Biomedical subjects
Publications and source records attributed to D M Dixon.
A case of laboratory-acquired sporotrichosis is described that was associated with research activities involving isolates of Sporothrix schenckii from the 1988 sporotrichosis epidemic in the USA. Infection occurred in the absence of apparent trauma or other predisposing factors. The possibility that S. schenckii can invade healthy and intact skin is suggested.
Five clinical and 69 environmental isolates from the largest U.S. epidemic of sporotrichosis were evaluated in NYLAR male mice following intravenous injection of 5 x 10(6) to 2 x 10(8) conidia per mouse. The clinical isolates and eight environmental isolates produced 100% mortality in groups of three mice each between 12 and 24 days after injection. These virulent isolates grew at 37 degrees C, were dematiaceous by virtue of melanin (melanized) on permissive media (e.g., potato dextrose agar), produced ovoid conidia borne sympodially on lateral conidiophores and pleurogenously about the main hyphal axis, and were identified as Sporothrix schenckii. Two melanized environmental isolates that grew at 35 degrees C but not at 37 degrees C were not virulent and had subtle morphological differences from S. schenckii. The remaining environmental isolates were not melanized, were not virulent, and were not S. schenckii; five were identified as Ophiostoma stenoceras and the remainder were identified as Sporothrix spp. Quantitative organ cultures revealed that clinical isolates grew exponentially in livers and testes, in contrast to an isolate of O. stenoceras that was eliminated from liver, lung, and spleen but that persisted in the testes throughout the 14-day sample period. This model helped to confirm the identification of S. schenckii isolates obtained from the environment.
DNA typing techniques were used to examine selected clinical and environmental isolates of Sporothorix spp. recovered from the 1988 sporotrichosis epidemic in multiple states of the United States. Previous studies indicated that isolates in one of the six morphologically or physiologically distinct groups (group I) obtained from environmental sources were Sporothrix schenckii and were the possible etiologic agents responsible for the epidemic. To assess this hypothesis at the genetic level, whole-cell DNA was extracted from selected clinical isolates and representative members of each of the six environmental groups subjected to endonuclease digestion and then analyzed by gel electrophresis. DNA types were assigned on the basis of restriction fragment length polymorphism patterns. One DNA type was common to clinical and group I isolates but was dissimilar from the DNA types exhibited by groups II to VI. In contrast, a variety of DNA types were associated with isolates in groups II to VI. The latter groups appeared to make up a heterogeneous collection of fungi, with some members of the same group having different DNA types but with others from different groups possessing identical DNA types. Thus, DNA typing studies confirmed that group I environmental isolates are indistinguishable from clinical isolates and that group II to VI isolates represent a complex of related fungi with similar Sporothrix anamorphs.
The spinal motor effects of galanin, which co-exists with 5-hydroxytryptamine (5-HT) and thyrotrophin-releasing hormone (TRH) in bulbospinal raphe neurones innervating spinal motoneurones, were examined by administering this neuropeptide through indwelling intrathecal cannulae to conscious adult Wistar rats. The acute effect of intrathecal galanin on spontaneous motor behaviour and the motor behaviours (back muscle contractions and wet-dog shakes) elicited by intrathecal injection of the non-selective 5-HT receptor agonist, 5-methoxy-N, N'-dimethyltryptamine (5-MeODMT) or the TRH analogue, RX 77368 analogue, RX 77368 (pGlu-His-3,3'-dimethyl-ProNH2), respectively, and the chronic effect of galanin on neurochemical markers for bulbospinal raphe neurones and spinal motoneurones were determined. Intrathecal galanin (0.1 to 10 micrograms) did not produce any notable motor behaviours when given alone, but pretreatment with the neuropeptide (0.1 micrograms) significantly attenuated both the number of wet-dog shakes and the amount of forepaw-licking induced by RX 77368, without affecting 5-MeODMT-induced back muscle contractions. Repeated intrathecal galanin administration (1 microgram, twice daily for 5 d) significantly elevated 5-HT (but not 5-hydroxyindoleacetic acid) and substance P-like immunoreactive (LI) levels and choline acetyltransferase (ChAT) activity in the dorsal, but not in the ventral, portion of the thoraco-lumbar spinal cord. In contrast, chronic intrathecal galanin did not alter the TRH- or calcitonin gene-related peptide (CGRP)-LI levels in either spinal cord region.(ABSTRACT TRUNCATED AT 250 WORDS)
The largest recorded epidemic of sporotrichosis in the United States occurred in 1988 and involved a total of 84 cases in 15 states. All cases were associated with Wisconsin-grown sphagnum moss. Twenty-one clinical isolates of Sporothrix schenckii and 69 environmental isolates of Sporothrix spp. from the epidemic were characterized and compared. The environmental isolates were recovered from 102 samples of sphagnum moss and other material by using direct plating techniques. Characteristics examined included macroscopic and microscopic morphology, conversion to a yeast phase, exoantigen reactions, and virulence in mice. On the basis of these studies, eight environmental isolates were identified as S. schenckii, five were identified as Ophiostoma stenoceras, and the remainder were identified as Sporothrix species. The environmental isolates of S. schenckii were recovered from moss samples from one Pennsylvania nursery and from three New York State Soil and Water Conservation districts, but none were recovered from moss directly from the bogs in Wisconsin.
The chemistry, activity, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and administration of fluconazole are reviewed. Fluconazole is a triazole antifungal agent labeled for use in the treatment of oropharyngeal and esophageal candidiasis and cryptococcal meningitis. Like the imidazoles, fluconazole inhibits the C-14 demethylation of lanosterol, but it has little or no effect on mammalian cytochrome P-450 enzymes. Fluconazole's activity in vitro does not reflect its effectiveness in vivo. Pharmacokinetic characteristics include water solubility and excellent bioavailability, low protein binding, extensive tissue distribution, and penetration into the cerebrospinal fluid. Fluconazole is eliminated primarily by the kidneys; dosage adjustments are necessary in patients with renal insufficiency. Studies have shown fluconazole to be effective in patients with cryptococcal meningitis and candidiasis, but the superiority of fluconazole over such agents as amphotericin B, ketoconazole, clotrimazole, and itraconazole remains to be proved. Fluconazole has shown varying degrees of success in the treatment of other systemic mycoses. The adverse effects of fluconazole are relatively infrequent and are primarily gastrointestinal. Tolbutamide, warfarin, rifampin, cyclosporine, and phenytoin interact with fluconazole. The drug is available in both oral and intravenous formulations. Fluconazole is a broad-spectrum antifungal drug that appears to be similar in efficacy to other antifungals in the treatment of some systemic mycoses. More studies must be completed before fluconazole can be recommended as a first-line antifungal therapy.
Epidermolytic proteases were partially purified from six strains of Candida albicans, four of which were isolated from patients with cutaneous diseases. Two of the strains exhibited a unique time-course of enzyme production compared to that previously reported, with detectable epidermolytic protease levels being significantly delayed. All epidermolytic proteases had pH and temperature optima of 4-4.5 and 35-37 degrees C, respectively. These conditions are consistent with the microenvironment of human skin, a habitat where an epidermolytic protease would appear to be an important advantage to the yeast. Candida epidermolytic proteases were more active against a substrate of normal human epidermis than that obtained from psoriatic patients. When human epidermis replaced bovine serum albumin as the protein source within the culture medium, the epidermolytic activity of the resultant enzyme was reduced by 9 and 25% for normal and psoriatic epidermis substrates, respectively. The proteases were found to contain major protein bands at 42 and 66 kDa. The ability of these same Candida strains to adhere to human epidermal cells was studied and found to be optimal at 35-37 degrees C within neutral pH values. Pepstatin, bovine brain gangliosides, and convalescent human serum all interfered with the adherence of the yeast to epidermal cells. A higher yeast-epidermal-cell adherence for Candida was demonstrated on normal rather than psoriatic epidermal cells, and after treating the cells with partially purified Candida protease.
[3H]Dynorphin A(1-8) is readily metabolised by rat lumbosacral spinal cord tissue in vitro, affording a variety of products including a significant amount (20% recovered activity) of [3H][Leu5]enkephalin. In the presence of the peptidase inhibitors bestatin, captopril, thiorphan, and leucyl-leucine, [3H][Leu5]enkephalin was the major metabolic product, accounting for 60% of recovered activity. Production of [3H][Leu5]enkephalin was seen across all gross brain regions. The enzyme responsible for the cleavage has an optimal substrate length of 8-13 amino acids and is inhibited by N-[1-(RS)-carboxy-2-phenylethyl]-Ala-Ala-Phe-p-aminobenzoate, a site-directed inhibitor of the metalloendopeptidase EC 3.4.24.15. However the enzymic breakdown also has properties in common with involvement of endo-oligopeptidase A. Possible consequences of the formation of [Leu5]-enkephalin from the smaller dynorphins are discussed.
1. The agonist action of the opioid peptide dynorphin A(1-8) on the myenteric plexus-longitudinal muscle of the guinea-pig ileum has been characterized. 2. The endogenous opioid peptide dynorphin A(1-8) was rapidly degraded by slices of myenteric plexus-longitudinal muscle of the guinea-pig ileum. 3. A product of the degradation was the delta-receptor preferring [Leu5]enkephalin. Levels of [Leu5]enkephalin were markedly increased in the presence of the peptidase inhibitors bestatin, thiorphan and captopril. 4. In the myenteric plexus dynorphin A(1-8) acted as a kappa-receptor agonist. In the presence of bestatin, thiorphan and captopril a mu-receptor agonist effect was observed. This mu-agonist action was lost in the presence of N-[1-(RS)-carboxy-2-phenylethyl]Ala-Ala-Phe-p-aminobenzoate, an inhibitor of the endopeptidase enzyme EC 3.4.24.15. 5. The results suggest that formation of [Leu5]enkephalin from dynorphin A(1-8) may be an important conversion process. The enzyme responsible may be the Zn2(+)-metalloendopeptidase, EC 3.4.24.15.
Dactylaria constricta var. gallopava (Cooke) Salkin et Dixon was found to cause fatal encephalitis in a 28-day-old, captivity-bred snowy owl chick (Nyctea scandiaca). The previously healthy bird suddenly developed ataxia, severe torticollis, and extensor rigidity of the legs. Since the animal did not improve with antibiotic or vitamin-mineral supplement therapy, the chick was euthanized 5 days after the onset of neurologic signs. At necropsy, all tissues except the brain were grossly normal. Cultures inoculated with blood from the brain and heart yielded a dematiaceous mould that subsequently proved to be D. constricta var. gallopava. This is the first report of natural central nervous system infection caused by D. constricta var. gallopava in a snowy owl.
Sporothrix cyanescens has been recovered from blood and a finger lesion at several medical centers in the United States. The morphology and physiology of these and three additional isolates were studied. S. cyanescens was distinguished from S. schenckii and S. fungorum by white to lavender colonial pigmentation and from S. schenckii also by the formation of secondary conidia. All isolates of S. cyanescens grew well at 37 degrees C, were cycloheximide susceptible, strongly urease positive, and benomyl resistant, failed to hydrolyze starch, and were inhibited by sodium chloride in vitro at a concentration of greater than or equal to 12%. Study of S. cyanescens in a murine model by using intravenous inoculation failed to demonstrate an invasive pathogenic potential. The validity of the transfer of S. cyanescens to the new genus Cerinosterus Moore is discussed.
A microbiological survey of the Mongolian gerbil, Meriones unguiculatus, revealed coagulase-negative staphylococci to be common inhabitants of representative animals derived from three different breeding colonies. The nasal area was most often culture positive, and Staphylococcus xylosus was a predominant species. S. xylosus was the only organism cultured from nasal dermatitis. These organisms were found to be susceptible in vitro to the majority of the antimicrobial agents tested. This survey indicates that the possible role of S. xylosus as an opportunistic pathogen warrants further investigation.
The purpose of this review is to characterize the environmental microbiology, hospital epidemiology, diagnosis and treatment of nosocomial aspergillosis. Appropriate environmental control measures are important in preventing or arresting an outbreak of nosocomial aspergillosis. These include selective environmental microbiological surveillance and floor to ceiling barriers during construction or renovation. These is particularly important for the bone marrow transplant units and units with persistently granulocytopenic patients. We have summarized the point source and cited or formulated the environmental correction measures relating to 25 outbreaks of nosocomial aspergillosis involving a total of more than 100 patients. The most frequent settings of nosocomial invasive aspergillosis occurred in granulocytopenic patients following respiratory infection from an airborne source, associated with hospital construction or contaminated ventilation systems.
An unusual fungus, probably traumatically introduced into the eye of a horse while grazing, was studied on various mycological media. Upon examination of colonies the organism produced bulbils and clearly exhibited the characteristics of a new species of Papulaspora, P. equi Shadomy & Dixon.
Melanized wild-type and melanin-deficient (Mel-) strains of Wangiella dermatitidis (Kano) McGinnis were tested for in vitro susceptibility to amphotericin B, flucytosine, amorolfine, ketoconazole, fluconazole, terbinafine, and itraconazole by using an agar dilution technique. Although the MICs of itraconzole obtained with seven of the eight Mel- strains were lower than those obtained with the melanized wild-type strains, there was no such trend observed with fluconazole, the other triazole tested. Furthermore, there was no apparent difference in MICs when comparing the melanized wild-type and the Mel-strains for the other drugs tested. Thus, no consistent increase in in vitro antifungal activity was found to be associated with a specific class of drug. Therefore, melanin does not appear to confer protection against some of the more important antifungal agents.
We report on a model of primary pulmonary aspergillosis occurring after intranasal instillation of concentrated suspensions of conidia of Aspergillus fumigatus in immunocompromised mice. Unconcentrated suspensions of inoculum contained ca. 2 x 10(7) conidia per ml (1x). These suspensions were concentrated by centrifugation, adjusted to give ca. 2 x 10(8) (10x) or 2 x 10(9) (100x) conidia per ml, and delivered in 30-microliters droplets to the nares of anesthetized mice. Mice were untreated or injected with cortisone acetate (CA) or cyclophosphamide (CY) in various dosage regimens. It was not possible to obtain mortality of more than 50% with sublethal immunosuppressive treatment and 1x fungus. In contrast, mortality followed a fungus dose response in mice receiving sublethal immunosuppression with either CA or CY. Mortality rates of up to 100% were obtained with 100x fungus and a single dose of CY (200 mg/kg) or CA (250 mg/kg) or three alternate doses (125 mg/kg per day) of CA prior to infection. This model is applicable to the study of acute, fatal primary pulmonary aspergillosis and chemotherapy trials.
Candida lipolytica was recovered from six patients in three different clinical centers. The index isolate caused a persistent fungemia with catheter-associated Candida thrombophlebitis, the second isolate was from a polymicrobial sinusitis, and the remaining four isolates were involved in tissue colonization. These and 20 other isolates were consistent in their morphological and physiological characteristics. All formed true hyphae and blastoconidia on cornmeal-Tween 80 agar and all assimilated glucose, glycerol, and erythritol. In a murine model of disseminated candidiasis, the index isolate that caused clinical fungemia caused no mortality and produced only two lesions on a kidney, as determined at necropsy. The nine isolates selected for in vitro antifungal susceptibility studies had intermediate susceptibilities to amphotericin B but were susceptible to ketoconazole. We conclude that C. lipolytica is a weakly virulent pathogen which may require an intravascular foreign body to cause fungemia.