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James D Cameron,1 Roland Asmar,2 Harry Struijker-Boudier,3 Kohji Shirai,4 Yuriy Sirenko,5 Yulia Kotovskaya,6 Jirar Topouchian71Monash Cardiovascular Research Centre, Clayton, Melbourne, Victoria, Australia; 2Roland Asmar, Foundation Medical Research Institutes, Paris, France; 3Department of Pharmacology, Maastricht University, Maastricht, The Netherlands; 4Department of Vascular Function, Sakura Hospital, Toho University, Tokyo, Japan; 5Institute of Cardiology, Kiev, Ukraine; 6ESH Hypertension Excellence Center of Peoples Friendship University of Russia, Moscow, Russia; 7Department of Diagnosis and Therapeutics, Hôtel-Dieu University Hospital, Paris, FranceAbstract: Central arterial structure and function comprise a primary determinant of vascular health, and are integral to the important concept of ventriculo-vascular coupling or interaction. Central aortic stiffening is a major influence on central blood pressure, and directly relates to coronary perfusion. The joint session of the International Society of Vascular Health (Eastern Region) and the Ukrainian Congress of Cardiology was held in Kiev, Ukraine, on September 23, 2011; it provided an expert forum to discuss arterial evaluations, clinical applications, and progress toward translating arterial protection into cardiovascular benefits. The conclusions of the expert panel were:1. Aortic stiffness is not presently a treatment target but may be useful for substratifying cardiovascular risk in individuals in order to better target the intensity of conventional therapy, and it may be useful in assessing response to treatment.2. Crosstalk between macro- and microcirculation in hypertension has important implications for pharmacological treatment. An antihypertensive regimen should abolish the vicious cycle between the increased resistance in the microcirculation and the increased stiffness of the larger arteries. Such treatment should be based on drugs with multiple actions on the vascular tree, or on drug combinations that target the various segments of the arterial system.3. Several blood pressure-independent mechanisms of large artery stiffness exist. Future considerations for clinical understanding of large artery stiffness should involve new drugs and new evaluation methods – with a focus on vascular health, for the initiation of cardiovascular prevention, for newly designed studies for treatment evaluation, and for new studies of drug combinations.4. Arterial stiffening is a sign of cardiovascular aging and is a major factor affecting the biomechanics of large arteries. Arterial stiffness is an attractive therapeutic target in terms of vascular aging. Healthy lifestyle, physical exercise, and smoking cessation are the most effective ways of preventing and treating early vascular aging. Long-term effects of cardiovascular drugs on arterial stiffness need to be further investigated.5. The emerging clinical data on the cardio ankle vascular index (CAVI) technique of arterial health assessment is presented, showing that the CAVI is elevated in aging, coronary artery diseases, chronic kidney disease, hypertension, diabetes mellitus, smoking, and stress. The CAVI decreased with the administration of statins, angiotensin II receptor blocking agents, and calcium channel blockers. The CAVI is suggested as an important predictor of cardiovascular diseases.Future development of a clinical understanding of large artery stiffness is important and should include consideration of new drugs and new evaluation methods, with a focus on vascular health aimed at cardiovascular prevention.Keywords: arterial stiffness, cardiovascular protection, hypertension, arterial hemodynamic evaluation

Gary S Goldfield,1–5 Lauren Marie Dowler,5 Mark Walker,6,7 Jameason D Cameron,3 Zachary M Ferraro,1 Eric Doucet,3 Kristi B Adamo1–31Healthy Active Living and Obesity Research Group, Children's Hospital of Eastern Ontario Research Institute, 2Department of Paediatrics, 3School of Human Kinetics, 4School of Psychology, University of Ottawa, 5Department of Psychology, Carleton University, 6Ottawa Hospital Research Institute, 7Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, ON, CanadaBackground: Excessive gestational weight gain is associated with postpartum weight retention and downstream child obesity. Dopamine plays a critical role in the regulation of energy intake and body weight. The purpose of this study was to examine the relationship between excessive gestational weight gain and dopamine pathway-related polymorphisms, namely the variable nucleotide tandem repeat in the 3´untranslated region (UTR) region of the SLC6A3 (DAT-1) dopamine transporter gene and the 30-base pair variable nucleotide tandem repeat polymorphism of the 5´UTR of the monoamine oxidase-A (MAO-A) gene.Methods: Ninety-three women of mean age 31.7 ± 4.2 years were recruited from the Ottawa and Kingston birth cohort and assessed at 12–20 weeks’ gestation. Mean body mass index was 22.7 ± 2.5 kg/m2. Excessive gestational weight gain was defined according to the 2009 Institute of Medicine guidelines based on body mass index. Genotype analyses were performed using polymerase chain reaction and agarose gel electrophoresis.Results: There was no relationship between the prevalence or magnitude of excessive gestational weight gain among women with the 3´ UTR single nucleotide polymorphism of the DAT-1 gene. However, 70% (19 of 27) of women carrying the MAO-A 4/4 (high activity) allele exceeded recommendations for gestational weight gain compared with 48% (32 of 60) of those with the pooled 3/3, 3/4, and 3/3.5 (low activity) alleles (P < 0.05). Similarly, those with the MAO-A 4/4 allele had significantly greater gestational weight gain than those with the 3/3, 3/4, or 3/3.5 pooled genotypes (19.3 ± 4.1 versus 17.0 ± 5.0 kg, P = 0.03).Conclusion: Carriers of the 4/4 variants of the MAO-A gene may be at increased risk for excessive gestational weight gain.Keywords: gestational weight gain, dopamine genes, monoamine oxidase-A

Sohei Nakamura1, Naofumi Hikita2, Ryoji Yamakawa1, Fukuko Moriya3, Hirohisa Yano3, Emiko Furusato4, J Douglas Cameron5, Elisabeth J Rushing41Department of Ophthalmology, Kurume University School of Medicine, Kurume, 2Fukubiru Hikita Eye Clinic, 3Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan; 4Department of Neuropathology and Ophthalmic Pathology, Armed Forces Institute of Pathology, Washington, DC, 5Departments of Ophthalmology and Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, USABackground: Adenoma of the retinal pigment epithelium (RPE) is a rare intraocular tumor that can simulate other pigmented tumors such as choroidal melanoma. We report a case of non-pigmented adenoma of the RPE initially diagnosed as choroidal hemangioma.Case report: A 42-year-old woman presented to Kurume University Hospital in November 1992 with an orange-yellow tumor nasal to the optic disc in the left fundus. The tumor was 9.0 × 9.0 mm in diameter, 6.0 mm thick, and was characterized by high intensity on T1-weighted magnetic resonance imaging (MRI), low intensity on T2-weighted MRI, and enhancement on gadolinium MRI. Fluorescein angiography revealed early hypofluorescence and late hyperfluorescence of the tumor and retinal feeder vessels. By April 1996, exudate had developed around the tumor margins. The patient was treated with external beam radiation therapy (20 Gy) in July 1996, but the tumor did not diminish in size. Subsequently, she developed extensive loss of vision due to total retinal detachment. Accordingly, her left eye was enucleated in June 2005 because of severe ocular pain due to absolute glaucoma. Histopathological examination indicated that the tumor was contiguous with the normal surrounding RPE and was composed of cords and tubules of mostly non-pigmented spindle-shaped cells with round to oval nuclei and a small amount of cytoplasm containing melanin granules. The tumor cells were immunoreactive for vimentin, S-100 protein, and cytokeratin 18. The final diagnosis was adenoma of the RPE.Conclusion: Adenoma of the retinal pigment epithelium may be associated with incompetent vessels leading to serous retinal detachment and extensive visual loss, and may exhibit clinical characteristics similar to choroidal hemangioma.Keywords: adenoma, choroidal hemangioma, histopathology, retinal pigment epithelium

Changes in smell function can modify feeding behaviour but there is little evidence of how acute negative energy balance may impact olfaction and palatability. In a within-subjects repeated measures design, 15 subjects (nine male; six female) aged 28.6±4.5 years with initial body weight (BW) 74.7±4.9 kg and body mass index (BMI) 25.3±1.4 kg/m(2) were randomized and tested at baseline (FED) and Post Deprivation (FASTED) for nasal chemosensory performance (Sniffin' Sticks) and food palatability (visual analogue scale). Significant main effects for time indicated improvements in the FASTED session for odor threshold, odor discrimination, and total odor scores (TDI), and for increased palatability. There were significant positive correlations between initial BW and the change in odor threshold (r=.52) and TDI scores (r=.53). Positive correlations were also noted between delta identification score and delta palatability (r=.68). When the sample was split by sex, only for females were there significant correlations between delta palatability and: delta BW (r=.88); delta odor identification (r=.94); and delta TDI score (r=.85). Fasting for 24h improved smell function and this was related to increased palatability ratings and initial BW. Further studies should confirm the role of BW and sex in the context of olfaction, energy deprivation and palatability. [ABSTRACT FROM AUTHOR]

BACKGROUND: Indices of arterial structure and stiffness are proposed as surrogate markers of cardiovascular disease in patients with chronic kidney disease (CKD), but no study examined multiple markers in the same population. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 315 subjects with stages 4 to 5 CKD, aged 24 to 79 years (mean age, 56.6 +/- 13.6 [SD] years), enrolled in the Atherosclerosis and Folic Acid Supplementation Trial. PREDICTORS: Carotid arterial intima-medial thickness (IMT; n = 315) and indices of arterial stiffness (n = 207), including aortofemoral pulse wave velocity (PWV[a-f]), systemic arterial compliance (SAC), and carotid-derived augmentation index. OUTCOMES: The primary outcome was a composite of all fatal and nonfatal cardiovascular events. RESULTS: During follow-up (median, 3.6 years), 95 cardiovascular events occurred. On Cox proportional-hazard modeling, mean maximum IMT, PWV(a-f), and SAC were predictive of the composite clinical end point of all cardiovascular events, but carotid-derived augmentation index was not (hazard ratio [HR] for every 0.01-mm increase in IMT, 1.09; P = 0.001; 95% confidence interval [CI], 1.03 to 1.14; HR for every 1-m/s increase in PWV(a-f), 1.18; P < 0.001; 95% CI, 1.12 to 1.25; HR for every 0.01-U/mm Hg decrease in SAC, 0.98; P = 0.01; 95% CI, 0.97 to 0.99). After adjustment for age, sex, blood pressure, diabetes, past cardiovascular disease, cholesterol level, and smoking, PWV(a-f) remained a significant independent predictor of cardiovascular events (adjusted HR, 1.12; P = 0.001; 95% CI, 1.05 to 1.20), but IMT and SAC did not. LIMITATIONS: Study power to analyze differences between predialysis and dialysis stages of CKD. CONCLUSIONS: PWV(a-f) is the only arterial index independently associated with cardiovascular outcome in patients with CKD. Copyright © 2007 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

Critical to the clinical management of a patient with malignant melanoma is an understanding of its natural history. As with most malignant disorders, prognosis is highly dependent on the clinical stage (extent of tumor burden) at the time of diagnosis. The patient's clinical stage at diagnosis dictates selection of therapy. We review the state of the art in melanoma staging, prognosis, and therapy. Substantial progress has been made in this regard during the past 2 decades. This progress is primarily reflected in the development of sentinel lymph node biopsies as a means of reducing the morbidity associated with regional lymph node dissection, increased understanding of the role of neoangiogenesis in the natural history of melanoma and its potential as a treatment target, and emergence of innovative multimodal therapeutic strategies, resulting in significant objective response rates in a disease commonly believed to be drug resistant. Although much work remains to be done to improve the survival of patients with melanoma, clinically meaningful results seem within reach. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study was to determine factors contributing to the biomechanical properties of coronary arteries in people with and without angiographic coronary artery disease (CAD).Background: The stiffness of the aorta is known to increase with increasing age and in the presence of CAD. However, little is known about the mechanics of coronary arteries, which may have important clinical consequences.Methods: Intravascular ultrasound was used to determine the mechanical properties of coronary arteries and plaque behavior in subjects with CAD (n = 38), those with chest pain but angiographically normal coronary arteries (N) (n = 9) and those early (<2 weeks) after cardiac transplant (T) (n = 14).Results: Coronary arteries dilated during systole in all groups, but cross-sectional compliance and distensibility were lowest in the proximal left anterior descending artery (LAD) in the subjects with CAD compared with the N and T groups (compliance: 1.2 +/- 0.2 vs. 1.7 +/- 0.5 and 2.7 +/- 0.6 x 10(-2) mm(2) mm Hg(-1) [mean +/- SEM] respectively, p < 0.02 CAD vs. T; distensibility: 0.8 +/- 0.2 vs. 1.7 +/- 0.5 and 1.7 +/- 0.3 x 10(-3) mm Hg(-1), p < 0.05 CAD vs. T). There was extensive plaque in the CAD group, and plaque was also present in the N group, but minimal atheroma was present in the T group. Plaque cross-sectional area diminished significantly during systole in both the LAD and circumflex arteries. Absolute changes were: 0.50 +/- 0.30, 0.33 +/- 0.11 and 0.68 +/- 0.13 mm(2) in the proximal LAD, distal LAD and proximal circumflex arteries, respectively. In subjects with atheroma, there was a significant correlation between cross-sectional compliance and plaque compression at all sites, and plaque compression was a significant determinant of cross-sectional compliance at both proximal sites in multiple regression analyses with age, mean arterial pressure and extent of plaque as the other independent variables.Conclusions: A major determinant of the systolic increase in coronary luminal area in patients with atheroma is a reduction in plaque cross-sectional area during systole. [ABSTRACT FROM AUTHOR]

Objectives: We sought to investigate the effects of intensive cholesterol reduction on large artery stiffness and blood pressure in normolipidemic patients with isolated systolic hypertension (ISH).Background: Isolated systolic hypertension is associated with elevated cardiovascular morbidity and mortality and is primarily due to large artery stiffening, which has been independently related to cardiovascular mortality. Cholesterol-lowering therapy has been efficacious in reducing arterial stiffness in patients with hypercholesterolemia, and thus may be beneficial in ISH.Methods: In a randomized, double-blinded, cross-over study design, 22 patients with stage I ISH received three months of atorvastatin therapy (80 mg/day) and three months of placebo treatment. Systemic arterial compliance was measured noninvasively using carotid applanation tonometry and Doppler velocimetry of the ascending aorta.Results: Atorvastatin treatment reduced total and low-density lipoprotein cholesterol and triglyceride levels by 36 +/- 2% (p < 0.001), 48 +/- 3% (p < 0.001) and 23 +/- 5% (p = 0.003), respectively, and increased high density lipoprotein cholesterol by 7 +/- 3% (p = 0.03). Systemic arterial compliance was higher after treatment (placebo vs. atorvastatin: 0.36 +/- 0.03 vs. 0.43 +/- 0.05 ml/mm Hg, p = 0.03). Brachial systolic blood pressure was lower after atorvastatin treatment (154 +/- 3 vs. 148 +/- 2 mm Hg, p = 0.03), as were mean (111 +/- 2 vs. 107 +/- 2 mm Hg, p = 0.04) and diastolic blood pressures (83 +/- 1 vs. 81 +/- 2 mm Hg, p = 0.04). There was a trend toward a reduction in pulse pressure (71 +/- 3 vs. 67 +/- 2 mm Hg, p = 0.08).Conclusions: Intensive cholesterol reduction may be beneficial in the treatment of patients with ISH and normal lipid levels, through a reduction in large artery stiffness. [ABSTRACT FROM AUTHOR]

The brain derived-neurotrophic factor (BDNF) Val66Met polymorphism causes functional changes in BDNF, and is associated with obesity and some psychiatric disorders, but its relationship to health-related quality of life (HRQoL) remains unknown. This study examined, in youth with obesity, whether carriers of the BDNF Val66met polymorphism Met-alleles (A/A or G/A) differed from noncarriers (G/G) on HRQoL. The participants were 187 adolescents with obesity. Ninety-nine youth were carriers of the homozygous Val/Val (G/G) alleles, and 88 were carriers of the Val/Met (G/A) or Met/Met (A/A) alleles. Blood samples were drawn in the morning after an overnight fast for genotyping. HRQoL was measured using the Pediatric-Quality of Life core version. Compared to carriers of the Val66Met Val (G/G) alleles, carriers of the Met-Alleles reported significantly higher physical -HRQoL (p = 0.02), school-related HRQoL, (p = 0.05), social-related HRQoL (p = 0.05), and total HRQoL (p = 0.03), and a trend for Psychosocial-HRQoL. Research is needed to confirm our findings and determine whether carriers of the BDNF Val66Met homozygous Val (G/G) alleles may be at risk of diminished HRQoL, information that can influence interventions in a high-risk population of inactive youth with obesity., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Methylphenidate (MPH) has been previously shown to increase resting energy expenditure (REE) in individuals of normal weight; however, the effects on individuals living with obesity are currently unknown. Ten individuals living with obesity were randomly assigned to undergo 60 days of MPH administration with a daily dose of 0.5 mg/kg body weight or a placebo control. REE was measured before and after the 60-day intervention. There was a trend toward significance for group × time interaction on REE (p = 0.082) with a large effect size (η 2  = 0.331), with MPH administration increasing REE compared to a decrease in placebo control. Preliminary findings from this pilot study show that MPH has the potential to counter the adaptive thermogenic process commonly seen in weight loss. This is a unique finding among pharmacotherapies, as no approved obesity drugs measurably impact REE., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Dobutamine effects on the relationships of the peak velocity of left ventricular (LV) long-axis systolic motion (s') with systolic excursion (SExc), systolic duration (SDur) and heart rate, of LV long-axis early diastolic excursion (EDExc) with SExc, and of the peak velocity of LV long-axis early diastolic motion (e') with EDExc, early diastolic duration (EDDur) and isovolumic relaxation time (IVRT') are unknown., Methods: Two groups of adult subjects, one young and healthy ( n  = 10), and one with impaired LV long-axis function ( n  = 10), were studied, with the aim of identifying consistent findings for the two groups and for the septal and lateral walls. Dobutamine was infused at doses of 5 and 10 µg/kg/min. The relationships between tissue Doppler imaging (TDI) variables acquired before and during dobutamine infusion were analysed using mixed effect multivariate regression modelling., Results: In both groups, heart rate increased and SDur decreased during dobutamine infusion, and there were independent inverse correlations of SDur with heart rate and dobutamine dose. In contrast, there was no change in EDDur during dobutamine infusion, and no consistent changes in IVRT' independent of heart rate. s' was positively correlated with SExc and inversely correlated with SDur, and there were positive correlations between EDExc and SExc and between e' and EDExc., Conclusion: Dobutamine increases s' due to effects on both systolic excursion and duration and it increases e' due to the associated increases in systolic and early diastolic excursion. A lack of effect on diastolic times does not support the presence of a lusitropic effect of dobutamine.