Circulating microRNAs and therapy-associated cardiac events in HER2-positive breast cancer patients: an exploratory analysis from NeoALTTO.

PURPOSE: The relevance of cardiotoxicity in the context of HER2-positive breast cancer is likely to increase with increasing patient treatment exposure, number of treatment lines, and prolonged survival. Circulating biomarkers to early identify patients at risk of cardiotoxicity could allow personalized treatment and follow-up measures. The aim of this study is to examine the relationship between circulating microRNAs and adverse cardiac events in HER2-positive breast cancer patients. METHODS: We based our work on plasma samples from NeoALTTO trial obtained at baseline, after 2 weeks of anti-HER2 therapy, and immediately before surgery. Eleven patients experienced either a symptomatic or asymptomatic cardiac event. Circulating microRNAs were profiled in all patients presenting a cardiac event (case) and in an equal number of matched patients free of reported cardiac events (controls) using microRNA-Ready-to-Use PCR (Human panel I + II). Sensitivity analyses were performed by increasing the number of controls to 1:2 and 1:3. Normalized microRNA expression levels were compared between cases and controls using the non-parametric Kruskal-Wallis test. RESULTS: Eight circulating microRNAs resulted differentially expressed after 2 weeks of anti-HER2 therapy between patients experiencing or not a cardiac event. Specifically, the expression of miR-125b-5p, miR-409-3p, miR-15a-5p, miR-423-5p, miR-148a-3p, miR-99a-5p, and miR-320b increased in plasma of cases as compared to controls, while the expression of miR-642a-5p decreases. Functional enrichment analysis revealed that all these microRNAs were involved in cardiomyocyte adrenergic signaling pathway. CONCLUSION: This study provides proof of concept that circulating microRNAs tested soon after treatment start could serve as biomarkers of cardiotoxicity in a very early stage in breast cancer patients receiving anti-HER2 therapy.

Mapping at the nanometer scale the effects of sea-salt derived chlorine on cinnabar and lead white by using delayed image extraction in ToF-SIMS.

In this work, an innovative analytical approach focused on the use of advanced imaging techniques for the chemical mapping of degradation and/or restoration products is proposed. A representative cross-section showing a very complex stratigraphy from the Saint Wilgefortis Triptych (Hieronymus Bosch), exhibited in the Galleria dell'Accademia di Venezia, was investigated. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) experiments were performed using a time-of-flight detector operating in the so-called delayed extraction mode. The time delay applied during the extraction of the secondary ions permitted mass spectra to be obtained with an excellent mass resolution and chemical maps with nanometer scale spatial resolution. The painting's cross-section was also analysed at the micrometer scale by micro-Fourier transform infrared spectroscopy (micro-FTIR). The combined analytical approaches highlighted the colocalization of lead chloride, oxychloride, and hydroxychloride ions, suggesting the transformation of lead white ((PbCO3)2Pb(OH)2) into laurionite (PbClOH). Furthermore, chlorine appears evenly diffused in the cinnabar (HgS) layer, inducing the alteration of its more external part into calomel (Hg2Cl2). In fact, from the chemical maps the presence in the sample of an unaltered portion of the cinnabar layer is evident. Such degradation products were probably due to the exposure of the painting to a chloride-rich atmosphere for a long time. This led to a global blackening of the painting. To protect the painting from aggressive chemical species, siloxane compounds were probably used as a modern restorative treatment. ToF-SIMS chemical maps revealed permeation of the silicon-based consolidants within the sample's cracks and no interaction products with the other constitutive materials of the painting were found. Finally, the presence of different lead soaps was detected in correspondence with the lead white layer.

Defined concatenated α6α1ß3γ2 GABAA receptor constructs reveal dual action of pyrazoloquinolinone allosteric modulators.

Pyrazoloquinolinones (PQs) have been extensively studied as modulators of GABAA receptors with different subunit composition, exerting modulatory effects by binding at α+/ß- interfaces of GABAA receptors. PQs with a substituent in position R7 have been reported to preferentially modulate α6- subunit containing GABAA receptors which are mostly expressed in the cerebellum but were also found in the olfactory bulb, in the cochlear nucleus, in the hippocampus and in the trigeminal sensory pathway. They are considered potentially interesting in the context of sensori-motor gating deficits, depressive-like behavior, migraine and orofacial pain. Here we explored the option to modify the lead ligands' R7 position. In the compound series we observed two different patterns of allosteric modulation in recombinantly expressed α6ß3γ2 receptors, namely monophasic and biphasic positive modulation. In the latter case the additional phase occurred in the nanomolar range, while all compounds displayed robust modulation in the micromolar range. Nanomolar, near silent binding has been reported to occur at benzodiazepine binding sites, but was not investigated at the diazepam insensitive α6+/γ2- interface. To clarify the mechanism underlying the biphasic effect we tested one of the compounds in concatenated receptors. In these constructs the subunits are covalently linked, allowing to form either the α6+/γ2- interface, or the α6+/ß3- interface, to study the resulting modulation. With this approach we were able to ascribe the nanomolar modulation to the α6+/γ2- interface. While not all compounds display the nanomolar phase, the strong modulation at the α6+/ß3 interface proved to be tolerant for all tested R7 groups. This provides the future option to introduce e.g. isotope labelled or fluorescent moieties or substituents that enhance solubility and bioavailability.

Metabolic profiling of polycystic ovary syndrome reveals interactions with abdominal obesity.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with metabolic disturbances including obesity, insulin resistance and diabetes mellitus. Here we investigate whether changes in the metabolic profile of PCOS women are driven by increased tendency to obesity or are specific features of PCOS related to increased testosterone levels. DESIGN AND METHODS: We conducted an NMR metabolomics association study of PCOS cases (n=145) and controls (n=687) nested in a population-based birth cohort (n=3127). Subjects were 31 years old at examination. The main analyses were adjusted for waist circumference (WC) as a proxy measure of central obesity. Subsequently, metabolite concentrations were compared between cases and controls within pre-defined WC strata. In each stratum, additional metabolomics association analyses with testosterone levels were conducted separately among cases and controls. RESULTS: Overall, women with PCOS showed more adverse metabolite profiles than the controls. Four lipid fractions in different subclasses of very low density lipoprotein (VLDL) were associated with PCOS, after adjusting for WC and correction for multiple testing (P<0.002). In stratified analysis the PCOS women within large WC strata (⩾98 cm) had significantly lower high density lipoprotein (HDL) levels, Apo A1 and albumin values compared with the controls. Testosterone levels were significantly associated with VLDL and serum lipids in PCOS cases with large WC but not in the controls. The higher testosterone levels, adjusted for WC, associated adversely with insulin levels and HOMA IR in cases but not in the controls. CONCLUSIONS: Our findings show that both abdominal obesity and hyperandrogenism contribute to the dyslipidaemia and other metabolic traits of PCOS which all may negatively contribute to the long-term health of women with PCOS.

Cryopreserving turkey semen in straws and nitrogen vapour using DMSO or DMA: effects of cryoprotectant concentration, freezing rate and thawing rate on post-thaw semen quality.

1. This study was designed to identify a suitable protocol for freezing turkey semen in straws exposed to nitrogen vapour by examining the effects of dimethylacetamide (DMA) or dimethylsulfoxide (DMSO) as cryoprotectant (CPA), CPA concentration, freezing rate and thawing rate on in vitro post-thaw semen quality. 2. Pooled semen samples were diluted 1:1 (v:v) with a freezing extender composed of Tselutin diluent containing DMA or DMSO to give final concentrations of 8% or 18% DMA and 4% or 10% DMSO. The semen was packaged in 0.25 ml plastic straws and frozen at different heights above the liquid nitrogen (LN2) surface (1, 5 and 10 cm) for 10 min. Semen samples were thawed at 4°C for 5 min or at 50°C for 10 s. After thawing, sperm motility, viability and osmotic tolerance were determined. 3. Cryosurvival of turkey sperm was affected by DMSO concentration. Freezing rate affected the motility of sperm cryopreserved using both CPAs, while thawing rates showed an effect on the motility of sperm cryopreserved using DMA and on the viability of sperm cryopreserved using DMSO. Significant interactions between freezing rate × thawing rate on sperm viability in the DMA protocol were found. 4. The most effective freezing protocol was the use of 18% DMA or 10% DMSO with freezing 10 cm above the LN2 surface and a thawing temperature of 50°C. An efficient protocol for turkey semen would improve prospects for sperm cryobanks and the commercial use of frozen turkey semen.

Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases.

Clinical response to methotrexate (MTX) treatment for children with juvenile idiopathic arthritis (JIA) displays considerable heterogeneity. Currently, there are no reliable predictors to identify non-responders: earlier identification could lead to a targeted treatment. We genotyped 759 JIA cases from the UK, the Netherlands and Czech Republic. Clinical variables were measured at baseline and 6 months after start of the treatment. In Phase I analysis, samples were analysed for the association with MTX response using ordinal regression of ACR-pedi categories and linear regression of change in clinical variables, and identified 31 genetic regions (P<0.001). Phase II analysis increased SNP density in the most strongly associated regions, identifying 14 regions (P<1 × 10(-5)): three contain genes of particular biological interest (ZMIZ1, TGIF1 and CFTR). These data suggest a role for novel pathways in MTX response and further investigations within associated regions will help to reach our goal of predicting response to MTX in JIA.

Relation of adiponectin, visfatin and bone mineral density in patients with metabolic syndrome.

BACKGROUND: Adipose tissue has been suggested to influence bone density and metabolism through the effect of some adipokines. However, whether adiponectin and visfatin may correlate with bone metabolism is still unclear. AIM: The aim of this study was to investigate the relationship of adiponectin and visfatin with bone density in patients with metabolic syndrome (MS). SUBJECTS: We enroled 72 consecutive patients with MS (25 males, 47 females; mean age 58.14±11 yr) and 40 control subjects. METHODS: Plasma adiponectin and visfatin levels were measured. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry (DXA) at the level of lumbar spine L2-L4 (BMD L2-L4) and femoral neck (BMD-Fn). RESULTS: MS patients had higher plasma visfatin and lower adiponectin levels than controls, (p<0.01 for both). Adiponectin was negatively correlated with BMD-Fn and BMD L2-L4 (r=-0.20, r=-0.24, respectively; p<0.05 for both) whereas plasma visfatin levels were positively correlated to BMD L2-L4 only in men (r=0.44; p<0.05). CONCLUSIONS: Our study shows that adiponectin and visfatin are oppositely associated with BMD. Although the mechanisms behind these correlations are unclear, a modulation of bone metabolism by these adipokines can be suggested.

Crustal structure in the Campanian region (Southern Apennines, Italy) from potential field modelling.

We present a 3D model of the main crustal boundaries beneath the Campanian region and the onshore and offshore surrounding areas, based on high-resolution potential field data. Our main objective is the definition of the main structural interfaces in the whole Campanian region from gravity and magnetic data, thanks to their ability to define them on a regional and continuous way. The complex morphology of the Mesozoic carbonate platform, which is fundamental to constrain the top of geothermal reservoir, was reconstructed by inverting the vertical gradient of gravity. We assumed local information from seismic models and boreholes to improve the model. We modeled the deep crustal structures by spectral analysis of Bouguer gravity and magnetic data. The inferred depth estimates indicate a shallow crystalline basement below the Tyrrhenian crust and the Apulian foreland and a significant depression beneath the Bradanic foredeep. The map of the Moho boundary shows a NE-SE verging trough below the Southern Apennine chain and two pronounced uplifts beneath the foreland and the Tyrrhenian crust. We also estimated the depth to the magnetic bottom, showing a thick magnetic crust below the mountain chain and shallow depths where the crustal heat flow is high. The models were compared with seismic sections along selected profiles; a good agreement was observed, despite of some inherent lower resolution for the gravity modelling from spectral methods. The regional covering and the continuity of our estimated crustal interfaces make it a new and valid reference for further geological, geophysical and geothermal studies, especially in areas such as northern and eastern Campania, where there is an incomplete geophysical and geological information.

Production and Easy One-Step Purification of Bluetongue Recombinant VP7 from Infected Sf9 Supernatant for an Immunoenzymatic Assay (ELISA).

Bluetongue (BT) is non-contagious, vector-borne viral disease of domestic and wild ruminants, transmitted by midges (Culicoides spp.) and is caused by Bluetongue virus (BTV). BTV is the type species of the Orbivirus genus within the Reoviridae family and possesses a genome consisting of 10 double-stranded RNA segments encoding 7 structural and 4 nonstructural proteins. Viral Protein 7 (VP7) is the major sera group-specific protein and is a good antigen candidate for immunoenzymatic assays for the BT diagnosis. In our work, BTV-2 recombinant VP7 (BTV-2 recVP7), expressed in Spodoptera frugiperda (Sf9) cells using a baculovirus system, was produced and purified by affinity chromatography from the supernatant of infected cell culture. The use of the supernatant allowed us to obtain a high quantity of recombinant protein with high purity level by an easy one-step procedure, rather than the multistep purification from the pellet. RecVP7-BTV2 was detected using a MAb anti-BTV in Western blot and it was used to develop an immunoenzymatic assay.

Risk of Salmonella transmission via cryopreserved semen in turkey flocks.

To investigate the possibility to carry pathogen bacteria in turkey flocks via cryopreserved semen, research was carried out 1) to investigate the microbial contamination of fresh and frozen thawed turkey semen and 2) to evaluate the effect of the freezing-thawing process on the survival of 3 serovars of Salmonella spp. experimentally inoculated in turkey semen. Five pools of semen diluted 4-fold were cooled, added with 8% of dimethylacetamide as a cryoprotectant, and aliquots of 80 muL were directly plunged into liquid nitrogen to form frozen pellets. Mesophilic viable counts, total and fecal coliforms, Enterobacteriaceae, enterococci, Campylobacter spp., and Salmonella spp. were investigated on fresh and thawed samples. Further, 5 pools of diluted semen were each divided into 3 subsamples, inoculated with 7.8 +/- 0.2 log cfu.mL(-1) of Salmonella Liverpool, Salmonella Montevideo, and Salmonella Braenderup, respectively, and cryopreserved before to assess the postthaw viability of Salmonella spp. strains. Fresh semen was highly contaminated by all of the saprophytic bacteria investigated and the cryopreservation process reduced the amount of mesophilic viable count and total coliforms (P < 0.05) and fecal coliforms, Enterobacteriaceae, and enterococci (P < 0.01) by about 1 log cfu.mL(-1). Conversely, neither Campylobacter spp. nor Salmonella spp. were found as endogenous bacteria in semen. In the inoculated semen, both Salmonella Liverpool, Salmonella Montevideo, and Salmonella Braenderup colonies were recovered postthaw, showing a significant reduction of 2.03 +/- 0.28, 3.08 +/- 0.22, and 2.72 +/- 0.23 log cfu.mL(-1), respectively, compared with the fresh semen (P < 0.001). In conclusion, the cryopreservation process allowed us to obtain a low reduction of microbial count both in endogenous saprophytic bacteria and artificially inoculated Salmonella spp. strains; therefore, the possibility of Samonella spp. transmission to flocks through the use of infected cryopreserved semen does exist.

Crustal structure of Sicily from modelling of gravity and magnetic anomalies.

We aim at modeling the main crustal and thermal interfaces of Sicily (Italy), a key area for understanding the geological complexity at the collisional boundary between the African and European plates. To this end, we analyze the gravity and magnetic fields, integrated with information from well logs, geology, heat flow, and seismic data. In order to make the most accurate description of the crustal structure of the area, we modeled with different methodologies the carbonate and crystalline top surfaces, as well as the Moho and the Curie isotherm surface. The reconstruction of the carbonate platform is achieved using a nonlinear 3D method constrained by the available seismic and borehole data. The crystalline top, the Curie, and the Moho are instead estimated by spectral analysis of both gravity and magnetic data. The results show a complex carbonate basement and a deep crystalline crust in central Sicily, with a prominent uplift beneath the Hyblean Plateau. Maps of the Moho and the Curie isotherm surface define a variable thermal and structural setting of Sicily, with very thin crust in the southern and eastern sectors, where high heat flow is found, and deep and cold crust below the Caltanissetta Basin.

Marginal adaptation of full-coverage CAD/CAM restorations: in vitro study using a non-destructive method.

AIM: Marginal fit of full-coverage crowns is a major requirement for long term success of this kind of restorations. The purpose of the study was to verify the marginal adaptation of computer assisted design (CAD)/computer assisted manufacturing (CAM) crowns on prepared teeth and on plaster dies. METHODS: Four couples of materials: zirconia-ceramic veneering (DC-Zircon, DCS Dental, Allschwill, CH/Cercon S, Degussa, DeguDent GmbH, Hanau, Germany), fiber-reinforced composite-composite veneering (DC-Tell, DCS Dental/Gradia, GC Europe, LEuven, Belgium), titanium-ceramic veneering (DC Titan, DCS Dental/Tikrom, Orotig, Verona, Italy) and titanium-composite veneering (DC Titan, DCS Dental/Gradia, GC Europe) were evaluated following the guidelines provided by ADA specific #8. Five crowns were fabricated for each material. Marginal gap values were measured at four points (0 degrees, 90 degrees, 180 degrees and 270 degrees starting from the centre of the vestibular surface) around the finishing line, on prepared teeth and on plaster dies at each step of the fabrication process. Digital photographs were taken at each reference point and a computer software was used to measure the amount of marginal discrepancy in microm. Statistical analysis was performed using t test at 95 percent confidence interval. RESULTS: All the tested materials, except for fiber-reinforced composite, show a marginal adaptation within the limits of ADA specification (25-40 microm). The application of veneering material causes decay in marginal adaptation, except for fiber-reinforced composite. CONCLUSION: Within the limitations of this study, it was concluded that marginal fit of CAD/CAM restoration is within the limits considered clinically acceptable by ADA specification #8. From the results of this in vitro study, it can be stated that CAD/CAM crowns produced with DCS system show a marginal adaptation within the limits of ADA specific #8, therefore milled CAD/CAM crowns can be considered a good alternative to more traditional waxing-investing-casting technique.

MicroRNAs and future therapeutic applications in cancer.

Every cellular process is likely to be regulated by microRNAs (miRNAs), and an aberrant expression signature of these small non-coding RNAs is a hallmark of several diseases, including cancer. miRNA expression profiling by microarray techniques has provided a powerful tool to reveal the involvement of these tiny molecules in tumor development and progression, showing that they are differentially expressed in tumors as compared to normal tissues. Moreover, specific miRNA signatures have been associated with histopathological and clinical features, suggesting a potential role of these molecules as prognostic and predictive markers. Focusing then on their biological effects and role in cancer, it has been shown that miRNAs can function as potential oncogenes or oncosuppressor genes, depending on the cellular context and on the target genes they regulate. The possibility to modulate miRNA expression either in vitro and in vivo by developing synthetic pre-miRNA molecules or antisense oligonucleotides have at the same time provided a powerful tool to a deeper comprehension of the molecular mechanisms regulated by these molecules, and suggested the intriguing and promising perspective of their possible use in therapy. Herein we review our current knowledge about the involvement of miRNAs in cancer, and their potential as diagnostic, prognostic and therapeutic tools.

A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors.

KIT or alpha-platelet-derived growth factor receptor (alpha-PDGFR) activating mutations are the pathogenic mechanisms that characterize gastrointestinal stromal tumors (GIST). Despite excellent responses to imatinib mesylate (IM), patients are relapsing. We developed an IM-resistant GIST cell line (GIST-R) from the IM-sensitive GIST882 cell line (GIST-S) by growing these cells in IM. Gene expression profiling (GEP) of GIST-S, GIST-R cells and two IM resistant GIST patients demonstrated that KIT is downregulated implying a major role in IM resistance. Instead, GIST-R cells have acquired IM resistance by overexpressing the oncogenic receptor tyrosine kinase - AXL - in a 'kinase switch'. Further, the two IM resistant GIST patients express AXL and not c-Kit, seen by immunohistochemistry (IHC). Real time reverse transcriptase-polymerase chain reaction and Western blotting of the GIST-S and GIST-R cells confirmed the switch from Kit to AXL. In GIST-R, AXL is tyrosine phosphorylated and its ligand growth-arrest-specific gene 6 is overexpressed implying autocrine activation. The kinase switch is associated with a morphological change from spindle to epithelioid. Molecular modeling of the kinase domain of mutant c-Kit (V654A) and AXL showed no binding to IM but efficient binding to MP470, a novel c-Kit/AXL kinase inhibitor. MP470 synergizes with docetaxel (taxotere) and is cytotoxic to GIST cells.

Remediation of waters contaminated with ionic herbicides by sorption on polymerin.

This study investigated the sorption of paraquat and 2,4-D on polymerin, the humic acid-like fraction of olive mill wastewater. Effects of pH, contact time, initial concentration and sorbent dosage on the sorption of both herbicides were studied. The sorption mechanism of paraquat on polymerin was consistent with the ion exchange of this herbicide with Ca, Mg and K natively occurring in the sorbent; in contrast, 2,4-D was bound to polymerin by hydrogen bonding. Simulated wastewaters contaminated with paraquat were purified after three sorption cycles on polymerin renewed at each cycle, at a solid/liquid ratio of 0.5, whereas those containing 2,4-D showed a maximal residue removal of 44% after two sorption cycles at the same ratio. The possible application of this model to other water-soluble herbicides, as well as the possible exploitation of polymerin as a bio-filter for the decontamination of pollution point sources is briefly discussed.

Bridging trees for posterior inference on ancestral recombination graphs.

We present a new Markov chain Monte Carlo algorithm, implemented in the software Arbores, for inferring the history of a sample of DNA sequences. Our principal innovation is a bridging procedure, previously applied only for simple stochastic processes, in which the local computations within a bridge can proceed independently of the rest of the DNA sequence, facilitating large-scale parallelization.

Cushing's syndrome patient who exhibited congestive heart failure.

Cushing's Syndrome (CS) may sometimes lead to dilated cardiomyopathy, even though this condition can be partially or completely reversed after treatment. In this article we report the case of a 28-yr-old woman with CS secondary to adrenal adenoma who exhibited congestive heart failure as an initial symptom. Two weeks before being admitted to our hospital, the patient started complaining of shortness of breath, orthopnea, paroxysmal nocturnal dyspnea and generalized edema. A physical examination did not reveal signs of hypercortisolism. Chest auscultation revealed bilateral diffused crepitation; blood pressure was 180/120 mmHg with heart rate of 90 beats/min. A chest X-ray showed a cardiac shade enlargement due to congestive heart failure. Transthoracic echocardiography demonstrated a dilated left ventricle and an impaired left ventricular systolic function. The patient's urinary cortisol excretion was elevated and circadian rhythm of cortisol was absent. ACTH level was low. In addition, plasma cortisol failed to decrease after administration of dexamethasone. An abdominal magnetic resonance imaging scan showed a 7-cm right adrenal mass. The patient was administered oxygen, spironolactone, ACE-inhibitor and the signs and symptoms of heart failure gradually improved. A laparoscopic right adrenalectomy was performed and pathological examination of the gland showed a benign adrenocortical adenoma. After the adrenalectomy the patient was started on hydrocortisone therapy and 5 months later the wall thickness of the left ventricle was within normal range and the patient's blood pressure was 130/80 mmHg. In conclusion we report the case of heart failure as the main clinical symptom in CS secondary to adrenal adenoma.

Symptomatic carotid stenosis. Diagnosis and treatment guidelines. Juridical and medico-legal approach.

An increasing body of health care regulations and the growing concern of physicians and patients about health care services have sharpened the debate surrounding the concept of quality in medicine. Once unknown terms such as audit, peer review, accreditation, ISO 9000, quality assurance (QA), continuous quality improvement (CQI) and risk management have become more familiar but also less clear. Following recent reports, medical error has been cited as a result of a health care system that has not yet fully embraced the tenets of quality management. A clearer explanation of definitions, knowledge and procedures is therefore needed. In Italy, the general debate on surgical risk led to a proposal to implement control systems that would monitor the work of each team member in the operating room, from the patient's arrival to transfer to the floor. But to understand the dynamics of doubtful cases, we need to start from new concepts that release the surgeon from the role of ''high priest in the surgery temple.'' Such concepts would underpin a process analysis of how much is effectively done and by whom. This means, on one hand, developing a greater awareness of one's role and competences, and on the other, delineating the stages within which each health care professional is expected to operate. Entering into the debate are the guidelines scientific societies have drawn up to rationalise and improve health care delivery through recommendations directed at optimizing the efficacy and efficiency of surgical intervention as the result of scientific evaluation and clinical observation. However, the critics in question do not always allow the surgeon to work under a medico-legal ''guarantee'' that covers his medical conduct. Further-more, they can be a double-edged sword in court if not adequately considered and critically evaluated with regard to a specific case, the object of censure and charge. In fact, they can be ''exploited'' as an instrument of accusation or defence in an arena where the mass media rush to blame the surgeon but later forget to duly report the acquittal of charges held against the surgeon. The present article examines the light and dark sides of guidelines, taking as an example those profiled by the Italian Society of Vascular and Endovascular Surgery and based on international guidelines for the treatment of symptomatic carotid stenosis.

[Transverse study of personality characteristics in patients with arterial hypertension]. / Studio trasversale sui caratteri di personalità in pazienti ipertesi.

OBJECTIVE: To verify whether hypertensive patients, with recent or old poor-controlled hypertension, asymptomatic for anxiety and/or depression, seem more disturbed in personality than normotensive patients. MATERIALS AND METHODS: 122 patients with arterial hypertension (62 women, 60 men, mean age 47 +/- 12.7 years, divided in new-hypertensive patients who don't take any drugs and old-hypertensive patients with a chronic therapy) and 65 normotensive subjects (37 women, 28 men, middle age 41 +/- 11.7 years) answered two self-extiming questionnaires: A.S.Q. by Krug and Cattel and C.D.Q. by Krug and Laughlin. For every group of variables it has been calculated the mean and standard deviation and statistical analysis was performed by Mann-Whitney's t test. A value of p < 0.05 was considered statistically significatant. RESULTS: 37 hypertensive patients (30.3%) were positive in the C.D.Q. and 34 (27.8%) in the A.S.Q. test. In the group of normotensive subjects, 13 (20%) were positive in C.D.Q. and 12 (8.4%) in A.S.Q. There was a statistic difference in C.D.Q and A.S.Q. between hypertensive and normotensive subjects. No statistic difference was found in C.D.Q. and A.S.Q. between new and old-hypertensives. CONCLUSIONS: The study has shown a significant higher level of anxiety and depression in hypertensive subjects as compared to normotensives. However, no significant difference in anxiety and depression levels was found between new- and old-hypertensive patients or in relation with the use of antihypertensive drugs.