Blocking the epithelial-to-mesenchymal transition pathway abrogates resistance to anti-folate chemotherapy in lung cancer.

Anticancer therapies currently used in the clinic often can neither eradicate the tumor nor prevent disease recurrence due to tumor resistance. In this study, we showed that chemoresistance to pemetrexed, a multi-target anti-folate (MTA) chemotherapeutic agent for non-small cell lung cancer (NSCLC), is associated with a stem cell-like phenotype characterized by an enriched stem cell gene signature, augmented aldehyde dehydrogenase activity and greater clonogenic potential. Mechanistically, chemoresistance to MTA requires activation of epithelial-to-mesenchymal transition (EMT) pathway in that an experimentally induced EMT per se promotes chemoresistance in NSCLC and inhibition of EMT signaling by kaempferol renders the otherwise chemoresistant cancer cells susceptible to MTA. Relevant to the clinical setting, human primary NSCLC cells with an elevated EMT signaling feature a significantly enhanced potential to resist MTA, whereas concomitant administration of kaempferol abrogates MTA chemoresistance, regardless of whether it is due to an intrinsic or induced activation of the EMT pathway. Collectively, our findings reveal that a bona fide activation of EMT pathway is required and sufficient for chemoresistance to MTA and that kaempferol potently regresses this chemotherapy refractory phenotype, highlighting the potential of EMT pathway inhibition to enhance chemotherapeutic response of lung cancer.

[Skin diseases observed in the dermatology departments of three French university teaching hospitals]. / Activité de consultation de trois services de dermatologie hospitalo-universitaires français.

BACKGROUND: We recently carried out a study concerning consultations by French dermatologists in private practice. We evaluated consultations at the dermatology departments of 3 university teaching hospitals in France. MATERIALS AND METHODS: This was a 2-month prospective study conducted in 2003 at the dermatology departments of the university teaching hospitals of Amiens, Lille and Rouen. Each consultant completed a questionnaire covering the duration of the study. The following data were recorded: consultation date, function of the consultant, study centre, type of consultation, type of disease, and whether or not the patient was hospitalised after the consultation. RESULTS: 7296 files were examined during the study. 38% of the consultations were performed by part-time hospital consultants, 29% by dermatology interns, 18% by hospital practitioners, 9% by university professors and 6% by clinical heads or assistant heads. The most commonly encountered diseases were allergies (17%), cancer (16%), arteriovenous disease (15%) and infectious disease (11%). Three types of consultation were identified: emergency consultations without an appointment, consultations by appointment for a specific problem and consultations by appointment without a specific problem. The number of resulting hospital admissions ranged from 2 to 10% of consultations, depending on the type of consultation and the role of the consultant in question. DISCUSSION: This study shows that in France, consultations at hospital dermatology departments differ greatly from those of dermatologists in private practice. The main diseases seen (cancer, arteriovenous disease, allergy, infectious dermatosis) accounted for the majority of hospitalisations in these departments. The organisation of hospital consultations is increasingly tending both towards treatment of highly specialised diseases through specifically oriented consultations and also towards the emergency treatment of certain forms of acute dermatosis.

[Efficiency of hepatitis C virus screening before and after blood transfusion]. / Evaluation médicoéconomique du suivi sérologique péritransfusionnel du virus de l'hépatite C.

UNLABELLED: Efficiency of a viral hepatitis C screening strategy before and after blood transfusion has to be evaluated. METHODS: Four screening strategies were virtually applied to the population of transfused patients at Rouen University Hospital during 1996 and then compared : the first without any systematic HCV screening test; the second with systematic testing both before and 3 months after transfusion; the third with systematic testing both before and 6 months after transfusion ; the last defined as systematic testing before transfusion only. The efficacy (i.e. number of positive tests), the efficiency (i.e. average cost per positive test) and the marginal costs of moving from a strategy to another one were assessed using decision analysis. RESULTS: The efficacy of systematic screening test before transfusion only (361 per positive test), systematic testing both before and three months after (523 per positive test) or six months after (488 per positive test) transfusion was similar, but the efficacy of the strategy without any systematic screening test (385 per positive test) was lower. The systematization of screening test both before, and three months, or 6 months after transfusion lead to a marginal cost of 619 , and 559 per positive test respectively. The systematization of testing before transfusion only lead to a marginal cost of 343 per positive test. Adding systematic testing after transfusion lead to a marginal cost of 5824 per positive test. CONCLUSION: Systematic screening tests before transfusion only can be considered as the most efficient strategy.

[Survival after blood transfusion: a study at Rouen university hospital]. / Facteurs de survie à six mois des patients transfusés: étude au CHU de Rouen.

UNLABELLED: The aim of this study was to estimate short term survival rate after blood transfusion according to various criteria. PATIENTS AND METHODS: Patients admitted and transfused from January, 1 until June, 30 1996 at Rouen university hospital were retrospectively included, and their status (alive or dead) was determined. The characteristics of patients admitted and transfused were compared to the overall population of inpatients. Independent factors associated with mortality six months after blood transfusion were evaluated using Cox model. RESULTS: During the study period, 1887 patients were transfused. These patients were older, more often admitted in surgical or in intensive care units, and had a longer duration of stay, than the overall inpatients population. The survival rate at six months in transfused patients was 76.1%. Mortality rate at six months was independently higher in patients aged 75 and older, in men, in patients admitted in intensive care units, or transfused with homologous fresh-frozen plasma or packed platelet blood cells. Mortality rate was lower in patients who underwent a surgical procedure, in children under 16, and in patients whose stay was classified in "Circulatory system disorders", "Musculoskeletal system and connective tissues disorders or trauma", or "Injuries, allergy or poisoning". CONCLUSION: In this study implemented in a teaching hospital inpatients receiving blood transfusion, the survival was mainly associated with the severity and characteristics of the diseases requiring transfusion.

Short-term effects of air pollution on mortality in the cities of Rouen and Le Havre, France, 1990-1995.

In this study, the authors examined the short-term effects of ambient air pollution on mortality across 2 French cities: Rouen and Le Havre. In Poisson regression models, which controlled for day-of-week effects, the authors used nonparametric smoothing to control for temporal trend, weather, and influenza epidemics. In Rouen, an interquartile range increase of 60.5-94.1 microg/m3 of ozone was associated with an increase of 4.1% (95% confidence interval = 0.6, 7.8) of total mortality. Daily variations in sulfur dioxide (interquartile range increase = 17.6-36.4 microg/m3) were also associated with an 8.2% increase (95% confidence interval = 0.4, 16.6) in respiratory mortality. An increase of 6.1% (95% confidence interval = 1.5, 10.9) of cardiovascular mortality was also observed with an interquartile range increase of nitrogen dioxide (i.e., 25.3-42.2 microg/m3). With respect to Le Havre, an interquartile range increase in daily levels of sulfur dioxide (11.3-35.6 microg/m3) was associated with an increase of approximately 3% (95% confidence interval = 0.8, 5) of cardiovascular mortality. For particulate matter less than or equal to 13 microm in diameter (interquartile increase = 21.5, 45.4 microg/m3), an increase of 6.2% (95% confidence interval = 0.1, 12.8) was observed. The estimates of pollutant effects and their standard deviations were slightly affected by the degree of smoothing temporal variations in this study. When low collinearity was present, the 2-pollutant models provided acceptable estimates of pollutant effects. They suggested that the ozone effect was independent of the Black Smoke effect, and that the effects of sulfur dioxide and nitrogen dioxide were unlikely to be confounded by ozone concentrations. However, high collinearity leads to large estimates of the pollutant coefficient variances and, therefore, leads to inaccurate estimates of pollutant effects. The analysis of the contributory effects of different pollutant mixtures requires further investigation in those instances in which high collinearity between pollutants is present.

Assessment of prolonged hospital stay attributable to surgical site infections using appropriateness evaluation protocol.

BACKGROUND: The accepted standard in estimating the stay prolongation attributable to surgical site infections is the matched-cohort study method (MCS), which is associated with selection bias. The Appropriateness Evaluation Protocol (AEP) has been used to estimate stay prolongation attributable to nosocomial infections but has not been validated specifically for surgical site infections. AIM OF THE STUDY: To compare estimates of stay prolongation attributable to surgical site infections after digestive surgery, obtained by AEP and by MCS. METHODS: Sixty-five surgical site infections after digestive tract surgery were analyzed by AEP and MCS. AEP stay prolongation was the number of days judged specifically appropriate for the care of surgical site infections. MCS stay prolongation was the difference of stay duration in surgical site infection cases and two controls matched by age, sex, and diagnosis-related groups. Sensitivity and specificity of AEP, and agreement between both methods, were calculated. RESULTS: The mean AEP stay prolongation was 3.5 days vs 7.2 days for MCS. The sensitivity of AEP was 58% and the specificity was 75%. The agreement between the two methods was poor. CONCLUSION: Surgical site infections after digestive tract surgery increased the hospital stay. Accurate estimations of a prolongation of stay will vary according to the method selected.

[Are early unforseen rehospitalizations inevitable?]. / Les réhospitalisations précoces imprévues sont-elles évitables?

We randomly selected 198 readmissions to an acute-care hospital within the 3 months following the last discharge during the year 1993 to describe the reasons for planned readmissions and to assess whether unplanned readmissions were appropriate and/or avoidable. 49.5% of readmissions were planned: for medical investigations (45%), surgery (30%), or medical treatments (such as chemotherapy) (18%). Among the 100 unplanned readmissions, 13% were assessed as inappropriate, and 37% as potentially avoidable. Given this high rate of potentially avoidable readmissions, there is a need to identify preventive interventions.

[Infant feeding until the age of 4 months old in Seine-Maritime]. / L'alimentation du nourrisson jusqu'à 4 mois en Seine-Maritime.

This study reports infant feeding practices during the first 4 months of life. A representative sample of 10% of the births in the Seine-Maritime department formed the subject of a questionnaire cohort study carried on at home by public health institution for infants specialized nurses. Among 1,407 interviewed mothers, 52% had been thinking about their future child feeding before birth, essentially with their circles, especially their husbands. The type of feeding had been chosen before pregnancy in 64.3% of cases. Earlier choices resulted more often in breast-feeding. 46.2% of mothers tried to breast-feed their children, however 17% among them discontinued when back home. Carrying out breast-feeding (median duration 10 weeks) delayed the feeding diversification and was associated with a lower frequency of health difficulties in children.

Salt and water retention and calcium blockade in uremia.

Blood pressure, echocardiography, and aortic and peripheral arterial pulse-wave velocity were studied in 40 hypertensive patients on long-term hemodialysis during a 24-week administration of nitrendipine (1,4-dihydro-2,6-dimethyl-4-[m-nitrophenyl]-3,5-pyridine-dicarboxylic acid ethyl methylester) monotherapy. In a double-blind placebo-randomized study, nitredipine effectively lowered the blood pressure (p less than 0.001) before hemodialysis without causing postdialysis hypotension. The antihypertensive effect of nitrendipine was greater in patients with significant salt and water retention, as indicated by interdialytic body weight gain (delta BW), that is, a significant correlation was observed between delta BW and the decrease in blood pressure (r = 0.72; p less than 0.001). The antihypertensive effect was not related to age, pretreatment plasma renin activity, or serum-ionized calcium concentration. After nitrendipine, a time-related decrease in aortic (p less than 0.005) and femoral (p less than 0.05) pulse-wave velocity was observed with a significant time-treatment interaction (p less than 0.01). Nitrendipine treatment did not influence left ventricular mass (which was positively correlated with delta BW; p less than 0.01) but was associated with an increase in the left ventricular ejection fraction. The increase in ejection fraction was correlated with changes in aortic pulse-wave velocity (r = 0.548; p less than 0.02) but not with changes in blood pressure (r = 0.352; p = 0.19) or delta BW.(ABSTRACT TRUNCATED AT 250 WORDS)

[Vital prognosis in fractures of the proximal femur. Study in 506 patients of 60 years of age and over]. / Pronostic vital des fractures de l'extrémité supérieure du fémur. Etude chez 506 patients de 60 ans et plus.

Five hundred and six patients aged 60 years or over admitted to hospital between 1977 and 1982 for a fracture of the upper end of the femur were the subject of a retrospective study to determine their mortality. Those with multiple injuries or affected by a pathological fracture were excluded. The median age of the population was 80 years, with a clear female predominance. Ageing appeared to be the main risk factor in fracture of the upper end of the femur. Surgical treatment was early, at a median of two days, and weightbearing was possible on the fifth day for half of the patients. The mean time in the surgical department was 15 days, followed by transfer to a nursing home or to a rehabilitation unit for two-thirds of the patients; 7.9 p. cent of patients died during their stay in the surgical department. The actuarial survival rate at one year was 64.7 p. cent and at five years was 35.3 per cent. Compared with the corresponding general population, a fracture of the upper end of the femur is accompanied by a persistently higher mortality for at least two years after the accident, more marked in relative values in men and in younger subjects. A multifactorial study of the prognostic factors using Cox's model showed that the mortality rose with age at the time of the fracture but was lower when the patient had previously been able to go out of the house and was of the female sex.(ABSTRACT TRUNCATED AT 250 WORDS)