Character Networks and Centrality

A character network represents relations between characters from a text; the relations are based on text proximity, shared scenes/events, quoted speech, etc. Our project sketches a theoretical framework for character network analysis, bringing together narratology, both close and distant reading approaches, and social network analysis. It is in line with recent attempts to automatise the extraction of literary social networks (Elson, 2012; Sack, 2013) and other studies stressing the importance of character- systems (Woloch, 2003; Moretti, 2011). The method we use to build the network is direct and simple. First, we extract co-occurrences from a book index, without the need for text analysis. We then describe the narrative roles of the characters, which we deduce from their respective positions in the network, i.e. the discourse. As a case study, we use the autobiographical novel Les Confessions by Jean-Jacques Rousseau. We start by identifying co-occurrences of characters in the book index of our edition (Slatkine, 2012). Subsequently, we compute four types of centrality: degree, closeness, betweenness, eigenvector. We then use these measures to propose a typology of narrative roles for the characters. We show that the two parts of Les Confessions, written years apart, are structured around mirroring central figures that bear similar centrality scores. The first part revolves around the mentor of Rousseau; a figure of openness. The second part centres on a group of schemers, depicting a period of deep paranoia. We also highlight characters with intermediary roles: they provide narrative links between the societies in the life of the author. The method we detail in this complete case study of character network analysis can be applied to any work documented by an index. Un réseau de personnages modélise les relations entre les personnages d'un récit : les relations sont basées sur une forme de proximité dans le texte, l'apparition commune dans des événements, des citations dans des dialogues, etc. Notre travail propose un cadre théorique pour l'analyse des réseaux de personnages, rassemblant narratologie, close et distant reading, et analyse des réseaux sociaux. Ce travail prolonge les tentatives récentes d'automatisation de l'extraction de réseaux sociaux tirés de la littérature (Elson, 2012; Sack, 2013), ainsi que les études portant sur l'importance des systèmes de personnages (Woloch, 2003; Moretti, 2011). La méthode que nous utilisons pour construire le réseau est directe et simple. Nous extrayons les co-occurrences d'un index sans avoir recours à l'analyse textuelle. Nous décrivons les rôles narratifs des personnages en les déduisant de leurs positions relatives dans le réseau, donc du discours. Comme étude de cas, nous avons choisi le roman autobiographique Les Confessions, de Jean- Jacques Rousseau. Nous déduisons les co-occurrences entre personnages de l'index présent dans l'édition Slatkine (Rousseau et al., 2012). Sur le réseau obtenu, nous calculons quatre types de centralité : le degré, la proximité, l'intermédiarité et la centralité par vecteur propre. Nous utilisons ces mesures pour proposer une typologie des rôles narratifs des personnages. Nous montrons que les deux parties des Confessions, écrites à deux époques différentes, sont structurées autour de deux figures centrales, qui obtiennent des mesures de centralité similaires. La première partie est construite autour du mentor de Rousseau, qui a symbolisé une grande ouverture. La seconde partie se focalise sur un groupe de comploteurs, et retrace une période marquée par la paranoïa chez l'auteur. Nous mettons également en évidence des personnages jouant des rôles intermédiaires, et de fait procurant un lien narratif entre les différentes sociétés couvrant la vie de l'auteur. La méthode d'analyse des réseaux de personnages que nous décrivons peut être appliquée à tout texte de fiction comportant un index.

Caution on the storage of waters and aqueous solutions in plastic containers for hydrogen and oxygen stable isotope analysis

RATIONALE The choice of containers for storage of aqueous samples between their collection, transport and water hydrogen (2H) and oxygen (18O) stable isotope analysis is a topic of concern for a wide range of fields in environmental, geological, biomedical, food, and forensic sciences. The transport and separation of water molecules during water vapor or liquid uptake by sorption or solution and the diffusive transport of water molecules through organic polymer material by permeation or pervaporation may entail an isotopic fractionation. An experiment was conducted to evaluate the extent of such fractionation. METHODS Sixteen bottle-like containers of eleven different organic polymers, including low and high density polyethylene (LDPE and HDPE), polypropylene (PP), polycarbonate (PC), polyethylene terephthalate (PET), and perfluoroalkoxy-Teflon (PFA), of different wall thickness and size were completely filled with the same mineral water and stored for 659?days under the same conditions of temperature and humidity. Particular care was exercised to keep the bottles tightly closed and prevent loss of water vapor through the seals. RESULTS Changes of up to +5 parts per thousand for d2H values and +2.0 parts per thousand for d18O values were measured for water after more than 1?year of storage within a plastic container, with the magnitude of change depending mainly on the type of organic polymer, wall thickness, and container size. The most important variations were measured for the PET and PC bottles. Waters stored in glass bottles with Polyseal (TM) cone-lined PP screw caps and thick-walled HDPE or PFA containers with linerless screw caps having an integrally molded inner sealing ring preserved their original d2H and d18O values. The carbon, hydrogen, and oxygen stable isotope compositions of the organic polymeric materials were also determined. CONCLUSIONS The results of this study clearly show that for precise and accurate measurements of the water stable isotope composition in aqueous solutions, rigorous sampling and storage procedures are needed both for laboratory standards and for unknown samples. Copyright (c) 2012 John Wiley & Sons, Ltd.

Management of patient dose and image noise in routine pediatric CT abdominal examinations.

The aim was to propose a strategy for finding reasonable compromises between image noise and dose as a function of patient weight. Weighted CT dose index (CTDI(w)) was measured on a multidetector-row CT unit using CTDI test objects of 16, 24 and 32 cm in diameter at 80, 100, 120 and 140 kV. These test objects were then scanned in helical mode using a wide range of tube currents and voltages with a reconstructed slice thickness of 5 mm. For each set of acquisition parameter image noise was measured and the Rose model observer was used to test two strategies for proposing a reasonable compromise between dose and low-contrast detection performance: (1) the use of a unique noise level for all test object diameters, and (2) the use of a unique dose efficacy level defined as the noise reduction per unit dose. Published data were used to define four weight classes and an acquisition protocol was proposed for each class. The protocols have been applied in clinical routine for more than one year. CTDI(vol) values of 6.7, 9.4, 15.9 and 24.5 mGy were proposed for the following weight classes: 2.5-5, 5-15, 15-30 and 30-50 kg with image noise levels in the range of 10-15 HU. The proposed method allows patient dose and image noise to be controlled in such a way that dose reduction does not impair the detection of low-contrast lesions. The proposed values correspond to high- quality images and can be reduced if only high-contrast organs are assessed.

The hotel industry and its importance in the technical and economic development of a region : the Lake Geneva case (1852-1914)

The historiography dedicated to tourism has emphasised how some socio-economic evolutions such as urbanisation, mechanisation of transport or the advent of leisure time in society have supported pleasure trips and therefore the development of the hotel industry. On the contrary, the research has too often neglected or at least minimised the impact of the hotel sector on a region's development. This contribution seeks to fill this gap by analysing the Geneva Lake region, one of the most important birthplaces of the European tourism. In this space not much touched by the first industrial revolution, the hotel business has in fact played the role of an economic motor, stimulating investment and employment. This dynamism provoked a domino effect on several other sectors of the economy (industry, bulding sector, banking). To please their customers, the hoteliers have not only given impulses on housing modernisation, but also to the revitalisation of transport, energy and communication networks. The necessity to remain on the state-of-the-art of technical issues, with the concern of competitiveness, has called forth an acceleration of the technology transfer and stimulated the constitution of technical know-how.

Contrasting the functional properties of GABAergic axon terminals with single and multiple synapses in the thalamus

Diverse sources of GABAergic inhibition are a major feature of cortical networks, but distinct inhibitory input systems have not been systematically characterized in the thalamus. Here, we contrasted the properties of two independent GABAergic pathways in the posterior thalamic nucleus of rat, one input from the reticular thalamic nucleus (nRT), and one "extrareticular" input from the anterior pretectal nucleus (APT). The vast majority of nRT-thalamic terminals formed single synapses per postsynaptic target and innervated thin distal dendrites of relay cells. In contrast, single APT-thalamic terminals formed synaptic contacts exclusively via multiple, closely spaced synapses on thick relay cell dendrites. Quantal analysis demonstrated that the two inputs displayed comparable quantal amplitudes, release probabilities, and multiple release sites. The morphological and physiological data together indicated multiple, single-site contacts for nRT and multisite contacts for APT axons. The contrasting synaptic arrangements of the two pathways were paralleled by different short-term plasticities. The multisite APT-thalamic pathway showed larger charge transfer during 50-100 Hz stimulation compared with the nRT pathway and a greater persistent inhibition accruing during stimulation trains. Our results demonstrate that the two inhibitory systems are morpho-functionally distinct and suggest and that multisite GABAergic terminals are tailored for maintained synaptic inhibition even at high presynaptic firing rates. These data explain the efficacy of extrareticular inhibition in timing relay cell activity in sensory and motor thalamic nuclei. Finally, based on the classic nomenclature and the difference between reticular and extrareticular terminals, we define a novel, multisite GABAergic terminal type (F3) in the thalamus.

Impact of physical activity on energy balance, food intake and choice in normal weight and obese children in the setting of acute social stress: a randomized controlled trial.

BACKGROUND: Psychological stress negatively influences food intake and food choices, thereby contributing to the development of childhood obesity. Physical activity can also moderate eating behavior and influence calorie intake. However, it is unknown if acute physical activity influences food intake and overall energy balance after acute stress exposure in children. We therefore investigated the impact of acute physical activity on overall energy balance (food intake minus energy expenditure), food intake, and choice in the setting of acute social stress in normal weight (NW) and overweight/obese (OW/OB) children as well as the impact of psychological risk factors. METHOD: After receiving written consent from their parents, 26 NW (BMI < 90(th) percentile) and 24 7-to 11-year-old OW (n = 5)/OB (n = 19, BMI ≥ 90(th) percentile) children were randomly allocated using computer-generated numbers (1:1, after stratification for weight status) to acute moderate physical or to sedentary activity for 30 min. Afterwards, all children were exposed to an acute social stressor. Children and their parents completed self-report questionnaires. At the end of the stressor, children were allowed to eat freely from a range of 12 different foods (6 sweet/6 salty; each of low/high caloric density). Energy balance, food intake/choice and obesity-related psychological risk factors were assessed. RESULTS: Lower overall energy balance (p = 0.019) and a decreased choice of low density salty foods (p < 0.001) in NW children compared with OW/OB children was found after acute moderate physical activity but not sedentary activity. Independent of their allocation, OW/OB children ate more high density salty foods (104 kcal (34 to 173), p = 0.004) following stress. They scored higher on impulsive behavior (p = 0.005), restrained eating (p < 0.001) and parental corporal punishment (p = 0.03), but these psychological factors were not related to stress-induced food intake/choice. Positive parenting tended to be related to lower intake of sweet high density food (-132 kcal, -277 to 2, p = 0.054). CONCLUSIONS: In the setting of stress, acute moderate physical activity can address energy balance in children, a benefit which is especially pronounced in the OW/OB. Positive parenting may act as a protective factor preventing stress-induced eating of comfort food. TRIAL REGISTRATION: clinicaltrials.gov NCT01693926 The study was a pilot study of a project funded by the Swiss National Science Foundation (CRSII3_147673).

Differential regulation of the expression of two high-affinity sulfate transporters, SULTR1.1 and SULTR1.2, in Arabidopsis

The molecular mechanisms regulating the initial uptake of inorganic sulfate in plants are still largely unknown. The current model for the regulation of sulfate uptake and assimilation attributes positive and negative regulatory roles to O-acetyl-serine (O-acetyl-Ser) and glutathione, respectively. This model seems to suffer from exceptions and it has not yet been clearly validated whether intracellular O-acetyl-Ser and glutathione levels have impacts on regulation. The transcript level of the two high-affinity sulfate transporters SULTR1.1 and SULTR1.2 responsible for sulfate uptake from the soil solution was compared to the intracellular contents of O-acetyl-Ser, glutathione, and sulfate in roots of plants submitted to a wide diversity of experimental conditions. SULTR1.1 and SULTR1.2 were differentially expressed and neither of the genes was regulated in accordance with the current model. The SULTR1.1 transcript level was mainly altered in response to the sulfur-related treatments. Split-root experiments show that the expression of SULTR1.1 is locally regulated in response to sulfate starvation. In contrast, accumulation of SULTR1.2 transcripts appeared to be mainly related to metabolic demand and is controlled by photoperiod. On the basis of the new molecular insights provided in this study, we suggest that the expression of the two transporters depends on different regulatory networks. We hypothesize that interplay between SULTR1.1 and SULTR1.2 transporters could be an important mechanism to regulate sulfate content in the roots

Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 × 10(-8)) loci, some including known iron-related genes (HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6) and others novel (ABO, ARNTL, FADS2, NAT2, TEX14). SNPs at ARNTL, TF, and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.

The effects of physiologically plausible connectivity structure on local and global dynamics in large scale brain models.

Functionally relevant large scale brain dynamics operates within the framework imposed by anatomical connectivity and time delays due to finite transmission speeds. To gain insight on the reliability and comparability of large scale brain network simulations, we investigate the effects of variations in the anatomical connectivity. Two different sets of detailed global connectivity structures are explored, the first extracted from the CoCoMac database and rescaled to the spatial extent of the human brain, the second derived from white-matter tractography applied to diffusion spectrum imaging (DSI) for a human subject. We use the combination of graph theoretical measures of the connection matrices and numerical simulations to explicate the importance of both connectivity strength and delays in shaping dynamic behaviour. Our results demonstrate that the brain dynamics derived from the CoCoMac database are more complex and biologically more realistic than the one based on the DSI database. We propose that the reason for this difference is the absence of directed weights in the DSI connectivity matrix.

Arbuscular mycorrhizal fungi: genetics of multigenomic, clonal networks and its ecological consequences

Arbuscular mycorrhizal fungi are thought to have remained asexual for 400 million years although recent studies have suggested that considerable genetic and phenotypic variation could potentially exist in populations. A brief discussion of these multigenomic organisms is presented. (C) 2003 The Linnean Society of London.

Overweight and eating disorders in primary care: a sentinella reporting in 2-20 years old patients

Aims: To describe overweight or eating disorders in primary care consultations of Swiss children or adolescents and analyze responses by physicians. Methods: 150 to 200 primary care physicians participating in the Swiss Sentinel Surveillance Network in collaboration with the Swiss Federal Office of Public Health register their consultations over one year for selected health conditions. We describe reports of consultations where overweight or eating disorders were identified in subjects aged 2-20 years by physicians, patients or their relatives, or referring professionals, between 29.12.2007 and 15.2.2008. Results: 189 consultations were registered in the first 7 weeks of declaration. A short majority concerned female (58%) and 12-20 years old (53%) patients. Half were reported by pediatricians, one third by general practitioners and the remaining minority by internists. The sample included two thirds of Swiss-German and one third of Swiss-French cases. In the male subgroup aged 2-20 and in female children aged 2-11, almost all reported consultations were characterized by overweight. Among female teenagers, underweight was reported in 29% whilst overweight was recorded in 60%. Anorexia was noted in 68% of reported consultations of underweight female teenagers. In underweight patients, advice given by physicians frequently covered both nutrition and physical activity (38%) or nutrition only (29%), while no specific recommendations were recorded for the remaining third. In case of overweight, for one half of consultations patients received both nutritional and physical activity recommendations, for 12% nutritional only, and for one quarter patients were not advised in these domains. No specific treatment was usually proposed to overweight patients (65%), except when bulimia was diagnosed; in such case, one third of patients were proposed a psychological/psychiatric treatment, whereas both psychological and pharmacological treatments were frequently offered for underweight teenagers. Therapy was most often motivated by physicians (50%) or by relatives (44%), more rarely by patients themselves (7%). Conclusions: These preliminary data indicate that in some primary care consultations of young patients with overweight or eating disorders, advice was not given on nutrition and physical activity. This observation needs to be later confirmed with the totality of the consultations registered in 2008 and reasons will be further investigated.

Automatic selection of tidal volume, respiratory frequency and minute ventilation in intubated ICU patients as start up procedure for closed-loop controlled ventilation.

OBJECTIVE: Before a patient can be connected to a mechanical ventilator, the controls of the apparatus need to be set up appropriately. Today, this is done by the intensive care professional. With the advent of closed loop controlled mechanical ventilation, methods will be needed to select appropriate start up settings automatically. The objective of our study was to test such a computerized method which could eventually be used as a start-up procedure (first 5-10 minutes of ventilation) for closed-loop controlled ventilation. DESIGN: Prospective Study. SETTINGS: ICU's in two adult and one children's hospital. PATIENTS: 25 critically ill adult patients (age > or = 15 y) and 17 critically ill children selected at random were studied. INTERVENTIONS: To stimulate 'initial connection', the patients were disconnected from their ventilator and transiently connected to a modified Hamilton AMADEUS ventilator for maximally one minute. During that time they were ventilated with a fixed and standardized breath pattern (Test Breaths) based on pressure controlled synchronized intermittent mandatory ventilation (PCSIMV). MEASUREMENTS AND MAIN RESULTS: Measurements of airway flow, airway pressure and instantaneous CO2 concentration using a mainstream CO2 analyzer were made at the mouth during application of the Test-Breaths. Test-Breaths were analyzed in terms of tidal volume, expiratory time constant and series dead space. Using this data an initial ventilation pattern consisting of respiratory frequency and tidal volume was calculated. This ventilation pattern was compared to the one measured prior to the onset of the study using a two-tailed paired t-test. Additionally, it was compared to a conventional method for setting up ventilators. The computer-proposed ventilation pattern did not differ significantly from the actual pattern (p > 0.05), while the conventional method did. However the scatter was large and in 6 cases deviations in the minute ventilation of more than 50% were observed. CONCLUSIONS: The analysis of standardized Test Breaths allows automatic determination of an initial ventilation pattern for intubated ICU patients. While this pattern does not seem to be superior to the one chosen by the conventional method, it is derived fully automatically and without need for manual patient data entry such as weight or height. This makes the method potentially useful as a start up procedure for closed-loop controlled ventilation.

Social and temporal organization in an ant colony

Ant colonies are known for their complex and efficient social organization that com-pletely lacks hierarchical structure. However, due to methodological difficulties in follow¬ing all ants of a colony, it was until now impossible to investigate the social and temporal organization of colonies. We developed a tracking system that allows tracking the posi¬tions and orientations of several hundred individually labeled ants continuously, providing for the first time quantitative long term data on all individuals of a colony. These data permit reconstructing trajectories, activity patterns and social networks of all ants in a colony and enable us to investigate ant behavior quantitatively in previously unpreceded ways. By analyzing the spatial positions and social interactions of all ants in six colonies for 41 days we show that ant colonies are organized in groups of nurses, nest patrollers and foragers. Workers of each group were highly interconnected and occupied similar spa¬tial locations in the nest. Groups strongly segregated spatially, and were characterized by unique behavioral signatures. Nurses spent most of their time on the brood. Nest patrollers frequently visited the rubbish pile, and foragers frequently visited the forag¬ing arena. In addition nurses were on average younger than nest patrollers who were, in turn, younger than foragers. We further show that workers had a preferred behav¬ioral trajectory and moved from nursing to nest patrolling, and from nest patrolling to foraging. By analyzing the activity patterns of all ants we show that only a third of all workers in a colony exhibit circadian rhythms and that these rhythms shortened by on av¬erage 42 minutes in constant darkness, thereby demonstrating the presence of a functional endogenous clock. Most rhythmic workers were foragers suggesting that rhythmicity is tightly associated with task. Nurses and nest patrollers were arrhythmic which most likely reflects plasticity of the circadian clock, as isolated workers in many species exhibit circadian rhythmicity. Altogether our results emphasize that ant colonies, despite their chaotic appearance, repose on a strong underlying social and temporal organization. - Les colonies de fourmis sont connues pour leur organisation sociale complexe et effi-cace, charactérisée par un manque absolu de structure hiérarchique. Cependant, puisqu'il est techniquement très difficile de suivre toutes les fourmis d'une colonie, il a été jusqu'à maintenant impossible d'étudier l'organisation sociale et temporelle des colonies de four-mis. Nous avons développé un système qui permet d'extraire en temps réel à partir d'images vidéo les positions et orientations de plusieurs centaines de fourmis marquées individuellement. Nous avons pu ainsi générer pour la première fois des données quanti-tatives et longitudinales relatives à des fourmis appartenant à une colonie. Ces données nous ont permis de reconstruire la trajectoire et l'activité de chaque fourmi ainsi que ses réseaux sociaux. Ceci nous a permis d'étudier de manière exhaustive et objective le com-portement de tous les individus d'une colonie. En analysant les données spatiales et les interactions sociales de toutes les fourmis de six colonies qui ont été filmées pendant 41 jours, nous montrons que les fourmis d'une même colonie se répartissent en trois groupes: nourrices, patrouilleuses et approvisionneuses. Les fourmis d'un même groupe interagis-sent fréquemment et occupent le même espace à l'intérieur du nid. L'espace propre à un groupe se recoupe très peu avec celui des autres. Chaque groupe est caractérisé par un comportement typique. Les nourrices s'affairent surtout autour du couvain. Les pa-trouilleuses font de fréquents déplacements vers le tas d'ordures, et les approvisionneuses sortent souvent du nid. Les nourrices sont en moyenne plus jeunes que les patrouilleuses qui, à leur tour, sont plus jeunes que les approvisionneuses. De plus, nous montrons que les ouvrières changent de tâche au cours de leur vie, passant de nourrice à patrouilleuse puis à approvisionneuse. En analysant l'activité de chaque fourmi, nous montrons que seulement un tiers des ouvrières d'une colonie présente des rythmes circadiens et que ces rythmes diminuent en moyenne de 42 minutes lorsqu'il y a obscurité constante, ce qui démontre ainsi la présence d'une horloge endogène. De plus, la plupart des approvi¬sionneuses ont une activité rythmique alors que les nourrices et patrouilleuses présentent une activité arythmique, ce qui suggère que la rythmicité est étroitement associée à la tâche. L'arythmie des nourrices et patrouilleuses repose probablement sur une plasticité de l'horloge endogène car des ouvrières de nombreuses espèces font preuve d'une ryth¬micité circadienne lorsqu'elles sont isolées de la colonie. Dans l'ensemble nos résultats révèlent qu'une colonie de fourmis se fonde sur une solide organisation sociale et tem¬porelle malgré son apparence chaotique.

Blood pressure modifies the association between serum adiponectin and uric acid, in a sex-dependent manner

Purpose: Plasma adiponectin and serum uric acid (SUA) levels are negatively correlated. To better understand the possible mechanisms linking adiponectin and uric acid, we analyzed whether the association between adiponectin and SUA differed by hypertension status (or blood pressure level) and by sex. Methods and materials: We analyzed data from the populationbased CoLaus study (Switzerland). Fasting plasma adiponectin levels were assessed by ELISA and SUA by uricase-PAP. Blood pressure (BP) was measured using a validated automated device and hypertension was defined as having office BP 140/90 mm Hg or being on current antihypertensive treatment. Results: In the 2897 men and 3181 women, aged 35-74, BMI (mean ± SD) was 26.6 ± 4.0 and 25.1 ± 4.8 Kg/m2, systolic blood pressure (SBP) was 132.2 ± 16.6 and 124.8 ± 18.3 mm Hg, median (interquartile range) plasma adiponectin was 6.2 (4.1-9.2) and 10.6 (6.9-15.4) mg/dL, and hypertension prevalence was 42.0% and 30.2%, respectively. The age- and BMI- adjusted partial correlation coefficients between log-adiponectin and SUA were 0.09 and 0.06 in normotensive men and women (P <0.01), and 0.004 (P = 0.88) and 0.15 (P <0.001) in hypertensive men and women, respectively. In median regression adjusted for BMI, insulin, smoking, alcohol consumption, menopausal status and HDL-cholesterol, there was a significant three-way interaction between SUA, SBP and sex for their effect on adiponectin (dependent variable, P = 0.005), as well as interactions between SBP and sex (P = 0.014) and between SUA and sex (P = 0.033). Conclusion: Plasma adiponectin and SUA are negatively associated, independently of BMI and insulin, in a population-based study in Caucasians. However, BP modifies this inverse relationship, as it was significant mainly in women with elevated BP. This observation suggests that the link between adiponectin and SUA may be mediated by sex hormones and the hypertension status.

Biodistribution of anti-CEA F(ab')2 fragments after intra-arterial and intravenous injection in patients with liver metastases due to colorectal carcinoma.

The biodistribution of simultaneous intra-arterial and intravenous injections of a radiolabelled anti-CEA MAb F(ab')2 fragment was studied in three patients with liver metastases from colorectal cancer. Identical MAb fragments, labelled with either 125I or 131I, were injected over a period of 30 min into the hepatic artery and into a peripheral vein. After 1 or 2 days, biodistribution was measured in the surgically removed metastases, normal tissue samples and blood. By tissue radioactivity counting, tumour uptake in the range 6.3-9.1% of injected dose per gram was found. Superimposable metastasis-to-blood and metastasis-to-normal liver ratios were obtained for both iodine isotopes in all three patients. The results indicate that the intra-arterial injection of MAb F(ab')2 fragments gives no measurable advantage over more convenient injections into a peripheral vein.