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The activity of liposomal nystatin against invasive pulmonary aspergillosis was investigated in persistently neutropenic rabbits. Treatment groups included liposomal nystatin at dosages of 1, 2 and 4 mg/kg/day intravenously, or amphotericin B deoxycholate 1 mg/kg/day administered intravenously after normal saline loading. As compared with untreated controls, liposomal nystatin administered at 2 and 4 mg/kg/day prolonged survival and reduced fungus-mediated tissue injury and excess lung weight at post-mortem in a similar manner to amphotericin B. Although amphotericin B was superior in clearing infected lung tissue, treatment with all regimens of liposomal nystatin led to a significant reduction in pulmonary fungal tissue burden. During treatment, ultrafast CT-scan demonstrated ongoing resolution of pulmonary lesions at 2 and 4 mg/kg/day, but not at 1 mg/kg/day. With the exception of mild increases in blood urea nitrogen (BUN) and serum creatinine values during treatment at 2 and 4 mg/kg/day, which were similar to those found in amphotericin B-treated rabbits, liposomal nystatin was well tolerated. Preliminary pharmacokinetic studies in non-infected animals established linear drug disposition of liposomal nystatin in plasma over the investigated dosage range and peak plasma levels above the MIC for the test strain after multiple daily dosing for 7 days. Liposomal nystatin increased survival and provided reduced tissue injury, effective microbiological clearance and tolerable side effects in experimental pulmonary aspergillosis in persistently neutropenic rabbits, thus providing a rational basis for further investigations in clinical trials.

To determine which brain region is responsible for the generation of sexual automatisms.

We determined the interrelations of chronological age, age at seizure onset, duration of seizure disorder, cognitive functioning (IQ), scales of activities of daily living, depressive mood disorder and measures of health-related quality of life (HRQOL). Furthermore, we investigated the association of the laterality of seizure onset zone and absence/presence of hippocampal atrophy and/or sclerosis (HA/HS) with measures of HRQOL, activities of daily living (ADL) and depressive mood disorder. In the setting of pre-surgical epilepsy evaluation, a sample of 56 patients with temporal lobe epilepsy (TLE) was studied using the Bonner Skalen für Epilepsie (BPSE) and the depression inventory D-S of von Zerssen. Patients reported high levels of dependency on others and poor coping capabilities. Our data also showed specific ADL-behaviour suggesting social withdrawal and isolation. Our results indicate emotional impairment as a major problem in TLE, because 45% of our patients scored in the depressive range of the D-S depression scale. Depression score was found to be a powerful predictor of self-reported quality of life after adjusting for seizure-related variables, demographic variables and cognitive functioning (IQ). The only scale showing a significant laterality effect was ADL-home. No relationship between the dependent measures of HRQOL, ADL-social, ADL-cultural, depressive mood disorder and laterality of the epileptogenic zone or absence/presence of HA/HS was found. HRQOL and depressive mood disorder are strongly interrelated indicating that patients with depressive symptoms report lower quality of life and specific patterns of ADL. HRQOL, ADL and depressive mood disorder are largely independent of biological markers such as laterality of seizure onset zone and absence/presence of HA/HS in TLE.

An 80-point genetic map [77 random-amplified polymorphic DNAs (RAPD), F (female sex expression), de (determinate), and ll (little leaf)] was constructed from a narrow cross in cucumber using the determinate, gynoecious, standard-sized leaf line G421 and the indeterminate, monoecious, little leaf line H-19. The map defined nine linkage groups and spanned ca. 600 cM with an average distance between markers of 8.4 ± 9.4 cM. The RAPD loci BC-551 and BC-592 were found to flank ll at 3.4 and 12.2 cM, respectively. The locus OP-L18-2 was linked (16 cM) to de, and the F locus was flanked by markers at 44 and 31 cM. One-hundred F3 families were used to identify quantitative trait loci (QTL) for sex expression, main stem length, number of lateral branches, days to anthesis, fruit number and weight, fruit length and diameter, and fruit length: diameter ratio in two replicated test locations (Wisconsin and Georgia). QTL on linkage group B explained major portions (R2 = ca. 2 to 74%) of the variation observed for sex expression, main stem length, lateral branch number, and fruit diameter (LOD = 2.1 to 29.8). Although ca. 62 to 74% of the variation for sex expression was associated with a putative QTL spanning the F locus (OP-AJ-2 to F and F to de), other regions (three) of the genome were important for the determination of sex in the F3 families examined depending upon environment. The number of genomic regions affecting main stem length (five) and number of lateral branches (three) coincided with expectations as determined by calculations of minimum number of genes in previous studies. Evaluation of QTL associated with several fruit number determinants of early, first-harvest yield demonstrating additive genetic variance (i.e., sex expression, main stem length, and number of laterals) suggests that marker-assisted selection may have utility for the development of determinate, multiple lateral branching germplasm suited for once-over mechanical harvesting in this population.

To investigate the potential use of SCH-39304 for the prevention and treatment of disseminated candidiasis in granulocytopenic patients, we studied its in vivo antifungal activity as preventive, early, and late treatments in three models (acute, subacute, and chronic) of disseminated candidiasis in persistently granulocytopenic rabbits. SCH-39304 was an effective as amphotericin B alone and fluconazole alone for the prevention of disseminated candidiasis. SCH-39304 alone and fluconazole alone were as effective as amphotericin B plus flucytosine for early treatment of subacute disseminated candidiasis. When treatment was delayed for 5 days to establish chronic disseminated candidiasis, SCH-39304 was less effective than amphotericin B plus flucytosine. In comparison with different treatment regimens, SCH-39304 was more effective in early and preventive treatment. Thus, SCH-39304 was comparable to treatment control regimens in prevention and early treatment of subacute disseminated candidiasis. SCH-39304 also was most effective in granulocytopenic rabbits with disseminated candidiasis when used for prevention or early treatment.

Results of qualitative and quantitative studies of prenatal skeletal development in Macaca mulattaare presented. Longitudinal radiographic observations were carried out on 20 monkeys of known gestational age, beginning on 120 days of gestation until the neonatal stage of skeletal development. These studies were based on multiple uterotomies on each pregnant female. The technique described provides accurate data on prenatal bone ossification, and permits an accurate estimation of fetal age in pregnant rhesus monkeys with unknown conception dates.

In order to further understand serum D-arabinitol (DA) as a marker for the diagnosis of disseminated candidiasis and for monitoring response to antifungal therapy, we studied the serum levels of this Candidacarbohydrate metabolite by rapid automated enzymatic assay in rabbits with experimental disseminated candidiasis. The enzymatic reaction steps were performed on a standard automated clinical chemistry analyser. As a correction for renal impairment, data were expressed as serum D-arabinitol/creatinine ratio (DA/Cr). Serum creatinine concentrations were determined from the same sample with the same instrument, thereby allowing rapid determination of the DA/Cr within one laboratory. The DA/Cr was determined in 321 samples from 132 rabbits. The mean serum DA/Cr in 31 normal non-infected rabbits was 1··51 ±± 0··2 µµmmg−−1dl−−1. Among 84 rabbits with disseminated candidiasis and pre-terminal samples, there was a direct correlation between DA/Cr and tissue concentration of Candida albicans(r=0··80; P<0··001). A threshold of elevated DA/Cr (≥≥ 3··0 µµmmg−−1dl−−1) was evident in rabbits with a tissue concentration of C. albicans≥≥ 3 ×× 104colony forming units (CFU) g−−1. Elevated DA/Cr was detected in 48 (89%) of 54 rabbits at a C. albicanstissue concentration of ≥≥ 3 ×× 104CFU g−−1vs. one (3%) of 30 rabbits with <3 ×× 104CFU g−−1(P<0··0001). Among all 101 rabbits with disseminated candidiasis, an elevated DA/Cr was detected at any point during infection in 60 (92%) of 65 rabbits having a C. albicanstissue concentration ≥≥ 3 ×× 104CFU g−−1vs. 13 (36%) of 36 rabbits with <3 ×× 104CFU g−−1(P<0··0001). The relationship between the tissue response to antifungal therapy and change in DA/Cr was then further analysed. Ten (91%) of 11 rabbits with a tissue-proven response to antifungal therapy (defined as ≥≥ 102-fold reduction of CFU g−−1in comparison to untreated controls) had a >50% reduction in elevated DA/Cr levels. By comparison, 10 (83%) of 12 treated rabbits with no response to therapy had persistently elevated DA/Cr levels (P<0··001). These findings provide an experimental basis for understanding the patterns of expression of serum DA in disseminated candidiasis and further indicate that serial DA/Cr measurements may be useful for diagnosis and therapeutic monitoring of disseminated candidiasis.

Cilofungin (LY-121019) is a fungicidal cell wall-active 1,3-beta-glucan synthetase inhibitor with a short plasma half-life and saturable nonlinear plasma pharmacokinetics. To optimize the in vivo efficacy of this compound, we studied the effects of its linear and nonlinear pharmacokinetics during continuous versus intermittent intravenous infusion of cilofungin in the treatment of experimental disseminated candidiasis in persistently granulocytopenic rabbits. Six groups of rabbits were studied, untreated controls (n = 32) and five cilofungin dosage regimen groups consisting of the following: 25 mg/kg of body weight intravenously twice daily (VLoINT) (n = 9); 50 mg/kg twice daily (LoINT) (n = 9); 90 mg/kg twice daily (HiINT) (n = 11); 5 mg/kg/h for 18 h/day (LoCI) (n = 7); and 10 mg/kg/h for 18 h/day (HiCI) (n = 7). All regimens achieved plasma concentrations exceeding the MIC for Candida albicans (0.25 microgram/ml). In vitro timed kill assays found that the fungicidal activity and rate of kill by cilofungin above the MIC for C. albicans was concentration dependent. At the lower dosage regimens (VLoINT, LoINT, and LoCI), cilofungin followed linear plasma pharmacokinetics, whereas at higher doses (HiCI and HiINT), nonlinear kinetics consistent with a saturated elimination pathway(s) were observed. Only HiCI and HiINT produced a 10(3)- to 10(4)-fold reduction in CFU per gram in candidiasis of the brain (P less than or equal to 0.001). HiCI and HiINT also significantly reduced infection in the choroid (P less than or equal to 0.05). All regimens, except VLoInt, significantly (P less than or equal to 0.01) reduced tissue infections in lung, liver, spleen, and kidney. However, only the regimens with nonlinear saturation kinetics (HiCI and HiINT) produced a 10(6) reduction in the spleen and a > 10(5) reduction of C. albicans in the kidney and liver. A simple doubling of the dosage from LoCI to HiCI resulted in tissue concentrations that were 10 times higher and a 10(2)- to 10(4)-fold-greater antifungal effect. There was a direct correlation (r2 = 0.83) between tissue concentrations of cilofungin and antifungal activity. Thus, continuous and intermittent infusion dosage regimens that elicit nonlinear saturation plasma pharmacokinetics of cilofungin were associated with increased antifungal activity against experimental disseminated candidiasis.

The aim of this study was to develop an operation for total thymectomy suitable for nonhuman primates. The thymus was removed from 24 macaque monkeys from fetal to adult life by a cervicothoracotomy and blunt gauze dissection. Mean wet weight of the thymus rose from 150 mg (range 50‐250 mg) in fetal animals to 2.5 gm (range 0.3‐4.2 gm) in prepubertal monkeys. Nonhuman primate thymic weight fell steadily and uniformly with age by over 300% when plotted as a function of body weight. This surgical technique appears to be a valid method of total thymectomy in macaque monkeys.

The significance of quantitative urine cultures in patients at risk for hematogenous disseminated candidiasis is controversial. While various concentrations of Candida spp. in urine have been suggested as critical cutoff points in the diagnosis of renal candidiasis, other investigators consider quantitative cultures less critical in diagnosing upper tract infections. To determine the significance of quantitative urine cultures in renal candidiasis, we studied serial quantitative urinary cultures of Candida albicans in a rabbit model of hematogenous infection. Of 197 urine samples from 34 infected animals, 144 were culture positive, with a sensitivity of 73.1% for urine cultures and a lower limit of detection of 10 CFU/ml. The yield of urine cultures varied according to severity and duration of infection. The mean renal and urinary concentrations of C. albicans from rabbits with subacute candidiasis differed significantly from those from rabbits with acute candidiasis (P = 0.013 and P < or = 0.001, respectively). During the first 4 days of subacute renal candidiasis, more than one-half of all urine cultures were negative for C. albicans. Only 12 (8.1%) of 148 urine cultures in animals with subacute renal candidiasis had concentrations of > 10(3) CFU/ml, 2.7% had concentrations of > 10(4) CFU/ml, and none were > or = 10(5) CFU/ml. By comparison, all urine cultures from the animals with lethal acute renal candidiasis had higher concentrations of C. albicans and were positive throughout the course of infection. Urinary concentrations of C. albicans were not predictive of the amount of Candida in the kidney (r < or = 0.49) and did not correlate with survival (r = 0.0232). However, the renal concentration of C. albicans (in CFU/gram) inversely correlated with the duration of survival (in days) of rabbits with renal candidiasis (r = 0.76; P < 0.001). These findings indicate that a negative urine culture in rabbits does not preclude the presence of renal candidiasis. The interpretation of a urine culture positive at any concentration, on the other hand, must involve an analysis of the risk factors for renal candidiasis, for any urinary concentration of C. albicans may reflect kidney infection.

To compare the reliability of clinical seizure lateralization in temporal lobe epilepsy patients with unitemporal and bitemporal independent interictal spikes and unilateral hippocampal atrophy or sclerosis (HA/HS) on MRI scan.

The distinction between upper versus lower urinary tract infection in patients with candiduria is a commonly encountered and therapeutically important diagnostic dilemma. Candidacasts have been reported in the urine of several individual case reports of human renal candidiasis. The specificity of Candidacasts would identify unequivocally a patient with upper urinary tract disease. Little is known, however, about the sensitivity and the formation of Candidacasts. We therefore studied the diagnostic yield, methods for detection and pathogenesis of Candidacast formation in serially collected urine specimens from immunologically intact and granulocytopenic rabbit models of haematogenous disseminated candidiasis. Refractile blastoconidia and pseudohyphae of Candidaencased in the granular matrix were seen on wet mounts while Candidastained a brilliant red in the fuschia pink tubular matrix on periodic acid Schiff (PAS) stained cytopathology filters. Among 24 rabbits with disseminated candidiasis, 11 (46%) had Candidacasts detectable by wet mount and PAS-stained urine filters in comparison to none of 10 non-infected immunologically normal controls (P=0··014). Fifteen (70%) of 21 episodes of Candidacasts were detected within the first 3 days of infection, indicating possible utility in the early diagnosis of renal candidiasis. No Candidacasts were detected in the urine of granulocytopenic rabbits, possibly due to the rapid destruction of tubules and abrogation of cast formation. This absence of detectable Candidain eight infected granulocytopenic rabbits differed significantly from that of 24 non-granulocytopenic infected rabbits, in which Candidacasts were detected in 11 (46%) (P=0··029). Candidacast formation occurred predominantly in the cortex. Histopathological examination demonstrated invasion of Candidainto the glomerular tufts and peritubular capillaries, followed by development of Candidacasts in the proximal and distal tubules, respectively. Detection of renal Candidacasts may be a useful diagnostic marker in distinguishing upper versus lower urinary tract candidiasis.

A unilamellar liposomal formulation of amphotericin B (LAmB) known as AmBisome was safely administered intravenously to 20 rabbits at 0.5, 1.0, 2.5, 5, or 10 mg/kg of body weight, whereas of 12 rabbits given desoxycholate amphotericin B (DAmB) intravenously at 0.5, 1.0, or 1.5 mg/kg, 2 died of acute cardiac toxicity when DAmB was administered at the highest dose. Single-dose LAmB (1 mg/kg) achieved a maximum concentration in serum (Cmax) of 26 +/- 2.4 micrograms/ml and an area under the curve to infinity (AUC0-infinity) of 60 +/- 16 micrograms.h/ml, while single-dose DAmB (1.0 mg/kg), by comparison, achieved a lower Cmax (4.7 +/- 0.2 micrograms/ml; P = 0.001) and a lower AUC0-infinity (30.6 +/- 2.2 micrograms.h/ml; P = 0.07). Following administration of a single dose of LAmB (10 mg/kg), a disproportionately higher Cmax (287 +/- 14 micrograms/ml) and AUC0-infinity (2,223 +/- 246 micrograms.h/ml) occurred, indicating saturable elimination. After chronic dosing (n = 4) with LAmB at 5.0 mg/kg/day for 28 days or DAmB at 1.0 mg/kg/day for 28 days, LAmB achieved daily peak levels of 122.8 +/- 5.8 micrograms/ml and trough levels of 34.9 +/- 1.8 micrograms/ml, while DAmB reached a peak of only 1.76 +/- 0.11 microgram/ml and a trough of 0.46 +/- 0.04 microgram/ml (P < or = 0.001). Significant accumulations of amphotericin B into reticuloendothelial organs were observed, with 239 +/- 39 micrograms/g found in the liver after chronic LAmB dosing (5 mg/kg/day), which was seven times higher than the 33 +/- 6 micrograms/g after DAmB dosing (1 mg/kg/day) (P = 0.002). Accumulation in kidneys, however, remained 14-fold lower (P =0.04) following LAmB dosing (0.87 +/- 0.61 microgram/g) than after DAmB dosing (12.7 +/- 4.6 microgram/g). Nephrotoxicity occurred in only one of four LAmB treated animals, while it occurred in all four chronically DAmB-treated animals: mild hepatozicity with transaminase elevations was seen in one LAmB-treated rabbit. We conclude that LAmB safely achieved higher Cmax(s) and AUC0-infinity(s) and demonstrated saturable, nonlinear elimination from plasma via reticuloendothelial organ uptake. Take reduced nephrotoxicity of LAmB correlated with diminished levels of amphotericin B in the kidneys.

The fetal surgery and fetal radiography utilized in longitudinal radiographic study of bone maturation in Macaca mulattaand their implications for fetal surgery are discussed. The novel technique of serial uterotomies and multiple exposure of the same fetus (two‐week intervals) starting on 120 days of gestation as well as anesthesia and surgical procedures are presented.

Pulmonary infiltrates in neutropenic hosts with invasive aspergillosis are due to vascular invasion and hemorrhagic infarction. In order to measure the effect of antifungal compounds on this organism-mediated tissue injury, we monitored the course of pulmonary infiltrates by serial ultrafast computerized tomography (UFCT) in persistently granulocytopenic rabbits with experimental invasive pulmonary aspergillosis. The course of pulmonary lesions measured by serial UFCT scans was compared with those measured by conventional chest radiography, histopathological resolution of lesions, and microbiological clearance of Aspergillus fumigatus. Treatment groups included either amphotericin B colloidal dispersion in dosages of 1, 5, and 10 mg/kg of body weight per day intravenously or conventional desoxycholate amphotericin B at 1 mg/kg/day intravenously. Therapeutic monitoring of pulmonary lesions by UFCT demonstrated a significant dose-response relationship. Lesions continued to progress in untreated controls, whereas lesions in treated rabbits initially increased and then decreased in response to antifungal therapy in a dosage-dependent manner (P < or = 0.05 to P < or = 0.005, depending upon the groups compared). This same trend of resolution of lesions in response to antifungal therapy was also demonstrated by postmortem examination and by microbiological clearance of the organism. These data indicated that amphotericin B colloidal dispersion at 5 and 10 mg/kg/day exerted a more rapid rate of clearance of lesions than conventional amphotericin B. UFCT was more sensitive than conventional chest radiography in detecting lesions due to invasive pulmonary aspergillosis (P < 0.05 to P < 0.005, depending upon the groups compared). These findings establish a correlation among UFCT-defined lesions, microbiological response, and resolution of pathologically defined lesions in experimental invasive pulmonary aspergillosis. Serial monitoring of UFCT-defined lesions of aspergillosis provides a novel system for determining the antifungal response of organism-mediated tissue injury.

The observations of Armstrong and Harrison,1 those of Sabin, Olitsky and Cox2 and, especially, those of Schultz and Gebhardt3 seem to show conclusively that certain chemical agents carefully applied to the olfactory mucosa of monkeys afford considerable protection against infection by subsequent intranasal instillation of poliomyelitis virus. The essential observations which have been made up to the present were summarized in a recent article by Schultz and Gebhardt4 and therefore do not need to be repeated here.This evidence, that a chemical agent such as 1 per cent zinc sulfate confers on monkeys a high degree of resistance against poliomyelitis virus for at least one month after treatment, suggests that such a prophylactic measure may deserve a trial in human beings during periods when poliomyelitis is prevalent. We have concerned ourselves primarily with devising a method of ap- plying the prophylactic treatments that can be easily

A review of the literature yields meager results in regard to the regeneration of the lining of the maxillary antrums following the complete (or incomplete) removal of the original membrane at the time of operation.Tonndorf1 reported the case of a patient who died of an abscess of the liver one month after a radical operation on the antrum, during which a complete removal of the lining had been done. He noted that a granulation tissue originating from the endosteum covered all parts of the antrum, and that ciliated columnar epithelium was growing in from the naso-antral opening. The outermost edge of the ingrowing epithelium was of the flat type, but farther back the ciliated type was evident. Goblet cells were also present in the epithelial covering.Skillern2 mentioned two cases in which inspection of the antrums through openings in the canine fossa some years after radical operations showed the

Catch-up growth is believed to result from a central nervous system mechanism that compares actual growth to a set point and adjusts growth velocity accordingly. Alternatively, we hypothesized that catch-up growth is intrinsic to the growth plate. To test this hypothesis, we infused dexamethasone phosphate for 4 weeks directly into one proximal tibial growth plate of 5-week old rabbits and infused vehicle into the contralateral growth plate. Growth velocity at each tibial growth plate was determined radiographically. Dexamethasone decreased the growth velocity of the treated growth plate by 37 ± 8 % (mean ± SEM, p < 0.01) compared to the control, causing a growth deficit of 4.8 ± 1.2 mm (p<0.01). After the end of the infusion, the growth velocity of the dexamethasone-treated growth plate rebounded above that of the control and ultimately corrected 52 ± 10 % of the deficit (p<0.01). Because the catch-up growth occurred solely within the dexamethasone-treated growth plate, we conclude that catch-up growth is intrinsic to the epiphyseal growth plate and cannot be explained by a systemic mechanism.

The distinction between upper versus lower urinary tract infection in patients with candiduria is a commonly encountered and therapeutically important diagnostic dilemma. Candida casts have been reported in the urine of several individual case reports of human renal candidiasis. The specificity of Candida casts would identify unequivocally a patient with upper urinary tract disease. Little is known, however, about the sensitivity and the formation of Candida casts. We therefore studied the diagnostic yield, methods for detection and pathogenesis of Candida cast formation in serially collected urine specimens from immunologically intact and granulocytopenic rabbit models of haematogenous disseminated candidiasis. Refractile blastoconidia and pseudohyphae of Candida encased in the granular matrix were seen on wet mounts while Candida stained a brilliant red in the fuschia pink tubular matrix on periodic acid Schiff (PAS) stained cytopathology filters. Among 24 rabbits with disseminated candidiasis, 11 (46%) had Candida casts detectable by wet mount and PAS-stained urine filters in comparison to none of 10 non-infected immunologically normal controls (P=0·014). Fifteen (70%) of 21 episodes of Candida casts were detected within the first 3 days of infection, indicating possible utility in the early diagnosis of renal candidiasis. No Candida casts were detected in the urine of granulocytopenic rabbits, possibly due to the rapid destruction of tubules and abrogation of cast formation. This absence of detectable Candida in eight infected granulocytopenic rabbits differed significantly from that of 24 non-granulocytopenic infected rabbits, in which Candida casts were detected in 11 (46%) (P=0·029). Candida cast formation occurred predominantly in the cortex. Histopathological examination demonstrated invasion of Candida into the glomerular tufts and peritubular capillaries, followed by development of Candida casts in the proximal and distal tubules, respectively. Detection of renal Candida casts may be a useful diagnostic marker in distinguishing upper versus lower urinary tract candidiasis.

In order to further understand serum D-arabinitol (DA) as a marker for the diagnosis of disseminated candidiasis and for monitoring response to antifungal therapy, we studied the serum levels of this Candida carbohydrate metabolite by rapid automated enzymatic assay in rabbits with experimental disseminated candidiasis. The enzymatic reaction steps were performed on a standard automated clinical chemistry analyser. As a correction for renal impairment, data were expressed as serum D-arabinitol/creatinine ratio (DA/Cr). Serum creatinine concentrations were determined from the same sample with the same instrument, thereby allowing rapid determination of the DA/Cr within one laboratory. The DA/Cr was determined in 321 samples from 132 rabbits. The mean serum DA/Cr in 31 normal non-infected rabbits was 1·51 ± 0·2 µm mg−1 dl−1. Among 84 rabbits with disseminated candidiasis and pre-terminal samples, there was a direct correlation between DA/Cr and tissue concentration of Candida albicans (r=0·80; P<0·001). A threshold of elevated DA/Cr (≥ 3·0 µm mg−1 dl−1) was evident in rabbits with a tissue concentration of C. albicans ≥ 3 × 104 colony forming units (CFU) g−1. Elevated DA/Cr was detected in 48 (89%) of 54 rabbits at a C. albicans tissue concentration of ≥ 3 × 104 CFU g−1 vs. one (3%) of 30 rabbits with <3 × 104 CFU g−1 (P<0·0001). Among all 101 rabbits with disseminated candidiasis, an elevated DA/Cr was detected at any point during infection in 60 (92%) of 65 rabbits having a C. albicans tissue concentration ≥ 3 × 104 CFU g−1 vs. 13 (36%) of 36 rabbits with <3 × 104 CFU g−1 (P<0·0001). The relationship between the tissue response to antifungal therapy and change in DA/Cr was then further analysed. Ten (91%) of 11 rabbits with a tissue-proven response to antifungal therapy (defined as ≥ 102-fold reduction of CFU g−1 in comparison to untreated controls) had a >50% reduction in elevated DA/Cr levels. By comparison, 10 (83%) of 12 treated rabbits with no response to therapy had persistently elevated DA/Cr levels (P<0·001). These findings provide an experimental basis for understanding the patterns of expression of serum DA in disseminated candidiasis and further indicate that serial DA/Cr measurements may be useful for diagnosis and therapeutic monitoring of disseminated candidiasis.