Development and validation of a Brief Diet Quality Assessment Tool in the French-speaking adults from Quebec.

BACKGROUND: The objective of this study was to develop and validate a short, self-administered questionnaire to assess diet quality in clinical settings, using the Alternative Healthy Eating Index (AHEI) as reference. METHODS: A total of 1040 men and women (aged 44.6 ± 14.4 y) completed a validated web-based food frequency questionnaire (webFFQ) and had their height and weight measured (development sample). Participants were categorized arbitrarily according to diet quality (high: AHEI score ≥ 65/110, low: AHEI score < 65/110) based on dietary intake data from the webFFQ. The Brief Diet Quality Assessment Tool was developed using a classification and regression tree (CART) approach and individual answers to the webFFQ among participants considered to have a plausible energy intake (ratio of reported energy intake to basal metabolic rate ≥ 1.2 and < 2.4; n = 1040). A second sample of 3344 older adults (aged 66.5 ± 6.4 y) was used to test the external validity of the Brief Diet Quality Assessment Tool (external validation sample). RESULTS: The decision tree included sequences of 3 to 6 binary questions, yielding 21 different pathways classifying diet quality as being high or low. In the development sample, the area under the receiver operating characteristic (ROC) curve of the predictive model was 0.92, with sensitivity, specificity and agreement values of 89.5, 83.9 and 87.2%. Compared with individuals having a low-quality diet according to the Brief Diet Quality Assessment Tool (mean AHEI 56.7 ± 11.4), individuals classified as having a high-quality diet (mean AHEI 71.3 ± 11.0) were significantly older, and had lower BMI, percent body fat and waist circumference, and had lower blood pressure, triglycerides, cholesterol/HDL ratio and fasting insulin as well as higher HDL-cholesterol concentrations (all P < 0.05). Similar results were observed in the external validation sample, although overall performance of the Brief Diet Quality Assessment Tool was slightly lower than in the development sample, with an area under the ROC curve of 0.79 and sensitivity, specificity and agreement values of 73.0, 69.0 and 71.3%, respectively. CONCLUSION: The CART approach yielded a simple and rapid Brief Diet Quality Assessment Tool that identifies individuals at risk of having a low-quality diet. Further studies are needed to test the performance of this tool in primary care settings.

Masked hypertension and effort-reward imbalance at work among 2369 white-collar workers.

Hypertension is an important risk factor of cardiovascular diseases, the leading cause of death worldwide. Adverse effects of psychosocial factors at work might increase the risk of masked hypertension, but evidences are still scarce. The objective of this study is then to determine whether adverse psychosocial work factors from the effort-reward imbalance (ERI) model are associated with the prevalence of masked hypertension in a population of white-collar workers. White-collar workers were recruited from three public organizations. Blood pressure was measured at the workplace for manually operated measurements (mean of the first three readings taken by a trained assistant) followed by ambulatory measurements (mean of all subsequent readings taken during the working day). Masked hypertension was defined as manually operated BP<140/90 mm Hg and ambulatory BP ⩾135/85 mm Hg. ERI exposure at work was measured using Siegrist's validated questionnaire. Blood pressure readings were obtained from 2369 workers (participation proportion: 85%). ERI exposure (OR: 1.53 (95% CI: 1.16-2.02) and high efforts at work (OR: 1.61 (95% CI: 1.13-1.29) were associated with masked hypertension, after adjusting for sociodemographic and cardiovascular risk factors. Workers exposed to an imbalance between efforts spent at work and reward had a higher prevalence of masked hypertension. High efforts at work might be of particular importance in explaining this association. Future studies should be designed to investigate how clinicians can include questions on psychosocial work factors to screen for masked hypertension and how workplace interventions can decrease adverse psychosocial exposures to lower BP.

[Performances of breast magnetic resonance imaging in the context of neoadjuvant chemotherapy for breast cancer to predict pathological complete response]. / Performances de l'imagerie par résonance magnétique au cours des chimiothérapies néoadjuvantes du cancer du sein pour prédire la réponse pathologique complète.

PURPOSE: The objective of this work was to estimate the reliability of MRI after neoadjuvant chemotherapy (NAC) for breast cancer to detect a residual tumour by comparing the tumoral size measured by MRI with the histological size. We also estimated the concordance of diagnosis of complete pathological response between histological examination and MRI. MATERIALS AND METHODS: We included all the patients who received a neoadjuvant chemotherapy for breast cancer in the university hospital of Tours from January, 2008 to December 31st, 2012 and in the comprehensive cancer centre of Rennes from January, 2008 till May 31st 201. We considered that the pathological response was complete (pCR) when there was no residual invasive tumour in the mammary surgical specimen. RESULTS: Two hundred and fifty-one women who received NAC for a non-metastatic breast cancer were included in the study: 103 in Tours and 148 in Rennes. Two women (0.8%) refused breast surgery whatever the type. One hundred and twenty-three (49%) women had a breast conservative surgery. One hundred and fifteen (45.8%) had a mastectomy and 11 (4.4%) had breast conservative surgery followed by mastectomy for positive margins. A complete pathological response was present in 54 cases (21.5%). We did not found any significant difference between characteristics of patients with pCR or not. CONCLUSION: Breast MRI remains the most performing examination to evaluate the initial tumoral size and the residual tumour after NAC, but does not add any value at mid or at the end of treatment for the patients to whom a mastectomy is decided at presentation. The correlation between the breast MRI and the histology size is not perfect, but at the moment, MRI stills of the most performing examination to predict the pCR.

Spreading depolarization triggered by elevated potassium is weak or absent in the rodent lower brain.

We examined in live coronal slices from rat and mouse which brain regions generate potassium-triggered spreading depolarization (SDKt). This technique simulates cortical spreading depression, which underlies migraine aura in the intact brain. An SDKt episode was evoked by increasing bath [K+]o and recorded as a propagating front of elevated light transmittance representing transient neuronal swelling in gray matter of neocortex, hippocampus, striatum, and thalamus. In contrast, SDKt was not imaged in hypothalamic nuclei or brainstem with exception of those nuclei near the dorsal brainstem surface. In rat slices, single neurons were whole-cell current clamped during SDKt. "Higher" neurons depolarized to near zero millivolts indicating SDKt generation. In contrast, seven types of neurons in hypothalamus and brainstem only slowly depolarized without generating SDKt, supporting our imaging findings. Therefore, SDKt is not a default of CNS neurons but rather displays a region-specific susceptibility, similar to anoxic depolarization, which we have proposed is correlated with a region's vulnerability to traumatic brain injury. In the higher brain, SDKt may be a vestigial spreading depolarization that originally evolved to shut down and vasoconstrict gray matter regions more exposed to impact and contusion.

Brainstem neurons survive the identical ischemic stress that kills higher neurons: insight to the persistent vegetative state.

Global ischemia caused by heart attack, pulmonary failure, near-drowning or traumatic brain injury often damages the higher brain but not the brainstem, leading to a 'persistent vegetative state' where the patient is awake but not aware. Approximately 30,000 U.S. patients are held captive in this condition but not a single research study has addressed how the lower brain is preferentially protected in these people. In the higher brain, ischemia elicits a profound anoxic depolarization (AD) causing neuronal dysfunction and vasoconstriction within minutes. Might brainstem nuclei generate less damaging AD and so be more resilient? Here we compared resistance to acute injury induced from simulated ischemia by 'higher' hippocampal and striatal neurons versus brainstem neurons in live slices from rat and mouse. Light transmittance (LT) imaging in response to 10 minutes of oxygen/glucose deprivation (OGD) revealed immediate and acutely damaging AD propagating through gray matter of neocortex, hippocampus, striatum, thalamus and cerebellar cortex. In adjacent brainstem nuclei, OGD-evoked AD caused little tissue injury. Whole-cell patch recordings from hippocampal and striatal neurons under OGD revealed sudden membrane potential loss that did not recover. In contrast brainstem neurons from locus ceruleus and mesencephalic nucleus as well as from sensory and motor nuclei only slowly depolarized and then repolarized post-OGD. Two-photon microscopy confirmed non-recoverable swelling and dendritic beading of hippocampal neurons during OGD, while mesencephalic neurons in midbrain appeared uninjured. All of the above responses were mimicked by bath exposure to 100 µM ouabain which inhibits the Na+/K+ pump or to 1-10 nM palytoxin which converts the pump into an open cationic channel. Therefore during ischemia the Na+/K+ pump of higher neurons fails quickly and extensively compared to naturally resilient hypothalamic and brainstem neurons. The selective survival of lower brain regions that maintain vital functions will support the persistent vegetative state.

Effort--reward imbalance and medically certified absence for mental health problems: a prospective study of white-collar workers.

OBJECTIVE: Little is known about the effects of psychosocial work factors on objectively assessed mental health problems leading to medically certified absence. Only one study has evaluated the prospective effects of effort-reward imbalance (ERI) at work with regards to this outcome. The present study aimed to evaluate the effects of ERI on the incidence of medically certified absence for mental health problems. METHODS: The study included 2086 white-collar workers (63.3% women) employed in public organisations in Quebec city. Participants were followed over a 9-year period. Medical absences from work were collected from employers' files and psychosocial factors were measured using the ERI questionnaire. Cox regression models were used to estimate the incidence of certified sickness absence due to mental health problems that lasted 5 workdays or more, while controlling for confounders. RESULTS: Workers exposed to ERI had a higher risk of a first spell of medically certified absence for mental health problems (HR=1.38, 95% CI 1.08 to 1.76) compared with unexposed workers. Low reward was significantly associated with a high risk among men (HR=2.80, 95% CI 1.34 to 5.89) but not in women. (HR=1.24, 95% CI 0.90 to 1.73). Effort at work had no effect on certified absence. All these effects were adjusted for potential confounders. CONCLUSIONS: ERI and low reward at work were prospectively associated with medically certified absence for mental health problems. These effects seem to differ by gender. Primary prevention that is aimed at reducing these stressors should be considered to help reduce the incidence of such severe mental health problems.

A distinct boundary between the higher brain's susceptibility to ischemia and the lower brain's resistance.

Higher brain regions are more susceptible to global ischemia than the brainstem, but is there a gradual increase in vulnerability in the caudal-rostral direction or is there a discrete boundary? We examined the interface between `higher` thalamus and the hypothalamus the using live brain slices where variation in blood flow is not a factor. Whole-cell current clamp recording of 18 thalamic neurons in response to 10 min O2/glucose deprivation (OGD) revealed a rapid anoxic depolarization (AD) from which thalamic neurons do not recover. Newly acquired neurons could not be patched following AD, confirming significant regional thalamic injury. Coinciding with AD, light transmittance (LT) imaging during whole-cell recording showed an elevated LT front that initiated in midline thalamus and that propagated into adjacent hypothalamus. However, hypothalamic neurons patched in paraventricular nucleus (PVN, n= 8 magnocellular and 12 parvocellular neurons) and suprachiasmatic nucleus (SCN, n= 18) only slowly depolarized as AD passed through these regions. And with return to control aCSF, hypothalamic neurons repolarized and recovered their input resistance and action potential amplitude. Moreover, newly acquired hypothalamic neurons could be readily patched following exposure to OGD, with resting parameters similar to neurons not previously exposed to OGD. Thalamic susceptibility and hypothalamic resilience were also observed following ouabain exposure which blocks the Na(+)/K(+) pump, evoking depolarization similar to OGD in all neuronal types tested. Finally, brief exposure to elevated [K(+)]o caused spreading depression (SD, a milder, AD-like event) only in thalamic neurons so SD generation is regionally correlated with strong AD. Therefore the thalamus-hypothalamus interface represents a discrete boundary where neuronal vulnerability to ischemia is high in thalamus (like more rostral neocortex, striatum, hippocampus). In contrast hypothalamic neurons are comparatively resistant, generating weaker and recoverable anoxic depolarization similar to brainstem neurons, possibly the result of a Na/K pump that better functions during ischemia.

A neuronal population in hypothalamus that dramatically resists acute ischemic injury compared to neocortex.

Pyramidal neurons (PyNs) of the cortex are highly susceptible to acute stroke damage, yet "lower" brain regions like hypothalamus and brain stem better survive global ischemia. Here we show for the first time that a "lower" neuron population intrinsically resists acute strokelike injury. In rat brain slices deprived of oxygen and glucose (OGD), we imaged anoxic depolarization (AD) as it propagated through neocortex or hypothalamus. AD, the initial electrophysiological event of stroke, is a front of depolarization that drains residual energy in compromised gray matter. The extent of AD reliably determines ensuing cortical damage, but do all CNS neurons generate a robust AD? During 10 min of OGD, PyNs depolarize without functional recovery. In contrast, magnocellular neuroendocrine cells (MNCs) in hypothalamus under identical stress generate a weak and delayed AD, resist complete depolarization, and rapidly repolarize when oxygen and glucose are restored. They recover their membrane potential, input resistance, and spike amplitude and can survive multiple OGD exposures. Two-photon microscopy in slices derived from a fluorescent mouse line confirms this protection, revealing PyN swelling and dendritic beading after OGD, whereas MNCs are not injured. Exposure to the Na(+)-K(+)-ATPase inhibitor ouabain (100 µM) induces AD similar to OGD in both cell types. Moreover, elevated extracellular K(+) concentration ([K(+)](o)) evokes spreading depression (SD), a milder version of AD, in PyNs but not MNCs. Therefore overriding the pump by OGD, ouabain, or elevated [K(+)](o) evokes a propagating depolarization in higher gray matter but not in MNCs. We suggest that variation in Na(+)-K(+)-ATPase pump efficiency during ischemia injury determines whether a neuronal type succumbs to or resists stroke.

Examining protection from anoxic depolarization by the drugs dibucaine and carbetapentane using whole cell recording from CA1 neurons.

As an immediate consequence of stroke onset, failure of the Na(+)-K(+)-ATPase pump evokes a propagating anoxic depolarization (AD) across gray matter. Acute neuronal swelling and dendritic beading arise within seconds in the future ischemic core, imaged as changes in light transmittance (ΔLT). AD is itself not a target for drug-based reduction of stroke injury because it is generated in the 1st min of stroke onset. Peri-infarct depolarizations (PIDs) are milder AD-like events that recur during the hours following AD and contribute to infarct expansion. Inhibiting PIDs with drugs could limit expansion. Two types of drugs, "caines" and σ(1)-receptor ligands, have been found to inhibit AD onset (and may also oppose PID initiation), yet their underlying actions have not been examined. Imaging ΔLT in the CA1 region simultaneously with whole cell current-clamp recording from CA1 pyramidal neurons reveal that the elevated LT front and onset of the AD are coincident. Either dibucaine or carbetapentane pretreatment significantly delays AD onset without affecting resting membrane potential or neuronal input resistance. Dibucaine decreases excitability by raising spike threshold and decreasing action potential (AP) frequency, whereas carbetapentane eliminates the fast afterhyperpolarization while accentuating the slow afterhyperpolarization to reduce AP frequency. Orthodromic and antidromic APs are eliminated by dibucaine within 15 min but not by carbetapentane. Thus both drugs reduce cortical excitability at the level of the single pyramidal neuron but through strikingly different mechanisms. In vivo, both drugs would likely inhibit recurring PIDs in the expanding penumbra and so potentially could reduce developing neuronal damage over many hours poststroke when PIDs occur.

Repeated exposure to effort-reward imbalance, increased blood pressure, and hypertension incidence among white-collar workers: effort-reward imbalance and blood pressure.

OBJECTIVES: To determine whether men and women with repeated ERI exposure have increased BP means or higher hypertension incidence over a 3-year follow-up. To examine the potential modifying effect of age and overcommitment. METHODS: The study cohort was composed of 1,595 white-collar workers (629 men and 966 women) assessed at baseline and 3-year follow-up. Ambulatory BP measures were taken every 15 min during a working day. ERI at work was self-reported using validated scales. BP means at follow-up and cumulative incidence of hypertension were respectively modeled with analyses of covariance (ANCOVA) and log-binomial regression. RESULTS: Among men, no association was observed between repeated ERI exposure and BP. Among women, age had a modifying effect. Women <45 years old exposed to ERI at both times had significantly higher BP means at follow-up (122.2/78.9 mmHg) than those unexposed (120.4/77.4 mmHg). In women ≥45 years old, the cumulative incidence of hypertension was 2.78 (95% CI: 1.26-6.10) times higher among those exposed to ERI at both times. Men and women in the higher tertile of overcommitment had higher BP means (men: 128.9/82.2 mmHg, women: 121.9/78.0 mmHg) than those in the lower tertile (men: 127.2/81.3 mmHg, women: 120.6/77.0 mmHg). CONCLUSION: This prospective study showed that, among women, repeated ERI exposure led to a significant age-specific increase in BP means and a major age-specific increase in hypertension incidence. These results suggest that primary intervention aimed at reducing ERI may contribute to lower BP and prevent hypertension in women.

Histological features and expression of enzymes implicated in melatonin synthesis in pineal parenchymal tumours and in cultured tumoural pineal cells.

Pineal parenchymal tumours (PPT) are rare neoplasms and there have been few in vitro studies. Their capacity for synthesizing and secreting melatonin has been only partially examined. We investigated the presence of messenger RNA (mRNA) encoding tryptophan hydroxylase (TPH), arylalkylamine N-acetyltransferase (AANAT), hydroxyindol-O-methyltransferase (HIOMT), three enzymes involved in melatonin synthesis, and c-myc, a tumoural marker, in 10 PPT, one papillary tumour of the pineal region (PTPR), cell cultures derived from four PPTs and from three other tumours of the pineal region, and in normal pineal gland. Moreover, protein expression of TPH was investigated in three PPT and PTPR. Quantitative real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry were used and the melatonin production by tumoural cells in vitro was analysed by radioimmunoassay. We showed that all the tumoural tissues and cells contained c-myc mRNA. mRNAs encoding TPH, AANAT and HIOMT were detected in all PPT, suggesting that tumour cells can synthesize melatonin. Only PPT expressed TPH protein. Cultured cells lost expression of transcripts throughout passages even if ultrastructural study revealed the presence of characteristic organelles in these tumoural cells. Nevertheless, the basal secretion of melatonin observed in one PPT culture is in favour of a maintained melatonin production and secretion by tumoural pinealocytes, but melatonin production was not stimulated by a beta noradrenergic agonist. Moreover, PTPR never expressed mRNA encoding TPH, AANAT and HIOMT. Our results may contribute to a better understanding of the biology of PTT and PTPR and may help to the diagnosis of these rare tumours.

Development and implementation of a participative intervention to improve the psychosocial work environment and mental health in an acute care hospital.

OBJECTIVES: To describe the development and implementation phases of a participative intervention aimed at reducing four theory grounded and empirically supported adverse psychosocial work factors (high psychological demands, low decision latitude, low social support, and low reward), and their mental health effects. METHODS: The intervention was realised among 500 care providers in an acute care hospital. A prior risk evaluation was performed, using a quantitative approach, to determine the prevalence of adverse psychosocial work factors and of psychological distress in the hospital compared to an appropriate reference population. In addition, a qualitative approach included observation in the care units, interviews with key informants, and collaborative work with an intervention team (IT) including all stakeholders. RESULTS: The prior risk evaluation showed a high prevalence of adverse psychosocial factors and psychological distress among care providers compared to a representative sample of workers from the general population. Psychosocial variables at work associated with psychological distress in the prior risk evaluation were high psychological demands (prevalence ratio (PR) = 2.27), low social support from supervisors and co-workers (PR = 1.35), low reward (PR = 2.92), and effort-reward imbalance (PR = 2.65). These results showed the empirical relevance of an intervention on the four selected adverse psychosocial factors among care providers. Qualitative methods permitted the identification of 56 adverse conditions and of their solutions. Targets of intervention were related to team work and team spirit, staffing processes, work organisation, training, communication, and ergonomy. CONCLUSION: This study adds to the scarce literature describing the development and implementation of preventive intervention aimed at reducing psychosocial factors at work and their health effects. Even if adverse conditions in the psychosocial environment and solutions identified in this study may be specific to the healthcare sector, the intervention process used (participative problem solving) appears highly exportable to other work organisations.

Effectiveness of a participative intervention on psychosocial work factors to prevent mental health problems in a hospital setting.

OBJECTIVES: To assess the effectiveness of a workplace intervention aimed at reducing adverse psychosocial work factors (psychological demands, decision latitude, social support, and effort-reward imbalance) and mental health problems among care providers. METHODS: A quasi-experimental design with a control group was used. Pre-intervention (71% response rate), and one-year post-intervention measures (69% response rate) were collected by telephone interviews. RESULTS: One year after the intervention, there was a reduction of several adverse psychosocial factors in the experimental group, whereas no such reduction was found in the control group. However, there was a significant deterioration of decision latitude and social support from supervisors in both experimental and control groups. There was also a significant reduction in sleeping problems and work related burnout in the experimental hospital, whereas only sleeping problems decreased in the control group while both client related and personal burnout increased in this hospital. The comparison between the experimental and control groups, after adjusting for pre-intervention measures, showed a significant difference in the means of all psychosocial factors except decision latitude. All other factors were better in the experimental group. CONCLUSION: Results suggest positive effects of the intervention, even though only 12 months have passed since the beginning of the intervention. Follow up at 36 months is necessary to evaluate whether observed effects are maintained over time. In light of these results, we believe that continuing the participative process in the experimental hospital will foster the achievement of a more important reduction of adverse psychosocial factors at work. It is expected that the intensity of the intervention will be directly related to its beneficial effects. Long term effects will however depend on the willingness of management and of staff to appropriate the process of identifying what contributes to adverse psychosocial factors at work and to adopt means to reduce them.

[Prospective epidemiological study on cutaneous melanomas in the Vendée area]. / Etude épidémiologique prospective des mélanomes cutanés en Vendée.

INTRODUCTION: The aim of this prospective study was to evaluate the incidence of melanoma in the Vendée area, coastal region of Eastern France, in 1997. PATIENTS AND METHODS: The 16 dermatologists in the Vendée area in 1997, grouped together in a local association, completed a sheet for each patient in whom a new melanoma had been diagnosed. During the same period, the hospital and private pathologists of the Vendée and surrounding areas reported their new cases of melanoma in patients residing at least six months of the year in the area. The data concerning the local population was supplied by the INSEE (French national institute of economic and statistical information) and the CPAM (French health authority) supplied data on the practitioners' activity. The raw and standardized incidence was calculated by the epidemiologist and the statistician of the local Vendée Cancer registry. RESULTS: One hundred fifteen new melanomas were diagnosed in Vendée in 1997, 97 by a dermatologist and 18 declared by a pathologist. There were 36 in situ and 79 invasive melanomas discovered in 68 women and 47 men (sex ratio: 1.46). The standardized rate of incidence according to the world model was of 98/100,000 for women and 7.8/100,000 for men. The frequency curve revealed two peaks: the first at 40-50 years of age and the second at 70-75. The mean Breslow index of the 79 invasive cancers was of 1.62 mm (range: 0.10-12.5 mm). The only statistically significant difference between the melanomas of the men and the women concerned the topography; there were more melanomas on the trunk in men and more melanomas on the lower limbs in the women. Forty-seven Dubreuilh melanomas were reported: 28 in situ and 19 invasive. DISCUSSION: This prospective study determined the incidence of melanoma in Vendée in 1997. The figures have been compared with those of the Vendée cancer registry, founded in April 1997, and with those of various published studies. The comparison was difficult because of the difference in study methodology. The only figures obtained in the same conditions are those of the cancer registry and we compared them with those of the Haut-Rhin, area of Eastern France: the incidence was similar for the women in the two areas and greater for the men in the Haut-Rhin with regard to the invasive melanomas. Conversely, 44 in situ melanomas were declared in the Haut-Rhin over a 3 year period versus 37 in Vendée over a period of 1 year. The increase in the incidence of melanoma in Vendée in the years to come should permit the evaluation of the impact of the various preventive campaigns.

[Prospective clinical study on new cutaneous melanomas in the Vendée area]. / Etude clinique prospective des nouveaux mélanomes en Vendée.

INTRODUCTION: In parallel to an epidemiological study on the new cases of melanoma reported in the Vendée area in 1997, private dermatologists conducted a clinical analysis of the characteristics of melanomas (including Dubreuilh's melanoma) and of the population concerned. PATIENTS AND METHODS: For each patient in whom a melanoma had been diagnosed, the dermatologists completed a standardized sheet that included the identification, phototype (comparing the distribution with that of the local population, studied in all the consultants during a randomly selected week), the personal and family history of melanoma, the existence of severe sunburn and exposure to artificial ultra-violet rays, the screening method, the time lapse before treatment, the impact of information campaigns, the number of nevi, atypical or not, and the characteristics of the tumor. The exeresis method and the histological characteristics (type, Clark's score and Breslow's index) were also noted. RESULTS: In 1997, the 16 local dermatologists diagnosed 97 melanomas in 55 women and 42 men with a mean age of 64 years. There was no statistically significant difference between the melanomas of the men and those of the women, other than their localization. Photoype II was significantly more frequent in the population exhibiting a melanoma. Sun exposure was moderate or intensive for three thirds of the patients. Past history of severe sunburn was twofold more frequent in the patients exhibiting a melanoma on the trunk. The association of many nevi was noted in a little more than half of the patients, and with atypical nevi in 5.2 p.cent. The elements that alerted the patients were recorded. The time lapse before diagnosis was calculated in months for nodular and in years for superficial melanomas. Clark's score and Breslow's index are presented in a table. DISCUSSION: Our study underlines several interesting features: the fairly high mean age on discovery, a high rate of invasive melanomas, and patients less well informed than in the Ile de France area. These results should open the debate on the best way to educate the population concerned so as to reduce the incidence of this malignant tumor.

Establishment of human tumoral ependymal cell lines and coculture with tubular-like human endothelial cells.

Ependymomas, rare neoplasms of the central nervous system, occur predominantly in children. They are highly vascularized, and histological findings show many perivascular rosettes of tumoral cells radially organized around capillaries. Treatment of ependymomas relies on surgery combined with radio- or chemotherapy, but the efficiency of chemotherapy is limited, probably because of their multidrug resistance (MDR) phenotype. Progress in the therapy of these neoplasms is dramatically limited by the absence of cell line models. We established conditions for the long-term culture of human tumoral ependymocytes and their 3D coculture in Matrigel with endothelial cells. Histological, immunological, and ultrastructural studies showed that the morphological features (microvilli, cilia, and caveolae) of these cultured cells were similar to those of the tumor in vivo. The cells expressed potential oncological markers related to the immature state of tumoral cells (nestin and Notch-1), their tumorigenicity [caveolae and epidermal growth factor-receptor (EGF-R)], or the MDR phenotype [P-glycoprotein (P-gp)]. The expression of P-gp, EGF-R, and caveolin-1 by these tumoral ependymocytes could be useful in studies on new drugs. This coculture model might represent a new powerful tool to study new therapeutic delivery strategies in tumoral cells.

Differential expression of somatostatin receptors in medulloblastoma.

OBJECT: Somatostatin receptors have been found on a variety of tumours like neuroendocrine breast or brain tumours. Their detection opens new diagnostic and therapeutic paths. The aim of this work was to investigate their expression in medulloblastomas. METHODS: Using both techniques, reverse transcriptase-polymerase chain reaction and immunohistochemistry, we analysed mRNA of different subtypes of somatostatin receptors in 15 medulloblastomas and the localisation of the subtype SSTR2 receptor at the cellular level in 13 medulloblastomas. All five subtypes mRNA were variably expressed in each medulloblastoma. The signal obtained after Southern blotting for SSTR2 receptor amplification was the highest as compared to the signal obtained for the other receptor subtypes. Immunostaining for SSTR2A receptor was present in every tumour specimen and was specifically located to the cellular membrane of neoplastic cells. No staining was identified at the level of peritumoral veins. CONCLUSION: The evidence of predominant expression of SSTR2 receptors in medulloblastomas opens interesting prospects for their diagnosis and therapy.

[Validity of occupational stress and decision latitude on health in the National Population Health Survey of 1994-95]. / Validité des indices de demande psychologique et de latitude décisionnelle utilisés dans l'Enquête nationale sur la santé de la population (ENSP) de 1994-95.

Psychosocial environment at work is now considered a health determinant. The National Population Health Survey (NPHS) of 1994-95 is the first study in which psychological demands and decision latitude at work were measured in a random sample of the Canadian population. However, psychometric properties of the scales used in NPHS to measure these factors are not known. The objective of the present paper was to evaluate some validity parameters of the scales used in the NPHS by comparison to the original scales recommended by Karasek to measure these factors. Results of the current study support the validity of the decision latitude scale. However, validity of the psychological demand scale is more limited.

[Impact of occupational stress on health status in Canada]. / Les contraintes psychosociales au travail chez les Canadiennes et les Canadiens.

Studies have shown that high psychological demands and low decision latitude may be involved in the development of major health problems. The objective of the current study was to describe the importance of these factors among the Canadian working population. The sample included 7,250 participants from the National Population Health Survey (NPHS) of 1994-95. Women were significantly more exposed than men to high psychological demands (56% versus 49%), to low decision latitude (61% versus 49%), and to these two factors simultaneously (33% versus 22%). The exposure to each of these factors was more frequent among younger and less educated people. Simultaneous exposure to both factors was more frequent among younger people and those with intermediate education level. There was a socio-economic gradient for the exposition to these factors. Some jobs with the highest exposure were identified.

Astrocytic alterations induced by HTLV type 1-infected T lymphocytes: a role for Tax-1 and tumor necrosis factor alpha.

In the neurological disease associated with HTLV-1 infected T lymphocytes infiltrated within the CNS are suspected of playing a prominent role in pathogenesis via inflammatory cytokines and the viral protein Tax-1. We hypothesized that T lymphocytes initiate functional perturbation in astrocytes, resulting in neuronal alteration as glial cells have a crucial role in CNS homeostasis. In particular, astrocytes manage the steady state level of glutamate and continuously provide metabolite precursors to neurons and oligodendrocytes. Using a model system of HTLV-1-infected T cells-astrocytes interaction, we show that after contact with T cells, astrocyte acquire a phenotype typical of gliosis: secretion of proinflammatory cytokines (TNF-alpha, IL-1alpha, IL-6) and matrix metalloproteinases (MMP-9, MMP-3). The concomitant increase in the expression of MMPs and of their endogenous inhibitors (TIMP-1 and TIMP-3) suggests a perturbation in MMP/TIMP balance. This may alter the extracellular matrix and, in turn, the cell environment. At a functional level, glutamate transport and catabolism are impaired in astrocytes. A decrease in glutamate uptake is associated with downregulated expression of glutamate transporters GLAST and GLT1. The expression of astrocytic enzyme of glutamate metabolism is modified with up-regulation of glutamine synthetase and down-regulation of glutamate dehydrogenase. The involvement of Tax-1 in these alterations, directly or indirectly via TNF-alpha, is shown. Altered glutamate uptake and catabolism associated with impairment in cell connectivity via MMP/TIMP imbalance could compromise the functional integrity of the CNS in general and that of neurons and oligodendrocytes in particular.