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Background: Perfluoroalkyl substances (PFAS) are man-made fluorinated chemicals, widely used in various types of consumer products, resulting in their omnipresence in human populations. The aim of this study was to describe current PFAS levels in European teenagers and to investigate the determinants of serum/plasma con-centrations in this specific age group.Methods: PFAS concentrations were determined in serum or plasma samples from 1957 teenagers (12-18 years) from 9 European countries as part of the HBM4EU aligned studies (2014-2021). Questionnaire data were post -harmonized by each study and quality checked centrally. Only PFAS with an overall quantification frequency of at least 60% (PFOS, PFOA, PFHxS and PFNA) were included in the analyses. Sociodemographic and lifestyle factors were analysed together with food consumption frequencies to identify determinants of PFAS exposure. The variables study, sex and the highest educational level of household were included as fixed factors in the multivariable linear regression models for all PFAS and each dietary variable was added to the fixed model one by one and for each PFAS separately.Results: The European exposure values for PFAS were reported as geometric means with 95% confidence intervals (CI): PFOS [2.13 mu g/L (1.63-2.78)], PFOA ([0.97 mu g/L (0.75-1.26)]), PFNA [0.30 mu g/L (0.19-0.45)] and PFHxS [0.41 mu g/L (0.33-0.52)]. The estimated geometric mean exposure levels were significantly higher in the North and West versus the South and East of Europe. Boys had significantly higher concentrations of the four PFAS compared to girls and significantly higher PFASs concentrations were found in teenagers from households with a higher education level. Consumption of seafood and fish at least 2 times per week was significantly associated with 21% (95% CI: 12-31%) increase in PFOS concentrations and 20% (95% CI: 10-31%) increase in PFNA concentrations as compared to less frequent consumption of seafood and fish. The same trend was observed for PFOA and PFHxS but not statistically significant. Consumption of eggs at least 2 times per week was associated with 11% (95% CI: 2-22%) and 14% (95% CI: 2-27%) increase in PFOS and PFNA concentrations, respectively, as compared to less frequent consumption of eggs. Significantly higher PFOS concentrations were observed for participants consuming offal (14% (95% CI: 3-26%)), the same trend was observed for the other PFAS but not statistically significant. Local food consumption at least 2 times per week was associated with 40% (95% CI: 19-64%) increase in PFOS levels as compared to those consuming local food less frequently.Conclusion: This work provides information about current levels of PFAS in European teenagers and potential dietary sources of exposure to PFAS in European teenagers. These results can be of use for targeted monitoring of PFAS in food. This work was supported by the European Union’s Horizon 2020 research and innovation programme under Grant agreement No 733032 HBM4EU (www.HBM4EU.eu), and received co-funding from the authors’ organizations: Riksmaten Adolescents: Riksmaten Adolescents was performed by the Swedish Food Agency with financial support from the Swedish Environmental Protection Agency and the Swedish Civil Contingencies Agency. NEB II: The Norwegian Institute of Public Health (NIPH) has contributed to funding of the Norwegian Environmental Biobank (NEB). The laboratory measurements have partly been funded by the Research Council of Norway through research projects (275903 and 268465) PCB cohort follow-up: PCB cohort follow-up received additional funding from the Ministry of Health of the Slovak Republic, program 07B0103. BEA: BEA study was funded by the Spanish Ministry of Agriculture, Fisheries and Food and the Instituto de Salud Carlos III (SEG 1321/15) SLO-CRP: The Slovenian SLO-CRP study was co-financed by the Joˇzef Stefan Institute program P1- 0143, and a national project “Exposure of children and adolescents to selected chemicals through their habitat environment” (grant agreement No. C2715-16-634802). CROME: CROME study was co-funded by the European Commission research funds of Horizon 2020. ESTEBAN: ESTEBAN study was funded by Sant´e Publique France and the French ministries of Health and the Environment. GerES V-sub: The funding of the German Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection is gratefully acknowledged. FLEHS IV: The Flemish Center of Expertise on Environment and Health is funded by the Government of Flanders, Department of Environment & Spatial Development. We are grateful to all teenagers and their families that participated in the studies. HBM4EU is co-financed under Horizon 2020 (grant agreement No 733032). FLEHS: We thank the field workers from the Provincial Institute of Hygiene and VITO for the sample and data collection. All collaborators of the scientific teams of the Flemish Center of Expertise on Environment and Health (https://www.milieu-en-gezondheid.be/en/about-the-cente r-0) and Karen Van Campenhout and Caroline Teughels from the Flemish Department of Environment & Spatial Development for their valuable input in the field work committee. Riksmaten Adolescents: Personnel from the regional Occupational and Environmental Medicine Divisions in Gothenburg, Linkoping, ¨ Lund, Stockholm, and Umeå are acknowledged for help with blood sampling. Jonathan P. Benskin and colleagues at the Department of Environmental Science and Analytical Chemistry, Stockholm University are acknowledged for the chemical analyses. PCB cohort follow-up: We wish to thank Dana Jureˇckova, ´ MD, PhD, head of Department of Pediatrics, hospital “Svet zdravia”, Michalovce and her personnel for blood sampling, questionnaire administration and examination of adolescents, personnel from the laboratory of biochemistry and haematology (AlphaMedical) in Michalovce, Slovakia, for blood samples processing and colleagues from RECETOX, Masaryk University, Brno, Czech Republic, for chemical analyses.

Coronary microvascular dysfunction (CMVD) plays a major role in the occurrence of cardiovascular events (CVE). We recently suggested the clinical potential of myocardial perfusion entropy (MPE) quantification from SPECT myocardial perfusion images (MPI) for the prognosis of CVE occurrence. We hypothesized that the quantification of MPE from SPECT MPI would allow the assessment of CMVD-related MPE variations in a preclinical model of type 2 diabetes (T2D) including treatment with the anti-diabetic incretin liraglutide (LIR).Optimal conditions for the preclinical quantification of MPE usingThe feasibility study identified dobutamine stress and acute NO synthase and cyclooxygenase inhibition as optimal conditions for the quantification of MPE, with significant increases in MPE being observed in T2D animals (P 0.01 vs controls). In the therapeutic study, T2D rats were hyperglycemic (5.5 ± 0.5 vs 1.1 ± 0.3 g/L for controls, P 0.001) and had a significantly lower left ventricular ejection fraction (LVEF) (65 ± 4% vs 74 ± 9%, P 0.01) and LV capillary density (2400 ± 300 vs 2800 ± 600 mmMPE quantification allowed the preclinical noninvasive assessment of CMVD. Both MPE and capillary density quantification suggested that LIR did not improve T2D-induced CMVD. The relevance of MPE for CMVD assessment warrants further clinical investigation.

Background Pulmonary arterial hypertension (PAH), is a rare manifestation of systemic lupus erythematosus (SLE), characterized by pulmonary arterial remodeling leading to right ventricular failure and death. To date, optimal management of SLE-associated PAH should be clarified, especially regarding the respective places of immunosuppressants and PAH vasodilator treatments. Case report We report the case of a 48-year-old woman with SLE and secondary Sjogren syndrome, associated with severe PAH and lupus peritonitis with massive ascites, who showed a remarkable response, both for SLE flare and PAH, to a treatment combining immunosuppressants and pulmonary arterial vasodilator treatment. Conclusion This observation highlights the interest of combining immunosuppressive therapy in SLE-PAH, whose modalities in association with PAH treatments should be clarified.

Risk stratification of patients with type 2 diabetes mellitus (T2D) remains suboptimal. We hypothesized that myocardial perfusion entropy (MPE) quantified from SPECT myocardial perfusion images may provide incremental prognostic value in T2D patients independently from myocardial ischemia.T2D patients with very high and high cardiovascular risk were prospectively included (n = 166, 65 ± 12 years). Stress perfusion defect was quantified by visual evaluation of SPECT MPI. SPECT MPI was also used for the quantification of rest and stress MPE. The primary end point was major adverse cardiac events (MACEs) defined as cardiac death, myocardial infarction (MI), and myocardial revascularization 3 months after SPECT.Forty-four MACEs were observed during a 4.6-year median follow-up. Significant differences in stress MPE were observed between patients with and without MACEs (4.19 ± 0.46 vs. 3.93 ± 0.40; P ≤ .01). By Kaplan-Meier analysis, the risk of MACEs was significantly higher in patients with higher stress MPE (log-rank P ≤ 01). Stress MPE and stress perfusion defect (SSS ≥ 4) were significantly associated with the risk of MACEs (hazard ratio 2.77 and 2.06, respectively, P .05 for both) after adjustment for clinical and imaging risk predictors as identified from preliminary univariate analysis. MPE demonstrated incremental prognostic value over clinical risk factors, stress test EKG and SSS as evidenced by nested models showing improved Akaike information criterion (AIC), reclassification (global continuous net reclassification improvement [NRI]: 63), global integrated discrimination improvement (IDI: 6%), and discrimination (change in c-statistic: 0.66 vs 0.74).Stress MPE provided independent and incremental prognostic information for the prediction of MACEs in diabetic patients.NCT02316054 (12/12/2014).

Thermoplastic Elastomer Vulcanized (TPE-V) syntactic foams made by Thermo-Expandable Microcapsules (TEMs) are becoming of a large interest for automotive industry. TPE-Vs combine advantages of class rubber compound properties with an easier manufacture process and are recyclable. Therefore, TPE-Vs are more and more used to manufacture automotive sealing system by an extrusion process, which is the focus of this research. Due to the two-phase structure of TPE-V, classical extrusion foaming technologies, such as chemical and physical foaming, are complex to be controlled. Thus, TEMs show an outstanding ability to be effective and produce repeatable microstructure with standard extrusion equipment. TEMs consist in a mixture of liquid hydrocarbons, encapsulated by a gas-proof polymeric shell. Exposed to elevated temperatures, the internal pressure drives the dilation of the TEMs, as a result a TPE-V syntactic foam is produced. The aim of this study is to understand where the expansion occurs and how can it be affected by extrusion process parameters. Temperature is a well-known key parameter to control final expansion of TEMs. Hence, measurements at high pressure and temperature were done to find out the location of expansion during extrusion process. Additionally, we have designed three groups of three dies to apply different pressure drops, pressure drop rates and residence time, inside the die. Under these process conditions, density, cell microstructure and viscosity have been investigated.

About 70% patients waiting for liver transplantation have a dyspnea. Two pulmonary vascular disorders can be associated with portal hypertension or chronic liver diseases: portopulmonary hypertension (PoPH) related to pulmonary small arteries remodeling and obstruction and hepatopulmonary syndrome (HPS) characterized by pulmonary capillaries dilatations and proliferations. PoPH is defined by the combination of pulmonary arterial hypertension (PAH) (mean pulmonary artery pressure [PAP]≥25mmHg, with normal pulmonary artery wedge pressure≤15mmHg and pulmonary vascular resistance [PVR]>3 Wood units [WU]) and portal hypertension. HPS is a triad of intrapulmonary vascular dilatations, hypoxemia (increased alveolar-arterial oxygen gradient) and liver disease or isolated portal hypertension. The pathophysiology of both syndromes is complex and poorly understood. PoPH and HPS have a negative impact on functional and vital prognosis in patients with portal hypertension. Liver transplantation is the established treatment standard in HPS. PoPH treatment is improved over the years with the use of specific PAH treatment despite the lack of randomized assay in this indication. Liver transplantation could be considered in PoPH leading to stabilization, improvement or recovery in selected patients (mean PAP

Background:COVID-19 survivors may have high risks of developing sarcopenia, which is associated to handicap, poor quality of life, higher healthcare costs, increased risk of falls, increased mortality (1).Objectives:To assess sarcopenia rate (which has not been described yet) following COVID-19 hospitalization and to highlights features associated with sarcopenic vs. non-sarcopenic patients.Methods:Major confirmed COVID-19 patients undergoing intensive care unit (ICU) or Pneumology Department admission in Strasbourg University Hospital between March and June 2020 were prospectively included. Muscle and cardio-respiratory evaluations were performed 3 months after discharge. Sarcopenic patients were compared to non-sarcopenic ones. A second muscle assessment 6 months after discharge was performed in patients with pathologic muscle tests.Results:127 patients were included, 39 (30.7%) not requiring ICU care, 88 (69.3%) requiring ICU care. The cohort consisted of 71% male patients, with a median age of 63 years [28-82]. Forty-one-percent were obese (BMI>30 kg/m2). Most individuals had preexisting comorbidities (82 patients, 70%), mainly hypertension and diabetes mellitus. The median total hospital stay duration was 22 days and up to 89 days. At the 3 months assessment, 17/127 (13%) patients were diagnosed with sarcopenia which comprised 6/17 (35%) severe sarcopenia (4.7% of the total cohort). At the 6 months assessment, only 4/15 (27%) of the initial sarcopenic patients remained sarcopenic (3% of the total cohort) and 3 of these 4 patients had severe sarcopenia. BMI (26,3 vs. 29,3, p=0.03), COPD (20% vs. 3%, p=0.03), comorbidities (93% vs. 67%, p=0.04), total hospital stay duration (33 vs. 20 days, p=0.03) and ICU stay duration (33 vs. 13 days, p=0.01) were significantly associated with sarcopenic vs. no sarcopenic patients. However, there was no significant difference concerning cardio-pulmonary evaluations between these two groups.Conclusion:We here highlighted a sarcopenia prevalence at 3 and 6 months following a hospitalization for COVID-19 of 13% and 3% respectively, occurring mainly in patients with comorbidities. Sarcopenia was not associated to worse cardio-pulmonary results in comparison with non-sarcopenic patients.References:[1]Di Filippo L, De Lorenzo R, D’Amico M, Sofia V, Roveri L, Mele R, et al. COVID-19 is associated with clinically significant weight loss and risk of malnutrition, independent of hospitalisation: A post-hoc analysis of a prospective cohort study. Clinical Nutrition [Internet]. oct 2020. https://linkinghub.elsevier.com/retrieve/pii/S0261561420305896Disclosure of Interests:None declared

About 70% patients waiting for liver transplantation have a dyspnea. Two pulmonary vascular disorders can be associated with portal hypertension or chronic liver diseases: portopulmonary hypertension (PoPH) related to pulmonary small arteries remodeling and obstruction and hepatopulmonary syndrome (HPS) characterized by pulmonary capillaries dilatations and proliferations. PoPH is defined by the combination of pulmonary arterial hypertension (PAH) (mean pulmonary artery pressure [PAP]≥25mmHg, with normal pulmonary artery wedge pressure≤15mmHg and pulmonary vascular resistance [PVR]3 Wood units [WU]) and portal hypertension. HPS is a triad of intrapulmonary vascular dilatations, hypoxemia (increased alveolar-arterial oxygen gradient) and liver disease or isolated portal hypertension. The pathophysiology of both syndromes is complex and poorly understood. PoPH and HPS have a negative impact on functional and vital prognosis in patients with portal hypertension. Liver transplantation is the established treatment standard in HPS. PoPH treatment is improved over the years with the use of specific PAH treatment despite the lack of randomized assay in this indication. Liver transplantation could be considered in PoPH leading to stabilization, improvement or recovery in selected patients (mean PAP35mmHg without severe right ventricular dysfunction and PVR4 WU).

Through their function as epigenetic readers of the histone code, the BET family of bromodomain-containing proteins regulate expression of multiple genes of therapeutic relevance, including those involved in tumor cell growth and inflammation. BET bromodomain inhibitors have profound antiproliferative and anti-inflammatory effects which translate into efficacy in oncology and inflammation models, and the first compounds have now progressed into clinical trials. The exciting biology of the BETs has led to great interest in the discovery of novel inhibitor classes. Here we describe the identification of a novel tetrahydroquinoline series through up-regulation of apolipoprotein A1 and the optimization into potent compounds active in murine models of septic shock and neuroblastoma. At the molecular level, these effects are produced by inhibition of BET bromodomains. X-ray crystallography reveals the interactions explaining the structure-activity relationships of binding. The resulting lead molecule, I-BET726, represents a new, potent, and selective class of tetrahydroquinoline-based BET inhibitors.

Sympathetic system abnormalities have been reported in sepsis-related cardiac dysfunction. The present study aimed at evaluating the potential of the norepinephrine radiolabeled analogue [Sepsis was induced in male Wistar rats by intraperitoneal injection of 10 mg·kgSepsis-induced modifications in cardiac sympathetic nervous system activity were evidenced by noninvasive in vivo

The addition of ezetimibe, an intestinal cholesterol absorption inhibitor, to statin therapy has recently shown clinical benefits in the Improved Reduction of Outcomes: Vytorin Efficacy International Trial by reducing low-density-lipoprotein (LDL) cholesterol levels more than statin therapy alone. Here, we investigated the mechanisms by which inhibition of intestinal cholesterol absorption might contribute to the clinically observed reduction in cardiovascular events by evaluating its effect on inflammatory plaque development in apolipoprotein E

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The discovery, synthesis and biological evaluation of a novel series of 7-isoxazoloquinolines is described. Several analogs are shown to increase ApoA1 expression within the nanomolar range in the human hepatic cell line HepG2.

Epigenetic mechanisms of gene regulation have a profound role in normal development and disease processes. An integral part of this mechanism occurs through lysine acetylation of histone tails which are recognized by bromodomains. While the biological and structural characterization of many bromodomain containing proteins has advanced considerably, the therapeutic tractability of this protein family is only now becoming understood. This paper describes the discovery and molecular characterization of potent (nM) small molecule inhibitors that disrupt the function of the BET family of bromodomains (Brd2, Brd3, and Brd4). By using a combination of phenotypic screening, chemoproteomics, and biophysical studies, we have discovered that the protein-protein interactions between bromodomains and acetylated histones can be antagonized by selective small molecules that bind at the acetylated lysine recognition pocket. X-ray crystal structures of compounds bound into bromodomains of Brd2 and Brd4 elucidate the molecular interactions of binding and explain the precisely defined stereochemistry required for activity.

Global developmental delay (GDD) is defined as evidence of significant delays in two or more developmental domains. Our study determined the cognitive skills of a cohort of young children with GDD. A retrospective chart review of all children diagnosed with GDD within a single developmental clinic was carried out. Scores on fine motor (Peabody Developmental Motor Scale 2), expressive language (Expressive One Word Picture Vocabulary Test) and receptive language (Reynell Developmental Language Scales or Clinical Evaluation of Language Fundamentals - Preschool 2) testing, and cognitive performance (Wechsler Preschool and Primary Scale of Intelligence, Third Edition) were obtained. A multiple regression analysis was performed and correlations obtained. Results from a total of 93 patients (86 males, seven females) were retained for analysis. Mean age was 3 years 8 months (SD 10mo, range 2.5-4.75y). Cognitive scores were widely distributed, with 73% of participants displaying a global IQ score of 70 or more, despite concurrent global delay. Significant correlation was present for fine motor and expressive language scores, when isolated and compared with cognitive performance (p values of 0.04 and 0.05 respectively). The conclusion was made that an initial diagnosis of GDD is not necessarily associated with objective cognitive impairment.

Reports of acute combined central and peripheral nervous system acquired inflammatory demyelination are rare in children. This study aimed to (1) define the clinical features and prognoses of patients with this entity; and (2) compare these patients with children presenting isolated acute central or peripheral nervous system demyelination. A retrospective chart review of 523 children with central or peripheral nervous system demyelination hospitalized between 1993-2006 was undertaken. Among these, 93 fulfilled criteria (clinical features and positive magnetic resonance imaging or electromyography/nerve conduction studies) for either acute central (n = 37; 39.8%) or peripheral (n = 43; 46%) nervous system demyelination, or a combination of the two (n = 13; 14%). Significant differences between groups were evident for age (median, 10 versus 7 versus 11 years, respectively; P = 0.047), admission to pediatric intensive care unit (8% versus 30% versus 58%, respectively; P = 0.001), length of hospital stay (median, 8 versus 9 versus 29 days, respectively; P < 0.001), treatment with steroids (52% versus 7% versus 75%, respectively; P < 0.001) and immunoglobulins (11% versus 81% versus 75%, respectively; P < 0.001), and poor evolution (3% versus 12% versus 54%, respectively; P = 0.002). This entity in children is not rare, and has a poorer outcome than isolated central or peripheral nervous system demyelination. Assessment is needed for a better understanding of risk factors, etiologies, management, and prognosis.

Few cases of simultaneous acute demyelination of the peripheral and central nervous systems are reported. Four patients diagnosed as having Guillain-Barré syndrome and acute disseminated encephalomyelitis during the same hospitalization are described herein. Two patients manifest an atypical form of Guillain-Barré syndrome, with magnetic resonance imaging of the head showing acute disseminated encephalomyelitis. A third patient has acute disseminated encephalomyelitis and develops Guillain-Barré syndrome during his hospitalization. A fourth patient demonstrates transverse myelitis that evolves into Guillain-Barré syndrome, with demyelination seen on brain magnetic resonance imaging. All patients are treated with intravenous immunoglobulins or corticosteroids. Three patients have a favorable outcome; 1 patient has a chronic inflammatory demyelinating polyradiculoneuropathy. Guillain-Barré syndrome and acute disseminated encephalomyelitis can occur simultaneously in the pediatric population. This may be explained by a shared epitope between peripheral and central nervous system myelin. Further research is necessary to better describe this entity and its prognosis.

With the advent of magnetic resonance imaging as a rapid and accurate way to diagnose arterial ischemic stroke, cerebrospinal fluid assessment is rarely performed, unless infectious or inflammatory processes are obvious. Recent advances in the understanding of the pathophysiology of childhood stroke have implicated a growing list of discrete or occult infectious and inflammatory conditions which may involve intracranial arteries and neighboring structures. Cerebrospinal-fluid assessment may allow the detection of markers identifying processes (including infectious, inflammatory, metabolic, and traumatic) potentially involved in cerebral vasculopathy and stroke. The analysis of cerebrospinal fluid in arterial ischemic strokes, including apparently idiopathic strokes, may yield essential information on pathophysiology, allowing for optimal therapeutic decisions and prognostic considerations.

(99m)Tc-[bis (dimethoxypropylphosphinoethyl)-ethoxyethylamine (PNP5)]-[bis (N-ethoxyethyl)-dithiocarbamato (DBODC)] nitride (N-PNP5-DBODC or N-DBODC5) is a new monocationic myocardial perfusion tracer. We sought to compare the myocardial uptake and clearance kinetics and organ biodistribution of (99m)Tc-N-DBODC5 with (99m)Tc-sestamibi and (99m)Tc-tetrofosmin.Seventy-five anesthetized Sprague-Dawley rats were injected intravenously with 22.2-29.6 MBq (99m)Tc-N-DBODC5 (n = 25), (99m)Tc-sestamibi (n = 25), or (99m)Tc-tetrofosmin (n = 25). Rats were euthanized at either 2, 10, 20, 30, or 60 min after injection and gamma-well counting was performed on excised organ (heart, lung, and liver) and blood samples. In 3 additional rats, serial in vivo whole-body gamma-camera imaging with each tracer was performed.(99m)Tc-N-DBODC5 cleared rapidly from the blood pool. At 2 min after injection, (99m)Tc-N-DBODC5 blood activity was significantly lower than either (99m)Tc-sestamibi or (99m)Tc-tetrofosmin (P0.01) and remained lower over 60 min. Myocardial (99m)Tc-N-DBODC5 uptake was rapid (2.9% +/- 0.1% injected dose/g at 2 min), and there was no significant clearance over 60 min, similar to (99m)Tc-sestamibi and (99m)Tc-tetrofosmin. All 3 tracers exhibited rapid lung clearance. Importantly, (99m)Tc-N-DBODC5 cleared more rapidly from the liver than either (99m)Tc-sestamibi or (99m)Tc-tetrofosmin. As early as 30 min after injection, (99m)Tc-N-DBODC5 heart-to-liver ratio was 5.7 +/- 1.0 versus 1.6 +/- 0.1 and 2.9 +/- 0.3 for (99m)Tc-sestamibi and (99m)Tc-tetrofosmin (P0.05). By 60 min, (99m)Tc-N-DBODC5 heart-to-liver ratio further increased to 18.4 +/- 2.0 compared with 2.6 +/- 0.2 and 5.8 +/- 0.7 for (99m)Tc-sestamibi and (99m)Tc-tetrofosmin (P0.001). The rapid blood pool, lung, and liver clearance of (99m)Tc-N-DBODC5 resulted in excellent-quality myocardial images within 30 min after injection.(99m)Tc-N-DBODC5 is a promising new myocardial perfusion tracer with superior biodistribution properties. The rapid (99m)Tc-N-DBODC5 liver clearance may shorten the duration of imaging protocols by allowing earlier image acquisition and may markedly reduce the problem of photon scatter from the liver into the inferoapical wall on myocardial images.

Bis(N-ethoxy,N-ethyldithiocarbamato)nitrido technetium (V) ((99m)Tc) ((99m)TcN-NOET) is a myocardial perfusion imaging agent demonstrating significant redistribution and currently in phase III clinical trials. Previous studies have suggested that (99m)TcN-NOET is bound intravascularly. Therefore, we sought to determine whether modifications in the vascular compartment would provide further insights into the mechanisms of (99m)TcN-NOET myocardial washout and redistribution.(99m)TcN-NOET cardiac washout was studied ex vivo in 15 isolated perfused rat hearts after bolus injection (1.5 MBq) in the absence (n = 6) or presence of bovine serum albumin ([BSA] 0.03%) with (n = 5) or without (n = 4) bound lipids. The intrinsic myocardial washout of the tracer was also studied in vivo in 6 dogs after intracoronary bolus injection of the tracer (0.75 MBq) before and after hyperlipidemia induced by intravenous administration of 300 mL of 20% intralipids (n = 3) or hyperemia induced by intravenous infusion of the adenosine A(2A) receptor agonist ATL-146e (0.3 micro g/kg/min; n = 6).On isolated hearts, there was no significant myocardial washout of (99m)TcN-NOET with Krebs-Henseleit buffer. Addition of BSA without bound lipids resulted in a significant cardiac washout of the tracer (P0.001 by repeated measures ANOVA). The presence of lipids bound to BSA further accelerated the washout rate of (99m)TcN-NOET (half-life [t(1/2)], 431.5 +/- 23.2 min vs. 242.9 +/- 63.2 min; P0.05). In vivo in dogs, intralipid administration significantly increased the intrinsic washout rate of (99m)TcN-NOET (t(1/2), 108.0 +/- 23.9 min vs. 51.8 +/- 11.8 min; P0.05). In addition, vasodilatation with ATL-146e resulted in a 4.9-fold increase in coronary flow (P0.05 vs. baseline) and a significantly faster intrinsic (99m)TcN-NOET myocardial washout (t(1/2), 81.1 +/- 12.1 min vs. 40.7 +/- 7.3 min; P0.05).The myocardial washout kinetics of (99m)TcN-NOET are affected by a variety of intravascular factors, supporting the hypothesis that the tracer is most likely localized on the vascular endothelium. The potential impact of variations in circulating lipid levels among patients on clinical imaging with (99m)TcN-NOET requires further investigation.

Bis(N-ethoxy,N-ethyldithiocarbamato)nitrido technetium (V) ((99m)Tc) ((99m)TcN-NOET) is a new myocardial perfusion imaging agent currently undergoing phase III clinical trials in the United States and in Europe. (99m)TcN-NOET cellular uptake has been shown to be inhibited by the calcium channel inhibitor verapamil in cultured newborn rat cardiomyocytes. However, the effect of verapamil on in situ (99m)TcN-NOET myocardial uptake remains unknown. Therefore, the aim of this study was to evaluate whether the inhibitory effect of verapamil on the cellular uptake of (99m)TcN-NOET shown in vitro could be reproduced in situ in a canine model of normal and ischemic myocardium.(99m)TcN-NOET uptake in normal and ischemic myocardium (70% flow reduction in the left anterior descending coronary artery) was measured in the absence or presence of verapamil (0.015 mg/kg/min x 10 min) in anesthetized, open-chest dogs (n = 17). Control animals were infused with adenosine (0.2 mg/kg/min) to match the verapamil-induced increase in flow.By verapamil treatment, a clinically relevant plasma concentration of the calcium channel inhibitor was attained (mean +/- SEM, 290 +/- 152 ng/mL). In normal myocardium (n = 8), regional blood flow at the time of (99m)TcN-NOET injection was not statistically different in verapamil- and adenosine-treated dogs (1.69 +/- 0.03 vs. 1.61 +/- 0.04 mL/min/g, respectively). (99m)TcN-NOET uptake was slightly higher in the presence of verapamil (0.39 +/- 0.01 vs. 0.38 +/- 0.01 counts per minute [cpm]/[Bq/kg]/g for adenosine; P = 0.04). However, no significant difference in (99m)TcN-NOET myocardial uptake was observed after normalization of the tracer uptake to regional myocardial blood flow. In ischemic myocardium (n = 9), regional blood flow was lower in verapamil-treated than in adenosine-treated animals (0.22 +/- 0.02 vs. 0.29 +/- 0.03 mL/min/g; P0.05). (99m)TcN-NOET uptake in the ischemic area was not inhibited by verapamil (0.09 +/- 0.01 vs. 0.10 +/- 0.01 cpm/[Bq/kg]/g; P = not significant).Verapamil does not inhibit (99m)TcN-NOET uptake in situ in normal and ischemic canine myocardium. These results suggest that verapamil should not affect (99m)TcN-NOET myocardial uptake in patients referred for myocardial perfusion imaging.

Seven bitches in early pregnancy (12.8 +/- 3.8 days after ovulation; group 1) and seven bitches in mid-pregnancy (32.0 +/- 1.53 days after ovulation; group 2) were used in this study. For each group, five bitches were treated with 0.10 mg aglepristone (Alizine) kg-1 and this dose was repeated 24 h later. Two control bitches received a placebo. Blood samples were collected at 6 h intervals to determine plasma concentrations of progesterone, dihydro-keto prostaglandin F2 alpha (PGFM), oxytocin, prolactin and cortisol. Parturition occurred in the four control bitches. All bitches treated with aglepristone aborted. In group 1, embryonic death occurred; in group 2, fetal expulsion occurred 60-132 h after administration of aglepristone. After pregnancy termination, the interoestrous interval of aglepristone-treated bitches was significantly shorter than that before treatment. Treatment with aglepristone did not modify plasma concentrations of progesterone, prostaglandin, oxytocin or cortisol within 24 h after its administration, but it induced, in mid-pregnancy (group 2) a discharge of prolactin within 12 h after its administration. As an abortifacient, aglepristone acted on the uterus and, therefore, did not have direct or immediate luteolytic properties. Termination of pregnancy occurred with high plasma progesterone concentrations. Fetal expulsion was characterized by an increase in the concentration of PGFM, but oxytocin and cortisol remained at basal concentrations.

To date, there has been no survey concerning psychiatric isolation rooms in France. We conducted a mail survey in 1993 involving all adult psychiatric care catchment areas covering the French departments. The survey revealed an estimated number of 1560 isolation rooms. Isolation rooms were considered as absolutely necessary in all the departments but also as an unsatisfactory solution by one-third of them. Isolation rooms were usually small and poorly adapted to efficient patient surveillance. Furthermore, equipment was often inadequate, particularly for noise and fire protection. A serious accident (fire, suicide, escape) was reported by large number of departments. The rooms were used for agitated psychotic (84%) and psychopathic (16) people. Although requested by the physician, but also in some cases by the patient, conditions of use and design of isolation rooms may be dangerous both for the patient and the nursing staff. Financial investment devoted to isolation rooms varies greatly and there is no specific control over the number of installation. Construction must comply with precise specifications defined in co-ordination with the experts involved.

La valeur predictive de l'anticorps anti-SS-B a ete testee sur 48 malades possedant dans leur serum cet anticorps, a l'exclusion de tout autre anticorps antinucleaire. 25 malades avaient un syndrome de Gougerot-Sjogren (SGS) franc et les 23 autres, sans syndrome sec, restaient en majorite inclasses sur le plan nosologique. L'analyse des signes cliniques et biologiques nous a permis d'observer une similitude assez marquee entre les deux groupes de malades. Nous deduisons que l'anticorps anti-SS-B n'est pas un marqueur biologique du SGS, mais qu'il revele un trouble dysimmunitaire inconstamment associe au syndrome sec. Ce trouble dysimmunitaire, a l'exception du syndrome sec, possede les memes caracteres cliniques et biologiques que le SGS systemique.

Angular distributions for the elastic scattering of /sup 40/Ca by /sup 40/Ca at E/sub c. m./ = 64.8, 71.8, 88, 93, 112.5, and 120 MeV and excitation functions at 60/sup 0/, 70/sup 0/, and 90/sup 0/ (c.m.) over the c.m. energy range 55--120 MeV have been measured. Strong-absorption-model and optical-model analyses are presented. The predictions of several theoretical interaction potentials are compared with the data. The absence of structure in the excitation functions is studied and explained by the large mass and charge of the colliding nuclei.

Broad structures have been observed in the incompletely relaxed part of the energy spectra of fragments emitted in the symmetrical reactions $^{40}\mathrm{Ca}$ + $^{40}\mathrm{Ca}$ at 284 MeV and $^{63}\mathrm{Cu}$ + $^{63}\mathrm{Cu}$ at 450 MeV. Excitation energies of these structures, angular distributions, and ($Z, N$) distributions leading to multiplicities for nucleon emission have been measured. They can be interpreted as being due to a predominantly direct reaction process, possibly proceeding through the excitation of highly collective high-energy modes in the region of giant resonances.

Evidence is presented for the observation of four structures in the incompletely relaxed part of the energy spectra of fragments emitted in the40Ca+40Ca reaction at 400 MeV. These structures appear to be produced in a direct process. Statistical evaporation processes from primary fragments cannot explain all the observed structures. Excitation of giant resonances is a plausible interpretation.

Air pollution contributes to the degradation of the reliability of telephone switching relays. To study pollution effects on the French crossbar telephone exchange system we conducted three studies: first, atmospheric analysis in some telephone central offices; second, surface analysis of contacts from telephone exchanges; and, third, laboratory simulation tests in order to accelerate the harmful effects of natural exposure. This paper reports the methods used, and gives some results on the 'behavior of connectors and relays in some aggressive atmospheres.

Resume Les auteurs rapportent une observation de spasme coronarien survenant lors de deux anesthesies successives chez un sujet opere d'un pontage aorto-bifemoral. Des troubles graves du rythme ventriculaire, mais fugaces et sans sequelles accompagnent ces accidents. Les elements de reconnaissance du spasme peranesthesique sont rappeles en soulignant les difficultes du diagnostic electrique. Chez le sujet predispose, l'induction anesthesique doit eviter certains facteurs favorisants tels que l'alcalose, la stimulation du systeme parasympathique et l'hypothermie. L'accent est mis sur l'efficacite du traitement preventif par les inhibiteurs calciques, et sur celle du traitement curatif par les derives nitres administres par voie intraveineuse.

Resume Un test intradermique a la phytohemagglutinine a ete pratique chez 153 sujets allergiques et chez 57 sujets temoins. L'introduction de 1 μg de phytohemagglutinine a provoque l'apparition de tests cutanes de type immediat et retarde. La reponse cultanee « retardeea ete observee moins souvent chez les allergiques (67,5 p. cent) que chez les temoins (86,1 p. cent). II a ete constate une concordance importante (88,4 p. cent) entre le test intradermique et le TTL a la phytohemagglutinine.

Deep inelastic fragment production in the symmetrical reaction 40 Ca on 40 Ca has been studied at E lab = 278 MeV, high above the Coulomb barrier. Kinetic energy distributions and angular distributions have been obtained for products in the Z = 8−22 region. The two-body nature of the mechanism is discussed. Sequential decay of primary fragments is shown to be important.

Inelastic scattering of 84 Kr on 232 Th has been measured at E =371 and 450 MeV and at different angles using the particle-gamma coincidence technique. It is found that for distances of closest approach smaller than about 20 fm the scattering of Kr on Th is mostly inelastic. At forward angles, the data are in agreement with predicted values from a Coulomb excitation program, but some differences are observed at backward angles.

The light product nuclei from the reaction 40 Ar + 232 Th at 295 MeV and at laboratory angles of 18° and 40°, were identified using combined ΔE  E and magnetic analysis techniques. The yield distributions and the kinetic energies of the reaction products have very distinct properties at these two angles. The data are consistent with the assumption of a predominant “quasi-elastic” reaction mechanism at 40° and a “deep inelastic” one at 18°. The isotopic dependence of the cross sections is not correlated with the ground state Q -values of the reaction. The experimental kinetic energies at 18° favour the interpretation that the observed nuclei are close to primary reaction products.

The (d, 3 He) reaction has been studied for targets of 16 O, 40 Ca and 58 Ni, to test DWBA predictions at high incident deuteron energy. Spectroscopic factors are obtained in local, zero-range, and in nonlocal, finite-range approximations.

Angular distributions of the ground state transitions in the reactions 11 B( 14 N, 15 O) 10 Be, 11 B( 14 N, 13 C) 12 C, 12 C( 11 B, 12 C) 11 B and 13 C( 12 C, 13 C) 12 C have been measured with a magnetic spectrometer as an identification system. The first two reactions (angular momentum transfer l = 2) measured at 41, 77 and 113 MeV show a clear damping of the oscillatory structures in the angular distributions. This effect was qualitatively reproduced by DWBA calculations which take into account a recoil phase, thus showing that the damping of the structures is due to the recoil of the transferred particle on the system. The reaction 11 B( 12 C, 11 B) 12 C ( l = 2) at 87 MeV with Q = 0 is well reproduced by the calculations, whereas the 13 C( 12 C, 13 C) 12 C reaction as the only l = 0 transition is in complete disagreement with theoretical expectations.

The angular distributions of inelastically scattered 155Mev protons from excited states of Li/sup 6/, Li/sup 7/, Be/sup 9/, B/sup 10/, B /sup 11/, C/sup 12/, and Ca/sup 40/ are measured. The measurements are used to determine the angular momentum, parity, excitation probability, etc. for these excited states. (T.F.H.)

Quasi-free proton-proton scattering has been studied at 156 MeV, using two magnetic spectrometers, localization spark chambers and an on-line computer. The overall energy resolution is 1.7−2.2 MeV. Summed energy spectra and angular distributions of components of these spectra are given. We deduce assignments for (1 d 5 2 ) −1 , (2 s 1 2 ) −1 , (1 p 1 2 ) −1 and (1 p 3 2 ) −1 states in 23 N,, 24 Mg and 28 Si, −(2 p 3 2 ) −1 and (2 s 1 2 ) −1 states in 64 Zn, (2 p 3 2 ) −1 and (1 f ) −1 states in 75 As and 90 Zr.