Association of Lifecourse Socioeconomic Status with Chronic Inflammation and Type 2 Diabetes Risk: The Whitehall II Prospective Cohort Study.

BACKGROUND: Socioeconomic adversity in early life has been hypothesized to "program" a vulnerable phenotype with exaggerated inflammatory responses, so increasing the risk of developing type 2 diabetes in adulthood. The aim of this study is to test this hypothesis by assessing the extent to which the association between lifecourse socioeconomic status and type 2 diabetes incidence is explained by chronic inflammation. METHODS AND FINDINGS: We use data from the British Whitehall II study, a prospective occupational cohort of adults established in 1985. The inflammatory markers C-reactive protein and interleukin-6 were measured repeatedly and type 2 diabetes incidence (new cases) was monitored over an 18-year follow-up (from 1991-1993 until 2007-2009). Our analytical sample consisted of 6,387 non-diabetic participants (1,818 women), of whom 731 (207 women) developed type 2 diabetes over the follow-up. Cumulative exposure to low socioeconomic status from childhood to middle age was associated with an increased risk of developing type 2 diabetes in adulthood (hazard ratio [HR] = 1.96, 95% confidence interval: 1.48-2.58 for low cumulative lifecourse socioeconomic score and HR = 1.55, 95% confidence interval: 1.26-1.91 for low-low socioeconomic trajectory). 25% of the excess risk associated with cumulative socioeconomic adversity across the lifecourse and 32% of the excess risk associated with low-low socioeconomic trajectory was attributable to chronically elevated inflammation (95% confidence intervals 16%-58%). CONCLUSIONS: In the present study, chronic inflammation explained a substantial part of the association between lifecourse socioeconomic disadvantage and type 2 diabetes. Further studies should be performed to confirm these findings in population-based samples, as the Whitehall II cohort is not representative of the general population, and to examine the extent to which social inequalities attributable to chronic inflammation are reversible. Please see later in the article for the Editors' Summary.

No Role for Cerebrospinal Fluid Myelin Basic Protein Levels in Patients Treated for Childhood Acute Lymphoblastic Leukemia.

INTRODUCTION: Central nervous system prophylaxis of childhood acute lymphoblastic leukemia has dropped rates of relapses but has been associated with neurotoxicity and imaging abnormalities. Predictors of neurotoxicity are lacking, because of inconsistency between clinical symptoms and imaging. Some have suggested that cerebrospinal fluid myelin basic protein (MBP) levels to be of potential interest. A retrospective analysis of MBP levels in correlation with clinical and radiologic data is presented. MATERIALS AND METHODS: MBP levels obtained at the time of intrathecals, charts, and neuroradiology reports were retrospectively analyzed. Academic achievement data were obtained from phone contacts with patients and families. RESULTS: We retrieved 1248 dosages of MBP in 83 patients, 381 neurologic examinations in 34 patients and 69 neuroradiologic investigations in 27 patients. Fifty-two patients had abnormal MBP levels. Radiologic anomalies were present in 47% of those investigated, 14% of them having school difficulties. Proportions of patients with school difficulties in the groups with abnormal MBP levels but no radiologic anomalies or with no radiologic investigations were 0% and 3%, respectively, which was lower than in the group of patients with normal MBP levels (100%, 22%, and 5%, respectively). DISCUSSION: Notwithstanding the retrospective character of our study, we conclude that there is limited usefulness of systematic dosage of MBP as indicator of treatment-induced neurotoxicity in acute lymphoblastic leukemia patients.

Potential exposure to hepatitis C virus through accidental blood contact in interventional radiology.

PURPOSE: To quantify the prevalence of accidental blood exposure (ABE) among interventional radiologists and contrast that with the prevalence of patients with hepatitis C virus (HCV) undergoing interventional radiology procedures. MATERIALS AND METHODS: A multicenter epidemiologic study was conducted in radiology wards in France. The risk of ABE to radiologists was assessed based on personal interviews that determined the frequency and type of ABE and the use of standard protective barriers. Patients who underwent invasive procedures underwent prospective sampling for HCV serologic analysis. HCV viremia was measured in patients who tested positive for HCV. RESULTS: Of the 77 radiologists who participated in 11 interventional radiology wards, 44% reported at least one incident of mucous membrane blood exposure and 52% reported at least one percutaneous injury since the beginning of their occupational activity. Compliance with standard precautions was poor, especially for the use of protective clothes and safety material. Overall, 91 of 944 treated patients (9.7%) tested positive for HCV during the study period, of whom 90.1% had positive viremia results, demonstrating a high potential for contamination through blood contacts. CONCLUSIONS: The probability of HCV transmission from contact with contaminated blood after percutaneous injury ranged from 0.013 to 0.030; the high frequency of accidental blood exposure and high percentage of patients with HCV could generate a risk of exposure to HCV for radiologists who perform invasive procedures with frequent blood contact. The need to reinforce compliance with standard hygiene precautions is becoming crucial for medical and technical personnel working in these wards.

Biological monitoring of exposure to solvents using the chemical itself in urine: application to toluene

Objective Biomonitoring of solvents using the unchanged substance in urine as exposure indicator is still relatively scarce due to some discrepancies between the results reported in the literature. Based on the assessment of toluene exposure, the aim of this work was to evaluate the effects of some steps likely to bias the results and to measure urinary toluene both in volunteers experimentally exposed and in workers of rotogravure factories. Methods Static headspace was used for toluene analysis. o-Cresol was also measured for comparison. Urine collection, storage and conservation conditions were studied to evaluate possible loss or contamination of toluene in controlled situations applied to six volunteers in an exposure chamber according to four scenarios with exposure at stable levels from 10 to 50 ppm. Kinetics of elimination of toluene were determined over 24 h. A field study was then carried out in a total of 29 workers from two rotogravure printing facilities. Results Potential contamination during urine collection in the field is confirmed to be a real problem but technical precautions for sampling, storage and analysis can be easily followed to control the situation. In the volunteers at rest, urinary toluene showed a rapid increase after 2 h with a steady level after about 3 h. At 47.1 ppm the mean cumulated excretion was about 0.005% of the amount of the toluene ventilated. Correlation between the toluene levels in air and in end of exposure urinary sample was excellent (r = 0.965). In the field study, the median personal exposure to toluene was 32 ppm (range 3.6-148). According to the correlations between environmental and biological monitoring data, the post-shift urinary toluene (r = 0.921) and o-cresol (r = 0.873) concentrations were, respectively, 75.6 mu g/l and 0.76 mg/g creatinine for 50 ppm toluene personal exposure. The corresponding urinary toluene concentration before the next shift was 11 mu g/l (r = 0.883). Conclusion Urinary toluene was shown once more time a very interesting surrogate to o-cresol and could be recommended as a biomarker of choice for solvent exposure. [Authors]

Closeness in relationships as a mediator between sexual abuse in childhood or adolescence and psychopathological outcome in adulthood.

The risk of adverse psychological outcomes in adult victims of childhood and adolescent sexual abuse (CSA) has been documented; however, research on possible mediating variables is still required, namely with a clinical perspective. The attachment literature suggests that secure interpersonal relationships may represent such a variable. Twenty-eight women who had experienced episodes of CSA, and 16 control women, were interviewed using Bremner's Early Trauma Inventory and the DSM-IV Global Assessment of Functioning; they also responded to Collins' Relationship Scales Questionnaire, evaluating adult attachment representations in terms of Closeness, Dependence and Anxiety. Subjects with an experience of severe abuse reported significantly more interpersonal distance in relationships (low index of Closeness) than other subjects. The index of psychopathological functioning was correlated with both the severity of abuse and attachment (low index of Closeness). Regression analysis on the sample of abused women revealed that attachment predicted psychopathology when abuse was controlled for, whereas abuse did not predict psychopathology when attachment was controlled for. Therefore, preserving a capacity for closeness with attachment figures in adulthood appears to mediate the consequences of CSA on subsequent psychopathological outcome.

Evaluation of exposure biomarkers in offshore workers exposed to low benzene and toluene concentrations.

Characterize ethylbenzene and xylene air concentrations, and explore the biological exposure markers (urinary t,t-muconic acid (t,t-MA) and unmetabolized toluene) among petroleum workers offshore. Offshore workers have increased health risks due to simultaneous exposures to several hydrocarbons present in crude oil. We discuss the pooled benzene exposure results from our previous and current studies and possible co-exposure interactions. BTEX air concentrations were measured during three consecutive 12-h work shifts among 10 tank workers, 15 process operators, and 18 controls. Biological samples were collected pre-shift on the first day of study and post-shift on the third day of the study. The geometric mean exposure over the three work shifts were 0.02 ppm benzene, 0.05 ppm toluene, 0.03 ppm ethylbenzene, and 0.06 ppm xylene. Benzene in air was significantly correlated with unmetabolized benzene in blood (r = 0.69, p < 0.001) and urine (r = 0.64, p < 0.001), but not with urinary t,t-MA (r = 0.27, p = 0.20). Toluene in air was highly correlated with the internal dose of toluene in both blood (r = 0.70, p < 0.001) and urine (r = 0.73, p < 0.001). Co-exposures were present; however, an interaction of metabolism was not likely at these low benzene and toluene exposures. Urinary benzene, but not t,t-MA, was a reliable biomarker for benzene at low exposure levels. Urinary toluene was a useful biomarker for toluene exposure. Xylene and ethylbenzene air levels were low. Dermal exposure assessment needs to be performed in future studies among these workers.

Visual representation of food in the brain : effects of repeated exposure and gut hormone secretion

The thesis at hand is concerned with the spatio-temporal brain mechanisms of visual food perception as investigated by electrical neuroimaging. Due to the increasing prevalence of obesity and its associated challenges for public health care, there is a need to better understand behavioral and brain processes underlying food perception and food-based decision-making. The first study (Study A) of this thesis was concerned with the role of repeated exposure to visual food cues. In our everyday lives we constantly and repeatedly encounter food and these exposures influence our food choices and preferences. In Study A, we therefore applied electrical neuroimaging analyses of visual evoked potentials to investigate the spatio-temporal brain dynamics linked to the repeated viewing of high- and low-energy food cues (published manuscript: "The role of energetic value in dynamic brain response adaptation during repeated food image viewing" (Lietti et al., 2012)). In this study, we found that repetitions differentially affect behavioral and brain mechanisms when high-energy, as opposed to low-energy foods and non-food control objects, were viewed. The representation of high-energy food remained invariant between initial and repeated exposures indicating that the sight of high-energy dense food induces less behavioral and neural adaptation than the sight of low-energy food and non-food control objects. We discuss this finding in the context of the higher salience (due to greater motivation and higher reward or hedonic valuation) of energy- dense food that likely generates a more mnemonically stable representation. In turn, this more invariant representation of energy-dense food is supposed to (partially) explain why these foods are over-consumed despite of detrimental health consequences. In Study Β we investigated food responsiveness in patients who had undergone Roux-en-Y gastric bypass surgery to overcome excessive obesity. This type of gastric bypass surgery is not only known to alter food appreciation, but also the secretion patterns of adipokines and gut peptides. Study Β aimed at a comprehensive and interdisciplinary investigation of differences along the gut-brain axis in bypass-operated patients as opposed to weight-matched non-operated controls. On the one hand, the spatio-temporal brain dynamics to the visual perception of high- vs. low-energy foods under differing states of motivation towards food intake (i.e. pre- and post-prandial) were assessed and compared between groups. On the other hand, peripheral gut hormone measures were taken in pre- and post-prandial nutrition state and compared between groups. In order to evaluate alterations in the responsiveness along the gut-brain-axis related to gastric bypass surgery, correlations between both measures were compared between both participant groups. The results revealed that Roux-en- Y gastric bypass surgery alters the spatio-temporal brain dynamics to the perception of high- and low-energy food cues, as well as the responsiveness along the gut-brain-axis. The potential role of these response alterations is discussed in relation to previously observed changes in physiological factors and food intake behavior post-Roux-en-Y gastric bypass surgery. By doing so, we highlight potential behavioral, neural and endocrine (i.e. gut hormone) targets for the future development of intervention strategies for deviant eating behavior and obesity. Together, the studies showed that the visual representation of foods in the brain is plastic and that modulations in neural activity are already noted at early stages of visual processing. Different factors of influence such as a repeated exposure, Roux-en-Y gastric bypass surgery, motivation (nutrition state), as well as the energy density of the visually perceived food were identified. En raison de la prévalence croissante de l'obésité et du défi que cela représente en matière de santé publique, une meilleure compréhension des processus comportementaux et cérébraux liés à la nourriture sont nécessaires. En particulier, cette thèse se concentre sur l'investigation des mécanismes cérébraux spatio-temporels liés à la perception visuelle de la nourriture. Nous sommes quotidiennement et répétitivement exposés à des images de nourriture. Ces expositions répétées influencent nos choix, ainsi que nos préférences alimentaires. La première étude (Study A) de cette thèse investigue donc l'impact de ces exposition répétée à des stimuli visuels de nourriture. En particulier, nous avons comparé la dynamique spatio-temporelle de l'activité cérébrale induite par une exposition répétée à des images de nourriture de haute densité et de basse densité énergétique. (Manuscrit publié: "The role of energetic value in dynamic brain response adaptation during repeated food image viewing" (Lietti et al., 2012)). Dans cette étude, nous avons pu constater qu'une exposition répétée à des images représentant de la nourriture de haute densité énergétique, par opposition à de la nourriture de basse densité énergétique, affecte les mécanismes comportementaux et cérébraux de manière différente. En particulier, la représentation neurale des images de nourriture de haute densité énergétique est similaire lors de l'exposition initiale que lors de l'exposition répétée. Ceci indique que la perception d'images de nourriture de haute densité énergétique induit des adaptations comportementales et neurales de moindre ampleur par rapport à la perception d'images de nourriture de basse densité énergétique ou à la perception d'une « catégorie contrôle » d'objets qui ne sont pas de la nourriture. Notre discussion est orientée sur les notions prépondérantes de récompense et de motivation qui sont associées à la nourriture de haute densité énergétique. Nous suggérons que la nourriture de haute densité énergétique génère une représentation mémorielle plus stable et que ce mécanisme pourrait (partiellement) être sous-jacent au fait que la nourriture de haute densité énergétique soit préférentiellement consommée. Dans la deuxième étude (Study Β) menée au cours de cette thèse, nous nous sommes intéressés aux mécanismes de perception de la nourriture chez des patients ayant subi un bypass gastrique Roux- en-Y, afin de réussir à perdre du poids et améliorer leur santé. Ce type de chirurgie est connu pour altérer la perception de la nourriture et le comportement alimentaire, mais également la sécrétion d'adipokines et de peptides gastriques. Dans une approche interdisciplinaire et globale, cette deuxième étude investigue donc les différences entre les patients opérés et des individus « contrôles » de poids similaire au niveau des interactions entre leur activité cérébrale et les mesures de leurs hormones gastriques. D'un côté, nous avons investigué la dynamique spatio-temporelle cérébrale de la perception visuelle de nourriture de haute et de basse densité énergétique dans deux états physiologiques différent (pre- et post-prandial). Et de l'autre, nous avons également investigué les mesures physiologiques des hormones gastriques. Ensuite, afin d'évaluer les altérations liées à l'intervention chirurgicale au niveau des interactions entre la réponse cérébrale et la sécrétion d'hormone, des corrélations entre ces deux mesures ont été comparées entre les deux groupes. Les résultats révèlent que l'intervention chirurgicale du bypass gastrique Roux-en-Y altère la dynamique spatio-temporelle de la perception visuelle de la nourriture de haute et de basse densité énergétique, ainsi que les interactions entre cette dernière et les mesures périphériques des hormones gastriques. Nous discutons le rôle potentiel de ces altérations en relation avec les modulations des facteurs physiologiques et les changements du comportement alimentaire préalablement déjà démontrés. De cette manière, nous identifions des cibles potentielles pour le développement de stratégies d'intervention future, au niveau comportemental, cérébral et endocrinien (hormones gastriques) en ce qui concerne les déviances du comportement alimentaire, dont l'obésité. Nos deux études réunies démontrent que la représentation visuelle de la nourriture dans le cerveau est plastique et que des modulations de l'activité neurale apparaissent déjà à un stade très précoce des mécanismes de perception visuelle. Différents facteurs d'influence comme une exposition repetee, le bypass gastrique Roux-en-Y, la motivation (état nutritionnel), ainsi que la densité énergétique de la nourriture qui est perçue ont pu être identifiés.

Victimization in Childhood of Male Sex Offenders: Relationship between Violence Experienced and Subsequent Offenses through Discourse Analysis

This study aims at better understanding how the form of childhood violence experienced and the type of offense subsequently committed affect how sex offenders recall punishments and difficult events. Fifty-four male perpetrators convicted of sexual offenses against children (SOCs) or against adults (SOAs) were interviewed in France, Belgium, and Switzerland using the Lausanne Clinical Interview (Entretien Clinique de Lausanne or LCI). Almost three-quarters of the sex offenders reported having been victimized during childhood. The correspondence analysis identified several factors that differentiated them. Their appraisal of the distressing event, method of coping with and distancing themselves from it, and how they dealt with emotions varied markedly depending on whether they recognized having experienced various forms of violence during childhood and on what type of offense they subsequently committed. Victimization can be identified as much by the events experienced as by their effect on the sex offender's discourse. Identification of these discursive indicators may lead to an improved therapeutic approach for potentially traumatic childhood experiences.

Occupational exposure of truck drivers to dust and polynuclear aromatic hydrocarbons: a pilot study in Geneva, Switzerland.

The exposure to dust and polynuclear aromatic hydrocarbons (PAH) of 15 truck drivers from Geneva, Switzerland, was measured. The drivers were divided between "long-distance" drivers and "local" drivers and between smokers and nonsmokers and were compared with a control group of 6 office workers who were also divided into smokers and nonsmokers. Dust was measured on 1 workday both by a direct-reading instrument and by sampling. The local drivers showed higher exposure to dust (0.3 mg/m3) and PAH than the long-distance drivers (0.1 mg/m3), who showed no difference with the control group. This observation may be due to the fact that the local drivers spend more time in more polluted areas, such as streets with heavy traffic and construction sites, than do the long-distance drivers. Smoking does not influence exposure to dust and PAH of professional truck drivers, as measured in this study, probably because the ventilation rate of the truck cabins is relatively high even during cold days (11-15 r/h). The distribution of dust concentrations was shown in some cases to be quite different from the expected log-normal distribution. The contribution of diesel exhaust to these exposures could not be estimated since no specific tracer was used. However, the relatively low level of dust exposure dose not support the hypothesis that present day levels of diesel exhaust particulates play a significant role in the excess occurrence of lung cancer observed in professional truck drivers.

Pregnancy outcome following maternal exposure to Mirtazapine: Preliminary results of a collaborative ENTIS study.

Introduction: Mirtazapine is a noradrenergic and serotonergic antidepressant mainly acting through blockade of presynaptic alpha-2 receptors. Published data on pregnancy outcome after exposure to mirtazapine are scarce. This study addresses the risk associated with exposure to mirtazapine during pregnancy. Patients (or Materials) and Methods: Multicenter (n = 11), observational prospective cohort study comparing pregnancy outcomes after exposure to mirtazapine with 2 matched control groups: exposure to any selective serotonin reuptake inhibitor (SSRI) as a diseasematched control group, and general controls with no exposure to medication known to be teratogenic or to any antidepressant. Data were collected by members of the European Network of Teratology Information Services (ENTIS) during individual risk counseling between 1995 and 2011. Standardized procedures for data collection were used in each center. Results: A total of 357 pregnant women exposed to mirtazapine at any time during pregnancy were included in the study and compared with 357 pregnancies from each control group. The rate of major birth defects between the mirtazapine and the SSRI group did not differ significantly (4.5% vs 4.2%; unadjusted odds ratio, 1.1; 95% confidence interval, 0.5-2.3, P = 0.9). A trend toward a higher rate of birth defects in the mirtazapine group compared with general controls did not reach statistical significance (4.2% vs 1.9%; OR, 2.4; 95% CI, 0.9-6.3; P = 0.08). The crude rate of spontaneous abortions did not differ significantly between the mirtazapine, the SSRI, and the general control groups (9.5% vs 10.4% vs 8.4%; P = 0.67), neither did the rate of deliveries resulting in live births (79.6% vs 84.3% in both control groups; P = 0.15). However, a higher rate of elective pregnancy-termination was observed in the mirtazapine group compared with SSRI and general controls (7.8% vs 3.4% vs 5.6%; P = 0.03). Premature birth (< 37 weeks) (10.6% vs 10.1% vs 7.5%; P = 0.38), gestational age at birth (median, 39 weeks; interquartile range (IQR), 38-40 in all groups; P = 0.29), and birth weight (median, 3320 g; IQR, 2979-3636 vs 3230 g; IQR, 2910-3629 vs 3338 g; IQR, 2967-3650; P = 0.34) did not differ significantly between the groups. Conclusion: This study did not observe a statistically significant difference in the rate of major birth defects between mirtazapine, SSRI-exposed, and nonexposed pregnancies. A slightly higher rate of birth defects was, however, observed in the mirtazapine and SSRI groups compared with the low rate of birth defects in our general controls. Overall, the pregnancy outcome after mirtazapine exposure in this study is very similar to that of the SSRI-exposed control group.

Distinct profiles of cytotoxic granules in memory CD8 T cells correlate with function, differentiation stage, and antigen exposure.

Cytotoxic CD8 T cells exert their antiviral and antitumor activity primarily through the secretion of cytotoxic granules. Degranulation activity and cytotoxic granules (perforin plus granzymes) generally define CD8 T cells with cytotoxic function. In this study, we have investigated the expression of granzyme K (GrmK) in comparison to that of GrmA, GrmB, and perforin. The expression of the cytotoxic granules was assessed in virus-specific CD8 T cells specific to influenza virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), or human immunodeficiency virus type 1 (HIV-1). We observed a dichotomy between GrmK and perforin expression in virus-specific CD8 T cells. The profile in influenza virus-specific CD8 T cells was perforin(-) GrmB(-) GrmA(+/-) GrmK(+); in CMV-specific cells, it was perforin(+) GrmB(+) GrmA(+) GrmK(-/+); and in EBV- and HIV-1-specific cells, it was perforin(-/+) GrmB(+) GrmA(+) GrmK(+). On the basis of the delineation of memory and effector CD8 T cells with CD45RA and CD127, the GrmK(+) profile was associated with early-stage memory CD8 T-cell differentiation, the perforin(+) GrmB(+) GrmA(+) profile with advanced-stage differentiation, and the GrmB(+) GrmA(+) Grmk(+) profile with intermediate-stage differentiation. Furthermore, perforin and GrmB but not GrmA and GrmK correlated with cytotoxic activity. Finally, changes in antigen exposure in vitro and in vivo during primary HIV-1 infection and vaccination modulated cytotoxic granule profiles. These results advance our understanding of the relationship between distinct profiles of cytotoxic granules in memory CD8 T cells and function, differentiation stage, and antigen exposure.

Solid phase microextraction as a short-term sampling technique for BTEX occupational exposure

Solid phase microextraction (SPME) has been widely used for many years in various applications, such as environmental and water samples, food and fragrance analysis, or biological fluids. The aim of this study was to suggest the SPME method as an alternative to conventional techniques used in the evaluation of worker exposure to benzene, toluene, ethylbenzene, and xylene (BTEX). Polymethylsiloxane-carboxen (PDMS/CAR) showed as the most effective stationary phase material for sorbing BTEX among other materials (polyacrylate, PDMS, PDMS/divinylbenzene, Carbowax/divinylbenzene). Various experimental conditions were studied to apply SPME to BTEX quantitation in field situations. The uptake rate of the selected fiber (75 microm PDMS/CAR) was determined for each analyte at various concentrations, relative humidities, and airflow velocities from static (calm air) to dynamic (> 200 cm/s) conditions. The SPME method also was compared with the National Institute of Occupational Safety and Health method 1501. Unlike the latter, the SPME approach fulfills the new requirement for the threshold limit value-short term exposure limit (TLV-STEL) of 2.5 ppm for benzene (8 mg/m(3))

Cytogenetic characterisation of childhood acute lymphoblastic leukemia in Nicaragua

BACKGROUND: Within the frame of a twinning programme with Nicaragua, The La Mascota project, we evaluated in our study the contribution of cytogenetic characterization of acute lymphoblastic leukemia (ALL) as prognostic factor compared to clinical, morphological, and immunohistochemical parameters. METHODS: All patients with ALL treated at the only cancer pediatric hospital in Nicaragua during 2006 were studied prospectively. Diagnostic immunophenotyping was performed locally and bone marrow or blood samples were sent to the cytogenetic laboratory of Zurich for fluorescence in situ hybridization (FISH) analysis and G-banding. RESULTS: Sixty-six patients with ALL were evaluated. Their mean age at diagnosis was 7.3 years, 31.8% were >or=10 years. Thirty-four patients (51.5%) presented with hyperleucocytosis >or=50 x 10(9)/L, 45 (68.2%) had hepatosplenomegaly. Immunophenotypically 63/66 patients (95%) had a B-precursor, 2 (3%) a T- and 1 (1.5%) a B-mature ALL. FISH analysis demonstrated a TEL/AML1 fusion in 9/66 (14%), BCR/ABL fusion in 1 (1.5%), MLL rearrangement in 2 (3.1%), iAMP21 in 2 (3.1%), MYC rearrangement in 1 (1.5%), and high-hyperdiploidy in 16 (24%). All patients but two with TEL/AML1 fusion and high-hyperdiploidy were clinically and hematologically in the standard risk group whereas those with poor cytogenetic factors had clinical high-risk features and were treated intensively. CONCLUSIONS: Compared to Europe, the ALL population in Nicaragua is older, has a higher proportion of poor prognostic clinical and hematological features and receives more intensive treatment, while patients with TEL/AML1 translocations and high-hyperdiploidy are clinically in the standard risk group. Cytogenetics did not contribute as an additional prognostic factor in this setting.

Response of the Pacific oyster Crassostrea gigas, Thunberg 1793, to pesticide exposure under experimental conditions.

Pesticide run-off into the ocean represents a potential threat to marine organisms, especially bivalves living in coastal environments. However, little is known about the effects of environmentally relevant concentrations of pesticides at the individual level. In this study, the suppression subtractive hybridisation technique was used to discover the main physiological function affected by a cocktail of three pesticides (lindane, metolachlor and carbofuran) in the Pacific oyster Crassostrea gigas. Two oyster populations exposed to different pollution levels in the wild were investigated. The pesticide concentrations used to induce stress were close to those found in the wild. In a time course experiment, the expression of three genes implicated in iron metabolism and oxidative stress as well as that of two ubiquitous stress proteins was examined. No clear regulation of gene or protein expression was found, potentially due to a low-dose effect. However, we detected a strong site- and organ-specific response to the pesticides. This study thus (1) provides insight into bivalve responses to pesticide pollution at the level of the transcriptome, which is the first level of response for organisms facing pollution, and (2) raises interesting questions concerning the importance of the sites and organs studied in the toxicogenomic field.