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Biomedical subjects

R E Gangnon

Publications and source records attributed to R E Gangnon.

6 recordsLinked to original sources

Predictors and outcomes of candiduria in renal transplant recipients.

BACKGROUND: The epidemiology of candiduria in renal transplantation is unknown. METHODS: We performed a nested case-control study to evaluate the epidemiology of candiduria in renal transplant recipients at the University of Wisconsin (Madison) over an 8-year period. RESULTS: Renal transplantations were performed on 1738 patients during this period, 192 of whom had 276 episodes of candiduria. Candida glabrata, which was recovered from 98 (51%) of 192 case patients, was the most common pathogen identified. Most case patients were asymptomatic. Independent predictors of candiduria were female sex (odds ratio [OR], 12.5; 95% confidence interval [CI], 6.7-23.0), intensive care unit admission (OR, 8.8; 95% CI, 2.3-35.0), antibiotic use during the month before candiduria (OR, 3.8; 95% CI, 1.7-8.3), presence of an indwelling bladder catheter (OR, 4.4; 95% CI, 2.1-9.4), diabetes (OR, 2.2; 95% CI, 1.3-3.9), neurogenic bladder (OR, 7.6; 95% CI, 2.1-27), and malnutrition (OR, 2.4; 95% CI, 1.3-4.4). Log-rank testing of Kaplan-Meier curves revealed that 60-day, 90-day, and cumulative survival rates were significantly different between case and control patients; there was no difference in the survival rate during the first 30 days after transplantation. A variety of regimens were used for treatment; 119 case patients (62%) underwent removal of the indwelling bladder catheter within 1 week after diagnosis of candiduria. Candiduria cleared in 148 case patients (77%). Treatment of candiduria was not associated with an improved survival rate. CONCLUSIONS: Candiduria occurs commonly in renal transplant recipients. Risk factors for candiduria in such persons are similar to those in hospitalized patients who have not received a transplant. Candiduria is associated with reduced survival rates among persons who have undergone renal transplantation; this is likely a marker for severity of illness. Treatment of asymptomatic candiduria in renal transplant recipients does not appear to result in improved outcome.

Adolescent↗

A weighted average likelihood ratio test for spatial clustering of disease.

We consider methods proposed for detecting localized spatial clustering. We propose a new test statistic, the weighted average likelihood ratio test, as an alternative to the spatial scan (maximum likelihood ratio) test statistic. Two different types of weights are considered. We propose an unbiased cluster selection criterion and evaluate the bias of the tests through simulation. We also examine the power of the tests through simulations and apply the methods to the well-known New York leukaemia data.

Cluster Analysis↗

Bayesian detection and modeling of spatial disease clustering.

Many current statistical methods for disease clustering studies are based on a hypothesis testing paradigm. These methods typically do not produce useful estimates of disease rates or cluster risks. In this paper, we develop a Bayesian procedure for drawing inferences about specific models for spatial clustering. The proposed methodology incorporates ideas from image analysis, from Bayesian model averaging, and from model selection. With our approach, we obtain estimates for disease rates and allow for greater flexibility in both the type of clusters and the number of clusters that may be considered. We illustrate the proposed procedure through simulation studies and an analysis of the well-known New York leukemia data.

Bayes Theorem↗

Latrunculin-A increases outflow facility in the monkey.

PURPOSE: To determine the effect of Latrunculin (LAT)-A, a macrolide that binds to G-actin, which leads to the disassembly of actin filaments, on shape, junctions, and the cytoskeleton of cultured bovine aortic endothelial cells (BAECs) and on outflow facility in living monkeys. METHODS: Latrunculin-A dose-time-response relationships in BAECs were determined by immunofluorescence and phase contrast light microscopy, facility by two-level constant pressure anterior chamber perfusion. RESULTS: In BAECs, LAT-A caused dose- and incubation time- dependent destruction of actin bundles, cell separation, and cell loss. Cell-cell adhesions were more sensitive than focal contacts. Recovery was also dose- and time-dependent. In monkeys, exchange intracameral infusion and topical application of LAT-A induced dose- and time-dependent several-fold facility increases. The facility increase was completely reversed within several hours after drug removal. However, for at least 24 hours after a single topical LAT-A dose, perfusion with drug-free solution caused an accelerated increase in facility beyond that attributed to normal resistance washout. CONCLUSIONS: Pharmacological disorganization of the actin cytoskeleton in the trabecular meshwork by specific actin inhibitors like LAT-A may be a useful antiglaucoma strategy.

Actins↗

Enthacrynic and acid effects on inner wall pores in living monkeys.

PURPOSE: The influence of the inner wall of Schlemm's canal on aqueous outflow facility remains poorly understood. We examined the relationship between inner wall pore characteristics and outflow facility in living primate eyes in which facility had been pharmacologically increased by ethacrynic acid (ECA) infusion and in contralateral control eyes. METHODS: Outflow facility (two-level constant pressure perfusion) was measured in eight pairs of living monkey eyes before and after administration of a bolus dose of either 0.125 mM ECA or vehicle. After exsanguination, eyes were fixed in situ under constant-pressure conditions (mean fixation pressure approximately 19 mm Hg). The density and diameter of inner wall pores and the number and area of platelet aggregates on the inner wall of Schlemm's canal were measured by scanning electron microscopy. RESULTS: In ECA-treated eyes, outflow facility increased 63% (P < 0.0001), intracellular pore density decreased 46% (P = 0.0094), intracellular pore size increased 27% (P = 0.049), platelet aggregate density increased 158% (P < 0.0001), and area covered by platelets increased 210% (P = 0.012) relative to contralateral controls. Although the average density and size of intercellular pores were essentially unaffected by ECA, an increased density of large (> or = 1.90 microm) intercellular pores was seen in ECA-treated eyes. The density of intracellular pores increased with the duration of fixative perfusion. Other than a weak negative correlation between outflow facility and intracellular pore density in ECA-treated eyes (P = 0.052), facility was not correlated with inner wall pore features. CONCLUSIONS: Our data are most consistent with a scenario in which ECA promotes formation of large intercellular pores in the inner wall of Schlemm's canal, which are then masked by platelet aggregates. Masking of intercellular pores, combined with fixation-induced alteration of inner wall pore density, greatly complicates attempts to relate facility to inner wall structure and suggests that in vivo pore density is smaller than in fixed tissue. Additionally, facility-influencing effects of ECA on the juxtacanalicular tissue cannot be excluded.

Animals↗

Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: Early Treatment Diabetic Retinopathy Study Report #18.

PURPOSE: To identify risk factors for the development of high-risk proliferative diabetic retinopathy (PDR) and for the development of severe visual loss or vitrectomy (SVLV) in eyes assigned to deferral of photocoagulation in the Early Treatment Diabetic Retinopathy Study (ETDRS). METHODS: Multivariable Cox models were constructed to evaluate the strength and statistical significance of baseline risk factors for development of high-risk PDR and of SVLV. RESULTS: The baseline characteristics identified as risk factors for high-risk PDR were increased severity of retinopathy, decreased visual acuity (or increased extent of macular edema), higher glycosylated hemoglobin, history of diabetic neuropathy, lower hematocrit, elevated triglycerides, lower serum albumin, and persons with mild to moderate nonproliferative retinopathy, younger age (or type 1 diabetes). The predominant risk factor for development of SVLV was the prior development of high-risk PDR. The only other clearly significant factor was decreased visual acuity at baseline. In the eyes that developed SVLV before high-risk proliferative retinopathy was observed, baseline risk factors were decreased visual acuity (or increased extent of macular edema), older age (or type 2 diabetes), and female gender. CONCLUSIONS: These analyses supported the view that the retinopathy-inhibiting effect of better glycemic control extends across all ages, both diabetes types, and all stages of retinopathy up to and including the severe nonproliferative and early proliferative stages and the possibility that reducing elevated blood lipids and treating anemia slow the progression of retinopathy.

Adolescent↗