bluuebunny/crossref_metadata_2025 huggingface dataset:
Sweet spot size of virtual acoustic imaging systems at asymmetric listener locations
Authors: Rose John , Nelson Philip , Rafaely Boaz , Takeuchi Takashi
Published: October 2002

Virtual acoustic imaging systems are effective when the listener’s head location is close to the head location assumed when the system was designed. The “sweet spot” refers to the spatial bubble of head location in which the system is still effective. Some of the previous work investigating the “stereo dipole” acoustic imaging system shows that for the traditional on-axis listener location the “sweet spot” is about ±5 cm for lateral head translations. Larger head movements than this require an update of the virtual acoustic imaging filters. The interest here is the “sweet spot” size at off-axis asymmetric listener locations or an understanding of how often one needs to update the filters to ensure the listener perceives a stable virtual image as they move. The examination of the off-axis “sweet spot” size comprises a theoretical acoustic analysis, computer simulations, and a subjective study. The simulations and subjective evaluation both demonstrate that the width of tolerable lateral head translations is comparable for the symmetric on-axis listener location and asymmetric listener locations that are as far as 25 cm off-axis.
An inversion for Biot parameters in water-saturated sand
Authors: Chotiros Nicholas P.
Published: October 2002

The discrepancy between acoustic measurements and the theoretical predictions was investigated in the case of water-saturated sand. Two theoretical models were considered: visco-elastic and poro-elastic solid models. The visco-elastic solid model could not be reconciled with reflection loss measurements and was rejected. The poro-elastic solid model using Biot’s theory [J. Acoust. Soc. Am. 103, 2723–2729 (1998)] as formulated by Stoll [J. Acoust. Soc. Am. 70, 149–156 (1981)] was an improvement. It was investigated using an inversion process. Operative values of grain bulk modulus and the frame bulk and shear moduli of water-saturated sand were inverted from simple measurements—reflection loss, compressional and shear wave speeds and attenuations. Although the inversion process is nonlinear, in practice, it is well behaved and converges quite rapidly to a unique solution. The issue of imprecisely known parameter values was handled in a probabilistic manner. The inversion results, using published laboratory and in situ measurements, showed that further improvement was needed. In an attempt to find a solution, two possible hypotheses are put forward. (1) Composite materials: The possibility that the frame may contain fluid and that the pore fluid may contain loose grains. (2) Independent coefficient of fluid content: The possibility that porosity may change with pore fluid pressure. Inversion results were encouraging for both hypotheses. It is difficult to say which of the two hypotheses is superior, and the two hypotheses are not mutually exclusive. The new hypotheses represent a significant advance because they have the potential to resolve the remaining discrepancies. At this stage, alternative interpretations of the data are possible.
The laterophysic connection: A novel specialization thought to enhance sound pressure sensitivity in butterflyfishes (Chaetodontidae, Chaetodon)
Authors: Webb Jacqueline F. , Smith W. Leo , Tricas Timothy C. , Ketten Darlene R.
Published: October 2002

Morphological specializations that enhance sound reception have been described among fishes, but sources of behaviorally-significant sound stimuli and sound transduction mechanisms are known for very few bony fishes. Butterflyfishes in the genus Chaetodon have a unique sensory specialization, the laterophysic connection (LC), defined anterior swim bladder extensions (horns) in association with medial openings in the lateral line canals of the cranial supracleithral bones. The LC is hypothesized to enhance sensitivity of both the lateral line and ear to sound pressure. Variation in LC morphology among species is defined by variation in soft tissues and is thought to be functionally significant. Preliminary field studies demonstrate that C. multicinctus produces sounds during agonistic interactions, thus providing a source of potentially relevant sound stimuli. Presence of an inflated swim bladder in close proximity to well-developed supracleithral openings in pelagic tholichthys stage individuals (15 mm SL) and horn development at the end of the tholichthys stage (25–29 mm SL) in C. ocellatus suggests that sound may also play an important role in the early life history of Chaetodon. [Work supported by the NSF IBN-9603896 to J.F.W.]
Colloidosomes: Selectively Permeable Capsules Composed of Colloidal Particles
Authors: Dinsmore A. D. , Hsu Ming F. , Nikolaides M. G. , Marquez Manuel , Bausch A. R. , Weitz D. A.
Published: October 2002

We present an approach to fabricate solid capsules with precise control of size, permeability, mechanical strength, and compatibility. The capsules are fabricated by the self-assembly of colloidal particles onto the interface of emulsion droplets. After the particles are locked together to form elastic shells, the emulsion droplets are transferred to a fresh continuous-phase fluid that is the same as that inside the droplets. The resultant structures, which we call “colloidosomes,” are hollow, elastic shells whose permeability and elasticity can be precisely controlled. The generality and robustness of these structures and their potential for cellular immunoisolation are demonstrated by the use of a variety of solvents, particles, and contents.
Waves of Larch Budmoth Outbreaks in the European Alps
Authors: Bjørnstad Ottar N. , Peltonen Mikko , Liebhold Andrew M. , Baltensweiler Werner
Published: October 2002

Spatially extended population models predict complex spatiotemporal patterns, such as spiral waves and spatial chaos, as a result of the reaction-diffusion dynamics that arise from trophic interactions. However, examples of such patterns in ecological systems are scarce. We develop a quantitative technique to demonstrate the existence of waves in Central European larch budmoth (
Zeiraphera diniana
Gn.) outbreaks. We show that these waves travel toward the northeast-east at 210 kilometers per year. A theoretical model involving a moth-enemy interaction predicts directional waves, but only if dispersal is directionally biased or habitat productivity varies across the landscape. Our study confirms that nonlinear ecological interactions can lead to complex spatial dynamics at a regional scale.
Grain Nucleation and Growth During Phase Transformations
Authors: Offerman S. E. , van Dijk N. H. , Sietsma J. , Grigull S. , Lauridsen E. M. , Margulies L. , Poulsen H. F. , Rekveldt M. Th. , van der Zwaag S.
Published: October 2002

The mechanical properties of polycrystalline materials are largely determined by the kinetics of the phase transformations during the production process. Progress in x-ray diffraction instrumentation at synchrotron sources has created an opportunity to study the transformation kinetics at the level of individual grains. Our measurements show that the activation energy for grain nucleation is at least two orders of magnitude smaller than that predicted by thermodynamic models. The observed growth curves of the newly formed grains confirm the parabolic growth model but also show three fundamentally different types of growth. Insight into the grain nucleation and growth mechanisms during phase transformations contributes to the development of materials with optimal mechanical properties.
An Inclusive Perspective
Authors: Selin Helaine
Published: October 2002

Mathematics Elsewhere
. An Exploration of Ideas Across Cultures. Marcia Ascher. Princeton University Press, Princeton, NJ, 2002. 219 pp. $24.95, £17.95. ISBN 0-691-07020-2.

In this follow-up to her earlier
Ethnomathematics
, Ascher discusses the treatment of topics such as views of time, the future, maps, and mathematical relations in a variety of traditional and small-scale cultures.
Proof, Amazement, and the Unexpected
Authors: Netz Reviel
Published: October 2002

Archimedes is now best known for shouting "Eureka" in the bath, and perhaps also for his
invention of the cunning machines that helped to defend Syracuse from the Roman fleet
during the Punic Wars in 212 BP. He is less famous for his most profound work--the subtle
deductions and rigorous, often counterintuitive, mathematical proofs of seemingly prosaic
problems. His path-breaking work has reached new prominence among scholars with the
rediscovery of a long-lost palimpsest copy of some of his writings, which for the first
time shows that Greek mathematicians could work with infinite sets of numbers.
ABOUT THE MAGNETIC FLUCTUATION EFFECT ON THE PHASE TRANSITION TO SUPERCONDUCTING STATE IN Al
Authors: SHOPOVA D. V. , TODOROV T. P. , TSVETKOV T. E. , UZUNOV D. I.
Published: October 2002

The free energy and the order parameter profile near the phase transition to the superconducting state in bulk Al samples are calculated within a mean-field-like approximation. The results are compared with those for thin films.
Gq-Coupled Receptor Agonists Mediate Cardiac Hypertrophy Via the Vasculature
Authors: Keys Janelle R. , Greene Emily A. , Koch Walter J. , Eckhart Andrea D.
Published: October 2002

The Gq-coupled receptor-signaling pathway has been implicated in the cardiac hypertrophic response to stress, but little is actually known about the contributions of Gq signaling in either the heart or the vasculature. Therefore, we developed a line of transgenic mice that express a peptide inhibitor of Gq (GqI) in vascular smooth muscle to determine if vascular Gq signaling was important in the cardiac hypertrophic response. After chronic administration of the Gq agonists phenylephrine, serotonin, and angiotensin II, we observed an attenuation of mean arterial blood pressure and an inhibition of cardiac hypertrophy in the transgenic mice with vascular-specific GqI expression. In contrast, cardiac GqI peptide expression did not attenuate the hypertension or the cardiac hypertrophy. Importantly, all mice were capable of cardiac hypertrophy, because direct β-adrenergic receptor stimulation induced a similar level of hypertrophy in both lines of transgenic mice. This clearly suggests that after chronic Gq-coupled receptor agonist administration, it is the hypertensive state induced by vascular Gq activation that mediates remodeling of the heart, rather than direct stimulation of cardiac Gq-coupled receptors. Thus, the contribution of vascular Gq-coupled signaling to the development of cardiac hypertrophy is significant and suggests that expression of the GqI peptide is a novel therapeutic strategy to lower Gq-mediated hypertension and cardiac hypertrophy.
Angiotensin II Triggers EGFR Tyrosine Kinase-Dependent Ca
2+
Influx in Afferent Arterioles
Authors: Che Qi , Carmines Pamela K.
Published: October 2002

We previously reported that inhibition of epidermal growth factor receptor tyrosine kinase activity attenuates renal arteriolar contractile responses to angiotensin II. We performed the present experiments to determine if epidermal growth factor receptor tyrosine kinase activity contributes to the afferent arteriolar intracellular [Ca
2+
] response to angiotensin II. Afferent arterioles were dissected from rat kidney and intracellular [Ca
2+
] was monitored with the use of fura-2. In normal Ringer’s bath containing 1.5 mmol/L Ca
2+
, basal intracellular [Ca
2+
] averaged 95±7 nmol/L and 100 nmol/L angiotensin II caused a rapid rise (peak Δ=75±10 nmol/L) that waned to a plateau averaging 24±5 nmol/L above baseline. Pretreatment with 100 nmol/L AG1478 (epidermal growth factor receptor tyrosine kinase inhibitor) reduced both the peak and the plateau stages of the angiotensin II response (peak Δ=42±7 nmol/L; plateau Δ=8±4 nmol/L). A structurally unrelated epidermal growth factor receptor tyrosine kinase inhibitor also suppressed the peak response to angiotensin II, whereas tyrosine phosphatase inhibition enhanced the plateau phase of the response. In the presence of 100 nmol/L extracellular Ca
2+
, the angiotensin II response was characterized by a peak of diminished magnitude (Δ=49±10 nmol/L;
P
<0.05 versus the response in normal Ringer’s bath) with no plateau, and this response was unaffected by AG1478. Moreover, angiotensin II stimulation of divalent cation influx (Mn
2+
quench of fura-2 fluorescence) was decreased significantly by AG1478. We conclude that epidermal growth factor receptor tyrosine kinase activity contributes to the afferent arteriolar intracellular [Ca
2+
] response to angiotensin II and that this process involves promotion of Ca
2+
influx.
Nonnarcotic Analgesic Use and the Risk of Hypertension in US Women
Authors: Dedier Julien , Stampfer Meir J. , Hankinson Susan E. , Willett Walter C. , Speizer Frank E. , Curhan Gary C.
Published: October 2002

Acetaminophen, aspirin, and other nonsteroidal anti-inflammatory drugs (NSAIDs) are widely consumed. Each is theoretically capable of elevating blood pressure by altering prostaglandin homeostasis; however, there is little prospective information on the relation between these agents and physician-diagnosed hypertension. We examined the association between the use of aspirin, acetaminophen, or NSAIDs and incident hypertension in a prospective cohort study of 51 630 women 44 to 69 years of age in 1990 who had no history of hypertension or chronic renal insufficiency. Analgesic use was assessed in 1990 by a mailed questionnaire, and the women were followed for 8 years. The primary outcome was physician-diagnosed hypertension reported on a follow-up biennial questionnaire. During 381 078 person-years of follow-up, 10 579 incident cases of hypertension were identified. Compared with nonusers, women who used aspirin or acetaminophen at least 1 day per month or NSAIDs 5 or more days per month were at a significantly higher risk for development of hypertension. After adjusting for potential confounders, the odds ratios for women in the highest frequency of use category (≥22 days per month) compared with no use were as follows: aspirin, 1.21 (95% CI, 1.13 to 1.30); acetaminophen, 1.20 (1.08 to 1.33); and NSAIDs, 1.35 (1.25 to 1.46). For each analgesic type, there was a significant trend toward an increased risk of incident hypertension with increasing frequency of use (
P
<0.001). Given the observed odds ratios, biologic plausibility, and the sizeable population at risk, health professionals should consider potential hypertensive effects of aspirin, acetaminophen, and NSAIDs when counseling their patients about the use of nonnarcotic analgesics.
Left Ventricular Mass
Authors: Myerson Saul G. , Montgomery Hugh E. , World Michael J. , Pennell Dudley J.
Published: October 2002

The study of left ventricular (LV) hypertrophy is hindered by problems with LV mass measurement by echocardiography. Both the M-mode and 2D area-length formulas for calculating LV mass assume a fixed geometric shape, which may be a source of error. We examined this hypothesis by using cardiovascular magnetic resonance images to eliminate the confounding effects of acoustic access and image quality. LV mass was measured directly in 212 healthy subjects by means of a standard 3D cardiovascular magnetic resonance technique. LV mass was also calculated by using the cube-function and area-length formulas with measurements from the magnetic resonance images. A comparison of serial measurements was made by examining the changes in LV mass by all 3 techniques in those completing an exercise program (n=140). The cube-function technique showed a consistent underestimation of LV mass of 14.3 g, and there were wide 95% limits of agreement (±57.6 g and ±46.3 g for cube-function and area-length techniques, respectively) when compared with 3D measurement. There were similarly wide limits of agreement for the change in mass (±55.2 g and ±44.8 g for cube-function and area-length, respectively). The assumption of geometric shape in the cube-function and area-length formulas resulted in significant variation in LV mass estimates from direct measurement by using a 3D technique. The technique cannot be recommended either at a single time point or for serial studies in small populations; 3D imaging techniques, such as cardiovascular magnetic resonance, are preferable.
Programming Effects of Short Prenatal Exposure to Dexamethasone in Sheep
Authors: Dodic Miodrag , Abouantoun Tamara , O’Connor Anne , Wintour E. Marelyn , Moritz Karen M.
Published: October 2002

Recent studies have linked fetal exposure to a suboptimal intrauterine environment with adult hypertension. The aims of the present study were to see whether prenatal dexamethasone administered intravenously to the ewe between 26 to 28 days of gestation (1) resulted in high blood pressure in male and female offspring and whether hypertension in males was modulated by testosterone status, and (2) altered gene expression for angiotensinogen and angiotensin type 1 (AT
1
) receptors in the brain in late gestation and in the adult. Basal mean arterial pressure (MAP) at 2 years of age was significantly higher in wethers exposed to prenatal dexamethasone (group D; 106±5 mm Hg, n=9) compared with the control group (group S; 91±3 mm Hg, n=8;
P
<0.01). Infusion of testosterone for 3 weeks had no effect on MAP in either treatment group. At 130 days of gestation, dexamethasone administered between 26 to 28 days of gestation (group DF; n=8), resulted in an increased expression of angiotensinogen in hypothalamus (in arbitrary units: 2.5±0.3 versus 1.3±0.3 in the saline group [group SF], n=10;
P
<0.05). In addition, there was higher expression of the AT
1
receptors in medulla oblongata in group DF (2.6±0.6 versus 1.1±0.2 in group SF;
P
<0.01). This effect of prenatal dexamethasone treatment was still evident in females at 7 years of age (group DA; n=5; 2.6±0.5 versus 1.1±0.2 in group SA; n=6,
P
<0.05). In conclusion, brief prenatal exposure of the pregnant ewe to dexamethasone leads to hypertension in adult animals of both sexes. Most interestingly, the mechanism leading to programming of hypertension might be linked with the brain angiotensin system.
Inhibitors of Histone Deacetylation Downregulate the Expression of Endothelial Nitric Oxide Synthase and Compromise Endothelial Cell Function in Vasorelaxation and Angiogenesis
Authors: Rössig Lothar , Li Huige , Fisslthaler Beate , Urbich Carmen , Fleming Ingrid , Förstermann Ulrich , Zeiher Andreas M. , Dimmeler Stefanie
Published: October 2002

The histone deacetylase (HDAC) inhibitor trichostatin A (TSA) inhibits hypoxia-stimulated angiogenesis. Endothelial nitric oxide synthase (eNOS)–derived NO is central to angiogenesis signaling in endothelial cells (ECs). We hypothesized that the HDAC-dependent regulation of angiogenesis may involve a modulatory effect on eNOS expression. The HDAC inhibitors TSA, butyric acid (BuA), and MS-275 time- and concentration-dependently suppressed eNOS protein levels to 41±2%, 46±12%, and 40±12% of control, respectively. In parallel, TSA and BuA also downregulated eNOS mRNA expression to 21±4% and 37±4% of control. TSA also attenuated the NO-dependent relaxation of porcine coronary arteries (
P
<0.0001, TSA 1 μmol/L) and prevented tube formation in a human angiogenesis assay. Although vascular endothelial growth factor substitution did not compensate for the inhibitory effect of TSA, exogenous NO reversed the inhibition of angiogenesis by TSA. To address the underlying signaling mechanism, we characterized the effect of TSA on eNOS gene transcription and mRNA half-life. Although TSA decreased both eNOS protein and mRNA levels, TSA paradoxically enhanced the activity of the eNOS promoter, and did not alter the eNOS transcription rate in nuclear run-on experiments, suggesting that TSA posttranscriptionally targets eNOS mRNA. These data indicate that HDAC-dependent mechanisms contribute to the regulation of eNOS expression in ECs.
Hydralazine Reduces the Quantal Size of Secretory Events by Displacement of Catecholamines From Adrenomedullary Chromaffin Secretory Vesicles
Authors: Machado José D. , Gómez José F. , Betancor Gema , Camacho Marcial , Brioso Miguel A. , Borges Ricardo
Published: October 2002

The effects of the antihypertensive agent hydralazine (1 to 100 nmol/L) on the exocytotic process of single adrenal chromaffin cells have been studied using amperometry. Hydralazine does not reduce the frequency of exocytotic spikes but rapidly slows the rate of catecholamine release from individual exocytotic events by reducing the quantal size of catecholamine exocytosis. Confocal and standard epifluorescence microscopy studies show that hydralazine rapidly accumulates within secretory vesicles. The blockade of the vesicular H
+
pump with bafilomycin A
1
inhibits hydralazine uptake. Experiments with permeabilized cells show that hydralazine displaces catecholamines from secretory vesicles. The drug also displaces vesicular Ca
2+
, as shown by fura-2 microfluorimetry. These data suggest that hydralazine acts, at least partially, by interfering with the storage of catecholamines. These effects of hydralazine occurred within seconds, and at the tissue concentrations presumably reached in antihypertensive therapy; these concentrations are a thousand times lower than those described for relaxing vascular tissues in vitro. We proposed that these novel effects could explain many of the therapeutic and side effects of this drug that are likely exerted in sympathetic nerve terminals.
Rac-Dependent Monocyte Chemoattractant Protein-1 Production Is Induced by Nutrient Deprivation
Authors: Lopes Neuza H.M. , Vasudevan Sanjay S. , Gregg David , Selvakumar Balakrishnan , Pagano Patrick J. , Kovacic Herve , Goldschmidt-Clermont Pascal J.
Published: October 2002

Under ischemic conditions, the vessel wall recruits inflammatory cells. Human aortic endothelial cells (HAECs) exposed to hypoxia followed by reoxygenation produce monocyte chemoattractant protein-1 (MCP-1); however, most experiments have been performed in the presence of nutrient deprivation (ND). We hypothesized that ND rather than hypoxia mediates endothelial MCP-1 production during ischemia, and that the small GTP-binding protein Rac1 and reactive oxygen species (ROS) are involved in this process. ND was generated by shifting HAECs from 10% to 1% FBS. Superoxide production by HAECs was increased 6 to 24 hours after ND, peaking at 18 hours. MCP-1 production was increased over a similar time frame, but peaked later at 24 hours. These effects were blocked by treatment with antioxidants such as superoxide dismutase mimetic and
N
-acetylcysteine (NAC), or NADPH oxidase inhibitors, DPI and gp91ds-tat. Superoxide and MCP-1 production were enhanced by RacV12 (constitutively active) in the absence of ND, and were inhibited by RacN17 (dominant-negative) adenoviral transduction under ND, suggesting that the small G-protein Rac1 is required. In conclusion, ND, an important component of ischemia, is sufficient to induce MCP-1 production by HAECs, and such production requires a functional Rac1, redox-dependent pathway.
Inhibition of Hypoxia-Induced Apoptosis by Modulation of Retinoblastoma Protein–Dependent Signaling in Cardiomyocytes
Authors: Hauck Ludger , Hansmann Georg , Dietz Rainer , von Harsdorf Rüdiger
Published: October 2002

Apoptotic cell death is an important mode of cell loss contributing to heart dysfunction. To analyze the importance of the E2F-dependent regulation of gene transcription in cardiomyocyte apoptosis, the function of cell cycle factors impinging on the retinoblastoma protein (pRb)/E2F pathway was investigated. In isolated neonatal ventricular myocytes, apoptotic cell death induced by hypoxia (deferoxamine, 100 μmol/L) specifically activated cyclin-dependent kinases (cdks) 2 and 3. Apoptotic cell death was inhibited by ectopic expression of cdk inhibitors p21
CIP
and p27
KIP1
but not p16
INK4
. In addition, apoptosis was also abrogated by forced expression of kinase dead mutant proteins of cdk2/3 but not of cdk4/6. Introduction of cdk inhibitors or dominant-negative cdk2/3 blocked pRb hyperphosphorylation and abrogated E2F-dependent gene transcription, including that of the E2F-responsive genes of proapoptotic caspase 3 and caspase 7. Moreover, introduction of constitutively active pRb and transcriptionally inert mutant E2F1/DP1 efficiently protected cardiomyocytes from apoptosis. In conclusion, these data demonstrate that cdk-specific inactivation of pRb and the subsequent activation of E2F-dependent gene transcription are required for cardiomyocyte apoptosis.
Vascular NAD(P)H Oxidase Triggers Delayed Cerebral Vasospasm After Subarachnoid Hemorrhage in Rats
Authors: Kim Dong Eun , Suh Young Suk , Lee Mi-Sook , Kim Ki Young , Lee Jeong Hyun , Lee Hyun Seung , Hong Ki Whan , Kim Chi Dae
Published: October 2002

Background and Purpose–

To clarify the role of vascular NAD(P)H oxidase in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH), both the activity and/or activation mechanisms of NAD(P)H oxidase in the cerebral vasculature and the effect of oxidase inhibition on SAH-induced cerebral vasospasm were assessed.

Methods—

The changes in the luminal perimeter of the middle cerebral artery were measured histologically after SAH was induced according to a 2-hemorrhage model in rats. The NAD(P)H oxidase activity in the cerebral vasculature was measured with a lucigenin assay at different time intervals from 12 hours to 14 days after injection of autologous blood into cisterna magna. The membrane translocation of p47phox and the protein expression of membrane subunits (gp91phox and p22phox) of NAD(P)H oxidase were analyzed using Western blot analysis.

Results—

The luminal perimeter of the middle cerebral artery started to decrease on day 1 and peaked on day 5 after a second injection of blood, and these changes were significantly ameliorated by treatment with an NAD(P)H oxidase inhibitor, diphenyleneiodonium. At 24 hours after the second injection of blood, both vascular production of superoxide anion and NAD(P)H oxidase activity were markedly increased with enhanced membrane translocation of p47phox, but by 48 hours the enzyme activity had regained normal values. However, no significant changes in the expression of gp91phox and p22phox were observed throughout the experiments.

Conclusions—

These findings suggest that the activation of NAD(P)H oxidase through enhanced assembly of the oxidase components in the early stages of SAH might contribute to the delayed cerebral vasospasm in SAH rats.
Control of Hypertension and Risk of Stroke Recurrence
Authors: Friday Gary , Alter Milton , Lai Sue-Min
Published: October 2002

Background and Purpose—

We investigated whether low blood pressure increases the risk of stroke recurrence.

Methods—

A cohort of 662 patients, obtaining care at the 8 acute care hospitals serving the Lehigh Valley in Pennsylvania, was enrolled within 1 month of an initial stroke and was followed twice annually for up to 4 years. Cox proportional hazard models were developed to examine the relationship between risk of recurrent stroke and blood pressure, controlling for other significant risk factors. Our analyses investigated both lowest follow-up and average follow-up blood pressures as predictors of stroke recurrence.

Results—

There were 52 recurrent strokes among the 535 patients (mean age, 71 years; 51% men) with follow-up blood pressure. The risk ratio for stroke recurrence for diastolic blood pressure ≥80 mm Hg compared with <80 mm Hg was 2.4 (95% CI, 1.38 to 4.27) and for systolic blood pressure ≥140 mm Hg compared with <140 mm Hg was also 2.4 (95% CI, 1.39 to 4.15). For isolated systolic blood pressure (>140/<90 mm Hg), the risk ratio was 2.2 (95% CI, 1.23 to 3.79) relative to <140/<90 mm Hg. Using the Cox model, we also showed that patients who had at least 1 measured diastolic blood pressure <80 mm Hg during follow-up had a reduced risk of stroke recurrence compared with those with diastolic blood pressures 80 to 90 mm Hg (0.4 versus 1.0; 95% CI, 0.21 to 0.88) even after controlling for the possible confounding factors of hypertension and atrial fibrillation on ECG. Myocardial infarction on ECG, history of transient ischemic attack, and diabetes mellitus were not significant predictors of increased risk of recurrent stroke.

Conclusions—

Our results imply that “lower is better” for blood pressure control as a goal in reducing stroke recurrence risk.
Prevention of Experimental Cerebral Vasospasm by Intracranial Delivery of a Nitric Oxide Donor From a Controlled-Release Polymer
Authors: Gabikian Patrik , Clatterbuck Richard E. , Eberhart Charles G. , Tyler Betty M. , Tierney Travis S. , Tamargo Rafael J.
Published: October 2002

Background and Purpose—

A reduction in the local availability of nitric oxide (NO) may play a role in the etiology of chronic cerebral vasospasm after subarachnoid hemorrhage (SAH). We investigated the toxicity and efficacy of a locally delivered NO donor from a controlled-release polymer in preventing experimental cerebral vasospasm in rats and rabbits, respectively.

Methods—

Diethylenetriamine/NO (DETA/NO) was incorporated into controlled release ethylene-vinyl acetate (EVAc) polymers. Twenty-eight rats were used in a dose-escalation toxicity study to establish a maximally tolerated dose of DETA/NO-EVAc polymer. In the efficacy experiment, 20 rabbits were assigned to 4 experimental groups (n=5 per group): sham operation; SAH only; SAH+empty EVAc polymer; and SAH+DETA/NO-EVAc polymer. Treatment was initiated 30 minutes after blood deposition. Basilar artery lumen patency was assessed 72 hours after hemorrhage to evaluate the efficacy of DETA/NO in preventing cerebral vasospasm.

Results—

In the toxicity study, a dose of 3.4 mg/kg was identified as the LD
20
(dose with 20% mortality during the study period) of this DETA/NO formulation. Brain histology revealed hemorrhage and ischemic changes at the implantation site associated with high concentrations of DETA/NO. In the efficacy study, treatment with DETA/NO-EVAc polymer resulted in a significant decrease in basilar artery vasospasm compared with no treatment (93.0±4.9% versus 71.4±11.9%;
P
=0.035) or compared with treatment with blank EVAc polymer (93.0±4.9% versus 73.2±6.4%;
P
=0.003).

Conclusions—

Local delivery of DETA/NO prevents vasospasm in the rabbit basilar artery. Local delivery of DETA/NO via polymers is a safe and effective strategy for preventing cerebral vasospasm after SAH in this model.
Long-Term Durability of Carotid Endarterectomy for Symptomatic Stenosis and Risk Factors for Late Postoperative Stroke
Authors: Cunningham E.J. , Bond R. , Mehta Z. , Mayberg M.R. , Warlow C.P. , Rothwell P.M.
Published: October 2002

Background and Purpose—

Carotid endarterectomy (CEA) reduces the risk of stroke ipsilateral to recently symptomatic severe carotid stenosis. Other techniques such as percutaneous transluminal angioplasty with stenting are currently being compared with CEA. Thus far, case series and several small, randomized, controlled trials of CEA versus percutaneous transluminal angioplasty (with and without stenting) have focused primarily on the 30-day procedural risks of stroke and death. However, long-term durability is also important. To determine the long-term risk of stroke after CEA and to identify risk factors, we studied patients in the European Carotid Study Trial (ECST), the largest published cohort with long-term follow-up by physicians after CEA.

Methods—

Risks of ipsilateral carotid territory ischemic stroke were calculated by Kaplan-Meier analysis starting on the 30th day after CEA in 1728 patients who underwent trial surgery. Risk factors were determined by Cox regression. For comparison, we also determined the “background” risk of stroke on medical treatment in the ECST in the territory of 558 previously asymptomatic contralateral carotid arteries with <30% angiographic stenosis (ECST method) at randomization.

Results—

The risks of disabling ipsilateral ischemic stroke and any ipsilateral ischemic stroke were constant after CEA, reaching 4.4% [95% confidence interval (CI), 3.0 to 5.8] and 9.7% (95% CI, 7.6 to 11.7), respectively, by 10 years. The equivalent ischemic stroke risks distal to contralateral <30% asymptomatic carotid stenoses were 1.9% (95% CI, 0.8 to 3.2) and 4.5% (95% CI, 1.5 to 7.4). Presentation with cerebral symptoms, diabetes, elevated systolic blood pressure, smoking, male sex, increasing age, and a lesser severity of preoperative stenosis were associated with an increased risk of late stroke after CEA, but plaque morphology and patch grafting were not.

Conclusions—

Although the risk of late ipsilateral ischemic stroke after CEA for symptomatic stenosis is approximately double the background risk in the territory of <30% asymptomatic stenosis, it is still only ≈1% per year and remains low for at least 10 years after CEA. This is the standard against which alternative treatments should be judged. Several risk factors may be useful in identifying patients at particularly high risk of late postoperative stroke.
Impact of Infectious Burden on Progression of Carotid Atherosclerosis
Authors: Espinola-Klein Christine , Rupprecht Hans-Jürgen , Blankenberg Stefan , Bickel Christoph , Kopp Helmuth , Victor Anja , Hafner Gerd , Prellwitz Wilfried , Schlumberger Wolfgang , Meyer Jürgen
Published: October 2002

Background and Purpose—

Recent findings suggest a causative role of infections in the pathogenesis of atherosclerosis. The extent of atherosclerosis and the prognosis of patients with atherosclerosis seem to be increased by the number of infections to which an individual has been exposed. In a prospective study, we evaluated the effect of 8 pathogens and the aggregate pathogen burden on the progression of carotid atherosclerosis.

Methods—

In 504 patients (74.9% men; age, 62.9±10 years), we measured intima-media thickness and prevalence of carotid artery stenosis. Follow-up measurements after a mean of 2.5 years were available in 427 patients (85%). Blood samples were taken, and IgG or IgA antibodies to
Chlamydia pneumoniae
,
Helicobacter pylori
,
Haemophilus influenzae
,
Mycoplasma pneumoniae
, cytomegalovirus, Epstein-Barr virus, and herpes simplex virus types 1 and 2 were measured. Statistical evaluation was performed with logistic regression procedures.

Results—

Elevated IgA antibodies against
C pneumoniae
(
P
<0.04) and IgG antibodies against Epstein-Barr virus (
P
<0.01) and herpes simplex virus type 2 (
P
<0.04) were associated with progression of atherosclerosis (increase of intima-media thickness ≥0.1 mm/y or progression of carotid stenosis) after adjustment for age, sex, cardiovascular risk factors, highly sensitive C-reactive protein, and statin intake. Infectious burden, divided into 0 to 3, 4 to 5, and 6 to 8 seropositivities, was significantly associated with progression of atherosclerosis, with odds ratios of 1.8 (95% confidence interval, 1.1 to 2.9) for 4 to 5 and 3.8 (95% CI, 1.6 to 8.8) for 6 to 8 compared with 0 to 3 seropositivities after adjustment.

Conclusions—

Our results support the hypothesis that the number of infectious pathogens to which an individual has been exposed independently contributes to the progression of carotid atherosclerosis.
Mechanism of Extracellular K
+
-Induced Local and Conducted Responses in Cerebral Penetrating Arterioles
Authors: Horiuchi Tetsuyoshi , Dietrich Hans H. , Hongo Kazuhiro , Dacey Ralph G.
Published: October 2002

Background and Purpose—

Extracellular concentration of potassium ion ([K
+
]
o
) may have a significant influence on the cerebral circulation in health and disease. Mechanisms of [K
+
]
o
-induced conducted vasomotor responses in cerebral arterioles, possibly linking microvascular regulation to neuronal activity, have not been examined.

Methods—

We analyzed vascular responses to small increases of [K
+
]
o
(up to 5 mmol/L) in isolated, cannulated, and pressurized rat cerebral arterioles (36.5±1.4 μm). [K
+
]
o
was elevated globally through extraluminal application or locally through micropipette, while arteriolar diameter was measured online.

Results—

Elevation of [K
+
]
o
(5 mmol/L) produced dilation that was inhibited by ouabain but not BaCl
2
. Locally applied [K
+
]
o
(3 to 5 mmol/L) produced a biphasic response (initial constriction followed by dilation), both of which were conducted to the remote site (distance 1142±68 μm). Endothelial impairment inhibited conducted but not local biphasic responses. Extraluminal ouabain attenuated local and conducted secondary dilation but not initial constriction. The local biphasic response was unaffected by extraluminal or intraluminal BaCl
2
. Extraluminal but not intraluminal BaCl
2
impaired both conducted constriction and dilation.

Conclusions—

In rat penetrating arteriole, (1) [K
+
]
o
(3 to 5 mmol/L) strongly regulates arteriolar tone and causes conducted vasomotor responses; (2) local responses to elevated [K
+
]
o
are endothelium independent but conducted responses are dependent on an intact endothelium; (3) smooth muscle Na
+
-K
+
-ATPase activation is the generator of conducted dilation; and (4) smooth muscle inward rectifier potassium channels sustain conduction. Our findings suggest that potassium-induced conducted vasomotor responses may link local neuronal activity to microvascular regulation, which may be attenuated in pathological conditions.
Prevalence of Atrial Fibrillation and Antithrombotic Prophylaxis in Emergency Department Patients
Authors: Scott Phillip A. , Pancioli Arthur M. , Davis Lisa A. , Frederiksen Shirley M. , Eckman John
Published: October 2002

Background and Purpose—

The emergency department (ED), as the point of first medical contact for many complaints referable to atrial fibrillation (AF) and a common source of primary care, occupies a unique position to identify AF patients at risk of stroke. This study evaluates that potential by determining the prevalence of AF in an ED population and assessing antithrombotic use in those patients with recurrent AF.

Methods—

This was a multicenter, retrospective, cross-sectional study of consecutive records of ED patients with AF identified by ECG between January and June 1998. American Heart Association and modified Stroke Prevention in Atrial Fibrillation criteria established high-risk patients and contraindications to anticoagulation, respectively.

Results—

We identified 866 records with ECG-proven AF in 78 787 patient visits for an estimated prevalence of 1.10% (95% CI, 1.03 to 1.17). We found that 556 records had a prior history of AF; of these, 221 (40%) used warfarin alone, 155 (28%) had antiplatelet therapy alone, 28 (5%) used both, and 152 (27%) had no antithrombotic therapy identified. Sixty-eight patients (12%; 95% CI, 0.10 to 0.15) were warfarin eligible and without antithrombotic therapy. An additional 64 (12%; 95% CI, 0.09 to 0.14) had antiplatelet therapy alone. In warfarin-eligible patients, no differences were identified between the anticoagulated and nonanticoagulated groups on the basis of age, sex, or race. Of patients on warfarin with a measured international normalized ratio, 61% (95% CI, 0.55 to 0.67) were outside the AHA-recommended range of 2.0 to 3.0.

Conclusions—

AF is a common finding in an ED population. Many are warfarin eligible and untreated or undertreated. Methods to increase anticoagulant use in this at-risk population warrant further investigation.
Natural History of Perihematomal Edema in Patients With Hyperacute Spontaneous Intracerebral Hemorrhage
Authors: Gebel James M. , Jauch Edward C. , Brott Thomas G. , Khoury Jane , Sauerbeck Laura , Salisbury Shelia , Spilker Judith , Tomsick Thomas A. , Duldner John , Broderick Joseph P.
Published: October 2002

Background and Purpose—

The natural history of perihematomal edema in human hyperacute spontaneous intracerebral hemorrhage (ICH) has not been well described.

Methods—

This study was a secondary analysis of a previously reported prospective, population-based study of hematoma growth in 142 patients with spontaneous ICH. Patients were first imaged within 3 hours of onset, then 1 and 20 hours later. We excluded patients with anticoagulant use (n=7), underlying aneurysm/vascular malformation (n=9), trauma (n=1), incomplete data (n=20), infratentorial ICH (n=17), and no consent (n=2), leaving an overall study population of 86 patients. From this overall group we further excluded patients with intraventricular extension (n=38), subsequent surgery (n=5), or death (n=2) before 20-hour postbaseline CT. This second, “restricted” analysis group of 41 patients was relatively devoid of clinical or radiological variables likely to confound edema measurement. Absolute and relative edema volumes (edema volume divided by hematoma volume) were descriptively summarized. Correlations between baseline edema volumes and relevant clinical and radiological variables were then performed.

Results—

Overall, median absolute edema volume increased from 6.93 to 14.4 cm
3
during the first 24 hours after ICH, and median relative edema volume increased from 0.47 to 0.81. In the restricted group, median absolute edema volume was 7.4 cm
3
at baseline and 11.0 cm
3
at 24 hours after ICH, and median relative edema volume increased from 0.55 to 0.81. Baseline relative edema volume was significantly negatively correlated with subsequent change in relative edema volume from baseline to 20-hour CT (
r
=0.57,
P
=0.0002) but was not significantly correlated with other clinical and radiological variables, including hematoma volume or change in hematoma volume.

Conclusions—

Perihematomal edema volume increases by approximately 75% during the first 24 hours after hyperacute spontaneous ICH. Patients with the least amounts of baseline relative edema volume were most likely to develop significant additional amounts of edema during the first 24 hours after spontaneous ICH.
Echo Contrast–Enhanced Transcranial Ultrasound
Authors: Zunker Peter , Wilms Henrik , Brossmann Joachim , Georgiadis Dimitrios , Weber Sepp , Deuschl Günther
Published: October 2002

Background and Purpose—

The present study was undertaken to determine the frequency of use of the ultrasound contrast agent (UCA) Levovist in routine transcranial ultrasound (TU). Additionally, we evaluated the diagnostic validity of contrast-enhanced TU using 3-dimensional time of flight MR angiography.

Methods—

Indication for the UCA was an insufficient evaluation of the intracranial arteries after a combined approach with transcranial color-coded Duplex and transcranial Doppler examination. We prospectively analyzed every patient referred for TU over 6 months. Additionally, over a 3-month period, TU results were compared with 3-dimensional time-of-flight MR angiography .

Results—

Indication for use of UCA was met in 61 of 687 patients (8.8%). After UCA application, a diagnostic result was achieved in 75% of cases during transtemporal and in 81% during transforaminal insonation. The sensitivity and specificity of TU in the diagnosis of intracranial stenosis were 83% and 82%, respectively.

Conclusions—

Use of UCA was necessary in 8.8% of the patients. A diagnostic benefit was achieved in 75% to 80% of cases. Contrast-enhanced TU demonstrated a high sensitivity and specificity in the diagnosis of intracranial stenosis.
Anatomy of Stroke, Part I
Authors: Caviness V. S. , Makris N. , Montinaro E. , Sahin N. T. , Bates J. F. , Schwamm L. , Caplan D. , Kennedy D. N.
Published: October 2002

Background and Purpose—

The clinical diagnosis and treatment of stroke, as well as investigations into the underlying pathophysiology of the disease, hinge on inferences from the anatomy of the stroke lesion. We describe an MRI-based system of topographic and volumetric analysis that considers distribution of infarct with respect to neuroanatomic structures, superficial and deep perfusion compartments, and gray and white matter tissue types.

Methods—

MRI-based 3-dimensional topographic and volumetric analysis of presumed MCA embolic stroke was performed months after the acute event in 21 subjects ranging in age from 34 to 75 years.

Results—

The topography of infarction was greatly variable, with virtually all regions of the MCA territory involved in at least 1 stroke in the series. In 14, there was involvement of the M1 as well as the M2 through M4 territories; in 6, there was involvement of only the M2 through M4 territories; and in 2, there was involvement of only the M1 territory. The volumes varied from 3.1 to 256 cm
3
, corresponding approximately to a range of 1% to 90% of the total MCA territory.

Conclusions—

The system of topographic and volumetric analysis is generally applicable to all strokes in the forebrain where the infarct is visualized in MRI, independent of vascular territory, clinical correlates, and interval between stroke and MRI. The results emphasize the variety of topographic patterns and lesion volumes of strokes. Intended long-range applications include correlation of outcome of stroke with predictions from acute-phase diffusion- and perfusion-weighted imaging and investigations of the potential benefit of therapeutic agents.
Anatomy of Stroke, Part II
Authors: Caviness V. S. , Makris N. , Montinaro E. , Sahin N. T. , Bates J. F. , Schwamm L. , Caplan D. , Kennedy D. N.
Published: October 2002

Background and Purpose—

The margin of a stroke is assumed to approximate a trace of the isobar of the perfusion threshold for infarction at the time that infarction occurred. Working from this hypothesis, we have analyzed stroke topography and volume in MR images obtained at a time remote from the stroke event. We have derived parameters from these images that may give information on local perfusion competence and microvascular architecture because they influenced the contour of stroke at the time infarction occurred.

Methods—

MR images were obtained months after presumed embolic middle cerebral artery stroke in 21 subjects. Volumetric analyses of image data were undertaken with respect to the tissue shape of stroke and scaling ratios of anatomic partitions involved in stroke.

Results—

For stroke confined to a single volume, the 3-dimensional form conforms to a parabola in which the height-to-width ratios are variable. The ratio for cortex is greater than that for underlying white matter. Scaling ratios indicate a close correlation between volume of cortex and radiata destroyed and total volume of stroke, but the relative proportions vary as a function of location within the M4 territory.

Conclusions—

Scaling ratios for cortex and radiata to stroke volume are consistent with vascular studies that depict a modular microvascular perfusion architecture for the cortex and underlying white matter. The stroke descriptors are inferred to be related to the competence of collateral perfusion at the time that stroke occurred. This inference may be tested by serial volumetric analysis of the perfusion-diffusion examination mismatch immediately and over the longer-term evolution of stroke.