Search

Cardiovascular disease (CVD) is the highest cause of death globally with more people dying annually from it than from any other cause. CVD is associated with modifiable risk factors (dyslipidaemia, hypertension and diabetes) and treating each of these factors lowers the risk of CVD. It is impossible to estimate the benefit of risk factor modification in the individual patient and extrapolating data from multiple trials is difficult. It would be useful to have a marker of risk that accurately estimates real time risk by measuring blood flow factors associated with the pathogenesis of atheroma. The aim of this preliminary study was to validate a low-cost measurement technique for obtaining blood flow velocity profiles and assess whether any of the measured and calculated factors, based on computational fluid dynamics (CFD) simulation, known to be associated with atheroma was associated with coronary heart disease (CHD), thus establishing its feasibility and acceptability as a clinical tool and suggesting areas for future research. Our study identified (i) that mean peak systolic (PS) velocity being associated with CHD; individuals without CHD: mean (SD) = 62.8 (16.1) cm/s, with CHD: mean (SD)  = 53.6 (17.3) cm/s, p  = 0.042; and (ii) that low-cost, portable ultrasound, which is routinely available in general practice, is a suitable assessment tool.

Background: Since its approval, the use of alteplase had been limited to patients aged ≤80 years., Aims: TESPI trial had been designed to evaluate whether alteplase treatment within 3 h in patients with acute ischemic stroke aged >80 years resulted in favorable benefit/risk ratio compared with standard care. The meta-analysis of randomized controlled trials was updated to put findings in the context of all available evidence., Methods: TESPI was a multicenter, open-label with blinded outcome evaluation, randomized, controlled trial. Main clinical endpoints were 90-day favorable functional outcome (mRS score 0-2) and mortality and symptomatic intracerebral hemorrhage. The trial was prematurely terminated for ethical reasons after publication of IST-3 trial which provided evidence of treatment benefit in elderly., Results: Of the planned 600 patients, 191 (88 assigned to alteplase) were enrolled. Overall, 24/83 (28.9%) alteplase patients had a favorable outcome compared to 22/95 (23.2%) controls (non-significant absolute difference of 5.7% for alteplase; OR 1.35, 95% CI 0.69-2.64, P  = 0.381). Rates of death were non-significantly lower in the alteplase patients (18.1% vs. 26.5%); rates of symptomatic intracerebral hemorrhage were similar between the two groups (5.9% vs. 5.1%). The updated meta-analysis showed consistent results with prior estimates and add weights., Conclusions: The effects of alteplase observed in this interrupted trial did not reach statistical significance, probably for the small numbers, but are consistent with and add weight to the sum total of the randomized evidence demonstrating that alteplase is beneficial in patients with acute ischemic stroke aged over 80 years, particularly if given within 3 h.

Background: The National Institutes of Health Stroke Scale (NIHSS) is the most widespread clinical scale used in patients presenting with acute stroke. The merits of the NIHSS include simplicity, quickness, and agreement between clinicians. The clinical evaluation on posterior circulation stroke remains still a limit of NIHSS., Methods: We assessed the application of a new version of NIHSS, the e-NIHSS (expanded NIHSS), adding specific elements in existing items to explore signs/symptoms of a posterior circulation stroke. A total of 22 consecutive patients with suspected vertebrobasilar stroke were compared with 25 patients with anterior circulation stroke using NIHSS and e-NIHSS., Results: We compared the NIHSS and e-NIHSS scores obtained by the 2 examiners, in patients with posterior circulation infarct (POCI), using the Wilcoxon test. Patients with POCI evaluated with e-NIHSS had an average of 2 points higher than patients evaluated with classical NIHSS. The difference was statistically significant (P < .05), weighted by the new expanded items., Conclusions: The NIHSS is a practical scale model, with high reproducibility between trained, different examiners, focused on posterior circulation strokes, with the same total score and number of items of the existing NIHSS. The e-NHISS could improve the sensitivity of NIHSS in posterior circulation stroke and could have an impact on clinical trials, as well as on outcomes. Further studies are needed to investigate a larger number of patients and the correlation between the e-NIHSS score and neuroimaging findings., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Intravenous thrombolysis is an effective treatment in acute stroke patients, but it increases the risk of intracerebral hemorrhages. Our aim is to establish if fibrinogen depletion increases the risk of intracerebral hemorrhage after intravenous thrombolysis for acute ischemic stroke., Methods: In 104 ischemic stroke patients, treated with intravenous thrombolysis, we assessed the rate of intracerebral hemorrhages documented by computed tomographic scan at 24 hours and within 7 days post-treatment. Fibrinogen levels were determined at 2 hours after therapy: patients were classified as belonging to "low fibrinogen group" if levels decreased to less than 2 g/L and/or by 25% or more. Fibrinogen levels and other known hemorrhagic risk factors were studied using univariate and multivariate analyses., Results: During the first 7 days, an intracerebral hemorrhage was detected in 24 patients (23.1%), and only 6 of these (5.8%) experienced symptomatic bleeding; 41 patients were included in the low fibrinogen group. Among the 24 hemorrhages, 18 occurred in the low fibrinogen group and 6 in the "normal fibrinogen group": the bleeding rate in the low fibrinogen group was significantly higher (43.9%) than that in the normal fibrinogen group (9.5%; odds ratio [OR] 7.43, P < .001). Univariate and multivariate analyses revealed that only clinical severity (OR 1.15, P < .001) and hypofibrinogenemia (OR 7.47, P < .001) were significantly associated with brain bleeding at 7 days and at 24 hours (P = .008)., Conclusions: An early fibrinogen reduction seems to increase the risk of intracerebral hemorrhage after rtPA treatment in ischemic stroke. Fibrinogen assessment could be a rapid, inexpensive, and widely available tool to help the identification of patients at higher risk of bleeding., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Three models of different stent designs implanted in a cerebral aneurysm, originating from the Virtual Intracranial Stenting Challenge '07, are meshed and the flow characteristics simulated using commercial computational fluid dynamics (CFD) software in order to investigate the effects of non-Newtonian viscosity and pulsatile flow. Conventional mass inflow and wall shear stress (WSS) output are used as a means of comparing the CFD simulations. In addition, a WSS distribution is presented, which clearly discriminates in favour of the stent design identified by other groups. It is concluded that non-Newtonian and pulsatile effects are important to include in order to avoid underestimating wss, to understand dynamic flow effects, and to discriminate more effectively between stent designs.

The Virtual Intracranial Stenting Challenge 2007 (VISC'07) is becoming a standard test case in computational minimally invasive cerebrovascular intervention. Following views expressed in the literature and consistent with the recommendations of a report, the effects of non-Newtonian viscosity and pulsatile flow are reported. Three models of stented cerebral aneurysms, originating from VISC'07 are meshed and the flow characteristics simulated using commercial computational fluid dynamics (CFD) software. We conclude that non-Newtonian and pulsatile effects are important to include in order to discriminate more effectively between stent designs.

The vascular architecture within a perforator flap is different from a conventional muscle or myocutaneous flap. The purpose of this paper is to understand the correlation between flow rate and flap size in perforator flaps. With extrapolation of these data, we have provided an indirect analysis of the venous drainage and its correlation with flap size. A prospective study was planned. Twenty-five patients were enrolled in this study: six patients were operated on using an anterolateral thigh (ALT) flap and 19 using a deep inferior epigastric artery perforator (DIEAP) flap. One month postoperatively, echo-colour-Doppler measurements were performed on pedicle and perforator arteries to calculate blood flow rate in the flaps. A correlation between weight and flow rate was analysed. Spearman rho statistic was calculated. A linear regression model was made from patient data of flow rate/flap weight and predicted values of flow per flap weight were calculated. Then, flow rate values of veins of various diameters were estimated using Hagen-Poiseuille's formula. Our data show that flow rate measured postoperatively on flap arteries is significantly correlated with flap weight [rho(23 d.f.)=0.725, P<0.01 (two-tailed)]. Moreover, we have calculated the minimum size of veins able to drain flaps of increasing weights with different patterns, i.e. our data show that veins of 1.30, 1.50 and 1.75 mm diameter could safely drain flaps of, respectively, 300, 500 and 900 g in weight. This can be useful preoperatively to estimate the risk of flap congestion and in planning additional drainage.

Purpose: The purpose of this study was to examine the effect of periarticular injection of hyaluronate into shoulders with supraspinatus tendinosis under echographic guide., Methods and Materials: The subjects were 56 patients with clinical, echographic and magnetic resonance diagnosis of supraspinatus tendinosis. They were divided in two groups by random sampling; 28 patients were assigned in SH group (sodium hyaluronate) and 28 patients in SC group (sodium chloride). The test drug was 20mg sodium hyaluronate (2ml, Hyalgan, Fidia SpA, Abano T., P.M. 500-700.000, 20mg/2ml)., Results: Preliminary results showed that sodium hyaluronate presented the highest efficacy in the improvement of clinical symptoms and recovery of functional status in patients with supraspinatus tendinosis in fact the mean V.A.S. score (Visual Analogue Scale) at 1 month after the end of the infiltrative cycle was 8.0 in the SC group vs. 2.8 in SH group and these numerical data were substantially unchanged also after 3 and 4 months., Conclusion: Hyaluronate injection under echographic guide should be use not only as a lubricant but also to prevent articular cartilage degeneration and cover and protect the articular cartilage; indeed sodium hyaluronate can decrease inflammatory joint process.

Wernicke encephalopathy (WE) is a rare but known complication of severe hyperemesis gravidarum caused by thiamine deficiency. This article presents an unusual case that occurred at our institution and reviews the 48 previously published cases of WE in pregnancy. Considering all the 49 cases, the mean (+/-standard deviation) patients' age was 26.7 +/- 4.9 years, the mean gestational age when WE manifested was 14.3 +/- 3.4 weeks, and the mean duration of vomiting and feeding difficulties was 7.7 +/- 2.8 weeks. Wernicke's classic triad (confusion, ocular abnormalities, and ataxia) manifested in only 46.9% (23 of 49) of the patients. Confusion affected 63.3% (31 of 49) of the patients, ocular signs 95.9% (47 of 49) and symptoms 57.1% (28 of 49), and ataxia 81.6% (40 of 49). Deterioration of consciousness affected 53.1% (26 of 49) of the subjects and memory impairment 61.2% (30 of 49). Complete remission of the disease occurred in only 14 of 49 cases. Symptom resolution required months and permanent impairments were common. The overall pregnancy loss rate, directly (spontaneous fetal loss) and indirectly (planned abortion) attributable to WE, was 47.9% (23 of 49). The diagnosis of WE is clinical and can be rapidly confirmed by magnetic resonance imaging. We emphasize the importance of thiamine supplementation to women with prolonged vomiting in pregnancy, especially before intravenous or parenteral nutrition. We also underline the necessity to promptly replace vitamin B1 when neurologic symptoms and/or signs develop in a patient with hyperemesis gravidarum.

Ketamine is a dissociative anesthetic with complex actions on the CNS. We investigated here the effects of ketamine anesthesia on somatosensory processing in the rat spinal cord, thalamus, and cerebral cortex, using the quantitative 2-deoxyglucose mapping technique. Unanesthetized or ketamine-anesthetized male Sprague-Dawley rats received a s.c. injection of a dilute formaldehyde solution (5%, 0.08 ml) into a forepaw, inducing prolonged noxious afferent input, or an equal volume of isotonic saline as a control stimulus. The 2-deoxyglucose experiments started 30 min after the injection. In the cervical enlargement of the spinal cord, ketamine had no significant effect on glucose metabolic rates in saline-injected animals, whereas it prevented the metabolic increases elicited by prolonged noxious stimulation in unanesthetized animals. At the thalamic level, ketamine increased glucose uptake in both saline- and formalin-injected rats in the lateral posterior, lateral dorsal, medial dorsal, gelatinosus, antero-ventral and antero-medial thalamic nuclei, whereas it decreased metabolic activity in the ventro-basal complex. At the cortical level, the drug increased metabolic activity in both control and formalin groups in the lacunosus-molecularis layer of the dorsal hippocampus, posterior parietal, retrosplenial, cingulate and frontal cortex; significant metabolic decreases were found in the CA1 region of the dorsal hippocampus and in the parietal 1 and 2 cortical areas. In the investigated brain regions, ketamine did not abolish noxious-evoked increases in glucose uptake, which were in fact enhanced in the forelimb cortex and in the lacunosus-molecularis layer of the hippocampus. The dissociation between the spinal and supraspinal effects of ketamine suggests a specific antinociceptive action on spinal circuits, in parallel with complex changes of the activity of brain circuits involved in somatosensory processing. More generally, this study shows that functional imaging techniques are able to quantitatively assess the effects of anesthetic drugs on nociceptive processing at different levels of the neuraxis.

The behavioral response to acute tissue injury is usually characterized by different phases, but the brain mechanisms underlying changes in pain-related behavior over time are still poorly understood. We aimed to analyze time-dependent changes in metabolic activity levels of 49 forebrain structures in the formalin pain model, using the autoradiographic 2-deoxyglucose method in unanesthetized, freely moving rats. We examined rats during the first phase of pain-related reactions ('early' groups), or during the third recovery phase, 60 min later, when the supraspinally mediated behavioral responses were reduced ('late' group). In the early groups, metabolic rates were bilaterally increased over control values in the periaqueductal gray, zona incerta and in several thalamic nuclei (anteroventral, centrolateral, lateral dorsal, parafascicular, posteromedial, submedius, ventromedial, and ventrobasal complex), as well as in the habenulae and in the parietal, cingulate, antero-dorsal insular, and anterior piriform cortex. A contralateral, somatotopically specific activation was found in the putative hindlimb representation area of the somatosensory cortex. In the late group, noxious-induced activation declined in most structures. However, metabolic rates were higher than controls in the periaqueductal gray and zona incerta and in two other structures not previously active: the prerubral area/field of Forel and the arcuate hypothalamic nucleus. These findings provide a time-dependent functional map of nociceptive and anti-nociceptive forebrain circuits during tonic pain. The parallel decrease in licking behavior and forebrain activity, at times when spinally mediated limb flexion responses were still present, suggests that endogenous antinociceptive systems may differently modulate spinal and supraspinal nociceptive networks following acute tissue injury.

CNS correlates of acute prolonged pain, and the effects of partial blockade of the central beta-endorphin system, were investigated by the quantitative 2-deoxyglucose technique in unanaesthetized, freely moving rats. Experiments were performed during the second, tonic phase of the behavioural response to a prolonged chemical noxious stimulus (s.c. injection of dilute formalin into a forepaw), or after minor tissue injury (s.c. saline injection). During formalin-induced pain, local glucose utilization rates in the CNS were bilaterally increased in the grey matter of the cervical spinal cord, in spinal white matter tracts and in several supraspinal structures, including portions of the medullary reticular formation, locus coeruleus, lateral parabrachial region, anterior pretectal nucleus, the medial, lateral and posterior thalamic regions, basal ganglia, and the parietal, cingulate, frontal, insular and orbital cortical areas. Pretreatment with anti-beta-endorphin antibodies, injected i.c.v., led to increased metabolism in the tegmental nuclei, locus coeruleus, hypothalamic and thalamic structures, putamen, nucleus accumbens, diagonal band nuclei and dentate gyrus, and in portions of the parietal, cingulate, insular, frontal and orbital cortex. In formalin-injected rats, pretreated with anti-beta-endorphin, behavioural changes indicative of hyperalgesia (increased licking response) were found, which were paralleled by a significant enhancement of functional activity in the anterior pretectal nucleus and in thalamo-cortical systems. A positive correlation was found between the duration of the licking response and metabolic activity of several forebrain regions. These results provide a map of the CNS pattern of metabolic activity during tonic somatic pain, and demonstrate a modulatory role for beta-endorphin in central networks that process somatosensory inputs.

Time-related changes in oculomotor function and of metabolic activity patterns in selected brain networks, as assessed by the quantitative 2-deoxyglucose technique, were investigated in Long-Evans rats following intraperitoneal administration of a ketamine anesthetic dose. During ketamine-induced anesthesia a nystagmic-like behavior was present, characterized by uni-directional slow ocular drifts with superimposed paroxystic bursts of quick (saccadic-like) eye movements; all quick movements were executed in the horizontal direction, were strictly confined to an ocular hemifield of vision, and were followed by a backward (centripetal) drift. A metabolic hyperactivity was found in the dorso-medial shoulder region of the frontal cortex, corresponding to the rat saccadic cortical generator area, whereas functional activity levels were decreased in cerebellum and in several brainstem regions, including portions of the reticular formation and medial vestibular nuclei, putatively indicated as the locus of the oculomotor neural integrator. Starting 2 h after drug injection, a gradual recovery of oculomotor function occurred, with the disappearance of slow ocular drifts. However, an almost uninterrupted sequence of individual saccades was still present. Significant metabolic increases were found at this time in the cingulate and frontal cortex, basal ganglia, superior colliculus, paramedian reticular formation and oculomotor nuclei, the cerebellar vermis and paraflocculus. In medial vestibular nuclei, metabolic levels were undistinguishable from controls. These results suggest different concentration-dependent actions of ketamine on cortical and subcortical circuits involved in saccade generation and gaze holding. These effects are likely to be related at least in part to antagonism of N-methyl-D-aspartate receptor-mediated functions.

Azathioprine (AZA) has a slight but consistent effect on clinical outcome in multiple sclerosis (MS), but very few data are available on magnetic resonance imaging (MRI) changes. We performed a retrospective study aimed to quantify changes of lesion load in two serial proton density weighted MRI sequences (TR 2500, TE 30, 1.5 T) at a mean interval of 2.5 years in 36 relapsing-remitting (RR) MS patients: 19 had been treated with AZA, beside steroids after relapses (AZA group), and 17 had been treated with steroids only (control group). All but 3 patients were in the early phase of the disease. Total lesion area (TLA) was measured by manual outlining method and the arbitrary score proposed by Ormerod (total score) was also calculated from the number and diameter of lesions. Lesion load was the same at baseline, but median percentage difference of TLA between first and second scan was + 15.6% in control, -43.7% in the AZA group (p < 0.05, Mann-Whitney test). The distribution of patients according to TLA change, assuming that an increase or decrease was significant if larger than 50%, was found to be significantly different in favor of AZA-treated patients (chi(2) = 35.92, p < 0.001). These results suggest an effect of AZA treatment on MRI lesion load in early RR MS: a larger prospective study is worthwhile.

Before 1975 the multiple sclerosis (MS) prevalence rate in Italy ranged from 4 to 21 cases per 100,000 inhabitants. In more recent studies the MS prevalence rate exceeded 30 cases per 100,000. We decided to perform an epidemiological survey in the province of Modena, Northern Italy, in order to clarify whether Italy should be considered as an area at high risk for MS like the countries of continental Europe. The mean annual incidence for the disease for the period 1970-1990 was 1.49 per 100,000, and the prevalence rate was 38.91 per 100,000 on December 31, 1990. These results indicate Modena is a high risk MS area.

Subcutaneous injection of a dilute formaldehyde solution (5 or 10%) into a hind paw induced, in the majority of rats, the appearance of 'mirror pain': licking the contralateral untreated hind paw 10-60 min after injection. Contralateral licking activity was much less frequent than the ipsilaterally directed one, but the overall intensities of the two responses were positively correlated. Qualitatively, the two behaviours were similar. Functional activity levels of the lumbar spinal cord, as revealed by the 2-deoxyglucose (2-DG) technique, were increased bilaterally over the first hour after unilateral hind limb formalin injection in unanesthetized, freely moving rats. The enhancement of the [14C]2-DG uptake could be detected both in dorsal and ventral horns, as well as in the gray matter surrounding the central canal, and the anterolateral and dorsolateral funiculi. These metabolic changes may reflect an enhancement of the functional activity of both interneuronal pools and units projecting to supraspinal centers, giving rise to a referred contralateral pain.

We have investigated the effects of propofol anaesthesia on the metabolic activity pattern of 35 regions of the rat brain and cervical spinal cord using the 14C-2-deoxyglucose technique. Anaesthesia was produced by an i.v. bolus of the commercial preparation of the drug (8 mg kg-1) and maintained with successive bolus administrations of 6 mg kg-1. Functional activity values (expressed as rates of local utilization of glucose) were reduced in 31 grey matter and two white matter structures in a propofol group relative both to saline-injected and vehicle-injected (aqueous emulsion containing 10% soya bean oil, 1.2% egg phosphatide and 2.25% glycerol) controls. Values from the two control groups did not differ significantly. Propofol-induced depression of metabolic activity was present in central nervous system regions belonging to sensory (auditory, visual and somatosensory), motor and limbic systems, including spinal cord grey matter. Mean percentage decreases ranged from 40% (vestibular nuclei) to 76% (cingulate cortex). Although these values may be slightly overestimated because of the modest increase in PaCo2 in the anaesthetized group, propofol appeared to elicit generalized reduction of central nervous system functional activity.

The functional activity pattern in the cervical enlargement of the spinal cord (as expressed by changes in local glucose utilization) was investigated by the semi-quantitative [14C]2-deoxyglucose technique 2 min ("early" group) or 60 min ("late" group) after injection of a small amount of dilute formalin (0.06-0.08 ml, 5%) in a forepaw of unanesthetized, freely-moving rats. Control animals were either injected with an equivalent volume of saline or simply handled. In both formalin groups a tonic flexion of the injected limb was present during the experiments, while supraspinal-integrated behavior (such as licking the affected paw) was sharply reduced in the late group. A bilateral increase of metabolic activity indexes, more pronounced on the ipsilateral side, was found in the "early" formalin-injected animals. The highest increase over control values was found in the medial part of the superficial (laminae I-II) region of the ipsilateral dorsal horn. However, the [14C]2-deoxyglucose uptake was found to be elevated over the whole extent of the dorsal horns, as well as in the gray matter surrounding the central canal, anterior horns and ipsilateral dorsolateral funiculus. In a parallel group of experiments performed in pentobarbital-anesthetized rats metabolic increases in the early period after formalin injection were less pronounced; they were only found in the ipsilateral side of the cord. In the "late" formalin group the overall metabolic changes were less conspicuous. They were mainly observed in the side ipsilateral to the injection, the highest increase being found in the deep portion (laminae V-VI) of the dorsal horn. Therefore, the spatial distribution of functional activation elicited during prolonged noxious stimulation in the spinal cord gray matter of unanesthetized rats varies according to time and changes in animal behavior.

Functional activity changes in 35 selected structures of the rat brainstem elicited by subcutaneous formalin injection in a forepaw were investigated by the [14C]2-deoxyglucose method in unanesthetized, freely moving animals. Experiments were initiated 2 min ("early" group) or 60 min ("late" group) after the injection. Treatment induced a significant increase of [14C]2-deoxyglucose uptake relative to controls in 17 structures of the "early" group, including portions of the bulbar, pontine and mesencephalic reticular formation, nucleus raphe magnus, median and dorsal raphe nuclei, the ventrolateral and dorsal subdivisions of the periaqueductal gray matter, deep layers of the superior colliculus and the anterior pretectal nucleus. Most changes were bilateral, with the exception of the increases observed in the nucleus reticularis paragigantocellularis and the lateral parabrachial area, which were contralateral, and the one in the mesencephalic reticular formation, which was ipsilateral to the injected paw. In pentobarbital-anesthetized rats a significant difference in metabolic activity values between formalin- and saline-injected animals was only detected at the medullary level. In the "late" unanesthetized formalin group functional activity levels were higher than controls in four structures, including the lateral reticular and paragigantocellular nuclei, contralaterally, and nucleus cuneiformis and ventrolateral periaqueductal gray matter, bilaterally. No between-groups difference was observed in visual or auditory structures. These results provide evidence for activation of several brainstem regions, which are conceivably involved in different sensory, motivational or motor circuits, during the initial phase of formalin-evoked noxious stimulation in unanesthetized animals. Functional changes blunted over time as did pain-related behavior integrated at the supraspinal level, but they persisted in some brainstem regions for which involvement in endogenous antinociceptive systems have been suggested. The mechanisms underlying these time-related changes need to be clarified.

Local cerebral blood flow (LCBF) was measured autoradiographically in newborn puppies by an indicator fractionation technique using 4-iodo-[14C]antipyrine as the diffusible indicator. Measurements were obtained in unanesthetized, normotensive animals, and the sensitivity of blood flow to hypercapnia and acute hypoxia was determined in 32 brain structures. LCBF in normal and hypoxic puppies was correlated with local cerebral glucose utilization (LCGU) obtained under the same experimental conditions (Duffy et al, 1982). In normocapnic (PaCO2 33 mm Hg) control animals, highest rates of blood flow were found in gray matter nuclei of the brainstem, in the medulla oblongata, and in the posterolateral nucleus of the thalamus (50 to 77 ml/100 gm/min); far lower flows were recorded among white matter structures (5 to 11 ml/100 gm/min). The vasodilatory response to both hypercapnia and hypoxia was greatest among brainstem gray matter structures, intermediate among cortical and diencephalic gray matter structures, and least in white matter. When LCBF was plotted as a function of LCGU for control animals, a positive linear correlation was obtained for all structures (p less than 0.001), implying that in newborns, as in adults, cerebral blood flow and metabolism are physiologically coupled. In hypoxic puppies, no consistent relationship between LCGU and LCBF could be demonstrated; however, there was suggestion that the two measurements correlated inversely, presumably reflecting enhanced anaerobic glycolysis in structures (e.g., hemispheric white matter) that were not adequately protected by compensatory hyperemia. White matter damage, a frequent complication of perinatal hypoxia-asphyxia, may be a consequence in part of the limited capacity of white matter to vasodilate in response to te chemical "signals" of hypercapnia and lactic acidosis.

A general purpose image processing system is described including B/W TV camera, high resolution image processor and display system (TESAK VDC 501), computer (DEC PDP 11/23), and monochrome and color monitors. Images may be acquired from a microscope equipped with a TV camera or using the TV in direct viewing; the A/D converter and the image processor provides fast (40 ms) and precise (512 X 512 data points) digitization of TV signal with a 256 gray levels maximum resolution. Computer programs have been developed in order to perform qualitative and quantitative analyses of autoradiographs obtained with the 2-DG method, which are written in FORTRAN and MACRO 11 Assembly Language. They include: (1) procedures designed to recognize errors in acquisition due to possible image shading and correct them via software; (2) routines suitable for qualitative analyses of the whole image or selected regions of it, providing the opportunity for pseudocolor coding, statistics, graphic overlays; (3) programs permitting the conversion of gray levels into metabolic rates of glucose utilization and the display of gray- or color-coded metabolic maps.

Monocular optokinetic stimulation ( OKS ) in Long-Evans rats enhances the uptake of [14C]2-deoxy-D-glucose (2-DG) in the pretectal nucleus of the optic tract (NOT) and superior colliculus (SC) contralaterally to the open eye regardless of the movement direction. Metabolic increases in NOT and SC are therefore found to be unrelated to the ocular nystagmus that in monocularly viewing rats follows only to OKS nasalward for the seeing eye. Since the oculomotor asymmetry has been attributed to the directional selective properties of NOT neurons responding to nasalward movement in the contralateral visual field but being inhibited by opposite ( temporalward ) movement, the enhanced 2-DG uptakes observed in the present experiments seem to represent the NOT excitatory metabolic work in the case of nasalward movement and the NOT inhibitory metabolic expenditure in the case of temporalward movement.

Local cerebral glucose utilization (LCGU) was measured in 36 neuroanatomical structures of normal awake, halothane-anesthetized, and hypoxic newborn puppies by the autoradiographic 2-[14C]deoxyglucose method. In normal animals, LCGU was highest in the vestibular nucleus and in other gray matter nuclei of the brainstem and declined in a caudal-to-rostral progression through the neuraxis (i.e., LCGU of cerebellum greater than thalamus approximately equal to caudate-putamen greater than cerebral cortex). Lowest rates of glucose metabolism were detected in white matter structures. Halothane anesthesia (1.5% inspired) caused few changes in local glucose metabolism, the most notable being decreased LCGU among structures of the auditory system (cochlear nucleus, lateral lemniscus, inferior colliculus) and increased LCGU in the interpeduncular nucleus. Acute systemic hypoxia (arterial oxygen tension of approximately 12 mm Hg) produced markedly heterogeneous effects on local glucose metabolism: LCGU was increased in some gray matter structures, decreased in the thalamus, and substantially increased in the subcortical white matter and corpus callosum. In puppies whose brains were frozen in situ after 55 minutes of hypoxia, the concentration of lactate was increased ten- to elevenfold in cortical gray and subcortical white matter, but the concentrations of glucose, adenosine triphosphate, and phosphocreatine declined to a greater extent in the white matter. The results suggest that during hypoxia the high rate of glycolysis in white matter exceeded substrate supply so that glucose availability became the limiting factor for local energy production. Such a mechanism may contribute to the white matter injury that often develops following hypoxic-ischemic insults in the perinatal period.

The effects of an anesthetic dose (100 mg/kg) of ketamine, a phencyclidine derivative, on local rates of cerebral glucose utilization (LCGU) and CBF (LCBF) have been investigated by the quantitative [14C]2-deoxy-glucose and [14C]iodoantipyrine techniques in the unparalyzed, spontaneously breathing rat. In ketamine-injected animals, LCGU was significantly increased in some limbic structures and decreased in inferior colliculus, vestibular, and cerebellar nuclei. The degree and spatial distribution of drug-induced changes was similar for local blood flow rates, LCBF being increased in limbic regions and decreased in the inferior colliculus. Although Paco2 values were higher in anesthetized animals, the pattern of LCBF/LCGU ratios was not significantly affected by ketamine in the 36 brain regions examined in this study. So, at least in the rat and at the anesthetic level studied here, a net vasodilatory in vivo effect was not observed. These results support the hypothesis that CBF changes induced by the drug in animals and man are primarily related to the metabolic effects exerted by ketamine on cerebral structures.

Following forty-five min of binocular optokinetic stimulation (OKS) the autoradiographic maps of [14C]-2-deoxy-D-glucose (2DG) assumption of Long-Evans brain reveal clearly different patterns of optical density within visual centres. The most superficial layers of superior colliculus (SC) and a pretectal area including the nucleus of the optic tract (NOT) appear symmetrically, strongly darker than other visual structures such as lateral geniculate nucleus (LGN) and visual cortex (VC). Whereas the lack of metabolic increase at LGN and VC levels entirely confirms the non-involvement of the geniculo-cortical path in mediating the optomotor response following OKS in Rodents, it is postulated that the symmetrical increase of 2DG uptake even upon unidirectional OKS found even at pretectal level may represent a commissural transfer of visual information between homologous pretectal areas like the nuclei of the optic tract.