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Fabric organization of the subendothelium of the human brain artery by polarized-light microscopy.

The thickened subendothelium of brain arteries that is characteristic of atherosclerosis was assessed for the directional organization of the two main birefringent components, smooth muscle cells and collagen. Thirty-three arteries from 16 autopsy cases were pressure fixed at 30, 60, 110, and 200 mm Hg, sectioned at a thickness of 7 microns , and stained with silver impregnation to enhance tissue birefringence. The intended focus of the study was on muscle organization, but it also included the collagen among the cells because of the coalignment of the two tissues and their similar staining properties for polarized-light microscopy. The birefringent medial fabric at all pressures was circumferentially oriented, with a mean deviation of the 33 sections of 1.4 degrees from circumferential with an average circular standard deviation of 3.5 degrees, thereby showing remarkable coherence. In contrast, the subendothelium showed great variability both in thickness and in organization. Many arteries had no measurable subendothelium, and others had as much as 100%, with some atherosclerotic lesions as much as 300% of the medial width. Measurements from the subendothelium revealed a helical arrangement of tissue, often divided into separate regions, with a balance of left- and right-handed helical components and generally with lower pitch angles in the layers adjacent to the lumen. The average circular standard deviation within individual subendothelial layers was 14.5 degrees.

Adult↗

Effects of coronary collaterals on regional myocardial function during temporary coronary occlusion and hypoxic coronary perfusion.

The effects of coronary collaterals on regional myocardial function during temporary ischemia and hypoxia were studied in 12 open-chest dogs. Using an ultrasonic dimension gauge, systolic segment shortening in the left anterior descending coronary artery (LAD) area was measured at 1 min after the following three experimental conditions: LAD occlusion and LAD hypoxic perfusion with nonoxygenated solutions at two different pressures (60 mmHg and 120 mmHg). Collateral function was assessed by both LAD diastolic retrograde pressure and the percentage of increase in left circumflex coronary flow at 1 min after LAD occlusion. Systolic segment shortening decreased less with hypoxic perfusion than with occlusion, however, this beneficial effect on regional contraction was greater at a perfusion pressure of 60 mmHg than at one of 120 mmHg. The magnitude of decrease of systolic shortening was variable among individual dogs but correlated linearly with each of the two collateral function indexes, not only during occlusion but also during hypoxic perfusion. In conclusion, the preventive effect of hypoxic coronary perfusion on the early decline of regional myocardial function, in comparison to the changes seen during ischemia, may depend on coronary collaterals in addition to its washout effect on metabolites. In order to maintain myocardial function, perfusion pressure should be at an optimal level.

Animals↗

Additive enhancement of implant fixation following combined treatment with rhTGF-beta2 and rhBMP-2 in a canine model.

BACKGROUND: Gaps at the interface between implant and bone increase the risk of diminished implant fixation and eventual loosening. The purpose of the present study was to determine if combined use of recombinant human transforming growth factor-beta 2 (rhTGF-beta2) and bone morphogenetic protein 2 (rhBMP-2) led to greater implant fixation strength in the presence of interface gaps than the use of either growth factor alone. METHODS: Twenty-eight skeletally mature adult male dogs received one porous-coated titanium implant in the proximal part of each humerus, for a total of fifty-six implantation sites. Spacers were used to establish an initial 3-mm gap between the implant and the host bone at all fifty-six sites. Forty-two implants were coated with hydroxyapatite-tricalcium phosphate and were used in three growth-factor-treatment groups in which the implants placed in the left humerus were loaded with 12 microg of rhTGF-beta2 (Group 1, seven animals), 25 microg of rhBMP-2 (Group 2, seven animals), or 12 microg of rhTGF-beta2 combined with 25 microg of rhBMP-2 (Group 3, seven animals). In these animals, the twenty-one implants that were placed in the right humerus were loaded with buffer only to serve as contralateral controls. In Group 4 (seven animals), the implants were not coated with hydroxyapatite-tricalcium phosphate, the gap in the left humerus was lightly packed with autogenous bone graft, and the gap in the right humerus was left empty to serve as a contralateral control. All animals were killed at twenty-eight days. The primary end points included three mechanical variables: fixation strength, interface stiffness, and energy to failure. Secondary end points included bone ingrowth and bone volume and trabecular architecture in the gap and in a region located 2 mm medial to the implantation site. RESULTS: The hydroxyapatite-tricalcium phosphate coating had no effect on implant fixation, bone ingrowth, or bone formation in the 3-mm gap. Individual growth factor treatments led to 2.3 to 3.2-fold increases in fixation strength and stiffness as compared with the values for the contralateral controls (p < 0.05). The combined growth factor treatment led to 5.7-fold increases in fixation strength and stiffness compared with the values for the contralateral controls (p < 0.01). Autogenous bone graft treatment was associated with 4.5 to 6.4-fold increases in implant fixation strength and stiffness as compared with the values for the contralateral controls (p < 0.01). Compared with the relevant contralateral controls, energy to failure was increased 3.5-fold in association with TGF-beta2 alone (p < 0.05), 4.5-fold in association with TGF-beta2 combined with BMP-2 (p < 0.01), and 2.5-fold in association with autogenous bone-grafting. As much as 63% of the variance in the mechanical end points was associated with variance in bone volume and architecture in the 3-mm gap and in the region of interest located 2 mm medial to the implantation site (p < 0.01). CONCLUSIONS: In this animal model, the combined use of TGF-beta2 and BMP-2 led to more secure mechanical fixation of the implant than did the use of either growth factor alone and demonstrated results that were similar to those associated with the use of autogenous bone graft.

Animals↗

Olfactory function evaluated by SPECT.

Few articles on neuroimaging techniques in the study of central and peripheral olfactory pathways are present in the literature. By Single Photon Emission Computed Tomography (SPECT), cortical perfusion increment after sensorial stimulation can be evaluated objectively. In the present research, 10 healthy adults underwent SPECT by CER.TO.96 cerebral tomograph, before and after olfactory stimulation with lavender-water. A variable degree of cortical activation was detected in all patients. Gyrus rectus (+24.5%), orbito-frontal cortex (right +26.6%, left +25.6%), and superior temporal (right +9.9%, left +5.5%) cortical areas were always activated. A slight perfusion increase was present in middle temporal (right +3.2%, left +2.1%) and parieto-occipital (right +0.4%, left +2%) regions. Five patients affected by posttraumatic anosmia were also investigated: they showed a perfusion increment markedly inferior to 0.5% in every olfactory area. SPECT is a rather diffused, easily performed technique which yields objective semi-quantitative information on brain perfusion. Hence, it can be regarded as a promising contribution in the fields of smell neurophysiology, clinical olfactometry, and medicolegal queries.

Adult↗

[Mapping and ablation of malignant ventricular arrhythmias].

Endocavitary investigations showed that the ventricular extrasystoles originated in the common ventricular myocardium (pulmonary infundibulum) in only 9 cases whereas the majority arose from the Parkinje system either on the anterior wall of the right ventricle or in septal region of the left ventricle. The extrasystoles arising from the Parkinje system and pulmonary infundibulum differed in their duration and polymorphism (128 +/- 18 ms vs 145 +/- 13 ms, p = 0.05; 3.3 +/- 2.7 morphologies vs 1.1 +/- 0.4, p < 0.001, respectively). During the extrasystoles, the local Pukinje potential preceded the ventricular activation by variable intervals, some of which were very long, up to 150 ms. Seven applications of radiofrequency were delivered on average per patient on the most distal part of the Purkinje system leading to ablation of the specific activation. The clinical results were spectacular: 88% of patients had no further episodes of ventricular fibrillation as demonstrated by analysis of the defibrillator with an average follow-up period of more than 34 months.

Catheter Ablation↗

Efficacy of therapeutic angiogenesis by intramyocardial injection of pCK-VEGF165 in pigs.

BACKGROUND: Intramyocardial injection of vascular endothelial growth factor (VEGF) plasmid DNA was studied to demonstrate improvement of regional myocardial function. METHODS: Twenty-one pigs that had undergone ligation of the left anterior descending coronary artery were randomly allocated to one of two treatments: intramyocardial injection of pCK-VEGF165 (VEGF group) or pCK-Null (control group) into the ischemic border zone. Electrocardiogram-gated single-photon emission computed tomography was performed 30 and 60 days after the coronary ligation. Segmental variables of perfusion and function were automatically quantified using a 20-segment model. In the segmental analysis, 119 segments were selected for analysis (71 segments in the VEGF group; 48 segments in the control group). Histologic analysis was also performed in the myocardial tissue of the ischemic border zone. RESULTS: At day 30, there were no significant differences in segmental perfusion, wall thickening, and wall motion between the two groups. In the VEGF group, all variables of perfusion, wall thickening, and wall motion were significantly improved at day 60 compared with those at day 30 (p < 0.05), while there were no differences in the control group. At day 60, perfusion (p = 0.018), wall motion (p = 0.004), and wall thickening (p = 0.068) of the VEGF group were improved compared with those of the control group. Histologic analysis showed that microcapillary density was significantly higher in the VEGF group than the control group (p < 0.001). CONCLUSIONS: Intramyocardial injection of pCK-VEGF165 significantly augmented neoangiogenesis in the ischemic area and improved regional myocardial function as well as myocardial perfusion.

Animals↗

Regional cerebral blood flow in the persistent vegetative state.

Regional cerebral blood flow (CBF) in eight patients in a persistent vegetative state was measured and compared with that in five healthy volunteers. The patients were classified into three groups: Group 1 (locked-in syndrome) consisted of a single patient, Group 2 (typical vegetative state) of five patients, and Group 3 (prolonged coma) of two patients. CBF was measured early after onset by single photon emission computed tomography with 123I-N-isopropyl-p-iodo-amphetamine and/or 99mTc-hexamethyl-propyleneamine oxime. The regions of interest (ROIs) were the bilateral frontal, temporal, parietal, occipital, and cerebellar areas and basal ganglia. The values obtained in these areas were averaged, and the ratio for each ROI [(the value in the ROI/the mean value) x 100] was calculated. "Hyperfrontal distribution" of CBF was found to be rare in both the normal condition and the vegetative state. Higher CBF values were noted in the left than in the right frontal area in four of the five volunteers but in only four of the eight patients. CBF distribution in the frontal lobe was characteristic for each group: Group 1 showed high CBF bilaterally, although the elevation was statistically significant only on the right side, and Group 3 exhibited significantly low values. In Group 2, CBF was variable but, for the most part, within normal limits. Awareness was closely correlated with frontal lobe function and alteration of CBF in the frontal region.

Adult↗

The basics of ventricular function.

There has been increasing interest in the study of ventricular function in the patient with congenital heart disease. Numerous indexes have been derived for the assessment of ventricular function, suggesting that none is ideal. While the derivation of some measures of ventricular function have relied on advanced mathematical principles, it is still possible for the non-mathematician to obtain important insights into ventricular function from an assessment of the events which underpin the cardiac cycle. In this review, I use the mechanics of the cardiac cycle to introduce basic concepts of ventricular function for the non-expert. In this way, I analyse ventricular systolic and diastolic performance and describe the contribution of regional variability of function to overall performance. This approach also highlights the role of the ventricle in overall cardiovascular and metabolic homeostasis.

Diastole↗

Thyroglossal duct cysts: variability of sonographic findings.

OBJECTIVE: The purpose of this study was to describe the sonographic features of thyroglossal duct cysts, emphasizing the variable sonographic appearances, and determine if the presence of infection or inflammation influences the sonographic appearance. MATERIALS AND METHODS: We reviewed the sonograms in 12 children (2 months-16 years old) with pathologically proven thyroglossal duct cysts (TDCs). The cysts were evaluated for location, size, cystic versus solid features, echogenicity, and wall thickness. The sonographic features then were compared with the pathologic findings. RESULTS: Sonograms of the 12 lesions showed that nine were midline at or near hyoid bone; two were to the right of midline in the submandibular region; and one was located to the left of midline in the neck. Cysts were from 0.5 cm to 4 cm in diameter. Five lesions were anechoic with no perceptible wall thickness. Seven lesions were hypoechoic. Two of the seven were homogeneously hypoechoic with thin borders. The remaining five lesions were hypoechoic but heterogeneous (complex). One lesion was hypoechoic with small anechoic spaces. Four lesions were largely cystic with dense internal echoes and thick walls. The presence of thick walls and internal echoes did not correlate with the presence or absence of inflammation on pathologic examination. No lesions in our series were hyperechoic. CONCLUSION: Our results indicate that TDCs have a variable sonographic appearance. Anechoic, homogeneously hypoechoic, and heterogeneous (complex) lesions occur. We found no correlation between the pathologic findings of infection and inflammation and the sonographic appearance of TDCs. Awareness of the variable sonographic appearance of the TDC is helpful when a midline lesion is encountered in the neck.

Adolescent↗

Analysis of left ventricular regional motility: a comparison of different methods.

Multiple gated blood pool (MUGA) and contrast ventriculographic studies were performed within 24 h in 80 patients, 20 with 120 normokinetic wall segments and 60 with wall motion abnormalities in 239 of 360 wall segments. Three methods of evaluation of the radionuclide ventriculograms were compared with the results of the biplane contrast ventriculography which served as a standard: (1) qualitative analysis of the cine mode, (2) analysis of parametric scans (amplitude and phase images) and the phase histogram obtained by Fourier analysis, (3) quantitative determination of regional ejection fraction. Normal values were obtained from 20 patients with normal wall motion in the contrast angiogram. The overall sensitivity for the detection of wall motion abnormalities of high degree was 96% for method 1, 95% for method 2, and 90% for method 3, for those of low degree 72% for method 1, 63% for method 2, and 75% for method 3. Combining methods 2 and 3 the sensitivity was increased to 99% for high grade and to 81% for low grade wall motion abnormalities. The two methods showed a complementary effect because of different sensitivities in dependence of the localization of the wall motion abnormality. Although a high efficiency for the evaluation of left ventricular function was provided by the qualitative analysis of the cine mode the combination of Fourier analysis and the determination of regional ejection fraction should be preferred. It increases the sensitivity for the detection of wall motion abnormalities. Moreover, it offers quantitative data which improve the reproducibility and decrease the observer variability.

Angiography↗

On crossed apraxia. Description of a right-handed apraxic patient with right supplementary motor area damage.

GP, a right-handed woman, without evidence of familial left-handedness, showed clearcut bilateral ideo-motor apraxia and oro-facial apraxia after a vascular lesion of the right hemisphere, encroaching upon the fronto-mesial region. She scored normally in most other cognitive tests, including language, but showed signs of callosal disconnection, left anarchic hand and mild unilateral spatial neglect. This cognitive profile points to the possibility of praxis being localized to the right hemisphere in this right-handed patient. We argue in favour of individual variability of praxis dominance, and maintain that this dominance might be completely right-sided in some subjects. Moreover the anatomical locus of GP's lesion points to the possible role that the frontal lobes (and more specifically the Supplementary Motor Area) play in the genesis of apraxia.

Agnosia↗

Functional anatomy of impaired selective attention and compensatory processing in autism.

In autism, physiological indices of selective attention have been shown to be abnormal even in situations where behaviour is intact. This divergence between behaviour and physiology suggests the action of some compensatory process of attention, one which may hold clues to the aetiology of autism's characteristic cognitive phenotype. Six subjects with autism spectrum disorders and six normal control subjects were studied with functional magnetic resonance imaging while performing a bilateral visual spatial attention task. In normal subjects, the task evoked activation in a network of cortical regions including the superior parietal lobe (P<0.001), left middle temporal gyrus (P=0.002), left inferior (P<0.001) and middle (P<0.02) frontal gyri, and medial frontal gyrus (P<0.02). Autistic subjects, in contrast, showed activation in the bilateral ventral occipital cortex (P<0.03) and striate cortex (P<0.05). Within the task condition, a region-of-interest comparison of attend-left versus attend-right conditions indicated that modulation of activation in the autistic brain as a function of the lateral focus of spatial attention was abnormally decreased in the left ventral occipital cortex (P<0.03), abnormally increased in the left intraparietal sulcus (P<0.01), and abnormally variable in the superior parietal lobe (P<0.03). These results are discussed in terms of a model of autism in which a pervasive defect of neural and synaptic development produces over-connected neural systems prone to noise and crosstalk, resulting in hyper-arousal and reduced selectivity. These low-level attentional traits may be the developmental basis for higher-order cognitive styles such as weak central coherence.

Adult↗

Role of the corpus callosum in the somatosensory activation of the ipsilateral cerebral cortex: an fMRI study of callosotomized patients.

To verify whether the activation of the posterior parietal and parietal opercular cortices to tactile stimulation of the ipsilateral hand is mediated by the corpus callosum, a functional magnetic resonance imaging (fMRI, 1.0 tesla) study was performed in 12 control and 12 callosotomized subjects (three with total and nine with partial resection). Eleven patients were also submitted to the tactile naming test. In all subjects, unilateral tactile stimulation provoked a signal increase temporally correlated with the stimulus in three cortical regions of the contralateral hemisphere. One corresponded to the first somatosensory area, the second was in the posterior parietal cortex, and the third in the parietal opercular cortex. In controls, activation was also observed in the ipsilateral posterior parietal and parietal opercular cortices, in regions anatomically corresponding to those activated contralaterally. In callosotomized subjects, activation in the ipsilateral hemisphere was observed only in two patients with splenium and posterior body intact. These two patients and another four with the entire splenium and variable portions of the posterior body unsectioned named objects explored with the right and left hand without errors. This ability was impaired in the other patients. The present physiological and anatomical data indicate that in humans activation of the posterior parietal and parietal opercular cortices in the hemisphere ipsilateral to the stimulated hand is mediated by the corpus callosum, and that the commissural fibres involved probably cross the midline in the posterior third of its body.

Adult↗

Bovine herpesvirus 4 genome: cloning, mapping and strain variation analysis.

The restriction map of the bovine herpesvirus 4 (BHV-4) genome (V. Test strain) was established for the restriction enzymes EcoRI, BamHI and HindIII by analysis of clones from a lambda library (Sau3AI partial digestion) and from a plasmid library (EcoRI fragments). One genome unit was defined as the length of the unique central part, flanked at both ends by one of the terminal tandem repeats called polyrepetitive DNA (prDNA) and was estimated to be 113 +/- 2 kbp. A restriction map of the prDNA of the V. Test strain showed internal 200 bp tandem repeats of different sequences. This region in the prDNA was highly polymorphic between BHV-4 strains, even in a viral DNA preparation from a plaque-purified strain. The right junction between the repeated and the unique sequence of the genome occurred at an almost constant site, but the left junction contained a modified prDNA and was variable between BHV-4 strains. The unique central part of the genome was very similar in the four strains under consideration, with a few variations due to the presence or absence of a restriction site and four length variations were observed, located at positions 0.006 to 0.034 (left end), 0.211 to 0.225, 0.864 to 0.881 and 0.962 to 0.984 (right end). The total length variation of 1 genome unit does not exceed 1 kbp.

Animals↗

Angiographic prediction of cardiac events after first acute transmural myocardial infarction. A prospective study of 108 patients.

108 patients with acute myocardial infarction (MI), aged 70 years or younger, underwent left ventriculography and coronary arteriography (mean one month) after infarction and were followed up for an average period of 22 months (range 5-47 months). The contribution of angiographic variables to a first cardiac event (death, recurrent infarction, coronary artery bypass grafting or congestive heart failure) was evaluated with Kaplan-Meier survival curve analysis and long-rank test. Patients with cardiac events had left ventricular dilation, systolic dysfunction, multivessel coronary disease and lack of residual flow to the infarct region. Multivariate analysis showed that left ventricular end-systolic volume (P less than 0.001), end-diastolic volume (P less than 0.01) and the number of the diseased coronary vessels (P less than 0.05) were of significance in predicting the outcome. This prospective study indicates that in survivors of first acute transmural MI, cardiac catheterization performed one month after infarction can provide additive prognostic information that can be used to stratify risk.

Adult↗

Effect of exercise position during stress testing on cardiac and pulmonary thallium kinetics and accuracy in evaluating coronary artery disease.

We compared the effects of symptom-limited upright and supine exercise on 201Tl distribution and kinetics in the heart and lungs of 100 consecutive patients. Our analysis was based on data obtained with a digital gamma camera in the 45 degrees left anterior oblique position at 5, 40, 240, and 275 min postadministration of [201Tl]chloride. We found significant differences in the results at the 5- and 40-min intervals; viz, higher cardiac and lower pulmonary thallium activity after upright exercise in 94 subjects at both intervals, and greater variability in total and regional cardiac thallium kinetics after supine exercise. With supine exercise, the relatively low initial cardiac activity, relatively high lung activity, and the greater variability in thallium kinetics combined to make interpretation of quantitative data and cardiac images difficult and less accurate with respect to detection of coronary artery disease. These observations have important implications for the interpreting physician when thallium stress tests are performed in the supine position.

Coronary Disease↗

Complexity affects regional cerebral blood flow change during sequential finger movements.

Brain regions activated with complex sequential finger movements were localized by measuring regional cerebral blood flow (rCBF) with positron emission tomography. Whereas the total number and frequency of finger movements were kept constant, the complexity of auditory cued sequential finger movements of the right hand varied, with sequence length as the independent variable. In four conditions of differing complexity, the bilateral primary sensorimotor area, left ventral premotor cortex, posterior supplementary motor area, right superior part of the cerebellum, and left putamen were consistently and equally activated. This finding suggests an executive role in running sequences, regardless of their length. The right dorsal premotor cortex (Brodmann area 6) and the right precuneus (Brodmann area 7) showed a linear increase of rCBF as sequence complexity increased. This finding is consistent with the hypothesis that these areas function in the storage of motor sequences in spatial working memory and the production of ongoing sequential movement with reference to that of buffered memory. A similar increase in the cerebellar vermis and the left thalamus likewise suggests a role of these subcortical structures in complexity of sequential finger movements. Conversely, the left inferior parietal lobule showed a decrease of rCBF as complexity increased. Because short-term phonological storage is localized to this area, we suggest that the visuospatial working memory system may suppress other systems not in use. Our findings suggest that complex sequential finger movements recruit a discrete set of brain areas, in addition to areas underlying the execution of simple movement sequences.

Adult↗

Inter-rater reliability of manual segmentation of the superior, inferior and middle frontal gyri.

Precise rules for locating the anatomical boundaries of the dorsolateral prefrontal cortex (DLPFC) or its subdivisions, i.e., superior, inferior and middle frontal gyri (SFG, IFG and MFG) on magnetic resonance images (MRI), have not been defined. The present study describes the inter-rater reliability of manual segmentation of the SFG, IFG and MFG using guidelines based on sulcal-gyral anatomical boundaries as well as the cytoarchitectonic features of the sub-regions of the prefrontal cortex (PFC). Variations in the application of these guidelines in different subjects to account for normal sulcal variability were developed using the atlas of Ono et al. (Ono, M., Kubik, S., Abernathey, C.D., 1990. Atlas of the Cerebral Sulci. Georg Thieme Verlag, New York). Based on previous cytoarchitectonic studies, the coronal plane of the anterior termination of olfactory sulcus (ATOS) was used as a landmark for delimiting the boundary between the frontal pole (FP) and the frontal gyri. The left hemisphere gray-matter volumes of the SFG, IFG and MFG were determined using a set of 10 MRIs (5 normal and 5 schizophrenia subjects) by two trained raters independently. The intra-class correlation coefficients (ICC) for the SFG, IFG and MFG volumes by the two raters were 0.97, 0.94 and 0.93, respectively. Thus, we describe a reliable method of parcellating the SFG, IFG and MFG, which constitute the DLPFC, a brain region involved in a variety of neuropsychiatric conditions.

Adolescent↗