Constraints on Dark Matter Properties from Observations of Milky Way Satellite Galaxies.

We perform a comprehensive study of Milky Way (MW) satellite galaxies to constrain the fundamental properties of dark matter (DM). This analysis fully incorporates inhomogeneities in the spatial distribution and detectability of MW satellites and marginalizes over uncertainties in the mapping between galaxies and DM halos, the properties of the MW system, and the disruption of subhalos by the MW disk. Our results are consistent with the cold, collisionless DM paradigm and yield the strongest cosmological constraints to date on particle models of warm, interacting, and fuzzy dark matter. At 95% confidence, we report limits on (i) the mass of thermal relic warm DM, m_{WDM}>6.5 keV (free-streaming length, λ_{fs}≲10h^{-1} kpc), (ii) the velocity-independent DM-proton scattering cross section, σ_{0}<8.8×10^{-29} cm^{2} for a 100 MeV DM particle mass [DM-proton coupling, c_{p}≲(0.3 GeV)^{-2}], and (iii) the mass of fuzzy DM, m_{ϕ}>2.9×10^{-21} eV (de Broglie wavelength, λ_{dB}≲0.5 kpc). These constraints are complementary to other observational and laboratory constraints on DM properties.

Detection of CMB-Cluster Lensing using Polarization Data from SPTpol.

We report the first detection of gravitational lensing due to galaxy clusters using only the polarization of the cosmic microwave background (CMB). The lensing signal is obtained using a new estimator that extracts the lensing dipole signature from stacked images formed by rotating the cluster-centered Stokes QU map cutouts along the direction of the locally measured background CMB polarization gradient. Using data from the SPTpol 500 deg^{2} survey at the locations of roughly 18 000 clusters with richness λ≥10 from the Dark Energy Survey (DES) Year-3 full galaxy cluster catalog, we detect lensing at 4.8σ. The mean stacked mass of the selected sample is found to be (1.43±0.40)×10^{14}M_{⊙} which is in good agreement with optical weak lensing based estimates using DES data and CMB-lensing based estimates using SPTpol temperature data. This measurement is a key first step for cluster cosmology with future low-noise CMB surveys, like CMB-S4, for which CMB polarization will be the primary channel for cluster lensing measurements.

Recommendation for hygiene and topical in neonatology from the French Neonatal Society.

We sought to establish guidelines for hygiene care in newborns based on a systematic review of the literature and grading of evidence using the Groupe de Réflexion et d'Evaluation de l'Environement des Nouveau-nés (GREEN) methodology. We examined 45 articles and 4 reports from safety agencies. These studies recommend a tub bath (rather than a sponge bath) for full-term infants and a swaddle bath for preterm newborns. They also recommend against daily cleansing of preterm infants. The literature emphasized that hygiene care must consider the clinical state of the newborn, including the level of awareness and behavioral responses. Hospitalized newborns treated with topical agents may also experience high exposure to potentially harmful excipients of interest. Caregivers should therefore be aware of the excipients present in the different products they use. In high-resource countries, the available data do not support the use of protective topical agents for preterm infants.Conclusions: We recommend individualization of hygiene care for newborns. There is increasing concern regarding the safety of excipients in topical agents that are used in neonatology. A multidisciplinary approach should be used to identify an approach that requires lower levels of excipients and alternative excipients. What is known: • Hygiene care is one of the most basic and widespread types of care received by healthy and sick newborns worldwide. • There is no current guideline on hygiene for preterm or hospitalized term newborn. What is new: • The French Group of Reflection and Evaluation of the environment of Newborns (GREEN) provided here guidelines based on the current body of evidence. • Caregivers should be aware of the many issues related to hygiene care of newborns including newborns' behavioral responses to hygiene care, exposition to excipients of interest, and the potential risk of protective topical agents in a preterm infant. provided here guidelines based on the current body of evidence. • Caregivers should be aware of the many issues related to hygiene care of newborns including newborns' possible behavioral responses to hygiene care, exposition to excipients of interest and the potential risk of protective topical agents in a preterm infant.

Wide-Field Lensing Mass Maps from Dark Energy Survey Science Verification Data.

We present a mass map reconstructed from weak gravitational lensing shear measurements over 139 deg2 from the Dark Energy Survey science verification data. The mass map probes both luminous and dark matter, thus providing a tool for studying cosmology. We find good agreement between the mass map and the distribution of massive galaxy clusters identified using a red-sequence cluster finder. Potential candidates for superclusters and voids are identified using these maps. We measure the cross-correlation between the mass map and a magnitude-limited foreground galaxy sample and find a detection at the 6.8σ level with 20 arc min smoothing. These measurements are consistent with simulated galaxy catalogs based on N-body simulations from a cold dark matter model with a cosmological constant. This suggests low systematics uncertainties in the map. We summarize our key findings in this Letter; the detailed methodology and tests for systematics are presented in a companion paper.

A novel protein kinase involved in Na(+) exclusion revealed from positional cloning.

Salinity is a major abiotic stress which affects crop plants around the world, resulting in substantial loss of yield and millions of dollars of lost revenue. High levels of Na(+) in shoot tissue have many adverse effects and, crucially, yield in cereals is commonly inversely proportional to the extent of shoot Na(+) accumulation. We therefore need to identify genes, resistant plant cultivars and cellular processes that are involved in salinity tolerance, with the goal of introducing these factors into commercially available crops. Through the use of an Arabidopsis thaliana mapping population, we have identified a highly significant quantitative trait locus (QTL) linked to Na(+) exclusion. Fine mapping of this QTL identified a protein kinase (AtCIPK16), related to AtSOS2, that was significantly up-regulated under salt stress. Greater Na(+) exclusion was associated with significantly higher root expression of AtCIPK16, which is due to differences in the gene's promoter. Constitutive overexpression of the gene in Arabidopsis leads to plants with significant reduction in shoot Na(+) and greater salinity tolerance. amiRNA knock-downs of AtCIPK16 in Arabidopsis show a negative correlation between the expression levels of the gene and the amount of shoot Na(+) . Transgenic barley lines overexpressing AtCIPK16 show increased salinity tolerance.

Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors.

Worldwide, 100 million people are expected to die this century from the consequences of nicotine addiction, but nicotine is also known to enhance cognitive performance. Identifying the molecular mechanisms involved in nicotine reinforcement and cognition is a priority and requires the development of new in vivo experimental paradigms. The ventral tegmental area (VTA) of the midbrain is thought to mediate the reinforcement properties of many drugs of abuse. Here we specifically re-expressed the beta2-subunit of the nicotinic acetylcholine receptor (nAChR) by stereotaxically injecting a lentiviral vector into the VTA of mice carrying beta2-subunit deletions. We demonstrate the efficient re-expression of electrophysiologically responsive, ligand-binding nicotinic acetylcholine receptors in dopamine-containing neurons of the VTA, together with the recovery of nicotine-elicited dopamine release and nicotine self-administration. We also quantified exploratory behaviours of the mice, and showed that beta2-subunit re-expression restored slow exploratory behaviour (a measure of cognitive function) to wild-type levels, but did not affect fast navigation behaviour. We thus demonstrate the sufficient role of the VTA in both nicotine reinforcement and endogenous cholinergic regulation of cognitive functions.

Acc homoeoloci and the evolution of wheat genomes.

The DNA sequences of wheat Acc-1 and Acc-2 loci, encoding the plastid and cytosolic forms of the enzyme acetyl-CoA carboxylase, were analyzed with a view to understanding the evolution of these genes and the origin of the three genomes in modern hexaploid wheat. Acc-1 and Acc-2 loci from each of the wheats Triticum urartu (A genome), Aegilops tauschii (D genome), Triticum turgidum (AB genome), and Triticum aestivum (ABD genome), as well as two Acc-2-related pseudogenes from T. urartu were sequenced. The 2.3-2.4 Mya divergence time calculated here for the three homoeologous chromosomes, on the basis of coding and intron sequences of the Acc-1 genes, is at the low end of other estimates. Our clock was calibrated by using 60 Mya for the divergence between wheat and maize. On the same time scale, wheat and barley diverged 11.6 Mya, based on sequences of Acc and other genes. The regions flanking the Acc genes are not conserved among the A, B, and D genomes. They are conserved when comparing homoeologous genomes of diploid, tetraploid, and hexaploid wheats. Substitution rates in intergenic regions consisting primarily of repetitive sequences vary substantially along the loci and on average are 3.5-fold higher than the Acc intron substitution rates. The composition of the Acc homoeoloci suggests haplotype divergence exceeding in some cases 0.5 Mya. Such variation might result in a significant overestimate of the time since tetraploid wheat formation, which occurred no more than 0.5 Mya.

[Internet information on head and neck oncology in French]. / Information Internet en langue française en oncologie ORL.

OBJECTIVE: Internet has become the first place where patients go when seeking information on their disease. The type and the quality of the medical information available on French-language websites is poorly known, especially in the field of head and neck surgery. The purpose of this study was to evaluate the quality of these sites. MATERIALS AND METHODS: We entered six keywords-"cancer du larynx", "cancer de l'amygdale", "cancer de la thyroïde", "carcinome papillaire de la thyroïde", "cancer de la langue", and "cancer de la parotide"-in two different search engines and, for each keyword, the first 50 websites were reviewed using the tool called DISCERN. With two head and neck surgeons, we rated their contents in terms of quality and comprehension. RESULTS: On 600 websites only 95 (16%) contained information that proved to be somewhat useful to patients. According to our scoring system, 8% of websites were found to be excellent, 24% good, 14% fairly good, 15% mediocre, 27% poor, and 12% very poor. Just over 60% of the websites were found to be clear. The study also showed that the order in which these websites were ranked in the search engine, their affiliation, the target population, or who financed them had little impact on quality. The websites were more likely to be high quality if they were managed by doctors and had bibliographical references as well as a date indicating a recent website update. CONCLUSION: This study again shows that the search for medical information on the Internet is time-consuming and often disappointing: very few websites provide information that is both clear and exhaustive. However, we also found that very few websites contained information that was seriously inaccurate. Given the growing popularity of the Internet, a high-quality French-language website specializing in head an neck surgery would be highly beneficial to patients, as would an ENT portal that would take them to selected websites, saving time and providing a guarantee of quality.

[Patient awareness and satisfaction of the Aurore perinatal network]. / Connaissance et satisfaction des femmes au sein du réseau de santé périnatal Aurore.

OBJECTIVES: Assess patient awareness, satisfaction and expectations three years after the implementation of the Aurore perinatal network. METHOD AND MATERIALS: Semi-guided interviews with 60 Aurore network perinatal patients, 20 having undergone in-utero transfers (IUT), 20 whose newborns were transferred to the neonate unit (NNT), and 20 post-delivery without IUT or NNT, between September 2007 and January 2007. RESULTS: Fifteen percent of patients were familiar with the Aurore perinatal network (9/60). The concepts of IUT and NNT were not associated with that of the perinatal network. The information provided helped 85 % of the patients to feel more secure (51/60). For 83 % of the patients with mother-child bond was maintained (50/60). In 90 % of cases, the teams included the father in the healthcare provision process (54/60). Patients had expectations on a greater consideration on the emotional aspect during a transfer. CONCLUSION: Few patients knew the perinatal network. They were globally satisified during a transfer, they insisted on the importance of staff empathy and availability.

[Early prenatal interview: implementation of a sheet link "carried" by patient. The Aurore perinatal network experience]. / Entretien prénatal précoce : mise en place d'une fiche de liaison << portée >> par la patiente. A propos de l'expérience du réseau périnatal Aurore.

INTRODUCTION: Early prenatal interview has needed the implementation of a new communication tool between follow-up pregnancy professionals: a link sheet filled and carried by patients. OBJECTIVE: To assess the utilization of link sheet by trained professionals, the contribution of the interview and the patient acceptation of the link sheet. MATERIALS AND METHOD: Descriptive survey from the database of link sheets returned by professionals to Aurore perinatal network and semi-guided interviews with 100 randomized patients. RESULT: One thousand one hundred and nineteen link sheets were sent to Aurore perinatal network by 55 professionals out of 78 trained. For primipare, precocious prenatal interview contribution has concerned health care security (60%) and emotional security (56%). For multipare, this contribution has concerned mainly emotional security (80%). No interviewed patient has refused link sheet principle. CONCLUSION: Link sheet principle, like implemented by Aurore perinatal network, seems pertinent to professionals and patients but it constitutes only one of the elements of network elaboration of personalized care.

[Cardiac sarcoidosis: a case report]. / Sarcoïdose cardiaque: à propos d'un cas.

Sarcoidosis is a systemic disease of unknown aetiology characterised by the formation of non caseating epithelioid cell granuloma, which can occur in virtually any organ. The involvement of the heart is an important prognostic factor in sarcoidosis. Early treatment prevents irreversible damage of the heart and seems to be associated with better prognosis.

Posthemicricoidectomy reconstruction with a composite hyoid-sternohyoid osseomuscular flap: the Rethi-Ward technique.

Our objective was to introduce a new technique for cricoid cartilage reconstruction. A 74-year-old male patient with a history of a 6-month progressively worsening dyspnea was found to have an extensive mass of the left cricoid cartilage. Although the extent of his disease would necessitate total laryngectomy, the patient underwent an open extended left hemicricoidectomy with reconstruction of the defect by a pedicled osseomuscular flap composed of the body of the hyoid bone and the contralateral sternohyoid muscle. Both frozen section and subsequent histopathological evaluation gave the diagnosis of a chondrosarcoma. A Montgomery T-tube was left in place for 3 months and was subsequently replaced by a tracheostomy tube to be removed 1 month later. Six months postoperatively, the patient remains in an excellent respiratory condition. The reconstructed site is patent without any signs of restenosis as up to date. We conclude that our technique appears to be a reliable alternative to total laryngectomy in cases of extended chondrosarcomas, as well as in cases where reconstruction of the cricoid cartilage is mandated. Further follow-up and additional cases are warranted.

[Oxytocin administration during spontaneous labour: Guidelines for clinical practice. Guidelines short text]. / Recommandations pour l'administration d'oxytocine au cours du travail spontané. Texte court des recommandations.

OBJECTIVES: To define the different stages of spontaneous labour. To determine the indications, modalities of use and the effects of administering synthetic oxytocin. And to describe undesirable maternal and perinatal outcomes associated with the use of synthetic oxytocin. METHOD: A systematic review was carried out by searching Medline database and websites of obstetrics learned societies until March 2016. RESULTS: The 1st stage of labor is divided in a latence phase and an active phase, which switch at 5cm of cervical dilatation. Rate of cervical dilatation is considered as abnormal below 1cm per 4hour during the first part of the active phase, and below 1cm per 2hours above 7cm of dilatation. During the latent phase of the first stage of labor, i.e. before 5cm of cervical dilatation, it is recommended that an amniotomy not be performed routinely and not to use oxytocin systematically. It is not recommended to expect the active phase of labor to start the epidural analgesia if patient requires it. If early epidural analgesia was performed, the administration of oxytocin must not be systematic. If dystocia during the active phase, an amniotomy is recommended in first-line treatment. In the absence of an improvement within an hour, oxytocin should be administrated. However, in the case of an extension of the second stage beyond 2hours, it is recommended to administer oxytocin to correct a lack of progress of the presentation. If dynamic dystocia, it is recommended to start initial doses of oxytocin at 2mUI/min, to respect at least 30min intervals between increases in oxytocin doses delivered, and to increase oxytocin doses by 2mUI/min intervals without surpassing a maximum IV flow rate of 20mUI/min. The reported maternal adverse effects concern uterine hyperstimulation, uterine rupture and post-partum haemorrhage, and those of neonatal adverse effects concern foetal heart rate anomalies associated with uterine hyperstimulation, neonatal morbidity and mortality, neonatal jaundice, weak suck/poor breastfeeding latch and autism. CONCLUSION: The widespread use of oxytocin during spontaneous labour must not be considered as simply another inoffensive prescription without any possible deleterious consequences for mother or foetus. Conditions for administering the oxytocin must therefore respect medical protocols. Indications and patient consent have to be report in the medical file.

Targeted in vivo expression of nicotinic acetylcholine receptors in mouse brain using lentiviral expression vectors.

Nicotinic acetylcholine receptors (nAChRs) in the brain exhibit diverse functional properties and ubiquitous distribution. Yet, except for providing a receptor for the exogenously applied nicotine of tobacco products, their role in the normal functioning of the brain has remained elusive. We have used a lentiviral expression vector to re-express the beta2 subunit specifically in the ventral tegmental area (VTA) of beta2-/- mice. The viral vector efficiently expresses beta2- subunit protein leading to new nAChR-binding sites. VTA neurons transduced by the lentiviral vector are responsive to intravenous nicotine when analyzed using in vivo electrophysiology. Nicotine-induced dopamine release from the nucleus accumbens (NuAcc) was also restored in re-expressing beta2-/- mice. Intra-VTA injection of nicotine was found to be reinforcing in both wild-type and beta2-subunit re-expressing beta2-/- mice, but not in beta2-/- mice. Furthermore, in the absence of applied nicotine, the spontaneous slow exploratory behavior of the mice was restored, whereas fast navigation did not change. This latter behavioral analysis suggests a role for beta2* nAChR, specifically expressed in the VTA, in mammalian cognitive function.

[Parental perception of their involvement in the care of their children in French neonatal units]. / Perception des parents de leur participation aux soins de leur enfant dans les unités de néonatologie en France.

BACKGROUND: The experience of becoming the parent of a sick or premature newborn can be particularly distressing for parents. They often encounter challenges to the development of their parenting roles. Perception of the hospital stay has never been analyzed on a large scale. OBJECTIVE: To analyze parents' perception of their involvement in the care of their newborn. METHODS: An internet-based survey started in France in February 2014 on the basis of a validated questionnaire composed of 222 neonatal care-related items. A quantitative and qualitative analysis was performed on the items dealing with parents' involvement until August 2014. RESULTS: The survey was completed by 1500 parents, 98 % of whom were mothers. The infants had a mean GA of 32 weeks and a mean birth weight of 1600g. Parents rated their first care of their infant with mixed emotions (joy, stress, etc.). Parents were willing to practice new skills through guided participation, even for more complex care. Skin-to-skin care was only proposed after 7 days for 20 % of the parents; 10 % of the parents did not feel secure during this practice. The need for privacy and professional guidance was essential for meaningful skin-to-skin contact. DISCUSSION: Parents' perception of participating actively in their infant's care was positive and they felt guided by the nursing team. Most of them would have been more active with guidance. Skin-to-skin care was appreciated and desired, but could become stressful if the conditions were not optimal.

[Prevention of spontaneous preterm birth (excluding preterm premature rupture of membranes): Guidelines for clinical practice - Text of the Guidelines (short text)]. / Recommandations pour la pratique clinique : prévention de la prématurité spontanée et de ses conséquences (hors rupture des membranes) ­ Texte des recommandations (texte court).

OBJECTIVES: To determine the measures to prevent spontaneous preterm birth (excluding preterm premature rupture of membranes)and its consequences. MATERIALS AND METHODS: The PubMed database, the Cochrane Library and the recommendations from the French and foreign obstetrical societies or colleges have been consulted. RESULTS: In France, premature birth concerns 60,000 neonates every year (7.4 %), half of them are delivered after spontaneous onset of labor. Among preventable risk factors of spontaneous prematurity, only cessation of smoking is associated to a decrease of prematurity (level of evidence [LE] 1). This is therefore recommended (grade A). Routine screening and treatment of vaginal bacteriosis in general population is not recommended (grade A). Asymptomatic women with single pregnancy without history of preterm delivery and a short cervix between 16 and 24 weeks is the only population in which vaginal progesterone is recommended (grade B). A history-indicated cerclage is not recommended in case of only past history of conisation (grade C), uterine malformation (Professional consensus), isolated history of pretem delivery (grade B) or twin pregnancies in primary (grade B) or secondary (grade C) prevention of preterm birth. A history-indicated cerclage is recommended for single pregnancy with a history of at least 3 late miscarriages or preterm deliveries (grade A).). In case of past history of a single pregnancy delivery before 34 weeks gestation (WG), ultrasound cervical length screening is recommended between 16 and 22 WG in order to propose a cerclage in case of length<25mm before 24 WG (grade C). Cervical pessary is not recommended for the prevention of preterm birth in a general population of asymptomatic women with a twin pregnancy (grade A) and in populations of asymptomatic women with a short cervix (Professional consensus). Although the implementation of a universal transvaginal cervical length screening at 18-24 weeks of gestation in women with a singleton gestation and no history of preterm birth can be considered by individual practitioners, this screening cannot be universally recommended. In case of preterm labor, (i) it is not possible to recommend one of the methods over another (ultrasound of the cervical length, vaginal examination, fetal fibronectin) to predict preterm birth (grade B); (ii) routine antibiotic therapy is not recommended (grade A); (iii) prolonged hospitalization (grade B) and bed rest (grade C) is not recommended. Compared with placebo, tocolytics are not associated with a reduction in neonatal mortality or morbidity (LE2) and maternal severe adverse effects may occur with all tocolytics (LE4). Atosiban and nifedipine (grade B), contrary to betamimetics (grade C), can be used for tocolysis in spontaneous preterm labour without preterm premature rupture of membranes. Maintenance tocolysis is not recomended (grade B). Antenatal corticosteroid administration is recommended to every woman at risk of preterm delivery before 34 weeks of gestation (grade A). After 34 weeks, evidences are not consistent enough to recommend systematic antenatal corticosteroid treatment (grade B), however, a course might be indicated in the clinical situations associated with the higher risk of severe respiratory distress syndrome, mainly in case of planned cesarean delivery (grade C). Repeated courses of antenatal corticosteroids are not recommended (grade A). Rescue courses are not recommended (Professional consensus). Magnesium sulfate administration is recommended to women at high risk of imminent preterm birth before 32WG (grade A). Cesarean is not recommended in case of vertex presentation (Professional consensus). Both planned vaginal or elective cesarean delivery is possible in case of breech presentation (Professional consensus). A delayed cord clamping may be considered if the neonatal or maternal state so permits (Professional consensus). CONCLUSION: Except for antenatal corticosteroid and magnesium sulfate administration, diagnostic tools or prenatal pharmacological treatments implemented since 30 years to prevent preterm birth and its consequences have not matched expectations of caregivers and families.

Ecological association between indoor radon concentration and childhood leukaemia incidence in France, 1990-1998.

The objective of this study was to evaluate the ecological association between indoor radon concentration and acute leukaemia incidence among children under 15 years of age in the 348 geographical units (zones d'emploi, ZE) of France between 1990 and 1998. During that period, 4015 cases were registered by the French National Registry of Childhood Leukaemia and Lymphoma. Exposure assessment was based on a campaign of 13 240 measurements covering the whole country. The arithmetic mean radon concentration was 85 Bq/m (range, 15-387 Bq/m) and the geometric mean, 59 Bq/m (range: 13-228 Bq/m). A positive ecological association, on the borderline of statistical significance (P=0.053), was observed between indoor radon concentration and childhood leukaemia incidence. The association was highly significant for acute myeloid leukaemia (AML) (P=0.004) but not for acute lymphocytic leukaemia (ALL) (P=0.49). The standardized incidence ratio (SIR) increased by 7, 3 and 24% for all acute leukaemia, ALL and AML, respectively, when radon concentration increased by 100 Bq/m. In conclusion, the present ecological study supports the hypothesis of a moderate association between indoor radon concentration and childhood acute myeloid leukaemia. It is consistent with most previous ecological studies. Since the association is moderate, this result does not appear inconsistent with the five published case-control studies, most of which found no significant association.

Enhanced antitumor activity of 5-fluorouracil in combination with 2'-deoxyinosine in human colorectal cell lines and human colon tumor xenografts.

We investigated the effects of 2'-deoxyinosine (d-Ino), a modulator yielding thymidine phosphorylase activity, on cellular pharmacology of 5-fluorouracil (FUra) in various human colorectal cell lines and its antitumoral activity when combined with FUra in human xenografts. Associating d-Ino with FUra increased by 38 up to 700 times the sensitivity of HT29 and FUra-resistant SW620 lines, respectively, but not of CaCO2 cells, although high levels of intracellular FdUMP and subsequent higher thymidylate synthase inhibition were observed. Cell death studies confirmed the ability of d-Ino to enhance both early and late apoptosis induced by FUra in HT29 and SW620 but not in CaCo2. Similarly, we showed that associating d-Ino increased by 68 up to 101% the Fas overexpression induced by FUra in HT29 and SW620 but not in CaCo2 cells. Anti-Fas and anti-FasL antibodies both partly reversed this increase of cell sensitivity, thus confirming the role Fas plays in the modulation of FUra toxicity by d-Ino. This Fas component could explain the discrepancy between the lines because CaCO2 has been described as insensitive to Fas-mediated apoptosis. Antitumor activity of the combination was next investigated in nude mice transplanted with SW620. Results showed that although FUra alone has little effect on SW620 xenografts (P > 0.05), associating d-Ino significantly reduced the tumor growth by 57% (P < 0.05). This study suggests that it is possible to reduce both in vitro and in vivo resistance to FUra by modulating the way the drug is converted after cellular uptake.

Metastasis of a small cell carcinoma from undetected origin to the pituitary gland--the otolaryngologist's view.

Tumour metastasis to the anterior pituitary-hypothalamic area is rare. We present a patient who had severe headache, bitemporal quadrant hemianopsia and an expanding mass in the sella turcica as revealed by MRI. Partial resection via a transsphenoidal approach was performed and postoperative radiation therapy was initiated. Immunohistochemical investigation identified the tumour as a metastatic small cell carcinoma whose primary site remained undetected for more than 12 months despite repeated oncological evaluations. We reviewed the literature on metastatic disease of the pituitary gland.

Combination of thymidine phosphorylase gene transfer and deoxyinosine treatment greatly enhances 5-fluorouracil antitumor activity in vitro and in vivo.

We reported previously that 5-fluorouracil (FUra) efficacy could be enhanced by increasing tumoral thymidine phosphorylase (TP) activity. Potentiated TP yield was achieved by either transfecting cells with human TP gene (A. Evrard et al., Br. J. Cancer, 80: 1726-1733, 1999) or associating FUra with 2'-deoxyinosine (d-Ino), a modulator providing the tumors with TP cofactor deoxyribose 1-phosphate (J. Ciccolini et al., Clin. Cancer Res., 6: 1529-1535, 2000). The purpose of the present work was to study the effects of a combined modulation (TP gene transfer + use of d-Ino) on the sensitivity to FUra of the LS174T human colorectal cell line. Results showed a near 4000 times increase of cell sensitivity in vitro after double (genetic + biochemical) modulation. This potentiation of tumor response was accompanied by a total change in the FUra anabolic pathway with a 5000% increase of cytosolic fluorodeoxyuridine monophosphate, a stronger and longer inhibition of thymidylate synthase, and 300% augmentation of DNA damage. Besides, whereas thymidine failed to inhibit FUra cytotoxicity in LS174T wild-type cells, the potentiation of the antitumor activity observed in the modulating regimen was partly reversed by thymidine, indicative of thymidylate synthase as the main drug target. The impact of this double modulation was next investigated in xenograft-bearing nude mice. Results showed that whereas FUra alone was completely ineffective on wild-type tumor growth, the size of TP-transfected tumors in animals treated with the FUra/d-Ino combination was reduced by 80% (P < 0.05). Our results suggest that FUra exhibits stronger antiproliferative activity when activated via TP through the DNA pathway and that high tumoral TP activity therefore leads to enhanced sensitivity to fluoropyrimidines.