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How to score arousals in preterm infants? Can we use recommendations of the Pediatric Wake-up Club?

Infants' arousals from sleep reflect the activation of various brain stem and cortical structures and their characteristics change with age. Arousal scoring based on the Pediatric Wake-up Club definition of arousal in infants was evaluated to determine whether arousals could be reliably identified and assessed in preterm infants also. Polygraphic recordings were made in seven stable preterm infants with a mean postconceptional age of 34.4 +/- 1.2 weeks. Fifty-two arousals were scored according to the guidelines of the Pediatric Wake-up Club (Consensus meeting in Brussels, 2002). Values of interest were assessed during the arousal period and during the 30-second periods before and after the arousal. The latter periods were subdivided into 10-second intervals and compared with the arousal period. The mean duration of arousal was 7 +/- 3 seconds. Respiratory rate was higher (35 +/- 15 bpm) during the arousal than in the periods preceding (29 +/- 14 bpm; p < 0.01) and following (29 +/- 11 bpm; p < 0.001) it. Heart rate decreased during the arousal (131 +/- 30 bpm) when compared with the preceding 10-second period (140 +/- 14 bpm; p < 0.05). We found that arousals in preterm infants can be reliably identified and assessed using the Pediatric Wake-up Club's arousal definition for term infants.

Arousal↗

Autoradiography in brain of Macaca fascicularis monkeys after injection of acetyl-DL-leucine [2-14C] (Tanganil).

Acetyl-DL-leucine [2-14C]: Tanganil a antivertigal drug has been injected intravenously in two macaca monkeys which have been sacrificed 2 and 5 minutes later. Radioactivity distribution has been studied by autoradiography in the brain. An important uptake of radioactivity is localized in the cortical structures and in several tisses such as nuclei of the vestibular system, including the inner ear.

Acetylation↗

Peak velocities of visually and nonvisually guided saccades in smooth-pursuit and saccadic tasks.

Smooth pursuit typically includes corrective catch-up saccades, but may also include such intrusive saccades away from the target as anticipatory or large overshooting saccades. We sought to differentiate catch-up from anticipatory and overshooting saccades by their peak velocities, to see whether the higher velocities of visually rather than nonvisually guided saccades in saccadic tasks may be found also in saccades in pursuit. In experiment 1, 12 subjects showed catch-up, anticipatory, and overshooting saccades to comprise 70.4% of all saccades in pursuit of periodic, 30 degrees/s constant-velocity targets. Catch-up saccades were faster than the others. Saccadic tasks were run as well, on 19 subjects, including the 12 whose pursuit data were analyzed, with target-onset, target-remaining (saccade to the remaining target when the other three extinguish), and antisaccade tasks. For 17 of the 19 subjects, antisaccade velocities were lower than for either target-onset or target-remaining tasks. Velocities for the target-remaining task were near those for target onset, indicating that target presence, not its onset, defines visually guided saccades. Error and reaction-time data suggest greater cognitive difficulty for target remaining than for target onset, so that the cognitive difficulty of typical nonvisually guided saccade tasks is not sufficient to produce their lowered velocity. To produce reliably, in each subject, catch-up and anticipatory saccades with comparable amplitude distributions, nine new subjects were asked in experiment 2 to make intentional catch-up and anticipatory saccades in pursuit, and were presented with embedded target jumps to elicit catch-up saccades, all with periodic target trajectories of 15 degrees/s and 30 degrees/s. Velocities of intentional anticipatory saccades were lower than velocities of intentional catch-up saccades, while velocities of intentional and embedded catch-up saccades were similar. Target-onset and remembered-target saccadic tasks were run, showing the expected higher velocity for the target-onset task in each subject. Both experiments demonstrate higher peak velocities for catch-up saccades than for anticipatory saccades, suggesting that cortical structures preferentially involved in nonvisually guided saccades may initiate the anticipatory and overshooting saccades in pursuit.

Calibration↗

Scanning small angle X-ray scattering analysis of human bone sections.

Scanning small-angle X-ray scattering (scanning SAXS) was applied for the first time on bone to compare results from SAXS directly with those from other position-sensitive methods, such as light and polarized light microscopy, back-scattered electron imaging, and radiographic imaging. Since scanning SAXS is a nondestructive method of investigation, images from all these techniques could be obtained from the same bone sections. Thus, it could be shown that both the collagen and the mineral crystals were predominantly aligned parallel to the trabeculae and, therefore, to principle stress directions. Moreover, the mean crystal thickness as determined by scanning SAXS was found to be different at various positions inside the trabecular and cortical structure. Finally, it could be shown that scanning SAXS is suitable for detecting local changes in bone material, e.g., due to fluoride treatment.

Adolescent↗

[Precision analysis of navigation-assisted implanted thoracic and lumbar pedicled screws. A prospective clinical study].

A prospective clinical trial was performed to study the accuracy of pedicle screw placement of consecutive computer-aided and conventional techniques. Concerning the clinical performance of the navigation system, the average time of matching has been 8.4 minutes per vertebrae. For evaluation of the results, only complete intraosseous placement of the pedicle screw has been defined as correct position. Any medial or lateral perforation of the cortical structure of the pedicle was recorded as malplacement. In the CT-controlled patients complete intrapedicular placement of the screw was obtained in 36 of 45 thoracic (80%) and in 22 of 27 navigated lumbar (81%) pedicles. In the conventional cohort group 27 of 34 (79%) thoracal and 43 of 52 (83%) lumbar screws were completely in. No radicular neurologic damage, caused by a malplaced transpedicular screw has been observed in both groups. In the presented study is shown, that the application of the computer-assisted freehand navigation can improve results concerning the precision of spinal screw placement. Although, the spinal navigator has to consider a learning curve for the clinical inauguration of the system and the qualification of the implant system for computer-assisted application.

Bone Plates↗

[Roentgen diagnosis and computerized tomography in inflammatory rheumatic diseases. Methods with a future?].

Plain-film radiography is an important and basic element in the assessment of inflammatory rheumatic diseases. Its various uses include assessment of inflammatory osseous destruction and the activity of inflammatory changes. Furthermore, the inflammatory collateral phenomena can indicate an acute clinical phase, and the articular soft tissue swelling and tenosynovitis are shown directly and indirectly very clearly. On the other hand, high-resolution computed tomography is very capable of showing cortical structures of bone complementary to MR. In some special clinical questions and anatomical regions, especially the axial skeleton, it delivers information of high specifity, partly for definitive diagnosis and partly for planning surgical procedures. The assessment of changes in the sacroiliac joints, sternoclavicular joints and craniocervical junction are domains of computed tomography.

Arthritis, Rheumatoid↗

Effects of lifetime volleyball exercise on bone mineral densities in lumbar spine, calcaneus and tibia for pre-, peri- and postmenopausal women.

To clarify the effects of habitual volleyball exercise on bone in women during the menopausal periods, we measured bone mineral densities (BMDs) of the lumbar spine, calcaneus and tibia every 12 months for 2 years and estimated factors related to the baseline values and annual loss rates. Forty Japanese female volleyball players 42-62 years of age, who had belonged to the district non-professional club for more than 10 years on average, were recruited. Twenty women had regular menstruation at the start, but 7 underwent menopause during the study. Fifty-nine healthy women who did not participate in habitual exercise, but were otherwise comparable with the players, were recruited as the controls. The lumbar and calcaneus BMDs were measured by dual-energy X-ray absorptiometry (DXA), and both the volumetric BMDs and cross-sectional geometry at the diaphysis of the tibia were measured by peripheral quantitative computed tomography. The baseline BMDs of all measured sites and the values of the cortical area and moment of inertia of the tibia in the players were significantly higher than the values in the control women. In the peri- and postmenopausal players, the baseline values of the lumbar and calcaneus BMDs related to total years of participating in regular exercises during adulthood including volleyball (TYE), body mass index (BMI) and years since menopause (YSM). Tibia cortical area and moment of inertia values related to TYE. Annual bone loss rates in the tibia and calcaneus of players were significantly smaller than those values in the controls. However, the bone loss rates in the lumbar spine did not differ significantly between the groups. The bone loss rate in the calcaneus was significantly related to the current number of training hours per week and YSM. The rate of bone loss in the tibia was related to BMI. These data indicated that the total number of years participating in exercise activity during adulthood have positive effects on lumbar and calcaneus BMDs and the cortical structure of the tibia. Habitual volleyball exercise apparently did not alleviate the menopause-related bone loss in the lumbar spine.

Absorptiometry, Photon↗

The acetylcholine releaser linopirdine increases parietal regional cerebral blood flow in Alzheimer's disease.

Centrally acting cholinergic drugs have been reported to increase regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT) in brain regions affected by Alzheimer's disease (AD). We studied the effects of the acetylcholine releaser linopirdine (LPD) on SPECT rCBF in patients with probable AD. Twenty-four AD patients (12 M, 12 F; mean age +/- SD = 68.9 +/- 8.2 years) and 13 healthy controls (8 M, 5 F; 68.4 +/- 8.0 years) participated. AD patients were scanned with 20 mCi of Tc99m-ECD at baseline and following 4 weeks of treatment with LPD 40 mg TID (n = 15) or placebo TID (n = 9) in a double-blind trial. Healthy subjects were scanned for comparison with baseline AD scans. Cortical/cerebellar rCBF ratios were derived for nine cortical structures. The combined parietal association cortex showed a 20.6% reduction in patients relative to controls. Patients treated with LPD showed an increase in parietal rCBF of 4.1 +/- 5.8%; whereas those treated with placebo showed a decrease of -2.0 +/- 7.4% (F = 5.13; df = 1, 22; P = 0.03). These data support the conclusion that rCBF abnormalities in AD are, in part, truly "functional" and can be selectively altered with pharmacological interventions. The parietal activation seen with LPD and other cholinergic AD drug therapies suggests the importance of measuring parietal lobe neuropsychological function in the course of evaluating these drugs.

Acetylcholine↗

Defensive reactions are counteracted by midazolam and muscimol and elicited by activation of glutamate receptors in the inferior colliculus of rats.

The inferior colliculus is involved in conveying auditory information of an aversive nature to higher cortical structures. Gradual increases in the electrical stimulation of this structure produce progressive aversive responses from vigilance, through freezing, until escape. Recently, we have shown that microinjections of NMDA into the inferior colliculus mimic these aversive effects and that the neural substrates responsible for learned escape behavior in the inferior colliculus are regulated by GABA-benzodiazepine mechanisms. In the present study, we extend these observations showing that unlearned aversive responses are also depressed by muscimol and midazolam, both GABA-benzodiazepine agonists, and that microinjection of glutamate, an excitatory amino acid, into the inferior colliculus can trigger freezing responses. Electrical stimulation of the inferior colliculus of rats placed inside an open field allowed the determination of thresholds for the aversive responses, alertness, freezing and escape. Systemic administration (3 and 5.6 mg/kg) as well as microinjections into the inferior colliculus of the anxiolytic compound midazolam (10, 20 and 40 nmol) caused increases in threshold for these aversive responses. Similar results were obtained following microinjections of the GABA-A agonist muscimol (0.1, 1 and 5 nmol) into this brainstem structure. Microinjections of low doses of glutamate (5 nmol), presumed to activate mainly AMPA/kainate receptors, into the ventrolateral division of the central nucleus of the inferior colliculus of rats placed inside a circular arena induced aversive reactions, characterized by freezing responses. However, higher doses of glutamate caused no apparent effects. GDEE, an AMPA/kainate receptor antagonist, inhibited, whereas AP7, a NMDA receptor antagonist, did not influence these responses. It is suggested that GABA-benzodiazepine processes modulate the expression of defensive reactions in the inferior colliculus and that activation of fast-acting excitatory amino acid receptors in this midbrain region can trigger the initial steps of the defense reaction without eliciting the motor explosive behavior usually seen following the activation of NMDA receptors.

Animals↗

Remote activation of referred phantom sensation and cortical reorganization in human upper extremity amputees.

Phantom limb sensation, whether painful or not, frequently occurs after peripheral nerve lesions. It can be elicited by stimulating body parts adjacent to the amputation site (referred to as phantom sensation) and it is often similar in quality to the stimulation at the remote site. The present study induced referred phantom sensations in two upper limb amputees. Neuroelectric source imaging (ESI) as well as functional magnetic resonance imaging (fMRI) was used to assess reorganization in primary somatosensory cortex (SI). Whereas recent studies found mislocalization of sensation related to stimulation mainly in regions adjacent and ipsilateral to the amputation site, we report here the elicitation of phantom sensation in the arm by stimulation in the lower body part both ipsi- and contralateral to the amputation in two arm amputees. The fMRI evaluation of one patient showed no shift in the location of the foot whereas ESI revealed major reorganization of the mouth region in primary somatosensory cortex in both patients. These data suggest that cortical structures other than SI might be contributing to the phenomenon of referred sensation. Candidate structures are the thalamus, secondary somatosensory cortex, posterior parietal cortex and prefrontal cortex.

Adult↗

Saccades to mentally rotated targets.

In order to investigate the role of mental rotation in the directional control of eye movements, we instructed subjects to make saccades in directions different from that of a visual stimulus (rotated saccades). Saccadic latency increased linearly with the amount of directional transformation imposed between the stimulus and the response. This supports the hypothesis that reorienting a saccade is accomplished through a mental rotation process. No differences were found in amplitude, duration, velocity, and curvature between rotated and visually guided saccades. Analogous to mental rotation tasks involving reaching arm movements, it is surmised that frontal/prefrontal cortical structures participate in rotated saccades by reorienting the intended saccadic direction. A linear increase in response time with the imposed directional transformation was also found in an analogous mental task not requiring a directed motor response, namely, mentally localizing a point in space at a certain angle from a stimulus direction. However, the speed of mental rotation was systematically lower than in the rotated saccade task. These findings indicate that mental rotation is a rather general mechanism through which directional transformations are achieved.

Adolescent↗

Effects of excitotoxic lesions in the ventral striatopallidal--thalamocortical pathway on odor reversal learning: inability to extinguish an incorrect response.

The role of the ventral striatopallidal pathway and related cortical areas in stimulus-reward association reversal behavior was studied by inducing bilateral lesions with the excitotoxin, N-methyl-D-aspartate (NMDA) at restricted sites in the system. The areas lesioned were the ventral pallidum (VP), the ventral striatum (VS), the medial prefrontal cortex (mPFC) [i.e., the prelimbic (PL) and infralimbic (IL) cortexes], and the orbital cortex [i.e., the dorsolateral orbital (DLO), ventral lateral orbital (VLO), and lateral orbital (LO) cortexes]. Rats with lesions of the dorsal caudate nucleus and putamen (CPu) served as a positive control in this study. Water-deprived rats were trained on a go, no-go two-odor olfactory discrimination task to respond to one odor (S+) with water as a reward and to suppress responding to the other odor (S-). The rats were then tested for their ability to reverse the associated stimuli. The number of errors made before successfully learning the stimulus-reward association were measured in relation to a sham lesion control group which did not receive injections of NMDA. In experimental rats, the lesions did not affect their ability to learn stimulus-reward associations for novel odors, but did result in an increase in the number of false alarms after the significance of the associated stimuli were reversed. That is, the lesioned animals persisted in responding to the formerly rewarded but now unrewarded stimulus. Rats with damage to the CPu did not show a significant effect when compared with the controls during reversal problems. The results support the hypothesis that the ventral striatopallidal system, together with related thalamic and frontal cortical structures, functions in reversal learning by suppressing inappropriate responses to stimuli that are no longer rewarded.

Animals↗

Establishment of a model of cortical bone repair in mice.

A model of cortical bone repair has been established for use in mice. The cortical defect consisted of a hole drilled through the entire diameter of the tibial diaphysis. The hematoma that initially filled the drill site was invaded by cells of mesenchymal appearance within 5 days of injury. Trabeculae of mineralized woven bone were present throughout the drill site by day 9. A reaction in the periosteum adjacent to the drill site, consisting of both new bone and cartilage formation, preceded deposition of bone tissue in the drill site. New woven bone was modeled to restore the marrow cavity to normal by 4 weeks after injury, and almost normal cortical structure was achieved by 6 weeks after injury. Immunohistochemical studies indicated that type III collagen was expressed within the drill site by day 5, reached a peak at day 7, and was diminished by day 9. In contrast, type I collagen was first detectable in the drill site at day 7, and staining was more intense by day 9. Osteopontin expression in the drill site coincided with the process of mineralization of new bone in this location. The model of bone repair described here provides a method for inducing reproducible bone lesions in a readily identifiable location in mice. It will be useful in the investigation of bone cell function in mouse strains that have been subjected to genetic manipulation.

Animals↗

Cortical bone histomorphometry of the iliac crest in normal black and white South African adults.

Fragility fracture rates in South African blacks (B) are lower than in whites (W). Since bone strength in many parts of the skeleton depends mainly on cortical bone, we examined iliac crest cortical bone from 97 B (49 male, 48 female) aged 22-80 and 111 W (60 male, 51 female) aged 21-84 histomorphometrically for differences between B and W and effects of age. B had thicker (P = 0.02) and less porous (P = 0.0007) cortices, fewer haversian (H) osteons (P < 0.0001), and greater endocortical (Ec) wall thickness (P < 0.0001). B also had thicker H (P = 0.0005) and Ec osteoid seams (P < 0.0001); greater Ec osteoid surface (P = 0.0005), Ec mineral apposition rate (P < 0.0001), and Ec bone formation rate (P = 0.038); and lower H (P = 0.0002) and Ec eroded surfaces (P = 0.029). Some of the differences were already present in subjects aged 21-30 years. Although cortical structure deteriorated with age in B and W, after age 40 Ec wall thickness declined only in W. Greater Ec mineral apposition and bone formation rates, i.e., greater osteoblast efficiency at the cellular and tissue levels, suggest better Ec bone preservation that may contribute to lower fragility fracture rates in B.

Adult↗

Pamidronate and osteoporosis prevention in liver transplant recipients.

Osteoporosis is a common complication in patients with end-stage liver disease and after orthotopic liver transplantation (LT), with resulting increasing fracture rate. In this study, we investigated the role of treatment with pamidronate in preventing further bone loss after LT. Eighty-five patients with end-stage liver disease were included in the study. Pamidronate 30 mg was given intravenously every 3 months after LT for the duration of 1 year to 43 patients with osteopenia or osteoporosis prior LT. The remainders served as controls. All patients received a supplementation of calcium and vitamin D. Bone mineral density (BMD) at the lumbar spine and the femoral neck, and markers of bone metabolism were measured before and 12 months after LT. Sixty-two BMD were available at 12 months; only paired BMD were evaluated. A significant increase in lumbar spine BMD was observed in pamidronate treated patients. No change was evident in controls. Femoral neck BMD decreased in both treated and untreated patients. Osteocalcin serum levels and deoxypyridinoline urinary excretion were significantly reduced by treatment. Our study suggests that pamidronate decreases bone turnover and is effective in preventing the course of bone loss after LT, however the efficacy, at the dosage regimen employed and in a follow-up of 12 months, appears to be limited to trabecular bone, with no effect on the cortical structure of the femur.

Adult↗

Functional differences in forebrain auditory regions during learned vocal recognition in songbirds.

Converging evidence implicates the auditory forebrain regions caudal medial mesopallium (formerly cmHV) and caudal medial nidopallium in the perceptual processing of conspecific vocalizations in songbirds. Little is known however, about more specific processing within these regions especially during song-based perceptual behaviors. One hallmark of the caudal medial mesopallium and caudal medial nidopallium, areas analogous to mammalian secondary auditory cortical structures, is their robust expression of the immediate-early-gene zenk in response to conspecific songs. Using European starlings operantly trained to recognize the songs of individual conspecifics, we show that the levels and patterns of zenk protein expression in the caudal medial nidopallium and caudal medial mesopallium differ when song recognition demands are placed on the system. In the caudal medial mesopallium, expression is significantly elevated above basal levels during the recognition of familiar songs, the acquisition of novel associations for familiar songs, and the acquisition of novel song discriminations. In the caudal medial nidopallium, however, expression is significantly elevated above basal levels only during the acquisition of novel song discriminations. The results directly implicate the caudal medial nidopallium and caudal medial mesopallium in at least a portion of the auditory processes underlying vocal recognition. Moreover, the observed differences between these regions imply the functional localization (or at least the concentration) of different auditory processing mechanisms within the caudal medial nidopallium and the caudal medial mesopallium.

Acoustic Stimulation↗

Are breaches in the glia limitans the primary cause of the micropolygyria in Fukuyama-type congenital muscular dystrophy (FCMD)? Pathological study of the cerebral cortex of an FCMD fetus.

A light and electron microscopic study of the brain of an 18-week fetus with a prenatal genetic diagnosis of Fukuyama-type congenital muscular dystrophy revealed a widespread mantle of abnormal neurogliomesenchymal tissue that covered a dysplastic cerebral cortex. In this area alone, the glia limitans that adjoined the abnormal mantle via one or two layers of basal lamina had frequent breaches, through which neuroglial elements extruded. In the most severely affected cortical region, which had only a rudimentary and fragmentary glia limitans, the majority of cortical neurons had migrated into the neurogliomesenchymal tissue. The massive overmigrated neurons still maintained a somewhat columnar arrangement, and the marked dysplasia abruptly shifted to a neurogliomesenchymal tissue-free normal cortical structure with an intact glia limitans, thus indicating essentially vertical overmigration of neurons without significant tangential migration of them. Together the above findings imply that breaches in the glia limitans may be the primary cause of the micropolygyria seen in this genetic disorder.

Cerebral Cortex↗

CAG repeat length and clinical features in three Italian families with spinocerebellar ataxia type 2 (SCA2): early impairment of Wisconsin Card Sorting Test and saccade velocity.

We report on the clinical, neuropsychological, neurophysiological, computerized eye movement, magnetic resonance imaging (MRI) and molecular findings from 17 individuals affected with spinocerebellar ataxia type 2 (SCA2) belonging to three families. The average age at onset of the symptoms was 35.6, 11.9 (mean, SD) years. The mean age at onset of the symptoms in the parents was 44.8, 8.2 years, and in the offspring it was 28.7, 7.2 years. In 12 parent-child pairs, the mean anticipation was -15.75, 9.1 years (range -8.1 to -23.3 years, t = -4.9, P = < 0.002). The mutated SCA2 alleles ranged from 38 to 42 CAG repeats, while the normal alleles ranged from 22 to 24 repeats, with 97% of the alleles having 22 repeats. Small differences in the number of CAG repeats influenced the age at onset and rate of progression of the disease considerably. Indeed, patients presenting with their first symptom at an age of 35 years or later with a slower course of the disease harboured between 38 and 39 repeats. In contrast, patients carrying > or = 40 CAG repeats manifested the disease prior to 30 years of age and had a faster disease progression toward incapacity. The presenting symptom was always gait ataxia. Slow saccades occured from the beginning of the disease despite normal delay, accuracy and smooth pursuit eye movements. The neuropsychological study showed early and selective impairment of conceptual reasoning ability, as detected by the Wisconsin Card Sorting Test (WCST). It is noteworthy that a significant mutual relationship was observed between performance on the WCST and saccade velocity. All of these findings favour the hypothesis that the disease process of SCA2 in regions other than the cerebellum and brain stem affects severely and early those cortical structures involved in the control of both visually guided saccades and WCST performance.

Adult↗