bluuebunny/crossref_metadata_2025 huggingface dataset:
Dysplastic Vessels After Surgery for Brain Arteriovenous Malformations
Authors: Stapf C. , Connolly E.S. , Schumacher H.C. , Sciacca R.R. , Mast H. , Pile-Spellman J. , Mohr J.P.
Published: July 2002

Background and Purpose

—

The cause and clinical significance of residual dysplastic vessels after surgery for brain arteriovenous malformations (AVM) are unclear. We studied predictors and frequency of residual dysplastic vessels on cerebral angiography after AVM surgery.

Methods

—

The 240 prospectively enrolled surgical patients from the New York AVM Databank underwent 269 AVM-related surgical procedures. Reported postoperative brain angiographic findings were classified post hoc as showing (1) persistent dysplastic vessels, (2) a residual AVM, (3) focal hyperemia in the surgical bed, (4) other changes, or (5) a normal angiogram. Univariate and multivariate models were applied to test for an association between residual dysplastic vessels and patient age, sex, preoperative AVM size, anatomic AVM location, number of embolization procedures before surgery, and the time interval between AVM surgery and the postoperative angiogram.

Results

—

Of the 224 documented postoperative angiograms, 78 (35%) showed dysplastic vessels, 24 (11%) had evidence for a residual AVM, 16 (7%) showed focal hyperemia, 6 (2%) revealed other findings, and 100 (45%) were normal. The number of cases showing angiographic evidence for dysplastic vessels was significantly associated with increasing size of the AVM (in millimeter increments;
P
=0.0001); the mean diameter of AVMs in patients showing dysplastic vessels after surgery was significantly larger (41 mm, SD ±14) than in those without residual dysplastic vessels (27 mm, SD ±13;
P
<0.001). Symptomatic postoperative intracerebral hemorrhage occurred in 4 patients (1%), in 2 of whom dysplastic vessels were seen on the postoperative angiogram.

Conclusions

—

The findings suggest that persistent dysplastic vessels may be found in approximately one third of angiograms after AVM surgery. Preoperative AVM size was found to be an independent predictor for the occurrence of dysplastic vessels on the postoperative angiogram.
Inflammation-Mediated Damage in Progressing Lacunar Infarctions
Authors: Castellanos Mar , Castillo José , García María M. , Leira Rogelio , Serena Joaquín , Chamorro Angel , Dávalos Antoni
Published: July 2002

Background and Purpose

—

The mechanisms underlying neurological deterioration in patients with lacunar infarction are not completely understood. In this study, we sought to investigate the role of proinflammatory molecules in the early worsening and outcome of acute lacunar stroke.

Methods

—

We performed a secondary analysis of 113 consecutive patients with lacunar infarction included within the first 24 hours of the onset of symptoms in a previous study aimed at investigating clinical and biochemical factors of early neurological deterioration (END). END was defined as a fall of ≥1 points in the motor items of Canadian Stroke Scale between inclusion and 48 hours. Poor outcome at 3 months was considered death or Barthel Index <85. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) were determined by enzyme-linked immunoabsorbent assay in blood samples obtained on admission.

Results

—

END was recorded in 27 patients (23.9%); poor outcome was noted in 26 (23%). Median (quartiles) concentrations in plasma of TNF-α [16.5 pg/mL (13.7 and 21.2 pg/mL) versus 7.5 pg/mL (6.2 and 9.0 pg/mL)], IL-6 [28.8 pg/mL (22.5 and 35.7 pg/mL) versus 11.5 pg/mL (8.5 and 16.2 pg/mL)], and ICAM-1 [285 pg/mL (219 and 315 pg/mL) versus 158 pg/mL (137 and 187 pg/mL)] were significantly higher in patients who had END than in those with nonprogressing strokes (
P
< 0.001). Significant differences were also observed between patients with poor and good outcome at 3 months. Logistic regression analysis after adjustment for potential confounders showed that TNF-α >14 pg/mL and ICAM-1 >208 pg/mL were independently associated with both END (OR, 511; 95% CI, 17 to 4937;
P
<0.001; and OR, 315; 95% CI, 17 to 5748;
P
< 0.001, respectively) and poor outcome at 3 months (OR, 3.0; 95% CI, 1.0 to 8.5;
P
=0.042; and OR, 4.2; 95% CI, 1.3 to 13.6;
P
<0.015, respectively).

Conclusions

—

High concentrations of inflammatory markers in blood are associated with END and poor functional outcome in lacunar infarctions. These findings suggest that inflammation contributes to brain injury in lacunar stroke.
Albumin Therapy of Transient Focal Cerebral Ischemia
Authors: Belayev Ludmila , Pinard Elisabeth , Nallet Helene , Seylaz Jacques , Liu Yitao , Riyamongkol Panomkhawn , Zhao Weizhao , Busto Raul , Ginsberg Myron D.
Published: July 2002

Background and Purpose

—

To study whether intravascular or hemodynamic factors contribute to the marked neuroprotective effect of albumin therapy in focal cerebral ischemia, 2 complementary methods were applied: laser-scanning confocal microscopy (LSCM) and laser-Doppler perfusion imaging (LDPI).

Methods

—

In the LSCM study, Sprague-Dawley rats were anesthetized with halothane/nitrous oxide, and a cranial window was placed over the dorsolateral frontoparietal cortex. Rats received 2-hour middle cerebral artery occlusion (MCAO) by an intraluminal suture and were treated with human albumin (1.25 g/kg; n=4) or saline (n=3) after 30 minutes of recirculation. Video images of cortical vessels were continually acquired and were digitized offline to measure diameters and fluorescent erythrocyte velocities. In the LDPI study, cortical perfusion was measured in anesthetized Sprague-Dawley rats that received 2-hour MCAO and were treated with albumin (2.5 g/kg; n=6) or saline (n=5) at 30 minutes after recirculation.

Results

—

In the LSCM study, MCAO was associated with arteriolar dilation and slowing of capillary and venular erythrocyte perfusion. During the first 15 to 30 minutes of postischemic recirculation, prominent foci of vascular stagnation developed within cortical venules, associated with thrombuslike foci and adherent corpuscular structures consistent in size with neutrophils. Saline administration failed to affect these phenomena, while albumin therapy was followed by significant increases in arteriolar diameter (≈12%;
P
=0.007) and by a prompt improvement of venular and capillary erythrocyte perfusion and a partial disappearance of adherent thrombotic material. Albumin therapy increased erythrocyte flow velocity in both capillaries (288±73% versus 76±18% in the saline group;
P
=0.023) and venules (2.7-fold [
P
=0.001] versus 1.0-fold in the saline group [
P
=NS]). In the LDPI study, cortical perfusion declined during MCAO and rose initially with recirculation (to ≈135% of baseline) in both groups. Mean cortical perfusion improved slightly (≈14%;
P
=NS) in albumin-treated animals.

Conclusions

—

These results reveal a beneficial effect of albumin therapy in reversing stagnation, thrombosis, and corpuscular adherence within cortical venules in the reperfusion phase after focal ischemia and support its utility in the treatment of acute ischemic stroke.
High Plasma Brain Natriuretic Polypeptide Level as a Marker of Risk for Thromboembolism in Patients With Nonvalvular Atrial Fibrillation
Authors: Shimizu Hiromi , Murakami Yo , Inoue Shin-ichi , Ohta Yoko , Nakamura Ko , Katoh Harumi , Sakne Takeshi , Takahashi Nobuyuki , Ohata Shuzo , Sugamori Takashi , Ishibashi Yutaka , Shimada Toshio
Published: July 2002

Background and Purpose

—

Assessment of left atrial appendage (LAA) function with transesophageal echocardiography is useful for detecting patients at high risk for thromboembolism as a result of atrial fibrillation (AF). A recent study reported that the atrium is the main source of brain natriuretic polypeptide (BNP) in AF patients without overt heart failure. The purpose of this study was to assess a possible relationship between LAA function and plasma BNP levels in nonvalvular AF.

Methods

—

Thirty-four consecutive patients with chronic nonvalvular AF (age, 69±9 years) underwent transesophageal echocardiography and plasma BNP measurement. Thirteen patients with a history of thromboembolism or echocardiographic evidence of thrombus (E + group) were compared with 21 AF patients without complications (E− group).

Results

—

The E+ group patients demonstrated greater impairment of LAA velocity and higher plasma BNP levels than the E− group patients (LAA velocity: 12±6 versus 31±17 cm/s,
P
<0.05; plasma BNP: 126±53 versus 86±45 ng/L,
P
<0.05). Overall analysis of the continuous variables with multiple logistic regression analysis revealed that BNP was a significant predictor of thromboembolism. There was a weak but significant negative correlation between plasma BNP levels and LAA flow velocity (
r
=0.38,
P
<0.05). No intergroup difference in plasma atrial natriuretic polypeptide levels was found.

Conclusions

—

The present data suggest the usefulness of measuring plasma BNP levels, which may reflect augmented atrial secretion of BNP from the impaired atrial myocardium, in detecting patients at high risk for thromboembolic complications in nonvalvular AF.
Predicting Outcome After Acute and Subacute Stroke
Authors: Counsell Carl , Dennis Martin , McDowall Michael , Warlow Charles
Published: July 2002

Background and Purpose

—

Statistical models to predict the outcome of patients with acute and subacute stroke could have several uses, but no adequate models exist. We therefore developed and validated new models.

Methods

—

Regression models to predict survival to 30 days after stroke and survival in a nondisabled state at 6 months were produced with the use of established guidelines on 530 patients from a stroke incidence study. Three models were produced for each outcome with progressively more detailed sets of predictor variables collected within 30 days of stroke onset. The models were externally validated and compared on 2 independent cohorts of stroke patients (538 and 1330 patients) by calculating the area under receiver operating characteristic curves (AUC) and by plotting calibration graphs.

Results

—

Models that included only 6 simple variables (age, living alone, independence in activities of daily living before the stroke, the verbal component of the Glasgow Coma Scale, arm power, ability to walk) generally performed as well as more complex models in both validation cohorts (AUC 0.84 to 0.88). They had good calibration but were overoptimistic in patients with the highest predicted probabilities of being independent. There were no differences in AUCs between patients seen within 48 hours of stroke onset and those seen later; between ischemic and hemorrhagic strokes; and between those with and without a previous stroke.

Conclusions

—

The simple models performed well enough to be used for epidemiological purposes such as stratification in trials or correction for case mix. However, clinicians should be cautious about using these models, especially in hyperacute stroke, to influence individual patient management until they have been further evaluated. Further research is required to test whether additional information from brain imaging improves predictive accuracy.
Prognostic Significance of Uric Acid Serum Concentration in Patients With Acute Ischemic Stroke
Authors: Chamorro Ángel , Obach Victor , Cervera Álvaro , Revilla Marian , Deulofeu Ramón , Aponte John H.
Published: July 2002

Background and Purpose

—

We sought to assess in 881 consecutive patients with acute ischemic stroke the clinical relevance in regard to functional outcome of the natural antioxidant uric acid measured at hospital admission.

Methods

—

Patients had serum uric acid (mg/dL) measured by standard procedures 18.2±15.5 hours from clinical onset. At hospital discharge (11.0±6.0 days), neurological impairment was classified as moderate/severe (Mathew score ≤75; n=304) or mild/absent (Mathew score >75; n=577). Demographics, atherosclerotic risk factors, history of organ disease, baseline neurological score, stroke subtype, infarction size, renal function, aspirin use before stroke, stroke therapy, diuretic use, and laboratory markers, including erythrocyte sedimentation rate, were analyzed in both outcome groups with the use of backward logistic regression.

Results

—

Increased uric acid values were found in men, hypertensives, alcohol drinkers, and patients with coronary, pulmonary, or renal diseases. Diabetic patients had lower uric acid levels on admission. Uric acid was directly associated with hematocrit (
P
=0.001), sodium (
P
=0.001), creatinine (
P
=0.001), and triglycerides (
P
=0.001) and inversely related with nonfasting glucose (
P
=0.001) levels. Neurological impairment on admission (
P
=0.001) and final infarction size on CT/MRI (
P
=0.01) were also inversely associated with uric acid. A logistic regression adjusted for confounders confirmed the following independent (odds ratio, 95% CI) good outcome predictors: age (0.97, 0.96 to 0.99), Mathew score on admission (1.14, 1.12 to 1.17), erythrocyte sedimentation rate (0.98, 0.97 to 0.99), infarction volume (0.98, 0.98 to 0.99), and uric acid (1.12, 1.00 to 1.25).

Conclusions

—

In patients with acute ischemic stroke, there is a 12% increase in the odds of good clinical outcome for each milligram per deciliter increase of serum uric acid. This finding reinforces the relevance of oxidative damage in ischemic stroke.
Vessel-Specific Stimulation of Protein Synthesis by Nitric Oxide Synthase Inhibition
Authors: Martens Fabrice M.A.C. , Demeilliers Bénédicte , Girardot Daphné , Daigle Christine , Dao Huy Hao , deBlois Denis , Moreau Pierre
Published: July 2002

Although conduit arteries develop hypertrophy after chronic NO synthesis blockade, resistance arteries remodel without hypertrophy under the same conditions. Similar findings have been described in essential hypertension. We postulated that this regional difference may be related to a heterogeneous effect of endogenous NO on proliferation along the vascular tree. Newly synthesized proteins were radiolabeled in vivo with [
3
H]
l
-leucine in basal conditions and during NO synthase inhibition, with or without PD98059 (inhibitor of the extracellular signal–regulated kinases [ERK] 1/2). Blocking the generation of NO by 3 different
l
-arginine analogues increased protein synthesis by an average of 75% in the aorta, in association with enhanced ERK 1/2 phosphorylation. PD98059 significantly reduced
l
-arginine analogue–induced protein synthesis and ERK 1/2 phosphorylation, confirming the involvement of ERK 1/2 as an important signaling element. In small arteries,
l
-arginine analogues did not influence the extent of protein synthesis, although phosphorylation of ERK 1/2 was also enhanced. To determine the role of NO in a condition of enhanced protein synthesis, angiotensin II was infused for 24 hours. Angiotensin II augmented protein synthesis in mesenteric arteries and the aorta, and was additive to NO synthase blockade in the aorta. In conclusion, endogenous NO exerts a tonic inhibitory influence on aortic growth, with limited impact on small arteries in basal and hypertrophic conditions. This heterogeneous role of NO on vascular growth may explain the heterogeneity of vascular remodeling observed in essential hypertension, a condition associated with endothelial dysfunction.
Hemodynamic and Autonomic Adjustments to Real Life Stress Conditions in Humans
Authors: Lucini Daniela , Norbiato Guido , Clerici Mario , Pagani Massimo
Published: July 2002

Psychological stress represents a risk factor for hypertension, but mechanisms are not known in detail. In this investigation we tested the hypothesis that real-life stress conditions produce changes in autonomic cardiac and vascular regulation that might differ in magnitude. University students, a well-established model of mild real-life stress, were examined shortly before a university examination, and a second time 3 months afterward, during holiday. Autonomic cardiovascular regulation was assessed by a noninvasive approach, based on autoregressive analysis of RR interval variability (V) and of systolic arterial pressure (SAP) V. The overall level of stress in the two sessions was gauged from the elevated salivary cortisol (5.6±0.5 versus 2.4±0.2 ng/mL,
P
<0.05) and altered cytokine profile (
P
<0.05). During the stress day, the RR interval was reduced and arterial pressure increased significantly; simultaneously, the normalized low frequency component of RRV (a marker of sympathetic modulation of the sinoatrial node) was increased and the index α (a measure of baroreflex gain) reduced. Concomitantly, the autonomic response to the sympathetic excitation produced by standing was altered: cardiac response was impaired and vascular responsiveness increased. Markers of autonomic regulation of the sinoatrial node correlated significantly with cortisol levels, both at rest and also considering standing induced changes, suggesting a gradual range of effects. The data support the concept that mild real-life stress increases arterial pressure and impairs cardiovascular homeostasis. These changes, assessable with spectral analysis of cardiovascular variability, might contribute, in susceptible individuals, to the link between psychological stress and increased cardiovascular risk of hypertension.
Src Autophosphorylation is an Early Event in Pressure-Mediated Signaling Pathways in Isolated Resistance Arteries
Authors: Rice Darian C. , Dobrian Anca D. , Schriver Suzanne D. , Prewitt Russell L.
Published: July 2002

Abstract—

Elevated blood pressure is associated with varying degrees of arterial growth and remodeling. The mechanisms by which mechanical stress is converted into cellular alteration have yet to be fully elucidated. Our laboratory has demonstrated that Src tyrosine kinases and the extracellular signal-regulated kinase subtype of the mitogen-activated protein kinase family mediate pressure-induced c-fos expression in rat mesenteric arteries. Others have reported involvement of integrin and growth factor receptor signaling pathways. Our goal was to determine the role of Src, focal adhesion kinase (FAK), and platelet-derived growth factor (PDGF) receptor signaling in the upstream initiation of these events. Pairs of rat mesenteric arteries were pressurized to 90 mm Hg (control), and then one was raised to 140 mm Hg for 1, 3, or 5 minutes. Western blotting revealed that Src-pY
418
was elevated 2.4-fold over control values at 1 minute and 2.8-fold at 3 minutes and returned to control at 5 minutes. Significant FAK-Y
397
phosphorylation was observed only after 3 and 5 minutes of pressure stimulus and was blocked entirely by Src inhibition. Src-pY
215
activity (associated with PDGF receptor activation) does not seem to be involved at any of the time points tested. These data demonstrate that Src-Y
418
autophosphorylation is an early event in pressure mechanotransduction and leads to activation of FAK-Y
397
. This finding suggests that Src may be the messenger that initiates and propagates the cellular growth response to pressure stimulus, and FAK is one of its downstream targets. Src phosphorylation due to PDGF receptor activation does not seem to be involved in the initial response.
Novel Receptors for Ouabain: Studies in Adrenocortical Cells and Membranes
Authors: Ward Stephen C. , Hamilton Bruce P. , Hamlyn John M.
Published: July 2002

Sodium-potassium pumps (Na pumps) are the only known plasma membrane receptors for cardiac glycosides. However, adrenocortical cells secrete an endogenous ouabain via an unknown mechanism that is subject to feedback inhibition via the cell surface. In addition, recent studies suggest that the induction of sustained hypertension by ouabain analogs in rats may be independent of Na pump inhibition. Accordingly, we used bovine adrenocortical cells and membranes to search for novel binding sites for ouabain. In high extracellular potassium solutions, the binding of ouabain to the Na pumps of cultured cells was suppressed, yet residual specific binding of
3
H-ouabain was observed. In high extracellular potassium, Scatchard analyses revealed a novel class of ouabain binding sites with high affinity (<50 nmol/L, <2.5×10
5
sites/cell) that was distinct from the low-affinity Na pump sites (>1 μmol/L, 4.5×10
6
sites/cell). Analysis of the kinetics for the dissociation of
3
H-ouabain from intact cells revealed components whose t
0.5
values were 6.5 minutes, 3.3 hours, and 33 hours and associated with novel sites, Na pumps, and lysosomal recycling, respectively. Studies with isolated membranes under ligand conditions where the participation of Na pumps was minimized revealed specific ouabain binding to novel sites that was saturable, time-dependent, of high affinity (K
d
≈15 nmol/L), and of low density (apparent B
max
=0.23 pmol/mg, c.f., Na pumps=10.2 pmol/mg). Ouabain binding to the novel sites was stimulated by high concentrations of KCl but was not affected by aldosterone or cortisol up to 30 μmol/L. Novel sites were not detected in skeletal muscle or liver membranes. Photoaffinity studies followed by SDS-PAGE showed ouabain-protectable labeling of membrane polypeptides with apparent molecular weights of 143, 113, and 65 kDa. We conclude that adrenocortical cells express ouabain receptors that are distinct from Na pumps. These novel receptors may be involved in the regulation and/or secretion of endogenous ouabain.
Expression and Cellular Localization of Classic NADPH Oxidase Subunits in the Spontaneously Hypertensive Rat Kidney
Authors: Chabrashvili Tinatin , Tojo Akahiro , Onozato Maristela Lika , Kitiyakara Chagriya , Quinn Mark T. , Fujita Toshiro , Welch William J. , Wilcox Christopher S.
Published: July 2002

Phagocytes generate superoxide anion (O
2
−
) by a classic, 5-component NADPH oxidase. O
2
−
contributes to hypertension in spontaneously hypertensive rats (SHR). Therefore, we tested the hypothesis that NADPH oxidase expression is enhanced in the SHR kidney. We also analyzed the localization of NADPH oxidase components in SHR kidney. Renal NADPH oxidase was quantified by reverse transcription-polymerase chain reaction and Western blotting and was localized in SHR and Wistar Kyoto rat (WKY) kidney by immunohistochemistry. The mRNA for 5 subunits of phagocyte NADPH oxidase, and also for MOX1 and RENOX (NOX4), was detected in adult rat kidney. Kidneys of adult (10 weeks old) SHR had a significantly (
P
<0.01) greater mRNA for p47phox (SHR 0.81±0.05 versus WKY 0.37±0.01, arbitrary unit), which was confirmed by Western blotting (SHR 0.58±0.04 versus WKY 0.42±0.04, arbitrary unit;
P
<0.05) and by immunohistochemistry. This higher p47phox protein expression was also detected in young prehypertensive SHR (SHR 0.61±0.05 versus WKY 0.39±0.04, arbitrary unit;
P
<0.01). The 10-week-old SHR contained more modest but significantly (
P
<0.05) greater protein for p67phox (SHR 0.54±0.02 versus WKY 0.46±0.02). Immunostaining localized p47phox, p67phox, and p22phox in vasculature, macula densa, distal convoluted tubule, cortical collecting duct, and outer and inner medullary collecting ducts. The kidney of SHR expresses genes for all the main components of phagocyte NADPH oxidase, RENOX, and MOX1. There is a prominent increase in the SHR kidney of the mRNA, and protein expression of p47phox in the vasculature, macula densa, and distal nephron, which precedes development of hypertension.
Inducible Nitric Oxide Synthase Inhibition Attenuates Renal Hemodynamics During Pregnancy
Authors: Alexander Barbara T. , Cockrell Kathy , Cline Farrah D. , Granger Joey P.
Published: July 2002

Acute, nonselective nitric oxide synthase inhibition in the pregnant rat decreases glomerular filtration rate and renal plasma flow, suggesting a role for nitric oxide in mediating renal vasodilation during pregnancy. As mid-gestation in the rat is associated with a significant increase in renal protein expression of inducible nitric oxide synthase, the aim of this study was to examine the role of inducible nitric oxide synthase in mediating renal hemodynamics changes at mid-gestation in the rat. At day 16 of pregnancy, glomerular filtration rate was significantly higher in pregnant rats compared with virgin rats (3.1±0.4 versus 2.7±0.3 mL/min, respectively;

P

<0.05), as was effective renal plasma flow (13.4±2.5 versus 10.9±2.2 mL/min, respectively;

P

<0.05). Acute administration of the inducible nitric oxide synthase selective inhibitor, AMT hydrochloride (750 nmol/h), markedly attenuated the increase in glomerular filtration rate observed in pregnant rats (2.3±0.2 mL/min,

P

<0.01 versus pregnant) without significantly altering glomerular filtration rate in virgin rats (2.1±0.2 mL/min). Acute AMT administration significantly decreased effective renal plasma flow in pregnant (8.9±1.8 mL/min,

P

<0.01 versus pregnant) and virgin rats (7.1±0.9 mL/min,

P

<0.05 versus virgin). Acute administration of EIT (380 nmol/h), another inducible nitric oxide synthase selective inhibitor, also attenuated pregnancy-induced increases in glomerular filtration rate (2.1±0.2, 2.8±0.3, and 2.3±0.3 mL/min; virgin, pregnant, and EIT, respectively) and effective renal plasma flow (8.5±1.1, 13.8±2.1, and 9.0±1.1 mL/min; virgin, pregnant, and EIT, respectively). Therefore, these findings suggest that inducible nitric oxide synthase may play an important role in mediating the renal hemodynamic changes that occur during normal pregnancy.
Prevalence of Hypertension in Hispanic and non-Hispanic White Populations
Authors: Lorenzo Carlos , Serrano-Rios Manuel , Martinez-Larrad Maria T. , Gabriel Rafael , Williams Ken , Gonzalez-Villalpando Clicerio , Stern Michael P. , Hazuda Helen P. , Haffner Steven
Published: July 2002

Mexican nationals in Mexico City and Mexican Americans in San Antonio, Tex, have a lower adjusted prevalence of hypertension than San Antonio non-Hispanic whites, especially after adjusting for the greater obesity of San Antonio Mexican Americans. The concomitant examination of a new study from Spain may better explain the association of genetic and environmental factors with hypertension. Three population-based epidemiological studies conducted in Mexico City, Spain, and San Antonio, Tex, were available for comparisons. Hypertension was defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or the use of antihypertensive medications. The prevalence of hypertension was independently associated with age, body mass index, glucose tolerance, and alcohol consumption, with comparable degrees of relationship in all 4 populations. Relative to San Antonio non-Hispanic whites, an excess prevalence of hypertension was observed in Spaniards (odds ratio [OR], 1.53; 95% confidence interval [95% CI], 1.24 to 1.90). A deficit in hypertension prevalence was statistically significant in Mexican nationals (OR, 0.67; 95% CI, 0.53 to 0.85) and close to significance in San Antonio Mexican Americans (OR, 0.86; 95% CI, 0.71 to 1.03). Thus, obesity, educational attainment, type 2 diabetes, glucose tolerance, and marked alcohol consumption (≥14 drinks/wk) do not fully explain the increased prevalence of hypertension in Spain and the lower prevalence of hypertension in Mexican-origin populations. Although we cannot conclude definitively that these differences are genetically driven, our results suggest no relationship between Spanish genetic admixture and the deficit in hypertension prevalence in Mexican-origin populations.
Soluble Epoxide Hydrolase Inhibition Lowers Arterial Blood Pressure in Angiotensin II Hypertension
Authors: Imig John D. , Zhao Xueying , Capdevila Jorge H. , Morisseau Christophe , Hammock Bruce D.
Published: July 2002

Epoxyeicosatrienoic acids (EETs) have antihypertensive properties and play a part in the maintenance of renal microvascular function. A novel approach to increase EET levels is to inhibit epoxide hydrolase enzymes that are responsible for conversion of biologically active EETs to dihydroxyeicosatrienoic acids (DHETs) that are void of effects on the preglomerular vasculature. We hypothesized that inhibition of soluble epoxide hydrolase (sEH) would lower blood pressure in angiotensin II (Ang II) hypertension. Rat renal cortical tissue was harvested and urine collected 2 weeks following implantation of an osmotic minipump containing Ang II (60 ng/min). Renal cortical sEH protein expression was significantly higher in Ang II hypertension compared with normotensive animals. Likewise, urinary 14,15-DHET levels were significantly increased in hypertensive compared with normotensive animals and averaged 8.1±1.3 and 2.7±1.1 ng/d; respectively. In additional experiments, the sEH inhibitor N-cyclohexyl-N-dodecyl urea (NCND; 3 mg/d) or vehicle (corn oil, 0.5 mL) was administered daily by intraperitoneal injection starting on day 10. Administration of NCND for 4 days lowered systolic blood pressure by 30 mm Hg in Ang II hypertensive animals, whereas the corn oil vehicle had no effect on blood pressure in normotensive or Ang II hypertensive animals. Measurement of blood pressure by indwelling arterial catheters in conscious animals with free movement in their cages confirmed that NCND had antihypertensive properties. Arterial blood pressure averaged 119±5 mm Hg in normotensive, 170±3 mm Hg in hypertensive and 149±10 mm Hg in NCND-treated, Ang II-infused animals. Administration of the potential metabolite of NCND, N-cyclohexylformamide to Ang II hypertensive rats did not lower the systolic blood pressure. These studies demonstrate that increased sEH expression in the Ang II hypertensive kidney leads to increased EET hydration. Moreover, sEH plays a role in the regulation of blood pressure, and inhibition of sEH during Ang II hypertension is antihypertensive.
Regulation of Intrarenal Angiotensin II in Hypertension
Authors: Navar L. Gabriel , Harrison-Bernard Lisa M. , Nishiyama Akira , Kobori Hiroyuki
Published: July 2002

Intrarenal angiotensin II (Ang II) is regulated by several complex processes involving formation from both systemically delivered and intrarenally formed substrate, as well as receptor-mediated internalization. There is substantial compartmentalization of intrarenal Ang II, with levels in the renal interstitial fluid and in proximal tubule fluid being much greater than can be explained from the circulating levels. In Ang II–dependent hypertension, elevated intrarenal Ang II levels occur even when intrarenal renin expression and content are suppressed. Studies in Ang II–infused rats have demonstrated that augmentation of intrarenal Ang II is due, in part, to uptake of circulating Ang II via an Ang II type 1 (AT
1
) receptor mechanism and also to sustained endogenous production of Ang II. Some of the internalized Ang II accumulates in the light and heavy endosomes and is therefore potentially available for intracellular actions. The enhanced intrarenal Ang II also exerts a positive feedback action to augment intrarenal levels of angiotensinogen (AGT) mRNA and protein, which contribute further to the increased intrarenal Ang II in hypertensive states. In addition, renal AT
1
receptor protein and mRNA levels are maintained, allowing increased Ang II levels to elicit progressive effects. The increased intrarenal Ang II activity and AGT production are associated with increased urinary AGT excretion rates. The urinary AGT excretion rates show a clear relationship to kidney Ang II content, suggesting that urinary AGT may serve as an index of Ang II–dependent hypertension. Collectively, the data support a powerful role for intrarenal Ang II in the pathogenesis of hypertension.
Albuminuria in Hypertension Is Linked to Altered Lysosomal Activity and TGF-β1 Expression
Authors: Russo Leileata M. , Osicka Tanya M. , Bonnet Fabrice , Jerums George , Comper Wayne D.
Published: July 2002

Increased intraglomerular pressure is considered a major factor for increased albumin excretion in hypertension. However, other factors should also be considered because recent studies in both humans and rats have demonstrated that proteins undergoing filtration and renal passage are extensively modified by renal cell lysosomal processing; >95% of albumin is degraded to peptides that are not detected by routine immunochemical assays. Changes in postglomerular lysosomal processing may therefore be responsible for the increased intact albumin excreted in hypertension-related kidney disease. We hypothesize that transforming growth factor-β, which is known to decrease lysosomal activity, may be upregulated in hypertension and may play a role in increased intact albumin excretion. The aims of this study were to determine the effect that hypertension has on (1) renal cell lysosomal processing of albumin and dextran sulfate, (2) glomerular permeability, and (3) renal transforming growth factor-β
1
expression. Spontaneously hypertensive rats and Wistar-Kyoto rats were used at 8, 16, and 24 weeks. We demonstrate that albuminuria in hypertension is linked to an inhibition of lysosomal processing as determined by (1) size exclusion chromatography analysis of urinary [
14
C]albumin structural integrity and (2) ion exchange analysis of urinary [
3
H]dextran sulfate. This inhibition gives rise to an increased proportion of radioimmunoassay detectable (intact) albumin and intact dextran sulfate independent of changes in glomerular capillary wall permeability as determined by the fractional clearance of [
3
H]Ficolls of various radii. These changes may be correlated with increased renal transforming growth factor-β
1
expression.
Prevalence of Left Ventricular Hypertrophy in Hypertensive Patients Without and With Blood Pressure Control
Authors: Mancia Giuseppe , Carugo Stefano , Grassi Guido , Lanzarotti Arturo , Schiavina Riccardo , Cesana Giancarlo , Sega Roberto
Published: July 2002

Previous studies have shown that in the population, only a minority of treated hypertensive patients achieve blood pressure (BP) control. Whether and to what extent this inadequate control has reflection on hypertension-related organ damage has never been systematically examined. In 2051 subjects belonging to the PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) Study population, we measured office, home, and 24-hour ambulatory BP values, together with echocardiographic left ventricular mass and wall thickness. Based on the fraction on antihypertensive treatment and on measurements of increased or normal office, home, or 24-hour ambulatory BP values, subjects were classified as normotensives, untreated hypertensives, treated hypertensives with inadequate BP control, and treated hypertensives with effective BP control. Compared with values in the normotensive group, left ventricular mass index, left ventricular wall thickness, and prevalence of left ventricular hypertrophy were markedly increased not only in untreated hypertensive patients but also in treated hypertensives with inadequate BP control. Echocardiographic abnormalities were less in treated hypertensives with BP control than in patients with inadequate BP control, but values were still clearly greater than in normotensive subjects. This was the case regardless whether BP control was assessed by office, home, and/or ambulatory values. Our data provide evidence that in the hypertensive fraction of the population, cardiac structural alterations can be frequently found in both the presence and absence of antihypertensive treatment. They also imply that even effective treatment of hypertension does not allow complete reversal of the cardiac organ damage characterizing high BP states.
Effect of Endothelin Blockade on Basal and Stimulated Forearm Blood Flow in Patients With Essential Hypertension
Authors: Martin Paul , Ninio Daniel , Krum Henry
Published: July 2002

Endothelin receptor antagonism lowers blood pressure in patients with essential hypertension, but the contribution of the endothelin system to increased vascular tone in these patients remains controversial. We used strain-gauge venous plethysmography to measure changes in basal and metabolically stimulated (peak reactive hyperemia [PRH]) forearm blood flow (FBF) induced by continuous intrabrachial infusion of SB 209670, a dual endothelin type A/endothelin type B receptor antagonist (ETRA) in 11 patients with hypertension and 12 healthy age-matched control subjects. In both groups, ETRA caused significant vasodilation (increase in FBF compared with baseline over the last 30 minutes of ETRA infusion: 75±12% in control subjects, 40±13% in hypertension patients;
P
<0.01 for both groups). By repeated-measures ANOVA, there was no greater increase in FBF after ETRA in hypertension patients compared with control subjects. In addition, FBF responses to PRH, expressed as percent change from baseline (prePRH), were similar in both groups (control subjects: preETRA, 1381±222%; during ETRA, 921±178%; and hypertension patients: preETRA, 1232±221%: during ETRA, 865±285%). We conclude that basal and stimulated vasodilation induced by short-term ETRA infusion in the forearm vasculature of hypertension patients is not increased compared with that of control subjects. An enhanced contribution of the endothelin system to vascular tone in hypertension patients could not be demonstrated using this experimental approach.
Nitric Oxide Modulation of Neurally Induced Proximal Tubular Fluid Reabsorption in the Rat
Authors: Wu Xiao Chun , Johns Edward J.
Published: July 2002

This study investigated the role of NO in mediating the renal sympathetic nerve–mediated increases in proximal tubular fluid reabsorption (Jva). In inactin-anesthetized Wistar rats, renal sympathetic nerve stimulation (15 V, 2 ms) at 0.75 and 1.0 Hz did not change blood pressure or glomerular filtration rate but did decrease urine flow and sodium excretion in a frequency-related fashion by 40% to 50% at 1.0 Hz (both,
P
<0.01). Renal nerve stimulation in control animals increased Jva by 11% at 0.75 Hz (
P
<0.05) and 31% at 1.0 Hz (
P
<0.01). Intraluminal
Nω
-nitro-
l
-arginine methyl ester (L-NAME) resulted in a higher basal Jva (19%,
P
<0.05), and renal nerve stimulation had no effect on Jva. When L-NAME plus sodium nitroprusside was present intraluminally, however, there were frequency-dependent increases in Jva that were similar in pattern and magnitude to the control rats. Introduction of the relatively selective nNOS blocker 7-nitroindazole intraluminally, at 10
−6
and 10
−4
M, raised basal Jva by 18% and 24%, respectively (
P
<0.01), and renal nerve stimulation did not change Jva. Intraluminal aminoguanidine (10
−4
M), a relatively selective iNOS blocker, did not affect basal Jva, which remained unchanged during renal nerve stimulation. These data are consistent with NO exerting a tonic inhibitory action on the basal levels of Jva, which, in part, is caused by NO generated by the nNOS isoform. Moreover, the findings have revealed that the presence of NO is necessary to ensure that renal nerves can stimulate fluid reabsorption by the proximal tubules, requiring NO generated from both nNOS and iNOS.
Blood Pressure Response to Heart Rate During Exercise Test and Risk of Future Hypertension
Authors: Miyai Nobuyuki , Arita Mikio , Miyashita Kazuhisa , Morioka Ikuharu , Shiraishi Tatsuo , Nishio Ichiro
Published: July 2002

Previous works have shown that exaggerated blood pressure response to exercise is a valid risk marker for future hypertension, yet the use of an exercise test as a means of early prediction of hypertension still requires methodological development and confirmation. The purpose of this study was to determine abnormal ranges of blood pressure responses in relation to heart rate increase during exercise and to examine the clinical utility of exercise blood pressure measurement in evaluating individual risk for developing hypertension. We examined exercise test data from a population-based sample of 1033 nonmedicated normotensive men (mean age, 42.9±8.5 years; range, 20 to 59 years). Percentile curves of systolic and diastolic blood pressure responses to relative heart rate increments during submaximal exercise were constructed using a third-order polynomial model with multiple regression analysis. Of the original study sample, a cohort of 726 subjects was followed for hypertensive outcome for an average period of 4.7 years. Progression to hypertension, defined as a blood pressure of ≥140/90 mm Hg or the initiation of antihypertensive therapy, was found in 114 subjects (15.4%). Kaplan-Meier survival estimates showed that the cumulative incidence of hypertension increased progressively with higher percentiles of systolic and diastolic blood pressure response (both,
P
<0.01). A Cox proportional survival analysis revealed a significantly increased risk for developing hypertension associated with exaggerated blood pressure response to exercise after multivariable adjustments for traditional risk factors (relative risk, 3.8; 95% confidence interval, 2.3 to 6.1). These results suggest that an exaggerated blood pressure response to heart rate during exercise is predictive of future hypertension independent of other important risk factors and lend further support to the concept that blood pressure measurement during exercise test is a valuable means of identifying normotensive individuals at high risk for developing hypertension.
Hypoxia-Inducible Factor-1α/Vascular Endothelial Growth Factor Pathway for Adventitial Vasa Vasorum Formation in Hypertensive Rat Aorta
Authors: Kuwahara Fumitaka , Kai Hisashi , Tokuda Keisuke , Shibata Rei , Kusaba Ken , Tahara Nobuhiro , Niiyama Hiroshi , Nagata Tsuyoshi , Imaizumi Tsutomu
Published: July 2002

The roles of adventitial vasa vasorum have been highlighted in vascular wall homeostasis. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor in physiological and pathophysiological conditions. However, little is known regarding the changes in adventitial vasa vasorum and the mechanism of the formation in hypertensive arteries. Accordingly, endothelial cell proliferation, adventitial vasa vasorum count, and expression of VEGF signaling axis proteins were examined in the ascending aorta of hypertensive Wistar rats that underwent suprarenal aortic constriction. Hypertension not only induced medial and adventitial thickening but also significantly increased adventitial vasa vasorum count by day 28. Preceding the medial thickening, BrdU
+
-proliferative endothelial cells were observed in the adventitia but not in the media and intima after day 3; they peaked at day 7 and remained modestly increased at day 28. The BrdU
+
endothelial cells showed induction of Ets-1, a transcription factor mediating angiogenic response of VEGF. Furthermore, concomitant expression of VEGF and a hypoxia-inducible transcription factor (HIF-1α) was observed in the outer layers of medial smooth muscle cells at day 3 and extended to the middle layers of medial smooth muscle cells at day 7, returning to lower levels by day 28. In conclusion, adventitial vasa vasorum formation was induced by hypertension through the HIF-1α/VEGF/Ets-1 pathway during hypertensive remodeling.
The Mulatto Advantage: The Biological Consequences of Complexion in Rural Antebellum Virginia
Authors: Bodenhorn Howard
Published: July 2002

Although historians have long noted that African-Americans of mixed-race in the antebellum Lower South were given economic and social preference over those with darker skin, they have denied that people of mixed race received special treatment in the antebellum Upper South as well. Examination of data on the registrations of free African-Americans in antebellum Virginia, however, reveals that adolescents and adults with lighter complexions tended to have a height advantage, which suggests that they enjoyed better nutrition.
The Historian and Art: A New Maturity
Authors: Rabb Theodore K.
Published: July 2002

The growing use of images by historians is strewn with pitfalls that are not always self-evident. The purpose of an image, its comprehensibility, its audience, the conventions that it observes, and the traditions that it accepts are among many features that can skew its ostensible message. Much about a period or situation can be learned that is otherwise not accessible, but caution is necessary when pictures, artifacts, or buildings are used as historical evidence.
The Quantitative Nature of a Visual Task Differentiates between Ventral and Dorsal Stream
Authors: Fias Wim , Dupont Patrick , Reynvoet Bert , Orban Guy A.
Published: July 2002

The aim of the present positron emission tomography (PET) study was to investigate how visual processing in dorsal and ventral streams depends on the quantitative nature of the task. In the same—different task, participants identified the presence of an orientation difference between two gratings, presented centrally in succession. In the quantification task, participants estimated the magnitude of the difference and compared it to a fixed standard. Detection of dimming of the fixation point was used as a control task. Visual input, motor responses, and performance were equated across tasks. Subtracting same— different from quantification yielded significant activation in the left superior parietal lobule and left ventral premotor cortex, consistent with results obtained in number-processing tasks. The reverse subtraction yielded activation in the right inferior temporal gyrus, in agreement with earlier results. These results demonstrate that a single attribute can be processed either in the ventral or dorsal stream, depending on the cognitive operations required by the tasks.
Using Virtual Environments in the Assessment of Executive Dysfunction
Authors: McGeorge Peter , Phillips Louise H. , Crawford John R. , Garden Sharin E. , Sala Sergio Della , Milne Alan B. , Hamilton Steven , Callender John S.
Published: July 2002

A study is reported into the role of virtual environments in the assessment of patients with executive dysfunction. Five patients and five matched controls entered the study. The patients did not differ significantly from normative values on the standard executive dysfunction measure, the Behavioural Assessment of the Dysexecutive Syndrome battery (Wilson, Alderman, Burgess, Emslie, & Evans, 1996); however, care staff reported the patients had problems planning. Patients and controls undertook both real and virtual environment multiple-errand planning tasks. The patients completed significantly fewer errands, and produced significantly worse plans than did controls in both the real and virtual environments. There was a significant correlation between performance in the real and virtual environments. The results suggest that virtual environments may provide a valid means of assessing planning impairments and that there may be patients with executive dysfunction (specifically planning deficits) that may not be detected by the currently available standardized tests.
Advanced Design Methodologies for the Production of Virtual Learning Environments for Use by People with Learning Disabilities
Authors: Brown David J. , Standen Penny J. , Proctor Tracy , Sterland Dominic
Published: July 2002

The authors have previously presented a methodology to guide the development of virtual learning environments (VLEs) for use by people with learning disabilities (Brown, Neale, Cobb, & Reynolds 1999). This paper presents the results of two sets of studies and shows how these studies enhance this methodology. The first set of studies are user-centered designs for VLE to teach horticultural-related employment, leisure, travel, and public presentation skills to young people with learning disabilities. These projects have allowed us for the first time to distill a set of design guidelines for the production of VLEs for use by people with a learning disability. The second set of studies aims to determine the tutoring strategies employed by support workers, teachers, and care providers when supporting people with learning disabilities using VLEs. These strategies will be embedded in the VLEs to further scaffold the learning process of our target users and allow us to expand the guidance given within the implementation component of the development methodology. These enhancements of the existing methodology are clearly developed within the paper and illustrated diagrammatically.