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PubMed1997

Quantifying the molecular structure of behavior: separate effects of caffeine, cocaine, and adenosine agonists on interresponse times and lever-press durations.

One difficulty in analyzing the molecular structure of behavior lies in reducing the data to a manageable size so that they can be described concisely but without a loss of important information. An approach to quantifying and comparing distributions of interresponse times (IRTs) and lever-press durations is described and then used to examine the acute effects of caffeine (an adenosine antagonist), cocaine, and three adenosine agonists in rats chronically consuming either tap water or water containing 1.0 mg/ml caffeine. The adenosine agonists used were R(-)N6-(2-phenylisopropyl)adenosine [R-PIA (preferential A1 receptor agonist)], 5'-(N-cyclopropyl)-carboxamidoadenosine [CPCA (preferential A2 agonist)], and 5'-N-ethylcarboxamidoadenosine [NECA (about equal agonist activity at A1 and A2 receptors)]. The rats' behavior was maintained under a Multiple Fixed-Interval (FI) 120 s, Duration > 5 s schedule of reinforcement. Under the FI schedule, the first lever-press after 120 s resulted in pellet delivery. Under the Duration > 5 s schedule, all lever-press durations greater than 5 s were reinforced. Molecular analyses of distributions of true IRTs (exclusive of lever-press durations) and lever-press durations were conducted by regressing percentiles of the distribution obtained from drug conditions against percentiles obtained from control conditions, a technique called empirical percentile-percentile analysis (or quantile-quantile analysis). The pattern of effects on response durations differed from that seen in IRTs. After acute administration of adenosine agonists, the distributions of lever-press durations under the FI schedule and subcriterion durations under the Duration > 5 s schedule were shifted rightward by a constant proportion, indicative of a generalized slowing of responding by these drugs. The effects of adenosine agonists on IRTs could be described by a power-function relationship whereby long IRTs were increased more than shorter ones. A rate-increasing dose of caffeine (10 mg/kg) did nothing to the molecular structure of lever-press durations or of IRTs, indicating that rate increases seen after this dose were due to an earlier onset of responding in the fixed-interval and were unaccompanied by disruptions in the physical execution of the response. The molecular structure of interresponse time distributions seen at the rate-decreasing dose of caffeine (60 mg/kg) resembled that of a rate-decreasing dose of cocaine, but not of the adenosine agonists. Both caffeine and cocaine produced a curvilinear relationship between drug and control percentiles such that very short IRTs were unaffected, but long ones were lengthened five- to 10-fold. This same dose of caffeine lengthened lever-press durations in a manner that resembled adenosine agonists but not cocaine. Percentile-percentile analyses reveal details about drug effects on the temporal structure of behavior and its physical execution that are not visible in molar analyses.

Adenosine↗
PubMed2005

Cystic fibrosis carriers have higher neonatal immunoreactive trypsinogen values than non-carriers.

Following cystic fibrosis (CF) neonatal screening implementation, a high frequency of heterozygotes has been reported among neonates with elevated immunoreactive trypsinogen (IRT) and normal sweat chloride levels. We studied the relationship between normal IRT values and CF heterozygosity: 10,000 neonates were screened for CF by IRT measurement and tested for 40 CF mutations; the 294 carriers detected were coupled with newborns negative to the same genetic testing, and the two groups' IRT levels compared. Heterozygotes had higher IRT levels than their controls (mean 35.32 vs. 27.58 microg/L, P<0.001). Even within normal trypsinogen range, the probability of being a CF carrier increases with neonatal IRT concentration.

Cystic Fibrosis↗
PubMed2002

Elderly patients have a favorable outcome after intracoronary radiation for in-stent restenosis.

Intracoronary radiation therapy (IRT) reduces recurrent in-stent restenosis (ISR) by inhibition of smooth muscle cell proliferation. The ability of these cells to replicate is limited with age due to changes in the telomeres. The purpose of this study was to assess the effect of age on outcomes following IRT for ISR. We evaluated 1,088 patients with 6-month clinical follow-up who were enrolled in radiation trials for ISR using gamma- and beta-emitters. Patients were analyzed within and between IRT (n = 861) or placebo therapy (n = 227) in four age groups (< 55, 55-65, 66-75, > 75 years). Baseline characteristics were similar within each age group of IRT patients, except elderly patients (> 75 years) had a lower rate of diabetes (28% in patients > 75 years; P = 0.008) and a higher rate of previous CABG (59% in patients > 75 years; P < 0.001). The rate of target lesion revascularization (TLR) was reduced in the elderly. TLR at 6 months was 18% in patients < 55 years, 21% in 55-65 years, 12% in 66-75 years, and 10% in patients > 75 (P = 0.009). The MACE rate at 6 months was 21% in patients < 55 years, 29% in 55-65 years, 26% in 66-75 years, and 17% in patients > 75 (P = 0.03). No effect of age was seen in placebo patients. IRT-treated patients had reduced MACE compared to placebo in all age groups, driven by reduced target vessel revascularization. Age was an independent predictor of MACE at 6 months (OR = 0.8; CI = 0.70-0.93; P = 0.004). Angiographic restenosis was not clearly associated with need for TLR in patients > 75 years. In elderly patients (> 75 years) treated with IRT for ISR, the rate of TLR was significantly reduced compared to younger patients. However, this reduction in TLR was not associated with a reduction in angiographic restenosis, suggesting that TLR should not be used as a surrogate for angiographic evaluation.

Age Factors↗
PubMed1991

Laboratory quality control issues related to screening newborns for cystic fibrosis using immunoreactive trypsin.

We have incorporated the IRT assay for CF to our newborn screening program, relying heavily on electronic data processing to optimize the test results in order to provide the most reliable data possible from the specimen at hand. We have established an internal cut-off of 100 ng/mL and an external referral of 180 ng/mL; this virtually eliminates the possibility that analytical imprecision will result in misidentifying a positive patient specimen. The relationship between IRT levels and various mutant forms of CF are not well established, and it is possible that various forms of CF may exhibit different levels of IRT in the first few days of life. We believe that IRT screening for CF could be a useful procedure for early identification of potential CF. However, by comparison with other newborn screening tests, its sensitivity, 90%, presents a concern. The expectation for PKU, hypothyroidism, MSUD, and galactosemia screening is 100% sensitivity. A false-negative usually results in litigation. The use of IRT in routine newborn screening will require considerable education of the general public and physicians receiving test results. Our program, along with many others, is anxiously watching the developments in the area of gene testing. We feel the relatively inexpensive IRT, used for mass screening can be successfully coupled with the more definitive (and expensive) gene test on a selected population to identify CF at the earliest possible age in a more effective manner. It is possible that in the near future gene probe tests will be applied in a cost effective manner to the initial filter paper specimen.

Cystic Fibrosis↗
PubMed1993

Screening for cystic fibrosis in dried blood spots of newborns.

We propose a newborn cystic fibrosis (CF) screening test based on the analysis of dried blood spot DNA by a strategy involving simple or multiplex denaturing gradient gel electrophoresis (DGGE) of PCR products of CFTR gene fragments, in conjunction with the immunoreactive-trypsin (IRT) assay. From May 1988 to May 1992 we have performed a neonatal screening programme of 42,000 newborns in Brittany. We identified 450 infants with an elevated IRT level. From this cohort, to evaluate the feasibility of measuring IRT in conjunction with mutation analysis in Guthrie cards, a pilot study was initially conducted on 200 individuals with normal IRT and 150 with raised IRT levels. Furthermore, a retrospective study was performed on 189 IRT positive cards, involving mutation scanning of exons 10 and 11 of the CFTR gene, which contains a number of frequent mutations including the deletion delta F508. We show that this approach has several implications for neonatal CF screening especially in decreasing the recall rate and detecting CF carriers.

Algorithms↗
PubMed1982

Variations with age of immunoreactive serum trypsin: higher reference ranges in "healthy" elderly people.

According to the literature, the mean values of immunoreactive serum trypsin (IRT) (RIA-gnost Hoechst) in controls vary considerably between 150 and 283 ng/ml. The reasons for these variations are unknown. The purpose of the present investigation was to study the variations of IRT in relation to age in adults. We studied 124 hospital controls, who were without evidence of pancreatic disease or renal insufficiency and who varied in age between 17 and 84 years. Utilizing the kit of Hoechst, IRT was determined in fasting serum specimens. The mean (+/- SD) in patients over 60 years was 469.6 +/- 197.4 ng/ml, in contrast to 309.1 +/- 118.9 ng/ml (30-59 years) and 209.7 +/- 80.7 (less than 30 years). Of cases over 60 years 36.5% had elevated IRT levels above 500 ng/ml. In 25 cases over 60 years no correlation was found between IRT levels and creatinine clearance and in eight of ten cases of this group with high IRT (greater than 500 ng/ml) the serum pancreatic isoamylase levels were normal. The data indicate that in the diagnosis of pancreatic disease the higher reference ranges in the elderly people have to be taken into account. The age-related higher reference ranges seem not to be due to subclinical renal disease nor to clinically evident pancreatic disease.

Adolescent↗
PubMedDate not supplied

Trypsin/creatinine clearance ratio and serum immunoreactive trypsin in digestive and pancreatic diseases.

The behavior of trypsin/creatinine clearance ratio (Ctr/Ccr) and serum immunoreactive trypsin (IRT) was evaluated in a total of 168 subjects with pancreatic cancer, chronic pancreatitis and non-pancreatic digestive diseases. Amylase/creatinine clearance ratio (Cam/Ccr) and serum amylase levels were also evaluated in order to establish their possible relationship with Ctr/Ccr and IRT values. Elevated Ctr/Ccr and IRT values were observed in several patients with pancreatic cancer and chronic pancreatitis. Abnormal IRT and Ctr/Ccr values were found in 28.2 and 4% of non-pancreatic digestive diseases, respectively. IRT and amylase serum levels showed consensual modifications, while Ctr/Ccr showed a behavior different from that of Cam/Ccr. Liver damage seems to play a role in increasing serum IRT levels of patients without pancreatic involvement, while the increased Ctr/Ccr seems to depend on other factors, for instance renal tubular dysfunction.

Adult↗
PubMed1996

Macular recovery time in diabetic children without retinopathy.

The aim of this study was to evaluate whether patients with initial diabetic nephropathy (defined as persistent microalbuminuria) have an impairment of macular recovery time and if this impairment changes in a long-term follow-up. Eighty insulin-dependent diabetic children without fluorescein angiographic signs of retinopathy and 80 controls were included in the study. All patients underwent nyctometry at the beginning of the study; diabetic children repeated the same test after 7 years. Diabetics were divided into two subgroups as regards presence of persistent microalbuminuria (albumin excretion rate > 20 micrograms/min/1.73 m2). At the beginning of the study, diabetics as a whole and normoalbuminuric patients showed similar data to controls, while microalbuminuric ones showed worse data at nyctometry (initial recovery time (IRT): 44.89 +/- 12.50; Summation method (SM): 509.1 +/- 312.0) in comparison with normoalbuminuric (IRT: 38.12 +/- 10.31, P = 0.010; SM 648.6 +/- 272.2, P = 0.036) and control subjects (IRT: 37.77 +/- 11.82, P = 0.004; SM: 661.5 +/- 297.5, P = 0.013). After 7 years, normoalbuminuric subjects showed a slight, but not significant worsening of nyctometry, while in microalbuminuric ones a significant difference between baseline and the end of follow-up was found (IRT: 44.89 +/- 12.50 vs. 52.91 +/- 13.9, P < 0.01; SM: 509.1 +/- 312.0 vs. 374.8 +/- 271.9, P < 0.05). Diabetic patients had a higher rate of abnormal IRT and SM than controls (P = 0.0004 and P = 0.0006, respectively). A higher number of patients in microalbuminuric subgroup than in normoalbuminuric one were found (both at baseline and at the end of follow-up) above the 95th centile of IRT (baseline 3 vs. 15; P = 0.0002; end of follow-up 5 vs. 23; P < 0.0001) and below the 5th centile of SM (baseline 5 vs. 14; P = 0.004; end of follow-up 5 vs. 19; P < 0.0001). Nyctometry was found more altered in microalbuminuric patients than in normoalbuminuric and controls. Unfortunately, there is a large overlap between the two diabetic subgroups and between diabetics and controls; for this reason, this technique is not suited for everyday practice.

Adolescent↗
PubMed1983

Cystic fibrosis screening by dried blood spot trypsin assay: results in 75,000 newborn infants.

Seventy-five thousand 5-day-old babies were screened for cystic fibrosis by blood spot immunoreactive trypsin (IRT) assay as part of a statewide screening program. IRT was elevated in 433 babies; retesting revealed persistent elevation in 38. Sweat testing confirmed cystic fibrosis in 35 babies and was normal in two babies, whose IRT remained elevated at the time of the test. Sweat testing was refused by one mother. Of the 35 babies with cystic fibrosis, 13 had meconium ileus or an already diagnosed affected sibling, but the diagnosis was unsuspected in 22, although all but four had some symptoms suggestive of cystic fibrosis. Stool trypsin activity at the time of the diagnostic screen was normal in nine and reduced in seven of the babies with cystic fibrosis. One baby did not have elevated IRT, and the cystic fibrosis was missed by the screening test. In a retrospective study of blood spot samples from 36 newborn infants, who were later diagnosed as having cystic fibrosis, all had IRT levels greater than in matched controls. Our study confirms that elevated IRT is characteristic of newborn babies with cystic fibrosis, and shows that this test is very specific and sensitive when used as a newborn screening test.

Australia↗
PubMed1984

Antagonism by CGS 8216 and Ro 15-1788, benzodiazepines antagonists, of the action of chlordiazepoxide on a timing behavior in rats.

Rats were trained to respond under a differential reinforcement of low rate (DRL) schedule of reinforcement. Pretreatment with relatively low doses of chlordiazepoxide (1-10 mg/kg) produced increases in total DRL responses and decreases in the numbers of reinforced responses. Chlordiazepoxide produced a shift in the interresponse time (IRT) distribution of DRL responses. Low doses of chlordiazepoxide shifted the IRT distribution of DRL responses. Low doses of chlordiazepoxide shifted the IRT distribution from the reinforced to the non-reinforced bins. In addition there was marked increase in the number of responses that occurred in the earliest IRT bin (0-3.75 sec). The highest dose of chlordiazepoxide (32 mg/kg) produced a decrease in total DRL responses and resulted in an even IRT distribution of responses. Both CGS 8216 and Ro 15-1788 had minimal effect on DRL responding when given alone. Ro 15-1788 had no effect at either 10 or 32 mg/kg, while CGS 8216 produced decreases in DRL responding at 32 and 100 mg/kg. Both Ro 15-1788 and CGS 8216 antagonized the effects of high and low chlordiazepoxide doses on total DRL responding and on the IRT distribution of responding.

Animals↗
PubMed2004

Analyzing psychopathology items: a case for nonparametric item response theory modeling.

The authors discuss the applicability of nonparametric item response theory (IRT) models to the construction and psychometric analysis of personality and psychopathology scales, and they contrast these models with parametric IRT models. They describe the fit of nonparametric IRT to the Depression content scale of the Minnesota Multiphasic Personality Inventory--2 (J. N. Butcher, W. G. Dahlstrom, J. R. Graham, A. Tellegen, & B. Kaemmer, 1989). They also show how nonparametric IRT models can easily be applied and how misleading results from parametric IRT models can be avoided. They recommend the use of nonparametric IRT modeling prior to using parametric logistic models when investigating personality data.

Adult↗
PubMed2006

Antidepressant-like effects of the corticotropin-releasing factor 1 receptor antagonist, SSR125543, and the vasopressin 1b receptor antagonist, SSR149415, in a DRL-72 s schedule in the rat.

The vasopressin 1b receptor antagonist, SSR149415, and the corticotropin-releasing factor 1 receptor antagonist, SSR125543, are orally active non-peptidic compounds with anxiolytic- and antidepressant-like activities in animal models. Presently, SSR149415 and SSR125543 were evaluated in a differential reinforcement of low-rate 72 s (DRL-72 s) schedule, a procedure known to respond differentially to antidepressants and anxiolytics. Male Wistar rats were trained to lever-press for food reinforcement, but only lever-presses occurring after a 72 s delay were reinforced; otherwise, presses were not rewarded, and the timer was reset to 0 s. The selective serotonin reuptake inhibitor, fluoxetine, and the benzodiazepine anxiolytic, diazepam, were tested in parallel. SSR149415 (10-30 mg/kg, i.p.) and SSR125543 (30 mg/kg, i.p.) increased the percentage of responses emitted in the inter-response time (IRT) bin (49-96 s), which resulted in a greater number of reinforced presses. Both compounds shifted the frequency distribution of responses toward longer IRT durations, with a preservation of the bell shape of the IRT distribution curve. Fluoxetine (10 mg/kg, i.p.) had an effect on DRL-72 s similar to that of SSR149415 and SSR125543. By contrast, diazepam increased the number of responses in IRT bin (0-12 s), and the IRT distribution curve was shifted toward shorter IRT durations and flattened. In summary, these results show that SSR149415 and SSR125543 displayed antidepressant-like activity in a DRL-72 s schedule in rat, confirming their therapeutic potential for the treatment of pathological states induced by chronic frustration such as depression.

Animals↗
PubMed1998

Malnutrition, gastroenteritis and trypsinogen concentration in hospitalised Aboriginal children.

OBJECTIVE: To explore relationships between malnutrition and pancreatic damage in hospitalised aboriginal children. METHODS: Immunoreactive trypsinogen (IRT) concentrations were measured in two populations of hospitalised aboriginal children in Australia: 472 children aged 0-3 years, in Alice Springs (Northern Territory); and 187 children aged 0-16 years in Mount Isa (Queensland). Correlation of whole blood IRT with height and weight z-scores, four-site skinfold thickness and upper arm circumference was sought. RESULTS: In Mount Isa, the geometric mean IRT concentration rose with decreasing weight z-score. The IRT concentration was otherwise unrelated to nutritional indices. Sixty percent of the 39 Mount Isa patients with gastroenteritis and 24.5% of the 358 Alice Springs patients with gastroenteritis had an IRT concentration in the upper quartile for their population, compared with 16% for patients with other diagnoses in both populations. CONCLUSIONS: A high IRT concentration in patients with low weight z-scores is a confounding effect of gastroenteritis, and may result from subclinical pancreatic disease in gastroenteritis.

Adolescent↗
PubMed2003

The reliability and predictive value of adolescents' reports of initial reactions to smoking.

A sample of 372 adolescents completed annual surveys regarding their initial reactions to smoking (IRTS) and their current smoking status. Each annual survey asked participants if they had the following five reactions the first time they smoked a cigarette: coughing, or feeling dizzy, sick, high, or relaxed. Time 1 IRTS data were collected within 1 year of the reported initial smoking experience, and Time 2 IRTS data were collected 1 year later. Kappa values for two IRTS items, coughing (.45) and dizziness (.40), indicated modest but acceptable reliability across a 1-year period, but the remaining items showed poor reliability (all < or =.31). Logistic regression analyses indicated that no IRTS item significantly predicted regular (at least weekly) smoking 1 year later. However, when IRTS and smoking status were assessed concurrently (at Time 2), reports of feeling relaxed and not coughing during the initial episode were significantly correlated with regular smoking. Participants who progressed from experimental to regular smoking from Time 1 to Time 2 were more likely to report relaxation as an initial reaction to smoking at Time 2 after denying relaxation at Time 1.

Adolescent↗
PubMed1991

Quantitation of energy expenditure by infrared thermography.

The objective of this study was to adapt infrared thermography (IRT) to measure heat loss in human beings. IRT images were digitized and a mean body surface temperature was computed; heat losses caused by radiation, convection, and evaporation were calculated by using these data. Because subjects were standing during the procedure a small amount of heat was conducted through the feet; this heat was ignored. Total heat loss measured by IRT was not significantly different from values calculated from simultaneous indirect calorimetry (IC) determinations in fasting health subjects and in postsurgical patients receiving a constant infusion of energy. In healthy subjects, after eating the patterns of response to IRT and IC were as predicted from previous direct calorimetry data. Heat loss measured by IC increased first, 30 min postprandially, followed by an increase in heat loss at 60 min as measured by IRT. It was concluded that IRT as a noninvasive method can be used to quantitate heat loss in human beings.

Adult↗
PubMed1994

Neonatal infection does not affect the immunoreactive trypsinogen screening test for cystic fibrosis.

We aimed to discover whether neonatal infection affected levels of the immunoreactive trypsin (IRT) assay, which is used as a screening test for cystic fibrosis. Forty babies who had clinical features suggesting infection had blood spot specimens for IRT taken at the same time as blood for culture. Of 27 babies believed clinically to have infection, 19 had positive blood cultures and eight had negative culture. In retrospect, 13 were not thought to have infection. The mean (SD) IRT results in these three groups were 15 (8), 11 (4), and 16 (6) micrograms/L, respectively. The mean (SD; range) IRT result for all 40 babies was 14 (7; 10-39). Not only did no babies have elevated IRT results at routine neonatal screening, but none have presented with clinical features suggestive of cystic fibrosis since hospital discharge. Neonatal infection does not appear to cause elevated IRT levels and should therefore not cause false-positive results in mass neonatal screening.

C-Reactive Protein↗
PubMed1988

Renal factors in serum trypsinogen 1 metabolism and excretion in chronic pancreatic disease.

In order to investigate the role of renal factors in affecting trypsinogen 1 metabolism and excretion in chronic pancreatic disease, serum immunoreactive trypsin (IRT), urinary IRT, gamma-glutamyltransferase (GGT), alpha-glucosidase (AGL) and RNase outputs and the molecular size distribution of serum and urine IRT were studied in 8 control subjects, 18 cases with pancreatic cancer, and 23 cases with chronic pancreatitis. Serum chromatography demonstrated that most immunoreactivity eluted as trypsinogen 1. Smaller amounts of immunoreactivity at higher molecular weights were also observed. Urine chromatography displayed both trypsinogen 1 and heavier molecular forms. An inverse linear correlation was noticed between creatinine clearance and serum trypsinogen 1 levels. Multiple regression analysis (urinary IRT output dependent and GGT, AGL, and RNase predictor variables) showed a significant linear correlation. RNase was found to be the most important parameter in explaining urinary IRT output. Mild variations in the glomerular function seem to be able to influence serum trypsinogen 1 levels. Urinary IRT excretion is principally explained by a disturbance in the tubular reabsorption of low molecular weight proteins, such as RNase.

Adult↗
PubMed2002

Beta-lactamases in ampicillin-resistant Escherichia coli isolates from foods, humans, and healthy animals.

TEM-, SHV-, and OXA-type beta-lactamases were studied by PCR with 124 ampicillin-resistant (AMP(r)) Escherichia coli isolates recovered from foods of animal origin (n = 20) and feces of humans (n = 49) and healthy animals (n = 55). PCR showed that 103 isolates were positive for TEM and negative for SHV and OXA. Three E. coli isolates showed a positive reaction for OXA, and one showed a positive reaction for SHV. The remaining 17 E. coli isolates were negative for the three enzymes by PCR. Fifty-seven of the 103 bla(TEM) amplicons were sequenced. Different molecular variants of bla(TEM-1) were found in 52 isolates: bla(TEM-1a) (n = 9), bla(TEM-1b) (n = 36), bla(TEM-1c) (n = 6), and bla(TEM-1f) (n = 1). Four inhibitor-resistant TEM (IRT) beta-lactamase-encoding genes were also detected: bla(TEM-30c) (IRT-2), bla(TEM-34b) (IRT-6), bla(TEM-40b) (IRT-11), and bla(TEM-51a) (IRT-15). A new bla(TEM) gene, named bla(TEM-95b), which showed a mutation in amino acid 145 (P-->A) was detected. It was found in a food isolate of chicken origin (AMP(r), amoxicillin-clavulanic acid susceptible). The promoter region in 24 bla(TEM) amplicons was analyzed, and the weak P3 promoter was found in 23 of them (bla(TEM-1) in 20 amplicons and bla(TEM-51a), bla(TEM-30c), and bla(TEM-95b) in 1 amplicon each). The strong Pa/Pb promoter was found only in the bla(TEM-34b) gene. No extended-spectrum beta-lactamases were detected. Mutations at position -42 or -32 in the ampC gene promoter were demonstrated in 4 of 10 E. coli isolates for which the cefoxitin MIC was >/=16 micro g/ml. Different variants of bla(TEM-1) and IRT bla(TEM) genes were found among the AMP(r) E. coli isolates from foods and the feces of humans and healthy animals, and a new gene, bla(TEM-95b) (P3), was detected.

Ampicillin↗