High-intensity focused ultrasound treatment in patients with refractory glaucoma.

PURPOSE: To assess the safety and efficacy of ultrasound coagulation of the ciliary body in refractory glaucoma. METHODS: This prospective multicenter interventional study was conducted in two Italian university-affiliated glaucoma centers: St. Orsola-Malpighi Teaching Hospital (Bologna, Italy) and University Eye Clinic of Genoa (Genoa, Italy). The main inclusion criterion was the diagnosis of glaucoma with a baseline intraocular pressure (IOP) ≥ 21 mmHg while on maximum topical and systemic medical hypotensive treatment. The EyeOP1 device (Eye Tech Care, Rillieux-la-Pape, France), which was employed in the study, uses miniaturized transducers to produce high-intensity focused ultrasound (HIFU). Treatment consisted of the sequential activation of each transducer lasting 4 s (group 1), 6 s (group 2) or 8 s (group 3). Hypotensive medications were interrupted after surgery and then prescribed only if postoperative IOP was ≥ 21 mmHg during follow-up visits. Patients were assessed before and 1, 7, 14, 30, 90 and 180 days after the procedure. Primary outcomes were the mean IOP reduction in the overall population and in groups 1, 2 and 3, and the rates of complete success, qualified success and failure. RESULTS: Thirty eyes (16 open-angle, 10 angle-closure and 4 neovascular glaucoma) of 30 patients were included. The mean preoperative IOP was 30.1 ± 10.5 mmHg. Twenty-nine patients completed the entire study follow-up; one patient exited from the study 3 months after HIFU and underwent trabeculectomy. At days 1 and 180, the mean IOP was significantly reduced (18.4 ± 7.2 and 20.2 ± 6.2 mmHg, respectively; all p < 0.0001). Group 3 patients (8-s ultrasound exposure time) showed a greater IOP reduction than the other two groups (-16.2 ± 8.3 for group 3 vs. -8.8 ± 6.6 for group 2 and -3.7 ± 6.5 for group 1; p = 0.02 and p < 0.001, respectively). Qualified and complete success was achieved in 23.3 and 46.7% of patients, respectively; treatment failure was recorded in 6.6%. CONCLUSIONS: Ultrasonic coagulation of the ciliary body is a safe and effective procedure for reducing IOP in refractory glaucoma. The increase in ultrasound exposure time appears to improve the response rate and the global efficacy of the procedure, with no detrimental effect on safety.

Zigzag and Checkerboard Magnetic Patterns in Orbitally Directional Double-Exchange Systems.

We analyze a t(2g) double-exchange system where the orbital directionality of the itinerant degrees of freedom is a key dynamical feature that self-adjusts in response to doping and leads to a phase diagram dominated by two classes of ground states with zigzag and checkerboard patterns. The prevalence of distinct orderings is tied to the formation of orbital molecules that in one-dimensional paths make insulating zigzag states kinetically more favorable than metallic stripes, thus allowing for a novel doping-induced metal-to-insulator transition. We find that the basic mechanism that controls the magnetic competition is the breaking of orbital directionality through structural distortions, and highlight the consequences of the interorbital Coulomb interaction.

Excess dietary sodium and inadequate potassium intake in Italy: results of the MINISAL study.

OBJECTIVE: As excess sodium and inadequate potassium intake are causally related to hypertension and cardiovascular disease, the MINISAL-GIRCSI Program aimed to provide reliable estimates of dietary sodium and potassium intake in representative samples of the Italian population. DESIGN AND METHODS: Random samples of adult population were collected from 12 Italian regions, including 1168 men and 1112 women aged 35-79 yrs. Electrolyte intake was estimated from 24 hour urine collections and creatinine was measured to estimate the accuracy of the collection. Anthropometric indices were measured with standardised procedures. RESULTS: The average sodium excretion was 189 mmol (or 10.9 g of salt/day) among men and 147 mmol (or 8.5 g) among women (range 27-472 and 36-471 mmol, respectively). Ninety-seven % of men and 87% of women had a consumption higher than the WHO recommended target of 5g/day. The 24 h average potassium excretion was 63 and 55 mmol, respectively (range 17-171 and 20-126 mmol), 96% of men and 99% of women having an intake lower than 100 mmol/day (European and American guideline recommendation). The mean sodium/potassium ratio was 3.1 and 2.8 respectively, i.e. over threefold greater than the desirable level of 0.85. The highest sodium intake was observed in Southern regions. Sodium and potassium excretion were both progressively higher the higher the BMI (p < 0.0001). CONCLUSIONS: These MINISAL preliminary results indicate that in all the Italian regions thus far surveyed dietary sodium intake was largely higher and potassium intake lower than the recommended intakes. They also highlight the critical association between overweight and excess salt intake.

Pigmented lichenoid drug eruption secondary to chloroquine therapy: an unusual presentation in lower lip.

Antimalarial drugs, like chloroquine, may produce hyperpigmentation of the oral mucosa, affecting most commonly the palate. Its pathogenesis is not clear; an increased production of melanin is currently believed to be the cause of this oral manifestation. The purpose of this study was to report a case of atypical oral mucosal hyperpigmentation secondary to antimalarial therapy. A 66-year-old, dark skinned woman was evaluated for oral pigmentation. The patient had a history of chloroquine therapy, and presented a diffuse blue-gray pigmentation in the hard palate and, mainly, in the lower lip. Diagnostic hypothesis were of physiologic pigmentation, drug-induced pigmentation, pigmentation associated with systemic diseases, smoker's melanosis and post-inflammatory pigmentation. Incisional biopsy was conducted and histopathological examination revealed lichenoid dermatitis and pigment incontinence. Fontana-Masson staining was positive for melanin, but Perl's iron staining was negative. The histopathological diagnosis was consistent with melanin incontinence related to drug-induced lichenoid reaction secondary to chloroquine therapy. Adequate correlation of clinical and microscopic aspects was essential for the definitive diagnosis, especially in atypical cases. This diagnosis is of great relevance for the patient, since the oral manifestation might be an early sign of ocular complications due to antimalarial therapy. Therefore, the identification of these oral manifestations indicates regular evaluations by an ophtalmologist, preventing greater complications of antimalarial therapy for the patient.

Unveiling unconventional magnetism at the surface of Sr2RuO4.

Materials with strongly correlated electrons often exhibit interesting physical properties. An example of these materials is the layered oxide perovskite Sr2RuO4, which has been intensively investigated due to its unusual properties. Whilst the debate on the symmetry of the superconducting state in Sr2RuO4 is still ongoing, a deeper understanding of the Sr2RuO4 normal state appears crucial as this is the background in which electron pairing occurs. Here, by using low-energy muon spin spectroscopy we discover the existence of surface magnetism in Sr2RuO4 in its normal state. We detect static weak dipolar fields yet manifesting at an onset temperature higher than 50 K. We ascribe this unconventional magnetism to orbital loop currents forming at the reconstructed Sr2RuO4 surface. Our observations set a reference for the discovery of the same magnetic phase in other materials and unveil an electronic ordering mechanism that can influence electron pairing with broken time reversal symmetry.

Evaluation of cell tolerability of a series of lipoamino acids using biological membranes and a biomembrane model.

The interaction of a series of amphiphilic 2-alkyl aminoacids (lipoamino acids, LAAs) with different cell cultures and biomembrane models was investigated. LAAs can be useful promoieties to modify the physico-chemical properties of many drugs, and in particular their lipophilicity. Tests were performed in vitro on mammalian cells (murine astrocytes) and human red blood cells (haemolysis), and in vivo on rabbit eye as alternative models to assess the tolerability or the potential damaging effects of these compounds on different biological systems. The mode of interaction of LAAs with pure phospholipid multilamellar liposomes, taken as a biomembrane model, was also analysed by differential scanning calorimetry experiments. Different tolerability/toxicity patterns were obtained in the various models; in particular, the most lipophilic terms of the series, methyl 2-aminohexadecanoate (LAA16), displayed haemolytic activity and toxicity for mouse astrocyte cultures. A specific assay confirmed that LAA16 acted at level of cell membranes, while neither any damaging effects on nucleus or apoptotic induction were observed. The shorter-chain LAAs and the tetradecyl homologue (LAA14) showed the best compatibility with the various cell models.

Does the Clock Drawing Test predict cognitive decline in older persons independent of the Mini-Mental State Examination? The FINE Study Group. Finland, Italy, The Netherlands Elderly.

OBJECTIVE: To evaluate the value of the Clock Drawing Test (CDT) in predicting cognitive deterioration over a 4-year period, independent of baseline cognitive status evaluated by the Mini-Mental State Examination (MMSE). DESIGN: A preplanned analysis of data collected during the second (1991) and the third (1995) follow-up of the Italian rural cohorts of the FINE Study (Finland, Italy, the Netherlands Elderly). SUBJECTS: Of the 427 men (mean age 77.6 +/- 4.1 years; range 72-90 years) interviewed in 1991, 264 survived and were reinterviewed in 1995. The study population included 247 persons who were interviewed and received a complete cognitive evaluation in both 1991 and in 1995. MEASUREMENTS: Cognitive assessment in 1991 included the MMSE, the Dementia Rating Scale (DRS), and the CDT. The CDT was classified as normal or pathological, based on previously established criteria. The MMSE and the DRS were repeated in 1995. RESULTS: Independent of age and baseline MMSE, score, subjects with pathological CDT compared with normal CDT had lower MMSE scores at follow-up (P < .01). These results were also confirmed by evaluating cognitive decline through its impact on change over time in daily life autonomy, as measured by the DRS (P < .01). Among persons scoring more than 21 on the MMSE, compared with persons with a normal CDT, those with pathological CDT performance were 5.4 (95% CI: 2.1-14.2) and 5.5 (95% CI: 1.6-19.6) times more likely to have a MMSE score below 21 and 18, respectively, 4 years later, independent of age and baseline MMSE score. CONCLUSIONS: Findings suggest that the CDT identifies older persons at high risk of cognitive decline and adds prognostic information that supplements the standard MMSE test.

Change in cardiovascular risk factors during a 10-year community intervention program.

The study describes changes in cardiovascular risk factors during 10 years of a community intervention program conducted in a rural area in Central Italy. Two areas were involved, one for treatment and one for reference. In 1983-84, 739 men and 859 women in the treatment area and 942 men and 1045 women in the control area, aged 20-69 years, were screened; total and HDL cholesterol, systolic and diastolic blood pressure, fasting blood glucose, smoking habit, weight and height were measured. Between 1983 and 1993 several intervention activities based on community medicine were carried out in the treatment area. They were based on interaction with the local socio-sanitary institutions and school system in order to influence individual persons, small groups and entire community. Major effort was addressed to mass health education, nutrition education, antismoking-propaganda and detection and treatment of hypertension, diabetes and hyperlipidemia.

[Cardiovascular risk factors in women in menopause]. / Fattori di rischio cardiovascolare nella donna in menopausa.

BACKGROUND: During menopause, women are more exposed to cardiovascular risk factors, some of them can be easily modified by primary and secondary prevention. This paper describes some demographic indicators and cardiovascular risk factors among Italian women. METHODS: This study describes the Italian women's cardiovascular risk, using the data collected and updated at the end of the 1990s, within the Cardiovascular Epidemiological Observatory, an Italian Collaborative Project of the Istituto Superiore di Sanità and the Italian Association of Cardiologists. RESULTS: Women aged 60 years and over represent 13% of the population; regional differences on mean values of cardiovascular risk factors are evident. Hypertension, hypercholesterolemia, diabetes and obesity are prevalent particularly in Southern Italy and among the social classes in the lowest education level. CONCLUSIONS: The data confirm the importance of the main objectives stated by the National Health Plan 1998-2000: promotion of healthier dietary habits, of physical activity, and reduction of smoking habits. This requires specific action to improve women's health condition, to provide for their special needs and to create awareness among women about the importance of preventive action also during the aging process.

Effects of combined dietary supplementation on oxidative and inflammatory status in dyslipidemic subjects.

BACKGROUND AND AIM: Dyslipidemia is one of the main risk factors for atherosclerosis, usually the underlying cause of cardiovascular diseases which are the major cause of morbidity and mortality in developed countries. The aim of this study was to assess the effects and the advantages of a combined dietary supplementation with PUFA n-3, vitamin E, niacin and gamma-oryzanol on lipid profile, inflammatory status and oxidative balance. METHODS AND RESULTS: Fifty-seven dyslipidemic volunteers were randomly assigned to receive: placebo (group A, 19 subjects); PUFA n-3 and vitamin E (group B, 18 subjects); the same as B plus gamma-oryzanol and niacin (group C, 20 subjects). Lipid profile, reactive oxygen species (ROS), total antioxidant capacity (TAC), vitamin E, interleukin 1-beta (IL1-beta), tumor necrosis factor (TNF-alpha) and thromboxane B2 (TXB2) were determined at baseline (T0) and after four months (T1). All dyslipidemic subjects showed, at baseline, oxidative stress and, after four months, all biochemical markers improved significantly in groups treated with dietary supplementation. Particularly in group C all lipid patterns improved significantly. CONCLUSIONS: Our findings demonstrate that the strategy of combining different compounds, which protect each other and act together at different levels of the lipid chain production, improves lipid profile, inflammatory and oxidative status, allowing us to reduce the dose of each compound under the threshold of its side effects.

Heart rate as a predictor of mortality: the MATISS project.

OBJECTIVES: This study sought to verify the independent role of heart rate in the prediction of all-cause, cardiovascular, and noncardiovascular mortality in a low-risk male population. METHODS: In an Italian population-based observational study, heart rate was measured in 2533 men, aged 40 to 69 years, between 1984 and 1993. Data on cardiovascular risk factors were collected according to standardized procedures. Vital status was updated to December 1997. RESULTS: Of 2533 men followed up (representing 24,457 person-years), 393 men died. Age-adjusted death rates for 5 heart rate levels showed increasing trends. The adjusted hazard rate ratios for each heart rate increment were 1.52 (95% confidence interval [CI] = 1.29, 1.78) for all-cause mortality, 1.63 (95% CI = 1.26, 2.10) for cardiovascular mortality, and 1.47 (95% CI = 1.19, 1.80) for noncardiovascular mortality. Relative risks between extreme levels were more than 2-fold for all endpoints considered. CONCLUSIONS: Heart rate is an independent predictor of cardiovascular, noncardiovascular, and total mortality in this Italian middle-aged male population.

Infection rate and spontaneous seroreversion of anti-hepatitis C virus during the natural course of hepatitis C virus infection in the general population.

BACKGROUND: Hepatitis C virus (HCV) infection is common worldwide but there are different prevalence rates in different countries. Data on the incidence of HCV in the general population are scarce. Spontaneous viral clearance occurs in 10-25% of infected individuals after acute infection yet controversy exists regarding the frequency of spontaneous clearance during the natural course of HCV infection in the general population. AIMS: Anti-HCV prevalence, HCV infection rate, and the kinetics of anti-HCV were studied in a cross section of the general population of central Italy. STUDY POPULATION AND METHODS: Anti-HCV prevalence (EIA-3 Ortho, RIBA-3 Ortho Chiron) was estimated in 3884 randomly selected individuals. Infection rate and antibody kinetics were estimated in 2032 participants for whom a second blood sample was taken after a median follow up of seven years. HCV-RNA determination by polymerase chain reaction was performed on follow up sera. RESULTS: The overall confirmed anti-HCV prevalence was 2.4%. Two participants seroconverted for anti-HCV, giving an overall infection rate of 1.4 cases per 10 000 person years (95% confidence interval 0.2-5.2 per 10 000 person years). Of the 36 individuals confirmed as anti-HCV positive at enrollment, seven (19.4%) showed complete seroreversion. Seven (87%) of the eight individuals with indeterminate results at enrollment were serologically non-reactive at the end of follow up. Of the 25 participants confirmed to be anti-HCV positive at both enrollment and follow up, 23 (92.0%) with stable serological profiles tested positive for HCV-RNA at the end of follow up. CONCLUSIONS: There is still a permanent risk, although low, of HCV spread in the general population in an area of low level endemicity. In this setting, a wide spectrum of modifications of viral and antibody patterns can be observed in HCV infected patients.

Hand-grip strength predicts incident disability in non-disabled older men.

OBJECTIVES: To verify if hand-grip performance in older men is a predictor of disability. DESIGN: Population-based prospective study. SETTING: A sample from the Italian rural cohorts of the FINE study (Finland, Italy, Netherlands Elderly), representative of the general population of elderly men surveyed in 1991 and 1995. PARTICIPANTS: 140 men aged 71-91 years who reported no disability in performing activities of daily living (ADLs), instrumental activity of daily living (IADLs) and mobility activities at baseline examination and provided information on their functional status at follow-up 4 years later. MEASUREMENTS: Disability was defined as needing help in performing ADLs, IADLs and mobility. Hand-grip strength was evaluated at baseline by a mechanical dynamometer. RESULTS: After adjusting for potential confounding variables, a lower concentration of high-density lipoprotein cholesterol was the only factor predicting disability in men aged 76 years or younger and only reduced hand-grip strength predicted incident disability in men 77 years or older. CONCLUSION: Poor hand strength as measured by hand-grip is a predictor of disability in older people. The hand-grip test is an easy and inexpensive screening tool to identify elderly people at risk of disability.