Biomedical subjects
Publications and source records attributed to M G Rinaldi.
A megabore column gas-liquid chromatographic method which uses nitrogen-phosphorus detection was developed for the analysis of fluconazole in plasma, serum, cerebrospinal fluid, or urine. The assay was linear from 0.2 to 200 micrograms/ml and had an average coefficient of variation of 7%. The suitability of the assay for pharmacokinetic studies was demonstrated.
Congenitally athymic (nu/nu) mice, mice defective in NK cell and macrophage function (bg/bg), and normal BALB/c mice were inoculated sc with 10 conidia of Fonsecaea pedrosoi (FP). In immunologically intact and immunodeficient mice, a local infection developed approximately 2 weeks post-inoculation and enlarged over 1-2 weeks. In bg/bg and normal nu/+ mice, lesions resolved within 5-6 weeks. However, nu/nu mice continued to have enlarging sc lesions during greater than 4-6 months of observation. These eventually metastasized. Lesions contained few hyphal elements and massive numbers of sclerotic bodies. Five weeks after inoculation, 10 conidia forming units/gm of tissue were recovered from lesions. Delayed type hypersensitivity and serum antibody to FP antigens were demonstrated. Adoptive transfer of lymphocytes from nu/+ mice was followed in 2 months by the resolution of the lesions.
A 58-year-old, alcoholic, diabetic man presented with multiple, ulcerated skin lesions and polymicrobial septicemia. Sporothrix schenckii was recovered from blood cultures and was resistant to amphotericin B by in vitro testing. Amphotericin B therapy failed, but the patient responded dramatically to itraconazole therapy, only to relapse 3 months after therapy was stopped. Reinstitution of itraconazole therapy has produced another dramatic response. This report is noteworthy for three reasons. First, to our knowledge, it represents only the second reported instance of fungemia with S schenckii that responded to medical therapy. Second, it illustrates that in vitro antifungal susceptibility tests may predict clinical infection response to drug therapy. Third, it suggests that itraconazole has significant promise in treating systemic sporotrichosis.
Zygomycosis represents an excellent example of an opportunistic fungal infection that generally occurs in the debilitated, immunocompromised, or acidotic host. Infections are usually fulminant, with etiologic agents exhibiting predilection for invasion of blood vessels with resultant infarction and necrosis. The spectrum of agents capable of inciding zygomycosis has broadened and the incidence has increased in contemporary medicine. Nevertheless, an increased index of suspicion, better mycological acumen, aggressive surgical debridement of diseased tissue, and prompt therapy with amphotericin B have rendered substantial improvement in the prognosis of an otherwise fatal infectious disease. Rapid and accurate diagnostic techniques and the availability of less toxic, efficacious antifungal agents should be sought after goals for the enhanced management of zygomycosis.
The number and types of opportunistic fungal pathogens are increasing dramatically. It is likely that this trend will continue as the numbers of immunosuppressed patients escalate. Both the clinician and laboratorian must maintain a high index of suspicion for mycoses in these settings. Responsible fungal agents may be classified across the entire fungal kingdom and include both yeasts and molds. In addition to the need for improved methods of diagnosis and therapy, it is truly time for medical professionals to "think fungus"!
The serial dilution assay (for example, an in vitro antimicrobic susceptibility test or a serum antibody titer assay) is an important technique in biomedical research. The structure of the experiment forces grouping of the threshold concentrations into intervals. Statistical methods to analyse threshold concentrations from a batch of serial dilution assays should account for the grouping of the data. Many traditional subject area analyses, however, ignore the grouped nature of the data. This article discusses the discrepancy between the traditional subject area approach and the usual statistical approach for analysing such grouped data.
The occurrence of human nocardiosis is increasing in both immunocompetent as well as immunosuppressed patients. We report three rare cases of primary lymphocutaneous Nocardia brasiliensis infection. The mode of inoculation in each case was that of a puncture wound that occurred 1-3 wk prior to the development of the clinically apparent infections. The original clinical diagnosis was erroneous in each case. A review of 16 previously reported cases is presented as well as a discussion of appropriate medical therapy.
Explore the source record for details and available documents.
The pharmacokinetics of itraconazole, an orally effective, broad-spectrum, systemic antifungal agent, were evaluated in five healthy male volunteers. Each subject was studied on days 1 and 15 at the following dosages: 100 mg once daily (regimen A), 200 mg once daily (regimen B), and 200 mg twice daily (regimen C). On each study day, itraconazole was administered with a standardized meal. Plasma samples were collected for 72 h postdose, and 24-h urine specimens were obtained. On day 1 of regimen C, plasma samples were collected following the second dose. Samples were assayed for itraconazole by a sensitive, reverse-phase, high-performance liquid chromatography method. Wide intersubject variations in itraconazole concentration in plasma versus time profiles were observed on all study days. Absorption appeared to be slow, with day 1 mean peak itraconazole concentrations in plasma of 110 ng/ml at 2.8 h (regimen A), 272 ng/ml at 3.0 h (regimen B), and 553 ng/ml at 3.4 h (regimen C). Mean peak itraconazole concentrations in plasma on day 15 were 412 ng/ml at 3.0 h (regimen A), 1,070 ng/ml at 4.4 h (regimen B), and 1,980 ng/ml at 6.0 h (regimen C). The steady state was achieved by day 13. Respective elimination half-lives on days 1 and 15 were 15 and 34 h (regimen A), 20.7, and 36.5 h (regimen B), and 25 and 41.7 h (regimen C), respectively. The areas under the plasma concentration versus time curves (0 to infinity) on day 1 were 1,320 (regimen A), 4,160 (regimen B), and 12,600 ng.h/ml (regimen C). With the exception of one patient on day 15 of regimen C, itraconazole was not detected in the urine. All data support dose-dependent pharmacokinetic behavior for itraconazole.
The salient morphologic and physiologic characteristics of 18 isolates of Scedosporium inflatum, a newly reported human pathogen, were compared with those of the morphologically similar fungi Scedosporium apiospermum, Scopulariopsis brevicaulis, and Scopulariopsis brumptii. The formation by S. inflatum of annelloconidia in wet clumps at the apices of annellides with swollen bases was found to be the most useful characteristic in differentiating this potential pathogen.
We initiated a comparative study of four methods of yeast inoculum preparation: a spectrophotometric method, the Wickerham card method, a hemacytometer method, and the Prompt inoculation system. The variability in inoculum size obtained when each method was applied to two strains each of Candida albicans, Candida tropicalis, Candida parapsilosis, Torulopsis glabrata, Cryptococcus neoformans, and Saccharomyces cerevisiae was analyzed in a single laboratory. Each method was performed in triplicate on the same day and on three separate days to provide estimates of within-day and between-day variations. Inoculum size was determined by viable colony counts. The greatest range of inoculum sizes was seen with the Wickerham card method. Viable counts ranged from 1.1 X 10(6) to 24.2 X 10(6) CFU/ml among the 12 yeast isolates. The greatest variation was observed with the Prompt system. Within-day coefficients of variation averaged 19% (range, 4 to 45%), and between-day coefficients of variation averaged 22% (range, 3 to 51%). Variation between laboratories was evaluated by comparing inoculum values obtained by each method in three different laboratories for two strains of C. albicans. The spectrophotometric method was the least variable and the Wickerham card and hemacytometer methods were the most variable methods between laboratories. The spectrophotometric method is recommended as the method of choice for preparation of a standardized inoculum suspension for susceptibility testing of yeasts.
Recently, reports have surfaced in which saprobic fungi, as well as fungi pathogenic for plants, seem to be evolving as human pathogens. While the bulk of infected patients are immunocompromised, many individuals appear to be immunocompetent. To our knowledge, this is the second known published case of maxillary sinusitis caused by Curvularia lunata in an immunocompetent patient. An interesting feature of this case is that the patient was treated with only surgery (débridement and irrigation) with complete resolution and no recurrence.
Curvularia lunata is a saprobic dematiaceous mould that resides primarily in soil (Ellis, 1966). Reports of human disease caused by this organism are rare but include: endocarditis, brain abscess, skin infections, onychomycosis, keratitis, pneumonia, disseminated disease, mycetoma, allergic bronchopulmonary disease, and one case of sinusitis. Since 1983, we have encountered five cases of paranasal sinusitis due to C. lunata. None of the patients suffered from known immunologic disorders or underlying debilitating diseases. These five cases are presented and the literature of human phaeohyphomycosis caused by Curvularia spp. is reviewed.
An 81-year-old man presented with a chronic, painful nodule on the palmar surface of the left fourth finger. As a former farm worker, the patient acknowledged frequent soil-contaminated wounds of the left hand 4 to 12 years previously, but he denied any recent trauma. The patient's other medical problems included a history of chronic immunoglobulin A gammopathy and a new pleural mass eroding into adjacent ribs on chest X-ray. The finger nodule was excised and consisted of an intact phaeohyphomycotic cyst which yielded growth of a darkly pigmented fungus. At 25 degrees C, the isolate formed annellidic yeast cells having dark-brown walls consistent with the recently described species Phaeoannellomyces elegans. In vitro antifungal susceptibility tests indicated resistance to amphotericin B and variable susceptibility to imidazoles. The lesion was excised, and the patient received no antifungal therapy. After 9 months of follow-up, the fungal infection shows no signs of recurrence.
Explore the source record for details and available documents.
We have reported 7 new cases of Bipolaris infection and 2 of Exserohilum infection, which demonstrate the capability of these 2 genera to cause invasive as well as "allergic" disease. As noted previously, it is likely that all of the cases of "Helminthosporium" and Drechslera infections reported in the literature were caused by Bipolaris or Exserohilum. Infections due to these 2 genera are probably more common than previously recognized. They should be included in the differential diagnosis of central nervous system and disseminated fungal disease, sinusitis, keratitis, peritonitis associated with continuous ambulatory peritoneal dialysis, and allergic bronchopulmonary disease. These various entities have distinct histopathologic characteristics. With disseminated disease in the immunocompromised patient, the most frequent findings are acute inflammation with prominent vascular invasion, thrombosis, and infarction. In contrast, granulomatous inflammation and leukocytoclastic vasculitis are seen in meningoencephalitis caused by these fungi. The histologic features of allergic bronchopulmonary disease and sinusitis are similar. A chronic inflammatory infiltrate of lymphocytes, plasma cells and eosinophils within edematous granulation tissue is found in addition to squamous metaplasia and thickening of the basement membrane. Infections caused by Bipolaris/Exserohilum and Aspergillus show many clinical and pathologic similarities despite the lack of taxonomic relationship between these fungi. Both cause disseminated disease in immunocompromised patients that is characterized by tissue necrosis and vascular invasion. Both cause central nervous system disease, osteomyelitis, and sinusitis and are associated with allergic bronchopulmonary disease. Sinusitis, the most common form of disease caused by Bipolaris and Exserohilum, occurs in otherwise healthy patients with nasal polyposis and allergic rhinitis. Although pathologic evidence of bone invasion may not be found, there frequently is radiographic evidence of invasive disease. Most patients who are treated initially with surgical debridement and amphotericin B have apparently been cured. However, longer follow-up will be necessary in these patients. Amphotericin B appears to be the treatment of choice for invasive infections caused by Bipolaris/Exserohilum species. Ketoconazole and other imidazole derivatives may also be effective in certain of the disease entities caused by these black moulds; however, their role has yet to be defined.(ABSTRACT TRUNCATED AT 400 WORDS)
We have described the first case of systemic Fusarium moniliforme infection complicating marrow transplantation. The infection was fulminant despite aggressive therapy. Review of previously reported cases of human Fusarium infection suggests that the skin is a common portal of infection.
Study of numerous living isolates of Bipolaris, Drechslera, Exserohilum, and Helminthosporium spp., as well as a mycological assessment of published case reports of phaeohyphomycosis attributed to these fungi, showed that Bipolaris australiensis, B. hawaiiensis, B. spicifera, Exserohilum longirostratum, E. mcginnisii, and E. rostratum are well-documented pathogens. Conidial shape, septation, and size, hilar characteristics, the origin of the germ tube from the basal cell and, to a lesser extent, from other conidial cells, and the sequence and location of the conidial septa are useful criteria for distinguishing these taxa.