bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Initial Corticosteroid Therapy on Coronary Artery Aneurysm Formation in Kawasaki Disease: A Meta-analysis of 862 Children
Authors: Wooditch Angela C. , Aronoff Stephen C.
Published: September 2005

Objective. Kawasaki disease is an acute vasculitis of infancy and childhood. When untreated, 15% to 25% of patients develop coronary artery aneurysms. Although the use of aspirin and intravenous immune globulin (IVIG) as initial therapy is well established, the role of corticosteroids is uncertain. The objective of this study was to identify clinical trials that compared the rate of coronary aneurysm formation after initial therapy with corticosteroids or an appropriate control and to determine the overall efficacy of corticosteroid therapy for the initial treatment of Kawasaki disease.

Methods. Published studies were identified by searches of the Medline and the Cochrane Central Register of Controlled Trials databases as well as hand searches of selected references. Studies were included when (1) all subjects had a stated diagnosis of Kawasaki disease; (2) a corticosteroid preparation was included as part of the initial management of the disease process; (3) a therapeutically matched control group was included for the entire study, or subsets of patients that received a therapeutic intervention identical to the experimental group except for the inclusion of a corticosteroid compound could be identified; and (4) 2-dimensional echocardiography or coronary artery catheterization was performed at least 2 weeks after therapy to detect the presence of coronary aneurysms. Included studies were evaluated for quality and heterogeneity. Meta-analysis was performed using a fixed-effects model.

Results. Eight studies fulfilled criteria for inclusion. Because 2 of these studies provided adequate detail to permit evaluation of 2 subgroups each, a total of 10 groups were available for evaluation. The significant heterogeneity that existed among the 10 studies (Q = 21.9, I2 = 59.0) was eliminated when 2 studies with markedly different study designs were removed (Q = 5.59, I2 = 0.00). Meta-analysis of the remaining 8 studies revealed a significant reduction in the incidence of coronary artery aneurysms among patients who received corticosteroid therapy plus aspirin ± IVIG compared with aspirin ± IVIG alone (odds ratio [OR] 0.546; 95% confidence interval [CI]: 0.371–0.803); the benefit of corticosteroid therapy was maintained when study subsets of aspirin alone (OR: 0.601; 95% CI: 0.392–0.921) or aspirin + IVIG (OR: 0.352; 95% CI: 0.136–0.909) were compared with matched regimens that contained corticosteroids.

Conclusion. The inclusion of corticosteroids in aspirin-containing regimens for the initial treatment of Kawasaki disease reduces the incidence of coronary aneurysms.
Human Umbilical Cord Blood–Derived CD133+ Cells Enhance Function and Repair of the Infarcted Myocardium
Authors: Leor Jonathan , Guetta Esther , Feinberg Micha S. , Galski Hanan , Bar Iris , Holbova Radka , Miller Liron , Zarin Parvin , Castel David , Barbash Israel M. , Nagler Arnon
Published: September 2005

The use of adult stem cells for myocardial tissue repair might be limited in elderly and sick people because their cells are depleted and exhausted. The present study was conducted to explore the potential of human umbilical cord blood (UCB) CD133+ progenitor cells for myocardial tissue repair in a model of extensive myocardial infarction (MI). CD133+ progenitor cells were isolated from newborn UCB. Cells (1.2–2 × 106) or saline (control) was infused intravenously 7 days after permanent coronary artery ligation in athymic nude rats. Left ventricular (LV) function was assessed before and 1 month after infusion by echocardiography. Tracking of human cells was performed by fluorescent in situ hybridization for human X and Y chromosomes or by immunostaining for HLA-DR or HLA-ABC. One month after delivery, LV fractional shortening improved by 42 ± 17% in cell-treated hearts and decreased by 39 ± 10% in controls (p = .001). Anterior wall thickness decreased significantly in controls but not in treated hearts. Microscopic examination revealed that the UCB cells were able to migrate, colonize, and survive in the infarcted myocardium. Human cells were identified near vessel walls and LV cavity and were occasionally incorporated into endothelial cells in six of nine cell-treated animals but not in controls. Scar tissue from cell-treated animals was significantly populated with autologous myofibroblasts as indicated by colocalization of HLA-DR and α-smooth muscle actin staining. In conclusion, the present work suggests that, after MI, intravenous delivery of human UCB-derived CD133+ cells can produce functional recovery by preventing scar thinning and LV systolic dilatation.
Validity of Maternal and Perinatal Risk Factors Reported on Fetal Death Certificates
Authors: Lydon-Rochelle Mona T. , Cárdenas Vicky , Nelson Jennifer L. , Tomashek Kay M. , Mueller Beth A. , Easterling Thomas R.
Published: September 2005

We sought to estimate the accuracy, relative to maternal medical records, of perinatal risk factors recorded on fetal death certificates. We conducted a validation study of fetal death certificates among women who experienced fetal deaths between 1996 and 2001. The number of previous births, established diabetes, chronic hypertension, maternal fever, performance of autopsy, anencephaly, and Down syndrome had very high accuracy, while placental cord conditions and other chromosomal abnormalities were reported inaccurately. Additional population-based studies are needed to identify strategies to improve fetal death certificate data.
Nonfatal Injuries Among Middle-School and High-School Students in Guangxi, China
Authors: Chen Guanmin , Smith Gary A. , Deng Shusong , Hostetler Sarah Grim , Xiang Huiyun
Published: September 2005

Objectives. We described nonfatal injuries and calculated injury rates among middle-school and high-school students in Guangxi, China.

Methods. Students were selected using multistage randomizing techniques, and nonfatal injuries in 1840 students from February 2002 to January 2003 were monitored with standardized injury forms. Risk factors for injury were identified in multivariate analyses.

Results. The annual overall injury rate was 32.3 per 100 students. Boys had a significantly higher injury rate than the girls (34.8 vs 30.3 per 100 students), and a significantly higher proportion of injuries in boys was caused by other students (28.1% vs 19.4%). A higher proportion of injuries in girls (40.7%) occurred at home. For both boys and girls, sports were the most common activities associated with injury. Injuries from falls were the leading cause of injury, and extremities were most frequently injured. Gender, age, ethnicity, and family income levels were identified as significant risk factors for injury in multivariate analyses.

Conclusions. Nonfatal injuries in middle-school and high-school students should be recognized as a significant public health concern in China.
Integrating Child Health Information Systems
Authors: Hinman Alan R. , Eichwald John , Linzer Deborah , Saarlas Kristin N.
Published: September 2005

The Health Resources and Services Administration and All Kids Count (a national technical assistance center fostering development of integrated child health information systems) have been working together to foster development of integrated child health information systems.

Activities have included: identification of key elements for successful integration of systems; development of principles and core functions for the systems; a survey of state and local integration efforts; and a conference to develop a common vision for child health information systems to meet medical care and public health needs.

We provide 1 state (Utah) as an example that is well on the way to development of integrated child health information systems.
Developmental Stages of Developmental Screening: Steps to Implementation of a Successful Program
Authors: Pinto-Martin Jennifer A. , Dunkle Margaret , Earls Marian , Fliedner Dane , Landes Cynthia
Published: September 2005

Through the use of 2-stage screening strategies, research studies have shown that autism spectrum disorders and other developmental disabilities can now be detected reliably and with greater validity and in children as young as 18 months of age. Screening and diagnostic practices in the medical and educational arena lag far behind clinical research, however, with the average patient age at time of diagnosis being 3 to 6 years.

We discuss the challenges of instituting universal developmental screening as part of pediatric care and present 2 models of existing or planned programs of early screening for autism spectrum disorder and developmental disability (1 in a community-based setting and 1 in a pediatric setting), and discuss the pros and cons of the different strategies.
Restraint Use Among Northwest American Indian Children Traveling in Motor Vehicles
Authors: Lapidus Jodi A. , Smith Nicole H. , Ebel Beth E. , Romero Francine C.
Published: September 2005

Objectives. We sought to estimate motor vehicle passenger restraint use among Northwest American Indian children 8 years old or younger and to determine factors associated with using proper (i.e., age and weight appropriate) passenger restraint systems.

Methods. We surveyed vehicles driven by members of 6 tribes in Idaho, Oregon, and Washington. Associations between proper restraint and child, driver, and vehicle characteristics were analyzed using logistic regression for clustered data.

Results. We observed 775 children traveling in 574 vehicles; 41% were unrestrained. Proper restraint ranged from 63% among infant seat-eligible children to 11% among booster seat-eligible children and was associated with younger child’s age (odds ratio (OR) per year = 0.60; 95% confidence interval (CI) = 0.48, 0.75), seating location (OR front vs rear=0.27; 95% CI=0.16, 0.44), driver seat belt use (OR=2.39; 95% CI=1.51, 3.80), and relationship (OR for nonparent vs parent=0.28; 95% CI=0.14, 0.58). More than half of drivers felt children could use an adult seat belt earlier than recommended guidelines, and 63% did not correctly identify whether their tribe had child safety seat laws.

Conclusions. Children in these communities are inadequately restrained. Restraint use was exceedingly low among booster-eligible children and children riding with unrestrained adults. Interventions emphasizing appropriate restraint use and enforcement of passenger safety laws could reduce the risk of injury or death in motor vehicle accidents.
Nonfatal Injuries Among US Children With Disabling Conditions
Authors: Xiang Huiyun , Stallones Lorann , Chen Guanmin , Hostetler Sarah G. , Kelleher Kelly
Published: September 2005

Objectives. We investigated the risk of nonfatal injury in US children with disabilities. Disability was defined as a long-term reduction in the ability to conduct social role activities, such as school or play, because of a chronic physical or mental condition.

Methods. Among 57 909 children aged 5–17 years who participated in the 2000–2002 National Health Interview Survey, we identified 312 children with vision/hearing disabilities, 711 with mental retardation, 603 with attention-deficit/hyperactivity disorder (ADD/HD), and 403 with chronic asthma. We compared nonfatal injuries in the past 3 months between children with disabling conditions and those without using injury rates and logistic regression analyses.

Results. Compared with children without a disability, a higher percentage of children with disabilities reported nonfatal injuries (4.2% for vision disability, 3.2% for mental retardation, 4.5% for attention-deficit/hyperactivity disorder, and 5.7% for asthma vs 2.5% for healthy children). After we controlled for confounding effects of sociodemographic variables, children with disabilities, with the exception of mental retardation, had a statistically significantly higher injury risk than those without disabling conditions.

Conclusions. Children with a disabling condition from vision/hearing disability, ADD/HD, or chronic asthma had a significantly higher risk for nonfatal injuries compared with children without a disabling condition. These data underscore the need to promote injury control and prevention programs targeting children with disabilities.
Moving Forward in Fall Prevention: An Intervention to Improve Balance Among Older Adults in Real-World Settings
Authors: Robitaille Yvonne , Laforest Sophie , Fournier Michel , Gauvin Lise , Parisien Manon , Corriveau Hélène , Trickey Francine , Damestoy Nicole
Published: September 2005

Objectives. We investigated the effectiveness of a group-based exercise intervention to improve balancing ability among older adults delivered in natural settings by staff in local community organizations.

Methods. The main component of the intervention consisted of biweekly group-based exercise sessions conducted over 12 weeks by a professional, coupled with home-based exercises. In a quasiexperimental design, 10 community organizations working with older adults offered the intervention to groups of 5 to 15 persons concerned about falls, while 7 organizations recruited similar groups to participate in the control arm of the study. Participants (98 experimental and 102 control) underwent balance assessments by a physiotherapist at registration and 3 months later.

Results. Eighty-nine percent of participants attended the 3-month measurement session (n=177). A linear regression analysis showed that after adjusting for baseline levels of balance and demographic and health characteristics, the intervention significantly improved static balance and mobility.

Conclusion. Structured, group-based exercise programs offered by community organizations in natural settings can successfully increase balancing ability among community-dwelling older adults concerned about falls.
Reevaluating the Benefits of Folic Acid Fortification in the United States: Economic Analysis, Regulation, and Public Health
Authors: Grosse Scott D. , Waitzman Norman J. , Romano Patrick S. , Mulinare Joseph
Published: September 2005

Before a 1996 US regulation requiring fortification of enriched cereal-grain products with folic acid, 3 economic evaluations projected net economic benefits or cost savings of folic acid fortification resulting from the prevention of pregnancies affected by a neural tube defect. Because the observed decline in neural tube defect rates is greater than was forecast before fortification, the economic gains are correspondingly larger.

Applying both cost–benefit and cost-effectiveness analytic techniques, we estimated that folic acid fortification is associated with annual economic benefit of $312 million to $425 million. The cost savings (net reduction in direct costs) were estimated to be in the range of $88 million to $145 million per year.
Decomposition in Extreme‐Rich Fens of Boreal Alberta, Canada
Authors: Turetsky Merritt R. , Ripley Shannon
Published: September 2005

Rich fens (minerotrophic peatlands with surface water pH > 5.5) have greater alkalinity and species richness than other boreal peatlands. We used short‐term laboratory incubations to quantify CO2 and CH4 production in peat from five extreme‐rich fens in Alberta. Carbon dioxide production rates averaged 48.29 ± 1.36 μmol CO2 g organic matter−1 d−1 across sites and sampling events. Peat from all sites produced CH4 during anaerobic incubations, leading to average anaerobic CH4 production rates of 359.53 ± 138.7 nmol CH4 g organic matter−1 d−1 However, methane frequently was consumed (oxidized) during aerobic incubations, leading to aerobic CH4 consumption rates averaging 75.2 ± 63.7 nmol CH4 g organic matter−1 d−1 across sites. Calculated rates of dissolved H2CO3 + HCO3− production averaged 59.7 ± 13.4 μmol g organic matter−1 d−1, suggesting that dissolved inorganic C is important to the overall C fluxes in these rich fens. Our results suggest that changing hydrologic conditions will influence the balance between methanogenesis and methanotrophy in rich fens, but that surface water chemistry, likely influenced by marl precipitation, also is important to decomposition. Rich fens are estimated to represent the most common wetland type in Alberta, and these peatland ecosystems could play an important role in trace gas emissions across boreal regions.
Spatial Distribution of Ammonium and Calcium in Optimally Fertilized Pine Plantation Soils
Authors: Edwards Ivan , Gillespie Andrew , Chen Jennifer , Johnsen Kurt , Turco Ronald
Published: September 2005

Commercial timber production is increasingly reliant on long‐term fertilization to maximize stand productivity, yet we do not understand the extent to which this practice homogenizes soil properties. The effects of 16 yr of optimal fertilization and optimal fertilization with irrigation (fertigation) on forest floor depth, pH, total organic carbon (TOC) and total nitrogen (TN) content, and concentrations of potentially plant available NH4+, Ca2+, Mg2+, and Al3+ in the fine root zone of monoculture loblolly pine (Pinus taeda L.) stands in North Carolina were examined. Generally, optimal fertilization significantly increased forest floor depth and the concentrations of potentially plant available NH4+, Ca2+, and Mg2+ No significant effects on TOC or TN were observed. However, differences were observed between optimally fertilized and fertigated treatments. Specifically, fertilization alone tended to retain more Ca2+ and Mg2+ in the root zone and to increase pH more than fertigation. Semivariogram analysis indicated optimal fertilization generally lead to a significant increase in the effective spatial autocorrelation ranges of NH4+ and Ca2+ at the end of the growing season, from approximately 25 m in controls to more than 100 m. However, optimally fertilized and fertigated plots differed in terms of their NH4+ and Ca2+ spatial autocorrelation ranges, with the ranges in fertigated plots being 1.5‐ to 2‐fold greater. A comparison of kriged maps of NH4+ and Ca2+ availability in fall 2000 and spring 2001 suggested that the spatial distribution of Ca2+, which has not been added to these soils for 6 yr, was stable, whereas the heterogeneity of NH4+ distribution increased post fertilization.
Podzolization in a Sand Pit in Northern Michigan
Authors: Bronick C. J. , Mokma D. L.
Published: September 2005

A study of podzolization during early soil development was conducted in a sand pit. The purpose of this study was to describe the effects of podzolization under jack pine (Pinus banksiana Lamb.) and red pine (Pinus resinosa Ait.) planted on C horizon material in the pit and to compare them with the undisturbed soil adjacent to the pit. The E, Bs, and C horizon materials were analyzed for organic matter (OM) by loss‐on‐ignition and optical density of the ammonium oxalate extract (ODOE), Al and Fe by ammonium oxalate extraction and plasma emission spectroscopy, pH, and color. After only 40 yr, soil colors indicated that there was evidence of eluviation and illuviation. Organic matter increased and pH decreased in surface horizons whereas, Al and to a lesser extent Fe showed indications of translocation. The Bs horizons that formed under jack pine tended to have more Al, Fe, and OM and higher ODOE values than those that formed under red pine. Podzolization was more visibly evident than chemically evident in the pit pedons. We classified four of the six pit pedons as Typic Udipsamments and the other two as Spodic Udipsamments and the two control pedons as Entic Haplorthods.
Growth Response of Eucalyptus regnans and Soil Changes following Periodic Fertilization
Authors: Ringrose C. , Neilsen W. A.
Published: September 2005

Increased demand for plantation hardwood production has resulted in the progression of Eucalyptus plantations onto soils of reasonable physical structure but low nutrient status. This study was undertaken to investigate the effects of periodic fertilization through 15 yr on stand growth and soil chemistry of a Eucalyptus regnans F. Mueller plantation on a high rainfall site in southern Tasmania. Substantial response to N fertilizer, applied as ammonium sulfate, were measured, but there was no response to P applied as single superphosphate, either alone or in combination with N. Annual applications of N fertilizer, for a period of 13 yr, at 100 kg N ha−1 yr−1 doubled volume growth from 125 to 281 m3 ha−1, at Age 19 yr. Long‐term fertilization resulted in the accumulation of nutrients within the forest floor and surface soils. Significant reductions in soil pH, from 4.5 to 3.6 in the surface soil, were associated with the highest rate of fertilization. Reductions in pH occurred with both nitrogenous and phosphatic fertilizers. Substantial reductions in exchangeable Mg concentrations in surface soils, from 258 to 71 mg kg−1 were also measured. The research highlights the balance needed between obtaining growth response and causing detrimental soil effects from long‐term fertilization.
Mineralogical Distinctions of Carbonates in Desert Soils
Authors: Kraimer Rebecca A. , Monger H. Curtis , Steiner Robert L.
Published: September 2005

Soil carbonate‐C is a large pool of C and, in desert environments, is the dominant type of C stored in soil. To more fully understand the global C cycle and the role of soil in C sequestration, it is important to recognize how C enters and leaves the carbonate pool, as well as identify the forms of carbonate that exist in the soil. In the Desert Project in southern New Mexico, soils formed in limestone and igneous (mostly quartz monzonite and some rhyolite) parent materials lie adjacent to each other, with climate, vegetation, topography, age, and, to a large extent, dust deposition constant across the soils of both parent materials. The purpose of this study was to determine if X‐ray diffractometry (XRD) can mineralogically identify the size fraction in which pedogenic carbonate occurs and discern differences among (i) pedogenic carbonate formed in limestone parent material, (ii) pedogenic carbonate formed in igneous parent material, and (iii) soil carbonate in the form of detrital limestone. The diffractograms revealed that the size fractions in which pedogenic carbonate occurs in a dolostone residuum are fine sand, silt, and clay. X‐ray diffraction could not discern differences in soil carbonate because calcite was the only carbonate mineral present in the samples of pedogenic carbonate formed in limestone parent material, pedogenic carbonate formed in igneous parent material and detrital limestone. Excepting the d‐spacing associated with a minor peak, statistical analysis found no significant differences in d‐spacings among the three types of soil carbonate. However, each of the three types of soil carbonate revealed significant differences in d‐spacings relative to those of the calcite reference. While XRD mineralogically revealed the size distribution of pedogenic carbonate formed in a dolostone residuum, for the purpose of C sequestration, XRD was unable to distinguish the three soil carbonate types.
Microbial Respiration and Organic Carbon Indicate Nutrient Cycling Recovery in Reclaimed Soils
Authors: Ingram Lachlan J. , Schuman Gerald E. , Stahl Peter D. , Spackman Lowell K.
Published: September 2005

Soil quality and the ability of soil to sustain nutrient cycling in drastically disturbed ecosystems will influence the establishment and maintenance of a permanent and stable plant community. We undertook research to evaluate a recently developed method to assess soil quality and nutrient cycling potential in a series of reclaimed soils. The method involves correlating the 3‐d flush of microbial respiration after a soil is rewetted against a range of soil biological parameters. Soils were sampled from a number of reclaimed coal mines, a reclaimed uranium mine, and native, undisturbed prairie. All sites were located in semiarid Wyoming. Soils were dried at 55°C, rewetted, and microbial respiration measured at 3 d (Cmin0–3d) and 21 d (Cmin0–21d). In addition, microbial biomass C (MBC), N mineralization (Nmin0–21d), soil organic C (SOC), and total N were also measured. Correlations between Cmin0–3d and the measured soil parameters in reclaimed and native soils were generally strong (r2 ≥ 0.45) and highly significant (P = 0.0001). Differences between reclaimed and native soils were observed, with native soils exhibiting more variability, possibly due to: differences in soil homogeneity/heterogeneity, the relative lability of the substrates present; different microbial communities; and differences in soil structural properties. Correlations between Cmin0–3d and the measured soil parameters in spoil material, while significant, were less well correlated. We believe this method is a relatively fast, accurate, and economical means by which soil quality and nutrient cycling can be ascertained. We estimated that a minimum concentration of 0.52% SOC or 0.89% soil organic matter (SOM) is necessary to sustain an adequate level of nutrient cycling in these reclaimed soils.
Scaling Relationships between Saturated Hydraulic Conductivity and Soil Physical Properties
Authors: Zeleke Takele B. , Si Bing Cheng
Published: September 2005

Saturated hydraulic conductivity (Ks) is an important soil hydraulic property that affects water flow and the transport of dissolved solutes. Obtaining sufficient and reliableKsdata for large‐scale process modeling is always a challenge due to the extremely high spatial variability. The objectives of this study were (i) to determine if a monofractal or multifractal approach is needed to describe the variability inKsand its soil surrogates, and (ii) to identify which soil property best reflects the spatial distribution ofKsacross a wider range of scales. Saturated hydraulic conductivity and soil physical property data were collected from a 384‐m transect, located at Smeaton, SK, Canada. Observation scale variability and relationships were examined using statistical and geostatistical methods. Statistical scale‐invariance was evaluated through the Hurst scaling parameter (H). Multiple scale variability and relationships were studied using multifractal and joint multifractal techniques. Results indicate that for all the studied variables 0.80 <H< 0.90, suggesting a certain degree of statistical scale‐invariance and long‐range dependency. At the observation scale, the variability inKswas significantly related to sand (SA) and silt (SI) distribution (R= 0.40 for SA and −0.39 for SI,P <0.01;n= 128), whereas, across a wider range of scales, the variability inKswas related only to clay (CL) and organic C (OC). The result indicates scale dependent relationships betweenKsand soil physical properties, which implies that the success of predictive models such as pedotransfer functions (PTFs) andKsaggregation techniques depends largely on the correspondence between observation and implementation scales.
Polymorphism of the interleukin‐1 receptor antagonist gene: A factor in susceptibility to rheumatoid arthritis in a Spanish population
Authors: Carreira Patricia E. , Gonzalez‐Crespo Maria R. , Ciruelo Elena , Pablos Jose L. , Santiago Begoña , Gomez‐Camara Agustin , Gomez‐Reino Juan J.
Published: September 2005

Objective

To assess whether an interleukin‐1 receptor antagonist gene (IL1RN) polymorphism is associated with disease susceptibility and/or severity in a Spanish population of patients with rheumatoid arthritis (RA).

Methods

An 86‐bp variable‐number tandem repeat polymorphism within IL1RN intron 2 was analyzed by polymerase chain reaction in genomic DNA obtained from 247 unrelated patients with RA (group A) and 287 healthy control subjects. The polymorphism analysis was repeated in a second group of 194 patients with RA (group B). Clinical information from patients in group A was used to compare activity and severity data in patients stratified according to the different alleles or genotypes. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to determine the strength of the association of the different alleles or genotypes with RA activity or severity.

Results

In the control group, the allelic frequencies were 76% for IL1RN*1 (4 repeats), 21% for IL1RN*2 (2 repeats), 3% for IL1RN*3 (5 repeats), and 0.3% for IL1RN*4 (3 repeats). In group A patients with RA, both the frequency (OR 1.47, 95% CI 1.1–1.96, P = 0.007) and carriage rate (OR 1.6, 95% CI 1.1–2.2, P = 0.01) of allele IL1RN*2 were significantly increased. The increased frequency of IL1RN*2 was confirmed in group B patients with RA (OR 1.44, 95% CI 1.1–1.97, P = 0.01). In patients with RA, homozygosity for IL1RN*2 was associated with an increased number of affected articular areas during the first year of followup but not with other parameters of disease activity or severity.

Conclusion

Our results suggest that IL1RN has a role in determining susceptibility to RA in the Spanish population.
Maternal antibody responses to the 52‐kd SSA/RO p200 peptide and the development of fetal conduction defects
Authors: Clancy Robert M. , Buyon Jill P. , Ikeda Keigo , Nozawa Kazuhisa , Argyle Dionne A. , Friedman Deborah M. , Chan Edward K. L.
Published: September 2005

Objective

To identify a finer level of antibody specificity for risk of congenital heart block (CHB) than reactivity to 52‐kd SSA/Ro (Ro 52).

Methods

Serum from mothers enrolled in the Research Registry for Neonatal Lupus and the observational PR Interval and Dexamethasone Evaluation (PRIDE) study was evaluated for reactivity against peptide aa200‐239 of Ro 52 (p200), recently reported to be associated with a higher risk of CHB.

Results

The majority of 156 Ro 52–positive sera tested were reactive with p200 (>3 SD above control), irrespective of the clinical status of the child. Optical density (OD) values of p200 did not differ significantly among mothers of children with CHB (mean ± SD 0.187 ± 0.363), mothers of children with rash (mean ± SD 0.176 ± 0.356), and mothers of children without neonatal lupus (mean ± SD 0.229 ± 0.315). Reactivity against p200 was found in 80 of 104 mothers of children with CHB (77%), 24 of 30 mothers of children with rash (80%), and 21 of 22 mothers who delivered healthy children and had no children with neonatal lupus (95%) (P not significant for all comparisons). Sera from 4 mothers of children with CHB with varied p200 titers (OD range 0.025–1.818) bound to the surface of nonpermeabilized apoptotic, but not proliferating, human fetal cardiocytes. In 32 Ro 52–positive women who completed the PRIDE study (22 with no child with neonatal lupus, 7 with a child with CHB, and 3 with a child with rash) in whom p200 levels were determined during pregnancy, the correlation between level of p200 (OD range 0.000–1.170) and maximal fetal PR interval (range 115–168 msec) was not significant (ρ = 0.107, P = 0.58).

Conclusion

Reactivity to p200 is a dominant but not uniform anti–Ro 52 response in women whose children have CHB. Since exposure to this antibody specificity was observed with a similar frequency in children without CHB born to mothers with anti–Ro 52, additional factors are necessary to convert risk to disease expression.
Differential acoustic properties of early cartilage lesions in living human knee and ankle joints
Authors: Hattori Koji , Takakura Yoshinori , Ishimura Masao , Tanaka Yasuhito , Habata Takashi , Ikeuchi Ken
Published: September 2005

Objective

Although numerous studies have been performed to determine whether there are histologic, biochemical, biomechanical, and metabolic differences between knee and ankle cartilage, none have investigated the presence of such differences in living human cartilage. We previously developed an ultrasonic evaluation system for articular cartilage that analyzes the A‐mode echogram using wavelet transformation. The current study was undertaken to determine whether the acoustic properties of living human cartilage differ between knee and ankle joints.

Methods

Twenty‐eight patients were subjected to ultrasonic evaluation under arthroscopy. After arthroscopic grading, the cartilage was measured using an ultrasonic probe. Two quantitative parameters were used, i.e., the maximum magnitude and the echo duration at the 95% interval of the maximum magnitude.

Results

In intact cartilage, the maximum magnitude and echo duration did not differ between the knee and the ankle. In lesional cartilage, in contrast, the maximum magnitude was higher, and the echo duration was shorter, in the ankle than in the knee. These differences were statistically significant.

Conclusion

Ultrasound findings could be used to judge the degree of early cartilage degeneration in vivo on the basis of objective data such as the maximum magnitude and echo duration. Because we were unable to quantitatively analyze the biochemical and biomechanical properties of the cartilage in this study, our biochemical and biomechanical findings are based only on qualitative assessment. Nevertheless, the results indicate that this ultrasonic evaluation system may be useful for elucidating the processes of articular cartilage degeneration in osteoarthritis.
Association between the abnormal expression of matrix‐degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions
Authors: Roach Helmtrud I. , Yamada Norikazu , Cheung Kelvin S. C. , Tilley Simon , Clarke Nicholas M. P. , Oreffo Richard O. C. , Kokubun Shoichi , Bronner Felix
Published: September 2005

Objective

To investigate whether the abnormal expression of matrix metalloproteinases (MMPs) 3, 9, and 13 and ADAMTS‐4 by human osteoarthritic (OA) chondrocytes is associated with epigenetic “unsilencing.”

Methods

Cartilage was obtained from the femoral heads of 16 patients with OA and 10 control patients with femoral neck fracture. Chondrocytes with abnormal enzyme expression were immunolocalized. DNA was extracted, and the methylation status of the promoter regions of MMPs 3, 9, and 13 and ADAMTS‐4 was analyzed with methylation‐sensitive restriction enzymes, followed by polymerase chain reaction amplification.

Results

Very few chondrocytes from control cartilage expressed the degrading enzymes, whereas all clonal chondrocytes from late‐stage OA cartilage were immunopositive. The overall percentage of nonmethylated sites was increased in OA patients (48.6%) compared with controls (20.1%): 20% versus 4% for MMP‐13, 81% versus 47% for MMP‐9, 57% versus 30% for MMP‐3, and 48% versus 0% for ADAMTS‐4. Not all CpG sites were equally susceptible to loss of methylation. Some sites were uniformly methylated, whereas in others, methylation was generally absent. For each enzyme, there was 1 specific CpG site where the demethylation in OA patients was significantly higher than that in controls: at −110 for MMP‐13, −36 for MMP‐9, −635 for MMP‐3, and −753 for ADAMTS‐4.

Conclusion

This study provides the first evidence that altered synthesis of cartilage‐degrading enzymes by late‐stage OA chondrocytes may have resulted from epigenetic changes in the methylation status of CpG sites in the promoter regions of these enzymes. These changes, which are clonally transmitted to daughter cells, may contribute to the development of OA.
Reticulocytes bearing C4d as biomarkers of disease activity for systemic lupus erythematosus
Authors: Liu Chau‐Ching , Manzi Susan , Kao Amy H. , Navratil Jeannine S. , Ruffing Margie J. , Ahearn Joseph M.
Published: September 2005

Objective

There is an urgent need for biomarkers with which to monitor disease activity in patients with systemic lupus erythematosus (SLE). We recently showed that abnormal levels of C4d, an activation‐derived fragment of complement component C4, are deposited on the surface of erythrocytes from patients with SLE. This study focused on reticulocytes, the youngest and shortest‐lived erythrocytes (lifespan 24–48 hours), with the objective of testing our hypothesis that when reticulocytes emerge from the bone marrow, they are immediately exposed to and acquire C4d at levels proportionate to the extent of complement activation at that time, thereby reflecting disease activity in SLE.

Methods

We conducted a cross‐sectional study of 156 patients with SLE, 140 patients with other diseases, and 159 healthy controls. Levels of C4d on the surface of reticulocytes were examined using a 2‐color flow cytometric assay. The results were analyzed for correlations with SLE disease activity.

Results

A wide range of increased levels of reticulocyte C4d was specifically detected in SLE patients. These levels fluctuated in SLE patients and correlated with clinical disease activity, as determined by the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus Activity Measure (SLAM). Specifically, in cross‐sectional analyses, patients with reticulocyte C4d levels in the highest quartile compared with those in the lowest quartile had significantly higher SELENA–SLEDAI (P = 0.00002) and SLAM (P = 0.02) scores. Longitudinal observation demonstrated that the reticulocyte C4d levels changed in relation to the clinical course in individual patients.

Conclusion

These findings support our hypothesis that C4d‐bearing reticulocytes may serve as biomarkers of disease activity in patients with SLE.
Association between PADI4 and rheumatoid arthritis: A replication study
Authors: Ikari Katsunori , Kuwahara Mahito , Nakamura Takahiro , Momohara Shigeki , Hara Masako , Yamanaka Hisashi , Tomatsu Taisuke , Kamatani Naoyuki
Published: September 2005

Objective

The peptidylarginine deiminase type 4 gene (PADI4) was recently reported to be associated with rheumatoid arthritis (RA) in a Japanese population. The presence of a single‐nucleotide polymorphism (SNP) located in intron 3 of PADI4 provided the strongest evidence of this association. Moreover, functional haplotypes that affect stability of transcripts were identified. However, subsequent research failed to confirm the observed association in a UK population. The present study was undertaken to further investigate the association of PADI4 with RA, using a series of population‐based samples from subjects with the same ethnic background as the subjects in the original study.

Methods

DNA samples were obtained from 1,230 Japanese RA patients and 948 ethnically matched controls. Genotyping was performed using 5′ allele discrimination assays. All samples were genotyped for 3 SNPs on PADI4 (padi4_94, padi4_104, and padi4_102), which comprised the reported haplotypes. Chi‐square testing was performed for a case–control study and the PENHAPLO program was used for haplotype estimation.

Results

All tested SNPs were found to show significant differences in frequency between cases and controls (P = 0.010–0.0008), which confirmed the association observed in the original study. Odds ratios calculated for allele frequencies were 1.23, 1.21, and 1.36 in padi4_94, padi4_104, and padi4_102 respectively.

Conclusion

Replication of association in individual samples strongly suggests that PADI4 is a true susceptibility gene for RA.
Development of spontaneous multisystem autoimmune disease and hypersensitivity to antibody‐induced inflammation in Fcγ receptor IIa–transgenic mice
Authors: Sardjono Caroline Tan , Mottram Patricia L. , Velde Nicholas C. van de , Powell Maree S. , Power David , Slocombe Ronald F. , Wicks Ian P. , Campbell Ian K. , McKenzie Steven E. , Brooks Mark , Stevenson Andrew W. , Hogarth P. Mark
Published: September 2005

Objective

The major human Fc receptor, FcγRIIa, is the most widespread activating FcR. Our aim was to determine the role of FcγRIIa in a transgenic mouse model of immune complex–mediated autoimmunity and to characterize the development of spontaneous autoimmune disease.

Methods

Arthritis was induced in normal and FcγRIIa‐transgenic mice by immunization with type II collagen (CII) or by transfer of arthritogenic anti‐CII antibodies. Also, mice that spontaneously developed autoimmune disease were assessed by clinical scoring of affected limbs, histology and serology, and measurement of autoantibody titers and cytokine production.

Results

FcγRIIa‐transgenic mice developed collagen‐induced arthritis (CIA) more rapidly than did archetypal CIA‐sensitive DBA/1 (H‐2q) mice, while nontransgenic C57BL/6 (H‐2b) mice did not develop CIA when similarly immunized. Passive transfer of a single dose of anti‐CII antibody induced a more rapid, severe arthritis in FcγRIIa‐transgenic mice than in nontransgenic animals. In addition, most immune complex–induced production of tumor necrosis factor α by activated macrophages occurred via FcγRIIa, not the endogenous mouse FcR. A spontaneous, multisystem autoimmune disease developed in aging (>20 weeks) transgenic mice (n = 25), with a 32% incidence of arthritis, and by 45 weeks, all mice had developed glomerulonephritis and pneumonitis, and most had antihistone antibodies. Elevated IgG2a levels were seen in mice with CIA and in those with spontaneous disease.

Conclusion

The presence of enhanced passive and induced autoimmunity, as well as the emergence of spontaneous autoimmune disease at 20–45 weeks of age, suggest that FcγRIIa is a very important factor in the pathogenesis of autoimmune inflammation and a possible target for therapeutic intervention.
Modulation of CD28 expression with anti–tumor necrosis factor α therapy in rheumatoid arthritis
Authors: Bryl Ewa , Vallejo Abbe N. , Matteson Eric L. , Witkowski Jacek M. , Weyand Cornelia M. , Goronzy Jorg J.
Published: September 2005

Objective

The immune system of patients with rheumatoid arthritis (RA) is characterized by the accumulation of CD4+ T cells deficient in CD28 expression and the up‐regulation of tumor necrosis factor α (TNFα). Previous in vitro studies have shown that TNFα induces transcriptional silencing of the CD28 gene. Because reduced expression of CD28 in T cells compromises immunocompetence, we examined whether CD28 expression is reduced in patients with RA in vivo and whether the reduction is related to TNFα.

Methods

Patients with RA and age‐matched individuals were recruited. Peripheral blood mononuclear cells were stained for CD3, CD4, CD8, CD28, TNF receptor I (TNFRI), and TNFRII, and analyzed by quantitative flow cytometry. The number of CD28 and TNFR molecules was monitored in a subgroup of patients with RA undergoing treatment with anti‐TNFα.

Results

In addition to higher frequencies of CD28null T cells, patients with RA had significantly reduced numbers of CD28 and TNFRI molecules on CD4+,CD28+ T cells. Normal expression could be restored in vitro by overnight culture, suggesting that CD28 in patients was modulated by exogenous factors. In contrast, treatment with TNFα in vitro resulted in further down‐regulation. CD28 expression was normalized in patients undergoing TNFα‐neutralizing therapy.

Conclusion

Overproduction of TNFα in RA induces a global down‐regulation of CD28 in CD4+ T cells and may cause reduced sensitivity to costimulatory signals in T cell responses.
Is there an association between the use of different types of nonsteroidal antiinflammatory drugs and radiologic progression of osteoarthritis?: The rotterdam study
Authors: Reijman M. , Bierma‐Zeinstra S. M. A. , Pols H. A. P. , Koes B. W. , Stricker B. H. C. , Hazes J. M. W.
Published: September 2005

Objective

To investigate the influence of the use of various types of nonsteroidal antiinflammatory drugs (NSAIDs) on progression of osteoarthritis (OA) of the hip and knee.

Methods

In 1,695 subjects (2,514 hips) and 635 subjects (874 knees) ages 55 years and older from the Rotterdam Study, radiographs of the hip and knee at baseline and followup (mean followup time 6.6 years) were evaluated. Radiologic OA (ROA) progression was defined as a minimum increase of 1 in the Kellgren/Lawrence grade or incident joint replacement at followup. The associations between the different types of NSAIDs and progression of ROA were assessed using multivariate logistic regression analysis.

Results

Those subjects who were receiving diclofenac >180 days had a 2.4‐fold increased risk (95% confidence interval [95% CI] 1.0–6.2) of progression of hip ROA and a 3.2‐fold increased risk (95% CI 1.0–9.9) of knee ROA, compared with those considered short‐term users (diclofenac for 1–30 days). These associations were adjusted for age, sex, body mass index, baseline ROA, followup time, and defined daily dosage.

Conclusion

These data suggest that diclofenac may induce accelerated progression of hip and knee ROA. Whether this occurs because of a true deleterious effect on cartilage or because of excessive mechanical loading on a hip following pain relief remains to be investigated.
Chronic arthritis down‐regulates peripheral μ‐opioid receptor expression with concomitant loss of endomorphin 1 antinociception
Authors: Li Zongming , Proud David , Zhang Chunfen , Wiehler Shahina , McDougall Jason J.
Published: September 2005

Objective

To determine whether peripheral administration of the endogenous μ‐opioid peptide endomorphin 1 could reduce knee joint pain, using animal models of acute and chronic arthritis.

Methods

Extracellular electrophysiologic recordings were made of rat knee joint primary afferent nerve activity in response to noxious hyperrotation of the joint. Neuronal activity was assessed before and following local injection of endomorphin 1. Comparisons were made between normal knees and knees with adjuvant‐induced monarthritis, tested at 48 hours and 1 week posttreatment. Expression of μ‐opioid receptors in the dorsal root ganglia ipsilateral to the chronically inflamed joints was determined by real‐time polymerase chain reaction (PCR) and immunohistochemical analysis.

Results

In normal knees, endomorphin 1 caused up to a 75% reduction in joint afferent nerve activity, which was blocked by the μ‐opioid receptor antagonist D‐Phe‐Cys‐Tyr‐D‐Trp‐Orn‐Thr‐Pen‐Thr‐amide. The inhibitory effect of endomorphin 1 was sustained in acutely inflamed knees. Conversely, in chronically inflamed joints, endomorphin 1 had no observable effect on the primary afferent nerve firing rate elicited by a noxious mechanical stimulus and, as such, was significantly different from the rate in normal joints. Immunohistochemical and real‐time PCR analysis of the L3–L5 dorsal root ganglia ipsilateral to the chronic arthritis lesion revealed a reduction in μ‐opioid receptor protein and gene expression compared with that in normal control animals.

Conclusion

Taken together, these results provide the first electrophysiologic evidence that selective activation of peripheral μ‐opioid receptors reduces normal knee joint mechanosensitivity to a noxious stimulus. Furthermore, the analgesic effect of endomorphin 1 is lost during chronic inflammation due to down‐regulation of μ‐opioid receptor expression in afferent nerve cell bodies. These findings begin to explain the ambiguous efficacy of peripherally administered μ‐opioid drugs in controlling chronic inflammatory joint pain.
Membrane chromatographic immunoassay method for rapid quantitative analysis of specific serum antibodies
Authors: Ghosh Raja
Published: September 2005

This paper discusses a membrane chromatographic immunoassay method for rapid detection and quantitative analysis of specific serum antibodies. A type of polyvinylidine fluoride (PVDF) microfiltration membrane was used in the method for its ability to reversibly and specifically bind IgG antibodies from antiserum samples by hydrophobic interaction. Using this form of selective antibody binding and enrichment an affinity membrane with antigen binding ability was obtained in‐situ. This was done by passing a pulse of diluted antiserum sample through a stack of microporous PVDF membranes. The affinity membrane thus formed was challenged with a pulse of antigen solution and the amount of antigen bound was accurately determined using chromatographic methods. The antigen binding correlated well with the antibody loading on the membrane. This method is direct, rapid and accurate, does not involve any chemical reaction, and uses very few reagents. Moreover, the same membrane could be repeatedly used for sequential immunoassays on account of the reversible nature of the antibody binding. Proof of concept of this method is provided using human hemoglobin as model antigen and rabbit antiserum against human hemoglobin as the antibody source. © 2005 Wiley Periodicals, Inc.