Distinct forebrain regions define a dichotomous astrocytic profile in multiple system atrophy.

The growing recognition of a dichotomous role of astrocytes in neurodegenerative processes has heightened the need for unraveling distinct astrocytic subtypes in neurological disorders. In multiple system atrophy (MSA), a rare, rapidly progressing atypical Parkinsonian disease characterized by increased astrocyte reactivity. However the specific contribution of astrocyte subtypes to neuropathology remains elusive. Hence, we first set out to profile glial fibrillary acidic protein levels in astrocytes across the human post mortem motor cortex, putamen, and substantia nigra of MSA patients and observed an overall profound astrocytic response. Matching the post mortem human findings, a similar astrocytic phenotype was present in a transgenic MSA mouse model. Notably, MSA mice exhibited a decreased expression of the glutamate transporter 1 and glutamate aspartate transporter in the basal ganglia, but not the motor cortex. We developed an optimized astrocyte isolation protocol based on magnetic-activated cell sorting via ATPase Na+/K+ transporting subunit beta 2 and profiled the transcriptomic landscape of striatal and cortical astrocytes in transgenic MSA mice. The gene expression profile of astrocytes in the motor cortex displayed an anti-inflammatory signature with increased oligodendroglial and pro-myelinogenic expression pattern. In contrast, striatal astrocytes were defined by elevated pro-inflammatory transcripts accompanied by dysregulated genes involved in homeostatic functions for lipid and calcium metabolism. These findings provide new insights into a region-dependent, dichotomous astrocytic response-potentially beneficial in the cortex and harmful in the striatum-in MSA suggesting a differential role of astrocytes in MSA-related neurodegenerative processes.

The morph server: a standardized system for analyzing and visualizing macromolecular motions in a database framework.

The number of solved structures of macromolecules that have the same fold and thus exhibit some degree of conformational variability is rapidly increasing. It is consequently advantageous to develop a standardized terminology for describing this variability and automated systems for processing protein structures in different conformations. We have developed such a system as a 'front-end' server to our database of macromolecular motions. Our system attempts to describe a protein motion as a rigid-body rotation of a small 'core' relative to a larger one, using a set of hinges. The motion is placed in a standardized coordinate system so that all statistics between any two motions are directly comparable. We find that while this model can accommodate most protein motions, it cannot accommodate all; the degree to which a motion can be accommodated provides an aid in classifying it. Furthermore, we perform an adiabatic mapping (a restrained interpolation) between every two conformations. This gives some indication of the extent of the energetic barriers that need to be surmounted in the motion, and as a by-product results in a 'morph movie'. We make these movies available over the Web to aid in visualization. Many instances of conformational variability occur between proteins with somewhat different sequences. We can accommodate these differences in a rough fashion, generating an 'evolutionary morph'. Users have already submitted hundreds of examples of protein motions to our server, producing a comprehensive set of statistics. So far the statistics show that the median submitted motion has a rotation of approximately 10 degrees and a maximum Calpha displacement of 17 A. Almost all involve at least one large torsion angle change of >140 degrees. The server is accessible at http://bioinfo.mbb.yale. edu/MolMovDB

PartsList: a web-based system for dynamically ranking protein folds based on disparate attributes, including whole-genome expression and interaction information.

As the number of protein folds is quite limited, a mode of analysis that will be increasingly common in the future, especially with the advent of structural genomics, is to survey and re-survey the finite parts list of folds from an expanding number of perspectives. We have developed a new resource, called PartsList, that lets one dynamically perform these comparative fold surveys. It is available on the web at http://bioinfo.mbb.yale.edu/partslist and http://www.partslist.org. The system is based on the existing fold classifications and functions as a form of companion annotation for them, providing 'global views' of many already completed fold surveys. The central idea in the system is that of comparison through ranking; PartsList will rank the approximately 420 folds based on more than 180 attributes. These include: (i) occurrence in a number of completely sequenced genomes (e.g. it will show the most common folds in the worm versus yeast); (ii) occurrence in the structure databank (e.g. most common folds in the PDB); (iii) both absolute and relative gene expression information (e.g. most changing folds in expression over the cell cycle); (iv) protein-protein interactions, based on experimental data in yeast and comprehensive PDB surveys (e.g. most interacting fold); (v) sensitivity to inserted transposons; (vi) the number of functions associated with the fold (e.g. most multi-functional folds); (vii) amino acid composition (e.g. most Cys-rich folds); (viii) protein motions (e.g. most mobile folds); and (ix) the level of similarity based on a comprehensive set of structural alignments (e.g. most structurally variable folds). The integration of whole-genome expression and protein-protein interaction data with structural information is a particularly novel feature of our system. We provide three ways of visualizing the rankings: a profiler emphasizing the progression of high and low ranks across many pre-selected attributes, a dynamic comparer for custom comparisons and a numerical rankings correlator. These allow one to directly compare very different attributes of a fold (e.g. expression level, genome occurrence and maximum motion) in the uniform numerical format of ranks. This uniform framework, in turn, highlights the way that the frequency of many of the attributes falls off with approximate power-law behavior (i.e. according to V(-b), for attribute value V and constant exponent b), with a few folds having large values and most having small values.

Functional, angiographic and intracoronary Doppler flow characteristics in symptomatic patients with myocardial bridging: effect of short-term intravenous beta-blocker medication.

OBJECTIVES: We sought to define the effects of short-term beta-adrenergic blocking medication on intracoronary flow characteristics, clinical symptoms and angiographic diameter changes in patients with severe myocardial bridging of the left anterior descending coronary artery. BACKGROUND: Controversy exists regarding the pathophysiology, clinical relevance and optimal therapy in symptomatic patients with myocardial bridges because antianginal drugs have not been systematically tested. METHODS: In 15 symptomatic patients with myocardial bridging of the left anterior descending coronary artery, maximal lumen diameter reductions were evaluated by quantitative coronary angiography. There were no angiographic signs of coronary artery disease. Coronary blood flow velocities (using a 0.014-in. [0.035 cm] Doppler guide wire) were measured at rest, during atrial pacing and during intravenous administration of a short-acting beta-blocker (esmolol, 50 to 500 micrograms/kg body weight per min) with continuous atrial pacing. RESULTS: The maximal angiographic systolic lumen diameter reduction within the myocardial bridges was 83 +/- 9% at rest, with a persistent diastolic diameter reduction of 41 +/- 11% (mean +/- SD). Short-term intravenous beta-blocker therapy decreased the diameter reduction during both systole (from 83 +/- 9% to 62 +/- 11%) and diastole (from 41 +/- 11% to 30 +/- 9%, both p < 0.001). The average diastolic peak flow velocity was higher within the myocardial bridges (33 +/- 13 cm/s) than the proximal (26 +/- 13 cm/s) and distal bridges (17 +/- 4 cm/s, both p < 0.001). During tachypacing, average diastolic peak flow velocity increased within the bridged segments to 63 +/- 21 cm/s versus 29 +/- 12 cm/s in the proximal and 20 +/- 4 cm/s in the distal bridges (both p < 0.001). Beta-receptor blockade produced a return to baseline values (average diastolic peak flow velocity within bridge 35 +/- 16 cm/s, p < 0.001). ST segment changes and symptoms were abolished with beta-blocker administration. CONCLUSIONS: In patients with myocardial bridges, administration of short-acting beta-blockers during atrial pacing alleviates anginal symptoms and signs of ischemia. This effect was mediated by a reduction of vascular compression and maximal flow velocities within the bridged coronary artery segment.

Normal mode analysis of macromolecular motions in a database framework: developing mode concentration as a useful classifying statistic.

We investigated protein motions using normal modes within a database framework, determining on a large sample the degree to which normal modes anticipate the direction of the observed motion and were useful for motions classification. As a starting point for our analysis, we identified a large number of examples of protein flexibility from a comprehensive set of structural alignments of the proteins in the PDB. Each example consisted of a pair of proteins that were considerably different in structure given their sequence similarity. On each pair, we performed geometric comparisons and adiabatic-mapping interpolations in a high-throughput pipeline, arriving at a final list of 3,814 putative motions and standardized statistics for each. We then computed the normal modes of each motion in this list, determining the linear combination of modes that best approximated the direction of the observed motion. We integrated our new motions and normal mode calculations in the Macromolecular Motions Database, through a new ranking interface at http://molmovdb.org. Based on the normal mode calculations and the interpolations, we identified a new statistic, mode concentration, related to the mathematical concept of information content, which describes the degree to which the direction of the observed motion can be summarized by a few modes. Using this statistic, we were able to determine the fraction of the 3,814 motions where one could anticipate the direction of the actual motion from only a few modes. We also investigated mode concentration in comparison to related statistics on combinations of normal modes and correlated it with quantities characterizing protein flexibility (e.g., maximum backbone displacement or number of mobile atoms). Finally, we evaluated the ability of mode concentration to automatically classify motions into a variety of simple categories (e.g., whether or not they are "fragment-like"), in comparison to motion statistics. This involved the application of decision trees and feature selection (particular machine-learning techniques) to training and testing sets derived from merging the "list" of motions with manually classified ones.

Phorbol ester activation of the protein kinase C pathway inhibits gonadotropin-releasing hormone gene expression.

The effects of the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA), an activator of protein kinase C (PKC), and the PKC inhibitor staurosporine on GnRH secretion and mRNA levels were studied in GT1-7 hypothalamic neuronal cells. Dose-response and time-course studies revealed that TPA (10(-8) M) acutely increased GnRH secretion 3-fold at 3-6 h, which then declined to baseline at 24 h, while it progressively decreased GnRH mRNA levels by 50% and 70% at 6 and 24 h, respectively. To ensure that these effects were due to activation and not down-regulation of PKC, cells were treated for 30 min with TPA (10(-8) M). This brief exposure to TPA also resulted in a decrease (60%) in GnRH mRNA levels at 6 h, with a 1.5- to 2-fold increase in GnRH secretion compared to control values, suggesting that activation of PKC decreases the pretranslational expression of GnRH while increasing GnRH secretion. Additional studies measured PKC activity and documented a shift from a cytosolic to a membrane fraction after incubation with TPA, again supporting PKC activation. Exposure of GT1-7 cells to staurosporine (10(-8) M), a PKC inhibitor, resulted in no change in the level of GnRH mRNA or secretion at 6 h. However, incubation with both TPA and staurosporine prevented the decrease in GnRH mRNA levels and partially blocked the increase in GnRH secretion induced by TPA. We conclude that TPA, by activating the PKC pathway, acutely increases GnRH secretion, but dramatically decreases GnRH gene expression. The exact mechanism of these divergent effects on the synthesis and secretion of GnRH remain to be elucidated.

Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial.

BACKGROUND: Recent reports describe discontinuation-emergent adverse events upon cessation of selective serotonin reuptake inhibitors including dizziness, insomnia, nervousness, nausea, and agitation. We hypothesized that interruption of fluoxetine treatment would be associated with fewer discontinuation-emergent adverse events than interruption of sertraline or paroxetine treatment, based on fluoxetine's longer half-life. METHODS: In this 4-week study, 242 patients with remitted depression receiving maintenance therapy with open-label fluoxetine, sertraline, or paroxetine for 4-24 months had their maintenance therapy interrupted with double-blind placebo substitution for 5-8 days. The Symptom Questionnaire (SQ), the Discontinuation-Emergent Signs and Symptoms checklist, the 28-item Hamilton Depression Rating Scale, and the Montgomery-Asberg Depression Rating Scale were used to assess somatic distress and stability of antidepressant response. RESULTS: Two hundred twenty patients (91%) completed the study. Following interruption of therapy, fluoxetine-treated patients experienced fewer discontinuation-emergent events than either sertraline-treated or paroxetine-treated patients (p < .001). The mean SQ somatic symptom scale score in fluoxetine-treated patients was significantly lower than that in sertraline-treated and paroxetine-treated patients (p < .001). Fluoxetine-treated patients also experienced less reemergence of depressive symptoms than sertraline-treated or paroxetine-treated patients (p < .001). CONCLUSIONS: Abrupt interruption of antidepressant therapy for 5-8 days was associated with the emergence of new somatic and psychological symptoms in patients treated with paroxetine and to a lesser degree sertraline, with few symptoms seen with fluoxetine.

Evaluation of segmental elastic properties of the aorta in normotensive and medically treated hypertensive patients by intravascular ultrasound.

DESIGN AND METHODS: Local elastic properties of the descending aorta at different levels were evaluated by means of intravascular ultrasound images and pressure measurements. For this purpose, 30 normotensive patients and 30 age-matched medically treated patients with essential hypertension, all undergoing diagnostic cardiac catheterization, were studied. RESULTS: Hypertension was well controlled in the essential hypertensives (137.1 +/- 6.79/74.5 +/- 2.65 mmHg). Systolic but not diastolic blood pressure in the hypertensive patients was significantly different from that of the normotensives (118.8 +/- 4.38/69.7 +/- 1.65 mmHg). The continuous loss of volume compliance with increasing distance from the heart was significantly higher in the hypertensives than in the normotensive patients [normotensives (1.45 +/- 0.19) x 10(-10) m5/N at the thoracic aorta, (0.08 +/- 0.05) x 10(-10) m5/N at the external iliac artery; hypertensives (0.81 +/- 0.09) x 10(-10) and (0.05 +/- 0.01) x 10(-10) m5/N at the corresponding sites]. Similarly, the hypertensives had an elevated elastic modulus proximal to the aortic bifurcation compared with the normotensives (244.47 +/- 44.06 versus 108.10 +/- 17.76 m/s, respectively). The decrease in buffering function of the vessel at this site is presumably caused by a turbulent flow pattern. Compared with the normotensives, the treated hypertensives had a significantly higher elastic modulus at each site where this was measured, whereas volume compliance and sectional compliance were lower. CONCLUSION: The differences in elastic modulus and compliance between hypertensive and normotensive patients seem disproportionate to the difference in systolic blood pressure (within the normal range in both the treated hypertensives and the normotensives). Therefore, normalization of high blood pressure by long-term antihypertensive treatment may not fully reverse changes, caused by arterial hypertension, in the viscoelastic properties of the arterial wall.

Effects of heart rate changes on left ventricular volume and ejection fraction: a 2-dimensional echocardiographic study.

The influence of heart rate on left ventricular (LV) volumes and ejection fraction (EF) using 2-dimensional (2-D) echocardiography during atrial pacing was analyzed. The study was performed in 13 normal control subjects, 23 patients with coronary heart disease and 8 patients with dilated cardiomyopathy. An electronic sector scanner (2.25 MHz, 84 degrees) was used. Under constant scanning of the left ventricle, heart rate was increased, in steps of 20 beats/min, from 80 to 140 beats/min. The 2-D echocardiograms were stored on videotape and analyzed off-line. The end-diastolic and end-systolic volumes (EDV and ESV) were determined using a disc method. Stroke volume (SV) and EF were calculated. Constant LV scanning was possible during atrial stimulation, as shown by the analysis of simultaneously recorded 2-D echocardiograms and cineventriculograms at different heart rates, revealing a constant position of the echocardiographic transducer. Simultaneous recordings of cineventriculography and 2-D echocardiography at 80 and 120 beats/min showed that despite differences in absolute values, percent changes of LV volumes and EF determined with both methods were similar. Thus, changes of LV function can be analyzed by 2-D echocardiography. In normal control subjects, an increase in heart rate of 10 beats/min reduced EDV by 4 ml, ESV by 2 ml, SV by 2 ml and EF by 1%, corresponding to percent reductions of 4, 2, 5 and -2%, respectively. In contrast, the absolute decreases in the patients were 6 ml, 1 ml, 5 ml and 2% and the percent changes 2%, 1%, 8% and 5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrastructural evidence for lymphatic capillaries in the primate choroid.

In the choroid of three cynomolgus monkeys (Macaca irus) and of one baboon (Papio anubis) lymphatic capillaries were demonstrated by transmission electron microscopy.

Epibulbar fibroma of the conjunctival substantia propria.

A 39-year-old black woman had a 12-year history of slowly progressive left temporal juxtalimbal conjunctival swelling. The lesion was freely movable over the surface of the globe and was believed to be situated within the substantia propria. Histopathologic evaluation of the excised tissue disclosed that it was a collagenous mass of lamellar architecture, with a hypocellular dispersion of mesenchymal cells and a scattering of capillaries in the absence of inflammation. Electron microscopic examination revealed that the lamellar arrangement had regular lobular subdivisions composed of collagen fibers approximately 50 nm in diameter. Compressed fibroblasts occupied the peripheries of the lobules; the former exhibited abundant rough-surfaced endoplasmic reticulum and failed to elaborate basement membrane material. Delicate processes of the fibroblasts extended into the centers of the collagenous aggregates. To our knowledge, this is the first convincingly documented case of an acquired fibroma of the substantia propria of the epibulbar conjunctiva. The differential diagnosis in this case included related fibroblastic and simulating nonfibroblastic lesions.

Effect of accelerated iron ions on the retina.

The eyes of rats were exposed to doses of 0.1 and 2.5 Gy of 450-MeV/amu 56Fe particles (LET approximately 195 keV/microns). The beam axes were oriented perpendicular to the central retina of the animals. Retinas were harvested immediately (less than 10 min), 24 h, 15 days, 136 days, and 186 days after the experiment. The retinas of animals of equivalent ages were sampled at the same intervals. By Day 15, the spatial densities of the pigment epithelial, photoreceptor, and bipolar cells in retinas irradiated with 2.5 Gy were 15 to 20% lower than those of the controls. The cellular density of the pigment epithelium returned to the control level by Day 186 while photoreceptor and bipolar cell numbers remained depressed. One and fifteen days after irradiation, the choroidal vessels showed signs of radiation damage. Exposure to 0.1 Gy did not affect the cellular density within the retina at the interval examined (186 days). None of the retinas showed evidence of track-specific injury that could be interpreted as microlesions or tunnel lesions.

The effect of accelerated argon ions on the retina.

It has been postulated that high energy heavy ions cause a unique form of damage in living tissue, which results from the high linear energy transfer of accelerated single particles. We have searched for these single-particle effects, so-called "microlesions," in composite electron micrographs of retinas of rats which had been irradiated with a dose of 1 Gy of 570 MeV/amu argon ions. The calculated rate of energy deposition of the radiation in the retina was about 100 keV/micron and the influence was four particles per 100 micron 2. Different areas of the irradiated retinas which combined would have been expected to be traversed by approximately 2400 particles were examined. We were unable to detect ultrastructural changes in the irradiated retinas distinct from those of controls. The spatial cellular densities of pigment epithelial and photoreceptor cells remained within the normal range when examined at 24 h and at 6 months after irradiation. These findings suggest that the retina is relatively resistant to heavy-ion irradiation and that under the experimental conditions the passage of high energy argon ions does not cause retinal microlesions that can be detected by ultrastructural analysis.

The fiber system of the choroidocapillaris.

In the central choroid of three cynomolgus monkeys (Macaca irus) and a baboon (Papio anubis) the shape of the choroidocapillary sinus is determined by a system of interstitial collagen fibers, the "fiber system of the choroidocapillaris". The inner leaflet of this system is Bruch's membrane. The outer leaflet consists of interwoven collagen bundles, covering the roof of the capillary sinus. Straight bundles of collagen fibers passing through connective tissue columns in the choroidocapillary sinus connect both leaflets. Forces created by changes in the arterial tone in the vascular stroma may be transmitted by the choroidocapillary fiber system to the elastic layer of Bruch's membrane.

Radiation retinopathy: electron microscopy of retina and optic nerve.

A 4 1/2 year old female was treated for embryonal rhabdomyosarcoma of the left orbit in 1975 with radiation (59.5 Gy in 5 weeks), followed by chemotherapy. An electroretinogram (ERG) in March, 1988 revealed cone responses 3% of normal and no rod responses in the left eye, and normal responses in the right eye. The eye was enucleated in April 1988. In the fovea no choroidocapillaris was seen at the intact Bruch's membrane, and the pigment epithelium was preserved only in small patches. No photoreceptor cells were seen in the areas devoid of pigment epithelial cells. The parafoveal and peripheral (30 degrees eccentricity) retina was better preserved. The thickness of the layer of rods and cones and of Henle's fiber layer was reduced. Very few outer segments were present. Macrophages had invaded the retinal tissue in moderate numbers. The retinal vessels were ensheathed by several layers of collagen fibrils. The spatial densities of pigment epithelial, cone, rod, and bipolar cells had been reduced. The optic nerve contained a total number of 1,022,000 nerve fibers.

Determination of left ventricular mass and circumferential wall thickness by three-dimensional reconstruction: in vitro validation of a new method that uses a multiplane transesophageal transducer.

Elevated left ventricular mass and increased wall thickness have important prognostic implications in clinical medicine. However, these parameters have been incompletely characterized by one- and two-dimensional echocardiography. Therefore this study was performed to validate in vitro measurement of left ventricular mass and circumferential wall thickness with a multiplane transesophageal transducer and three-dimensional reconstruction. Results for mass measurements were also compared with a standard method for the determination of left ventricular mass, the Penn convention. Fourteen necropsied left ventricles were scanned in a water bath by a volume-rendering, three-dimensional reconstruction system. There was an excellent correlation and high agreement for determination of three-dimensional left ventricular mass (r = 0.98; standard error of the estimate [SEE] = 9.6 gm; y = 1.02x + 0.46) and wall thickness (r = 0.93; SEE = 1.4 mm; y = 0.95x + 1.64) compared with anatomic measurements. Left ventricular mass by a simulated Penn convention revealed a lower correlation and larger error compared with three-dimensional measurements (r = 0.72; SEE = 42.8 gm; y = 1.01x + 9.61). Therefore determination of left ventricular mass by three-dimensional reconstruction was validated in vitro and was superior to one-dimensional echocardiographic methods.

Three-dimensional echocardiographic determination of left ventricular volumes and function by multiplane transesophageal transducer: dynamic in vitro validation and in vivo comparison with angiography and thermodilution.

The goal of this study was to validate 3-dimensional echocardiography by multiplane transesophageal transducer for the determination of left ventricular volumes and ejection fraction in an in vitro experiment and to compare the method in vivo with biplane angiography and the continuous thermodilution method. In the dynamic in vitro experiment, we scanned rubber balloons in a water tank by using a pulsatile flow model. Twenty-nine measurements of volumes and ejection fractions were performed at increasing heart rates. Three-dimensional echocardiography showed a very high accuracy for volume measurements and ejection fraction calculation (correlation coefficient, standard error of estimate, and mean difference for end-diastolic volume 0.998, 2.3 mL, and 0.1 mL; for end-systolic volume 0.996, 2.7 mL, and 0.5 mL; and for ejection fraction 0.995, 1.0%, and -0.4%, respectively). However, with increasing heart rate there was progressive underestimation of ejection fraction calculation (percent error for heart rate below and above 100 bpm 0.59% and -8.6%, P < .001). In the in vivo study, left ventricular volumes and ejection fraction of 24 patients with symmetric and distorted left ventricular shape were compared with angiography results. There was good agreement for the subgroup of patients with normal left ventricular shape (mean difference +/-95% confidence interval for end-diastolic volume 5.2+/-6.7 mL, P < .05; for end-systolic volume -0.5+/-8.4 mL, P = not significant; for ejection fraction 2.4%+/-7.2%, P = not significant) and significantly more variability in the patients with left ventricular aneurysms (end-diastolic volume 23.1+/-56.4 mL, P < .01; end-systolic volume 5.6+/-41.0 mL, P = not significant; ejection fraction 4.9%+/-16.0%, P < .05). Additionally, in 20 critically ill, ventilated patients, stroke volume and cardiac output measurements were compared with measurement from continuous thermodilution. Stroke volume as well as cardiac output correlated well to thermodilution (r = 0.89 and 0.84, respectively, P < .001), although both parameters were significantly underestimated by 3-dimensional echocardiography (mean difference +/-95% confidence interval = -6.4+/-16.0 mL and -0.6+/-1.6 L/min, respectively, P < .005).

Evaluation of regional systolic function in hypertrophic cardiomyopathy and hypertensive heart disease: a three-dimensional echocardiographic study.

Assessment of regional left ventricular (LV) function in patients with asymmetric LV hypertrophy is difficult with two-dimensional echocardiography mainly because of factors such as LV geometry, structure, regional wall stress, and ischemia. Multiplane transesophageal echocardiography with three-dimensional reconstruction of cross-sectional images was used for quantitative evaluation of regional wall thickness and fractional thickening. Fifteen patients (56 +/- 13 years old) with hypertrophic cardiomyopathy (LV ejection fraction 71% +/- 4%), 15 (62 +/- 13 years) with hypertensive heart disease (ejection fraction 66% +/- 8%) and 15 (53 +/- 11 years) healthy control subjects (ejection fraction 61% +/- 5%) were included in the analysis. Regional function was studied in four parallel equidistant short-axis cross sections from base to apex of the reconstructed left ventricle. In 15 degree intervals, 24 wall thickness measurements in each cross section were made at end-diastole and end-systole after endocardial and epicardial border tracing. A total of 192 measurements were obtained in each patient, and absolute wall thickening and fractional thickening were calculated. Absolute and fractional wall thickening showed a significant inverse relation to end-diastolic wall thickness in all heart conditions (r = 0.71, p < 0.0001). Regions of normal wall thickness in diseased patients were not hyperdynamic when compared with normal control subjects. Significant impairment in fractional thickening at identical end-diastolic thickness was observed in the septum compared with the lateral free wall in both hypertrophic cardiomyopathy and hypertensive heart disease. Thus regional systolic function is inversely related to end-diastolic wall thickness. The decrease in regional systolic function with increasing LV hypertrophy was similar in idiopathic and hypertensive cardiomyopathy. In both types of hypertrophy, significant differences in systolic function were observed in septal and lateral wall segments of similar wall thickness. This indicates that factors other than end-diastolic wall thickness influence myocardial thickening in patients with hypertrophy and preserved global function.

Moving the retina: choroidal modulation of refractive state.

The chick eye is able to change its refractive state by as much as 7 D by pushing the retina forward or pulling it back; this is effected by changes in the thickness of the choroid, the vascular tissue behind the retina and pigment epithelium. Chick eyes first made myopic by wearing diffusers and then permitted unrestricted vision developed choroids several times thicker than normal within days, thereby speeding recovery from deprivation myopia. Choroidal expansion does not occur when visual cues are reduced by dim illumination during the period of unrestricted vision. Furthermore, in chick eyes presented with myopic or hyperopic defocus by means of spectacle lenses, the choroid expands or thins, respectively, in compensation for the specific defocus imposed. Consequently, when the lenses are removed, the eye finds its refractive error suddenly of opposite sign, and the choroidal thickness again compensates by changing in the opposite direction. If a local region of the eye is made myopic by a partial diffuser and then given unrestricted vision, the choroid expands only in the myopic region. Although the mechanism of choroidal expansion is unknown, it might involve either a increased routing of aqueous humor into the uveoscleral outflow or osmotically generated water movement into the choroid. The latter is compatible with the increased choroidal proteoglycan synthesis either when eyes wear positive lenses or after diffuser removal.

Sensitivity of cross-sectional echocardiography in detection of impaired global and regional left ventricular function: prospective study.

In order to establish the sensitivity and specificity of cross-sectional echocardiography for detection of global and regional left ventricular function a prospective study was performed in 80 patients suspected of having coronary artery disease. Twenty four hours before heart catheterization, cross-sectional echocardiograms were recorded in the apical RAO-equivalent view and high quality echocardiograms were obtained in 71/80 patients (89%). M-mode echocardiograms of the left ventricle could be performed in 56/71 patients (79%). Based on normal values sensitivity and specificity of cross-sectional echocardiography were calculated in comparison to cineventriculography. For fractional shortening (normal value greater than 25%) sensitivity measured 46% and specificity 93%, and when the E-point septal separation was measured (normal value less than 7 mm), sensitivity increased to 73% and specificity was 84%. For detection of increased end-diastolic volume (less than 155 ml) sensitivity reached 84% and specificity 98% and for increased end-systolic (less than 70 ml) volume it was 86 and 97%, respectively. A depressed left ventricular ejection fraction (greater than 49%) was found with a sensitivity of 93% and specificity of 100%. Regional left ventricular wall motion, analyzed by an area method, revealed for anterior wall motion a sensitivity of 68% and a specificity of 94%, whereas for posterior wall motion sensitivity reached 80% and specificity 96%. Regression equation between the number of pathological segments and left ventricular ejection fraction for cineventriculography was given by Y = -4.06 X + 73.4, r = 0.93 and for cross-sectional echocardiography by Y = -3.69 X + 62.6, r = 0.85. We conclude that cross-sectional echocardiography can be used as a screening method to detect impaired left ventricular function. It is superior to M-mode echocardiography. Reduced regional function of the posterior wall can be found with high sensitivity, but depressed motion of the anterior wall may be overlooked.