Biomedical subjects

J E Bennett

Publications and source records attributed to J E Bennett.

At least 73 records · Page 4Linked to original sources

PubMed1988

Efficacies of four antifungal agents in experimental murine sporotrichosis.

Four antifungal agents, amphotericin B, SDZ 89-485, itraconazole, and terbinafine, were tested for efficacy in a murine model of systemic sporotrichosis. Survival in the groups treated with amphotericin B, SDZ 89-485, and itraconazole was significantly better than that of control infected mice. However, these agents did not wholly protect the infected mice, as tail and paw lesions, whole-body radiographs, and positive cultures from survivors showed evidence of dissemination. Terbinafine-treated mice had the same or poorer survival as control infected mice, despite documented drug absorption.

Amphotericin B↗

PubMed1988

An enzymatic method for 5-fluorocytosine.

We developed an enzymatic method for determination of 5-fluorocytosine in serum, using creatine iminohydrolase (EC 3.5.4.21), the Cobas-Bio analyzer, and an extant ammonia method. Analytical recovery (y) of drug added to serum (x) was good, with y = 0.97x-0.7, Sy.x = 3.6, r = 0.997 (n = 65) over the range 6.25 to 150 mg/L. Comparison with an HPLC method (x) showed good agreement: y = 0.98x + 1.34, Sy.x = 3.7 (n = 37), as analyzed with the Deming debiased regression. Precision was good, CVs being less than 3% for within-run and less than 6% for between-run controls. Ammonia, amphotericin B, glucose, urea, and hemolysis do not interfere, but bilirubin shows analyte-dependent interference and lipemia interferes when triglycerides exceed 5 g/L. This assay is accurate, inexpensive, and easy to perform. It can be easily adapted for routine or emergency use.

Aminohydrolases↗

PubMed1987

Galactomannan antigenemia and antigenuria in aspergillosis: studies in patients and experimentally infected rabbits.

Purified galactomannan (GM) from Aspergillus fumigatus was used in both a radioimmunoassay and an enzyme-linked immunoassay for antigen detection. Results of the two tests seemed interchangeable. By one or both assays, GM was detected in serum from four of 12 rabbits lethally infected with A. fumigatus in concentrations ranging from 108 to 356 ng/ml. Serum antigen was detected in only two of 12 patients with invasive aspergillosis. Results of assay for GM in urine were far more encouraging. Urinary GM was detectable throughout the course of lethal aspergillosis in all 16 rabbits, in concentrations of 24-1,900 ng/ml. Urine from seven of 13 patients with invasive aspergillosis had GM concentrations of 1-83 ng/ml. Antigen excretion roughly paralleled extent of disease.

Animals↗

PubMed1987

Receptor-mediated clearance of Aspergillus galactomannan.

The fate of radiolabeled Aspergillus fumigatus galactomannan was studied after intravenous injection into rabbits and rats. At 1 hr, the liver contained 35% of the injected dose in rabbits and 30% in rats. Excretion of galactomannan into the urine, measured in rabbits, was another major catabolic route and accounted for 35% of the dose by 24 hr. Immunization of rabbits increased hepatic uptake and decreased urinary excretion. Hepatic uptake in unimmunized rats could be decreased by Saccharomyces cerevisiae mannan, alpha-methyl mannoside, and N-acetylglucosamine, known inhibitors of the macrophage mannose receptor. Autoradiography showed hepatic radiolabeled galactomannan to be concentrated in Kupffer cells, which express the mannosyl receptor for glycoproteins. Macrophage mannosyl receptors may constitute a general mechanism for clearing fungal mannans from the bloodstream.

Acetylglucosamine↗

PubMed1987

Urease inhibition by EDTA in the two varieties of Cryptococcus neoformans.

Cryptococcus neoformans var. neoformans (74 isolates) and C. neoformans var. gattii (44 isolates) were used to test urease activity after growth on both yeast extract-glucose-peptone agar (YEPG) and on YEPG supplemented with 100 microM EDTA. Every isolate grown on YEPG agar for 48 h at 30 degrees C produced a positive reaction within 1 h in a modified rapid urease assay at 37 degrees C. However, isolates grown on YEPG with 100 microM EDTA showed a distinct pattern which corresponded to their varietal status. All but 1 of 74 C. neoformans var. neoformans isolates (98.7%) produced a positive reaction within 1 to 4 h, while none of 44 C. neoformans var. gattii isolates produced a positive reaction within the same period. The urease inhibition results and the canavanine-glycine-bromthymol blue agar test results showed 100% correlation among isolates of C. neoformans var. gattii and 98.7% correlation among isolates of C. neoformans var. neoformans. Two representative isolates of C. neoformans var. gattii (serotypes B and C) were further tested for urease during a prolonged incubation period in urea broth. These isolates failed to show a positive reaction even after 11 h of incubation. The uptake of EDTA was negligible in the two varieties. Extracts of cells grown on YEPA agar showed a high level of urease activity in both varieties. Extracts of cells grown on the agar with 100 microM EDTA showed a marked reduction (86%) of urease activity in one isolate of C. neoformans var. gattii but showed only a 30% reduction in one isolate of C. neoformans var. neoformans. Based on these results, the differential effect of EDTA on the two varieties of C. neoformans appeared to be due to greater inhibition of urease synthesis in C. neoformans var. gattii.

Cryptococcus↗

PubMed1987

Oxidative killing of Aspergillus fumigatus proceeds by parallel myeloperoxidase-dependent and -independent pathways.

The relative importance of several oxygen intermediates in fungicidal action against opsonized Aspergillus fumigatus conidia was investigated with monocytes from normal volunteers and patients with either chronic granulomatous disease or myeloperoxidase (MPO) deficiency. Results from experiments in which catalase, taurine, mannitol, or glucose-glucose oxidase were added to these phagocytes indicated that the MPO-hydrogen peroxide-halide system and an MPO-independent oxidative system exerted comparable conidiacidal activity. These findings offer a plausible explanation for the susceptibility of patients with chronic granulomatous disease to invasive Aspergillus infections; their phagocytes fail to generate hydrogen peroxide, a substrate necessary for both systems. Patients with MPO deficiency are not known to be predisposed to invasive aspergillosis, suggesting that an MPO-independent oxidative system may provide an alternative mechanism for the oxidative killing of Aspergillus spp.

Aspergillus fumigatus↗

PubMed1986

Paracoccidioidomycosis case report: cure with amphotericin B and triple sulfa.

A man developed paracoccidioidomycosis with non-productive cough and changes on chest roentgenogram one year following agricultural work in Ecuador. Oropharyngeal and nasal lesions developed 2 years later. This chronic fungal infection is typically difficult to cure, and relapses are common. After treatment with 2.5 g of amphotericin B and a 3-year course of triple sulfa, our patient remained free of disease during 12 years of follow-up.

Aged↗

PubMed1986

Inhibition of complement by culture supernatants of Aspergillus fumigatus.

Aspergillus fumigatus produced a water-soluble extracellular material that inhibited the opsonization of fungal cells by normal human serum. Blastospores of Cryptococcus neoformans and conidia from A. fumigatus or Aspergillus niger were used as fungal targets for ingestion by human monocytes. The opsonic inhibitor from A. fumigatus was found to decrease binding of complement component C3b to fungal surfaces by selectively interfering with activation of the alternative complement pathway. Inhibition of complement did not appear to result simply from proteolysis, as judged by the minimal degradation of casein and of purified C3 and C4. The complement-inhibiting activity was partially labile to heating at 100 C and could be concentrated by using dialysis tubing with a 10,000-dalton exclusion limit. Aspergillus flavus, which is also a pathogen for humans, also produced this activity; A. niger did not. We speculate that this material may represent a pathogenesis factor for Aspergillus species.

Aspergillus fumigatus↗

PubMed1986

Rapid enzymatic method for measurement of serum flucytosine levels.

Creatinine iminohydrolase (EC 3.5.4.21) quantitatively releases ammonia from flucytosine (5FC) as well as from creatinine. Using 39 sera from eight patients receiving the combination of amphotericin B with 5FC, we demonstrated that this rapid enzymatic reaction provides a valid measure of 5FC levels. The correlation coefficients (r), comparing this method with 5FC bioassay and high-pressure liquid chromatography measurements, were 0.78 and 0.87, respectively. This technique offers a precise alternative to the currently employed methods of measuring 5FC levels. In contrast to other methods, this enzymatic technique is rapid, simple, inexpensive, and has the potential for widespread availability.

Aminohydrolases↗

PubMed1986

Surgical treatment of congenital breast asymmetry.

Congenital breast asymmetry of sufficient severity to prompt surgical consultation is rare. The present study evaluated 40 patients who were treated for breast asymmetry at the Indiana University Medical Center. Objective measurements have been correlated with a subjective evaluation of symmetry to elucidate the goals of successful treatment. The surgical experience of the entire group is summarized and the patients who returned for follow-up are assessed.

Adolescent↗

PubMed1986

Breast volume and anthropomorphic measurements: normal values.

Fifty-five consecutive female volunteers were evaluated. Linear measurements of the breast and nipple position were determined to fixed points on the chest wall. Volume determination was done by a standard chest-wall casting technique. A highly significant difference was found between left and right breasts in the axilla-to-nipple distance and nipple-to-midline measurements. A significant difference was also found in the distance from the lowest point of the breast (patient upright) to the nipple. Analysis of the volumetric difference between right and left breasts did not achieve statistical significance.

Adolescent↗

PubMed1986

Prolactin levels in hypothyroid and euthyroid infants during the first week of life.

A radioimmunoassay (RIA) procedure was devised for the estimation of PRL in eluates of dried whole blood from filter paper. Levels of PRL were measured in newborn blood obtained during the first week of life from 530 infants of normal birthweight (greater than 2500 g) with normal T4 values, 114 infants of normal birthweight with low T4 values (T4 less than 6.0 micrograms/dl), 47 infants with congenital hypothyroidism, 57 infants of low birthweight (less than 2500 g) with normal T4 values, and 114 infants of low birthweight with low T4 values. Examination of PRL concentrations among comparably aged infants from the various groups revealed that the mean PRL values of the hypothyroid group were consistently greater than those of any of the other groups of infants regardless of the mean T4 levels. With the exception of the hypothyroid infants, the groups with both the lowest mean T4 concentrations and mean body weights also had the lowest mean PRL values.

Birth Weight↗

PubMed1986

Bioassay for SF 86-327, a new antifungal agent.

A bioassay with Trichophyton mentagrophytes is described for SF 86-327, an allylamine antifungal agent. SF 86-327 serum concentrations were measured by bioassay in 117 serum sampler from five patients receiving 500 mg/day. The peak, trough, and area under the concentration-time curve were determined after the first dose and at steady state. Drug accumulation occurred with prolonged therapy.

Antifungal Agents↗

PubMed1986

Results of a survey of antifungal susceptibility tests in the United States and interlaboratory comparison of broth dilution testing of flucytosine and amphotericin B.

In a survey of 350 laboratories, 41 of 210 respondents indicated that they performed antifungal susceptibility tests. Two-thirds performed 20 or fewer tests per year, and most used a broth dilution method to test amphotericin B and flucytosine activity against Candida albicans. The broth dilution procedure of S. Shadomy and A. Espinel-Ingroff (p. 647-653, in E.H. Lennette, ed., Manual of Clinical Microbiology, 3rd ed., 1980) was the method most frequently cited, and therefore this method was used to test the susceptibility of five isolates of C. albicans and one of Saccharomyces cerevisiae to amphotericin B and flucytosine in seven research laboratories. Agreement among replicates performed on the same day by each laboratory was excellent for both drugs, all values being within 1 twofold drug dilution. Precision from week to week for each laboratory was also good, with 95 and 92% of values being within 1 drug dilution for amphotericin B and flucytosine, respectively. Interlaboratory precision, however, was poor. For amphotericin B, values varied 8- to 32-fold, and for flucytosine, they varied 32- to greater than 512-fold. We conclude that antifungal susceptibility testing is currently being performed in small volumes by numerous laboratories in the United States and that results from one laboratory may not agree with results from another. Improved standardization of fungal susceptibility tests is necessary before their results can be generally applied to clinical situations.

Amphotericin B↗

PubMed1986

Assessment of new radioimmunoassay kit for determining urinary albumin at low concentrations: comparison with radial immunodiffusion.

The assay characteristics of a new radioimmunoassay kit for determining urinary albumin at low concentrations were studied. The sensitivity for urinary albumin was 2 mg/l, the analytical range 2 to 40 mg/l, and interassay coefficient of variation less than 12%. In a method comparison study entailing diabetic urine samples covering an albumin concentration of 2 to 150 mg/l the kit compared adequately with radial immunodiffusion (mean difference between methods = 2 mg/l; residual standard deviation = 4.6 mg/l), absolute variation between methods increasing with the concentration. The kit required much less skill than radial immunodiffusion but its capital and running cost were higher.

Albuminuria↗

PubMed1986

Assessment of immunochemical methods for determining low concentrations of albumin in urine.

Four immunochemical methods (radioimmunoassay, RIA; radial immunodiffusion, RID; immunoturbidimetry, IT; enzyme-linked immunosorbent assay, ELISA) for measuring urinary albumin at low concentrations were assessed for their assay characteristics and practicability. Precision and accuracy were comparable between the methods when studied individually. We made a method comparison, with RIA as reference, using urine samples from diabetic patients with albumin concentrations ranging from 1 to 120 mg/L. There was no significant systematic difference between RID and RIA, but IT and ELISA gave consistently lower values than RIA, the mean differences being 1.8 (p less than 0.01) and 9.7 mg/L (p less than 0.001), respectively. Random error, compared with that for RIA, was in increasing order: RID (residual SD = 3.8 mg/L); IT (4.3 mg/L); ELISA (7.3 mg/L). The difference between the methods increased with the albumin concentration. Operational cost was highest with IT, lowest with RIA. Capital cost was highest with RIA and lowest with RID, which required most technical skill. ELISA had intermediate overall costs.

Albuminuria↗

PubMed1986

Tolerance to cryptococcal polysaccharide in cured cryptococcosis patients: failure of antibody secretion in vitro.

Ten patients cured of cryptococcosis and 14 normal volunteers were immunized with subcutaneous injections of cryptococcal polysaccharide (CPS). Peripheral mononuclear cells cultured from the volunteers 7 days post-immunization secreted significant amounts of IgM, IgA and IgG antibody to CPS in vitro. In cell cultures obtained 7 days after immunization of patients, nine of 10 had neither IgM nor IgG antibody response to CPS, and eight lacked anti-CPS IgA. Depletion of T lymphocytes from patients' cell cultures did not promote specific antibody secretion to CPS by B cells. The intense, prolonged antigenaemia with CPS that accompanies cryptococcosis may be responsible for the failure of cured patients to have circulating anti-CPS-secreting cells after immunization.

Adult↗

PubMed1985

Cutaneous postirradiation sarcoma. Ultrastructural evidence of pluripotential mesenchymal cell derivation.

A 75-year-old man developed synchronous multicentric cutaneous sarcomas and basal cell carcinoma of the face 57 years after receiving irradiation for acne. During the previous 30 years he had been treated many times for actinic keratoses and basal cell carcinomas. Surgical treatment had included total nasectomy, excision, and replacement of the skin of the upper and lower lips and the chin. Due to the multiplicity of morphologic patterns, it was difficult to subtype the sarcomas. Ultrastructural studies showed histiocyte-like, fibroblast-like and vasoformative cells suggesting an origin from a pluripotential mesenchymal stem cells.

Acne Vulgaris↗