Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “IRT”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1973

The effect upon simple animal behavior of different frequencies of reinforcement, Part II: separate control of the reinforcement of different IRTs.

Rats' responding was stabilized for over 35 days on 4-min variable-interval reinforcement. Reinforcements per hour for 4-sec wide classes of interresponse times were then separately controlled by adjusting those for each class to the variable-interval values that had just prevailed. This produced little or no change in interresponse times, indicating that the new procedure was substantially equivalent to a variable-interval schedule. The variable-interval schedule produced a high and stable conditional probability of interresponse times in the 0- to 4-sec class, associated with a peak in reinforcements per hour for this class. Reducing the reinforcements per hour for this class while raising that for another class (by 3.3 reinforcements per hour) significantly reduced the conditional probability of 0- to 4-sec interresponse times. Restoring the 3.3 reinforcements per hour to the 0- to 4-sec class significantly elevated the conditional probability of interresponse times in this class. Hence, it is concluded that the distribution of interresponse times produced by a subject during some variable-interval schedules is determined partly by the relative reinforcement of different interresponse times that the variable-interval schedule provided.Reprinted from Part II of the Final Report of Research under Contract DA-49-007-MD-408 with the Medical Research and Development Board, Office of the Surgeon General, Department of the Army, 31 December 1954. Edwin B. Newman, Responsible Investigator; Douglas Anger, Research Assistant and author of report. Experimental work done in the Psychological Laboratories of Harvard University.

Journal Article↗
PubMedDate not supplied

Profile of drug effects on temporally spaced responding in rats.

A differential reinforcement of low rate schedule was used with rats to test 15 psychotropic drugs. The computer analysis was based on interresponse time (IRT). Mean IRT, IRT standard deviation, median IRT, IRT midrange, modal IRT, frequency of modal IRT, and an efficiency index, in addition to numbers of responses and reinforcements and the IRT histogram were obtained for each rat in each drug test. An increase in number of responses and a peak shift to shorter IRTs in the histograms were observed with amphetamine, methamphetamine, priradrol and nicotine, as reported by many other investigators. Decrease in IRT midrange and less change in number of responses were observed with diazepam and chlordiazepoxide. Long pauses were found with LSD-25, 2,5-dimethoxy-4-methylamphetamine (DOM) and mescaline. In a factor analysis, the following main factors were obtained. High values in factor loading a1 were observed with chlorpromazine, chlordiazepoxide, pentobarbital, imipramine, nialamide, LSD-25, DOM and mescaline. With these drugs, mean IRT and IRT standard deviation were also high. Values for a2, were high with amphetamine, methamphetamine, pipradrol and nicotine. High a3 values were observed in some rats with chlorpromazine, diazepam, chlordiazepoxide, pentobarbital, pipradrol and caffeine. The changes in a3 values were correlated with changes in the IRT midrange. These results may be valuable in classifying new compounds in drug screening programs as being of the amphetamine type, nicotine type, diazepam type of LSD-25 type.

Animals↗
PubMed2006

Development and characterization of dried blood spot materials for the measurement of immunoreactive trypsinogen.

OBJECTIVES: In response to increasing numbers of states in the US that test newborn babies for cystic fibrosis (CF), the Newborn Screening Quality Assurance Programme initiated a pilot proficiency testing programme for immunoreactive trypsinogen (IRT), the biomarker for CF. Dried blood spot specimens (DBS) were used to evaluate the performance of laboratories that screen babies for CF. METHODS: DBS were prepared from human whole blood enriched with physiologically relevant levels of IRT. Various methods of making IRT-enriched DBS were used to optimize the recovery and stability of the biomarker, including preparation of DBS from either intact or lysed red blood cells, varying the timing of IRT addition to blood before dispensing onto filter paper, adding a protease inhibitor cocktail, and treating serum with charcoal before IRT enrichment. The recovery and stability of IRT in DBS were assessed. Newborn screening laboratories were offered the opportunity to test blind-coded DBS in the pilot PT programme. RESULTS: IRT was stable in the filter paper matrix when stored for one year at either -20 degrees C or 4 degrees C. Fifty percent more IRT was recovered from DBS prepared with lysed red blood cells where the IRT was added to blood just before dispensing; however, protease inhibitors did not improve IRT recovery. CONCLUSIONS: IRT in the DBS matrix is stable and can be shipped worldwide under ambient conditions. Optimal IRT recovery was achieved by adjustment of DBS production practices. Laboratories receiving specimens accurately measured IRT by a variety of commercial and in-house methods.

Charcoal↗
PubMed2006

Genetic and physiologic correlates of longitudinal immunoreactive trypsinogen decline in infants with cystic fibrosis identified through newborn screening.

OBJECTIVES: To characterize the time course and physiologic significance of decline in serum immunoreactive trypsinogen (IRT) levels in infants with cystic fibrosis (CF) by mode of diagnosis and genotype, and to examine IRT heritability. STUDY DESIGN: We studied longitudinal IRT measurements in 317 children with CF. We developed statistical models to describe IRT decline. Pancreatic disease severity (Mild or Severe) was assigned using CF genotype and was confirmed in 47 infants through fat malabsorption studies. RESULTS: Infants with severe disease exhibited IRT decline with non-detectable levels typically seen by 5 years of age. Infants with mild disease exhibited a decline in the first 2 years, asymptomatically approaching a level greater than published norms. IRT and fecal fat were inversely correlated. IRT values in infants with meconium ileus (MI) were significantly lower than newborn-screened infants at birth. The high proportion of shared variation in predicted IRT values among sibling pairs with severe disease suggests that IRT is heritable. CONCLUSIONS: IRT declines characteristically in infants with CF. Lower IRT values in newborns with MI suggest increased pancreatic injury. Furthermore, IRT is heritable among patients with severe disease suggesting genetic modifiers of early CF pancreatic injury. This study demonstrates heritability of a statistically modeled quantitative phenotype.

Biomarkers↗
PubMed2004

The effects of morphine on the production and discrimination of interresponse times.

Recent experiments suggest that the effects of drugs of abuse on the discrimination of the passage of time may differ for experimenter-imposed and subject-produced events. The current experiment examined this suggestion by determining the effects of morphine on the discrimination of interresponse times (IRTs). Pigeons pecked a center key on a random-interval 20-s schedule of matching-to-sample trials. Once the interval had timed out, a choice trial randomly followed either a short (2- to 3-s) or long (6- to 9-s) IRT on the center key. Pecking the side key lit one color produced food after a short IRT, and pecking the side key lit the other color produced food after a long IRT. Two experimental phases differed in the functional role of the different key colors. Under control conditions, the IRT distributions had two modes, one at the lower bound of the short category and a smaller one at the lower bound of the long category. Pigeons accurately categorized the duration of the IRTs: One key color was pecked following short IRTs and the other key color was pecked following long IRTs. Morphine flattened the IRT distribution and reduced the accuracy of categorizing IRTs. Categorization of long IRTs was particularly disrupted. Morphine did not produce overestimation of time as assessed by the production or categorization of IRTs. These results are similar to those obtained previously for the effects of morphine on the discrimination of the duration of experimenter-imposed events.

Animals↗
PubMed1995

Human intermediate reticular zone: a cyto- and chemoarchitectonic study.

The primary aim of this study was to provide a comprehensive account of the morphology, topography, and frequency of tyrosine hydroxylase- and substance P-like (TH-LI, SP-LI) immunoreactive neurons of the human intermediate reticular zone (IRt), the putative autonomic zone of the medullary reticular formation. A further aim is to examine the IRt from a three-dimensional perspective using computer reconstruction techniques and compare its relationship with other structures in the rest of the medullary reticular formation. Six adult human brains were obtained from individuals with no sign of cerebral disease and were perfusion fixed. Free-floating transverse sections were immunostained with monoclonal antibodies against tyrosine hydroxylase and substance P by the avidin-biotin-peroxidase technique. The entire IRt displays TH-LI cell bodies and fibers, and thus it is readily distinguishable from the neighbouring gigantocellular and parvicellular reticular nuclei. In contrast, SP-LI cells are restricted to the external part of the IRt that is found in the open medulla, while SP-LI fibers are more widely distributed. The IRt displays TH-LI neurons which are fusiform, oval, and round in shape. The SP-LI neurons of the IRt are primarily oval and fusiform. In preparations stained for Nissl substance, IRt cells were classified as pigmented and nonpigmented. A characteristic feature of the IRt is that its cells are larger (20 +/- 4 micrograms) than those of the laterally adjoining parvicellular (12 +/- 2 micrograms) and clearly smaller than those of the medially adjoining gigantocellular nuclei (33 +/- 6 micrograms). The shape of the IRt is in keeping with the radial organization of the medulla with zones emanating from the fourth ventricle. Three-dimensional computer reconstructions of the cell plots show that 1) TH-LI neurons extend through the entire IRt and densely packed in the rostral part of the ventrolateral IRt and 2) SP-LI neurons are found only in the rostral half of the medulla oblongata.

Aged↗
PubMed2006

Immunoreactive trypsin levels in neonates with meconium ileus.

Serum immunoreactive trypsin (IRT) is used as a screening test for cystic fibrosis (CF) in neonates in many countries. Variations in IRT levels are observed in healthy and cystic neonates within the first few weeks of life. Fifteen percentage of CF neonates present with meconium ileus (MI). We hypothesised that there may be differences in serum IRT levels in cystic babies with simple and complicated MI. The aim of this study was to investigate the serum levels of IRT in neonates with CF presenting with MI. IRT levels were sequentially measured in neonates (n = 29) with CF with intestinal obstruction due to simple or complicated MI. These were compared to levels obtained from non-cystic neonates/controls admitted with a variety of other intra-abdominal pathologies (n = 49) IRT levels were significantly higher in the CF-MI group than the non-cystic controls (P < 0.001). There was no statistical difference in IRT levels between the simple or complicated MI groups. In the MI group there was no statistical difference between those who required operation, no difference between the pre- and post-operative IRT levels and no significant relationship between IRT levels and birth weight or gestation. Serum IRT levels are significantly elevated in neonates with CF and MI compared with non-cystic, non-MI neonates. The results of this observational study highlight that a single raised level of IRT in a neonate should prompt the analysis for CF regardless of any underlying surgical pathology.

Biomarkers↗
PubMed2006

A survey of newborn screening for cystic fibrosis in Europe.

BACKGROUND: Cystic fibrosis (CF) is a recessively inherited condition caused by mutation of the CFTR gene. Newborn infants with CF have raised levels of immuno-reactive trypsinogen (IRT) in their serum. Measurement of IRT in the first week of life has enabled CF to be incorporated into existing newborn screening (NBS) blood spot protocols. However, IRT is not a specific test for CF and NBS therefore requires a further tier of tests to avoid unnecessary referral for diagnostic testing. Following identification of the CFTR gene, DNA analysis for common CF-associated mutations has been increasingly used as a second tier test. The aim of this study was to survey the current practice of CF NBS programmes in Europe. METHOD: A questionnaire was sent to 26 regional and national CF NBS programmes in Europe. RESULTS: All programmes responded. The programmes varied in number of infants screened and in the protocols employed, ranging from sweat testing all infants with a raised first IRT to protocols with up to four tiers of testing. Three different assays for IRT were used; in the majority (24) this was a commercially available kit (Delfia). A number of programmes employed a second IRT measurement in the 4th week of life (as the IRT is more specific at this point). Nineteen programmes used DNA analysis for common CFTR mutations on samples with a raised first IRT. Three programmes used a second IRT measurement on infants with just one recognised mutation to reduce the number of infants referred for sweat testing. Referral to clinical services was prompt and diagnosis was confirmed by sweat testing, even in infants with two recognised mutations in most programmes. Subsequent clinical pathways were less uniform. Multivariate analysis demonstrated a relationship between the age of diagnosis and the timing of the first IRT. More sweat tests were undertaken if the first IRT was earlier and the diagnosis was later. CONCLUSIONS: Annually these programmes screen approximately 1,600,000 newborns for CF and over 400 affected infants are recognised. The findings of this survey will guide the development of European evidence based guidelines and may help new regions or nations in the development and implementation of NBS for cystic fibrosis.

Cystic Fibrosis↗
PubMed2005

Markedly elevated neonatal immunoreactive trypsinogen levels in the absence of cystic fibrosis gene mutations is not an indication for further testing.

AIMS: To investigate the immunoreactive trypsinogen (IRT) values above the usual 99th centile laboratory cut-off and determine the value of offering further testing to those infants with a markedly elevated IRT but no cystic fibrosis transmembrane regulator (CFTR) gene mutation identified by the screening programme. METHODS: All babies born in Victoria, Australia, between 1991 and 2003, were screened by IRT followed by CF gene mutation analysis. RESULTS: Of the 806,520 babies born, 9268 with the highest IRT levels had CFTR mutation analysis. There were 123 DeltaF508 homozygotes and 703 heterozygotes (86 with CF, 617 carriers). A total of 8442 babies had no CFTR gene mutation, of whom 18 (0.21%) had CF. The total number of CF babies with IRT greater than the laboratory cut-off was 227 (2.4%). The IRT results of the CF patients were distributed normally, with the majority above the laboratory cut-off of newborn IRT results. There was no evidence of an excess of babies with CF in the very highest levels of IRT above the 99th centile. CONCLUSIONS: Only a small proportion of babies with a neonatal IRT >99th centile have CF. Additional CF testing for infants with an elevated IRT but no CFTR gene mutation has an extremely low yield, no matter how high the IRT result.

Biomarkers↗
PubMed1976

Reinforcement rate and interresponse time differentiation.

Reinforcement rate and differential reinforcement of IRTs were independently manipulated to assess their relative contribution to the control of interresponse times (IRTs). Modified percentile reinforcement schedules (Platt, 1973) allowed control of reinforcement rate while longest or shortest IRTs were selectively reinforced. In the absence of differential IRT reinforcement, mean IRT decreased with increasing reinforcement rate. Compared to this small effect of reinforcement rate, reinforcement of long IRTs produced large changes in mean IRT at constant reinforcement rates. No interaction of reinforcement rate and IRT reinforcement was detected. The demonstration of large IRT changes in the absence of reinforcement-rate changes indicates the precedence of IRT reinforcement over molar reinforcement-rate correlations in the determination of IRTs in these procedures.

Journal Article↗
PubMed1993

Application of DNA analysis in a population-screening program for neonatal diagnosis of cystic fibrosis (CF): comparison of screening protocols.

We compare two protocols for newborn screening for cystic fibrosis (CF). The first uses the immunoreactive trypsinogen (IRT) assay with a cutoff of > or = 180 ng/ml and a sweat test to identify CF patients. The second uses the IRT assay with a 100 ng/ml cutoff in conjunction with direct analysis for the delta F508 CF transmembrane conductance regulator (CFTR) mutation in a two-tiered (i.e., IRT/DNA) protocol, followed by a sweat test. We screened 220,865 newborns from Wisconsin for CF, using the IRT protocol identifying 369 infants with an elevated IRT, of whom 46 were found to have CF. Another 7 CF patients were identified who had a false-negative IRT level. The CF incidence in the white population was 1 in 3,431 (carrier incidence of 1 in 30). The IRT protocol had a sensitivity of 87% and a positive predictive value of 12.5%. We subsequently used the IRT/DNA protocol to screen 21,258 infants. Of 518 infants with an IRT level > or = 100 ng/ml, 24 carried at least one copy of the delta F508 CFTR mutation, and 4 of these infants were found to have CF, yielding a positive predictive value for this protocol of 16.7%. Direct comparison of the positive predictive value of the two protocols is not valid, because of the different populations screened. However, had the IRT protocol been used on the IRT/DNA cohort, 50 infants, including the 4 with CF, would have received sweat tests, yielding a positive predictive value of 8%. Because of the small sample size, this positive predictive value is not significantly different from that obtained for the IRT/DNA test. However, from a practical point of view the IRT/DNA approach does decrease considerably the number of sweat tests that must be undertaken. The number of false positives for the IRT protocol (46 in 21,258) is increased significantly compared with that for the IRT/DNA approach (20 in 21,258; P < .001). The incidence of delta F508 carriers detected in cohorts with an elevated IRT level was increased compared with the incidence in the general population. The direct costs for the IRT/DNA approach (100 ng/ml) were $11,374 per CF patient detected, compared with $10,187 per CF patient detected for the IRT protocol. Therefore, we conclude that the IRT/DNA approach to CF newborn screening decreases the number of false-positive subjects contacted, without a significant increase in cost.

Analysis of Variance↗
PubMed1984

Immunoreactive trypsin in the adult respiratory distress syndrome.

With the purpose of studying the role of proteinases in the development of ARDS, plasma levels of immunoreactive trypsin (IRT) and amylase were measured in 43 intensive care patients at risk of developing ARDS (22 polytrauma, seven abdominal surgery, four burns, two DIC and eight pancreatitis). Twenty four of these 43 patients developed ARDS and 31 presented abnormal IRT values (above 70 micrograms/L). Twenty-one of these 31 patients had ARDS; a significant correlation thus appeared between ARDS and abnormal IRT values. In nine patients, IRT values were higher than 800 micrograms/L and remained high for 3 to 4 days. A statistically significant correlation also appeared between abnormal IRT and septic phenomena: 20 patients with high IRT values presented septic problems. When IRT values were high, amylase values were often also abnormal: 12 of 23 patients with high IRT had abnormal amylase levels (the eight patients with documented pancreatitis were excluded); no other clinical signs or symptoms of pancreatitis were present in these patients. IRT could be one of the mediators of ARDS in septic patients. It is not clear that the pancreas is the origin of IRT in all cases.

Abdomen↗