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I Polacheck

Publications and source records attributed to I Polacheck.

At least 19 recordsLinked to original sources
PubMed1999

Heteroresistance to fluconazole and voriconazole in Cryptococcus neoformans.

Cryptococcus neoformans isolates that exhibited unusual patterns of resistance to fluconazole and voriconazole were isolated from seven isolates from two different geographical regions: one isolate from an Israeli non-AIDS patient and six serial isolates from an Italian AIDS patient who had suffered six recurrent episodes of cryptococcal meningitis. Each isolate produced cultures with heterogeneous compositions in which most of the cells were susceptible, but cells highly resistant to fluconazole (MICs, >/=64 microg/ml) were recovered at a variable frequency (7 x 10(-3) to 4.6 x 10(-2)). Evidence showed that this type of resistance is innate and is unrelated to drug exposure since the Israeli patient had never been treated with azoles or any other antimycotic agents. Analysis of clonal subpopulations of these two strains showed that they exhibited heterogeneous patterns of resistance. The number of subpopulations which grew on fluconazole or voriconazole agar declined progressively with increasing azole concentration without a sharp cutoff point. For the Italian serial isolates, the number of clonal populations resistant to fluconazole (64 microg/ml) and voriconazole (1 microg/ml) increased steadily, yielding the highest number for the isolate from the last episode. Attempts to purify a sensitive subpopulation failed, but clones highly resistant to fluconazole (100 microg/ml) and moderately resistant to voriconazole (1 microg/ml) always produced a homogeneous population of resistant cells. Upon maintenance on drug-free medium, however, the majority of the homogeneously resistant cells of these subclones lost their resistance and returned to the stable initial heteroresistant phenotype. The pattern of heteroresistance was not affected by the pH or osmolarity of the medium but was influenced by temperature. The resistance appeared to be suppressed at 35 degrees C and was completely abolished at 40 degrees C. Although heterogeneity in azole resistance among subpopulations of single isolates has been reported for Candida species, the transient changes in expression of resistance under different growth conditions reported here have not been observed in fungal pathogens.

Acquired Immunodeficiency Syndrome↗
PubMed1999

A novel injectable water-soluble amphotericin B-arabinogalactan conjugate.

New, stable, highly water-soluble, nontoxic polysaccharide conjugates of amphotericin B (AmB) are described. AmB was conjugated by a Schiff-base reaction with oxidized arabinogalactan (AG). AG is a highly branched natural polysaccharide with unusual water solubility (70% in water). A high yield of active AmB was obtained with the conjugates which were similarly highly water soluble and which could be appropriately formulated for injection. They showed comparable MICs for Candida albicans and Cryptococcus neoformans (MICs, 0.1 to 0.2 microg/ml). The reduced AmB conjugate, which was synthesized at pH 11 for 48 h at 37 degrees C, was nonhemolytic and was much safer than conventional micellar AmB-deoxycholate. It was the least toxic AmB-AG conjugate among those tested with mice (maximal tolerated dose, 50 mg/kg of body weight), and histopathology indicated no damage to the liver or kidneys. This conjugate, similarly to the liposomal formulation (AmBisome), was more effective than AmB-deoxycholate in prolonging survival. It was more effective than both the liposomal and the deoxycholate formulations in eradicating yeast cells from target organs. The overall results suggest that after further development of the AmB-AG conjugate, it may be a potent agent in the treatment of fungal infections.

Amphotericin B↗
PubMed1998

Rhinocerebral mucormycosis treated with amphotericin B colloidal dispersion in three patients.

Rhinocerebral mucormycosis (zygomycosis) primarily affects diabetic or immunosuppressed patients and typically progresses rapidly, necessitating surgical excision and antifungal therapy with amphotericin B. Large doses of amphotericin B are required for cure, causing significant renal toxicity. Amphotericin B colloidal dispersion (ABCD; Amphocil, Sequus Pharmaceuticals, Menlo Park, CA) is a 1:1 complex of cholesteryl sulfate and amphotericin B, which results in significant reduction of toxicity, especially nephrotoxicity. We describe three patients with life-threatening rhinocerebral mucormycosis treated with ABCD. All patients had high serum creatinine levels due to prior treatment with amphotericin B; these levels reverted to normal during treatment with ABCD. Two patients with diabetes mellitus were cured after receiving a combination of surgery and ABCD therapy. The third patient, who had myelodysplastic syndrome, had an initial good response, with cure of the fungal infection; however, he eventually died of his primary illness. To the best of our knowledge, this is the first detailed clinical description of the treatment of mucormycosis with ABCD.

Adult↗
PubMed1997

Increasing fungal isolation from clinical specimens: experience in a university hospital over a decade.

The local patterns of fungal isolates were studied by a retrospective analysis of fungal species isolated from clinical specimens in a university hospital in Jerusalem. Between 1984 and 1993, 5630 fungi [4071 patient unique isolates (PUI)] were isolated and identified. During the study decade, the annual incidence of all isolates increased 2.7-fold, and PUI increased 1.6-fold. Candida albicans accounted for 61% of PUI; urine was the source of 53%. The intensive care units (ICUs) and the Bone Marrow Transplantation (BMT) Department had the highest incidence of fungal isolation. The following trends were observed: (1) a decrease in the relative frequency of C. albicans and increase in Candida tropicalis; (2) increased number of isolates from urine, surgical wounds and intra-abdominal sites; (3) increased number of isolates from ICUs and BMT. Fungi are emerging as important hospital-acquired pathogens in tertiary care and teaching hospitals, and are associated with high rates of morbidity and mortality. It is important to be familiar with the local patterns of fungal isolation in order to improve treatment.

Adolescent↗
PubMed1996

Saponins as antimycotic agents: glycosides of medicagenic acid.

The continuous search for new antimycotic drugs is a consequence of the broad use of immunosuppressive drugs and broad-spectrum antibiotics, high number of AIDS patients, and widespread dermatophyte infections. The concern with increased resistance due to widespread and prolonged antifungal treatment, particularly with azoles, is noteworthy. Our efforts were focused on medicagenic acid derivatives isolated from alfalfa and on semisynthetic ones. In general, these materials exhibited potent fungistatic effects against several plant pathogens and human dermatophytes. Furthermore, they were fungicidal against medically important yeasts, showing a most impressive activity against Cryptococcus neoformans, the minimal fungicidal concentration (MFC) value of the gluco derivative of medicagenic acid, compound G2, is 4 micrograms/ml. The mode of action as well as the structure-activity relationships of these compounds were studied. Compound G2, when applied topically, was effective in curing skin lesions of guinea pigs infected with the dermatophyte Trichophyton mentagrophytes and good skin tolerance to the drug was noted. Furthermore, it had a life-prolonging effect on mice infected with C. neoformans and recently, liposomes containing compound G2 were used efficiently as a drug delivery system in treatment of murine cryptococcosis and candidiosis.

Animals↗
PubMed1996

Conjunctival oculosporidiosis in east Africa caused by Rhinosporidium seeberi.

BACKGROUND AND OBJECTIVE: Conjunctival rhinosporidiosis is an infectious disease rarely recorded outside the Indian subcontinent. The disease is caused by Rhinosporidium seeberi, an endosporulating microorganism of uncertain taxonomic classification. We report a series of cases manifesting this infection. MATERIAL AND METHODS: The demographic, clinical, and histopathologic data of 14 cases of conjunctival rhinosporidiosis on record at our Ophthalmic Pathology Laboratory were reviewed. RESULTS: All cases were from East Africa; 10 were from Malawi and 4 from Kenya. Ten specimens were from males and three from females. Their age ranged from 7 to 20 years. All patients were treated by surgical excision, and no recurrence was recorded. None of the cases was diagnosed clinically as rhinosporidiosis. Histologically, all stages of the organism's life cycle could be found in the excised tissue, from small trophocytes to large sporangia-containing sporoblasts. There were changes in histochemical stainings with growth and maturation. In general, the inflammation was of chronic nongranulomatous type. CONCLUSIONS: Conjunctival rhinosporidiosis is a rare infectious disease that typically appears in young males in rural regions, and that can be treated by surgical excision. It typically causes chronic nongranulomatous inflammation. Various stages of the R seeberi life cycle can be seen in the affected tissue.

Adolescent↗
PubMed1995

Efficacy evaluation of a novel submicron miconazole emulsion in a murine cryptococcosis model.

Submicron emulsions of miconazole were stabilized by using a combination of three emulsifiers comprising phospholipids, poloxamer, and deoxycholic acid (DCA). The presence of DCA was vital for prolonged emulsion stability owing to its contribution to the elevated zeta potential of the emulsion. Further, the results by the phospholipid surface labelling colorimetric technique clearly suggested that poloxamer molecules interacted with phospholipid polar-head groups of the mixed DCA-phospholipid interfacial film, resulting in the stabilization of the emulsion by a steric enthalpic entropic mechanism. The plain emulsion vehicle was well tolerated up to a dose of 0.6 ml injected i.v. to BALB/c mice. The maximum tolerated dose of miconazole was 80 and 250 mg/kg in Daktarin i.v. (a marketed product) and emulsion, respectively, showing an improved safety ratio of 1 to 3 in favor of the emulsion. These results tended to confirm that the adverse effects associated with Daktarin i.v. injection should be associated with the vehicle rather than with the miconazole itself. In a murine cryptococcosis model, only one mouse out of ten remained alive by day 15 in the infected group treated with Daktarin i.v., while in the miconazole emulsion treated group, mice began to die from day 16 up to day 25 post inoculation. Thus, the multiple-dose treatment with the miconazole emulsions improved the protection offered to the infected mice. However, the therapeutic levels of miconazole that were reached in the target organ (brain) were lower than those required for complete eradication of Cryptococcus neoformans, which is known to multiply preferentially in the brain.

Animals↗
PubMed1995

Adherence of Candida albicans to epithelial cells: studies using fluorescently labelled yeasts and flow cytometry.

Candida albicans adherence to epithelial cells is the first step in the infectious process, but in spite of its importance, current methods for the quantitative measurement of adherence of C. albicans to epithelial cells in vitro have some serious limitations. They are based on filtration assays and either microscopic or radiometric analysis. The adherence reaction is usually carried out with a large excess of yeasts (100-fold) over epithelial cells in order to perform the microscopic analysis, which is slow, subjective and limited to 100-200 cells and thus lacks statistical power. The radiometric analysis fails to measure individual cells. A method for measuring yeast adherence that overcomes these problems has been developed. It is based on labelling the yeasts with the fluorogenic marker 2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester (BCECF) prior to the adherence reaction, and analysing 10(4) epithelial cells by flow cytometry, while nonbound yeasts are excluded by gating. Two subpopulations of buccal epithelial cells (BECs) which differ in their mean fluorescence intensities per cell (MFIs) were observed: one with MFI which did not exceed nonspecific fluorescence, and the other with MFI as high or higher than the MFI of labelled yeasts. The two subpopulations represent yeast-free and yeast-binding epithelial cells, respectively, and the MFI increment of the BECs is a quantitative measure of the extent of yeast adherence. Control experiments confirming previously described basic features of adherence, such as enhanced adherence at increasing yeast excess, diminished adherence of trypsin-treated or heat-inactivated yeasts, and the differential adherence of various Candida species, supported the validity of the assay. The possibility of studying adherence reliably at low yeast:epithelial cell ratios, which better mimic adhesion as it occurs in vivo, is an important advantage of the assay. New findings, using this method, included the observation that exfoliated BECs from diabetic patients exhibited the same capacity for C. albicans adherence as cells from healthy controls, and that epithelial cells from early human ontogenic stages had a significantly lower adherence level than those from later stages.

Adult↗
PubMed1993

Synthesis and antifungal activity of medicagenic acid saponins on plant pathogens: modification of the saccharide moiety and the 23 alpha substitution.

The study of structure-antifungal activity relationships of medicagenic acid saponins was widened to include synthetic glycosides of mannose, galactose, cellobiose, and lactose as well as a 23 alpha-hydroxymethyl analog of medicagenic acid, namely, methyl 2 beta,3 beta-dihydroxy-23 alpha-hydroxymethyl-delta (12)-oleanene-28 beta-carboxylate, against Sclerotium rolfsii, Rhizoctonia solani, Trichoderma viride, Aspergillus niger, and Fusarium oxysporum. The native glucose-containing saponin was a more effective antifungal agent than the aforementioned saponins, except in the case of the cellobiose-containing derivative and F. oxysporum. A carboxyl substituent at the 23 alpha position of the sapogenin brought about higher fungistatic activity than a methyl carboxylate which, in turn, was more effective than an hydroxymethyl group at the same position.

Antifungal Agents↗
PubMed1993

Efficacy evaluation of a novel submicron amphotericin B emulsion in murine candidiasis.

A submicron amphotericin B (AmB) sterile emulsion with a mean droplet size of approximately 100 nm was prepared. The emulsion was stable at 4 degrees C over a period of 4 months. The acute toxicity results showed that the maximum tolerated dose of the AmB emulsion was 2.0 mg kg-1 as compared to 0.5 mg kg-1 for a commercial deoxycholate suspension, Fungizone. Efficacy evaluations of submicron AmB emulsion compared to Fungizone were performed in a murine candidiasis model using either a single or a multiple daily dose administration of 0.4 mg kg-1. Survival (100%) was observed up to 15-18 days post-infection in mice treated with AmB emulsion or Fungizone, while all control non-treated animals had died after 9 days in both single and multi-treatment experiments. Survival (50%) was obtained after 35 days in the single treatment, and 40 days in the multi-treatment, experiment with AmB emulsion, while treatment with Fungizone gave 50% survival after 15 and 20 days, respectively. The overall results indicate that in murine candidiasis, treatment with AmB submicron emulsion was more effective than Fungizone, suggesting a potential therapeutic application.

Amphotericin B↗
PubMed1993

Disseminated visceral fusariosis treated with amphotericin B-phospholipid complex.

Fusariosis, a rare infectious disease of the immunocompromised host, is relatively resistant to amphotericin B (AmB) or other antifungal agents. We describe a 5-year follow-up of a 40 year old woman with T-type acute lymphoblastic leukemia who following chemotherapy developed prolonged high fever, chills, night sweats, and severe weakness. Liver function tests were impaired and abdominal computerized tomography (CT) showed multiple lesions in the liver and abnormal structure of the spleen. A laparotomy revealed multiple granulomas containing Fusarium sp. in the liver, and the spleen was heavily infiltrated by the same fungus. The patient failed to respond to the conventional AmB dosage form (Fungizone) even after a total dose of 3.0 g was given, and developed significant renal impairment. AmB was complexed (in a mole ratio of 1:16) with a mixture of the phospholipids dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol (mixed in 7:3 mole ratio). The resulting drug complex, AmB-PLC, was then administered (1-4 mg/kg/day, total dose 4.2 g) and subsequently the patient was cured of all symptoms of fusariosis. There were only mild side effects and no nephrotoxicity was evident. On the contrary, marked improvement of the renal function tests occurred during AmB-PLC treatment. Eight months later, she developed a spinal lesion with dense consistency in L5 and S1, and after receiving another course of AmB-PLC (3.1 g) she recovered completely. In a 2 year follow-up period the patient had no further relapse of the fungal disease. Subsequent chemotherapy given for relapse of the leukemia was followed by a new fungal infection, which was treated with AmB-cholesteryl sulfate complex (Amphocil).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Aspergillus quadrilineatus, a new causative agent of fungal sinusitis.

Aspergillus quadrilineatus was found to be the etiologic agent of pansinusitis in a patient suffering from acute nonlymphoblastic leukemia and who had undergone allogeneic bone marrow transplantation. A. quadrilineatus was cultured from biopsy specimens of the maxillary sinus, and tissue sections with fungal stains showed a necrotic area containing dichotomously branching septate hyphae, which is morphologically consistent with Aspergillus species. The patient was successfully treated with a combination of surgical debridement, granulocyte transfusions, and intravenous administration of amphotericin B-cholesterol sulfate colloidal dispersion. This is the first report of an infection caused by A. quadrilineatus.

Adult↗
PubMed1992

Development of DNA probes for early diagnosis and epidemiological study of cryptococcosis in AIDS patients.

We report the isolation of middle-repetitive DNA sequences from Cryptococcus neoformans that are species and variety specific. These probes were used for assessing strain relatedness among cryptococcal isolates from patients with and without AIDS who were from Zaire and the United States. Five distinct hybridization patterns were observed for the 60 isolates examined, regardless of the restriction enzyme used for digestion. The most common pattern among the isolates from the patients without AIDS was also the most common among the isolates from the patients with AIDS who were from the United States and was the only pattern observed for all isolates tested from patients with AIDS who were from Zaire. On the basis of the high specificity and sensitivity of the signals observed by hybridization, we suggest that these sequences provide a means for both biotyping and early diagnosis of C. neoformans.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Endocarditis caused by Blastoschizomyces capitatus and taxonomic review of the genus.

Blastoschizomyces capitatus Salkin, Gordon, Samsonoff et Rieder was found to be the etiologic agent of endocarditis in a patient with a prosthetic mitral valve. Cultures inoculated with peripheral blood and portions of the valve yielded B. capitatus. Examination of stained tissue sections revealed the presence of fungal filaments morphologically consistent with this organism. The salient characteristics of B. capitatus and the factors contributing to its recognition as a distinct taxon are described.

Aged↗
PubMed1992

The identification and tracking of Candida albicans isolates from oral lesions in HIV-seropositive individuals.

Restriction fragment polymorphism analysis was used to investigate the identity and genotypic relatedness of Candida albicans strains isolated from human immunodeficiency virus (HIV)-infected patients with or without oral candidiasis and from some of their sexual partners. Use of the species-specific DNA probe Ca3 revealed that most subjects carried a single distinct C. albicans strain throughout the course of the study, during both symptomatic and asymptomatic periods. Sexual partners were more likely to carry the same or similar C. albicans isolates than unrelated subjects, raising the possibility of transmission via intimate contact. One patient appeared to acquire his partner's isolate, which then became predominant in both partners in subsequent isolations. These findings indicate that recurrent oral candidiasis is usually caused by a single persistent strain unique to each patient, but that in some cases transmission via intimate contact may occur between sexual partners.

AIDS-Related Opportunistic Infections↗
PubMed1992

Cytokine-induced resistance to microbial infections in normal, immunosuppressed and bone marrow transplanted mice.

We studied the efficacy of in vivo and in vitro treatments with IL-1, IL-2, IL-3, and GM-CSF in the protection against bacterial (Salmonella typhimurium), fungal (Candida albicans) and viral (influenza virus A/PR8) infections, of normal, sublethally irradiated and lethally irradiated, bone marrow (BM) reconstituted mice. In parallel, the cytokines were tested for their ability to potentiate hematopoietic activity in vitro and in vivo. We demonstrate that, under the experimental conditions employed, IL-1 had the best protective activity against the three micro-organisms in both normal and immunocompromised mice when administered in vivo. Administration of IL-2 led to increased resistance in normal but not in immunodeficient mice, whereas GM-CSF had no beneficial effects. In contrast, preincubation of BM cells in these cytokines, singly or combined, prior to transplantation to lethally irradiated mice, did not confer protection against subsequent infection, although it increased the number of BM derived CFU-GM in culture (except in the case of IL-2). Administration of IL-1 or GM-CSF to BM transplanted mice facilitated WBC recovery, whereas IL-2 delayed it. Collectively, the data suggest that IL-1, alone or combined with other cytokines, may be beneficial in the prevention or treatment of microbial infections in immunocompromised and BM transplanted patients. It can also be concluded that enhanced hematopoietic recovery may not always coincide with the development of resistance to micro-organisms.

Animals↗