bluuebunny/crossref_metadata_2025 huggingface dataset:
Progress report on the continent ileostomy
Authors: Kock Nils G. , Myrvold Helge E. , Nilsson Lars O.
Published: May 2006

In this paper, our 11 years of experience with the continent ileostomy is reported. Follow‐up was conducted in 280 patients with a continent ileostomy, and the results were analyzed. There was a 2.5% operative mortality rate overall, but in the last 118 consecutive patients, no operative deaths occurred. The incidence of early postoperative complications was 17% overall, and 27% in the group of patients with Crohn's disease. After modification of the operative technique, the incidence of spontaneous nipple valve desinvagination has decreased and the incidence of revisional surgery because of malfunction of the nipple valve has been reduced from 54% to 32%. Thirteen reservoirs have been removed, 5 inpatients with ulcerative colitis (2%) and 8 in patients with Crohn's disease (16%). Recurrence of Crohn's disease has occurred in 17 of 49 patients. The recurrences were confined to the ileal segment proximal to the reservoir in 6 patients, to the reservoir only in 5 patients, and to both the reservoir and the distal ileum in 6 patients. In 14 of these patients, surgical removal of diseased gut has been performed. There were 257 patients left for evaluation of the functional results. Of 29 patients from the early series without a nipple valve, 25 never used ileostomy appliances. Of 228 patients with a nipple valve, 221 (97%) were continent. The continent ileostomy procedure previously has been afflicted with high early and late complication rates. With growing experience and the introduction of methodologic modifications, the incidence of complications has been markedly reduced and, in most patients, complete continence has been achieved.
Autografts of normal and hyperplastic human parathyroid: Experience in eleven patients with immunoassay monitoring of function in seven
Authors: Raaf John H. , Samaan Naguib , Hickey Robert C.
Published: May 2006

Parathyroid autografts were implanted in 11 patients at this institution. Four patients had total or subtotal parathyroidectomy and implantation for parathyroid hyperplasia or adenoma, while 7 had one or more parathyroids removed and implanted during total thyroidectomy for carcinoma of the thyroid. Hyperplastic parathyroid was implanted in 4 instances and normal parathyroid in 7. Recurrent hyperparathyroidism occurred in 1 patient with an implanted adenoma who was returned to a normocalcemic state by partial reexcision (“titration”) of the implanted tissue.

All implants were placed in muscle pockets, a single site being used for patients receiving normal parathyroid tissue, and multiple sites for patients receiving hyperplastic glands. Those patients receiving forearm implants were followed up by serial parathyroid hormone determinations in venous blood drawn from both arms. In all cases, elevated levels were found on the implanted side, as compared to the contralateral control side.
Progress in transfusion therapy and treatment of bleeding problems in aortic aneurysm surgery
Authors: Worthington Marion M.
Published: May 2006

Blood transfusion for extensive cardiovascular procedures differs from one center to another depending on the local donor supply and the regional philosophy of efficient utilization. Our initial experience was obtained with the exclusive use of whole blood, no other products being available. Some centers still rely heavily on this, or on modified whole blood. Others use a variable number of units of whole blood, followed by specific hemocomponents that may be limited in supply. Since 1976, we have used the specific component therapy approach to supply all patient needs, including those associated with cardiovascular surgery. Our success depends as much on surgical skill, teamwork, and excellent communication as on the rapid availability of an adequate supply of hemocomponents. When problems occur during or after operation, immediate consultation with the blood bank staff and the availability of excellent technical and consultative expertise in blood coagulation are invaluable in the rapid restoration of the jeopardized patient.
Progress in treatment of ascending aortic aneurysms due to dissection, arteriosclerosis, or cystic medial degeneration
Authors: Kouchoukos Nicholas T.
Published: May 2006

The recent results of surgical treatment of ascending aortic aneurysms caused by dissection, arteriosclerosis, or cystic medial degeneration are reviewed. Important technical advances and the various techniques currently employed are examined. Recent improvements in the results of surgical treatment of acute dissections have resulted in a more aggressive surgical approach with early operative intervention. For patients with cystic medial degeneration treated by supracoronary graft replacement of the ascending aorta and aortic valve replacement, late development of aneuryms of the sinuses of Valsalva suggests that composite graft replacement to exclude the aortic sinuses may be the preferred method of treatment.
Treatment of acute and chronic traumatic rupture of the descending thoracic aorta
Authors: Williams Thomas E. , Vasko John S. , Kakos Gerard S. , Cattaneo Stephen M. , Meckstroth Charles V. , Kilman James W.
Published: May 2006

Techniques have undergone much change since the first successful repair of an acute traumatic rupture of the descending thoracic aorta was performed by Klassen at our hospital in 1959. It is interesting that we are returning to the techniques which worked so well in that case. Using this approach, which involves virtual elimination of the use of cardiopulmonary bypass, and evaluating each patient individually for the use of a shunt, we have reduced our mortality rate from 61% (8 deaths among 13 patients) during the period 1959–1974, to 6% (1 death among 17 patients) in the last 5 years. We believe that these data confirm the validity of this approach in the management of acute blunt descending thoracic aortic rupture. Prevention of spinal cord ischemia has become the primary concern for continuing clinical and laboratory investigation.
Use of topical rectal therapy to preserve the rectum in surgery of ulcerative colitis
Authors: Gallone Luigi , Olmi Luciano , Marchetti Vincenzo
Published: May 2006

Colectomy with ileorectal anastomosis was performed in 27 patients affected by ulcerative colitis during the period 1969–1977. In 23 the presence of proctitis required topical rectal therapy to prepare the rectum for ileoproctostomy. Topical use of corticosteroids and sulfasalazine by daily retention enemas caused a regression of proctitis and allowed a safe ileorectal anastomosis. After the surgical procedure, protective treatment of the rectal mucosa was continued for life with minimal dosages of the same drugs by daily enemas. Dexamethasone and 6‐methylprednisolone in saline solution proved to be suitable corticosteroids for topical use and produced no undesirable long‐term side effects. In some patients the steroids were replaced by sulfasalazine per rectum in a daily maintenance dosage. This method of rectal care after colectomy and ileorectal anastomosis prevented relapses of proctitis and kept the rectal mucosa in good condition during follow‐up periods of 1 to 9 years. The safety of the topical treatment is directly related to performance of proctoscopic examinations at regular intervals. Provided these conditions are satisfied, colectomy with ileorectal anastomosis should be the standard surgical treatment of ulcerative proctocolitis.
Diversity Challenges in Community Research and Action: The Story of a Special Issue of AJCP
Authors: Bond Meg A. , Harrell Shelly P.
Published: May 2006

Community research and action often involve managing difficult diversity‐related dilemmas. However, the literature on diversity tends to focus on success stories that tie up very complex issues into neatly‐packaged case studies or lists of specific recommendations. This article introduces a special issue of the American Journal of Community Psychology that was rooted in the belief that it is within the stories of the challenges that the complexity of the political, historical, social, and psychological dynamics of diversity are most evident. The special issue includes 22 detailed narratives of dilemmas related to multiple dimensions of diversity including race, ethnicity, gender, class, sexual orientation, disability, and religion. We asked contributing authors to divide their papers into three primary subsections: (1) context, (2) Challenge and Response, and (3) Reflections. We do the same in telling the story of how this edited collection evolved.
Ultrasound elasticity imaging
Authors: Svensson W. E. , Amiras D.
Published: May 2006

Before the advent of diagnostic imaging, palpation was one of the main methods of clinical investigation for the evaluation of tumours. Malignant tumours feel harder that benign ones and this physical property is related to their coefficient of elasticity. Direct comparison of tissue images before and after application of a force is too crude a measure of elasticity except at extremes of differences in elasticity. Analysis of the raw imaging data, which contains very much more information than can be displayed for visual perception, can detect very much smaller differences in elasticity.

The radio frequency data of returning ultrasound echoes contain much more data than appears in an ultrasound image. Comparison, of the datasets of uncompressed tissue with compressed tissue, of a region of interest allows production of a strain (elasticity) image of that same region of interest. Change in tissue which is not visible on B-mode (greyscale) imaging can now be detected with real time strain imaging which is beginning to be developed on commercial ultrasound equipment. The information obtained with strain/elasticity imaging is now showing potential in influencing management of patients with breast problems.
Introduction to the Special Issue on Specification Analysis and Verification of Reactive Systems
Authors: DELZANNO GIORGIO , ETALLE SANDRO , GABBRIELLI MAURIZIO
Published: May 2006

This special issue is inspired by the homonymous ICLP workshops that took place during ICLP 2001 and ICLP 2002. Extending and shifting slightly from the scope of their predecessors (on verification and logic languages) held in the context of previous editions of ICLP, the aim of the SAVE workshops was to bring together researchers interested in the use of computational logic as a tool for the specification, the analysis and the validation of systems, with particular emphasis on emerging technologies such as World Wide Web and E-Commerce, (protocols for) Smart Cards and Mobile Telephony, Wireless Technology, Hybrid Systems, Real-Time and Distributed systems, etc.
Overview of the Issue
Authors: BROWN JEFFREY , HABERMAN STEVEN , MILEVSKY MOSHE , ORSZAG MIKE
Published: May 2006

The second issue of the fifth volume of the JPEF features 4 research articles, and a book review section. The first article is by Estelle James, Guillermo Martinez and Augusto Iglesias and looks at: “The payout stage in Chile: Who annuitizes and why?” Low rates of voluntary annuitization are a major issue in defined contribution pension designs. Yet, in Chile, about 2/3 of individuals choose to annuitize instead of taking programmed withdrawals. The paper examines the reasons for this high rate of annuitization and concludes that it is due to the combination of a competitive market in annuities and the relatively constrained alternatives available to individuals. The paper nevertheless finds some evidence of adverse selection in the Chile annuity market.
Differential modulation of NR1‐NR2A and NR1‐NR2B subtypes of NMDA receptor by PDZ domain‐containing proteins
Authors: Iwamoto Takashi , Yamada Yasue , Hori Kei , Watanabe Yoshifumi , Sobue Kenji , Inui Makoto
Published: May 2006

The PSD‐95/Dlg/ZO‐1 (PDZ) domain‐containing proteins MALS and PSD‐95 localize to post‐synaptic densities and bind the COOH‐termini of NR2 subunits of the NMDA receptor. The effects of MALS‐2 and PSD‐95 on the channel activity of NMDA receptors were compared using the Xenopus oocyte expression system. Both MALS‐2 and PSD‐95 increased the current response of the NR1‐NR2B receptor to l‐glutamate. In contrast, the current response of the NR1‐NR2A receptor was increased by PSD‐95 but not by MALS‐2. MALS‐2 had no effect either on the potentiation of NR1‐NR2A or NR1‐NR2B channel activity by protein kinase C, or on Src‐mediated potentiation of NR1‐NR2A activity, whereas PSD‐95 almost completely inhibited the effects of these protein kinases. Construction of chimeras of MALS‐2 and PSD‐95 revealed that the first two PDZ domains and two NH2‐terminal cysteine residues are essential for the inhibitory effects of PSD‐95 on protein kinase C‐mediated potentiation of NR1‐NR2A and NR1‐NR2B channel activity, respectively. The second of the three PDZ domains of PSD‐95 was required for its inhibition of Src‐mediated potentiation of NR1‐NR2A activity. These results indicate that the NR1‐NR2A and NR1‐NR2B receptors are modulated differentially by MALS‐2 and PSD‐95, and that similar regulatory effects of PSD‐95 on these receptors are achieved by distinct mechanisms.
The neuronal SAPK/JNK pathway is altered in a murine model of hyperhomocysteinemia
Authors: Robert Karine , Santiard‐Baron Dominique , Chassé Jean‐Francois , Paly Evelyne , Aupetit Joelle , Kamoun Pierre , London Jacqueline , Janel Nathalie
Published: May 2006

Deficiency in cystathionine beta synthase (CBS) leads to high plasma homocysteine concentrations and causes hyperhomocysteinemia, a common risk factor for vascular disease, stroke and possibly neurodegenerative diseases. Various neuronal diseases have been associated with hyperhomocysteinemia, but the molecular mechanisms of homocysteine toxicity are unknown. We investigated the pathways involved in the pathological process, by analyzing differential gene expression in neuronal tissues. We used a combination of differential display and cDNA arrays to identify genes differentially expressed during hyperhomocysteinemia in brain of CBS‐deficient mice. In this murine model of hyperhomocysteinemia, both plasma and brain homocysteine concentrations were high. Several genes were found to be differentially expressed in the brains of CBS‐deficient mice, and the identities of some of these genes suggested that the SAPK/JNK pathway was altered in the brains of CBS‐deficient mice. We therefore investigated the activation of proteins involved in the SAPK/JNK cascade. JNK and c‐Jun were activated in the hippocampal neurones of CBS‐deficient mice, suggesting that the SAPK/JNK pathway may play an important role in the development of neuronal defects associated with hyperhomocysteinemia.
Lipid rafts identified as locations of ectodomain shedding mediated by Meltrin β/ADAM19
Authors: Wakatsuki Shuji , Kurisaki Tomohiro , Sehara‐Fujisawa Atsuko
Published: May 2006

Meltrin β (Mel β, also called ADAM19) is a member of the ADAM (adisintegrin and metalloprotease) family, which are membrane‐anchored glycoproteins that play crucial roles in various biological processes. Many intercellular signaling molecules are membrane‐anchored proteins, which are proteolytically processed after becoming membrane‐bound, to liberate their extracellular domains (ectodomain shedding). Genetic and biochemical studies have shown that some ADAMs participate in these events. We found previously that Mel β can cleave the extracellular region of the membrane‐anchored β‐exon‐containing Neuregulin‐1 (NRG β1) protein, which is one of the main ligands for the neural ErbB receptor. Mel β‐deficient mice showed developmental defects in the nervous system. These observations raise the possibility that the NRG ectodomain shedding mediated by Mel β is closely related to the neural development. Here we show that Mel β‐mediated ectodomain shedding of NRG β1 takes place in the lipid rafts of neurons. The lipid rafts localization of Mel β requires its membrane‐anchoring region, and NRG β1 ectodomain shedding is not enhanced if Mel β cannot reach the lipid rafts. These results indicate that localization of Mel β in lipid rafts is critical for its ectodomain shedding.
PIP3 is involved in neuronal polarization and axon formation
Authors: Ménager Céline , Arimura Nariko , Fukata Yuko , Kaibuchi Kozo
Published: May 2006

Recent experiments in various cell types such as mammalian neutrophils and Dictyostelium discoideum amoebae point to a key role for the lipid product of PI 3‐kinase, PIP3, in determining internal polarity. In neurons, as a consequence of the elongation of one neurite, the axon is specified and the cell acquires its polarity. To test the hypothesis that PI 3‐kinase and PIP3 may play a role in neuronal polarity, and especially in axon specification, we observed localization of PIP3 visualized by Akt‐PH‐GFP in developing hippocampal neurons. We found that PIP3 accumulates in the tip of the growing processes. This accumulation is inhibited by addition of PI 3‐kinase inhibitors. Those inhibitors, consistently with a role of PIP3 in process formation and elongation, delay the transition from stage 1 neurons to stage 3 neurons, and both axon formation and elongation. Moreover, when the immature neurite contacts a bead coated with laminin, a substrate known to induce axon specification, PIP3 accumulates in its growth cone followed by a rapid elongation of the neurite. In such conditions, the addition of PI 3‐kinase inhibitors inhibits both PIP3 accumulation and future axon elongation. These results suggest that PIP3 is involved in axon specification, possibly by stimulating neurite outgrowth. In addition, when a second neurite contacted the beads, this neurite rapidly elongates whereas the elongation of the first laminin‐contacting neurite stops, consistently with the hypothesis of a negative feedback mechanism from the growing future axon to the other neurites.
Quasiclassical trajectory study of O(D1)+N2O→NO+NO: Classification of reaction paths and vibrational distribution
Authors: Kawai Shinnosuke , Fujimura Yo , Kajimoto Okitsugu , Yamashita Takefumi
Published: May 2006

Quasiclassical trajectory calculations for the planar reaction of O(D1)+N2O→NO+NO are performed on a newly constructed ab initio potential energy surface. In spite of the reduced dimension approximation, the agreement between the computational and experimental results is largely satisfactory, especially on the similar amount of excitation of the two kinds of NO products found by Akagi et al. [J. Chem. Phys. 111, 115 (1999)]. Analyzing the initial condition dependence of the trajectories, we find that the trajectories of this reaction can be classified into four reaction paths, which correspond to respective areas in the space of initial condition. In one of the four paths, a long-lived stable complex is formed in the course of reaction, whereas the other three paths have direct mechanism. Contradictory to conventional understanding of the chemical reaction dynamics, the direct paths show more efficient energy exchange between the NO stretching modes than that with a long-lived intermediate. This indicates that the vibrational mode coupling along the short-lived paths is considerably stronger than expected.
Is there a higher-order mode coupling transition in polymer blends?
Authors: Moreno Angel J. , Colmenero Juan
Published: May 2006

We present simulations on a binary blend of bead-spring polymer chains. The introduction of monomer size disparity yields very different relaxation times for each component of the blend. Competition between two different arrest mechanisms, namely, bulklike dynamics and confinement, leads to an anomalous relaxation scenario for the fast component, characterized by sublinear time dependence for mean squared displacements, or logarithmic decay and convex-to-concave crossover for density-density correlators. These anomalous dynamic features, which are observed over time intervals extending up to 4 decades, strongly resemble predictions of mode coupling theory for nearby higher-order transitions. Chain connectivity extends anomalous relaxation over a wide range of blend compositions.
Optical bleaching effect in InN epitaxial layers
Authors: Pačebutas V. , Aleksejenko G. , Krotkus A. , Ager J. W. , Walukiewicz W. , Lu Hai , Schaff William J.
Published: May 2006

Large optical bleaching effect was found in epitaxial InN layers from Z-scan measurements at 1.054μm laser wavelength. Optical transmittance increases nearly five times at the largest light intensities used in experiment. The bleaching recovery time shorter than 3ps was evidenced from time-resolved measurements at this wavelength, which is much faster than the electron lifetimes of 40 and 240ps determined on two epitaxial layers by visible pump-terahertz probe technique. Spectral investigations of the bleaching effect performed in the wavelength range from 1to1.55μm support the conclusions on a narrow band gap of InN.
Registration of single quantum dots using cryogenic laser photolithography
Authors: Lee Kwan H. , Green Alex M. , Taylor Robert A. , Sharp David N. , Scrimgeour Jan , Roche Olivia M. , Na Jong H. , Jarjour Anas F. , Turberfield Andrew J. , Brossard Frederic S. F. , Williams David A. , Briggs G. Andrew D.
Published: May 2006

We have registered the position of single InGaAs quantum dots using a cryogenic laser photolithography technique. This is an important advance towards the reproducible fabrication of solid-state cavity quantum electrodynamic devices, a key requirement for commercial exploitation of quantum information processing. The quantum dot positions were registered with an estimated accuracy of 50nm by fabricating metal alignment markers around them. Photoluminescence spectra from quantum dots before and after marker fabrication were identical except for a small redshift (∼1nm), probably introduced during the reactive ion etching.
Self-assembled endotaxial α-FeSi2 nanowires with length tunability mediated by a thin nitride layer on (001)Si
Authors: Chen S. Y. , Chen H. C. , Chen L. J.
Published: May 2006

Endotaxial growth of self-assembled α-FeSi2 nanowires (NWs) on (100)Si has been achieved by combining reactive deposition epitaxy and nitride-mediated epitaxy. The length and the length/width aspect ratio of metallic α-FeSi2 NWs could be increased more than 12 and 6 folds to 2 μm, and 200 respectively, with a narrow width of 5–10nm after prolonged annealing. The adjustment capability is attributed to the diminished flux of Fe adatoms mediated by the Si3N4 barrier layer to allow more complete shape transition. The scheme represents a degree of control on the morphology of self-assembled epitaxial silicide NWs not achievable otherwise.
Thin-film adhesion measurement using laser-generated high-power surface acoustic wave
Authors: Kireev V. , Liu Y. , Braiman Y. , Radhakrishnan B. , Hsueh C. H. , Becher P. F.
Published: May 2006

A method of the interfacial adhesion measurements utilizing the generation and monitoring of high-power surface acoustic wave has been reported. High-power surface acoustic wave was generated by surface optical breakdown in a transparent dielectric substrate. Modification of the tension-to-shear stresses ratio with film thickness was demonstrated. The normal stress generated at the interface is about one order of magnitude higher compared to those reported in laser spallation experiments; therefore stronger interfaces can be tested with less damage to the substrate.
Electron trap level in a GaN nanorod p-n junction grown by molecular-beam epitaxy
Authors: Park Y. S. , Park C. M. , Park C. J. , Cho H. Y. , Lee Seung Joo , Kang T. W. , Lee S. H. , Oh Jae-Eung , Yoo Kyung-Hwa , Son Min-Soo
Published: May 2006

We have studied the electrical properties of a GaN nanorod p-n junction diode by deep level transient spectroscopy measurements. The p-n junction nanorods were patterned on a SiO2 substrate by using e-beam lithography. In order to confirm the formation of p-n junction, cathodoluminescence and current-voltage measurements, as a function of temperature, were made. The current-voltage curve exhibits strong temperature dependence, suggesting that thermionic emission over a barrier dominates. This barrier most likely corresponds to emission from a deep level in the band. The deep level appears to be an electron trap at Ec-0.40eV below the conduction band with a capture cross section of 2.22×10cm2 near the depletion region of the p-n junction.
Effects of salinity on the survival, growth and development of tadpoles of the brown tree frog, Litoria ewingii
Authors: Chinathamby Kavitha , Reina Richard D. , Bailey Paul C. E. , Lees Belinda K.
Published: May 2006

We investigated the effects of 4% seawater (sw), 8% sw, 12% sw and 16% sw (1.4 g NaCl L–1, 2.8 g NaCl L–1, 4.2 g NaCl L–1 and 5.6 g NaCl L–1, respectively) on survival, mass and development of larvae of the brown tree frog, Litoria ewingii. Salinity of 16% sw significantly decreased survival of tadpoles such that 39% of tadpoles in 16% sw treatment survived to metamorphosis compared with 92% in the control group (freshwater). Growth (mass) of 16% sw tadpoles (0.048 g ± 0.005 g) slowed significantly during early development compared with control tadpoles (0.105 g ± 0.004 g); however, there was no significant difference in final metamorphosis mass between 16% sw (0.192 g ± 0.008 g) and control tadpoles (0.226 ± 0.006 g). Time taken to reach metamorphosis was greater for 16% sw tadpoles (84 ± 1.8 days) than for control tadpoles (55 ± 0.84 days). Tadpoles at salinity concentrations of 4% sw, 8% sw and 12% sw were significantly heavier than control tadpoles at metamorphosis. Our results show that moderate levels of salinity (16% sw) are sufficient to significantly reduce survival and retard development of tadpoles of L. ewingii.
Genomic islands of differentiation between house mouse subspecies
Authors: Harr Bettina
Published: May 2006

Understanding the genes that contribute to reproductive isolation is essential to understanding speciation, but isolating such genes has proven very difficult. In this study I apply a multilocus test statistic to >10,000 SNP markers assayed in wild-derived inbred strains of house mice to identify genomic regions of elevated differentiation between two subspecies of house mice, Mus musculus musculus and M. m. domesticus. Differentiation was high through ∼90% of the X chromosome. In addition, eight regions of high differentiation were identified on the autosomes, totaling 7.5% of the autosomal genome. Regions of high differentiation were confirmed by direct sequencing of samples collected from the wild. Some regions of elevated differentiation have an overrepresentation of genes with host–pathogen interactions and olfaction. The most strongly differentiated region on the X has previously been shown to fail to introgress across a hybrid zone between the two subspecies. This survey indicates autosomal regions that should also be examined for differential introgression across the hybrid zone, as containing potential genes causing hybrid unfitness.
How reliable are empirical genomic scans for selective sweeps?
Authors: Teshima Kosuke M. , Coop Graham , Przeworski Molly
Published: May 2006

The beneficial substitution of an allele shapes patterns of genetic variation at linked sites. Thus, in principle, adaptations can be mapped by looking for the signature of directional selection in polymorphism data. In practice, such efforts are hampered by the need for an accurate characterization of the demographic history of the species and of the effects of positive selection. In an attempt to circumvent these difficulties, researchers are increasingly taking a purely empirical approach, in which a large number of genomic regions are ordered by summaries of the polymorphism data, and loci with extreme values are considered to be likely targets of positive selection. We evaluated the reliability of the “empirical” approach, focusing on applications to human data and to maize. To do so, we considered a coalescent model of directional selection in a sensible demographic setting, allowing for selection on standing variation as well as on a new mutation. Our simulations suggest that while empirical approaches will identify several interesting candidates, they will also miss many—in some cases, most—loci of interest. The extent of the trade-off depends on the mode of positive selection and the demographic history of the population. Specifically, the false-discovery rate is higher when directional selection involves a recessive rather than a co-dominant allele, when it acts on a previously neutral rather than a new allele, and when the population has experienced a population bottleneck rather than maintained a constant size. One implication of these results is that, insofar as attributes of the beneficial mutation (e.g., the dominance coefficient) affect the power to detect targets of selection, genomic scans will yield an unrepresentative subset of loci that contribute to adaptations.
Greater allergenicity of topical ketoprofen in contact dermatitis confirmed by use
Authors: Diaz Ruth L. , Gardeazabal Jesus , Manrique Pilar , Ratón Juan A. , Urrutia Ignacio , Rodríguez‐Sasiain Jose M , Aguirre Carmelo
Published: May 2006

The use of topical non‐steroidal anti‐inflammatory drugs (NSAIDs) is very popular in spite of their doubtful efficacy and high number of generally not serious, but preventable, adverse effects, especially photoallergy. The allergenic potential of different topical NSAIDs was determined by performing a retrospective observational study of the period 1996–2001 and comparing the cases of allergy and photoallergy with the use of each topical NSAID. The diagnoses were obtained from a review of the clinical records of patch/photopatch testing carried out in the dermatology departments of 2 public hospitals in Bizkaia (Spain). The use of the different topical NSAIDs was obtained from invoices sent to the National Health System and the Reporting odds ratio (ROR) and Proportional reporting ratio (PRR) disproportionality estimates of the FEDRA database of the Spanish Pharmacovigilance System. A total of 139 contact reactions to topical NSAIDs were found with ketoprofen being responsible for 28% of the allergies and 82% of the contact photoallergies in spite of not being the most used topical NSAID (third in the ranking, diclofenac was the first). The ROR for ketoprofen was 3.9 (2.4–6.4) and the PRR 3.4 (2.1–5.5), thus confirming the possibility of a warning signal. The results support the need for regulatory action on topical ketoprofen.
Determination of hexavalent chromium in cosmetic products by ion chromatography and postcolumn derivatization
Authors: Kang Eun Kyung , Lee Somi , Park Jin‐Hee , Joo Kyung‐Mi , Jeong Hye‐Jin , Chang Ih Seop
Published: May 2006

Chromium hydroxide green [Cr2O(OH)4] and chromium oxide green (Cr2O3) are colouring agents for use in cosmetic products. These colourants may contain chromium (VI), which cause skin allergies through percutaneous adsorption on the skin. Eye shadow is a representative cosmetic product in which significant colourants are used. We analysed the chromium (VI) in the eye shadows by ion chromatography and post column derivatization. We optimize conditions of chromium (VI) analysis in eye shadows. During the pretreatment procedure, there are no exchange of chromium (III) to chromium (VI). This method has a limit of quantification for chromium (VI) of 1.0 μg l−1, recovery rate of 100 ± 3% and analysis time less than 10 min. This result is 300 times more sensitive than the high‐performance liquid chromatography method. We applied the optimized method to analyse 22 eye shadows and 6 colouring agents. 2 out of 22 of the products contained more than 5 mg l−1. In our previous work, 5 mg l−1 of Cr represented a threshold level. There was much more Cr(VI) in the colouring agents. The Cr(VI) in one of the colouring agents was 97.6 mg l−1.
Skin condition associated with intensive use of alcoholic gels for hand disinfection: a combination of biophysical and sensorial data
Authors: Houben Evi , De Paepe Kristien , Rogiers Vera
Published: May 2006

Although hand hygiene is an important and inexpensive measure to prevent nosocomial infections in clinical settings, the compliance of healthcare workers remains low. In Europe, alcoholic hand disinfection is first choice, but there exists a limited user acceptability due to estimated adverse effects on skin condition. This study was designed to investigate skin tolerance to alcohol‐based disinfecting gels and changes in skin condition depending on humectant concentration, alcohol grades, as well as type of alcohol used. A comparison of 6 alcohol‐based gels was made based on a randomized double‐blind study under in use conditions for 1 day. Skin condition was evaluated by measuring transepidermal water loss (TEWL), stratum corneum hydration, apparent skin pH, redness and degree of scaliness. With respect to user acceptability, all gels were sensorially evaluated using a questionnaire. We saw that none of the alcohol‐based gels, applied under in use conditions, altered TEWL or caused irritation. All gels hydrated the skin, proportionally to their glycerine content, and decreased skin pH. Elevated ethanol concentrations resulted in increased scaliness. Sensorial assessment revealed less appreciation for isopropanol. From this study, it was concluded that gels containing an elevated glycerine concentration and 70% (v/v) ethanol are preferred.
Hydrolysed wheat proteins present in cosmetics can induce immediate hypersensitivities
Authors: Laurière Michel , Pecquet Catherine , Bouchez‐Mahiout Isabelle , Snégaroff Jacques , Bayrou Olivier , Raison‐Peyron Nadia , Vigan Martine
Published: May 2006

Cosmetics containing hydrolysed wheat proteins (HWP) can induce rare but severe allergic reactions. 9 patients, all females without common wheat allergy, but with contact urticaria to such cosmetics, were studied. 6 of them also experienced generalized urticaria or anaphylaxis to foods containing HWP. All patients had low to moderate levels of immunoglobulin (Ig)E specific of wheat flour (f4) or gluten (f79). Their sensitivity to HWP and their tolerance to unmodified wheat proteins extracted from grains were confirmed using skin tests. Immunoblotting analyses showed that IgE from all patients reacted with almost all HWP tested. Reactions generally occurred with large random peptide aggregates. IgE reacted also with unmodified grain proteins, which contrasted with skin tests results. They reacted always with salt soluble proteins but variably with gluten proteins. No reaction occurred with gliadins in patients without associated immediate hypersensitivity to food containing HWP. These results show the role of hydrolysis on the allergenicity of wheat proteins, both through skin or digestive routes. At least part of the epitopes involved is pre‐existing in unmodified wheat proteins. The aggregation of peptide bearing these epitopes and others created by hydrolysis, along with the increased solubility and the route of exposure, are possible factors of the allergenicity of HWP.
Microgravity: the immune response and bone
Authors: Zayzafoon Majd , Meyers Valerie E , McDonald Jay M
Published: May 2006

Summary:  Exposure to microgravity during space flight affects almost all human physiological systems. The affected systems that are of key importance to human space exploration are the musculoskeletal, neurovestibular, and cardiovascular systems. However, alterations in the immune and endocrine functions have also been described. Bone loss has been shown to be site specific, predominantly in the weight‐bearing regions of the legs and lumbar spine. This phenomenon has been attributed to a reduction in bone formation resulting from a decrease in osteoblastic function and an increase in osteoclastic resorption. In order to examine the effects of microgravity on cellular function here on earth, several ground‐based studies have been performed using different systems to model microgravity. Our studies have shown that modeled microgravity (MMG) inhibits the osteoblastic differentiation of human mesenchymal stem cells (hMSCs) while increasing their adipogenic differentiation. Here, we discuss the potential molecular mechanisms that could be altered in microgravity. In particular, we examine the role of RhoA kinase in maintaining the formation of actin stress fibers and the expression of nitric oxide synthase under MMG conditions. These proposed mechanisms, although only examined in hMSCs, could be part of a global response to microgravity that ultimately alters human physiology.
Fos/AP‐1 proteins in bone and the immune system
Authors: Wagner Erwin F. , Eferl Robert
Published: May 2006

Summary: The skeleton and the immune system share a variety of different cytokines and transcription factors, thereby mutually influencing each other. These interactions are not confined to the bone marrow cavity where bone cells and hematopoietic cells exist in proximity but also occur at locations that are target sites for inflammatory bone diseases. The newly established research area termed ‘osteoimmunology’ attempts to unravel these skeletal/immunological relationships. Studies towards a molecular understanding of inflammatory bone diseases from an immunological as well as a bone‐centered perspective have been very successful and led to the identification of several signaling pathways that are causally involved in inflammatory bone loss. Induction of receptor activator of nuclear factor (NF)‐κB ligand (RANKL) signals by activated T cells and subsequent activation of the key transcription factors Fos/activator protein‐1 (AP‐1), NF‐κB, and NF for activation of T cells c1 (NFATc1) are in the center of the signaling networks leading to osteoclast‐mediated bone loss. Conversely, nature has employed the interferon system to antagonize excessive osteoclast differentiation, although this counteracting activity appears to be overruled under pathological conditions. Here, we focus on Fos/AP‐1 functions in osteoimmunology, because this osteoclastogenic transcription factor plays a central role in inflammatory bone loss by regulating genes like NFATc1 as well as the interferon system. We also attempt to put potential therapeutic strategies for inflammatory bone diseases in perspective.
Motivations for methamphetamine cessation among young people in northern Thailand
Authors: German Danielle , Sherman Susan G. , Sirirojn Bangorn , Thomson Nick , Aramrattana Apinun , Celentano David D.
Published: May 2006

Aim  To understand factors influencing cessation intentions among young Thai methamphetamine (MA) users, a population with dramatically increasing rates of MA use.

Design and participants  A total of 48 in‐depth interviews conducted between March 2002 and January 2003 with current and recent MA users aged 15–29 years.

Setting  Chiang Mai city and surrounding district, Thailand.

Measurement  Interviews addressed family history, drug use patterns and influences, cessation history, drug treatment experiences and sexual behavior. Data were analyzed inductively using the constant comparative method common to grounded theory methods. Atlas‐ti was used for data management.

Findings  Cessation intentions were motivated by a range of internal and external influences, including attitudes towards continued MA use shaped by recognition of negative impact on self and others; influence of family, peers, partners and community stigma; perceptions on cessation and drug treatment; and external facilitators and situational barriers, such as extensive peer pressure and drug availability. In most cases, multiple factors operated simultaneously. Some variation according to duration of use and treatment status was observed.

Conclusions  Evidence‐based interventions addressing MA use among Thai young people are urgently needed. These data support the continuation of evidence‐based drug treatment at levels adequate to address the population need and implementation a multi‐faceted approach that aims to enhance identified cessation influences in this population and minimize contextual barriers to cessation.
Flux and stability: individual fluctuations, regression towards the mean and collective changes in alcohol consumption
Authors: Skog Ole‐Jørgen , Rossow Ingeborg
Published: May 2006

Aim  First, to extend the predictions of the collectivity theory of drinking cultures to contexts of ordinary panel data, thereby integrating collective change and individual fluctuations in consumption. Secondly, to develop a technique for controlling the regression towards the mean effect, in order to estimate the pattern of individual change, net of this effect.

Design  The task is, first and foremost, to develop a theoretical model, guided by earlier contributions and empirical results. The applicability of the model is illustrated through re‐analyses of panel data on annual intake of alcoholic beverages from the Finnish alcohol reform in 1968–69, and Norwegian panel data from 1975 to 1976.

Findings  The model offers a reasonable fit to the data. It is demonstrated that a previous attempt at controlling the regression effect has overlooked a methodological complication, and therefore underestimates the real change.

Conclusion  Analysis of the Finnish data demonstrates that the large increase in average consumption was due to approximately the same percentage‐wise increase in the consumption level of drinkers at all levels, when the regression effect was controlled for. Thus, in absolute terms the increase was largest among the heavier drinkers.
Treatment with a thiazolidinedione increases eye protrusion in a subgroup of patients with type 2 diabetes
Authors: Dorkhan Mozhgan , Lantz Mikael , Frid Anders , Groop Leif , Hallengren Bengt
Published: May 2006

Objective  Changes in eye protrusion in patients treated with pioglitazone.

Design  Open‐label prospective.

Patients  Thirty‐six patients with type 2 diabetes and HbA1c ≥ 6·5% were included in a study where pioglitazone was added to current therapy with metformin and sulphonylurea.

Measurements  The degree of eye protrusion before and 26 weeks after treatment with pioglitazone was measured using Krahn's exophthalmometer.

Results  Thirteen patients (group A) exhibited an increase of ≥ 2 mm and 23 patients (group B) exhibited an increase of < 2 mm (P between groups = 0·036). Patients of group A vs. group B had the same BMI, HbA1c and mean doses of pioglitazone, but had lower levels (mean ± SD) of adiponectin in µg/ml at the start (4·9 ± 2·1) vs. (7·1 ± 2·5), P = 0·017 and at the end of study (10·2 ± 4) vs. (14·9 ± 5), P = 0·007. Patients with thyroid disturbance were more frequent in group A (five vs. one), P = 0·02. In a logistic regression analysis, thyroid disturbance, low adiponectin levels and pioglitazone dose predicted a significant change in eye protrusion.

Conclusions  A subgroup of patients with type 2 diabetes treated with pioglitazone responded with increased eye protrusion. This subgroup showed decreased plasma concentration of adiponectin and more frequent thyroid disturbance, and was treated with higher doses of pioglitazone. The relationship between insulin resistance, thyroid disturbance and thiazolidinedione‐induced eye protrusion should be further studied.
Circadian hydrocortisone infusions in patients with adrenal insufficiency and congenital adrenal hyperplasia
Authors: Merza Z. , Rostami‐Hodjegan A. , Memmott A. , Doane A. , Ibbotson V. , Newell‐Price J. , Tucker G. T. , Ross R. J.
Published: May 2006

Objective  Conventional hydrocortisone therapy in adrenal insufficiency cannot provide physiological replacement. We have explored the potential of circadian delivery of hydrocortisone as proof of concept for such therapy delivered in modified‐release tablet formulation.

Methods  We investigated whether the circadian intravenous infusion of hydrocortisone could improve control of ACTH and androgen levels. Two healthy subjects, two patients with Addison's disease and two patients with congenital adrenal hyperplasia (CAH) were studied.

Results  In patients on thrice daily oral hydrocortisone, peak serum cortisol levels were higher than in normal subjects and overnight levels were very low. Patients had very high plasma ACTH levels before their morning dose of hydrocortisone, both at the beginning and at the end of their conventional oral therapy: mean ± SEM 311·8 ± 123·2 and 311·2 ± 85·4 ng/l, respectively. In the patients with CAH, serum 17‐hydroxyprogesterone levels were also elevated: 550 and 642 nmol/l at the beginning and 550 and 777 nmol/l at the end of conventional treatment, respectively. The overall 24‐h mean cortisol levels were similar for conventional oral hydrocortisone and the circadian infusion. At 0700 h, ACTH levels were much higher on conventional treatment than after circadian infusion: mean ± SEM 311·2 ± 85·4 vs. 70·5 ± 45·0 ng/l, respectively (P < 0·05). The same pattern was observed in 17‐hydroxyprogesterone levels, which were 550 and 777 nmol/l after conventional treatment and 3 and 64 nmol/l after circadian infusion.

Conclusions  In patients with poor biochemical control of Addison's disease and CAH, a 24‐h circadian infusion of hydrocortisone can decrease morning ACTH and 17‐hydroxyprogesterone levels to near normal.
Variants implicated in cortisone reductase deficiency do not contribute to susceptibility to common forms of polycystic ovary syndrome
Authors: Draper Nicole , Powell Brenda L. , Franks Steve , Conway Gerard S. , Stewart Paul M. , McCarthy Mark I.
Published: May 2006

Objective  There are close phenotypic similarities between cortisone reductase deficiency (CRD), a rare abnormality of cortisone metabolism, and polycystic ovary syndrome (PCOS). As there is evidence that CRD results from digenic mutations involving the genes encoding 11β‐hydroxysteroid dehydrogenase type 1 (HSD11B1) and hexose‐6‐phosphate dehydrogenase (H6PD), we sought to establish whether CRD‐associated variants in these genes, individually or in combination, influence susceptibility to PCOS.

Design  Case‐control, family‐based association and quantitative‐trait analyses.

Patients  A UK case sample comprising 256 nuclear families ascertained from a PCOS offspring and 213 singleton PCOS cases plus 549 control subjects.

Measurements  All subjects were genotyped for CRD‐related variants in HSD11B1 (rs12086634) and H6PD (rs6688832). Testosterone was measured with an in‐house radioimmunoassay using ether extraction and dextran‐coated charcoal separation.

Results  Case‐control analyses revealed no differences in genotype distribution between PCOS and controls for rs12086634 or rs6688832 (both P = 0·84). Three per cent of cases and 2·4% of controls had genotype combinations (three or more variant alleles at the two sites) considered characteristic of CRD (P = 0·73). There were no departures from expectation in the family‐based association studies, and no significant associations between genotypes (individually or in combination) and BMI, WHR or testosterone.

Conclusions  The variants in HSD11B1 and H6PD typed, though implicated in causation of CRD, do not influence susceptibility to PCOS. It seems likely that additional variants within these genes are required for the development of CRD.