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Contrasts and correlations in effect-size estimation.

This article describes procedures for presenting standardized measures of effect size when contrasts are used to ask focused questions of data. The simplest contrasts consist of comparisons of two samples (e.g., based on the independent t statistic). Useful effect-size indices in this situation are members of the g family (e.g., Hedges's g and Cohen's d) and the Pearson r. We review expressions for calculating these measures and for transforming them back and forth, and describe how to adjust formulas for obtaining g or d from t, or r from g, when the sample sizes are unequal. The real-life implications of d or g calculated from t become problematic when there are more than two groups, but the correlational approach is adaptable and interpretable, although more complex than in the case of two groups. We describe a family of four conceptually related correlation indices: the alerting correlation, the contrast correlation, the effect-size correlation, and the BESD (binomial effect-size display) correlation. These last three correlations are identical in the simple setting of only two groups, but differ when there are more than two groups.

Analysis of Variance↗

Taxon sampling, correlated evolution, and independent contrasts.

Independent contrasts are widely used to incorporate phylogenetic information into studies of continuous traits, particularly analyses of evolutionary trait correlations, but the effects of taxon sampling on these analyses have received little attention. In this paper, simulations were used to investigate the effects of taxon sampling patterns and alternative branch length assignments on the statistical performance of correlation coefficients and sign tests; "full-tree" analyses based on contrasts at all nodes and "paired-comparisons" based only on contrasts of terminal taxon pairs were also compared. The simulations showed that random samples, with respect to the traits under consideration, provide statistically robust estimates of trait correlations. However, exact significance tests are highly dependent on appropriate branch length information; equal branch lengths maintain lower Type I error than alternative topological approaches, and adjusted critical values of the independent contrast correlation coefficient are provided for use with equal branch lengths. Nonrandom samples, with respect to univariate or bivariate trait distributions, introduce discrepancies between interspecific and phylogenetically structured analyses and bias estimates of underlying evolutionary correlations. Examples of nonrandom sampling processes may include community assembly processes, convergent evolution under local adaptive pressures, selection of a nonrandom sample of species from a habitat or life-history group, or investigator bias. Correlation analyses based on species pairs comparisons, while ignoring deeper relationships, entail significant loss of statistical power and as a result provide a conservative test of trait associations. Paired comparisons in which species differ by a large amount in one trait, a method introduced in comparative plant ecology, have appropriate Type I error rates and high statistical power, but do not correctly estimate the magnitude of trait correlations. Sign tests, based on full-tree or paired-comparison approaches, are highly reliable across a wide range of sampling scenarios, in terms of Type I error rates, but have very low power. These results provide guidance for selecting species and applying comparative methods to optimize the performance of statistical tests of trait associations.

Biological Evolution↗

Evolution of floral display in Eichhornia paniculata (Pontederiaceae): direct and correlated responses to selection on flower size and number.

Trade-offs between flower size and number seem likely to influence the evolution of floral display and are an important assumption of several theoretical models. We assessed floral trade-offs by imposing two generations of selection on flower size and number in a greenhouse population of bee-pollinated Eichhornia paniculata. We established a control line and two replicate selection lines of 100 plants each for large flowers (S+), small flowers (S-), and many flowers per inflorescence (N+). We compared realized heritabilities and genetic correlations with estimates based on restricted-maximum-likelihood (REML) analysis of pedigrees. Responses to selection confirmed REML heritability estimates (flower size, h2 = 0.48; daily flower number, h2 = 0.10; total flower number, h2 = 0.23). Differences in nectar, pollen, and ovule production between S+ and S- lines supported an overall divergence in investment per flower. Both realized and REML estimates of the genetic correlation between daily and total flower number were r = 1.0. However, correlated responses to selection were inconsistent in their support of a trade-off. In both S- lines, correlated increases in flower number indicated a genetic correlation of r = -0.6 between flower size and number. In contrast, correlated responses in N+ and S+ lines were not significant, although flower size decreased in one N+ line. In addition, REML estimates of genetic correlations between flower size and number were positive, and did not differ from zero when variation in leaf area and age at first flowering were taken into account. These results likely reflect the combined effects of variation in genes controlling the resources available for flowering and genes with opposing effects on flower size and number. Our results suggest that the short-term evolution of floral display is not necessarily constrained by trade-offs between flower size and number, as is often assumed.

Animals↗

Morphology of proliferating and non-proliferating tumor cell nuclei in glioblastomas correlates with preoperative data from proton-MR-spectroscopy.

In contrast to the growing interest in proton-MR-spectroscopy (1HMRS) for preoperative examination of patients with brain tumors, there is nearly no knowledge about a correlation between data from 1HMRS and histomorphology as confirmed by quantitative morphological methods. Whether a correlation can be confirmed between data from 1HMRS and quantitative histomorphology of glioblastomas representing the most frequent type of brain tumors was investigated in the present study. Furthermore, it was of interest, whether correlations between spectroscopic data and histomorphology can be confirmed for proliferating and non-proliferating tumor cell nuclei independently. Using stringent inclusion criteria for this study, 24 patients were investigated by means of preoperative 1HMRS and by means of digital image analysis of paraffin sections from the surgical specimen. Proliferating and non-proliferating tumor cell nuclei were investigated separately in the region with the highest proliferative activity in each tumor using immunohistological staining for the proliferation marker Ki67. Main results showed highly significant correlations between total creatine and variables of nuclear size, as well as correlations between choline and variables of nuclear shape. These results were confirmed for both proliferating and non-proliferating tumor cell nuclei. A significant correlation between N-acetyl-aspartate level and topometric variables (number of neighbors per nucleus, variables describing distances between tumor cell nuclei) was confirmed for proliferating tumor cell nuclei. Discriminant analysis provided a good separation of cases with high and with low values for these spectroscopic variables based on histomorphometric data. In conclusion, the results confirm a direct correlation between data from preoperative 1HMRS and histomorphological characteristics of glioblastomas supporting the biological relevance of spectroscopic data for the examination of brain tumor patients.

Cell Nucleus↗

Specific brain protein changes correlated with behaviourally effective brain transplants.

The objective of this study was to identify cellular proteins that are associated with foetal brain transplants effective in reinstating memory function in adult rats with brain lesions. Quantitative memory deficits can be created in rats by lesioning the cholinergic projection system, using ibotenic acid. Previous work suggested that injection of cell suspensions prepared from presumptive cholinergic cells of foetal basal forebrain into adult brain, after such lesions, are most effective in restoring cognitive function. It was not clear, however, whether it was the cholinergic nature of the transplants that was critical for their success or whether other factors were involved. In this study, the proteins present in transplanted tissues and control brains were analysed by two-dimensional polyacrylamide gel electrophoresis to identify markers for the cells that were specifically correlated with restoration of cognitive function. On each gel, the relative optical densities of the same 33 selected proteins were measured on an interactive computerised image analyser. The amount of each protein was compared between treatment groups and correlated with four behavioural measurements. Seven of the proteins analysed had levels of expression that were either related to transplantation or correlated with behavioural performance. The proteins of interest were divided into the following three groups: (1) transplant-related proteins, (2) cholinergic transplant-specific proteins, and (3) behaviour-related proteins. Notable among the proteins of interest was one of the cholinergic transplant-specific proteins that was positively correlated with three of the four behavioural measurements and was also the only protein among those analysed that was significantly correlated with choline acetyltransferase (ChAT) levels. This has been identified, by immunoblotting, as glial fibrillary acidic protein, an astrocytic cell marker. These results suggest, therefore, that at least two cell types, astrocytes and ChAT(+)-staining cells, play an important role in the successful recovery of cognitive function. This study also identified possible protein markers for cognitive performance. The level of expression of two of the proteins analysed was not affected by lesioning or transplantation, but was significantly correlated with behaviour. One of these proteins, whose amounts correlated negatively with behavioural measurements, has been identified as neurone-specific enolase, a brain-specific neuronal cell marker.

Animals↗

Gender-specific correlations of plasminogen activator inhibitor-1 and tissue plasminogen activator levels with cardiovascular disease-related traits.

BACKGROUND: The purpose of this study was to examine the correlations between plasma levels of plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA) and cardiovascular disease-related traits in a general population and whether these correlations differed between females and males. METHODS: Plasma PAI-1 and t-PA antigen levels and C-reactive protein (CRP), HDL-cholesterol, triglycerides, total cholesterol, systolic blood pressure, diastolic blood pressure, urinary albumin excretion, and glucose were measured in the population-based PREVEND study in Groningen, the Netherlands (n = 2527). RESULTS: Except for CRP and total cholesterol levels, all traits were significantly different between gender (P < 0.001). PAI-1 levels were correlated with all measured cardiovascular disease-related traits (P < 0.01) in both females and males. Except for urinary albumin excretion, similar results, albeit less significant, were found for t-PA levels. Age-adjusted correlations between PAI-1 and CRP, triglycerides, total cholesterol, systolic blood pressure, and diastolic blood pressure differed significantly between females and males (P < 0.01). Many of the gender differences were predominantly present between premenopausal females and males. CONCLUSION: PAI-1 and t-PA levels were correlated with cardiovascular disease-related traits in subjects obtained from the general population and several of these correlations differed across gender. The correlations found in the present study suggest the presence of coordinated patterns of cardiovascular risk factors and indicate which traits might influence PAI-1 and t-PA levels and thereby provide a framework and potential tool for therapeutic intervention to reduce thromboembolic events in the general population.

Adult↗

Blood ionized magnesium concentrations during cardiopulmonary bypass and their correlation with other circulating cations.

BACKGROUND AND AIM: The recent introduction of new measurement technology (using ion specific electrodes) makes intraoperative evaluation of blood ionized magnesium (Mg2+, or iMg)--the bioactive fraction of circulation magnesium--possible. The goals of this study were: (1) to examine the longitudinal pattern(s) of change in blood iMg during cardiopulmonary bypass (CPB); and (2) to determine the relationship of iMg to Ca2+ (iCa), K, pH, Na, and hematocrit (Hct) during CPB. METHODS: Blood was collected serially before, during, and after CPB on 30 patients undergoing elective coronary artery bypass graft procedures and the iMg was measured with an AVL Scientific Corp., model 988-4 instrument. RESULTS: Overall, 73% of iMg results were abnormally low, 50% during CPB. Some cases had both hypo- and hyperionized magnesemic episodes. There were low iCa during CPB in 97% of cases. Using Spearman's rank order correlations and p < 0.05, iMg and K were directly correlated before, during, and after bypass, suggesting their parallel movement between tissue and blood. iMg and iCa were directly correlated before, and inversely correlated after, CPB, but unassociated during bypass. iMg and Na were inversely correlated after bypass in all cases. iMg was inversely correlated to pH and positively correlated to Hct during CPB only, and only in patients with concurrent association of iMg and iCa. CONCLUSIONS: Blood iMg depletion occurs frequently in CPB patients. iMg changes are not readily predictable. The association of intraoperative iMg depletion with postsurgical atrial fibrillation--reported to have a hypomagnesemic connection- should be investigated.

Adult↗

Correlation between liver morphology and haemodynamics in alcoholic liver disease.

In 32 alcoholic patients the degree of hepatic architectural destruction was graded (preserved architecture, nodules alternating with preserved architecture, totally destroyed architecture) and related to portal pressure. A significant positive correlation was found between degree of architectural destruction and wedged-to-free hepatic vein pressure (W-FHVP) (p less than 0.001). The degree of necrosis, fatty change and inflammation showed no correlation with portal pressure, whereas a significant positive correlation was found between the occurrence of Mallory bodies and W-FHVP (p less than 0.01) and between degree of fibrosis and W-FHVP (p less than 0.001). In 22 of the patients, hepatic blood flow (HBF) was measured and in these patients hepatic resistance was calculated (W-FHVP/HBF). A significant positive correlation was found between fibrosis and hepatic resistance (p less than 0.01). Further, hepatic architectural destruction (p less than 0.01) was positively correlated to hepatic resistance. Necrosis, fatty change, occurrence of Mallory bodies or inflammation showed no significant correlation with hepatic resistance. Mean hepatocyte volume was calculated in 29 patients, but no correlation was found with haemodynamic variables. The present data substantiate the concept that established portal hypertension in alcoholic liver disease is mainly accomplished by a derangement in hepatic architecture, whereas parenchymal changes, including hepatocyte size, are of less importance.

Adult↗

Units in the cerebral cortex of the anaesthetized rat and the correlations between their discharges.

1. Extracellular records have been made of spontaneous unitary activity in the cortex of the anaesthetized rat. If the animal is anaesthetized with sufficient urethane almost to abolish reflex contractions of leg muscles when a hind paw is stimulated, two types of spontaneously active unit are found. One type of unit is found in all areas of the cortex which have been studied, and gives high voltage discharges. The other has only been foun in restricted areas of cortex and gives low voltage discharges. 2. The activity of the former type of unit has been analysed. In the unstimulated animal, groups of relatively frequent discharges are separated by periods of quiescence. Apart from this, the discharge pattern appears irregular on naked-eye examination. Synchronous with these periods of frequent discharge, the electrocorticogram exhibits rapid oscillations. Peripheral stimulation of the animal can modify the pattern of discharge of this type of unit. Details of these observations are described. 3. The results are described of experiments in which simultaneous records have been taken from pairs of units in the cerebral cortex. The intensity of correlation between the two units has been measured as a function of temporal displacement (lag) between the two records. 4. With fairly deep urethane anaesthesia, the highest correlation between the two unitary discharges occurs at zero lag if the two units are close together or if they are far apart but in the same coronal line, e.g. if the recording electrodes lie in homologous areas of the two cerebral hemispheres. If one unit is in the anterior pole of a hemisphere and the other in the posterior pole, the discharges are usually synchronous. However, it has sometimes been found that the anterior of the pair of units discharges impulses which precede those of the posterior unit by up to 100 msec. The highest intensity of correlation is then appropriately displaced to 100 msec. 5. The correlation fluctuates rhythmically with a period of 1-8-2 sec, slowly damps out and is symmetrical around the point of highest correlation. 6. Increasing the sensory bombardment of the cortex reduces or abolishes the correlation between the activity of pairs of units. 7. Under Nembutal anaesthesia sufficient to abolish reflex contractions of leg muscles when a hind paw is pinched, no spontaneous cortical unitary activity has been found. When anaesthesia is ligher, spontaneous activity does occur and consists of bursts of up to six impulses at a frequency of 300-500/sec. When simultaneous records from two units have been made, no correlation has been found between their activity.

Anesthetics, Intravenous↗

Comparison and correlation of neisseria meningitidis serogroup B immunologic assay results and human antibody responses following three doses of the Norwegian meningococcal outer membrane vesicle vaccine MenBvac.

The prediction of efficacy of Neisseria meningitidis serogroup B (MenB) vaccines is currently hindered due to the lack of an appropriate correlate of protection. For outer membrane vesicle (OMV) vaccines, immunogenicity has primarily been determined by the serum bactericidal antibody (SBA) assay and OMV enzyme-linked immunosorbent assay (ELISA). However, the opsonophagocytic assay (OPA), surface labeling assay, whole blood assay (WBA), and salivary antibody ELISA have been developed although correlation with protection is presently undetermined. Therefore, the aim of the study was to investigate further the usefulness of, and relationships between, MenB immunologic assays. A phase II trial of the OMV vaccine, MenBvac, with proven efficacy was initiated to compare immunologic assays incorporating the vaccine and six heterologous strains. Correlations were achieved between the SBA assay, OMV ELISA, and OPA using human polymorphonuclear leukocytes and human complement but not between an OPA using HL60 phagocytic cells and baby rabbit complement. Correlations between the surface labeling assay, the SBA assay, and the OMV ELISA were promising, although target strain dependent. Correlations between the salivary antibody ELISA and other assays were poor. Correlations to the WBA were prevented since many samples had results greater than the range of the assay. The study confirmed the immunogenicity and benefit of a third dose of MenBvac against the homologous vaccine strain using a variety of immunologic assays. These results emphasize the need for standardized methodologies that would allow a more robust comparison of assays between laboratories and promote their further evaluation as correlates of protection against MenB disease.

Adult↗

Correlation of simultaneously obtained capillary, venous, and arterial blood gases of patients in a paediatric intensive care unit.

AIMS: To investigate the correlation of pH, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), base excess (BE), and bicarbonate (HCO3) between arterial (ABG), venous (VBG), and capillary (CBG) blood gases. METHODS: Patients admitted to the paediatric intensive care unit (PICU) in Cukurova University between August 2000 and February 2002 were enrolled. RESULTS: A total of 116 simultaneous venous, arterial, and capillary blood samples were obtained from 116 patients (mean age 56.91 months, range 15 days to 160 months). Eight (7%) were neonates. Sixty six (57%) were males. pH, PCO2, BE, and HCO3 were all significantly correlated in ABG, VBG, and CBG. Correlation in PO2 was also significant, but less so. Correlation between pH, PCO2, PO2, BE, and HCO3 was similar in the presence of hypothermia, hyperthermia, and prolonged capillary refilling time. In hypotension, correlation in PO2 between VBG and CBG was similar but disappeared in ABG-VBG and ABG-CBG. CONCLUSIONS: There is a significant correlation in pH, PCO2, PO2, BE, and HCO3 among ABG, VBG, and CBG values, except for a poor correlation in PO2 in the presence of hypotension. Capillary and venous blood gas measurements may be useful alternatives to arterial samples for patients who do not require regular continuous blood pressure recordings and close monitoring of PaO2. We do not recommend CBG and VBG for determining PO2 of ABG.

Adolescent↗

Atypical hyperplasia of the breast: mammographic appearance and histologic correlation.

The mammograms and histologic slides of 58 cases of atypical hyperplasia (AH) of the breast were retrospectively reviewed to determine the geographic correlation (direct, near, or remote) between mammographic abnormalities (if present) and the histologic findings. A direct mammographic-histologic correlation was found in 24 of the 58 cases (41%), near correlation in 15 (26%), and remote correlation in 19 (33%). Clustered microcalcifications were the most common mammographic abnormality that was directly correlated with AH at histologic examination. Atypical ductal hyperplasia was much more frequently associated with a direct mammographic-histologic correlation than was atypical lobular hyperplasia (48% vs 9%). The authors conclude that, although no pathognomonic appearance of AH was discovered, mammographic abnormalities similar to those of small cancers could be directly correlated with histologic findings in 41% of cases. Since AH has been shown to be associated with a five- to tenfold increased risk of subsequent invasive carcinoma, frequent clinical and at least yearly mammographic follow-up is suggested once AH is discovered.

Adult↗

Is there a correlation between ventricular fibrillation cycle length and electrophysiological and anatomic properties of the canine left ventricle?

We hypothesized that myocardial infarction-related alterations in ventricular fibrillation (VF) cycle length (VFCL) would correlate with changes in local cardiac electrophysiological and anatomic properties. An electrophysiological study was performed in normal, subacute, and chronic infarction mongrel dogs. VF was induced by programmed electrical stimulation and mean and minimum early and late VFCL was determined and correlated with local electrophysiological and anatomic properties. Effective refractory period (ERP), activation recovery time (ART), ERP/ART ratio, threshold, and ERP and ART dispersion were determined at 112 sites on the anterior left ventricle. Wave front progression was analyzed over a 2-s period. The extent of local tissue necrosis and of myocardial fiber disarray was also evaluated. The early mean VFCL was significantly longer in the subacute infarction (149 +/- 35 ms) and chronic infarction dogs (129 +/- 18 ms) compared with control dogs (102 +/- 15 ms; P < 0.0001 for both comparisons) as was the early minimum VFCL with similar trends seen during late VF. Complete epicardial reentrant circuits were significantly more common in normal dogs (4.3 +/- 2.4, 22.4% of cycles) than in subacute (0.75 +/- 0.96, 5.3% of cycles, P < 0.05 vs. normal) and chronic infarction dogs (1.3 +/- 1.3, 7.5% of cycles, P < 0.05 vs. normal). There was a poor correlation between the mean and minimum early and late VFCL and local electrophysiological and anatomic properties (R(2) < 0.2 for all comparisons) with a much better correlation between average mean and minimum VFCL (over the entire plaque) and global ERP and ART dispersion during early and late VF. In conclusion, VFCL in normal and infarcted myocardium shows a poor correlation with local ventricular electrophysiological and anatomic properties measured in sinus rhythm. However, there was a much better correlation between the average VFCL with global dispersion of repolarization. The lack of correlation between local VFCL and refractoriness and the infrequent occurrence of epicardial reentry suggests that intramural reentry may be the primary mechanism of VF in this model.

Animals↗

Temporal correlation of measurements of airway hyperresponsiveness in ovalbumin-sensitized mice.

Airway hyperresponsiveness, airway inflammation, and reversible airway obstruction are physiological hallmarks of asthma. These responses are increasingly being studied in murine models of antigen exposure and challenge, using whole body plethysmography to noninvasively assess airway hyperresponsiveness. This approach infrequently has been correlated with indexes of airway hyperresponsiveness measured by invasive means. Furthermore, correlation with quantitative histological data for tissue infiltration by inflammatory and immune cells, particularly in the wall of airways, during daily airway challenge is lacking. To address these uncertainties, we used C57BL/6 mice that were immunized with ovalbumin or vehicle (saline) and sensitized to aerosolized ovalbumin or vehicle 8 days later. The mice were subsequently exposed to aerosolized ovalbumin or vehicle, respectively, on days 14-22. We assessed airway hyperresponsiveness to methacholine noninvasively on days 14, 15, 18, or 22; we studied the same mice 24 h later while they were anesthetized for invasive analyses of airway hyperresponsiveness. Plasma total IgE concentration was significantly higher in the ovalbumin-treated mice compared with the vehicle-treated mice, but this did not correlate with eosinophil number. Peak airway hyperresponsiveness measured by either approach correlated early during daily antigen challenge (days 14 and 15), but this correlation was lost later during subsequent daily antigen challenges (days 18 and 22). On days 14 and 15, peak airway hyperresponsiveness correlated with transmigration of neutrophils and macrophages, but not lymphocytes, in the peribronchovascular connective tissue sheaths. This extravascular accumulation was found to be focal by three-dimensional microscopy. We conclude that, although ovalbumin treatment changed lung function in mice, correlation between noninvasive and invasive measures of peak airway hyperresponsiveness was inconsistent.

Animals↗

Correlation of primate caudate neural activity and saccade parameters in reward-oriented behavior.

Changes in the reward context are associated with changes in neuronal activity in the basal ganglia as well as changes in motor outputs. A typical example is found in the caudate (CD) projection neurons and saccade parameters. It raised the possibility that the changes in CD neuronal activity contribute to the changes in saccade parameters. To examine this possibility, we calculated the correlation coefficients (CORs) of the firing rates of each neuron with saccade parameters (peak saccade velocity and latency) on a trial-by-trial basis. We then calculated the mean CORs separately for two CD populations: reward-enhanced type neurons (RENs) that showed enhanced activity and reward-depressed type neurons (RDNs) that showed depressed activity when reward was expected. The activity of RENs was positively correlated with the saccadic peak velocity and negatively correlated with the saccade latency. The activity of RDNs was not significantly correlated with the saccade parameters. We further analyzed the CORs for RENs, a major type of CD neurons. First, we examined the time courses of the CORs using a moving time window (duration: 200 ms). The positive correlation with the saccade velocity and the negative correlation with the saccade latency were present not only in the peri-saccadic period but also during the pre- and postcue periods. Second, we asked whether the CORs with the saccade parameters were direction-selective. A majority of RENs were more active before contralateral saccades (contralateral-preferring neurons) and their activity was correlated more strongly with contralateral saccades than with ipsilateral saccades. A minority of RENs, ipsilateral-preferring neurons, showed no such preference. These results are consistent with the hypothesis that CD neuronal activity exerts facilitatory effects on contralateral saccades and that the effects start well before saccade execution. Furthermore, a multiple regression analysis indicated that changes in activity of some, but not all, CD neurons could be explained by changes in saccade parameters; a major determinant was reward context (presence or absence of reward). These results suggest that, while a majority of CD neurons receive reward-related signals, only some of them can make a significant contribution to change saccadic outputs based on expected reward.

Animals↗

Axonal projections of caudal ventrolateral medullary and medullary raphe neurons with activity correlated to the 10-Hz rhythm in sympathetic nerve discharge.

1. This is the first study to map the axonal projections of medullary neurons that are elements of the network responsible for the 10-Hz rhythm in sympathetic nerve discharge (SND) of urethan-anesthetized cats. Spike-triggered averaging and coherence analysis were used to identify caudal ventrolateral medullary (CVLM) and medullary raphe neurons with activity correlated to this component of SND. Spike-triggered averaging showed that CVLM neurons fired significantly earlier (17 ms on the average) than raphe neurons during the 10-Hz slow wave in inferior cardiac postganglionic SND. This observation raised the possibility that CVLM neurons are a source of the discharges of raphe neurons that are correlated to SND. 2. Nineteen of 47 CVLM neurons with activity correlated to the 10-Hz rhythm in SND were antidromically activated by micro-stimulation of the raphe. The longest onset latency of antidromic activation was 19.9 +/- 2.8 (SE) ms, a value comparable with the difference in firing times of CVLM and raphe neurons during the naturally occurring 10-Hz slow wave in inferior cardiac SND. In most cases the response likely reflected activation of an axonal branch of the CVLM neuron, because the onset latency of antidromic activation could be changed dramatically by moving the stimulating microelectrode as little as 0.2 mm within the raphe. Also, the onset latency of antidromic activation of nine CVLM neurons was significantly shortened (25.0 +/- 2.5 vs. 16.7 +/- 2.7 ms) when the stimulus intensity was raised above threshold. 3. The hypothesis that the axons of CVLM neurons with activity correlated to the 10-Hz rhythm in SND terminated on and excited raphe neurons was supported by the following observations. First, CVLM neurons could not be antidromically activated by stimuli applied to sites in tracks located 1.5-2 mm lateral to the midline, contralateral to the neuronal recording site; thus their axons did not cross the midline. Second, some CVLM neurons could be antidromically activated by stimuli applied to sites in only one of the tracks through the midline; thus it is unlikely that their axons were destined for more rostral or caudal portions of the brain stem. Third, 37% of the raphe neurons with activity correlated to the 10-Hz rhythm were synaptically activated by microstimulation of the CVLM, with a minimum onset latency of 18.1 +/- 2.6 ms. This value was not significantly different than the longest onset latency of antidromic activation of CVLM neurons by raphe stimulation. 4. CVLM neurons with activity correlated to the 10-Hz rhythm in SND could not be antidromically activated by microstimulation of the rostral ventrolateral medulla (RVLM) or thoracic spinal cord. Thus CVLM neurons are not a direct source of the 10-Hz discharges of RVLM or preganglionic sympathetic neurons. 5. Eight of 41 raphe neurons with activity correlated to the 10-Hz rhythm in SND were antidromically activated by microstimulation of the CVLM. The latency of the antidromic response of six raphe neurons was shortened from 15.2 +/- 3.1 to 11.9 +/- 3.1 ms by raising stimulus current above threshold, implying the existence of local axonal branching. The onset latency of antidromic activation of five raphe neurons was changed by moving the stimulating microelectrode within the CVLM. 6. The axons of at least some of these raphe neurons likely terminated in the CVLM, because higher current was required to antidromically activate these neurons from sites in a track located 0.5 mm further laterally, and they were not antidromically activated by microstimulation of the RVLM. Also 32% of the CVLM neurons were either excited or inhibited by microstimulation of the raphe. The minimum onset latency of synaptic activation (18.3 +/- 4.2 ms) or inhibition (10-20 ms) of CVLM neurons by raphe stimulation was similar to the longest onset latency of antidromic activation of raphe neurons by CVLM microstimulation. 7. These data are consistent with the view

Animals↗

[Correlation of hematologic parameters with bone marrow and spleen uptake in FDG PET].

OBJECTIVE: To assess the relationship between various hematologic parameters and bone marrow (BM) and splenic uptake of FDG in PET imaging. MATERIAL AND METHODS: 29 patients with Hodgkin's disease (HD) referred for baseline FDG PET imaging before treatment and without evidence of bone marrow (BM) involvement were included in the study. Splenic uptake also was analyzed in 18 patients without splenic involvement. BM and splenic activity were visually graded on a 3 point scale. Activity pattern was classified as homogeneous or heterogeneous. Semi-quantitative analysis was also performed by drawing regions of interest (ROI) over the spine and spleen. ROIs also were drawn over right lung and liver. FDG uptake ratios for the spine and spleen in comparison with the lung and liver were generated. Visual scoring of marrow and splenic uptake, and the various ratios were correlated with hemoglobin (Hb), white blood cell (WBC), and platelet counts, and correlation coefficients were calculated. RESULTS: In 27/29 patients (93 %) BM and in 18/18 patients (100 %) spleen uptake was diffuse. There was a direct correlation between BM and spleen uptake of FDG with increasing WBC, which was stronger than the inverse correlation seen with Hb (the lower the Hb the greater the uptake). Correlation with platelet counts was weaker. CONCLUSION: There is a correlation between hematologic parameters such as Hb, WBC and platelet counts and the uptake of FDG in BM and spleen in PET imaging. Knowledge of this correlation should help to better interpret and understand PET imaging.

Adolescent↗

Insulin-like growth factor I correlates with protein intake estimated from the normalized protein catabolic rate in hemodialysis patients.

BACKGROUND/AIM: Malnutrition and catabolism are predominant problems in patients undergoing hemodialysis. The aim of this study was to clarify the relationship between insulin-like growth factor I (IGF-I), the serum levels of which are influenced by nutrition and which by itself promotes amino acid uptake, and insulin-like growth factor binding protein 1 (IGFBP-1), known to regulate serum (s) IGF-I and protein intake, in end-stage renal disease patients. METHODS: Thirty hemodialysis patients were studied, and s-IGF-I and s-IGFBP-1 levels were measured by radioimmunoassay. The s-IGF-I method used was validated according to a reference method. The s-IGF-I standard deviation (SD) score was calculated, giving the individual deviation from the mean of a reference population. The protein intake was estimated both directly by 3-day food recall by a dietician and indirectly by normalized protein catabolic rate (PCRn). RESULTS: The mean serum IGF-I level was 166 +/- 10 microgr;g/l, corresponding to a normal s-IGF-I SD score (0.5 +/- 0.3). S-IGFBP-1 was elevated threefold to 101 +/- 11 microg/l as compared with normal subjects. The s-albumin was 39.9 +/- 0.5 g/l and the s-bicarbonate 24 +/- 0.4 mmol/l. There were significant correlations between s-IGF-I SD score or s-IGF-I (log-transformed) and PCRn (r = 0.37, p < 0.004, and r = 0.41, p < 0.001, respectively). The s-IGF-I/s-IGFBP-1 ratio was also positively correlated with PCRn (r(s) = 0.36, p < 0.007, by Spearman's rank correlation). The s-albumin was inversely correlated with log s-IGFBP-1 (r = -0.38, p < 0.01) and positively with the s-IGF-I/s-IGFBP-1 ratio (r = 0.36, p < 0.007) but not with s-IGF-I (p < 0.13). Serum total cholesterol, triglycerides, and total body fat as percentage of body weight correlated with s-IGF-I (r = 0.47, p < 0.004, r = 0.45, p < 0.01, and r = 0.42, p < 0.004, respectively) as well as with the s-IGF-I SD score. No correlations were seen between s-IGF-I and protein or caloric intake by direct estimates from dietary food recalls. CONCLUSIONS: The s-IGF-I and the s-IGF-I/s-IGFBP-1 ratio were correlated with estimates of protein intake of the patients calculated from urea kinetics (PCRn) but not with direct estimates by the dietitian. The s-IGF-I SD score and the ratio s-IGF-I/s-IGFBP-1 might be a tool to monitor anabolic status and to select hemodialysis patients for therapeutic intervention with recombinant human IGF-I and/or recombinant human growth hormone to counteract catabolism.

Adult↗