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Biomedical subjects

L L Gosey

Publications and source records attributed to L L Gosey.

4 recordsLinked to original sources

Antifungal susceptibility testing: practical aspects and current challenges.

Development of standardized antifungal susceptibility testing methods has been the focus of intensive research for the last 15 years. Reference methods for yeasts (NCCLS M27-A) and molds (M38-P) are now available. The development of these methods provides researchers not only with standardized methods for testing but also with an understanding of the variables that affect interlaboratory reproducibility. With this knowledge, we have now moved into the phase of (i) demonstrating the clinical value (or lack thereof) of standardized methods, (ii) developing modifications to these reference methods that address specific problems, and (iii) developing reliable commercial test kits. Clinically relevant testing is now available for selected fungi and drugs: Candida spp. against fluconazole, itraconazole, flucytosine, and (perhaps) amphotericin B; Cryptococcus neoformans against (perhaps) fluconazole and amphotericin B; and Aspergillus spp. against (perhaps) itraconazole. Expanding the range of useful testing procedures is the current focus of research in this area.

Animals↗

Host defense against Mycobacterium-avium complex.

Mycobacterium-avium complex (MAC) is an intracellular pathogen and the most common cause of widely disseminated bacterial infection in patients with the acquired immunodeficiency syndrome (AIDS). MAC is infrequently seen in other immunocompromised adults, suggesting that the host defense defect allowing for MAC infection is relatively unique for AIDS. A system was developed for studying the immune response to MAC infection, utilizing MAC isolated from patients with AIDS and monocytes from normal controls and patients with AIDS. Phagocytosis, superoxide anion (SOA) production, and killing were measured. Monocytes from normal controls and AIDS patients were identical with respect to phagocytosis of MAC. In contrast, baseline SOA production was elevated in monocytes from patients compared to normal monocytes and was minimally augmented in response to either phorbol myristate acetate or MAC. Fourteen-day kinetic studies revealed in patients and controls a biphasic pattern with 50-99% killing of AIDS-derived MAC initially, followed always by a rapid outgrowth of surviving bacilli. Despite a modest enhancement of MAC killing by normal but not patients' monocytes pretreated with either recombinant interferon-gamma or recombinant tumor necrosis factor-alpha, outgrowth of MAC was always observed in both, typically faster in patients than in controls. Even monocytes in the presence of lymphocytes stimulated with interleukin-2 did not demonstrate enhanced MAC killing. In contrast, high-titered anti-MAC immune serum derived from a patient with polymyositis and disseminated MAC significantly enhanced the killing of MAC by monocytes from both AIDS patients and healthy controls and prevented their outgrowth. These findings suggest that the host defense defect allowing for MAC infection appears not to reside in the monocyte and that the in vitro lymphocyte functions examined in this study do not appear to play a major role. What role specific antibody plays in vivo in preventing disseminated MAC is uncertain, but the lack of such antibody may help explain the propensity for AIDS patients to develop systemic infection.

Adjuvants, Immunologic↗

Use of lysis-centrifugation (isolator) and radiometric (BACTEC) blood culture systems for the detection of mycobacteremia.

Patients with acquired immune deficiency syndrome may develop infection with mycobacteria, particularly Mycobacterium avium-M. intracellulare (MAI). These infections can frequently be associated with demonstrable mycobacteremia with the organism. In this study, we compared the sensitivity of a radiometric (BACTEC system; Johnston Laboratories, Inc., Towson, Md.) liquid medium culture system with that of conventional solid mycobacterial culture media for cultures of blood from these patients. Both systems were inoculated with blood concentrate prepared by lysis-centrifugation (Isolator; Du Pont Co., Wilmington, Del.). Of 46 acquired immune deficiency syndrome patients whose blood was cultured, 28% had cultures positive for MAI. Patients had from less than 1 to more than 100 MAI colonies per ml of blood. Lowenstein-Jensen and Middlebrook 7H11 agars were comparable in recovery of MAI. BACTEC 12A vials containing double the standard volume of medium (4 ml) were more sensitive and were positive slightly earlier than vials containing the standard volume (2 ml). Conventional media detected 98% of positive cultures; BACTEC vials containing double volumes of medium detected 94% of positive cultures, whereas single-volume vials detected 77%. BACTEC vials were positive approximately 5 to 6 days sooner than slants or plates containing conventional media. For a few cultures, the use of unconcentrated blood was compared with the use of Isolator-concentrated blood by using each of these as inocula for BACTEC vials. Results for these cultures suggested that, although the use of Isolator-concentrated blood resulted in greater sensitivity than the use of unconcentrated blood would, the use of unconcentrated blood would still result in the detection of at least 78% of positive cultures.

Acquired Immunodeficiency Syndrome↗

Advantages of a modified toluidine blue O stain and bronchoalveolar lavage for the diagnosis of Pneumocystis carinii pneumonia.

A modified toluidine blue O staining technique for Pneumocystis carinii is described. An easily prepared sulfation reagent made with sulfuric and acetic acids was used. The stain can be employed for bronchoalveolar lavages and lung tissue touch preparations. Most background material was removed by the sulfation reagent, slides were generally easy to read, and time from receipt of a specimen to reporting of results was approximately 1 h. P. carinii cysts were more easily visualized with this stain than in slides stained with modified methylene blue, Gram, Gram-Weigert, and standard toluidine blue O procedures. The importance of certain procedural aspects of subsegmental bronchoalveolar lavage, by which most of the specimens were obtained, is also emphasized.

Humans↗