Biomedical subjects

A Andremont

Publications and source records attributed to A Andremont.

At least 37 records · Page 2Linked to original sources

PubMed1999

In vivo fate and immune pulmonary response after nasal administration of microspheres loaded with phosphorylcholine-thyroglobulin.

Phosphorylcholine is a widely occurring hapten which is present in the cell wall of many prokaryotes. It is, therefore, an attractive candidate for the development of a vaccine against many bacterial diseases. Poly(D,L-lactide-co-glycolide) microspheres loaded with phosphorylcholine linked to thyroglobulin (PC-Thyr) as protein carrier were prepared. The effect of the protein concentration on antigen encapsulation and release as well as on microsphere morphology has been investigated. When administered intranasally, PC-Thyr-loaded microspheres were taken up by epithelial cells of the nasopharyngeal associated lymphoid tissue and induced a specific IgA and IgG response in pulmonary secretions as well as a strong systemic immune response in BALB/c mice.

Administration, Intranasal↗

PubMed1999

Systemic lupus erythematosus-associated catastrophic antiphospholipid syndrome occurring after typhoid fever: a possible role of Salmonella lipopolysaccharide in the occurrence of diffuse vasculopathy-coagulopathy.

We report a case of well-documented typhoid fever in a 30-year-old woman with inactive systemic lupus erythematosus with asymptomatic lupus anticoagulant and high-titer anticardiolipin antibody (aCL). Despite prompt eradication of the Salmonella typhi obtained with appropriate antibiotic therapy, multiple organ system dysfunction occurred. The central nervous system was involved, with ischemic infarcts in the occipital lobes. High-dose corticosteroid therapy failed to improve the neurologic manifestations, which responded to repeated plasmapheresis. A sharp fall in aCL and anti-beta2-glycoprotein I antibody titers was recorded before the start of plasmapheresis. At the same time, IgM and IgG antibodies to Salmonella group O:9 lipopolysaccharide became detectable; the IgM antibodies disappeared within 4 months, whereas the IgG antibodies remained detectable during the next 13 months. Despite treatment with high-dose corticosteroids and cyclophosphamide, rapidly progressive glomerulonephritis developed, leading to chronic renal failure. There is convincing evidence of a link between the S. typhi infection and the ensuing catastrophic syndrome in this patient, probably precipitated by bacterial antigens.

Adult↗

PubMed1999

Emergence and spread in French hospitals of methicillin-resistant Staphylococcus aureus with increasing susceptibility to gentamicin and other antibiotics.

Oxacillin (methicillin) resistance in methicillin-resistant Staphylococcus aureus (MRSA) is associated with an increased incidence of resistance to other antibiotics, which has increased since it was first reported in 1969. In 1992 a new phenotype of MRSA arose in France; this was characterized by a heterogeneous expression of resistance to oxacillin and susceptibility to various antibiotics, including gentamicin but also tetracycline, minocycline, lincomycin, pristinamycin, co-trimoxazole, rifampin, and fusidic acid. In French hospitals a longitudinal nationwide surveillance of antibiotic resistance in S. aureus has allowed for the detection of changes in antibiotic susceptibility profiles. Seven French clinical laboratories (six from the mainland and one from the West Indies) reported the results of susceptibility testing of 57,347 S. aureus strains isolated in their institutes between 1992 and 1998. Over a 7-year period the incidence of isolation of gentamicin-susceptible MRSA (GS-MRSA) strains has steadily increased to represent, in 1998, 46.8 to 94.4% of the MRSA strains, irrespective of the overall incidence of MRSA. Two predominant types recognized by pulsed-field gel electrophoresis (PFGE) accounted for the majority of the GS-MRSA in different mainland hospitals, both differing from the predominant type observed in the French West Indies. Some GS-MRSA and gentamicin-resistant MRSA (GR-MRSA) strains had closely related PFGE profiles, and hybridization studies confirmed the lack in GS-MRSA of the aac6'-aph2" gene, which confers resistance to all aminoglycosides, with conservation of the ant4' gene, which confers resistance to kanamycin, tobramycin, and amikacin. Thus, it is likely that certain GS-MRSA strains could have emerged from GR-MRSA strains by excision or deletion of the aac6'-aph2" gene.

Cross Infection↗

PubMed1998

Development of ciprofloxacin-loaded nanoparticles: physicochemical study of the drug carrier.

This paper describes the optimization of the preparation of ciprofloxacin-loaded polyethylbutylcyanoacrylate (PEBCA) nanoparticles. The association of ciprofloxacin with nanoparticles was performed by emulsion polymerization, but successful entrapment was only obtained in the presence of acetone in the polymerization medium. This preparation process led to a stable ciprofloxacin nanoparticle suspension, with a mean size value twice as high as that obtained in the absence of drug, and an association efficiency of 82%. Moreover, the molecular weight value of ciprofloxacin nanoparticles was shown to be reduced as compared with unloaded nanoparticles. Drug release from the colloidal carrier in medium containing esterase was found to be very slow (a maximum of 51.5% after 48 h), suggesting that this release resulted from bioerosion of the polymer matrix. Interestingly, it was observed that 30.5% of the initial amount of ciprofloxacin was not detectable by HPLC analysis after nanoparticle preparation and corresponded either to ciprofloxacin covalently bound to PEBCA or to ciprofloxacin chemically degraded during the polymerization process. 19F-NMR analysis demonstrated that ciprofloxacin entrapped into nanoparticles was only in its neutral form. The measurements of molecular weight suggest the participation of the antibiotic as an anionic polymerization initiator, leading to the formation of a chemical bond between some of the drug and the polymer. These data allowed us to propose a model describing the association of ciprofloxacin with PEBCA nanoparticles obtained by emulsion polymerization.

Anti-Infective Agents↗

PubMed1998

[Cholera in a Paris resident with no history of travel. A case report].

BACKGROUND: Cases of imported cholera are frequently observed, but cholera almost never occurs in subjects who have never travelled to an endemic area. In the last 30 years, 4 cases have been reported. We report an indigenous case diagnosed in Paris in September 1996. CASE REPORT: The patient was hospitalized for severe dehydration and acute renal failure. Cultures of a fecal specimen grew Vibrio cholerae O1 Ogawa serotype. An epidemiological study was conducted to identify the vehicle and mode of contamination and suggested that this case was associated with the consumption of fresh sorrel imported from West Africa. No other cases were identified in contacts of the patient. DISCUSSION: Asymptomatic carriage of V. cholerae is rare. However, air travel has allowed people to arrive in non-endemic areas during the incubation period. The agent may also be transported in contaminated foods. Cholera should be suspected in all adults presenting acute watery diarrhea with severe dehydration. History taking should also look for risk exposure and these patients should be systematically asked about possible exposures.

Acute Kidney Injury↗

PubMed1998

Mucosal immunogenicity elicited in mice by oral vaccination with phosphorylcholine encapsulated in poly (D,L-lactide-co-glycolide) microspheres.

Poly(D,L-lactide-co-glycolide) microspheres loaded with phosphorylcholine linked to thyroglobulin (PC-Thyr) as protein carrier were prepared. The entrapment efficiency reached 80% when the initial protein:polymer ratio was 1:8. Ninety-four percent of the loaded microspheres had a diameter < or = 10 microns. The encapsulation process did not alter PC-Thyr absorbance nor PC antigenic reactivity. Oral administration of these microspheres induced a specific IgA response in intestinal, pulmonary and vaginal secretions, as well as a strong specific systemic immune response in female Balb/c mice. This suggests the need to explore further the potential ability of PC-Thyr loaded microspheres to protect against infections caused by PC-bearing microorganisms which invade or colonize different mucosal sites.

Administration, Oral↗

PubMed1998

Drug targeting by polyalkylcyanoacrylate nanoparticles is not efficient against persistent Salmonella.

PURPOSE: We have investigated the efficacy of colistin and ciprofloxacin, free or bound to polyalkylcyanoacrylate nanoparticles, for the targeting and eradication of Salmonella persisting in the organs of the mononuclear phagocyte system. METHODS: A model of persistent S. typhimurium infection was developed in C57BL/6 mice using i.v. inoculation of the plasmid-cured strain C53. RESULTS: In vivo and ex vivo experiments showed that the persisting bacteria seem to evolve to a nongrowing state during experimental salmonellosis. In vivo treatment with free or nanoparticle-bound colistin did not significantly reduce the number of viable Salmonella C53, either in the liver or the spleen of infected mice. In contrast, in vivo treatment with ciprofloxacin led to a significant decrease of bacterial counts in the liver whatever the stage of infection and the form used. However, none of the treatments were able to sterilize the spleen or the liver. In ex vivo experiments, colistin was only active against bacteria recovered during the early phase of infection, whereas ciprofloxacin exerted its activity at all times postinfection. CONCLUSIONS: We suggest that the micro-environment in which the bacterial cells persist in vivo probably causes dramatic changes in their susceptibility to antimicrobial agents.

Animals↗

PubMed1998

Neutropenic infections: a review of the French Febrile Aplasia Study Group trials in 608 febrile neutropenic patients.

From 1986 to 1992, the Febrile Aplasia Study Group conducted a series of studies involving severely neutropenic patients. The average duration of neutropenia was 21 days, following chemotherapy for leukaemia, or chemotherapy/radiotherapy as part of a conditioning regimen for autologous or allogeneic bone marrow transplantation. A total of 591 evaluable febrile episodes were randomized to treatment with either ceftazidime 3 g daily + amikacin (the reference regimen; n=246), ceftazidime alone (n=98), ceftazidime + vancomycin (n=77), ceftazidime + ciprofloxacin (n=64) or piperacillin/tazobactam + amikacin (n=106). Only three patients treated with the reference dose of ceftazidime died or suffered serious morbidity from infections caused by Gram-negative bacteria. Piperacillin/tazobactam + amikacin was the only antibiotic regimen to have an effect significantly different from the reference regimen. Piperacillin/tazobactam + amikacin produced a higher rate of defervescence at 72 h (P=0.003), fewer days of fever (P < 0.001), fewer superinfections (P=0.018), a less frequent requirement for addition of vancomycin (P=0.01) and a higher incidence of treatment judged to be a 'complete success' (enduring defervescence without a change in antibiotics) (P=0.04). Despite the improved control of Gram-positive microorganisms, the infection-related death rate remained unchanged from 1987 to 1992. An increase in disseminated aspergillosis compensated for the reduction in lethal Gram-positive septicaemia.

Amikacin↗

PubMed1998

Earlier positivity of central-venous- versus peripheral-blood cultures is highly predictive of catheter-related sepsis.

To diagnose catheter-related sepsis without removing the catheter, we evaluated the differential positivity times of cultures of blood drawn simultaneously from central venous catheter and peripheral sites. In a 450-bed cancer reference center, simultaneous central- and peripheral-blood cultures were prospectively performed for patients with suspicion of catheter-related sepsis over an 18-month period. Data for 64 patients for whom the same microorganisms were found when central- and peripheral-blood samples were cultured were retrospectively reviewed by two independent physicians blinded to the differential positivity time values in order to establish or refute the diagnosis of catheter-related sepsis. The diagnosis was established in 28 cases, refuted in 14, and indeterminate in the remaining 22. The differential positivity time was significantly greater for patients with catheter-related sepsis (P < 10(-4)). A cutoff limit of +120 min had 100% specificity and 96.4% sensitivity for the diagnosis of catheter-related sepsis. These results strongly suggest that measurement of the differential positivity time might be a reliable tool facilitating the diagnosis of catheter-related sepsis in patients with an indwelling catheter.

Catheterization, Central Venous↗

PubMed1998

Synthesis and in vitro antibacterial activity of catechol-spiramycin conjugates.

The first synthesis of siderophore conjugates of two macrolide antibiotics, spiramycin 1 and neospiramycin 2, which are unable to penetrate the outer membrane of gram-negative bacteria are described. These novel conjugates were prepared by regioselective acylation of a hydroxyl function of 1 and 2 with a dihydroxybenzoic Fe(III) complexing ligand linked via a carboxyl group containing spacer to the macrolide antibiotics. The preliminary biological evaluation of these novel conjugates under standard and iron depleted conditions has shown that their antibacterial activity was comparable to that of spiramycin 1 and neospiramycin 2.

Anti-Bacterial Agents↗

PubMed1997

Single-step polymerase chain reaction for combined gene detection and epidemiological typing in three bacterial models.

We describe a new polymerase chain reaction (PCR) for combined gene detection and epidemiological typing (COGEDET), which allows bacterial typing and gene detection in a one-step assay. This assay, in which target gene-specific primers are used under low-stringency annealing conditions, was evaluated on 32 Staphylococcus aureus strains using toxic shock syndrome toxin 1 (tst) primers, 30 Clostridium difficile strains using toxin A (toxA) primers, and 30 Escherichia coli strains using cytotoxic necrotizing factor (cnf) primers. Typing performances with COGEDET were compared to those of conventional random amplification polymorphic DNA (RAPD), and gene detection performances, to those of conventional PCR followed by Southern blot hybridization. Concordances between conventional PCR/Southern blot and COGEDET were 96.9, 100 and 96.7% for the detection of the tst, toxA and cnf genes, respectively. Discriminatory indexes for the conventional RAPD and COGEDET techniques were similar in the three bacterial species tested. These results show that the COGEDET assay can replace two separate assays for typing and genes detection respectively, thus saving both technicians' time and reagents.

Bacterial Toxins↗

PubMed1997

Decontamination of polymerase chain reaction reagents for detection of low concentrations of 16S rRNA genes.

We describe a polymerase chain reaction (PCR) that allowed detection of rRNA consensus sequences from the DNA extracted from a wide range of bacterial species in amounts as low as 10 fg. To avoid false positive results with universal primers for 16S rRNA PCR, contaminating DNA had to be eliminated from the polymerase preparations. Decontamination was undertaken before PCR to optimize treatment with DNaseI, and was followed by DNase inactivation at 94 degrees C for 50 min, which eliminated contaminating DNA at concentrations of up to 100 pg. After optimization of PCR conditions for each polymerase. Deep Vent Exo-polymerase (New England Biolabs, Beverly, MA), and super-Taq polymerase (HT Biotechnology, Cambridge, UK) were more effective than Ampli-Taq polymerase (Perkin-Elmer Cetus, Norwalk CT), Ampli-Taq LD polymerase (Perkin-Elmer Cetus) or Deep-vent polymerase (New England Biolabs). The technique described in this article might prove to be a universal method for PCR detection of small numbers of unidentified bacteria in usually sterile clinical sites, such as blood and cerebrospinal fluids, in which a broad spectrum of pathogens can be expected.

DNA, Bacterial↗

PubMed1997

Evaluation of growth promotion and inhibition from mycobactins and nonmycobacterial siderophores (Desferrioxamine and FR160) in Mycobacterium aurum.

Heterologous mycobactins and the synthetic FR160 [N4-nonyl,N1,N8-bis(2,3-dihydroxybenzoyl) spermidine hydrobromide (C3 0H4 6N3, O6 Br)] promoted growth in Mycobacterium aurum in low concentrations. They were otherwise highly inhibitory, as opposed to homologous mycobactin, which was strictly growth promoting. Desferrioxamine B (Desferal) had no significant effect on growth.

Cell Division↗

PubMed1997

Protective immunity against Salmonella typhimurium elicited in mice by oral vaccination with phosphorylcholine encapsulated in poly(DL-lactide-co-glycolide) microspheres.

Encapsulation of vaccines in biodegradable microspheres provides excellent mucosal immunogens with a high potential for immunization against bacterial infections. We tested the protective immunity elicited by intragastric vaccination with phosphorylcholine (PC) encapsulated in poly(DL-lactide-co-glycolide) (DL-PLG) microspheres against Salmonella typhimurium in a mouse model of invasive intestinal infection. We chose PC as the antigen because it was found to elicit an immune response after intestinal exposure of mice to PC-bearing S. typhimurium and because anti-PC immunity protects mice against Streptococcus pneumoniae, another PC-bearing microorganism. Mice were primed intragastrically on days 1, 2, and 3 and boosted on days 28, 29, and 30 with PC (280 microg) coupled to porcine thyroglobulin (PC-thyr) encapsulated in DL-PLG microspheres, free PC-thyr, or blank microspheres. A significant rise in anti-PC immunoglobulin A (IgA) titers, as measured by an enzyme-linked immunosorbent assay, was observed in the intestinal secretions after immunization with PC-loaded microspheres, compared to the titers of mice immunized with free PC-thyr or blank microspheres. This antibody response peaked 14 days after the last boost and correlated with a highly significant resistance to oral challenge by S. typhimurium C5 (P < 10(-3)). Control mice were primed intraperitoneally on day 1 with 15 microg of PC in complete Freund's adjuvant and boosted on days 10, 14, and 20 with the same dose without adjuvant but via the same route. In these mice, the levels of anti-PC IgA in intestinal secretions were equivalent to those of the mice intragastrically immunized with PC-loaded microspheres, but protection was significantly weaker, suggesting that either the IgAs were not functional or that other immune mechanisms are important in protection. Taken together, our results highlight the potential of antigen encapsulation in DL-PLG microspheres for eliciting protective immunity against invasive intestinal bacterial diseases and suggest that a similar strategy could be used against diseases caused by other PC-bearing microorganisms.

Administration, Oral↗

PubMed1996

Phase I study of a recombinant adenovirus-mediated gene transfer in lung cancer patients.

BACKGROUND: Despite vigorous efforts at curbing tobacco consumption and aggressive combined-modality treatment programs, both the incidence of and the mortality from lung cancer have remained virtually unchanged in the last 10 years. More effective innovative therapies are clearly needed. The direct transfer into tumor cells of tumor suppressor genes or toxic gene products that specifically promote tumor cell death and spare nonmalignant cells is a potentially novel anticancer treatment approach that should be investigated. PURPOSE: On the basis of compelling preclinical data, we initiated a phase I study involving six patients with inoperable lung cancer and an endobronchial lesion accessible by bronchoscopy. Our purpose was to evaluate the feasibility, tolerance, and clinical, biologic, and immunologic effects of the intratumoral administration of a recombinant, replication-deficient adenovirus (rAd.RSV beta-gal), using the Rous sarcoma virus promoter to drive transcription of the Escherichia coli lacZ marker gene that encodes for the bacterial enzyme beta-galactosidase (beta-gal). METHODS: From June 1994 through April 1995, six patients (five males and one female) were enrolled in the trial. A single dose of recombinant virus suspension containing 10(7) or 10(8) plaque-forming units (PFU) was injected intratumorally into two successive cohorts of three patients. Eligible patients received concomitant chemotherapy. Patients were kept under isolation conditions from 3 days before the injection was given until virus excretion was undetectable. Biopsy specimens of the tumor and surrounding mucosa were collected on the 8th day and at 1, 2, and 3 months after injection. They were analyzed by cell culture, polymerase chain reaction (PCR), and beta-gal expression for the presence of recombinant adenovirus. So that the risk of virus recombination or complementation could be minimized, wildtype adenovirus carriers among the hospital staff (identified by PCR) were excluded from contact with patients who were potentially excreting recombinant virus. RESULTS: beta-gal was expressed in tumor biopsy specimens of three patients (one who received the 10(7) PFU dose level and two who received 10(8)). Bronchoalveolar lavage specimens collected immediately after injection were positive for recombinant adenovirus when analyzed in culture and by PCR. All biologic fluids were negative for recombinant virus as judged by PCR after day 12, with the exception of bronchoalveolar lavage specimens (positive PCR up to 90 days in two of three patients treated with 10(8) PFU). The blood samples obtained from the three patients treated with 10(8) PFU showed positive PCR results immediately after virus injection. Patients were kept in isolation for a median of 17 days. The most common toxic effects were moderate bleeding (occurring in two patients) during bronchoscopy and fever (seen in four patients). Endoscopic and clinically objective antitumor responses were seen in four patients, including one patient who showed a complete response by pathologic evaluation. The median survival for the patients was 12.5 months (range, 3-16+ months). Throughout the study, hospital staff remained negative for recombinant adenovirus infection. CONCLUSIONS: This ongoing phase I study has demonstrated that a recombinant adenovirus-mediated marker gene, such as rAd.RSV beta-gal, can be safely introduced into humans and that the gene product is expressed by lung tumor cells of the host.

Adenoviridae↗

PubMed1996

Intracellular distribution of ampicillin in murine macrophages infected with Salmonella typhimurium and treated with (3H)ampicillin-loaded nanoparticles.

The intracellular distribution of (3H)ampicillin-loaded polyisohexylcyanoacrylate nanoparticles was studied in murine macrophages (peritoneal cells and the J774 cell line) infected by Salmonella typhimurium C5, using ultrastructural autoradiography. Ampicillin penetration and retention into the cells obviously increased by means of nanoparticles. After short-term (2-4 h) treatment with the nanoparticle formulation, numerous intracellular bacteria were seen to be in the process of destruction. The tritium labelling was located in the cell cytoplasm and inside vacuoles in which bacteria undergoing degradation were often present. After long-term (12 h) treatment, numerous spherical bodies (d: 100 nm to 500 nm) and larger forms (2 microns) were seen in the vacuoles. Radioactivity was mainly found to be localized on the spherical bodies, indicating marked damaging action of the ampicillin on the bacterial walls. The targeting of ampicillin therefore allowed its penetration into the macrophages and vacuoles infected with S. typhimurium.

Ampicillin↗

PubMed1996

Random amplified polymorphic DNA typing versus pulsed-field gel electrophoresis for epidemiological typing of vancomycin-resistant enterococci.

Sixty vancomycin-resistant vanA mutant Enterococcus faecium (VRE) isolates, collected during a 40-month period from 48 patients hospitalized in a French Cancer Referral Center, were typed by using random amplified polymorphic DNA (RAPD), and the results were compared with those previously obtained by typing with SmaI pulsed-field gel electrophoresis (PFGE), which is currently recognized as the "gold standard." The discriminating power of RAPD typing, with seven primers and 11 combinations of primers, was tested on 18 strains, and only the most discriminating combination was further tested on the whole collection. We compared the epidemiological usefulness of RAPD typing of 60 clinical VRE isolates with that of SmaI PFGE typing. With primers AP4 and ERIC1R, RAPD generated 30 patterns versus the 36 patterns generated by SmaI PFGE. However, this did not hamper the epidemiologically correct clustering of 15 related strains and the detection of multiple colonization in nine patients. We conclude that this simple RAPD technique is well suited to the epidemiological typing of VRE and the monitoring of its nosocomial spread.

Bacterial Typing Techniques↗

PubMed1995

Totally implanted catheters to reduce catheter-related infections in patients receiving interleukin-2: a 2-year experience.

A high incidence of bacterial infections has been previously reported during interleukin-2 (IL-2) treatment, mainly due to catheter-related infections. Antibiotic prophylaxis has been successfully used to decrease such infections. The goal of this study was to evaluate an alternative way to reduce catheter-related infections in IL-2-treated patients by the use of totally implanted catheters. A total of 74 patients with metastatic renal cell carcinoma, referred to our institution to receive IL-2 from March 1989 to July 1991, were included in this prospective study. IL-2 was given on a 2-days-a-week schedule (24 x 10(6) IU m-2 day-1) either alone (41 patients) or in association with interferon gamma (33 patients). All these patients were prospectively evaluated for fever, bacteremia and line-site infection. Seven patients (9.5%) had one (2 patients) or more (5 patients) positive blood cultures with Staphylococcus aureus. Antibiotics were used only in 5 patients, and the catheter had to be removed in only 2 of these patients. In the other patients, no further infection developed despite the lack of antibiotics. Moreover, 9 patients had positive blood cultures with Staphylococcus epidermidis (1.9% of total number of blood cultures). In conclusion, a totally implanted catheter appears to reduce the incidence of infections in IL-2-treated patients, at least on a 2-days-a-week schedule.

Antineoplastic Agents↗