed, ASA eliminated the differences in FBF, PFBF and AUC 5 between DM and control subjects. Thus increased release of vasodilator prostanoids, rather than of NO, appears to account for skeletal muscle hyperaemia in Type I diabetes.
Effect of ciprofloxacin on the activation of the transcription factors nuclear factor κB, activator protein-1 and nuclear factor-interleukin-6, and interleukin-6 and interleukin-8 mRNA expression in a human endothelial cell line
Authors: GALLEY Helen F. , DHILLON Jatinder K. , PATERSON Ross L. , WEBSTER Nigel R. 
Published: August 2015

Quinolone antibiotics such as ciprofloxacin modify immune and inflammatory responses in some cells. We have shown previously that ciprofloxacin decreases the accumulation of interleukin (IL)-6 protein from a human endothelial cell line, whilst IL-8 protein production was increased. It is not known whether this occurs through effects on transcription and mRNA expression. We therefore investigated the effect of ciprofloxacin on mRNA for IL-6 and IL-8, and on three transcription factors known to be involved in the regulation of these cytokines. We investigated the effect of ciprofloxacin on tumour necrosis factor α- and IL-1β-mediated activation of the transcription factors nuclear factor κB (NFκB), activator protein-1 (AP-1) and nuclear factor IL-6 (NF-IL-6) using an electrophoretic mobility shift assay, and the effect on expression of mRNA for IL-6 and IL-8 by reverse transcriptase–PCR in the EAhy926 endothelial cell line. Ciprofloxacin decreased IL-6 mRNA (P < 0.05) and increased IL-8 mRNA (P < 0.05) expression. Ciprofloxacin did not modulate activation of NFκB or AP-1. However, NF-IL-6 binding was decreased in the presence of 100 µg/ml ciprofloxacin (P < 0.05). The study shows that ciprofloxacin-mediated decreased IL-6 release by a human endothelial cell line is reflected by decreased mRNA expression and decreased NF-IL-6 but not NFkB or AP-1 activation. Increased IL-8 mRNA in response to ciprofloxacin was not reflected by altered transcription factor activation and may represent increased mRNA stability.
Mesenteric hyporesponsiveness in cirrhotic rats with ascites: role of cGMP and K+ channels
Authors: ATUCHA Noemí M. , ORTÍZ M. Clara , FORTEPIANI Lourdes A. , NADAL Francisco Javier A. , MARTÍNEZ-PRIETO Concepción , GARCÍA-ESTAÑ Joaquín 
Published: August 2015

The mechanisms that mediate hyporesponsiveness to vasoconstrictors in liver cirrhosis are not completely established. In the present study we have explored the role of NO and potassium channels by studying the pressor response to methoxamine in rats with carbon tetrachloride-induced cirrhosis with ascites. Experiments were performed in the isolated and perfused mesenteric arterial bed of control rats and of cirrhotic rats with ascites. Pressor responses to methoxamine, an α-adrenergic agonist, were analysed under basal conditions, after inhibition of guanylate cyclase with Methylene Blue (MB; 10 µM), after inhibition of NO synthesis with NG-nitro-L-arginine (L-NNA; 100 µM) and after blockade of potassium channels with tetraethylammonium (TEA; 3 mM). Compared with those from controls, preparations from cirrhotic rats showed a lower pressor response to methoxamine (maximum: controls, 114.4±6.8 mmHg; cirrhotic rats, 74.7±7.3 mmHg). Pretreatment with MB or L-NNA increased the responses in both groups, but without correcting the lower than normal response of the cirrhotic rats. Pretreatment with TEA alone did not modify the responses as compared with the untreated groups. Pretreatment with TEA plus MB or TEA plus L-NNA also potentiated the responses, and the responses of the cirrhotic animals were greater than those of the groups treated with MB or L-NNA alone. However, no treatment completely normalized the lower response of the mesenteries from cirrhotic animals, suggesting that factors other than NO and potassium channels also participate, although to a lesser degree, in the lower pressor response of the mesenteric arterial bed of animals with cirrhosis. These results confirm that NO and potassium channels are important mediators of the lower vascular pressor response of the mesenteric bed of cirrhotic rats with ascites. This effect seems to be mediated by the NO-dependent formation of cGMP and by the NO-dependent and -independent activation of potassium channels.
Acute effects of oxygen and carbon dioxide on retinal vascular network geometry in hypertensive and normotensive subjects
Authors: CHAPMAN N. , HAIMES G. , STANTON A. V. , THOM S. A. , HUGHES A. D. 
Published: August 2015

The optimal design of vascular networks maximizes circulatory efficiency while minimizing power costs. We investigated the effects of acute changes in vascular tone on retinal arteriolar network geometry. Six hypertensive and six normotensive subjects each breathed air, 5% CO2 (with 12% O2), and 100% O2 for 5 min periods in random order. Retinal photographs were taken at the end of each test period. Bifurcation angles and arteriolar diameters were measured using operator-directed image analysis, and junction exponents were calculated. Arteriolar diameters narrowed on breathing O2. The magnitude of this change was significantly greater in normotensive than in hypertensive subjects. Angles narrowed in normotensive subjects, but not significantly in hypertensive subjects. Arteriolar diameters increased significantly on breathing CO2 in normotensive but not in hypertensive subjects, but there were no changes in angles. Despite changes in diameter, junction exponents did not change under any conditions. Vascular reactivity in the retinal arteriolar bed appears to be diminished in hypertensive subjects. The failure of junction exponents to change, despite alterations in diameter, suggests that arteriolar diameters at retinal bifurcations adhere to optimality principles when exposed to acute vasoactive stress. As vasoconstriction is associated with the narrowing of bifurcation angles, previous observations showing narrowed angles in hypertensive subjects could be explained by increased tone in the retinal arteriolar bed.
Low-frequency heart rate variability: reproducibility in cardiac transplant recipients and normal subjects
Authors: LORD S. W. , SENIOR R. R. , DAS M. , WHITTAM A. M. , MURRAY A. , MCCOMB J. M. 
Published: August 2015

Heart rate variability is a measure of autonomic nervous influence on the heart. It has been suggested that it could be used to detect autonomic reinnervation to the transplanted heart, but the reproducibility of the measurement is unknown. In the present study, 21 cardiac transplant recipients and 21 normal subjects were recruited. Three measurements of heart rate variability were performed during the day: in the morning, in the early afternoon and in the late afternoon. These tests were then repeated 1 week later and then again 1 week after that, making nine tests in all. The within-subject S.D. was 0.49 log units in normal subjects and 0.79 log units in transplant recipients. In both cases, this is about 15% of the population range. There was significant variation in heart rate variability between different times of day in both groups, and from day to day in transplant recipients. It was concluded that the reproducibility of measurements of heart rate variability is low, and that differences between measurements performed at different times of day should be interpreted with caution.
Homocysteine and thiol metabolites in vitamin B12 deficiency
Authors: RANGANATH L. R. , BAINES M. , ROBERTS N. B. 
Published: August 2015

Homocysteine metabolism is increasingly implicated in a diverse group of clinical disorders, including atheromatous vascular disease. We studied the disposition of homocysteine via the trans-sulphuration pathway, plasma glutathione peroxidase (GPx) activity and plasma levels of the sulphated hormone dehydro-epiandrosterone sulphate (DHEAS) in six vitamin B12-deficient human subjects before and after 2 weeks of vitamin B12 repletion, both in the fasting state and following an oral methionine load (0.1 g/kg body weight). Fasting plasma total homocysteine concentrations fell (P = 0.03) and total cysteine concentrations rose significantly (P = 0.048) after treatment for 2 weeks with vitamin B12 injections. The magnitude of the mean fall in the fasting concentration of homocysteine (38.8 µmol/l) was similar to the mean rise in cysteine levels (36.0 µmol/l) following vitamin B12 therapy. Circulating levels of homocysteine were increased at 4 h after a methionine load when compared with fasting levels, both before and after vitamin B12 repletion (P = 0.003 for both). Total cysteinyl-glycine was lower post-methionine than in the fasting state following vitamin B12 therapy (P = 0.007). Fasting plasma GPx fell significantly after 2 weeks of vitamin B12 therapy (P = 0.05). The change in plasma GPx between the fasting state and 4 h after methionine loading was significantly different pre- and post-vitamin B12 therapy (P = 0.05). The present study provides indirect support to the hypothesis that defects in the trans-sulphuration and remethylation of homocysteine produce hyperhomocysteinaemia in vitamin B12 deficiency in human subjects. Elevated homocysteine levels directly or indirectly may up-regulate GPx. Sulphation status, as measured by plasma DHEAS, was unchanged.
Cardiovascular regulation during head-up tilt in healthy 20–30-year-old and 70–75-year-old men
Authors: GABBETT Tim J. , WESTON Shane B. , BARRETT Rod S. , GASS Greg C. 
Published: August 2015

This study compared the heart rate, finger arterial pressure (AP) and electromyographic (EMG) activity of selected anti-gravity muscles during the initial and prolonged phases of orthostatic stress in healthy young and older men. Beat-by-beat recordings of heart rate, finger systolic pressure, diastolic pressure and mean AP were made during supine rest and 5 min of 90 ° head-up tilt (HUT) in 18 young (23±1 years) and 15 older (73±1 years) men. The EMG activity of the soleus, tibialis anterior and vastus medialis muscles was recorded. During the first 30 s following 90 ° HUT (immediate response), the young men exhibited significant (P &lt; 0.05) decreases in finger systolic pressure, diastolic pressure and mean AP, followed by a sustained increase in finger AP during the 5 min following 90 ° HUT (prolonged response). The immediate and prolonged finger AP and diastolic pressure responses were not significantly different (P &gt; 0.05) from the values at supine rest for the older men. The mean root mean square EMG activity of the soleus, tibialis anterior and vastus medialis muscles during 90 ° HUT was not significantly different (P &gt; 0.05) from that at supine rest for either group. These results demonstrate that, when compared with healthy older men, young men show larger reductions in finger AP during the initial phase of orthostatic stress. However, during the prolonged phase of orthostatic stress, older men maintain resting finger AP, whereas young men demonstrate a reflex overshoot in finger AP. Finally, differences in lower-limb anti-gravity muscle activation do not account for the contrasting finger AP responses of healthy young and older men.
Effects of oral combined hormone replacement therapy on platelet aggregation in postmenopausal women
Authors: TEEDE Helena J. , MCGRATH Barry P. , TURNER Alan , MAJEWSKI Harry 
Published: August 2015

The effects of combined oestrogen/progestin hormone replacement therapy (HRT) on platelet aggregation were studied using women on HRT or placebo. The study involved 32 postmenopausal women (aged 50–75 years) who were enrolled in a double-blind randomized controlled trial, and who received either oral continuous combined HRT (Kliogest®; 2 mg of oestradiol+1 mg of norethisterone) or placebo for a minimum of 6 months. Platelet aggregation was measured by whole-blood impedance aggregometry in response to the agonists collagen, arachidonic acid and ADP. To determine whether the effects of oestrogen on platelets were influenced by platelet-derived nitric oxide, exposure to collagen was repeated in the presence of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). Mean platelet volume was similar in the two groups. Compared with the placebo group, the women on HRT had similar rates and maximum values of platelet aggregation in response to collagen, arachidonic acid and ADP. Addition of L-NMMA did not alter the aggregation response to collagen in either the HRT or the placebo group. In conclusion, postmenopausal women on oral combined continuous HRT comprising oestradiol and norethisterone had similar whole-blood platelet aggregation rates and maximum platelet aggregation responses to higher doses of platelet agonists when compared with those on placebo. The endogenous platelet nitric oxide system did not appear to affect aggregation in either group.