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Hemispheric differences in variability of fissural patterns in parasylvian and cingulate regions of human brains.

We have determined different patterns of fissurization in Broca's area, the gyrus of Heschl, the planum temporale, the inferior parietal lobe, and the cingulate sulcus. Such patterns were asymmetrically distributed, indicating increased folding on the left side in most cases. More folding can sometimes be related to a larger cortical area, resulting in increased processing capacities in the respective brain region. Furthermore, the brain regions associated with the asymmetrical sulci are involved in lateralized functions. Of special interest are the asymmetries observed in regions corresponding to the inferior parietal lobe (the accessory postcentral sulcus and the intraparietal sulcus), which, according to recent studies, is involved in linguistic working memory. We did not detect a tendency of distinct fissurization patterns in a given brain region to be associated with specific patterns in other fissures, indicating that the different fissure types develop independently in each brain region and can therefore be determined by local processes. These descriptions are of relevance to imaging studies that intend to establish correspondences between gross morphology and functional parameters such as behavior and brain activation.

Adult↗

Automatic backscatter analysis of regional left ventricular systolic function using color kinesis.

Assessment of regional wall motion by 2-dimensional echocardiography can be performed by either semiquantitative wall motion scoring or by quantitative analysis. The former is subjective and requires expertise. Quantitative methods are too time-consuming for routine use in a busy clinical laboratory. Color kinesis is a new algorithm utilizing acoustic backscatter analysis. It provides a color encoded map of endocardial motion in real time. In each frame a new color layer is added; the thickness of the color beam represents endocardial motion during that frame. The end-systolic image has multiple color layers, representing regional and temporal heterogeneity of segmental motion. The purpose of this study was to validate the use of color kinesis for semiquantitative analysis of regional left ventricular systolic function and quantitatively in measurement of endocardial excursion. Semiquantitative wall motion scoring was performed in 18 patients using both 2-dimensional echo and color kinesis. Scoring was identical in 74% of segments; there was 84% agreement in definition of normal vs. abnormal. There was less interobserver variability in wall motion scoring using color kinesis. Endocardial excursion was quantified in 21 patients. 70% of the imaged segments were suitable for analysis. Correlation between 2-dimensional echocardiographic measurements and color kinesis was excellent, r = 0.87. The mean difference in excursion as measured by the 2 methods was -0.05 +/- 2.0 mm. In conclusion, color kinesis is a useful method for assessing regional contraction by displaying a color map of systolic endocardial excursion. This algorithm may improve the confidence and accuracy of assessment of segmental ventricular function by echocardiographic methods.

Adult↗

Ultrasonographic examination of the left kidney, the urinary bladder, and the urethra in cows.

The purpose of the present study was to determine the position, dimensions and structure of the left kidney, the urinary bladder and the urethra in cattle by use of ultrasonography. The left kidney, the urinary bladder and the urethra of 12 healthy, Swiss Braunvieh cows were examined transrectally using a 5.0 MHz linear transducer 10 times within two weeks. The lobulation of the kidney in cattle could be visualized ultrasonographically. The echogenicity of various renal structures differed. The renal cortex was hyperechoic in comparison to the relative hypoechoic renal medullary pyramids. The urinary bladder was always visible but its diameter varied greatly. The vertical diameter of the left kidney was 6.2 +/- 1.0 cm in the region of the renal hilus. In 7 cows the thickness of renal cortex and medulla was between 2.0 and 2.3 cm. The diameter of the renal sinus varied from 1.1 to 2.5 cm. The interassay coefficients of variation of the variables measured varied between 8.5 and 16.5%. It was concluded that the ultrasonographic values determined in this study can be used as references for the diagnosis of morphologic changes in the bovine left kidney.

Animals↗

Consequences of prolonged inhalation of ozone on F344/N rats: collaborative studies. Part IX: Changes in the tracheobronchial epithelium, pulmonary acinus, and lung antioxidant enzyme activity.

The effect of ozone on the respiratory system is not confined to a single region or a specific cell type. Ozone-induced injury can occur at all levels of the respiratory system. However, the effects of this oxidant gas throughout the tracheobronchial tree and the lung parenchyma can be highly variable. The doses of ozone delivered to the various regions may also be different, and these differences may have a significant effect on the extent of injury. To examine the effects of chronic exposure to ozone on the lungs, we used a systematic sampling approach to perform morphometric, histochemical, and enzymatic analyses of selected airway generations and pulmonary acini arising from short and long airway paths of the tracheobronchial tree. The objectives of this study were to define compositional, cytochemical, and architectural changes that occur in epithelial cells of the airways and major tissue components of the pulmonary acini after 20 months of exposure to 0.0, 0.12, 0.5, or 1.0 parts per million (ppm)* ozone in male and female F344/N rats. We found in the trachea and bronchi significant alterations in stored secretory product following exposure to ozone, but no changes in epithelial thickness or the volume density of nonciliated cells. The volume density of nonciliated cells was significantly increased in terminal bronchioles arising from a long airway path (caudal region) of the left lung. The predominant change within the pulmonary acini was the extension of bronchiolar epithelium beyond the bronchiole-alveolar duct junction into alveoli. This change was concentration-dependent and site-specific, with ventilatory units arising from a short path (cranial region) of the left lung in male rats being most affected. The antioxidant enzymes superoxide dismutase, glutathione peroxidase, and glutathione S-transferase were significantly elevated in the distal bronchiole to central acinus following 20 months of exposure to 0.5 or 1.0 ppm ozone. Changes in antioxidant enzyme levels were more variable in other airway generations. We conclude that the effects of long-term (20-month) exposure to ozone are dose-dependent and site-specific along the tracheobronchial tree and pulmonary acini of the lungs. With the tissue sampling strategies used in this study, for the first time microdosimetric relations between ozone concentrations and biological changes in precisely delineated regions of the lungs can be defined along the entire lower respiratory tract.

Analysis of Variance↗

External evaluation of regional cardiac lymph drainage in intact dogs.

After coronary occlusion, interruption of cardiac lymphatic flow reduces the proportion of creatine kinase depleted from the heart appearing in blood. Accordingly, characterization of cardiac lymph flow should be helpful in refining enzymatic estimates of infarct size. In the present study, 99mTc-sulfur colloid, a potential tracer for imaging cardiac lymphatic structures, was injected intramurally into selected regions of the heart in 17 dogs. Serial images of the chest were obtained for 24 hours with a scintillation camera, after which the animals were killed and the cardiac and other mediastinal nodes removed and assayed for radioactivity. Analysis of the images and counts in vitro demonstrated a consistent drainage pathway between the anterior left ventricular wall and the cardiac node. Other areas of the heart exhibited variable drainage patterns. After injection into the anterior left ventricular wall, in both open-chest dogs (n = 3) and in closed-chest dogs via a percutaneous, subxiphoid approach (n = 3) with a specially designed, collared needle, the cardiac node was visualized within 2 minutes. Activity in the cardiac node region reached a peak within 40 minutes in five of six dogs and accumulated greater than 1000 counts/min in five of six dogs before plateauing. In three additional dogs subjected to cardiac lymphatic occlusion five or six days prior to anterior left ventricular injection, appearance of radioactivity in the cardiac node was markedly delayed and maximum activity was far less than that in controls. Thus, regional cardiac lymph flow from the anterior left ventricular wall can be assessed semiquantitatively with a radionuclide imaging technique, potentially useful in refinement of enzymatic estimates of infarct size.

Animals↗

Left inferior parietal dominance in gesture imitation: an fMRI study.

The inability to imitate gestures is an essential feature of apraxia. However, discrepancies exist between clinical studies in apraxic patients and neuroimaging findings on imitation. We therefore aimed to investigate: (1) which areas are recruited during imitation under conditions similar to clinical tests for apraxic deficits; (2) whether there are common lateralized areas subserving imitation irrespective of the acting limb side; and also (3) whether there are differences between hand and finger gestures. We used fMRI in 12 healthy, right handed subjects to investigate the imitation of four types of variable gestures that were presented by video clips (16 different finger and 16 different hand gestures with either the right or the left arm). The respective control conditions consisted of stereotyped gestures (only two gestures presented in pseudorandom order). Subtraction analysis of each type of gesture imitation (variable>stereotyped) revealed a bilateral activation pattern including the inferior parietal cortex Brodmann Area (BA 40), the superior parietal cortex, the inferior frontal cortex (opercular region), the prefrontal motor cortex, the lateral occipito-temporal junction, and the cerebellum. These results were supported by statistical conjunction of all four subtraction analyses and by the common analysis of all four types of gesture imitation. The direct comparison of the right and left hemispheric activation revealed a lateralization to the left only of the inferior parietal cortex. Comparisons between different types of gesture imitation yielded no significant results. In conclusion, gesture imitation recruits bilateral fronto-parietal regions, with significant lateralization of only one area, namely the left inferior parietal cortex. These in vivo data indicate left inferior parietal dominance for gesture imitation in right handers, confirming lesion-based theories of apraxia.

Adult↗

Secondary ocular involvement in systemic "memory" B-cell lymphocytic leukemia.

OBJECTIVE: Recently, B-cell chronic lymphocytic leukemia (B-CLL) has been subdivided into "naive" B-CLL and "memory" B-CLL on the basis of the presence of somatic mutations in the variable region of the immunoglobulin heavy chain gene (IgH). The aim of the current paper was to report the clinical, histopathologic, and molecular biologic findings of intraocular and ocular adnexal involvement in a patient with systemic B-CLL. DESIGN: Case report. INTERVENTION: Treatment consisted of systemic chemotherapy, conjunctival biopsies, and, ultimately, enucleation of the left eye. METHODS: Histopathologic findings of a bone marrow biopsy, the conjunctival biopsies, and the enucleated eye were compared. Further, extensive immunohistochemistry, polymerase chain reaction (PCR) for the detection of heavy chain (IgH) gene rearrangement, gene scan analysis, and DNA sequencing were performed on all tissues. RESULTS: The tumor manifestations in all specimens demonstrated similar morphologic and immunophenotypic characteristics, consistent with the diagnosis of B-CLL. Immunoglobulin-H PCR and gene scan analysis showed that the B-CLL infiltrates consisted of B cells derived from the same clone. DNA sequencing demonstrated the presence of eight somatic mutations in the variable region of IgH, consistent with "memory" B-CLL. CONCLUSIONS: Secondary ocular manifestations of B-CLL occur relatively commonly during disease progression. In the current case of memory B-CLL, ocular manifestation of the disease occurred 16 years after initial diagnosis, agreeing with clinical studies suggesting that a less aggressive course is seen in "memory" B-CLL than its counterpart, "naive" B-CLL. Somatic mutation analysis in the variable region of IgH in B-CLL should be part of routine staging investigations to aid the prediction of the individual clinical course in B-CLL patients and to determine new therapeutic strategies.

Antibodies, Monoclonal↗

Neural systems for word meaning modulated by semantic ambiguity.

One important issue in neuroimaging research on language is how the brain processes and represents lexical semantics. Past studies with various paradigms reveal that the left inferior prefrontal and mid-superior temporal regions play a crucial role in semantic processing. Those studies, however, typically utilize words having a precise and dominant meaning as stimuli and have not manipulated lexico-semantic ambiguity, a key feature of human language, as an experimental variable. Here, we used a word generation paradigm to examine whether neuroanatomical networks for meaning are modulated by lexical ambiguity. We found that, compared with semantically precise words, semantically ambiguous words were mediated by strong brain activations in the left dorsal-lateral frontal areas, the anterior cingulate, and the right inferior parietal lobe. Semantically precise words, instead, were associated with the left inferior prefrontal and mid-superior temporal sites. These findings indicate that semantic analysis of written words is a dynamic process involving coordination of widely distributed neural subsystems, which are weighted by semantic ambiguity.

Adult↗

Cortical variability and asymmetry in normal aging and Alzheimer's disease.

The onset of Alzheimer's disease (AD) is accompanied by a complex and distributed pattern of neuroanatomic change, difficult to distinguish clinically from dynamic alterations in normal aging. Extreme variations in the sulcal patterns of the human cortex have made it difficult to identify diffuse and focal variations in cortical structure in neurodegenerative disease. We report the first comprehensive 3D statistical analysis of deep sulcal structure in vivo, in both normal aging and dementia. High-resolution 3D T1-weighted fast SPGR (spoiled GRASS) MRI volumes were acquired from 10 patients diagnosed with AD (NINCDS-ARDRA criteria; age: 71.9 +/- 10.7 years) and 10 normal subjects matched for age (72.9 +/- 5.6 years), gender, educational level and handedness. Scans were digitally transformed into Talairach stereotaxic space. To determine specific patterns of cortical variation in dementia patients, 3D average and probabilistic maps of primary deep sulci were developed for both normal and AD groups. Major sulci (including supracallosal, cingulate, marginal, parieto-occipital, anterior and posterior calcarine sulci, and Sylvian fissures) were modeled as complex systems of 3D surfaces using a multi-resolution parametric mesh approach. Variations and asymmetries in their extents, curvature, area and surface complexity were evaluated. Three-dimensional maps of anatomic variability, structural asymmetry and local atrophy indicated severe regionally selective fiber loss in AD. A midsagittal area loss of 24.5% at the corpus callosum's posterior midbody (P < 0.025) matched increases in structural variability in corresponding temporo-parietal projection areas. Confidence limits on 3D cortical variation, visualized in 3D, exhibited severe increases in AD from 2 to 4 mm at the callosum to a peak SD of 19.6 mm at the posterior left Sylvian fissure. Normal Sylvian fissure asymmetries (right higher than left; P < 0.0005), mapped for the first time in three dimensions, were accentuated in AD (P < 0.0002), and were greater in AD than in controls (P < 0.05). Severe AD-related increases in 3D variability and asymmetry may reflect disease-related disruption of the commissural system connecting bilateral temporal and parietal cortical zones, regions known to be at risk of early metabolic dysfunction, perfusion deficits and selective neuronal loss in AD.

Aged↗

Temporal lobe activations of "feeling-of-knowing" induced by face-name associations.

"Feeling-of-Knowing" (FOK) refers to the sense of what one knows and is a component of the human metamemory system. We investigated the neural correlates of the FOK induced by face-name associations using the Recall-Judgment-Recognition paradigm. Data were gathered using event-related functional magnetic resonance imaging (fMRI). We analyzed the fMRI data with parametric analyses of six FOK ratings while compensating for the effects of unbalanced response latencies among trials ("variable duration parametric analysis"). Regions showing a significant linear relationships with the FOK ratings (FOK regions) were the bilateral ventral, dorsal, and anterior prefrontal regions; the medial frontal regions; the medial surface regions; the left parietal regions; the bilateral superior temporal and nearby regions; the right anterior temporal region; and the bilateral thalami/basal ganglia. Most of the active areas in the prefrontal regions were common to those found in our previous FOK studies of general knowledge (Kikyo, H., Ohki, K., Miyashita, Y., 2002. Neural correlates for feeling-of-knowing: an fMRI parametric analysis. Neuron 36, 177-186). However, in this study, we found robust activations of the temporal regions near to the regions that were related to the higher-order information processing of face images or semantic information processing of the to-be-recalled person. Those results suggest that the information related to the higher-order visual features of a face, which was represented in the temporal cortex, was activated by the top-down signal from the prefrontal cortex, and that this cooperation between the temporal and prefrontal cortices may contribute to the FOK.

Adult↗

Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance.

Cellular therapy for myocardial injury has improved ventricular function in both animal and clinical studies, though the mechanism of benefit is unclear. This study was undertaken to examine the effects of cellular injection after infarction on myocardial elasticity. Coronary artery ligation of Lewis rats was followed by direct injection of human mesenchymal stem cells (MSCs) into the acutely ischemic myocardium. Two weeks postinfarct, myocardial elasticity was mapped by atomic force microscopy. MSC-injected hearts near the infarct region were twofold stiffer than myocardium from noninfarcted animals but softer than myocardium from vehicle-treated infarcted animals. After 8 wk, the following variables were evaluated: MSC engraftment and left ventricular geometry by histological methods, cardiac function with a pressure-volume conductance catheter, myocardial fibrosis by Masson Trichrome staining, vascularity by immunohistochemistry, and apoptosis by TdT-mediated dUTP nick-end labeling assay. The human cells engrafted and expressed a cardiomyocyte protein but stopped short of full differentiation and did not stimulate significant angiogenesis. MSC-injected hearts showed significantly less fibrosis than controls, as well as less left ventricular dilation, reduced apoptosis, increased myocardial thickness, and preservation of systolic and diastolic cardiac function. In summary, MSC injection after myocardial infarction did not regenerate contracting cardiomyocytes but reduced the stiffness of the subsequent scar and attenuated postinfarction remodeling, preserving some cardiac function. Improving scarred heart muscle compliance could be a functional benefit of cellular cardiomyoplasty.

Animals↗

A load-independent in vivo model for evaluating therapeutic interventions in injured myocardium.

Although cardiomyocyte damage is normally irreversible, gene therapy and somatic cell transfer offer potential for improving function in damaged regions of the heart. However, in ischemic models of injury, variability in depth, size, and location of damage compromises statistical evaluation of in vivo function. We have adapted cryoablation to create a reproducible, posterior, transmural lesion within rabbit myocardium in which small changes in function are measurable in vivo. Before and at 2 and 6 wk postinjury, in vivo left ventricular intracavitary pressure and myocardial segment length were measured. Regional indexes of performance, segmental stroke work (SW), and percent systolic shortening (SS) were significantly decreased (P < 0.001) postcryoinjury as was the slope (Mw) of the linear preload recruitable SW relationship between SW and end-diastolic segment length (P = 0.0001). Decreased SW, SS, and Mw correlated with wall thinning, loss of myocytes, presence of fibroblasts, and transmural scar formation. Reproducible changes in regional myocardial performance in vivo postcryoinjury suggest that this is a reasonable model for evaluating novel therapies for cardiovascular disease.

Animals↗

Effect of beta-blockade by metoprolol on global and regional left ventricular myocardial perfusion in coronary heart disease.

Utilizing semiselective 133Xenon injections and gamma camera recording, global and regional left ventricular myocardial perfusion were recorded under the influence of beta-blockade by metoprolol in 9 patients with angiographically proven coronary artery disease. Metoprolol reduced the rate--pressure variable in every patient, the mean reduction amounting to 24% (P less than 0.01). With one exception, the global left ventricular myocardial flow followed the change in the rate-pressure variable. No significant differences were detected in the flow responses of areas distal to only moderate coronary obstructions (less than 75%) and areas distal to significant (less than 75%) obstructions. The same was true when areas of asynergic contractions were compared with areas of normal contractions, or when areas supplied by collaterals were compared with areas devoid of collateral vessels. It is concluded that the reduction in myocardial flow after metoprolol is due to the reduction of the myocardial oxygen consumption, and no redistribution of flow occurs.

Adult↗

Intramyocardial variability in integrated backscatter: effects of coronary occlusion and reperfusion.

The present study was undertaken to characterize regional myocardial alterations of reflected ultrasound during the cardiac cycle in normal, ischemic, and postischemic reperfused myocardium. Time-averaged integrated backscatter (IB) and cardiac cycle-dependent amplitude modulation were measured from subepicardial, midmyocardial, and subendocardial regions of the left ventricular apex and the midportion of the right ventricular free wall under normal conditions (n = 5), after 1 hr of 100% acute left anterior descending (LAD) occlusion (n = 8), and after 15 min LAD occlusion plus 120 min reperfusion (n = 5) in anesthetized, ventilated open-chest dogs. A significant increase in time-averaged IB was observed in the subepicardium, the midmyocardium, and the subendocardium during ischemia and reperfusion, but there was no intramyocardial variability. Cardiac cycle-dependent amplitude modulation of IB was significantly higher in the normal subendocardium than in the subepicardium (4.3 +/- 0.6 vs 2.9 +/- 0.8 dB, p less than .01) and midmyocardium (2.8 +/- .05 dB, p less than .01). This transmural gradient in amplitude modulation was abolished during ischemia and reperfusion. We conclude that cardiac cycle-dependent amplitude modulation in IB has a transmural dependence in the normal myocardium and this is abolished during acute myocardial ischemia.

Animals↗

Hemispace differences in the visual perception of size in left hemiParkinson's disease.

The visual perception of size in different regions of external space was studied in Parkinson's disease (PD). A group of patients with worse left-sided symptoms (LPD) was compared with a group with worse right-sided symptoms (RPD) and with a group of age-matched controls on judgements of the relative height or width of two rectangles presented in different regions of external space. The relevant dimension of one rectangle (the 'standard') was held constant, while that of the other (the 'variable') was varied in a method of constant stimuli. The point of subjective equality (PSE) of rectangle width or height was obtained by probit analysis as the mean of the resulting psychometric function. When the standard was in left space, the PSE of the LPD group occurred when the variable was smaller, and when the standard was in right space, when the variable was larger. Similarly, when the standard rectangle was presented in upper space, and the variable in lower space, the PSE occurred when the variable was smaller, an effect which was similar in both left and right spaces. In all these experiments, the PSEs for both the controls and the RPD group did not differ significantly, and were close to a physical match, and the slopes of the psychometric functions were steeper in the controls than the patients, though not significantly so. The data suggest that objects appear smaller in the left and upper visual spaces in LPD, probably because of right hemisphere impairment.

Aged↗

Comparison of nuclear scintigraphy and acetaminophen absorption as a means of studying gastric emptying in horses.

OBJECTIVE: To evaluate the correlation between halftime of liquid-phase gastric emptying (T50), determined with nuclear scintigraphy using technetium Tc 99m pentetate, and absorption variables of orally administered acetaminophen. ANIMALS: 6 mature horses. PROCEDURE: Technetium Tc 99m pentetate (10 mCi) and acetaminophen (20 mg/kg of body weight) were administered simultaneously in 200 ml of water. Serial left and right lateral images of the stomach region were obtained with a gamma camera, and T50 determined separately for counts obtained from the left side, the right side and the geometric mean. Power exponential curves were used for estimation of T50 and modified R2 values for estimation of goodness of fit of the data. Serial serum samples were taken, and acetaminophen concentration was determined, using fluorescence polarization immunoassay. Maximum serum concentration (Cmax), time to reach maximum serum concentration (Tmax), area under the curve for 240 minutes and the absorption constant (Ka) were determined, using a parameter estimation program. Correlations were calculated, using the Spearman rank correlation coefficient. RESULTS: Correlations between T50 and Tmax and between T50 and Ka were significant. CONCLUSIONS AND CLINICAL RELEVANCE: Tmax and Ka are valuable variables in the assessment of liquid-phase gastric emptying using acetaminophen absorption. Acetaminophen absorption may be a valuable alternative to nuclear scintigraphy in the determination of gastric emptying rates in equine patients with normally functioning small intestine.

Acetaminophen↗

Ventricular preload alters intravascular and extravascular resistances of coronary collaterals.

Coronary collateral blood flow is determined by both the collateral vessel resistance and a waterfall mechanism. The aim of this study was to determine which of these two mechanisms predominates during alteration of ventricular preload. The left anterior descending coronary artery of 12 anesthetized dogs was cannulated, and the distal vasculature was completely embolized with 25-micron diameter microspheres. Retrograde blood flow (RBF) was collected when the cannula was opened to the atmosphere, and the outflow tubing height was adjusted to provide a variable back pressure. RBF is back pressure-dependent at higher back pressures, and the slope in this region of the constructed pressure-flow relationship determines the collateral conductance. The transition point between the back pressure-dependent and a back pressure-independent region indicates a waterfall pressure impinging on the collateral vessels. At a left ventricular diastolic pressure of 9.3 mmHg, mean RBF, collateral conductance, and the collateral waterfall pressure were 7.3 ml/min, 0.175 ml.min-1.mmHg-1, and 30.1 mmHg, respectively. Corresponding values when preload was reduced to 3.5 mmHg were 9.3 ml/min, 0.186 ml.min-1.mmHg-1, and 23.7 mmHg, all changes being significant. Mean contribution to the overall increase in RBF was 0.5 ml/min for the conductance and 1.2 ml/min for the waterfall mechanism (P less than 0.05), or 29 and 71%, respectively. The results indicate that the extravascular resistance mechanism mediates the collateral flow response to a greater degree than the intravascular resistance during variations in preload. The increase in slope of the conductance portion of the relationship was not accompanied by a concomitant increase in slope of the back pressure-independent region. These data further support a collateral waterfall, and not collateral vessel compliance, as the basis for the back pressure-independent portion of the pressure-flow relationship.

Animals↗