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PURPOSE: To evaluate the growth of premenarchal patients with anorexia nervosa. METHODS: Growth parameters were measured semi-annually in 16 subjects with anorexia nervosa until 1 year post-menarche. RESULTS: Despite the accelerated growth that followed nutritional rehabilitation, the patients did not achieve their genetic height potential. [ABSTRACT FROM AUTHOR]

Background: Congenital hypothyroidism (CH) is the most common preventable cause of intellectual disability. The recommended starting dose of levothyroxine (LT4) is between 10 and 15 μg/kg, an extremely wide range. We hypothesized that a sizable proportion of newborns treated for CH at the higher end of the dosage range become biochemically hyperthyroid at a follow-up visit., Methods: This study is a retrospective chart review of infants with CH between 2002 and 2012., Results: Of the 104 patients included in this analysis, the average age at diagnosis was 11 days and the average starting dose of LT4 was 12±2.5 μg/kg. At follow-up, 36.5% required a dose reduction because of iatrogenic hyperthyroxinemia, 51% required no dose adjustment and 12.5% required a dose increase due to an elevated thyroid stimulating hormone (TSH). The starting doses of LT4 for those requiring a dose reduction, those not requiring an adjustment and those requiring an increase in the dose were 13.2±2.4, 11.5±2.1 and 10.3±2.6 μg/kg/day, respectively (p≤0.0001). Of the 34% of infants treated with an initial dose of >12.5 μg/day, 57.1% required a dose reduction at follow-up, compared to 26.1% of those whose initial starting dose was ≤12.5 μg/kg/day (p=0.007)., Conclusions: Following the guidelines for initiating therapy for CH, 36.5% of the infants required a dose reduction for iatrogenic hyperthyroxinemia. These infants received a higher dose of LT4 than the infants who either required no adjustment or required an increase in the dose. A narrower range for initial dosing in CH may be appropriate.

Background: Malassezia pachydermatis is part of the normal flora of canine skin. Malassezia hypersensitivity is recognized as a trigger for clinical signs of atopic dermatitis (AD) in some dogs. Determinations of Malassezia hypersensitivity are often made with intradermal testing (IDT), which may have limited availability in a first-opinion veterinary practice., Hypothesis/objectives: The purpose of this study was to compare immediate IDT reactivity to M. pachydermatis with results of an enzyme-linked immunosorbent assay (ELISA) designed to detect anti-Malassezia IgE., Animals: Eighty-four dogs with a clinical diagnosis of AD., Methods: Multi-allergen IDT was performed on all dogs. Serum testing for allergen-specific IgE against a panel of common environmental allergens and M. pachydermatis was performed by ELISA using the FcεRIα receptor fragment as a detection reagent, with results reported as adjusted optical density (OD). A receiver operating characteristic (ROC) curve was used to analyse the results of the two tests., Results: The median adjusted OD of the anti-Malassezia IgE ELISA for dogs reactive and nonreactive to M. pachydermatis on IDT was 0.137 and 0.024, respectively. Analysis of the ROC curve suggested a cut-off point for the anti-Malassezia ELISA that yielded a sensitivity of 77.0% and a specificity of 89% relative to IDT results., Conclusions and Clinical Importance: Substantial agreement was demonstrated between IDT reactivity and anti-Malassezia IgE as detected by the FcεRIα receptor reagent. Although correlation with a clinical diagnosis of Malassezia dermatitis was not attempted in this study, the results indicate that the ELISA may be used to demonstrate the presence of immediate-type Malassezia hypersensitivity in dogs with AD., (© 2014 ESVD and ACVD.)

Background: The Pediatric Nutrition Series (PNS) consists of ten online, interactive modules and supplementary educational materials that have utilized web-based multimedia technologies to offer nutrition education for pediatric trainees and practicing physicians. The purpose of the study was to evaluate pediatric trainees' engagement, knowledge acquisition, and satisfaction with nutrition modules delivered online in interactive and non-interactive formats., Methods: From December 2010 through August 2011, pediatric trainees from seventy-three (73) different U.S. programs completed online nutrition modules designed to develop residents' knowledge of counseling around and management of nutritional issues in children. Data were analyzed using SPSS version 19. Both descriptive and inferential statistics were used in comparing interactive versus non-interactive modules. Pretest/posttest and module evaluations measured knowledge acquisition and satisfaction., Results: Three hundred and twenty-two (322) pediatric trainees completed one or more of six modules for a total of four hundred and forty-two (442) accessions. All trainees who completed at least one module were included in the study. Two-way analyses of variance (ANOVA) with repeated measures (pre/posttest by interactive/non-interactive format) indicated significant knowledge gains from pretest to posttest (p < 0.002 for all six modules). Comparisons between interactive and non-interactive formats for Module 1 (N = 85 interactive, N = 95 non-interactive) and Module 5 (N = 5 interactive, N = 16 non-interactive) indicated a parallel improvement from the pretest to posttest, with the interactive format significantly higher than the non-interactive modules (p < .05). Both qualitative and quantitative data from module evaluations demonstrated that satisfaction with modules was high. However, there were lower ratings for whether learning objectives were met with Module 6 (p < 0.03) and lecturer rating (p < 0.004) compared to Module 1. Qualitative data also showed that completion of the interactive modules resulted in higher resident satisfaction., Conclusions: This initial assessment of the PNS modules shows that technology-mediated delivery of a nutrition curriculum in residency programs has great potential for providing rich learning environments for trainees while maintaining a high level of participant satisfaction.

Tissue-mimicking phantoms and software for quantifying the ability of human observers to detect small low-echo spheres as a function of depth have been developed. Detectability is related to the imager's ability to delineate the boundary of a 3-D object such as a spiculated tumor. The phantoms accommodate a broad range of transducer shapes and sizes. Three phantoms are described: one with 2-mm-diameter spheres (for higher frequencies), one with 3.2-mm-diameter spheres (for lower frequencies) and one with 4-mm-diameter spheres (for lower frequencies). The spheres are randomly distributed in each phantom. The attenuation coefficients of spheres and surroundings are nearly identical; thus, compromising shadowing or enhancement distal to spheres does not occur. Reproducibility results are given for pairs of independent data sets involving eight different combinations of scanner, transducer and console settings. The following comparison results are also reported: (i) only the selected frequency differs; (ii) transducers and scan parameters are nearly the same but manufacturers differ; (iii) ordinary B-scanning, spatial compounding and tissue harmonic imaging are addressed. The phantoms and software promise to be valuable tools for scanning system and setup comparisons and for acceptance testing., (Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Screening for dyslipidemia poses some challenges. Nonfasting lipid profiles frequently have elevated triglycerides. In addition, in the standard lipid profile, low-density lipoprotein (LDL) cholesterol is a calculated value rather than a direct measurement and is triglyceride dependent. Non-high-density lipoprotein cholesterol (non-HDL-C) is an alternative method to assess for dyslipidemia and provides a single estimate of all atherogenic apolipoprotein B-containing lipoproteins., Objective: To calculate the non-HDL-C in adolescents with diabetes and to evaluate risk factors associated with an elevated non-HDL-C and to compare the prevalence of dyslipidemia, defined by non-HDL-C, with the prevalence of dyslipidemia defined by LDL cholesterol in the SEARCH study., Methods: Data were collected from 502 adolescent patients with diabetes and analyzed. Non-HDL-C was calculated and levels were categorized into normal, borderline, and high based on the National Cholesterol Education Program., Results: Lipid profile was performed in 370 patients, 92% of whom had type 1 diabetes. In the 339 subjects with type 1 diabetes, mean hemoglobin A1c (HbA1c) of those with normal non-HDL-C (8.6%) was significantly lower than the HbA1c of those with high non-HDL-C (9.6%) (P = .005). Subjects with normal non-HDL-C had a lower body mass index (BMI) z-score (0.4 ± 0.8) than the group with borderline and high non-HDL-C (0.75 ± 0.9%), P = .002. In the 31 subjects with type 2 diabetes, the mean HbA1c of those with normal non-HDL-C (8.1%) and those with borderline non-HDL-C (7.0%) was significantly lower than the mean HbA1c of those with high non-HDL-C (11.8%) (P = .04, and P = .009, respectively). In addition, the subjects with normal non-HDL-C had a lower BMI z-score (1.3 ± 1.3) than the group with borderline and high non-HDL-C (2.2 ± 0.6%), P = .03. The prevalence of dyslipidemia using non-HDL-C was similar to prevalence rates using LDL-C in the SEARCH study., Conclusions: In adolescents with diabetes, non-HDL-C is increased with poorer diabetes control and higher BMI. It appears to be a superior nonfasting lipid screening test for adolescents with diabetes that can be readily calculated on a randomly obtained rather than fasting sample., (Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Non-synonymous mutations affecting both alleles of PCSK1 (proprotein convertase 1/3) are associated with obesity and impaired prohormone processing. We report a proband who was compound heterozygous for a maternally inherited frameshift mutation and a paternally inherited 474kb deletion that encompasses PCSK1, representing a novel genetic mechanism underlying this phenotype. Although pro-vasopressin is not a known physiological substrate of PCSK1, the development of central diabetes insipidus in this proband suggests that PCSK1 deficiency can be associated with impaired osmoregulation., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

The strain image contrast of some in vivo breast lesions changes with increasing applied load. This change is attributed to differences in the nonlinear elastic properties of the constituent tissues suggesting some potential to help classify breast diseases by their nonlinear elastic properties. A phantom with inclusions and long-term stability is desired to serve as a test bed for nonlinear elasticity imaging method development, testing, etc. This study reports a phantom designed to investigate nonlinear elastic properties with ultrasound elastographic techniques. The phantom contains four spherical inclusions and was manufactured from a mixture of gelatin, agar and oil. The phantom background and each of the inclusions have distinct Young's modulus and nonlinear mechanical behavior. This phantom was subjected to large deformations (up to 20%) while scanning with ultrasound, and changes in strain image contrast and contrast-to-noise ratio between inclusion and background, as a function of applied deformation, were investigated. The changes in contrast over a large deformation range predicted by the finite element analysis (FEA) were consistent with those experimentally observed. Therefore, the paper reports a procedure for making phantoms with predictable nonlinear behavior, based on independent measurements of the constituent materials, and shows that the resulting strain images (e.g., strain contrast) agree with that predicted with nonlinear FEA.

The development of phantom materials for elasticity imaging is reported in this paper. These materials were specifically designed to provide nonlinear stress/strain relationship that can be controlled independently of the small strain shear modulus of the material. The materials are mixtures of agar and gelatin gels. Oil droplet dispersions in these materials provide further control of the small strain shear modulus and the nonlinear parameter of the material. Since these materials are mostly water, they are assumed to be incompressible under typical experimental conditions in elasticity imaging. The Veronda-Westman model for strain energy density provided a good fit to all materials used in this study. Materials with a constant gelatin concentration (3.0% dry weight) but varying agar concentration (0.6-2.8% dry weight) demonstrated the same power law relationship between elastic modulus and agar concentration found for pure agar (1.89 +/- 0.02), consistent with percolation theory, and provided a consistent nonlinearity parameter of 4.5 +/- 0.3. The insights provided by this study will form the basis for stable elastography phantoms with stiffness and nonlinear stress/strain relationships in the background that differ from those in the target.

Introduction: Twenty-four hour ambulatory blood pressure (ABPM) is emerging as a valuable tool to assess blood pressure (BP) changes in children with type 1 diabetes mellitus (DM1). Hypertension (HTN) is an important risk factor for, and may be an important indicator of diabetic nephropathy. Early accurate identification of HTN in DM1 may improve outcomes., Aim: To evaluate BP in adolescents with DM1 using 24-hour ABPM, and to identify risk factors associated with abnormal blood pressure., Method: The ABPM of 105 children with DM1 was reviewed. Mean systolic BP (sBP) percentile was determined from the National High Blood Pressure Education Program (NHBPEP) tables. The patients with abnormal sBP were compared to those with normal sBP with respect to age, race, sex, body mass index (BMI) percentile, duration of DM1, average hemoglobin A1c (HbA1c) over the preceding year, and family history of hypertension., Results: Mean sBP was normal in 71%, whereas 23% had pre-hypertension, and 6% had stage 1 hypertension. Those who had abnormal sBP (pre-hypertension and stage 1 hypertension) had higher HbA1c (p = 0.023) and were more likely to be male (p = 0.03) than those with normal sBP., Conclusion: Stage 1 hypertension is present in 6%, and pre-hypertension in 23% of adolescents with DM1. Poor diabetes control and male gender appear to be risk factors for abnormal sBP as measured by 24-hour ambulatory blood pressure monitoring.

Objective: The purpose of this study was to screen adolescents with type 1 diabetes using ambulatory blood pressure monitoring (ABPM) to 1) test the hypothesis that using a preset sleep time results in an overdiagnosis of abnormal nocturnal dipping in systolic blood pressure and 2) assess the reproducibility of an abnormal nocturnal systolic blood pressure dip., Research Design and Methods: For aim 1, ABPM from 53 adolescent patients with type 1 diabetes was reviewed. Nocturnal dips in systolic blood pressure calculated by actual sleep time were compared with those from a preset sleep time. For aim 2, blood pressure monitoring from 98 patients using actual reported sleep time was reviewed. Reproducibility of the nocturnal dip in systolic blood pressure was assessed in a subset of "nondippers.", Results: For aim 1, the actual mean +/- SE decline in nocturnal systolic blood pressure was 11.6 +/- 4.7%, whereas the mean decline in nocturnal systolic blood pressure calculated using the preset sleep time was 8.8 +/- 4.9% (P < 0.0001). For aim 2, 64% of patients had a normal nocturnal decline in systolic blood pressure (14.9 +/- 3.1% mmHg), whereas 36% had an abnormal dip (5.7 +/- 2.8% mmHg). Repeat ABPM performed in 22 of the 35 nondippers revealed that only 36% had abnormal systolic dipping confirmed on the repeat ABPM., Conclusions: The use of actual reported sleep time is required to accurately determine the nocturnal dip in systolic blood pressure. Repeating ABPM in nondippers is essential to confirm this abnormality.

Twenty-four hour ambulatory blood pressure monitoring (ABPM) is a valuable tool in the pediatric and adolescent population with type 1 diabetes. It provides useful information not readily available from sporadic clinic blood pressure (BP) measurements and a more reliable estimation of the subject's BP over an extended period of time. Ambulatory blood pressure monitoring is gaining popularity with clinicians and investigators alike. The American Heart Association has recently issued recommendations for the use of ABPM in children and adolescents. We have incorporated ABPM into our adolescent diabetes practice and present useful information for clinicians planning to initiate 24 h ABPM in their clinical practice.

Accurate determination of the complex shear modulus of soft tissues and soft-tissue-like materials in the 10-300 Hz frequency range is very important to researchers in MR elastography and acoustic radiation force impulse (ARFI) imaging. A variety of instruments for making such measurements has been reported, but none of them is easily reproduced, and none have been tested to conform to causality via the Kramers-Kronig (K-K) relations. A promising linear oscillation instrument described in a previous brief report operates between 20 and 160 Hz, but results were not tested for conformity to the K-K relations. We have produced a similar instrument with our own version of the electronic components and have also accounted for instrumental effects on the data reduction, which is not addressed in the previous report. The improved instrument has been shown to conform to an accurate approximation of the K-K relations over the 10-300 Hz range. The K-K approximation is based on the Weichert mechanical circuit model. We also found that the sample thickness must be small enough to obtain agreement with a calibrated commercial rheometer. A complete description of the improved instrument is given, facilitating replication in other labs.

Two anthropomorphic uterine phantoms were developed that allow assessment and comparison of strain imaging systems adapted for use with saline-infused sonohysterography (SIS). Tissue-mimicking (TM) materials consist of dispersions of safflower oil in gelatin. TM fibroids are stiffer than the TM myometrium/cervix, and TM polyps are softer. The first uterine phantom has 3-mm-diameter TM fibroids distributed randomly in TM myometrium. The second uterine phantom has a 5-mm and 8-mm spherical TM fibroid, in addition to a 5-mm spherical and a 12.5-mm-long (medicine capsule-shaped) TM endometrial polyp protruding into the endometrial cavity; also, a 10-mm spherical TM fibroid projects from the serosal surface. Strain images using the first phantom show the stiffer 3-mm TM fibroids in the myometrium. Results from the second uterine phantom show that, as expected, parts of inclusions projecting into the uterine cavity will appear very stiff, whether they are stiff or soft. Results from both phantoms show that although there is a five-fold difference in the Young's moduli values, there is not a significant difference in the strain in the transition from the TM myometrium to the TM fat. These phantoms allow for realistic comparison and evolution of SIS strain imaging techniques and can aid clinical personnel to develop skills for SIS strain imaging.

Context: The kindred described is the only known instance of a germ line loss of function mutation of estrogen receptor (ER)-alpha., Objective: Our objective was to assess the impact of a loss of function mutation in the ER-alpha gene on histomorphometry, bone volumetric density, bone geometry and skeletal growth, and ER-alpha heterozygosity on spine density and adult height in an extended pedigree., Design and Participants: A longitudinal follow-up of the propositus with homozygous loss of function mutation of ER-alpha and single contact evaluation of the kindred were performed., Main Outcome Measures: Iliac crest bone biopsy and peripheral quantitative computed tomography of propositus with serial measures of areal spine bone mineral density (aBMD) by dual-energy x-ray absorptiometry and bone age were performed. Members of pedigree were evaluated for ER-alpha mutation carrier status and spine aBMD., Results: Bone biopsy revealed marked osteopenia (cortex: 641 microm), low trabecular volume (10.6%), decreased thickness (76.2 microm), normal trabecular number, and low activation frequency (0.099/yr). Radial periosteal circumference was similar, endosteal circumference larger, and trabecular and cortical volumetric bone mineral density markedly lower (158 and 1092 mg/cm(3), respectively) than controls. Spine aBMD at age 28.5 yr (0.745 g/cm(2)) decreased to 0.684 g/cm(2) (Z score -3.85) in 3.5 yr. Bone age advanced from 15-17.5 yr. Kindred analysis revealed that gene carriers had spine aBMD Z scores less than zero (P = 0.003), but carriers and nonmutant members were similar (-0.84 +/- 0.26 vs. -0.64 +/- 0.16)., Conclusion: Homozygous ER-alpha disruption markedly affects bone growth, mineral content, and structure but not periosteal circumference. ER-alpha heterozygosity appears to not impair spine aBMD.

This paper evaluates the performance of a level set algorithm for segmenting the endocardium in short-axis ultrasound images. The evaluation is carried out using an anthropomorphic ultrasound phantom. Details of the phantom design, including comparison of the ultrasound parameters with in-vitro measurements, are included. In addition to measuring segmentation accuracy, the effectiveness of the energy minimization scheme is also determined. It is argued that using the phantom along with global minimization algorithms (simulated annealing and random search) makes is possible to assess the minimization strategy.

This paper presents an algorithm for estimating the location of the breast surface from scattered ultrawideband (UWB) microwave signals recorded across an antenna array. Knowing the location of the breast surface can improve imaging performance if incorporated as a priori information into recently proposed microwave imaging algorithms. These techniques transmit low-power microwaves into the breast using an antenna array, which in turn measures the scattered microwave signals for the purpose of detecting anomalies or changes in the dielectric properties of breast tissue. Our proposed surface identification algorithm consists of three procedures, the first of which estimates M points on the breast surface given M channels of measured microwave backscatter data. The second procedure applies interpolation and extrapolation to these M points to generate N > M points that are approximately uniformly distributed over the breast surface, while the third procedure uses these N points to generate a 3-D estimated breast surface. Numerical as well as experimental tests indicate that the maximum absolute error in the estimated surface generated by the algorithm is on the order of several millimeters. An error analysis conducted for a basic microwave radar imaging algorithm (least-squares narrowband beamforming) indicates that this level of error is acceptable. A key advantage of the algorithm is that it uses the same measured signals that are used for UWB microwave imaging, thereby minimizing patient scan time and avoiding the need for additional hardware.

Acoustic output measurements of diagnostic ultrasound scanners are currently performed in water and derated to approximate in situ values. The derating scheme ignores nonlinear propagation of sound waves and has been shown in previous numerical and experimental studies to tend to underestimate relevant pressure and intensity values in tissue mimicking media. This work describes an alternative method, which uses a tissue-mimicking liquid with attenuation coefficient slope of 0.3 dB/cm/MHz, speed of sound of 1,540 m/s and nonlinearity parameter B/A of 7.5. The acoustic properties of this liquid are stable for at least 2 y after production. Initial results using a single M-mode configuration are presented. These results confirm that derating can significantly underestimate the pulse intensity integral and peak rarefactional pressure.

The purpose of this study was to evaluate various ultrasonic properties of breast phantoms developed for use in qualifying investigators for participation in the American College of Radiology Imaging Network (ACRIN) protocol 6666, "Screening Breast Ultrasound in High-Risk Women." Specifically, a tool was sought to consistently measure the performance of radiology personnel in detecting and characterizing lesions similar to those expected with screening breast ultrasonography (US). The phantoms are equivalent to one another except for the randomization of positions of 14 of the 17 simulated lesions. The lesions differ in depth and ultrasonic properties. Representative values of propagation speed, attenuation, relative echogenicity, and mass density are reported for all tissue-mimicking components. Beam refraction occurs at the interface between the subcutaneous fat layer and the glandular parenchyma and can result in beam distortion artifacts similar to those encountered in clinical breast US., (Copyright (c) RSNA, 2006.)

Two equivalent anthropomorphic breast phantoms were constructed, one for use in ultrasound elastography and the other in magnetic resonance (MR) elastography. A complete description of the manufacturing methods is provided. The materials used were oil-in-gelatin dispersions, where the volume percent oil differentiates the materials, primarily according to Young's moduli. Values of Young's moduli are in agreement with in vitro ranges for the corresponding normal and abnormal breast tissues. Ultrasound and nuclear magnetic resonance (NMR) properties are reasonably well represented. Phantoms of the type described promise to aid researchers who are developing hardware and software for elastography. Examples of ultrasound and MR elastograms of the phantoms are included to demonstrate the utility of the phantoms. Also, the level of stability of elastic properties of the component materials is quantified over a 15-month period. Such phantoms can serve as performance-assessing intermediaries between simple phantoms (consisting, for example, of homogeneous cylindrical inclusions in a homogeneous background) and a full-scale clinical trial. Thus, premature clinical trials may be avoided.

A set of five tissue-mimicking phantoms with cylindrical inclusions were produced for assessing long-term stability of geometry and elastic properties and assessing accuracy of determination of elastic properties. The base aqueous materials were either gelatin or a mixture of agar and gelatin. Stiffness was controlled by selection of the volume percent consisting of microscopic safflower oil droplets. Cylinder diameters remained unchanged within 1% or 2% over many months. Strain ratios from elastograms of the phantoms were stable over many months, implying that elastic contrasts were also stable. Test samples, called production samples, for measurement of Young's moduli were made at the time of manufacture of each phantom and were stored separately from one another. Each production sample was homogeneous and consisted of either inclusion material or background material. For all five phantoms, it was found that the elastic contrast computed using Young's modulus values determined using the production samples accurately represented the true elastic contrasts in the corresponding phantom. This finding was established by the fact that the (true) elastic contrasts determined using samples excised from the phantoms themselves agreed with the elastic contrasts obtained using the homogeneous production samples.

A set of three cubic one-litre phantoms containing spherical simulated lesions was produced for use in comparing lesion detection performance of different elastography systems. The materials employed are known to be stable in heterogeneous configurations regarding geometry and elastic contrast identical with (storage modulus of lesion material) / (storage modulus of background material), and regarding ultrasound and NMR properties. The materials mimic soft tissues in terms of elastic, ultrasound and NMR properties. Each phantom has only one value of elastic contrast (3.3, 4.6 or 5.5) and contains arrays of 1.6 mm, 2 mm, 3 mm and 4 mm diameter spherical simulated lesions. All the spheres of a given diameter are arranged in a regular array with coplanar centres. Elastograms of an array made with ultrasound allow determination of the depth range over which lesions of that diameter and elastic contrast can be detected. Two phantoms are made from agar-plus-gelatin-based materials, and one is made from oil-in-gelatin dispersions. The methods for producing the phantoms are described in detail. Lesion detection performances for two ultrasound systems, both operating at about 7.5 MHz and focused at about 5 cm, were quantified with distinctions between the two systems demonstrated. Neither system was capable of detecting any of the 1.6 mm lesions. Phantoms such as these should be useful in research labs that are refining hardware and/or software for elastography.

Five 9 cm x 9 cm x 9 cm phantoms, each with a 2-cm-diameter cylindrical inclusion, were produced with various dry-weight concentrations of agar and gelatin. Elastic contrasts ranged from 1.5 to 4.6, and values of the storage modulus (real part of the complex Young's modulus) were all in the soft tissue range. Additives assured immunity from bacterial invasion and can produce tissue-mimicking ultrasound and NMR properties. Monitoring of strain ratios over a 7 to 10 month period indicated that the mechanical properties of the phantoms were stable, allowing about 1 month for the phantom to reach chemical equilibrium. The only dependable method for determining the storage moduli of the inclusions is to make measurements on samples excised from the phantoms. If it is desired to produce and accurately characterize a phantom with small inclusions with other shapes, such as an array of small spheres, an auxiliary phantom with the geometry of the cylindrical inclusion phantoms or the equivalent should be made at the same time using the same materials. The elastic contrast can then be determined using samples excised from the auxiliary phantom. A small increase of about 10% in volume of the cylindrical inclusions occurred-a tolerable increase. Interestingly, the smallest increase (about 5%) occurred in the phantom with the largest elastic contrast.

We propose and characterize oil-in-gelatin dispersions that approximate the dispersive dielectric properties of a variety of human soft tissues over the microwave frequency range from 500 MHz to 20 GHz. Different tissues are mimicked by selection of an appropriate concentration of oil. The materials possess long-term stability and can be employed in heterogeneous configurations without change in geometry or dielectric properties due to osmotic effects. Thus, these materials can be used to construct heterogeneous phantoms, including anthropomorphic types, for narrowband and ultrawideband microwave technologies, such as breast cancer detection and imaging systems.

Objective: As are the attenuation coefficient and sound speed, the backscatter coefficient is a fundamental ultrasonic property that has been used to characterize many tissues. Unfortunately, there is currently far less standardization for the ultrasonic backscatter measurement than for the other two, as evidenced by a previous American Institute of Ultrasound in Medicine (AIUM)-sponsored interlaboratory comparison of ultrasonic backscatter, attenuation, and speed measurements (J Ultrasound Med 1999; 18:615-631). To explore reasons for these disparities, the AIUM Endowment for Education and Research recently supported this second interlaboratory comparison, which extends the upper limit of the frequency range from 7 to 9 MHz., Methods: Eleven laboratories were provided with standard test objects designed and manufactured at the University of Wisconsin (Madison, WI). Each laboratory was asked to perform ultrasonic measurements of sound speed, attenuation coefficients, and backscatter coefficients. Each laboratory was blinded to the values of the ultrasonic properties of the test objects at the time the measurements were performed., Results: Eight of the 11 laboratories submitted results. The range of variation of absolute magnitude of backscatter coefficient measurements was about 2 orders of magnitude. If the results of 1 outlier laboratory are excluded, then the range is reduced to about 1 order of magnitude. Agreement regarding frequency dependence of backscatter was better than reported in the previous interlaboratory comparison. For example, when scatterers were small compared with the ultrasonic wavelength, experimental frequency-dependent backscatter coefficient data obtained by the participating laboratories were usually consistent with the expected Rayleigh scattering behavior (proportional to frequency to the fourth power)., Conclusions: Greater standardization of backscatter measurement methods is needed. Measurements of frequency dependence of backscatter are more consistent than measurements of absolute magnitude.

Objective: Current determinations of diagnostic ultrasound exposure parameters (eg, peak rarefactional pressure and pulse intensity integral) are intended to correspond to propagation through soft tissue with a propagation speed of 1540 m/s and attenuation of 0.3 dB x cm(-1) x MHz(-1). These current measurements are made in water, which has very little attenuation, and a linear derating factor is applied to approximate 0.3 dB x cm(-1) x MHz(-1) attenuation. The fact that propagation through water as well as through soft tissue involves nonlinear propagation is not directly addressed. A better way to determine exposure parameters would be to use a liquid that has the desired tissue-mimicking properties, including a value of the nonlinearity parameter B/A representative of soft tissue. To be of practical use in the laboratory, the ultrasonic properties of this liquid must remain stable and spatially uniform for many months or years without need for periodic mixing by the user., Methods: Fifty-two samples of fat-free milk that was concentrated to one third of its original volume by ultrafiltration were created. Each sample was preserved by a different method. The speed of sound, attenuation, and nonlinearity parameter B/A of each sample were periodically monitored by narrowband through-transmission techniques., Results: Six of the 52 samples remained liquid and retained acceptably stable acoustic properties over 22 months of storage at room temperature., Conclusions: Fat-free milk, concentrated via ultrafiltration and preserved in 1 of 6 different methods, has been found to be a stable tissue-mimicking liquid with acoustic properties appropriate for use in exposimetry.

Glucocorticoids have been prescribed for several decades in treating adrenal insufficiency of various etiologies. These drugs are also heavily used in treating non-endocrine disease. This article will focus on adverse side effects encountered in the chronic use of different types of glucocorticoids in children and young adults with endocrine causes of adrenal insufficiency. Dosing guidelines are discussed with a view toward minimizing the common co-morbidities of growth suppression, excess weight gain, and osteopenia, among others. This article also discusses the use of several inhibitors of adrenal steroid biosynthesis and one glucocorticoid receptor antagonist for the medical treatment of Cushing syndrome.

Previous reported data from our laboratory demonstrated the temperature dependence of propagation speed and attenuation of canine tissue in vitro at discrete temperatures ranging from 25 to 95 degrees C. However, concerns were raised regarding heating the same tissue specimen over the entire temperature range, a process that may introduce irreversible and, presumably, cumulative tissue degradation. In this paper propagation speed and attenuation vs temperature are measured using multiple groups of samples, each group heated to a different temperature. Sample thicknesses are measured directly using a technique that uses both transmitted and reflected ultrasound pulses. Results obtained using 3 and 5 MHz center frequencies demonstrate a propagation speed elevation of around 20 m/s in the 22-60 degrees C range, and a decrease of 15 m/s in the 60-90 degrees C range, in agreement with previous results where the same specimens were subjected to the entire temperature range. However, sound speed results reported here are slightly higher than those reported previously, probably due to more accurate measurements of sample thickness in the present experiments. Results also demonstrate that while the propagation speed varies with temperature, it is not a function of tissue coagulation. In contrast, the attenuation coefficient depends on both tissue coagulation effects and temperature elevation.

Reliable housekeeping gene controls are critical for measuring and comparing gene expression at the transcription level by Northern blot and RT-PCR. In order to develop such controls for studying cytokine mRNA expression in dogs, DNA sequence encoding a full-length canine HPRT protein has been obtained. Numerous primer pairs derived from the canine HPRT sequence have been tested on canine genomic DNA as well as cDNA. The data from the present study suggest that there may be processed HPRT pseudogenes in dogs. Three pairs of canine HPRT primers designed and tested in the present study were able to differentiate between cDNA and genomic DNA under specific PCR conditions. These primers would be useful controls for measurement of mRNA expression by RT-PCR in the dog., (Copyright 2004 Elsevier B.V.)

Since both estrogen and androgen are present in each sex, it has been difficult to discern the exact role that each sex steroid plays in skeletal physiology. However, studying clinical syndromes in which there is either only estrogen or androgen action has allowed us to gain insight into the unique role that each sex steroid plays in the growing skeleton. In complete androgen insensitivity syndrome (AIS) the only functional sex steroid receptor is that for estrogen. Effected XY females have a pubertal growth spurt that is typical of normal females, both in magnitude and timing. Individuals with AIS have a mild reduction in bone density but it is difficult to distinguish whether this is the result of androgen resistance or estrogen deficiency. These observations suggest that estrogen action only is sufficient to induce a normal pubertal growth spurt, epiphyseal maturation, and near normal bone mineral accretion in women. Until recently, the skeletal effects of estrogen were not thought to be of importance in the male. Conventional wisdom dictated that, in the male, testosterone mediated these skeletal changes. The notion that estrogen is of little importance in the male has been challenged by the recent discovery of two human syndromes in which estrogen action is lacking. In males with either estrogen resistance (inability to respond to circulating estrogen) or aromatase deficiency (inability to synthesize estradiol), as a result of the lack of estrogen action, a pubertal growth spurt does not appear to occur. Furthermore, complete epiphyseal maturation does not take place allowing for continued growth in adulthood and resultant tall stature. Finally normal bone mineral accretion does not take place resulting in severe osteoporosis. These findings indicate that estrogen plays a critical role in skeletal physiology of males as well as females., (Copyright 2003 Wiley-Liss, Inc.)

To identify risk factors associated with the development of diabetic ketoacidosis (DKA) in new-onset type 1 diabetes mellitus, a retrospective chart review of 139 new onset type 1 diabetes patients from 1995 to 1998 was conducted. Categorical data were examined with contingency table analysis. Age range was 0.5 to 18 years. Overall, 38% of the patients presented in DKA. Sixty-two percent of the patients with either Medicaid or no insurance presented in DKA compared to 34% of the patients with private insurance, odds ratio 3.17 (92% CI 1.2-8.3) p = 0.03. Sixty-eight percent of patients in whom the diagnosis was missed (n = 25) presented in DKA (mean age, 5.4 +/- 4.4 years) compared to 32% in whom the diagnosis was not missed (mean age, 8.8 +/- 4.0 years) odds ratio 4.6 (95% CI 1.9-11.7), p = 0.0012; age p = 0.00019. Lack of private insurance, although a risk factor for the development of DKA, did not increase the likelihood of a missed diagnosis. Lack of private insurance (a proxy for socioeconomic status) and young age are apparent risk factors for the development of ketoacidosis. Misdiagnosis by the physician at initial patient encounter is especially prevalent in the young child but not related to insurance. Both increased public awareness and greater medical alertness are necessary to reduce the high rates of DKA in new-onset type 1 diabetic children.

A ten-month study is presented of materials for use in heterogeneous elastography phantoms. The materials consist of gelatin with or without a suspension of microscopic safflower oil droplets. The highest volume percent of oil in the materials is 50%. Thimerosal acts as a preservative. The greater the safflower oil concentration, the lower the Young's modulus. Elastographic data for heterogeneous phantoms, in which the only variable is safflower oil concentration, demonstrate stability of inclusion geometry and elastic strain contrast. Young's modulus ratios (elastic contrasts) producible in a heterogeneous phantom are as high as 2.7. The phantoms are particularly useful for ultrasound elastography. They can also be employed in MR elastography, although the highest achievable ratio of longitudinal to transverse relaxation times is considerably less than is the case for soft tissues.

Canine infections with Leishmania infantum are important as a cause of serious disease in the dog and as a reservoir for human visceral leishmaniasis (VL). Accurate diagnosis of canine infections is essential to the veterinary community and for VL surveillance programs. A standardized ELISA using a purified recombinant antigen (rK39) specific to VL was compared to the immunofluorescent antibody test (IFAT) as the standard. The ELISA was developed, optimized and evaluated using sera from 6368 dogs. The standardized ELISA and IFAT results were highly concordant. The timing and pattern of ELISA and IFAT seroconversion in dogs followed prospectively after natural infections were very similar. Antibodies reacting with rK39 were more common in asymptomatic canine infections than reported for subclinical human VL. The rK39 ELISA is a relatively simple and rapid assay for assessing the infection status of dogs, and is an alternative to IFAT, especially when screening large numbers of samples.

Previous studies have shown that piglets weaned to a liquid milk replacer (MR), rather than a typical dry diet (DD) regimen, have improved growth rates and deposit more energy as body fat. In the present study, we used this model to determine whether changes in the expression of genes linked to the regulation of adiposity were related to the accelerated fat accretion. We also determined whether the increase in body fat was sustained throughout a substantial proportion of the growth curve. At weaning (19 plus minus 2 days of age), 96 piglets were placed in 12 replicate pens per diet (4 pigs per pen, 2 barrows and 2 gilts), and fed a liquid MR or conventional DD regimen for 5 weeks. Thereafter, 6 barrows and 6 gilts pigs from each diet were killed for determination of whole body chemical composition (less gastrointestinal contents). The remaining pigs were assigned randomly to weight target groups (60, 85, and 110 kg), placed in individual pens, and fed a conventional dietary regimen until killed at their respective weight targets for tissue sampling and determination of whole body chemical composition. Over the 5-week period in which the MR was fed, the growth rate of the pigs consuming the MR exceeded that of the pigs fed the DD by 36% (P <.05). Fat gain in these pigs was increased to 1.8 times that of the pigs fed the DD, and percentage body fat was 45% greater (P <.05). Acetyl Co-A carboxylase (ACC) activity (per mg of adipose extract protein) was not different between the two diet groups at the conclusion of the 5-week period, or at 110 kg body weight. During the MR period, actual protein gain was increased (P <.05) 22% in the pigs fed the MR as well. By 110 kg of body weight, body fat was reduced (P <.05) by 7.7% (total fat mass) and 8.3% (percentage of body weight basis) in the pigs fed MR vs. the DD group. The expression of the peroxisome proliferator activated receptors (PPAR) alpha and gamma was not influenced by diet or by body weight. Expression of the obese gene was independent of diet, but was greater (P <.09) in pigs at 110 kg body weight than at 60 kg. These data provide additional evidence that piglets weaned to liquid diets have greater rates of growth and deposit more body fat, but that this difference subsides quickly when a typical dry dietary regimen is imposed. Furthermore, the biochemical changes responsible for the increased adiposity are independent of changes in the expression of the obese or PPAR genes, at least at the mRNA level.

The use of liquid brominated hydrocarbons to form a planar reflecting interface with water is described. Gravity-based planar reflecting surfaces with known reflection coefficients can be used in system characterization for quantitative ultrasonics, and a set of surfaces with a range of reflection coefficients allows calibration of the output power and receiver gain of ultrasonic imaging systems. The substances reported here are immiscible in water and form interfaces with water, resulting in a broad range of acoustic reflection coefficients. Reflection coefficients were measured at temperatures from 18-24 degrees C for "pure" substances and for mixtures of two brominated hydrocarbons. Results show that reflection coefficients are weakly dependent on temperature and that, at a specific temperature, a significant range of arbitrarily small reflection coefficients is available, in the case of the mixtures, by the appropriate choice of weight-percents of the two brominated hydrocarbons.

Materials that simultaneously mimic soft tissue in vivo for magnetic resonance imaging (MRI), ultrasound (US), and computed tomography (CT) for use in a prostate phantom have been developed. Prostate and muscle mimicking materials contain water, agarose, lipid particles, protein, Cu++, EDTA, glass beads, and thimerosal (preservative). Fat was mimicked with safflower oil suffusing a random mesh (network) of polyurethane. Phantom material properties were measured at 22 degrees C. (22 degrees C is a typical room temperature at which phantoms are used.) The values of material properties should match, as well as possible, the values for tissues at body temperature, 37 degrees C. For MRI, the primary properties of interest are T1 and T2 relaxations times, for US they are the attenuation coefficient, propagation speed, and backscatter, and for CT, the x-ray attenuation. Considering the large number of parameters to be mimicked, rather good agreement was found with actual tissue values obtained from the literature. Using published values for prostate parenchyma, T1 and T2 at 37 degrees C and 40 MHz are estimated to be about 1,100 and 98 ms, respectively. The CT number for in vivo prostate is estimated to be 45 HU (Hounsfield units). The prostate mimicking material has a T1 of 937 ms and a T2 of 88 ms at 22 degrees C and 40 MHz; the propagation speed and attenuation coefficient slope are 1,540 m/s and 0.36 dB/cm/MHz, respectively, and the CT number of tissue mimicking prostate is 43 HU. Tissue mimicking (TM) muscle differs from TM prostate in the amount of dry weight agarose, Cu++, EDTA, and the quality and quantity of glass beads. The 18 microm glass beads used in TM muscle increase US backscatter and US attenuation; the presence of the beads also has some effect on T1 but no effect on T2. The composition of tissue-mimicking materials developed is such that different versions can be placed in direct contact with one another in a phantom with no long term change in US, MRI, or CT properties. Thus, anthropomorphic phantoms can be constructed.

The hormone-sensitive and lipoprotein lipases are critical determinants of the metabolic adaptation to starvation. Additionally, the uncoupling proteins have emerged with potential roles in the metabolic adaptations required by energy deficiency. The objective of this study was to evaluate the expression (mRNA abundance) of uncoupling proteins 2 and 3 and that of hormone-sensitive and lipoprotein lipase in the adipose tissue and skeletal muscle of the pig in relationship to feed deprivation. Thirty-two male castrates (87 kg +/- 5%) were assigned at random to fed and feed-deprived treatment groups. After 96 hr, the pigs were euthanized and adipose and skeletal muscle tissue obtained for total RNA extraction and nuclease protection assays. Feed deprivation increased uncoupling protein 3 mRNA abundance 103-237% (P < 0.01) in longissimus and red and white semitendinosus muscle. In contrast, the increase in uncoupling protein 3 mRNA in adipose tissue was only 23% (P < 0.06), and adipose uncoupling protein 2 mRNA was not influenced (P > 0.66) by feed deprivation. The increased abundance of uncoupling protein 2 mRNA in the longissimus muscle of feed-deprived pigs was small (22%), but significant (P < 0.04). The expression of hormone-sensitive lipase was increased 46% and 64% (P < 0.04) in adipose tissue and longissimus muscle, respectively, by feed deprivation, whereas adipose lipoprotein lipase expression was reduced (P < 0.01) to 20% of that of the fed group. Longissimus lipoprotein lipase expression in the feed-deprived group was 37% of that of the fed group (P < 0.01), and similar reductions were detected in red and white semitendinosus muscle. Overall, these findings indicate that uncoupling protein 3 expression in skeletal muscle is quite sensitive to starvation in the pig, whereas uncoupling protein 2 changes are minimal. Furthermore, we conclude that hormone-sensitive lipase is upregulated at the mRNA level with prolonged feed deprivation, whereas lipoprotein lipase is downregulated.

We describe a patient with Duchenne muscular dystropy and growth hormone deficiency in whom treatment with human growth hormone for 2 years resulted in improved growth velocity without any detrimental effect on muscle strength.

An 18 kDa protein isolated from saliva of the cat flea, Ctenocephalides felis, elicits a positive intradermal skin test (IDST) in 100 and 80% of experimental and clinical flea allergic dogs, respectively. Using solid-phase enzyme-linked immuno assay (ELISA), this protein detected IgE in 100 and 80% of experimental and clinical flea allergic dogs, respectively. A cDNA (pFSI) encoding a full-length Cte f 1 protein was isolated from a C. felis salivary gland cDNA library, using a combination of PCR and hybridization screening. This cDNA is 658 bp in length, and contains an open reading frame of 528 bp. The open reading frame encodes a protein of 176 amino acids, consisting of an 18 amino acid signal sequence and a 158 amino acid mature protein. The calculated molecular weight and pI of the mature protein are 18106 Da and 9.3, respectively. The protein, named Cte f 1, is the first novel major allergen described for canine flea allergy. Recombinant Cte f 1 (rCte f 1) was expressed in Escherichia coli, Pichia pastoris and baculovirus infected Trichoplusia ni cells. Approximately, 90% of the rCte f 1 expressed in E. coli accumulated in insoluble inclusion bodies, which could be refolded to a soluble mixture of disulfide isomers with partial IgE binding activity. Small quantities of an apparently correctly refolded form of rCte f 1, which had IgE binding activity equal to the native antigen, was isolated from the soluble fraction of E. coli cells. However, P. pastoris and baculovirus infected insect cells expressed and secreted a fully processed, correctly refolded and fully active form of rCte f 1. Mass spectrometry analysis of the active forms of rCte f 1confirmed that eight intact disulfide bonds were present, matching the number observed in the native allergen. The relative ability of rCte f 1 to bind IgE in the serum of flea allergic animals, produced in these three expression systems, matched that of the native allergen. Competition ELISA demonstrated that approximately 90% of the specific IgE binding to native Cte f 1 could be blocked by the different forms of rCte f 1.

In a study involving 10 different sites, independent results of measurements of ultrasonic properties on equivalent tissue-mimicking samples are reported and compared. The properties measured were propagation speed, attenuation coefficients, and backscatter coefficients. Reasonably good agreement exists for attenuation coefficients, but less satisfactory results were found for propagation speeds. As anticipated, agreement was not impressive in the case of backscatter coefficients. Results for four sites agreed rather well in both absolute values and frequency dependence, and results from other sites were lower by as much as an order of magnitude. The study is valuable for laboratories doing quantitative studies.