Disseminated candidiasis is a life-threatening infection in immunosuppressed cancer patients; also, at risk are transplant recipients, surgical and burn patients, and AIDS victims. Because of the lack of rapid and reliable diagnostic techniques (antimortem blood cultures are positive in only 25-50% of cases) and the protean nature of symptoms, 80% of the cases are not diagnosed early enough to permit effective treatment. The proposed work is based upon rapid gas chromatographic-mass spectrometric techniques for the quantification in serum of arabinitol, a unique metabolite of Candida and eight polyols.
Specific aims : 1) Monitoring serum arabinitol concentrations (conc.): Does a sudden increase of arabinitol conc. to """"""""above normal"""""""" signal the onset of fungal infection? Do increasing arabinitol conc. indicate progression of the disease? Do one or two """"""""above normal"""""""" arabinitol values followed by return to normal represent transient fungemia? Could the monitoring of arabinitol conc. guide the intensification or cessation of antifungal therapy? Do arabinitol conc. decrease with successful antifungal therapy? Will antifungal therapy be more effective and less toxic when initiated at an early stage, possibly before the onset of clinical symptoms, as indicated by increasing arabinitol concentrations? 2) Improve specificity: Are serum polyol values useful for the differentiation of increased arabinitol conc. caused by Candida septicemia from those resulting from renal insufficiency in the absence of fungal infections? Can the separation/quantification of D and L arabinitol be used for differentiation of renal insufficiency? Are there additional characteristic biochemical markers of Candida? 3) Extension of applications: Can the arabinitol conc. of sputum or bronchial washings aid the diagnosis of esophageal candidiasis? Are there diagnostic uses of the arabinitol and/or polyol concentrations in urine and spinal fluid? Techniques proposed, particularly the monitoring of patients are risk, should permit early definitive diagnosis of disseminated candidiasis which, in turn, will permit more effective and less toxic therapy. Success of this work will directly benefit patients with potentially fatal Candida infections.
| Roboz, J; Katz, R N (1992) Diagnosis of disseminated candidiasis based on serum D/L-arabinitol ratios using negative chemical ionization mass spectrometry. J Chromatogr 575:281-6 |
| Christensson, B; Roboz, J (1991) Arabinitol enantiomers in cerebrospinal fluid. J Neurol Sci 105:234-9 |
| Roboz, J; Kappatos, D; Holland, J F (1990) Polyol concentrations in serum during hemodialysis. Clin Chem 36:2082-6 |
| Roboz, J; Nieves, E; Holland, J F (1990) Separation and quantification by gas chromatography-mass spectrometry of arabinitol enantiomers to aid the differential diagnosis of disseminated candidiasis. J Chromatogr 500:413-26 |
| Roboz, J; Kappatos, D C; Holland, J F (1987) Role of individual serum pentitol concentrations in the diagnosis of disseminated visceral candidiasis. Eur J Clin Microbiol 6:708-14 |
