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Background: In patients with pneumonia or acute respiratory distress syndrome who survived hospitalization, one-year mortality can affect up to one third of discharged patients. Therefore, significant long-term mortality after COVID-19 respiratory failure could be expected. The primary outcome of the present study was one-year all-cause mortality in hospitalized COVID-19 patients., Methods: Observational study of COVID-19 patients hospitalized at Papa Giovanni XXIII Hospital (Bergamo, Italy), during the first pandemic wave., Results: A total of 1326 COVID-19 patients were hospitalized. Overall one-year mortality was 33.6% (N 446/1326), with the majority of deaths occurring during hospitalization (N=412, 92.4%). Thirty-four patients amongst the 914 discharged (3.7%) subsequentely died within one year. A third of these patients died for advanced cancer, while death without a cause other than COVID-19 was uncommon (8.8% of the overall post-discharge mortality). In-hospital late mortality (i.e. after 28 days of admission) interested a population with a lower age, and fewer comorbidities, more frequentely admitted in ICU. Independent predictors of post-discharge mortality were age over 65 years (HR 3.19; 95% CI 1.28-7.96, p-value=0.013), presence of chronic obstructive pulmonary disease (COPD) (HR 2.52; 95% CI 1.09-5.83, p-value=0.031) or proxy of cardiovascular disease (HR 4.93; 95% CI 1.45-16.75, p-value=0.010), and presence of active cancer (HR 3.64; 95% CI 1.50-8.84, p-value=0.004), but not pneumonia severity., Conclusions: One-year post-discharge mortality depends on underlying patients' comorbidities rather than COVID-19 pneumonia severity per se. Awareness among physicians of predictors of post-discharge mortality might be helpful in structuring a follow-up program for discharged patients., Competing Interests: Declarations of Competing Interest The authors have no conflict of interest in relationship with the present manuscript., (Copyright © 2022 SPLF and Elsevier Masson SAS. All rights reserved.)

The increasing demand for renewable energy production entails the development of novel green technologies, among them the use of biomass for energy generation. Industrial processes raise new issues regarding emerging risks for the health of people working in biogas plants and of nearby communities. The potential epidemiological and environmental impacts on human health related to biogas plants were assessed by means of a review of the available literature. Nineteen papers published between 2000 and 2022 were identified through electronic database search using search strings. The selected works are epidemiological studies and environmental monitoring studies, which aimed at investigating what are the health risk factors for biogas plant workers and for people living in the surrounding communities. The results of the epidemiological studies revealed a potential exposure to endotoxins and fungi that are associated with respiratory symptoms. Furthermore, the results from the environmental monitoring studies showed significant concentrations of particulate matter, microbial agents, endotoxins, and VOCs in occupational settings. In conclusion, the results of this literature review suggest that further analyses through an integrated approach combining environmental and health data are necessary for a comprehensive understanding of the potential risks associated with the uptake of biogas technology.

Benzodiazepine (BDZ) misuse is a growing health problem, with 1-2% of patients under BDZ treatment meeting the criteria for use disorder or dependence. Although BDZ addiction potential has been known for decades, much remains unknown its effects on brain functions. The aim of this study was to assess the neuropsychological and neurophysiological profile of a group of chronic insomniacs taking long-term high doses of benzodiazepine. We recruited 17 consecutive patients admitted to our third-level Sleep Medicine Unit for drug discontinuation (7 males, mean age 49.2 ± 11.2 years, mean education 13.7 ± 3.9 years, mean daily diazepam-equivalent BDZ: 238.1 ± 84.5 mg) and 17 gender/age-matched healthy controls (7 males, mean age 46.8 ± 14.1 years, mean education 13.5 ± 4.5 years). We performed a full neuropsychological evaluation of all subjects and recorded their scalp event-related potentials (Mismatch-Passive Oddball-Paradigm and Active Oddball P300 Paradigm). Patients with chronic insomnia and BDZ use disorder showed a profound frontal lobe executive dysfunction with significant impairment in the cognitive flexibility domain, in face of a preserved working, short and long-term memory. In patients, P300 amplitude tended to be smaller, mainly over the frontal regions, compared to controls. BDZ use disorder has a severe cognitive impact on chronic insomnia patients. Long-term high-dose BDZ intake should be carefully evaluated and managed by clinicians in this specific patient population, especially in relation to risky activities.

Background: An aspect of COVID-19 baffling physicians is the presentation of patients with acute respiratory failure, but normal mental faculties and no perception of dyspnea (i.e. "silent hypoxemia"). The aim of this study was to investigate the frequency, characteristics, and outcome of COVID-19 patients with silent hypoxemic status and comparing them with a symptomatic severity-matched group., Methods: This is a retrospective monocentric observational study involving all patients with PCR confirmed SARS-CoV-2 pneumonia, admitted at Papa Giovanni XXIII Hospital, Bergamo (Italy) from Emergency Department due to acute respiratory failure, during the first Italian pandemic peak (February-April 2020)., Results: Overall 28-day mortality in 1316 patients was 26.9%. Patients who did not report dyspnea at admission (N 469, 35.6%) had a lower 28-day mortality (22.6 vs. 29.3%, P=0.009). The severity matching analysis (i.e. PaO2/FiO2 and imaging) led to the identification of two groups of 254 patients that did not differ for sex prevalence, age, BMI, smoking history, comorbidities, and PaCO2 at admission. The use of CPAP during the first 24 hours, such as the need of endotracheal intubation (ETI) during the overall admission were significantly lower in matched patients with silent hypoxemia, whereas 28-day mortality resulted similar (P=0.21)., Conclusions: Lack of dyspnea is common in patients suffering from severe COVID-19 pneumonia leading to respiratory failure, since up to a third of them could be asymptomatic on admission. Dyspnea per se correlates with pneumonia severity, and prognosis. However, dyspnea loses its predictive relevance once other findings to evaluate pneumonia severity are available such as PaO2/FiO2 and imaging. Silent hypoxemic patients are less likely to receive CPAP during the first 24 hours and ETI during the hospitalization, in spite of a comparable mortality to the dyspneic ones.

Long-term pulmonary sequelae in COVID-19 patients are currently under investigation worldwide. Potential relationships between blood sampling and functional and radiological findings are crucial to guide the follow-up. In this study, we collected and evaluated clinical status, namely symptoms and patients’ reported outcome, pulmonary function tests (PFT), laboratory tests, and radiological findings at 3- and 12-months post-discharge in patients admitted between 25 February and 2 May 2020, and who survived severe COVID-19 pneumonia. A history of chronic pulmonary disease or COVID-19-unrelated complications were used as exclusion criteria. Unenhanced CTs were analyzed quantitatively (compromising lung volume %) and qualitatively, with main patterns of: ground-glass opacity (GGO), consolidation, and reticular configuration. Patients were subsequently divided into groups based on their radiological trends and according to the evolution in the percentage of compromised lung volume. At 12 months post-discharge, seventy-one patients showed significantly improved laboratory tests and PFT. Among them, 63 patients also underwent CT examination: all patients with negative CT findings at three months (n = 14) had negative CT also at 12 months; among the 49/63 patients presenting CT alterations at three months, 1/49 (2%) normalized, 40/49 (82%) improved, 7/49 (14%) remained stably abnormal, and 1/49 (2%) worsened. D-dimer values were low in patients with normal CT and higher in cases with improved or stably abnormal CT (median values 213 vs. 329 vs. 1000 ng/mL, respectively). The overall compromised lung volume was reduced compared with three months post-discharge (12.3 vs. 14.4%, p < 0.001). In stably abnormal CT, the main pulmonary pattern changed, showing a reduction in GGO and an increase in reticular configuration. To summarize, PFT are normal in most COVID-19 survivors 12 months post-discharge, but CT structural abnormalities persist (although sensibly improved over time) and are associated with higher D-dimer values.

The increasing success of populist and radical-right parties is one of the most remarkable developments in the politics of advanced democracies. We investigate the impact of industrial robot adoption on individual voting behavior in 13 western European countries between 1999 and 2015. We argue for the importance of the distributional consequences triggered by automation, which generates winners and losers also within a given geographic area. Analysis that exploits only cross-regional variation in the incidence of robot adoption might miss important facets of this process. In fact, patterns in individual indicators of economic distress and political dissatisfaction are masked in regional-level analysis, but can be clearly detected by exploiting individual-level variation. We argue that traditional measures of individual exposure to automation based on the current occupation of respondents are potentially contaminated by the consequences of automation itself, due to direct and indirect occupational displacement. We introduce a measure of individual exposure to automation that combines three elements: 1) estimates of occupational probabilities based on employment patterns prevailing in the preautomation historical labor market, 2) occupation-specific automatability scores, and 3) the pace of robot adoption in a given country and year. We find that individuals more exposed to automation tend to display higher support for the radical right. This result is robust to controlling for several other drivers of radical-right support identified by earlier literature: nativism, status threat, cultural traditionalism, and globalization. We also find evidence of significant interplay between automation and these other drivers., Competing Interests: The authors declare no competing interest.

How does emigration affect fertility in the country of origin? We address this question by estimating counterfactual fertility during the Great Recession in order to understand what the effect of the recession on fertility would be in the absence of emigration. Between 2009 and 2014, Southern European countries suffered from harsh economic instability, which triggered a sharp drop in fertility and a spike in emigration. We focus on Italy, exploiting the richness of the Italian Administrative Registry of Italians Residing Abroad (AIRE), which records information about all Italian citizens moving their residence abroad, as well as Italian birth records. Using an instrumental variable approach, which helps overcome endogeneity issues in the fertility-migration relationship, we find a positive impact of emigration on the total fertility rate at the Italian province level. This result suggests that emigrants are selected among those individuals who have a lower risk of having children. Therefore, in the absence of emigration, counterfactual fertility would have been lower than it actually is. Such a positive effect of out-migration on fertility in the area of origin could thereby lead to an underestimation of the effect of the recession on fertility., (Copyright © 2021 The Authors.)

Background: Gender-related factors might affect vulnerability to Covid-19. The aim of this study was to describe the role of gender on clinical features and 28-day mortality in Covid-19 patients., Methods: Observational study of Covid-19 patients hospitalized in Bergamo, Italy, during the first three weeks of the outbreak. Medical records, clinical, radiological and laboratory findings upon admission and treatment have been collected. Primary outcome was 28-day mortality since hospitalization., Results: 431 consecutive adult patients were admitted. Female patients were 119 (27.6%) with a mean age of 67.0 ± 14.5 years (vs 67.8 ± 12.5 for males, p = 0.54). Previous history of myocardial infarction, vasculopathy and former smoking habits were more common for males. At the time of admission PaO 2 /FiO 2 was similar between men and women (228 [IQR, 134-273] vs 238 mmHg [150-281], p = 0.28). Continuous Positive Airway Pressure (CPAP) assistance was needed in the first 24 h more frequently in male patients (25.7% vs 13.0%; p = 0.006). Overall 28-day mortality was 26.1% in women and 38.1% in men (p = 0.018). Gender did not result an independent predictor of death once the parameters related to disease severity at presentation were included in the multivariable analysis (p = 0.898). Accordingly, the Kaplan-Meier survival analysis in female and male patients requiring CPAP or non-invasive ventilation in the first 24 h did not find a significant difference (p = 0.687)., Conclusion: Hospitalized women are less likely to die from Covid-19; however, once severe disease occurs, the risk of dying is similar to men. Further studies are needed to better investigate the role of gender in clinical course and outcome of Covid-19.

Implementing the Ecosystem Approach in marine ecosystems is moving from preliminary steps-dedicated to defining the optimal features for indicators and developing efficient indicator frameworks-towards an operational phase where multisector marine management decisions are executed using this information. Within this operational context, emergent ecosystem properties are becoming quite promising as they have been demonstrated to be globally widespread and repeatable, and to be quite effective in detecting significant state variations of complex systems. Biomass accumulation across TLs (CumB-TL) combines two important emergent properties of an ecosystem (energy flow, in terms of transfer efficiency, and storage, expressed as biomass), both amenable to detecting rapid ecosystem change. However, for further application, it is crucial to understand which types of drivers an indicator is sensitive to and how robust it is in relation to modifications of the external conditions and/or the system state. Here we address some outstanding questions of these CumB-TL curves related to their sensitivity to various drivers by carrying out a global scale assessment (using data from 62 LMEs) over six decades (1950-2010). We confirm the consistency of the S-pattern across all the LMEs, independent from latitude, ecosystem, environmental conditions, and stress level. The dynamics of the curve shape showed a tendency to stretch (i.e. decrease of steepness), in the presence of external disturbance and conversely to increase in steepness and shift towards higher TL in the case of recovery from stressed conditions. Our results suggest the presence of three main types of ecosystem dynamics, those showing an almost continuous increase in ecological state over time, those showing a continuous decrease in ecological state over time, and finally those showing a mixed behaviour flipping between recovering and degrading phases. These robust patterns suggest that the CumB-TL curve approach has some useful properties for use in further advancing the implementation of the Ecosystem Approach, allowing us to detect the state of a given marine ecosystem based on the dynamics of its curve shape, by using readily available time series data. The value of being able to identify conditions that might require management actions is quite high and, in many respects, represents the main objective in the context of an Ecosystem Approach, with large applications for detecting and responding to global changes in marine ecosystems., (© 2019 John Wiley & Sons Ltd.)

Background: In the framework of 'Doing more does not mean doing better - Choosing Wisely Italy' health professionals, general population and healthcare advocacy associations are widely involved. PartecipaSalute-Mario Negri IRCCS and Altronconsumo organized a survey in order to assess the opinions and behaviors of people toward unnecessary tests and drugs., Methods: An online survey was distributed by Altroconsumo to a voluntary panel of 6304 Italian citizens covering the whole of the country and by PartecipaSalute-Mario Negri IRCCS through the PartecipaSalute website, e-mail lists, website articles, lay journals and Facebook., Results: In all 1006 people reached by Altroconsumo, and 355 volunteers of healthcare advocacy associations reached by PartecipaSalute responded. Respondents usually decides on their treatment together with the physician, respectively 50% for general population and 64% for volunteers of healthcare advocacy associations. The respondents are aware of the question of over-use of drugs and tests (80%), more often among the volunteers of healthcare advocacy associations (86%). Over-use is considered a problem mostly for economic reasons among the general population, while in the advocacy associations the risks for patients' health is considered more important., Conclusion: These findings suggest that patients do not always ask for more, especially if they receive an answer to their questions and clarifications about unnecessary treatments. There is a need for further understanding of the factors influencing decision-making aimed at achieving good care. Engaging the public and patients at all levels of healthcare is essential for a valuable use of health resources., (© The Author 2018. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Background: Low vitamin D levels have been associated with autoimmune disorders and, then, with the Hashimoto's autoimmune thyroiditis (AT), the most common autoimmune disease. Obesity is characterized by lower vitamin D levels and higher risk to develop autoimmune diseases. The aim of the study was to examine the possibility of an association between AT and decreased 25(OH) vitamin D (25(OH)D) levels in a cohort of otherwise healthy overweight and obese subjects., Materials and Methods: Two hundred sixty one overweight subjects (mean age: 40.9 + 15.6 years, 200 women and 61 men) were enrolled for this study. All of them did not show any clinically evident metabolic or chronic diseases (i.e. hypertension, diabetes mellitus, renal failure, etc.) and did not use any kind of drug. Serum fasting levels of 25(OH)D, anti-thyroid peroxidase (TPO-Ab) and antithyroglobulin (TG-Ab) antibodies, free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), glucose, uric acid and lipids (triglycerides, total, HDL and LDL cholesterol) were measured. Demographic, anthropometric and clinical parameters (age, body mass index (BMI), waist circumference, blood pressure) were also assessed., Results: Fifty five percent of all subjects (144/261) showed vitamin D deficiency (≤ 20 ng/ml), and 17% of all individuals had AT (45/261). The percentage of subjects having vitamin D deficiency was significantly higher among those with AT (31 of 45, 69%) than in those without AT (113 of 216, 52%) (χ2= 4.1, p = 0.042). TSH levels were significantly higher in subjects with AT as compared to those without AT (M-W = 7715.5, p < 0.0001). The final logistic model of a multivariate analysis, performed with AT as the dependent variable and sex, age, BMI category, 25(OH)D category, and HDLcholesterol and TSH levels as the independent ones, showed that patients with AT were more likely to have deficiency of 25(OH)D (p = 0.031) and higher TSH (p < 0.005) levels. Seventy six percent of patients with vitamin D deficiency (110 of 144) were obese whereas 59% of patients without vitamin D deficiency were obese (69 of 117) (p=0.003). Waist circumference was different between subjects with deficiency or normal 25 (OH) D levels (p=0.016)., Conclusion: This study clearly shows that vitamin D deficiency is significantly associated to AT in overweight and obese subjects and confirms that obesity is associated to lower vitamin D circulating levels. We suggest that screening for AT should be suggested in all obese subjects with vitamin D deficiency and that vitamin D deficiency should be researched in all obese subjects with AT., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Purpose: The only drugs available to treat alveolar echinococcosis (AE) are mostly parasitostatic and in many cases prescribed for life. Decision criteria for discontinuation rely on the absence of parasitic viability. The aim of the present study is to search for candidate proteins that may exhibit good potential as biomarkers for viability., Experimental Design: Sixteen serum samples (five healthy controls, 11 patients with AE), are used. AE-patients are classified into three groups "Cured" (n = 2), "ABZ-responders" (n = 4) and "ABZ-nonresponders" (n = 5). Immunoreactive proteins from vesicular fluid (VF) are identified and quantified by LC-MS/MS analysis after immunoprecipitation (IP) using all 16 serum samples., Results: Shotgun analysis of VF lead to the identification of 107 E. multilocularis proteins. Comparative proteomics reveal nine proteins more abundant in IP eluates from ABZ-nonresponder patients (cathepsin b, prosaposin a preprotein, actin modulator protein, fucosidase alpha L1 tissue, gluthatione-S-tranferase, beta galactosidase, elongation factor 2, H17g protein tegumental antigen, and NiemannPick C2 protein)., Conclusions and Clinical Relevance: Detection of antibodies against these proteins by ELISA could be helpful to monitor the course of alveolar echinococcosis under albendazole (ABZ) treatment., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: Nocturnal eating behavior is shared by patients affected by a parasomnia, sleep-related eating disorder (SRED), and several eating disorders such as night eating syndrome (NES) and binge-eating disorder (BED); however, the differential clinical features of these patients have been poorly studied, with persisting difficulties in defining the borders between these pathologies. The aim of this study was to evaluate polysomnographic and personality characteristics of nocturnal eaters to further differentiate the syndromes., Methods: During a period of six months, consecutive patients complaining of nocturnal eating were asked to participate to the study. Twenty-four patients who were found to eat during the polysomnographic recording (PSG) study, and gender-matched control subjects were included. All subjects underwent a full-night video-PSG study and a psychometric assessment including the Eating Disorder Inventory (EDI-2), the self-rating Bulimic Investigatory Test-Edinburgh (BITE), the Temperament and Character Inventory (TCI), and the Barratt Impulsivity Scale (BIS)., Results: Nocturnal eaters showed a mild reduction in sleep efficiency and duration due to a moderate sleep fragmentation, whereas the percentage of each sleep stage was not significantly affected. Nocturnal eaters scored higher at many subscales of the EDI-2, at the BITE symptoms subscale, and at the BIS attentional impulsivity subscale., Conclusion: The psychological characteristics found in our patients with NES seem to be typical for patients affected by eating disorders, and support the hypothesis that the nocturnal behavior of these individuals is due to an eating disorder; however, specific traits also allow differentiation of NES from BED., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Many European citizens regularly consult homeopathic doctors. Especially for children there is very little data available about the reasons they visit a homeopathic doctor. What are the expectations of the parents consulting a Homeopath MD with their child, who are they and last but not least are they satisfied with their initiative? This study including 773 children from six European countries and Brazil is aimed to look at parent-proxy satisfaction with homeopathic treatment prescribed for their children by a homeopathic doctor after a follow-up of two months. The questionnaire was developed from the methodology used in a survey of adults published in 2002., Method: An initial questionnaire included demographic information and questions for assessing health-related Quality of Life (QoL). A follow-up questionnaire collected data on changes in QoL., Results: The demographic characteristics of respondents showed more male children (53.1%) but more female parent-proxies (93.4%). 73.7% of respondents had previously tried conventional treatments; 26.3% non-conventional approaches. Satisfaction with the medical homeopathic consultation was high. Reported differences between baseline and final QoL ondexes are positive for all four studied conditions. It range from 3.206 to 10.188. Considering 7% as a reference value for "minimal clinical difference", this is reached for 2 on 4 conditions (8.473 and 10.188). Changes in complaint limitations visual scales are positive, even if uncertain for skin complaints and influenced parents satisfaction. Conclusions on clinical impact must be cautious. 4.2% of patients experienced side-effects which they attribute to homeopathic treatment. 10.1% of patients reported significant aggravation at the beginning of homeopathic treatment, 19% slight aggravation of symptoms., Conclusions: The satisfaction of parents using a medical homeopathic approach for their children is linked to the perceived competence of the doctor homeopath, the perceived improvement of the main complaint limitations and the completeness of the received information., (Copyright © 2014 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.)

Background: Many patients throughout the world consult homeopathic medical doctors. Using a similar methodology as in a first survey published in 2002 a second survey was done including 919 adults receiving homeopathic treatment in six European countries and Brazil aimed to look at who are they, their reasons for consultations and expectations and satisfaction with homeopathy prescribed by a homeopathic doctor after a follow-up time of six months., Method: An initial questionnaire included demographic information and questions for assessing health-related Quality of Life (QoL). A follow-up questionnaire collected data on changes in QoL., Results: 77% patients had initially used conventional treatments and 23% other non-conventional treatments. Satisfaction of patients with the medical homeopathic consultation is high. The difference between the final QoL scores after six months and the baseline are positive. Reported differences between baseline and final index range from 3.87 to 10.41 depending on diagnosis. Taking 7% as a reference value for 'minimal clinically significant difference', this is reached for 3 of 8 conditions. Changes in complaint limitations visual scales are positive. Conclusions on clinical impact must be cautious. 6% of the patients experienced side-effects which they attributed to homeopathic treatment. 7.8% of the patients reported significant aggravation at the beginning of the homeopathic treatment and 26.2% slight aggravation of symptoms., Conclusions: The satisfaction of patients using a medical homeopathic approach is linked to the perceived competence of the doctor homeopath, the perceived improvement of the main complaints limitations and the time dedicated to them by the doctor., (Copyright © 2014 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.)

Objective: In the SAVE-trial we evaluated the safety, reliability and improvements of patient management using the BIOTRONIK Home Monitoring®-System (HM) in pacemaker (PM) and implanted cardioverter defibrillator (ICD) patients., Design: 115 PM (Module A) and 36 ICD-patients (Module B) were recruited 3 months after implantation., Patients: 65 patients in Module A were randomised to HM-OFF and had one scheduled outpatient clinic follow-up(FU) per year, whereas patients randomised to HM-ON were equipped with the mobile transmitter and discharged without any further scheduled in-office FU. In Module B 18 patients were randomised to HM-OFF and followed by standard outpatient clinic controls every 6 months; 18 patients were randomised to HM-ON receiving remote monitoring plus one outpatient clinic visit per year; unscheduled follow-ups were performed when necessary., Results: The average follow-up period was 17.1 ± 9.2 months in Module A and 26.3 ± 8.6 months in Module B. In both modules, the number of FUs per year was significantly reduced (Module A HM-ON 0.29 ± 0.6 FUs/year vs HM-OFF 0.53 ± 0.5 FUs/year; p b 0.001; Module B HM-ON 0.87 ± 0.25 vs HM-OFF 1.73 ± 0.53 FU/year,p b 0.001). Cost analysis was significantly lower in the HM-ON group compared to the HM-OFF group (18.0 ± 41.3 and 22.4 ± 26.9 € respectively; p b 0.003). 93% of the unscheduled visits in Module B were clinically indicated,whereas 55% of the routine FUs were classified as clinically unnecessary., Conclusion: Remote home monitoring of pacemaker and ICD devices was safe, reduced overall hospital visits, and detected events that mandated unscheduled visits.

Objectives: Nocturnal eating is a common symptom of two clinical conditions with different pathogenesis and needing different therapeutic approaches: Sleep Related Eating Disorder (SRED) and Night Eating Syndrome (NES). The first is considered a parasomnia while the second is an eating disorder; however, the distinction between SRED and NES is still a controversial matter. The aim of this study was to better define psychological, behavioral, and polysomnographic characteristics of the two syndromes., Methods: An eating disorders' specialist tested a group of 28 nocturnal eaters diagnosed as affected by SRED by a sleep expert, following the current criteria of the international classification of sleep disorders, to find out if any of them was affected by NES according to the criteria suggested by both sleep and eating disorders specialists during the first international meeting on Night Eating Syndrome (Minneapolis, 2009) and if they had specific psychological or polysomnographic characteristics., Results: Twenty-two subjects were diagnosed to be affected by NES. They scored higher on the physical tension subscale of the Sleep Disturbance Questionnaire (SDQ) and on the mood and sleep subscale of the Night Eating Questionnaire (NEQ), but there were no other significant differences between SRED and NES patients nor for age, Body Mass Index (BMI), or gender distribution., Conclusions: The overlap between the symptomatology and the polysomnographic characteristics of the two pathologies and the difficulty in making a differential diagnosis between NES and SRED indicate the need for an update of the diagnostic criteria for SRED, as was recently done for NES., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: Our study aimed to analyze the predictive value of intra-operative bypass graft flow measurements for long-term mortality., Methods: A total of 1593 consecutive coronary artery bypass graft (CABG) patients routinely underwent intra-operative bypass graft flow measurements with the transit-time flow meter (TTFM: Cardiomed(®)). The results of the flow measurements and the demographics were analyzed retrospectively., Results: The mean follow-up was 3.8 years (0.5-8.8 years) with no losses to follow-up. Overall mortality was 10.1%. The preoperative left ventricular ejection fraction (LVEF) (echocardiograph) was the highest independent predictor of long-term survival (hazard ratio 0.97, p = 0.004) in all groups. The univariate analysis for the CABG I group showed that besides LVEF, female gender (hazard ratio 3.6, p = 0.02) was also significant. For the CABG II group, additive EuroSCORE (European System for Cardiac Operative Risk) (ES) (hazard ratio 1.4, p = 0.0001) and age (hazard ratio 1.1, p = 0.001) were significant. In the CABG III group, ES (hazard ratio 1.2, p < 0.0001), age (hazard ratio 1.04, p = 0.001), IMA (hazard ratio 0.5, p < 0.0001) and concomitant aortic valve replacement (AVR) (hazard ratio 2.1, p = 0.03) were significant, in addition to the LVEF., Conclusion: With quality-controlled surgeons checked by intra-operative TTFM, accurate quantification of preoperative LVEF significantly predicts long-term outcome. Effective bypass graft flows failed to predict outcome in CABG patients, regardless of the degree of coronary artery disease (CAD) and concomitant AVR., (Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Background: EUR-1008 (Zenpep [pancrelipase]) is a new, enteric-coated, porcine-derived pancreatic enzyme product (PEP) developed for the treatment of cystic fibrosis (CF) patients with malabsorption associated with exocrine pancreatic insufficiency (EPI). Unlike currently marketed PEPs, EUR-1008 contains the label-claimed lipase content. Safety and efficacy were assessed in younger (<7 years) and older (> or =7 years) CF patients with EPI., Methods: Two multicenter studies were conducted: a randomized, double-blind, placebo-controlled, crossover trial in patients > or =7 years of age (N=34) and a supplemental, open-label study in children <7 years of age (N=19). Use of any medications altering gastric pH/motility was prohibited during the studies. Outcome measures in the randomized trial included changes in the coefficient of fat absorption (CFA), coefficient of nitrogen absorption (CNA), and signs/symptoms of malabsorption for EUR-1008 vs. placebo. Outcome measures in the supplemental study included safety and response (defined as no steatorrhea and no overt signs/symptoms of malabsorption) to EUR-1008 vs. previous enzyme treatment., Results: In the randomized trial, EUR-1008 treatment compared to placebo resulted in a significantly higher mean CFA (88.3% vs. 62.8%, respectively) and CNA (87.2% vs. 65.7%, respectively) (both p<0.001) and reduced the incidence of malabsorption signs and symptoms in 32 evaluable patients. In the supplemental study, 11 of 19 patients met the criteria for responder with EUR-1008 at the end of the study vs. 10 of 19 patients at screening (previous PEP), and improvements in clinical symptoms were reported with EUR-1008 treatment. EUR-1008 was safe and well tolerated, and no serious drug-related AEs were reported in either study., Conclusions: EUR-1008 was safe, well tolerated, and effective in CF patients of all ages with EPI-associated malabsorption in two clinical trials. Treatment led to clinically and statistically significant improvements in CFA and CNA in the randomized study, and control of malabsorption and clinical symptoms in both studies.

The perioperative risk for patients with pacemakers or implanted cardioverter/defibrillators (ICD) is mainly dependent on the underlying disease. However, severe to life-threatening complications of the implanted system can occur due to electromagnetic interference in the environment of the operation. These complications can be prevented or adequately treated by taking special precautions and measures. Even though the currently available data on the optimal perioperative management to pacemakers and ICDs is still unsatisfactory, the increasing clinical relevance of this topic was the reason for the formulation of recommendations by an interdisciplinary working group in Austria.

Aims: We compared pacing rate adaptation based on closed loop stimulation (CLS) or accelerometer sensor (AS) during acute mental and physical stress in the same patient., Methods and Results: One month after Protos (Biotronik, Germany) pacemaker implantation, 131 chronotropically incompetent patients were randomized to AS or CLS for 3 months with crossover. Arithmetic and 6 min walk tests were performed in the non-rate-adaptive mode and AS and CLS rate-adaptive modes, respectively. At the end, patients had to select the individually preferred pacemaker sensor. Heart rate during mental stress was higher (3.0 +/- 9.2 bpm) in the CLS than in the AS mode (P = 0.004). Benefit in the walking distance compared with non-rate-adaptive pacing was similar for the two modes: added 27 +/- 96 m (AS, P = 0.013) and 30 +/- 116 m (CLS, P = 0.025). At the end of the walk, heart rate was higher by 4.8 +/- 21.4 bpm in AS than in CLS (P = 0.049). Twice as many patients preferred CLS over AS (P < 0.01)., Conclusion: The arithmetic test was associated with a significantly higher heart rate for CLS than for AS, showing a greater sensitivity of CLS-based rate adaptation to mental stress. Performance during physical stress was comparable. Patients preferred CLS.

Background: Health-related quality of life (HRQL) is increasingly accepted as an outcome measure when considering the effectiveness of therapeutic interventions. Little is known about the HRQL of patients with different clinical circumstances before and after pacemaker implantation (PMI). The purpose of this study was to investigate the influence of clinical symptoms and ECG diagnoses as predictors of improved HRQL in patients referred for PMI., Methods: Sixty eight patients with different indications for PMI completed the MacNew Heart Disease Health-related Quality of Life Questionnaire (MacNew) and the Short Form-36 Health Survey (SF-36) before and one, three and six months after PMI. Symptoms, ECG indications and pacing mode were collected using the European Pacemaker Patient Identification Card codes., Results: Within the first month after PMI overall Mac-New but not SF-36 scores improved significantly and was maintained during the entire 6 month follow up period. Improvement in HRQL as measured with the MacNew was rather related to baseline symptoms and ECG diagnosis than to the pacing mode., Conclusion: The important finding of this study is that improved HRQL seen after PMI appears to be largely driven by baseline symptoms and the ECG diagnoses rather than the pacing mode of the device.

Background: Frequent and unnecessary right ventricular apical pacing increases the risk of atrial fibrillation or congestive heart failure. We evaluated a new pacing algorithm, managed ventricular pacing (MVP) which automatically changes modes between AAI/R and DDD/R in patients receiving pacemakers for symptomatic bradycardia., Methods: Patients were randomized to the MVP mode or DDD/R mode for 1 month and then crossed over to the alternate pacing modality for an additional month. On completion of the crossover phase, the pacing mode selected was individualized and patients were followed for an additional 4 months., Results: Of the 129 patients who successfully completed the crossover study, the cumulative percent ventricular pacing was significantly reduced in the MVP mode (median 1.4%) compared to the DDD/R mode (median 89.6%, 94.0% relative reduction; 95% CI 89.3-98.8%, P < 0.001). Patients with sinus node disease (SND, n = 51) when compared to patients with AV block (AVB) (n = 68) experienced a greater reduction in ventricular pacing with the MVP mode compared to the DDD/R mode (median relative reduction 99.1%; 95% CI 97.5-99.9% vs median relative reduction 60.1%; 95% CI 16.7-93.9% P < 0.001). The reduced percent ventricular pacing during MVP was sustained over longer term follow-up., Conclusions: The majority of patients with a bradycardia indication for cardiac pacing do not require ventricular pacing most of the time. The MVP mode significantly reduces unnecessary right ventricular pacing. This mode benefits even patients with intermittent AVB and is sustained over longer term follow-up.

Little is known about the HRQL of pacemaker patients due to the limited availability of disease-specific instruments. The aim of the Pacemaker Patients Quality of Life (PAPQoL) study was to determine the psychometric properties for the MacNew Heart Disease Health-related Quality of Life Questionnaire (MacNew) in patients before and after pacemaker implantation. Patients with a given indication for pacemaker therapy (N = 68) completed two self-administered HRQL instruments, the SF-36, a well-known and psychometrically sound health survey, and the MacNew, a reliable and valid heart-disease-specific HRQL instrument, before and one, three and six months after pacemaker implantation. We assessed disease severity with the New York Heart Association (NYHA) classification. Test-retest reliability, intra-class correlation, Cronbach's alpha, validity coefficients, sensitivity analyses (effect sizes) and confirmatory factor analysis were carried out. The MacNew demonstrated adequate reliability (Cronbach's alpha and ICCs > 0.80 on all scales), validity (correlations between similar SF-36 and MacNew subscales > 0.80), and responsiveness (all effect sizes > or = 0.67) in pacemaker patients. The MacNew demonstrates adequate psychometric properties for evaluating HRQL in patients before and after pacemaker implantation.

Objectives: In this single-center study we reviewed our experience with a significant number of cardiac myxoma cases occurring over the past two decades., Patients and Methods: Cardiac myxomas represented 86% of all surgically treated cardiac tumors at our center. Specifically, there were 49 consecutive patients, each with at least one myxoma. A detailed clinical, immunological, and echocardiographic long-term examination of 37 patients revealed one recurrent myxoma., Results: Most myxomas originated from the left atrium (87.7%), but also much less frequently from the mitral valve (6.1%), from the right atrium (4.1%), and from the left and right atria (2.0%). The myxomas produced a prolapse into the left ventricle in 40.8% of the patients, mitral stenosis in 10.2%, and threatened left ventricular outflow tract obstruction in 2.0%. Multiple myxomas were found in 20.4% of the patients. Cardiac signs appeared in 93.9% of the patients. Preoperative embolic events had occurred in 26.5%. Immunologic alterations were present in 87.5%. For resection, a bilateral atriotomy was used. An additional aortotomy was needed to expose one mitral valve myxoma. Postoperatively, 81.1% of the patients remained without cardiac symptoms. The early mortality rate was 2.0% and the late mortality rate was 6.1%. Long-term prognosis was excellent with an actuarial survival rate of 0.74. Specific immunologic alterations were found in 71.4% of the patients. The actuarial freedom from reoperation of the myxoma was 0.96. The rate of reoperations was low with 2.0% after 24 years., Conclusions: Myxomas were usually detected and operated on in symptomatic patients. A high index of suspicion seems important for early diagnosis. Immunologic findings may play an additional role in confirming the diagnosis and the recurrence of a myxoma. Immediate surgical treatment was indicated because of the high risk of embolization or of sudden cardiac death. Also, a familial genesis must be excluded in myxoma patients.

A pilot survey of 1025 patients receiving homeopathic treatment in six European countries is reported. An initial questionnaire included demographic information and questions from health-related Quality of Life (QoL) scales. A follow-up questionnaire collected data on changes in QoL. The demographic characteristics of respondents were similar to previous studies. 82.8% of respondents had previously tried conventional treatments. Satisfaction with consultations was high. The changes of QoL status are positive but weak. 2.7% of patients experienced side-effects which they attribute to homeopathic treatment. 7.8% of patients reported significant aggravation at the beginning of the homeopathic treatment, 25.4% slight aggravation of symptoms. A new survey should be performed with a better motivation of doctors and patients. Further description of treatment would be helpful.

Pacing threshold is not a stable value during the pacemaker's life. It is affected by many physiological, pharmacological and pathophysiological factors. A pacing system able to confirm capture and automatically adjust its output to the actual pacing threshold is highly desirable for a prolonged battery life and maximal patient safety. The Autocapture(TM) of St. Jude Medical and the Capture Management(TM) of Medtronic are currently available on the market. The key feature is the measurement of the evoked response (ER) signal by the pacemaker for capture confirmation. In case of loss of capture, the Autocapture(TM) System delivers a back up safety pulse of 4.5 Volt and 0.49 ms and starts a new threshold search. The pacemaker adapts its output to 0.3V/0.25V above the newly measured threshold. This system needs bipolar leads with low polarization for the first generation in Microny® and Regency® pacemakers; in the second generation with Affinity® and Integrity® pacemakers various bipolar leads are suitable. The Capture Management(TM) System of Medtronic, available in the Kappa® DR 700 series, performs a two point automatic threshold search once every day during rest. The output is determined by the programmed safety margin (nominal 1.5×voltage threshold). A backup pulse is only delivered during the threshold search. No special electrodes are necessary.    These functions were shown to work safely and efficaciously in multicenter trials to decrease the current consumption with a prolongation of battery life up to 142%. The patients safety was increased by identifying changes of the capture threshold over time and adjusting the pacing stimulus. The conventional safety margins of 100% might not be safe for all patients. We also learned much about lead maturation and lead instability by the possibility of continuous follow-up of threshold changes in a larger group of leads in order to identify the risk group of about 10% of patients with late threshold increase and lead instability.

Objectives: Left ventricular hypertrophy in patients with critical aortic stenosis (AS) is an adaptive process that compensates for high intracavitary pressure and reduces systolic wall stress followed by an increase in myocardial masses. In the present prospective clinical trial, we investigated long-term compensatory changes in left ventricular geometry and function after aortic valve replacement using mechanical bileaflet prostheses with the main emphasis on the small-sized aortic annulus and valve prosthesis-patient mismatch., Methods: A total of 58 patients with critical AS were assigned to the following groups according to the predictive value of prosthetic valve area index (VAI): group EXMIS: 29 patients (VAI < or =0.99), expected mismatch; group NOMIS: 29 patients (VAI < or =0.99), no mismatch. At controls T(0) (before operation/operation (OP), T(1) and T(2) (4 and 20 months after OP) the left ventricular geometry was recorded by means of Imatron electron beam tomography and the transprosthetic velocities were measured by echocardiography., Results: Statistical analysis showed a consistent reduction in the absolute (P=0.04) and indexed (P=0.04) left ventricular myocardial mass for both cohorts; furthermore, there was a significant difference between EXMIS and NOMIS patients concerning the factors, time and mass reduction (P=0.005), because of distinct baselines. A logistic regression report revealed preoperative cardiac output, absolute left ventricular myocardial mass, perfusion, body surface area and the native valve orifice area as predicting coefficients and factors for a minimum mass reduction of 25%. We explain a mathematical formula that turned out to be the most sensitive for correctly classified factors., Conclusions: The left ventricular geometry and transprosthetic velocities resulted in the same postoperative recovery for both EXMIS and NOMIS patients. The presented data showed that valve prosthesis-patient mismatch had no influence in several stepwise logistic regression models. We conclude that modern mechanical bileaflet prostheses allow both acceptable hemodynamics and recovery of left ventricular hypertrophy, even in small aortic annuli.

The grounds for liability with robotic surgery include damage to patients, causality, illegality and guilt. The patient must receive very comprehensive information on the treatment under consideration, his/her risk and what will be done in the case of technical failure. The surgeon operating the robotic device is obliged to provide normal conscientious care and state-of-the-art treatment. In addition, there is possible neglect of supervisory duties vis-à-vis other hospital personnel to be considered. A special problem is posed by a forensic physician who lacks experience in robotic surgery. There should be a surgeon at the operating table who is at least equally skilled as the surgeon operating the monitor. Robotic surgery must ultimately be at least as effective as conventional surgery, if not better. It must, however, be borne in mind that in cases involving this new technology, it is that patient who is the pioneer.

A life-threatening left ventricular outflow tract obstruction developed in a 26-year-old man because of a very uncommon myxoma emerging from the ventricular side of the mitral valve. Immediate surgical treatment was indicated because of high-risk factors reported herein. After transaortic resection of a single myxoma, the progress of this patient has been excellent, especially as a familial myxoma could be excluded.

From 1990 to 1999, 2,853 ventricular and 1,084 atrial bipolar leads of various manufacturers (Medtronic, Biotronik, Vitatron, Ela, Pacesetter and Stöckert) were implanted during first implantations of pacemakers at the University of Graz, Dept. of Cardiac Surgery. Surgical complications with the need of reintervention were analyzed during a follow up period of up to 10 years. The overall lead-related complication rate for ventricular bipolar leads was 6.5% (187 of 2,853) and 5.3% (58 of 1,084) for atrial bipolar leads. Early complications within the first month were higher in the atrium (5.3% versus 2.2% in the ventricle), primarily due to dislocation, late complications were higher in the ventricle (4.3% versus 2% in the atrium) due to insulation problems and lead fracture. Insulation material had a marked influence with a higher failure rate in some leads with polyurethane insulation compared with silicone. Therefore we recommend a close follow-up of bipolar polyurethane leads by measurement of chronic impedance in order to assess insulation problems as early as possible.

Background: Risk evaluation comparing the minimally invasive and standard aortic valve operations has not been studied., Methods: Four surgeons were randomly assigned to perform the minimally invasive (L-shaped sternotomy) (group 1) or the conventional (group 2) operation in 120 patients exclusively., Results: In both groups (n = 60) a CarboMedics prothesis was implanted in 90% of patients. There was no significant difference in the cross-clamping period (group 1, 60 minutes; range, 35 to 116 minutes), in the duration of extracorporal circulation (group 1, 84 minutes; range, 51 to 179 minutes) or in the time from skin-to-skin (group 1, 195 minutes; range, 145 to 466 minutes). Patients in group 1 were extubated earlier (p<0.001), the postoperative blood loss was less (p<0.001), and the need for analgesics was reduced (p<0.05). In 5 patients in group 1 a redo operation was required for bleeding (p>0.05), 3 patients in group 1 required a redo operation because of paravalvular leakage or endocarditis (p>0.05), the 30-day mortality rate was 1.6%. Overall the survival rate was 95% in group 1 and 97% in group 2 (mean follow-up, 294 days; range, 30 to 745 days)., Conclusion: The advantages of minimally invasive aortic valve operation include reduced trauma from incision and duration of ventilation, decreased blood loss and postoperative pain, the avoidance of groin cannulation, and a cosmetically attractive result. Simple equipment is used with a high degree of effectiveness and with no sacrifice of safety. Our study demonstrated the practicability and reliability of this new method.

After twenty-five years of therapy with different unifocal pacemaking systems, an 84-year old male patient developed a nonseptic pacemaker decubitus. A rare incidental finding of invasive ductal carcinoma of the right mammary gland was surgically treated by a generous excision of the tumor and by consecutive modified radical mastectomy. According to published literature, the association of invasive ductal carcinoma arising from a pacemaker pocket decubitus and followed by curative treatment has not been previously reported. We do conclude that pacemaker generators in close relationship to the mammary gland should be considered with suspicion.

The neuropharmacological effects of repeated oral doses of dexfenfluramine (DF; 1.25-10 mg/kg, twice daily for 21 days) were examined in rats and related to the drug brain levels. Results were compared with fluoxetine (FL) given at similar doses relative to its anorectic ED50. Both drugs dose-dependently slowed body weight gain and reduced brain serotonin (5-HT). However, at 1.25 mg/kg DF caused only a slight and transient decrease in cortical 5-HT. Comparable doses of FL (6.25-12.5 mg/kg) lowered 5-HT more than DF, besides slightly reducing striatal dopamine. At higher doses DF markedly reduced 5-HT in all regions, and to a lesser extent noradrenaline in hippocampus. There was a negative relationship between 5-HT and log total active drug levels and the indole was approximately halved at drug levels about 50 times lower with DF than FL. However, the ratio between drug levels causing marked 5-HT reductions and those considered anorectic was similar for DF and FL because brain levels at the anorectic ED50 were higher with FL than DF. Long-lasting reductions of 5-HT were also observed but recovery was only consistently slow beginning from 5 mg/ kg DF. Comparable doses of FL could not be used because its general toxicity leads to the death of rats after only 2-4 multiples of its anorectic ED50.

Atrial electrical activities during hypothermic, K(+)-induced cardioplegic arrest correlate with an increased incidence of postoperative supraventricular dysrhythmias in coronary artery bypass graft patients. Surface electrocardiogram (ECG) (S-ECG) may be insufficiently sensitive to detect such activity intraoperatively, and invasive methods are impractical and traumatic. From induction of anesthesia until the end of surgery, esophageal ECG signals were detected with a new bipolar esophageal probe and a new high-resolution preamplifier (frequency range 0.01-2000 Hz). The S-ECG and the esophageal ECG (E-ECG) were evaluated independently in 18 patients. Eight of 18 patients presented during cardioplegic arrest a mean of 483 +/- 119 high-amplitude, biphasic P components (mean amplitude 0.7 +/- 0.1 mV, range 0.35-1.15 mV) per patient (mean 36 +/- 6 [5-59] potentials/min) similar to those coinciding with the surface ECG P-waves during sinus rhythm. Six of these eight patients presented a mean of 29 +/- 11 low atrial activities (mean amplitude 0.14 +/- 0.023 mV; range 0.1-0.25 mV) per patient (mean 8.4 +/- 5.6 [2.3-48] potentials/min) in the E-ECG. In the S-ECG, one patient of these eight presented 26 P waves during cardioplegic arrest simultaneously with activities in the E-ECG. During the first 5 days, seven of eight (88%) patients with atrial activities in the E-ECG versus 3 of 10 (30%) patients without atrial activities developed supraventricular tachyarrhythmias postoperatively (P < 0.05). This new high-resolution E-ECG device detected in a beat-to-beat technique more atrial activity during cardioplegic arrest than a S-ECG and offered the advantages of artifact exclusion and better prediction of postoperative supraventricular dysrhythmias.

Background and Aims of the Study: Aortic valve replacement (AVR) in the small aortic root (SAR) has always been a severe challenge with an uncertain surgical outcome. The purpose of this study was to assess the surgical and clinical performance of 19 mm and 21 mm CarboMedics valves (CPHV) based on a review of valve-related morbidity and mortality over a period of six years., Methods: A total of 361 patients undergoing aortic valve replacement (AVR) with the CPHV between January 1989 and August 1995 was subdivided and studied. (i) Group A patients (n = 137) received 19 mm or 21 mm prostheses; subgroup AI (n = 85) underwent isolated AVR and subgroup AII (n = 52) underwent AVR with associated cardiac procedures. (ii) Group B patients (n = 224) were given 23 mm or larger prostheses; subgroup BI (n = 147) underwent isolated AVR and subgroup BII (n = 77) underwent AVR with concomitant cardiac procedures., Results: Hospital mortality was group A 7.3% versus group B 4.9%. Cumulative survival after six years was 83.7% in AI and 76.9% in AII versus 72.1% in BI and 77.4% in BII. There were no significant statistical differences between the subgroups concerning cardiac mortality. Thromboembolic events occurred with a linearized rate of 1.41%/pty in group A versus 1.03%/pty in group B, the incidence of anticoagulant-related major hemorrhage was 1.41%/pty in group A versus 1.20%/pty in group B and that of periprosthetic leakage 1.69%/pty in group A versus 1.89%/pty in group B., Conclusion: Our results demonstrate that this bileaflet prosthesis is highly efficient in patients with small aortic roots undergoing AVR with or without associated procedures.

Flunarizine (35 mg/kg), but not haloperidol and trifluperazine, counteracted the initial indole depletion induced by D-fenfluramine (dF) in vivo (5 mg/kg), without affecting ex vivo [3H]-serotonin (5-HT) uptake by synaptosomes or changing the brain concentrations of the parent drug and its main active metabolite, D-norfenfluramine (dNF). The long-term indole depletion induced by repeated doses of dF (5 mg/kg, b.i.d. for 4 days) was also reversed by flunarizine pretreatment. Flunarizine, methiothepin, and trifluperazine, but not haloperidol, reduced in vitro the Ca(2+)-dependent [3H]5-HT release stimulated by 0.5 microM dF and dNF from superfused synaptosomes. At the concentrations used in release experiments the drugs were not active on [3H]5-HT uptake nor on the calcium-calmodulin protein kinase activity, thus excluding an effect on the uptake carrier or on phosphorylation of synaptic proteins involved in exocytosis, respectively. The drugs did not consistently affect [3H]5-HT release induced by depolarization, or dNF-induced [3H]dopamine release in vitro. The fact that flunarizine, as methiothepin and 5-HT uptake inhibitors, counteract dF-induced indole depletion in vivo suggests a relation between the reduction of the Ca(2+)-dependent release of [3H]5-HT induced by dF in vitro and the protective effect on the short- and long-lasting depletion of indoles induced in vivo by high doses of dF.

The effects of pretreatment with inducers of hepatic cytochrome P450 isoenzymes (phenobarbital, dexamethasone and beta-naphthoflavone) on the metabolism of d-fenfluramine (d-F) and its acute and long-lasting indole-depleting effects were studied in rats, in an effort to obtain further information on the importance of hepatic drug metabolism in relation to its neurochemical actions. Twenty-four hours after the last dose of each inducer, rats were injected with d-F hydrochloride (5 mg/kg, IP) and killed at various times thereafter for parallel determination of indoles and drug concentrations in plasma and brain. Additional rats were treated as above and killed 1 week after d-F hydrochloride (5 and 10 mg/kg) to study the recovery of indole in the cortex, a particularly sensitive brain area. Phenobarbital and beta-naphthoflavone and, to a lesser degree, dexamethasone, stimulated the metabolism of d-F, as evidenced by a decrease in plasma and brain areas under the curve (AUC) compared to vehicle-treated rats. This indicated that multiple isoenzymes are capable of mediating the drug's metabolism, primarily by N-dealkylation to d-norfenfluramine (d-NF). None of the inducers raised plasma and brain AUC of the nor-derivative, and in fact phenobarbital and particularly beta-naphthoflavone reduced it. These different effects were even apparent in rats given d-NF (2.5 mg/kg), indicating that both phenobarbital and beta-naphthoflavone also stimulate the sequential metabolism of the nor-metabolite (by N-deamintaion) which, however, is apparently enhanced most actively by beta-naphthoflavone-inducible forms of P-450.(ABSTRACT TRUNCATED AT 250 WORDS)

The original Fontan operation was employed for patients with tricuspid atresia, but its application has been extended to a broad spectrum of congenital cardiac defects with a functional or anatomical single ventricle. From 1989 to 1995, 35 patients (23 males, 12 females) underwent a modified Fontan procedure; their age ranged from 14 months to 15 years (mean 5.1 a). Indications for operation were the following: D(S)ILV = 16, TA = 9, MA = 3, TGA with straddling AV-valve = 2, DORV = 4 and criss-cross heart = 1. The same surgical technique was utilized in all patients with redirection of the systemic venous return by means of a bidirectional cavopulmonary anastomosis and an intraatrial baffle, adaptable to all the various forms of underlying anatomy. Associated anomalies such as dextrocardia, coarctation, anomalous systemic or pulmonary venous return, subaortic stenosis and situs anomalies were present in 26%, 9%, 26%, 9%, and 20%, respectively. 12 patients were presumed to be at high risk and underwent a two-stage procedure (n = 7 bidirectional Glenn preceding the definitive repair and n = 5 a fenestration of the intraatrial baffle). Risk factors in our group of patients were: age under 2 years, abnormal systemic venous drainage, stenotic pulmonary arteries, PVR over 2 Wood units, mPAP over 15 mmHg, AV-valve incompetence, subaortic obstruction and ventricular dysfunction. Two patients had failure of the total cavo-pulmonary connection necessitating the take-down to a bidirectional Glenn anastomosis in the early postoperative period, with one death. Hospital mortality was 24% (n = 8). One child did not survive complications following the fenestration closure 4 months postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Troponin-T is one of the contractile proteins of the myocardium. Its release into the circulation indicates various degrees of myocardial cell damage. Troponin-T may be measured in serum with a recently developed enzyme immunoassay. This immunoassay was used to evaluate the preoperative myocardial cell damage in patients with stable and unstable angina undergoing elective coronary artery bypass graft surgery, and it was compared with conventional assays of creatine kinase (CK) MB isoenzyme activity and mass., Methods: Twenty-one patients with unstable angina and 31 with stable angina were studied. Troponin-T, CK-MB activity, and CK-MB mass were measured 24 h before anesthesia and surgery, immediately before induction of anesthesia, before and after cardiopulmonary bypass, at the end of surgery, and 24 h afterward., Results: In 90% (19 of 21) of the patients with unstable angina, troponin-T was increased 24 h before anesthesia (median 0.33 microgram/l, range 0.15-5.2 micrograms/l), whereas only 3% (1 of 31) of the patients with stable angina had increased values (median 0.0 microgram/l, range 0.0-0.53 microgram/l). The difference was statistically significant (P < 0.001). The same profile was found in patients with and without unstable angina immediately before induction of anesthesia (86% [18 of 21] and 0%, respectively) and before cardiopulmonary bypass (62% [13 of 21] and 0%, respectively). In contrast to troponin-T, CK-MB activity was increased in only 0-14% of patients with unstable angina, and CK-MB mass was increased in only 9-24%. After bypass troponin-T increased in both groups (P < 0.01), but there was no longer a statistically significant difference between the groups. Twelve percent (4 of 31) of the patients in the stable angina group and 28% (6 of 21) in the unstable group had major cardiac events (P not significant)., Conclusions: The study data suggest that many patients with unstable angina undergoing elective coronary artery bypass graft surgery have already increased troponin-T levels preoperatively, although conventional biochemical markers such as CK-MB activity and mass are at a normal range. Increased troponin-T and normal CK-MB concentrations may reflect some degree of ischemic myocardial cell damage. Because of the small number of patients in the study, the influence of preoperative myocardial injury on perioperative outcome could not be clarified.

1. The effects of acute and repeated equiactive anorectic doses (ED50) of recently marketed 5-hydroxytryptamine (5-HT) uptake inhibitors on the content of brain indoles were compared in rats in relation to the brain regional concentrations of unchanged drug and its known active metabolite. 2. Single intraperitoneal (i.p.) doses of the anorectic ED50 of fluoxetine (35 mumol kg-1), fluvoxamine (60 mumol kg-1), paroxetine (20 mumol kg-1) and sertraline (49 mumol kg-1) slightly reduced brain 5-hydroxyindoleacetic acid (5-HIAA), with regional differences, this being compatible with 5-HT uptake blockade. Only fluvoxamine and sertraline significantly enhanced the content of 5-HT in the cortex. 3. The regional sensitivity to the acute effect of a given drug was not related to any preferential drug distribution, as these compounds distributed almost uniformly in the brain areas considered (cortex, striatum and hippocampus). 4. Repeating the same doses twice daily, i.p. for 14 days, however gave a different picture, fluvoxamine having little or no effect on the content of indoles and fluoxetine, paroxetine and sertraline lowering both 5-HT and 5-HIAA in all the brain regions compared to pair-fed control animals, 1 h after the last dose. 5. One week later only fluoxetine-treated animals still had reduced brain 5-HT, this probably being related to the accumulation of its main metabolite norfluoxetine in rat brain after chronic dosing. 6. Further studies on the relationship between the long-term neurochemical changes and anorectic activity are required but it appears from these results that anorectic drugs with similar acute effects on 5-HT uptake may differ in their long-term effects on 5-HT mechanisms.

1. The effect of the CCKA receptor antagonist, devazepide (100 mg kg-1) on meal parameters during the initial phase of the dark period was studied in free-feeding rats by use of a procedure for continuously monitoring feeding patterns. 2. In a second experiment, the effect of devazepide on the reduction in meal parameters induced by the 5-hydroxytryptamine (5-HT) releaser and uptake inhibitor, (+)-fenfluramine (1.5 mg kg-1) in 4 h food-deprived rats was examined. 3. The hypophagic effect of an intraperitoneal injection of cholecystokinin (CCK-8, 4 micrograms kg-1) was studied in rats treated with the 5-HT receptor antagonist, metergoline (1 and 2 mg kg-1). 4. Devazepide increased the size of the first meal in free-feeding, but not in 4 h food-deprived rats and partially antagonized the effect of (+)-fenfluramine on the size and duration of the first meal. The reduction in eating rate induced by (+)-fenfluramine was not modified by devazepide. No changes in (+)-fenfluramine or (+)-norfenfluramine levels were found in the brain of rats treated with devazepide. 5. The effect of CCK-8 on meal size was completely antagonized by 2 mg kg-1 metergoline. A significant interaction was also found between 2 mg kg-1 metergoline and CCK-8 as regards their effect on the inter-meal interval. 6. The results suggest a reciprocal interaction between 5-HT and CCK-8 in enhancing the satiating effect of food in rats.

The importance of d-norfenfluramine in regard to the indole-depleting action of d-fenfluramine has not been well studied in sensitive animal species. The present study therefore examined the intensity and time course of the neurochemical effects of i.p. injected d-fenfluramine (2.5 and 5 mg/kg) and d-norfenfluramine (2.5 mg/kg) in vehicle- and SKF-525A-pretreated rats, relating the effects to the brain concentration-time profiles of the drug and its active metabolite. At the lower dose d-fenfluramine caused only a small, short-lasting decrease in brain serotonin (5-HT) without affecting the 5-hydroxyindoleacetic acid (5-HIAA). Higher doses affected both 5-HT and 5-HIAA (50-60 and 30-40% reductions, respectively), the effect being maximal for at least 8 h. d-Norfenfluramine reduced the brain content of 5-HT and 5-HIAA less (by about 30%) than 5 mg/kg d-fenfluramine did. Brain concentrations of d-norfenfluramine at the time of the maximal depletion of indoles were close to those of the metabolite after 5 mg/kg d-fenfluramine, indicating that the acute indole-depleting effects did not depend solely on the brain concentrations of its nor-metabolite. SKF-525A changed the metabolite-to-parent drug ratios in brain without appreciably influencing the action of d-fenfluramine. However, the maximum decrease in indole content caused by 2.5 mg/kg d-fenfluramine in SKF-525A-pretreated rats was only 12% of the control level, although the brain concentration of unchanged drug was comparable to that after 5 mg/kg d-fenfluramine in vehicle-pretreated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The present study investigated the anorectic activity of d-fenfluramine (d-F) and the relationship with brain levels of unchanged drug and its metabolite d-norfenfluramine (d-NF) in marmosets, relating them to neurochemical effects on the serotoninergic system. d-F and d-NF were equally active in reducing food intake (ED50 about 3 mg/kg, p.o.). However, the brain concentrations of the metabolite required to reduce food intake after synthetic d-NF were more than twice those after d-F, indicating that d-NF contributes to but does not completely explain the anorectic effect of d-F. At this dose d-F did not appreciably modify the serotonin (5-HT) and 5-hydroxyindoleacetic (5-HIAA) contents of the brain regions examined, except for a slight enhancement of 5-HIAA in hippocampus. In vitro in brain cortical synaptosomes d-F inhibited [3H]5-HT uptake more potently than d-NF, as in other species. d-F and d-NF showed similar potency in stimulating [3H]5-HT release, in a Ca++ dependent manner. The tritium released by d-F and d-NF appeared to be mainly unmetabolized [3H]5-HT. Like in other species the marmoset too has saturable and specific [3H]d-F binding sites, for which d-NF has lower affinity. d-F and d-NF have low affinities for 5-HT receptor subtypes, except that d-NF has appreciable affinity for 5-HT1C and 5-HT1D receptors. Unlike in rodents but similarly to primates in the striatum the pharmacology of 5-HT receptors seems to correspond to the 5-HT1D subtype.(ABSTRACT TRUNCATED AT 250 WORDS)

Six years after the first aortic valve replacement with the Starr-Edwards Silastic ball prosthesis at Oregon Health Sciences University, the model 1260 was implanted in a 44-year-old patient at our department. During 24 years no signs of dysfunction, thromboembolism, thrombosis, periprosthetic leaks or hemolysis were observed. Material test showed no signs of fatigue. The dimension of the Silastic poppet was found to be one millimeter less than the original specifications of these poppets and there were some lipid infiltrations. Functionally the poppet was found to be nonvariant. Histologic findings detected focal hyalinization and giant cells without signs of acute inflammation or ulceration. With regard to its reliability and durability, the Starr-Edwards valve prosthesis should not be viewed with disfavor.