bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Birth Control Service Utilization By Offering Services Prerelease Vs Postincarceration
Authors: Clarke Jennifer G. , Rosengard Cynthia , Rose Jennifer S. , Hebert Megan R. , Peipert Jeffrey , Stein Michael D.
Published: March 2006

Objectives. We examined whether incarcerated women would substantially increase birth control initiation if contraceptive services were available within the prison compared with after their release back into the community.

Methods. During phase 1 of the study, a nurse educator met with women at the Rhode Island Adult Correctional Institute and offered them referrals for contraceptive services at a community health clinic after their release. During phase 2, contraceptive services were offered to women during their incarceration.

Results. The majority of the participants (77.5%) reported a desire to initiate use of birth control methods. Within 4 weeks of their release, 4.4% of phase 1 participants initiated use of a contraceptive method, compared with 39.1% of phase 2 participants (odds ratio [OR]=14.6; 95% confidence interval [CI]=5.5, 38.8).

Conclusions. Provision of contraceptive services to women during their incarceration is feasible and greatly increases birth control initiation compared to providing services only in the community.
Justice and Fairness in the Kennedy Krieger Institute Lead Paint Study: the Ethics of Public Health Research on Less Expensive, Less Effective Interventions
Authors: Buchanan David R. , Miller Franklin G.
Published: March 2006

The Kennedy Krieger lead paint study stirred controversial questions about whether research designed to develop less expensive interventions that are not as effective as existing treatments can be ethically warranted. Critics questioned the social value of such research and alleged that it sanctions a double standard, exploits participants, and is complicit in perpetuating the social injustice.

In response, we demonstrate the propriety of conducting research on interventions that can be extended to the population in need by stipulating the limited conditions in which it is ethically warranted and providing fair terms of participation. We contend that the failure to conduct such research causes greater harm, because it deprives disadvantaged populations of the benefits of imminent incremental improvements in their health conditions.
The Associations Between Victimization, Feeling Unsafe, and Asthma Episodes Among US High-School Students
Authors: Swahn Monica H. , Bossarte Robert M.
Published: March 2006

We examined the associations between victimization, missed school because of feeling unsafe, and asthma episodes among US high-school students using the 2003 Youth Risk Behavior Survey. Cross-sectional analyses on adolescents with asthma (n=1943) showed that any victimization and missed school because of feeling unsafe significantly increased the odds of having an asthma episode in the past year (adjusted odds ratio [OR]=1.45; 95% confidence interval [CI] = 1.07, 1.95 and adjusted OR = 2.93; 95% CI = 1.90, 4.53, respectively). Victimization and feeling unsafe are important but poorly understood risk factors for asthma.
Immunization Initiation Among Infants in the Oregon Health Plan
Authors: Henderson Jessica W. , Arbor Susan A. , Broich Steven L. , Peterson Judy Mohr , Hutchinson Jean E.
Published: March 2006

Infants who start receiving immunizations on time are more likely to be up to date at age 2 years. Among 39708 infants aged 3 months covered by the Oregon Health Plan (expanded Medicaid), those who did not have health care coverage within the first month of life were less likely to start receiving immunizations on time. Also at risk were infants in foster care, in subadoptive care, who were blind or disabled, who were Native American or Black, or whose mothers were not covered by the Oregon Health Plan.
Soil Processes Affected by Sixteen Grassland Species Grown under Different Environmental Conditions
Authors: Dijkstra Feike A. , Hobbie Sarah E. , Reich Peter B.
Published: March 2006

Plant species, and their interactions with the environment, determine both the quantity and chemistry of organic matter inputs to soils. Indeed, countless studies have linked the quality of organic matter inputs to litter decomposition rates. However, few studies have examined how variation in the quantity and chemistry of plant inputs, caused by either interspecific differences or changing environmental conditions, influences the dynamics of soil organic matter. We studied the effects of 16 grassland species from 4 functional groups (C3 and C4 grasses, forbs, and legumes) growing under ambient and elevated CO2 (560 ppm) and N inputs (4 g m−2 yr−1) on soil carbon (C) and nitrogen (N) dynamics after 4 yr in a grassland monoculture experiment in Minnesota, USA. Specifically, we related soil C and N dynamics to variation among species and their responses to the CO2 and N treatments in plant biomass and chemistry of roots, the dominant detrital input in the system. The 16 species caused much larger variation in plant litter inputs and chemistry, as well as soil C and N dynamics, than the CO2 and N treatment. Not surprising, variation in the quantity of plant inputs to soils contributed to up to a two‐fold variation in microbial biomass and amount of respired nonlabile soil C. Root N concentration (across species and CO2 and N treatments) was significantly negatively related to decomposition of nonlabile soil C and positively related to net N mineralization. Greater labile C inputs decreased rates of net N mineralization, likely because of greater N immobilization. Thus, of the traits examined, plant productivity, tissue N concentration, and labile C production such as from rhizodeposition were most important in causing variation in soil C and N dynamics among species and in response to altered atmospheric CO2 and N supply.
Determining Vertical Root and Microbial Biomass Distributions from Soil Samples
Authors: Cook Freeman J. , Kelliher Francis M.
Published: March 2006

When vertical density distributions of root or microbial biomass are calculated using each sampling interval's midpoint as the depth coordinate, the calculated distribution is biased if it is a nonlinear function with depth. In the root biomass literature, distributions are often described by a power function R ∝ βz, where β is a decay coefficient and z is depth. A common alternative formulation is an exponential function, R ∝ , where Zr is a characteristic length scale. These functions are equivalent when Zr = −1/ln β, so the data according to either function may be unified. The bias can be eliminated by representing the vertical distribution with a continuous function, integrating it over the sampling interval, and using a least squares method to determine the function's parameters. The bias increased by nearly threefold when the sampling interval increased from 0.01 to 1 m. As the sampling interval increases, the bias shifts the function down the z axis. This results in the intercept increasing with increasing sampling interval. When a single profile was sampled at different intervals, the function's intercept and Zr changed. The parameter Zr changed fivefold when the sampling interval increased from 0.1 to 0.5 m, while the calculated fraction of roots above a depth of 0.1 m decreased threefold for the same change in sampling interval. Beneath a tropical forest where root biomass and microbial respiration were sampled throughout the same soil profile, the corresponding microbial and root biomass length scales averaged 0.17 m and differed by only 11%.
Correcting Wall Flow Effect Improves the Heat‐Pulse Technique for Determining Water Flux in Saturated Soils
Authors: Gao Jianying , Ren Tusheng , Gong Yuanshi
Published: March 2006

Heat‐pulse sensors are promising tools that can provide rapid measurements of soil water fluxes. The main objective of this study was to determine whether wall flow could be a main reason for discrepancies between measured and heat‐pulse water flux densities. Heat‐pulse measurements were obtained with a range of water flux densities imposed on packed soil columns of three saturated media: glass beads, a sandy loam soil, and a sandy clay loam soil. Water flux density was calculated from the thermal properties of the media and the ratio of temperature changes at downstream and upstream positions. A novel finding from this study was that in packed columns, wall flow was responsible for the deviations between water flux estimates from heat‐pulse data and water flux measured from outflow, and the magnitude of wall flow was largely determined by soil texture. An amplification factor, 1.12 for the sandy loam and 1.24 for the sandy clay loam, was introduced to correct the influence of wall flow, which reduced the errors of the heat‐pulse measurements to within 5%. We demonstrated that wall flow was able to explain quantitatively the “reduced convection” theory proposed by earlier researchers. Under the experimental conditions, heat transfer by dispersion was of minor importance.
In situ Mineralization of Dairy Cattle Manures as Determined using Soil‐Surface Carbon Dioxide Fluxes
Authors: Rochette Philippe , Angers Denis A. , Chantigny Martin H. , Gagnon Bernard , Bertrand Normand
Published: March 2006

Decomposition rates of organic amendments in agricultural soils provide information on nutrient release and on changes in soil C stocks. They are usually determined using incubation of soil samples under controlled conditions. Our objective was to study decomposition of liquid and solid dairy cattle manures under field conditions following application to a loamy and a clay soil. Manures were applied in two consecutive years to silage corn at rates equivalent to 150 kg ha−1 total N providing 119 to 202 kg C ha−1 Soil‐surface CO2 fluxes, temperature and water content were monitored weekly in manured and control (mineral fertilizer) plots. Initial decomposition rates following manure application were much slower in the first than in the second year. This lag phase was attributed to cool soil temperatures and to the time required by the soil microflora to adapt to a first addition of this exogenous organic substrate. During the first year, mineralization of manure organic C was lower in the clay (52% of manure C) than in the loamy (75%) soil, presumably as a result of less favorable aeration conditions and greater physical protection of organic substrates in the clay. Equal mineralization rates of liquid and solid manures during both years in the loamy soil indicated that the two manure types had similar decomposability. Slower decomposition of the solid than the liquid manure in the clay soil was attributed to poorer mixing with the soil (presence of clods) resulting in reduced access to the solid manure for soil decomposers. The results of this study evidenced that under field conditions manure C decomposition is not determined solely by manure characteristics but also by interactions between the manure type and soil physical properties such as texture.
Aligning Theme and Information Structure to Improve the Readability of Technical Writing
Authors: Moore N. A. J.
Published: March 2006

The readability of technical writing, and technical manuals in particular, especially for second language readers, can be noticeably improved by pairing Theme with Given and Rheme with New. This allows for faster processing of text and easier access to the “method of development” of the text. Typical Theme-Rheme patterns are described, and the notion of the “point of a text” is introduced. These concepts are applied to technical writing and the reader is then invited to evaluate the improvements in readability in a small sample of texts.
Scaffolding Novice Instructional Designers' Problem-Solving Processes Using Question Prompts in a Web-Based Learning Environment
Authors: Ge Xun , Chen Ching-Huei , Davis Kendrick A.
Published: March 2006

The present study investigated the effects of question prompts in scaffolding novice instructional designers solving ill-structured, instructional design problems in a Web-based learning environment. The effects of question prompts were studied under different prompting conditions (Question-Elaboration vs. Question-Guidance), taking into consideration various levels of learners' prior knowledge and experience. The study employed a comparative, multiple-case study design using the technique of think-aloud protocols, which were followed by interviews. Eight graduate students from the program of Instructional Design and Technology participated in the study. While the qualitative findings supported the previous research on the advantages of question prompts in scaffolding ill-structured problem solving, they also shed light on the specific cognitive and metacognitive functions, as well as limitations, of question prompts in different conditions. The study has implications for designing instructional scaffolds for supporting ill-structured problem solving of various domains in a Web-based learning environment.
International Consumer Protection: Writing Adequate Instructions for Global Audiences
Authors: Lipus Teresa
Published: March 2006

In 2003, the United States exported nearly $720 billion in goods. Businesses that trade in the global market have a legal and ethical duty to make their products reasonably safe, and technical communicators who write the documentation for those products have a legal and ethical duty to protect international consumers by writing adequate instructions. Writing documentation for products that will be distributed internationally requires not only the ability to communicate clearly, but also awareness of the relevant product liability laws, the cultural variables, and the expectations of international audiences. This article first argues that devoting company resources to produce adequate instructions for international users is both practical and ethical, then provides a brief overview of the consumer protection measures that the top U.S. trade partners have implemented, and finally presents guidelines for developing adequate instructions for international audiences.
An Exploratory Study of Adoption of Software and Hardware by Faculty in the Liberal Arts and Sciences
Authors: Yohon Teresa , Zimmerman Don
Published: March 2006

Universities and colleges are investing millions of dollars in information technology infrastructure to support teaching, research, and service, and thousands of dollars annually in faculty training programs. And yet, many college graduates entering the workforce lack adequate technology skills. To ascertain the frequency of faculty adoption of information technology, we surveyed a random sample of faculty in the liberal arts and sciences departments in our university. Overall faculty members ( n = 174) reported a low usage of information technology for teaching, though the rate of software adoption is higher than the rate of hardware adoption. While opportunities to learn technology are available, about two-thirds of the faculty members have not completed the available seminars and workshops on information technologies but prefer more informal ways of learning information technology, such as talking with other faculty members.
Sustained Dialogue: How Students are Changing their Own Racial Climate
Authors: Parker Priya Narayan
Published: March 2006

Sustained Dialogue, used in the past to ease international tensions, is finding its way into colleges and universities that wish to change unhealthy race-based attitudes and behaviors. The campus approach brings small groups of students from widely different backgrounds together for a year of deep conversation.
A novel gas chromatographic method to measure sorption of dense gases into polymers
Authors: Galia Alessandro , Abduljawad Mohamed , Scialdone Onofrio , Filardo Giuseppe
Published: March 2006

A novel experimental approach to determine the solubility of gaseous compounds inside polymers is here described. The method is based on the gas chromatographic determination of the composition of the fluid phase at equilibrium with the polymer. To take into account the effect of the volume swelling on the measurement a suitable probe, nonabsorbable by the polymer, was added to the fluid phase. Under the adopted configuration the apparatus can operate up to 35 MPa and 80°C. This experimental technique has been used to determine the solubility of carbon dioxide in poly(vinylidene fluoride) using argon as a probe. The latter was chosen because it is negligibly absorbed by the polymer and does not significantly alter the chemical potential of CO2. The uncertainty of the method in the determination of the solubility was estimated for each experimental points by error analysis. © 2006 American Institute of Chemical Engineers AIChE J, 2006
Behavioral and temperamental features of children with Costello syndrome
Authors: Galéra Cédric , Delrue Marie‐Ange , Goizet Cyril , Etchegoyhen Kattalin , Taupiac Emmanuelle , Sigaudy Sabine , Arveiler Benoît , Philip Nicole , Bouvard Manuel , Lacombe Didier
Published: March 2006

Costello syndrome (CS) is a rare genetic condition due to germline mutations in HRAS proto‐oncogene and characterized by increased birth weight, postnatal growth retardation, distinctive facial appearance, typical medical problems (including feeding problems in the neonatal period), cutaneous anomalies, and developmental delay. Outgoing personality has often been noted in case reports, but few studies have focused specifically on the behavioral aspects of CS. A preliminary survey described irritability in younger patients with improvement between age 2 and 4, but a standardized psychometric tool was not used. A second study using the Child Behavior Checklist (CBCL) showed relatively high (albeit subclinical) levels of internalizing problems. These descriptive investigations lacked a control group. We describe a comparative survey to evaluate the behavioral and temperamental features of children with CS. We conducted a cross‐sectional assessment using the CBCL and the Emotionality, Activity, Shyness, Sociability (EAS) temperament questionnaire to evaluate behavior and temperament in 11 CS children (2 years 5 months to 9 years) comparing them to 33 gender‐ and age‐matched children without disability. The results suggest that the high levels of internalizing problems found before age 4 in CS patients might decrease with age. They also point to possible “hyperemotionality.” Further studies using a larger sample size and IQ‐matched control groups are needed to more accurately characterize individuals with this rare syndrome. © 2006 Wiley‐Liss, Inc.
Fumarase deficiency caused by homozygous P131R mutation and paternal partial isodisomy of chromosome 1
Authors: Zeng Wen‐Qi , Gao Hanlin , Brueton Louise , Hutchin Tim , Gray George , Chakrapani Anupam , Olpin Simon , Shih Vivian E.
Published: March 2006

We report on the first case of fumarase deficiency (FD) caused by uniparental isodisomy. An affected patient was found to be homozygous for the P131R mutation in the FH gene. In this nonconsanguineous family, the unaffected father was found to be heterozygous for the same mutation, and the mother was found to be homozygous wild‐type. Analysis of chromosome 1 markers showed that the patient inherited both paternal alleles with complete absence of the maternal homolog. The two copies of the paternal chromosome 1 are heterodisomic for most of the chromosome except the distal 1q region which is isodisomic for the mutant alleles of the FH gene. The genotypes of other chromosome markers are consistent with the patient inheriting alleles from both parents. Although FD is an autosomal recessive disorder, the effects of uniparental disomy (UPD) should be considered in genetic counseling since the recurrence risk of an affected child is significantly reduced when the disorder is due to UPD. © 2006 Wiley‐Liss, Inc.
A prospective study of PHACE syndrome in infantile hemangiomas: Demographic features, clinical findings, and complications
Authors: Metry D.W. , Haggstrom A.N. , Drolet B.A. , Baselga E. , Chamlin S. , Garzon M. , Horii K. , Lucky A. , Mancini A.J. , Newell B. , Nopper A. , Heyer G. , Frieden I.J.
Published: March 2006

PHACE (OMIM no. 606519) is a neurocutaneous syndrome that refers to the association of large, plaque‐like, “segmental” hemangiomas of the face, with one or more of the following anomalies: posterior fossa brain malformations, arterial cerebrovascular anomalies, cardiovascular anomalies, eye anomalies, and ventral developmental defects, specifically sternal defects and/or supraumbilical raphe. The etiology and pathogenesis of PHACE is unknown, and potential risk factors for the syndrome have not been systematically studied. The purpose of this study was thus to determine (1) the incidence of PHACE and associated anomalies among a large cohort of hemangioma patients, (2) whether certain demographic, prenatal or perinatal risk factors predispose infants to this syndrome, and (3) whether the cutaneous distribution of the hemangioma can be correlated to the types of anomalies present. We undertook a prospective, cohort study of 1,096 children with hemangiomas, 25 of whom met criteria for PHACE. These 25 patients represented 20% of infants with segmental facial hemangiomas. Compared to previous reports, our PHACE patients had a higher incidence of cerebrovascular and cardiovascular anomalies. Two developed acute arterial ischemic stroke during infancy, while two with cardiovascular anomalies showed documented evidence of normalization, suggesting that both progressive and regressive vascular phenomena may occur in this syndrome. Correlation to the anatomic location of the hemangioma appears to be helpful in determining which structural abnormalities might be present. A comparison of demographic and perinatal data between our PHACE cases and the hemangioma cohort overall showed no major differences, except a trend for PHACE infants to be of slighter higher gestational age and born to slightly older mothers. Eighty‐eight percent were female, a finding which has been noted in multiple other reports. Further research is needed to determine possible etiologies, optimal evaluation, and outcomes. © 2006 Wiley‐Liss, Inc.
Reporting genetic results in research studies: Summary and recommendations of an NHLBI working group
Authors: Bookman Ebony B. , Langehorne Aleisha A. , Eckfeldt John H. , Glass Kathleen C. , Jarvik Gail P. , Klag Michael , Koski Greg , Motulsky Arno , Wilfond Benjamin , Manolio Teri A. , Fabsitz Richard R. , Luepker Russell V.
Published: March 2006

Prospective epidemiologic studies aid in identifying genetic variants associated with diseases, health risks, and physiologic traits. These genetic variants may eventually be measured clinically for purposes of diagnosis, prognosis, and treatment. As evidence of the potential clinical value of such information accrues, research studies face growing pressure to report these results to study participants or their physicians, even before sufficient evidence is available to support widespread screening of asymptomatic persons. There is thus a need to begin to develop consensus on whether and when genetic findings should be reported to participants in research studies. The National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group on Reporting Genetic Results in Research Studies to discuss if, when, and how genetic information should be reported to study participants. The Working Group concluded that genetic test results should be reported to study participants when the associated risk for the disease is significant; the disease has important health implications such as premature death or substantial morbidity or has significant reproductive implications; and proven therapeutic or preventive interventions are available. Finally, the Working Group recommended procedures for reporting genetic research results and encouraged increased efforts to create uniform guidelines for this activity. Published 2006 Wiley‐Liss, Inc.
Synthesis and Antioxidant Activity of New Tetrahydro‐Naphthalene‐Indole Derivatives as Retinoid and Melatonin Analogs
Authors: Ates‐Alagoz Zeynep , Coban Tulay , Buyukbingol Erdem
Published: March 2006

A number of retinoid‐related compounds represent classes of antioxidative and proapoptotic agents with promising potential in the treatment of neoplastic diseases. Indeed, the synthetic retinoid amide fenretinide [N‐(4‐hydroxyphenyl)retinamide] induces apoptosis of cancer cells and acts as a chemotherapeutic drug in cancer therapy. In the present work, and as a continuation of our studies on retinoid‐type compounds, the synthesis of melatonin retinamide derivatives was studied as a novel series of melatonin retinoids, using the condensation reaction sequence involving tetrahydrotetramethylnaphthalene carboxylic acid and appropriate melatonin‐type moieties. Despite of the weak DPPH inhibition activity pattern of the synthesized compounds, some of them showed a strong inhibition on lipid peroxidation (IVa–b, Va,andVIIa–c,88, 96, 90, 94, 93, and 86%, respectively at 10–4M concentration) when melatonin (85% at 10–4M concentration) was used as a reference compound.
Molecular Structure and QSAR Study on Antispasmodic Activity of some Xanthoxyline Derivatives
Authors: dos Santos Rodrigo , Kuhnen Carlos Alberto , Yunes Rosendo Augusto
Published: March 2006

Semi‐empirical molecular orbital calculations at AM1 level were done with the aim to investigate the structure‐activity relationships of antispasmodic activities of ten 2‐(X‐benzyloxy)‐4,6‐dimethoxyacetophenones with X = H, 4′‐F, 4′‐NO2, 4′‐CH3, 4′‐Cl, 3′,4′‐(CH3)2, 4′‐OCH3, 4′‐Br, 4′‐OCH2C6H5, and 4′‐C(CH3)3, against acetylcholine‐induced contraction of the guinea pig ileum. The most significant quantum chemical descriptors for this series of compounds were the net atomic charges, nucleophilic and electrophilic frontier electron density, HOMO and LUMO orbitals, and reactivity indices. While no significant correlations were found employing molecular parameters such as heat of formation, dipole moment, molecular polarizability, and so on, good correlations were obtained using the reactivity indices of HOMO and LUMO orbitals at specific atoms of the molecules. These results indicate that the spatial distribution of HOMO and LUMO orbitals over these specific atoms play an important role for an increase of biological activity.
Synthesis of Substituted 3‐Anilino‐5‐phenyl‐1,3‐dihydro‐ 2H‐1,4‐benzodiazepine‐2‐ones and their Evaluation as Cholecystokinin‐Ligands
Authors: Offel Michael , Lattmann Pornthip , Singh Harjit , Billington D. C. , Bunprakob Yodchai , Sattayasai Jintana , Lattmann Eric
Published: March 2006

3‐Amino‐1,4‐benzodiazepines as well as chemically related diverse amines were prepared from oxazepam and subsequently screened on the cholecystokinin receptor in a radiolabel binding assay. Oxazepam 2 was activated via its 3‐chloro‐1,4‐benzodiazepine intermediate 3 and was reacted with a large series of aliphatic and aromatic amines. The substituted 3‐anilino‐1,4‐benzodiazepine structure was identified as lead structure in a diverse series of 3‐amino‐1,4‐benzodiazepines 4‐38 and the full SAR (structure‐activity relationship) optimisation provided 3‐anilinobenzodiazepines 16–38 with CCK1 receptor selectivity to CCK2. The compounds 18, 24, 28 and 33 have shown affinities at the CCK1 receptor of 11, 10, 11 and 9 nM, respectively. These equipotent CCK1 ligands were fully evaluated in behaviour pharmacological essays. An antidepressant effect was identified in the tail suspension‐ and the Porsolt swimming‐test. The ED50 values for 24 and 28 were determined in these assays as 0.46 and 0.49 mg/kg. The mixed antagonist 37 showed in addition to the antidepressant effects anxiolytic properties.
Synthesis and Antifungal Activity of 2‐Aryl‐1,2,4‐triazolo[1,5‐a]pyridine Derivatives
Authors: Luo Yun , Hu Yongzhou
Published: March 2006

A series of novel antifungal triazole derivatives 2‐aryl‐1,2,4‐triazolo[1,5‐a]pyridine 9a–m were synthesized and tested in vitro for their growth inhibitory activities against C. albicans and T. rubrum. The MIC values indicate that the activities of three compounds were superior or comparable to fluconazole against both tested fungi, worthy of further investigation of its antifungal activities.
Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: Two‐year clinical and radiographic results from the TEMPO study, a double‐blind, randomized trial
Authors: van der Heijde Désirée , Klareskog Lars , Rodriguez‐Valverde Vicente , Codreanu Catalin , Bolosiu Horatiu , Melo‐Gomes Jose , Tornero‐Molina Jesus , Wajdula Joseph , Pedersen Ronald , Fatenejad Saeed ,   TEMPO Study Investigators
Published: March 2006

Objective

To evaluate the efficacy, including radiographic changes, and safety of etanercept and methotrexate (MTX), used in combination and alone, in patients with rheumatoid arthritis (RA) in whom previous treatment with a disease‐modifying antirheumatic drug other than MTX had failed.

Methods

Patients with RA were treated with etanercept (25 mg subcutaneously twice weekly), oral MTX (up to 20 mg weekly), or combination therapy with etanercept plus MTX through a second year, in a double‐blinded manner. Clinical response was assessed using American College of Rheumatology (ACR) criteria and the Disease Activity Score (DAS), in a modified intent‐to‐treat analysis with the last observation carried forward (LOCF) and in a population of completers. Radiographs of the hands, wrists, and forefeet were scored for erosions and joint space narrowing at annual intervals.

Results

A total of 503 of 686 patients continued into year 2 of the study. During the 2 years, significantly fewer patients receiving combination therapy withdrew from the study (29% of the combination therapy group, 39% of the etanercept group, and 48% of the MTX group). Both the LOCF and the completer analyses yielded similar results. The ACR 20% improvement (ACR20), ACR50, and ACR70 responses and the remission rates (based on a DAS of <1.6) were significantly higher with combination therapy than with either monotherapy (P < 0.01). Similarly, improvement in disability (based on the Health Assessment Questionnaire) was greater with combination therapy (P < 0.01). The combination therapy group showed significantly less radiographic progression than did either group receiving monotherapy (P < 0.05); moreover, radiographic progression was significantly lower in the etanercept group compared with the MTX group (P < 0.05). For the second consecutive year, overall disease progression in the combination therapy group was negative, with the 95% confidence interval less than zero. Adverse events were similar in the 3 treatment groups.

Conclusion

Etanercept in combination with MTX reduced disease activity, slowed radiographic progression, and improved function more effectively than did either monotherapy over a 2‐year period. No increase in toxicity was associated with combination treatment with etanercept plus MTX.
Targeting of angiogenic endothelial cells at sites of inflammation by dexamethasone phosphate–containing RGD peptide liposomes inhibits experimental arthritis
Authors: Koning Gerben A. , Schiffelers Raymond M. , Wauben Marca H. M. , Kok Robbert J. , Mastrobattista Enrico , Molema Grietje , ten Hagen Timo L. M. , Storm Gert
Published: March 2006

Objective

To investigate whether RGD peptide–exposing long circulating polyethylene glycol (PEG) liposomes (RGD‐PEG–L) targeted to αvβ3 integrins expressed on angiogenic vascular endothelial cells (VECs) are able to bind VECs at sites of inflammation and whether such liposomes containing dexamethasone phosphate (DEXP) can be used as carriers to interfere with the development of experimental arthritis.

Methods

Binding and internalization of RGD‐PEG–L were studied by fluorescence‐activated cell sorting and confocal microscopy using fluorescently labeled liposomes. Radiolabeled liposomes were used to test in vivo pharmacokinetics and inflammation site targeting in lipopolysaccharide (LPS)–induced inflammation and adjuvant‐induced arthritis (AIA) in rats. In vivo inflammation targeting was visualized by intravital microscopy using fluorescently labeled RGD‐PEG–L. Therapeutic efficacy of DEXP‐encapsulating RGD‐PEG–L compared with nontargeted liposomes was evaluated in rats with AIA.

Results

RGD‐PEG–L bound to and were taken up by proliferating human VECs in vitro. In vivo, increased targeting of radiolabeled RGD‐PEG–L to areas of LPS‐induced inflammation in rats was observed. Specific association with the blood vessel wall at the site of inflammation was confirmed by intravital microscopy. One single intravenous injection of DEXP encapsulated in RGD‐PEG–L resulted in a strong and long‐lasting antiarthritic effect in rat AIA.

Conclusion

RGD‐targeted PEG liposomes represent an endothelial cell–specific drug delivery system that targets VECs at sites of inflammation. Use of these liposomes to deliver DEXP to VECs at arthritis‐affected sites proved efficacious in rat adjuvant arthritis. These data indicate that VECs have an essential role in the inflammation process and suggest the possibility of using VEC targeting for therapeutic intervention in inflammatory processes such as arthritis.
Inhibition of systemic sclerosis dermal fibroblast type I collagen production and gene expression by simvastatin
Authors: Louneva Natalia , Huaman Gonzalo , Fertala Joanna , Jiménez Sergio A.
Published: March 2006

Objective

To examine whether statins are capable of modulating collagen gene expression in cultured systemic sclerosis dermal fibroblasts.

Methods

Cultured dermal fibroblasts from 3 patients with diffuse systemic sclerosis of recent onset were treated with 5 μM and 10 μM of simvastatin for 3 or 4 days. Morphologic features, cytotoxicity, and type I collagen production and messenger RNA (mRNA) levels in the fibroblasts were examined. The effects of mevalonate, geranylgeranyl pyrophosphate (GGPP), and farnesyl pyrophosphate (FPP), which are lipids downstream from the hydroxymethylglutaryl–coenzyme A block, were also examined. Transient transfections with COL1A1 promoter‐reporter constructs and electrophoretic gel mobility shift assays were utilized to examine COL1A1 transcription and Sp1 and CCAAT‐box binding factor (CBF) binding.

Results

Simvastatin did not cause morphologic changes or cytotoxicity in the fibroblasts, even after 4 days of treatment. Type I collagen production and mRNA levels showed a potent and dose‐related inhibition following 3 and 4 days of treatment. The inhibition of collagen gene expression by simvastatin was completely reversed by mevalonate and GGPP, but not by FPP. The statin effects occurred at the transcriptional level and involved the proximal COL1A1 promoter region encompassing −174 bp. A significant reduction in Sp1 and CBF binding activity was also found in simvastatin‐treated cells.

Conclusion

Simvastatin is a powerful inhibitor of type I collagen gene expression in normal and systemic sclerosis fibroblasts. The pleiotropic protective effects of statins on various endothelial and immune cell functions in conjunction with their potent inhibitory effects on type I collagen gene expression suggest that statins may be effective therapeutic agents in systemic sclerosis.
Ectopic calcification among families in the Azores: Clinical and radiologic manifestations in families with diffuse idiopathic skeletal hyperostosis and chondrocalcinosis
Authors: Bruges‐Armas Jácome , Couto Ana Rita , Timms Andrew , Santos Margarida R. , Bettencourt Bruno Filipe , Peixoto Maria José , Colquhoun Katherine , McNally Eugene G. , Carneiro Victor , Herrero‐Beaumont Gabriel , Brown Matthew A.
Published: March 2006

Objective

Twelve families that were multiply affected with diffuse idiopathic skeletal hyperostosis (DISH) and/or chondrocalcinosis, were identified on the island of Terceira, The Azores, potentially supporting the hypothesis that the 2 disorders share common etiopathogenic factors. The present study was undertaken to investigate this hypothesis.

Methods

One hundred three individuals from 12 unrelated families were assessed. Probands were identified from patients attending the Rheumatic Diseases Clinic, Hospital de Santo Espírito, in The Azores. Family members were assessed by rheumatologists and radiologists. Radiographs of all family members were obtained, including radiographs of the dorsolumbar spine, pelvis, knees, elbows, and wrists, and all cases were screened for known features of chondrocalcinosis.

Results

Ectopic calcifications were identified in 70 patients. The most frequent symptoms or findings were as follows: axial pain, elbow, knee and metacarpophalangeal (MCP) joint pain, swelling, and/or deformity, and radiographic enthesopathic changes. Elbow and MCP joint periarticular calcifications were observed in 35 and 5 patients, respectively, and chondrocalcinosis was identified in 12 patients. Fifteen patients had sacroiliac disease (ankylosis or sclerosis) on computed tomography scans. Fifty‐two patients could be classified as having definite (17%), probable (26%), or possible (31%) DISH. Concomitant DISH and chondrocalcinosis was diagnosed in 12 patients. Pyrophosphate crystals were identified from knee effusions in 13 patients. The pattern of disease transmission was compatible with an autosomal‐dominant monogenic disease. The mean age at which symptoms developed was 38 years.

Conclusion

These families may represent a familial type of pyrophosphate arthropathy with a phenotype that includes peripheral and axial enthesopathic calcifications. The concurrence of DISH and chondrocalcinosis suggests a shared pathogenic mechanism in the 2 conditions.
Evaluation of classical complement pathway activation in rheumatoid arthritis: Measurement of C1q–C4 complexes as novel activation products
Authors: Wouters Diana , Voskuyl Alexandre E. , Molenaar Esmeralda T. H. , Dijkmans Ben A. C. , Hack C. Erik
Published: March 2006

Objective

Novel activation products that are stable and minimally susceptible to in vitro artefacts have recently been described in the classical complement pathway. The present study assessed circulating levels of these products, i.e., covalent complexes between the recognition molecule of the classical pathway (C1q) and activated C4, in plasma samples from patients with rheumatoid arthritis (RA) to establish the relationship between these levels and the clinical and immunologic parameters in these patients.

Methods

C1q–C4 levels were measured in plasma samples from 41 patients with active RA and 43 patients with inactive RA. These levels were related to other complement activation products and to disease activity according to the Disease Activity Score in 28 joints (DAS28), using Spearman's rank correlations.

Results

C1q–C4 plasma levels were significantly higher in patients with active RA as compared with patients with RA in clinical remission (median 3.3 arbitrary units [AU], range 0.4–13.4 versus 1.7 AU, range 0.2–5.5; P = 0.0001), suggesting that activation of the classical complement pathway reflects disease activity. This was supported by a significant correlation between C1q–C4 levels and the DAS28 (r = 0.398, P = 0.0002). Levels of other complement activation products, such as activated C4 (C4b/c), were also significantly elevated in patients with active disease compared with patients with inactive disease (P = 0.03), and were correlated with C1q–C4 levels (r = 0.329, P = 0.002). Levels of C1q–C4 complexes were higher in synovial fluid samples than in plasma samples from the 4 patients tested.

Conclusion

Systemic complement activation via the classical pathway in patients with RA correlates with disease activity. These results indicate that C1q–C4 complexes may be used as a biomarker for RA.
Peripheral blood T lymphocytes from patients with early rheumatoid arthritis express RANKL and interleukin‐15 on the cell surface and promote osteoclastogenesis in autologous monocytes
Authors: Miranda‐Carús María‐Eugenia , Benito‐Miguel Marta , Balsa Alejandro , Cobo‐Ibáñez Tatiana , Pérez De Ayala Carlos , Pascual‐Salcedo Dora , Martín‐Mola Emilio
Published: March 2006

Objective

To investigate the osteoclastogenic potential of T cells from the peripheral blood (PB) and synovial fluid (SF) of patients with rheumatoid arthritis (RA) on autologous monocytes, and to study the cytokines implicated in this process.

Methods

T cells and monocytes were isolated from the PB of 20 healthy subjects and 20 patients with early RA, and from the SF of 20 patients with established RA. Autologous T cell/monocyte cocultures were established in the absence of exogenous cytokines or growth factors in order to examine spontaneous ex vivo osteoclast differentiation by tartrate‐resistant acid phosphatase staining and calcified matrix resorption activity.

Results

Surface RANKL was expressed on freshly isolated T cells from the PB of patients with early RA and the SF of patients with established RA. In addition, surface interleukin‐15 (IL‐15) was detected on freshly isolated T cells and monocytes from the PB of patients with early RA and the SF of patients with established RA. Autologous T cell/monocyte cocultures derived from the SF of patients with established RA and from the PB of patients with early RA, but not from the PB of healthy controls, resulted in osteoclast differentiation that was significantly inhibited by osteoprotegerin (OPG) and by neutralizing monoclonal antibodies to IL‐15, IL‐17, tumor necrosis factor α (TNFα), and IL‐1β. OPG, anti‐TNFα, and anti–IL‐1β demonstrated a cooperative inhibitory effect. At 1‐year followup, surface RANKL and IL‐15 and ex vivo osteoclastogenesis were no longer observed on PB T cells or monocytes from patients with early RA in whom clinical remission had been achieved with treatment.

Conclusion

T cells are important contributors to the pathogenesis of bone erosions in RA through interaction with osteoclast precursors of the monocyte/macrophage lineage.
The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities: A large, randomized, placebo‐controlled trial
Authors: Westhovens Rene , Yocum David , Han John , Berman Alberto , Strusberg Ingrid , Geusens Piet , Rahman Mahboob U. ,   START Study Group
Published: March 2006

Objective

To assess the risk of serious infections following 22 weeks of infliximab therapy, and to further characterize the safety profile of infliximab in combination with background treatments during 1 year in patients with rheumatoid arthritis (RA) with various comorbidities.

Methods

Patients with active RA despite receiving methotrexate (MTX) were randomly assigned to receive infusions of placebo (group 1, n = 363), 3 mg/kg infliximab (group 2, n = 360), or 10 mg/kg infliximab (group 3, n = 361) at weeks 0, 2, 6, and 14. At week 22, patients in placebo group 1 began receiving 3 mg/kg infliximab, and patients in group 3 continued to receive an infliximab dose of 10 mg/kg. Patients in group 2 who failed to meet predefined response criteria received increasing doses of infliximab in increments of 1.5 mg/kg.

Results

At week 22, the relative risk of developing serious infections in groups 2 and 3, compared with group 1, was 1.0 (95% confidence interval [95% CI] 0.3–3.1, P = 0.995) and 3.1 (95% CI 1.2–7.9, P = 0.013), respectively. The incidence of serious adverse events was 7.8% in groups 2 and 3 compared with 7.5% in group 1. From week 22 to week 54, 11.8%, 9.9%, and 10.3% of patients in groups 1, 2, and 3, respectively, reported occurrences of serious adverse events. Through week 54, 1 patient in group 1, 2 patients in group 2, and 4 patients in group 3 developed active tuberculosis.

Conclusion

The risk of serious infections in patients receiving the approved infliximab dose of 3 mg/kg plus MTX was similar to that in patients receiving MTX alone. Patients receiving the unapproved induction regimen of 10 mg/kg infliximab plus MTX followed by a 10 mg/kg maintenance regimen had an increased risk of serious infections through week 22.
Disc space narrowing as a new risk factor for vertebral fracture: The OFELY study
Authors: Sornay‐Rendu Elisabeth , Allard Chloé , Munoz Françoise , Duboeuf François , Delmas Pierre D.
Published: March 2006

Objective

In a previous cross‐sectional analysis, we found a positive association between disc space narrowing (DSN) and vertebral fracture. The aim of the present study was to analyze prospectively the risk of vertebral and nonvertebral fractures in women with spine osteoarthritis (OA).

Methods

Using radiographs, spine OA was evaluated in 634 postmenopausal women from the OFELY (Os des Femmes de Lyon) cohort (mean ± SD age 61.2 ± 9 years). Prevalence and severity of spine OA were assessed by scoring osteophytes and DSN. Incidental clinical fractures were prospectively registered during annual followup, and vertebral fractures were evaluated by radiography every 4 years.

Results

During an 11‐year followup, fractures occurred in 121 women, including 42 with vertebral fractures. No association was found between osteophytes and the risk of fracture. In contrast, DSN was associated with an increased risk of vertebral fractures but not of nonvertebral fractures. After adjusting for confounding variables, the presence of DSN was associated with a marked increased risk of vertebral fractures, with an odds ratio of 6.59 (95% confidence interval 1.36–31.9). In addition, 95% of incident vertebral fractures were located above the disc with the most severe narrowing.

Conclusion

This longitudinal study shows that, despite a higher bone mineral density (BMD), women with spine OA do not have a reduced risk of fracture and that DSN is significantly associated with vertebral fracture risk. The location of DSN and of incident vertebral fractures suggests that disc degeneration impairs the biomechanics of the above spine, which leads to the increased risk of vertebral fractures, independent of BMD. We suggest that DSN is a newly identified risk factor for vertebral fracture that should be taken into consideration when assessing vertebral fracture risk in postmenopausal women.