bluuebunny/crossref_metadata_2025 huggingface dataset:
Changing Patterns of Interest Intermediation in the European Union
Authors: Kohler-Koch Beate
Published: June 2007

It is Part of Conventional Wisdom That Organized interests have a considerable impact on European policies and that economic interests in particular have had a greater influence on EC affairs than the European Parliament. Nevertheless, they have attracted relatively little academic attention in comparison with that devoted to parliamentary interest representation. This is even more astonishing if we take account of the leading role given to interest groups by the neo-functionalistic approach, which has dominated integration theory for a long time.
Terrorism and Human Rights
Authors: Gearty Conor
Published: June 2007

Since the formal invocation of the Universal Declaration of Human Rights in 1948, much global discourse has been shaped by those principles, to the extent that one could without exaggeration describe the period as an ‘age of human rights’. But will and indeed can that survive the perceived danger arising from violent acts of terrorism? Is this now an ‘age of terrorism’– or at least, an ‘age of counter-terrorism’– in which human rights are being accorded a secondary status? This article considers those contentions and also advocates particular roles for those who work in the human rights field.
Prenatal Alcohol Exposure and Offspring Growth at 18 Months of Age: The Predictive Validity of Two Measures of Drinking
Authors: Day Nancy L. , Goldschmidt Lidush , Robles Nadine , Richardson Gale , Cornelius Marie , Taylor Paul , Geva Diklah , Stoffer David
Published: June 2007

This is an analysis of the effect of prenatal alcohol exposure on growth of the offspring at 18 months of age. In this prospective study, a cohort of women was interviewed at the end of each trimester of pregnancy, at delivery, and at 8 and 18 months. Offspring were examined at each follow‐up point. Two drinking scales, average daily volume (ADV) and frequent heavy drinking (FHD), were used to explore the effect of different patterns of drinking. We found significant relationships between both prenatal FHD and ADV and offspring growth at 18 months. A significant and inverse relationship was found between ADV during the second and the third trimesters of pregnancy and weight, height, and head circumference at 18 months. Frequent heavy drinking during all three trimesters predicted a significant decrease in head circumference at 18 months. FHD during the second trimester was significantly related to weight and height at 18 months. Analyses demonstrated that ADV was a better predictor of growth deficits than FHD.
Bromocriptine in the Treatment of Alcohol Dependence
Authors: Dongier Maurice , Vachon Luc , Schwartz George
Published: June 2007

A double‐blind controlled study of the effects of bromocriptine on drinking behavior and associated symptoms in ambulatory alcoholics showed a marked improvement in both treatment and control groups. However, significant differences in favor of the medication were observed in psychopathological measures, and trends in the same direction in most of the other efficacy parameters.
Vitamin B6 Metabolism and Binding to Proteins in the Blood of Alcoholic and Nonalcoholic Men
Authors: Fonda Margaret L.
Published: June 2007

Blood obtained from nonalcoholic and alcoholic subjects was incubated with 100 nm [3H]pyridoxine to study its uptake and metabolism by erythrocytes and the binding of vitamin B6 metabolites to proteins in plasma and erythrocytes. Erythrocytes of the alcoholics accumulated tritium faster than those of the controls; however, they contained the same total amount of tritiated compounds by 15 min. After incubation for 30 min, the erythrocytes had converted most of the pyridoxine to pyridoxal phosphate and pyridoxal. Pyridoxal‐P remained in the erythrocytes, and ?40% of the pyridoxal diffused into the plasma. [3H]Pyridoxal and [3H]pyridoxal‐P levels in the erythrocytes and plasma of the alcoholics were similar to those in the controls. However, dialyzed hemolysates of the alcoholics had more [3H]pyridoxal and a lower percentage of [3H]pyridoxal‐P than those of the controls. The total concentration of plasma pyridoxal‐P was lower in the alcoholics than in the controls and did not change upon incubation of whole blood with pyridoxine or upon dialysis. The erythrocytes of the alcoholics and controls had similar concentrations of pyridoxal‐P that increased 2.5‐fold upon incubation of whole blood with pyridoxine for 30 min and returned to the initial concentrations upon dialysis. The amount of [3H]pyridoxal and [3H]pyridoxal‐P bound to protein was assessed by treating hemolysate and plasma samples with borohydride before dialysis. More 3H was bound to protein in the erythrocytes than in the plasma. The amount of protein‐bound 3H in the erythrocytes of the alcoholics was lower than that of the controls, whereas the amount of protein‐bound 3H in plasma was similar in both groups. It is concluded that less of the pyridoxal‐P and pyridoxal was protein bound, and the pyridoxal‐P was more susceptible to hydrolysis to pyridoxal by phosphatases in the erythrocytes of the alcoholics compared with the controls.
Brain GABA‐Transaminase and Monoamine Oxidase After Chronic Ethanol Treatment in Rats
Authors: Sherif Fathi , Wahlstöbm Göran , Oreland Lars
Published: June 2007

The activities of γ‐aminobutyrate aminotransferase (GABA‐T) and monoamine oxidase (MAO‐A and ‐B) were estimated in various brain regions of rats exposed to ethanol for 90 weeks. During the first period (weeks 1–58), the rats had access to both ethanol (10% w/v) and water during a 24‐hr interval at the end of each week. At this point, the animals were given either a saline injection (intraperito‐neally, group 1) or an ethanol injection (2.0 g/kg ip, group 2). During the second period (weeks 59–90), the rats in groups 1 and 2 had continuous access to both ethanol and water. The third group was composed of untreated control rats. Compared with controls, there was an increase of 20–45% in the mean brain GABA‐T activity in both groups of ethanol‐treated rats. However, analysis of the data for the individual ethanol‐treated rats revealed a considerable difference in brain GABA‐T activity. Thus, ‐30% of the ethanol‐treated rats showed approximately twice the activity of rats in the exposed groups and in the control group. There was no connection between ethanol intake, water intake, or body weight and GABA‐T activity in any of the brain regions examined. There was no effect of ethanol in vitro on the activity of GABA‐T in the brain cortex in concentrations of 20–100 mki, whereas acetaldehyde inhibited the activity by 15% at these concentrations. The present results suggest that there is a bimodal distribution with respect to the effect of ethanol on rat brain GABA‐T activity. With regard to MAO, the activities (both forms) in the brain remained unaffected after 90 weeks of ethanol treatment.
Verbal Learning and Memory in Children with Fetal Alcohol Syndrome
Authors: Mattson Sarah N. , Riley Edward P. , Delis Dean C. , Stern Catherine , Jones Kenneth Lyons
Published: June 2007

Children with fetal alcohol syndrome (FAS) were administered the California Verbal Learning Test‐Children's Version, a word list leaming task that assesses immediate and delayed recall and recognition memory. When compared with matched control children, the chlldren with FAS had difficulty learning and recalling the words after a delay period and tended to make an increased number of intrusion and perseverative errors. In addition, they had difficulty discriminating target words from distracter words and made more false‐positive errors on recognition testing. Some of these deficits persisted even when mental age was controlled. The results suggest that children with FAS have profound verbal learning and memory deficits, and that some of these deficits cannot be accounted for even when mental age is considered. Furthermore, the results are consistent with deficits in encoding verbal information and impairment in response inhibition capabilities.
Welcome to the Neighborhood? Long‐Term Impacts of Moving to Low‐Poverty Neighborhoods on Poor Children's and Adolescents' Outcomes
Authors: Fauth Rebecca C. , Leventhal Tama , Brooks‐Gunn Jeanne
Published: June 2007

This study examined 7‐year follow‐up data from the Yonkers Project, a study of a 1985 court‐ordered neighborhood desegregation program in Yonkers, NY. Low‐income Black and Latino families residing in impoverished neighborhoods who were randomly selected to relocate to publicly funded townhouses in middle‐class communities and demographically similar families who were not selected to move were interviewed. Self‐ and parent‐report data on 8–18‐year‐old children and youth's educational outcomes, problem behavior, and parent–child relations were examined (N=221). Youth 15–18 years of age who relocated to more advantaged neighborhoods reported lower school performance and more hyperactive behavior problems and substance use than peers who remained in impoverished neighborhoods. Program effects on parenting also emerged, with mover parents reporting less stringent monitoring and harsh disciplinary techniques than stayers. Family economic resources and neighborhood conditions, assessed approximately 5 years before, accounted for some of the program effects at 7 years.
Cumulative Risk for Early Sexual Initiation Among American Indian Youth: A Discrete‐Time Survival Analysis
Authors: Mitchell Christina M. , Whitesell Nancy Rumbaugh , Spicer Paul , Beals Janette , Kaufman Carol E. ,   The Pathways of Choice and Healthy Ways Project Team
Published: June 2007

Approximately 3 million teens are diagnosed with a sexually transmitted disease (STD) annually; STDs rates for American Indian young adults are among the highest of any racial/ethnic group. An important risk factor for STDs is early initiation of sex. In this study, we examined risk for early initiation with 474 American Indian youth ages 14–18, using 11 risk factors from three developmentally important microsystems (family, school, peers) along with several individual characteristics; a cumulative risk index was also calculated. Discrete‐time survival analyses showed that predictors of early initiation differed by gender. For young men, younger initiation of sex was predicted by lower grades, liking school less, having peers with less prosocial attitudes, a greater likelihood of having used alcohol or drugs at first sex, and having higher sensation‐seeking. For young women, earlier initiation was related to having mothers who had their first child at an early age and who had less formal education, to having parents who had divorced, dropping out of high school, using alcohol/drugs at first sex, and higher sensation‐seeking. Higher cumulative risk was associated with elevated risk of sexual initiation, although the degree of added risk varied with age for women. Cumulative risk deserves broader attention in understanding the early initiation of sexual intercourse.
Profiling Chemokines, Cytokines and Growth Factors in Human Early Pregnancy Decidua By Protein Array
Authors: Engert Sabine , Rieger Lorenz , Kapp Michaela , Becker Jürgen C. , Dietl Johannes , Kämmerer Ulrike
Published: June 2007

Problem In human decidua, a significant increase of leukocytes including CD56++CD16–uterine natural killer (uNK) cells and CD14+monocytes has been observed with the onset of pregnancy. The mechanisms required for the recruitment of those cells to the uterus are still under debate. Cytokines and chemokines have been suggested as key factors for the regulation of these complex cellular migration and interaction processes.

Method of study Investigation of the expression patterns of cytokines, chemokines and growth factors in human decidual tissue (7–8 weeks of gestation) was performed by protein array analysis. Isolated decidual leukocytes, i.e. CD56++CD16–uNK, CD14+monocytes as well as cytotrophoblast (CTB) and stromal cells were tested separately.

Results This analysis revealed the production of monocyte attracting chemokines (GRO, MCP‐1), angiogenetic substances (EGF, VEGF, Angiogenin) as well as granulocyte activating peptides (ENA‐78, IL‐1β, RANTES, IL‐8) by decidual tissue and its cell subsets.

Conclusion The observed pattern supports the role of decidua as a tissue which promotes angiogenesis, attracts monocytes and modulates the function of the latter.
Beyond Conceptual Change: Using Representations to Integrate Domain‐Specific Structural Models in Learning Mathematics
Authors: Singer Florence Mihaela
Published: June 2007

ABSTRACT—Effective teaching should focus on representational change, which is fundamental to learning and education, rather than conceptual change, which involves transformation of theories in science rather than the gradual building of knowledge that occurs in students. This article addresses the question about how to develop more efficient strategies for promoting representational change across cognitive development. I provide an example of an integrated structural model that highlights the underlying cognitive structures that connect numbers, mathematical operations, and functions. The model emphasizes dynamic multiple representations that students can internalize within the number line and which lead to developing a dynamic mental structure. In teaching practice, the model focuses on a counting task format, which integrates a variety of activities, specifically addressing motor, visual, and verbal skills, as well as various types of learning transfer.
Preparation and Certification of Re‐Os Dating Reference Materials: Molybdenites HLP and JDC
Authors: Du Andao , Wu Shuqi , Sun Dezhong , Wang Shuxian , Qu Wenjun , Markey Richard , Stain Holly , Morgan John , Malinovskiy Dmitry
Published: June 2007

Two Re‐Os dating reference material molybdenites were prepared. Molybdenite JDC and molybdenite HLP are from a carbonate vein‐type molybdenum‐(lead)‐uranium deposit in the Jinduicheng‐Huanglongpu area of Shaanxi province, China. The samples proved to be homogeneous, based on the coefficient of variation of analytical results and an analysis of variance test. The sampling weight was 0.1 g for JDC and 0.025 g for HLP. An isotope dilution method was used for the determination of Re and Os. Sample decomposition and pre‐concentration of Re and Os prior to measurement were accomplished using a variety of methods: acid digestion, alkali fusion, ion exchange and solvent extraction. Negative thermal ionisation mass spectrometry and inductively coupled plasma‐mass spectrometry were used for the determination of Re and 187Os concentration and isotope ratios. The certified values include the contents of Re and Os and the model ages. For HLP, the Re content was 283.8 ± 6.2 μg g−1, 187Os was 659 ± 14 ng g−1 and the Re‐Os model age was 221.4 ± 5.6 Ma. For JDC, the Re content was 17.39 ± 0.32 μg g−1, 187Os was 25.46 ± 0.60 ng g−1 and the Re‐Os model age was 139.6 ± 3.8 Ma. Uncertainties for both certified reference materials are stated at the 95% level of confidence. Three laboratories (from three countries: PR. China, USA, Sweden) joined in the certification programme. These certified reference materials are primarily useful for Re‐Os dating of molybdenite, sulfides, black shale, etc.
Proposal for International Agreement on Ca Notation Resulting from Discussions at Workshops on Stable Isotope Measurements Held in Davos (Goldschmidt 2002) and Nice (EGS‐AGU‐EUG 2003)
Authors: Eisenhauer Anton , Nägler Thomas F. , Stille Peter , Kramers Jan , Gussone Nikolaus , Bock Barbara , Fietzke Jan , Hippler Dorothee , Schmitt Anne‐Désirée
Published: June 2007

A proposal is made to standardise the reporting of Ca isotope data to the δ44Ca/40Ca notation (or δ44Ca/42Ca) and to adopt NIST SRM 915a as the reference standard.
Activity‐dependent control of bulk endocytosis by protein dephosphorylation in central nerve terminals
Authors: Clayton Emma L. , Evans Gareth J. O. , Cousin Michael A.
Published: June 2007

Bulk endocytosis is the process by which nerve terminals retrieve large amounts of synaptic vesicle membrane during periods of strong stimulation intensity. The process is rapidly activated and is most probably calcium dependent in a similar manner to synaptic vesicle exocytosis. This article briefly summarizes the current knowledge of bulk endocytosis with respect to its activation, kinetics and molecular mechanism. It also presents recent data from our laboratory showing that the dephosphorylation of a group of endocytosis proteins called the dephosphins by the Ca2+‐dependent protein phosphatase calcineurin is key to the activity‐dependent stimulation of the process. Possible downstream effectors of calcineurin are discussed such as the large GTPase dynamin I and its phosphorylation‐dependent interaction partner syndapin I.
Simulations and Measurements of Sliding Friction Between Rough Surfaces in Point Contacts: From EHL to Boundary Lubrication
Authors: Wang Wen-zhong , Wang Shun , Shi Fanghui , Wang Yu-cong , Chen Hai-bo , Wang Hui , Hu Yuan-zhong
Published: June 2007

This paper presents a numerical approach to simulate sliding friction between engineering surfaces with 3D roughness in point contacts. The numerical approach is developed on the basis of the deterministic solutions of mixed lubrication, which is able to predict the locations where the asperity contacts occur, and the pressure distribution over both lubrication and contact areas. If the friction coefficients over the contacting asperities have been determined, total friction force between the surfaces can be calculated by summing up the two components, i.e., the boundary friction contributed by contacting asperities and the shear stress in hydrodynamic regions. The frictions from asperity contact were determined in terms of a limiting shear stress or shear strength of boundary films while the fluid shear stress in the lubrication areas was calculated using different rheology models for the lubricant, in order to find which one would be more reliable in predicting fluid tractions. The simulations covered the entire lubrication, regime, including full-film Elastohydrodynamic Lubrication (EHL), mixed lubrication, and boundary lubrication. The results, when being plotted as a function of sliding velocity, give a Stribeck-type friction curve. This provides an opportunity to study friction change during the transition of lubrication conditions and to compare friction performance on different rough surfaces, which is of great value in engineering practice. Experiments were conducted on a commercial test device—universal material tester (UMT) to measure friction at a fixed load but different sliding velocities in reciprocal or rotary motions. The results also give rise to the Stribeck friction curves for different rough surfaces, which are to be compared with the results from simulations. The samples were prepared with typical machined surfaces in different roughness heights and textures, and in point contacts with steel ball. Results show that there is a general agreement between the experiments and simulations. It is found that surface features, such as roughness amplitude and patterns, may have a significant effect on the critical speed of transition from hydrodynamic to mixed lubrication. In the regime of mixed lubrication, rougher samples would give rise to a higher friction if the operation conditions are the same.
Identification of Force Coefficients in a Squeeze Film Damper With a Mechanical End Seal—Centered Circular Orbit Tests
Authors: San Andrés Luis , Delgado Adolfo
Published: June 2007

The damping capability of squeeze film dampers (SFDs) relies on adequate end sealing to prevent air ingestion and entrapment. The paper presents the parameter identification procedure and force coefficients of a test SFD featuring a mechanical seal that effectively eliminates lubricant side leakage. The test damper reproduces an aircraft application intended to contain the lubricant in the film lands for extended periods of time. The test damper journal is 2.54cm in length and 12.7cm in diameter, with a nominal clearance of 0.127mm. The SFD feed end is flooded with oil, while the discharge end contains a recirculation groove and four orifice ports. In a companion paper (San Andrés and Delgado, 2006, ASME J. Eng. Gas Turbines Power, 119, to be published) single frequency–unidirectional load excitation tests were conducted, without and with lubricant in the squeeze film lands, to determine the seal dry-friction force and viscous damping force coefficients. Presently, tests with single frequency excitation loads rendering circular centered orbits excitations are conducted to identify the SFD force coefficients. The identified parameters include the overall system damping and the individual contributions from the squeeze film, dry friction and structural damping. The identified system damping coefficients are frequency and motion amplitude dependent due to the dry friction interaction at the mechanical seal interface. Identified squeeze film force coefficients, damping, and added mass, are in good agreement with predictions based on the full film, short length damper model.
Life-history traits in green toad (Bufo viridis) populations: indicators of habitat quality
Authors: Sinsch Ulrich , Leskovar Christoph , Drobig Anja , König Astrid , Grosse Wolf-Rüdiger
Published: June 2007

Five life-history traits (age and size at maturity, longevity, potential reproductive life span, age-dependent growth rate) were investigated in four Bufo viridis Laurenti, 1768 (=  Pseudepidalea viridis (Laurenti, 1768)) populations that inhabited localities at similar altitude (60–100 m above sea level) and latitude (50°N–51°N, Germany), but that differed in habitat quality (i.e., human land use within a radius of 1 km around the breeding site). The age of 374 males and of 127 females collected during the breeding period was estimated using skeletochronology on phalange bones. We tested the hypothesis that sex and habitat quality account for detectable amounts of local variation in life-history traits. Significant sexual size dimorphism was present in all populations. Gender-specific variation in size was mainly accounted for by age, but also to a minor extent by habitat quality. In males, age at maturity varied between 1 and 3 years and was the only life-history trait that was significantly related to the intensity of human land use. In contrast, land-use indices covaried significantly with female longevity (6–15 years) and potential reproductive life span (5–12 years). Our pilot study suggests that, in B. viridis, life-history traits derived from the local age structure may be useful as indicators of habitat quality.
Anti-Inflammatory Effect of Dohongsamultang through Inhibition of Nuclear Factor-κB Activation in Peripheral Blood Mononuclear Cells of Patients with Cerebral Infarction
Authors: Kim Su-Jin , Jeong Hyun-Ja , Park Sei-Uk , Moon Byung-Soon , Moon Phil-Dong , An Nyeon-Hyoung , Lee Kang-Min , Hong Seung-Heon , Kim Hyung-Min , Um Jae-Young
Published: June 2007

The Korean indigenous medicine "Dohongsamultang (DHSMT)" has long been used for various cerebrovascular diseases. However, the exact mechanism for the anti-inflammatory effect of DHSMT is not completely understood. The aim of the present study is to elucidate how DHSMT modulates the inflammatory reaction in lipopolysaccaride (LPS)-stimulated peripheral mononuclear cells from cerebral infarction (CI) patients. Production and expression of cytokine was measured via the ELISA and RT-PCR methods. The level of nuclear factor-kappa B (NF-κB)/Rel A protein and NF-κB DNA binding activity were determined via the Western blot analysis and transcription factor enzyme-linked immunoassay. It showed that DHSMT inhibited the production of TNF-α, IL-1β, and IL-6 induced by LPS in a dose-dependent manner ( p < 0.05). The maximal inhibition rates for TNF-α, IL-1β, and IL-6 production by DHSMT were about 50.18%, 32.13%, and 38.03%, respectively. DHSMT inhibited the TNF-α mRNA expression in a dose-dependent manner. We also showed that the inhibitory effect of DHSMT is through the suppression of the NF-κB pathway. The study suggests an important molecular mechanism by GMGHT to reduce inflammation, which might explain its beneficial effect in the regulation of inflammatory reactions.
DESIGN AND ANALYSIS OF AN EFFICIENT RECURSIVE LINKING ALGORITHM FOR CONSTRUCTING LIKELIHOOD BASED GENETIC MAPS FOR A LARGE NUMBER OF MARKERS
Authors: TEWARI S. , BHANDARKAR S. M. , ARNOLD J.
Published: June 2007

A multi-locus likelihood of a genetic map is computed based on a mathematical model of chromatid exchange in meiosis that accounts for any type of bivalent configuration in a genetic interval in any specified order of genetic markers. The computational problem is to calculate the likelihood (L) and maximize L by choosing an ordering of genetic markers on the map and the recombination distances between markers. This maximum likelihood estimate (MLE) could be found either with a straightforward algorithm or with the proposed recursive linking algorithm that implements the likelihood computation process involving an iterative procedure is called Expectation Maximization (EM). The time complexity of the straightforward algorithm is exponential without bound in the number of genetic markers, and implementation of the model with a straightforward algorithm for more than seven genetic markers is not feasible, thus motivating the critical importance of the proposed recursive linking algorithm. The recursive linking algorithm decomposes the pool of genetic markers into segments and renders the model implementable for hundreds of genetic markers. The recursive algorithm is shown to reduce the order of time complexity from exponential to linear in the number of markers. The improvement in time complexity is shown theoretically by a worst-case analysis of the algorithm and supported by run time results using data on linkage group-II of the fungal genome Neurospora crassa.
Histological and Molecular Classification of Chronic Myeloproliferative Disorders in the Age of JAK2: Persistence of Old Questions despite New Answers
Authors: Hussein Kais , Bock Oliver , Kreipe Hans
Published: June 2007

The discovery of the Janus kinase 2 gain-of-function V617F mutation (JAK2V617F) provided a major breakthrough in the understanding of Philadelphia chromosome-negative chronic myeloproliferative disorders (Ph– CMPD). Among haematologic neoplasm the mutation appears to be almost specific for Ph– CMPD but the different entities comprising polycythaemia vera (PV), essential thrombocythaemia and chronic idiopathic myelofibrosis (CIMF) are not discriminated by the mutation. It is unclear how the diversity with heterogeneous clinical and pathoanatomical presentations comes about. It has been suggested that differences in JAK2V617F gene dosage or different degrees to which the haematologic lineages are affected by the mutation could explain the heterogeneity of morphology and prognosis. Indeed the mutation mediates a PV-like phenotype but with regard to myelofibrosis JAK2V617F does not appear to be a causative factor. Megakaryocytes are homozygous in the majority of fibrotic CIMF and PV, whereas JAK2V617F heterozygosity is predominantly encountered in prefibrotic CIMF and essential thrombocythaemia but transition from hetero- to homozygosity with onset of fibrosis is rare. In conclusion, JAK2V617F provides a valuable adjunct to the diagnosis of Ph– CMPD, in particular with regard to discrimination from reactive proliferations, but the challenge of correct subtyping and hence prognostication persists for clinicians and bone marrow pathologists.
Chronic Myeloproliferative Disorders: The Role of Tyrosine Kinases in Pathogenesis, Diagnosis and Therapy
Authors: Macdonald Donald , Cross Nicholas C.
Published: June 2007

The term chronic myeloproliferative disorders was originally used by Damashek to describe the link amongst a group of acquired blood diseases. Recent molecular genetic analysis has provided a scientific basis for this observation. Underlying myeloproliferative disorders are acquired abnormalities of tyrosine kinase genes. These may be chromosomal translocations resulting in the creation of a fusion kinase gene, examples of which include ABL, FGFR, and PDGFR as seen in disorders CML, 8p11 myeloproliferative syndrome, atypical CML and chronic eosinophilic leukaemia. The second group of tyrosine kinase abnormalities are point mutations in JAK2, a cytosolic TK. This abnormality is seen in 30–97% of cases of MPD with the phenotype PV, ET or CIMF.
Histopathology in the Diagnosis and Classification of Acute Myeloid Leukemia, Myelodysplastic Syndromes, and Myelodysplastic/Myeloproliferative Diseases
Authors: Orazi Attilio
Published: June 2007

In spite of the impressive advances in the area of molecular pathology, bone marrow morphology remains the diagnosis cornerstone to identify the various subtypes of myeloid neoplasms. Morphological examination of the bone marrow requires both bone marrow aspirate and bone marrow trephine biopsy. Immunohistochemistry of bone marrow biopsy with markers reactive in paraffin-embedded tissues represents a powerful diagnostic tool; its results can be easily correlated with those obtained by other techniques such as flow cytometry and genetic analysis, and above all, the clinical findings. The role of the bone marrow biopsy will be particularly stressed in this review article. Particular emphasis is being given to the correct identification of cases of myeloid neoplasms associated with myelofibrosis and for which the bone marrow biopsy represents the only available diagnostic mean. Moreover, the often low cellular yield of the bone marrow aspirate in these cases may also be insufficient to obtain adequate cytogenetic information. Such cases include two subtypes of acute myeloid leukemia which typically cause diagnostic difficulties: acute megakaryoblastic leukemia and acute panmyelosis with myelofibrosis (acute myelosclerosis). Acute myeloid leukemia with multilineage dysplasia, therapy-related myelodysplastic syndrome/therapy-related acute myeloid leukemia and de novo myelodysplastic syndromes (MDS) will also be discussed. The value of bone marrow biopsy in this group of disorders is generally well established. In MDS, in particular, bone marrow biopsy may help in confirming a suspected diagnosis by excluding reactive conditions in which dyshematopoietic changes may also be observed. It can increase the diagnostic accuracy and helps in refining the IPPS risk evaluation system. Among the alterations detected by bone marrow biopsy, a prognostically important finding is the presence of aggregates or clusters of immature myeloid precursor cells (myeloblasts and promyelocytes). These can also be identified by immunohistochemistry with CD34, an antigen expressed in progenitor and early precursor marrow cells, which can be used to demonstrate pathological accumulations of blasts in aggressive subtypes of myeloid neoplasms. Immunohistologic analysis is especially helpful in cases of MDS with fibrosis and cases with hypocellular marrows (hypoplastic MDS). In both of these variants, the presence of reticulin fibrosis or fatty changes in the bone marrow can make accurate disease characterization very difficult or impossible using bone marrow aspirates. Finally, the important group of the myelodysplastic/myeloproliferative disorders can only be accurately categorized by a careful multiparametric approach in which the bone marrow biopsy exerts a pivotal role.
Prognostic Factors and Impact of Treatment in Melanoma Brain Metastases: Better Prognosis for Women?
Authors: Hofmann Maja A. , Hernandez Coll Stefanie , Küchler Ingeborg , Kiecker Felix , Wurm Reinhard , Sterry Wolfram , Trefzer Uwe
Published: June 2007

Background: Brain metastases are a common consequence in patients with stage IV melanoma associated with a grim prognosis. Objective: The objective of this study was the examination of prognostic factors and the evaluation of different treatment options. Methods: A consecutive series of 133 patients with melanoma brain metastases with regard to prognostic factors and the impact on survival were analyzed. Results: 82 patients had involvement of only the cerebrum at the initial diagnosis, whereas in 7 patients only the cerebellum and the brainstem were involved. Seizures (n = 29) were the single most often reported symptom. The overall median survival time was 24 weeks (1–196) from diagnosis of brain metastases. Women had a significantly longer survival with 36 weeks (3–196) compared to 17 weeks (1–159) for men. Multivariate analysis has established as significant prognostic factors: female gender, number of brain metastases, surgery, chemotherapy, radiotherapy and corticosteroid application. Conclusion: With regard to the prognostic factors, an improved survival can be achieved in this patient group using more elective treatment options, also with emphasis on corticosteroids.
Outbreak of Tropical Rat Mite (Ornithonyssus bacoti) Dermatitis in a Home for Disabled Persons
Authors: Baumstark J. , Beck W. , Hofmann H.
Published: June 2007

Five mentally handicapped individuals living in a home for disabled persons in Southern Germany were seen in our outpatient department with pruritic, red papules predominantly located in groups on the upper extremities, neck, upper trunk and face. Over several weeks 40 inhabitants and 5 caretakers were affected by the same rash. Inspection of their home and the sheds nearby disclosed infestation with rat populations and mites. Finally the diagnosis of tropical rat mite dermatitis was made by the identification of the arthropod Ornithonyssus bacoti or so-called tropical rat mite. The patients were treated with topical corticosteroids and antihistamines. After elimination of the rats and disinfection of the rooms by a professional exterminator no new cases of rat mite dermatitis occurred. The tropical rat mite is an external parasite occurring on rats, mice, gerbils, hamstersand various other small mammals. When the principal animal host is not available, human beings can become the victim of mite infestation.
Improving Culture Conditions for Temporomandibular Joint Disc Tissue Engineering
Authors: Johns D.E. , Athanasiou K.A.
Published: June 2007

Background: The temporomandibular joint (TMJ) is extremely important for activities like eating and talking, which can become painful and difficult for patients with TMJ dysfunction. Tissue engineering is a potential alternative to current surgical interventions through replacement of diseased or injured tissue with a functional construct. Since research with TMJ disc cells began relatively recently, optimal culturing conditions must be determined. Methods: Metabolic additives, L-glutamine, L-alanyl-L-glutamine, sodium pyruvate, and insulin, were examined for their effects on TMJ disc cells in monolayer. Effects of L-proline were examined in three-dimensional (3-D) culture at concentrations of 0, 25 and 100 mg/l. Results: The combination of L-glutamine, sodium pyruvate, and insulin improved cell proliferation rates without affecting collagen production or gene expression. No differences were observed in mechanical properties of the engineered constructs; however, collagen and glycosaminoglycan quantities normalized to cell number decreased at the highest concentration of L-proline. Conclusion: This work identified supplements for 2-D monolayer expansion. Other supplements or culture conditions still need to be investigated for 3-D tissue production. This work improves upon porcine TMJ disc cell culturing conditions, taking us closer to being able to engineer the TMJ disc.
Are Distributions of Secondary Osteon Variants Useful for Interpreting Load History in Mammalian Bones?
Authors: Skedros John G. , Sorenson Scott M. , Jenson Nathan H.
Published: June 2007

Background/Aims: In cortical bone, basic multicellular units (BMUs) produce secondary osteons that mediate adaptations, including variations in their population densities and cross-sectional areas. Additional important BMU-related adaptations might include atypical secondary osteon morphologies (zoned, connected, drifting, elongated, multiple canal). These variants often reflect osteonal branching that enhances toughness by increasing interfacial (cement line) complexity. If these characteristics correlate with strain mode/magnitude-related parameters of habitual loading, then BMUs might produce adaptive differences in unexpected ways. Methods: We carried out examinations in bones loaded in habitual torsion (horse metacarpals) or bending: sheep, deer, elk, and horse calcanei, and horse radii. Atypical osteons were quantified in backscattered images from anterior, posterior, medial, and lateral cortices. Correlations were determined between atypical osteon densities, densities of all secondary osteons, and associations with habitual strain mode/magnitude or transcortical location. Results: Osteon variants were not consistently associated with ‘tension’, ‘compression’, or neutral axis (‘shear’) regions, even when considering densities or all secondary osteons, or only osteon variants associated with relatively increased interfacial complexity. Similarly, marrow- and strain-magnitude-related associations were not consistent. Conclusion: These data do not support the hypothesis that spatial variations in these osteon variants are useful for inferring a habitual bending or torsional load strain history.
Prevalence of Minor Musculoskeletal Anomalies in Children with Congenital Hypothyroidism
Authors: El Kholy Mohamed , Fahmi Marwa E. , Nassar Ayman E. , Selim Samia , Elsedfy Heba H.
Published: June 2007

In the last decade a high frequency of extrathyroidal congenital anomalies has been reported in infants with congenital hypothyroidism (CH) detected by neonatal screening. In the present study the occurrence of additional congenital malformations (CM) in a cohort of children with confirmed primary CH due to thyroid dysgenesis was investigated. A high prevalence of extrathyroidal major congenital anomalies (15.9%), more than 5-fold higher than that reported in the Egyptian population (2.7%), was found. The cardiac and musculoskeletal systems were the most commonly involved, comprising 9.09 and 47.72% of all anomalies, respectively. The high prevalence of musculoskeletal anomalies in this study was mostly due to minor anomalies as brachydactyly and digitalization of thumbs. The type of dysgenesis (i.e. aplastic, ectopic or hypoplastic) as well as the severity of hypothyroidism, as assessed by TSH and T4 levels at diagnosis, had no relation with the occurrence of extrathyroidal abnormalities.
Acceleration of Luteinizing Hormone Pulse Frequency in Adolescent Girls with a History of Central Precocious Puberty with versus without Hyperandrogenism
Authors: Escobar María Eugenia , Ropelato María Gabriela , Ballerini María Gabriela , Gryngarten Mirta Graciela , García Rudaz María Cecilia , Veldhuis Johannes D. , Barontini Marta
Published: June 2007

Some adolescents with a history of idiopathic central precocious puberty (ICPP) develop hyperandrogenism. Hypothesis: Luteinizing hormone (LH) hypersecretion could be a common mechanism underlying ICPP and polycystic ovary syndrome. Aim: To explore the GnRH-LH axis in those patients. Design: To compare overnight LH secretion in 7 healthy adolescents (CG) with that in patients with prior ICPP [5 with (CPPA) and 7 without (CPPB) hyperandrogenism]. To analyze daytime LH secretion in those patients. Methods: LH secretion was quantified by immunofluorometry and deconvolution analysis. Results: Nighttime mean LH (international units/liter) was higher in CPPA (6.9 ± 1.5) than in CPPB (3.2 ± 0.4, p < 0.05) and CG (2.9 ± 0.4, p < 0.01). Deconvolution analysis revealed a greater nighttime LH frequency (pulses/hour) both in CPPA (0.91 ± 0.06, p < 0.01) and CPPB (0.74 ± 0.02, p < 0.05) than in CG (0.45 ± 0.07). CPPA patients maintained a higher frequency than CPPB. Pulsatile LH production was greater in CPPA than in CG (50 ± 12 vs. 18 ± 3 IU/l/day, p < 0.01). Daytime mass of LH released per burst and pulsatile production rate were significantly greater in CPPA than in CPPB patients. Conclusions: Hyperandrogenic adolescents with prior ICPP show increased pulsatile LH secretion. Augmentation of LH pulsatility may predispose to or cause hyperandrogenism in some adolescents with a history of precocious puberty.
A Novel Method Combining Linkage Disequilibrium Information and Imputed Functional Knowledge for tagSNP Selection
Authors: Rochat R.H. , de las Fuentes L. , Stormo G. , Davila-Roman V.G. , Charles Gu C.
Published: June 2007

Analyses of high-density SNPs in genetic studies have the potential problems of prohibitive genotyping costs and inflated false discovery rates. Current methods select subsets of representative SNPs (tagSNPs) using information either on potential biologic functionality of the SNPs or on the underlying linkage disequilibrium (LD) structure, but not both. Combining the two types of information may lead to more effective tagSNP selection. The proposed method combines both functional and LD information using a weighted factor analysis (WFA) model. The WFA was applied to the dense SNP collection from 129 genes sequenced by the SeattleSNPs Program for Genomic Application. TagSNPs selected by WFA were compared with those selected by an LD-based method. WFA allowed prioritization of SNPs that would otherwise share equivalent ranking due to underlying LD structure alone. Furthermore, WFA consistently included SNPs not selected by function or by LD alone. A literature review of a subset of genes revealed that SNPs selected by WFA were more likely represented in published reports.
Brain Stem Cells Adopt a Pituitary Fate after Implantation into the Adult Rodent Pituitary Gland
Authors: U Hoi Sang , Wu Bian , Wilkes Nathan , Ho Allen , Saljooque Farid
Published: June 2007

Fetal brain stem cells (RSCs) have been induced to express pituitary phenotypes in vitro in co-cultures with GH3 cells and by exposure to GH3-conditioned media. In the current studies, we graft RSCs into the pituitary glands of adult rat to investigate whether grafted RSCs can be induced by the native gland to acquire pituitary properties. Grafted cells survive for 4 weeks and express Pit-1, GH, FSH, LH, ACTH, TSH and to a lesser extent PRL indicating that inductive influences are operative in vivo as well. This demonstrates that pluripotential cells can be induced to acquire properties of tissues different from their organ of origin likely through the action of cell-cell contact and local tissue factors.
A Randomized Controlled Trial of Hydrocortisone Against Hyponatremia in Patients With Aneurysmal Subarachnoid Hemorrhage
Authors: Katayama Yoichi , Haraoka Jo , Hirabayashi Hidehiro , Kawamata Tatsuro , Kawamoto Keiji , Kitahara Takao , Kojima Jun , Kuroiwa Toshihiko , Mori Tatsuro , Moro Nobuhiro , Nagata Izumi , Ogawa Akira , Ohno Kikuo , Seiki Yoshikatsu , Shiokawa Yoshiaki , Teramoto Akira , Tominaga Teiji , Yoshimine Toshiki
Published: June 2007

Background and Purpose—

Hyponatremia is common after aneurysmal subarachnoid hemorrhage (SAH). It is caused by natriuresis, which induces osmotic diuresis and decreases blood volume, contributing to symptomatic cerebral vasospasm (SCV). Hypervolemic therapy to prevent SCV will not be efficient under this condition. We conducted a randomized controlled trial to assess the efficacy of hydrocortisone, which promotes sodium retention in the kidneys.

Methods—

Seventy-one SAH patients were randomly assigned after surgery to treatment with either a placebo (n=36) or 1200 mg/d of hydrocortisone (n=35) for 10 days and tapered thereafter. Both groups underwent hypervolemic therapy. The primary end point was the prevention of hyponatremia.

Results—

Hydrocortisone prevented excess sodium excretion (
P
=0.04) and urine volume (
P
=0.04). Hydrocortisone maintained the targeted serum sodium level throughout the 14 days (
P
<0.001), and achieved the management protocol with lower sodium and fluid (
P
=0.007) supplementation. Hydrocortisone kept the normal plasma osmolarity (
P
<0.001). SCV occurred in 9 patients (25%) in the placebo group and in 5 (14%) in the hydrocortisone group. No significant difference in the overall outcome was observed between the 2 groups.

Conclusions—

Hydrocortisone overcame excess natriuresis and prevented hyponatremia. Although there was no difference in outcome, hydrocortisone supported efficient hypervolemic therapy.
Venous Ulcers: Microcirculatory Improvement and Faster Healing with Local Use of Pycnogenol®
Authors: Belcaro G. , Cesarone M. R. , Errichi B. M. , Ledda A. , Di Renzo A. , Stuard S. , Dugall M. , Pellegrini L. , Rohdewald P. , Ippolito E. , Ricci A. , Cacchio M. , Ruffini I. , Fano F. , Hosoi M.
Published: June 2007

Chronic venous insufficiency (CVI) causes a well-defined microangiopathy described as venous hypertensive microangiopathy (VHM) leading to venous ulcerations. VHM is mainly observed in the distal part of the leg, in the perimalleolar region. In VHM edema is the consequence of increased capillary pressure and reduced local clearance, and this affects local perfusion. The healing of venous ulcers is usually very slow. Many treatments are available, but there is still no standard. Oral Pycnogenol® is effective in venous disease and particularly in controlling edema. The aim of this study was the evaluation of the local effects of Pycnogenol on ulcers healing associated with venous hypertension. The study lasted 6 weeks including 18 patients (16 completed the study) with venous ulcerations. The oral treatment with Pycnogenol was compared with a combination treatment including oral and local treatment. In subjects treated with the combination treatment (oral and local), venous ulcers healed better (there was a faster reduction in ulcerated area) in comparison with oral treatment only. According to this pilot study Pycnogenol appears to have an important role in local treatment of venous ulcers improving healing and signs/symptoms.
Cardiovascular Responses to Swimming
Authors: Alexiou S. , Haritonidis K. , Deligiannis A.
Published: June 2007

The authors examined cardiovascular responses to long-distance fin swimming as compared to freestyle swimming. Elite male fin swimmers (n=17) swam 8 km in the open sea (group A) and 17 top freestyle endurance swimmers (group B) swam 6 km in the open sea. The swimming times of the 2 groups did not differ significantly. The heart rate and mean blood pressure were higher in group B than in group A after exercise. As estimated from the systolic time intervals (STI), total electromechanical systole index (QS2I) and electrical systole index (QTI) increased and QT-QS2 decreased in both types of swimming. These changes were more marked in fin swimmers. Moreover, the preejection period (PEPI) and the preejection period to left ventricular ejection time ratio (PEP/LVET) significantly decreased in both groups, while LVET remained constant in the 2 swimming events. Likewise, the amount of change in PEP/LVET was more pronounced in group A. Finally, only the QT-QS2 changes were associated with performance efforts in both groups. Therefore, there are quantitative cardiovascular differences between these types of swimming that should be primarily attributed to the different muscle mass effort involved.
Perioperative Sublingual Isosorbide Dinitrate for the Prevention of Cardiac Complications in Cardiac Patients Undergoing Noncardiac Surgery
Authors: RuDusky Basil M.
Published: June 2007

One hundred fifty-two consecutive patients with a known or suspected diagnosis of atherosclerotic coronary artery disease were administered 5 mg sublingual isosorbide dinitrate 2 hours and/hour preoperatively and every 4 hours postoperatively for 3 days, for the prevention of cardiovascular morbidity and mortality, which could result from various noncardiac surgical procedures; 125 patients received general anesthesia. Cardiovascular complications occurred in 3 patients (1.9%). Two patients did not enter the study, owing to side effects of the medication (1.3%). The complications were 1 each (0.6%) of the following: atrial fibrillation, hypotension, and cardiac arrest. Mortality was 0%. These results are exceptionally favorable when compared to the average cardiovascular morbidity rate of 2.8% to 49% in patients assigned to various risk stratifications in the medical literature.