bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell Proliferation Activity of Proliferating Bile Duct after Bile Duct Ligation in Rats
Authors: Yoshioka K. , Mori A. , Taniguchi K. , Mutoh K.
Published: May 2005

The cell proliferation activity of proliferating bile ducts produced by bile duct ligation (BDL) in rats was examined histologically, immunohistochemically, and ultrastructurally. Proliferating bile ducts, which were similar to normal bile ducts, increased with time after BDL. The cell proliferation activity of proliferating bile ducts, measured using proliferating-cell nuclear antigen and 5-bromo-2′-deoxyuridine antibodies, tended to be high at 1 and 3 days after BDL and decreased progressively at 2 to 4 weeks after BDL. On the other hand, α-smooth muscle actin-positive myofibroblast-like cells increased continuously after BDL. These findings indicate that there is a negative correlation between the cell proliferation activity of proliferating bile ducts and that of myofibroblast-like cells.
Autoantibodies against intrinsic factor (IF) measured with an ELISA using recombinant human IF as both catching and detecting reagent
Authors: Nexo Ebba , Nooroya Ben , Hvas Anne-Mette , Christensen Anna Lisa , Waters Harry
Published: May 2005

The aim was to develop and validate an assay for measuring autoantibodies against human intrinsic factor (IF). For this purpose 1.25pmol of recombinant IF was coupled to each well. Samples (100μL of plasma diluted 1:1) were incubated for 1h, followed by 30min with the detection reagent (biotinylated IF, 3.3pmol/mL). Samples were obtained from healthy blood donors (n=141) and patients with suspected vitamin B
Antibody titer against malondialdehyde-modified LDL compares with HDL cholesterol concentration in identifying angiographically verified coronary artery disease. Comparison of tests by ROC analysis
Authors: Rontu Riikka , Metso Saara , Jaakkola Olli , Nikkilä Matti , Jokela Hannu , Lehtimäki Terho
Published: May 2005

Antibody titer against malondialdehyde (MDA)-modified low-density lipoprotein (LDL) has been found to be associated with atherosclerosis, but it has not been established whether it would detect subjects with coronary artery disease (CAD). In the present study, receiver-operating characteristic (ROC) analysis was used to compare the diagnostic accuracy of the antibody titer against MDA-modified LDL and high-density lipoprotein (HDL) and LDL cholesterol levels in discrimination between subjects with (n=51) and without (n=35) angiographically verified 3-vessel CAD. As a result, the antibody titer against MDA-modified LDL was lower in subjects with CAD compared with subjects without CAD (p<0.0001). The area under the ROC plot was 0.822 (95% CI, 0.727 to 0.918) for the antibody titer and 0.769 (95% CI, 0.661 to 0.876) for the HDL cholesterol concentration. Both the antibody titer and the plasma HDL cholesterol level were more accurate markers of CAD than the LDL cholesterol level. As a conclusion, our results indicate that the antibody titer against MDA-modified LDL discriminates between subjects with widespread CAD and those without CAD similarly as the HDL cholesterol concentration. Moreover, the antibody titer against MDA-modified LDL is inversely correlated with the risk of severe CAD.
α-Tocopherol as an antiretroviral therapy supplement for HIV-1-infected patients for increased lymphocyte viability
Authors: de Souza Júnior Odilon , Treitinger Arício , Baggio Giovana Lotici , Michelon Cleonice , Verdi Júlio Cesar , Cunha Joel , Ferreira Silvia I. A. C. P. , Spada Celso
Published: May 2005

The aim of our study was to evaluate the benefits of supplementation with 800mg/day of α-tocopherol with regard to cellular viability in HIV-1 seropositive patients undergoing anti-retroviral therapy. A total of 29 patients participated in the study, of whom 14 were given the supplement and 15 a placebo. The analyses were carried out before treatment commenced and after 60, 120 and 180days. The plasma levels ofHIV-1 RNA showed a significant decrease as a consequence of treatment time in the groups studied (p=0.0001), although the difference between the treatments over time was not verified (p=0.7343). The percentage of viable lymphocytes showed a significant increase as a consequence of treatment time in both groups studied (p=0.0002) and a significant difference between the treatments over time (p=0.0472). The percentage of lymphocytes in apoptosis showed a significant reduction over time (p=0.0003), as well as a significant difference between the treatments over time (p=0.0321). The significant increase in cellular viability indicates that supplementation with α-tocopherol offers an additional positive effect on cellular preservation in HIV-1 individuals undergoing anti-retroviral therapy; however, it represents an additional risk of anti-retroviral therapeutic failure, possibly due to drug-drug interaction involving up-regulation of metabolic clearance.
Estimation of the limit of detection with a bootstrap-derived standard error by a partly non-parametric approach. Application to HPLC drug assays
Authors: Linnet Kristian
Published: May 2005

A recently proposed procedure for estimating the limit of detection (LoD) of an assay using a partly non-parametric approach is applied to five HPLC drug assays. The non-parametrically determined 95th percentile of the blank measurements (LoB) is obtained as the value of the
Pitfall in the high-throughput quantification of whole blood cyclosporin A using liquid chromatography-tandem mass spectrometry
Authors: Vogeser Michael , Spöhrer Ute
Published: May 2005

In a growing number of laboratories the technique of liquid chromatography-tandem mass spectrometry is used for the quantification of cyclosporin A in whole blood, employing cyclosporin D as the internal standard. Cyclosporin A is extensively metabolized in vivo; in liquid chromatography-tandem mass spectrometry respective metabolites can give rise to both parent and product ions that are isobaric with ions commonly used for the detection of cyclosporin A and cyclosporin D, respectively. In this article it is demonstrated that limited chromatography with co-elution of such metabolites together with cyclosporin A and cyclosporin D can lead to incorrect results.
Evaluation of a rapid bedside test for the quantitative determination of C-reactive protein
Authors: Esposito Susanna , Tremolati Elena , Begliatti Enrica , Bosis Samantha , Gualtieri Laura , Principi Nicola
Published: May 2005

Regardless of its origin, any condition associated with inflammation is accompanied by an increase in serum C-reactive protein levels. This study compared the results of a rapid test for the bedside assay of C-reactive protein (QuikRead CRP, Orion Corporation, Orion Diagnostica, Espoo, Finland) with those of a standard laboratory assay in samples taken from 231 children aged less than 14years (126 males; median age 4.7years) attending the Emergency Department of Milan University's Institute of Pediatrics because of acute respiratory infection. The two methods showed similar median C-reactive protein levels (standard laboratory assay: 34.7mg/L, range 4–199mg/L; QuikRead CRP: 33.3mg/L, range <8–196mg/L; p=0.779) and a similar distribution of children with C-reactive protein levels of <20mg/L, 20–70mg/L and >70mg/L. This study shows for the first time that the rapid QuikRead CRP test can be performed at the bedside or in an outpatient clinic and, in less than 5min, gives the same quantitative results as those obtained using a more complex routine laboratory method.
Power function of the reference change value in relation to cut-off points, reference intervals and index of individuality
Authors: Iglesias Natàlia , Petersen Per Hyltoft , Ricós Carmen
Published: May 2005

The reference change value, defined as RCV=1.96×2
Small-scale actinide(III) partitioning processes in miniature hollow fibre modules
Authors: Geist Andreas , Weigl Michael , Gompper Klaus
Published: May 2005

Miniature hollow fibre modules were fabricated and used as phase contactors for chemical liquid–liquid extraction. They were tested for americium(III) selective extraction, using three different extractants of relevance to the European Partitioning and Transmutation strategy. Americium could be removed from the feed phase to >99.9% in all cases. Only few ten millilitres of feed phases were consumed running a test. This is the major advantage of the miniature hollow fibre modules over commercially available modules which have been used previously.
Effect of ammonium, carbonate and fluoride concentration on the uranium recovery by resins
Authors: Ladeira Ana C. Q. , Morais Carlos A.
Published: May 2005

Uranium in solution can be precipitated over a wide pH range, from acidity and alkalinity, depending upon the solution and the precipitant used. The precipitate is generally filtered and the solution resultant contains uranium that should be recovered. This work is aimed at the selection of an appropriate resin for uranium recovery from alkaline solutions in the presence of ammonia, carbonate and fluoride. The ability of uranium extraction of 3 types of polymeric strong base resin was assessed. Laboratory solutions were prepared to determine the influence of the ions like ammonia, carbonate and fluoride on the uranium recovery by resins. The uranium concentration was 100 mg/L and the solution pH ranged from 9.2 to 10.4. The results, obtained by batch experiments, showed that excess of carbonate and fluoride completely inhibit uranium uptake in the pH range studied. Even low concentrations of fluoride and carbonate decrease uranium adsorption by resins. The optimum concentration was below 2.5 g/L (0.04 mol/L) and 5.0 g/L (0.26 mol/L) for carbonate and fluoride, respectively. The presence of high concentration of ammonia up to 20 g/L (1.20 mol/L) did not inhibit the uranium exchange process. Among the three types of resins studied IRA 910U was the most promising adsorbent for uranium at the conditions employed in this work.
Release of contaminant U(VI) from soils
Authors: Zheng Zuoping , Wan Jiamin
Published: May 2005

The retention, mobility, and bio-availability of U(VI) in contaminated soils depend strongly on release of U(VI). Laboratory batch experiments were performed to evaluate the factors (ionic strength of the extraction solution and solution volume to solid mass ratio) controlling the release of U(VI) from contaminated soil at Oak Ridge, Tennessee. Increase in ionic strength shows an evident effect on U(VI) release as indicated by the increase in release rates and associated release mass of U(VI). The ratio of solution volume to solid mass (V/M) has a significant impact on the release of U(VI). Increase in the V/M ratio shows a negligible effect on the U(VI) release over a 4-day period. However, at Day 30 and Day 120, larger V/M ratios cause greater U(VI) release. The maximum U(VI) concentrations observed in the release experiments are in the range of schoepite solubility estimated under conditions relevant to the experiments, suggesting that schoepite solubility primarily controls the U(VI) release, but that solubilization and desorption effects cannot be distinguished using macroscopic methods.
Catechol functionalized aminopropyl silica gel: synthesis, characterization and preconcentrative separation of uranium(VI) from thorium(IV)
Authors: Metilda P. , Gladis J. Mary , Rao T. Prasada
Published: May 2005

A novel solid phase extractant is prepared by chemically immobilizing catechol with diazotized aminopropyl silica gel. The resulting catechol functionalized silica gel (CASG) was characterized by FTIR, and microanalysis and was used for selective enrichment of uranium(VI) from other inorganic ions. The optimum pH range for maximum sorption of uranium(VI) and thorium(IV) was found to be in the range 3.5–6.0. The above actinides were eluted with 10 cm3 of 1.0 mol dm−3 HCl and determined by using an Arsenazo III spectrophotometric procedure. The calibration graph was rectilinear over the uranium(VI) concentration in the range 2–100 μg dm−3 with a relative standard deviation of 2.15% (for 25 μg of uranium(VI) present in 1.0 dm3 of sample). The validation of the developed preconcentration procedure was carried out by analyzing marine sediment (MESS-3, NRC, Canada) and soil (IAEA soil-7, Austria) reference materials. The developed preconcentration method enables a simple instruments like a spectrophotometer gave comparable values of uranium(VI) to that of standard inductively coupled plasma-mass spectrometric values during the analysis of real soil and sediment samples.
Semi-remote production of [64Cu]CuCl2 and preparation of high specific activity [64Cu]Cu-ATSM for PET studies
Authors: Szajek Lawrence P. , Meyer W. , Plascjak P. , Eckelman W. C.
Published: May 2005

The PET radionuclide Cu-64 (t
1/2 = 12.7 h) can be easily produced utilizing the nuclear reaction 64Ni(p,n)64Cu. A high Cu-64 production rate was obtained using high-purity enriched nickel metal on the internal tangential target of the CS-30 cyclotron. Radio-copper was isolated after column chromatography using a semi-remote apparatus. Use of reagents with little or no carrier copper yields high specific activity Cu-64 pharmaceuticals prepared from the isolated [64Cu]CuCl2. [64Cu]Cu-ATSM was prepared in greater than 1.21±0.40 Ci/mmol (45±15 GBq/mmol) at EOB.
Empirical relation between the adsorption properties of elements on gold surfaces and their volatility
Authors: Eichler R.
Published: May 2005

A correlation is established between thermodynamic data for hypothetical macroscopic amounts of elements and experimentally accessible data on gold surfaces. The correlation between the experimentally determined standard adsorption enthalpies of elements on gold surfaces and their standard sublimation enthalpies is shown to be valid over a broad data range for various elements from light noble gases (Kr) up to heavy metals (Pb, Bi). This type of correlation is indispensable to derive thermodynamic data for macroscopic amounts of elements from results of adsorption chromatographic experiments with single atom amounts. It is also necessary to predict the behavior of single atoms from given or estimated thermochemical data. The conditions under which this correlation is valid are elaborated. Finally, predicted data for the elements 112 and 114 are used to link them to the corresponding sublimation or adsorption data. The obtained prediction intervals are of exceptional importance for the design of sophisticated experimental setups for the chemical investigation of transactinide elements on a single atom scale.
Diffusion and sorption of U(VI) in compacted bentonite studied by a capillary method
Authors: Wang X. K. , Chen C. L. , Zhou X. , Tan X. L. , Hu W. P.
Published: May 2005

Diffusion and sorption of U(VI) in compacted bentonite were studied using a capillary method. The experiments were carried out at room temperature in 0.1 M NaClO4solutions at pH 7.0±0.1. Effects of contact time, solution concentration and bentonite bulk density on diffusion were also investigated. The results fit the Fick's second law very well and are in good agreement with the literature data for similar bentonite dry densities [3]. TheKdvalues from capillary method are in most cases lower than those from batch experiments. The interlaminary space of the compacted bentonite contributes significantly to the sorption of uranium. The apparent diffusion coefficientDaof diffusion derived from the experiments are used to simulate its diffusion in compacted bentonite and the results indicate that several meters of compacted bentonite is enough to prevent the diffusion of from the repository to the environment.
The effect of water treatment on the presence of particle-bound210Po and210Pb in groundwater
Authors: Vesterbacka P. , Hämäläinen K. , Lehto J.
Published: May 2005

The distribution of210Po and210Pb in various particle-size fractions in Finnish groundwater was studied at five private homes. Each site had water treatment equipment comprising either an ion exchange unit or a granular activated carbon filter. Samples of both raw and treated water were filtered using pore sizes ranging from 450 nm to 100 kDa and the activity concentration of210Po and210Pb in the filtrate was determined. In untreated groundwater 86% of210Pb, on average, was found in the large particle fraction (>450 nm). However, in Fe- and Mn-rich water with a high Fe/Mn ratio and in organic-rich water, the majority of210Pb was found in either the intermediate particle (100 kDa–450 nm) or small particle (<100 kDa) fractions. Compared to210Pb,210Po was bound more to the intermediate and small particle fraction. After water treatment,210Pb was found most frequently in the large particle fraction. The size distribution of particle-bound210Po was not as clear as that for210Pb, and in treated water,210Po was more evenly distributed among fractions. The ion exchange unit removed210Pb and210Po bound to the intermediate or small particle fraction, whereas the efficiency of the activated carbon filters in removing210Pb and210Po was independent of the particle size.
On the transport and speciation of ruthenium in high temperature oxidising conditions
Authors: Backman Ulrika , Lipponen Maija , Auvinen Ari , Tapper Unto , Zilliacus Riitta , Jokiniemi Jorma K.
Published: May 2005

In this paper, the transport and speciation of ruthenium under conditions simulating an air ingress accident was studied. Ruthenium dioxide was exposed to an oxidising environment at high temperatures (>1200 °C) in a tubular flow furnace. At these conditions, volatile ruthenium species were formed. A major part of the released ruthenium was deposited in the tube as RuO2. Depending on the experimental conditions, 12–35 wt. % of the released ruthenium was trapped in the outlet filter as RuO2 particles. At completely dry conditions using stainless steel tubes, only 0.1–0.2 wt. % of the released ruthenium reached the trapping bottle as gaseous RuO4. However, when alumina was applied as tube material or the atmosphere contained some water vapour and silver seed particles, the fraction of gaseous ruthenium reaching the trapping bottle increased to 5 wt. % which is close to thermodynamic equilibrium. This indicates that RuO2 does not catalyse the decomposition of RuO4.
Discontinuation of estrogen replacement therapy in GH-treated hypopituitary women alters androgen status and IGF-I
Authors: Christiansen Jens Juel , Fisker Sanne , Gravholt Claus Højbjerg , Bennett Paul , Svenstrup Birgit , Andersen Marianne , Feldt-Rasmussen Ulla , Christiansen Jens Sandahl , Jørgensen Jens Otto Lunde
Published: May 2005

Objective and design: Compared with their male counterparts, healthy females secrete more growth hormone (GH) and those with GH-deficiency have lower insulin-like growth factor I (IGF-I) levels and are less responsive to GH substitution. To test whether this gender difference is related to sex hormones we measured androgen status and IGF-I related parameters in 38 hypopituitary women (mean (range) age 41.5 (20–58) years) during continued GH substitution as compared with a control group of 38 healthy women matched for age and menopausal status. Twenty six patients were studied twice: with estrogen replacement and after 28 days of estrogen discontinuation in a randomised design.

Results: The patients were androgen deficient compared with controls (median, range), dehydroepiandrosterone sulphate (DHEAS): 185 (99–7800) nmol/l vs 4400 (820–13 000) nmol/l, P = < 0.001; androstenedione: 0.5 (0.1–7.1) nmol/l vs 4.3 (1.6–8.8) nmol/l, P = < 0.001; dihydrotestosterone (DHT): 0.13 (0.09–0.54) nmol/l vs 0.55 (0.09–0.89) nmol/l, P = < 0.001; testosterone: 0.28 (0.09–1.56) nmol/l vs 1.1 (0.71–2.24) nmol/l, (P = < 0.001); free testosterone: 0.004 (0.001–0.030) nmol/l vs 0.016 (0.001–0.030) nmol/l, P = < 0.001. The circulating levels of IGF-I, IGF-II, IGF-binding protein 1 (IGFBP-1), and IGFBP-3 did not differ between patients and controls. The subgroup of patients receiving hydrocortisone (HC) replacement (n = 24) had significantly lower levels of androgens (suppressed by 80–100%) as well as IGF-I and IGFBP-3 as compared with the patients not receiving HC. IGF-I was correlated to free testosterone in patients (r = 0.57, P = 0.0005) as well as controls (r = 0.43, P = 0.008), and free testosterone was a significant positive predictor of IGF-I. Estrogen discontinuation induced an increase in IGF-I (167 ± 15 vs 206 ± 14 μg/l, P = 0.005 and IGFBP-3 (3887 ± 139 vs 4309 ± 138 μg/l, P = 0.0005). Estrogen discontinuation was associated with a significant increase in median (range) free testosterone (0.004 (0–0.02) vs 0.0065 (0–0.03) nmol/l, P = 0.001) and a significant decrease in median (range) sex-hormone binding globulin (SHBG; 93 (11–278) vs 55.5 (20–142) nmol/l, P = 0.001). ΔIGF-I correlated with ΔSHBG (r = −0.45 P = 0.033) and ΔIGFBP-3 (r = 0.67 P = < 0.001). In a regression model ΔE2, Δtestosterone, ΔSHBG and ΔIGFBP-3 explained 93% of the variation in ΔIGF-I.

Conclusions: Androgen levels are low in hypopituitary women and free testosterone correlates with IGF-I. Discontinuation of estrogen replacement in these patients induces elevations in IGF-I as well as free testosterone, and ΔIGF-I correlated positively with Δfree testosterone. These effects may contribute to the gender differences observed in the GH–IGF axis in healthy adults as well as in the responsiveness of hypopituitary patients to GH substitution.
Evidence for protein and mRNA TSHr expression in fibroblasts from patients with thyroid-associated ophthalmopathy (TAO) after adipocytic differentiation
Authors: Agretti Patrizia , De Marco Giuseppina , De Servi Melissa , Marcocci Claudio , Vitti Paolo , Pinchera Aldo , Tonacchera Massimo
Published: May 2005

Objective: Thyroid-associated ophthalmopathy (TAO) is a chronic autoimmune disorder characterized by an increased volume of adipose/connective tissue in the human orbit.

Design: The aim of this study was to investigate the thyrotropin receptor (TSHr) expression in orbital fibroblasts from TAO patients undergoing adipocytic differentiation.

Methods: Retro-ocular tissue and skin were obtained from five patients undergoing orbital decompression surgery for TAO and placed in culture. Proliferating fibroblasts were subjected to adipocytic differentiation for 10 days. Total RNA was isolated from fibroblasts and was reverse transcribed. TSHr mRNA levels were determined by real-time PCR. cAMP was determined by radioimmunoassay (RIA) after fibroblast incubation with the substances to test.

Results: Orbital differentiated fibroblasts became rounded and acquired lipid droplets. The amount of TSHr mRNA in these fibroblasts was higher than fibroblasts not subjected to adipocytic differentiation. Immunocytochemical analysis showed TSHr protein in differentiated orbital fibroblasts. Differentiated orbital fibroblasts stimulated with bovine (b) TSH showed a cAMP production greater than that in paired undifferentiated cultures. A specific thyroid-inhibiting antibody (TBAb) inhibited cAMP production after bTSH challenge, and a thyroid-stimulating antibody (TSAb) stimulated cAMP production in differentiated fibroblasts.

Conclusions: We suggest that orbital fibroblasts subjected to adipocytic differentiation increase TSHr expression that responds specifically to bTSH and TSAb stimulation, and to TBAb inhibition.
Octreotide in insulinoma patients: efficacy on hypoglycemia, relationships with Octreoscan scintigraphy and immunostaining with anti-sst2A and anti-sst5 antibodies
Authors: Vezzosi Delphine , Bennet Antoine , Rochaix Philippe , Courbon Frédéric , Selves Jannick , Pradere Bernard , Buscail Louis , Susini Christiane , Caron Philippe
Published: May 2005

Objective: We studied the efficacy of octreotide treatment on hypoglycaemia in patients with insulinoma and its relationships with Octreoscan scintigraphy and the presence of tumoral somatostatin receptors sst2A and sst5.

Design and methods: 17 patients with insulinoma were evaluated using (i) evaluation of blood glucose, insulin and C-peptide during a short 100 μg octreotide test in fasting patients and/or treatment over 8 days–8 months with octreotide, (ii) Octreoscan scintigraphy and (iii) immunostaining of the tumor with anti-sst2A and anti-sst5.

Results: Octreotide was effective on hypoglycaemia in 10/17 patients. Octreoscan scintigraphy detected 4/17 insulinomas. sst2A receptor was detected in 7/17 insulinomas and sst5 in 15/17 insulinomas. Octreotide was effective on hypoglycaemia in those seven patients with sst2A receptor-expressing insulinoma, and in three patients with undetectable sst2A receptor and detectable sst5; it was ineffective in six patients whose tumor expressed the sst5 receptor with undetectable sst2A and in one patient with undetectable sst2A and sst5 receptor.

Conclusions: Octreotide is an effective treatment of hypoglycaemia in more than 50% of patients with insulinoma. Detection of responsive patients was better based on a positive short test with subcutaneous octreotide than on the results of Octreoscan scintigraphy. Positive anti-sst2 receptor immunostaining is associated with efficacy of octreotide treatment, but does not account for all cases of responsiveness to octreotide. Expression of sst5 receptor does not appear to explain per se the efficacy of octreotide on sst2A-negative insulinomas.
Inhibitory effect of alcohol on ghrelin secretion in normal man
Authors: Calissendorff Jan , Danielsson Olle , Brismar Kerstin , Röjdmark Sven
Published: May 2005

Background: Human appetite is stimulated by alcohol but the underlying mechanism is unknown. It is possible that hunger-stimulating hormones are mediators of this effect of alcohol. Ghrelin stimulates hunger, but how alcohol affects human ghrelin secretion has never been studied before.

Objective: To investigate whether alcohol ingestion exerts an acute influence on serum ghrelin concentrations in healthy subjects.

Subjects and design: Eight healthy non-obese subjects participated in the study. All were investigated on two occasions (experiments A and B). Alcohol (0.55 g ethanol/kg body weight) was ingested in experiment A, and drinking-water in experiment B. Venous blood was collected before, and 30 and 60 min after consumption of the drinks. Serum concentrations of ghrelin, cortisol and ethanol were determined and neuropeptide Y (NPY) concentrations were determined in plasma.

Results: Alcohol lowered the ghrelin level by 13.9±5.0% at 30 min and by 17.5±2.6% at 60 min, in contrast to drinking-water which was without significant effect. Serum levels of cortisol and insulin were similar after alcohol and water as was plasma NPY.

Conclusion: Alcohol has an acute inhibitory influence on human ghrelin secretion but no measurable effect on the secretion of NPY and cortisol. Hence, none of these hormones mediate the orexigenic effect of the drug.
Clinical and molecular evidence for DAX-1 inhibition of steroidogenic factor-1-dependent ACTH receptor gene expression
Authors: Zwermann Oliver , Beuschlein Felix , Lalli Enzo , Klink Albrecht , Sassone-Corsi Paolo , Reincke Martin
Published: May 2005

Background: The ACTH receptor (ACTH-R) is a member of the seven transmembrane domain receptor super-family. In non-functional adrenal adenomas and adrenocortical carcinomas, ACTH-R expression is low. However, no inhibitory factor for ACTH-R expression has been defined to date. DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia congenita, critical region on the X chromosome, gene-1) is a general repressor of steroid production, inhibiting steroidogenic factor-1 (SF-1)-dependent expression of multiple steroidogenic enzymes. The aim of this study was to investigate whether ACTH-R gene transcription is affected by DAX-1 and whether this mechanism is involved in down-regulation of ACTH-R expression in adrenocortical tumors.

Methods: We screened 22 adrenocortical tumors for ACTH-R and DAX-1 mRNA expression by Northern blot. For in vitro analyses we co-transfected mouse Y1 adrenocortical carcinoma cells with the luciferase reporter gene vector pGL3 containing full-length constructs of human (h) or mouse (m) ACTH-R promoter together with a DAX-1 expression plasmid. These experiments were also performed using ACTH-R promoter 5′-deletion constructs and constructs mutated at the SF-1-binding sites.

Results: We found a negative correlation between DAX-1 and ACTH-R mRNA expression (R = −0.47, P < 0.02). Accordingly, in vitro expression of DAX-1 significantly reduced hACTH-R and mACTH-R promoter activity by 89 and 55% respectively. DAX-1 inhibition was also present in the shortest construct of a series of 5′-deletion constructs of the human promoter extending from −64 to +40 bp relative to the transcription start site. Mutation of the SF-1-binding sites within the hACTH-R promoter resulted in reduced or abolished DAX-1 inhibition, arguing for a mechanism that involves SF-1 for DAX-1 inhibition.

Conclusions: These data support the concept that DAX-1 is a major repressor of ACTH-R gene expression in vitro and in vivo.
Evaluation of insulin-like growth factor II, cyclooxygenase-2, ets-1 and thyroid-specific thyroglobulin mRNA expression in benign and malignant thyroid tumours
Authors: Fuhrer D , Eszlinger M , Karger S , Krause K , Engelhardt C , Hasenclever D , Dralle H , Paschke R
Published: May 2005

Objective: We evaluated three markers (insulin-like growth factor II (IGF-II), cyclooxygenase-2 (COX-2) and ets-1) of thyroid growth stimulation and cell transformation together with a thyroid-specific marker (thyroglobulin (Tg)) for their potential to differentiate benign and malignant follicular thyroid neoplasia (FN).

Design and methods: mRNA expression levels were determined by real-time PCR in 100 snap-frozen thyroid samples: 36 benign thyroid nodules with different histology and function (19 cold (CTN) and 17 toxic thyroid nodules (TTN)), 36 corresponding normal thyroid tissues of the same patients, eight Graves’ disease (GD) thyroids, 10 follicular thyroid carcinomas (FTC) and 10 papillary thyroid carcinomas (PTC).

Results: Mean IGF-II and COX-2 levels were not significantly altered between benign and malignant thyroid nodules (IGF-II) or nodular (FTC, TTN, CTN) and normal thyroid tissues (COX-2). In contrast, eight- to tenfold upregulation of ets-1 was observed in PTC and three- to fourfold upregulation of ets-1 was observed in FTC (and GD) compared with benign thyroid nodules and normal thyroid tissues. In addition, thyroglobulin mRNA expression was markedly downregulated (50- to 100-fold) in FTC, PTC and GD samples compared with benign nodular and normal thyroid tissues. Hence an ets-1/Tg ratio >20 distinguished differentiated thyroid cancer from benign nodular or normal thyroid tissue. We then studied ets1- and Tg mRNA expression levels in fine needle aspiration cytology (FNAC) samples. However, in a consecutive series of 40 FNAC samples only equivocal results were obtained on 38 benign and two malignant (FTC) thyroid tumour samples.

Conclusions: Upregulation of ets-1 and downregulation of Tg mRNA expression occur in differentiated thyroid cancer and may facilitate pre-operative identification of thyroid malignancy depending on further evaluation of these potentially promising markers in a larger series of benign and malignant thyroid tumours and their FNAC samples.
Quality of Evidence-Based Pediatric Guidelines
Authors: Boluyt Nicole , Lincke Carsten R. , Offringa Martin
Published: May 2005

Objective. To identify evidence-based pediatric guidelines and to assess their quality.

Methods. We searched Medline, Embase, and relevant Web sites of guideline development programs and national pediatric societies to identify evidence-based pediatric guidelines. A list with titles of identified guidelines was sent to 51 leading pediatricians in the Netherlands, who were asked to select the 5 most urgent topics for guideline development. Three pediatrician reviewers appraised the available guidelines on the 10 most frequently mentioned topics with the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument.

Results. A total of 215 evidence-based pediatric guidelines were identified; of these, 17 guidelines on the 10 most frequently mentioned topics were appraised. The AGREE instrument rates guidelines among 6 domains. For the scope and purpose domain, the mean score was 84% of the maximal mark. For stakeholder involvement, the mean score was 42%, with 12 guidelines (71%) scoring <50%. For rigor of development, the mean score was 54%, with 5 guidelines (29%) scoring <50%. For clarity and presentation, the mean score was 78%, with 4 guidelines (24%) scoring <50%. For applicability and editorial independence, performance was poor, with mean scores of 19% and 40%, respectively. Low scores were partly attributable to poor reporting. After considering all domain scores, the reviewers recommended 14 of 17 guidelines (82%) to be used in local practice.

Conclusions. The current volume of pediatric guidelines categorized as evidence based in popular databases is large. Overall, these guidelines scored well, compared with other studies on guideline quality in fields outside pediatrics, when assessed for quality with the AGREE instrument. This holds especially for guidelines published or endorsed by the American Academy of Pediatrics or registered in the National Guideline Clearinghouse.
Completeness and Complexity of Information Available to Parents From Newborn-Screening Programs
Authors: Fant Kathryn E. , Clark Sarah J. , Kemper Alex R.
Published: May 2005

Background. In 2000, the American Academy of Pediatrics (AAP) Task Force on Newborn Screening published a blueprint for the future of newborn screening that included recommendations for information provided to parents about screening.

Objectives. To evaluate the completeness of educational material provided by newborn-screening programs and to measure the reading level and complexity of the material.

Methods. Telephone survey of newborn-screening programs (n = 51) followed by content analysis of educational material.

Results. All 51 programs responded (response rate: 100%); 47 of these programs made educational material available. None of the material included all elements recommended in the blueprint. Benefits of screening (98%) and how parents would be notified of results (87%) were included more often than the risks of screening (19%), possibility of a false-positive result (13%), importance of (34%) and how to respond to (28%) a positive result, and the storage and use of residual samples (11%). The median readability grade level was 10. Grade-level complexity of the material was not associated with completeness according to the AAP criteria.

Conclusions. Parent educational materials for newborn-screening programs do not meet the standard recommended by the AAP, and there are important variations between programs in the information provided to parents. Continuing research is needed to measure progress toward the goals outlined within the blueprint and to assess how these changes impact the care provided through newborn-screening programs.
Racial and Ethnic Differences in Asthma Diagnosis Among Children Who Wheeze
Authors: Akinbami Lara J. , Rhodes Julia C. , Lara Marielena
Published: May 2005

Background. Racial and ethnic disparities exist in reported childhood asthma prevalence, but it is unclear if disparities stem from true prevalence differences or a different likelihood of receiving a diagnosis from a health professional. Concern has been raised that asthma may be underdiagnosed, particularly among minority children who have more restricted access to high-quality health care.

Objective. To examine racial/ethnic differences among currently symptomatic children in acquiring an asthma diagnosis to determine if relative underdiagnosis among minorities exists. Children for whom no symptoms were reported (a group that includes those with well-controlled symptoms) were excluded from the analysis.

Methods. The 1999 National Health Interview Survey includes a nationally representative sample of children with reported wheezing symptoms. We included children 3 to 17 years old in the study and analyzed racial/ethnic differences in asthma diagnosis, controlling for young age, gender, parental education, single-parent household, central-city residence, region of residence, health insurance, having a usual place of care, and parent-reported severity of wheezing symptoms.

Results. Among those reported to have wheezed in the past year (n = 946), 83% of Puerto Rican, 71% of non-Hispanic black, and 65% of Mexican children were diagnosed with asthma compared with 57% of non-Hispanic white children. Using non-Hispanic white children as the reference group, the approximate adjusted relative risk for physician diagnosis of asthma given wheezing in the past year was 1.43 (95% confidence interval [CI]: 1.04, 1.63) for Puerto Rican, 1.22 (95% CI: 1.03, 1.37) for non-Hispanic black, and 1.19 (95% CI: 0.94, 1.39) for Mexican children. Minority children were reported to have greater severity of wheezing symptoms. Even after accounting for this increased severity, children in racial and ethnic minority groups were as or more likely to have a reported asthma diagnosis than non-Hispanic white children.

Conclusions. Our findings do not provide evidence for the hypothesis that symptomatic minority children are underdiagnosed with asthma compared with non-Hispanic white children. To the contrary, among currently symptomatic children, minority children were more likely to be diagnosed than non-Hispanic white children even after accounting for the higher wheezing severity among minority children.
Use of Cholecystokinin-Octapeptide for the Prevention of Parenteral Nutrition-Associated Cholestasis
Authors: Teitelbaum Daniel H. , Tracy Thomas F. , Aouthmany Moustafa M. , Llanos Adolfo , Brown Morton B. , Yu Sunkyung , Brown Marilyn R. , Shulman Robert J. , Hirschl Ronald B. , Derusso Patricia A. , Cox Jeanne , Dahlgren Jacqueline , Groner Jonathan I. , Strouse Peter J.
Published: May 2005

Objective. To determine whether cholecystokinin-octapeptide (CCK-OP) would prevent or ameliorate parenteral nutrition-associated cholestasis (PNAC) among high-risk neonates treated with total parenteral nutrition.

Study Design. This was a multicenter, double-blind, randomized, controlled trial conducted between 1996 and 2001.

Patients. Neonates at risk for the development of PNAC included very low birth weight neonates and those with major surgical conditions involving the gastrointestinal tract.

Setting. Tertiary care hospitals.

Intervention. Patients were randomized to receive CCK-OP (0.04 μg/kg per dose, twice daily) or placebo. Eligible infants were all <30 days of age. Patients were enrolled within 2 weeks after birth or within 7 days after surgery.

Outcome Measures. The primary outcome measure was conjugated bilirubin (CB) levels, which were measured weekly. Secondary outcome measures included incidence of sepsis, times to achieve 50% and 100% of energy intake through the enteral route, number of ICU and hospital days, mortality rate, and incidences of biliary sludge and cholelithiasis.

Results. A total of 243 neonates were enrolled in the study. CCK-OP administration did not significantly affect CB levels (1.76 ± 3.14 and 1.93 ± 3.31 mg/dL for CCK-OP and placebo groups, respectively; mean ± SD). Secondary outcome measures also were not significantly affected by the study drug.

Conclusions. Use of CCK-OP failed to reduce significantly the incidence of PNAC or levels of CB. CCK-OP had no effect on other secondary measures and should not be recommended for the prevention of PNAC.
Childhood Femur Fractures, Associated Injuries, and Sociodemographic Risk Factors: A Population-Based Study
Authors: Rewers Arleta , Hedegaard Holly , Lezotte Dennis , Meng Katy , Battan F. Keith , Emery Kathryn , Hamman Richard F.
Published: May 2005

Objective. The objectives of this study were to determine the incidence of femur fractures in Colorado children, to assess underlying causes, to determine the prevalence and predictors of associated injuries, and to identify potentially modifiable risk factors.

Methods. The study population included all Colorado residents who were aged 0 to 17 years at the time of injury between January 1, 1998, and December 31, 2001. Cases of femur fracture were ascertained using the population-based Colorado Trauma Registry and International Classification of Diseases, Ninth Revision, Clinical Modification codes 820.0 to 821.39. Associated injuries with an Abbreviated Injury Scale of 2 or higher were classified into 5 categories. Poisson regression, small area analysis, and multivariate logistic regression were used to identify predictors of femur fractures and associated injuries, respectively.

Results. During the study period, 1139 Colorado children (795 boys, 344 girls) sustained femur fractures, resulting in the incidence of 26.0 per 100000 person-years. Rates were higher in boys than in girls in all age groups (overall risk ratio: 2.19; 95% confidence interval: 1.92–2.47) but did not differ by race/ethnicity. Femur fractures that were caused by nonaccidental trauma showed more distal and combined shaft + distal pattern; their incidence did not differ by gender or race but was higher in census tracts with more single mothers and less crowded households. Associated injuries were present in 28.6% of the cases, more often in older children. Fatalities occurred only among children with associated injuries. Children who were involved in nonaccidental trauma, motor vehicle crashes, or auto-pedestrian accidents were 16 to 20 times more likely to have associated injuries than those with femur fractures as a result of a fall. In small-area analysis, the incidence of femur fractures in infants and toddlers was higher in census tracts characterized by higher proportion of Hispanics, single mothers, and more crowded households. Among children 4 to 12 years of age, the incidence was higher in census tracts with fewer single-family houses and more crowded households. Finally, the incidence of femur fractures among teenagers was higher in rural tracts and those with a higher proportion of Hispanics.

Conclusions. Femur fractures and associated injuries remain a major cause of morbidity in children. Predictors of femur fractures change with age; however, the risk is generally higher among children who live in the areas with lower socioeconomic indicators.
Relationship Between Age of Ear Piercing and Keloid Formation
Authors: Lane Joshua E. , Waller Jennifer L. , Davis Loretta S.
Published: May 2005

Objective. Keloids occur commonly after trauma to the skin, with ear piercing being a well-known inciting event. We surveyed 32 patients with keloids resulting from ear piercing, to examine a potential relationship between age of piercing and keloid formation.

Methods. A total of 32 consecutive patients completed a survey about ear-piercing and keloid formation. Fisher's exact test was used for data analysis.

Results. Fifty percent (n = 16) of surveyed patients developed a keloid after their first piercing. Twenty surveyed patients developed keloids with subsequent piercings. Those who had piercings at ≥11 years of age were more likely to develop keloids (80%) than were those who had piercings at <11 years of age (23.5%).

Conclusions. Keloids are more likely to develop when ears are pierced after age 11 than before age 11. This observation holds true for patients with a family history of keloids. Given the difficulty and cost of treating keloids, prevention remains the best approach. Patients with a family history of keloids should consider not having their ears pierced. If this is not an option, then piercing during early childhood, rather than later childhood, may be advisable. Primary care physicians and pediatricians should educate children and their parents about the risk of keloid formation.
Posttraumatic Stress Responses in Children: Awareness and Practice Among a Sample of Pediatric Emergency Care Providers
Authors: Ziegler Michael F. , Greenwald Michael H. , DeGuzman Michael A. , Simon Harold K.
Published: May 2005

Background. Research suggests that up to 4 of 5 children experience symptoms of an acute stress response (ASR) after a motor vehicle–related injury, and ∼25% will develop posttraumatic stress disorder (PTSD). The degree to which physicians recognize this problem has not been reported. Our objective was to evaluate current awareness and practices of a cohort of pediatric emergency care providers regarding posttraumatic stress in children.

Methods. Participants were identified from a list of the American Academy of Pediatrics Section on Emergency Medicine and surveyed on their awareness of ASR after motor vehicle–related injury, risk factors for developing PTSD, and practices regarding emergency department (ED) interventions. Surveys from physicians not practicing clinical emergency medicine were excluded.

Results. Of 322 surveys returned, 287 responses met inclusion criteria. Among these respondents, 198 (69%) were pediatric emergency medicine board certified or eligible and 260 (91%) practiced in a designated pediatric ED. Only 20 of 287 respondents (7%) believed that children were likely to develop symptoms of posttraumatic stress at levels previously described. Also in contrast to recent literature, 248 respondents (86%) felt that severity of injury was associated with future development of PTSD. Associated parental injury was identified accurately as a risk factor by 250 respondents (87%). Of interest, only 31 respondents (11%) were aware of any available tools to assess risk for PTSD. In addition, 56 of 287 respondents (20%) indicated that they would not use such tools in the ED, most commonly citing time and cost constraints. Finally, only 52 respondents (18%) reported giving any verbal guidance and only 9 (3%) provided any written instructions about posttraumatic stress to their patients and families.

Conclusions. Findings suggest that physicians underestimate the likely development of an ASR and PTSD in the pediatric population. At present, few physicians offer written or even verbal instruction related to the development of posttraumatic symptoms. Physician education along with a systematic approach of assessment and intervention is necessary to address the gap between underrecognition of this concern and desired clinical practice.