bluuebunny/crossref_metadata_2025 huggingface dataset:
Autoreactivity of Serum Immunoglobulin to Periodontal Tissue Components: A Pilot Study
Authors: Koutouzis Theofilos , Haber Derek , Shaddox Luciana , Aukhil Ikrammudin , Wallet Shannon M.
Published: March 2009

Background: Periodontal diseases are inflammatory diseases resulting in the destruction of tissues of the periodontium. Although bacteria must be present for periodontal disease to occur, a susceptible host is also required, which is determined by genetic, environmental, and acquired factors. One such factor, autoimmunity, may play a role in the tissue destruction. Data indicate that some antibodies that occur in the gingival lesion are directed to host tissue components, such as type I collagen, although investigations of other periodontal autoimmune targets are limited.

Methods: Histologic sections and extracts from periodontally healthy teeth and the associated soft tissues were probed with serum from localized aggressive periodontitis (LAgP), chronic periodontitis (CP), and periodontally healthy subjects to determine autoreactivity to components of the periodontium. Any autoreactivity observed was characterized further by mass spectrometry and enzyme‐linked immunosorbent assay.

Results: Autoreactivity to components of the periodontium was observed in CP and LAgP. Known autoimmune targets, such as collagen and heat shock protein, were identified along with multiple potential autoimmune targets, including members of the extracellular matrix, such as vimentin, spectrin, filamin, actin, lamin, keratin, and tubulin. Finally, it was determined that the autoreactivity observed in LAgP was more severe and diverse than that observed in CP.

Conclusion: These data demonstrated that autoimmune reactivity can play a role in the tissue destruction of periodontal disease but that the nature of the autoreactivity may differ based on the type and/or stage of periodontal disease.
Ossifying Fibromyxoid Tumor in the Mandibular Gingiva: Case Report and Review of the Literature
Authors: Nonaka Cassiano F.W. , Pacheco Domingos F.S. , Nunes Rodrigo P.A. , Freitas Roseana de A. , Miguel Márcia Cristina da Costa
Published: March 2009

Background: Ossifying fibromyxoid tumors (OFTs) are uncommon soft tissue neoplasms. Only one case arising in the gingiva has been described.

Methods: A 21‐year‐old woman presented with a painless exophytic mass located in the right posterior mandibular gingiva, which was identified 6 months earlier. Radiographs showed irregular calcifications inside the lesion, discrete irregularity of alveolar bone, and integrity of buccal and lingual cortical bone. An incisional biopsy was performed based on the clinical diagnostic hypothesis of peripheral ossifying fibroma or peripheral giant cell granuloma. Microscopic features were compatible with the diagnosis of ossifying fibroma. The entire mass was excised and submitted to histopathologic and immunohistochemical analysis.

Results: Histopathologic analysis revealed proliferation of round to spindle‐shaped cells arranged in cords and nests and embedded in a fibromyxoid matrix. An incomplete shell of bone trabeculae located beneath the fibrous pseudocapsule was observed at the periphery. Immunohistochemical analysis showed positivity for vimentin and S‐100 protein and negativity for smooth muscle actin, muscle‐specific actin, and glial fibrillary acidic protein. The definitive diagnosis was OFT. The patient showed no clinical signs of recurrence 7 months after surgical excision.

Conclusions: OFTs located in the gingiva are extremely rare. At this site, these tumors are clinically indistinguishable from other reactive or neoplastic lesions. Although many cases present an indolent biologic behavior, the local recurrence of OFTs has been reported; therefore, long‐term follow‐up is mandatory.
Association of Cigarette Smoking With Superoxide Dismutase Enzyme Levels in Subjects With Chronic Periodontitis
Authors: Agnihotri Rupali , Pandurang Pratibha , Kamath Shobha U. , Goyal Rahul , Ballal Suhas , Shanbhogue Ashwini Y. , Kamath Ullas , Bhat G. Subraya , Bhat K. Mahalinga
Published: March 2009

Background: Smoking, which is an important risk factor for periodontitis, induces oxidative stress in the body and causes an imbalance between reactive oxygen species (ROS) and antioxidants, such as superoxide dismutase (SOD). In the present study, the influence of smoking on the periodontium was determined by estimating the levels of SOD in light and heavy smokers with periodontitis.

Methods: Seventy subjects in the age range of 20 to 55 years, including 60 smokers and 10 non‐smokers (controls), were selected. Clinical parameters recorded were plaque index (PI), probing depth (PD), and attachment loss (AL). Smokers were divided into light smokers (<10 cigarettes/day) and heavy smokers (≥10 cigarettes/day) and into three subgroups: healthy, mild periodontitis, and moderate periodontitis. Gingival crevicular fluid (GCF) and saliva samples were collected. SOD levels were analyzed using spectrophotometric assay.

Results: The mean levels of SOD in the GCF and saliva of smokers were decreased compared to controls. Intra‐ and intergroup analyses showed a significant reduction in the levels of SOD in the GCF and saliva of heavy smokers compared to light smokers and the control group.

Conclusions: There was a progressive reduction in SOD levels from healthy non‐smokers to light smokers to heavy smokers. These findings highlight the need to augment the efforts of smoking‐cessation programs. The benefits of reduced smoking and improved antioxidant levels may motivate smoking cessation.
Optimization of Milling Plugs With Coil Tubing on the Pinedale Anticline
Authors: Perry B. , McCluskey A.
Published: March 2009

One main challenge facing the Shell Pinedale Anticline completions is effectively drilling 21 plugs per well throughout a 6500′ hydraulically fractured completion interval (7,500′ – 14,000′ TMD) in a safe, timely, and cost effective manner. Ths process of drilling plugs has improved considerably with respect to time, cost, and environmental impact since drilling and completions operations ramped up in 2002.

Early bottom hole assembly (BHA) designs used for the drilling of plugs with coiled tubing (CT) were limited to drilling approximately 4-6 plugs before tripping out of hole for a new mill or motor. In addition to the long cycle times, this BHA design also resulted in high frequency of sticking, disconnects, and costly fishing jobs. Since no advanced flowback equipment or layouts were used on early drill outs, all gas was flared. Improvements to all aspects of the drilling process, such as BHA design and flowback layout, have led to routinely drilling up as many as 21 composite bridge plugs, with one coiled tubing trip, limited flaring of gas, and reduced cycle time of less than 24 hours from rig up to rig down.

This paper will focus on four main areas of improvement: 1) Bottom Hole Assembly (BHA) improvements; mill design, motor performance 2) Surface equipment improvements resulting in limited flaring, 3) Composite plug selection, 4) CT selection – taper, grade, size.
First Coiled Tubing Swellable-Packer Deployment in the Middle East
Authors: Noguera Jose , Sierra Leopoldo , Jorgensen Thomas
Published: March 2009

This paper describes the rigless deployment of two swellable-packer assemblies used to isolate a set of perforations in a horizontal cased-hole completion. The purpose of this application was to provide a cost-effective method of isolating a high water-saturated zone in an extended lateral and to facilitate the production of hydrocarbon from the rest of the perforations.

The candidate selected for this application was a horizontal cased-hole well with five sets of perforations in which the water cut increased from 0 to 60% in less than two years of production. A production and water-detection log was acquired and confirmed the top set of perforations as the water-entry point.

Several rigless alternatives, including chemical treatments, inflatable packers, and oil-swellable packers, were evaluated as potential solutions to isolate the perforations. The complexity of placement of chemical water-shutoff treatments in horizontal sections and previous unsuccessful isolations with inflatable packers aided in the selection of an oil-swellable packer as the most suitable solution.

The rigless deployment of two swellable-packer assemblies with 250 ft of blank section to straddle the water-intrusion zone while complying with the necessary well-control barriers presented an operational challenge that was overcome by combining slickline with coiled tubing (CT) services. The solution allowed successful placement of both assemblies in the horizontal section.
Safer, Faster, and More-Reliable Operations With Next-Generation Offshore Coiled Tubing Unit
Authors: Burgos R. , Mallalieu R. , Yusoff A. Mohd , Wicaksono K.
Published: March 2009

Most coiled tubing (CT) interventions are performed in a rigless environment. In fact, this is one of the important drivers for the widespread acceptance and continued growth of the technique for well servicing, especially in the offshore domain where the logistical costs are higher and operational challenges are more complex.

Unlike land-based CT operations where integration is straightforward, the issues of equipment packaging for offshore integration is daunting. Overcoming limitations of crane-load lift capacity and deck space constraints are just part of the problem. Offshore CT units (CTU) are typically packaged as separate modules with components that require integration before any well intervention activity can begin. Rig up and operational efficiency are important design considerations for offshore CTU packages, but overall safety and regulatory compliance are of paramount concern.

A new CTU configuration designed to meet the stringent demands of offshore CT operations was recently introduced. The design focused on key integration and HSE issues relating to the rig-up process. Results from more than 500 jobs performed during a 2-year period, in far eastern offshore environments indicated significant improvements in overall operational efficiency. In addition, the new designs met predefined HSE performance objectives, particularly during equipment rig-up phase.
Optimizing the Most Common CT Operation in the US: Findings From More Than 60 Composite Frac Plug Underbalanced Milling Operations in the Piceance Basin
Authors: Castro L. , Clark B.
Published: March 2009

The advent of multi-zone stimulation techniques has created an increasing need for zonal isolation devices, such as composite bridge and frac plugs. Bringing the well on to production requires that these devices be removed from the wellbore effectively and in a timely fashion. Milling composite frac plugs (CFP) using coiled tubing (CT) and positive displacement motors (PDM) is one of the most common and effective methods in the industry. Where formation properties allow, overbalanced CFP milling is routinely performed with high degrees of success. However, underbalanced milling operations that use nitrogen as a circulation aid pose additional challenges. Further, efforts to optimize the technique are often limited by the numerous parameters involved which reduce the repeatability of successful results.

This paper presents the lessons learned from over sixty underbalanced CFP milling operations performed in the Piceance Basin. The results shown are uniquely relevant due to the fact that the operations involved in this study were performed within the same field, using the same type and size of PDM, mill, CFP, and CT. Very rarely can all these variables be kept as constants. Additionally, the same core field personnel were used over a one year period. This elevated level of consistency allows the author to focus on key controllable CT variables of the operation. The paper will review the optimization and results of: two-phase flow rates, PDM stalling, milling profiles and optimum wellhead pressures.

Reviewing the field data has resulted in improved operational efficiencies by empirically developing two concepts: the "milling profile" and the "optimum milling wellhead pressure". These improvements will be discussed in the paper.
Utilizing Field Data to Validate Finite Element Analysis Modeling of a Coiled Tubing Intervention Stack on a North Slope of Alaska Well
Authors: Newman K. R. , Traugott D. A. , Deckert Steven
Published: March 2009

BP Exploration in Alaska were planning Coiled Tubing (CT) operations on wells that have components in the wellhead stack with 2-9/16", 5,000 psi components at the bottom of the stack. There was a concern that the CT intervention stack and associated equipment could damage these small wellhead components during the well intervention process.

A finite-element analysis (FEA) was performed of the intervention stack, followed by a field test in which a bending moment and force measuring gauge was used to measure the actual moments and forces being applied. Results from the field test were used to improve the FEA modeling.This paper presents the results from the modeling and the field test, and discusses the conclusions from this study.
Severe Infantile Carnitine Palmitoyltransferase II Deficiency in 19-Week Fetal Sibs
Authors: Meir Karen , Fellig Yakov , Meiner Vardiella , Korman Stanley H. , Shaag Avraham , Nadjari Michel , Soffer Dov , Ariel Ilana
Published: March 2009

Antenatal presentation of carnitine palmitoyltransferase type II deficiency due to mutations in the CPT2 gene has been rarely reported. We report an Ashkenazi Jewish family with 3 terminated pregnancies for multicystic kidneys and/or hydrocephalus. Fetal autopsy after termination of the couple's 4th pregnancy (sib 2) showed renal parenchyma replaced by cysts that appeared to increase in diameter toward the medulla. Fetopsy after termination of the 7th pregnancy (sib 3) revealed micrognathia; hypospadias; cystic renal dysplasia; hepatosteatosis; and lipid accumulation in the renal tubular epithelium, myocardium, and skeletal muscle. Microvascular proliferative changes and focal polymicrogyria were seen in the brain. A beta-oxidative enzyme deficiency was suspected. CPT2 gene analysis showed a homozygous complex haplotype for the F448L mutation associated with a c.del1238_1239AG (p.Q413fs) truncating mutation in exon 4. Carnitine palmitoyltransferase type II deficiency should be included in the differential diagnosis in fetuses of Ashkenazi origin with multicystic kidneys and unusual cerebral findings.
Evaluation of the volumes of cranial cavities in Cavalier King Charles Spaniels with Chiari-like malformation and other brachycephalic dogs as measured via computed tomography
Authors: Schmidt Martin J. , Biel Miriam , Klumpp Stephan , Schneider Matthias , Kramer Martin
Published: March 2009

Objective—To measure the absolute and relative volumes of cranial vaults of Cavalier King Charles Spaniels (CKCSs) and other brachycephalic dogs for the purpose of evaluating a possible association between the volume of the caudal fossa (fossa caudalis cerebri; CF) and existence of Chiari-like malformation (CLM) and syringohydromyelia in CKCSs.

Animals—40 CKCSs and 25 brachycephalic dogs.

Procedures—The intracranial vault of all dogs was evaluated via computed tomography followed by magnetic resonance imaging. Volumes of the CF and the rostral and medial fossa (fossa rostralis et medialis cerebri) were determined. The ratio of the absolute volumes was calculated as the volume index (VI).

Results—All CKCSs had cranial characteristics consistent with CLM. There were no significant differences between CKCSs and brachycephalic dogs with respect to the VI and absolute volumes of the CF and rostral and medial fossas. The CKCSs without syringohydromyelia (n = 26) had a median VI of 0.1842, and CKCSs with syringohydromyelia (14) had a median VI of 0.1805. The median VI of other brachycephalic dogs was 0.1864. The VI did not differ among these 3 groups.

Conclusions and Clinical Relevance—Results of this study suggested that descent of the cerebellum into the foramen magnum and the presence of syringohydromyelia in CKCSs are not necessarily associated with a volume reduction in the CF of the skull.
Single- and multiple-dose pharmacokinetics of marbofloxacin after oral administration to rabbits
Authors: Carpenter James W. , Pollock Christal G. , Koch David E. , Hunter Robert P.
Published: March 2009

Objective—To determine the pharmacokinetics of marbofloxacin after oral administration every 24 hours to rabbits during a 10-day period.

Animals—8 healthy 9-month-old female New Zealand White rabbits.

Procedures—Marbofloxacin (5 mg/kg) was administered orally every 24 hours to 8 rabbits for 10 days. The first day of administration was designated as day 1. Blood samples were obtained at 0, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours on days 1 and 10 of marbofloxacin administration. Plasma marbofloxacin concentrations were quantitated by use of a validated liquid chromatography–mass spectrometry assay. Pharmacokinetic analysis of marbofloxacin was analyzed via noncompartmental methods.

Results—After oral administration, mean ± SD area under the curve was 10.50 ± 2.00 μg·h/mL and 10.90 ± 2.45 μg·h/mL, maximum plasma concentration was 1.73 ± 0.35 μg/mL and 2.56 ± 0.71 μg/mL, and harmonic mean terminal half-life was 8.0 hours and 3.9 hours for days 0 and 10, respectively.

Conclusions and Clinical Relevance—Marbofloxacin administered orally every 24 hours for 10 days appeared to be absorbed well and tolerated by rabbits. Administration of marbofloxacin at a dosage of 5 mg/kg, PO, every 24 hours is recommended for rabbits to control infections attributable to susceptible bacteria.
Effects of larkspur (Delphinium barbeyi) on heart rate and electrically evoked electromyographic response of the external anal sphincter in cattle
Authors: Green Benedict T. , Pfister James A. , Cook Daniel , Welch Kevin D. , Stegelmeier Bryan L. , Lee Stephen T. , Gardner Dale R. , Knoppel Edward L. , Panter Kip E.
Published: March 2009

Objective—To determine whether larkspur-derived N-(methylsuccinimido) anthranoyllycoctonine (MSAL)-type alkaloids alter heart rate and electrically evoked electromyographic (eEMG) response of the external anal sphincter (EAS) in cattle and whether these effects can be reversed by acetylcholinesterase inhibitors.

Animals—12 beef heifers and 4 cows.

Procedures—3 or 4 heifers were used in 1 or 2 of 7 dose-response experiments; heart rate and EAS eEMG response were assessed before and 24 hours after oral treatment with larkspur (doses equivalent to 0.5 to 15 mg of MSAL-type alkaloids/kg). In 3 subsequent experiments, 3 heifers (1 of which was replaced with another heifer in the control experiment) each received 10 mg of MSAL-type alkaloids/kg and were injected IV with physostigmine (0.04 mg/kg), neostigmine (0.04 mg/kg), or saline (0.9% NaCl) solution 24 hours later, prior to assessment. Additionally, EAS eEMG response was measured in 4 cows before and after epidural administration of 2% lidocaine hydrochloride.

Results—Larkspur-treated heifers developed dose-related increases in heart rate and decreases in EAS eEMG response. Twenty-four hours after administration of MSAL-type alkaloids, neostigmine decreased heart rate but did not affect eEMG response, whereas physostigmine did not affect heart rate but caused a 2-fold increase in eEMG response. In cows, epidural anesthesia did not alter eEMG response, suggesting that transdermal stimulation of the EAS pudendal innervation did not occur.

Conclusions and Clinical Relevance—In cattle, cardiac effects and muscle weakness or loss of EAS eEMG response induced by larkspur-derived MSAL-type alkaloids were reversed by neostigmine or physostigmine, respectively. Treatment with anticholinesterase inhibitors may alter the clinical effects of larkspur poisoning in cattle.
Molecular Docking Studies and Anti-enzymatic Activities of Thai Mango Seed Kernel Extract Against Snake Venoms
Authors: Leanpolchareanchai Jiraporn , Pithayanukul Pimolpan , Bavovada Rapepol , Saparpakorn Patchreenart
Published: March 2009

The ethanolic extract from seed kernels of Thai mango (MSKE) (Mangifera indica L. cv. ‘Fahlun’) (Anacardiaceae) and its major phenolic principle (pentagalloyl glucopyranose) exhibited dose-dependent inhibitory effects on enzymatic activities of phospholipase A2 (PLA2), hyaluronidase and L-amino acid oxidase (LAAO) of Calloselasma rhodostoma (CR) and Naja naja kaouthia (NK)venoms by in vitro tests. The anti-hemorrhagic and anti-dermonecrotic activities of MSKE against both venoms were clearly supported by in vivo tests. Molecular docking studies indicated that the phenolic molecules of the MSKE could selectively bind to the active sites or their proximity, or modify conserved residues that are critical for the catalysis of PLA2, and selectively bind to the LAAO binding pocket of both CR and NK venoms and thereby inhibit their enzymatic activities. The results imply a potential use of MSKE against snake venoms.
Fieldservers and Sensor Service Grid as Real-time Monitoring Infrastructure for Ubiquitous Sensor Networks
Authors: Honda Kiyoshi , Shrestha Aadit , Witayangkurn Apichon , Chinnachodteeranun Rassarin , Shimamura Hiroshi
Published: March 2009

The fieldserver is an Internet based observation robot that can provide an outdoor solution for monitoring environmental parameters in real-time. The data from its sensors can be collected to a central server infrastructure and published on the Internet. The information from the sensor network will contribute to monitoring and modeling on various environmental issues in Asia, including agriculture, food, pollution, disaster, climate change etc. An initiative called Sensor Asia is developing an infrastructure called Sensor Service Grid (SSG), which integrates fieldservers and Web GIS to realize easy and low cost installation and operation of ubiquitous field sensor networks.
Efficiency of CYP2C9 Genetic Test Representation for Automated Pharmacogenetic Decision Support
Authors: Hoffman M. A. , Arnoldi C. , Bray B. E. , Mitchell J. A. , Deshmukh V. G.
Published: March 2009

Objectives: We investigated the suitability of representing discrete genetic test results in the electronic health record (EHR) as individual single nucleotide polymorphisms (SNPs) and as alleles, using the CYP2C9 gene and its polymorphic states, as part of a pilot study. The purpose of our investigation was to determine the appropriate level of data abstraction when reporting genetic test results in the EHR that would allow meaningful interpretation and clinical decision support based on current knowledge, while retaining sufficient information in order to enable reinterpretation of the results in the context of future discoveries.

Methods: Based on the SNP & allele models, we designed two separate lab panels within the laboratory information system, one containing SNPs and the other containing alleles, built separate rules in the clinical decision support system based on each model, and evaluated the performance of these rules in an EHR simulation environment using real-world scenarios.

Results: Although decision-support rules based on allele model required significantly less computational time than rules based on SNP model, no difference was observed on the total time taken to chart medication orders between rules based on these two models.

Conclusions: Both, SNP- and allele-based models, can be used effectively for representing genetic test results in the EHR without impacting clinical decision support systems. While storing and reporting genetic test results as alleles allow for the construction of simpler decision-support rules, and make it easier to present these results to clinicians, SNP-based model can retain a greater amount of information that could be useful for future reinterpretation.
A Simple Modeling-free Method Provides Accurate Estimates of Sensitivity and Specificity of Longitudinal Disease Biomarkers
Authors: Pouteil-Noble C. , Toussaint S. , Villar E. , Rabilloud M. , Subtil F.
Published: March 2009

Objective: To assess the time-dependent accuracy of a continuous longitudinal biomarker used as a test for early diagnosis or prognosis.

Methods: A method for accuracy assessment is proposed taking into account the marker measurement time and the delay between marker measurement and outcome. It dealt with markers having interval-censored measurements and a detection threshold. The threshold crossing times were assessed by a Bayesian method. A numerical study was conducted to test the procedures that were later applied to PCR measurements for prediction of cytomegalovirus disease after renal transplantation.

Results: The Bayesian method corrected the bias induced by interval-censored measurements on sensitivity estimates, with corrections from 0.07 to 0.3. In the application to cytomegalovirus disease, the Bayesian method estimated the area under the ROC curve to be over 75% during the first 20 days after graft and within five days between marker measurement and disease onset. However, the accuracy decreased quickly as that delay increased and late after graft.

Conclusions: The proposed Bayesian method is easy to implement for assessing the time-dependent accuracy of a longitudinal biomarker and gives unbiased results under some conditions.
Psoriatic Arthritis Spondylitis Radiology Index: A Modified Index for Radiologic Assessment of Axial Involvement in Psoriatic Arthritis
Authors: LUBRANO ENNIO , MARCHESONI ANTONIO , OLIVIERI IGNAZIO , D’ANGELO SALVATORE , SPADARO ANTONIO , PARSONS WENDY J. , CAULI ALBERTO , SALVARANI CARLO , MATHIEU ANTONIO , PORTER GUY , HELLIWELL PHILIP S.
Published: March 2009

Objective.

To develop and validate a modified index for assessing the radiologic axial involvement in psoriatic arthritis (PsA) in a group of patients with established disease.

Methods.

Patients were included on clinical and/or radiologic criteria. The modified index combined features of existing radiologic indices for ankylosing spondylitis (AS) with the addition of scores for the facet joints of the cervical and lumbar regions. Scores for the BathAS Radiology Index (BASRI), the modified Stoke AS Scoring System (mSASSS), and the new index were obtained from current radiographs. The construct validity of the new index was assessed by examining the correlation with patient reported outcomes, such as the Revised Leeds Disability Questionnaire (RLDQ) and BathAS Functional Index (BASFI), and anthropometric measures.

Results.

Radiographs were available for 73 patients (54 men, 19 women, mean age 49.4 ± 11.0 yrs, mean disease duration 14.0 ± 7.9 yrs). Due to difficulty in visualizing and interpreting the lumbar facet joints, only the cervical facet joints were included in the new score, called the PsA Spondylitis Radiology Index (PASRI). Overall, the PASRI resulted in less missing data than the mSASSS, but had less complete data than the BASRI. The PASRI also had fewer zero scores than the mSASSS and the score range for the PASRI exceeded that of the mSASSS and the BASRI. Correlation with anthropometric and patient reported outcomes was good for both the PASRI and BASRI, with both these measures outscoring the mSASSS.

Conclusion.

The PASRI encompasses a greater range of the spinal radiologic features of PsA, provides a greater score range and fewer zero scores, and correlates well with anthropometric and patient reported measures.
The Rheumatoid Arthritis Disease Activity Index-5 in Daily Use. Proposal for Disease Activity Categories
Authors: RINTELEN BERNHARD , HAINDL PIA M. , SAUTNER JUDITH , LEEB BARBARA A. , DEUTSCH CHRISTOPH , LEEB BURKHARD F.
Published: March 2009

Objective.

To establish thresholds for rheumatoid arthritis (RA) activity categories according to the RA Disease Activity Index-5 (RADAI-5).

Methods.

Three hundred ninety-two patients with RA were categorized according to Disease Activity Score 28-joint count (DAS28), Clinical Disease Activity Index (CDAI), and their satisfaction (PATSAT) with disease status. These measures built the basis for the calculation of disease activity limits for the RADAI-5. Patient assessments simultaneously meeting the identical DAS28, CDAI, and PATSAT categories were taken as the references to establish the thresholds for the respective RADAI-5 categories by calculating the third quartile of the corresponding RADAI-5 values. Subsequently, these new thresholds were applied to all assessments.

Results.

Seven hundred fifty-eight assessments in 392 patients (2 assessments median/patient) could be obtained, most patients having mild to moderate disease according to DAS28 and CDAI. Calculating the third quartile, the RADAI-5 thresholds were as follows: 0.0–1.4 for a remission-like state, 1.6–3.0 for mild disease activity, 3.2–5.4 for moderate, and 5.6–10.0 for high disease activity. Categorization according to the RADAI-5 showed a normal distribution, while DAS28 and CDAI were somewhat shifted to the left. DAS28 and CDAI levels, as well as tender and swollen joint counts and physician’s global assessment and erythrocyte sedimentation rate, proved to be highly significantly different within the different RADAI-5 categories (Kruskal-Wallis test p < 0.001).

Conclusion.

RADAI-5 thresholds for RA activity could be elaborated. Patient self-report questionnaires may substitute composite disease activity scores and may contribute significantly to improving documentation in routine patient care.
Laboratory identification of lupus anticoagulants
Authors: Smock Kristi J. , Rodgers George M.
Published: March 2009

Lupus anticoagulants (LA) are acquired autoantibodies that can cause antiphospholipid syndrome. LAs prolong phospholipid‐dependent coagulation tests, acting as nonspecific inhibitors that are neutralized in the presence of excess phospholipid. However, there is no gold standard test and the testing is influenced by a number of variables. This article summarizes laboratory testing for LAs, with particular focus on technical issues and limitations of testing. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.
Late‐onset neutropenia following RCHOP chemotherapy in diffuse large B‐cell lymphoma
Authors: Lai Gillianne Geet Yi , Lim Soon‐Thye , Tao Miriam , Chan Alexandre , Li Huihua , Quek Richard
Published: March 2009

Rituximab has been associated with the development of late‐onset neutropenia (LON). As only heterogeneous studies have been conducted, its incidence and clinical course remain unclear. We aim to: (1) study the incidence and clinical relevance of WHO grade 3/4 LON in a uniform group of patients with diffuse large B‐cell lymphoma (DLBCL) in complete remission following curative rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (RCHOP) chemotherapy; (2) ascertain predictive factors for LON. The 121 eligible patients identified from our prospectively maintained database were followed up for occurrence of WHO grade 3/4 LON. The clinical course of LON was documented, and its relationship with patient‐ and tumor‐related factors was analyzed. With a median follow‐up of 883 days (range, 265–1762), 13.2% had developed LON of grade 3/4. The median time to neutrophil nadir was 129 days (range, 39–277). The median time to recovery was 69 days (range, 3–349) and occurred in all except two patients. Only one episode of nonlife threatening bacterial culture‐positive urinary tract infection and pulmonary tuberculosis, both occurring in the same patient was documented. Results of Fischer's exact test revealed that age, stage, LDH level, ECOG, marrow involvement, and hematologic parameters did not predict for LON development. WHO grade 3/4 LON is not infrequent in patients with DLBCL receiving RCHOP. Even so, it is reassuring that LON is self‐limiting and unassociated with life‐threatening infection. A watchful waiting approach is appropriate in majority of patients who develop LON following RCHOP. Am. J. Hematol., 2009. © 2009 Wiley‐Liss, Inc.
Sustained effects of nonallele‐specific Huntingtin silencing
Authors: Drouet Valérie , Perrin Valérie , Hassig Raymonde , Dufour Noëlle , Auregan Gwennaelle , Alves Sandro , Bonvento Gilles , Brouillet Emmanuel , Luthi‐Carter Ruth , Hantraye Philippe , Déglon Nicole
Published: March 2009

Objective

Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin (htt) protein. No cure is available to date to alleviate neurodegeneration. Recent studies have demonstrated that RNA interference represents a promising approach for the treatment of autosomal dominant disorders. But whether an allele‐specific silencing of mutant htt or a nonallele‐specific silencing should be considered has not been addressed.

Methods

We developed small hairpin RNA targeting mutant or wild‐type htt transcripts, or both.

Results

We confirmed the therapeutic potential of sihtt administered with lentiviral vectors in rodent models of HD and showed that initiation of small interfering RNA treatment after the onset of HD symptoms is still efficacious and reduces the HD‐like pathology. We then addressed the question of the impact of nonallele‐specific silencing and demonstrated that silencing of endogenous htt to 25 to 35% in vivo is altering several pathways associated with known htt functions but is not inducing overt toxicity or increasing striatal vulnerability up to 9 months after treatment.

Interpretation

These data indicate that the coincident silencing of the wild‐type and mutant htt may be considered as a therapeutic tool for HD. Ann Neurol 2009;65:276–285
Promotion of central nervous system remyelination by induced differentiation of oligodendrocyte precursor cells
Authors: Mi Sha , Miller Robert H. , Tang Wei , Lee Xinhua , Hu Bing , Wu Wutain , Zhang Yiping , Shields Christopher B. , Zhang Yongjie , Miklasz Steven , Shea Diana , Mason Jeff , Franklin Robin J. M. , Ji Benxiu , Shao Zhaohui , Chédotal Alain , Bernard Frederic , Roulois Aude , Xu Janfeng , Jung Vincent , Pepinsky Blake
Published: March 2009

Objective

Repair of demyelinated axons in diseases such as multiple sclerosis requires activation of the myelination program in existing or newly recruited oligodendrocyte precursor cells (OPCs). The control of OPC differentiation and initiation of myelination during repair is poorly understood. In this study, we test the ability of anti–LINGO‐1 reagents to promote myelination in vitro and remyelination in the rodent adult central nervous system in vivo.

Methods

The effects of LINGO‐1 antagonists on the differentiation of OPCs and the promotion of myelination has been assayed using a combination of coculture and slice culture preparations. Using three different animal models of demyelination and remyelination, we morphologically and functionally assessed the effects of LINGO‐1 antagonists on OPC differentiation and myelin repair.

Results

The data indicate that in vitro treatment with antagonists of LINGO‐1 promote OPC differentiation and myelination, whereas in vivo remyelination is accelerated in lysophosphatidylcholine‐ or cuprizone‐induced demyelination. This remyelination is associated with enhanced OPC differentiation and functional recovery of conduction velocities in demyelinated axons.

Interpretation

Our studies demonstrate that LINGO‐1 antagonism promotes OPC differentiation and remyelination, and suggest LINGO‐1 functions as an inhibitor of OPC differentiation to retard central nervous system remyelination. Ann Neurol 2009;65:304–315
Variant Creutzfeldt–Jakob disease in France and the United Kingdom: Evidence for the same agent strain
Authors: Brandel Jean‐Philippe , Heath Craig A. , Head Mark W. , Levavasseur Etienne , Knight Richard , Laplanche Jean‐Louis , Langeveld Jan PM. , Ironside James W. , Hauw Jean‐Jacques , Mackenzie Jan , Alpérovitch Annick , Will Robert G. , Haïk Stéphane
Published: March 2009

Objective

Variant Creutzfeldt–Jakob disease (vCJD) was first reported in the United Kingdom in 1996. Since then, the majority of cases have been observed in the United Kingdom where there was a major epidemic of bovine spongiform encephalopathy. France was the second country affected. To address the hypothesis of the involvement of a common strain of agent, we have compared clinical, neuropathological, and biochemical data on vCJD patients from both countries.

Methods

In France and the United Kingdom, epidemiological and clinical data were obtained from analysis of medical records and direct interview of the family of the patients using the same standardized questionnaire in both countries. When brain material was available, we performed with similar methods a comparative study of brain lesions and PrPres glycoform ratios in both vCJD populations.

Results

Clinical data, genetic background, neuropathological finding, and biochemical findings in the 185 patients observed in France (n = 23) and the United Kingdom (n = 162) were similar except for age at death. Currently, blood transfusion is a risk factor identified only in the United Kingdom.

Interpretation

The close similarity between the cases of vCJD in France and the United Kingdom supports the hypothesis that a common strain of infectious agent is involved in both countries. The 5‐year delay in the peak that we observed in France compared with the United Kingdom fits well with the increase in the importation of beef products to France from the United Kingdom between 1985 and 1995. Ann Neurol 2009;65:249–256
Excitotoxicity‐induced endocytosis confers drug targeting in cerebral ischemia
Authors: Vaslin Anne , Puyal Julien , Clarke Peter G. H.
Published: March 2009

Objective

Targeting neuroprotectants specifically to the cells that need them is a major goal in biomedical research. Many peptidic protectants contain an active sequence linked to a carrier such as the transactivator of transcription (TAT) transduction sequence, and here we test the hypothesis that TAT‐linked peptides are selectively endocytosed into neurons stressed by excitotoxicity and focal cerebral ischemia.

Methods

In vivo experiments involved intracerebroventricular injection of TAT peptides or conventional tracers (peroxidase, fluorescein isothiocyanate‐dextran) in young rats exposed to occlusion of the middle cerebral artery at postnatal day 12. Cellular mechanisms of uptake were analyzed in dissociated cortical neuronal cultures.

Results

In both models, all tracers were taken up selectively into stressed neurons by endocytosis. In the in vivo model, this was neuron specific and limited to the ischemic area, where the neurons displayed enhanced immunolabeling for early endosomal antigen‐1 and clathrin. The highly efficient uptake of TAT peptides occurred by the same selective mechanism as for conventional tracers. All tracers were targeted to the nucleus and cytoplasm of neurons that appeared viable, although ultimately destined to die. In dissociated cortical neuronal cultures, an excitotoxic dose of N‐methyl‐D‐aspartate induced a similar endocytosis. It was 100 times more efficient with TAT peptides than with dextran, because the former bound to heparan sulfate proteoglycans at the cell surface, but it depended on dynamin and clathrin in both cases.

Interpretation

Excitotoxicity‐induced endocytosis is the main entry route for protective TAT peptides and targets selectively the neurons that need to be protected. Ann Neurol 2009;65:337–347
A KCNQ channel opener for experimental neonatal seizures and status epilepticus
Authors: Raol YogendraSinh H. , Lapides David A. , Keating Jeffery G. , Brooks‐Kayal Amy R. , Cooper Edward C.
Published: March 2009

Objective

Neonatal seizures occur frequently, are often refractory to anticonvulsants, and are associated with considerable morbidity and mortality. Genetic and electrophysiological evidence indicates that KCNQ voltage‐gated potassium channels are critical regulators of neonatal brain excitability. This study tests the hypothesis that selective openers of KCNQ channels may be effective for treatment of neonatal seizures.

Methods

We induced seizures in postnatal day 10 rats with either kainic acid or flurothyl. We measured seizure activity using quantified behavioral rating and electrocorticography. We compared the efficacy of flupirtine, a selective KCNQ channel opener, with phenobarbital and diazepam, two drugs in current use for neonatal seizures.

Results

Unlike phenobarbital or diazepam, flupirtine prevented animals from experiencing development of status epilepticus when administered before kainate. In the flurothyl model, phenobarbital and diazepam increased latency to seizure onset, but flupirtine completely prevented seizures throughout the experiment. Flupirtine was also effective in arresting electrographic and behavioral seizures when administered after animals had developed continuous kainate‐induced status epilepticus. Flupirtine caused dose‐related sedation and suppressed electroencephalographic activity but did not result in respiratory suppression or result in any mortality.

Interpretation

Flupirtine appears more effective than either of two commonly used antiepileptic drugs, phenobarbital and diazepam, in preventing and suppressing seizures in both the kainic acid and flurothyl models of symptomatic neonatal seizures. KCNQ channel openers merit further study as potential treatments for seizures in infants and children. Ann Neurol 2009;65:326–336
Boratome als Spinträger in zwei‐ und dreidimensionalen Systemen
Authors: Kaim Wolfgang , Hosmane Narayan S. , Záliš Stanislav , Maguire John A. , Lipscomb William N.
Published: March 2009

Die ungewöhnliche Bindung von Bor in Organoboranen oder Oligoborclustern tritt nicht nur in diamagnetischen Molekülen auf, sondern auch in paramagnetischen Systemen, die gemischtvalente Verbindungen und Oligoboran/Carboran‐Clusterradikale umfassen. Das Bild zeigt das einfach besetzte Molekülorbital des Radikalions [C4B8R4H8].− gemäß DFT‐Rechnungen.

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Paramagnetische Verbindungen mit mindestens teilweise borzentriertem Elektronenspin lassen sich herstellen, indem entweder durch planare, π‐konjugierte organische Systeme verbrückte Boratome als idealtypische Elektronenakzeptoren verwendet werden oder indem die dreidimensionale, delokalisierte Bindung in mehrkernigen Boranen, Halogenboranen oder Carboranclustern genutzt wird. Das Konzept der Gemischtvalenz kann so von organischen und Übergangsmetallverbindungen auf Verbindungen der Hauptgruppenelemente übertragen werden. Mithilfe der Dichtefunktionaltheorie lässt sich die sehr variable Spinverteilung nachvollziehen.
Schooling Behavior of Light‐Powered Autonomous Micromotors in Water
Authors: Ibele Michael , Mallouk Thomas E. , Sen Ayusman
Published: March 2009

Grüppchenbildung: Silberchlorid‐Mikropartikel (rot) bewegen sich in Wasser unter UV‐Bestrahlung durch Diffusiophorese. Jedes AgCl‐Partikel gibt Ionen ab, auf die die anderen Partikel reagieren und sich zu Bereichen mit höherer Partikelkonzentration gruppieren. Photochemisch inaktive Siliciumdioxid‐Partikel (blau) werden durch die Ionenabgabe dazu stimuliert, sich den AgCl‐Partikeln anzunähern und diese zu umgeben.

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Tetraazuliporphyrin Tetracation
Authors: Sprutta Natasza , Maćkowiak Stanisław , Kocik Marzena , Szterenberg Ludmiła , Lis Tadeusz , Latos‐Grażyński Lechosław
Published: March 2009

Am Scheideweg: Ein einzigartiges kohlenstoffüberbrücktes Annulenmotiv – das Dehydroquatyrin – ist Teil der Molekülstruktur des Tetraazuliporphyrintetrakations (siehe Bild). Der Makrocyclus, der sich an der Schnittstelle zwischen Annulen‐, Carbokationen‐ und Porphyrinchemie befindet, wird durch Kondensation von Azulen mit Arylaldehyden und nachfolgende Oxidation erhalten. Die meso‐Positionen des Tetrakations können durch Anionen oder Nucleophile angegriffen werden.

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Practical Microwave Synthesis for Organic Chemists.Strategies, Instruments, and Protocols. Herausgegeben von C. Oliver Kappe, Doris Dallinger und Shaun Murphree.
Authors: Van der Eycken Erik V.
Published: March 2009

Wiley‐VCH, Weinheim 2008. 300 S., geb., 59.00 €.—ISBN 978‐3527320974

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Iron‐Catalyzed Dehydrogenative Coupling of Tertiary Silanes
Authors: Itazaki Masumi , Ueda Kensuke , Nakazawa Hiroshi
Published: March 2009

A variety of tertiary silanes, even those with functional substituents, undergo an unprecedented iron‐catalyzed dehydrogenative coupling (see scheme) in a convenient approach to disilanes, including unsymmetrical disilanes and polymers with SiSi bonds in the backbone. Consideration of the catalytic reaction pathway revealed the intermediacy of a hydrido(disilyl)iron(IV) complex.

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Copper‐Catalyzed Direct C Arylation of Heterocycles with Aryl Bromides: Discovery of Fluorescent Core Frameworks
Authors: Zhao Dongbing , Wang Wenhai , Yang Fei , Lan Jingbo , Yang Li , Gao Ge , You Jingsong
Published: March 2009

A window of opportunity: A general copper‐catalyzed CH bond‐activation path allows arylation of heterocycles with a wide range of aryl bromides (see scheme). The reaction shows excellent regioselectivity and exhibits good functional group tolerance. The 8‐aryl xanthines exhibit fluorescence in a variety of solvents and show promise as reagents for biological imaging.

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Complementary use of natural and artificial wetlands by waterbirds wintering in Doñana, south‐west Spain
Authors: Kloskowski Janusz , Green Andy J. , Polak Marcin , Bustamante Javier , Krogulec Jarosław
Published: March 2009

The Doñana wetland complex (SW Spain) holds more wintering waterfowl than any other wetland in Europe.

This study focused on the use made by 12 common waterbirds (eight ducks and four waders) of the natural seasonal marshes in Doñana National Park (DNP) and the adjacent Veta la Palma (VLP) fish ponds created in the early 1990s. Data used were from aerial and terrestrial surveys collected between October and February during six consecutive winters from 1998/99 to 2003/04. Changes in distribution of each bird taxon were related to changes in the extent of flooded marshes within DNP. Up to 295 000 ducks were counted in VLP during dry periods, and up to 770 000 in DNP when it was flooded.

The timing and extent of flooding in DNP was highly variable, but there was a consistent pattern in which ducks concentrated in VLP during dry months and winters but redistributed to DNP as more of it was flooded. This refuge effect was also strong for black‐tailed godwits Limosa limosa, but much less so for other waders. Waders feed mainly on invertebrates, and invertebrate biomass in VLP was found to be higher than in DNP. Ducks feed mainly on seeds and plant material, which are more abundant in DNP when flooded.

When water levels in DNP were stable over the course of a winter, or controlled for in multivariate models, the numbers of ducks at VLP declined over time, probably due to reduced availability of plant foods. In contrast, numbers of waders at VLP were more stable, and their invertebrate prey became more abundant over time, at least in the winter 2003/4.

In this extremely important wetland complex, the value of natural and artificial wetlands for wintering waterbirds are complementary, providing suitable habitat for different species and for different conditions in a highly variable Mediterranean environment.

Copyright © 2009 John Wiley & Sons, Ltd.