Biomedical subjects

A Y Toledano

Publications and source records attributed to A Y Toledano.

15 recordsLinked to original sources

PubMed2001

Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation.

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 kappa 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 kappa 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 kappa = 0.82 and 0.80). Interobserver agreement was substantial (kappa = 0.66) and improved after the consensus meeting (kappa = 0.70; P =.02). When statistical analysis was performed using 4 clinically relevant separations (BE; IND and LGD; HGD; carcinoma), mean intraobserver kappa improved from 0.64 to 0.68 (both substantial) after the consensus meeting, and mean interobserver kappa 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 kappa 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 (kappa = 0.43 at both times). Interobserver agreement was substantial for HGD/carcinoma (kappa = 0.65), moderate to substantial for BE (kappa = 0.58), fair for LGD (kappa = 0.32), and slight for IND (kappa = 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 32:368-978.

Algorithms↗

PubMed2001

Potential of computer-aided diagnosis to reduce variability in radiologists' interpretations of mammograms depicting microcalcifications.

PURPOSE: To evaluate whether computer-aided diagnosis can reduce interobserver variability in the interpretation of mammograms. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Biopsy↗

PubMed1999

CD4(+) T cells eliminate MHC class II-negative cancer cells in vivo by indirect effects of IFN-gamma.

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 immunodeficient mice, we show that anti-IFN-gamma treatment abolishes the CD4(+) T cell-mediated rejection of the tumor cells in vivo. The tumor cells were MHC class II negative, and IFN-gamma did not induce MHC class II expression in vitro. Therefore, the tumor-specific antigenic peptide must be presented by host cells and not the tumor cells. Tumor cells transduced to secrete IFN-gamma had a markedly reduced growth rate in severe combined immunodeficient mice, but IFN-gamma did not inhibit the growth of the tumor cells in vitro. Furthermore, tumor cells stably expressing a dominant-negative truncated form of the murine IFN-gamma receptor alpha chain, and therefore insensitive to IFN-gamma, nevertheless were rejected by the adoptively transferred CD4(+) T cells. Thus, host cells, and not tumor cells, seem to be the target of IFN-gamma. Together, these results show that CD4(+) T cells can eliminate IFN-gamma-insensitive, MHC class II-negative cancer cells by an indirect mechanism that depends on IFN-gamma.

Amino Acid Sequence↗

PubMed1999

Generalized estimating equations for ordinal categorical data: arbitrary patterns of missing responses and missingness in a key covariate.

We propose methods for regression analysis of repeatedly measured ordinal categorical data when there is nonmonotone missingness in these responses and when a key covariate is missing depending on observables. The methods use ordinal regression models in conjunction with generalized estimating equations (GEEs). We extend the GEE methodology to accommodate arbitrary patterns of missingness in the responses when this missingness is independent of the unobserved responses. We further extend the methodology to provide correction for possible bias when missingness in knowledge of a key covariate may depend on observables. The approach is illustrated with the analysis of data from a study in diagnostic oncology in which multiple correlated receiver operating characteristic curves are estimated and corrected for possible verification bias when the true disease status is missing depending on observables.

Biometry↗

PubMed1998

Improving the efficiency of survey research in postoperative patients.

STUDY OBJECTIVE: To increase the contact rate with eligible patients for quality assurance/improvement surveys by modifying survey rounds to accommodate the schedules of individual nursing units. DESIGN: Two-phase, interventional time series study. SETTING: Postoperative inpatients at a university hospital. PATIENTS: 498 adult postoperative inpatients who remained hospitalized during the second postoperative day. INTERVENTIONS: Between the first and second measurement periods, efforts were made to learn the schedule of each nursing unit and to improve the efficiency of survey rounds so that a larger proportion of patients could be contacted. MEASUREMENTS AND MAIN RESULTS: The contact rate for eligible patients was improved from 66% to 80% (p < 0.01). Improvement during the second period was attributed to fewer patients being away from the nursing unit (20% vs. 12%, p < 0.05) or otherwise occupied by attending physicians on rounds (9% vs. 4%, p < 0.05). CONCLUSION: Strategies individualized to patient care units can improve the efficiency and credibility of inpatient survey research. We describe the strategies most helpful in improving the efficiency of survey rounds at one medical center.

Adult↗

PubMed1998

Effective analgesia after bilateral tubal ligation.

UNLABELLED: Postpartum bilateral tubal ligation is a brief surgical procedure with minimal tissue injury, yet postoperative recovery times and analgesia requirements are often disproportionately large. To evaluate the analgesic efficacy of local anesthetic infiltration, 20 parturients scheduled for elective minilaparotomy and bilateral tubal ligation with either spinal or epidural anesthesia participated in this prospective, randomized, controlled, double-blind trial. All patients received IV metoclopramide 10 mg and ketorolac 60 mg intraoperatively, as well as preincisional infiltration of the infraumbilical skin incision with 0.5% bupivacaine. Infiltration of bilateral uterine tubes and mesosalpinx was performed with either 0.5% bupivacaine (n = 10) or isotonic sodium chloride solution (saline) (n = 10). IV meperidine (25 mg every 3 min as needed) was given to treat pain in the postanesthesia care unit (PACU). The total amount of meperidine administered in the PACU was significantly larger in the saline group than in the bupivacaine group. Pain scores at 30, 45, 60, 75, and 90 min postoperatively and on the seventh postoperative day were significantly lower in the bupivacaine group than in the saline group. During tubal ligation, infiltration of uterine tubes and mesosalpinx with 0.5% bupivacaine significantly enhanced analgesia both in the immediate postoperative setting and on the seventh postoperative day compared with infiltration with sodium chloride. IMPLICATIONS: During bilateral tubal ligation with either spinal or epidural anesthesia, preemptive analgesia using IV ketorolac, IV metoclopramide, and infiltration of the incised skin and uterine tubes with 0.5% bupivacaine allowed 9 of 10 patients to recover with no pain, nausea, vomiting, or cramping and to maintain good analgesia for 7 days postoperatively.

Adult↗

PubMed1997

Effects of information on the reinforcing, subjective, and psychomotor effects of nitrous oxide in healthy volunteers.

The purpose of this study was to characterize the reinforcing, subjective, and psychomotor effects of nitrous oxide (N2O) in healthy volunteers who were given different amounts of information regarding the drugs they were being administered in the experiment. A choice procedure was used in which subjects first sampled a placebo and a given concentration of N2O and then chose between the two. N2O concentration varied across the four-session experiment from 10-40%. Besides choice, subjective and psychomotor effects served as dependent measures. In the INFORMED group (n = 11), subjects were told at the beginning of each sampling trial what concentration of N2O they were inhaling or whether they were inhaling 100% oxygen (placebo). They were also informed about the prototypic effects of N2O (e.g. tingling or numbing, euphoria, dysphoria) and oxygen (e.g. no discernible effects). In the NON-INFORMED group (n = 11), subjects were only told at the beginning of each sampling trial that the drugs they would be inhaling came from one of six classes of drugs. Thirty percent N2O was chosen by a significantly higher proportion of subjects than expected by chance in the INFORMED group, but not in the NON-INFORMED group. Further, the probability of choosing 20-40% N2O was higher in the INFORMED group than in the NON-INFORMED group. Subjective effects of N2O were not affected by the information manipulation. Psychomotor performance at the highest N2O concentration tested (40%) was impaired to a greater extent in the NON-INFORMED than in the INFORMED group. We conclude that the reinforcing effects of N2O, and perhaps the impairing effects, can be modulated by telling subjects beforehand that they are inhaling N2O and what effects they might be expected to experience from the drug.

Administration, Inhalation↗

PubMed1997

The effects of alcohol history on the reinforcing, subjective and psychomotor effects of nitrous oxide in healthy volunteers.

The purpose of this study was to characterize the reinforcing, subjective and psychomotor effects of nitrous oxide in healthy volunteers with different alcohol histories. Subjects were divided into two groups: light drinkers (n = 9) and moderate drinkers (n = 10). A choice procedure was used in which subjects first sampled placebo and a given concentration of nitrous oxide, and then chose between the two. Nitrous oxide concentration varied across the four-session experiment from 10-40%. Besides choice, subjective and psychomotor effects served as dependent measures. The majority of subjective effects of nitrous oxide, and its psychomotor-impairing effects, did not vary as a function of drinking group. However, a Wilcoxon rank sum test showed that the median number of times moderate drinkers chose nitrous oxide (three) was significantly higher than the median number of times light drinkers chose nitrous oxide (one). This study provides suggestive evidence that the reinforcing effects of nitrous oxide are modulated by alcohol history.

Administration, Inhalation↗

PubMed1997

Ischemia induces significant changes in purine nucleoside concentration in the retina-choroid in rats.

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.

Adenosine↗

PubMed1997

Modulating effects of a cold water stimulus on opioid effects in volunteers.

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 "coasting (spaced out)," "high (drug "high")," "sleepy (drowsy, tired)," and "lightheaded". In contrast, some of butorphanol'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.

Adult↗

PubMed1997

Adenosine receptor blockade and nitric oxide synthase inhibition in the retina: impact upon post-ischemic hyperemia and the electroretinogram.

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.

Analysis of Variance↗

PubMed1996

Ordinal regression methodology for ROC curves derived from correlated data.

We present an approach for the analysis of correlated ROC data, using ordinal regression models in conjunction with generalized estimating equations. The approach applies to the analysis of degree-of-suspicion data derived from multiple interpretations of the same diagnostic study and from the examination of the same patients with multiple diagnostic modalities. The regression models make it possible to incorporate patient and reader characteristics into the analysis, without having to resort to stratification. We illustrate the potential of the approach with analysis of data from two studies in diagnostic oncology.

Diagnosis↗

PubMed1996

The effects of a cold-water immersion stressor on the reinforcing and subjective effects of fentanyl in healthy volunteers.

The reinforcing and subjective effects of fentanyl, an opioid analgesic, were tested in ten healthy volunteers without histories of drug abuse, as a function of the temperature of a water bath in which the volunteers' forearms were immersed. The temperatures were body-temperature (37 degrees C), moderately cold (10 degrees C), and very cold (2 degrees C). A discrete-trial choice procedure was used in which, in each session, volunteers sampled 50 micrograms of fentanyl (delivered as a bolus via an infusion pump) and saline, and then on three successive trials, chose between the two. Volunteers then had to immerse their non-dominant forearm in the water bath 5 min after a drug delivery. Fentanyl was chosen on 77% of choice occasions in the 10 degrees C and 2 degrees C water conditions, which was significantly different from chance levels, and on 60% of choice occasions in the 37 degrees C water condition, which did not differ from chance levels. Several subjective effects of fentanyl were also modulated by the temperature of the water bath. We conclude that in the context of a painful stimulus, 50 micrograms of fentanyl functions as a reinforcer in non-drug abusers.

Adult↗

PubMed1996

The reinforcing effects of brief exposures to nitrous oxide in healthy volunteers.

The reinforcing and subjective effects of brief (about 1.5 min) exposures to nitrous oxide, ranging from inspired concentrations of 20-80% in oxygen, were examined in 11 healthy volunteers. A choice procedure was used in which during each of four sessions, subjects first sampled a given concentration of nitrous oxide and placebo oxygen, and then chose between the two. 20, 40, 60 and 80% nitrous oxide were chosen by five, four, three, and three subjects, respectively--these choice levels did not exceed that of chance. All concentrations had psychoactive effects, and in general, concentration-related subjective effects were found. We conclude that in a medical setting, nitrous oxide inhaled in a manner similar to that when used recreationally in a naturalistic setting, does not function as a reinforcer across a wide range of concentrations, in subjects with a modest lifetime history of psychoactive drug use.

Adult↗

PubMed1995

Inhibition of tumor growth by elimination of granulocytes.

As observed for many types of cancers, heritable variants of ultraviolet light-induced tumors often grow more aggressively than the parental tumors. The aggressive growth of some variants is due to the loss of a T cell-recognized tumor-specific antigen; however, other variants retain such antigens. We have analyzed an antigen retention variant and found that the variant tumor cells grow at the same rate as the parental tumor cells in vitro, but grew more rapidly than the parental cells in the T cell-deficient host. The growth of the variant cells was stimulated in vitro by factors released from tumor-induced leukocytes and by several defined growth factors. In addition, the variant cancer cells actually attracted more leukocytes in vitro than the parental cells. Furthermore, elimination of granulocytes in vivo in nude mice by a specific antigranulocyte antibody inhibited the growth of the variant cancer, indicating that this tumor requires granulocytes for rapid growth.

Animals↗