Mark Ruddel

Diagnosis and therapeutic monitoring of invasive candidiasis by rapid enzymatic detection of serum d-arabinitol

BACKGROUND Using a rapid automated enzymatic assay, we prospectively investigated serum D-arabinitol (DA), a biochemical marker of invasive candidiasis, in a large population of high-risk patients to determine its potential diagnostic, therapeutic, and prognostic significance in invasive candidiasis. PATIENTS AND METHODS A total of 3,223 serum samples were collected from 274 patients with cancer. Serum DA concentrations were determined in coded serum samples analyzed by rapid enzymatic assay. Creatinine also was analyzed in the same system to determine a serum DA and creatinine ratio (DA/Cr). The sensitivity, specificity, correlation with therapeutic response, and prognostic significance were analyzed for all patient study groups. RESULTS A DA/Cr of > or = 4.0 mumol/L per mg/dL was detected in 31 (74%) of all 42 cases of fungemia and 25 (83%) of the 30 cases of the subset of persistent fungemia. Elevated DA/Cr was detected in 4 (40%) of 10 patients with tissue-proven, deeply invasive candidiasis and negative blood cultures (eg, hepatosplenic candidiasis or localized abscess) and 7 (44%) of 16 cases of deep mucosal candidiasis (eg, esophageal candidiasis). Elevated serial DA/Cr levels also were detected in persistently febrile and granulocytopenic patients requiring empirical amphotericin B. Among 26 assessable cases of fungemia, abnormally elevated DA/Cr values were detected in 14 (54%) before, 10 (38%) after, and 2 (8%) simultaneously with the first microbiologic report of fungemia. The trends of serial DA/Cr values correlated with therapeutic response in 29 (85%) of 34 patients with assessable cases of fungemia, decreasing in 8 (89%) of 9 patients with clearance of fungemia and increasing in 21 (84%) of 25 patients with persistence of fungemia. Among the 34 assessable patients with fungemia, mortality was directly related to the trend of serial DA/Cr determinations over time: 71% among fungemic patients who had persistently elevated or increasing DA/Cr, and 18% among the fungemic patients who had resolving DA/Cr or never had elevated DA/Cr (P < 0.01). CONCLUSIONS Rapid enzymatic detection of DA in serially collected serum samples from high-risk cancer patients permitted detection of invasive candidiasis, early recognition of fungemia, and therapeutic monitoring in DA-positive cases. Serially collected serum DA determinations complement blood cultures for improving detection and monitoring therapeutic response in patients at risk for invasive candidiasis.

Intravenous Fluorescein Interference With Clinical Laboratory Tests

The results of laboratory tests performed after fluorescein angiography may be erroneous because of interference by intravenous fluorescein. We investigated this potential interference in four adults at intervals of five minutes, three hours, six hours, and 12 hours after fluorescein injection. We used a panel of serum and urine chemistry tests on seven commonly used instruments. A significant change in the reported concentration of a serum or urine analyte was defined as a result beyond +/- 3 coefficients of variation of the preinjection baseline value for the test on a specific instrument. The determinations of creatinine, total protein, cortisol, digoxin, quinidine, and thyroxine in serum were affected by intravenous fluorescein. The urine tests were unaltered. The physician must be aware of the problem of interpreting clinical chemistry results after fluorescein angiography.

Rapid measurement of insulin using the Abbott IMx: application to the management of insulinoma

Background: Patients with multiple endocrine neoplasia (type 1) often present with multiple pancreatic endocrine tumours, such as insulinomas. A major difficulty in the surgical treatment of such patients is identifying which tumours are functionally active and therefore need to be resected for a cure. The objective of this study was to develop a rapid insulin assay that could be used intraoperatively for identifying insulinomas from pancreatic aspirates. Methods: By reducing the incubation time and by increasing the sample volume, a rapid insulin assay was developed on the IMx analyser. This was used to measure insulin from tissue aspirates collected from suspected insulinomas under ultrasound guidance. Results: The rapid insulin assay (y) could be performed in 14 min and showed a good correlation with the standard IMx (x) insulin assay (y=0·808x+0·04; r 2=0·986). Using the rapid insulin assay on pancreatic tissue aspirates, insulinomas could be readily distinguished from normal pancreatic tissue or from non-functional adenomas based on a marked increase in insulin content. Conclusion: In summary, a new rapid assay for insulin is described that compares favourably to the standard IMx insulin assay and can potentially be used intraoperatively on pancreatic aspirates for identifying functionally active insulinomas.