Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats.

Two forms of the neurodegenerative disorder spinocerebellar ataxia are known to be caused by the expansion of a CAG (polyglutamine) trinucleotide repeat. By screening cDNA expression libraries, using an antibody specific for polyglutamine repeats, we identified six novel genes containing CAG stretches. One of them is mutated in patients with spinocerebellar ataxia linked to chromosome 12q (SCA2). This gene shows ubiquitous expression and encodes a protein of unknown function. Normal SCA2 alleles (17 to 29 CAG repeats) contain one to three CAAs in the repeat. Mutated alleles (37 to 50 repeats) appear particularly unstable, upon both paternal and maternal transmissions. The sequence of three of them revealed pure CAG stretches. The steep inverse correlation between age of onset and CAG number suggests a higher sensitivity to polyglutamine length than in the other polyglutamine expansion diseases.

Probabilistic multicompartmental model for interpreting DGT kinetics in sediments.

Extensive research has been performed on the use of the DIFS (DGT-Induced Fluxes in Soils and Sediments) model to interpret diffusive gradients in thin-film, or DGT, measurements in soils and sediments. The current report identifies some areas where the DIFS model has been shown to yield poor results and proposes a model to address weaknesses. In particular, two major flaws in the current approaches are considered: (i) many studies of accumulation kinetics in DGT exhibit multiple kinetic stages and (ii) several combinations of the two fitted DIFS parameters can yield identical results, leaving the question of how to select the 'best' combination. Previously, problem (i) has been addressed by separating the experimental data sets into distinct time segments. To overcome these problems, a model considering two types of particulate binding sites is proposed, instead of the DIFS model which assumed one single particulate pool. A probabilistic approach is proposed to fit experimental data and to determine the range of possible physical parameters using Probability Distribution Functions (PDFs), as opposed to single values without any indication of their uncertainty. The new probabilistic model, called DGT-PROFS, was tested on three different formulated sediments which mainly differ in the presence or absence of iron oxides. It was shown that a good fit can be obtained for the complete set of data (instead of DIFS-2D) and that a range of uncertainty values for each modeling parameter can be obtained. The interpretation of parameter PDFs allows one to distinguish between a variety of geochemical behaviors, providing useful information on metal dynamics in sediments.

Reconstructing historical trends of Berre lagoon contamination from surface sediment datasets: influences of industrial regulations and anthropogenic silt inputs.

These last decades, the Berre lagoon (in southeastern France) has been deeply affected since the 1930s by strong inputs of contaminants associated with industrial development and since 1966 by huge inputs of freshwater and silts due to the installation of a hydroelectric power plant. Surveys of the surface sediment contamination have been sparsely performed since 1964 for management and research purposes. These surveys were performed by various laboratories that investigated different chemicals and sampling areas using different analysis protocols. Therefore, the available data are disconnected in time and space and differ in quality. In order to reconstruct coherent time series of sediment contamination from this heterogeneous datasets and to discuss the influences of industrial and hydroelectric discharges we used a statistical approach. This approach is based on Principal Component Analysis (PCA) and Fuzzy clustering analysis on data from one extensive survey realized on surface sediments in 1976. The PCA allowed identifying two geochemical indexes describing the main surface sediment geochemical characteristics. The fuzzy clustering analysis on these indexes allowed identifying sub-areas under the specific influence of industrial or hydroelectric discharges. This allowed us to reconstruct, for each sub-area, a coherent and interpretable long-term time series of sediment contamination from the available database. Reconstructed temporal trends allowed us to estimate: (i) the overall decrease of sediment contamination since the mid-1970 attributed to industrial discharge regulations enacted at this period and (ii) the dilution of the concentrations of sediment bound contaminants induced by the hydroelectric power plant and its associated particulate matter inputs.

[Normal childbirth: physiologic labor support and medical procedures. Guidelines of the French National Authority for Health (HAS) with the collaboration of the French College of Gynaecologists and Obstetricians (CNGOF) and the French College of Midwives (CNSF) -- Text of the Guidelines (short text)]. / Accouchement normal : accompagnement de la physiologie et interventions médicales. Recommandations de la Haute Autorité de Santé (HAS) avec la collaboration du Collège National des Gynécologues Obstétriciens Français (CNGOF) et du Collège National des Sages-Femmes de France (CNSF) ­ Texte des recommandations (texte court).

OBJECTIVE: The objective of these guidelines is to define for women at low obstetric risk modalities that respect the physiology of delivery and guarantee the quality and safety of maternal and newborn care. METHODS: These guidelines were made by a consensus of experts based on an analysis of the scientific literature and the French and international recommendations available on the subject. RESULTS: It is recommended to conduct a complete initial examination of the woman in labor at admission (consensus agreement). The labor will be monitored using a partogram that is a useful traceability tool (consensus agreement). A transvaginal examination may be offered every two to four hours during the first stage of labor and every hour during the second stage of labor or before if the patient requests it, or in case of a warning sign. It is recommended that if anesthesia is required, epidural or spinal anesthesia should be used to prevent bronchial inhalation (grade A). The consumption of clear fluids is permitted throughout labor in patients with a low risk of general anesthesia (grade B). It is recommended to carry out a "low dose" epidural analgesia that respects the experience of delivery (grade A). It is recommended to maintain the epidural analgesia through a woman's self-administration pump (grade A). It is recommended to give the woman the choice of continuous (by cardiotocography) or discontinuous (by cardiotocography or intermittent auscultation) monitoring if the conditions of maternity organization and the permanent availability of staff allow it and, after having informed the woman of the benefits and risks of each technique (consensus agreement). In the active phase of the first stage of labor, the dilation rate is considered abnormal if it is less than 1cm/4h between 5 and 7cm or less than 1cm/2h above 7cm (level of Evidence 2). It is then recommended to propose an amniotomy if the membranes are intact or an oxytocin administration if the membranes are already ruptured, and the uterine contractions considered insufficient (consensus agreement). It is recommended not to start expulsive efforts as soon as complete dilation is identified, but to let the presentation of the fetus drop (grade A). It is recommended to inform the gynecologist-obstetrician in case of nonprogression of the fetus after two hours of complete dilation with sufficient uterine dynamics (consensus agreement). It is recommended not to use abdominal expression (grade B). It is recommended to carry out preventive administration of oxytocin at 5 or 10 IU to prevent PPH after vaginal delivery (grade A). In the case of placental retention, it is recommended to perform a manual removal of the placenta (grade A). In the absence of bleeding, it should be performed 30minutes but not more than 60minutes after delivery (consensus agreement). It is recommended to assess at birth the breathing or screaming, and tone of the newborn to quickly determine if resuscitation is required (consensus agreement). If the parameters are satisfactory (breathing present, screaming frankly, and normal tonicity), it is recommended to propose to the mother that she immediately place the newborn skin-to-skin with her mother if she wishes, with a monitoring protocol (grade B). Delayed cord clamping is recommended beyond the first 30seconds in neonates, not requiring resuscitation (grade C). It is recommended that the first oral dose (2mg) of vitamin K (consensus agreement) be given systematically within two hours of birth. CONCLUSION: These guidelines allow women at low obstetric risk to benefit from a better quality of care and optimal safety conditions while respecting the physiology of delivery.

[Human Resources for Unplanned Activities in Obstetrics and Gynecology. Consensus statements by the CNGOF, CARO, CNSF, FFRSP, SFAR, SFMP and SFN]. / Ressources humaines pour les activités non programmées en gynécologie-obstétrique. Propositions élaborées par le CNGOF, le CARO, le CNSF, la FFRSP, la SFAR, la SFMP et la SFN.

OBJECTIVE: To determine a minimum threshold of human resources (midwives, obstetricians and gynecologists, anesthesiology and intensive care units, pediatricians) to ensure the safety and quality of unplanned activities in Obstetrics and Gynecology. MATERIALS AND METHODS: Consultation of the MedLine database, the Cochrane Library and the recommendations of authorities. Meetings of representative members in different modes of practice (university, hospital, liberal) under the aegis of and belonging to the French College of Obstetricians and Gynecologists (CNGOF), the French Society of Anesthesia and Resuscitation (SFAR), the French Society of Neonatalogy (SFN), the French Society of Perinatal Medicine (SFMP), the French College of Midwives (CNSF), the French Federation of Perinatal Care Networks (FFRSP) with elaboration of a re-read text by external experts, in particular by the members of the Boards of Directors of these authorities and of Club of Anesthesiology-Intensive Care Medicine in Obstetrics (CARO). RESULTS: Different minimum thresholds for each category of caregivers were proposed based on the number of births/year. These proposed minimum thresholds can be modulated upwards according to the types (level I, IIA, IIB or III) or the activity (existence of an emergency reception service, maternal-fetal and/or surgical activity of resort or referral). Due to peak activity and the possibility of unpredictable concomitance of urgent medical procedures, it is necessary that organizations plan to use resource persons. The occupancy rate of the target beds of a maternity ward must be 85%. CONCLUSION: These proposed minimum thresholds are intended to help caregivers providing non-scheduled perinatal as well as Obstetrics and Gynecology care to make the most of the human resources allocated to institutional bodies to ensure their safety and quality.

Combination of 13C/ 113Cd NMR, potentiometry, and voltammetry in characterizing the interactions between Cd and two models of the main components of soil organic matter.

This work allowed the characterization of the Cd-binding sites of two compounds taken as models for exudates, the main components of soil organic matter (SOM). The studied compounds were exopolysaccharides (EPS), specifically exudates of roots (polygalacturonic acid) and of soil bacteria (Phytagel). Potentiometric acid-base titrations were performed and fitting of the obtained results indicated the presence of two main classes of acidic sites, defined by their pKa values, for both EPS but of a different nature when comparing the two compounds. The two studied exopolysaccharides presented different acidic/basic site ratios: 0.15 for Phytagel and 0.76 for polygalacturonic acid. Spectroscopic techniques (13C/113Cd NMR, FTIR) distinguished different Cd surroundings for each of the studied EPS, which is in agreement with the titration results. Furthermore, these analyses indicated the presence of -COOH and -OH groups in various proportions for each exopolysaccharide, which should be linked to their reactivity towards cadmium. Cadmium titrations (voltammetric measurements) also differentiated different binding sites for each compound and allowed the determination of the strength of the Cd-binding site of the EPS. Fitting of the results of such voltammetric measurements was performed using PROSECE (Programme d'Optimisation et de Speciation Chimique dans l'Environnement), a software coupling chemical speciation calculation and binding parameter optimization. The fitting, taking into account the Cd2+/H+ competition towards exopolysaccharides, confirmed the acid-base titrations and spectroscopic analyses by revealing two classes of binding sites: (i) one defined as a strong complexant regarding its Cd2+-EPS association (logK = 9-10.4) and with basic functionality regarding H+-EPS association (pKa = 11.3-11.7), and (ii) one defined as a weak complexant (logK = 7.1-8.2) and with acidic functionality (pKa = 3.7-4.0). Therefore the combination of spectroscopic analyses, voltammetry, and fitting allowed the precise characterization of the binding sites of the studied exopolysaccharides, mimicking the main SOM components. Furthermore, the binding parameters obtained by fitting can be used in biogeochemical models to better define the role of key SOM compounds like exudates of roots and of soil bacteria on trace metal transport or assimilation.

[Utility of interferon gamma assays for diagnosis of tuberculosis in children]. / Que faut-il penser des tests sanguins in vitro pour le diagnostic de la tuberculose en pédiatrie?

In vitro assays that measure the interferon gamma production by T cells incubated with specific antigen of Mycobacterium tuberculosis may be useful in the diagnosis of tuberculosis in children. Compared to Mantoux test, these tests are easier to perform and have a greater specificity, especially because they do not cross-react with BCG vaccine and with most of environmental Mycobacteria. However, their sensitivity is not well evaluated in children. To date in pediatrics, they can be associated with Mantoux test for the diagnosis of active tuberculosis. In the diagnosis of latent tuberculosis infection, larger studies with commercial kits are required.

Solitary parathyroid adenoma: a rare cause of primary hyperparathyroidism in children.

Solitary parathyroid adenoma is a rare cause of primary hyperparathyroidism in children. We report the cases of four children, aged 7 to 14 years old, who presented with a variety of symptoms (growth retardation, glomerulonephritis, pathological fracture, mood swings). Diagnosis was based on clinical examination, imaging, and biochemical analysis. Treatment consisted of surgical excision of the adenoma. As diagnosis was delayed in all four patients, we recommend systematically checking serum calcium levels in children with certain nonspecific symptoms. Adenoma resection usually restores normal serum calcium levels and, hence, avoids further complications.

[New blood tests for diagnosis of infection with Mycobacterium tuberculosis]. / Les nouveaux tests diagnostiques de la tuberculose.

INTRODUCTION: A major challenge in tuberculosis (TB) control is the diagnosis and the treatment of latent tuberculosis infection. STATE OF THE ART: At the time, the diagnosis is based on tuberculin skin test (TST). TST is not specific, has poor sensitivity and is not easy to perform. PERSPECTIVES: Two interferon-based tests for the diagnosis of tuberculosis have just been licensed. These tests have some advantages on TST. They require only a blood sample and their results are not dependent on the examinator. Their specificity is higher than TST because they don't cross-react with BCG vaccination and with most of the environmental Mycobacterium species. Their sensitivity is higher for the diagnosis of active tuberculosis too. For latent tuberculosis, the interferon-gamma assays show a better correlation with the exposure to Mycobacterium tuberculosis than TST. The ability to detect TB of the two tests seem to be reduced in immunocompromised patients, specially in medically ones. CONCLUSIONS: Interferon-gamma assays seems to be useful tools in TB detection, but these good results have to be confirmed in larger studies with unselected patients.

[Treatment of visceral leishmaniasis in children]. / Le traitement de la leishmaniose viscérale infantile.

Visceral Leishmania infantum leishmaniasis is endemic in the south of France. For many years the mainstay for treatment of infected children was pentavalent antimony: meglumine antimoniate (Glucantime) or sodium stibogluconate (Pentostam). However these drugs are poorly tolerated and resistance similar to that observed in the treatment of Indian visceral Leishmania donovani leishmaniasis has been reported. Currently liposomal amphotericin B is being used instead of antimony for treatment of visceral leishmaniasis in children in France. In addition to being well tolerated, liposomal amphotericin B is almost 100% effective. It can be administered in six intravenous injections of 3-4 mg/kg each (days 1 to 5 then day 10). A two-day protocol (10 mg/kg/d) that would reduce overall cost by shortening the duration of hospitalization is now being studied. Another oral drug, i.e., miltefosine, has been successfully used for treatment of visceral leishmaniasis in India. However it has not been evaluated for treatment of Mediterranean visceral leishmaniasis.

Iron isotope fingerprints of redox and biogeochemical cycling in the soil-water-rice plant system of a paddy field.

The iron isotope composition was used to investigate dissimilatory iron reduction (DIR) processes in an iron-rich waterlogged paddy soil, the iron uptake strategies of plants and its translocation in the different parts of the rice plant along its growth. Fe concentration and isotope composition (δ56Fe) in irrigation water, precipitates from irrigation water, soil, pore water solution at different depths under the surface water, iron plaque on rice roots, rice roots, stems, leaves and grains were measured. Over the 8.5-10cm of the vertical profiles investigated, the iron pore water concentration (0.01 to 24.3mg·l-1) and δ56Fe (-0.80 to -3.40‰) varied over a large range. The significant linear co-variation between Ln[Fe] and δ56Fe suggests an apparent Rayleigh-type behavior of the DIR processes. An average net fractionation factor between the pore water and the soil substrate of Δ56Fe≈-1.15‰ was obtained, taking the average of all the δ56Fe values weighted by the amount of Fe for each sample. These results provide a robust field study confirmation of the conceptual model of Crosby et al. (2005, 2007) for interpreting the iron isotope fractionation observed during DIR, established from a series of laboratories experiments. In addition, the strong enrichment of heavy Fe isotope measured in the root relative to the soil solution suggest that the iron uptake by roots is more likely supplied by iron from plaque and not from the plant-available iron in the pore water. Opposite to what was previously observed for plants following strategy II for iron uptake from soils, an iron isotope fractionation factor of -0.9‰ was found from the roots to the rice grains, pointing to isotope fractionation during rice plant growth. All these features highlight the insights iron isotope composition provides into the biogeochemical Fe cycling in the soil-water-rice plant systems studied in nature.

Impact of irrigating rice paddies with groundwater containing arsenic in Bangladesh.

Soil and soil-water As profiles were obtained from 4 rice paddies in Bangladesh during the wet growing season (May-November), when surface water with little arsenic is used for irrigation, or during the dry season (January-May), when groundwater elevated in arsenic is used instead. In the upper 5 cm of paddy soil, accumulation of 13+/-12 mg/kg acid-leachable As (n=11) was observed in soil from 3 sites irrigated with groundwater containing 80-180 microg/L As, whereas only 3+/-2 mg/kg acid-leachable As (n=8) was measured at a control site. Dissolved As concentrations averaged 370+/-340 microg/L (n=7) in the upper 5 cm of the soil at the 3 sites irrigated with groundwater containing 80-180 microg/L As, contrasting with soil water As concentrations of only 18+/-7 microg/L (n=4) over the same depth interval at the control site. Despite the accumulation of As in soil and in soil water attributable to irrigation with groundwater containing elevated As levels, there is no evidence of a proportional transfer to rice grains collected from the same sites. Digestion and analysis of individual grains of boro winter rice from the 2 sites irrigated with groundwater containing 150 and 180 microg/L As yielded concentrations of 0.28+/-0.13 mg/kg (n=12) and 0.44+/-0.25 mg/kg (n=12), respectively. The As content of winter rice from the control site was not significantly different though less variable (0.30+/-0.07; n=12). The observations suggest that exposure of the Bangladesh population to As contained in rice is less of an immediate concern than the continued use of groundwater containing elevated As levels for drinking or cooking, or other potential consequences of As accumulation in soil and soil-water.

A weighted bootstrap method for the determination of probability density functions of freshwater distribution coefficients (Kds) of Co, Cs, Sr and I radioisotopes.

The objective of the study was to provide global probability density functions (PDFs) representing the uncertainty of distribution coefficients (Kds) in freshwater for radioisotopes of Co, Cs, Sr and I. A comprehensive database containing Kd values referenced in 61 articles was first built and quality scores were affected to each data point according to various criteria (e.g. presentation of data, contact times, pH, solid-to-liquid ratio, expert judgement). A weighted bootstrapping procedure was then set up in order to build PDFs, in such a way that more importance is given to the most relevant data points (i.e. those corresponding to typical natural environments). However, it was also assessed that the relevance and the robustness of the PDFs determined by our procedure depended on the number of Kd values in the database. Owing to the large database, conditional PDFs were also proposed, for site studies where some parametric information is known (e.g. pH, contact time between radionuclides and particles, solid-to-liquid ratio). Such conditional PDFs reduce the uncertainty on the Kd values. These global and conditional PDFs are useful for end-users of dose models because the uncertainty and sensitivity of Kd values are taking into account.

[Tonsillectomy in 2005]. / L'amygdalectomie en 2005.

During the past years, the number of tonsillectomies (only palatine tonsils are taken off) has decreased, indications for surgery have changed. A multi-disciplinal group of paediatricians tried to elaborate the state of the art in the field. Tonsils are the first line defense of high respiratory tract. The immune functions of their lymphoid tissue are multiple: mucosal antigens capture, presentation to lymphocytes, antigens specific proliferation of lymphocytes T and B, differentiation of lymphocytes in effectors lymphocytes and immune lymphocytes. Epithelial cells on the tonsils' surface express non-specific defense. These facts explain partly tonsils' hypertrophy. Tonsillectomy has no general immune consequences. In 2002, in France, 75,000 tonsillectomies were realized, of which 90% were in children. Tonsil's hypertrophy is the major indication, mandatory when sleep apnoeas exist. The main historical tonsillectomy indication for recurrent tonsillitis should decrease due to a more precise diagnostic (rapid test at bed site), an efficient antibiotics therapy and better care for pain. Other indications are scarce. Surgery, feasible from 9 months of age, requires a brief general anaesthesia and has very few contra-indications. The technique, operator dependent, relies on his experience. The only potentially severe complication is an haemorrhage due to scab fall between the eighth and twelfth days. It requires explanation and a written note given to parents. The possibility of lack of feeding and voice modification, usually transitory, should be known. Multiple consequences of tonsillectomy especially allergy have been alleged. Since the years 1980, it is well established that pre-existing allergy or asthma are not a contraindication. More, its deleterious impact on allergic children has not been demonstrated. Last, a gain of weight post-tonsillectomy is possible and could become a risk if excessive.

[Pediatric features of an influenza A seasonal outbreak and its burden in pediatric emergency rooms and pediatric departments]. / Caractéristiques d'une épidémie de grippe A chez l'enfant (2003-2004). Impact sur l'activité des services d'urgences et de médecine pédiatriques.

AIM OF THE STUDY: To describe epidemiological features of an outbreak of flu A in hospitalized children and to evaluate the flu's burden in pediatric and pediatric emergencies departments. POPULATION AND METHODS: Multicenter prospective study in 2 pediatric university hospitals, in Marseille, France. Nasal swabs for flu A were performed in all the febrile children admitted during winter 2003-2004. Pre and postoutbreak admissions in pediatric and pediatric emergencies departments were compared too. RESULTS: During the outbreak, 941 children were admitted and 605 were tested for flu A. Nasal swabs were positive in 111. Attack's rate was 11.8%. In these children, infants under 2 years were 66%. Respiratory forms were uncommon, although febrile seizures and digestive troubles were much frequent. The mean hospitalization duration was almost 4 days. Flu A outbreak finally increased the pediatric and pediatric emergencies departments rates of admission, of 48% and 37% respectively. CONCLUSION: Flu is frequently underestimated in children, especially in infants. Clinical forms are various. Child's vaccination is questionable in France.

[Clinical tolerance of cutaneous antiseptics in 3,403 patients in France]. / Tolérance clinique des antiseptiques cutanés chez 3 403 malades en pratique de ville.

INTRODUCTION: We prospectively studied the prevalence and the clinical forms of adverse cutaneous reactions associated with the main antiseptics used in France, the incidence of which is not well known. PATIENTS AND METHODS: Patients were included by 773 French dermatologists from May to June 2003. The 8 first consecutive adult patients for whom ambulatory treatment with a cutaneous antiseptic was prescribed were included. Patients were evaluated at inclusion and after treatment, either in person or by telephone. All reported adverse cutaneous reactions were validated by two independent experts. RESULTS: 3,403 patients (61% women, 39% men; mean age: 47) were included. Antiseptics were indicated for ambulatory surgery (45%), technical procedures (33%), and in combination with other treatments for various dermatoses, wounds and burns (12%). The 6 most widely used treatments (96% of prescriptions) were hexamidine (37%), chlorhexidine-benzalkonium (28%), chlorhexidine-alcohol (16.5%), aqueous chlorhexidine (7%), polyvidone iodine (6%) and hexamidine-chlorhexidine (1.8%). The antiseptic was prescribed for application by dabbing (57%) or spraying (40%), twice daily for a mean 10 days (3-30 days). A transient burning sensation was noticed by 4 to 7% of the patients, without any significant difference between antiseptics. Twelve adverse events were reported: contact dermatitis in 9 patients, persistent burning sensation in 2 and yellow discoloration of the skin in one. This latter case, caused by the colour of the antiseptic, cannot be considered as an adverse event. Furthermore one patient with contact dermatitis should have not been included because he had a history of cutaneous reaction related to the use of the same antiseptic. Therefore only 10 cutaneous reactions were eventually taken into account (overall prevalence=2.9 per thousand, ranging from 0% to 0.5% according to the antiseptic). There was no significant difference in terms either of the antiseptic used or the site of the treated lesion. A history of contact dermatitis was associated with a significant risk of adverse reaction (OR=7.2; CI 95: 2.0-26.4; p=0.007). The median time from onset of treatment to appearance of contact dermatitis was 4 days (0-90 days). The condition resolved following discontinuation of treatment; spontaneously in 5 patients and with dermocorticoid therapy in 5 others. DISCUSSION: The results of this study give a precise idea of how the antiseptics are used by French dermatologists in clinical practice in outpatients and how often their use is complicated by the occurrence of adverse cutaneous reactions. The low rate of such reactions (2.9 per thousand) in our study is thus in contrast with the impression given by the large number of publications related to this complication. It also tempers the high rates of sensitisation to various antiseptics found in selected at-risk patients. The most common adverse event observed was contact dermatitis and a history of this condition conferred a significant risk of cutaneous reaction. CONCLUSION: Although cutaneous antiseptics are well tolerated with a low prevalence of adverse reactions, generally mild, they should nevertheless be prescribed with caution in patients with a history of contact dermatitis.

A screening method to identify genes commonly overexpressed in carcinomas and the identification of a novel complementary DNA sequence.

We describe a differential screening method for cDNA libraries which used a combination of subtracted and PCR-amplified cDNA probes, and which can be applied to the selection of genes expressed in multiple tissues. This technique was used to identify genes commonly overexpressed in breast and basal cell carcinomas. These represent stromally dependent, invasive tumors with and without metastatic capacity. Thus, this screening sought to identify genes involved in the early stages of tumor progression. We identified a total of 16 genes, including c-erbB-2 and tissue inhibitor of metalloproteinases 3 whose products have been implicated in tumorigenesis or invasion. We also identified a novel sequence (D52) showing little homology with others described in any species, which maps to the human chromosomal band 8q21. In situ RNA hybridizations of breast carcinoma sections indicated that the D52 gene was expressed in cancer cells, whereas other genes identified in the differential screening were expressed in fibroblastic or inflammatory cells within the tumor stroma. Thus, the procedure developed in this study selected genes expressed in a diversity of cell types, indicating its potential usefulness in other systems.

[Extrapulmonary infections due to Mycoplasma pneumoniae]. / L'infection extrapulmonaire à Mycoplasma pneumoniae.

Pneumonia is the main site of infection with Mycoplasma pneumoniae in paediatric age. Nevertheless it can also give rise to other manifestations, with or without respiratory involvement. In the present review are described some unusual clinical features of M. pneumoniae in children. Encephalitis and meningoencephalitis is the most frequent neurological manifestation, but cases of meningitis, myelitis, and polyradiculitis, have been reported. Cardiac involvement is potentially severe, including pericarditis and myocarditis. Cold agglutinin haemolytic anaemia is the most frequent haematologic manifestation. Skin, renal, gastro-intestinal, osteoarticular, and other manifestations have also been reported in the literature. The pathogeny of these extrapulmonary infections is not fully elucidated and the treatment remains partly controversial. Extrapulmonary complications can occur as a result of direct invasion and/or autoimmune response.

[Mefloquine versus halofantrine in children suffering from acute uncomplicated falciparum malaria]. / Méfloquine versus halofantrine dans le traitement de l'accès simple à Plasmodium falciparum de l'enfant voyageur.

AIM OF THE STUDY: To evaluate mefloquine versus halofantrine in children suffering from acute uncomplicated falciparum malaria. MATERIAL AND METHODS: Prospective non randomized study in hospitalized children during one year. Acute falciparum malaria was defined by fever and a positive thin and/or thick smear. Malaria was presumed to have been contracted in Comoros archipelago and/or Madagascar 6 months previously. Patients were excluded, when quinine had to be used, according to World Health Organization's severity criteria. RESULTS: Forty-nine children were included: 29 were treated with halofantrine and 20 with mefloquine. Patients features in the two groups of treatment were identical, with exception for the mean time between first clinical signs and diagnosis (shorter in mefloquine group). Fever's and hospitalization's duration under treatment were similar. An increase in QTc interval was frequently observed in patients treated with halofantrine (56 versus 0%), although patients with mefloquine experienced vomiting (45 versus 0%). Relapses seemed to be more frequent with halofantrine (14 versus 0%). DISCUSSION: Halofantrine and mefloquine are efficient for falciparum malaria treatment in our pediatric series, despite a high rate of adverse events. Mefloquine's tolerance may probably be improved with changes in regimen and dose. Relapses are more frequent with a single first treatment of halofantrine, than with mefloquine. Unfortunately, features of a second halofantrine treatment are not defined.

[First-line liposomal amphotericin B for pediatric visceral leishmaniasis in southern France]. / Amphotéricine B liposomale en première intention dans la leishmaniose viscérale infantile en région Provence-Alpes-Côte-d'Azur-Corse.

AIMS OF THE STUDY: First, to describe liposomal amphotericin B (AmBisome use as first line treatment of pediatric visceral leishmaniasis and secondly, to evaluate the incidence of the disease in southern France (Provence - Alpes - Côte d'Azur - Corse). MATERIAL AND METHODS: Retrospective chart review of children referred for visceral leishmaniasis from 1996 to 2003. RESULTS: Thirty-two children under 15 years of age and suffering from visceral leishmaniasis were treated with liposomal amphotericin B as first line treatment. Clinical and biological features were usual: age <5 years, no immunodeficiency, spleen enlargement and fever, cytopenia. In this population, treatment effectiveness was evaluated to 97% (one relapse). Under treatment, patients quickly improved. Drug regimens varied from 18 to 24 mg/kg (day 1 to 5, and day 10). Four other children were not treated with first-line liposomal amphotericin B during the period. Thus, the incidence of pediatric visceral leishmaniasis was evaluated to be 0.61/100,000 children <15 years/year in the region (2.74 in the Alpes-Maritimes department, French Riviera, and 0.6 in the Bouches-du-Rhône department, Marseilles area). CONCLUSION: Liposomal amphotericin B treatment is usual for children referred for visceral leishmaniasis in this region. This treatment may be approved regarding the high level of effectiveness and the low number of adverse events. A two days drug regimen with 20 mg/kg should be evaluated. Moreover, the incidence of the pediatric visceral leishmaniasis in southern France is decreasing, but local variations may be observed.