Résultats et enseignements d’une stratégie innovante de prise en charge des nausées et vomissements chimio-induits

Current chemotherapy-induced nausea and vomiting management guidelines recommend taking into account the emetogenic potential of the chemotherapy employed as well as individual risk factors to such effects. We performed an interventional prospective study to assess the impact of an innovating therapeutic optimization strategy. The latter combines current guidelines application to a specific consultation in order to individualize the treatment. This study included 170 patients and covered a total of 1,746 days of various chemotherapies. Among these patients, 86.5% never vomited and 53.8% never had any nausea or vomiting. These results seem generally better than the ones found in the literature with all kinds of chemotherapies. Regarding them, we have attempted to highlight the determining criteria for a successful antiemetic treatment.     

HIV-1 transmission in the male genital tract

HIV-1 is mainly a sexually transmitted infection, and epithelial surfaces covering genital mucosa are the primary site of HIV-1 transmission. Although male circumcision was reported to reduce male acquisition of HIV-1 by 60%, the initial mechanisms of HIV-1 transmission in the male genitals remain elusive. We established two novel models of the adult human foreskin epithelium that allowed for polarized infection via the mucosal pole with either HIV-1-infected cells that are present in all secretions vectorizing HIV-1 or cell-free HIV-1. Efficient HIV-1 transmission occurs following 1 hr of polarized exposure of the inner, but not outer, foreskin to mononuclear cells highly infected with HIV-1, but not to cell-free virus. HIV-1-infected cells form viral synapses with apical foreskin keratinocytes, leading to polarized budding of HIV-1, which is rapidly internalized by Langerhans cells (LCs) in the inner foreskin. In turn, LCs form conjugates with T-cells, thereby transferring HIV-1. Seminal plasma from HIV-negative men mixed with cervico-vaginal secretions from HIV-positive women, which mimics the in-vivo mixture of these genital fluids during woman-to-man HIV-1 sexual transmission, decreases HIV-1 infection at the foreskin. Our results rationalize at the cellular level the apparent protective outcome of circumcision against HIV-1 acquisition by men.     

The use of a porcine intestinal cell model system for evaluating the food safety risk of Bacillus cereus probiotics and the implications for assessing enterotoxigenicity

The use of porcine intestinal cell lines in assessing toxicity of Bacillus cereus probiotics in conjunction with animal challenge trials with toxigenic B. cereus was investigated. Toxigenic and toxin deletion mutants of B. cereus and two probiotic strains (Paciflor and Toyocerin) were examined for bacterial attachment, cytotoxicity and ability to induce nitric oxide as markers of toxicity. Both cytotoxicity and production of nitric oxide were detected in wild-type toxigenic strains and the Paciflor probiotic strain but not Toyocerin. Attachment of B. cereus was low (less than 1%) in all strains. Discrimination between toxigenic B. cereus and the probiotic strains was possible semi-quantitatively via dilution. Despite cytotoxicity in vitro, challenge experiments using 10(8)-10(9) spores of the toxigenic B. cereus NVH75/95 in weaned piglets did not induce diarrhoea or intestinal lesions. Thus, the pig small intestinal epithelial intestinal cell line PSI is appropriate for identification of potential toxicity in B. cereus strains and sets a low threshold for risk of enterotoxicity to humans.     

ftz-f1 and Hr39 opposing roles on EcR expression during Drosophila mushroom body neuron remodeling

Developmental axon pruning is a general mechanism that is required for maturation of neural circuits. During Drosophila metamorphosis, the larval-specific dendrites and axons of early γ neurons of the mushroom bodies are pruned and replaced by adult-specific processes. We found that the nuclear receptor ftz-f1 is required for this pruning, activates expression of the steroid hormone receptor EcR-B1, whose activity is essential for γ remodeling, and represses expression of Hr39, an ftz-f1 homologous gene. If inappropriately expressed in the γ neurons, HR39 inhibits normal pruning, probably by competing with endogenous FTZ-F1, which results in decreased EcR-B1 expression. EcR-B1 was previously identified as a target of the TGFβ signaling pathway. We found that the ftz-f1 and Hr39 pathway apparently acts independently of TGFβ signaling, suggesting that EcR-B1 is the target of two parallel molecular pathways that act during γ neuron remodeling.     

Twenty-five years of epidemiological recording on myeloid malignancies: data from the specialized registry of hematologic malignancies of C?te d’Or (Burgundy,France)

Background

Epidemiological data on myeloid malignancies are very rare in the literature due to a lack of registration by cancer registries until 2000. The Registry of Hematologic Malignancies of the Côte d’Or Department in France has, however, steadfastly registered data on cases occurring in the Department since 1980, resulting, to date, in a database of over 5,000 cases classified according to the ICD-O-3 classification, following the most recent World Health Organization classification criteria.

Design and Methods

Twenty-five years of data on myeloid malignancies, including acute myeloid leukemia, myeloproliferative neoplasms, myelodysplastic syndromes and myelodysplastic/myeloproliferative syndromes were analyzed. World population standardized incidence rates were calculated as were as observed and relative survival.

Results

Incidence rates per 100,000 inhabitants/year were 2.5 for acute myeloid leukemia, 1.3 for myelodysplastic syndromes, 3.2 for myeloproliferative neoplasms and 0.6 for myelodysplastic/myeloproliferative syndromes. It was found that the incidence rate of myelodysplastic syndromes increased significantly over the period. The median overall survival is 8.9 months for patients with acute myeloid leukemia, 33.8 months for patients with myelodysplastic syndromes, 91.7 months for those with myeloproliferative neoplasms and 26.6 months for patients with myelodysplastic/myeloproliferative syndromes. Observed and relative 20-year survival rates are, respectively, 12% and 13% in acute myeloid leukemia, 2% and 6% in myelodysplastic syndromes and 20% and 34% in myeloproliferative neoplasms.

Conclusions

These population-based data on myeloid malignancies are the first data collected over such a long period and provide interesting information for clinicians and public health authorities, particularly given the paucity of other long-term, population-based data from cancer registries.     

Immune reconstitution inflammatory syndrome associated with HIV and leprosy

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is an unusual inflammatory reaction to an opportunistic infection that occurs in human immunodeficiency virus (HIV)-positive patients with profound immunosuppression during the reconstitution of the immune system in the initial months of highly active antiretroviral treatment. OBSERVATIONS: We describe 3 cases of leprosy occurring in patients treated with a combination of 3 antiretroviral drugs who fulfilled the criteria for IRIS. A reactional state occurred in all 3 cases. Two of the 3 patients presented an unusual ulcerous progression of the lesions not generally observed in cases of leprosy. The outcome was favorable in all 3 cases. The frequency of IRIS associated with leprosy in French Guiana and Martinique is estimated at 3 cases per 1000 HIV-positive patients receiving highly active antiretroviral treatment. CONCLUSION: Leprosy should be recognized as an IRIS-associated infection with possibility of atypical presentation.     

Effects of in vivo chronic hydrocarbons pollution on sanitary status and immune system in sea bass (Dicentrarchus labrax L.)

Following the development of an experimental system to expose adult fish to low and stable concentration of pollutant over a prolonged period, the in vivo effects of hydrocarbons on sanitary status, i.e. the health status of fish with regard to chemical pollution, and immune system in sea bass, Dicentrarchus labrax were assessed. A total of 90 fish were acclimated for 15 days, then 45 fish were exposed to the water soluble fraction (WSF) of Arabian crude oil, similar to a complex pollution by hydrocarbons chronically observed in situ in estuaries, while the 45 other control fish sustained the same experimental conditions in clean seawater. After 21 days of exposure, 30 contaminated and control fish were sampled, then 30 other fish were collected after a 15 day recovery period in clean sea water. PAH concentrations in crude oil, WSF, muscles and bile were measured by gas chromatography coupled with mass spectrometry analysis. White blood cell counts and differential leucocyte counts were determined by classical haematology methods. Cell mortality and phagocytosis activity of leucocytes were analyzed by flow cytometry. Haemolytic alternative complement activity and stress parameters were analyzed in blood plasma by spectrophotometry. After a 21 day exposure period to a mixture of 41 parent/alkylated-PAHs (835 ± 52/85 ± 1 5 ng L(-1)). Fish flesh was contaminated by a bioconcentration of naphthalene very closed to the Reference Dose for Oral Exposure estimated by US-EPA's Integrated Risk Information System, causing a potential risk for human consumers. A leucopenia due to a lymphopenia, a rise in leucocyte mortality and a decrease in phagocytosis activity were noted in contaminated fish compared to controls. All these results may be explained by the damage to membrane cells integrity by uptake of PAHs and suggested an impairment of specific and nonspecific immune systems. After a 15 day recovery period, effects were reversible for sanitary status and an offset in immunity was noted by a significant increase in leucocytes in contaminated fish compared to controls.