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F Dromer

Publications and source records attributed to F Dromer.

50 records · Page 3Linked to original sources
PubMed1991

Improved amphotericin B activity by a monoclonal anti-Cryptococcus neoformans antibody: study during murine cryptococcosis and mechanisms of action.

Current therapy of cryptococcosis is unsatisfactory, particularly in patients with AIDS. Experimental cryptococcosis models in DBA/2 mice were used to determine whether the murine monoclonal anticryptococcal antibody (designated E1) might potentiate the chemotherapeutic effect of amphotericin B (AmB). According to the inoculum size, these mice died spontaneously from acute pneumonia (high inoculum) or from brain swelling (lower inoculum). AmB and E1 together significantly improved the survival of mice in both models compared with AmB alone. The mechanisms by which E1 might potentiate AmB activity were investigated in vitro. When cryptococci were preincubated with AmB or another polyene antibiotic, nystatin, there was an augmented binding of E1. AmB enhanced phagocytosis by unstimulated peritoneal macrophages in the presence of E1 or normal rabbit immunoglobulins. Normal and immune IgG deserve further study to determine under what circumstances the chemotherapeutic effect of AmB can be enhanced.

Amphotericin B↗
PubMed1990

Improvement of amphotericin B activity during experimental cryptococcosis by incorporation into specific immunoliposomes.

Cryptococcosis is an opportunistic infection that is responsible for increased morbidity and mortality in patients with the acquired immunodeficiency syndrome. The high toxicity of the antifungal agent that is mainly used against cryptococcosis, amphotericin B (AMB), accounts for the need for new treatments, especially in patients with the acquired immunodeficiency syndrome because of the high relapse rate of cryptococcosis. Drug targeting may be one of these alternate treatments. Since we have demonstrated that an immunoglobulin G1 (IgG1) anti-Cryptococcus neoformans serotype A monoclonal antibody (E1) was protective during experimental cryptococcosis in mice, we investigated whether specific targeting of AMB with liposomes that bear E1 would improve the therapeutic index of the drug. For that purpose, in vitro and in vivo experiments were designed to compare the specificities and activities of these liposomes with those of control immunoliposomes bearing a nonrelated IgG1 monoclonal antibody (CY34). The immunoliposomes were prepared by covalently linking E1 or CY34 and small unilamellar vesicles. When immunoliposomes were incubated with yeast cells, only E1-bearing liposomes recognized C. neoformans. In vivo, mice that were treated 24 h after infection with one injection of AMB (0.12 mg/kg of body weight) intercalated into E1-bearing liposomes survived significantly longer than did those given the same dose of AMB alone or AMB intercalated into nontargeted liposomes or control immunoliposomes. None of the mice that were given control treatments did statistically better than those that were given AMB. Keeping in mind that this kind of therapy requires knowledge of the antigenic type of the infecting organism, the results suggest that specific targeting of small doses of AMB improve the efficacy of AMB and might be an alternative to the use of larger doses of AMB.

Amphotericin B↗
PubMed1989

Role of IgG and complement component C5 in the initial course of experimental cryptococcosis.

Although cellular immunity has a crucial role during cryptococcosis, several in vitro studies have pointed out the importance of IgG anti-Cryptococcus neoformans antibodies and complement components during phagocytosis of the yeast by polymorphonuclear leucocytes and monocytes. We investigated the role of complement and specific antibodies in host defences against experimental cryptococcosis, using a monoclonal IgG1 antibody (E1) specific for cryptococcal capsular polysaccharide, and mice congenitally sufficient or deficient in the fifth component of complement (C5). During in vitro experiments, E1 and the normal mouse serum from C5-sufficient and -deficient mice were unable to inhibit the growth of C.neoformans. However, E1 was an efficient opsonin for the ingestion of C. neoformans by mouse peritoneal macrophages, acting in synergy with normal mouse serum. In vivo, E1 was protective in heavily infected C5-deficient mice (DBA/2) dying from an early acute pneumonia, but not in C5-sufficient mice (BALB/c) and in DBA/2 mice infected with a smaller inoculum dying from a late progressive meningo-encephalitis. Although protection against pneumonia is attributed to a local recruitment of phagocytes in C5-sufficient mice, this was not observed in C5-deficient mice protected with E1. In this case, IgG anti-C. neoformans antibodies seem to be an alternative for an efficient opsonization of the yeasts. Altogether, these data suggest that two main mechanisms may protect infected mice from an early fatal pneumonia: the efficient opsonization of the yeast by complement and the recruitment of phagocytes in infected tissues.

Animals↗
PubMed1989

Incorporation of amphotericin B (AMB) into liposomes alters AMB-induced acute nephrotoxicity in rabbits.

To investigate the protective effect of liposomes on acute amphotericin B (AMB) renal toxicity, we compared in rabbits the acute toxicity of 4 mg/kg of free-AMB and 4 or 10 mg/kg of liposomal AMB (L-AMB) during 90 min after antibiotic infusion. Free-AMB exhibited immediate nephrotoxicity with a 44% decrease of the glomerular filtration rate and alteration of tubular cell membrane permeability expressed as increases in urinary pH (6.5 vs. 4.7), potassium fractional excretion (95% vs. 30%) and sodium fractional excretion (26% vs. 4%). Urinary excretion of the lysosomal enzyme N-acetylglucosaminidase was unchanged by free-AMB. Incorporation of AMB into liposomes prevented the toxic effects of free-AMB on glomerular filtration and tubular cells membrane, but significantly increased N-acetylglucosaminidase urinary excretion (380 and 180% in animals receiving 4 and 10 mg/kg of L-AMB, respectively). Absolute AMB urinary excretion during the experiment was unchanged by liposomes and was always less than 1% of the total dose administered. Liposomes alone exhibited no toxicity. These results suggest that liposomes could increase the interaction between AMB and lysosomes leading to an additional mechanism of cellular injury. They admonish close monitoring of renal function and enzymuria in clinical situations in which L-AMB is being used.

Amphotericin B↗
PubMed1988

Genetic control of the humoral response to cryptococcal capsular polysaccharide in mice.

Cryptococcus neoformans is responsible for opportunistic infections in patients with cellular immune defects. However, C. neoformans-specific capsular polysaccharide antibodies have been shown to participate in host defenses during cryptococcosis. We investigated the humoral response after primary immunization in various inbred strains of mice and the genetic control. Our data strengthen the arguments for the T-independent type-2 nature of cryptococcal antigen, since CBA/N mice were unable to produce specific antibodies. They show that the influence of the genetic background is predominant for the good response with at least four independent autosomal genes governing this response, including an Igh control as reported for other polysaccharides. Immunization of intra-H-2 recombinant mice on a B10 background allowed us to identify a major histocompatibility complex control located in the subregion E alpha. The genetic control of antibody production following immunization with cryptococcal polysaccharide might explain the high variability of humoral responses during cryptococcosis.

Animals↗
PubMed1988

Community-acquired pneumonia. Importance of initial noninvasive bacteriologic and radiographic investigations.

During a one-year epidemiologic survey of acute community-acquired pneumonia, we prospectively investigated in 116 adult nonimmunocompromised patients (a) the importance of initial noninvasive investigations (ie, blood culture and quantitative sputum culture) and the value of the initial radiologic type of pneumonia in diagnosing of the etiologic agent, and (b) the management of pneumonia. Quantitative sputum culture or blood culture (or both) permitted bacteriologic diagnosis in 44 percent of the cases. The radiologic types found were segmental or alveolar densities in 75 patients (65 percent), patchy alveolar densities in 11 (9 percent), mixed opacities in 26 (22 percent), and interstitial infiltrates in four (3 percent). We observed that (a) the prognosis was identical whether a bacteriologic diagnosis was made or not, (b) the Gram stain, an inexpensive procedure, was as contributive for bacteriologic diagnosis as quantitative sputum culture, diagnosis as (c) blood cultures were poorly contributive in patients without severe infections, and (d) alveolar densities were associated with a bacterial infection in 90 percent of the cases of known etiology. On the basis of these results, a pragmatic strategy of initial management of community-acquired pneumonia is proposed.

Adult↗
PubMed1988

Cryptococcus neoformans antibody levels in patients with AIDS.

Anti-Cryptococcus neoformans capsular polysaccharide (CPS) antibodies were measured by ELISA in patients with AIDS related complex or AIDS without a known history of cryptococcosis and in heterosexual healthy controls. Total and IgG anti-CPS antibody activity was rarely detected in patients, with mean levels lower than in controls, whereas IgM antibody activity was similar in the 3 groups. Since both humoral and cellular immunity appear to be of great importance during cryptococcosis, the inability of AIDS patients to synthetize specific IgG antibodies could impair an alternative host defence mechanism to cellular immunity.

AIDS-Related Complex↗
PubMed1987

Production, characterization, and antibody specificity of a mouse monoclonal antibody reactive with Cryptococcus neoformans capsular polysaccharide.

Two monoclonal immunoglobulin G1 antibodies reacting with Cryptococcus neoformans capsular polysaccharide (CNPS) were produced in mice by using a carefully defined procedure for immunization with unmodified CNPS purified from C. neoformans serotype A. Since the antibodies were found to have the same pattern of specificity, only one of them (E1) is described. This anti-CNPS monoclonal antibody reacted with the glucuronoxylomannan component of CNPS but not with the constituent monosaccharides or with the mannose alpha(1----3)-linked oligosaccharide structures present on CNPS. E1 appeared to be specific for C. neoformans serotype A by agglutination of whole cells; it was specific for soluble CNPS A by gel immunoprecipitation. However, indirect immunofluorescence and competitive-binding enzyme-linked immunosorbent assay experiments showed low levels of cross-reactivity with serotypes B and D but not with serotype C. Concentrations 10,000 times higher for serotypes B and D cells than for serotype A cells were required for a 50% inhibition of E1 anti-CNPS A activity as measured by enzyme-linked immunosorbent assay. Among the other yeasts tested, a cross-reaction was only detected with Trichosporon beigelii. The four serotypes of C. neoformans could be distinguished based on intensities and patterns of fluorescence in an indirect immunofluorescence assay using the monoclonal anti-CNPS A antibody. Monoclonal anti-CNPS A antibodies could be useful for fundamental studies on the glucuronoxylomannan structure, as well as for clinical applications such as serotyping and possibly the serological diagnosis of cryptococcosis.

Animals↗
PubMed1987

Protection of mice against experimental cryptococcosis by anti-Cryptococcus neoformans monoclonal antibody.

Humoral immunity does not play a prominent role during experimental cryptococcosis. However, previous studies have shown that immunoglobulin G (IgG) anti-Cryptococcus neoformans antibodies can mediate cell-dependent yeast killing in vitro. Therefore, the protective effect of a previously described monoclonal IgG1 anti-C. neoformans antibody (E1) administered intraperitoneally 24 h before intravenous infection with a C. neoformans serotype A strain was evaluated in mice. Heavily infected (3 X 10(6) cells) untreated mice died in 2.9 +/- 0.5 (standard deviation) days. Survival time was 17.9 +/- 1.6 days for mice treated with 100 micrograms of E1 and 3.0 +/- 0.7 days for mice treated with 100 micrograms of a monoclonal IgG1 anti-thyroglobulin antibody used as a control. Protection was dose dependent and required at least 10 micrograms of E1 (mean antibody concentration in serum +/- standard deviation, 6.6 +/- 2.3 micrograms/ml). Insufficient concentrations of IgG anti-C. neoformans antibody could explain previous negative results obtained with polyclonal immune serum. After infection with a smaller inoculum (5 X 10(3) to 5 X 10(4)), the protective effect of E1 was confirmed by the presence of fewer CFUs in the spleens and brains of treated mice than in those of controls. CFU were still detected in the brains of protected mice 5 days after infection, although soluble antigen was negative in sera. These results suggest that passive serotherapy with monoclonal IgG antibodies could participate in the prevention or treatment of experimental cryptococcosis.

Animals↗
PubMed1985

Effects of urinary pH on renal interactions between probenecid and cefsulodin in rabbits.

The effect of urinary pH on renal interaction of cefsulodin and probenecid was tested in rabbits. Probenecid was reabsorbed in acidic urine (fractional excretion [FE] = 8 +/- 4%) and secreted in alkaline urine (FE = 492 +/- 258%). Renal excretion of cefsulodin alone was not affected by the urinary pH (FE = ca. 100%). In acidic urine, probenecid significantly reduced tubular secretion of cefsulodin (FE = 74 +/- 8%). An inverse pattern was observed in alkaline urine (FE = 122 +/- 18%).

Animals↗
PubMed1984

Gentamicin, netilmicin, dibekacin, and amikacin nephrotoxicity and its relationship to tubular reabsorption in rabbits.

The role of the tubular reabsorption of aminoglycosides in nephrotoxicity was considered. The tubular reabsorption rate, fractional reabsorption, and net balance, expressed as the excreted to infused aminoglycoside ratio, were concomitantly studied in male rabbits by continuous infusion of gentamicin, netilmicin, dibekacin, and amikacin. Aminoglycoside nephrotoxicity was evaluated by creatinine levels in serum and pathological renal damage after 14 days of a low- or high-dose regimen, comprising either eight, hourly intramuscular injections of gentamicin, netilmicin, or dibekacin (4 mg/kg) or amikacin (16 mg/kg); twelve, hourly intramuscular injections of gentamicin, netilmicin, or dibekacin (15 mg/kg) or amikacin (60 mg/kg); or injections of saline for the control group. Aminoglycosides exhibited three degrees of tubular reabsorption: gentamicin had the highest, netilmicin had the lowest, and dibekacin and amikacin had intermediate degrees of reabsorption. Nephrotoxicity associated with alteration in renal histology was observed with gentamicin and, to a lesser extent, with dibekacin in the high-dose regiment. No nephrotoxicity was noted with netilmicin or amikacin compared with the control group. Concentrations of the aminoglycosides in renal cortex and serum were not predictive of renal toxicity. Except for amikacin, which appeared to exhibit the lowest intrinsic renal toxicity, nephrotoxicity was correlated with the tubular reabsorption of each aminoglycoside. It was concluded that aminoglycoside renal toxicity can be determined by two major factors: importance of transport into tubular cells and intrinsic intracellular toxicity.

Amikacin↗
PubMed1984

Renal disposition of ceftazidime illustrated by interferences by probenecid, furosemide, and indomethacin in rabbits.

Excretion of ceftazidime (C), a new cephalosporin antibiotic, has been reported to occur unexpectedly through glomerular filtration only, without being significantly affected by probenecid. We investigated renal tubular disposition of C in rabbits by calculating its rates of fractional excretion, net tubular secretion, and absolute excretion. During continuous intravenous infusion of C, 3 mg of furosemide (F), 15 mg of probenecid (P), or 2 mg of indomethacin (I) per kg was injected intravenously as a bolus. Equilibrium dialysis showed that the percentage of C bound to serum proteins (14 +/- 5%) was not altered by F, P, or I. Fractional excretion of C was 94 +/- 22, 65 +/- 21, 182 +/- 36, and 98 +/- 3% for the drug given alone and after injection of F, P, and I, respectively. For 15 min after P injection, we observed net tubular secretion of C (404 +/- 276 micrograms/min). The C absolute excretion rate was significantly reduced by I compared with the absolute excretion rate for the control (405 +/- 104 versus 696 +/- 157 micrograms/min). We conclude that (i) C undergoes bidirectional transport in the nephron, revealed by the effects of F and P, with a nil net C balance; (ii) F and P have opposite unexpected effects on tubular handling of C, possibly due to competition for C secretion processes; (iii) I reduces C excretion solely by decreasing its glomerular-filtered load; and (iv) tubular handling of C differs from that of previously studied cephalosporins.

Animals↗
PubMedDate not supplied

An outbreak of acute pulmonary histoplasmosis in members of a trekking trip in Martinique, French West Indies.

BACKGROUND: Thirteen clustered cases of American histoplasmosis, a deep mycosis caused by Histoplasma capsulatum and acquired through inhalation of airborne spores was reported. Twenty-five persons traveled in Martinique, French West Indies. Thirteen underwent trekking and passed through a mountain tunnel full of bats (tunnel group). The 12 others performed canyoning and did not go through the tunnel (control group). Fifteen days after exposure, 1 patient of the tunnel group developed fever, chills, and cough. METHODS: The index case was diagnosed in the hospital, but 12 cases where initially diagnosed as prolonged influenza. All individuals were contacted and submitted to a phone questionnaire. They were asked about eventual occurrence of influenzalike symptoms, about activities practiced, and the notion of contact with bats. All were invited to have clinical examinations, chest x-ray films, and blood samplings. Serologic testing for histoplasmosis was performed by immunodiffusion. Clinical evidence of infection with H. capsulatum was obtained in all the remaining patients of the tunnel group and in none in the control group. Symptoms occurred with an acute onset in 11 to 23 days: fever and chills, severe asthenia, headaches, digestive tract involvement, and then cough, dyspnea, hepatic involvement. Pulmonary micro- or macronodules and mediastinal adenopathies were seen on radiograph and/or computed tomography scan. RESULTS: H. capsulatum serologic tests were positive in all 13 cases with presence of specific M and or H precipitins, 5 to 13 weeks after exposure, and were negative in control group. All patients were treated with itraconazole 200 mg per day during at least 2 months. Treatment was well tolerated; patients progressively recovered. Clinical and serologic follow-up was obtained for some patients at 1 and 4 years. The present study reports the first large outbreak of histoplasmosis acquired in Martinique. CONCLUSION: Histoplasmosis still occurs and is potentially serious. In patients returning from endemic areas, presenting prolonged influenzalike symptoms, clinicians should look for previous possible exposure to Histoplasma.

Acute Disease↗