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Morphology of the anterior cingulate gyrus in patients with schizophrenia: relationship to typical neuroleptic exposure.

OBJECTIVE: The anterior cingulate gyrus is a pivotal component of brain networks directing affective and cognitive functions, and abnormalities of the anterior cingulate gyrus may be involved in the pathophysiology of schizophrenia. However, magnetic resonance imaging studies of the morphology of this region have been few and the results inconsistent. Many of the studies have not accounted for confounding factors such as gender, handedness, or clinical variables such as neuroleptic exposure. METHOD: The morphology and clinical correlates of the anterior cingulate gyrus were evaluated in a group of 30 right-handed male subjects with schizophrenia and a comparison group matched for age, sex, and handedness. The patient group was specifically designed to provide measures of multiple phenomenological differences such as severity of illness, duration of illness, and exposure to typical neuroleptics. RESULTS: The patient group had a significantly larger left anterior cingulate gyrus volume relative to comparison subjects, whereas right anterior cingulate gyrus volume did not differ between groups. Depth of the left anterior cingulate gyrus was significantly correlated with neuroleptic exposure, indicating that greater exposure to neuroleptics was associated with greater cortical depth of this region. There was no significant relationship between anterior cingulate gyrus morphology and duration of illness or severity of symptoms. CONCLUSIONS: Anterior cingulate gyrus depth in subjects with schizophrenia is directly related to typical medication exposure (the greater the exposure, the thicker the anterior cingulate gyrus) but not to other clinical variables such as length of illness or symptom severity. Future research is needed to determine the functional consequences of these changes and relationship to atypical neuroleptic use.

Adult↗

Regional variability of stretch reflex amplitude in the cat medial gastrocnemius muscle during a postural task.

The relationship between local fibre stretch velocity (mechanical input) and the corresponding local reflex electromyographic (EMG) amplitude (a measure of the neural output) was assessed to determine the contribution of muscle spindle feedback in postural control. We hypothesized that traditionally measured input variables (e.g., the velocity of an external movement or whole muscle velocity) may not accurately represent the mechanical input to the muscle spindles, especially when the background forces are small. Three cats were trained to stand on pedestals while ankle rotations were applied to the left hindlimb. EMG and fiber movement in both proximal and distal regions of the muscle were recorded in addition to muscle length and tendon force. We found that local muscle velocity was correlated poorly with whole muscle velocity, demonstrating that internal and external muscle movements are often dissimilar, particularly during tasks that involve modest levels of muscle activation. Local EMG reflex amplitudes were correlated well with the corresponding local fiber stretch velocities (R values ranging from 0.5 to 0.8) but not with muscle stretch velocity. The lack of crossed correlations between fiber stretch velocities and reflex EMG amplitudes measured in proximal versus distal regions of the muscle suggests the presence of a local reflex component. It is concluded that changes in local muscle fiber length represent the mechanical input to spindles better than changes in the total muscle length. Additionally, spindles have a specific role in the reflex activation of nearby muscle fibers.

Animals↗

Regional variation in the timing and extent of left ventricular wall motion in normal subjects.

Right anterior oblique cineangiograms from 19 subjects without evidence of heart disease were analysed to assess regional non-uniformity in the time of onset of systolic inward motion, amplitude of systolic motion, time of peak inward motion, and wall motion during the isovolumic relaxation period. The left ventricular silhouette was digitised frame by frame for a full cardiac cycle. These four wall motion variables were quantitatively measured along 40 chords drawn from equally spaced points on the end diastolic silhouette to the nearest point on the end systolic silhouette. Onset of systolic inward motion was significantly non-uniform, being delayed by up to 120 ms in the anterior apical chords compared with the areas of earliest inward motion near the base of the heart. More uniformity was noted in time of peak inward motion; the differences between regions were not statistically significant. Amplitude of systolic motion was significantly less at the apical and mid-anterior segments than elsewhere in the heart. Wall motion during the isovolumic relaxation period is outward and greatest in the mid-anterior segments, but inward in the proximal inferior segments and mitral valve region. These data suggest that contraction of muscle fibres in the anterior apical segments is initially isometric due to the considerable afterload at the onset of contraction, this afterload being the result of earlier contraction elsewhere in the ventricle. This may partly explain the propensity for aneurysms to be located in the anterior apical region. When the timing and extent of wall motion in disease states are analysed, account must be taken of the non-uniformity in the normal heart.

Adult↗

Characterization of the genome structure of Bombyx mori densovirus (China isolate).

The genome of Bombyx mori densovirus (China isolate), termed as BmDNV-3, is composed of two kinds of different single-stranded linear DNA molecules (VD1 and VD2). In this study, the viral DNA molecules were purified and cloned into pUC119 vector, and the complete nucleotide sequence was determined. Sequence analysis showed that VD1 genome consisted of 6,543 nts including inverted terminal repeats (ITRs) of 224 nts, and VD2 genome consisted of 6,022 nts including ITRs of 524 nts. Comparison of the complete genome sequence between BmDNV-3 and BmDNV-2 (Yamanashi isolate) showed an identity of 98.4% in VD1 and 97.7% in VD2, with a total number of 228 bp substitutions, 11 bp deletions and 3 bp insertions found in BmDNV-3. A single nucleotide "A" deletion at nt 1589 in BmDNV-3 caused a frame shift mutation and brought about a premature stop codon, thus dividing VD2 of BmDNV-3 into two ORFs (named VD2 ORF1a and VD2 ORF1b) within that region, while there was only one ORF (named VD2 ORF1) in the corresponding region of BmDNV-2 (Yamanashi isolate). Comparative polymorphisms of ORFs and ITR regions of the two viral genomes showed that highly variable regions were mainly located in VD1 ORF3, VD1 ORF4, VD2 ORF2, and ITRs of BmDNV-3. Northern blots analysis revealed that VD1 had 1.1 kb and 1.5 kb transcripts from the left half of its plus strand, and one transcript about 3.3 kb from the right half of its minus strand. Sequencing of 3' and 5' RACE products showed that the 1.1 kb transcript started at nt 290 and ended at nt 1437, the 1.5 kb transcript started at nt 1423 and ended at nt 2931, and the 3.3 kb transcript started at nt 6287 and ended at nt 2922. These results help us to further understand the variation between different DNV genera and its possible causes, providing clues for studying the evolutionary history of densoviruses.

Amino Acid Sequence↗

Effects of percutaneous transluminal coronary angioplasty: intracoronary thrombolysis with urokinase in acute myocardial infarction.

Coronary angiography and percutaneous transluminal coronary angioplasty (PTCA) were performed in 32 patients with evolving acute myocardial infarction. Of the 25 patients with complete occlusion of an infarct-related coronary artery, in 18 (72%) the occluded vessel was successfully opened by an intracoronary infusion of urokinase. With a small dose of urokinase the successful recanalization was achieved in only 25%; with a larger dose it was achieved in 94%. After PTCA, all patients received glucose-insulin-potassium solution for 76 hours. Repeat angiography 42 days later showed a patent coronary artery in 12 (group A) of 18 patients with successful PTCA. In group A, left ventricular ejection fraction increased from 51 +/- 13% to 72 +/- 10% (p less than 0.01) and regional wall shortening from 4.5 +/- 9.5% to 29 +/- 19% (p less than 0.01). In contrast, these variables did not change significantly in patients with unsuccessful PTCA or late reocclusion of an infarct-related vessel (group B). These data suggest that successful PTCA with sustained patency of an infarct-related coronary artery has a beneficial effect on the salvage of the jeopardized myocardium, and glucose-insulin-potassium therapy may enhance the beneficial effect of PTCA.

Adult↗

Clinical use of ultrashort-lived radionuclide krypton-81m for noninvasive analysis of right ventricular performance in normal subjects and patients with right ventricular dysfunction.

The ultrashort-lived radionuclide krypton-81m, eluted in 5% dextrose from a bedside rubidium-81m generator, was intravenously infused for rapid imaging of the right-sided heart chambers in the right anterior oblique projection adjusted for optimal right atrioventricular separation. Left-sided heart and lung background was minimized by rapid decay and efficient exhalation of krypton-81m, requiring no algorithm for background correction. A double region of interest method decreased the variability in the assessment of ejection fraction to 5%. In 10 normal subjects, 11 patients with pulmonary hypertension, 4 patients with right ventricular outflow tract obstruction and 4 patients with right ventricular infarction, right ventricular ejection fraction determined by krypton-81m equilibrium blood pool imaging ranged from 14 to 76%. The correlation between these values and those determined by cineangiography according to Simpson's rule was close: r = 0.93 for all data points (p less than 0.001), r = 0.92 for studies at rest (p less than 0.001) and r = 0.93 for exercise studies (p less than 0.001). Exercise-related changes in right ventricular function revealed a disturbed functional reserve with pulmonary hypertension and right ventricular infarction, whereas in compensated right ventricular outflow tract obstruction there was a physiologic increase in ejection fraction with exercise (p less than 0.001). Thus, equilibrium-gated right ventricular imaging using ultrashort-lived krypton-81m is a simple, accurate and reproducible method with potential for serial assessment of right ventricular ejection fraction in a variety of right ventricular anatomic and functional abnormalities, both at rest and during exercise. Advantages of this method include an extremely low radiation dose to patients and clear right atrioventricular separation without the need to correct for background activity.

Adult↗

Smoking: a major predictor of left ventricular function after occlusion of the left anterior descending coronary artery.

The major predictors of left ventricular function after coronary artery occlusion were assessed in 108 consecutive patients who had complete occlusion of the left anterior descending artery as the only important lesion demonstrated at angiography between June 1978 and June 1983. A scoring system was used to identify regional damage on left ventriculograms. Forty two patients were classified as having good left ventricular function and 66 as having varying degrees of impairment. Apart from a history of myocardial infarction, the only variables discriminating between those with good and those with impaired left ventricular function were the area of distribution of the artery beyond the occlusion and cigarette smoking. Hypertension, hypercholesterolaemia, family history of vascular disease, diabetes, obesity, duration of angina, age, and presence of identifiable collaterals were not discriminators. Smoking was itself significantly associated with a history of infarction; but after controlling for this, smoking exerted a significant additional effect on the amount of left ventricular damage. It is concluded that smoking is not only a risk factor for myocardial infarction in patients with single left anterior descending artery occlusion, but that it is also a major factor in determining the extent of associated left ventricular damage.

Adult↗

Diastolic time fraction as a determinant of subendocardial perfusion.

Diastolic time fraction (DTF) has been recognized as an important determinant for subendocardial perfusion, but microsphere studies in which DTF was the independent variable are practically absent. In 21 anesthetized goats, the left coronary main stem was artificially perfused at controlled pressure. DTF was varied by pacing the heart, vagus stimulation, or administration of dobutamine. Regional coronary flow was measured with fluorescent microspheres under full adenosine dilation. Perfusion pressure (P(c)) was defined as mean coronary arterial pressure minus minimal left ventricular pressure. Regional flow conductances (flow/P(c)) were as follows: for the subendocardium, C(endo) = -0.103 + 0.197 DTF + 0.00074 P(c) (P < 0.001); for the midmyocardium, conductance = -0.048 + 0.126 DTF + 0.00049 P(c) (P < 0.001); and for the subepicardium, C(epi) was not significant. C(endo)-DTF relations demonstrated a finite value for DTF at which flow is zero, implying that, at physiological pressures, systolic subendocardial flow limitation extends into diastole. The DTF corresponding to an equal conductance in subendocardium and subepicardium (DTF1) was inversely related to P(c): DTF1 = 0.78 - 0.003 P(c) (P < 0.01). When heart rate and P(c) were held constant and dobutamine was administered (5 goats), contractility doubled and DTF increased by 39%, resulting in an increase of C(endo) of 40%. It is concluded that 1) DTF is a determinant of subendocardial perfusion, 2) systolic compression exerts a flow-limiting effect into diastole, and 3) corresponding to clinical findings on inducible ischemia we predict that, under hyperemic conditions, C(endo) < C(epi) if P(c) is lower than approximately 75% of a normal aortic pressure and heart rate >80 beats/min.

Animals↗

Effect of arterial blood pressure and ventilation gases on cardiac depression induced by coronary air embolism.

In this study the time course of cardiac depression after selective intracoronary injection of air bubbles was investigated in six anesthetized pigs (30 +/- 2 kg) with different mixtures of ventilation gases and different mean arterial blood pressures (MAP). Air bubbles of 150 microns diam were injected into the left anterior descending coronary artery (LADCA) in a volume of 2 microliters/kg body wt. In each animal an injection of air bubbles was applied during ventilation with N2-O2 and a MAP of 77 +/- 3 mmHg (N2-O2/low pressure) or 111 +/- 3 mmHg (N2-O2/high pressure) and during ventilation with pure O2 and a MAP of 77 +/- 3 mmHg (O2/low pressure) or 110 +/- 3 mmHg (O2/high pressure). Systemic hemodynamic variables such as left ventricular pressure, its peak first derivatives, and MAP changed < 10% after injection of air bubbles. During N2-O2/low pressure, systolic segment length shortening in the LADCA region (SS-LADCA) decreased from baseline and did not return to baseline within the 10 min after injection of air bubbles. During N2-O2/high pressure and O2/low pressure, SS-LADCA was decreased between 60 and 120 s, whereas for O2/high pressure this period was from 60 to 90 s. By calculating the time integral of the deviation from baseline of SS-LADCA, it could be demonstrated that the depression of regional myocardial function was less severe during O2/high pressure and O2/low pressure than during N2-O2/low pressure. We conclude that, when coronary air embolism occurs during hypertension and during ventilation with pure O2 instead of a normal N2-O2 mixture, the resulting depression of regional myocardial function is reduced.

Animals↗

Lacunar thalamic infarcts and amnesia.

Six cases with CT scan evidence of paramedian thalamic lacunar infarcts in the region of the paramedian thalamic arteries (4 unilateral left and 2 bilateral) are described. The main acute symptoms included disorders of consciousness, hypersomnia and sometimes vertical gaze paresis. An amnesic syndrome of variable degree and duration was observed in all cases, and in 1 of them was still present 2 years after the onset. In addition, we report a case of lateral thalamic infarction, which showed a predominantly aphasic (transcortical sensory type) clinical picture.

Aged↗

Regional cerebral glucose metabolism and attention in adults with a history of childhood autism.

Sixteen high-functioning adults with a history of childhood autism and 26 normal control subjects underwent [18F]fluoro-2-deoxyglucose positron-emission tomography to assess regional cerebral glucose metabolic rate (GMR). Autistic patients had a left > right anterior rectal gyrus asymmetry, as opposed to the normal right > left asymmetry in that region. Patients also showed low GMR in the left posterior putamen and high GMR in the right posterior calcarine cortex. Brain regions with GMR > 3 SD from the normal mean were more prevalent in patients than in control subjects. This variable pattern of abnormal activity is consistent with heterogeneous neurophysiological etiology; group differences in striatum and cortex may represent a final common pathway.

Adolescent↗

Histology of the trachea and lung of Siphonops annulatus (Amphibia, Gymnophiona).

The structure of the trachea and lung of Siphonops annulatus was studied in ten specimens of routinely fed animals. The trachea is constituted mainly by incomplete cartilage rings lined by a respiratory epithelium (ciliated and mucous cells) with variable morphology according to the region observed. A rich vascularization of this organ suggests its participation in blood-air gas exchange. The right lung in this species is developed and the left one is atrophied. This organ is constituted mainly by longitudinal septa formed by connective tissue, smooth muscle cells and blood capillaries. These structures are covered by pneumocytes of one type only, which present cytoplasmic particles that have been related with surfactant activity described in the lung of Gymnophiona.

Amphibians↗

Multiple mucosal neuromatosis.

Four children aged 3 months to 14 years presenting with multiple mucosal neuromatosis (MMN) and having medullary carcinoma of the thyroid (MCT) along with various other associated features are reported. All patient had screening test for pheochromocytoma. Thyroid gland and Neuromatous growths were subjected to histological examination for confirmatory diagnosis. All patients were subjected to total thyroidectomy with removal of regional lymph nodes. They were evaluated periodically for a variable post-operative period at 2 to 4 years. The first degree relatives were also screened. One of the four children had left sided pheochromocytoma which responded satisfactorily to the adrenalectomy. Prophylactic total thyroidectomy with annual/biannual critical review to detect recurrence is advocated. It is recommended that first degree relatives of familial MMN Syndrome should also be subjected to annual screening in view of its autosomonal dominant transmission.

Adolescent↗

Isolation and functional comparison of bovine cardiac troponin T isoforms.

We report on the isolation of two bovine cardiac troponin isoforms which differ in sequence near the amino terminus of troponin T (Risnik, V. V., Verin, A. D., and Gusev, N. B. (1985) Biochem. J. 225, 549-552). The isoforms were isolated by direct separation on DEAE-cellulose and were also obtained by reconstitution of urea-dissociated subunits. The two isoforms were compared for their effects on processes involving interactions of troponin with tropomyosin and actin. The two isoforms had similar abilities to promote tropomyosin polymerization. They allowed equal potentiation, by high concentration of myosin subfragment 1, of the thin filament-activated MgATPase rate. In the presence of lower concentrations of myosin subfragment 1, the MgATPase rate was 96% sensitive to Ca2+, regardless of which troponin isoform was present. The Ca2+ concentration required to activate the MgATPase rate was similar but not identical for thin filaments containing one isoform or the other. In the presence of the smaller isoform, the Ca2+-activation curve is shifted 0.1 to 0.15 pCa units to the left. At 10(-6) M Ca2+ the MgATPase rate is 50% greater when the smaller troponin T isoform is present than when the larger is present. These results indicate that the variable region of troponin T influences the overall response of the thin filament to Ca2+, and raises the possibility that regulation of this region by mRNA splicing may modulate muscle function.

Actin Cytoskeleton↗

Angiotensin II type 2 receptors and cardiac hypertrophy in women with hypertrophic cardiomyopathy.

The development of left ventricular hypertrophy in subjects with hypertrophic cardiomyopathy (HCM) is variable, suggesting a role for modifying factors such as angiotensin II. Angiotensin II mediates both trophic and antitrophic effects, via angiotensin II type 1 (AT(1)-R) and angiotensin II type 2 (AT(2)-R) receptors, respectively. Here we investigated the effect of the AT(2)-R gene A/C(3123) polymorphism, located in the 3' untranslated region of exon 3, on left ventricular mass index (LVMI) in 103 genetically independent subjects with HCM (age, 12 to 81 years). LVMI and interventricular septum thickness were determined by 2D echocardiography. Extent of hypertrophy was quantified by a point score (Wigle score). Plasma prorenin, renin, and ACE were determined by immunoradiometric or fluorometric assays, and genotyping was performed by polymerase chain reaction. In men, no associations between AT(2)-R genotype and any of the measured parameters were observed, whereas in women, LVMI decreased with the number of C alleles (211+/-19, 201+/-18, and 152+/-10 g/m(2) in women with the AA, AC, and CC genotype, respectively; P=0.015). Similar C allele-related decreases in women were observed for interventricular septum thickness (P=0.13), Wigle score (P=0.05), plasma renin (P=0.03), and plasma prorenin (P=0.26). Multiple regression analysis revealed that the AT(2)-R C allele-related effect on LVMI (beta=-30.7+/-11.1, P=0.010) occurred independently of plasma renin, the AT(1)-R gene A/C(1166) polymorphism, or the ACE gene I/D polymorphism. In conclusion, AT(2)-Rs modulate cardiac hypertrophy in women with HCM, independently of the circulating renin-angiotensin system. These data support the contention that AT(2)-Rs mediate antitrophic effects in humans.

Adult↗

Efficacy of plantar loading parameters during gait in terms of reliability, variability, effect of gender and relationship between contact area and plantar pressure.

BACKGROUND: The purpose of this study was to determine plantar pressure and contact areas of the foot inside the athletic shoe during activity. The objectives were to determine if plantar pressure and contact area measurements collected on multiple trials from the same subject were reliable, to determine the variability of measurements between subjects as compared to that found between steps within a single subject, to determine the relationship between contact area and plantar pressure, and to ascertain whether there were any systematic gender differences in these measurements. METHODS: Sixteen healthy adults volunteered for participation in the first part of the study that was designed to determine reliability and variability of the testing methodology. A separate group of fifty healthy high school and collegiate athletes participating in soccer, field hockey, basketball, and lacrosse comprised the second part of the study that was designed to investigate gender differences in terms of normalized midfoot plantar pressure and contact area, and the interrelationship between the two measurements. Data were collected during the midstance phase of gait, using the Pedar in-shoe measurement system (Novel GMBH, St. Paul, MN). Athletes wore their own athletic shoes and performed walking trials on a surface similar to that used in their sport. The foot was divided into four regions based on radiographic measurements. RESULTS: The midfoot region demonstrated excellent reliability across multiple trials of the same subject in contact area and plantar pressure, and the variability between steps within a single subject was small when compared to that between subjects. Normalized midfoot contact area and plantar pressure values were highly correlated with r values of 0.862 on the left foot and .912 on the right foot. No significant differences were found in normalized midfoot contact area or plantar pressure values between males and females. CONCLUSIONS: The Pedar in-shoe pressure measurement system can be used reliably to quantify contact area and plantar pressure beneath the midfoot region during the midstance phase of gait. This measurement technique can now be used in risk factor studies designed to identify individuals at risk for injury to the foot, ankle, and other lower extremity structures.

Adult↗

Scintiscan characteristics of normal thyroid gland in a region of known iodine intake.

Morphological features of a normal thyroid gland in a geographical region where the daily iodine intake is about 1 mg are established. The mean weight of the thyroid gland is 31.3 gm with a range from 19 to 43 gm. Oblique length of the right lobe is 5.0 cm and that of the left lobe 4.8 cm. The surface area of the right and left lobes is 9.7 and 9.1 cm2, respectively. The weight of the thyroid gland calculated on the basis of the scan obtained with 99mTcO4 is quite variable and shows poor correlation (gamma = 0.40) with the weight obtained on the basis of I-131 scan. It is suggested that the criteria of normalcy be established regionally based on iodine intake, and that an isotope of iodine be used in calculating the weight of thyroid gland for dosimetry purposes.

Diet↗

Calcium scoring of the coronary artery by electron beam CT: how to apply an individual attenuation threshold.

OBJECTIVE: Our aim was to assess the inter- and intraindividual variability of the attenuation threshold used to identify coronary artery calcification on electron beam CT and to illustrate a new threshold method. MATERIALS AND METHODS: We measured the soft-tissue attenuation of regions surrounding the coronary arteries at the level of the left main coronary artery ostium (high level) and at the bottom of the heart (low level) in 48 consecutive patients (22 men, 26 women). Mean +/- 2 standard deviations (SD) of soft-tissue attenuation and variance of soft-tissue density and SDs were calculated at each level for every patient. It was assumed that setting an attenuation threshold greater than or equal to 3 SDs above that of soft tissue at each myocardial level would eliminate 99.5% of all scatter artifacts, allowing precise identification of calcific deposits. RESULTS: For the entire patient cohort, the average soft-tissue attenuation was 41 H and 35 H at the high and low levels, respectively (p < 0.01), indicating a large intraindividual variability. The SDs of soft-tissue attenuation measured by the computer software at the high and low levels were not different (26 H at the high level and 28 H at the low level; p = not significant). However, the calculated SD of the individual mean soft-tissue attenuation was 5 H at the high level and 8 H at the low level, again indicating a large intraindividual variability (p < 0.01). The addition of 3 measured SDs above the mean individual soft-tissue attenuation predicted a mean threshold of 120 and 121 H at the high and low levels, respectively, but with a wide interindividual variability (83-193 H at the high level and 79-242 H at the low level). There was a strong correlation between body weight and SD of soft-tissue attenuation at the low level (r = 0.75, p < 0.001) and a weaker but statistically significant correlation between weight and SD of soft-tissue attenuation at the high level (r = 0.51, p < 0.001). CONCLUSION: For the patients in this study, a threshold of 120 H for the detection of coronary calcification by electron beam CT seemed more appropriate than a threshold of 130 H, which is currently in use. However, given the great inter- and intraindividual variability, a biologic threshold tailored to the individual patient and to each individual imaging level should be used instead of a fixed threshold.

Aged↗