bluuebunny/crossref_metadata_2025 huggingface dataset:
Graphical presentation of distributions of risk in screening
Authors: Morris J K , Wald N J
Published: August 2005

Objective: The screening performance of tests involving multiple markers is usually presented visually as two Gaussian relative frequency distributions of risk, one curve relating to affected and the other to unaffected individuals. If the distribution of the underlying screening markers is approximately Gaussian, risk estimates based on the same markers will usually also be approximately Gaussian. However, this approximation sometimes fails. Here we examine the circumstances when this occurs.

Setting: A theoretical statistical analysis.

Methods: Hypothetical log Gaussian relative distributions of affected and unaffected individuals were generated for three antenatal screening markers for Down's syndrome. Log likelihood ratios were calculated for each marker value and plots of the relative frequency distributions were compared with plots of Gaussian distributions based on the means and standard deviations of these log likelihood ratios.

Results: When the standard deviations of the distributions of a perfectly Gaussian screening marker are similar in affected and unaffected individuals, the distributions of risk estimates are also approximately Gaussian. If the standard deviations differ materially, incorrectly assuming that the distributions of the risk estimates are Gaussian creates a graphical anomaly in which the distributions of risk in affected and unaffected individuals plotted on a continuous risk scale intersect in two places. This is theoretically impossible. Plotting the risk distributions empirically reveals that all individuals have an estimated risk above a specified value. For individuals with more extreme marker values, the risk estimates reverse and increase instead of continuing to decrease.

Conclusion: It is useful to check whether a Gaussian approximation for the distribution of risk estimates based on a screening marker is valid. If the value of the marker level at which risk reversal occurs lies within the set truncation limits, these may need to be reset, and a Gaussian model may be inappropriate to illustrate the risk distributions.
Neonatal screening for sickle cell disorders in Ouagadougou, Burkina Faso: a pilot study
Authors: Kafando Eléonore , Sawadogo Mamadou , Cotton Frédéric , Vertongen Fanchon , Gulbis Béatrice
Published: August 2005

Objectives: To determine the incidence of sickle cell disorders (SCDs) and the feasibility of a neonatal screening programme in Ouagadougou.

Methods: During 2000, 2003 and 2004, 2341 cord blood samples obtained in five maternity hospitals in Ouagadougou were screened for SCDs using an isoelectric focusing technique. The feasibility of a neonatal screening programme was evaluated.

Results: The incidence of SCD was 1:57; 14 neonates were homozygous for haemoglobin (Hb)S and 27 were compound heterozygotes for HbSC. Thirty-two neonates were homozygous for HbC. The incidence of the HbC trait was 1:6; incidence of the HbS trait was 1:14. A centralized laboratory for neonatal screening of SCDs was established.

Conclusions: SCDs should be considered a major public health problem in Ouagadougou. A neonatal screening programme should be implemented, but to be effective it requires strategies adapted to the local situation.
Some current issues in breast cancer screening
Authors: Duffy Stephen W
Published: August 2005

Randomized trials of mammography have demonstrated the efficacy of mammographic screening for breast cancer in terms of preventing deaths, but various issues of particular interest remain, including:

• quantification of overdiagnosis;

• evaluation of service screening outside the research setting;

• absolute benefit in terms of number needed to screen per life saved;

• which types of tumours benefit most from early detection;

• use of screening data to investigate tumour biology and natural history.

This paper describes examples of approaches to the above issues, along with some important results.
Evaluation of visual inspection with acetic acid (VIA), Lugol's iodine (VILI), cervical cytology and HPV testing as cervical screening tools in Latin America: This report refers to partial results from the LAMS (Latin AMerican Screening) study
Authors: Sarian L O , Derchain S F , Naud P , Roteli-Martins C , Longatto-Filho A , Tatti S , Branca M , Eržen M , Serpa-Hammes L , Matos J , Gontijo R C , Bragança J F , Lima T P , Maeda M Y S , Lörincz A , Dores G B , Costa S , Syrjänen S , Syrjänen K
Published: August 2005

Objectives: To assess the performance indicators of visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI) in four Latin American centres participating in the ongoing Latin AMerican Screening (LAMS) study, in settings with moderate incidence of cervical disease and with poorly to moderately well-organized cervical cancer screening.

Setting: Three Brazilian centres (São Paulo, Campinas and Porto Alegre) and one Argentine centre (Buenos Aires) recruited a total of 11,834 healthy women to undergo VIA, VILI, conventional Pap smear and Hybrid Capture II (HCII).

Methods: Women who had a positive result from any of these tests were subjected to colposcopy and biopsies (if necessary), and women with high-grade cervical intraepithelial neoplasia (CIN) were properly treated. To control for verification bias, 5% of women with normal tests were referred for colposcopy, as were 20% of HCII-negative women.

Results: Data on VIA ( n=11,834), VILI ( n=2994), conventional Pap smear ( n=10,138) and HCII ( n=4195) were available for test comparisons, calculating sensitivity, specificity, and positive and negative predictive values. Overall test positivity was 11.6% for VIA, 23.0% for VILI, 2.2% for Pap smear (LSIL threshold), 1.1% for Pap smear (HSIL threshold) and 17.1% for HCII. VIA was positive in 61.8% of the women with CIN 1, 57.0% of those with CIN 2, 35.0% of women with CIN 3 and in 21 of 28 (75%) of women with cancer. Approximately 10% of women with no detectable disease had an abnormal VIA. Regarding VILI, 83.3% of women diagnosed with CIN 1 and 62.5% of those with CIN 3 had an abnormal test. VILI failed to detect one of three cases of cancer. Both the sensitivity, specificity and positive predictive value of VIA and VILI in detecting CIN 2 or CIN 3 could be significantly improved depending on the combination with Pap smear or HCII (sensitivity up to 100.0% and specificity up to 99.8%).

Conclusions: The LAMS study failed to reproduce the performance figures obtained with VIA and VILI (as stand-alone tests) in some other settings, where the prevalence of cervical disease was higher. However, a combined use of VIA or VILI with the Pap test or HCII allowed specific detection of cervical abnormalities.
Research and policy: reflections on their relationship
Authors: Saunders Lesley
Published: August 2005

English

The main argument in this article – based on a professorial lecture given in 2004 at the Institute of Education, London – is that, for evidence-informed policy making to be more than a rhetorical ploy, there need to be more and better activities and environments that are expressly designed to be conducive to sustained interaction between researchers and policy makers. After setting out arguments in favour of the ‘rationalist ideal’ which lies behind the expectation that research should aim to influence policy making in the public sector, the author discusses some particular examples to show how the ingrained differences in culture between research and policy can be overcome, or at least mitigated.
What works to promote evidence-based practice? A cross-sector review
Authors: Walter Isabel , Nutley Sandra , Davies Huw
Published: August 2005

English

This article presents results from a systematic review of the effectiveness of different mechanisms for promoting research use across the health, social care, criminal justice and education sectors. Findings suggest that research use is enhanced by interactions between researchers and research users, and by providing a supportive context for the uptake of research or research-based practice. Strategies using multiple mechanisms to encourage research use are also often successful. More research is needed to draw firm conclusions about the effectiveness of other approaches or of combining specific strategies. Despite this, some key lessons emerge about effective methods for implementing evidence-based policy and practice (EBPP).
Partnerships between health and social care under ‘New Labour’: smoke without fire? A review of policy and evidence
Authors: Glendinning Caroline , Dowling Bernard , Powell Martin
Published: August 2005

English

Since coming to power in 1997, the New Labour government has placed heavy emphasis on partnerships – between organisations, services and professionals – as the preferred means of delivering coordinated health and social care services. This article aims to provide a critical overview and synthesis of both the discourse and the practice associated with this policy imperative. First, it summarises the range of policies that have promoted health and social care partnerships since 1997. It then discusses the definitions and rationales that have been proposed for these partnerships and some of the challenges involved in evaluating their ‘success’. This is followed by a critical examination of the available evidence for the ‘success’ of recent partnerships between the health and social care sectors. The article concludes with some reflections on the evidence that partnerships constitute either an effective method of service planning and delivery or a distinctive ‘Third Way’ mode of governance in relation to these particular public sector services.
The Retroreflective Array as a New Optical Element in Atomic Absorption Spectroscopy
Authors: Hsieh You-Zung , Johnson Eric T. , Sacks Richard D. , Morris Michael D.
Published: August 2005

A retroreflective array is used in the phase conjugate configuration to compensate for refractive noise in flame atomic absorption spectroscopy. The system is shown to provide reductions in refractive noise by a factor of five to seven, using the Mn 403.1-nm line. The compensation provides 10–50% increase in sensitivity in noisy flames.
Measurement Methods for Atomic Fluorescence and Laser-Enhanced Ionization Spectrometries with a Copper-Vapor Pumped Dye Laser
Authors: Rutledge M. J. , Tremblay M. E. , Winefordner J. D.
Published: August 2005

Several correction methods for several types of spectral and electrical interferences with a copper-vapor pumped dye laser system are presented. A tunable pulsed dye laser pumped with a copper vapor laser was used to excite the atomic fluorescence of Li, Na, In, and Fe and the atomic ionization of Li, In, and Fe. Correction methods used involved either modulation of the pulsed laser output and subsequent subtraction of noise or electrical bandwidth limitation of the signals to enhance the signal to high-frequency laser noise ratio. These methods are shown to provide a significant reduction in high-frequency interference, a major noise source with this type of pump laser. These three correction methods are shown to provide a significant improvement in the detection power of both laser-enhanced ionization and fluorescence methods. Limits of detection are presented for each correction method.
Sampling and Analytical Characteristics of an Electrically Vaporized Thin-Film Plasma in an External Magnetic Field
Authors: Albers D. , Tisack M. , Sacks R.
Published: August 2005

A magnetic field of a few kilogauss oriented normal to the electric field in the plasma generated by a capacitive discharge through a thin silver film is used to obtain an ExB drift motion of the plasma. The plasma current is used to generate the magnetic field in a coil surrounding the plasma. The plasma drift motion is used to confine the plasma to the region near the surface of the plastic substrate which originally supported the thin film and the powder or solution residue sample. The result is greater interaction of the plasma with the sample, as illustrated by more rapid vaporization of the sample, reduced effects of particle size on analyte radiation intensity, and significantly improved shot-to-shot reproducibility. While analyte line intensities frequently are lower in the ExB plasma, line-to-background intensity ratios may be greater if an optical mask is used to block radiation near the substrate surface.
FT-IR Photoacoustic Spectra of Some Solid Organometallic Complexes of Chromium, Manganese, Rhenium, and Iron
Authors: Butler Ian S. , Xu Zhen H. , Werbowyj Rita S. , St.-Germain Francois
Published: August 2005

FT-IR photoacoustic spectra have been measured at room temperature in the near- and mid-IR range (4700–500 cm−1) for the solid organometallic compounds: CpM(CO)3 (Cp = η5-C5H5; M = Mn, Re); CpMn(CO)2(CS); [CpFe(CO)2]2; [CpMo(CO)3]2; BzCr(CO)3 (Bz = η6-C6H6); BzCr(CO)2(CS); M2(CO)10 (M = Mn, Re); and Fe2(CO)9. Vibrational assignments have been made for the fundamentals and the binary overtone and combination regions. It is much simpler to obtain data for the 4700–3500 cm−1 near-IR region with the use of PA rather than transmission IR spectroscopy with alkali halide disks since there are no problems with scattering or internal multiple reflectance. FT-IR photoacoustic spectroscopy is a convenient, nondestructive analytical method that should prove extremely useful to organometallic chemists for the rapid identification of their compounds in the solid state.
Computer-Assisted Spectroscopic Analysis Using Orthonormalized Reference Spectra. Part II: Application to the Identification of Pure Compounds
Authors: Nyden Marc R. , Pallister John E. , Sparks Daniel T. , Salari Amid
Published: August 2005

A new method for the identification of substances from their corresponding infrared spectrum is described. This method, which makes use of an orthonormal reference library, is compared with two established methods which use metrics based on the scalar products and absolute differences between the unidentified and reference spectra. The most notable advantage of the orthonormal method is that it is capable of identifying the components in mixtures which result from incomplete chromatographic separations.
Pump/Probe Spectroscopy by Asynchronous Optical Sampling
Authors: Elzinga Paul A. , Lytle Fred E. , Jian Yanan , King Galen B. , Laurendeau Normand M.
Published: August 2005

We report the first results from a new pump/probe technique called asynchronous optical sampling (ASOPS). The method employs a mode-locked, frequency-doubled Nd:YAG laser operating at a repetition rate of 81.5970000 MHz as the pump laser, and a synchronously pumped dye laser (R6G) operating at a repetition rate of 81.5870000 MHz as the probe laser system. The 10-kHz beat frequency produces a repetitive relative phase walk-out of the pump and probe pulses which replaces the optical delay line used in conventional instruments. Studies of rhodamine B in methanol demonstrate that the instrument response is proportional to pump power, probe power, and sample absorptance. The fluorescence lifetime of 4 × 10−5 M rhodamine B is determined to be 2.3 ns.
Interferometric Determination of the Refractive Index of Liquids by Difference IR Spectroscopy
Authors: Heise H. M.
Published: August 2005

A simple interferometric determination for the refractive index of liquids in the infrared is presented. The transmittance spectra of the liquid sample are recorded with two cells. One cell is assembled with a window material of high refractive index, producing interference fringes from multiple reflections (Fabry-Perot etalon); the other cell yields negligible interference as it is constructed from window material with a refractive index matched to that of the sample. By absorbance subtraction it is possible to eliminate most of the absorbance features, and the resulting channel spectrum can be used for the refractive index determination without the use of iterations and Kramers-Kronig transformation. The limitations are given by a theoretical consideration for Lorentzian band shapes, and two experimental examples are presented.
Correlation of Crystal Morphology and Structure Using a Modified X-Ray Film Technique
Authors: Musselman Ronald L. , Schneider Annegret A. G.
Published: August 2005

A convenient technique for the determination of the orientation of a solid-state molecule with respect to its crystalline morphology is presented. The process is especially suitable for spectroscopists wishing to orient crystals in preparation for polarized spectroscopy. Correlation of reciprocal axes with the crystal faces is accomplished by pinholes through a 0-level Weissenberg x-ray diffraction photograph, which allows assignment of spindle angles to lateral positions on the film. The correlation is extended to ORTEP drawings where a scaled-down crystal morphology is included in a standard crystal structure plot, enabling a clear picture of molecular orientations within a crystal. Viewing normal to actual crystal faces allows determination of molecular projections onto desired faces for alignment prior to polarized spectroscopy.
Freeze-Drying Fourier Transform Infrared Attenuated Total Reflection Spectroscopy of Surface Adsorbed Layers. Hydration of Adenosine-5'-Phosphoric Acid
Authors: BăDilescu Simona , Sandorfy Camille
Published: August 2005

A new methodology, suitable for spectral measurements on polar, biologically important molecules, has been developed. The capability of the thallium bromide iodide ATR crystal to adsorb water has been examined and the hydrated crystal surface was used as a substrate for the adsorbed molecules. Diagnostic bands for adsorbed water are reported. A freeze-drying procedure was used to adsorb adenosine-5'-phosphate molecules on the hydrated ATR crystal, and FT-IR spectra of the system were recorded. Different hydrated species of adenosine-5'-monophosphate adsorbed on a water-screened ATR crystal have been observed. The broad bands at 935, 950, and 970 cm−1 are assigned to phosphate groups adsorbed on the thallium bromide-iodide crystal screened by low, medium, and high water coverage, respectively. The high sensitivity of the method is emphasized. The proposed ATR method may be useful for the study of membrane-associated phenomena and models of real-life biological systems with a low solute concentration.
Correlation of Adsorption/Desorption Processes on Pigment Surfaces
Authors: McKenzie Martin T.
Published: August 2005

An approach utilizing diffuse reflectance FT-IR is described whereby the desorption of carbon monoxide from a pigment surface is correlated with the adsorption of two organo-functional silane materials, 3-chloropropylsilane (CPS) and 3-methacryloxypropyltrimethoxysilane (MPS). Correlation of observables from a single set of measurements provides an efficient means to determine the results of adsorption as a function of adsorbate structure and treatment solution concentration.
Differential Dual-Beam Thermal Lensing Spectrometry: Determination of Lanthanides
Authors: Berthoud Thierry , Delorme Nathalie
Published: August 2005

This paper describes a differential dual-beam thermal lensing setup which involves two continuous lasers and two cells placed one just behind the other on the beampath. A tunable excitation laser creates the thermal lensing effect in the two cells, whereas the (He-Ne) laser, colinear to the excitation beam, probes the variation of the index of refraction due to the absorption in each cell. The differential response is achieved by placing the solvent in the first cell and the solvent with analyte in the second cell. The positions of the two cuvettes are optimized in order to maximize differential thermal lensing effect detection. This differential instrument allows compensation of 95–98% of the thermal lensing solvent effect. Thermal lensing spectra of two lanthanide ions (Nd3+, Pr3+), both in no complexing solution (HClO4) and in carbonate medium, are discussed. Analytical determinations of these elements with detection limits in the range of 10−6 mole per liter are observed.
Determination of Azo Dyes by Resonance-Enhanced Raman Spectroscopy
Authors: Womack James D. , Vickers Thomas J. , Mann Charles K.
Published: August 2005

An examination of the feasibility of using Raman spectroscopy to determine strongly absorbing solutes has been made, with the use of the azo dyes Eriochrome Blue SE, Eriochrome Black T, and Eriochrome Blue Black B as target compounds. These compounds are representative of the large class of dyes which are not easily determined because of their low volatility. They also are examples of compounds which absorb strongly, causing pronounced nonlinear behavior when attempts are made to use resonance-enhanced bands to improve analytical limits of detection, and which produce intense fluorescence which interferes with Raman bands when the strong 514-nm band of the argon-ion laser is used for excitation. The efficacy of internal standard correction for eliminating the effects of self-reversal and variation in intensity of the exciting beam is demonstrated. Limits of detection for the three compounds listed above are 99 ppb, 340 ppb, and 1.5 ppm, respectively.
What Has Marketing Learned from Richard Johnson?
Authors: Huber Joel
Published: August 2005

Richard Johnson has had a remarkable career in an era that integrated the use of computers and mathematical models into marketing research. This article summarizes his contributions in terms of theoretical advances, practical solutions, and the development of a culture that links the academic and practitioner worlds. The author speculates on the personality traits that made Johnson so successful and ways that his critical roles can be fulfilled by others in the future.
When Two Rights Make a Wrong: Searching Too Much in Ordered Environments
Authors: Diehl Kristin
Published: August 2005

In electronic shopping, screening tools are used to sort through many options, assess their fit with a consumer's utility function, and recommend options in a list ordered from predicted best to worst. When the most promising options are at the beginning of the list, even seemingly advantageous factors (e.g., lower search cost, greater selection) that prompt consideration of more options degrade choice quality by (1) lowering the average quality of considered options and (2) lowering customers' selectivity in focusing attention on the more mediocre rather than the better options from the actively considered set. Study 1 shows that lowering search costs diminishes choice quality in an ordered environment. Study 2 shows that presenting consumers with the top 50 rather than the top 15 recommendations has the same effect. Study 3 shows that greater accuracy motivation in combination with lower search cost diminishes choice quality because consumers are encouraged to consider a wider range of options (lower-quality consideration sets), which ultimately leads to worse choices.
Strategic Fit in Industrial Alliances: An Empirical Test of Governance Value Analysis
Authors: Ghosh Mrinal , John George
Published: August 2005

The exclusion of firm-specific considerations in the standard (economizing calculus) approach to buyer–supplier ties makes the large variations in the types of contracts used within the same industry unexplainable. This article tests Ghosh and John's (1999) strategizing calculus model that purports to close this gap. The core organizing principle of this model is a three-way fit among firm resources, investments, and governance that yields the highest net receipts. From this principle, the authors derive predictions and test them using data from 193 original equipment manufacturers that engage independent component suppliers. The data show that investments must be aligned with more complete contract terms (e.g., fixed prices, “hard” designs) to yield cost reduction outcomes for all firms. However, investments must be aligned with more incomplete contracts (e.g., cost-plus prices, “soft” designs) to yield end-product enhancement outcomes, but only for firms with relatively small downstream market margins. Firms with larger downstream market margins find that the previous alignment reduces end-product enhancements. These results are robust to checks for common method bias and alternative estimation procedures. The authors discuss practical guidelines for the desired tightness of supplier contract terms from the three-way fit principle.
Schnelle Entfernungsmessung für Laserscanner (Fast Distance Measurement for Laser Scanning)
Authors: Wölfelschneider Harald , Blug Andreas , Baulig Claudia , Höfler Heinrich
Published: August 2005

Der vorliegende Beitrag beschreibt das Prinzip der Entfernungsmessung mittels moduliertem Laserstrahl und Phasenmessung. Die wichtigsten Einflussfaktoren wie Rauschen, Modenstruktur des Lasers und Übersprechen sind weitgehend quantifiziert und mögliche Gegenmaßnahmen erläutert. Das realisierte Messmodul ist in der Lage, mit einer Messrate bis zu einem MHz Entfernungen im Zehn-Meter-Bereich zu messen. Ergebnisse sind anhand der Applikation Lichtraumprofilmessung gezeigt.
Low-dose GH improves exercise capacity in adults with GH deficiency: effects of a 22-month placebo-controlled, crossover trial
Authors: Bollerslev Jens , Hallén Jostein , Fougner Kristian J , Jørgensen Anders Palmstrøm , Kristo Cybele , Fagertun Hans , Gudmundsen Ola , Burman Pia , Schreiner Thomas
Published: August 2005

Fifty-five patients with adult-onset GH deficiency (mean age, 49 years) were enrolled in a placebo-controlled, crossover study to investigate the effects of GH therapy on exercise capacity, body composition, and quality of life (QOL). GH and placebo were administered for 9 months each, separated by a 4-month washout period. GH therapy was individually dosed to obtain an IGF-I concentration within the normal range for age and sex. The final mean daily dose of GH was 1.2 IU/day for men and 1.8 IU/day for women. Mean IGF-I concentration at baseline was higher in men than in women (95±33 vs 68±41 μg/l respectively; P < 0.04) and increased to a similar level on GH therapy. Body fat mass was reduced by 1.9±2.9 kg and lean body mass was increased by 1.8±2.8 kg (P = 0.0001 for each) with GH treatment. Total and low-density cholesterol levels decreased. Absolute maximal oxygen uptake increased by 6% (P = 0.01), relative to body weight by 9% (P = 0.004), and there was a trend toward increased endurance performance by 7% (P = 0.07). There were no significant effects on QOL. In conclusion, treatment with a low, physiologic dose of GH produced positive effects on body composition and lipids and improved exercise capacity, likely to be of clinical relevance. No changes in QOL were seen, possibly because of a good QOL at baseline.
A new heterozygous mutation of the FOXL2 gene is associated with a large ovarian cyst and ovarian dysfunction in an adolescent girl with blepharophimosis/ptosis/epicanthus inversus syndrome
Authors: Raile K , Stobbe H , Tröbs R B , Kiess W , Pfäffle R
Published: August 2005

Blepharophimosis/ptosis/epicanthus inversus syndrome (BPES), an autosomal dominant syndrome in which eyelid malformation is associated with (type I BPES) or without premature ovarian failure (type II BPES). Mutations of a putative winged helix/forkhead transcription factor FOXL2 account for both types of BPES. We report on a 16-year-old adolescent girl with blepharophimosis and ptosis. Subsequently she developed oligomenorrhea, secondary amenorrhea for 6 months, and an extremely large cyst of one ovary. The cyst contained 8 l of cyst fluid and histopathology displayed a large corpus luteum cyst. Following laparotomy, gonadotropin levels were elevated (LH 17.2 U/l, FSH 29.4 U/l) and estradiol levels decreased (67 pmol/l). Because of clinical aspects of BPES and abnormal ovarian function we suspected a mutation of herFOXL2gene and found a new in-frame mutation (904_939dup36) on one allele, leading to a 12 alanine expansion within the polyalanine domain. We conclude that theFOXL2mutation 904_939dup36 may account not only for blepharophimosis and ptosis but also for ovarian dysfunction and growth of the large corpus luteum cyst. In contrast to knownFOXL2mutations with polyalanine expansions and association with BPES type II, clinical aspects of our girl may indicate some degree of ovarian dysfunction that might finally lead to BPES type I with premature ovarian failure.
The occurrence of permanent thyroid failure in patients with subclinical postpartum thyroiditis
Authors: Azizi F
Published: August 2005

Objective: The long-term effect of the subclinical form of postpartum thyroid dysfunction (PPTD) has not been well established. This study was conducted to evaluate the outcome of permanent hypothyroidism in a large cohort of women with PPTD.

Design and methods: Of 213 women with PPTD, 172 (81%) returned for follow-up. There were 27 (16%) with subclinical (group 1) and 145 (84%) with overt hypothyroidism (group 2). They were all treated with levothyroxine for 23 ± 16 months and followed-up for thyroid function after thyroxine (T4) withdrawal.

Results: In group 1, the time of occurrence of PPTD was longer, serum T4 was higher and TSH was lower than in group 2. After T4 withdrawal, 59 and 64% of patients became hypothyroid in groups 1 and 2 respectively; however, serum TSH was increased in group 2 as compared with group 1 (29.7 ± 8.4 vs 16.4 ± 15.4 mU/l, P < 0.002). The duration of euthyroidism, serum free T4 and triiodothyronine indices and thyroperoxidase antibodies were not significantly different between the two groups.

Conclusion: It was concluded that a high percentage of patients with the subclinical form of PPTD proceed to permanent thyroid failure. The timely recognition of mild to severe cases of PPTD is important for the improvement of life for mothers and infants.
Decreased circulating levels of active ghrelin are associated with increased oxidative stress in obese subjects
Authors: Suematsu Mina , Katsuki Akira , Sumida Yasuhiro , Gabazza Esteban C , Murashima Shuichi , Matsumoto Kazutaka , Kitagawa Nagako , Akatsuka Hajime , Hori Yasuko , Nakatani Kaname , Togashi Kenji , Yano Yutaka , Adachi Yukihiko
Published: August 2005

Objective: To investigate the relationship between active ghrelin and oxidative stress in obese subjects.

Design: We measured the plasma levels of free 8-epi-prostaglandin F2α (8-epi-PGF2α, a reliable and systemic marker of oxidative stress) and the active form of ghrelin in 17 obese and 17 normal subjects. The biologically active forms of ghrelin were measured using a commercially available radio-immunoassay kit and free 8-epi-PGF2α was measured using an enzyme immunoassay kit.

Results: The circulating level of active ghrelin was significantly decreased (20.4 ± 2.6 vs 40.9 ± 3.9 fmol/ml, P < 0.01) while that of 8-epi-PGF2α was significantly increased (61.5 ± 9.6 vs 17.3 ± 3.4 pg/ml, P < 0.01) in obese subjects compared with normal subjects. The plasma levels of active ghrelin and 8-epi-PGF2α were significantly correlated in obese (r = −0.507, P < 0.05) and in all (r = −0.577, P < 0.01) subjects. Multivariate analysis showed that the plasma levels of active ghrelin and 8-epi-PGF2α were significantly and independently correlated in all subjects (F = 7.888, P < 0.01).

Conclusions: There is an inverse correlation between circulating levels of active ghrelin and oxidative stress in obesity. Low circulating levels of active ghrelin may enhance oxidative stress and the process of atherosclerosis in obese subjects.
The metabolism of isoforms of human adiponectin: studies in human subjects and in experimental animals
Authors: Peake Philip W , Kriketos Adamandia D , Campbell Lesley V , Shen Yvonne , Charlesworth John A
Published: August 2005

Objective: Little is known of the metabolism of different isoforms of adiponectin. We therefore (a) characterised the size distribution of human adiponectin in relation to gender, body composition and following a challenge with a fat meal or oral glucose in humans, and (b) studied the metabolism of isoforms of human adiponectin in rabbits.

Method: Electrophoresis, blotting and chromatography were used to characterise human adiponectin in 36 healthy subjects, including 15 with at least two first-degree relatives with type 2 diabetes, before and after consumption of a fatty meal or glucose. The metabolism of column-fractionated human adiponectin was studied in rabbits, some of which were coinjected with insulin.

Results: Females had a higher proportion of high molecular weight (HMW) and hexameric adiponectin (P= 0.002 and 0.004 respectively), and a lower proportion of trimers (P< 0.0001) than males. Females also showed a strong negative relationship between body fat measures and the proportion of HMW adiponectin. There were no differences in isoforms between insulin-resistant and -sensitive subjects, or following oral glucose or a fat meal. Adiponectin in rabbits had an extravascular/intravascular ratio of 0.71, and a half-life (T1/2) of 14.3 h. Metabolism was not influenced by insulin or reduction of sulphydryl bonds. HMW and trimeric isoforms had a significantly different T1/2 of 13.0 and 17.5 h respectively (P< 0.05), and these isoforms did not interconvertin vivo.

Conclusions: Human adiponectin is present as trimers, hexamers and HMW forms. Females had a higher proportion and absolute amount of HMW species compared with males, and female, but not male, subjects showed a strong negative relationship between measures of body fat, and the proportion of HMW species. These isoforms did not respond to challenge in man with a fatty meal or oral glucose, and in the rabbit, to injected insulin. HMW adiponectin was more rapidly metabolised than the trimeric form, but both were stablein vivo, and did not interconvert. We conclude that human adiponectin is much longer-lived than is the case with other hormones, a finding with positive implications for the potential to supplement levels of adiponectin in man.
Hypoxia-induced leptin production in human trophoblasts does not protect from apoptosis
Authors: Meißner Udo , Spranger Robert , Lehner Manfed , Allabauer Ida , Rascher Wolfgang , Dötsch Jörg
Published: August 2005

Objective: Theob-gene product, leptin, is an important regulator of placental and fetal development during pregnancy. Leptin, being induced by hypoxia in the placenta, is a known pro-apoptotic molecule in adipose tissue but is also known to inhibit apoptosis in other tissues like neuroblastoma cells. Based on these findings, we investigated if leptin has a pro- or anti-apoptotic effect on a trophoblastic cell line (JAr cells) in the presence or absence of oxygen.

Methods and results: Measurement of leptin in the supernatant by using ELISA showed hypoxia-induced leptin production in JAr cellsin vitro. This could be confirmed by a leptin-specific RT-PCR. By analyzing leptin and/or hypoxia exposed cells with FACS cytometry we found that JAr cells can cope with hypoxia down to oxygen tensions of 1%. At this level, only a small number of cells underwent apoptosis. Interestingly, leptin added to the culture medium in high concentrations was not able to interfere with the rate of proliferation or apoptosis in these cells independent of the oxygen tension. Finally, an anti-caspase-3 and anti-caspase-9 Western blot was performed. Again, no difference in the expression of caspase-3 and -9 under the conditions tested was seen.

Conclusions: These results show that leptin, produced by placental cells after hypoxiain vitro, has no influence on the rate of proliferation of these cells. Furthermore, it does not influence apoptotic pathways in the trophoblastic cell line tested under hypoxic and non-hypoxic conditions.
Extended clinical phenotype, endocrine investigations and functional studies of a loss-of-function mutation A150V in the thyroid hormone specific transporter MCT8
Authors: Biebermann Heike , Ambrugger Petra , Tarnow Patrick , von Moers Arpad , Schweizer Ulrich , Grueters Annette
Published: August 2005

Objective: Thyroid hormones, besides having other functions, are known to be essential for the development of the human brain. Recently the monocarboxylate transporter 8 (MCT8) was identified as a thyroid hormone transporter which is expressed in different regions of the human brain. Here we describe in detail the clinical and biochemical features in response to thyroid hormone administration of a boy carrying an MCT8 mutation (A150V) in the second transmembrane domain.

Methods: To study the functional impact of the mutation we performed triiodothyronine (T3) uptake, immunofluorescence and dimerization studies.

Results: Thyroid hormone (l-thyroxine (LT4) and LT3) administration did not result in any significant clinical changes; however, with high doses of LT4, alone or in combination with T3, TSH suppression was achieved. We could show a robust uptake of 125I-T3 for wild type (WT) MCT8, whereas no specific uptake could be detected for the mutant A150V. Subcellular localization of WT and mutant MCT8 revealed a strong cell surface expression for the WT MCT8, in contrast to A150V, which is mostly retained intracellularly with only weak cell surface expression. We could also demonstrate for the first time that WT MCT8 as well as the mutant are able to form multimers.

Conclusion: Our findings open a wide field of possible interaction within the central nervous system and will help to understand the crucial role of MCT8 in early fetal brain development.
Glucagon inhibits ghrelin secretion in humans
Authors: Arafat M A , Otto B , Rochlitz H , Tschöp M , Bähr V , Möhlig M , Diederich S , Spranger J , Pfeiffer A F H
Published: August 2005

Objective: It is well known that i.m. glucagon administration stimulates GH and cortisol release in humans, although the mechanisms are unclear. These effects are similar to those described for ghrelin on somatotroph and corticotroph function. The aim of the present study was to investigate the role of ghrelin in mediating the stimulatory effects of glucagon and to evaluate the effect of glucagon on ghrelin secretion.

Design and methods: We studied the endocrine and metabolic response to i.m. glucagon administration in 24 subjects (14 men, 10 women; age 19–65 years; body mass index, 25.3 ± 1 kg/m2), who were shown to have an intact anterior pituitary function as evaluated before enclosure.

Results: Serum ghrelin concentrations fell significantly at 30, 60, 120 and 180 min after glucagon administration (means ± s.e.m.; baseline, 377.9 ± 34.5 pg/ml; nadir, 294.6 ± 28.3 pg/ml (60 min); P < 0.01). Conversely, i.m. glucagon elicited an increase in GH (baseline, 1.5 ± 0.4 μg/l; peak, 14.2 ± 2.7 μg/l (180 min); P < 0.01) and cortisol concentrations (baseline, 452.6 ± 35.2 nmol/l; peak, 622.1 ± 44 nmol/l (180 min); P < 0.01). The changes in ghrelin concentration at both 120 and 180 min were still significant after correction for glucose and insulin (P < 0.05).

Conclusions: We show that i.m. glucagon decreases ghrelin significantly. Therefore, the already known stimulatory effects of i.m. glucagon on cortisol and GH are not mediated by a change in ghrelin concentrations. The mechanisms underlying the ghrelin suppression after i.m. glucagon are unlikely to include glucose or insulin variations and need to be further elucidated.
Xenotransplantation of porcine neonatal islets of Langerhans and Sertoli cells: a 4-year study
Authors: Valdés-González Rafael A , Dorantes Luis M , Garibay G Nayely , Bracho-Blanchet Eduardo , Mendez Armando J , Dávila-Pérez Roberto , Elliott Robert B , Terán Luis , White David J G
Published: August 2005

Objective: Porcine islets of Langerhans for xenotransplantation into humans have been proposed as a solution to the shortage of human donors. Rejection is one of the main constraints. This study presents the results of a clinical trial using a novel method for transplanting and immunoprotecting porcine islets in type 1 diabetic patients.

Design: A 4-year follow up of a clinical trial involving 12 patients, with no immunosuppressive drugs at any point. Eleven age matched untransplanted diabetics served as controls.

Methods: We have developed a procedure for protecting neonatal porcine islets by combining them with Sertoli cells and placing them in a novel subcutaneous autologous collagen-covered device.

Results: In the patients in the treatment group, no complications arose and no porcine endogenous retrovirus infection was detected. Half of the patients showed a significant reduction in insulin requirements compared with both their pre transplant levels and controls, and this reduction was maintained for up to 4 years. Two patients became insulin-independent for several months. Porcine insulin was detected in three patients’ sera following glucose stimulation up to 4 years post transplant. Three years post transplant, one of four devices was removed from four patients, and the presence of insulin-positive cells in the transplant was demonstrated by immunohistology in all 4 patients.

Conclusions: Long-term cell survival with concurrent positive effects on metabolic control are possible by this technique.
Inhibition of pituitary type 2 deiodinase by reverse triiodothyronine does not alter thyroxine-induced inhibition of thyrotropin secretion in hypothyroid rats
Authors: Cettour-Rose P , Visser T J , Burger A G , Rohner-Jeanrenaud F
Published: August 2005

Objectives: Intrapituitary triiodothyronine (T3) production plays a pivotal role in the control of TSH secretion. Its production is increased in the presence of decreased serum thyroxine (T4) concentrations and the enzyme responsible, deiodinase type 2 (D2), is highest in hypothyroidism. In order to document the role of this enzyme in adult rats we developed an experimental model that inhibited this enzyme using the specific inhibitor, reverse T3 (rT3).

Methods: Hypothyroidism was induced with propylthiouracil (PTU; 0.025 g/l in drinking water) which in addition blocked deiodinase type 1 (D1) activity, responsible for the rapid clearance of rT3 in vivo. During the last 7 days of the experiment, the hypothyroid rats were injected (s.c.) for 4 days with 0.4 or 0.8 nmol T4 per 100 g body weight (bw) per day. For the last 3 days, the same amount of T4 was infused via s.c. minipumps. In additional groups, 25 nmol rT3/100 g bw per day were added to the 3-day infusion of T4.

Results: Infusion of 0.4 nmol T4/100 g bw per day did not affect the high serum TSH levels, 0.8 nmol T4/100 g bw per day decreased them to 57% of the hypothyroid values. The infusions of rT3 inhibited D2 activity in all organs where it was measured: the pituitary, brain cortex and brown adipose tissue (BAT). In the pituitary, the activity was 27%, to less than 15% of the activity in hypothyroidism. Despite that, serum TSH levels did not increase, serum T4 concentrations did not change and the changes in serum T3 were minimal.

Conclusions: We conclude that in partly hypothyroid rats, a 3-day inhibition of D2 activity, without concomitant change in serum T4 and minimal changes in serum T3 levels, is not able to upregulate TSH secretion and we postulate that this may be a reflection of absent or only minimal changes in circulating T3 concentrations.
The threshold of bone mineral density for vertebral fractures in female patients with primary hyperparathyroidism
Authors: Kaji Hiroshi , Yamauchi Mika , Chihara Kazuo , Sugimoto Toshitsugu
Published: August 2005

Background and objective: Primary hyperparathyroidism (pHPT) is one of the causal diseases that induce secondary osteoporosis. Although patients with pHPT have reduced bone mineral density (BMD) especially at the cortical bone, there have been controversies about risk of fracture. Moreover, no reports have been available about the threshold of BMD for fractures in pHPT patients.

Methods: BMD values were measured by dual-energy x-ray absorptiometry at lumbar spine, femoral neck and distal one third of radius. Various indices were compared in 116 female pHPT patients and 716 control subjects. Moreover, we analyzed relationship between the cut-off values of BMD and the prevalence of vertebral fractures in pHPT and control subjects.

Results: The prevalence of subjects with vertebral fractures was lower in pHPT patients, compared with that of control subjects. Age and body height were significantly higher and lower in pHPT women with vertebral fractures, respectively. Lumbar spine BMD was significantly lower in pHPT women with vertebral fractures, presumably due to their increased age. There were no differences in femoral neck and radius BMD or in bone metabolic indices between pHPT women with and without vertebral fractures. On the other hand, age-matched BMD was not significantly different between both groups at any measured site. Cut-off values of BMD at lumbar spine and femoral neck were lower in postmenopausal pHPT patients, compared with those of the postmenopausal control group. Moreover, cut-off values of BMD at radius was much lower in postmenopausal pHPT patients, compared with those of the postmenopausal control group (pHPT vs control (g/cm2): 0.670 vs 0.706 at lumbar spine; 0.549 vs 0.570 at femoral; 0.394 vs 0.474 at radius). Sensitivity and specificity of vertebral fractures was lower in pHPT patients, compared with those in control group.

Conclusions: The present cross-sectional study demonstrated that thresholds of BMD for vertebral fractures were lower especially at radial bone in female patients with pHPT, compared with those in the control group.
Auxological and endocrine phenotype in a population-based cohort of patients with PROP1 gene defects
Authors: Lebl Jan , Vosáhlo Jan , Pfaeffle Roland W , Stobbe Heike , Černá Jana , Novotná Dana , Zapletalová Jiřina , Kalvachová Božena , Hána Václav , Weiss Vladimír , Blum Werner F
Published: August 2005

Objective: Multiple pituitary hormone deficiency (MPHD) may result from defects of transcription factors that govern early pituitary development. We aimed to establish the prevalence of HESX1, PROP1, and POU1F1 gene defects in a population-based cohort of patients with MPHD and to analyse the phenotype of affected individuals.

Design and methods: Genomic analysis was carried out on 74 children and adults with MPHD from the Czech Republic (including four sibling pairs). Phenotypic data were collected from medical records and referring physicians.

Results: One patient carried a heterozygous mutation of POU1F1 (71C > T), and 18 patients (including three sibling pairs) had a PROP1 mutation (genotypes 150delA/301delGA/9/, 301delGA/301-delGA/8/, or 301delGA/349T > A/1/). A detailed longitudinal phenotypic analysis was performed for patients with PROP1 mutations (n = 17). The mean ( ±s.d.) birth length SDS of these patients (0.12 ± 0.76) was lower than expected based on their mean ( ±s.d.) birth weight SDS (0.63 ± 1.27; P = 0.01). Parental heights were normal. The patients’ mean ( ±s.d.) height SDS declined to −1.5 ± 0.9, −3.6 ± 1.3 and −4.1 ± 1.2 at 1.5, 3 and 5 years of age, respectively. GH therapy, initiated at 6.8 ± 3.2 years of age (mean dose: 0.022 mg/kg per day), led to substantial growth acceleration in all patients. Mean adult height (n = 7) was normal when adjusted for mid-parental height. ACTH deficiency developed in two out of seven young adult patients.

Conclusions: PROP1 defects are a prevalent cause of MPHD. We suggest that testing for PROP1 mutations in patients with MPHD might become standard practice in order to predict risk of additional pituitary hormone deficiencies.
The Sacred and Profane in Islamic Cordoba
Authors: Safran Janina M
Published: August 2005

This article investigates the sacred and profane in Islamic Cordoba in the ninth and tenth centuries of the Common Era to develop a distinct perspective on Muslim communal identity in al-Andalus (Islamic Spain and Portugal), and as an inquiry into how the definition of the sacred and profane in an Islamic city may be informed by, or speak to, the context of a multi-confessional society. The study approaches the sacred as a social construct with social meaning, and thus directs our view to the mundane dimensions of the sacred.