Standard Error Of The Difference Research Articles

Distribution-based criteria for change in health-related quality of life in Parkinson's disease

Background and objective To be useful, results from health-related quality of life (HRQoL) measures must be interpretable. The objective of this article is to examine statistical (distributional) approaches to interpretability. The standard error of measurement (SEM) and the standard error of the difference (Sdiff) are used in data on individuals with Parkinson's disease to calculate the minimum change scores required to be statistically meaningful for each dimension of an instrument to assess HRQoL in Parkinson's disease, the PDQ-39. Methods Data was collected from both a community and a clinic study; in both studies the PDQ-39 was administered at baseline and follow-up. Results The patterns of SEMs and Sdiffs were similar both across time periods and between samples, for all dimensions except Social Support. Conclusions The results suggest that, for example, six points change on a 0–100 transformed scoring of the Mobility dimension may be considered on distributional grounds a minimum meaningful change. The demonstrated consistency across occasions and types of sample of SEMs and Sdiff for the majority of the dimensions of the PDQ-39, is evidence of the theoretically claimed advantage of this measure of sample independence, and supports use of this distributional approach to minimum meaningful change.

Microphysical cross validation of spaceborne radar and ground polarimetric radar

Ground-based polarimetric radar observations along the beam path of the Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR), matched in resolution volume and aligned to PR measurements, are used to estimate the parameters of a gamma raindrop size distribution (RSD) model along the radar beam in the presence of rain. The PR operates at 13.8 GHz, and its signal returns can undergo significant attenuation due to rain, which requires compensation to adequately assess the rain rate. The current PR algorithm used for attenuation correction of the reflectivity is cross-validated using ground-based dual-polarization radar measurements. Data from the Texas and Florida Underflights (TEFLUN-B) campaign and TRMM Large-scale Biosphere Atmosphere (LBA) experiment are used in the analysis. The statistical behavior of the raindrop size distribution parameters are presented along the vertical profile through the rain layer, which is used to evaluate the PR attenuation correction and rainfall algorithms. The PR rain rate estimates are compared to ground radar estimates. The standard error of the difference between the rainfall estimates from PR and ground radar was within the error of the rainfall estimates from the two instruments. Though no systematic differences between PR attenuation-corrected reflectivity and ground radar reflectivity measurements are observed, there may exist some undercorrection and overcorrection on a beam-by-beam basis. Comparison of the normalized reflectivity versus rainfall relation between PR and ground polarimetric radar is also presented.

Effects of different transition diets on energy balance, blood metabolites and reproductive performance in dairy cows

The objective of this study was to evaluate the effect of diets differing in energy density (ED) in the last 4 weeks of the dry period and in the first 8 weeks of lactation on energy balance (EB), blood metabolites and reproductive performance. Three diets (grass silage:straw 75:25 on a dry matter basis (SS), grass silage (S) and grass silage+3 kg/day of concentrates (C)) pre-calving and two diets (4 kg (LC) or 8 kg/day of concentrates (HC)+grass silage ad libitum) post-calving were combined in a 3×2 factorial design. Sixty second-lactation Holstein–Friesian cows were blocked according to expected calving date and body condition score into groups of six and were then allocated at random to the treatments. Individual feeding started on average 34 days prior to parturition and measurements were made until the end of the 8th week of lactation. Net energy (NE) intake increased (5.6, 6.5 and 9.0 UFL/cow per day; (standard error of the difference (S.E.D.)=0.22) and EB improved pre-calving as the ED of the diet increased. Post-calving, milk energy output was significantly different between pre-calving treatments at 10.5, 11.6 and 12.7 UFL/day (S.E.D.=0.48) for SS, S and C respectively. Cows on the highest ED diet pre-calving (C) had a greater degree of negative energy balance (NEB) than cows on the lowest ED diet pre-calving (SS) for 7 of the first 8 weeks of lactation. At calving, cows on C had a lower plasma urea concentration than those on S and cows on SS had a lower plasma bile acid concentration than those on S. At week 2 post-calving, C had a higher plasma β-hydroxybutyrate concentration than SS and a higher plasma protein concentration than SS or S. Post-calving, cows receiving HC had higher NE intakes averaged over the first 8 weeks of lactation and lower NEB in each of the first 8 weeks of lactation than those on LC. Plasma glucose and bile acid concentrations were higher on HC compared to LC at week 2 post-calving. Plasma urea concentrations were lower ( P<0.05) on HC compared to LC.

Influence of Number of Surfaces and Observers on Statistical Power in a Multiobserver ROC Radiographic Caries Detection Study

The aim of the study was to evaluate the influence of the number of surfaces (N_surf) and the number of observers (N_obs) on the statistical power of a study comparing the diagnostic accuracies of radiographic systems used for approximal caries lesion detection. A data set consisting of 338 surfaces examined by 10 independent observers using four radiographic systems was available. The presence of a caries lesion was assessed from a 5-point confidence scale. The true lesion diagnosis was established by histological validation. ROC curve areas (A_zs) were used to express the diagnostic accuracy of the observers with the radiographic systems. Assuming that the A_zs were tested by a two-way analysis of variance, we performed a simulation study in order to evaluate how the power of this statistical analysis depended on N_surf and N_obs. As a measure of the statistical power we used the standard error of the difference between the expected A_zs of two systems. The simulations were made with N_surf in the range from 25 to 338 and N_obsfrom 2 to 10. The simulations showed that the power increased as a function of the total number of evaluations per system (N_surf× N_obs), but how this number was attained in relation to the number of surfaces and observers had only marginal influence on the power. Thus, from a statistical point of view it may be concluded, provided that data are analyzed by a two-way analysis of variance, that study designs for comparing the accuracy of several systems can be composed freely in relation to the number of surfaces and observers as long as the total number of evaluations per system are identical.

Phthalate and alkyl phenol concentrations in soil following applications of inorganic fertiliser or sewage sludge to pasture and potential rates of ingestion by grazing ruminants.

Soil concentrations of dioctyl phthalate (DOP) and the alkyl phenols, octyl phenol (OP) and nonyl phenol (NP), after repeated surface applications of sewage sludge to pastures, were investigated. Liquid sludge was applied at a rate of 2.25 tonnes dry matter (DM) per hectare to each of three treated (T) plots on three occasions during the summer and two occasions in the early spring over a period of 2.5 years. Control (C) plots were treated with inorganic fertiliser containing amounts of nitrogen equivalent to those applied to the treated plots. At between 69 and 81 days after the application of sludge, 15 separate soil samples were collected from one half of each of the plots (Experiment 1). Concentrations (microg g(-1)) of DOP were higher (P < 0.001) than those of NP, while those of OP were generally below detectable levels. Mean soil concentrations of DOP were not significantly different in T and C plots [0.233 vs. 0.155 microg g(-1); standard error of the difference (SED) = 0.046; not significant (NS)], partly because there was already a relatively large amount of DOP present. NP concentrations were, however, significantly higher in T than in C plots (0.021 vs. 0.013 microg g(-1) SED = 0.002; P < 0.05). There was no consistent change over time in the mean soil concentrations of these compounds when sampled at intervals of 3-6 months. Concentrations in soil samples collected at monthly intervals following sludge application indicated that the variation in concentrations of these endocrine-disrupting compounds (EDC) was unrelated to time since sludge application. Rates of soil ingestion, expressed as the percentage of DM intake represented by soil, were higher during the winter than the summer (5.40 vs. 1.17; SED = 0.360; P < 0.001) and estimated daily intakes of DOP and NP were up to 150 microg and 8 microg, respectively. It is concluded that the application of sewage sludge to pasture does not increase soil concentrations of phthalate (as DOP) or alkyl phenols. Thus, the risk of increased exposure to these EDC as a result of sludge application is small. However, the small effect of sludge application on soil concentrations may be largely a reflection of the relatively high concentrations of DOP already present in the soil, which may be biologically significant.

Rumen digestibility of starch and nitrogen in near-isogenic lines of wheat

Comparisons between cereal species have shown that wheat starch is fermented more rapidly in the rumen than starch from maize, barley, potato or sorghum, probably due to the protein matrix surrounding the starch granules, but there are few comparisons of starch digestion from different cultivars of wheat. Although wheat varieties are classified as being hard or soft, genetic factors affecting nutritional value cannot be evaluated using name alone because any two named varieties may be distantly or closely related. Near-isogenic lines allow the nutritional implications of specific characteristics to be investigated against a comparatively uniform genetic background. The purpose of this study was to investigate genetic effects on starch and nitrogen degradation kinetics in sacco for four pairs of near-isogenic wheat lines. Pair A comprised one hard and one soft line; Pair B comprised two hard lines, one of which contained the 1B/1R rye translocation; Pair C comprised a hard line with the 1B/1R rye translocation and a soft wheat without the 1B/1R translocation; Pair D comprised two lines differing in the visco-elastic properties of dough. Minor differences in the soluble and degradable fractions of starch and nitrogen were found within pairs. Only in Pair C, where the 1B/1R translocation was accompanied by a change in hardness, was there a significant effect on effective rumen starch and nitrogen degradability (soft non-1B/1R versus hard 1B/1R, starch digestibility=0.86 versus 0.88, standard error of the difference (S.E.D.) 0.001; nitrogen degradability=0.80 versus 0.76, S.E.D. 0.008). Rumen by-pass starch was influenced mainly by the starch content of the wheat rather than differences in rumen digestion. It is concluded that in ruminants, unlike poultry, genetic differences in wheats have very little impact on their overall nutritive value, which is determined mainly by total starch content.

Reliable Change Formula Query: Temkin et al. reply

Hinton-Bayre (2000) raises a point that may occur to many readers who are familiar with the Reliable Change Index (RCI). In our previous paper comparing four models for detecting significant change in neuropsychological performance (Temkin et al., 1999), we used a formula for calculating Sdiff, the measure of variability for the test–retest difference, that differs from the one Hinton-Bayre has seen employed in other studies of the RCI. In fact, there are two ways of calculating Sdiff—a direct method and an approximate method. As stated by Jacobson and Truax (1991, p. 14), the direct method is to compute “the standard error of the difference between the two test scores” or equivalently [begin square root](s12 + s22 − 2s1s2rxx′)[end square root] where si is the standard deviation at time i and rxx′ is the test–retest correlation or reliability coefficient. Jacobson and Truax also provide a formula for the approximation of Sdiff when one does not have access to retest data on the population of interest, but does have a test–retest reliability coefficient and an estimate of the cross-sectional standard deviation, i.e., the standard deviation at a single point in time. This approximation assumes that the standard deviations at Time 1 and Time 2 are equal, which may be close to true in many cases. Since we had the longitudinal data to directly calculate the standard error of the difference between scores at Time 1 and Time 2, we used the direct method. Which method is preferable? When the needed data are available, it is the one we used.

A comparison of digestibility of some concentrate feed ingredients in cattle and sheep

An experiment was carried out to compare the digestibility of five concentrate ingredients (barley, beet pulp, citrus pulp, maize gluten feed and grain screenings) in cattle or sheep, fed at ≈1.2 maintenance. Four wether sheep and four steers were fed each concentrate, which comprised ≈800 g/kg of the dietary dry matter (DM). The remaining 200 g/kg was a hay/soyabean meal mixture whose digestibility was determined simultaneously in another four sheep and cattle. Following diet introduction and adaptation, faeces were collected for a 10-day period. Across diets, there was no difference ( p >0.05) between sheep and cattle in digestibility of organic matter (OM, 0.784 and 0.78, respectively, standard error of the difference (s.e.d.), 0.0049), crude protein (0.586 and 0.577, respectively, s.e.d. 0.0192), or neutral detergent fibre (0.632 and 0.628, respectively, s.e.d. 0.0116). However, cattle digested the OM (0.749 vs. 0.724, p <0.05, s.e.d. 0.0106) of maize gluten feed better than sheep, but there were no significant differences ( p >0.05) between sheep and cattle with any of the other four feeds. These results do not support previous conclusions that sheep digest concentrates better than cattle, but they do suggest that there are differences within specific feeds.

Variability of abdominal adipose tissue measurements using computed tomography in prepubertal girls.

To determine the variability of measuring regional adipose tissue area using abdominal computed tomography (CT) in normal-weight, prepubertal girls. Measurements of abdominal CT were performed twice, 6 weeks apart. Sixty-one normal-weight, prepubertal girls (age: 4.8-10.3 y, mean (s.d.) BMI: 16.7 +/- 1.5 kg/m2). Abdominal adipose tissue by CT at baseline and 6 weeks later. There were no significant differences between visits 1 and 2 with regard to the children's average abdominal CT derived intraabdominal adipose tissue (21.64 cm2 vs 23.74 cm2) and subcutaneous adipose tissue (62.49 cm2 vs 65.28 cm2). The Pearson coefficient of correlation (r), P-value, total coefficient of variation (CV) and standard error of the difference (SEdelta) for intra-individual measurements between visits 1 and 2 by abdominal CT were: total abdominal adipose tissue, r = 0.94, P < 0.0001, CV = 12.34%, SEdelta 2.25 cm2; subcutaneous abdominal adipose tissue, r = 0.96, P < 0.0001, CV = 10.67%, SEdelta = 1.57 cm2; and intraabdominal adipose tissue, r = 0.67, P < 0.0001, CV = 21.5%, SEdelta = 1.11 cm2. The mean ratios of intraabdominal to subcutaneous adipose tissue on visits 1 and 2 were 0.42 +/- 0.2 and 0.44 +/- 0.24, respectively. Regional adipose tissue area measurements using abdominal CT were reliable in healthy, normal-weight, prepubertal girls.

Effects of season and nutrition on growth hormone and insulin-like growth factor-I in male red deer

GH and insulin-like growth factor (IGF)-I are important components of the growth axis. We undertook to determine how plasma levels of these hormones altered with different seasonal and nutritional states in young male red deer to provide an insight into how the growth axis changes under these conditions. Growth rate alters dramatically with season in male red deer, providing an opportunity to sample the same animals at two different growth rates within a short period of time. GH was measured every 15 min for 24 h in the fed state and after a 48-h fast, during slow growth in winter (23 June to 16 July), and during rapid growth in spring (8 September to 2 October). At the end of each sampling period, the animals were treated with N-methyl-D, L-aspartic acid (NMDA) (5 mg/kg live weight) and sampled for a further 1 h, 45 min. Glucose and IGF-I were measured hourly during each sampling period. Live weight was measured at weekly intervals. GH was secreted in a characteristic pattern in which pulses tended to occur in rapid succession, termed a volley, that was separated from the subsequent volley by a period of baseline GH levels, termed a latent period. There were more GH pulses/24 h in the fasted state than in the fed state in winter (12.4 vs. 7.8, standard error of the difference [SED] = 1.07, P < 0.001) and in spring (11.5 vs. 8.8, SED = 1.04, P < 0.05). The increased number of GH pulses in the fasted state could be attributed to a higher number of pulses per volley (winter = 3.7 vs. 2.5, SED = 0.16, P < 0.001; spring = 3.1 vs. 2.8, SED = 0.19). Consequently, the volleys were wider in the fasted state than the fed state (winter = 197 min vs. 122 min, SED = 25, P < 0.05; spring = 173 min vs. 154 min, SED = 24, P > 0.05), and the latent periods between volleys were shorter in the fasted state than the fed state (winter = 175 min vs. 280 min, SED = 14, P < 0.001; spring = 183 min vs. 262 min, SED = 11, P < 0.001). The main differences between seasons in the fed state were larger amplitude pulses (12.4 vs. 8.3 ng/ml, SED = 1.57, P < 0.05) and higher mean GH concentrations (4.1 vs. 2.3 ng/ml, SED = 0.44, P < 0.01) in spring than in winter. The number of volleys and the intravolley pulse interval did not change significantly with nutritional state or season. NMDA administration was followed by an increase in GH with higher GH levels found in the fed state than in the fasted state in both seasons. Fed animals also had a larger initial increase in GH (until 60 min post NMDA) than fasted animals in spring (P < 0.01). Plasma IGF-I was higher in the fed state than the fasted state in both winter (315 vs. 221 ng/ml, SED = 21.0, P < 0.001) and spring (651 vs. 494 ng/ml, SED = 37.5 P < 0.001) and in the fed state was higher in spring than in winter (SED = 29.1, P < 0.001). Blood glucose was higher in the fed state than fasted state in winter (6.1 vs. 5.5 mmol/l, SED = 0.07, P < 0.001) and there was a strong trend toward this same effect in spring although it did not reach statistical significance (6.0 vs. 5.7 mmol/l, SED = 0.26, P > 0.05). Growth rate in winter at 117 g/day was less than that in spring when 220 g/day was recorded (SED = 36.8, P < 0.05). These results demonstrate that the secretory pattern of GH and plasma IGF-I levels alter in response to changes in season and nutrition. The alterations in response to a 48-h fast show that the control of GH and IGF-I secretion may be rapid and is probably a response to maintain energy balance, whereas alterations with season reflect long term control that underlies the seasonal growth pattern of the animal.

Effects of season and nutrition on growth hormone and insulin-like growth factor-I in male red deer.

GH and insulin-like growth factor (IGF)-I are important components of the growth axis. We undertook to determine how plasma levels of these hormones altered with different seasonal and nutritional states in young male red deer to provide an insight into how the growth axis changes under these conditions. Growth rate alters dramatically with season in male red deer, providing an opportunity to sample the same animals at two different growth rates within a short period of time. GH was measured every 15 min for 24 h in the fed state and after a 48-h fast, during slow growth in winter (23 June to 16 July), and during rapid growth in spring (8 September to 2 October). At the end of each sampling period, the animals were treated with N-methyl-D, L-aspartic acid (NMDA) (5 mg/kg live weight) and sampled for a further 1 h, 45 min. Glucose and IGF-I were measured hourly during each sampling period. Live weight was measured at weekly intervals. GH was secreted in a characteristic pattern in which pulses tended to occur in rapid succession, termed a volley, that was separated from the subsequent volley by a period of baseline GH levels, termed a latent period. There were more GH pulses/24 h in the fasted state than in the fed state in winter (12.4 vs. 7.8, standard error of the difference [SED] = 1.07, P < 0.001) and in spring (11.5 vs. 8.8, SED = 1.04, P < 0.05). The increased number of GH pulses in the fasted state could be attributed to a higher number of pulses per volley (winter = 3.7 vs. 2.5, SED = 0.16, P < 0.001; spring = 3.1 vs. 2.8, SED = 0.19). Consequently, the volleys were wider in the fasted state than the fed state (winter = 197 min vs. 122 min, SED = 25, P < 0.05; spring = 173 min vs. 154 min, SED = 24, P > 0.05), and the latent periods between volleys were shorter in the fasted state than the fed state (winter = 175 min vs. 280 min, SED = 14, P < 0.001; spring = 183 min vs. 262 min, SED = 11, P < 0.001). The main differences between seasons in the fed state were larger amplitude pulses (12.4 vs. 8.3 ng/ml, SED = 1.57, P < 0.05) and higher mean GH concentrations (4.1 vs. 2.3 ng/ml, SED = 0.44, P < 0.01) in spring than in winter. The number of volleys and the intravolley pulse interval did not change significantly with nutritional state or season. NMDA administration was followed by an increase in GH with higher GH levels found in the fed state than in the fasted state in both seasons. Fed animals also had a larger initial increase in GH (until 60 min post NMDA) than fasted animals in spring (P < 0.01). Plasma IGF-I was higher in the fed state than the fasted state in both winter (315 vs. 221 ng/ml, SED = 21.0, P < 0.001) and spring (651 vs. 494 ng/ml, SED = 37.5 P < 0.001) and in the fed state was higher in spring than in winter (SED = 29.1, P < 0.001). Blood glucose was higher in the fed state than fasted state in winter (6.1 vs. 5.5 mmol/l, SED = 0.07, P < 0.001) and there was a strong trend toward this same effect in spring although it did not reach statistical significance (6.0 vs. 5.7 mmol/l, SED = 0.26, P > 0.05). Growth rate in winter at 117 g/day was less than that in spring when 220 g/day was recorded (SED = 36.8, P < 0.05). These results demonstrate that the secretory pattern of GH and plasma IGF-I levels alter in response to changes in season and nutrition. The alterations in response to a 48-h fast show that the control of GH and IGF-I secretion may be rapid and is probably a response to maintain energy balance, whereas alterations with season reflect long term control that underlies the seasonal growth pattern of the animal.

Graphical Comparison of Nonparametric Curves

Nonparametric curves occur in a wide variety of contexts, including repeated measurements mean profiles, survivor functions and in different types of smoothing techniques such as nonparametric regression and density estimation. In some cases confidence bands can be attached to these curves as an indication of the variability of estimation. This is more difficult in the case of nonparametric regression and density estimation where bias is present. In the important case of the comparison of two curves, attention can be focused instead on whether there are differences between the curves. In this paper, the idea of a reference band for the comparison of two curves is introduced The band is derived from the standard error of the difference between the two curves at each point. The bands have a simple hypothesis testing interpretation which applies equally well to smoothing methods where bias occurs. It does not remove the need for a global test of effects of interest, but it can be very useful as a graphical means of exploring where any identified differences might lie, or of explaining why apparent differences do not actually contribute strong evidence of statistical significance to the global comparison of curves. Reference bands for equality are derived and explored in a variety of settings. Reference bands for parallelism are also derived for nonparametric regression models. Reference bands for parametric models, against which nonparametric regression and density estimates can be compared, are derived for linearity and for normality.

The effect of food deprivation on the expression of foraging and exploratory behaviour in the growing pig

Growing pigs spend considerable time orally manipulating their environment including straw and their pen-mates, leading to problems such as tail biting. It is unclear if this active behaviour reflects either foraging motivation, exploratory motivation or a combination of both. This problem is exacerbated by the possibility that both motivational systems share certain behavioural elements. The aim of this experiment was to determine the extent to which appetitive foraging is separable from intrinsic exploration by manipulating both feeding motivation and the novelty of the external environment. The behaviour of 12 growing male pigs was recorded during tests lasting 35 min whilst placed in a familiar test arena with a woodbark/sand foraging substrate. Tests were conducted in blocks lasting 8 days during which pigs were fed a commercial food either ad libitum (Treatment H) or at a 20% reduction thereof (Treatment L). A replicated Latin square design allowed pigs to be twice provided with either novel objects, food (50 g) or nothing in a specific ‘targetarea’ of substrate at either feeding level. Food restriction although not affecting locomotion resulted in an increase in the proportion of time spent rooting the substrate (0.05 vs. 0.08 for H versus L pigs respectively; standard error of the difference (SED) 0.008; P < 0.01), a decrease in the proportion of time spent lying (0.17 vs. 0.12; SED 0.027; P < 0.05), and an increase in the proportion of time spent in the target-area (0.05 vs. 0.08; SED 0.011; P < 0.05), with no effect of novel object presentation in any case. The presentation of novel objects resulted in an increase in the rate of visits to the target-area (0.30, 0.23 and 0.24 for novel objects, food and control treatments respectively; SED 0.025 visits min −1; P < 0.05) which was independent of feeding level. These results indicate that the increase in rooting and decrease in lying is a reflection of an increased level of feeding motivation produced by food restriction. Rooting was an expression of appetitive foraging as it was unaffected by novel object presentation. The increase in frequency of visits to the target-area due to novel object presentation was an expression of intrinsic exploration as it was independent of feeding motivation. Therefore, it was concluded that appetitive foraging behaviour and intrinsic exploration can be experimentally separated by the controlled manipulation of both feeding motivation and specific environmental stimuli.

Intertester reliability of measurements obtained with the KT-1000 on patients with reconstructed anterior cruciate ligaments.

Clinicians frequently measure anterior tibial displacement on patients following surgical reconstruction for a torn anterior cruciate ligament (ACL). Little is known about the reliability of measurements of anterior tibial displacement obtained on patients following an ACL reconstruction. The purpose of this study was to describe the degree of error associated with repeated measurements of anterior tibial displacement on patients with reconstructed ACLs. Random pairs of physical therapists used the KT-1000 to measure the anterior tibial displacement of 30 subjects. Each pair of examiners took measurements according to the manufacturer's instructions. Examiners took three sets of measurements while applying 6.8, 9.1, and 13.6 kg (15, 20, and 30 lbs) of force to the handle of the KT-1000. Intraclass correlation coefficients (ICC 2,1) and the standard error of the difference (SED) were calculated to describe the intertester reliability of the mean of three measurements of anterior tibial displacement at each force level and of the individual measurements at each force level. The SED was then multiplied by 2 to provide a 95% confidence estimate of the magnitude of error present with KT-1000 measurements. The SED estimates the magnitude of change in anterior tibial displacement necessary to infer that a real change in anterior tibial displacement has occurred. Clinicians can be 95% confident that changes in anterior tibial displacement of greater than 5 mm (+/- 2 SED) during KT-1000 tests at 6.8, 9.1, or 13.6 kg (15, 20, or 30 lbs) of force indicate that a true change in anterior tibial displacement has occurred.

Mineralocorticoid induced hypertension and noradrenaline spillover in man.

This study examined haemodynamics and noradrenaline spillover in five normal men before and on day 7 of oral fludrocortisone treatment, 0.3 mg/day. Resting systolic (105 to 115 mm Hg, standard error of the difference +/- 2.0, p < 0.01) and diastolic (65 to 73 mm Hg, +/- 3.0, p < 0.05) blood pressure increased, as did cardiac output, from 5.0 to 5.7 L/min (+/- 0.1, p < 0.01). Calculated total peripheral resistance fell from 21.2 to 20.0 mm Hg/L/min (+/- 0.4, p < 0.05). Fludrocortisone produced a fall in plasma potassium, renin and aldosterone concentrations and haematocrit and a rise in body weight. Cold pressor responses were increased by fludrocortisone, from 7.5 to 20 mm Hg (+/- 3.0, p < 0.01), and forearm vascular resistance rose 12 arbitrary resistance units (R) before and 36 R units after treatment (+/- 5.0, p < 0.01). Total body spillover of noradrenaline was decreased from 9.48 to 7.36 ng/kg/min (+/- 0.86, p < 0.05). There were no changes in forearm noradrenaline spillover at rest or during cold pressor stimulation. It appears unlikely that the sympathetic nervous system plays a major role in the pathogenesis of mineralocorticoid hypertension in man.

Cardiac sympathetic nervous activity in congestive heart failure. Evidence for increased neuronal norepinephrine release and preserved neuronal uptake.

Increased concentrations of norepinephrine in coronary sinus plasma reported in congestive heart failure (CHF) could result from increased cardiac sympathetic nerve firing and norepinephrine release or from failure of neuronal uptake mechanisms to recapture released norepinephrine. We have applied neurochemical indexes of cardiac sympathetic nerve function in heart failure patients to delineate the underlying neural pathophysiology. Cardiac norepinephrine synthesis, assessed from the cardiac overflow of the norepinephrine precursor dihydroxyphenylalanine (DOPA), intraneuronal metabolism estimated from the overflow of the intraneuronal metabolite dihydroxyphenylglycol (DHPG), neuronal norepinephrine reuptake assessed from the fractional extraction of plasma-tritiated norepinephrine and production of tritiated DHPG across the heart, and norepinephrine spillover to plasma were examined in eight patients with CHF caused by coronary artery disease (left ventricular ejection fraction of 26 +/- 5%, mean +/- SEM) and 14 age-matched healthy subjects. Cardiac norepinephrine spillover was increased eightfold in CHF subjects (127 ng/min versus 14 ng/min in healthy subjects; standard error of the difference [SED], 8 ng/min; P < .002), and cardiac DOPA was increased twofold (P < .02). The fractional extraction of tritiated norepinephrine across the heart was marginally less in CHF subjects (0.63 versus 0.73 in normal subjects; SED, 0.02), but the extent to which pharmacological neuronal uptake blockade with desipramine reduced the cardiac extraction of tritiated norepinephrine (by 71% versus 73% in normal subjects) and reduced the production of tritiated DHPG derived from uptake and intraneuronal metabolism of tritiated norepinephrine was similar in CHF patients and healthy subjects. The marked increase in norepinephrine spillover from the heart in CHF attributable to coronary artery disease results primarily from an increase in sympathetic nerve firing and neuronal release of norepinephrine, not from faulty neuronal reuptake of norepinephrine.

Hydrocortisone-Induced Hypertension in Men: The Role of Cardiac Output

In previous studies we have shown that administration of 200 mg/day hydrocortisone (cortisol) to normal subjects raises blood pressure and cardiac output, with no change in total peripheral resistance or resting forearm vascular resistance. We have tested the hypothesis that this rise in cardiac output is essential for the rise in blood pressure (BP). Six normal volunteer men, aged 22 to 34 years, took part in two studies of 10 days, in random order, at least 4 weeks apart. Placebo (Study A) or 50 mg atenolol orally, 12 hourly (Study B), was given on days 1 to 10 and 50 mg cortisol orally, 6 hourly, on days 5 to 10. Blood pressure and cardiac output (Fick technique, alternative Doppler) were measured on days 4 and 10. In Study A (placebo and cortisol) systolic BP rose from 116 to 125 mm Hg (standard error of the difference, SED 1.5), P < .01, and in Study B (atenolol and cortisol) from 109 to 120 mm Hg (SED 1.5), P < .01. Cardiac output (indirect Fick) rose from 4.8 +/- 0.01 to 5.9 +/- 0.2 L/min, P < .01, in A, and was unchanged in Study B, 4.4 +/- 0.1 to 4.4 +/- 0.2 L/min. Cardiac output measured by Doppler method was similar in pattern, 5.1 +/- 0.2 to 6.7 +/- 0.2 L/min (P < .01) in A and 5.7 +/- 0.2 to 5.8 +/- 0.2 in B. Calculated peripheral resistance fell in Study A and increased in Study B.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in calcium metabolism in young people at risk for primary hypertension. The Dutch Hypertension and Offspring Study.

Several disturbances in calcium metabolism have been reported in primary hypertensive subjects. It is, however, not clear whether these alterations predate the development of hypertension or occur as a consequence of high blood pressure. We studied indexes of calcium metabolism in three groups of normotensive children with different familial predispositions for hypertension, based on parental blood pressure levels, with two, one, or no hypertensive parents. Plasma intact parathyroid hormone [1-84] was higher in the offspring of hypertensive parents compared with offspring of normotensive parents (difference, 0.58 pmol/L; standard error of the difference [SED], 0.24; p = 0.02). Mean serum calcium levels were slightly reduced in the offspring of two hypertensive parents (-0.019 mmol/L, SED = 0.013, p = 0.17). Plasma magnesium and phosphate levels were lower in the offspring of hypertensive parents (-0.032 mmol/L [SED = 0.016, p = 0.05] and -0.045 mmol/L [SED = 0.024, p = 0.05], respectively). Mean 1.25-dihydroxyvitamin D3 levels were similar among the groups. No differences in dietary intake of calcium, phosphate, or fiber were found. Urinary calcium excretion per 24 hours and the ratio of 24-hour urinary calcium excretion to daily calcium intake were somewhat higher in the offspring of hypertensive parents. Renal fractional excretion of calcium was similar in the offspring of two hypertensive parents, and renal fractional excretion of phosphate was lower in the offspring of two hypertensive parents compared with offspring of two normotensive parents (-1.50%, SED = 0.74, p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise training reduces the sympathetic component of the blood pressure-heart rate baroreflex in man

1. Exercise training reduces resting sympathetic activity, but the effects on sympathetic activation or withdrawal during baroreflex responses to blood pressure perturbations are controversial. The purpose of this study was to investigate the effects of training on both the vagal and sympathetic reflex heart rate responses to blood pressure changes. 2. Using 10 healthy males in a randomized cross-over design, we examined the effects of three 30 min cycling sessions at 70% of maximal capacity for 4 weeks on the steady-state reflex heart rate responses to perturbations in mean arterial pressure induced with injections of nitroprusside and phenylephrine. The method provides a sigmoidal relationship between changes in heart rate and blood pressure. The upper plateau (maximum tachycardia in response to blood pressure reduction) and lower plateau (maximum bradycardia in response to blood pressure elevation) are mainly mediated by the cardiac sympathetics and vagus, respectively. The slope of the relationship is a measure of reflex gain. 3. Training, which increased maximal oxygen consumption by 13 +/- 2% (mean +/- standard error of the difference), reduced supine and standing blood pressures by 3 +/- 1/3 +/- 1 mmHg (P less than 0.05) and 4 +/- 1/2 +/- 2 mmHg (P less than 0.05 for systolic), respectively, whereas resting heart rate was lowered by 6 +/- 1 beats/min (P less than 0.05). Reflex sensitivity in the presence of functioning vagus and sympathetics was not altered with training, but the vagal component of sensitivity, as assessed after sympathetic blockade with propranolol, was significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Secretion and Renal Clearance of Atrial Natriuretic Peptide in Normal Man: Effect of Salt Restriction

1. Previous studies of endogenous atrial natriuretic peptide (ANP) in humans have examined changes in plasma levels, rather than regional secretion and clearance of the peptide. Using arterial and selective venous catheterization and sampling, and measurement of regional organ flow, we measured haemodynamics, cardiac secretion of ANP and renal clearance of ANP in six healthy volunteers at rest, on a normal sodium diet. 2. Salt restriction decreases plasma concentrations of ANP. We assessed the contribution of the heart and kidney to this decrease, by measuring cardiac secretion and renal clearance of ANP at the termination of a low salt diet. 3. Twenty-four hour urinary sodium excretion fell on the low salt diet from 163 to 29 mmol/day [standard error of the difference (SED)+/- 14, P less than 0.001]. Body weight decreased on salt restriction from 76.4 to 75.4 kg (SED +/- 0.33, P less than 0.05). Brachial mean arterial pressure fell by 6% (P less than 0.05), but right atrial pressure was unchanged. Renal vein plasma renin activity increased by 56% with sodium restriction (P less than 0.01), whereas arterial ANP concentrations fell by 39% (P less than 0.05). 4. Coronary sinus ANP levels fell from 417 to 268 pg/ml (SED +/- 74, P less than 0.05), whereas renal vein concentrations were unaltered. There was a 47% decrease in cardiac secretion of ANP in the low salt state (P less than 0.05). Net extraction of ANP across the kidney (about two-thirds) and renal clearance of ANP were unchanged on the low salt diet. Thus decreased plasma ANP with sodium restriction is due to reduced cardiac secretion.