Papers by Alicia Toledano
European Radiology, 2010
Objective: To compare the clinical performance of digital breast tomosynthesis (DBT) with that of... more Objective: To compare the clinical performance of digital breast tomosynthesis (DBT) with that of digital mammography (FFDM) in a diagnostic population.
Clinical pharmacology and therapeutics, 1997
Methylnaltrexone is a quaternary opioid antagonist with limited ability to cross the blood-brain ... more Methylnaltrexone is a quaternary opioid antagonist with limited ability to cross the blood-brain barrier that has the potential to antagonize the peripherally mediated gastrointestinal effects of opioids. In recent trials in human volunteers, we demonstrated that intravenous methylnaltrexone prevented morphine-induced changes in gastrointestinal motility and transit, without affecting analgesia. In this study, 14 healthy volunteers were first given three ascending oral doses of methylnaltrexone to obtain safety and tolerance data (phase A study). In phase B, these subjects were then given single-blind oral placebo and intravenous placebo, followed by randomized, double-blind oral placebo and intravenous morphine (0.05 mg/kg) or oral methylnaltrexone (19.2 mg/kg, an established highest and safe dose based on previous administrations of two smaller doses of 0.64 mg/kg and 6.4 mg/kg in phase A) and intravenous morphine (0.05 mg/kg). Oral-cecal transit time was assessed by the pulmonary...
Clinical Pharmacology & Therapeutics, 1996
Methylnaltrexone is a quaternary opioid antagonist with limited ability to cross the blood-brain ... more Methylnaltrexone is a quaternary opioid antagonist with limited ability to cross the blood-brain barrier and the potential to antagonize the peripherally mediated effects of opioids. The effectiveness of methylnaltrexone in preventing morphine-induced changes in gastrointestinal motility and transit without affecting analgesia was evaluated in humans. Twelve healthy volunteers were given intravenous placebo, placebo plus 0.05 mg/kg morphine, or 0.45 mg/kg methylnaltrexone plus 0.05 mg/kg morphine. Oral-cecal transit time was assessed by the pulmonary hydrogen measurement technique, and analgesia was measured with use of the cold-pressor test. Morphine significantly increased oral-cecal transit time from 104.6 +/- 31.1 minutes (mean +/- SD) to 163.3 +/- 39.8 minutes (p < 0.01). Methylnaltrexone prevented 97% of morphine-induced increase in oral-cecal transit time (106.3 +/- 39.8 minutes; not significant compared with baseline; p < 0.01 compared with morphine alone). Methylnaltrexone did not affect the analgesic effect of morphine on both pain intensity and pain bothersomeness ratings. At a higher dose of morphine (0.1 mg/kg), our preliminary results indicated that 0.45 mg/kg methylnaltrexone also prevented the morphine-induced delay in oral-cecal transit time, with no effect on analgesia. Methylnaltrexone may be a useful adjunct to opioids for the relief of opioid-induced constipation.
Radiology, 2001
To evaluate whether computer-aided diagnosis can reduce interobserver variability in the interpre... more To evaluate whether computer-aided diagnosis can reduce interobserver variability in the interpretation of mammograms. Ten radiologists interpreted mammograms showing clustered microcalcifications in 104 patients. Decisions for biopsy or follow-up were made with and without a computer aid, and these decisions were compared. The computer was used to estimate the likelihood that a microcalcification cluster was due to a malignancy. Variability in the radiologists' recommendations for biopsy versus follow-up was then analyzed. Variation in the radiologists' accuracy, as measured with the SD of the area under the receiver operating characteristic curve, was reduced by 46% with computer aid. Access to the computer aid increased the agreement among all observers from 13% to 32% of the total cases (P <.001), while the kappa value increased from 0.19 to 0.41 (P <.05). Use of computer aid eliminated two-thirds of the substantial disagreements in which two radiologists recommended biopsy and routine screening in the same patient (P <.05). In addition to its demonstrated potential to improve diagnostic accuracy, computer-aided diagnosis has the potential to reduce the variability among radiologists in the interpretation of mammograms.
Statistical methods in medical research, Jan 11, 2014
The development and implementation of quantitative imaging biomarkers has been hampered by the in... more The development and implementation of quantitative imaging biomarkers has been hampered by the inconsistent and often incorrect use of terminology related to these markers. Sponsored by the Radiological Society of North America, an interdisciplinary group of radiologists, statisticians, physicists, and other researchers worked to develop a comprehensive terminology to serve as a foundation for quantitative imaging biomarker claims. Where possible, this working group adapted existing definitions derived from national or international standards bodies rather than invent new definitions for these terms. This terminology also serves as a foundation for the design of studies that evaluate the technical performance of quantitative imaging biomarkers and for studies of algorithms that generate the quantitative imaging biomarkers from clinical scans. This paper provides examples of research studies and quantitative imaging biomarker claims that use terminology consistent with these definiti...
Human Pathology, 2001
Morphologic assessment of dysplasia in Barrett esophagus, despite limitations, remains the basis ... more Morphologic assessment of dysplasia in Barrett esophagus, despite limitations, remains the basis of treatment. We rigorously tested modified 1988 criteria, assessing intraobserver and interobserver reproducibility. Participants submitted slides of Barrett mucosa negative (BE) and indefinite (IND) for dysplasia, with low-grade dysplasia (LGD) and high-grade dysplasia (HGD), and with carcinoma. Two hundred fifty slides were divided into 2 groups. The first 125 slides were reviewed, without knowledge of the prior diagnoses, on 2 occasions by 12 gastrointestinal pathologists without prior discussion of criteria. Results were analyzed by statistics, which correct for agreement by chance. A consensus meeting was then held, establishing, by group review of the index 125 slides, the criteria outlined herein. The second 125-slide set was then reviewed twice by each of the same 12 pathologists, and follow-up statistics were calculated. When statistical analysis was performed using 2 broad diagnostic categories (BE, IND, and LG v HG and carcinoma), intraobserver agreement was near perfect both before and after the consensus meeting (mean ؍ 0.82 and 0.80). Interobserver agreement was substantial ( ؍ 0.66) and improved after the consensus meeting ( ؍ 0.70; P ؍ .02). When statistical analysis was performed using 4 clinically relevant separations (BE; IND and LGD; HGD; carcinoma), mean intraobserver improved from 0.64 to 0.68 (both substantial) after the consensus meeting, and mean interobserver improved from 0.43 to 0.46 (both moderate agreement). When statistical analysis was performed using 4 diagnostic categories that required distinction between LGD and IND (BE; IND; LGD; HGD and carcinoma), the pre-consensus meeting mean intraobserver was 0.60 (substantial agreement), improving to 0.65 after the meeting (P < .05). Interobserver agreement was poorer, with premeeting and postmeeting mean values unchanged ( ؍ 0.43 at both times). Interobserver agreement was substantial for HGD/carcinoma ( ؍ 0.65), moderate to substantial for BE ( ؍ 0.58), fair for LGD ( ؍ 0.32), and slight for IND ( ؍ 0.15). The intraobserver reproducibility for the diagnosis of dysplasia in BE was substantial. Interobserver reproducibility was substantial at the ends of the spectrum (BE and HG/carcinoma) but slight for IND. Both intraobserver and interobserver variation improved overall after the application of a modified grading system developed at a consensus conference but not in separation of BE, IND, and LGD. The criteria used by the group are presented. HUM PATHOL 32:368-378. Copyright
Proceedings of The National Academy of Sciences, 1999
CD4+ T cells can eliminate tumor cells in vivo in the absence of CD8+ T cells. We have CD4+ T cel... more CD4+ T cells can eliminate tumor cells in vivo in the absence of CD8+ T cells. We have CD4+ T cells specific for a MHC class II-restricted, tumor-specific peptide derived from a mutant ribosomal protein expressed by the UV light-induced tumor 6132A-PRO. By using neutralizing mAb specific for murine IFN-gamma and adoptive transfer of CD4+ T cells into severe combined
Vision Research, 1997
We preformed this study to determine the effect on ocular blood flow and the electroretinogram of... more We preformed this study to determine the effect on ocular blood flow and the electroretinogram of either nitric oxide synthase (NOS) inhibition, adenosine receptor blockade or the combination of both after 1 hr of ocular ischemia. Thirty-seven cats under general anesthesia were subjected to 1 hr of complete ischemia in one eye by raising the intraocular pressure above systolic blood pressure. The other eye in each animal served as a non-ischemic control. Arterial blood gas tension, systemic arterial pressure, body temperature, hematocrit, and anesthetic level were controlled in each experiment. Cats were divided into four groups. Group 1 received normal saline injections [intravenous (i.v.) and intravitreal], Group 2 adenosine receptor blockade (0.1 ml of 0.01 M 8-sulfophenyltheophylline intravitreal) and saline i.v., Group 3 NOS inhibition (30 mg/kg l-NG-nitroarginine-methyl-ester i.v.) and saline intravitreal, and Group 4 intravitreal adenosine receptor blockade and NOS inhibition i.v. A subset of Group 3 received l-arginine to investigate the reversibility of NOS inhibition, after the blood flow measurements were completed. Five minutes after the end of ischemia, blood flows in retina and choroid were measured using injections of radioactively labeled microspheres. Electroretinographic (ERG) studies were carried out before treatment, before ischemia, during ischemia, and 1, 2, 3, and 4 hr after ischemia ended. NOS inhibition significantly reduced basal blood flow in the choroid, and in the retina when combined with adenosine receptor blockade. Adenosine receptor blockade completely attenuated post-ischemic hyperemia in the retina, but retinal hyperemia reappeared when adenosine receptor blockade and NOS inhibition were combined. Adenosine receptor blockade had no effect on ERG recovery after ischemia. NOS inhibition led to a reduction of ERG a- and b-wave amplitudes in control eyes, that could be reversed by l-arginine. Nitric oxide (NO) appears to be a significant factor in the regulation of basal blood flow in the choroid. Adenosine appears to be a major mediator of retinal hyperemia after 60 min of ischemia. Since NOS inhibition appeared to have direct effects on ERG wave amplitudes, short-term ERG studies may be of limited use in assessing the role of NO in postischemic recovery of the retina. Our observations correlate well with the emerging role of NO as a neurotransmitter in the retina.
Psychopharmacology, 1997
The purpose of this study was to characterize the effect of a painful stimulus on morphine and bu... more The purpose of this study was to characterize the effect of a painful stimulus on morphine and butorphanol effects in healthy non-drug abusing volunteers. Thirteen subjects with no history of opiate dependence participated in a randomized, placebo-controlled, double-blind, crossover trial in which each subject received saline, 2 mg/70 kg butorphanol, and 10 mg/70 kg morphine, IV, in each of two conditions, periodic forearm immersions into either ice-cold water (2 degrees C) or into warm water (37 degrees C). Both opioids reduced self-reported ratings of pain intensity, indicative of analgesia. Several of the subjective effects of morphine were attenuated either during or in between cold-water immersions, including visual analog scale ratings of &quot;coasting (spaced out),&quot; &quot;high (drug &quot;high&quot;),&quot; &quot;sleepy (drowsy, tired),&quot; and &quot;lightheaded&quot;. In contrast, some of butorphanol&#39;s subjective effects were increased by the cold-water manipulation. Morphine impaired psychomotor performance during one of the warm-water immersions, but not during the cold-water immersions. Psychomotor impairment induced by butorphanol was not affected by water temperature. This study provides evidence that opioid effects can be modulated by a painful stimulus in humans.
Pharmacoepidemiology and Drug Safety, 2004
Purpose To document which established criteria for logistic regression modeling researchers consi... more Purpose To document which established criteria for logistic regression modeling researchers consider when using propensity scores in observational studies. Methods We performed a systematic review searching Medline and Science Citation to identify observational studies published in 2001 that addressed clinical questions using propensity score methods to adjust for treatment assignment. We abstracted aspects of propensity score model development (e.g. variable selection criteria, continuous variables included in correct functional form, interaction inclusion criteria), model discrimination and goodness of fit for 47 studies meeting inclusion criteria.
New England Journal of Medicine, 2008
screening. The accuracy of CTC as a screening tool among asymptomatic adults has not been well de... more screening. The accuracy of CTC as a screening tool among asymptomatic adults has not been well defined.
Nature Medicine, 1995
Activation of transcription of the Egr-1 gene by X-rays is regulated by the promoter region of th... more Activation of transcription of the Egr-1 gene by X-rays is regulated by the promoter region of this gene. We linked the radiation-inducible promoter region of the Egr-1 gene to the gene encoding the radiosensitizing and tumoricidal cytokine, tumour necrosis factor-alpha (TNF-alpha) and used a replication-deficient adenovirus to deliver the Egr-TNF construct to human tumours growing in nude mice. Combined treatment with Ad5.Egr-TNF and 5,000 cGy (rad) resulted in increased intratumoral TNF-alpha production and increased tumour control compared with treatment with Ad5.Egr-TNF alone or with radiation alone. The increase in tumour control was achieved without an increase in normal tissue damage when compared to tissue injury from radiation alone. Control of gene transcription by ionizing radiation in vivo represents a novel method of spatial and temporal regulation of gene-based medical treatments.
Journal of the American College of Cardiology, 1995
Journal of the American College of Cardiology, 2006
OBJECTIVES-In this study we intend to characterize phosphocreatine (PCr) recovery kinetics with p... more OBJECTIVES-In this study we intend to characterize phosphocreatine (PCr) recovery kinetics with phosphorus-31 ( 31 P) magnetic resonance spectroscopy in symptomatic peripheral arterial disease (PAD) patients compared with control subjects and determine the diagnostic value and reproducibility of this parameter.
Journal of Cardiothoracic and Vascular Anesthesia, 1996
To test the safety and report on limiting technical considerations, including optimal dosing of A... more To test the safety and report on limiting technical considerations, including optimal dosing of Albunex (Molecular Biosystems, Inc, Mallinckrodt Medical, St. Louis, MO) for myocardial opacification after intra-aortic root injections during cardiac surgery. This was a prospective randomized study with a control group who did not receive Albunex and a group who received intra-aortic root injections of Albunex. Multicenter (two) independent university hospitals. 32 patients scheduled for elective coronary artery bypass surgery were evaluated after individual informed consent was obtained. 2 to 8 mL of Albunex were injected before and after coronary revascularization. Quality of enhancement in each of four regions of the left ventricle was assessed from a short-axis mid-papillary ultrasound image by three experienced observers blinded to dose. Electrocardiogram (ECG), creatine phosphokinase (CPK) (MB fraction), and hemodynamics were evaluated at baseline and throughout the study period for up to 72 hours. No differences were noted between groups with respect to preoperative and postoperative CPK enzymes (CPK-MB fraction), ECG changes, hemodynamics, requirements for separation from CPB, need for postoperative inotropes, time to extubation, and time to discharge from the intensive care unit. The average total dose of Albunex injected was 19 mL +/- 4 (0.25 mL/kg). A single dose of 4.2 +/- 1.2 mL (0.05 mL/kg) appeared to offer optimal enhancement of contrast effect for myocardial perfusion assessment. Albunex is safe and easy to use for myocardial opacification when administered via an antegrade cardioplegia catheter into the aortic root during CPB.
Journal of Cardiothoracic and Vascular Anesthesia, 1998
Intraoperative myocardial contrast echocardiography was used to determine whether the identificat... more Intraoperative myocardial contrast echocardiography was used to determine whether the identification of regional myocardial flow patterns during revascularization could predict myocardial contractile function immediately after separation from cardiopulmonary bypass (CPB) and at 1 month after coronary artery bypass grafting (CABG) surgery. A prospective, open-labeled, longitudinal analysis. Two independent university hospitals. Twenty patients, during and up to 1 month after CABG. The contrast agent Albunex (Mallenckrodt Medical, Inc, St Louis, MO) was injected into the aortic root during CPB. Myocardial contrast echocardiography opacification of flow was graded from intraoperative transesophageal echocardiographic images of the left ventricle in the short-axis, midpapillary view. The same myocardial images were also evaluated for regional wall motion abnormalities at 15, 30, and 60 minutes, 24 hours, 5 to 8 days, and 1 month after CPB. Logistic regression analysis was used to analyze the flow scores and regional function data from identical segments. Regional flow represented by contrast enhancement was assessed in 70% of the myocardial regions (55 of 80 possible segments; 95% confidence interval [CI], 61 to 76). Flow was more easily evaluated in the posterior region (95%) than in the anterior (70%) or septal regions (60%), and least likely evaluated in the lateral regions (50%). Regional wall motion was scored in 84% of the myocardial regions (469 of 560 possible regions). Function (segmental wall motion) was assessed in all regions with equal success. Segmental function and flow scores were matched to the same regions 66% of the time (53 of 80 possible series; 95% CI, 55 to 76). Regional myocardial contrast flow patterns did not predict myocardial function at 15, 30, or 60 minutes after separation from CPB. However, contrast opacification of flow did predict regional myocardial function at 1 week (p &lt; or = 0.05) and at 1 month (p &lt; or = 0.01) after CABG surgery. The probability that myocardial function would be normal at 1 month was 0.62 when intraoperative flow opacification was abnormal and 0.98 when flow opacification was normal. For patients with normal flow, the estimated odds of having normal myocardial function were 3.33 times those of patients with abnormal flow at 1 week (odds ratio, 3.33; 95% CI, 1.09 to 10.19) and 18.5 times those of patients with abnormal flow at 1 month (95% CI, 2.44 to 140.48). Intraoperative application of myocardial contrast echocardiography to determine regional flow patterns after revascularization may help differentiate conditions of left ventricular systolic dysfunction immediately after separation from CPB for CABG surgery and appear to predict myocardial function at 1 month.
International Journal of Radiation Oncology*Biology*Physics, 2007
Purpose-Accurate target definition is considered essential for sophisticated, image-guided radiat... more Purpose-Accurate target definition is considered essential for sophisticated, image-guided radiation therapy; however, relatively little information has been reported that measures our ability to identify the precise shape of targets accurately. We decided to assess the manner in which eight "experts" interpreted the size and shape of tumors based on "real life" contrast-enhanced CT scans.
Gastroenterology, 2003
No multicenter study has been reported evaluating the performance and interobserver variability o... more No multicenter study has been reported evaluating the performance and interobserver variability of computerized tomographic colonography. The aim of this study was to assess the accuracy of computerized tomographic colonography for detecting clinically important colorectal neoplasia (polyps &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=10 mm in diameter) in a multi-institutional study. A retrospective study was developed from 341 patients who had computerized tomographic colonography and colonoscopy among 8 medical centers. Colonoscopy and pathology reports provided the standard. A random sample of 117 patients, stratified by criterion standard, was requested. Ninety-three patients were included (47% with polyps &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=10 mm; mean age, 62 years; 56% men; 84% white; 40% reported colorectal symptoms; 74% at increased risk for colorectal cancer). Eighteen radiologists blinded to the criterion standard interpreted computerized tomography colonography examinations, each using 2 of 3 different software display platforms. The average area under the receiver operating characteristic curve for identifying patients with at least 1 lesion &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=10 mm was 0.80 (95% lower confidence bound, 0.74). The average sensitivity and specificity were 75% (95% lower confidence bound, 68%) and 73% (95% lower confidence bound, 66%), respectively. Per-polyp sensitivity was 75%. A trend was observed for better performance with more observer experience. There was no difference in performance across software display platforms. Computerized tomographic colonography performance compared favorably with reported performance of fecal occult blood testing, flexible sigmoidoscopy, and barium enema. A prospective study evaluating the performance of computerized tomography colonography in a screening population is indicated.
Experimental Eye Research, 1997
Adenosine, produced from the decomposition of adenosine triphosphate, is believed to provide prot... more Adenosine, produced from the decomposition of adenosine triphosphate, is believed to provide protective effects during ischemia. On the other hand, adenosine metabolites may serve as precursors for oxygen free radical formation. The time course of formation of adenosine and its purine metabolites was studied during retinal ischemia in rats. Concentrations of adenosine and its purine nucleoside metabolites inosine, hypoxanthine, and xanthine in the retina-choroid of ketamine\xylazine-anesthetized rats were measured during retinal ischemia using high performance liquid chromatography. Quantitative measurements were made possible in the small tissue mass through the use of internal standards. Ischemia was induced by ligation of the central retinal artery. In each rat, one eye was ischemic while the other served as a non-ischemic control. Eyes were frozen in situ at 1, 5, 10, 20, 30, 60, and 120 min of ischemia. The retina-choroid was then removed from the frozen eyes and analysed. Significant increases in the concentrations of adenosine, inosine, and hypoxanthine in ischemic compared to control retina-choroid were detectable within 1 to 5 min of the onset of ischemia, and within 10 min for xanthine. Increase in adenosine concentration in ischemic relative to control retina-choroid plateaued at 30 min of ischemia, while inosine and hypoxanthine concentrations increased continuously. The increase in xanthine concentration was exponential throughout the measurement period. This study documented the time-related changes in purine nucleoside concentration during ischemia. Prolonged ischemia results in ongoing production of xanthine, which by serving as a precursor for oxygen free radical formation, could be a pathogenic factor in prolonged retinal ischemia.
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Papers by Alicia Toledano