Human Echolocators Have Better Localization Off Axis.

Here, we report novel empirical results from a psychophysical experiment in which we tested the echolocation abilities of nine blind adult human experts in click-based echolocation. We found that they had better acuity in localizing a target and used lower intensity emissions (i.e., mouth clicks) when a target was placed 45° off to the side compared with when it was placed at 0° (straight ahead). We provide a possible explanation of the behavioral result in terms of binaural-intensity signals, which appear to change more rapidly around 45°. The finding that echolocators have better echo-localization off axis is surprising, because for human source localization (i.e., regular spatial hearing), it is well known that performance is best when targets are straight ahead (0°) and decreases as targets move farther to the side. This may suggest that human echolocation and source hearing rely on different acoustic cues and that human spatial hearing has more facets than previously thought.

Human Click-Based Echolocation of Distance: Superfine Acuity and Dynamic Clicking Behaviour.

Some people who are blind have trained themselves in echolocation using mouth clicks. Here, we provide the first report of psychophysical and clicking data during echolocation of distance from a group of 8 blind people with experience in mouth click-based echolocation (daily use for > 3 years). We found that experienced echolocators can detect changes in distance of 3 cm at a reference distance of 50 cm, and a change of 7 cm at a reference distance of 150 cm, regardless of object size (i.e. 28.5 cm vs. 80 cm diameter disk). Participants made mouth clicks that were more intense and they made more clicks for weaker reflectors (i.e. same object at farther distance, or smaller object at same distance), but number and intensity of clicks were adjusted independently from one another. The acuity we found is better than previous estimates based on samples of sighted participants without experience in echolocation or individual experienced participants (i.e. single blind echolocators tested) and highlights adaptation of the perceptual system in blind human echolocators. Further, the dynamic adaptive clicking behaviour we observed suggests that number and intensity of emissions serve separate functions to increase SNR. The data may serve as an inspiration for low-cost (i.e. non-array based) artificial 'cognitive' sonar and radar systems, i.e. signal design, adaptive pulse repetition rate and intensity. It will also be useful for instruction and guidance for new users of echolocation.

The effect of hypnotic training programs on the academic performance of students.

The main objective of the present study was to empirically verify the effect of hypnotic training programs on the academic performance of students. A pre and posttest design was used. Two experimental and two control groups (total sample N=119) of volunteer second year psychology students at the University of Stellenbosch in South Africa comprised the sample. One of the experimental groups was exposed to active alert hypnosis and the other to relaxation hypnosis. One control group was exposed to progressive relaxation, while the other did not receive any intervention. The participants' April grades were used as a pretest, while their June grades served as a posttest. The two hypnotic training programs had a significant effect on the academic achievement of the participants, which was not found in the control groups. Regarding the efficacy of the two programs, however, no significant difference was found.

Imidazoline receptors, non-adrenergic idazoxan binding sites and alpha 2-adrenoceptors in the human central nervous system.

Both [3H]clonidine and [3H]idazoxan bind to alpha 2 adrenoceptors. The former also labels imidazoline receptors, and the latter non-adrenergic idazoxan binding sites. In order to investigate whether the imidazoline receptors and non-adrenergic idazoxan binding sites are identical, we compared the binding characteristics of [3H]clonidine and [3H]idazoxan to these sites by radioligand binding experiments on ultra-thin slices and homogenates of human striatum. A good correlation was found between the effect of different ions on the binding characteristics of [3H]clonidine and [3H]idazoxan, and the affinities of most competing drugs. However, clonidine and rilmenidine displayed a 100- and 10-fold lower affinity, respectively, for the idazoxan binding sites than for the imidazoline receptors. Autoradiography with [3H]clonidine showed that high densities of imidazoline receptors were present in the striatum, pallidum, gyrus dentatus of the hippocampus, amygdala, and substantia nigra. Moderate densities were found throughout the cerebral cortex, thalamus and several brainstem nuclei including the nucleus olivarius inferior. Low densities were seen in the cerebellum, spinal cord and pituitary gland. As for the non-adrenergic sites labelled by [3H]idazoxan, the imidazoline receptors can be found in all major brain areas examined. However, there are some striking differences between the concentrations of imidazoline receptors and non-adrenergic idazoxan binding sites in certain brain regions. To reconcile distribution and pharmacologic data, we propose that imidazoline receptors and non-adrenergic idazoxan binding sites represent different proteins or protein complexes and that at least in the nucleus reticularis lateralis and the striatum, imidazoline receptors and non-adrenergic idazoxan binding sites may be physically associated. The regional distribution of alpha 2 adrenoceptors within the human CNS was determined by quantitative autoradiography with [3H]RX821002. The highest densities of alpha 2 adrenoceptors were found in the cerebral and cerebellar cortex, and certain regions in the medulla oblongata (floor of the IV ventricle, reticular formation, hypoglossal nucleus and nucleus olivarius inferior). No alpha 2 adrenoceptors were detected in the pituitary gland. There exists no relationship between the distribution pattern of imidazoline receptors and alpha 2 adrenoceptors, indicating that these binding sites are independent from each other.

Identification of a D1 dopamine receptor, not linked to adenylate cyclase, on lactotroph cells.

1. We studied the lactotroph cells of the rat by both in vivo and in vitro pharmacological techniques for the presence of D1-receptors. Both approaches revealed the presence of D2-receptor, stimulated by quinpirole (resulting in an inhibition of prolactin secretion) and blocked by domperidone. 2. Administration of fenoldopam, the most selective D1-receptor agonist currently available, resulted in a dose-dependent decrease of prolactin secretion in vivo (after pretreatment with alpha-methyl-p-tyrosine) and in vitro (cultured pituitary cells). This increase was dose-dependently blocked by the selective D1-receptor antagonist, SCH 23390, and although the effect of fenoldopam was less than that obtained by D2-receptor stimulation, these data suggest that a D1-receptor also controls prolactin secretion. 3. In order to detect the location of these dopamine receptors, autoradiographic studies were performed by use of [3H]-SCH 23390 and [3H]-spiperone as markers for D1- and D2-receptors, respectively. Specific binding sites for [3H]-SCH 23390 were demonstrated. Fenoldopam dose-dependently reduced [3H]-SCH 23390 binding, but had no effect on [3H]-spiperone binding. Immunocytochemical labelling of prolactin cells after incubation with [3H]-SCH 23390 revealed that the granulae and hence, D1 binding sites were present on the lactotroph cells. 4. Radioligand binding studies performed on membranes from anterior pituitary cells revealed the presence of the D2-receptor (54 fmol mg-1 protein) with a Kd of 0.58 nM for [3H]-spiperone, but failed to detect D1-receptors. 5. Finally, we studied the effect of dopamine and of fenoldopam on the adenosine 3':5'-cyclic monophosphate (cyclic AMP) content of anterior pituitary cells. Although cyclic AMP increased upon prostacyclin administration, indicating an intact adenylate cyclase system, fenoldopam failed to increase the cyclic AMP production. 6. It is tempting to speculate that fenoldopam reduces prolactin secretion through interaction with a non-cyclase-linked D1-receptor on the lactotroph cells.

Identification of ?(2) adrenergic receptors in human frontal cortex membranes by binding of [(3)H]RX 821002, the 2-methoxy analog of [(3)H]idazoxan.

The antagonist [(3)H]idazoxan binds with comparable affinity to ?(2) adrenergic receptors and to phentolamine-displaceable non-stereoselective sites in human frontal cortex membranes. In contrast, idazoxan analogs possessing alkyl and alkoxy substituents at the 2-position of the benzodioxan moiety (i.e. RX 821002: 2-methoxy-1,4-[6,7-(3)H]benzodioxan-2-yl-2-imidazolin HCl, 43.8 Ci/mmol) possess 300-1200 times lower affinity for the non-stereoselective sites. Their affinity for the ?(2) receptors is increased as well, resulting in more than a 1000-fold selectivity towards the receptors as compared to the non-stereoselective sites. [(3)H]RX 821002, the 2-methoxy analog of idazoxan possesses an approx. 10-fold higher affinity for the ?(2) receptors (K(D) = 2.8 nM than [(3)H]idazoxan (K(D) = 24 nM) and about equal affinity as [(3)H]rauwolscine (K(D) = 3.6 nM). [(3)H]Rauwolscine binds with comparable affinity to ?(2) receptors and to 5-HT(1A) receptors, and competition studies indicate that the K(i) value of unlabelled RX 821002 for the 5-HT(1A) receptors (30 nM) is about one order in magnitude above its K(i) value for the ?(2) receptors (4.1 nM). Labelling of the 5-HT(1A) receptors by [(3)H]RX 821002 and by [(3)H]rauwolscine can be prevented by selective masking with 8-OH-DPAT (30 nM) or 5-HT (0.3 ?M). Under these conditions, specific binding of [(3)H]RX 821002 to the ?(2) receptors represents 84% of total binding (at its K(D)), as compared to 77% for [(3)H]rauwolscine and 20% for [(3)H]idazoxan. [(3)H]RX 821002 labels the ?(2) receptors as a single class of non-cooperative sites. Association and dissociation kinetics are very fast at 37 degrees C. Antagonist competition curves are steep with Hill coefficients close to one and the agonist curves can be analysed in terms of two affinity sites, confirming the antagonistic properties of [(3)H]RX821002. About 60% of the ?(2) receptors possess high agonist affinity.

Efaroxan (RX 821037) is a potent and selective ?(2)-adrenoceptor antagonist in human frontal cortex membranes.

The antagonist [(3)H]idazoxan binds with comparable affinity to ?(2) adrenergic receptors and to non-adrenergic "idazoxan sites" in human frontal cortex membranes (K(D) = 23 and 28 nM). RX 811033, the 2-ethyl derivative of idazoxan, displays about equal affinity for the ?(2) receptors as idazoxan but much lower affinity for the idazoxan sites (K(i) = 19 nM and 28 ?M). Compared to RX 811033, efaroxan (RX 821037) has a dihydrobenzylfuranyl ring system instead of a benzodioxan ring. Nevertheless, efaroxan and RX 811033 bind with equal high affinity to the ?(2) receptors and with equal low affinity to the idazoxan sites. Radioligand binding studies with [(3)H]RX 821002, the 2-methoxy derivative of [(3)H]idazoxan, confirm that efaroxan is an ?(2) adrenergic antagonist possessing high affinity for the ?(2) receptors and high ?(2) receptor/idazoxan site-selectivity in the human frontal cortex.

Alpha 2A adrenoceptors and non-adrenergic idazoxan binding sites in calf brain and retina are distinct from those in human brain.

alpha 2 Adrenoceptors in membrane preparations of human and calf frontal cortex and of calf retina can be labelled by the antagonists [3H]idazoxan, [3H]rauwolscine and [3H]RX 821002. Present and previous data indicate that [3H]idazoxan possesses the highest affinity for the alpha 2 adrenoceptors in the calf tissues, whereas [3H]rauwolscine displays the highest affinity for those in the human frontal cortex. Competition binding experiments with adrenergic and serotonergic drugs further support the notion that the alpha 2 adrenoceptors in calf frontal cortex and retina are similar, but distinct from the receptors in human frontal cortex. The alpha 2 adrenoceptors in the three investigated tissues display low affinity for the antagonist prazosin, which suggests that they all belong to the alpha 2A subclass. The competition binding curves of the alpha 2A adrenoceptor subtype-selective agonist oxymetazoline are shallow, but undergo a rightward shift and steepening in the presence of GTP. The shallow curves can therefore be attributed to the coupling of the alpha 2 adrenoceptors to G proteins. The different binding characteristics of the alpha 2A adrenoceptors from the investigated human and bovine tissues are likely to reflect species-related differences in protein structure. [3H]Idazoxan binds also to non-adrenergic sites in membrane preparations from the three tissues. However, the affinity of [3H]idazoxan for these sites in calf cortex and retina is appreciably lower than for those in human cortex. The species-related differences of the non-adrenergic idazoxan binding sites may be due to differences in protein structure or even to differences in gene-product.

Autoradiographic distribution of alpha 2 adrenoceptors, NAIBS, and 5-HT1A receptors in human brain using [3H]idazoxan and [3H]rauwolscine.

The regional distribution of [3H]idazoxan and [3H]rauwolscine was studied autoradiographically in human brain. [3H]Idazoxan binds with high affinity to alpha 2 adrenoceptors as well as to non-adrenergic sites (NAIBS). [3H]Rauwolscine, besides binding to alpha 2 adrenoceptors, also binds to 5-HT1A receptors. Both radioligands labelled the same population of alpha 2 adrenoceptors, defined as the epinephrine-displaceable binding component. The highest densities of alpha 2 adrenoceptors occur in the leptomeninges, cerebral cortex and claustrum; lower densities were visualised in the basal ganglia, thalamus, pons, substantia nigra, cerebellum and medulla oblongata; no alpha 2 adrenoceptors were detected in amygdala and nucleus ruber. NAIBS were present in all the examined brain areas, with the highest densities found in the basal ganglia and substantia nigra. The finding that certain brain regions, such as the amygdala, contained NAIBS but no detectable alpha 2 adrenoceptors, suggests that the binding sites are independent from each other. The regional distribution of 5-HT1A receptors labelled by [3H]rauwolscine is in agreement with previous studies using [3H]8-OH-DPAT.

[3H]rauwolscine behaves as an agonist for the 5-HT1A receptors in human frontal cortex membranes.

The alpha 2 adrenergic antagonist [3H]rauwolscine binds with comparable nanomolar affinity to alpha 2 adrenoceptors and the nonadrenergic 5-HT1A receptors sites in human frontal cortex membranes. Addition of 0.5 mM GTP into the incubation medium produces a significant decrease in the amount of [3H]rauwolscine binding sites (Bmax = 230 +/- 16 and 115 +/- 11 fmol/mg protein in the absence and presence of GTP, respectively). The affinity for [3H]rauwolscine remains unchanged (i.e. KD = 40 +/- 0.9 nM and 4.1 +/- 1 nM). This effect of GTP can be attributed to decreased binding of the radioligand to the 5-HT1A receptors. GTP decreases binding of [3H]rauwolscine to nearly the same level as the one corresponding to the alpha 2 adrenoceptors in membranes from both the human frontal cortex and hippocampus. The venom of the marine cone snail, Conus tessulatus, preferentially inhibits [3H]rauwolscine binding to 5-HT1A receptors as compared with the alpha 2 adrenoceptors. Following complete masking of the 5-HT1A receptors by this venom. GTP no longer affects the saturation binding characteristics of [3H]rauwolscine for the remaining alpha 2 adrenoceptors. Nucleotides decrease the binding of [3H]rauwolscine to the 5-HT1A receptors with an order of potencies (i.e. GTP gamma S greater than GPP(NH)P much greater than GDP greater than GTP much greater than ATP) that is typical for nucleotide-mediated receptor-G protein dissociation. This suggests that [3H]rauwolscine is a 5-HT1A receptor agonist and this conclusion is compatible with earlier functional studies, indicating that rauwolscine (as well as yohimbine) has agonistic properties at the level of 5-HT autoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

What intracranial tissues in humans contain sumatriptan-sensitive serotonin 5-HT1-type receptors?

We investigated the presence of sumatriptan-sensitive serotonin (5-HT)1 receptors in different human tissues by using a radioligand-binding technique with [3H]5-HT. Sumatriptan displaced [3H]5-HT from frontal cortical and striatal membranes in a biphasic manner, with a high-affinity site corresponding to binding to the 5-HT1D receptor. In blood platelet membranes, sumatriptan displaced [3H]5-HT with a 100-fold lower affinity. Sumatriptan failed to displace [3H]5-HT in membranes from large cerebral arteries, pial vessels, coronary arteries and dura mater. These findings suggest that either there are no sumatriptan-sensitive 5-HT1 receptors on intracranial blood vessels or they are so small in number that they cannot be detected by the radioligand-binding technique. Other mechanisms, possibly centrally mediated, may be responsible for the antimigraine action of sumatriptan.

Effect of indomethacin in preventing surgically induced miosis.

A double-blind study was performed on 64 patients to assess the effect of preoperative indomethacin in comparison with a placebo in preventing surgically induced miosis during extracapsular cataract extraction. One drop of indomethacin or placebo was instilled at 7.00 p.m. and at 9.00 p.m. the night before surgery and 2 hours, 1 hour, and 15 minutes preoperatively. The pupil diameter was recorded at different stages of the operation. It was found that indomethacin as compared with the placebo significantly reduced the amount of pupil constriction during the operation, making the removal of lens material and the implantation of an intraocular lens easier. The indomethacin is thought to act by inhibiting prostaglandin synthesis caused by iris trauma during surgery.

Cyclic AMP content and invasive capacity of metastatic variants of the BW-5147 murine T-cell lymphoma.

The invasive behaviour of 8 lymphoma cell lines were tested by an in vitro monolayer invasion assay. The metastatic cell lines (TAM 4D1.2, DCH10Sp, TAM 4D6.2, E4 and BWLi) were more invasive than their non-metastatic counterparts (TAS 5C4, BWO and DCH 10). There was a positive correlation between their invasiveness and the PGE1- and forskolin stimulated cellular cAMP levels. Invasiveness and basal cAMP levels could not be correlated. Pretreatment with pertussis toxin (50 ng/ml) for 24 hours provoked did not significantly affect the basal and PGE1-stimulated cAMP levels in all cells. Yet, the toxin catalysed the ADP-ribosylation of 40 kDa components in all cells and provoked a significant increase in the invasiveness of non-metastatic cell lines and a decrease in the invasiveness of metastatic cell lines. These data suggest that the invasiveness of T-lymphoma cell lines might be controlled by a complex interplay between different signal transducing pathways in the membrane, rather than by the intracellular level of cAMP.

Chemical defence in a sawfly: genetic components of variation in relevant life-history traits.

Larvae of several tenthredinid sawfly species readily release droplets of haemolymph through their integument when attacked by predators. This defence mechanism via 'bleeding' is characterised by a low integument resistance and a high haemolymph deterrence. Both traits are variable, and negatively correlated among species. We sought to determine if such differences in the propensity to bleed also occur intraspecifically by studying the heritability of traits potentially associated with the bleeding phenomenon in the turnip sawfly Athalia rosae ruficornis Jakovlev (Hymenoptera: Tenthredinidae, Allantinae). For three European populations, heritabilities were estimated in the laboratory in a parent-offspring and a full-sib design for haemolymph deterrence (measured as concentration of sequestered glucosinolate), integument resistance, body mass of eonymph and adult, and developmental time. Within A. rosae, no significant negative phenotypic correlation was found between the two traits directly related to the defence mechanism: integument resistance and haemolymph deterrence. However, the significant heritabilities found for these traits in the full-sib analysis (0.39 and 0.35, respectively, for males in the Swiss population) show that the variation has a genetic component. While full-sib analysis revealed highly significant heritabilities for most traits in all the three populations, parent-offspring regression revealed little or no evidence of heritable variation. Effects of common environment for siblings and variation in the host-plant quality between insect generations are likely to be the main factors explaining these differences. A consequence of such host-plant variation in the wild might be that genetic variation of such chemical defensive traits is largely invisible to natural selection.

Demic structure and its relation with the distribution of an adaptive trait in Danish flea beetles.

The flea beetle Phyllotreta nemorum is an oligophagous species using crucifers as host plants. In Denmark two populations have been found which use Barbarea vulgaris ssp. arcuata (G-type) as a host plant, whereas this plant is unsuitable for the survival of the majority of P. nemorum. In the locations in which these two populations occur, alternative host plants are also present. The plants occur in patches, some of which contain a mixture of host plants. In this study of allozyme variation, genetic differentiation between P. nemorum using different host plants in patches in the two different localities was studied hierarchically to assess substructuring of the populations. Evidence was found for low, but significant, amounts of genetic differentiation between (sub)populations using spatially separated plant patches at a distance of approximately 100 m to 1 km (theta = 0.009) and between localities approximately 44 km apart (theta = 0.026), and there was an association between genetic differentiation and geographical distance. No genetic differentiation was found between beetles from different host plants with overlapping local distributions. No evidence was thus found for sympatric host race formation. The geographical distribution of genes enabling P. nemorum to use B. vulgaris as a host plant (100% 'resistant' beetles in samples from B. vulgaris, but much fewer on patches containing only alternative host plants) contrasts with the relatively low amount of genetic differentiation at the neutral allozyme loci. This distribution of 'resistant' beetles (to B. vulgaris defence) is likely to be influenced by local differences in selection and asymmetric gene flow.

Hyperaemic colour duplex scanning for the detection of aortoiliac stenoses. A comparative study with intra-arterial pressure measurement.

OBJECTIVES: Intra-arterial pressure measurement is considered the "gold standard" for the haemodynamic evaluation of aortoiliac lesions. When compared to pressure measurement duplex scanning fails to detect some of the haemodynamically significant lesions. To improve the assessment of the haemodynamic significance of these lesions by duplex scanning, the flow-related duplex parameters delta PSV and EDV at rest and after exercise were compared with intra-arterial pressure gradients before and during increased blood flow. PATIENTS AND METHODS: Forty-five aortoiliac segments with an isolated stenosis were studied prospectively. Doppler samples were taken at the site of the stenosis both at rest and after exercise on a bicycle ergometer, followed by intraarterial pressure measurement at rest and during pharmacologically induced increased blood flow. RESULTS: At rest a delta PSV (delta PSVr) of 1.6 m/s showed a sensitivity and specificity of 85% and 88%, respectively. After exercise a delta PSV (delta PSVe) of 1.6 m/s showed a sensitivity of 100% at the cost of only a slight reduction in specificity when compared to delta PSVr. The end diastolic velocity at rest (EDVr) had only limited clinical value. The EDV after exercise (EDVe) provided important information if the velocity was 0.5 m/s or lower or if the velocity was 1.6 m/s or greater. CONCLUSION: The delta PSV and the EDV after exercise can be of value in the assessment of the haemodynamic significance of aortoiliac stenoses.

Influence of the collateral function of the circle of Willis on hemispherical perfusion during carotid occlusion as assessed by transcranial colour-coded duplex ultrasonography.

OBJECTIVES: to investigate the collateral potential of the circle of Willis with transcranial colour-coded duplex ultrasonography and common carotid artery (CCA) compression. MATERIALS AND METHODS: in 46 atherosclerotic patients without cerebrovascular disease, the functional patency of the collaterals of the circle of Willis, the anterior and posterior communicating arteries, was assessed. The Peak Systolic Velocity (PSV) decrease in the middle cerebral artery (MCA) during CCA compression between complete and incomplete circles was compared. RESULTS: in 10 (22%) patients a complete and in 36 (78%) patients an incomplete circle of Willis was found, mainly due to non-functioning posterior communicating arteries. In hemispheres with collateral supply through both the anterior and the posterior communicating artery, the median PSV decrease in the MCA during CCA compression was 43%. When the posterior, anterior or both communicating arteries (1 hemisphere) were missing the PSV decrease was 58% (p =0.003), 70% (p =0.001) and 75%, respectively. CONCLUSIONS: collateral flow from the basilar to the carotid territory is often hampered by non-functioning posterior communicating arteries. A non-functioning anterior communicating artery is rare. A complete collateral circulation provides better perfusion of the MCA during carotid occlusion as compared with collateral supply through only the anterior or the posterior communicating artery in the case of an incomplete circle of Willis.

Manganese effects on the human neuroblastoma cell line SK-ER3.

SK-ER3 cells were recently demonstrated to represent a valuable model for the study of estrogen-inducible differentiation of neural cells in culture. This system may constitute an important tool also for the analysis of the effects of neurotoxic drugs. The present study demonstrates that short term exposure to Mn causes increased proliferation rate of SK-ER3 cells regardless of their differentiation. Long term treatment causes cell death in undifferentiated cells at concentrations of the metal as low as 100 nM. When the cells are differentiated with estrogens, death is observed only with a Mn concentration two orders of magnitude higher. Measurement of neurite extension and quantitation of tyrosine hydroxylase content after long-term exposure to the metal allow the conclusion that Mn does not alter the state of differentiation of SK-ER3 cells induced by the treatment with the hormone. The study underlines the importance of studying the effect of Mn in proliferating neural cells and demonstrates the toxic role of micromolar concentrations of the metal in fully differentiated neural cells. Since other authors produced evidence of effects of the metal on cell death and proliferation only at millimolar concentrations, and none described its proliferative activity, the model utilized in the present study seems to be of particular interest.

Interobserver variation of colour duplex scanning of the popliteal,tibial and pedal arteries.

OBJECTIVES: to determine interobserver variation in the measurement of Peak Systolic Velocity (PSV) and grading of disease by means of Duplex scanning (DS) in the popliteal, tibial and pedal arteries. DESIGN: prospective validation study. MATERIALS: twenty-four consecutive patients with severe claudication (n=6), ischaemic rest pain (n=11) and tissue loss (n=7). METHODS: two vascular technologists independently examined the popliteal, tibial and pedal arteries. The PSV was recorded in 15 arterial segments that were graded with B-mode and Doppler parameters as fully patent, severely diseased or occluded. Concordance in PSV recordings was expressed as intraclass correlation coefficients (ICC). Agreement in artery assessment was expressed as weighted kappa-values. RESULTS: the ICC for PSV measurements was 0.90 (95% CI, 0.86 to 0.93) within the popliteal and tibial arteries and 0.64 (95% CI, 0.37 to 0.81) within the pedal arteries. Agreement for grading disease was good within the popliteal and tibial arteries (kappa 0.66, 95% CI, 0.58 to 0.74), and moderate within the pedal arteries (kappa 0.54, 95% CI 0.33 to 0.74). The presence of diabetes or stage of disease did not influence interobserver agreement. CONCLUSION: interobserver agreement of DS is good within the popliteal and tibial arteries and moderate within the pedal arteries.