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The Eastern-Europe region (EER), is a complex geotectonic area that captures part of the Alpine-Himalayan Orogen, the subduction of multiple NeoTethys Branches and part of the East European Craton. It is one of the most exciting geological areas in Europe due to a diversity of tectonic processes acting within it: extensional basin evolution, oceanic subduction, post-collisional volcanism, as well as active crustal deformation associated with the push of the Adria plate or the pull of the actively detaching Vrancea slab. This makes EER an excellent natural laboratory to study the behaviour of the lithosphere–asthenosphere system in a heterogeneous tectonic setting. To investigate the lateral heterogeneity and physical properties of the crust in the EER, we use ambient seismic noise data recorded by the vertical components of broad-band stations that have been operational between 1999 and 2020 in Eastern Europe and surrounding regions. We used this significant amount of data and the latest processing techniques of the ambient seismic noise field based on the continuous wavelet transform to compute cross-correlations between various station pairs, turning every available seismic station into a virtual source. The coda of the interstation cross-correlograms were used to determine coda quality factors (Qc) of Rayleigh waves in four different period ranges (3.0–5.0, 5.0–10.0, 10.0–20.0 and 20.0–30.0 s) and to invert them in the 2-D space, constructing the highest resolution attenuation tomography of the region. Our results reveal high attenuation features throughout the northeast Pannonian region, the Bohemian Massif, the East Carpathians and the Moesian Platform. Nevertheless, our findings do not emphasize a close correlation between the depth of sedimentary basins and attenuation features identified at longer periods. In addition, Qc variations are larger at short periods, indicating higher heterogeneity in the uppermost crust of Eastern Europe. Our findings demonstrate the higher efficiency of noise correlation approaches relative to earthquake data analyses investigating Qc at low frequencies. [ABSTRACT FROM AUTHOR]

The evolution of the Sicily Channel Rift Zone (SCRZ) is thought to accommodate the regional tectonic stresses of the Calabrian subduction system. Much of the observations we have today are either limited to the surface or to the upper crust or deeper from regional seismic tomography, missing important details about the lithospheric structure and dynamics. It is unclear whether the rifting is passive from far‐field extensional stresses or active from mantle upwelling beneath. We measure Rayleigh‐and Love‐wave phase velocities from ambient seismic noise and invert for 3‐D shear‐velocity and radial anisotropic models. Variations in crustal S‐velocities coincide with topographic and tectonic features. The Tyrrhenian Sea has a ∼10 km thin crust, followed by the SCRZ (∼20 km). The thickest crust is beneath the Apennine‐Maghrebian Mountains (∼55 km). Areas experiencing extension and intraplate volcanism have positive crustal radial anisotropy (VSH > VSV); areas experiencing compression and subduction‐related volcanism have negative anisotropy. The crustal anisotropy across the Channel shows the extent of the extension. Beneath the Tyrrhenian Sea, we find very low sub‐Moho S‐velocities. In contrast, the SCRZ has a thin mantle lithosphere underlain by a low‐velocity zone. The lithosphere‐asthenosphere boundary rises from 60 km depth beneath Tunisia to ∼33 km beneath the SCRZ. Negative radial anisotropy in the upper mantle beneath the SCRZ is consistent with vertical mantle flow. We hypothesize a more active mantle upwelling beneath the rift than previously thought from an interplay between poloidal and toroidal fluxes related to the Calabrian slab, which in turn produces uplift at the surface and induces volcanism. Plain Language Summary: The Calabrian arc system in the central Mediterranean is undergoing multiple tectonic processes of subduction and lithospheric extension. Various models explain the evolution of this complex system but lack detail on the extension and rifting along the arc, particularly across the Sicily Channel. We use seismic data from 83 stations to image the seismic velocity of the lithosphere and asthenosphere below the region in high resolution. We map areas experiencing extension and compression and observe that these coincide with active seismicity and volcanism. We find that the Sicily Channel has a thinner than average crust, a thin mantle lithospheric lid, and is underlain by a low shear‐velocity zone. Polarized shear velocities suggest mantle upwelling beneath the rift that produces uplift at the surface and induces volcanism. Our results provide new constraints on the evolution of the Calabrian slab and on the interplay between poloidal and toroidal fluxes of subduction zones. Key Points: Positive seismic radial anisotropy highlights the extent of rifting across the Sicily ChannelThe lithosphere beneath the Sicily Channel Rift Zone is thin, underlain by low seismic shear velocities and negative radial anisotropyNegative radial anisotropy in the upper mantle beneath the Sicily Channel suggests upwelling from slab‐related poloidal flow [ABSTRACT FROM AUTHOR]

Early evaluation of cardiovascular (CV) risk in hypertensive patients is of primary importance and studies of retinal vessels can be helpful. The aim of this study is to assess the correlation between retinal vessel changes and target organ damage (TOD), expressed as left ventricular remodelling (LVR) or hypertrophy (LVH). We evaluated 60 treated hypertensive individuals (mean age 60.9±13.3 years). On the basis of echocardiographic results, we divided the subjects showing the presence of TOD and subjects without TOD into Groups A and B, respectively. Both groups underwent a non-mydriatic digital retinography. The obtained vessel images were analysed using dedicated software in order to calculate AVR (arteriovenular ratio), index of the retinal arteriolar narrowing. The data analyses confirmed a mean AVR value of 0.86 in Group B and a mean value of 0.77 in Group A. AVR index was also analysed in a subgroup of A with evidence of LVR, and mean value was 0.76. The same procedure was carried out with subgroup of A with LVH and AVR index resulted 0.77. In all comparisons, P-value was statistically significant (P<0.05). Our findings provide evidence that in hypertensive patients retinal AVR correlates with the presence of TOD, in this study in the context of LVR and LVH. In conclusion, AVR offers a direct vision retinal microcirculation and, also, indirectly, provides information of the left ventricular geometric pattern in hypertensive patients; thus, AVR may have an important role in global CV risk stratification and could possibly be used for optimising the hypertensive patient management. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profiles of mavrilimumab, a human monoclonal antibody targeting the granulocyte-macrophage colony-stimulating factor receptor-α, in subjects with rheumatoid arthritis (RA).Methods: A randomised, double-blind, placebo-controlled, dose-escalating phase I study in subjects with RA who received stable methotrexate treatment for ≥3 months before enrolment.Subjects: received single intravenous escalating doses of mavrilimumab (0.01-10.0 mg/kg) or placebo.Results: 32 subjects were enrolled in this study (1 unblinded subject at 0.01 mg/kg and another at 0.03 mg/kg were followed by five sequential double-blinded cohorts, n=6 each, treated with 0.1, 0.3, 1.0, 3.0 and 10.0 mg/kg, respectively). Adverse events were mild or moderate and were reported with similar frequency across all treatment cohorts. One subject (10.0 mg/kg) experienced moderate face and neck urticaria during infusion that resolved with symptomatic treatment. Systemic clearance of mavrilimumab approached that of endogenous IgG at doses >1.0 mg/kg; pharmacodynamic activity was confirmed in the 1.0 and 3.0 mg/kg cohorts by suppression of suppressor of cytokine signalling 3 mRNA transcripts. In exploratory analyses, reductions of acute phase reactants were observed in subjects with elevated C-reactive protein (>5 mg/l) and erythrocyte sedimentation rate (≥20.0 mm/h) at baseline. No significant change in Disease Activity Score 28-joint assessment (DAS28) was seen in any of the cohorts. In mavrilimumab-treated subjects (n=15) with baseline DAS28 >3.2, mean disease activity (DAS28) was significantly reduced at 4 weeks.Conclusion: In this first-in-human study, mavrilimumab showed preliminary evidence of pharmacodynamic activity. Importantly, the safety and pharmacokinetic profiles of mavrilimumab support further clinical studies in RA.Trial Registration Number: NCT00771420. [ABSTRACT FROM AUTHOR]

In Italy, serological screening is recommended to prevent congenital toxoplasmosis as part of the antenatal care protocol. Our study investigates (1) adherence to screening among Italian and migrant women and (2) specific T. gondii seroprevalence among hospitalized puerperas in Brescia and Udine, in northern Italy. All migrants (Group B) and a random Italian sample (Group A) filled in a questionnaire. Serological screening was rated as adequate when performed before conception or by the 12th week of gestation, and periodically repeated during pregnancy whenever negative. Ninehundred and twenty-two (922) puerperas were enrolled (Group A: 743; Group B: 179). Mean gestational age at first antenatal visit was 9.3 week, significantly more delayed in migrants (11.2w vs 8.9w; P < 0.0001). Toxoplasmosis was mentioned as a potential vertically transmitted infection by 380/922 (41.2%), but only by 13.4% of migrants ( P < 0.0001). Anti-Toxoplasma IgG-Ab tested positive in 319/892 (35.8%), while the information was missing for 9 and 21 women resulted untested. Patients from northern Africa had an higher (AOR 3.63%; P = 0.002), while Asian patients a lower (AOR 0.33; P = 0.045) probability of being immune. A late screening was recorded in 115/848 (13.6%) women (Group A: 9.35%; Group B: 31.9%; P < 0.0001) and 82.1% of eligible migrants were not correctly monitored for toxoplasmosis during pregnancy. A late toxoplasma serological test in migrant women precludes the timely application of preventive measure and may represent an indicator of suboptimal antenatal care. [ABSTRACT FROM AUTHOR]

The article presents a study which focuses on examining the effects of treatment with rituximab plus methotrexate on the improvement of patient-reported outcomes in patients with active rheumatoid arthritis (RA). These patients, who also experienced response to anti-tumor necrosis factor therapy, were assessed for treatment effects on pain, functional disability, quality of life and disease activity.

OBJECTIVE: To determine the safety and efficacy of additional courses of rituximab in patients with rheumatoid arthritis (RA). METHODS: An open-label extension analysis of RA patients previously treated with rituximab was conducted. Patients who had participated in any of 3 double-blind trials were eligible for additional courses (2 infusions of 1,000 mg given 2 weeks apart) if they exhibited a swollen joint count and tender joint count of >/=8 with >/=16 weeks elapsing after the previous course. Safety was assessed in patients receiving all or a portion of a rituximab course. Efficacy was assessed 24 weeks after each course, using the American College of Rheumatology 20% criteria for improvement (ACR20), ACR50, ACR70, European League Against Rheumatism (EULAR) response criteria, Disease Activity Score in 28 joints, the disability index of the Health Assessment Questionnaire, and Short Form 36 scores, stratified according to prior tumor necrosis factor (TNF) inhibitor exposure. RESULTS: A total of 1,039 patients received >/=1 course of rituximab. Of these, 570 received 2 courses, 191 received 3 courses, and 40 received 4 courses, for a total of 1,669 patient-years. Irrespective of prior TNF inhibitor exposure, ACR20 responses were comparable at week 24 after course 1 and at week 24 after course 2 (65% versus 72%), as were ACR50 and ACR70 responses. EULAR moderate/good responses were also comparable in course 2 relative to course 1 (88% versus 79%), with EULAR remission occurring in a 2-fold higher proportion of patients after course 2 than after course 1 (13% versus 6%). The most common adverse events, which were mild-to-moderate acute infusion-related events, decreased with each course. The serious infection rate after course 1 (5.1 per 100 patient-years) remained stable through additional courses. The proportion of patients with circulating IgM and IgG levels below the lower limit of normal (LLN) increased with subsequent courses; however, serious infection rates in these patients (5.6 per 100 patient-years in patients with low IgM levels and 4.8 per 100 patient-years in patients with low IgG levels were comparable with those in patients with immunoglobulin levels above the LLN (4.7 per 100 patient-years). Patients with human antichimeric antibody (9.2%) did not exhibit decreasing efficacy or present additional safety concerns. CONCLUSION: These findings indicate that patients treated with repeated courses of rituximab have sustained clinical responses with no new adverse events. [ABSTRACT FROM AUTHOR]

Isolated ambulatory hypertension is a condition characterized by elevated ambulatory but normal clinic blood pressure (BP), and has been reported to be associated with increased cardiovascular risk in untreated subjects. However, little is known about the relationship between this condition and intermediate end points such as target organ damage (TOD) in treated hypertensives. We investigated the impact of isolated ambulatory hypertension on left ventricular hypertrophy (LVH) and microalbuminuria (MA) in a selected sample of treated nondiabetic hypertensives with effective and prolonged clinic BP control (BP<140/90?mmHg). Clinic BP measurements, routine diagnostic procedures, echocardiography and 24-h urine collection for MA, were undertaken in 80 patients (mean age 53±8 years) with essential hypertension attending our hospital outpatient centre at baseline and after an average follow-up of 30 months. At follow-up evaluation BP status was assessed by self-measurement of BP and ambulatory BP monitoring (ABPM). At the follow-up visit, 51 out of 80 patients (63.7%) reached a BP control according to ABP (average daytime BP<132/85?mmHg) criteria (group I) whereas the remaining 29 did not (group II); home BP was controlled (BP<135/85?mmHg) in all members of group I and in 86%of group II. In the overall study population, mean Sokolow voltage, LV mass index (LVMI) and urinary albumin excretion (UAE) decreased compared to baseline from 24.1±5.0 to 18.9±5.1?mm (P<0.05), 115.6±24.1 to 97.7±21.6?g/m2 (P<0.01), 11.8±23.7 to 5.8±14.9?mg/24?h (P<0.05), respectively. The prevalence of ECG LVH, altered LV patterns and MA fell from 7.5 to 2.5%(P=NS), from 45 to 25 (P<0.01) and from 13.7 to 5.1%(P<0.05), respectively. However, when data were analysed separately for the two groups a significant decrease of echo LVH and MA was found only in patients with controlled ABP. LVMI and MA decreased from 117.1±23.1 to 95.9±22.1?g/m2 (P<0.01) and 12.8±24.7 to 4.1±5.7?mg/24?h (P<0.05) in group I, and from 114.1±24.8 to 102.3±20.3 (P=NS) and 11.9±22.1 to 6.3±18.1?mg/24?h (P=NS) in group II. In conclusion, in the present study isolated ambulatory hypertension in treated patients is associated with a lack of regression in cardiac and extracardiac TOD, suggesting that a tight BP control throughout the 24?h plays a key role in lowering hypertension-induced structural and functional alterations at cardiac and renal level.Journal of Human Hypertension (2005) 19, 471-477. doi:10.1038/sj.jhh.1001850 Published online 3 March 2005 [ABSTRACT FROM AUTHOR]

Objective. To describe the prevalence of advanced retinal microvascular lesions and their associations with cardiac and extracardiac signs of target organ damage (TOD) in a large selected hypertensive population. Methods. A total of 2172 non-diabetic untreated and treated uncomplicated essential hypertensives consecutively attending for the first time our hospital outpatient hypertension clinic and included in the Evaluation of Target Organ Damage in Hypertension (ETODH), an observational ongoing registry of hypertension-related TOD, were considered for this analysis. Advanced hypertensive retinopathy was defined by the presence of any of the following lesions: flame-shaped haemorrhages, soft exudates or cotton wool spots and papilloedema. Left ventricular hypertrophy (LVH), carotid structural abnormalities, such as plaques and intima media (IM) thickening, and microalbuminuria were diagnosed according to the 2003 ESH/ESC guidelines criteria. Results. Among the whole study population, 33 patients (1.5%) were found to have advanced hypertensive retinopathy. Patients with these retinal lesions were similar to those without for age, body mass index, known duration of hypertension, smoking habit, total serum cholesterol, fasting blood glucose and prevalence of antihypertensive treatment; whereas mean systolic and diastolic blood pressures were higher in the former group. The prevalence rates of LVH, carotid plaques, carotid IM thickening and microalbuminuria in patients with and without retinopathy were 57%, 67%, 69%, 19% and 25%, 47%, 44%, 12%, respectively. In a multivariate logistic regression analysis, advanced retinopathy was significantly associated with LVH (OR?=?4.0), carotid IM thickening (OR?=?2.9), carotid plaques (OR?=?2.8), but not with microalbuminuria. Conclusions. Our study indicates that: (i) advanced retinopathy is a rare finding in non-diabetic hypertensive patients seen in a specialist setting; (ii) a strong relation exists between retinal microvascular lesions and cardiac and macrovascular markers of TOD. [ABSTRACT FROM AUTHOR]

Despite the impressive increase of home blood pressure monitoring (BPM) among hypertensive patients over the last few years, a limited number of studies have analysed the rate of home BPM and its relationship with target blood pressure (BP) control, in representative samples of the hypertensive population. The objectives of the study were first to evaluate the prevalence of home BPM in a large selected group of treated hypertensive patients referred to our outpatient hypertension hospital clinic. Second, to assess the rate of satisfactory clinic BP control in patients with or without familiarity with home BPM. In all, 1350 consecutive hypertensive patients who attended our hypertension centre during a period of 12 months and were regularly followed up by the same medical team were included in the study. After informed consent all patients underwent the following procedures: (1) accurate medical history (implemented by a structured questionnaire on demographic and clinical characteristics, including questions concerning home BPM); (2) physical examination; (3) clinic BP measurement; (4) routine examinations; and (5) standard 12-lead electrocardiogram. A total of 897 patients (66%) out of 1350 (687 men, 663 women, age 58.6±12.3 years, mean clinic BP 141±16/87±9?mmHg ) were regularly practising home BPM. In this group of patients, home BPM was associated with a significantly greater rate of satisfactory BP control (49.2 vs 45.6%, P<0.01). Patients performing home BPM were more frequently men (54 vs 46%, P<0.02 ) younger (average age 57.8±12.0 vs 60.3±12.7 years , P<0.001) and with a higher educational level (defined by more than 8 years of school, 71 vs 55%, P<0.05) than their counterparts. There were no significant differences in duration of hypertension, hypercholesterolaemia, obesity, smoking, diabetes, associated cardiovascular diseases, left ventricular hypertrophy and compliance with drug treatment. This study demonstrates that: (1) home BPM is widely performed by hypertensive patients managed in a hypertension hospital clinic; (2) this practice is associated with a significantly higher rate of clinic BP control; and (3) age, male gender and educational level influence the adoption of home BPM.Journal of Human Hypertension (2004) 18, 725-731. doi:10.1038/sj.jhh.1001737 Published online 22 April 2004 [ABSTRACT FROM AUTHOR]

A number of studies have shown that a smaller than normal nocturnal blood pressure (BP) decrease is associated with cardiovascular disease. However, no large prospective studies have examined the reliability of nocturnal dipping within individuals. The aim of our study was to investigate the short-term variability of nocturnal BP fall in a large cohort of patients with recently diagnosed essential hypertension. In all, 414 uncomplicated never treated hypertensive patients referred to our outpatient hypertension hospital clinic (mean age 46±12 years; 257?M, 157 F) prospectively underwent: (1) repeated clinic BP measurements; (2) routine examinations recommended by WHO/ISH guidelines; and (3) ambulatory BP monitoring (ABPM) twice within a 4-week period. Dipping pattern was defined as a reduction in the average systolic and diastolic BP at night greater than 10% compared to average daytime values. Overall, 311 patients (75.1%) showed no change in their diurnal variations in BP. Of the 278 patients who had a dipping pattern on the first ABPM, 219 (78.7%) confirmed this type of profile on the second ABPM, while 59 (21.3%) showed a nondipping pattern. Among 37 dipper patients with >20% of nocturnal systolic BP decrease (extreme dippers), only 16 (43.2%) had this marked fall in BP on the second ABPM. Of the 136 patients who had a nondipping pattern on the first ABPM, 92 (67.6%) confirmed their initial profile on the second ABPM, while 44 (32.4%) did not. Patients with reproducible nondipping profile were older (48±12 years) than those with reproducible dipping profile (44±12 years, P<0.05). These findings indicate that: (1) short-term reproducibility of nocturnal fall in BP in untreated middle-aged hypertensives is rather limited: overall, one-fourth of patients changed their initial dipping patterns when they were studied again after a few weeks; (2) this was particularly true for extreme dipping and nondipping patterns; (3) abnormalities in nocturnal BP fall, assessed by a single ABPM, cannot be taken as independent predictors of increased cardiovascular risk.Journal of Human Hypertension (2004) 18, 503-509. doi:10.1038/sj.jhh.1001681 Published online 29 January 2004 [ABSTRACT FROM AUTHOR]

Unsatisfactory blood pressure (BP) control so often described in treated hypertensive populations is also explained by insufficient physicians' awareness of experts' guidelines. We assessed awareness of current recommendations about hypertension management in a general practice setting, using the World Health Organization/International Society of Hypertension (WHO/ISH) 1999 guidelines as reference. In a regionwide survey, a total of 5133 physicians (three-quarters of all active general practitioners in Lombardy, a region of north-western Italy) were contacted by letter and received a multiple choice 10-item questionnaire. Data on physicians' demographic characteristics, information on hypertension prevalence and their perception of BP control among their patients were also requested in an additional form. The number of answers in agreement with WHO/ISH guidelines was used as an awareness measure. This was considered adequate if correct answers to six out of 10 questions, including an appropriate definition of hypertension, were provided. Of the 1256 returned questionnaires (a 24.5% response rate), 1162 were suitable for analysis. The mean score of correct answers was 5.3 points and only 20.1% of the study population correctly answered at least six of the questions (including that on the definition of hypertension in the elderly). Guidelines awareness was negatively related to increase in physicians' age and duration of clinical practice and by the male gender. Finally, the physicians reported a high rate of achieved BP control, and those who were considered to have achieved highest rates (>75%) of control in their patients had a lower rate of adequate knowledge than those who reported less-successful therapeutic results (18 vs 25%, P<0.01), suggesting that they ignored or disregarded the goal BP recommended by the guidelines. This large regional survey shows that a sufficient degree of guidelines awareness is present in a minority of primary-care physicians in... [ABSTRACT FROM AUTHOR]

To investigate whether in recently diagnosed essential hypertensives a reduced nocturnal fall in blood pressure (BP), established on the basis of two 24-h ambulatory blood pressure monitorings (ABPM) is related to a greater cardiovascular damage. In all, 355 consecutive, recently diagnosed, never-treated essential hypertensives referred for the first time to our outpatient clinic were included in the study. Each patient underwent the following procedures: (1) two 24-h ABPMs performed within 3 weeks, (2) 24-h urinary collection for microalbuminuria, (3) nonmydriatic photography of ocular fundi, (4) echocardiography, (5) carotid ultrasonography. We defined nondipping profile as a night-day systolic and diastolic fall ?10 % (mean of two ABPMs). A dipper BP profile was found in 238 patients, whereas in 117 patients a nondipper profile was present. The two groups were similar for age, gender, body mass index, smoking habit, clinic BP, 48-h BP and heart rate, while, by definition, night-time systolic and diastolic BP were significantly higher in nondippers than in dippers (130/81 vs 121/74 mmHg, P< 0.0001).The prevalence of left ventricular hypertrophy (LVH) defined by four different criteria: (a) LV mass index (LVMI) ?125?g/m2 in both genders; (b) LVMI ?134?gm2 in men and ?110 in women; (c) LVMI?125?g/m2 in men and ?110?g/m2 in women; (d) LVMI?51?g/m2.7 in men and ?47?g/m2.7 in women was significantly higher in nondippers than in dippers (a: 12 vs 7%, P<0.05; b: 16 vs 7%, P<0.01; c: 20 vs 11%, P<0.01; d: 35 vs 23% P<0.02) and this finding was associated with a significant increase in aortic root and left atrium dimensions. There were no differences between the two groups in the prevalence of carotid and retinal changes and microalbuminuria. In conclusion our findings suggest that never-treated hypertensives with a reduced BP fall in the night time, defined on the basis of two... [ABSTRACT FROM AUTHOR]

It has been clearly demonstrated that ageing and arterial hypertension are both associated with an increased prevalence of left ventricular hypertrophy (LVH), which is a powerful risk factor for cardiovascular (CV) events. The objective of this study was to assess the impact of echocardiographic LVH in profiling the absolute CV risk stratification according to the 1999 World Health Organization-International Society of Hypertension (WHO/ ISH) guidelines in elderly hypertensive patients. A total of 223 never-treated elderly patients (≥65 years) with essential hypertension (98 men, 125 women, mean age 72 ± 5 years) referred to our outpatient hospital clinic were included in the study. They underwent the following procedures: (1) medical history, physical examination, and clinic blood pressure; (2) routine blood chemistry and urine analysis and (3) electrocardiogram. The risk was initially stratified according to the routine procedures suggested by WHO/ISH guidelines and subsequently reassessed by adding the results of echocardiography (LVH as left ventricular mass index >51 g/m[sup 2.7] in men and >47g/m[sup 2.7] in women). According to routine classification, 56% (n = 125) were medium-risk patients, 29% (64) high-risk and 15% (34) very-high-risk patients. The overall prevalence of LVH was 56% (48% in medium-risk and 62% in high-risk or very-high-risk patients, P< 0.01). A marked change in risk stratification was observed when echocardiographic LVH was taken into consideration: medium-risk patients decreased to 29% and high-risk patients rose to 56% (P<0.01). In conclusion, ultrasound assessment of cardiac target organ damage is extremely useful in obtaining a more valid assessment of global cardiovascular risk in elderly hypertensives, because stratification based on diagnostic routine procedures can underestimate the overall risk in a large fraction (48%) of medium-risk subjects. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the diagnostic approach to recently diagnosed hypertensive patients by primary care physicians in Italy and to find out whether general practitioners manage these patients according to 1999 WHO/ISH guideline recommendations. In total, 228 consecutive patients (117 men and 111 women, mean age 51±12 years) with recently diagnosed hypertension (<2 years) referred for the first time to six outpatient hypertension centres throughout Italy were included in the study. The primary care physicians' approach was evaluated during the specialist visit by a specific questionnaire containing detailed questions about diagnostic work-up and treatment made at the time of the first diagnosis of hypertension. At the study visit, 71% of the patients were on treatment with antihypertensive drugs and 18.7% of them had blood pressure (BP) values lower than 140/90 mmHg. A complete clinical and laboratory evaluation according to the minimum work-up suggested by the guidelines had been carried out in only 10% of the patients. A full physical examination had been performed in 60% of the patients, electrocardiogram in 54%, serum total cholesterol in 53%, glucose in 49%, creatinine in 49%, urine analysis in 46%, potassium in 42%, and fundus oculi in 19%. Additional investigations such as ambulatory BP monitoring, echocardiogram, carotid ultrasonogram, and microalbuminuria had been carried out in a minority of patients (21, 18, 9, and 3%, respectively). The impact on hypertension guidelines on patients' management in everyday primary care practice appears marginal. Thus, our findings indicate that the majority of general practitioners manage hypertensive patients according to a simple BP-based approach rather than a more integrated approach based on global risk stratification. [ABSTRACT FROM AUTHOR]

Aims: (1) To evaluate the prevalence of clinic blood pressure (BP) control in a large sample of treated hypertensives followed in our hypertension clinic during the year 2000, and to compare it with our 1997 data. (2) To investigate the prevalence of left ventricular hypertrophy (LVH) according to different levels of BP control. Methods and results: One thousand consecutive hypertensive patients who attended our hypertension hospital clinic in a period of 7 months during the year 2000 and who had regularly been followed by the same medical team were included in the study. LVH was assessed using two different electrocardiographic criteria (Sokolow-Lyon and Cornell). This population had similar clinical characteristics of a cohort including 700 patients seen at our centre during 1997 in which BP control rate was 34% (Cuspidi et al. , J Hypertens 1999; 17: 835-41). During follow-up, 441 of the treated patients had clinic BP < 140/90 mmHg, 283 < 150/95 mmHg and 276 ≥ 150/95 mmHg, indicating that BP control was satisfactory in 44.1%, borderline in 28.3% and unsatisfactory in 27.6% of the cases. Thirty-five patients (3.6%) had LVH according to Cornell criteria and 25 (2.6%) according to Sokolow criteria. A significantly lower prevalence of LVH was detected in patients with optimal BP control (< 130/85 mmHg) compared to those with unsatisfactory BP (2.3% vs 9.4%, respectively, p < 0.01). Conclusion: The study demonstrates that: (1) hypertensive patients in a hypertension clinic have satisfactory BP control in 44.1% of cases, indicating a significant improvement of BP control in this clinical setting during the last 3 years; (2) prevalence of LVH is significantly related to BP control. [ABSTRACT FROM AUTHOR]

Left ventricular (LV) concentric remodelling is an adaptive change in cardiac geometry frequently observed in arterial hypertension. This study was addressed to investigate the extent of extracardiac target organ damage (TOD) in patients with LV concentric remodelling. Two groups of never-treated essential hypertensives, 31 with normal LV geometry (group I, relative wall thickness: 0.39) and 31 with LV concentric remodelling (group II, relative wall thickness: 0.47) matched for age, sex, body mass index and mean 24-h systolic blood pressure (BP), were included in the study. They underwent clinical and laboratory examination, 24-h ambulatory BP monitoring (ABPM), 24-h urinary collection for microalbuminuria, non-mydriatic photography of ocular fundi, echocardiography and carotid ultrasonography. In both groups age (I: 51 ± II years; II:51 ± 11 years), body mass index (I: 25 ± 3 kg/m²; II: 26 ± 3 kg/m²), clinic and 24-h ABPM values (I: 149 ± 11/95 ± 8, 142 ± 11/91 ± 7 mm Hg; II: 150 ± 11/98 ± 9, 142 ± 12/92 ± 9mm Hg) were similar by design. There were no differences between patients with normal LV geometry and with LV concentric remodelling in LVM index (97 ± 16 vs 99 ± 16), carotid intima-media thickness (0.7 ± 0.02 vs 0.7 ± 0.02) and carotid plaques prevalence (35% vs 35%). Furthermore, no significant differences among the two groups were found in the prevalence of retinal changes and microalbuminuria. These results suggest that in hypertensive patients with similar BP and LVMI levels, LV concentric remodelling is not associated with more prominent TOD. [ABSTRACT FROM AUTHOR]

Objective: To investigate in a selected population of patients with a recently diagnosed essential hypertension the short-term intrasubject variability of diurnal changes in blood pressure (BP). Methods: Two hundred and eight consecutive, recently diagnosed, never treated essential hypertensives (119 men, 89 women, 46 ± 12 years) underwent 24-h ambulatory BP monitoring (ABPM) twice within 3 weeks. Dipping pattern was defined as a reduction in average systolic and diastolic BP at night greater than 10% compared to average daytime values. Results: 177 subjects (85%) showed no change in their diurnal variations in BP. Of the 159 subjects who had a dipping pattern on first ABPM, 134 (90.6%) confirmed this type of profile on the second ABPM, while 15 (9.4%) showed a non-dipping pattern. Of the 59 subjects who had a non-dipping pattern on the first ABPM, 43 (72.2%) confirmed their initial profile on the second ABPM, while 16 (28.8%) did not. Conclusion: These findings indicate that short-term reproducibility of diurnal changes in BP in early phases of untreated essential hypertension, characterized by a large prevalence of dipping pattern, is overall satisfactory. However, our study underlines that also in this particularly selected population of hypertensives the definition of non-dipping status on the basis of a single ABPM remains unreliable in about one-third of patients. [ABSTRACT FROM AUTHOR]

Background: Hypertensive patients with left ventricular hypertrophy (LVH) need a prompter and more intensive pharmacological treatment than subjects without evidence of cardiac involvement. So the detection of LVH plays an important role for decision-making in hypertensives. Objective: To evaluate the impact of different echocardiographic criteria to define LVH in a more precise stratification of absolute cardiovascular risk in hypertensives without target organ damage (TOD) as assessed by routine investigations. Methods: A total of 100 never treated patients with grade 1 and 2 essential hypertension (53 men, 47 women, age 44 ± 12 years) referred for the first time to our outpatient clinic were included in the study. They underwent the following procedures: (1) family and personal medical history, (2) clinic blood pressure (BP) measurement, (3) routine blood chemistry and urine analysis, (4) electrocardiogram, (5) echocardiogram. Risk was stratified according to the criteria suggested by the 1999 WHO-ISH guidelines. TOD was initially evaluated by routine procedures only, and subsequently reassessed by using six different echocardiographic criteria to recognise LVH: (a) left ventricular mass index (LVMI) >120 g/m[SUP2] in men and 100 g/m[SUP2] in women; (b) 125 g/m[SUP2] in men and 110 g/m[SUP2] in women; (c) 134 g/m[SUP2] in men and 110 g/m[SUP2] in women; (d) 125 g/m[SUP2] in men and 125 g/m[SUP2] in women; (e) 51 g/m[SUP2.7] in men and 47 g/m[SUP2.7] in women; (f) 126 g/m in men and 105 g/m in women. Results: According to the first classification based on routine investigations, 46% were low risk and 54% were medium risk patients. Significant changes in risk stratification were obtained when LVH was assessed by echocardiography. A percentage of patients, ranging from 9 (f) to 25% (d), were found to having LVH according to different criteria, and consequently moved from low and medium risk strata to high risk stratum. Conclusions: The detection of LVH... [ABSTRACT FROM AUTHOR]

Background: Left ventricular hypertrophy (LVH) and increased carotid intima-media thickness (IMT) represent independent risk factors for cardiovascular disease. Objective: To evaluate the prevalence of echocardiographic LVH and common carotid artery (CCA) intima-media (IM) thickening by different criteria in a large sample of hypertensive patients referred to our Hypertension Clinic. Methods: Echocardiograms and ultrasonographic carotid examinations have been performed in 640 consecutive hypertensives referred to our outpatient's hypertension unit. LVH was diagnosed using six different criteria, when left ventricular mass index (LVMI) exceeded (a)100 g/m 2 in women and 120 g/m 2 in men, (b) 110 g/m 2 in women and 125 g/m 2 in men, (c) 110 g/m 2 in women and 134 g/m 2 in men, (d) 125 g/m 2 in both sexes, (e) 47 g/h 2.7 in women and 51 g/h 2.7 in men, (f) 105 g/h in women and 126 g/h in men. Thickening of CCA IM was identified using three partition values; when IMT was (a) ≥0.8 mm; (b) ≥0.9 mm; (c) ≥1.0 mm in both sexes. Results: Echocardiographic and ultrasonographic examinations of sufficient quality to be analysed were obtained in 611 patients (95.2%). Prevalence of LVH ranged from 18.6% (d) to 42.2% (f) and was significantly higher in men than in women by criteria (d) and (e), but slightly higher in women when using criteria (a) and (c). Eccentric hypertrophy was the most frequent type of LVH independently of the criteria used. Prevalence of IM thickening ranged from 14.7% (c) to 44.2% (a). Significant correlations between left ventricular mass (LVM)/body surface area, LVM/height and LVM/height 2.7 , and carotid IM thickness were found ( r = 0.41; p < 0.0001; r = 0.31; p < 0.0001; r = 0.30; p < 0.0001, respectively). Conclusion: The prevalence of LVH and CCA IM thickening in hypertensive patients is markedly dependent on the partition values used to define these markers of target organ damage. Considering the pivotal role of LVH and CCA IM thickening in assessing the global cardiovascular risk profile in hypertensives, improved standardization in defining LVH and carotid IM thickening is needed. [ABSTRACT FROM AUTHOR]

The effects of dopexamine on the renal circulation have been examined to show whether any augmentation of renal blood flow (RBF) was secondary to the effect of the drug on cardiac output (CO) or whether it had any additional direct renal vasodilator activity. Eight male patients with mild to moderate hypertension, who were undergoing renal vein catheterization for renin estimation, were studied. Dose related increments in RBF (baseline (B)=504 ml·min; after treatment (D)=605 ml·min), CO (B=5.9 l·min; D=6.7 l·min), heart rate (B=77 beats/min; D=100 beats/min) and systolic blood pressure (B=143 mmHg; D=166 mmHg) were observed on administration of dopexamine 3 µg·kg·min, with insignificant changes in diastolic blood pressure (B=84.4 mmHg; D=90 mmHg) and total peripheral resistance (B=17.85; D=17.25 Units). There was a slight but significant reduction in renal vascular resistance (B=20.59, D=18.75). The ratio of RBF to CO (%) confirmed that the increase in RBF due to dopexamine hydrochloride was greater that attributable to the increase in CO or perfusion pressure alone (RBF/CO B=8.5%, D=9%), consistent with selective renal vasodilation. The fall in renin activity and lack of systemic vasodilatation suggest that this was a DA-receptor mediated effect. [ABSTRACT FROM AUTHOR]

Propranolol and practolol were tested in patients with repeated daily occurrence of spontaneous angina. Twenty-one showed ST segment depression (type I) and 15 ST segment elevation (type II) during angina. The efficacy of the treatment was evaluated in subjective (number of reported episodes of pain) and objective terms (number of episodes of electrocardiographic abnormalities documented during periods of continuous recording): practolol was fully effective in 42 per cent and propranolol in 38 per cent of type I cases; in type II angina 73 per cent of the cases fully responded to propranolol, none of the patients in this group given practolol improved. The study also showed that: (a) the effects on angina are strictly dose-dependent, and optimal results are achieved at individualized doses; (b) within the same subject the response may be preferential to one beta-blocker as opposed to the other; (c) propranolol is more effective in type II angina; (d) the occurrence of heart failure is uncommon even with high doses of beta blockers;(e) the relief of angina is due to prevention of ischaemia and not to a placebo or anaesthetic effect; (f) the prevention of ischaemia is not adequately explained by reduction of the mechanical effort and the oxygen need of the myocardium; (g) the antianginal effect is possibly dissociated from the beta blockade of the heart. The hypothesis that beta-blocking agents influence the conronary vasomotion is discussed. [ABSTRACT FROM PUBLISHER]

The function of both right and left sides of the heart was studied during spontaneous attacks of angina pectoris at rest in 7 patients showing ST depression (type I) and 4 showing ST elevation (type II) during the attack. In none of the 44 type I attacks and 29 type II attacks which were recorded did circulatory changes; the latter were different in the two groups. Type I attacks showed: a) a brief fall in arterial pressure, accompanied by b) a rise of right atrial and pulmonary wedge pressures and c) a decrease of cardiac output, right and left stroke work, the mean rate of systolic ejection, and indirect left ventricular pre-ejection dP/dt. In the course of the attack a hypertensive phase followed, which was paralleled by an increase of heart rate, cardiac output, left and right stroke work, and mean systolic ejection rate, left dP/dt; right atrial pressure and wedge pressure remained raised. All of the circulatory functions started to revert towards the pre-attack levels coincident with the waning phase of the electrocardiographic alteration, the latter occurring either spontaneously or after nitroglycerin. Type II attacks for the entire duration of the electrocardiographic changes showed: a) a reduction of arterial pressure, cardiac output, right and left stroke work, mean systolic ejection rate, and left dP/dt, b) a rise of right atrial and wedge pressures, and c) quite small changes of heart rate. When the electrocardiogram started to revert to the pre-attack aspect, the cardiac function rapidly improved and, after a supernormal phase, returned to the basal levels in about 2 minutes. It is concluded: 1) that no circulatory factor interfering with the mechanical effort of the heart is responsible for eliciting spontaneous angina: 2) that in type I attacks right and left ventricular impairment occurs which recovers rapidly, possibly through a sympathetic compensation; 3) that in type II attachs dysfunction of both sides of the heart occurs and persists throughout the episode of electrocardiographic alteration; 4) that the dynamic impairment is probably more severe in type I than in type II angina. [ABSTRACT FROM PUBLISHER]

Muir-Torre syndrome (MTS) is an autosomal dominant disorder characterized by the presence of at least one sebaceous gland tumour and a minimum of one visceral malignant tumour. Recently. microsatellite instability (MSI) has been detected in the tumours of patients with MTS and germline mutations of the hMSH2 and hMLH1 mismatch repair genes have been detected in some patients with this syndrome. To determine if the tumours of patients with MTS have widespread genomic instability and whether loss of heterozygosity (LOH) in the chromosomal regions containing hMSH2 and hMLH1 is detectable, MSI and LOH were examined at 10 dinucleotide repeats on chromosomes 2p, 3p, 5q, 9p, 17p and 18q. Data were obtained from six sebaceous gland tumours and two adenocarcinomas of the colon from three patients of two Muir-Torre families. MSI was detected at more than half of the loci tested in all sebaceous tumours examined. In addition, there was LOH at D2S119 in one sebaceoma and one sebaceous carcinoma from one patient. The colon carcinomas from two patients showed MSI at five of the 10 loci analysed. These results show that widespread MSI is a feature of tumours in patients with MTS. In addition, the finding of LOH at D2S119, a marker located in the vicinity of hMSH2, in sebaceous tumours of one patient indicates that this gene may have a pathogenetic role in this patient. [ABSTRACT FROM AUTHOR]

A middle-aged man was admitted to our department because of sleep-wake cycle disorders (alternating hypersomnia and sleeplessness), bipolar behavioural disturbances and marked fluctuations in blood pressure and heart rate. Neither evident precipitating stimuli nor an obvious cause for his illness were found. When tests that normally activate intrinsic autonomic responses were performed, two distinct circulatory patterns were recognized. During hypersomnia (phase A), cardiovascular reflex activity was blunted or abolished and orthostasis could not be maintained. The clinical, biochemical, behavioural pictures and the observed decrease in sympathetic outflow resembled the effects of clonidine administration. On the contrary, during sleeplessness (phase B) the autonomic pathways were functionally integral and orthostatic hypotension was not detected. The clinical, biochemical, behavioural features and cardiovascular overactivity closely mimicked the abrupt withdrawal syndrome encountered with clonidine. Three hypothetical mechanisms are advanced to explain this intriguing case as well as the acute and chronic relief of our patient's clinical problem following institution of clonidine therapy (phase C). The role played by central alpha adrenoceptors in integrating sleep-wake, cardiovascular and behavioural functions is also suggested. [ABSTRACT FROM PUBLISHER]

Attacks of Prinzmetal's variant form of angina pectoris are spontaneous, recur cyclically, and present unequivocal electrocardiographic alterations: they are ideal for a detailed haemodynamic study. [ABSTRACT FROM PUBLISHER]

Four patients with Prinzmetal's variant angina pectoris were subjected to continuous electrocardiographic recording. In three of them several episodes of ST segment elevation unaccompanied by pain were recorded. In one patient, identical electrocardiographic alterations were observed both in presence or in absence of pain, while in the others a good correlation was evident between pain and severity of the electrocardiographic abnormalities. In two patients transmural myocardial infarction complicated the course of the angina. In contrast to the classical findings, in these patients the attacks of chest pain did not cease after the infarction, but became more frequent and severe. The electrocardiographic alterations of the anginal episodes occurred in the same myocardial areas involved by the infarction, so that a reversible superposition of electrocardiographic signs of acute ischaemia on those of recent necrosis was observed. [ABSTRACT FROM PUBLISHER]

Although deep brain stimulation (DBS) is a clinically effective therapy for patients with advanced Parkinson's disease (PD), its physiological effects on the brain and possible actions on non-motor functional systems remain largely unknown. This study evaluated the effects of DBS of the subthalamic nucleus (STN) on neurophysiological variables and on cardiovascular physiology. Nine patients affected by PD undergoing chronic DBS of the STN have been studied. We performed electroencephalography (EEG), somatosensory (SEPs) and visual evoked potentials (VEPs), exteroceptive masseteric silent period and sympathetic skin response (SSR) studies with DBS ON and OFF. To assess the effects of stimulation on the cardiovascular system the tilt test and plasma renin activity were studied. When we turned the DBS OFF, both SEP N20 and the VEP P100 component increased significantly in amplitude whereas the SSR decreased in amplitude and increased in latency. Although plasma renin activity tended to increase with DBS OFF, its modification induced by postural changes and blood pressure values did not significantly differ with DBS ON and OFF. We conclude that DBS of the STN in PD, besides inducing a clinical improvement, induces several non-motor effects. [ABSTRACT FROM AUTHOR]