Efficacy and safety of autologous haematopoietic stem cell transplantation in systemic sclerosis: a systematic review of the literature.

We aimed to assess the efficacy of autologous haematopoietic stem cell transplantation (HSCT) for skin sclerosis (SSc) and lung function in SSc. We performed a systematic literature review in the PubMed and Scopus databases from the earliest records to March 2016. We assessed study quality using the Cochrane tool for randomized studies, the Newcastle-Ottawa Scale for controlled cohort studies and an 18-item quality-appraisal checklist for case series. The primary outcome was the improvement of skin thickening using the modified Rodnan Skin Score (mRSS). The secondary outcome was efficacy on lung function, using diffusing capacity of the lungs for carbon monoxide and forced vital capacity (FVC). The safety of the procedure was evaluated. The literature search identified 431 citations. There were 38 studies involving a total of 344 patients who fulfilled our inclusion criteria. No meta-analysis was performed due to a high heterogeneity. There was a significant improvement in mRSS in the majority of the reports (P < 0·05), and the results were sustained for up to 8 years after autologous HSCT. The randomized studies and the four cohort studies each showed a slight but statistically significant improvement in FVC at 1 or 2 years. The treatment-related mortality calculated by pooling patients of 35 studies (336 patients with a follow-up up to 146 months) was 8·3% after autologous HSCT and 1% in cyclophosphamide-treated groups. Despite heterogeneity among the studies, we determined that autologous HSCT significantly improved cutaneous fibrosis and slightly improved FVC. Safety of autologous HSCT is acceptable given the severity of the disease. This systematic review was registered on PROSPERO, number CRD42016027951.

A mechanistic model for m-xylene treatment with a peat-bed biofilter.

The painting of vehicles in the automobile industry generates large quantities of gaseous emissions which contain volatile organic compounds (VOC) like xylenes. This polluted air has a high moisture content and a temperature around 15-20 degrees C. It is thus possible to consider its treatment by a biological way. In this paper, laboratory tests are described which led to the choice of packing material to make a biofilter having good removal efficiency. Moreover this technique is known for its simplicity and low energy cost. The maximum treatment capacity was obtained with peat. A mathematical model which makes it possible to specify the different limiting steps of the process was carried out. This considered both physical parameters of the biofilter and properties of the biofilm. By choosing a lower Henry's constant than typical air:water system, we obtain a better simulation of the xylenes concentration according to the biofilter length and applied load.

New pyridoquinoline derivatives as potential inhibitors of the fluoroquinolone efflux pump in resistant Enterobacter aerogenes strains.

Enterobacter aerogenes, one of the most frequently isolated nosocomial pathogens in France, is exhibiting increasing multidrug resistance mechanisms associated with a change in membrane permeability. For drugs of the quinolone family, mutations in the target and active efflux play a prominent role in the resistance. We report here the effect of several pyridoquinoline derivatives that restore a noticeable fluoroquinolone accumulation to resistant strains that overexpress the MarA activator. Studies of the energy-dependent quinolone efflux indicate that the most efficient derivatives tested probably inhibit the resistance process by acting as substrate competitors on the pump extruding intracellular norfloxacin.

Membrane permeability modifications are involved in antibiotic resistance in Klebsiella pneumoniae.

Two Klebsiella pneumoniae strains selected according to their high cross-resistance pattern to cephalosporins were characterized by (i) outer membrane protein content such as OmpA or nonspecific porins, (ii) MICs of various cephalosporins and unrelated antibiotics, (iii) beta-lactamase production, and (iv) active efflux of fluoroquinolones. An association of porin deficiency and beta-lactamase production induced a noticeable cephalosporin resistance. In addition to these mechanisms, the presence of an active efflux participating in high-level fluoroquinolone resistance was identified in one strain. The decrease of antibiotic uptake associated with efflux explains the Klebsiella adaptation against the drugs present in the environment.

Influence of heavy metals on the resistance of mice toward infection.

Previous studies have shown that heavy metals may exert marked immunomodulatory effects, at least in rodents, despite some discrepancies. However, the mechanism of their influence on the immune system is still unclear. As host resistance assays against experimental infections are generally considered as the most relevant criteria when predicting the immunotoxicity of drugs and chemicals, the effects of lead acetate, nickel chloride and sodium selenite on the resistance toward experimental Klebsiella pneumoniae infection was investigated in mice, with particular emphasis on the interference of the time of toxic exposure with the infectious challenge. Interestingly, one single intraperitoneal dose of 24 mg/kg lead or 4 mg/kg nickel enhanced the resistance of mice against Klebsiella pneumoniae when administered 24 hours before the infectious challenge, whereas host resistance proved to be impaired when the same dose was injected 5 hours after the infectious challenge. A 3-day pretreatment with 8 or 12 mg/kg lead also enhanced the resistance of mice but decreased it with 0.5 or 1 mg/kg nickel. In all cases, sodium selenite increased the resistance of mice toward infection. As lead, nickel and selenium appear to exert complex and possibly opposite effects on antibody response and phagocytosis, it remains to establish which immunotoxic consequences if any, an acute or chronic exposure to these heavy metals is likely to have in man.

[Chemotactic response of human polynuclear neutrophils after in vivo administration of spiramycin]. / Réponse chimiotactique des polynucléaires neutrophiles humains après administration in vivo de spiramycine.

The chemotactic response of polymorphonuclear leukocytes using the agarose method, has been studied in six healthy volunteers, immediately prior and after a 5-day oral administration of spiramycin, 6 million units per day. The influence of spiramycin proved to be small as the directed and spontaneous migration were decreased by 21% and 18% respectively. Despite the fact that spiramycin can penetrate into leukocytes, these results indicate that no clinically relevant alterations of chemotaxis are likely under therapeutic conditions.

Effects of josamycin on polymorphonuclear leucocyte chemotaxis.

The effects of josamycin on the chemotactic response of blood polymorphonuclear leucocytes were studied. After oral administration of 2 g/day or 50 mg/kg/day for five days in man and rats respectively, polymorphonuclear chemotaxis was reduced by 20%. After in-vitro incubation with 10 mg/l josamycin chemotaxis was unaltered, whereas a 15% decrease was noted with 25 mg/l josamycin. These data suggest that josamycin is unlikely to severely impair chemotaxis in patients.

Effects of erythromycin, josamycin and spiramycin on rat polymorphonuclear leukocyte chemotaxis.

The effects of three macrolide antibiotics were studied on rat polymorphonuclear leukocyte chemotaxis. Rats were given 25 mg/kg twice a day of either erythromycin, josamycin or spiramycin by gastric intubation for 5 days. In all cases, chemotaxis was found to be impaired by 10-20% only. As macrolides are known to reach high intracellular concentrations within polymorphonuclear leukocytes, our results suggest that these antibiotics are unlikely to exert a deleterious influence on the chemotactic response of treated patients.

[New technic of therapeutic abortion: aspiration]. / Nouvelle technique d'avortement thérapeutique: l'aspiration.

PIP: A new technique for therapeutic abortion, aspiration, is described. Necessary equipment includes a vacuum aspirator, cannulae of glass or pyrex, and a container for the debris. After anesthesia and cervical dilation, the uterine contents are aspirated via the cannula; observation of the products in the glass cannula enables the operator to judge this accurately. The method is less traumatic than classical methods and carries a smaller risk of postoperative complications. In addition, its use may reduce the risk of metastasis in hydatidiform mole.^ieng