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PubMed2003

The feasibility of applying item response theory to measures of migraine impact: a re-analysis of three clinical studies.

BACKGROUND: Item response theory (IRT) is a powerful framework for analyzing multiitem scales and is central to the implementation of computerized adaptive testing. OBJECTIVES: To explain the use of IRT to examine measurement properties and to apply IRT to a questionnaire for measuring migraine impact--the Migraine Specific Questionnaire (MSQ). METHODS: Data from three clinical studies that employed the MSQ-version 1 were analyzed by confirmatory factor analysis for categorical data and by IRT modeling. RESULTS: Confirmatory factor analyses showed very high correlations between the factors hypothesized by the original test constructions. Further, high item loadings on one common factor suggest that migraine impact may be adequately assessed by only one score. IRT analyses of the MSQ were feasible and provided several suggestions as to how to improve the items and in particular the response choices. Out of 15 items, 13 showed adequate fit to the IRT model. In general, IRT scores were strongly associated with the scores proposed by the original test developers and with the total item sum score. Analysis of response consistency showed that more than 90% of the patients answered consistently according to a unidimensional IRT model. For the remaining patients, scores on the dimension of emotional function were less strongly related to the overall IRT scores that mainly reflected role limitations. Such response patterns can be detected easily using response consistency indices. Analysis of test precision across score levels revealed that the MSQ was most precise at one standard deviation worse than the mean impact level for migraine patients that are not in treatment. Thus, gains in test precision can be achieved by developing items aimed at less severe levels of migraine impact. CONCLUSIONS: IRT proved useful for analyzing the MSQ. The approach warrants further testing in a more comprehensive item pool for headache impact that would enable computerized adaptive testing.

Adolescent↗
PubMed1998

Phenotypic study of resistance of beta-lactamase-inhibitor-resistant TEM enzymes which differ by naturally occurring variations and by site-directed substitution at Asp276.

At this time an amino acid substitution at position 276 in the TEM-1 enzyme is associated with an additional substitution at position 69 in natural beta-lactamase-inhibitor-resistant (IRT) beta-lactamases. The effect of the Asn276-->Asp substitution on resistance was assessed with the Asn276Asp variant, generated by site-directed mutagenesis. The mutant was resistant to beta-lactamase inhibitors, but the MICs of amoxicillin combined with clavulanic acid or tazobactam were strikingly different for E. coli strains producing the Asn276Asp variant and those producing naturally occurring IRTs with single or double substitutions. The inhibitory effects of clavulanic acid and tazobactam were the same in IRTs with substitutions at position 69 (IRT-5 and IRT-6). The effect of clavulanic acid on the MICs of amoxicillin for the Asn276Asp variant was greater than that of tazobactam. In IRTs with double substitutions, at positions 69 plus 276 (IRT-4, IRT-7, and IRT-8) or 69 plus 275 (IRT-14), tazobactam was a more potent inhibitor than clavulanic acid. The effect of the Asn276-->Asp substitution on the values of the kinetic constants and the concentration required to inhibit by 50% the hydrolysis of benzylpenicillin confirms that this single mutation is responsible for resistance to beta-lactamase inhibitors. Molecular modeling of the Asn276Asp mutant shows that Asp276 can form two salt bonds with Arg244 close to the penicillin-binding cavity. The addition of the Asp276 mutation to that preexisting at position 69 confers a higher selective advantage to bacteria, as shown by the reduction in beta-lactamase inhibitor efficiencies of the double variants. Therefore, the emergence of multiple mutations in TEM beta-lactamases by virtue of the use of beta-lactamase inhibitors increases selection pressure resulting in the convergent evolution of resistant strains.

Amoxicillin↗
PubMed2005

Superiority of sirolimus eluting stent compared with intracoronary beta radiation for treatment of in-stent restenosis: a matched comparison.

OBJECTIVE: To compare acute and follow up clinical and angiographic results after treatment of in-stent restenosis (ISR) by sirolimus eluting stents (SES) with results obtained after intracoronary radiation therapy (IRT). DESIGN: Matched pair analysis. METHODS: 62 consecutive ISR lesions (< 30 mm lesion length, reference diameter < 3.5 mm) in 62 patients were treated with SES. From a database of 174 lesions (n = 141 patients) treated for ISR by intracoronary beta radiation, 62 lesions (62 patients) were pair matched with the SES group for diabetes mellitus, lesion length, vessel size, and pattern of ISR. Six month angiographic and 12 month clinical follow up results were obtained. RESULTS: Baseline clinical and angiographic characteristics were similar between the groups (not significant). SES implantation resulted in significantly lower postprocedural in-lesion diameter stenosis than did IRT (mean (SD) 14.2 (9.5)% v 21.1 (10.6)%, p = 0.001), significantly higher minimum lumen diameter at follow up (1.91 (0.58) v 1.55 (0.72) mm, p = 0.005), and a higher net gain (1.16 (0.55) v 0.77 (0.70) mm, p = 0.002). Angiographic binary in-lesion restenosis rate at six months was 11% in the SES group and 29% in the IRT group (p = 0.046). In 16 ISR lesions SES were used after failed IRT and in 46 lesions for first time ISR. In-lesion late loss was higher after use of SES for failed IRT than after use of SES for first time ISR (0.61 (0.67) mm v 0.24 (0.41) mm, p = 0.018). In a multivariate analysis prior failed IRT was the only independent predictor for recurrent restenosis after SES for ISR (p = 0.052, odds ratio 5.8). Six patients (10%) in the SES group and 17 patients (27%) in the IRT group underwent target lesion revascularisation during the 12 months of follow up (p = 0.022). CONCLUSIONS: In this non-randomised matched cohort SES achieved acute and follow up results superior to IRT for treatment of ISR even if cases of failed IRT are included. Failed IRT is a predictor of impaired SES effectiveness.

Beta Particles↗
PubMed1985

Effects of estradiol on insulin receptor distribution in primary cultures of R3230AC mammary adenocarcinoma of the rat.

The influence of 17 beta-estradiol on insulin receptor distribution was studied in primary cultures of R3230AC mammary tumors prepared from intact or ovariectomized Fischer rats. [125I] Insulin binding to plasma membrane (IRS) and to solubilized cells (IRt) was measured, and intracellular insulin binding (IRi) was calculated by the difference between the two; calculated IRi agreed well with measured IRi of solubilized cells that were pretreated with trypsin to remove IRs. Scatchard analysis of saturation studies on IRs and IRt displayed typical curvilinearity and were roughly parallel with comparable Ke and Kd values for high affinity sites, but tumors from ovariectomized rats displayed more sites per cell. Insulin receptors relative to time in culture showed an early decline in IRt and IRs for both types of cells, followed by a gradual return to similar IRt values; in both types of cells, however, the proportion of IRs was increased compared to their initial distribution. Cells from both types of host animals displayed an insulin dose-related down-regulation with both IRt and IRs decreased. Short exposure (24 h) to 17 beta-estradiol in vitro also reduced IRs and IRt, but to a lesser extent than insulin, whereas longer exposure to estradiol (48 h) caused a continued reduction in IRs but not IRt. Compared to cells exposed to estradiol for 24 h in vitro, cultured cells treated with progesterone demonstrated an increased IRs, a marginal effect upon exposure to higher doses of testosterone, and reduced IRt, IRs, and IRi in response to dexamethasone. Monohydroxytamoxifen, an antiestrogen, displayed an unusual pattern, inducing a reduction in IRt and IRs at the lower doses but not at the higher doses studied. Degradation of [125I]insulin was examined in cells that were insulin down-regulated in the absence or presence of various levels of estradiol; the steroid hormone appeared to reduce degradation of [125I]insulin when lower levels of insulin were employed. The presence of estradiol in the medium enhanced the reappearance of IRt during the first 10 h after removal of the insulin that caused down-regulation. In conjunction with our previous observations in vivo, we conclude that 1) estradiol in vitro can decrease (down-regulate) insulin receptors on the plasma membrane of R3230AC mammary tumors; 2) the steroid may reduce degradation of internalized [125I]insulin; and 3) the steroid may enhance insulin receptor reappearance after insulin down-regulation. These estrogen-insulin interactions could play a role in the regulation of growth and metabolism of this hormone-responsive experimental mammary carcinoma.

Adenocarcinoma↗
PubMed1975

Interresponse time changes as a function of water deprivation and amphetamine.

Drug effects on operant behavior are often characterized by their effects on rate of responding, usually expressed as the number of responses per unit of time. The time between two consecutive responses constitutes an interresponse time (IRT), and this measure has been used also to characterize the effects of drugs on operant behavior. IRTs which occur during a session can be classified on a statistical basis as: 1) short-IRT, an IRT(s) of short duratio generated by high-frequency responses; 2) pause, an IRT of long duratio generated by low-frequency responses; and 3) post-reinforcement pause, an IRT which immediately follows reinforcement. This investigation used three schedules of water reinforcement (fixed-ratio 20, fixed-interval 90-seconds and variable-interval 20-seconds) to examine how these IRT classes are influenced by changes in water deprivation conditions or amphetamine administration. Base-line IRT distributions depended upon the schedule of reinforcement. Changes induced by doses of amphetamine or alterations in level of water deprivation were compared and contrasted. Short-IRTs that characterized fixed-ratio 20 performance were resistant to change with increasing doses of amphetamine, but were increased in duration with decreasing water deprivation. Animals responding on a fixed-interval 90-second schedule showed a decreased postreinforcement pause after amphetamine, but an increased postreinforcement pause after access to water. An additional experiment studied the combined effects of presession water consumption and d-amphetamine administration on variable interval performances. Making water available before the session lowered the amphetamine dose-response curve along the vertical axis, suggesting that amphetamine did not mimic satiation. In most cases the effect of amphetamine and changing levels of water deprivation were dissimilar in their effects on IRT distributions, suggesting that amphetamine does not exert its major action on behavior through its adipsic effect.

Amphetamine↗
PubMed1994

Buspirone, gepirone, ipsapirone, and zalospirone have distinct effects on the differential-reinforcement-of-low-rate 72-s schedule when compared with 5-HTP and diazepam.

The effects of four serotonin (5-HT)-1A compounds (buspirone, gepirone, ipsapirone and zalospirone) were compared with 5-hydroxytryptophan (5-HTP) [a 5-HT precursor with antidepressant (AD) efficacy], and diazepam (a benzodiazepine anxiolytic), on a differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule. Past research has shown that AD and anxiolytic compounds each have distinct effects on the DRL 72-s interresponse time (IRT) distribution profile. In the present paper, the profile of the IRT distribution was quantitatively characterized by three metrics: burst ratio, peak location and peak area. 5-HTP shifted the IRT distribution peak toward longer IRT durations, increased reinforcement rate and decreased response rate. The profile of the IRT distribution was not disrupted by 5-HTP. Diazepam disrupted the IRT distribution and increased bursting. In general, the arylpiperazine, 5-HT1A compounds increased reinforcement rate, decreased response rate and disrupted the profile of the IRT distribution. The effects of the four arylpiperazine 5-HT1A compounds on the IRT distribution profile were different from the AD profile of 5-HTP and the benzodiazepine anxiolytic profile of diazepam. Disruption of the IRT distribution by buspirone, gepirone, ipsapirone and zalospirone may result from decreased 5-HT transmission mediated by the presynaptic, somatodendritic 5-HT1A receptor.

5-Hydroxytryptophan↗
PubMed1993

The role of brain dopamine in response initiation: effects of haloperidol and regionally specific dopamine depletions on the local rate of instrumental responding.

Two experiments were undertaken to investigate dopaminergic involvement in the local rate of responding on a fixed ratio 5 (FR5) instrumental lever pressing schedule. Rats were trained to press a lever for food reinforcement on a FR5 schedule, and a computer program was used to record the interresponse time (IRT) for each response. The IRT is the time between each lever pressing response, which is equal to the reciprocal of the local response rate. After several weeks of training, rats received i.p. injections of the dopamine antagonist haloperidol (HP; 0.1, 0.2 and 0.4 mg/kg). HP produced a dose-related decline in overall response number. In addition, HP dramatically altered the IRT distribution. HP-treated rats showed a dose-related reduction in the proportion of IRTs with low time values (high local rates of responding), and a corresponding increase in the relative number of IRTs with high time values (low local rates of responding). In the second experiment, the neurotoxic agent 6-hydroxydopamine was injected directly into the nucleus accumbens, medial neostriatum or ventrolateral neostriatum in order to determine the effects of DA depletion on lever pressing performance. Dopamine depletion in all regions significantly reduced lever pressing, and dopamine-depleted rats had substantial changes in their IRT distributions. Rats with dopamine depletions showed significant reductions in the proportion of IRTs with low time values, and increases in the relative number of IRTs with high time values. The greatest reductions in response number and the most pronounced alterations of the IRT distribution were shown by rats with ventrolateral neostriatal dopamine depletions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Patient doses in gamma-intracoronary radiotherapy: the Radiation Burden Assessment Study.

PURPOSE: To determine accurately the radiation burden of both patients and staff from intracoronary radiotherapy (IRT) with (192)Ir and to investigate the importance of IRT in the patient dose compared with interventional X-rays. METHODS AND MATERIALS: The Radiation Burden Assessment Study (RABAS) population consisted of 9 patients undergoing gamma-IRT after percutaneous transluminal coronary angioplasty and 14 patients undergoing percutaneous transluminal coronary angioplasty only as the control group. For each patient, the dose to the organs and tissues from the internal and external exposure was determined in detail by Monte Carlo N-particle simulations. Patient skin dose measurements with thermoluminescence dosimeters served as verification. Staff dosimetry was performed with electronic dosimeters, thermoluminescence dosimeters, and double film badge dosimetry. RESULTS: With respect to the patient dose from IRT, the critical organs are the thymus (58 mGy), lungs (31 mGy), and esophagus (27 mGy). The mean effective dose from IRT was 8 mSv. The effective dose values from interventional X-rays showed a broad range (2-28 mSv), with mean values of 8 mSv for the IRT patients and 13 mSv for the control group. The mean dose received by the radiotherapist from IRT was 4 microSv/treatment. The doses to the other staff members were completely negligible. CONCLUSION: Our results have shown that the patient and personnel doses in gamma-IRT remain at an acceptable level. The patient dose from IRT was within the variations in dose from the accompanying interventional X-rays.

Adult↗
PubMed2003

Item response theory: applications of modern test theory in medical education.

CONTEXT: Item response theory (IRT) measurement models are discussed in the context of their potential usefulness in various medical education settings such as assessment of achievement and evaluation of clinical performance. PURPOSE: The purpose of this article is to compare and contrast IRT measurement with the more familiar classical measurement theory (CMT) and to explore the benefits of IRT applications in typical medical education settings. SUMMARY: CMT, the more common measurement model used in medical education, is straightforward and intuitive. Its limitation is that it is sample-dependent, in that all statistics are confounded with the particular sample of examinees who completed the assessment. Examinee scores from IRT are independent of the particular sample of test questions or assessment stimuli. Also, item characteristics, such as item difficulty, are independent of the particular sample of examinees. The IRT characteristic of invariance permits easy equating of examination scores, which places scores on a constant measurement scale and permits the legitimate comparison of student ability change over time. Three common IRT models and their statistical assumptions are discussed. IRT applications in computer-adaptive testing and as a method useful for adjusting rater error in clinical performance assessments are overviewed. CONCLUSIONS: IRT measurement is a powerful tool used to solve a major problem of CMT, that is, the confounding of examinee ability with item characteristics. IRT measurement addresses important issues in medical education, such as eliminating rater error from performance assessments.

Clinical Competence↗
PubMed1996

Interstitial radiation and hyperthermia in the Dunning R3327 prostate tumour model: therapeutic efficacy depends on radiation dose-rate, sequence and frequency of heating.

To determine the most effective means by which to apply the combined treatments of local tumour hyperthermia (LTH) with interstitial low dose-rate irradiation (IRT) we examined the significance of such factors as dose-rate of radiation, and the sequence and frequency of hyperthermia applications in the anaplastic Dunning prostate tumour subline R3327-AT1. IRT was carried out by the insertion of a single Ir-192 seed into the center of the tumour. For LTH treatments, the tumour-bearing leg was positioned in a circulating constant temperature water bath (43.5 +/- 0.1 degrees C) for 35 min. Neither LTH treatment alone nor the insertion of a dummy seed produced any change in tumour growth compared with sham-treated controls. With regard to the sequence of heating and IRT our results showed that during a 72-h treatment time (30 Gy, 40 cGy/h) a single heat treatment given just before the start of IRT was more efficient (TER = 1.47) in terms of growth delay than LTH given in the middle or the end of radiation treatment (TER approximately 1.0). The growth delay for both the 20 and 40 cGy/h groups appear to be linear with increasing dose for the IRT as well as the IRT + LTH groups. The higher dose-rate was more effective especially with respect to long-term delay in tumour growth in some of the animals. As TER at 40 cGy/h decreased subsequently with increasing treatment time from 1.47 to 1.25 at 60 Gy, we conclude that for treatment times > 72 h, one LTH just before IRT might not be sufficient. If multiple heat treatments are applied during a comparable time course, two LTH treatments one just before the start, the other at the end yielded the greatest local tumour control. In contrast, three LTH given daily were not more effective than the one LTH given just before the start of IRT. These data indicate a clear thermal enhancement of low dose-rate irradiation, with maximal sensitization when hyperthermia was given just before IRT. For multiple heatings a better understanding of the underlying mechanisms of sequencing and timing hopefully provides guidelines how to apply optimally both modalities in the treatment of cancer.

Animals↗
PubMed1990

Exocrine pancreatic function (serum immunoreactive trypsin, fecal chymotrypsin, and pancreatic isoamylase) in Indian diabetics.

Forty-nine patients with tropical calcific pancreatitis (TCP), 51 insulin-dependent diabetics (IDDMs), 87 non-insulin-dependent diabetics (NID-DMs), and 66 nondiabetic controls were studied to evaluate their exocrine pancreatic function by measurement of serum immunoreactive trypsin (IRT, normal for white caucasians from the U.K. of 140-414 micrograms/L), pancreatic isoamylase (PIA, normal of 35-125 U/L), and fecal chymotrypsin (FCT, normal of greater than 6.6 u/g). The majority of patients were studied within 1 year of diagnosis. TCP subjects included 7 nondiabetics, 6 with impaired glucose tolerance (IGT-TCP), and 36 diabetics [fibrocalculous pancreatic diabetes (FCPD)]. There was evidence of active pancreatitis (IRT greater than 800 micrograms/L) and partial preservation of function in nondiabetic TCP subjects [median IRT of 220 micrograms/L (range of 102-1,360 micrograms/L), FCT of 2.2 u/g (range 0.7-12.8 u/g)] and also in IGT-TCP subjects [IRT of 370 micrograms/L (range of 30-1,360 micrograms/L), FCT of 4.2 u/g (range of 1-38 u/g)]. FCPDs showed severely diminished exocrine function [IRT of 50 micrograms/L (range of 0-184 micrograms/L), FCT of 0.23 u/g (range of 0-10.4 u/g)]; none showed IRT greater than 800 micrograms/L. IDDMs and NIDDMs also showed diminished exocrine pancreatic function in approximately 30 and approximately 10%, respectively. Controls showed a wide range of IRT and FCT concentrations; IRT concentrations tended to be higher than those reported in white Caucasians from the U.K. Three controls, one IDDM, and two NIDDMs showed "pancreatic" IRT concentrations in the absence of symptoms. PIA concentrations were diminished in FCPD but were similar in IDDM and NIDDM subjects compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1999

Diversity of TEM mutants in Proteus mirabilis.

In a survey of resistance to amoxicillin among clinical isolates of Proteus mirabilis, 10 TEM-type beta-lactamases were characterized: (i) the well-known penicillinases TEM-1 and TEM-2, the extended-spectrum beta-lactamases (ESBLs) TEM-3 and TEM-24, and the inhibitor-resistant TEM (IRT) TEM-44 and (ii) five novel enzymes, a penicillinase TEM-57 similar to TEM-1, an ESBL TEM-66 similar to TEM-3, and three IRTs, TEM-65, TEM-73, and TEM-74. The penicillinase TEM-57 and the ESBL TEM-66 differed from TEM-1 and TEM-3, respectively, by the amino acid substitution Gly-92-->Asp (nucleotide mutation G-477-->A). This substitution could have accounted for the decrease in pIs (5.2 for TEM-57 and 6.0 for TEM-66) but did not necessarily affect the intrinsic activities of these enzymes. The IRT TEM-65 was an IRT-1-like IRT (Cys-244) related to TEM-2 (Lys-39). The two other IRTs, TEM-73 and TEM-74, were related to IRT-1 (Cys-244) and IRT-2 (Ser-244), respectively, and harbored the amino acid substitutions Leu-21-->Phe and Thr-265-->Met. In this study, the ESBLs TEM-66, TEM-24, and TEM-3 were encoded by large (170- to 180-kb) conjugative plasmids that exhibited similar patterns after digestion and hybridization with the TEM and AAC(6')I probes. The three IRTs TEM-65, TEM-73, and TEM-74 were encoded by plasmids that ranged in size from 42 to 70 kb but for which no transfer was obtained. The characterization of five new plasmid-mediated TEM-type beta-lactamases and the first report of TEM-24 in P. mirabilis are evidence of the wide diversity of beta-lactamases produced in this species and of its possible role as a beta-lactamase-encoding plasmid reservoir.

Alleles↗
PubMed1989

Serum immunoreactive trypsin in tropical pancreatic diabetes syndrome.

Fifteen patients with tropical pancreatic diabetes syndrome (TPDS), 16 insulin-dependent diabetics (IDD), 27 non-insulin-dependent diabetics (NIDD) and 14 normal subjects, all from India, were investigated for markers of beta-cell (C-peptide) and exocrine (immunoreactive trypsin; IRT) reserve. IRT and C-peptide concentrations were the lowest in TPDS, lower than normal in IDD, and not significantly different from normal in NIDDs. There was a highly significant correlation (rs = 0.93; P less than 0.0001) between IRT and C-peptide (measured in 50% of patients and controls) concentrations when all diabetic groups were combined. Such a correlation was absent when TPDS patients were considered in isolation, largely because of the markedly low IRT concentration. Fourteen of 15 patients (93%) with TPDS had subnormal IRT concentrations, of which 11 had IRT values of less than 50 micrograms/L. These IRT values are similar to those previously reported in cystic fibrosis. Only 6 of 16 IDDs (38%) had subnormal IRT concentrations, of which only one was below 50 micrograms/L. These data suggest that exocrine pancreatic reserve is markedly diminished in TPDS and that a subnormal IRT concentration may be a useful biochemical marker for this form of diabetes.

Adolescent↗
PubMed2001

Relationship between work of breathing provided by a ventilator and patients' inspiratory drive during pressure support ventilation; effects of inspiratory rise time.

Inspiratory drive and work of breathing provided by a ventilator (WOBv) during pressure support ventilation (PSV) were examined in 15 patients. At PSV 10 and 15 cm H2O during CPAP 5 cm H2O, patients with low P0.1 (<4.2 cm H2O, n=9) showed WOBv 0.57 and 0.92 J/l, those with high P0.1 (>4.2 cm H2O, n=6) showed 0.31 and 0.62 J/l respectively. WOBv was smaller and pressure-time product of oesophageal pressure (PTP) was significantly larger in high P0.1 patients. Peak inspiratory flow for low P0.1 patients increased as PSV level increased but high P0.1 patients showed no significant change. In a lung model, effects of inspiratory rise time (IRT) and PSV were studied at high and low inspiratory drives by using ventilators with (Servo 300) and without (Mallinckrodt 7200a) adjustable IRT. With 7200a, PSV 10 cm H2O during low drive was compared with PSV 10 and 15 cm H20 during high drive. In Servo 300, PSV 10 cm H2O (IRT 0.6 and 0.0 sec) during low drive was compared with PSV 10 cm H20 (IRT 0.6 and 0.0 sec) and PSV 15 cm H2O (IRT 0.6 sec) during high drive. Raising PSV and shortening IRT both increased peak inspiratory flow. Initial inspiratory flow increased in inverse proportion to IRT, but higher PSV had a little effect. WOBv with high drive was less than with low drive. Higher PSV preserved WOBv by increasing tidal volume. Shortening IRT recruited WOBv by increasing initial inspiratory flow without changing airway pressure and tidal volume. Compared with higher PSV, shorter IRT reduced PTP more. In conclusion, WOBv decreased as inspiratory drive increased due to inability to increase inspiratory flow. Increasing initial inspiratory flow was more effective than raising PSV to preserve inspiratory assistance of PSV at high inspiratory drive.

Adult↗
PubMed1997

Newborn screening for cystic fibrosis in Wisconsin: comparison of biochemical and molecular methods.

OBJECTIVES: To evaluate neonatal screening for cystic fibrosis (CF), including study of the screening procedures and characteristics of false-positive infants, over the past 10 years in Wisconsin. An important objective evolving from the original design has been to compare use of a single-tier immunoreactive trypsinogen (IRT) screening method with that of a two-tier method using IRT and analyses of samples for the most common cystic fibrosis transmembrane regulator (CFTR) (DeltaF508) mutation. We also examined the benefit of including up to 10 additional CFTR mutations in the screening protocol. METHODS: From 1985 to 1994, using either the IRT or IRT/DNA protocol, 220 862 and 104 308 neonates, respectively, were screened for CF. For the IRT protocol, neonates with an IRT >/=180 ng/mL were considered positive, and the standard sweat chloride test was administered to determine CF status. For the IRT/DNA protocol, samples from the original dried-blood specimen on the Guthrie card of neonates with an IRT >/=110 ng/mL were tested for the presence of the DeltaF508 CFTR allele, and if the DNA test revealed one or two DeltaF508 alleles, a sweat test was obtained. RESULTS: Both screening procedures had very high specificity. The sensitivity tended to be higher with the IRT/DNA protocol, but the differences were not statistically significant. The positive predictive value of the IRT/DNA screening protocol was 15.2% compared with 6.4% if the same samples had been screened by the IRT method. Assessment of the false-positive IRT/DNA population revealed that the two-tier method eliminates the disproportionate number of infants with low Apgar scores and also the high prevalence of African-Americans identified previously in our study of newborns with high IRT levels. We found that 55% of DNA-positive CF infants were homozygous for DeltaF508 and 40% had one DeltaF508 allele. Adding analyses for 10 more CFTR mutations has only a small effect on the sensitivity but is likely to add significantly to the cost of screening. CONCLUSIONS: Advantages of the IRT/DNA protocol over IRT analysis include improved positive predictive value, reduction of false-positive infants, and more rapid diagnosis with elimination of recall specimens.

Apgar Score↗
PubMedDate not supplied

Screening for fever by remote-sensing infrared thermographic camera.

BACKGROUND: Following the severe acute respiratory syndrome (SARS) outbreak, remote-sensing infrared thermography (IRT) has been advocated as a possible means of screening for fever in travelers at airports and border crossings, but its applicability has not been established. We therefore set out to evaluate (1) the feasibility of IRT imaging to identify subjects with fever, and (2) the optimal instrumental configuration and validity for such testing. METHODS: Over a 20-day inclusive period, 176 subjects (49 hospital inpatients without SARS or suspected SARS, 99 health clinic attendees and 28 healthy volunteers) were recruited. Remotely sensed IRT readings were obtained from various parts of the front and side of the face (at distances of 1.5 and 0.5 m), and compared to concurrently determined body temperature measurements using conventional means (aural tympanic IRT and oral mercury thermometry). The resulting data were submitted to linear regression/correlation and sensitivity analyses. All recruits gave prior informed consent and our Faculty Institutional Review Board approved the protocol. RESULTS: Optimal correlations were found between conventionally measured body temperatures and IRT readings from (1) the front of the face at 1.5m with the mouth open (r=0.80), (2) the ear at 0.5 m (r=0.79), and (3) the side of the face at 1.5m (r=0.76). Average IRT readings from the forehead and elsewhere were 1 degrees C to 2 degrees C lower and correlated less well. Ear IRT readings at 0.5 m yielded the narrowest confidence intervals and could be used to predict conventional body temperature readings of < or = 38 degrees C with a sensitivity and specificity of 83% and 88% respectively. CONCLUSIONS: IRT readings from the side of the face, especially from the ear at 0.5 m, yielded the most reliable, precise and consistent estimates of conventionally determined body temperatures. Our results have important implications for walk-through IRT scanning/screening systems at airports and border crossings, particularly as the point prevalence of fever in such subjects would be very low.

Adolescent↗
PubMedDate not supplied

Interstitial hyperthermia and interstitial radiotherapy of a rat rhabdomyosarcoma; effects of sequential treatment and consequences for clonogenic repopulation.

Animal tumour experiments have been performed to elucidate the interactions between interstitial hyperthermia (IHT) and interstitial radiotherapy (IRT), and to obtain information about the most effective sequence of these treatment modalities. Experimental tumours, transplanted in the flank of Wag/Rij rats, were treated with IHT for 0.5 h at 44 degrees C, and with IRT using low dose-rate (LDR) iridium-192 sources. Both tumour cure probability and the fraction of clonogenic cells in vitro after different IHT and IRT treatments in vivo, were used as endpoints. The sequence of a short (0.5 h) IHT treatment followed by an extended LDR-IRT treatment lasting up to 10 days appeared to be very effective, and resulted in a significant thermal enhancement ratio of 1.34 at the 50% tumour cure probability level. A not significantly increased thermal enhancement of 1.06 was found when the same IHT treatment followed IRT. The level of clonogenic cell survival after IHT alone is high (0.24 +/- 0.08) compared with that after an IRT dose of 20 Gy (0.017 +/- 0.004). Clonogenic cell repopulation started 2-4 days after the in vivo treatment irrespective of the type of treatment. The in vivo combination of IHT and LDR-IRT resulted in lower surviving fractions compared with IRT alone, regardless of the time interval between the end of treatment and in vitro clonogenic assay. IHT followed by LDR-IRT appeared to be the most effective treatment in terms of tumour cure. The in vivo/in vitro studies indicated that the effect of hyperthermia is mainly attributed to radiosensitization, possibly by partial inhibition of sublethal damage repair processes during the subsequent irradiation. The hyperthermia-induced cytotoxicity was of minor importance as estimated from the surviving clonogenic fraction.

Animals↗
PubMed2006

Five-year clinical follow up after intracoronary radiation for the prevention of in-stent restenosis.

Intracoronary radiation therapy (IRT), utilizing both gamma- and beta-emitting radiation sources, is considered to be a safe and effective treatment for in-stent restenosis (ISR). Although no longer in clinical use, a significant number of patients were treated in the past with IRT, and their long-term outcomes have not been well documented. The aim of the present analysis was to document the long-term outcomes of all patients who underwent IRT at our institution for the prevention of recurrence of ISR. Data were collected from 132 patients (148 irradiated lesions) treated with IRT at our institution between March 1999 and January 2004. Clinical and angiographic data were collected over a 5-year period. Patients were divided into 2 groups: those with failed IRT (n = 65), defined as a procedure that resulted in a major adverse cardiac event: death, myocardial infarction, target lesion revascularization, target vessel revascularization or coronary artery bypass graft surgery at any time during the follow-up period, and patients with successful IRT (n = 67). Both groups were identical regarding baseline clinical and angiographic characteristics, with the exception of a higher percentage of multivessel disease and diffuse restenosis in patients who failed IRT (p = 0.01). At 1-year follow up, slightly less than half (43%) of those patients in the failure group experienced a major adverse cardiac event. During the long-term follow up period, half of all patients who underwent IRT at our institution experienced a major adverse cardiac event, 61 patients (46%) either died or underwent a revascularization procedure, 16 patients (24%) had a myocardial infarction or died, and 55 patients (42%) required repeat coronary revascularization. The average time to develop a major adverse cardiac event was 14.6 +/- 15 months. Therefore, during long-term follow up following IRT for the prevention of ISR, half of all patients developed a major cardiovascular event, mainly due to the need for repeat revascularization procedures.

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