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Biomedical subjects

P H Lagrange

Publications and source records attributed to P H Lagrange.

At least 73 records · Page 4Linked to original sources

Novel, plasmid-encoded, TEM-derived extended-spectrum beta-lactamase in Klebsiella pneumoniae conferring higher resistance to aztreonam than to extended-spectrum cephalosporins.

A clinical isolate of Klebsiella pneumoniae was more resistant to aztreonam than to cefotaxime and ceftazidime. It produced a clavulanate-susceptible beta-lactamase with an isoelectric point of 6.3 which readily hydrolyzed penicillins, cefotaxime, and ceftazidime, but which hydrolyzed aztreonam poorly. The enzyme was encoded by a gene on a 15-kb plasmid; the gene hybridized with an intragenic DNA probe of blaTEM.

Anti-Bacterial Agents↗

[Bactericidal activity of cells of the immune system].

The acquisition of a bactericidal activity by the cellular immune system is one of the mechanisms of prime importance for the development of the cellular resistance to infection. It involves the specific recognition of the pathogenic microorganism associated with the direct or indirect activation of effector cells. The in vivo type of replication of the infectious microorganism provides the adaptive response of the host. This response differs according to extracellular or intracellular multiplying microorganism. The acquired resistance to extracellular multiplying bacteria (ie, capsulated bacteria) is linked to the B cell production of specific antibodies that are associated with the activated complement fragments, that enable bacterial opsonization, activation and recruiting of polymorphonuclear phagocytes. These cells did acquired a greater capacity to ingest and to kill bacteria at sites of infection. Such phenomenon could be also associated with acute purulent necrotizing lesions. On the other hand, intracellular multiplying bacteria are mostly associated with chronic granulomatous non pyogenic lesions, and such bacteria are also able to survive and to replicate into the non activated professional mononuclear phagocytes. The acquired resistance against such bacteria is linked to the occurrence of a non specific bactericidal capacity of macrophages, that inhibit and/or kill replicative intracellular microorganisms. Such macrophage bactericidal capacity is dependent upon the gradual and stepwise cellular activation provided by several extracellular and membrane associated signals. Sequential signals are produced by the specific recognition of committed T CD4+ lymphocytes mediated by the infected macrophages through the MHC class 2 restriction of the peptide presentation. One of the major signal of cellular communication to induce macrophage priming involves the production of Interferon gamma (IFN gamma). Secondary signals are needed to induced full macrophage activation defined by phenotypic, metabolic and functional alterations which include their acquired increase capacity to kill intracellular bacteria and tumor cells. Secondary signals involve the production of cytokines such as TNF alpha, IL2 and GM-CSF being transduced by bacterial cell wall products (such as lipopolysaccharide, teichoic acid, or lipoarabinomanan) or by the calcitriol pathway recently described during mycobacterial infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗

[Action of teicoplanin on coagulase negative staphylococci in hospital units of the hospital Hôtel-Dieu in Paris].

Teicoplanin, a glycopeptide antibiotic, is active against Staphylococci, with the exception of some strains of coagulase negative Staphylococci (SCN). Determination of the in vitro activity of teicoplanin by standard disk methodology is not sufficient, and has to be confirmed by the determination of the minimal inhibitory concentration (MIC) for all strains presenting an inhibition zone diameter below 17 mm. We have studied during four months, the susceptibility of SCN to teicoplanin isolated from different units of the hospital, and in particular from the haematology unit (HU). 186 strains were isolated, 35 p. cent from HU and 65 p. cent from the other units of the hospital. All strains belonged to 11 species: 136 S. epidermidis, 14 S. haemolyticus, 8 S. lugdunensis, 5 S. warneri, 4 S. saprophyticus, 3 S. sciuri, 3 hominis, 2 S. chromogens, 2 xylosus, 2 S. cohnii and 1 S. schleiferi. Twenty five strains out of 186 (13.4%) presented a MIC of 8 or 16 mg/l (MIC verified by the agar dilution method): 7 S. haemolyticus, 16 S. epidermidis, 1 S. warneri et 1 S. capitis. During this study SCN resistant to teicoplanin were never isolated. Twelve out of 25 came from the HU, which correspond to 18 p. cent of the isolated strains in this unit. This result was not significantly different, compared to that of the other units.

Dose-Response Relationship, Drug↗

[Are antibiotics immunomodulators?].

This review of the literature, although non complete, involving different observations, experiments and documented demonstrations, suggest the real importance of the interrelations existing between, the pathogenic bacteria, the specific and non specific reactions of the normal or infected host and the antibiotics. The bacterial infections are potent immunomodulators by causing significant alterations in one or more mediators of homeostasis (coagulation, complement, inflammation), inducing cellular and tissular alterations more or less dramatic depending upon the number, the virulence of the bacteria and the immune status of the host. Antibiotics in reducing the number of the infecting pathologic bacteria, in modifying their pathologic and virulence factors might them be considered as immunorestoring molecules. On the other hand, when large numbers of bacteria are killed rapidly by bactericidal antibiotics, their cytoplasmic enzymes or bacterial cell wall structures, are rapidly released locally and are able to amplify the various systems involved in the deleterious inflammatory reaction. Thus depending on their dose and their mode of action, antibiotics could be considered as immunomodulators, albeit indirectly in modifying the pathophysiology of the host, in inhibiting or enhancing the release of immunoreactive bacterial molecules. Moreover antibiotics have been shown to interfere directly on the non specific and specific defenses mechanisms. Until the recent years, only the immunotoxicological aspect has been evaluated, involving mostly the immunopharmacologic screening of the antibiotics effects on phagocytic cells or on the effectors of the immune responses. Several recent examples are given that illustrate a new approach looking at the molecular level of the cellular action of antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

Evaluation of a chemiluminometric immunoassay for detection of Chlamydia trachomatis in the urine of male and female patients.

A chemiluminometric immunoassay (Magic Lite Chlamydia) for detection of Chlamydia trachomatis antigens in first-void urine samples was compared with cell culture using urogenital swabs from 221 men and 242 women. The rate of isolation of Chlamydia trachomatis was 23.5% in men, nearly 80% of whom had symptoms of urethritis, and 8.3% in women, in whom both cervix and urethra samples were tested. In urine sediments from men and women respectively the chemiluminometric assay showed a sensitivity of 80.8% and 70%, a specificity of 97% and 95%, a positive predictive value of 89.4% and 58.3%, and a negative predictive value of 94.3% and 97.2%. Discrepancies between results obtained with the chemiluminometric assay and cell culture were resolved using two polymerase chain reaction techniques to test urogenital samples. The detection of Chlamydia trachomatis in urine samples with the chemiluminometric assay was confirmed to be superior for screening symptomatic men with urogenital infections than women as a lower prevalence population.

Adolescent↗

Different time course patterns of local expression of delayed-type hypersensitivity to sheep red blood cells in mice.

The delayed-type hypersensitivity (DTH) reaction, a peripheral expression of cell-mediated immunity is still a crucial in vivo immunological test. Nevertheless, the biological significance of its time course remains unclear. Thus, an exhaustive study of DTH was undertaken in mice immunized with increasing doses of sheep red blood cells (SRBC) inoculated intravenously (iv) or subcutaneously. The results showed that overall DTH reactions peaked at 18 hr except in mice iv immunized with the lowest doses (10(5) and 10(6)) and elicited at Day 4. The protracted DTH reaction was shown to be associated with an histological picture of tuberculin-type reaction. A part of the 18-hr DTH reaction is mediated by serum in mice inoculated with large doses of SRBC; nevertheless, numeration by limiting dilution analysis of circulating DTH cells showed that the frequency of these cells correlates with the 18-hr DTH level. The protracted DTH shown at 42 and 48 hr, 4 days after immunization with 10(5) and 10(6) SRBC, could not be transferred in naive recipients with immune spleen cells; it was independent of the antigen life span and did not result from immunization modulation at the bone marrow level on recruitable cells.

Animals↗

Trypanosoma cruzi infection in immunosuppressed mice.

Groups of 10 mice were challenged with 10(4) trypomastigotes of the Y strain of Trypanosoma cruzi. Cyclophosphamide (200 mg per kg) was used for immunosuppression and administered two days before infection in one group and on day 5 after infection in a second group. Enhancement of infection was more drastic in the second group, with a uniform acceleration of mortality and no clearance of the blood parasites. Electron microscopy showed that the hepatocytes were colonized by T. cruzi and that the invasion of the liver, spleen and lungs was associated with secondary infection by bacteria, which may be one of the cases of acceleration of mortality in infected mice. It was suggested that immunosuppressive therapy may favor unexpected symptoms and tissue localization of parasites in patients with Chagas' disease.

Animals↗

False-positive HIV antigens related to emergence of a 25-30 kD protein detected in organ recipients.

OBJECTIVE: The routine screening of organ donors for HIV-1 since 1985 has markedly reduced the risk of acquiring infection in organ recipients. However, commercial HIV-1 p24-antigen assays reveal false-positive reactivity in certain recipients. This observation will be discussed here. METHODS: Post-transplantation sera collected sequentially from different organ recipients were tested for HIV antigen: 79 samples were from 14 kidney recipients, 57 from seven bone-marrow allografts and 18 from two heart recipients. Neutralization assays to determine specificity were performed on reactive samples. Immunoblots prepared from sera containing high levels of antigens were tested by Western blot using polyclonal anti-HIV sera. RESULTS: Abbott HIV-1-EIA kits detected non-neutralizable antigens in early post-transplantation sera from 12 kidney, five bone-marrow and two heart recipients. Using in-house immunoblots prepared from positive non-neutralizing antigen sera, a 25-30 kD protein was detected and shown to be the cause of the false HIV antigen cross-reactivity. CONCLUSION: False-positive HIV antigens related to the emergence of a 25-30 kD protein in early post-transplantation sera are detectable in transplant recipients.

Adolescent↗

Intracellular activity of zidovudine (3'-azido-3'-deoxythymidine, AZT) against Salmonella typhimurium in the macrophage cell line J774-2.

The antibacterial effect of zidovudine (AZT) has been demonstrated both in vitro and in vivo with experimental models of gram-negative bacterial infections. It has been associated with the absence or low occurrence of nontyphoid Salmonella infections in AIDS patients treated with AZT. Using the macrophage cell line J774-2, we demonstrate the inhibition of intracellular growth of Salmonella typhimurium by AZT. This effect is obtained with one-half of the MIC (1 microgram/ml) of AZT for S. typhimurium. Inhibition of intracellular growth is observed after 4 h of incubation and persists at 24 h. Maximal inhibition is shown at a concentration of 128 micrograms/ml, and no further effect is observed with higher concentrations. When the inhibitory effect of AZT is compared with that of pefloxacin or that of ceftriaxone at half their MICs (0.2 and 0.02 microgram/ml, respectively), AZT and pefloxacin give better results than ceftriaxone. In this study, using an intracellular model, we show that AZT is able to inhibit the intracellular multiplication of S. typhimurium at a minimal effective concentration lower than the MIC, indicating its potential for antibacterial accumulation in the macrophages.

Drug Resistance, Microbial↗

[Allergic granulomatous nodule of the conjunctiva disclosing onchocerciasis].

A new case of conjunctival allergic nodule is reported in a Guinean man. This lesion was first described by Ashton and Cook in 1979. Histologically, this nodule consists of amorphous eosinophilic material surrounded by epithelioid and giant cells arranged in a pallisade; some eosinophils are often found in the inflammatory reaction. This lesion usually resolves spontaneously. In documented cases, nematodes and particularly filaria such as Mansonella perstans are usually isolated. Our observation is the first documented case with Onchocerca volvulus. Microfilariae were detected by examination of normal saline containing the biopsy specimen. The new major antifilarial treatment ivermectin was associated.

Adult↗

Studies of the thymus in Chagas' disease: III. Colonization of the thymus and other lymphoid organs of adult and newborn mice by Trypanosoma cruzi.

Among newborn and adult euthymic and athymic mice infected intraperitoneally with 10(2) or 10(4) trypomastigotes, neonates and adult athymic animals exhibited greater susceptibility with heavier colonization of central and peripheral lymphoid organs. Contiguity was also found to be a significant factor in colonization: after similar inocula, the parasitic load in the thymus was comparable in adults and neonates when the former were infected by subcutaneous injection in the anterior neck. In the nude athymic mice, the Y (reticulotropic) strain and the CL (myotropic) strain exhibited similar invasiveness, suggesting that the host immune response modulated the tissular tropism of these strains seen in the heterozygous littermates (Nu/+). The bone marrow was heavily infected; parasites were found in chondrocytes and cells of the mononucleate phagocytic system. Ultrastructural studies of infected thymus specimens showed that the corticomedullary architecture was unaltered and that both macrophages and epithelial cells were infected: both these cell types were infected in vitro.

Adult↗

[Physiopathologic mechanisms in bacterial infection and antibiotics].

There are basically three mains determinants of effective antimicrobial therapy: pharmacodynamic, pharmaceutical and pharmacokinetic. The pharmacodynamic characteristics of an antibiotic describe its mechanisms of action and its safety profile, that is largely defined in vitro. Its pharmaceutical aspects deal with the formulation of the drug. And the pharmacokinetic determinants deal with those process involved in drug absorption, distribution, metabolism and excretion. The fact that antimicrobial drugs are used in an infected host need to reconsider its possible interactions with the induced non specific and specific host defense reactions. Such inflammatory reactions could modify the pharmacodynamic characteristics, the tissue and cellular distribution of a given antibiotic. Moreover define antibiotics, acting themselves on bacterial structure which are proinflammatory, or cellular compartments involved in the defense mechanisms, such as macrophages, might also interfere indirectly or directly on the expression of the inflammatory reactions associated with bacterial infections. Better knowledges about interelationships between the effects of antimicrobial drugs on the pathophysiological mechanisms induced by bacterial, viral parasitic and fungal infection are warranted.

Anti-Bacterial Agents↗

BCG: a modifier of immune responses to parasites.

The use of BCG (Bacille Calmette-Guerin) as an adjuvant is well-established for vaccination against leprosy and tuberculosis. Dominique Frommel and Phillippe Lagrange discuss the effects of BCG in the control of parasite infections, particularly leishmaniasis, and the possibility of the development of anti-parasite recombinant BCG vaccines.

Journal Article↗