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PubMed1998

Exercise performance in patients with dilated cardiomyopathy: relationship to resting left ventricular function.

Relationship between maximal exercise tolerance and resting indexes of left ventricular systolic and diastolic function were evaluated in 35 men, aged 55.1 +/- 10.4 years, with dilated cardiomyopathy. Clinical diagnosis of dilated cardiomyopathy was confirmed with M-mode echocardiography (M-mode echocardiographic end-diastolic dimension >55 mm, fractional shortening <25%, increased E point septal separation). Coronary angiography was considered mandatory for exclusion of patients with coronary artery disease. Patients with mitral regurgitation (> or =grade 2) and rhythm other than sinus were excluded. According to the functional classification of New York Heart Association 6 patients were in class I, 11 in class II, 12 in class III and 6 in class IV. Left ventricular ejection fraction (LVEF), stroke volume (SV) and left ventricular end-diastolic pressure (LVEDP) were measured with contrast angiography. Peak early (VE) and late (VA) transmitral filling velocities and their ratio (E/A), isovolumetric relaxation time (IRT) and deceleration time (DT) were computed from pulsed wave Doppler echocardiograms. On completion of all resting measurements, patients underwent symptom limited upright treadmill exercise testing using a modified Naughton protocol and maximal exercise performance metabolic equivalent work load (NETS) was calculated from the speed, incline and length of time at the stage using standard tables to make interpatient comparisons. Significant correlation has been found between NYHA class and METS (r= -0.77, P<0.001). However NYHA class II and NYHA class III patients were found to have similar METS (P=0.317). Patients were further divided into two groups on the basis of exercise data. Group I consisted of 22 patients with relatively preserved exercise tolerance (> or =4 METS) and Group II included 13 patients with impaired exercise tolerance (> or =4 METS). This arbitrary classification was based upon previously described survival differences in these two groups. There were no differences between two groups in terms of age, gender distribution (all were male), heart rate and arterial blood pressure. LVEF, LVEDP, stroke volume, VE, VA, E/A, IRT and DT were also similar between two groups. Strong positive correlation was observed between LVEDP and VE (r=0.74) while IRT and VA negatively correlated with LVEDP (r= -0.77 and r= -0.81 respectively) but neither of resting indexes of left ventricular systolic and diastolic function showed significant correlation with METS and exercise duration.

Cardiomyopathy, Dilated↗
PubMed2002

Non-radioactive PCR-SSCP with a single PCR step for detection of inhibitor resistant beta-lactamases in Escherichia coli.

A method based on PCR-SSCP has been developed to detect presumptive Inhibitor-Resistant TEM (IRT) beta-lactamases in Escherichia coli. The capacity of this technique to differentiate genes from 11 control strains encoding IRT beta-lactamases was evaluated with PCR products digested with RsaI. All the bla(TEM) genes studied could be distinguished by their electrophoretic mobilities. Applied to 29 epidemiologically unrelated clinical isolates of E. coli resistant to amoxicillin-clavulanate (MIC, > or =32 microg/ml), the electrophoretic mobilities of the digested bla(TEM) PCR products were identical to those of the reference bla(TEM-1A) (6 strains) and bla(TEM-1B) (18 strains) genes. The remaining five bla(TEM) PCR products displayed SSCP profiles different from those of the reference bla(TEM) genes and their nucleotide sequence identified them as bla(TEM-1C) in one strain, bla(TEM-30/IRT-2) in two strains, bla(TEM-37/IRT-8) in one strain, and bla(TEM-40/IRT-11) in one isolate. Overexpression of the wild-type bla(TEM-1) gene, as detected by high-level resistance to beta-lactams and enzyme assay, accounted for resistance in the 24 E. coli containing bla(TEM-1). We report a simple one PCR step SSCP that can be used in epidemiological studies for rapid preliminary detection of IRT beta-lactamases; identification should be confirmed by sequence data.

Amoxicillin↗
PubMed2001

Variations of intracavitary applicator geometry during multiple HDR brachytherapy insertions in carcinoma cervix and its influence on reporting as per ICRU report 38.

PURPOSE: This paper examines the extent of variation in the applicator geometry during multiple high dose rate (HDR) intracavitary brachytherapy (ICBT) applications and its impact on reporting as per ICRU report 38. MATERIALS AND METHODS: Eighty orthogonal radiographs from 20 consecutive patients of carcinoma cervix (FIGO stages, IIA-IIIB) having four HDR ICBT applications of 6 Gy each at weekly intervals following teletherapy were evaluated. The applicator consisted of a flexible intrauterine tandem (IUT) independent of the ovoid assembly. The applicator geometry was evaluated in terms of: alpha angle, beta angle, intrauterine length (IUTL), interovoid (IOV), os to right ovoid (ORT) and os to left ovoid (OLT) distances along with vertical (VDL) and anteroposterior displacements (ADL) of the os with respect to the ovoids. The Cartesian co-ordinates (X, Y, and Z) of the IUT tip, centre of both ovoids and os were also measured. Doses to right point A (ARD), left point A (ALD), along with a reference volume of 6 Gy for ICRU height (IRH), width (IRW), thickness (IRT) and volume (IRV) were estimated for each application. RESULTS: Highly significant differences (P<0.001) between four insertions in any given patient across 20 patients for alpha angle, beta angle, IUTL, IOV, ORT, VDL, co-ordinates of the IUT, ovoids and os were observed, except for ADL (P=0.041) and OLT (P=0.247). As a consequence, variations were observed in ARD (P=0.027), ALD (P=0.017); IRH, IRW, IRT and IRV (all P<0.001). Applicator factors which influenced the various dose specification parameters were: beta angle and ORT for both ARD and ALD; UTLN, VDL and ORT for IRH; UTLN and IOV for IRW; UTLN for IRT and VDL for the 6 Gy IRV. CONCLUSIONS: A significant variation of the applicator geometry and its movement was observed in patients undergoing multiple HDR ICBT. This could have implications for reporting dose and volume specifications as required by ICRU report 38.

Brachytherapy↗
PubMed1996

External beam and intraluminal radiotherapy for locally advanced bile duct cancer: role and tolerability.

BACKGROUND AND PURPOSE: Cholangiocarcinoma is rare but carries a poor prognosis. Radiotherapy has been used either as an adjuvant treatment following surgical resection of tumour or for palliation. The purpose of this study was to assess the feasibility and morbidity of accelerated external beam radiotherapy with or without intraluminal radiotherapy in the treatment of locally advanced bile duct cancer. MATERIALS AND METHODS: Thirty eight patients were treated. Surgical procedures performed prior to radiotherapy were extended hepatectomy (3), hepaticojejunostomy with tumour resection (6), palliative biliary-enteric bypass (6), biopsy (4), Whipple's procedure (1), gastrojejunostomy (1) and cholecystectomy (1). Twenty patients received external beam radiotherapy (ERT). Six patients received one Phase of ERT and 12 received two Phases, separated by a 2-week gap. Dose per Phase was 22.5 Gy in 10 twice daily fractions. After 1989, dose per Phase was increased to 27.5 Gy. One patient received Phase I ERT (30.0 Gy) using conventional fractionation and one patient received an uninterrupted, conventionally fractionate course of treatment (50.0 Gy). Fourteen patients received both ERT and intraluminal radiotherapy (IRT) using iridium-192 (192Ir) wire passed through a percutaneous, transhepatic catheter (median dose, ERT 23.8 Gy + IRT 40.0 Gy). In addition, four patients received IRT alone (median dose 45.0 Gy at 1 cm radius). Patients were followed for at least 42 months. RESULTS: Median overall survival was 15 months. Overall survival for the whole group at 1,2 and 3 years was 59.6%, 32.5% and 16.2%. Thirty four patients died of disease. Radiotherapy caused acute toxicity in seven patients. According to RTOG/EORTC criteria toxicity was Grade 1 in four cases, Grade 2 in two cases and Grade 3 in one case. Two patients developed gastrointestinal bleeding as a late complication of radiotherapy. CONCLUSIONS: Accelerated external beam radiotherapy with or without intraluminal radiotherapy is feasible and associated with acceptable toxicity when used in the management of advance cholangiocarcinoma.

Bile Duct Neoplasms↗
PubMed2003

Power analysis in randomized clinical trials based on item response theory.

Patient relevant outcomes, measured using questionnaires, are becoming increasingly popular endpoints in randomized clinical trials (RCTs). Recently, interest in the use of item response theory (IRT) to analyze the responses to such questionnaires has increased. In this paper, we used a simulation study to examine the small sample behavior of a test statistic designed to examine the difference in average latent trait level between two groups when the two-parameter logistic IRT model for binary data is used. The simulation study was extended to examine the relationship between the number of patients required in each arm of an RCT, the number of items used to assess them, and the power to detect minimal, moderate, and substantial treatment effects. The results show that the number of patients required in each arm of an RCT varies with the number of items used to assess the patients. However, as long as at least 20 items are used, the number of items barely affects the number of patients required in each arm of an RCT to detect effect sizes of 0.5 and 0.8 with a power of 80%. In addition, the number of items used has more effect on the number of patients required to detect an effect size of 0.2 with a power of 80%. For instance, if only five randomly selected items are used, it is necessary to include 950 patients in each arm, but if 50 items are used, only 450 are required in each arm. These results indicate that if an RCT is to be designed to detect small effects, it is inadvisable to use very short instruments analyzed using IRT. Finally, the SF-36, SF-12, and SF-8 instruments were considered in the same framework. Since these instruments consist of items scored in more than two categories, slightly different results were obtained.

Health Status↗
PubMed1997

Assessment of mitral A-wave transit time to cardiac outflow tract and isovolumic relaxation time of left ventricle in the appropriate and small-for-gestational-age human fetus.

Mitral A-wave transit time (Ta; ms) from the mitral valve to the left ventricular outflow tract and left ventricular isovolumic relaxation time (IRT) were studied by pulsed Doppler ultrasound in 17 appropriate-for-gestational-age fetuses (AGA, 30-39 wk) and 12 small-for-gestational-age fetuses (SGA, 30-36 wk). Ta was measured from the peak of the A-wave to the peak of the reflected A-wave (Ar) from the left ventricular wall. IRT was determined from the interval between the aortic valve closure artefact and the onset of transmitral flow. The mean Ta in the SGA fetus (42 +/- 7 [1 SD] ms) was significantly shorter (p < 0.03) than in the AGA fetus (47 +/- 11 [1 SD] ms), whereas this was not so for IRT (51 +/- 8 [1 SD] ms vs. 60 +/- 15 [1 SD] ms). In the SGA fetus, a positive correlation (r = +0.82, p < 0.01) was established between Ta (ms) and gestational age. No such correlation existed for the AGA fetus. It is speculated that, in the SGA fetus, the shorter Ta may reflect an increase in left ventricular stiffness.

Adolescent↗
PubMed2001

Can non-shivering thermogenesis in brown adipose tissue following NA injection be quantified by changes in overlying surface temperatures using infrared thermography?

We aimed to investigate whether infra red thermography (IRT) can be used to measure and quantify non-shivering thermogenesis (NST) in the short-tailed field vole Microtus agrestis, by directly comparing it with a standard method, i.e. metabolic response following Noradrenaline injection (NA). Mean skin surface temperature overlying Brown adipose tissue (BAT) depot was 0.82 degrees C higher than mean surface temperature that did not overly BAT. The difference in temperature increased by 1.26 degrees C after NA was administered. Mean skin surface temperature overlying BAT increased by 0.32 degrees C after NA was administered; however, surface temperature decreased by 1.32 degrees C after saline was administered. Mean skin surface temperature overlying BAT did not change significantly between warm and cold acclimated voles; in contrast metabolic peak following NA injection significantly increased in cold acclimated voles. There was no significant correlation between change in surface temperature after NA injection and metabolic peak following NA injection. The results of this study suggest that IRT is not a sensitive enough method to measure changes in NST capacity in BAT following NA injection, or to detect changes in NST capacity induced by cold acclimation. However, IRT can distinguish between skin surfaces overlying BAT and skin surfaces that do not.

Journal Article↗
PubMed2001

Equivalence of hyperfractionated and continuous brachytherapy in a rat tumor model and remarkable effectiveness when preceded by external irradiation.

PURPOSE: In clinical brachytherapy, there is a tendency to replace continuous low-dose-rate (LDR) irradiation by either single-dose or fractionated high-dose-rate (HDR) irradiation. In this study, the equivalence of LDR treatments and fractionated HDR (2 fractions/day) or pulsed-dose-rate (PDR, 4 fractions/day) schedules in terms of tumor cure was investigated in an experimental tumor model. METHODS AND MATERIALS: Tumors (rat rhabdomyosarcoma R1M) were grown s.c. in the flank of rats and implanted with 4 catheters guided by a template. All interstitial radiation treatment (IRT) schedules were given in the same geometry. HDR was given using an (192)Ir single-stepping source. To investigate small fraction sizes, part of the fractionated HDR and PDR schedules were applied after an external irradiation (ERT) top-up dose. The endpoint was the probability of tumor control at 150 days after treatment. Cell survival was estimated by excision assay. RESULTS: Although there was no fractionation effect for fractionated HDR given in 1 or 2 fractions per day, TCD(50)-values were substantially lower than that for LDR. A PDR schedule with an interfraction interval of 3 h (4 fractions/day), however, was equivalent to LDR. The combination of ERT and IRT resulted in a remarkably increased tumor control probability in all top-up regimens, but no difference was found between 2 or 4 fractions/day. Catheter implantation alone decreased the TCD(50) for single-dose ERT already by 17.4 Gy. Cell viability assessed at 24 h after treatment demonstrated an increased effectiveness of interstitial treatment, but, after 10 Gy ERT followed by 10 Gy IRT (24-h interval), it was not less than that calculated for the combined effect of these treatments given separately. CONCLUSION: In full fractionation schedules employing large fractions and long intervals, the sparing effect of sublethal damage repair may be significantly counteracted by reoxygenation. During 3-h intervals, however, repair may be largely completed with only partial reoxygenation causing PDR schedules to be less effective than fractionated HDR, and equivalent to LDR. Brachytherapy with clinically sized fractions after a large external top-up dose showed a remarkable increase in tumor control rate with no effect of fractionation (up to 4 fractions/day), which could not be fully explained by differences in dose distribution or in the cell viability assessed after treatment. This suggests a longer lasting effect on cell survival or radiosensitivity associated with catheter implantation shortly after the top-up dose.

Animals↗
PubMed2002

Assessing tobacco beliefs among youth using item response theory models.

Successful intervention research programs to prevent adolescent smoking require well-chosen, psychometrically sound instruments for assessing smoking prevalence and attitudes. Twelve thousand eight hundred and ten adolescents were surveyed about their smoking beliefs as part of the Teenage Attitudes and Practices Survey project, a prospective cohort study of predictors of smoking initiation among US adolescents. Item response theory (IRT) methods are used to frame a discussion of questions that a researcher might ask when selecting an optimal item set. IRT methods are especially useful for choosing items during instrument development, trait scoring, evaluating item functioning across groups, and creating optimal item subsets for use in specialized applications such as computerized adaptive testing. Data analytic steps for IRT modeling are reviewed for evaluating item quality and differential item functioning across subgroups of gender, age, and smoking status. Implications and challenges in the use of these methods for tobacco onset research and for assessing the developmental trajectories of smoking among youth are discussed.

Adolescent↗
PubMedDate not supplied

Effect of postnatal exposure to a PCB mixture in monkeys on multiple fixed interval-fixed ratio performance.

Behavioral impairment as a consequence of PCB exposure beginning in utero has been reported in both humans and animals. The present study assessed the behavioral consequences of postnatal exposure to PCBs. Male monkeys (Macaca fascicularis) were dosed from birth to 20 weeks of age with 7.5 microgram(s)/kg/day of a PCB mixture representative of the PCBs typically found in human breast milk (eight monkeys) or vehicle (four monkeys). At 4 years of age, performance under a multiple fixed interval (FI)-fixed ratio (FR) schedule of reinforcement was assessed. The FI component was more sensitive to disruption as a result of PCB exposure than was the FR component. PCB-exposed monkeys displayed shorter mean interresponse times (IRTs) than controls, particularly during the earlier sessions of the experiment. Similarly, the increase in pause time characteristic of the acquisition of typical FI performance emerged more slowly across sessions in the PCB-treated group. However, the number of short IRTs (less than 5 s) remained greater in the treated group compared to controls over the 48-session duration of the experiment. On the FR component, control monkeys decreases the mean pause time across sessions whereas the PCB-treated group did not; there were no differences between groups for absolute value of average IRT or pause time. The results of this study extend previous research in this cohort of monkeys, and provide further evidence that PCB exposure limited to the early postnatal period and resulting in environmentally relevant body burdens produces long-term behavioral effects.

Adipose Tissue↗
PubMed2001

[Evaluation of 47,213 infants in neonatal screening for cystic fibrosis, using pancreatitis-associated protein and immunoreactive trypsinogen assays].

OBJECTIVES: The increasing evidence of the benefits of neonatal screening for cystic fibrosis (CF) indicates that this procedure could soon be implemented throughout France. The screening strategy currently used involves the detection of infants with elevated levels of immunoreactive trypsinogen (IRT) (approximately 1% of the population), followed by the detection of CFTR gene mutations. However, genetic analysis has certain drawbacks, the most important of which being the management of heterozygotes, and in France the requirement by law of previous informed consent. In cases of CF, pancreatic alterations are already present in utero. A previous study has demonstrated the value of pancreatitis-associated protein (PAP) as a screening test for CF, and has indicated that a feasible two-stage strategy could involve the following: 1) selection of infants with elevated PAP levels; 2) in this group of infants, subsequent detection of those with elevated IRT levels for direct CF diagnosis by the sweat test thereby avoiding the use of genetic analysis. The study aim was to evaluate this strategy in a large number of neonates. METHODS AND RESULTS: The aforementioned strategy was evaluated in a prospective study involving 47,213 infants in the Provence region of France. In infants with a PAP > 7.5 ng/mL (1.28%), 176 had an elevated IRT level > 700 ng/mL (0.37%). In this limited population sample (0.37% of the total), the sweat test diagnosed five cases of CF. A sixth case involving the monozygous twin of an infant with diagnosed CF remained undetected, probably because of a registration error. Genetic analysis confirmed the diagnosis, and also detected another case in an infant with two CFTR mutations but with a normal phenotype at 20 months of age. As the observed incidence was similar to that which had previously been reported, and as no further case was subsequently detected two years after the end of the study, this indicated that the sensitivity of this screening strategy was satisfactory. Its specificity makes the direct diagnosis of CF cases by the sweat test feasible, without further selection by genetic analysis. CONCLUSION: The PAP/IRT technique for CF detection seems to be suitable for mass screening, without the drawbacks of genetic testing.

Acute-Phase Proteins↗
PubMed2003

[National neonatal screening program for cystic fibrosis: management and organization].

France has decided to add to the national neonatal screening program (Phenylketonuria, Hypothyroidism, Congenital Adrenal Hyperplasia, Sickle cell disease) the screening of cystic fibrosis (CF). The screening of CF will be implemented in all regions of France by the end of 2002 and will cover all newborn (near 800,000/year). Based on the recommendation of the French Screening Foundation, the project has been approved by the Health Ministry and will be financed by the social security. CF neonatal screening is now technically feasible and reliable. The proposed methodology includes: immunoreactive trypsin (IRT) dosage on all newborns at day 3 (by radioimmunology "Cis Bio" or immunofluorescence "Delfia") followed by genotype CFTR analysis if IRT level is above 60 micrograms/L. Screening for 29 mutations is planned. If genotype is negative, control of IRT at day 21 will be obtained. Several requirements are included in the program: a protocol of care for the newly diagnosed CF in a specialised CF center; information to all parents of newborns; results of CFTR genotype has to be given during a clinical visit, even if negative. This screening program should allow to screen 98% of the cystic fibrosis patients before the age of 1 month. In order to ensure perfect efficacy, the CF screening program will be evaluated and modified if necessary.

Cystic Fibrosis↗
PubMed2003

Newborn screening programmes for cystic fibrosis.

We review the current situation with respect to newborn cystic fibrosis screening (NCFS) across the world. The challenges of establishing an NCFS programme are reflected in the diversity of those programmes identified. All employ an initial immunoreactive trypsinogen (IRT) measurement during the first week of life. If this is positive, a second IRT analysis at 4 weeks of age improves the specificity of the test; most programmes have, however, moved to DNA analysis at this point, which improves their sensitivity. Incorporating DNA analysis results in the identification of carriers, which may have implications for families but is generally considered positive. Some programmes have incorporated a second IRT test as well as DNA analysis, either to increase the sensitivity of the test in an area with a low DeltaF508 frequency or to reduce the number of infants requiring a sweat test. Whichever algorithm is selected, the implementation of a successful programme relies on clear pathways and good information for parents.

Cystic Fibrosis↗
PubMed2006

Toward an alcohol use disorder continuum using item response theory: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

BACKGROUND: Item response theory (IRT) was used to determine whether the DSM-IV diagnostic criteria for alcohol abuse and dependence are arrayed along a continuum of severity. METHOD: Data came from a large nationally representative sample of the US population, 18 years and older. A two-parameter logistic IRT model was used to determine the severity and discrimination of each DSM-IV criterion. Differential criterion functioning (DCF) was also assessed across subgroups of the population defined by sex, age and race-ethnicity. RESULTS: All DSM-IV alcohol abuse and dependence criteria, except alcohol-related legal problems, formed a continuum of alcohol use disorder severity. Abuse and dependence criteria did not consistently tap the mildest or more severe end of the continuum respectively, and several criteria were identified as potentially redundant. The drinking in larger amounts or for longer than intended dependence criterion had the greatest discrimination and lowest severity than any other criterion. Although several criteria were found to function differentially between subgroups defined in terms of sex and age, there was evidence that the generalizability and validity of the criterion forming the continuum remained intact at the test score level. CONCLUSIONS: DSM-IV diagnostic criteria for alcohol abuse and dependence form a continuum of severity, calling into question the abuse-dependence distinction in the DSM-IV and the interpretation of abuse as a milder disorder than dependence. The criteria tapped the more severe end of the alcohol use disorder continuum, highlighting the need to identify other criteria capturing the mild to intermediate range of the severity. The drinking larger amounts or longer than intended dependence criterion may be a bridging criterion between drinking patterns that incur risk of alcohol use disorder at the milder end of the continuum, with tolerance, withdrawal, impaired control and serious social and occupational dysfunction at the more severe end of the alcohol use disorder continuum. Future IRT and other dimensional analyses hold great promise in informing revisions to categorical classifications and constructing new dimensional classifications of alcohol use disorders based on the DSM and the ICD.

Adult↗
PubMed2003

Applications of computerized adaptive testing (CAT) to the assessment of headache impact.

OBJECTIVE: To evaluate the feasibility of computerized adaptive testing (CAT) and the reliability and validity of CAT-based estimates of headache impact scores in comparison with 'static' surveys. METHODS: Responses to the 54-item Headache Impact Test (HIT) were re-analyzed for recent headache sufferers (n = 1016) who completed telephone interviews during the National Survey of Headache Impact (NSHI). Item response theory (IRT) calibrations and the computerized dynamic health assessment (DYNHA) software were used to simulate CAT assessments by selecting the most informative items for each person and estimating impact scores according to pre-set precision standards (CAT-HIT). Results were compared with IRT estimates based on all items (total-HIT), computerized 6-item dynamic estimates (CAT-HIT-6), and a developmental version of a 'static' 6-item form (HIT-6-D). Analyses focused on: respondent burden (survey length and administration time), score distributions ('ceiling' and 'floor' effects), reliability and standard errors, and clinical validity (diagnosis, level of severity). A random sample (n = 245) was re-assessed to test responsiveness. A second study (n = 1103) compared actual CAT surveys and an improved 'static' HIT-6 among current headache sufferers sampled on the Internet. Respondents completed measures from the first study and the generic SF-8 Health Survey; some (n = 540) were re-tested on the Internet after 2 weeks. RESULTS: In the first study, simulated CAT-HIT and total-HIT scores were highly correlated (r = 0.92) without 'ceiling' or 'floor' effects and with a substantial reduction (90.8%) in respondent burden. Six of the 54 items accounted for the great majority of item administrations (3603/5028, 77.6%). CAT-HIT reliability estimates were very high (0.975-0.992) in the range where 95% of respondents scored, and relative validity (RV) coefficients were high for diagnosis (RV = 0.87) and severity (RV = 0.89); patient-level classifications were accurate 91.3% for a diagnosis of migraine. For all three criteria of change, CAT-HIT scores were more responsive than all other measures. In the second study, estimates of respondent burden, item usage, reliability and clinical validity were replicated. The test-retest reliability of CAT-HIT was 0.79 and alternate forms coefficients ranged from 0.85 to 0.91. All correlations with the generic SF-8 were negative. CONCLUSIONS: CAT-based administrations of headache impact items achieved very large reductions in respondent burden without compromising validity for purposes of patient screening or monitoring changes in headache impact over time. IRT models and CAT-based dynamic health assessments warrant testing among patients with other conditions.

Computer Systems↗
PubMed2001

Prevalence of CFTR mutations in hypertrypsinaemia detected through neonatal screening for cystic fibrosis.

Nowadays, most of the neonatal screening programs for cystic fibrosis (CF) combine the assay of immunoreactive trypsinogen (IRT) with the analysis of the most common mutations of the CFTR gene. The efficiency of this strategy is now well established, but the identification of heterozygotes among neonates with increased IRT is perceived as a drawback. We proposed to assess the heterozygosity frequency among the children with hypertrypsinaemia detected through the CF screening program implemented in Brittany (France) 10 years ago, to describe the CFTR mutations detected in them and to determine the frequency of the IVS8-5T variant. The molecular analysis relies, in our protocol, on the systematic analysis of three exons of the gene (7-10-11). A total of 160,019 babies were screened for CF in western Brittany between 1992 and 1998. Of the 1964 newborns with increased IRT (1.2%), 60 were CF and 213 were carriers. Heterozygosity frequency was 12.8%), i.e. 3 times greater than in the general population (3.9%; p < 10(-6)), Variability of mutations detected in carriers was greater than in CF children (21 mutations versus 10) and a high proportion of mild mutations or variants (A349V, R297Q, R347H, V317A, G544S, R553G, etc) was observed in carriers. The allelic frequency of the 5T (5.6%) was not significantly increased in this cohort. This study is consistent with previous ones in finding a significantly higher rate of heterozygotes than expected among neonates with hypertrypsinaemia. The strategy of screening used here allows to highlight the variability of mutations detected in heterozygotes and to show that severe mutations, as well as mild mutations, have been observed in neonates with hypertrypsinaemia. If there is no doubt that neonatal hypertrypsinaemia is associated with an elevated frequency of carriers, the underlying mechanisms remain obscure.

Alleles↗
PubMed2002

Comparison of two different protocols of neonatal screening for cystic fibrosis.

The results of two different protocols of neonatal cystic fibrosis (CF) screening in the Lazio region of Italy are reported. The first study, conducted from 1992 to 2000 on about 200,000 newborns, consisted of an immunoreactive trypsin (IRT) protocol without mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, referred to as the IRT/IRT protocol. Approximately 5% of the newborns with a positive first IRT test were also positive at the second test; approximately 57% of the newborns with a high IRT level at the second test were subsequently found to be affected by CF. In September 1998, a second protocol that included mutation analysis (IRT/DNA/IRT protocol) was started. Comparison of the two different screening protocols in terms of sensitivity in detecting CF patients demonstrated that the IRT/DNA/IRT protocol is more effective because it is able to detect a higher number of CF patients than the IRT/IRT protocol. In the same period, in addition to the overall diagnosis performed on a screening basis, 64 other subjects were identified as being affected by CF on the basis of symptomatic findings. The overall incidence of CF (screening + symptoms) was 1 : 2982, while that for carriers was 1 : 27. The sensitivity of the screening program increased over the period from 1992 to 2000, with the enhanced sensitivity in the past 2 years being due to the introduction of the IRT/DNA/IRT protocol.

Cystic Fibrosis↗
PubMed1984

The temporal structure of reinforcement: VI. Local determinants of response topography as determined by analysis of interresponse times.

Rats chronically exposed to intracranial reinforcement tend to respond in brief, well-organized response episodes. In these studies, rats implanted with electrodes aimed at the medial forebrain bundle were permitted sufficient stimulation access to allow the generation of episodic patterns. Interresponse times (IRTs) were collected and examined for indications of systematic trends within individual episodes. Analysis within and between subjects suggested three trends. First, intervals between successive responses within episodes declined for the initial 10-15 responses, at which point they reached a stable asymptote. Second, the degree of this trend varied with the length of time separating successive episodes. At very short times between episodes, little declining trend in initial IRTs was evident. Third, IRTs systematically increased prior to episode termination. These findings suggest that local response topography in spontaneously initiated and organized episodes may reflect the cumulating and subsequently dissipating influence of a priming process. The organizing properties of the priming process suggest that it is a significant motivational influence.

Animals↗