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Myeloperoxidase (MPO) plays important roles in disease by increasing oxidative and nitrosative stress and oxidizing lipoproteins. Here we report N-acetyl lysyltyrosylcysteine amide (KYC) is an effective inhibitor of MPO activity. We show KYC inhibits MPO-mediated hypochlorous acid (HOCl) formation and nitration/oxidation of LDL. Disulfide is the major product of MPO-mediated KYC oxidation. KYC (≤4,000 μM) does not induce cytotoxicity in bovine aortic endothelial cells (BAECs). KYC inhibits HOCl generation by phorbol myristate acetate (PMA)-stimulated neutrophils and human promyelocytic leukemia (HL-60) cells but not superoxide generation by PMA-stimulated HL-60 cells. KYC inhibits MPO-mediated HOCl formation in BAEC culture and protects BAECs from MPO-induced injury. KYC inhibits MPO-mediated lipid peroxidation of LDL whereas tyrosine (Tyr) and tryptophan (Trp) enhance oxidation. KYC is unique as its isomers do not inhibit MPO activity, or are much less effective. Ultraviolet-visible spectral studies indicate KYC binds to the active site of MPO and reacts with compounds I and II. Docking studies show the Tyr of KYC rests just above the heme of MPO. Interestingly, KYC increases MPO-dependent H₂O₂ consumption. These data indicate KYC is a novel and specific inhibitor of MPO activity that is nontoxic to endothelial cell cultures. Accordingly, KYC may be useful for treating MPO-mediated vascular disease.

Activated leukocytes and polymorphonuclear neutrophils (PMN) release myeloperoxidase (MPO), which binds to endothelial cells (EC), is translocated, and generates oxidants that scavenge nitric oxide (NO) and impair EC function. To determine whether MPO impairs EC function in sickle cell disease (SCD), control (AA) and SCD mice were treated with N-acetyl-lysyltyrosylcysteine-amide (KYC). SCD humans and mice have high plasma MPO and soluble L-selectin (sL-selectin). KYC had no effect on MPO but decreased plasma sL-selectin and malondialdehyde in SCD mice. MPO and 3-chlorotyrosine (3-ClTyr) were increased in SCD aortas. KYC decreased MPO and 3-ClTyr in SCD aortas to the levels in AA aortas. Vasodilatation in SCD mice was impaired. KYC increased vasodilatation in SCD mice more than 2-fold, to ∼60% of levels in AA mice. KYC inhibited MPO-dependent 3-ClTyr formation in EC proteins. SCD mice had high plasma alanine transaminase (ALT), which tended to decrease in KYC-treated SCD mice (P = 0.07). KYC increased MPO and XO/XDH and decreased 3-ClTyr and 3-nitrotyrosine (3-NO₂Tyr) in SCD livers. These data support the hypothesis that SCD increases release of MPO, which generates oxidants that impair EC function and injure livers. Inhibiting MPO is an effective strategy for decreasing oxidative stress and liver injury and restoring EC function in SCD.

The tight skin mouse (Tsk(-/+)) is a model of scleroderma characterized by impaired vasoreactivity, increased oxidative stress, attenuated angiogenic response to VEGF and production of the angiogenesis inhibitor angiostatin. Low-level light therapy (LLLT) stimulates angiogenesis in myocardial infarction and chemotherapy-induced mucositis. We hypothesize that repetitive LLLT restores vessel growth in the ischemic hindlimb of Tsk(-/+) mice by attenuating angiostatin and enhancing angiomotin effects in vivo. C57Bl/6J and Tsk(-/+) mice underwent ligation of the femoral artery. Relative blood flow to the foot was measured using a laser Doppler imager. Tsk(-/+) mice received LLLT (670 nm, 50 mW cm(-2), 30 J cm(-2)) for 10 min per day for 14 days. Vascular density was determined using lycopersicom lectin staining. Immunofluorescent labeling, Western blot analysis and immunoprecipitation were used to determine angiostatin and angiomotin expression. Recovery of blood flow to the ischemic limb was reduced in Tsk(-/+) compared with C57Bl/6 mice 2 weeks after surgery. LLLT treatment of Tsk(-/+) mice restored blood flow to levels observed in C57Bl/6 mice. Vascular density was decreased, angiostatin expression was enhanced and angiomotin depressed in the ischemic hindlimb of Tsk(-/+) mice. LLLT treatment reversed these abnormalities. LLLT stimulates angiogenesis by increasing angiomotin and decreasing angiostatin expression in the ischemic hindlimb of Tsk(-/+) mice., (© 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.)

The present study examined to what extent professional boxing compromises cerebral haemodynamic function and its association with CTBI (chronic traumatic brain injury). A total of 12 male professional boxers were compared with 12 age-, gender- and physical fitness-matched non-boxing controls. We assessed dCA (dynamic cerebral autoregulation; thigh-cuff technique and transfer function analysis), CVRCO₂ (cerebrovascular reactivity to changes in CO₂: 5% CO₂ and controlled hyperventilation), orthostatic tolerance (supine to standing) and neurocognitive function (psychometric tests). Blood flow velocity in the middle cerebral artery (transcranial Doppler ultrasound), mean arterial blood pressure (finger photoplethysmography), end-tidal CO₂ (capnography) and cortical oxyhaemoglobin concentration (near-IR spectroscopy) were continuously measured. Boxers were characterized by fronto-temporal neurocognitive dysfunction and impaired dCA as indicated by a lower rate of regulation and autoregulatory index (P<0.05 compared with controls). Likewise, CVRCO₂ was also reduced resulting in a lower CVRCO₂ range (P<0.05 compared with controls). The latter was most marked in boxers with the highest CTBI scores and correlated against the volume and intensity of sparring during training (r=-0.84, P<0.05). These impairments coincided with more marked orthostatic hypotension, cerebral hypoperfusion and corresponding cortical de-oxygenation during orthostatic stress (P<0.05 compared with controls). In conclusion, these findings provide the first comprehensive evidence for chronically impaired cerebral haemodynamic function in active boxers due to the mechanical trauma incurred by repetitive, sub-concussive head impact incurred during sparring training. This may help explain why CTBI is a progressive disease that manifests beyond the active boxing career.

Hemolysis can saturate the hemoglobin (Hb)/heme scavenging system, resulting in increased circulating cell-free Hb (CF-Hb) in hereditary and acquired hemolytic disease. While recent studies have suggested a central role for intravascular hemolysis and CF-Hb in the development of vascular dysfunction, this concept has stimulated considerable debate. This highlights the importance of determining the contribution of CF-Hb to vascular complications associated with hemolysis. Therefore, a novel Hb-binding peptide was synthesized and linked to a small fragment of apolipoprotein E (amino acids 141-150) to facilitate endocytic clearance. Plasma clearance of hE-Hb-b10 displayed a rapid phase t(1/2) of 16 min and slow phase t(1/2) of 10 h, trafficking primarily through the liver. Peptide hE-Hb-B10 decreased CF-Hb in mice treated with phenylhydrazine, a model of acute hemolysis. Administration of hE-Hb-B10 also attenuated CF-Hb in two models of chronic hemolysis: Berkeley sickle cell disease (SS) mice and mice with severe hereditary spherocytosis (HS). The hemolytic rate was unaltered in either chronic hemolysis model, supporting the conclusion that hE-Hb-B10 promotes CF-Hb clearance without affecting erythrocyte lysis. Interestingly, hE-Hb-B10 also decreased plasma ALT activity in SS and HS mice. Although acetylcholine-mediated facialis artery vasodilation was not improved by hE-Hb-B10 treatment, the peptide shifted vascular response in favor of NO-dependent vasodilation in SS mice. Taken together, these data demonstrate that hE-Hb-B10 decreases CF-Hb with a concomitant reduction in liver injury and changes in vascular response. Therefore, hE-Hb-B10 can be used to investigate the different roles of CF-Hb in hemolytic pathology and may have therapeutic benefit in the treatment of CF-Hb-mediated tissue damage.

Introduction: Although carotid artery stenosis and coronary artery disease often coexist, many debate which patients are best served by combined concurrent revascularization (carotid endarterectomy [CEA]/coronary artery bypass graft [CABG]). We studied the use of CEA/CABG in New England and compared indications and outcomes, including stratification by risk, symptoms, and performing center., Methods: Using data from the Vascular Study Group of New England from 2003 to 2009, we studied all patients who underwent combined CEA/CABG across six centers in New England. Our main outcome measure was in-hospital stroke or death. We compared outcomes between all patients undergoing combined CEA/CABG to a baseline CEA risk group comprised of patients undergoing isolated CEA at non-CEA/CABG centers. Further, we compared in-hospital stroke and death rates between high and low neurologic risk patients, defining high neurologic risk patients as those who had at least one of the following clinical or anatomic features: (1) symptomatic carotid disease, (2) bilateral carotid stenosis >70%, (3) ipsilateral stenosis >70% and contralateral occlusion, or (4) ipsilateral or bilateral occlusion., Results: Overall, compared to patients undergoing isolated CEA at non-CEA/CABG centers (n = 1563), patients undergoing CEA/CABG (n = 109) were more likely to have diabetes (44% vs 29%; P = .001), creatinine >1.8 mg/dL (11% vs 5%; P = .007), and congestive heart failure (23% vs 10%; P < .001). Patients undergoing CEA/CABG were also more likely to take preoperative beta-blockers (94% vs 75%; P < .001) and less likely to take preoperative clopidogrel (7% vs 25%; P < .001). Patients undergoing CEA/CABG had higher rates of contralateral carotid occlusion (13% vs 5%; P = .001) and were more likely to undergo an urgent/emergent procedure (30% vs 15%; P < .001). The risk of complications was higher in CEA/CABG compared to isolated CEA, including increased risk of stroke (5.5% vs 1.2%; P < .001), death (5.5% vs 0.3%; P < .001), and return to the operating room for any reason (7.6% vs 1.2%; P < .001). Of 109 patients undergoing CEA/CABG, 61 (56%) were low neurologic risk and 48 (44%) were high neurologic risk but showed no demonstrable difference in stroke (4.9% vs 6.3%; P = .76), death, (4.9 vs 6.3%; P = .76), or return to the operating room (10.2% vs 4.3%; P = .25)., Conclusions: Although practice patterns in the use of CEA/CABG vary across our region, the risk of complications with CEA/CABG remains significantly higher than in isolated CEA. Future work to improve patient selection in CEA/CABG is needed to improve perioperative results with combined coronary and carotid revascularization., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Dental standards play a vital and important role in society by contributing to the quality and safety levels of products used in dental treatments by dental professionals as well as the hygiene products used by the general public. Few members of the public or indeed many dentists fully appreciate the contribution made by ISO international dental standards to the safety and quality of dental care. Further more the United Kingdom played a significant role in the establishment of the international standards organisation (ISO). The first two meetings of the dental international standards committee took place in England. In this article Derek W. Jones outlines the significant and important role played by the UK during the fifty years of dental international standards.

Morbidly obese patients present safe patient handling challenges to emergency department (ED) personnel. Emergency departments are often ill-equipped to safely manage the patient of this size. The purpose of this study was to develop an assessment tool to determine ED readiness to safely manage the morbidly obese patient. Published guidelines by the Facility Guidelines Institute and the National Association of Bariatric Nurses were used for tool development. The tool assesses policy, equipment, space/structural requirements, and patient handling and -moving tasks. A 2-phase, nonexperimental, exploratory study in a convenience sample of 5 EDs was conducted, applying a usability testing model to determine the usability and utility of the tool. Four of 5 hospital EDs agreed that the tool was easy to use and helpful in determining their readiness to safely manage the morbidly obese patient. The tool was found to be usable on a limited basis. Additional application of the tool on a larger scale is recommended.

Background/objective: Previous clinical trials have documented that soy protein reduces low-density lipoprotein cholesterol and increases high-density lipoprotein (HDL) cholesterol compared with milk protein. However, the effect of soy protein on lipids compared with carbohydrate has not been not well studied. We examined the effect of soy and milk protein supplementation on lipids and lipoproteins compared with carbohydrate among adults without hypercholesterolemia., Subjects/methods: We conducted a randomized, double-blind, 3-phase crossover trial among 352 US adults with serum total cholesterol level of <240 mg/dl from September 2003 to April 2008. Trial participants were assigned to 40 g/day supplementation of soy protein, milk protein or complex carbohydrate from wheat each for 8 weeks in random order with a 3-week washout period between interventions. Overnight fasting blood samples were collected at the termination of each intervention phase., Results: Compared with carbohydrate, soy protein supplementation was significantly associated with a net change (95% confidence interval (CI)) in total cholesterol and total/HDL cholesterol ratio of -3.97 mg/dl (-7.63 to -0.31, P=0.03) and -0.12 (-0.23 to -0.01, P=0.03), respectively. Compared with milk protein, soy protein supplementation was significantly associated with a net change (95% CI) in HDL and total/HDL cholesterol ratio of 1.54 mg/dl (0.63 to 2.44, P=0.0009) and -0.14 (-0.22 to -0.05, P=0.001), respectively. Compared with carbohydrate, milk protein supplementation was significantly associated with a net change (95% CI) in HDL of -1.13 mg/dl (-2.05 to -0.22, P=0.02)., Conclusions: This randomized controlled trial indicates that soy protein, but not milk protein, supplementation improves the lipid profile among healthy individuals.

Adventitial cystic disease of the vein is a rare vascular anomaly with 32 reported cases. A 5-year-old boy initially presented with painless leg swelling. He was misdiagnosed with deep vein thrombosis and treated with 3 months of warfarin. When swelling failed to improve, a magnetic resonance venogram showed a mural cystic lesion of the left common femoral vein. In the operating room, the cyst was excised, relieving the obstructive effect and restoring flow. The swelling resolved within days. This is the first reported case of adventitial cystic disease of the vein occurring in a pediatric patient., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

The apoAI mimetic 4F was designed to inhibit atherosclerosis by improving HDL. We reported that treating tight skin (Tsk(-/+)) mice, a model of systemic sclerosis (SSc), with 4F decreases inflammation and restores angiogenic potential in Tsk(-/+) hearts. Interferon regulating factor 5 (IRF5) is important in autoimmunity and apoptosis in immune cells. However, no studies were performed investigating IRF5 in myocardium. We hypothesize that 4F differentially modulates IRF5 expression and activation in Tsk(-/+) hearts. Posterior wall thickness was significantly increased in Tsk(-/+) compared to C57Bl/6J (control) and Tsk(-/+) mice with 4F treatment assessed by echoradiography highlighting reduction of fibrosis in 4F treated Tsk(-/+) mice. IRF5 in heart lysates from control and Tsk/+ with and without 4F treatment (sc, 1 mg/kg/d, 6-8 weeks) was determined. Phosphoserine, ubiquitin, ubiquitin K(63) on IRF5 were determined on immunoprecipitates of IRF5. Immunofluorescence and TUNEL assays in heart sections were used to determine positive nuclei for IRF5 and apoptosis, respectively. Fluorescence-labeled streptavidin (SA) was used to determine endothelial cell uptake of biotinylated 4F. SA-agarose pulldown and immunoblotting for IRF5 were used to determine 4F binding IRF5 in endothelial cell cytosolic fractions and to confirm biolayer interferometry studies. IRF5 levels in Tsk(-/+) hearts were similar to control. 4F treatments decrease IRF5 in Tsk(-/+) hearts and decrease phosphoserine and ubiquitin K(63) but increase total ubiquitin on IRF5 in Tsk(-/+) compared with levels on IRF5 in control hearts. 4F binds IRF5 by mechanisms favoring association over dissociation strong enough to pull down IRF5 from a mixture of endothelial cell cytosolic proteins. IRF5 positive nuclei and apoptotic cells in Tsk(-/+) hearts were increased compared with controls. 4F treatments decreased both measurements in Tsk(-/+) hearts. IRF5 activation in Tsk(-/+) hearts is increased. 4F treatments decrease IRF5 expression and activation in Tsk(-/+) hearts by a mechanism related to 4F's ability to bind IRF5.

Background: Reports of the effect of low temperatures on ciliary beat frequency (CBF) are conflicting, and the effect on ciliary beat pattern has not been reported. We aimed to clarify this association and determine whether cooling of cilia may allow ciliary function to be assessed without the need of expensive high-speed video microscopy., Methods: Fourteen nasal brush biopsy samples were collected, and the CBF and beat pattern of undisrupted ciliated edges were evaluated. Two methods were used to strictly control changes in temperature: One enabled rapid transitory measurements during cooling and warming, and the other was used to maintain accurate low temperatures over longer periods of time., Results: A sigmoid relationship between CBF and temperature was observed. CBF decreased with cooling and increased with warming. Ciliary function was unaffected by the direction of temperature change and was maintained down to 2°C. The percentage of dyskinetic cilia observed at 2°C or 4°C was unchanged from that at 37°C., Conclusions: Contrary to previous research, our data show that cilia continue to beat with a normal pattern at temperatures as low as 2°C. Slowing of cilia by cooling may allow detailed analysis of ciliary beat pattern without the need of expensive high-speed video microscopy.

Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by oxidative stress, impaired vascular function, and attenuated angiogenesis. The tight-skin (Tsk(-/+)) mouse is a model of SSc that displays many of the cellular features of the clinical disease. We tested the hypotheses that abnormal fibrillin-1 expression and chronic phospholipid oxidation occur in Tsk(-/+) mice and, furthermore, that these factors precipitate a prooxidant state, collagen-related protein expression, apoptosis, and mesenchymal transition in endothelial cells cultured on Tsk(-/+) extracellular matrix. Human umbilical vein endothelial cells were seeded on microfibrils isolated from skin of C57BL/6J (control) and Tsk(-/+) mice in the presence or absence of chronic pretreatment with the apolipoprotein Apo A-I mimetic D-4F (1 mg·kg(-1)·day(-1) ip for 6 to 8 wk). Nitric oxide-to-superoxide anion ratio was assessed 12 h after culture, and cell proliferation, apoptosis, and phenotype were studied 72 h after culture. Tsk(-/+) mice demonstrated abnormal "big fibrillin" expression (405 kDa) by Western blot analysis compared with control. Endothelial cells cultured on microfibrils prepared from Tsk(-/+) mice demonstrated reduced proliferation, a prooxidant state (reduced nitric oxide-to-superoxide anion ratio), increased apoptosis, and collagen-related protein expression associated with mesenchymal transition. Chronic D-4F pretreatment of Tsk(-/+) mice attenuated many of these adverse effects. The findings demonstrate that abnormal fibrillin-1 expression and chronic oxidative stress mediate endothelial mesenchymal transition in Tsk(-/+) mice. This mesenchymal transition may contribute to the reduction in angiogenesis that is known to occur in this model of SSc.

From 2005 to 2006, approximately 3 of 8 adults in the United States had blood pressure (BP) in the prehypertensive range of 120 to 139/80 to 89 mm Hg and roughly 1 in 8 adults had BP in the range of 130 to 139/85 to 89 mm Hg, which is referred to as high normal BP or stage 2 prehypertension. Adults with stage 2 prehypertension are also roughly twice as likely as adults with normotension to suffer cardiovascular disease. The Seventh Report of the Joint National Committee on Hypertension recommended only lifestyle changes for most prehypertensive patients. BP in the range of 120 to 129/80 to 84 mm Hg is also associated with increased risk but roughly half of that of stage 2 prehypertension., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The relationship between high-density lipoprotein and pulmonary function is unclear. To determine mechanistic relationships we investigated the effects of genetic deletion of apolipoprotein A-I (apoA-I) on plasma lipids, paraoxonase (PON1), pro-inflammatory HDL (p-HDL), vasodilatation, airway hyperresponsiveness and pulmonary oxidative stress, and inflammation. ApoA-I null (apoA-I(-/-)) mice had reduced total and HDL cholesterol but increased pro-inflammatory HDL compared with C57BL/6J mice. Although PON1 protein was increased in apoA-I(-/-) mice, PON1 activity was decreased. ApoA-I deficiency did not alter vasodilatation of facialis arteries, but it did alter relaxation responses of pulmonary arteries. Central airway resistance was unaltered. However, airway resistance mediated by tissue dampening and elastance were increased in apoA-I(-/-) mice, a finding also confirmed by positive end-expiratory pressure (PEEP) studies. Inflammatory cells, collagen deposition, 3-nitrotyrosine, and 4-hydroxy-2-nonenal were increased in apoA-I(-/-) lungs but not oxidized phospholipids. Colocalization of 4-hydroxy-2-nonenal with transforming growth factor beta-1 (TGFbeta-1 was increased in apoA-I(-/-) lungs. Xanthine oxidase, myeloperoxidase and endothelial nitric oxide synthase were increased in apoA-I(-/-) lungs. Dichlorodihydrofluorescein-detectable oxidants were increased in bronchoalveolar lavage fluid (BALF) in apoA-I(-/-) mice. In contrast, BALF nitrite+nitrate levels were decreased in apoA-I(-/-) mice. These data demonstrate that apoA-I plays important roles in limiting pulmonary inflammation and oxidative stress, which if not prevented, will decrease pulmonary artery vasodilatation and increase airway hyperresponsiveness.

Objective: To examine the use of surgical procedures for Crohn's disease since the introduction of infliximab., Summary Background Data: Prior studies have shown that the overall rate of surgery for Crohn's disease has not changed significantly since the introduction of infliximab, an immunomodulator considered particularly effective in treating Crohn's fistulas. How infliximab has affected individual rates of specific types of procedures, particularly surgery for intestinal fistulas, is unknown., Methods: We used the Nationwide Inpatient Sample to identify all hospital admissions for Crohn's disease for each year from 1993 through 2004. Cases of Crohn's disease and relevant surgical interventions were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes. Using US Census data to establish population denominators, trends in population-based rates of use of these procedures were examined over time. Trends were tested for significance with Spearman rank correlation tests., Results: From 1993 to 2004, there was no statistically significant change in population-based rates of small bowel and right colon resection, while rates of left colon resection, other colon resection, and rectal resection declined moderately. However, rates of surgical repair of fistulas of the small intestine, the most commonly performed fistula operation, increased by 60%, from 1.5 per 1,000,000 in 1993 to 2.4 per 1,000,000 in 2004 (P = 0.04)., Conclusions: During the period of adoption of infliximab as a novel treatment for Crohn's disease, overall rates of bowel resections have either remained relatively stable or decreased moderately, while rates of small bowel fistula repair have increased significantly. These findings call into question the effectiveness of infliximab in preventing the need for surgery for Crohn's disease at the population level.

Background: A proposed mechanism of intestinal injury in necrotizing enterocolitis (NEC) involves vascular dysfunction through altered nitric oxide synthase (NOS) activity. We hypothesize that this dysfunction results in an imbalance in nitric oxide (*NO) and superoxide (O(2)(*-)) production by the intestinal vascular endothelium, which contributes to the intestinal injury seen in NEC., Materials and Methods: Neonatal rat pups were divided into two groups. Control pups were breast fed and housed with their mother. Experimental NEC pups were housed separately and either exposed to formula feeding and 5% to 10% hypoxia alone (FF/H) or with the addition of lipopolysaccharide (FF/H/LPS). Mesenteries from each group were analyzed for *NO and O(2)(*-) production with and without NOS inhibition by N(G)-monomethyl-L-arginine (L-NMMA). Western blot analysis for eNOS, phosphorylated eNOS (phospho-eNOS), and inducible NOS (iNOS) was performed, and each terminal ileum was graded for intestinal injury by histology., Results: Histology revealed mild intestinal injury (grade 1-2 on a 4-point scale) in the FF/H group and severe injury (grade 3-4) in the FF/H/LPS group. The FF/H cohort had significantly increased *NO and lower O(2)(*-) production, while the FF/H/LPS group shifted to significantly decreased *NO and increased O(2)(*-) production. L-NMMA inhibited >50% of O(2)(*-) production in all three groups but only inhibited *NO production in control and FF/H pups. Western blot analysis revealed increased levels of phospho-eNOS in FF/H pups and increased iNOS in FF/H/LPS pups., Conclusions: This study demonstrates in the progression of NEC, intestinal ischemia is associated with a shift from *NO to O(2)(*-) production, which is NOS-dependent. Potentially greater injury results from impaired vasodilatation and over-production of reactive oxygen species., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Congenital esophageal stenosis (CES) is a rare congenital abnormality that is difficult to diagnose and often masquerades as other types of structural esophageal disease. We report three cases of CES with different presenting symptoms. We advocate for balloon dilation as the preferred first approach to therapeutic intervention. CES is an important clinical entity in the evaluation of pediatric esophageal disorders and should be suspected in young infants with dysphagia.

Introduction: The purpose of this study was to quantify muscle strength and endurance in power grip., Method: Workers (74 M and 74 F, 18-72 years) squeezed a dynamometer for a 60 s, 18-cycle test. Initial strength (IS) and final strength (FS) were calculated as the mean peak force for cycles 1-3 and 16-18, respectively. Endurance was defined by the strength decrement index (SDI) where SDI = (IS - FS)/IS x 100. A grip strength-endurance analyzer was constructed from IS and SDI data which were depicted on two parallel, linearly scaled axes. Discrete IS and SDI scores were connected on each axis with a vector. The vector (Vmag) was measured directly from the analyzer and its direction identified from its slope. Integer scales transformed discrete IS and SDI scores into individual strength-endurance performance scores (SEPS)., Results: Better than 95% of the sample (n > or = 141) scored within acceptable test ranges defined as the combined sample mean +/- 2SD, for SDI, Vmag and SEPS. Vmag was the best predictor for SEPS. Linear regression for SEPS was SEPS (combined) = 0.09 (Vmag) - 0.29: (SEE = 0.829). The analyzer revealed individual scores outside acceptable ranges for injured and uninjured efforts., Conclusion: The development of a power grip strength-endurance analyzer provided a simple method to graph individual power grip performances. Converting strength and endurance scores to integers and summing them (SEPS) provided a simple means to represent individual estimates of power grip strength-endurance performance.

Hypertension prevalence rates in Mississippi are currently the highest in our country. Hypertension treatment and control rates are less than ideal. Our best hope is in prevention of hypertension through healthier lifestyles with more physical activity, fewer calories, and lower dietary sodium intake. A commitment by physicians to overcome clinical inertia and achieve control in most patients will be necessary for us to make progress.

The American Heart Association's (AHA's) mission is "to build healthier lives, free of cardiovascular diseases and stroke." This first article in a 2-part series will serve to present an overview of the work the AHA has undertaken to translate evidence into practice for healthcare professionals. It describes the extensive work of the AHA to support and further the delivery of evidence-based medicine, which includes the following: (1) supporting scientific discovery and the next generation of healthcare professionals and researchers; (2) disseminating scientific information; (3) developing evidence-based guidelines and statements; (4) creating and advocating for the implementation of performance indicators/measures; (5) developing clinical decision support and quality improvement tools; and (6) developing directed-cause campaigns, all of which can lead to improved patient care. This article also discusses the need for novel approaches and some of the AHA's evolving strategies to help address gaps in care. The second article, which will be published shortly after this one, will examine the AHA's efforts to engage and empower healthcare consumers to become more involved with their own health and health care.

Spectrin is the backbone of the erythroid cytoskeleton; sph/sph mice have severe hereditary spherocytosis (HS) because of a mutation in the murine erythroid alpha-spectrin gene. sph/sph mice have a high incidence of thrombosis and infarction in multiple tissues, suggesting significant vascular dysfunction. In the current study, we provide evidence for both pulmonary and systemic vascular dysfunction in sph/sph mice. We found increased levels of soluble cell adhesion molecules in sph/sph mice, suggesting activation of the vascular endothelium. We hypothesized that plasma hemoglobin released by intravascular hemolysis initiates endothelial injury through nitric oxide (NO) scavenging and oxidative damage. Likewise, electron paramagnetic resonance spectroscopy showed that plasma hemoglobin is much greater in sph/sph mice. Moreover, plasma from sph/sph mice had significantly higher oxidative potential. Finally, xanthine oxidase, a potent superoxide generator, is decreased in subpopulations of liver hepatocytes and increased on liver endothelium in sph/sph mice. These results indicate that vasoregulation is abnormal, and NO-based vasoregulatory mechanisms particularly impaired, in sph/sph mice. Together, these data indicate that sph/sph mice with severe HS have increased plasma hemoglobin and NO scavenging capacity, likely contributing to aberrant vasoregulation and initiating oxidative damage.

Hypertension is a major cause of disease burden in all racial and ethnic groups and in both developing and developed regions and countries. Much of the racial and ethnic disparity in cardiovascular outcomes can be attributed to the excess burden of hypertension. Racial and ethnic differences in blood pressure occur because of biology and sociology. Causes of racial differences in blood pressure likely begin early in life and reflect the complex relationship of these gene and environment interactions. Hypertension treatment and control remain less than optimal worldwide, and awareness is still a problem in many racial and ethnic groups. Instituting lifestyle changes for the primary prevention and treatment of hypertension among the general population would decrease prevalence and be effective in eliminating many racial and ethnic differences. This review highlights racial and ethnic differences in the prevalence and incidence of hypertension and identifies contributing factors associated with these differences.

This paper briefly reviews the logic surrounding the controversial banning of dental amalgam by the Norwegian government. The very small contribution from dentistry to environmental mercury pollution and the significant advantages of amalgam as a dental restorative are emphasised.

African Americans have higher reported hypertension prevalence and lower control rates than other ethnic groups in the United States. Hypertension prevalence, awareness, treatment, and control (outcomes) and potentially associated demographic, lifestyle, comorbidity, and health care access factors were examined in 5249 adult participants (3362 women and 1887 men) aged 21 to 94 years enrolled in the Jackson Heart Study. Hypertension prevalence (62.9%), awareness (87.3%), treatment (83.2%), and control (66.4%) were high. Control declined with advancing age; estimates for all of the outcomes were higher for women compared with men. Lower socioeconomic status was associated with prevalence and control. Smoking was negatively associated with awareness and treatment, particularly among men. Comorbidities (diabetes, chronic kidney disease, and cardiovascular disease), likely driven by the high rates of obesity, correlated with hypertension prevalence, awareness, treatment, and control. Lack of health insurance was marginally associated with poorer control, whereas use of preventive care was positively associated with prevalence, awareness, and treatment, particularly among men. In comparisons with the 1994-2004 National Health and Nutrition Examination Survey data adjusted to Jackson Heart Study sex, age, and socioeconomic status distribution, control rates among Jackson Heart Study participants appeared to be higher than in their national counterparts and similar to that of whites. These results suggest that public health efforts to increase awareness and treatment among African Americans have been relatively effective. The Jackson Heart Study data indicate that better control rates can be achieved in this high-risk population.

We have developed a whole blood thrombin generation (TG) assay whereby TG is initiated with a low-tissue factor concentration and monitored using a fluorogenic thrombin substrate. Significantly higher values were found in blood samples from 50 patients with a history of venous thromboembolism (VTE) compared with 31 healthy controls (HC), for peak height (P = 0.0034) and endogenous thrombin potential (ETP) (P = 0.0027). Results from 31 VTE patients and the 31 controls in the absence of corn trypsin inhibitor (CTI) showed significantly higher values in the VTE group for peak height (P = 0.0013) and ETP (P = 0.002). In the presence of CTI, significantly higher values were only seen in ETP (P = 0.024). No significant increases in TG were found using platelet poor (PPP) or -rich (PRP) plasma with or without CTI. The whole blood TG assay in the absence or presence of CTI showed a higher proportion (25/50 and 12/31, respectively) of raised peak height and/or ETP values than plasma assays (PPP 9/50 and 5/31 respectively and PRP 13/50 and 6/31, respectively). Our results show the whole blood TG assay is more sensitive for determining the increases in TG in patients with a history of VTE than PPP and PRP TG assays.

International dental standards are vital in maintaining the safety and quality of both the products and materials used by dental professionals and the many oral health products used by members of the general public, yet many dentists will be unaware of the role standards play in their daily practice. In this article, Derek W. Jones outlines the vital work of the International Standards Organization and highlights how standards pervade nearly every dental procedure.

Systemic sclerosis (scleroderma, SSc) is an autoimmune, connective tissue disorder that is characterized by impaired vascular function, increased oxidative stress, inflammation of internal organs, and impaired angiogenesis. Tight skin mice (Tsk(-/+)) have a defect in fibrillin-1, resulting in replication of many of the myocardial and vascular features seen in humans with SSc. D-4F is an apolipoprotein A-I (apoA-I) mimetic that improves vascular function in diverse diseases such as hypercholesterolemia, influenza, and sickle cell disease. Tsk(-/+) mice were treated with either phosphate-buffered saline (PBS) or D-4F (1 mg.kg(-1).day(-1) for 6-8 wk). Acetylcholine and flow-induced vasodilation were examined in facialis arteries. Proinflammatory HDL (p-HDL) in murine and human plasma samples was determined by the cell-free assay. Angiostatin levels in murine and human plasma samples were determined by Western blot analysis. Hearts were examined for changes in angiostatin and autoantibodies against oxidized phosphotidylcholine (ox-PC). Angiogenic potential in thin sections of murine hearts was assessed by an in vitro vascular endothelial growth factor (VEGF)-induced endothelial cell (EC) tube formation assay. D-4F improved endothelium-, endothelial nitric oxide synthase-dependent, and flow-mediated vasodilation in Tsk(-/+) mice. Tsk(-/+) mice had higher plasma p-HDL and angiostatin levels than C57BL/6 mice, as did SSc patients compared with healthy control subjects. Tsk(-/+) mice also had higher triglycerides than C57BL/6 mice. D-4F reduced p-HDL, angiostatin, and triglycerides in the plasma of Tsk(-/+) mice. Tsk(-/+) hearts contained notably higher levels of angiostatin and autoantibodies against ox-PC than those of control hearts. D-4F ablated angiostatin in Tsk(-/+) hearts and reduced autoantibodies against ox-PC by >50% when compared with hearts from untreated Tsk(-/+) mice. Angiogenic potential in Tsk(-/+) hearts was increased only when the Tsk(-/+) mice were treated with D-4F (1 mg.kg(-1).day(-1), 6-8 wk), and cultured sections of hearts from the D-4F-treated Tsk(-/+) mice were incubated with D-4F (10 microg/ml, 5-7 days). Failure to treat the thin sections of hearts and Tsk(-/+) mice with D-4F resulted in loss of VEGF-induced EC tube formation. D-4F improves vascular function, decreases myocardial inflammation, and restores angiogenic potential in the hearts of Tsk(-/+) mice. As SSc patients have increased plasma p-HDL and angiostatin levels similar to the Tsk(-/+) mice, D-4F may be effective at treating vascular complications in patients with SSc.

Acute lung injury (ALI) carries a high mortality in critically ill patients. Recent reports correlate elevated concentrations of endothelium-derived microparticles (EMPs) with diseases of endothelial dysfunction. Many of these diseases have ALI sequelae. We hypothesize that EMPs contribute to endothelial cell (EC) dysfunction and development of ALI. To test this hypothesis, we treated isolated vessels with EMPs and examined changes in vasodilation. Endothelial cell cultures were incubated with EMPs and examined for changes in stimulated nitric oxide (*NO) production and nitric oxide synthase (eNOS) activation. Finally, EMPs were injected into rats and mice and lungs examined for ALI. In both mouse and human ex vivo vessel preparations, we found a marked attenuation of endothelium-mediated vasodilation after EMP treatment (4 x 10(6)/mL). This dysfunction was not corrected by pretreatment of EMPs with free radical scavengers. Coincubation of EMPs with EC cultures yielded a three-fold reduction in A23187-stimulated *NO release. Western analysis of these cells showed a corresponding decrease in eNOS phosphorylation at Ser1179 and a decrease in hsp90 association. Measurements of lung permeability, myeloperoxidase activity, and histology of EMPs-treated Brown Norway rats demonstrated pulmonary edema, neutrophil recruitment, and compromise of the endothelial-alveolar barrier as a second hit phenomenon. In C57BL/6 mice, exogenous EMPs caused a significant rise in pulmonary capillary permeability both as a primary and secondary injury. These findings demonstrate EMPs are capable of inducing significant lung injury at pathophysiologically relevant concentrations. Endothelium-derived microparticles inhibit endothelium-mediated vasodilation and *NO generation from eNOS. Once elucidated, EMP mechanisms of inducing ALI and endothelial dysfunction may present new therapeutic targets.

Measures of adherence to hypertension guidelines have historically been based on prescription data or physician survey data regarding treatment practices. These methods have limitations that decrease their accuracy. As part of a randomized controlled study testing the effects of pharmacist/physician collaboration on adherence to hypertension guidelines, the investigators and an expert panel developed a JNC 7 measurement tool. The final guideline adherence measurement tool includes 22 explicit criteria in four domains of care. An exploratory factor analysis, conducted to assess the structure of the tool, suggests three underlying treatment dimensions in hypertension care. The adherence measurement tool will allow researchers to link specific elements of care to improved blood pressure control. In addition, use of the tool will provide clinicians with a taxonomy for evaluating practice and describing the effect of improved patient care on patient outcomes., (Journal of Human Hypertension (2006) 20, 426-433. doi:10.1038/sj.jhh.1002005; published online 16 March 2006.)

Previously we showed L-4F, a novel apolipoprotein A-I (apoA-I) mimetic, improved vasodilation in 2 dissimilar models of vascular disease: hypercholesterolemic LDL receptor-null (Ldlr(-/-)) mice and transgenic sickle cell disease mice. Here we determine the mechanisms by which D-4F improves vasodilation and arterial wall thickness in hypercholesterolemic Ldlr(-/-) mice and Ldlr(-/-)/apoA-I null (apoA-I(-/-)), double-knockout mice. Ldlr(-/-) and Ldlr(-/-)/apoA-I(-/-) mice were fed Western diet (WD) with and without D-4F. Oral D-4F restored endothelium- and endothelial NO synthase (eNOS)-dependent vasodilation in direct relationship to duration of treatments and reduced wall thickness in as little as 2 weeks in vessels with preexisting disease in Ldlr(-/-) mice. D-4F had no effect on total or HDL cholesterol concentrations but reduced proinflammatory HDL levels. D-4F had no effect on plasma myeloperoxidase concentrations but reduced myeloperoxidase association with apoA-I as well as 3-nitrotyrosine in apoA-I. D-4F increased endothelium- and eNOS-dependent vasodilation in Ldlr(-/-)/apoA-I(-/-) mice but did not reduce wall thickness as it had in Ldlr(-/-) mice. Vascular endothelial cells were treated with 22(R)-hydroxycholesterol with and without L-4F. 22(R)-Hydroxycholesterol decreased NO (*NO) and increased superoxide anion (O2*-) production and increased ATP-binding cassette transporter-1 and collagen expression. L-4F restored *NO and O2*- balance, had little effect on ATP-binding cassette transporter-1 expression, but reduced collagen expression. These data demonstrate that although D-4F restores vascular endothelial cell and eNOS function to increase vasodilation, HDL containing apoA-I, or at least some critical concentration of the antiatherogenic lipoprotein, is required for D-4F to decrease vessel wall thickness.

Background: The contact system (CS) proteins, factor XII and prekallikrein are thought to have roles in blood coagulation and fibrinolysis. Recent research has suggested that the CS proteins might be more important in fibrinolysis and cell function than in coagulation. Most studies on fibrinolysis have used plasma or euglobulin assays, ignoring the influence of cellular elements of blood on the fibrinolytic process., Objective and Methods: In order to study both coagulation and fibrinolysis in whole blood (WB), we have developed a thromboelastography (TEG) assay to investigate both coagulation and fibrinolysis in the same blood sample. In this assay, named urokinase (UK) induced fibrinolysis in thromboelastography (UKIFTEG), TEG is performed on recalcified citrated WB in the presence of UK. Large variations in Ly60 (percentage lysis 60 min after clot formation) were obtained between different donors with the same UK concentration. The UKIFTEG assay was therefore performed using UK concentrations that gave Ly60 values in the approximate range of 20-40%., Results: The effect of CS activation was investigated in the presence or absence of celite (10 mg mL(-1) blood). Celite shortened the clotting time (CT), and increased Ly60 values. Factor XIIa (FXIIa) and plasma kallikrein (KK) produced concentration dependent reductions in CT (significant at concentrations of 1303 and 2600 ng mL(-1) blood, respectively) and increased Ly60 values (significant at concentrations of 652 and 1300 ng mL(-1) blood, respectively)., Conclusions: Our results show that CS activation and both FXIIa and KK produce reductions in clotting time and enhanced fibrinolysis in UKIFTEG.

Objective: To investigate whether the favourable cardiovascular disease (CVD) risk factor profile of habitual exercisers is attributable to exercise or leanness., Design: Cross-sectional study of 113 nonsmoking men aged 30-45 y. CVD risk factors were compared in exercisers (n=39) and sedentary men (n=74), and in subgroups of lean exercisers (n=37), lean sedentary men (n=46) and obese sedentary men (n=28). Waist girth was used to identify lean (<100 cm) and abdominally obese (> or =100 cm) subgroups., Measurements: Blood pressure, physical activity (7-day recall), physical fitness (maximum oxygen consumption) and fasted lipoproteins, apolipoprotein (apo) B, triglycerides, glucose and fibrinogen., Results: Exercisers were fitter and leaner than sedentary men and had a better CVD risk factor profile. Total cholesterol, LDL-cholesterol and apo B concentrations were lower in lean exercisers than in lean sedentary men, suggesting that exercise influences these risk factors. Indeed, time spent in vigorous activity was the only significant predictor of total cholesterol and LDL-cholesterol in multiple linear regression models. Exercise status had little influence on triglycerides and HDL-cholesterol (HDL-C), and unfavourable levels were only evident among obese sedentary men. Waist girth was the sole predictor of triglycerides and HDL-C, explaining 44 and 31% of the variance, respectively., Conclusions: These findings suggest that the CVD risk factor profile of habitual exercisers is attributable to leanness and exercise. Leanness is associated with favourable levels of HDL-C and triglycerides, while exercise is associated with lower levels of total cholesterol, LDL-cholesterol and apo B.

Objective: The design, overall methods, and major phenotypes for the all-African-American Jackson Heart Study (JHS) are detailed., Methods: Participants were enrolled from the three counties that make up the Jackson, Mississippi metropolitan area. Relatives of selected participants were recruited to develop a large, nested family cohort. Participants provided extensive medical and social history, had an array of physical and biochemical measurements and diagnostic procedures, and provided genomic DNA., Results: Data and biologic materials have been collected from 5302 adult African Americans, including 1499 members of 291 families. Participants have a high prevalence of diabetes, hypertension, obesity, and related disorders., Discussion: The JHS dataset and biologic materials (serum, DNA, and cryopreserved cells) offer a valuable resource for the study of diseases that are of particular importance to African Americans.

High-resolution single-photon emission computed tomography (SPECT) imaging in small animals tends to use long imaging times and large injected doses due to the poor sensitivity of single pinhole gamma cameras. To increase sensitivity while maintaining spatial resolution, we designed and constructed a multipinhole collimator array to replace the parallel hole collimators of a Ceraspect human SPECT brain scanner. The Ceraspect scanner is composed of an annular NaI(TI) crystal within which the eight pinhole collimators (1-mm-diameter holes) rotate while projecting nonoverlapping images of the object onto the stationary annular crystal. In this manner, only one-eighth of a collimator rotation is required to acquire a full circle orbit tomographic data set. The imaging field of view (FOV) has a diameter of 25.6 mm in the transverse direction, which is sufficient to encompass a mouse in the transverse direction. The axial FOV is 25.6 mm at the center of the FOV and 13.9 mm at the edge of the transverse FOV. Data are currently acquired in step-and-shoot mode; however, the system is capable of list mode acquisition with the collimator continuously rotating. Images are reconstructed using a cone-beam ordered subsets expectation maximization method. The reconstructed spatial resolution of the system is 1.7 mm and the sensitivity at the center of the FOV is 13.8 cps/microCi. A whole-body bone scan of a mouse injected with [Tc-99 m]MDP clearly revealed skeletal structures such as the ribs and vertebral bodies. These preliminary results suggest that this approach is a good tradeoff between resolution and sensitivity and, with further refinement, may permit dynamic imaging in living animals.

A 64-year-old woman was transferred for investigation of a mediastinal mass, biopsy of which showed a diffuse large B-cell lymphoma. She was also found to have an antiphospholipid antibody. The pre-operative coagulation screen showed a prolonged activated partial thromboplastin time, 71.3 s (normal range, 26-36 s), which was not corrected by the addition of normal plasma. The dilute Russell's viper venom time was positive. Anti-cardiolipin assay was strongly positive, immunoglobulin M was 153 AU; immunoglobulin G was normal, 3.1 AU. Assays of factors VIII, IX and XI showed higher concentrations with increasing dilutions in one-stage factor assays from 1: 10 to 1: 80 suggestive of an inhibitor. Factor XII was 9 U/dl and results were unaffected by increasing dilution, suggesting specific antibodies to factor XII. The factor XII antigen was 40 U/dl. The patient had immunoglobulin M auto-antibodies to factor XII.

This study was designed to investigate the effect of exercise intensity on cardiorespiratory fitness and coronary heart disease risk factors. Maximum oxygen consumption (Vo(2 max)), lipid, lipoprotein, and fibrinogen concentrations were measured in 64 previously sedentary men before random allocation to a nonexercise control group, a moderate-intensity exercise group (three 400-kcal sessions per week at 60% of Vo(2 max)), or a high-intensity exercise group (three 400-kcal sessions per week at 80% of Vo(2 max)). Subjects were instructed to maintain their normal dietary habits, and training heart rates were represcribed after monthly fitness tests. Forty-two men finished the study. After 24 wk, Vo(2 max) increased by 0.38 +/- 0.14 l/min in the moderate-intensity group and by 0.55 +/- 0.27 l/min in the high-intensity group. Repeated-measures analysis of variance identified a significant interaction between monthly Vo(2 max) score and exercise group (F = 3.37, P < 0.05), indicating that Vo(2 max) responded differently to moderate- and high-intensity exercise. Trend analysis showed that total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and fibrinogen concentrations changed favorably across control, moderate-intensity, and high-intensity groups. However, significant changes in total cholesterol (-0.55 +/- 0.81 mmol/l), low-density lipoprotein cholesterol (-0.52 +/- 0.80 mmol/l), and non-high-density lipoprotein cholesterol (-0.54 +/- 0.86 mmol/l) were only observed in the high-intensity group (all P < 0.05 vs. controls). These data suggest that high-intensity training is more effective in improving cardiorespiratory fitness than moderate-intensity training of equal energy cost. These data also suggest that changes in coronary heart disease risk factors are influenced by exercise intensity.

The polarized Raman spectra of partially deuteriated taurine [(ND3+)0.65(NH3+)0.35(CH2)2SO3-] crystals from x(zz)x and x(zy)x scattering geometries of the Ag and Bg irreducible representations of the factor group C2h are reported. The temperature-dependent Raman spectra of partially deuteriated taurine do not reveal any evidence of the structural phase transition undergone by normal taurine at about 250 K, but an anomaly observed in the 180 cm-1 band at approximately 120 K implies a different dynamic for this band (which is involved in a pressure-induced phase transition) in the deuteriated crystal.

Phospholipid binding proteins, including factor XII (FXII), are known to be targeted by antiphospholipid antibodies (aPA). Factor XII antibodies (FXIIab) have been described in some patients with the antiphospholipid syndrome (APS) and have been shown to lead to reduced levels of FXII. The antigenic binding site(s) and the pathophysiological effects of FXIIab are unknown. In an attempt to elucidate the binding site of these antibodies, immobilized plasma kallikrein was used to cleave FXII into its 52-kDa heavy-chain (HCFXII) and 28-kDa light-chain (LCFXII) components. Plasma samples from 12 female patients with definite APS and FXIIab were investigated for the presence of antibodies to FXII, HCFXII and LCFXII. All but one patient's plasma reacted to FXII, HCFXII and LCFXII in a similar manner. One patient gave markedly reduced positivity to HCFXII and LCFXII, suggesting that the FXIIab in this patient had a higher affinity for the intact FXII molecule. To further investigate the antigenic binding site(s) of FXII, 150 biotinylated peptides of the known FXII sequence were synthesized using a Multipin(TM) peptide synthesis procedure. The IgG and IgM fractions of the 12 patients' plasma were purified by affinity chromatography. The synthesized peptides were captured on streptavidin plates and individual patients' purified FXIIab assayed against the peptides in a modified enzyme-linked immunosorbent assay (ELISA). Two regions were identified as possible antigenic binding site(s) for FXIIab: one in the growth factor domain and the other in the catalytic domain.

The structural variability of lateral ventricles is poorly understood notwithstanding that enlarged size has been identified as an unspecific marker for psychiatric illness, including schizophrenia. This paper explores the effects of heritability and genetic risk for schizophrenia reflected in ventricular size and structure. We examined ventricular size and shape in the MRI studies of monozygotic (MZ) twin pairs discordant for schizophrenia (DS), healthy MZ twin pairs, healthy dizygotic twin pairs, and healthy nonrelated subject pairs. Heritability and effect due to disease were analyzed in two tests. First, heritability was examined by ventricle similarity between pairs of co-twins. Results show that co-twin ventricle shape similarity decreases with decreasing genetic identity, an effect not seen in the volume analysis. Co-twin shape similarity of healthy MZ twins did not differ from DS MZ twins. Second, the disease effect was examined through the ventricular differences of DS subjects to a template shape representing healthy subjects. Affected DS twins showed shape differences from healthy subjects on the left and right sides. Interestingly, unaffected DS twins also showed significant shape differences from healthy subjects for both sides. Volume comparisons did not show differences between these groups. Locality of shape difference suggests that the ventricular shape of the anterior and posterior regions is under genetic influence in both healthy controls and schizophrenia patients. Affected and unaffected groups demonstrate main shape differences, compared with healthy controls, only in the posterior region. Our results suggest that genetics have a stronger influence on the shape of lateral ventricles than do the disease-related changes in schizophrenia.

Accurate measurement of blood pressure is essential to classify individuals, to ascertain blood pressure-related risk, and to guide management. The auscultatory technique with a trained observer and mercury sphygmomanometer continues to be the method of choice for measurement in the office, using the first and fifth phases of the Korotkoff sounds, including in pregnant women. The use of mercury is declining, and alternatives are needed. Aneroid devices are suitable, but they require frequent calibration. Hybrid devices that use electronic transducers instead of mercury have promise. The oscillometric method can be used for office measurement, but only devices independently validated according to standard protocols should be used, and individual calibration is recommended. They have the advantage of being able to take multiple measurements. Proper training of observers, positioning of the patient, and selection of cuff size are all essential. It is increasingly recognized that office measurements correlate poorly with blood pressure measured in other settings, and that they can be supplemented by self-measured readings taken with validated devices at home. There is increasing evidence that home readings predict cardiovascular events and are particularly useful for monitoring the effects of treatment. Twenty-four-hour ambulatory monitoring gives a better prediction of risk than office measurements and is useful for diagnosing white-coat hypertension. There is increasing evidence that a failure of blood pressure to fall during the night may be associated with increased risk. In obese patients and children, the use of an appropriate cuff size is of paramount importance.