Parsplana vitrectomy alone versus parsplana vitrectomy combined with phacoemulsification for the treatment of rhegmatogenous retinal detachment: a randomized study.

BACKGROUND: To compare parsplana vitrectomy (PPV) with and without phacoemulsification to treat rhegmatogenous retinal detachment (RRD). METHODS: Subjects aged 48-65 years with RRD in a phakic eye due to superior retinal tears with an overall extension of retinal breaks < 90° underwent to PPV alone (group A); or PPV plus phacoemulsification (phacovitrectomy, PCV, group B). Post-operative follow-up visits occurred at 1 week, 1 month (m1), 3 months (m3), and 6 months (m6) after surgery. The main outcome was the rate of retinal reattachment. Secondary outcomes included best-corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), and cataract progression (in the lens-sparing [PPV-alone] group). RESULTS: In this initial phase of the study a total of 59 patients (mean age: 55 years, 59 eyes) were enrolled: 29 eyes in group A and 30 eyes in group B. Both groups had similar gas tamponade. During the follow-up there were three cases of RRD recurrence in group A and one in group B. The relative risk of recurrence in group A was 3.22 times higher but the difference was not significant (p = 0.3). The two groups were also similar in terms of BCVA and IOP variation. At m3, CMT was significantly higher in group B (p = 0.014). In group A, cataract progression was significant at m6 (p = 0.003). CONCLUSIONS: In a cohort of RRD patients selected according to their preoperative clinical characteristics, PPV was comparable to PCV in terms of the rate of retinal reattachment after 6 months. TRIAL REGISTRATION: ISRCTN15940019 . Date registered: 15/01/2021 (retrospectively registered).

The epidemiology of Moebius syndrome in Italy.

BACKGROUND: The epidemiology of Moebius syndrome (MBS) is difficult to assess. In the present study, we investigated the epidemiology of MBS in a well-defined population within a precise geographical area. MATERIALS AND METHODS: Our university hospital is the only national referral center for the diagnosis and treatment of MBS. Participants in this cross-sectional study were patients affected by MBS who had been periodically followed by our medical staff since 1998. Most of the patients were referred to our hospital by the Italian Association of Moebius Syndrome (AISMO). Demographic data necessary for study purposes were made available in the AISMO database, updated to April 2018. Subjects were assigned to geographical macroareas that are conventionally used in surveys and epidemiological investigations by the Italian National Institute of Statistics. The rates and prevalence of MBS cases were calculated on the basis of the last available survey of the Italian population. Each study parameter was then calculated with reference to the whole country and macroarea partition. The sex rate and the corresponding prevalence were calculated with respect to the weighted whole population and to the respective sex population. Chi-square analysis was adopted to investigate possible differences among geographical regions and/or sexes. A p value < 0.05 was considered statistically significant. RESULTS: One hundred and sixty-four out of 212 MBS patients fulfilled our inclusion criteria. All cases occurred in Caucasian patients and were sporadic. The median age at diagnosis was 3.6 years, ranging from 0 to 55 years; this range was significantly reduced to 0-5 years (median age at diagnosis: 2.2 years) in patients included after 2007. The calculated prevalence at birth was 0.06 cases per 10,000 live births, with an overall prevalence of 0.27/100,000, without any sex or geographical predominance. CONCLUSIONS: The prevalence of MBS observed herein, rounded for possible underestimation, was 0.3/100,000 people, without any regional difference in the distribution of cases. Our data confirm the rarity of the disease on a national level.

Assessment of Choroidal Neovascularization Perfusion: A Pilot Study With Laser Speckle Flowgraphy.

Purpose: The purpose of this study was to quantify perfusion in the area of choroidal neovascularization (CNV) using laser speckle flowgraphy (LSFG) before and after intravitreal anti-vascular endothelial growth factor (VEGF) injection. Methods: Retrospective case series. Fifteen eyes of 15 patients with treatment-naïve CNV due to age-related macular degeneration (AMD) and with available LSFG images were included. The main outcome was the mean blur rate (MBR) quantified as a measure of perfusion within the CNV area observed on indocyanine green angiography. Twelve patients had available longitudinal data until one month after the injection, used to evaluate changes in perfusion, central macular thickness (CMT), visual acuity, and ocular perfusion pressure. Reproducibility of LSFG measurements was investigated at each time point from two images taken within five minutes. Results: Intraclass correlation coefficients for LSFG measurements were higher than 0.8 indicating excellent reproducibility. There was a significant decrease in perfusion after one week (-26.4 ± 14.4%; P = 0.027), whereas, after one month, perfusion was no longer significantly different from baseline (P = 0.121). CMT showed a progressive decrease over the follow-up period. Changes in perfusion were strongly correlated with changes in CMT after one week, but not thereafter. Conclusions: This pilot study suggests a method to select a region in the CNV area to quantify perfusion using LSFG. MBR could represent a parameter possibly related to regrowth of the CNV after anti-VEGF treatment. Large-scale studies are needed to assess the usefulness of LSFG in defining re-treatment criteria for neovascular AMD. Translational Relevance: LSFG technology to quantify perfusion could provide useful biomarkers for therapeutic management of CNV.

Comparative Analysis of the Safety and Functional Outcomes of Anterior versus Retropupillary Iris-Claw IOL Fixation.

PURPOSE: To compare the functional and clinical outcomes of the iris-claw intraocular lens (IOL) placed on the anterior versus posterior surface of the iris. PATIENTS AND METHODS: A multicenter, retrospective study. Data on eyes that underwent anterior or retropupillary iris-claw IOL implantation because of inadequate capsular support secondary to complicated cataract surgery, trauma, and dislocated/opacified IOLs since January 2015 were analyzed. For study inclusion, evaluation results had to be available in the medical records both preoperatively and at 1 and 12 months after implantation. The following parameters were compared between the groups: best-corrected distance visual acuity (BCDVA), spherical and cylindrical refractive error, endothelial cell density (ECD), central macular thickness (CMT), and percentage and type of postoperative complications. RESULTS: In total, 60 eyes of 60 patients aged 73 ± 13 years were included: 28 eyes (47%) involved anterior, and 32 eyes (53%) retropupillary, iris-claw IOL fixations. Preoperatively, the groups were similar in all parameters except for a significantly higher proportion of retropupillary fixations in patients who had previously experienced a closed-globe trauma (p=0.03). The groups showed comparable improvements in BCDVA after surgery (final BCDVA: 0.34 ± 0.45 vs. 0.37 ± 0.50 logMAR in the anterior and retropupillary placement groups, respectively). During follow-up, no group difference was observed in refractive error or CMT. Both groups experienced similarly marked ECD loss and showed similar incidence of postoperative complications, with cystoid macular edema being the most common complication. Multivariable linear regression showed that BCDVA at 1 month was the best predictor of the final BCDVA. CONCLUSIONS: Anterior chamber and posterior chamber iris-claw IOL fixations proved equally effective and safe for aphakic correction in eyes with inadequate capsular support.

Optical coherence tomography is a useful tool in the differentiation between true edema and pseudoedema of the optic disc.

PURPOSE: To assess the usefulness of spectral-domain optical coherence tomography (SD-OCT) peripapillary retinal nerve fiber layer (RNFL) thickness measurement in discriminating early phase optic disc edema (ODE) from pseudoedema (PODE). METHODS: Hospital-based, multicenter, cross-sectional study involving external patients referred for recent identification of "presumed ODE". Patients underwent SD-OCT optic nerve head (ONH) RNFL thickness measurement at their first evaluation. In 155 of these, the causative etiology was subsequently ascertained and the respective eyes (one per patient) were assigned to the ODE (95 eyes) or PODE (60 eyes) group. Admission SD-OCT data were retrieved and used for the analysis. ROC curve analysis was used to calculate specificity, sensitivity and predictive value (PV) of the RNFL values. RESULTS: The PODE group was significantly younger than the ODE group (p = 0.007). The average and any single-quadrant RNFL thickness was significantly higher in the ODE group compared with the PODE and control groups. The average and the inferior quadrant thicknesses tested the most powerful parameters to differentiate ODE from PODE. A cutoff value of ≥ 110 µm for the average area, or of ≥ 150 µm for the inferior quadrant was associated with maximal sensitivity and specificity with positive PV greater than 80%. CONCLUSIONS: The SD-OCT evaluation of the peripapillary RNFL achieved good specificity, sensitivity and positive PV in discriminating between ODE and PODE. Despite the correct differential diagnosis between these categories still relies on a careful medical history taking and other ancillary testing, we proved the usefulness of SD-OCT RNFL measurement in supporting the diagnostic process.

Variability of Crops' Compositional Characteristics: What Do Experimental Data Show?

Common pillar across the risk assessment strategies implemented worldwide for genetically modified plants is the comparison of their compositional profile to that of conventional counterparts deemed safe. If differences are observed, those that cannot be attributed to natural variation are further evaluated for their safety relevance. This principle is clear, but its implementation is challenging. Here we first discuss the difficulties of estimating natural variation of crop-specific compositional end-points and the various attempts made, together with their advantages and limitations. Second we present the empirical distribution curves of compositional end-points for two crops bearing a large commercial interest worldwide, maize and soybean. These curves provide novel information on end-point specific variability relevant for further progressing in the risk assessment process.

Ranking brain areas encoding the perceived level of pain from fMRI data.

Pain perception is thought to emerge from the integrated activity of a distributed brain system, but the relative contribution of the different network nodes is still incompletely understood. In the present functional magnetic resonance imaging (fMRI) study, we aimed to identify the more relevant brain regions to explain the time profile of the perceived pain intensity in healthy volunteers, during noxious chemical stimulation (ascorbic acid injection) of the left hand. To this end, we performed multi-way partial least squares regression of fMRI data from twenty-two a-priori defined brain regions of interest (ROI) in each hemisphere, to build a model that could efficiently reproduce the psychophysical pain profiles in the same individuals; moreover, we applied a novel three-way extension of the variable importance in projection (VIP) method to summarize each ROI contribution to the model. Brain regions showing the highest VIP scores included the bilateral mid-cingulate, anterior and posterior insular, and parietal operculum cortices, the contralateral paracentral lobule, bilateral putamen and ipsilateral medial thalamus. Most of these regions, with the exception of medial thalamus, were also identified by a statistical analysis on mean ROI beta values estimated using the time course of the psychophysical rating as a regressor at the voxel level. Our results provide the first rank-ordering of brain regions involved in coding the perceived level of pain. These findings in a model of acute prolonged pain confirm and extend previous data, suggesting that a bilateral array of cortical areas and subcortical structures is involved in pain perception.

Accuracy of funduscopy to identify true edema versus pseudoedema of the optic disc.

PURPOSE: Differential diagnosis between acute optic disc edema (ODE) and optic disc pseudoedema (PODE) may be a clinical challenge even for well-trained ophthalmologists. Funduscopy remains the first-line investigation. The aim of this study was to assess the accuracy, sensitivity, and specificity of funduscopy in differentiating ODE from PODE. METHODS: This was an observational, cross-sectional, two-center study of subjects referred for presumed acute ODE. During funduscopy, each observer completed a form concerning the presence/absence of the 10 conventional signs of ODE. Seventy-four patients with ODE and 48 subjects with PODE were included in the analysis. Accuracy, sensitivity, and specificity from all possible combinations of signs were calculated by support vector machine (SVM) analysis. RESULTS: As a single sign, the swelling of the peripapillary retinal nerve fiber layer had the highest accuracy (0.92; 95% confidence interval [CI], 0.82-0.97). Little variation was observed when more than fours signs were present. The best four-sign combinations were SWELLING, HEMORRHAGES, papilla ELEVATION, and CONGESTION of peripapillary vessels (accuracy, 0.93; 95% CI, 0.83-0.98; sensitivity, 0.95; specificity, 0.89). The presence of retinal or choroidal folds appeared to be a pathognomonic sign of true ODE (100% sensitivity) but had a low rate of presentation (23%). CONCLUSIONS: The presence of at least four ophthalmoscopic signs (with the sign "swelling" included) gives the highest accuracy. Furthermore, peripapillary retinal folds seem to be related exclusively to ODE because they were never observed in our PODE group. These data may be useful for clinicians when evaluating patients referred for presumed optic disc edema in the acute phase.

Ophthalmologic and systemic features in möbius syndrome an italian case series.

PURPOSE: To describe clinical features in a large series of Möbius syndrome (MBS) cases, investigating whether specific neuro-ophthalmologic patterns of disease may provide further insight into MBS pathogenesis. DESIGN: Observational, prospective study. PARTICIPANTS: Fifty-five affected subjects. METHODS: To make an MBS diagnosis, the criteria recommended in the First Scientific Conference on Möbius Syndrome were followed. Patients who did not meet the minimal criteria were classified as Möbius-like cases and were considered separately. Complete ophthalmologic evaluation, eyelid measurements, presence of abnormal tearing, and ocular motility also were assessed. MAIN OUTCOME MEASURES: Pattern of ocular motility alteration, visual function disturbances, and eyelid and tearing defect. RESULTS: Forty-six sporadic cases of true MBS were identified, with 3 specific patterns of ocular motility alterations. Pattern A, consisting of orthotopia in primary position with a complete defect in both abduction and adduction ocular movements, was found in 41% of cases. Pattern B, with large-angle esotropia, crossed fixation, and a relative sparing of convergence and adduction, was documented in 50% of cases. Pattern C, characterized by a large-angle exotropia in primary position with torticollis, absence of convergence, and vertical eye misalignment, was present in the minority of the patients (9%). Bilateral complete facial nerve palsy with lagophthalmos was present in 83% of patients; lacrimation showed abnormalities in 33% of cases. Visual acuity was good or impaired only moderately in all tested patients. Binocular function was testable in 31 of 46 patients, and all of them showed a complete absence of stereopsis with suppressive scotoma. CONCLUSIONS: Based on the observed 3 different ocular motility defect patterns, the most compatible site and extension of the brainstem damage was inferred. Each pattern may reflect a different type of injury likely occurred during embryogenesis. The comparison of the characteristics of this series with those reported in different geographic areas supports the evidence that MBS does not differ phenotypically worldwide. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

A regularization algorithm for decoding perceptual temporal profiles from fMRI data.

In several biomedical fields, researchers are faced with regression problems that can be stated as Statistical Learning problems. One example is given by decoding brain states from functional magnetic resonance imaging (fMRI) data. Recently, it has been shown that the general Statistical Learning problem can be restated as a linear inverse problem. Hence, new algorithms were proposed to solve this inverse problem in the context of Reproducing Kernel Hilbert Spaces. In this paper, we detail one iterative learning algorithm belonging to this class, called ν-method, and test its effectiveness in a between-subjects regression framework. Specifically, our goal was to predict the perceived pain intensity based on fMRI signals, during an experimental model of acute prolonged noxious stimulation. We found that, using a linear kernel, the psychophysical time profile was well reconstructed, while pain intensity was in some cases significantly over/underestimated. No substantial differences in terms of accuracy were found between the proposed approach and one of the state-of-the-art learning methods, the Support Vector Machines. Nonetheless, adopting the ν-method yielded a significant reduction in computational time, an advantage that became more evident when a relevant feature selection procedure was implemented. The ν-method can be easily extended and included in typical approaches for binary or multiple classification problems, and therefore it seems well-suited to build effective brain activity estimators.

Erythrocyte transmembrane electron transfer in haemodialysis patients.

BACKGROUND AND AIMS: Patients with chronic renal failure, especially those treated with haemodialysis, have an increased risk of developing atherosclerotic vascular disease probably as a result of enhanced oxidative stress. The human cell membrane possesses electron transfer systems which protect against extracellular pro-oxidant challenge. We evaluated (1) the erythrocyte velocity of ferricyanide reduction (RBC vfcy) in 25 uraemic patients (aged 25-71 years; 14 males), (2) the changes induced by a single haemodialysis session and (3) biomarkers of oxidative stress. METHODS AND RESULTS: Before and after a mid-week dialysis session, we measured RBC vfcy, erythrocyte glutathione (RBC GSH), plasma and red cell membrane malondialdehyde (P and RBC MDA), plasma sulphydryl groups (P SH), plasma vitamin C levels and haemolysis percentage. Pre-dialysis RBC GSH (0.68+/-0.13 vs 0.80+/-0.13 mg/mL, p<0.01), P SH (266+/-74 vs 406+/-78 micromol/L, p<0.01) and plasma vitamin C (7.0+/-5.1 vs 21.5+/-8.5mg/L, p<0.001) were lower than in 25 age-sex-matched healthy controls; P MDA (1.57+/-0.52 vs 0.54+/-0.29 nmol/mL, p<0.001), RBC MDA (0.42+/-0.13 vs 0.34+/-0.16 nmol/mL, p<0.05) and haemolysis (1.2+/-0.3 vs 0.7+/-0.3%, p<0.001) were increased. Baseline RBC vfcy did not differ from normals (13.1+/-5.2 vs 12.9+/-3.2 mmol/mL/h). Following dialysis, RBC vfcy (to 8.9+/-4.5 mmol/mL/h, p<0.001) decreased, as well as P MDA, RBC MDA and plasma vitamin C (to 2.5+/-1.4 mg/L, p<0.001), whereas P SH groups increased (to 413+/-99 micromol/L, p<0.001); haemolysis percentage remained high. RBC vfcy values were correlated to RBC GSH and vitamin C levels. CONCLUSIONS: Uraemic patients showed signs of oxidative stress. Pre-dialysis RBC vfcy is maintained in the normal range on account of a reduced intracellular content of GSH and in spite of low plasma ascorbate. A single haemodialysis treatment reduced biomarkers of protein and lipid oxidation but markedly impaired transmembrane electron transfer, which could be explained by acute depletion of electron donors.

Tissue kallikrein gene polymorphisms induce no change in endothelium-dependent or independent vasodilation in hypertensive and normotensive subjects.

BACKGROUND: Tissue kallikrein (TK) generates Lys-bradykinin, which is then converted to bradykinin and releases nitric oxide (NO) from endothelial cells via B2 receptors. TK gene inactivation in mice causes severe endothelial dysfunction, which is also a hallmark of human primary hypertension (PH). Healthy carriers of a loss-of-function Arg to His substitution at position 53 (R53H) of the TK gene exhibit paradoxical arterial eutrophic remodeling. We therefore investigated the impact of this and other TK gene single nucleotide polymorphisms (SNPs) on endothelium-dependent vasodilatation (EDV) and endothelium-independent vasodilatation (EIV) in PH patients and normotensive (NT) subjects. METHODS: The TK gene SNPs were genotyped blind to the phenotype by sequencing. We compared EDV and EIV vasodilatation across TK genotypes in 131 uncomplicated PH patients and 51 healthy NT subjects. EDV and EIV were assessed as the forearm blood flow response to a graded infusion of acetylcholine and sodium nitroprusside, respectively. We also evaluated the impact of the SNPs on NO-mediated EDV and on reactive oxygen species (ROS)-induced NO breakdown with the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine or vitamin C, respectively. RESULTS: Genotypes and allele frequencies were in Hardy-Weinberg equilibrium and similar in PH and NT. EDV was lower in PH patients than in NT subjects. No TK genotype affected either EDV or EIV per se, or via interaction with gender and age. NO inhibition and scavenging of ROS showed no TK genotype effect on EDV. Similar conclusions were obtained with haplotype analysis. CONCLUSIONS: These results do not support the contention that TK gene SNPs have a major impact in determining NO-mediated responses to acetylcholine.

Clustering of insulin resistance with vascular dysfunction and low-grade inflammation in type 2 diabetes.

Vascular dysfunction, low-grade inflammation, insulin resistance, and impaired fibrinolysis have each been reported to be present in type 2 diabetes, but their relationships, and the role of obesity, have not been investigated. We measured insulin sensitivity (euglycemic clamp), forearm blood flow responses to graded local acetylcholine (Ach) and sodium nitroprusside (SNP) infusions, plasma concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, von Willebrand factor (vWF), plasminogen activator inhibitor (PAI)-1, tissue plasminogen activator (tPA), and high-sensitivity C-reactive protein (hs-CRP) in 81 diabetic patients. When patients were stratified by insulin resistance, more severe insulin resistance was associated (P < 0.05) with overweight, central fat distribution, hypertension, and dyslipidemia (with similar sex distribution, age, fasting plasma glucose, and HbA1c). With regard to vascular function, both endothelium-dependent (Ach) (-22, -40, and -52%; P < 0.0001) and -independent (SNP) (-3, -7, and -27%; P < 0.02) vasodilatation were progressively reduced across insulin resistance tertiles. In multivariate analysis, inflammatory markers (IL-6, hs-CRP, and TNF-alpha) were independently associated with insulin resistance and fasting glycemia, fibrinolytic markers PAI-1 and tPA with insulin resistance and central fat distribution, and vascular indexes (vWF, Ach, and SNP vasodilation) with insulin resistance and obesity or cytokines (TNF-alpha or IL-6). In type 2 diabetes, insulin resistance is associated with vascular dysfunction/damage, impaired fibrinolysis, and low-grade inflammation independently of obesity and poor glycemic control.

Endothelial dysfunction and oxidative stress in chronic renal failure.

Uremic patients have an increased incidence of cardiovascular disease (CVD), endothelial dysfunction and oxidative stress that can contribute to cardiovascular (CV) events. To assess the relationship between endothelial dysfunction, oxidative stress and renal failure severity, we studied 40 patients (age 57 +/- 7 yrs, 24 males) affected by chronic kidney disease (CKD) K/DOQI stage 3-5 (serum creatinine (Cr) 5.6 +/- 2.2 mg/dL) on conservative treatment, 20 uremic patients (age 57 +/- 12 yrs, 13 males) on hemodialysis (HD) and 30 healthy controls (56 +/- 12 yrs, 20 males). Before and 2 hr after oral vitamin C (2 g) administration, we measured brachial artery endothelium-dependent vasodilation (flow mediated dilation (FMD)) to reactive hyperemia following 5 min of forearm ischemia and the response to sublingual glyceril trinitrate (GTN). Measurements were made by high-resolution ultrasound and computerized analysis. FMD was lower in CKD patients than in controls (5.3 +/- 2.2 vs. 6.9 +/- 2.8%; p<0.01) and was further reduced in HD patients (3.6 +/- 2.7; p<0.01 vs. CKD patients). Response to GTN was similar in all groups. FMD was related to Cr clearance (r=0.42; p<0.01) in CKD patients, while it related inversely to Kt/V(urea) (r=-0.52; p<0.05) in HD patients. After vitamin C administration, FMD was significantly enhanced in HD (4.7 +/- 2.4%; p<0.01 vs. baseline), but not in CKD patients. Response to GTN was unaffected. However, vitamin C load reduced oxidative stress markers, and increased plasma antioxidant capability in both groups. In conclusion, the reduced endothelium-dependent dilation in the brachial artery of CKD patients is related to renal failure severity. HD patients showed a more marked alteration, which seems to be related, at least in part, to increased oxidative stress.

The T-786C and Glu298Asp polymorphisms of the endothelial nitric oxide gene affect the forearm blood flow responses of Caucasian hypertensive patients.

OBJECTIVES: We sought to investigate whether two polymorphisms located in the promoter (T(-786)C) and exon 7 (Glu298Asp) of the endothelial nitric oxide (NO) synthase (eNOS) gene affected agonists-mediated NO release. BACKGROUND: Endothelial dysfunction can be genetically determined. Therefore, we investigated whether two polymorphisms located in the eNOS gene affected agonists-mediated NO release. METHODS: We compared endothelial-dependent and -independent vasodilation of the different eNOS genotypes in a cross-sectional study on 187 subjects, of whom 137 were uncomplicated essential hypertensive patients (PH) (49 +/- 9 years, 151 +/- 11/99 +/- 5 mm Hg) and 50 healthy normotensive subjects (NT) (43 +/- 16 years, 123 +/- 10/78 +/- 7 mm Hg). Endothelial-dependent and -independent vasodilation was assessed as the forearm blood flow response to incrementally increasing doses of acetylcholine (0.15, 0.45, 1.5, 4.5, 15 microg/100 ml/min) and sodium nitroprusside (1, 2, 4 microg/100 ml/min), respectively. Genotyping was performed with melting curve analysis (Lightcycler) of polymerase chain reaction products from acceptor (5' end-labeled with LCRed 640) and donor probes (3' end-labeled with fluorescein) specific for each polymorphism. The genotype distribution of T(-786)C (CC = 21.9%, CT = 48.7%, TT = 29.4%) and Glu298Asp (GG = 39.0%, GT =51.9%, TT = 9.1%) was similar in PH and NT. A repeated measure analysis of variance showed a blunting of endothelium-dependent vasodilation in PH compared with NT (p < 0.001). A significant effect of the T(-786)C (p = 0.002) but not of the Glu298Asp (p = NS) eNOS polymorphism on endothelial-dependent vasodilation was found. However, we also detected a significant interaction between the T(-786)C and Glu298Asp polymorphism (p < 0.001). No effect on either polymorphism on endothelial-independent vasodilation was seen. CONCLUSIONS: The T(-786)C promoter polymorphism and its interaction with exon 7 Glu298Asp affect endothelium-dependent vasodilation in mild-to-moderate PH patients and NT Caucasian subjects.

Myocardial ultrasonic backscatter in hypertension: relation to aldosterone and endothelin.

A disproportionate accumulation of fibrillar collagen is a characteristic feature of hypertensive heart disease, but the extent of myocardial fibrosis may differ in different models of hypertension. In experimental studies, aldosterone and endothelins emerge as important determinants of myocardial fibrosis. Changes in myocardial extracellular matrix and collagen deposition can be estimated noninvasively by analysis of the ultrasonic backscatter signal, which arises from tissue heterogeneity within the myocardium and describes myocardial texture. This study was designed to investigate the relations between myocardial integrated backscatter and circulating aldosterone and immunoreactive endothelin in human hypertension. The study population consisted of 56 subjects: 14 healthy normotensive volunteers and 42 hypertensive patients (14 with primary aldosteronism, 7 with renovascular hypertension, and 21 with essential hypertension). The patients with essential and secondary hypertension were matched for age, gender, body mass index, and blood pressure. Myocardial integrated backscatter at diastole was 19.8+/-2.0 and 20.8+/-2.9 decibels in normotensive control subjects and patients with essential hypertension and significantly higher in patients with primary aldosteronism (27.4+/-3.8 decibels, P<0.01) and renovascular hypertension (26.8+/-4.8 decibels, P<0.01). In the population as a whole, as well as in the hypertensive subpopulation, myocardial integrated backscatter was directly related to plasma aldosterone (r=0.73 and 0.71, P<0.01 for both) and immunoreactive endothelin (r=0.60 and 0.56, P<0.01 for both). The data of this study suggest that in human hypertension, circulating aldosterone and immunoreactive endothelin may induce alterations in left ventricular myocardial texture, possibly related to increased myocardial collagen content.