Comparative analysis of full-time, half-time, and quarter-time myocardial ECG-gated SPECT quantification in normal-weight and overweight patients.

BACKGROUND: The introduction of a camera-based dose-reduction strategy in myocardial perfusion imaging (MPI) clinical setting entails the definition of objective and reproducible criteria for establishing the amount of activity to be injected. AIM: The aim is to evaluate the impact of count statistics on the estimation of summed-scores (SS), end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF). METHODS: Data rest/stress ECG-gated SPECT (2-day protocol and 8 MBq·kg-1) were acquired with Bright View gamma camera and Astonish algorithm for 40 normal-weight and 40 overweight patients. Assuming that count statistics of shorter acquisition time may simulate that of lower injected activity, three simultaneous scans (full-time, half-time, and quarter-time scans) were started at the same time but with different acquisition time/projection (30, 15 and 8 seconds). RESULTS: A significant difference between SS values of half-time and quarter-time stress scans was found for overweight group (P = .006). Post hoc test showed significant differences for ESV (P < .05), EDV (P < .01) and EF (P < .05) between half-time and quarter-time scans for both patient groups. CONCLUSIONS: The reduction of the count-statistics to a quarter of the MPI reference influenced negatively the quantification in overweight patients. The decrease of radiopharmaceutical activity to 25% of the reference seems practicable for normal-weight patients, while it is more appropriate an activity reduction limited to 50% for overweight and obese patients.

The role of the dorsolateral prefrontal cortex in retrieval from long-term memory depends on strategies: a repetitive transcranial magnetic stimulation study.

The ability to associate a name to a face is a crucially relevant task in daily life. In this study, we investigated the neuronal basis of face-name retrieval in young subjects using repetitive transcranial magnetic stimulation (rTMS) over the left or right dorsolateral prefrontal cortex (DLPFC). The experimental task was composed of two study phases: an encoding phase and a retrieval phase. During the encoding phase, subjects saw a face (familiar or unfamiliar) followed by a name. During the retrieval phase, they saw the face together with two names and had to choose the name that was correctly associated with the face. rTMS was delivered only during retrieval. In addition, we evaluated the use of memory strategies during the task. Accordingly, subjects were subdivided into two groups: strategy users (SU) and no-strategy users (NSU). No rTMS effects were present for familiar face-name pairs, probably due to a ceiling effect. However, for unfamiliar face-name pairs, the different use of memory strategies resulted in different rTMS effects. The SU group showed a selective interference effect after right DLPFC stimulation, whereas the NSU group showed an effect after left DLPFC stimulation. Importantly, the overall performance of the two groups was comparable. We suggest that during memory retrieval the left DLPFC might be recruited when the subject does not apply deliberately a retrieval strategy whereas there is a shift to the right DLPFC if cognitive control processes that are engaged by strategies are needed to guide episodic retrieval.

The IGF-I/IGFBP-3 system in gingival crevicular fluid and dependence on application of fixed force.

BACKGROUND: During application of orthodontic force on the tooth, various molecular parameters associated with tissue remodeling are changed. IGF-I is a regulatory protein produced during periodontal regeneration. IGF binding proteins-3 (IGFBP-3), a specific IGF-I binding protein, is the major regulatory factor of IGF-I activity. OBJECTIVES: We tested the hypothesis that changes in the IGF-I/ IGFBP-3 system occur during fixed force application to the tooth and that these changes are detectable in the gingival crevicular fluid (GCF). METHODS: IGFBP-3 and IGF-I secretion into gingival crevicular fluid (GCF) was analyzed by Western blotting and immunoradiometric assay (IRMA), respectively, in GCF of 6 healthy subjects just prior to and during orthodontics treatment using fixed appliances. RESULTS: We observed a significant time-dependent decrease of IGFBP-3 content in GCF during orthodontic treatment (4 h and 10 days). Reduction in levels of intact, glycosylated 47 kDa form of IGFBP-3 was associated with its degradation and the appearance of intermediate breakdown products. IGF-I levels were significantly increased 4 h after application of orthodontic force, while they were significantly reduced 10 days after the start of treatment. CONCLUSIONS: IGFBP-3 secretion into GCF and its molecular structure are modified by the fixed force of orthodontic treatment. Alterations in IGFBP-3 appear to be unrelated to the binding to IGF-I, suggesting an IGF-independent role of this binding protein in tooth movement.

Comparison between iloprost and alprostadil in the treatment of Raynaud's phenomenon.

OBJECTIVE: The prostanoids iloprost and alprostadil are widely used to treat ischaemic changes in patients with Raynaud's phenomenon (RP), but the optimal regimen is poorly defined. We evaluated whether there are differences between iloprost and alprostadil, in terms of either clinical efficacy or of laboratory data, with the aim of assisting in the treatment of connective tissue disease (CTD)-associated RP. METHODS: Twenty-one women with CTD-associated RP were given intravenous iloprost (11 patients) or alprostadil (10 patients) cyclically (5 consecutive days, followed by 1 day every 30 days). Clinical efficacy (RP symptoms, skin score, digital ulcers) and circulating levels of von Willebrand factor (VWf), tissue plasminogen activator (tPA), thrombomodulin (TM) and Type III procollagen N-terminal propeptide (PIIINP) were evaluated by enzyme-linked immunoassay at different intervals. RESULTS: The overall benefits of iloprost and alprostadil were similar. RP improved in 45% versus 90% of patients; ulcers in 60% versus 40% of patients (iloprost versus alprostadil). Skin score did not significantly change with either drug. Circulating VWf decreased with either drug (iloprost -6.2%, alprostadil -9.4%), while tPA, TM, and PIIINP remained unchanged. Side effects were only minor and less frequent with alprostadil. CONCLUSION: Iloprost and alprostadil were both of benefit in CTD-associated RP, without significant differences in either clinical efficacy or circulating markers. However, ease of handling and the lower price favours alprostadil.

The integration of parallel and serial processing mechanisms in visual search: evidence from eye movement recording.

We examined timing and scanning paths of eye movements during a visual search task, in which subjects had to detect, as quickly as possible, the presence or absence of a target among distractors [Q-like element among O stimuli (QvsO) and vice-versa (OvsQ)]. According to an influential theory [Treisman, A. & Gelade, G. (1980) Cognitive Psychol, 12, 97--136; Treisman, A. & Sato, S. (1990) J. Exp. Psychol. Hum. Percept. Perform., 16, 459--478], only tasks yielding nonflat search functions (OvsQ) involve focal attention. Alternative models propose that all kinds of visual search are resolved by a biased competitive process, working in parallel across the visual field. Data show that QvsO and OvsQ tasks are characterized by quantitative rather than by qualitative differences in search strategy. No differences between the two tasks were found regarding either the percentage of saccades foveating single stimulus items or the timing of the button response with respect to the onset of the last foveation saccade within a trial. Furthermore, the number of saccades made during search predicted very accurately the time required to accomplish the task and fixation times were independent of the number of stimulus items. On the basis of our results there is no reason to postulate the occurrence of shifts of visuospatial attention, other than those associated with the executions of saccadic eye movements, which are driven by a parallel feature analysis of the visual scene, in both types of search tasks. A time-limited competitive model for attentive target identification, in which both parallel (competitive) and serial (attentive) processing mechanisms are integrated, can account for these findings, providing a unified conceptual framework for all kinds of visual search.

Homocysteine concentration in primary and systemic sclerosis associated Raynaud's phenomenon.

OBJECTIVE: To investigate whether patients with systemic sclerosis (SSc) have raised homocysteine (Hcy) plasma levels, thought to be an independent risk factor for vascular disease, and to study the relationship between Hcy and endothelial damage, and between Hcy and methylene-tetrahydrofolate reductase (MTHFR) genotypes, and patients' vitamin nutritional status, which are among the more frequent causes of hyperhomocysteinemia. METHODS: We measured Hcy, von Willebrand factor (vWF), folic acid, and vitamin B12 plasma levels and analyzed the frequencies of MTHFR mutations in 30 patients with SSc and 12 patients with primary Raynaud's phenomenon (RP); 29 healthy subjects served as controls. RESULTS: Patients with SSc had higher Hcy and vWF concentrations than those with RP (p < 0.01 and p < 0.02, respectively) or controls (p < 0.02 and p < 0.0001, respectively). Folic acid and vitamin B12 were lower in SSc than in RP (p < 0.01 and p < 0.02, respectively) or controls (p < 0.05). MTHFR genotype did not influence Hcy, folate, or vitamin B12 concentrations, but patients homozygous for the mutant gene had higher vWF levels. CONCLUSION: Patients with SSc, but not those with RP, had significantly higher Hcy and vWF plasma levels. Nutritional rather than inherited factors seem to have a pathogenic role in SSc hyperhomocysteinemia.

Posture and movement: coordination and control.

Studies are reviewed that address the problem of the variables controlled in the maintenance of body posture and generation of limb movement. Vestibulospinal and neck reflexes cancel each other in response to roll, but not in response to pitch of the animal. In pitch trunk orientation is not effectively stabilized in space. Instead, limb length and orientation relative to the vertical are accurately controlled in normal cats pitched statically and dynamically by variable angles. Control of limb geometry may even take precedence over the control of the projected centre of mass. Coordinate transformation results in a constraint of planar covariation of the elevation angles at all limb segments in cat posture. Because the same constraint applies also to human locomotion, we suggest that sharing the same laws of intersegmental coordination for the control of posture and locomotion helps to assure the maintenance of dynamic equilibrium during movement. Moreover, because several neural sites encode posture and movement in gravity-based reference frames, alignment in register of spatial information derived from multiple sensors and directed to multiple effectors is made possible.

Cyfra 21-1 - a new tumor-marker for lung-cancer.

Among 20 known cytokeratins, cytokeratin fragment 19 is a 40 kD acidic molecule whose distibution is restricted to simple or pseudo-stratified epitelia, such as the epithelial layer of the bronchial tree. An immunoradiometric assay, CYFRA 21-1, was used to detect a fragment of cytokeratin 19 in the serum of 90 subjects and compared with serum levels of CEA, NSE and TPA. Sixty-seven consecutive patients with lung cancer and 23 healthy subjects were tested. Cut-off values for tumor markers were considered as the 95% of specificity versus controls. There were 32 adenocarcinomas, 29 squamous carcinomas and 6 other tumors. Increased serum levels of CYFRA 21-1 were found in lung cancer patients compared to controls [1.6 (0.2-3.2) versus 0.5 (0.2-1.8): p<0.001]. In our study TPA was more sensitive than CYFRA 21-1: 49% versus 40%; when we combined both markers the sensitivity increased to 63%. Significant difference in values were found before and after surgery in serum levels of 34 operated patients: p<0.01. We found higher levels of soluble cytokeratin 19 in lung cancer patients and in the adenocarcinoma subgroup. This study does not support the exclusive use of soluble cytokeratin 19 as a specific marker of lung cancer and not only in squamous carcinoma subgroup. This suggested that diagnostic and prognostic sensitivity increase when CYFRA 21-1 and TPA or other markers are combined.

Independent control of limb position and contact forces in cat posture.

1. It has previously been demonstrated that a set of geometric and kinetic parameters are invariant in cats standing at their preferred interfoot distance and weight distribution. Thus the length and the angle of orientation relative to the vertical of each limb axis remain approximately constant when the supporting platform is tilted in the sagittal plane. The direction of the tangential contact forces is similarly constrained in response to horizontal translations. The main aim of the present study is to assess whether or not the control of limb position is independent of the control of the contact forces at the feet. To this end we have examined cat posture under a number of different conditions expressly designed to increase the range of postural variability. We considered that if the specification of limb position is a mere byproduct of the neural control of contact forces (or vice versa), geometric and kinetic parameters would covary interdependently. If instead limb position and contact forces are controlled in parallel and independently of each other, they will tend to follow different laws of variation. 2. Limb position and contact forces were measured in intact cats standing freely on a support platform. In a first series of experiments the pitch angle of the platform was randomly changed, as were the interfoot distance and head orientation. In another series of experiments cats were tilted in the presence of an external load tending to shift the weight distribution. The same load was applied in two different manners: 1) it made contact with a very limited surface of the body, and 2) it was attached by means of a long vest that made contact with most of the trunk and produced abnormal somesthesic cues to the body. 3. The range of different experimental conditions resulted in substantial trial-to-trial variations of the length and orientation of the axis of the limbs, as well as variations of the magnitude and orientation of the net contact forces. We found that the changes of the orientation of the contact force vector are uncorrelated with the corresponding changes of limb orientation, thus providing a first line of evidence in favor of the existence of a separate neural control of geometric and kinetic parameters. 4. Another line of evidence is provided by the specific form of the laws of variation of geometric parameters and tangential forces in different animals. Under normal (unloaded) conditions the values of the limb joint angles tend to covary linearly.(ABSTRACT TRUNCATED AT 400 WORDS)

Coordinate transformations in the control of cat posture.

1. Global geometric variables represent high-order parameters in the control of cat posture. In particular, limb length and orientation are accurately controlled in response to tilts of the support platform. There is now electrophysiological evidence, obtained in anesthetized cats, that spinal sensory neurons projecting to the cerebellum are broadly tuned to limb length and orientation. Limb length and orientation specify the position of the limb end-points in body-centered polar coordinates. They define an intended posture in a global manner, leaving the detailed geometric configuration of the limbs undetermined. The planar covariation of limb joint angles described in the accompanying paper suggests the existence of an intermediate processing stage that transforms endpoint coordinates into the angular coordinates of the joints (inverse mapping). In this paper we address the question of the nature of this coordinate transformation. Because the number of degrees of freedom of angular motion in each limb exceeds that of endpoint motion in world space, several different angular configurations are compatible with any given endpoint position in world space. Thus the problem of coordinate transformation is a priori indeterminate. We have tested a number of different hypotheses. 2. Coordinate transformation could be accomplished implicitly by means of discrete kinematic synergies. Any given geometric configuration of the limb would result from a weighed combination of only two distinct patterns of angular covariations, the first pattern affecting selectively limb length and the second pattern affecting limb orientation. This decomposition, however, was found in only a few sporadic cases. 3. We also tested the possibility that the coordinate transformation involves the Moore-Penrose generalized inverse. We found that this algorithm produces a planar covariation of the joint angles, but with an orientation orthogonal to the experimental plane. By contrast, a linear transformation with constant, position-independent terms can fit the experimental plane of angular covariations but predicts large errors in endpoint position. 4. The particular orientation in joint space of the experimental plane, coupled with the scatter of data points around the plane, bears a specific implication for the problem of inverse mapping. The experimental plane crosses the constant position lines (the loci of all possible changes of the joint angles that correspond with an invariant position of the endpoint) at an acute angle. Consequently the specification of limb orientation is little sensitive to joint configurations: relatively small changes in orientation can be produced by large changes in joint configurations.(ABSTRACT TRUNCATED AT 400 WORDS)

Parallel processing of multisensory information concerning self-motion.

Cats trained to stand on a platform exhibit postural responses to dynamic tilting that appear to be based on an internal reference model of body geometry and the environment rather than directly on sensory inputs, as in a classical reflex chain. The data presented show an independent control of global variables of limb geometry, the length and the orientation, resulting from a parallel processing of multisensory inputs into separate central representations of body tilt. Limb length and orientation changes have completely different response dynamics and can be decoupled by appropriate manipulation of sensory information about self-motion.

The control of limb geometry in cat posture.

1. The aim of this study is to address the problem of the controlled variable in quadrupedal stance. In particular, we considered whether the projection of the centre of mass of the body on the support surface or the joint torques or the geometrical configuration of the limbs are primarily controlled. 2. Cats were trained to stand freely on a platform which could be tilted in the sagittal plane by up to +/- 20 deg. The normal and tangential components of the contact forces at each paw were measured by means of load cells. The position of limb joints was recorded by means of the ELITE system. 3. The projection of the centre of body mass on the platform, as well as the orientation and length of limb axes, varied to only a limited extent with tilt angle. In particular, the limb axes were closely lined up with the vertical, as were the vectors of the contact forces at the paws. As a result, the torques at the proximal joints (scapula and hip) were close to zero and the torques at the other joints varied little with table tilt. 4. In order to test the different hypotheses on postural control, an external load (10-20% of the animal weight) was applied to the cat forequarters. The projected centre of mass consistently shifted forwards, contrary to the hypothesis that this parameter is controlled in stance. Instead, the geometry of limb posture remained unmodified after load application, even though the torques at forelimb joints were much greater than in the control. 5. This postural behaviour showed no sign of adaptation over a period of 24 h of continuous load application. 6. It is concluded that limb geometry is primarily controlled in stance. The results are discussed in the context of current notions on hierarchical control and body scheme.

The role of preparation in tuning anticipatory and reflex responses during catching.

The pattern of muscle responses associated with catching a ball in the presence of vision was investigated by independently varying the height of the drop and the mass of the ball. It was found that the anticipatory EMG responses comprised early and late components. The early components were produced at a roughly constant latency (about 130 msec) from the time of ball release. Their mean amplitude decreased with increasing height of fall. Late components represented the major build-up of muscle activity preceding the ball's impact and were accompanied by limb flexion. Their onset time was roughly constant (about 100 msec) with respect to the time of impact (except in wrist extensors). This indicates that the timing of these responses was based on an accurate estimate of the instantaneous values of the time-to-contact (time remaining before impact). The mean amplitude of the late anticipatory responses increased linearly with the expected momentum of the ball at impact. The reflex responses evoked by the ball's impact consisted in a short-latency coactivation of flexor and extensor muscles at the elbow and wrist joints. Their mean amplitude generally increased with the intensity of the perturbation both in the stretched muscles and in the shortening muscles. We argue that both the anticipatory and the reflex coactivation are centrally preset in preparation for catching and are instrumental for stabilizing limb posture after impact. A model with linear, time-varying viscoelastic coefficients was used to assess the neural and mechanical contributions to the damping of limb oscillations induced by the ball's impact. The model demonstrates that (1) anticipatory muscle stiffening and anticipatory flexion of the limb are synergistic in building up resistance of the hand to vertical displacement and (2) the reflex coactivation produces a further increment of hand stiffness and viscosity which tends to offset the decrement which would result from the limb extension produced by the impact.

Adaptation to suppression of visual information during catching.

We address the problem of whether and how adaptation to suppression of visual information occurs in catching behavior. To this end, subjects were provided with advance information about the height of fall and the mass of a ball and an auditory cue signaled the time of release. Adaptation did occur, as indicated by the unimpaired ability to catch the ball without vision; however, it involved a major reorganization of the muscle responses. The subjects were unable to produce anticipatory activity consistently, but preset the responses elicited by the impact. These responses were more complex and prolonged than those observed in the control experiments (with vision). In particular, medium- and long-latency responses were much larger, and the changes in elbow, wrist, and metacarpophalangeal angles following impact were more oscillatory than in the control. The general pattern of the EMG responses switched from that characteristic of catching with vision to that characteristic of catching without vision from the first trial of each experiment. However, the responses produced without vision were calibrated adaptively in the course of an experiment. In fact, the limb oscillations induced by the impact were significantly larger in the first trial than in the following trials. This seems to suggest that the parameters of the responses are adjusted based on an internal model of the dynamic interaction between the falling ball and the limb. This model is initially constructed from a priori knowledge on impact parameters and is subsequently updated on the basis of the kinesthetic and cutaneous information obtained during the first trial.

Optokinetic nystagmus: modeling the velocity storage mechanism.

To account for the oscillatory behavior of the optokinetic after-nystagmus (OKAN), a nonlinear model of the optokinetic system is proposed here that includes 2 first-order storage elements interconnected in a negative feedback loop. The adequacy of the model is tested by comparing its predictions with experimental data available in the literature. In addition, the question of the contribution of the storage element responsible for secondary OKAN (OKAN II) to the dynamic properties of the optokinetic nystagmus (OKN) is addressed. The results show that the model is compatible with all modifications of the OKAN time course observed under various experimental situations. By comparing computer simulations and experimental data, it is inferred that (1) the dynamic properties of the optokinetic system during OKN and during OKAN are different; (2) the switching in velocity storage dynamics is not determined by the light-dark transition, but is induced whenever nystagmic slow phase velocity (SPV) is not sustained by an appropriate retinal slip error signal; (3) although no signs of adaptation are seen during OKN, the storage element responsible for OKAN II becomes charged during optokinetic stimulation; and (4) the time constants of the integrators are affected by the parameters of the preceding optokinetic stimulation.

Anticipatory and reflex coactivation of antagonist muscles in catching.

Reflex and anticipatory coactivation of antagonist muscles is demonstrated to occur when human subjects catch a ball. Amplitude and time course of the electromyographic (EMG) responses are strongly modulated by the presence of visual information. It is argued that these responses are centrally preset to stabilize the limb after ball impact.

On the role of vestibulo-ocular reflex plasticity in recovery after unilateral peripheral vestibular lesions.

Although adaptive plasticity is a well-known feature of the vestibulo-ocular reflex (VOR), deficits in VOR performance after unilateral labyrinthectomy are poorly compensated in a large percentage of cats. To assess whether VOR plastic capabilities are affected by labyrinthectomy, forced oscillation in front of a patterned surround was imposed in unilaterally labyrinthectomized cats. This experimental paradigm has been shown to be very effective in inducing adaptive VOR gain changes in intact animals. We demonstrate that plasticity of VOR gain is still present both in acute and chronic stages following vestibular lesions. By contrast, forced oscillation did not significantly alter the lesion-induced asymmetry of responses. We conclude that VOR gain control mechanisms are not used to their fullest possible extent in a large percentage of animals suffering unilateral vestibular damage.

Vestibular nuclear neuron activity in chronically hemilabyrinthectomized cats.

The activity of central vestibular neurons (Vn) of the horizontal canal system was recorded in chronically hemilabyrinthectomized cats and compared with that of labyrinth intact animals. In both groups the cerebellar vermis was removed in order to assess the efficacy of the vestibular brainstem commissure alone by means of polarizing currents applied to the labyrinths. Experiments were carried out under Ketamine anaesthesia. In control animals the mean resting rates of type I and type II Vn measured 22.4 +/- 14.0 and 27.5 +/- 14.6 imp/s respectively, and the type I responses occurred ca. 3 X more frequently than type II. In the lesioned animals a drastic reduction of the number of type I responses was found on the deafferented side, while that on the intact side remained normal. The resting rates of type I Vn on the two sides did not differ significantly from each other but were significantly lower than those of control animals. In contrast, type II responses were present on the deafferented side, but almost completely missing on the intact side. Applying polarizing stimuli in control animals, it was found that both labyrinths have similar weight in driving Vn. In lesioned animals, no major changes in the efficacy of the commissural path were found when polarizing stimuli were applied to the intact side. It is concluded that vestibular nerve section causes a severe loss of type I responses in the vestibular nuclei on the side of the lesion which apparently is not compensated by an adaptive change in the commissural path and, therefore, may be mainly responsible for the VOR asymmetry observed concomitantly.