bluuebunny/crossref_metadata_2025 huggingface dataset:
Municipal Storm Water Management
Authors: Prochaska C. A. , Zouboulis A. I.
Published: April 2005

Enlargement of urbanization and industrial activities around the countryside have significantly altered the natural landscape of watersheds.

This, in turn, has adversely affected both the quantity and the quality of storm water runoff and has contributed to the chemical, physical, and biological impairment of receiving waters. Several studies have shown that heavy metals, synthetic organics, pesticides, fuels, waste oils, and pathogens commonly contaminate storm water that originates from urban and industrial areas. To help improve the quality of storm water discharges, the U.S. Congress amended the Clean Water Act in 1987, which directs the Environmental Protection Agency (EPA) to develop the National Pollutant Discharge Elimination System (hereafter termed NPDES). Under NPDES regulations, the municipalities must develop storm water management plans that include specific controls to reduce the discharge of pollutants to the maximum extent practicable.

The municipal storm water management programs all involve similar elements. These include mainly public information/participation, elimination of illegal discharges, public agency activities, control of industrial/commercial storm water discharges, new development management, storm water treatment, program evaluation, and monitoring.
Processing of Sludge
Authors: Turoviskiy Izrail S.
Published: April 2005

Wastewater sludge is a high moisture suspension in which water is bound by small solid particles. The main parts of the sludge solids are organic and contain different types of microorganisms, pathogenic bacteria, viruses, and parasites. On the other hand, sludge contains valuable organic macronutrients, such as nitrogen, phosphorus, potassium, and micronutrients, such as elements and metals. Wastewater sludge is hazardous waste which must be stored, disposed of, or be reused in accordance with standards and regulations based on the treatment level provided.

The main purpose of treatment is to prepare sludge for removal from wastewater treatment plants and to produce biosolids that can be used as a soil amendment and conditioner. To achieve this goal, treatment processes of sludge should include thickening and dewatering to decrease sludge volume and moisture and disinfection and stabilization to control odor, pathogens, and vectors.
Sludge Treatment and Disposal
Authors: Spinosa Ludovico
Published: April 2005

The management of sewage sludge is a major problem in wastewater treatment. Sludge amounts to about 2% by volume of processed sewage, but handling it accounts for up to 50% of total operating costs. Furthermore, during the last few years, there has been a worldwide movement toward a common strategy for any kind of waste; the priorities are reusing waste materials and taking advantage of their energy content.

Treatment of sludge is aimed at rendering it suitable for use or disposal at minimum cost. The low solids concentration (2–3%), and the presence of pathogens, heavy metals, organic pollutants and potentially putrescible organic matter are the main problems to be faced and solved. Other factors influencing sludge processing technology are the need to extract as much energy and material as possible from the sludge itself and the introduction of stricter regulations that require higher levels of treatment before disposal.
Solidification/Stabilization of Hazardous Solid Wastes
Authors: Ioannidis Th. A. , Zouboulis A. I.
Published: April 2005

Solidification and stabilization (denoted hereafter as S/S) waste treatment processes involve mixing specialized additives or reagents with hazardous waste materials to reduce, by physical or chemical means, the solubility or mobility of contaminants in the surrounding environmental matrix. Solidification and stabilization are closely related; both use several chemical, physical, and thermal processes, or an appropriate combination of them, to detoxify hazardous wastes.

Solidification
refers to processes that encapsulate a waste to form a solid material and to restrict the migration of contaminant by decreasing the available surface area, which is exposed to leaching, when contacting liquids and also by coating the waste with low‐permeability materials. Solidification can be accomplished by a chemical reaction between the hazardous waste and the binding (solidifying) reagents or by the application of mechanical processes (e.g., compaction).

Stabilization
refers to processes that involve chemical reactions, which reduce the leachability of the product (stabilized waste). Stabilization immobilizes the hazardous materials or reduces their solubility through appropriate chemical reactions. The physical nature of the waste may or may not be changed by this process.

The S/S technology may not be applicable at polluted sites, containing wastes that include organic compounds, especially when volatile organic contaminants are present. The application of mixing and heating processes, associated with the hydration of binders, may release organic vapors. Pretreatment, such as air stripping or incineration, may be used to remove the volatile organics during preliminary treatment and to prepare the waste for the S/S of residues. The chemical composition of the contaminated matrix, the amount of water present, and the ambient temperature also affect the application of S/S technologies.
Aqueous Behavior of Elements in a Flue Gas Desulfurization Sludge Disposal Site
Authors: Castaldi Frank J.
Published: April 2005

Flue gas desulfurization (FGD) systems are end of process pollution abatement techniques used primarily for removing sulfur dioxide from coal‐fired utility and industrial boiler combustion gases. The technology has also been successfully applied to Claus sulfur recovery unit tail gas and sulfuric acid plant tail gas streams. Sulfur dioxide (SO2) and particulate emissions are controlled by a flue gas scrubber system. The scrubber is often designed as an integral part of the steam generation plant. It consists of a two‐stage venturi‐absorber scrubber module designed to treat boiler flue gas. The flue gas from the boiler enters the air quality control system through a common plenum. The gas stream is sent to the individual scrubber modules from this plenum.
Using Ecosystem Processes in a ConstructedWetland to Treat Mine Wastewater inIreland
Authors: O'Sullivan Aisling D. , Otte Marinus L.
Published: April 2005

The development and expansion of industrial and agricultural activities in the Western world has led to a corresponding increase in the release of potentially toxic chemicals into the environment. Although growth has had many socioeconomic benefits, it has also led to negative implications for wetland ecosystems. For instance, the intensive farming practices developed in Ireland in the 1970s led to eutrophic (overenriched) rivers and lakes as a result of inadvertent inputs of excess nitrogen and phosphorus. This resulted in algal blooms, subsequent fish mortality, and reduced biodiversity of aquatic systems. The breaching of tailings dam walls in mine storage ponds has also resulted in catastrophic impacts on neighboring watersheds, which in many circumstances has led to irreversible ecosystem damage. Therefore, a balance is sought between reducing undesirable impacts while facilitating positive economic progress. By understanding the complex processes that affect the biogeochemistry and cycling of contaminants in aquatic ecosystems, innovative treatment technologies can be applied to mitigate and treat these wastes.
Wastewater Characterization
Authors: Kazmi Absar Ahmad
Published: April 2005

An understanding of the nature of wastewater is fundamental to the design and operation of wastewater collection, treatment, and reuse facilities. Wastewater is characterized in terms of its physical, chemical, and biological composition. Greater emphasis is being placed on wastewater characterization because of its changing characteristics and the imposition of stricter limits on wastewater discharges that are used beneficially. Thorough characterization of wastewater in the design and optimization of biological treatment processes is increasingly important due to the advent of process modeling. Process modeling for activated sludge, as it is currently conceived, requires experimental assessment of kinetic and stoichiometric constants.
Wastewater Sludge
Authors: Turoviskiy Izrail S.
Published: April 2005

The Environmental Protection Agency (EPA) has defined sewage sludge as any solid, semisolid, or liquid residue removed during the treatment of municipal wastewater or domestic sewage, including solids removed during primary, secondary, or advanced wastewater treatment, scum, septage, and sewage sludge products. Instead of using the term sludge, some specialists have used the terms residual, sediments, solids, slime‐solid, or biosolids, depending on its condition or its usefulness and whether it meets the applicable criteria for that particular term.

Sludge is a suspension including solid and semisolid materials separated and generated from the liquid wastewater stream of a treatment plant during purification of municipal wastewater, industrial wastewater, or natural water in mechanical, biological, or physicochemical facilities.
Technologies for Arsenic Removal from Contaminated Water Sources
Authors: Katsoyiannis I. , Zouboulis A.
Published: April 2005

The majority of established arsenic removal technologies can be divided into three main categories, depending on the specific mechanism that is responsible for removing arsenic. These categories are usually referred as coagulation–precipitation, membrane, and sorption processes.

Three processes in this group have been developed for arsenic removal; aluminum or iron coagulation, lime softening, as well as a combination of iron and manganese removal with arsenic.

Two types of membrane processes remove arsenic efficiently from water sources: reverse osmosis and electrodialysis.

Adsorption processes are another category of arsenic removal technologies; they are based on the adsorption of arsenic onto suitable adsorbing media. Two different technologies have been applied to remove arsenic, activated alumina and ion exchange.
Biosolids
Authors: Turoviskiy Izrail S.
Published: April 2005

Wastewater treatment processes remove organics, inorganic materials, and contaminants in sludge. Biosolids are treated municipal wastewater sludge that can be beneficially used, especially as a soil amendment, in accordance with standards.

The Water Environment Federation (WEF) has adopted a policy of encouraging the use of the word “biosolids” in place of sludge to promote public acceptance of reused materials. Land application of biosolids has been and continues to be successfully implemented by many countries. Many countries have rules and regulations associated with biosolids reuse and disposal. Almost all rules are based on reducing pathogens and pollutants. However, rules and regulations vary in different countries. Criteria and methods of obtaining results to determine the use of biosolids also vary.
Constructed Wetlands
Authors: Langergraber Guenter
Published: April 2005

The term constructed wetlands describes artificial wetlands designed to improve water quality. A constructed wetland is a complex mixture of water, substrate, plants, litter (fallen plant material), and a variety of microorganisms (most importantly, bacteria). The mechanisms for improving water quality include settling of suspended particulate matter; filtration and chemical precipitation; chemical transformation; adsorption and ion exchange on surfaces of plants, substrate, and litter; breakdown, transformation, and uptake of pollutants and nutrients by microorganisms and plants; and predation and natural die‐off of pathogens.

Constructed wetlands provide the optimal treatment conditions found in natural wetlands but have the flexibility of being constructed. For optimal support of the treatment mechanisms, various types of constructed wetlands optimized for different applications are used. Free‐water‐surface constructed wetlands and subsurface‐flow constructed wetlands are the main types of constructed wetlands. The applications include treatment of domestic, industrial, and agricultural wastewaters, storm water, and landfill leachate.

Wetland treatment systems are effective in treating organic matter, nitrogen, phosphorus, and additionally for decreasing the concentrations of heavy metals, organic chemicals, and pathogens. A good pre‐treatment for suspended solids is essential for long‐term operation.
Detergents
Authors: Jahan Kauser
Published: April 2005

Detergents are formulations that have cleaning and solubilization properties. Their main fields of application are industry (cleaning products, food, industrial processing), household (laundry, dishwashing), and personal care (soaps, shampoos, cosmetics). Detergents consist of surface‐active agents known as surfactants and other subsidiary components that include boosters, builders, and fillers. In 1996, the production of surfactants including soaps was reportedly around 30 × 109 kg per year worldwide. Detergents are thus environmentally important because they are used in huge quantities. Historically, potential detergent contamination of the environment followed when the use of soap‐based detergents changed to synthetic detergents. Detergents are discharged to the environment typically through wastewater treatment plant effluent and the use of sewage sludge on land. Industrial discharges to surface waters, oil spills, and surfactant‐enhanced remediation of contaminated soil can also be other sources. Biological treatment of wastewater typically removes 95% of the detergents and their metabolites. However, recent research has generated scientific and regulatory concern because certain detergents and their metabolites appear toxic to aquatic organisms. These studies also indicate that detergent metabolites are also more toxic than their parent compounds. The complexity of detergent products, it has also been shown, leads to synergistic effects.
Ecological Wastewater Management
Authors: Langergraber Guenter
Published: April 2005

Conventional sanitation concepts are neither an ecological nor an economical solution for rural areas in both industrialized and developing countries. Ecological sanitation (EcoSan) represents a holistic approach toward ecologically and economically sound sanitation. The underlying aim is to close nutrient and water cycles with as small an expenditure on material and energy as possible to contribute to sustainable development. EcoSan is a systemic approach and an attitude. Single technologies are only a means to an end. Therefore, EcoSan‐technologies may range from nearly natural wastewater treatment techniques to compost toilets, simple household installations, and to complex, mainly decentralized systems. These technologies are not ecological per se but only in relation to the observed environment. Promotion of EcoSan concepts, therefore, is the strategy for achieving the goal—closing the loop in wastewater management and sanitation.
Inside Front Cover: Self‐Assembly of SiO2 Nanowires and Si Microwires into Hierarchical Heterostructures on a Large Scale (Adv. Mater. 8/2005)
Authors: Hu J. , Bando Y. , Zhan J. , Yuan X. , Sekiguchi T. , Golberg D.
Published: April 2005

The inside cover shows a scanning electron micrograph of a novel hierarchical heterostructures, as reported by Hu and co‐workers on p. 971. The heterostructures are formed from Si core microwires covered by dense, aligned SiO2 nanowires, thus forming multiple junctions to the cores. The inset shows a schematic of the Sn‐catalyzed vapor–liquid–solid growth mechanism. These materials are envisaged to become important for optical fibers, low‐dimensional waveguides, scanning near‐field optical microscopes and high‐bandwidth optical signal processing devices.
Reduced p53 in peripheral blood mononuclear cells from patients with rheumatoid arthritis is associated with loss of radiation‐induced apoptosis
Authors: Maas Kevin , Westfall Matthew , Pietenpol Jennifer , Olsen Nancy J. , Aune Thomas
Published: April 2005

Objective

Patients with autoimmune disorders exhibit highly reproducible gene expression profiles in their peripheral blood mononuclear cells. This profile includes, at least in part, a collection of underexpressed genes that encode proteins that inhibit cell cycle progression and stimulate apoptosis. We aimed to determine whether this gene expression profile confers functional liability on lymphocytes from patients with rheumatoid arthritis (RA).

Methods

Viability studies in response to a panel of proapoptotic stimuli revealed that T lymphocytes from patients with RA were resistant to gamma radiation–induced apoptosis, a process known to be dependent on p53. To assess p53 function in RA peripheral blood mononuclear cells, baseline levels of p53 protein and TP53 transcript were measured in patients with RA and controls. The cellular p53 response to gamma radiation was also assessed by immunoblotting.

Results

Lymphocytes from patients with RA had lower baseline levels of TP53 messenger RNA (mRNA) and p53 protein than did those from control subjects and were deficient in their ability to increase p53 after exposure to gamma radiation. A subgroup of patients with RA had a second biochemical defect characterized by expression of very low baseline levels of checkpoint kinase 2 mRNA and protein.

Conclusion

We conclude that defects in the expression of TP53 mRNA and, in a subgroup, defects in expression of CHK2 mRNA, lead to severe defects in apoptosis in patients with RA. We hypothesize that this liability may contribute to autoimmunity.
Patients seen for standard rheumatoid arthritis care have significantly better articular, radiographic, laboratory, and functional status in 2000 than in 1985
Authors: Pincus Theodore , Sokka Tuulikki , Kautiainen Hannu
Published: April 2005

Objective

A comprehensive quantitative analysis of measures of disease activity and joint damage has not been available to compare patients in different eras in the same clinical setting. This study was undertaken to determine whether the clinical status of patients with rheumatoid arthritis (RA) has improved on average in recent years.

Methods

A quantitative cross‐sectional evaluation, which included joint count, radiographic, laboratory, patient questionnaire, and physical function measures, and therapies, was performed in 125 consecutive RA patients seen from 1984 through 1986 (“1985 cohort”). A virtually identical assessment was performed in 150 patients seen from 1999 through 2001 (“2000 cohort”), in the same weekly academic clinic. Measures were compared using descriptive statistics and a median regression model, adjusted for age, duration of disease, level of formal education, and rheumatoid factor.

Results

Patients in 1985 had significantly poorer status compared with those in 2000: median 12 versus 5 swollen joints, Larsen radiographic score 20 versus 3, erythrocyte sedimentation rate 33 mm/hour versus 20, and modified Health Assessment Questionnaire 1.0 versus 0.4 (P < 0.019). Severe Disease Activity Scores >5.1 were seen in 69% of 1985 patients, compared with 30% in 2000. Methotrexate was taken by 10% of patients in 1985, versus 76% in 2000. The proportion of patients not taking any disease‐modifying antirheumatic drugs was 66% in 1985 versus 13% in 2000.

Conclusion

Patients receiving standard care for RA in this setting had significantly better status, including radiographic scores, in 2000 than in 1985, associated with aggressive treatment strategies, prior to the introduction of biologic agents.
Effect of oral glucosamine on cartilage degradation in a rabbit model of osteoarthritis
Authors: Tiraloche Gabrielle , Girard Christiane , Chouinard Luc , Sampalis John , Moquin Luc , Ionescu Mirela , Reiner Agnes , Poole A. Robin , Laverty Sheila
Published: April 2005

Objective

To determine whether oral glucosamine alleviates cartilage degradation in an animal model of osteoarthritis (OA).

Methods

The effect of 8 weeks of daily oral glucosamine hydrochloride on degeneration of articular cartilage was evaluated in rabbits in which anterior cruciate ligament transection (ACLT) was performed to induce OA. Animals were treated with glucosamine (n = 16) or a placebo (n = 16) and necropsied at 11 weeks. Seven unoperated rabbits served as controls. The articular cartilage was evaluated macroscopically and histologically and analyzed for total type II collagen and glycosaminoglycan (GAG) content.

Results

Histologic analysis revealed that loss of proteoglycan, based on Safranin O–fast green staining, was significantly reduced in the lateral tibial plateau cartilage of ACL‐transected limbs in the glucosamine group compared with ACL‐transected limbs in the placebo group, with a similar, but not significant, trend for the lateral femoral condylar cartilage. Likewise, macroscopic analysis of cartilage showed that the lateral tibial plateau alone had a significantly lower rate of disease in the glucosamine group, which was consistent with the results of the independent histologic assessment. However, no significant treatment effect was detected when composite histologic scores were analyzed. A significant reduction in GAG content was observed in the femoral condyles of placebo‐treated ACL‐transected joints, but not in the same region of glucosamine‐treated ACL‐transected joints, compared with their respective contralateral unoperated joints.

Conclusion

Oral administration of glucosamine had a detectable, site‐specific, partial disease‐modifying effect in this model of OA. From a clinical perspective, the administration of glucosamine did not prevent fibrillation and/or erosions of the articular cartilage in all of the treated animals, and no effects were detected in the medial joint compartments.
Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: Results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT)
Authors: Antoni Christian E. , Kavanaugh Arthur , Kirkham Bruce , Tutuncu Zuhre , Burmester Gerd R. , Schneider Udo , Furst Daniel E. , Molitor Jerry , Keystone Edward , Gladman Dafna , Manger Bernhard , Wassenberg Siegfried , Weier Ralf , Wallace Daniel J. , Weisman Michael H. , Kalden Joachim R. , Smolen Josef
Published: April 2005

Objective

To investigate the efficacy and tolerability of infliximab therapy for the articular and dermatologic manifestations of active psoriatic arthritis (PsA).

Methods

One hundred four patients with PsA in whom prior therapy with at least 1 disease‐modifying antirheumatic drug (DMARD) had failed were recruited into this investigator‐initiated, multicenter, randomized, double‐blind, placebo‐controlled clinical trial. During the initial blinded portion of the study, patients received infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, and 14. After week 16, patients initially assigned to receive placebo crossed over to receive infliximab 5 mg/kg every 8 weeks through week 50, while patients initially randomized to infliximab continued to receive active treatment at the same dose through week 50. The primary efficacy outcome was achievement of the American College of Rheumatology 20% criteria for improvement in rheumatoid arthritis (ACR20) at week 16. Additional predefined clinical efficacy assessments included the Psoriasis Area and Severity Index (PASI) score, the ACR50 and ACR70 criteria, the Disease Activity Score in 28 joints, the Health Assessment Questionnaire, ratings of enthesitis and dactylitis, and the Psoriatic Arthritis Response Criteria score.

Results

The proportion of infliximab‐treated patients who achieved an ACR20 response at week 16 (65%) was significantly higher than the proportion of placebo‐treated patients who achieved this response (10%). In addition, 46% of infliximab‐treated patients achieved an ACR50 response, and 29% achieved an ACR70 response; no placebo‐treated patient achieved these end points. Among patients who had PASI scores of ≥2.5 at baseline, 68% of infliximab‐treated patients achieved improvement of ≥75% in the PASI score at week 16 compared with none of the placebo‐treated patients. Continued therapy with infliximab resulted in sustained improvement in articular and dermatologic manifestations of PsA through week 50. The incidence of adverse events was similar between the treatment groups.

Conclusion

Therapy with infliximab at a dose of 5 mg/kg significantly improved the signs and symptoms of arthritis, psoriasis, dactylitis, and enthesitis in patients with active PsA that had been resistant to DMARD therapy. With continued infliximab treatment, benefits were sustained through 50 weeks. The benefit‐to‐risk ratio appeared favorable in this study population.
Successful treatment with intraarticular infliximab for resistant knee monarthritis in a patient with spondylarthropathy: A role for scintigraphy with 99mTc‐infliximab
Authors: Conti Fabrizio , Priori Roberta , Chimenti Maria Sole , Coari Giulio , Annovazzi Alessio , Valesini Guido , Signore Alberto
Published: April 2005

Positive experiences with intraarticular infliximab have been reported in patients with rheumatoid arthritis, ankylosing spondylitis, and Behçet's disease. We used intraarticular infliximab to treat resistant knee monarthritis in a patient with spondylarthropathy. Clinical and laboratory improvement was associated with improvement in scintigraphic findings. This approach is less expensive than intravenous administration of infliximab. We suggest that selection of candidates for this innovative therapy should be guided by anti–tumor necrosis factor α scintigraphy.
An opposing time‐dependent immune‐modulating effect of the sympathetic nervous system conferred by altering the cytokine profile in the local lymph nodes and spleen of mice with type II collagen–induced arthritis
Authors: Härle Peter , Möbius Daniel , Carr Daniel J. J. , Schölmerich Jürgen , Straub Rainer H.
Published: April 2005

Objective

The sympathetic nervous system (SNS) seems to play a proinflammatory role in the early asymptomatic phase of arthritis, but its role in the late stages of chronic arthritis is not well known. The purpose of this study was to examine the effects of the SNS on late‐stage chronic arthritis in mice with type II collagen–induced arthritis (CIA).

Methods

We tested the effects of the SNS by ablating sympathetic nerves at different time points in mice with CIA. Early sympathectomy was performed 7 days before immunization. Late sympathectomy was performed on day 56. Cytokine stimulation assays were performed on local lymph node cells and spleen cells, and levels of interleukin‐10 (IL‐10), IL‐4, tumor necrosis factor α (TNFα), and interferon‐γ (IFNγ) were determined.

Results

Animals with CIA that underwent early sympathectomy showed significantly lower arthritis scores than the controls. In contrast, animals that underwent late sympathectomy had significantly increased arthritis scores compared with controls. On day 0, lymph node cells from animals subjected to early sympathectomy had increased levels of IL‐10 and IL‐4 and unchanged levels of TNFα and IFNγ compared with those from untreated animals. This indicates an immune‐stimulating property of the SNS in draining lymph nodes. On day 80, lymph node cells and spleen cells from animals subjected to late sympathectomy showed increased levels of TNFα and IFNγ compared with those from nonsympathectomized controls with CIA. This indicates an immune‐depressing property of the SNS in draining lymph nodes and spleen. Arthritis per se largely diminished sympathetic nerve fiber density in synovium on day 80 (P < 0.01).

Conclusion

The effect of the SNS is bimodal, enhancing or depressing levels of proinflammatory and antiinflammatory cytokines. This feature is dependent on the time point of immune system activation and the respective compartment. The SNS supports inflammation during the asymptomatic phase of CIA, whereas it inhibits inflammation during the chronic symptomatic phase.
The incidence and natural history of Raynaud's phenomenon in the community
Authors: Suter Lisa G. , Murabito Joanne M. , Felson David T. , Fraenkel Liana
Published: April 2005

Objective

Raynaud's phenomenon (RP) is a common disorder, yet its incidence and natural history are unknown. Our objective was to determine the incidence and natural history of RP not associated with a connective tissue disease in a large, community‐based population.

Methods

Using serial examinations of the Framingham Heart Study offspring cohort, we collected data regarding RP symptoms for 717 women and 641 men over a 7‐year period. We used validated criteria for RP classification and categorized participants as having incident, persistent, or remitted RP. We performed sex‐specific analyses of RP status by age, body mass index, vibratory tool use, season of examination, state of residence, use of antihypertensive medications, and smoking status.

Results

The mean ± SD age of participants was 53.5 ± 10 years. The incidence of RP was 2.2% in women (n = 14) and 1.5% in men (n = 9). Of the 78 women and 50 men who had RP at baseline, 36% of women (n = 28) and 36% of men (n = 18) had persistent RP. RP remitted in 64% of women (n = 50) and 64% of men (n = 32), with 41 women and 25 men meeting no or only 1 RP criterion at followup. RP episodes were infrequent and rarely interfered with daily activities.

Conclusion

This is the first prospective study to determine the incidence and natural history of RP in a community‐based cohort. Our data demonstrate that RP not associated with a connective tissue disease is frequently a transient phenomenon and rarely interferes with daily activities.
New classification of HLA–DRB1 alleles supports the shared epitope hypothesis of rheumatoid arthritis susceptibility
Authors: du Montcel Sophie Tezenas , Michou Laetitia , Petit‐Teixeira Elisabeth , Osorio José , Lemaire Isabelle , Lasbleiz Sandra , Pierlot Céline , Quillet Patrick , Bardin Thomas , Prum Bernard , Cornelis François , Clerget‐Darpoux Françoise
Published: April 2005

Objective

The shared epitope hypothesis was formulated to explain the involvement of HLA–DRB1 in rheumatoid arthritis (RA). However, several studies, which considered only the HLA–DRB1 alleles shown to be associated with RA risk, rejected this hypothesis. In this report, we propose that a different classification of HLA–DRB1 alleles be considered, based on the amino acid sequence at position 70–74.

Methods

The fit of both HLA–DRB1 classifications was tested in 2 groups of RA patients. All subjects were recruited through the European Consortium on Rheumatoid Arthritis Families, and included 100 patients with isolated RA and 132 patients with at least 1 affected sibling.

Results

The new classification produced risk estimates that fit all of the observed data, i.e., the distribution of the HLA–DRB1 genotype in the 2 patient groups, and the distribution of parental alleles shared by affected sibpairs. The risk of developing RA under this new classification depends on whether the RAA sequence occupies position 72–74 but is modulated by the amino acid at position 71 (K confers the highest risk, R an intermediate risk, A and E a lower risk) and by the amino acid at position 70 (Q or R confers a higher risk than D).

Conclusion

A new classification based on amino acid sequence allows us to show that the shared epitope RAA sequence at position 72–74 explains the data, with the risk of developing RA modulated by the amino acids at positions 70 and 71.
Continuous indices of core data set measures in rheumatoid arthritis clinical trials: Lower responses to placebo than seen with categorical responses with the American College of Rheumatology 20% criteria
Authors: Pincus Theodore , Amara Ingrid , Koch Gary G.
Published: April 2005

Objective

To describe indices that are continuous counterparts of categorical responses to the American College of Rheumatology 20% improvement criteria (ACR20), ACR50, and ACR70, which extend rheumatoid arthritis (RA) clinical trial results and recognize clinical worsening (as well as improvement) with active and placebo treatments.

Methods

Data from a clinical trial of leflunomide, methotrexate, and placebo treatment over 1 year were reanalyzed. Percent change was computed for each of the 7 components of the ACR core set of outcome measures. Four continuous indices were computed: 1) ACR‐N (lowest of 3 values: number of swollen joints, number of tender joints, and median of the other 5 measures); 2) composite (median of all 7 measures [3 patient and 3 assessor measures plus erythrocyte sedimentation rate]); 3) patient‐only (median of physical function, pain, and global status); and 4) assessor‐only (median of number of swollen joints, number of tender joints, and global status). Means, medians, categorical 20%, 50%, and 70% responses, and continuous probability plots were computed according to each index for the 3 treatment groups and were compared with one another and with standard ACR20, ACR50, and ACR70 responses.

Results

Mean levels of improvement calculated using the different methods, in patients taking leflunomide, placebo, and methotrexate, respectively, were as follows: ACR‐N 20%, −12%, and 13%; composite 43%, 9%, and 33%; patient‐only 36%, 0%, and 26%; assessor‐only 50%, 20%, and 44%; and ACR20 52%, 26%, and 46%. Differences between leflunomide and placebo were 30–36%, and differences between methotrexate and placebo were 24–26%.

Conclusion

Continuous indices may be an informative addition to categorical ACR 20%, 50%, or 70% responses to compare efficacies of various treatments in RA, and to describe lower responses to placebo by recognizing worsening as well as improvement.
Fibroblast expression of the coactivator p300 governs the intensity of profibrotic response to transforming growth factor β
Authors: Bhattacharyya Swati , Ghosh Asish K. , Pannu Jaspreet , Mori Yasuji , Takagawa Shinsuke , Chen Guofen , Trojanowska Maria , Gilliam Anita C. , Varga John
Published: April 2005

Objective

Transforming growth factor β (TGFβ) induces profibrotic responses in normal fibroblasts, and plays a fundamental role in the pathogenesis of fibrosis in scleroderma (systemic sclerosis [SSc]). The intensity of cellular responses elicited by cytokines is modulated by transcriptional coactivators such as the histone acetylase p300. The objective of these studies was to delineate the physiologic role of p300 in Smad‐dependent profibrotic responses elicited by TGFβ.

Methods

Ectopic p300 was transiently expressed in normal dermal fibroblasts. Cellular p300 levels were suppressed using p300‐specific ribozymes. The regulation of gene expression was examined by transient transfection assays, Northern blotting, and immunoblot analysis. The expression of p300 in normal and scleroderma fibroblasts was evaluated by confocal microscopy and immunoblotting, and p300 levels in skin from mice with experimental scleroderma were assessed by immunohistochemistry.

Results

In normal fibroblasts, TGFβ induced an increase in the levels of p300. Forced expression of ectopic p300 in these cells dramatically enhanced the magnitude of TGFβ responses, whereas selective depletion of p300 using ribozyme resulted in abrogation of TGFβ‐induced collagen synthesis and promoter activity. Furthermore, TGFβ lost its ability to induce Smad‐dependent transcription in p300‐depleted fibroblasts. These responses could be fully rescued with ectopic p300. Abrogation of Smad‐mediated TGFβ signaling was not due to alterations in the levels or the ligand‐dependent phosphorylation or intracellular trafficking of endogenous Smads. Immunohistochemical analysis demonstrated substantially increased p300 expression in lesional skin from mice with chronic graft‐versus‐host disease, an animal model of scleroderma. Furthermore, levels of p300 were 2–3–fold higher in cultured fibroblasts derived from SSc patients than in fibroblasts from matched normal controls.

Conclusion

These results establish, for the first time, that the coactivator histone acetylase p300, itself a target of TGFβ regulation, is an essential component of the cellular TGFβ signal transduction pathways mediating stimulation of collagen synthesis in fibroblasts. Since the cellular abundance of p300 appears to govern the intensity of profibrotic responses elicited by TGFβ, elevated p300 expression in lesional tissue may contribute to the progression of skin fibrosis in scleroderma.
Activation of the type I interferon system in primary Sjögren's syndrome: A possible etiopathogenic mechanism
Authors: Båve Ullvi , Nordmark Gunnel , Lövgren Tanja , Rönnelid Johan , Cajander Stefan , Eloranta Maija‐Leena , Alm Gunnar V. , Rönnblom Lars
Published: April 2005

Objective

The etiopathogenesis of primary Sjögren's syndrome (SS) is largely unknown. In other autoimmune diseases, type I interferon (IFN) may play a pivotal role by triggering and sustaining the disease process. We therefore aimed to determine whether patients with primary SS had an activated type I IFN system.

Methods

Salivary gland biopsy specimens and sera from patients with primary SS were investigated for the occurrence of IFNα‐producing cells and measurable IFNα levels, respectively. The ability of primary SS sera together with apoptotic or necrotic cells to induce IFNα production in normal peripheral blood mononuclear cells was examined. The IFNα inducer was characterized, and IFNα‐producing cells were identified. Clinical data were correlated with the IFNα‐inducing capacity of primary SS sera.

Results

Numerous IFNα‐producing cells were detected in salivary gland biopsy specimens, despite low serum IFNα levels. Autoantibodies to RNA‐binding proteins, combined with material released by necrotic or late apoptotic cells, were potent inducers of IFNα production in plasmacytoid dendritic cells (PDCs). This appeared to be attributable to RNA‐containing immune complexes triggering PDCs by means of RNA and interaction with Fcγ receptor IIa. The IFNα‐inducing capacity of sera was associated with positive results of a labial salivary gland biopsy (focus score ≥1) and with dermatologic, hematologic, and pulmonary manifestations.

Conclusion

Patients with primary SS have an activated type I IFN system. Although virus may initiate the production of IFN, the continued IFNα synthesis is caused by RNA‐containing immune complexes that activate PDCs to prolong IFNα production at the tissue level. This IFNα promotes the autoimmune process by a vicious circle–like mechanism, with increased autoantibody production and formation of more endogenous IFNα inducers.
Need for information and for involvement in decision making among patients with rheumatoid arthritis: A questionnaire survey
Authors: Neame Rebecca , Hammond Alison , Deighton Christopher
Published: April 2005

Objective

To measure the need for information about rheumatoid arthritis (RA) and the level of desire for involvement in treatment decisions among patients with RA. To examine the relationship between these preferences and what factors (sociodemographic, disease, treatment, level of disability, and level of knowledge about RA) associate with these preferences.

Methods

Questionnaire surveys were mailed to a randomly selected group of 600 patients with RA. Need for information and desire for involvement in decision making were measured using a validated tool (the Autonomy Preference Index).

Results

The response rate was 57.3%. The need for information was very high. Information seeking preference scores (median 82.5, interquartile range 80.0–92.5) were significantly higher (P < 0.001) than decision making preference scores (mean ± SD 56.4 ± 13.6). Need for information and for decision making were both higher in women than men, and associations with these needs differed in men and women. However, younger age and greater knowledge of RA predicted greater need for decision making. There was no correlation between need for information and for involvement in treatment decisions for either sex (women: rs = 0.09, P = 0.19; men: rs = −0.06, P = 0.54).

Conclusion

There was a high level of need for information among patients with RA. Desire for involvement in treatment decision making was significantly lower and did not correlate with need for information. Associations with these needs differed for men and women.
Redesigning the care of fragility fracture patients to improve osteoporosis management: A health care improvement project
Authors: Harrington J. Timothy , Barash Harvey L. , Day Sherry , Lease Joellen
Published: April 2005

Objective

To develop new processes that assure more reliable, population‐based care of fragility fracture patients.

Methods

A 4‐year clinical improvement project was performed in a multispecialty, community practice health system using evidence‐based guidelines and rapid cycle process improvement methods (plan‐do‐study‐act cycles).

Results

Prior to this project, appropriate osteoporosis care was provided to only 5% of our 1999 hip fracture patients. In 2001, primary physicians were provided prompts about appropriate care (cycle 1), which resulted in improved care for only 20% of patients. A process improvement pilot in 2002 (cycle 2) and full program implementation in 2003 (cycle 3) have assured osteoporosis care for all willing and able patients with any fragility fracture. Altogether, 58% of 2003 fragility fracture patients, including 46% of those with hip fracture, have had a bone measurement, have been assigned to osteoporosis care with their primary physician or a consultant, and are being monitored regularly. Only 19% refused osteoporosis care. Key process improvements have included using orthopedic billings to identify patients, referring patients directly from orthopedics to an osteoporosis care program, organizing care with a nurse manager and process management computer software, assigning patients to primary or consultative physician care based on disease severity, and monitoring adherence to therapy by telephone.

Conclusion

Reliable osteoporosis care is achievable by redesigning clinical processes. Performance data motivate physicians to reconsider traditional approaches. Improving the care of osteoporosis and other chronic diseases requires coordinated care across specialty boundaries and health system support.
Impact of ultrasound imaging on local corticosteroid injections of symptomatic ankle, hind‐, and mid‐foot in chronic inflammatory diseases
Authors: d'Agostino Maria‐Antonietta , Ayral Xavier , Baron Gabriel , Ravaud Philippe , Breban Maxime , Dougados Maxime
Published: April 2005

Objective

To assess the impact of ultrasonography (US) on local corticosteroid (CS) injections of painful ankle, hindfoot, and midfoot in chronic inflammatory diseases.

Methods

Consecutive patients with chronic rheumatic diseases admitted to the hospital for local CS injections of painful ankle, hindfoot, or midfoot were enrolled in this study. Clinical and radiographic evaluation was performed by the physician in charge of CS injections, and US examination was performed by an independent examiner blinded to the clinical and radiologic findings. According to a randomized weekly‐periods design, the physician planned CS injections either aware (G1 group) or unaware (G2 group) of US results. In the latter case, he was nonetheless informed of US results after he had performed the injections. Impact of this information on the treatment planning was assessed in all cases. Prognostic impact of US was also evaluated by comparing the change in global assessment of efficacy of CS injections, in activity of the disease, and in the Western Ontario and McMaster Universities (WOMAC) subscales after 1 and 3 months, between G1 and G2 groups.

Results

The knowledge of US findings led the physician to change his decision of local CS injections in 56 (82%) of 68 patients studied. Among 1,131 assessed sites, by clinical, radiographic, and US evaluation, injection was cancelled in 37 (15%) of 242 proposed sites, whereas it was decided in 74 (8%) additional sites. After 1 month, there was an improvement in G1 as compared with G2 groups. The mean ± SD change in WOMAC physical function subscale was 15.6 ± 17.5 in G1 versus 8 ± 13 in G2 (P = 0.0305). After 3 months, only the global assessment of efficacy of CS injections was statistically greater in G1 than in G2 group (P = 0.0170).

Conclusion

US frequently led the physician to change his diagnosis of inflammatory lesions in painful foot, and consequently his planning of CS injections. Moreover, US could improve the response to local treatment.
Indirect cost assessment in patients with rheumatoid arthritis (RA): Comparison of data from the health economic patient questionnaire HEQ‐RA and insurance claims data
Authors: Merkesdal Sonja , Ruof Joerg , Huelsemann Jan Leo , Mittendorf Thomas , Handelmann Silke , Mau Wilfried , Zeidler Henning
Published: April 2005

Objective

To render information on the accuracy of patient‐reported indirect cost data compared with payer‐derived data of the real indirect costs on a patient‐by‐patient basis concerning disease‐related productivity losses in rheumatoid arthritis (RA).

Methods

The assessment of indirect cost data was part of a clinical, multicenter, randomized RA trial. A total of 234 patients of working age with a diagnosis of RA (according to 1987 American College of Rheumatology criteria) were recruited. Demographics of the cohort were mean age 53 years, mean disease duration 8 years, 76% were women, and all had membership in the regional statutory health insurance plan. Every 3 months corresponding indirect cost data were derived for the cohort from a health economic questionnaire for cost assessment in patients with RA and the payer's database over a period of 18 months. Comparative statistical analyses were performed between patient‐reported and insurance claims data.

Results

The mean annual productivity losses due to sick leave amounted to 14 and 17 days per patient (questionnaire versus payer data), and productivity losses due to work disability amounted to 3 days (both); monetary valuation renders overall costs of €1,240 and €1,590, respectively. The difference of 17% in overall productivity losses is not significant. Comparison of productivity losses reveals a strong correlation of r = 0.83 in those due to sick leave and of κ = 0.84 in those due to work disability between questionnaire and payer data.

Conclusion

The comparison of questionnaire and payer data shows that RA patients report their productivity losses adequately. Indirect cost assessment should therefore be included in further RA trials and observational studies.