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The pressing need for multifunctional materials in medical settings encompasses a wide array of scenarios, necessitating specific tissue functionalities. A critical challenge is the occurrence of biofouling, particularly by contamination in surgical environments, a common cause of scaffolds impairment. Beyond the imperative to avoid infections, it is also essential to integrate scaffolds with living cells to allow for tissue regeneration, mediated by cell attachment. Here, we focus on the development of a versatile material for medical applications, driven by the diverse time-definite events after scaffold implantation. We investigate the potential of incorporating graphene oxide (GO) into polycaprolactone (PCL) and create a composite for 3D printing a scaffold with time-controlled antibacterial and anti-adhesive growth properties. Indeed, the as-produced PCL-GO scaffold displays a local hydrophobic effect, which is translated into a limitation of biological entities-attachment, including a diminished adhesion of bacteriophages and a reduction of E. coli and S. aureus adhesion of ∼81% and ∼69%, respectively. Moreover, the ability to 3D print PCL-GO scaffolds with different heights enables control over cell distribution and attachment, a feature that can be also exploited for cellular confinement, i.e., for microfluidics or wound healing applications. With time, the surface wettability increases, and the scaffold can be populated by cells. Finally, the presence of GO allows for the use of infrared light for the sterilization of scaffolds and the disruption of any bacteria cell that might adhere to the more hydrophilic surface. Overall, our results showcase the potential of PCL-GO as a versatile material for medical applications. [ABSTRACT FROM AUTHOR]

Reports on a new experimental approach to the size estimation of the hot spot induced by ionizing particles in a Josephson tunnel junction. Investigation of the physics of the hot spot by detecting its action on Abrikosov vortices; Change of the static magnetic field in the junction area and change in the critical value of Ic; Sample preparation and characterization.

It is now established that the gastric pathogen Helicobacter pylori has the ability to form biofilms in vitro as well as on the human gastric mucosa. The aim of this study is to evaluate the antimicrobial effects of Clarithromycin on H. pylori biofilm and to enhance the effects of this antibiotic by combining it with Alginate Lyase, an enzyme degrading the polysaccharides present in the extracellular polymeric matrix forming the biofilm. We evaluated the Clarithromycin minimum inhibition concentration (MIC) on in vitro preformed biofilm of a H. pylori. Then the synergic effect of Clarithromycin and Alginate Lyase treatment has been quantified by using the Fractional Inhibitory Concentration index, measured by checkerboard microdilution assay. To clarify the mechanisms behind the effectiveness of this antibiofilm therapeutic combination, we used Atomic Force Microscopy to analyze modifications of bacterial morphology, percentage of bacillary or coccoid shaped bacteria cells and to quantify biofilm properties. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1584-1591, 2016 [ABSTRACT FROM AUTHOR]

Background:Despite the recognised contribution of the stroma to breast cancer development and progression, the effective targeting of the tumor microenvironment remains a challenge to be addressed. We previously reported that normal fibroblasts (NFs) and, notably, breast cancer-associated fibroblasts (CAFs) induced epithelial-to-mesenchymal transition and increases in cell membrane fluidity and migration in well- (MCF-7) and poorly-differentiated (MDA-MB-231) breast cancer cells. This study was designed to better define the role played, especially by CAFs, in promoting breast tumor cell migration.Methods:Fibroblast/breast cancer cell co-cultures were set up to investigate the influence of NFs and CAFs on gene and protein expression of Stearoyl-CoA desaturase 1 (SCD1), the main enzyme regulating membrane fluidity, as well as on the protein level and activity of its transcription factor, the sterol regulatory element-binding protein 1 (SREBP1), in MCF-7 and MDA-MB-231 cells. To assess the role of SREBP1 in the regulation of SCD1 expression, the desaturase levels were also determined in tumor cells treated with an SREBP1 inhibitor. Migration was evaluated by wound-healing assay in SCD1-inhibited (by small-interfering RNA (siRNA) or pharmacologically) cancer cells and the effect of CAF-conditioned medium was also assessed. To define the role of stroma-derived signals in cancer cell migration speed, cell-tracking analysis was performed in the presence of neutralising antibodies to hepatocyte growth factor, transforming growth factor-β or basic fibroblast growth factor.Results:A two to three fold increase in SCD1 mRNA and protein expression has been induced, particularly by CAFs, in the two cancer cell lines that appear to be dependent on SREBP1 activity in MCF-7 but not in MDA-MB-231 cells. Both siRNA-mediated and pharmacological inhibition of SCD1 impaired tumor cells migration, also when promoted by CAF-released soluble factors. Fibroblast-triggered increase in cancer cell migration speed was markedly reduced or abolished by neutralising the above growth factors.Conclusion:These results provide further insights in understanding the role of CAFs in promoting tumor cell migration, which may help to design new stroma-based therapeutic strategies. [ABSTRACT FROM AUTHOR]

Chemically inert coatings on Havar® entrance foils of the targets for [18F] production via proton irradiation of enriched water at pressurized conditions are needed to decrease the amount of ionic contaminants released from Havar®. In order to find the most effective protective coatings, the Nb-based coating microstructure and barrier properties have been correlated with deposition parameters such as substrate temperature, applied bias, deposition rate and sputtering gas pressure. Aluminated quartz used as a substrate allowed us to verify the protection efficiency of the desirable coatings as diffusion barriers. Two modelling corrosion tests based on the extreme susceptibility of aluminum to liquid gallium and acid corrosion were applied. Pure niobium coatings have been found to be less effective barriers than niobium–titanium coatings. But niobium oxide films, according to the corrosion tests performed, showed superior barrier properties. Therefore multi-layered niobium–niobium oxide films have been suggested, since they combine the high thermal conductivity of niobium with the good barrier properties of niobium oxide. [ABSTRACT FROM AUTHOR]

In this paper we present a simple and robust method to realize highly ordered arrays of stretched and suspended DNA molecules over the millimeter length scale. To this end we used an ad hoc designed superhydrophobic surface made of high aspect-ratio silicon pillars, where we deposited a droplet containing genomic DNA. A precise positioning of DNA strands was achieved by shaping the silicon pillars so that sharpened features resembling tips were included. Such features allowed us to accurately control the droplet de-wetting dynamics, pinning DNA strands in a well-defined position above pillars. The proposed technique has the potential to positively impact on the development of novel DNA chips for genetic analysis. [ABSTRACT FROM AUTHOR]

Background Specific food-dependent exercise-induced anaphylaxis ( S- FDEIAn) is a distinct form of food allergy in which symptoms are elicited by exercise performed after ingesting food to which the patient has become sensitised. Non-specific FDEIAn ( NS- FDEIAn) is a syndrome provoked by exercise performed after ingesting any food. Objective We sought to identify the culprit allergenic molecules in patients with FDEIAn, combining 'classic' allergy testing with an allergenic molecule-based microarray approach for Ig E detection. Methods All subjects were evaluated who reported at least one episode of anaphylaxis in association with physical exercise performed within 4 h after a meal. We performed skin prick tests ( SPT) with commercial food extracts, prick plus prick tests ( P + P) with fresh foods ( P + P), and serum specific Ig E assays by means of both the Immuno CAP ( CAP) and the ISAC 89 microarray system ( ISAC). Results Among our 82 FDEIAn patients, the most frequent suspected foods were tomato, cereals, and peanut. SPT, P + P, and CAP displayed different degrees of sensitivity. Each test disclosed some positivities not discovered by others. Seventy-nine subjects were positive to at least one food (49 to more than 20), whereas three were negative. All suspected foods were positive to at least one of SPT, P + P, and CAP. When tested using the ISAC, 64 (78%) subjects were positive to Pru p 3 [peach lipid transfer protein ( LTP)], 13 were positive to other food allergen molecules, and five displayed negative results to all food allergenic molecules. Overall, 79 patients probably had S- FDEIAn and the other 3 NS- FDEIAn. Conclusions Multiple food hypersensitivity represents a clinical hallmark of a large percentage of FDEIAn patients. The very high prevalence of Ig E to the LTP suggests a role of this allergen group in causing S- FDEIAn. [ABSTRACT FROM AUTHOR]

Objective To collect medical data on women's boxing. Design Cross-sectional and longitudinal study. Setting Medical examinations requested by Italian laws. Participants A retrospective study was conducted on all female boxing competitions in Italy from April 2001 to December 2007. Sixty-one amateur female boxers were evaluated longitudinally. Interventions (1) Retrospective study: All pre-/postmatch medical reports were analysed. (2) Prospective study: Breast, gynaecologic, brain, eyes, ear, nose and throat examinations were carried out. Main outcome measurements (1) Retrospective study: Any injury assessed before/after the match. (2) Prospective study: Health problems which could be related to boxing activity. Results (1) Retrospective study: Data from 5600 examinations were collected. Precompetition, a medical problem was recorded in three athletes (one conjunctiva hyperemia, one zygomatic bruise, one eyelid haematoma). Post competition, 51/2800 medical checks showed mild common injuries, such as soft tissue facial lesions, epistaxis and hand-wrist problems. Only one concussion was recorded with hospitalisation (for a thorough evaluation). Another athlete was hospitalised for a nasal fracture. (2) Prospective study: Two fibroadenomas, three ovarian cysts and one intramural uterine myoma were diagnosed. In four boxers, non-specific electroencephalographic abnormalities were detected, however, with a normal brain MRI in three (the fourth is still waiting for the radiologic procedure). Nasal septum deviation was common (42.6%) and a transmissive hypoacusia was observed in two athletes. No major eye injuries were reported. Conclusions Female boxing seems to be a safe sport with a very low incidence of events requiring hospitalisation. No specific diseases in female boxers could be observed, in particular regarding the breast and reproductive system. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To collect medical data on women's boxing. DESIGN: Cross-sectional and longitudinal study. SETTING: Medical examinations requested by Italian laws. PARTICIPANTS: A retrospective study was conducted on all female boxing competitions in Italy from April 2001 to December 2007. Sixty-one amateur female boxers were evaluated longitudinally. INTERVENTIONS: (1) Retrospective study: All pre-/postmatch medical reports were analysed. (2) Prospective study: Breast, gynaecologic, brain, eyes, ear, nose and throat examinations were carried out. MAIN OUTCOME MEASUREMENTS: (1) Retrospective study: Any injury assessed before/after the match. (2) Prospective study: Health problems which could be related to boxing activity. RESULTS: (1) Retrospective study: Data from 5600 examinations were collected. Precompetition, a medical problem was recorded in three athletes (one conjunctiva hyperemia, one zygomatic bruise, one eyelid haematoma). Post competition, 51/2800 medical checks showed mild common injuries, such as soft tissue facial lesions, epistaxis and hand-wrist problems. Only one concussion was recorded with hospitalisation (for a thorough evaluation). Another athlete was hospitalised for a nasal fracture. (2) Prospective study: Two fibroadenomas, three ovarian cysts and one intramural uterine myoma were diagnosed. In four boxers, non-specific electroencephalographic abnormalities were detected, however, with a normal brain MRI in three (the fourth is still waiting for the radiologic procedure). Nasal septum deviation was common (42.6%) and a transmissive hypoacusia was observed in two athletes. No major eye injuries were reported. CONCLUSIONS: Female boxing seems to be a safe sport with a very low incidence of events requiring hospitalisation. No specific diseases in female boxers could be observed, in particular regarding the breast and reproductive system. [ABSTRACT FROM AUTHOR]

Moderate exercise and intense physical training are associated with increased life expectancy (LE). Boxing is characterized by intentional and repetitive head blows, sometimes causing brain injury, possibly reducing LE. We examined a sample of male athletes born between 1860 and 1930 selected from the international "hall of fame" inductees in baseball (n = 154), ice hockey (n = 130), tennis (n=83), football (n=81), boxing (n=81), track and field (n = 59), basketball (n = 58), swimming (n=37) and wrestling (n=32). In boxing, we analyzed the number of disputed bouts/rounds and career records. Sports were also analyzed according to physiological demand and occurrence and kind of contact (intentional, unintentional). The Kaplan-Meier product limit method was used to compare survival curves (significance: p≤0.05). Median LE of the samples was 76.0 yrs and no differences were observed in different sports, although it was lower in boxers (73.0 yrs) and higher in tennis players (79.0 yrs). Sports of different physiological demand were similar in respect to LE. No differences in LE were found related to occurrence and kind of impact. Similar LE was found in boxers of different weight or career records. In conclusion, this study indicates that LE in top-level athletes is unaffected by the type of discipline, and not related to physiological demand and intentional contact. [ABSTRACT FROM AUTHOR]

In the context of an R&D program aiming at developing new fabrication techniques, three bulk Niobium 3 GHz seamless SRF cavities were produced by spinning at INFN Legnaro. These prototype cavities for different nominal thicknesses were tested at IPN Orsay in the temperature range 1.7–4.2 K. In the course of the experiments, several parameters were investigated: surface resistance R s vs. temperature T, magnetic penetration depth as function of T and Lorentz forces detuning factor K. Electromagnetic simulations were also performed. The results obtained are reported and discussed. The characteristics Q 0 vs. E acc of the three cavities showed field emission and the RF tests were limited by the power available. Moreover, the energy gap was deduced from the R s vs. T results and compared to data previously reported on niobium leading to a good agreement. Finally, these cavities seem to be more sensitive (i.e. higher detuning factor) to Lorentz forces detuning compared to cavities of same geometry produced by deep drawing and electron beam welding. [ABSTRACT FROM AUTHOR]

Objective:To assess the effects of a diet rich in protein of animal origin in comparison to one with a protein intake of about 15% of the total daily calories on body composition and arterial function.Design:Randomized prospective study with parallel groups. Body weight (BW), blood pressure (BP), main parameters of carbohydrate and lipid metabolism, body mass composition by bioelectrical impedance analysis, forearm blood flow at rest and in the postischaemic phase by strain gauge plethysmography and flow-mediated dilation of the brachial artery by echography were measured at baseline and after 6 months of the dietary intervention.Subjects:In total, 15 clinically healthy male volunteers, regularly performing a mixed training three times weekly for 90 min.Intervention:The participants were randomly prescribed a diet with high (1.9 g/kg BW) or normal (1.3 g/kg BW) protein content.Statistical analysis:Differences between means were evaluated by the t-tests for paired or unpaired data and by one way analysis of variance. The strength of correlation between variables was investigated by bivariate Pearson correlation.Results:Serum cholesterol significantly decreased with both diets in comparison to baseline values, whereas BW was slightly but significantly reduced only by the high-protein (HP) diet. No change was detected in BP and the other metabolic parameters. Body mass composition was not significantly modified by either diet. On the other hand, postischaemic flow-mediated dilation of the brachial artery was enhanced by the sole normal protein (NP) diet, whereas no change in the forearm blood flow, both at rest and in the postischaemic phase, was detected.Conclusions:These preliminary results indicate that HP diet was found to be not useful in increasing the muscle mass in comparison to a NP intake. In contrast to this, the latter diet seems to enhance the endothelial function of the arterial vessels with a more pronounced dilatation of the lumen in response to the increase in blood flow.European Journal of Clinical Nutrition (2006) 60, 643–649. doi:10.1038/sj.ejcn.1602363; published online 7 December 2005 [ABSTRACT FROM AUTHOR]

Left ventricular hypertrophy (LVH) is prognostically relevant, associated with major cardiovascular risk factors and with atherosclerosis. However, whether LVH is independently associated with impaired coronary flow reserve (CFR) and with endothelial dysfunction is disputed. We assessed the relationship of LV mass and systolic function to CFR and endothelial function in new discovered never treated subjects with essential arterial hypertension, but without coronary artery disease or microalbuminuria. LVH, ejection fraction (EF) and stress-corrected midwall shortening (MWS, a measure of myocardial contractility) were assessed by echocardiography. CFR was assessed by single-photon emission computed tomography and dipyridamole infusion. Endothelial function was evaluated by assessing 1-min postischaemic flow-mediated dilatation of the brachial artery (FMD); nitroglycerine-mediated dilatation (NMD) of the same brachial artery was used as measure of nonendothelium-dependent vasodilatation. In approximately 1 year, we enrolled 21 subjects who met stringent inclusion criteria (47±10 years old, 26.6±2.8 kg/m2, 78% men). Five patients showed LVH. Multivariate analyses showed a significant negative correlation of LV mass index with FMD (β=−0.61, P<0.05) but not with NMD, neither with CFR. Stress-corrected MWS showed independent correlation with CFR (β=0.51, P<0.05). Thus, in clinically healthy, new discovered hypertensive subjects, never treated and mostly in the early stage of arterial hypertension, LVH can be associated with endothelial dysfunction while maximal dipyridamole- dependent CFR may be preserved; nevertheless, a cardiac phenotype presenting with tendency to impaired myocardial contractility, assessed by stress-corrected MWS, showed association with lower CFR in the early stage of arterial hypertension.Journal of Human Hypertension (2005) 19, 941–950. doi:10.1038/sj.jhh.1001921; published online 4 August 2005 [ABSTRACT FROM AUTHOR]

Background: Female boxing has been permitted in Italy since 2001. According to the latest italian laws, athletes applying to become boxers have to pass a pre-participation medical examination. Objective: To collect novel medical information from the pre-participation visits and mandatory pre- competition and post-competition examinations for all fights involving Italian female boxers in 2002- 2003. Methods: A retrospective study on all official female boxing competitions in Italy from January 2002 to October 2003 was conducted. A prospective study on 28 amateur female boxers was also carried out. Results: Retrospective study: data from 664 examinations were collected. Pre-match examinations were negative. After competitions, 19/645 visits showed some injuries, with mild, soft tissue facial lesions, epistaxis, and hand-wrist problems being the most common. Prospective study: no major lesions were found during the study. One fibroadenoma, one ovarian cyst, and one intramural uterine myoma were found. One boxer was referred to a neurologist because of non-specific electroencephalographic (EEG) abnormalities, which persisted six months later. On a re-admission examination, which was needed because of a contest that was stopped because the referee judged that she was receiving blows to the head that were dangerous, one boxer showed non-specific EEG alterations and nystagmus. A cerebral magnetic resonance imaging scan was normal. She was allowed to participate in competitions again when her EEG returned to normal and clinical signs disappeared. Deviation of the nasal septum was quite common (68%). No major eye injuries were reported. Conclusion: Probably because of the correct preventive medical approach, female boxing is much safer than expected, and no major lesions (requiring hospital admission) were reported. Any lesions to the breast and reproductive system could not be considered to be boxing related. [ABSTRACT FROM AUTHOR]

The objective of the study was to analyze the presence of myocardial damage in relation to official boxing matches. Low-energy chest wall impact could be responsible for sudden cardiac death, i.e. commotio cordis. As boxing is a traumatic sport in which thoracic hits usually occur, it seems interesting to know if there are any significant cardiac changes during official bouts. Fifteen amateur boxers, participating in the semifinals of the Italian Championship were investigated. A standard ECG before, immediately after, 1 hour and 12 hours after the match were obtained from each athlete to analyze atrio-ventricular conduction, QRS axis and duration, and ventricular repolarization. A blood sample was also obtained before and 12 hours after the match for analysis of total-creatin-phosphokinase, myoglobin, and T-troponin. After the fight, the following significant changes were encountered: higher QRS voltages, lowering of J-point and ST segment in lateral leads, higher ST-slope, lower T-wave amplitude, shorter T-wave peak time, and shorter QT interval. When the last 2 parameters were corrected for heart rate, no differences were observed for QTc, while T-wave peak time significantly increased. All these changes persisted until one hour after the match. Moreover, 3/15 boxers (20%) showed marked ventricular repolarization anomalies in lateral leads after the contest, persisting for 12 hours in one case. However, no athlete had clinical and humoral signs of myocardial damage following the match. It was concluded that no clinical and humoral signs of myocardial damage were found after amateur boxing matches, although ventricular repolarization abnormalities can be found on ECG in 20% of boxers, probably due to sympathetic hyper-activity related to the agonistic event. [ABSTRACT FROM AUTHOR]

The objective of the study was to analyze the presence of myocardial damage in relation to official boxing matches. Low-energy chest wall impact could be responsible for sudden cardiac death, i.e. commotio cordis. As boxing is a traumatic spurt in which thoracic hits usually occur, it seems interesting to know if there are any significant cardiac changes during official bouts. Fifteen amateur boxers, participating in the semifinals of the Italian Championship were investigated. A standard ECG before, immediately after, 1 hour and 12 hours after the watch were obtained from each athlete to analyze atrio-ventricular conduction, QRS axis and duration, and ventricular repolarization. A blood sample was also obtained before and 12 hours after the match for analysis of total-creatin-phosphokinase, myoglobin, and T-troponin. After the fight, the following significant changes were encountered: higher QRS voltages, lowering of J-point and ST segment in lateral leads, higher ST-slope, lower T-wave amplitude, shorter T-wave peak time, and shorter QT interval. When the last 2 parameters mere corrected for heart rate, no differences were observed for QTc, while T-wave peak time significantly increased. All these changes persisted until one hour after the match. Moreover, 3/15 boxers (20%) showed marked ventricular repolarization anomalies in lateral leads after the contest, persisting for 12 hours in one case. However, no athlete had clinical and humoral signs of myocardial damage following the match. It was concluded that no clinical and humoral signs of myocardial damage were found after amateur boxing matches, although ventricular repolarization abnormalities can be found on ECG in 20% of boxers, probably due to sympathetic hyper-activity related to the agonistic event. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To investigate the prevalence of ocular injuries in a large population of boxers over a period of 16 years, in particular, the most severe lesions that may be vision threatening. METHODS: Clinical records of the medical archive of the Italian Boxing Federation were analysed. A total of 1032 boxers were examined from February 1982 to October 1998. A complete ophthalmological history was available for 956, who formed the study population (a total of 10 697 examinations). The following data were collected: age when started boxing; duration of competitive boxing career (from the date of the first bout); weight category; a thorough ocular history. The following investigations were carried out: measurement of visual acuity and visual fields, anterior segment inspection, applanation tonometry, gonioscopy, and examination of ocular fundus. Eighty age matched healthy subjects, who had never boxed, formed the control group. RESULTS: Of the 956 boxers examined, 428 were amateur (44.8%) and 528 professional (55.2%). The median age at first examination was 23.1 (4.3) years (range 15-36). The prevalence of conjunctival, corneal, lenticular, vitreal, ocular papilla, and retinal alterations in the study population was 40.9% compared with 3.1% in the control group (p< or =0.0001). The prevalence of serious ocular findings (angle, lens, macula, and peripheral retina alterations) was 5.6% in boxers and 3.1% in controls (NS). CONCLUSIONS: Boxing does not result in a higher prevalence of severe ocular lesions than in the general population. However, the prevalence of milder lesions (in particular with regard to the conjunctiva and cornea) is noteworthy, justifying the need for adequate ophthalmological surveillance. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prevalence of ocular injuries in a large population of boxers over a period of 16 years, in particular, the most severe lesions that may be vision threatening. Methods: Clinical records of the medical archive of the Italian Boxing Federation were analysed. A total of 1032 boxers were examined from February 1982 to October 1998. A complete ophthalmological history was available for 956, who formed the study population (a total of 10 697 examinations). The following data were collected: age when started boxing; duration of competitive boxing career (from the date of the first bout); weight category; a thorough ocular history. The following investigations were carried out: measurement of visual acuity and visual fields, anterior segment inspection, applanation tonometry, gonioscopy, and examination of ocular fundus. Eighty age matched healthy subjects, who had never boxed, formed the control group. Results: Of the 956 boxers examined, 428 were amateur (44.8%) and 528 professional (55.2%). The median age at first examination was 23.1 (4.3) years (range 15-36). The prevalence of conjunctival, corneal, lenticular, vitreal, ocular papilla, and retinal alterations in the study population was 40.9% compared with 3.1% in the control group (p &les; 0.0001). The prevalence of serious ocular findings (angle, lens, macula, and peripheral retina alterations) was 5.6% in boxers and 3.1% in controls (NS). Conclusions: Boxing does not result in a higher prevalence of severe ocular lesions than in the general population. However, the prevalence of milder lesions (in particular with regard to the conjunctiva and cornea) is noteworthy, justifying the need for adequate ophthalmological surveillance. [ABSTRACT FROM AUTHOR]

AIMS: To assess inter- and intra-study reproducibility of myocardial contrast echocardiography (MCE) imaging for quantitative measurement of myocardial perfusion rate in humans in ambulatory setting. METHODS AND RESULTS: In 20 subjects, we performed 2 MCE tests 20-40 min apart on the same day under the same standardized protocol, and evaluated single-reader between-study and between-reading reproducibility of assessment of indicators of myocardial perfusion rate, such as the slope of video-intensity change k, and the factors A (peak video-intensity) and B (background video-intensity after bubble destruction) and the product k X A. The region of interest was placed at the mid-posterior interventricular septal wall visualized in apical 4-chamber view. In a sub-analysis, we evaluated indicators of myocardial perfusion rate comparing subjects with normal vs. those with subnormal ejection fraction (EF). Inter-study reproducibility of assessment of k was relatively low (intraclass correlation coefficient = 0.36), whereas intra-study reproducibility was fair (intraclass correlation coefficient = 0.61). The parameters k X A and B showed higher reproducibility than the k (inter- and intra-study intraclass correlation coefficients 0.64 and 0.75, 0.74 and 0.91, respectively). For reference, reproducibility data of the depth of the region of interest, of EF and CO were excellent. k and k X A were lower in subjects with low vs. those with normal EF. Only k and k X A were lower in subjects with subnormal than in those with normal EF. CONCLUSIONS: The MCE-derived indicator of myocardial perfusion rate k X A showed fairly good between-study and between-reading reproducibility. [ABSTRACT FROM AUTHOR]

While left ventricular (LV) structure and function differ between hypertensive women and men, it remains unclear whether sex affects regression of LV hypertrophy with antihypertensive treatment. We analysed paired echocardiograms in 500 men and 347 women enrolled in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study at baseline and after 12 months of antihypertensive treatment with either losartan or atenolol. At enrolment, 177 women and 242 men were randomized to losartan-based treatment and 161 women and 247 men were randomized to atenolol-based treatment (sex difference=NS). After 12 months of antihypertensive treatment, blood pressure was lowered similarly in women (152/83 from 174/97?mmHg) and men (149/85 from 173/99?mmHg; both P<0.001, sex difference=NS), without significant change in body weight in either sex. Cardiac output and pulse pressure/stroke volume were equivalently reduced in both sexes (-0.2 vs -0.1?l/min and both -0.20?mmHg/ml/m2, respectively; both P=NS). Absolute LV mass change after 12 months of antihypertensive treatment was greater in men than in women (-30 vs -24?g, P=0.01). However, after adjusting for baseline LV mass and randomized study treatment, LV mass reduction was greater in women than in men (-33 vs -23?g, P=0.001). LV mass regression was greater in women, by 8.0±2.8?g, after adjusting for baseline LV mass and randomized study treatment. After consideration of baseline LV mass and randomized study treatment, antihypertensive treatment regressed LV hypertrophy more in women. Further studies are needed to identify the mechanisms and prognostic implications of this sex-related difference.Journal of Human Hypertension (2004) 18, 411-416. doi:10.1038/sj.jhh.1001708 Published online 25 March 2004 [ABSTRACT FROM AUTHOR]

We wanted to investigate whether urine albumin/creatinine ratio (UACR) and left ventricular (LV) mass, both being associated with diabetes and increased blood pressure, predicted cardiovascular events in patients with hypertension independently. After 2 weeks of placebo treatment, clinical, laboratory and echocardiographic variables were assessed in 960 hypertensive patients from the LIFE Echo substudy with electrocardiographic LV hypertrophy. Morning urine albumin and creatinine were measured to calculate UACR. The patients were followed for 60±4 months and the composite end point (CEP) of cardiovascular (CV) death, nonfatal stroke or nonfatal myocardial infarction was recorded. The incidence of CEP increased with increasing LV mass (below the lower quartile of 194?g to above the upper quartile of 263?g) in patients with UACR below (6.7, 5.0, 9.1%) and above the median value of 1.406?mg/mmol (9.7, 17.0, 19.0%***). Also the incidence of CV death increased with LV mass in patients with UACR below (0, 1.4, 1.3%) and above 1.406?mg/mmol (2.2, 6.4, 8.0%**). The incidence of CEP was predicted by logUACR (hazard ratio (HR)=1.44** for every 10-fold increase in UACR) after adjustment for Framingham risk score (HR=1.05***), history of peripheral vascular disease (HR=2.3*) and cerebrovascular disease (HR=2.1*). LV mass did not enter the model. LogUACR predicted CV death (HR=2.4**) independently of LV mass (HR=1.01* per gram) after adjustment for Framingham risk score (HR=1.05*), history of diabetes mellitus (HR=2.4*) and cerebrovascular disease (HR=3.2*). *P<0.05, **P<0.01, ***P<0.001. In conclusion, UACR predicted CEP and CV death independently of LV mass. CV death was predicted by UACR and LV mass in an additive manner after adjustment for Framingham risk score and history of CV disease.Journal of Human Hypertension (2004) 18, 453-459. doi:10.1038/sj.jhh.1001711 Published online 15 April 2004 [ABSTRACT FROM AUTHOR]

Impaired myocardial flow reserve (MFR) has been demonstrated in hypertension, and has been associated with peripheral vascular changes. We investigated whether MFR was impaired and associated with structural and/or functional vascular changes in hypertensive patients without evidence of coronary artery disease (CAD). We measured left ventricular (LV) mass index by echocardiography and MFR by positron emission tomography in 33 unmedicated, hypertensive patients with electrocardiographic LV hypertrophy without CAD, and 15 age- and gender-matched normotensive subjects. We also measured 24-h ambulatory blood pressure, minimal forearm vascular resistance (MFVR) by plethysmography, media:lumen ratio in isolated, subcutaneous resistance arteries by myography, intima-media cross-sectional area of the common carotid artery, and flow-mediated (FMD) and nitroglycerin-induced dilatation (NID) of the brachial artery by ultrasound. Compared to the controls, the patients had impaired MFR (2.4 (95% CI 1.95-2.8) vs 3.4 (2.7-4.2), P<0.01) due to increased resting myocardial blood flow (MBF) (0.82 (0.73-0.91) vs 0.65 (0.56-0.75)?ml/g?min), and decreased dipyridamole-stimulated MBF (1.80 (1.55-2.1) vs 2.3 (1.80-2.8) ml/g?min, both P<0.05). The difference in resting MBF disappeared (80 (74-87) vs 86 (74-97)?µl/kg?mmHg, NS) when normalized for blood pressure and heart rate. MFR correlated negatively to median 24-h systolic blood pressure (r=-0.50, P<0.01) as well as to LV mass index (r=-0.45, P<0.05) and MFVR in men (r=-0.47, P<0.05), and positively to FMD (r=0.44, P<0.05) and NID (r=0.40, P<0.05). Hypertensive patients with electrocardiographic LV hypertrophy without CAD had impaired MFR associated with cardiovascular hypertrophy and vasodilatory dysfunction. This suggests that MFR is impaired by LV hypertrophy and structural/functional vascular damage in the coronary and noncoronary circulation.Journal of Human Hypertension (2004) 18, 445-452. doi:10.1038/sj.jhh.1001716 Published online 11 March 2004 [ABSTRACT FROM AUTHOR]

Mild-to-moderate aortic and mitral regurgitation are frequently detected by echocardiogram in asymptomatic hypertensive patients. Our goal was to assess the prevalence and impact of mild-to-moderate mitral and/or aortic regurgitation on left ventricular (LV) structure and function in patients with hypertension and LV hypertrophy (LVH). Hypertensive patients with ECG LVH enrolled in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography substudy were evaluated. Among 939 patients with needed LV measurements and Doppler data, 242 had mild (1+) valvular regurgitation, and 51 patients had moderate (2+ or 3+) regurgitation of one or both valves. In analyses adjusting for gender, patients with mild mitral and/or aortic regurgitation had larger LV internal dimensions (5.25 vs 5.33?cm, P<0.05), higher LV mass indexed for body surface area (122 vs 125?g/m2, P<0.05) or height2.7 (55.4 vs 57.3, P<0.05), and larger left atrial diameter. Patients with moderate regurgitation of one or both valves had larger LV chambers (5.25 vs 5.9?cm, P<0.001), greater mean LV mass (232 vs 248?g, P<0.001) and LV mass indexed for body surface area or height2.7, and higher Doppler stroke volume. Patients with moderate valvular regurgitation also had a higher prevalence of LVH due to an increased prevalence of eccentric LVH. There were no differences among groups defined by the presence and severity of valvular regurgitation in cardiac output, total peripheral resistance, or pulse pressure/stroke volume, indicating that the observed inter-group differences in LV geometry were not due to differences in the haemodynamic severity of hypertension. Hypertensive patients with mild-to-moderate mitral or aortic valvular insufficiency have additional LV structural and functional changes that may affect prognosis.Journal of Human Hypertension (2004) 18, 431-436. doi:10.1038/sj.jhh.1001715 Published online 25 March 2004 [ABSTRACT FROM AUTHOR]

We investigated whether inappropriately high left ventricular (LV) mass, defined as observed LV mass exceeding the level of individual LV mass predicted from gender, height, and stroke work, may be associated with an imbalance between growth-promoting and growth-inhibitory factors and/or structural vascular changes. In 53 patients with hypertension and electrocardiographic LV hypertrophy, 24-h ambulatory blood pressure (BP); echocardiographic LV mass, stroke volume and stroke work; minimal forearm vascular resistance (MFVR); and intima-media cross-sectional area in common carotid arteries (IMA) were evaluated after 2 weeks of placebo treatment. Serum insulin, plasma epinephrine, norepinephrine, endothelin, angiotensin II, aldosterone, and brain natriuretic peptide (BNP) were also measured. High observed LV mass was related to high IMA (r=0.46, P<0.001), MFVR (in men: r=0.36, P<0.05), 24-h ambulatory systolic BP (r=0.30, P=0.06), and lower plasma angiotensin II (r=-0.33, P<0.05), but not to other circulating growth factors. Stroke work was similarly related to IMA (r=0.42, P<0.01), MFVR (in men: r=0.41, P<0.05), and plasma angiotensin II (r=-0.32, P<0.05). Inappropriate LV mass, identified by the ratio between observed LV mass and the value predicted for gender, height, and stroke work, was not significantly related to any of the arterial or neurohormonal variables. In this small series of older hypertensive patients, inappropriate LV mass was not significantly related to arterial changes or to measured circulating growth factors, although weak relations cannot be excluded. Alternatively, inappropriately high LV mass might be related to unmeasured factors such as local myocardial alterations in growth factors and/or genetic predisposition to develop excessive LV hypertrophy.Journal of Human Hypertension (2004) 18, 437-443. doi:10.1038/sj.jhh.1001720 Published online 11 March 2004 [ABSTRACT FROM AUTHOR]

To assess the influence of age on changes in left ventricular (LV) mass and geometry during antihypertensive treatment, we related age to clinical and echocardiographic findings before and after 4 years of antihypertensive treatment in a subset of 560 hypertensive patients without known concurrent disease in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, which randomized patients to blinded losartan- or atenolol-based treatment. Patients ?65 years (older group) included more women and patients with isolated systolic hypertension or albuminuria (all P<0.05). Compared to patients <65 years, older patients had higher pulse pressure, LV mass, and prevalence of concentric hypertrophy at baseline (78 vs 69?mmHg, 234 vs 224?g, and 28 vs 16%, respectively, all P<0.01), while the mean blood pressure did not differ. Over 4 years, reductions in LV mass and the mean blood pressure were similar in both groups, but older patients more often had residual hypertrophy (31 vs 15%, P<0.001) with a preponderance of eccentric geometry. In multivariate analysis of 4-year change in LV mass controlling for baseline mass, larger hypertrophy reduction was associated with losartan treatment, while age, gender, body mass index, and 4-year change in pulse pressure and albuminuria did not enter (Multiple R?2=0.40, P<0.001). Thus, in up-to-80-year-old hypertensive patients with left ventricular hypertrophy, age did not significantly attenuate hypertrophy reduction during antihypertensive treatment, although residual hypertrophy was more prevalent in older patients as a consequence of higher initial LV mass.Journal of Human Hypertension (2004) 18, 417-422. doi:10.1038/sj.jhh.1001718 Published online 22 April 2004 [ABSTRACT FROM AUTHOR]

Conventional definitions of left ventricular (LV) hypertrophy do not account for interindividual differences in loading conditions. We may define LV mass as inappropriately high when exceeding 128% of theoretical values predicted by gender, height2.7, and stroke work, which explain up to 82% of the variability of LV mass in normal reference subjects. In 652 participants in the Losartan Intervention For Endpoint reduction in hypertension study without clinically overt cardiovascular disease or diabetes, we investigated whether inappropriately high LV mass is associated with relevant LV abnormalities independent of traditional definition of LV hypertrophy (ie, LV mass index >116?g/m2 in men and >104?g/m2 in women). The study sample was divided into three groups: patients with inappropriately high LV mass but without LV hypertrophy were compared to patients with LV hypertrophy and to patients with appropriate LV mass and without LV hypertrophy. Patients with inappropriately high but nonhypertrophic LV mass had higher body mass index and relative wall thickness, and lower LV myocardial systolic function, than patients with appropriate LV mass or patients with LV hypertrophy. In multivariate analyses, inappropriately high LV mass was independently associated with lower myocardial systolic function independent of LV hypertrophy and other covariates. Inappropriately high LV mass was also associated with prolonged isovolumic relaxation time and lower mitral E/A ratio independent of covariates. In conclusion, inappropriately high LV mass was associated with relevant, often preclinical, manifestations of cardiac disease in the absence of traditionally defined echocardiographic LV hypertrophy and concentric geometry.Journal of Human Hypertension (2004) 18, 423-430. doi:10.1038/sj.jhh.1001719 Published online 22 April 2004 [ABSTRACT FROM AUTHOR]

Abstract Background Erythrocyte membrane modifications in patients with cholestasis are supposed to reflect those of hepatocytes. Methods Erythrocyte membrane composition (cholesterol, phospholipids, fatty acids, protein sulphydrils and carbonyls) was assessed and related to the stage of liver disease in patients with primary biliary cirrhosis before and after 1 year of ursodeoxycholate treatment. Results Compared with controls, patients showed lower levels of protein sulphydrils (28·9 ± 7·1 vs. 65·6 ± 1·8 nmol mg[sup -1] prot) and accumulation of carbonyls (4·7 ± 1·7 vs. 1·4 ± 0·1 nmol mg[sup -1] prot). Phosphatidylethanolamine level was lower in stage III–IV cirrhosis while phosphatidylcholine and cholesterol levels were higher; as a consequence the phosphatidylcholine/sphingomyelin ratio was higher than in controls (4·25 ± 0·55 in the I–II stage and 2·89 ± 0·44 in the stage III–IV vs. 1·61 ± 0·30). These changes were particularly evident in patients with more advanced stages of liver disease. Protein sulphydrils and carbonyls, phosphatidylethanolamine and cholesterol levels correlated (P < 0·05) with the histological stage of the liver disease, serum and membrane cholesterol levels were significantly related (r = 0·66, P < 0·05). One year of ursodeoxycholate administration was accompanied by major changes of the membrane lipid composition, partial reversal of protein oxidation, and improvement of serum parameters. Conclusions This study indicates that major alterations in protein status and lipid composition occur in erythrocyte membrane of patients with primary biliary cirrhosis. These changes were more pronounced in patients with advanced liver disease. Ursodeoxycholate was able to revert in part serum and erythrocyte alterations, especially in patients with early stages of liver disease. [ABSTRACT FROM AUTHOR]