bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebrospinal fluid leakage into the subdural space: possible influence on the pathogenesis and recurrence frequency of chronic subdural hematoma and subdural hygroma
Authors: Kristof Rudolf A. , Grimm Jochen M. , Stoffel-Wagner Birgit
Published: February 2008

Object

The purpose of this study was to clarify whether cerebrospinal fluid (CSF) leakage into the subdural space is involved in the genesis of chronic subdural hematoma (CSDH) and subdural hygroma (SH) and to clarify whether this leakage of CSF into the subdural space influences the postoperative recurrence rate of CSDH and SH.

Methods

In this prospective observational study, 75 cases involving patients treated surgically for CSDH (67 patients) or SH (8 patients) were evaluated with respect to clinical and radiological findings at presentation, the content of β -trace protein (β TP) in the subdural fluid (βTPSF) and serum (βTPSER), and the CSDH/SH recurrence rate. The βTPSF was considered to indicate an admixture of CSF to the subdural fluid if βTPSF/βTPSER > 2.

Results

The median β TPSF level for the whole patient group was 4.29 mg/L (range 0.33–51 mg/L). Cerebrospinal fluid leakage, as indicated by βTPSF/βTPSER > 2, was found to be present in 93% of the patients with CSDH and in 100% of the patients with SH (p = 0.724). In patients who later had to undergo repeated surgery for recurrence of CSDH/SH, the βTPSF concentrations (median 6.69 mg/L, range 0.59–51 mg/L) were significantly higher (p = 0.04) than in patients not requiring reoperation (median 4.12 mg/L, range 0.33–26.8 mg/L).

Conclusions

As indicated by the presence of βTP in the subdural fluid, CSF leakage into the subdural space is present in the vast majority of patients with CSDH and SH. This leakage could be involved in the pathogenesis of CSDH and SH. Patients who experience recurrences of CSDH and SH have significantly higher concentrations of βTPSF at initial presentation than patients not requiring reoperation for recurrence. These findings are presented in the literature for the first time and have to be confirmed and expanded upon by further studies.
Neurosurgery patients' feelings about the role of residents in their care: a qualitative case study
Authors: Knifed Eva , July Julius , Bernstein Mark
Published: February 2008

Object

The role of residents in surgery is not clearly explained to patients. The authors undertook a study to explore the level of knowledge and anxiety in patients regarding residents' involvement in their surgery.

Methods

Qualitative case study methodology was used. Thirty face-to-face interviews of patients were conducted prior to elective neurosurgery. Interviews were transcribed and subjected to modified thematic analysis by 4 reviewers. The majority of patients had a postsecondary education, and there was substantial religious and ethnic diversity among them. Most underwent craniotomy for brain tumor.

Results

Six prominent themes arose from the analysis: 1) the level of knowledge about residents is low; 2) the level of anxiety about residents is low; 3) it is desirable for patients to meet the residents before surgery; 4) residents' educational needs are understood and supported; 5) anxiety was not increased by the interview; and 6) patients trust in the medical system.

Conclusions

Patients appear to be unaware of the role of residents in their surgical care but do not seem anxious about it. Trust in the medical system helps patients proceed with risky operations. Surgeons could be more forthcoming with patients about the role of residents.
Harvested human neurons engineered as live nervous tissue constructs: implications for transplantation
Authors: Huang Jason H. , Zager Eric L. , Zhang Jun , Groff Robert F. , Pfister Bryan J. , Cohen Akiva S. , Grady M. Sean , Maloney-Wilensky Eileen , Smith Douglas H.
Published: February 2008

Object

Although neuron transplantation to repair the nervous system has shown promise in animal models, there are few practical sources of viable neurons for clinical application and insufficient approaches to bridge extensive nerve damage in patients. Therefore, the authors sought a clinically relevant source of neurons that could be engineered into transplantable nervous tissue constructs. The authors chose to evaluate human dorsal root ganglion (DRG) neurons due to their robustness in culture.

Methods

Cervical DRGs were harvested from 16 live patients following elective ganglionectomies, and thoracic DRGs were harvested from 4 organ donor patients. Following harvest, the DRGs were digested in a dispase–collagenase treatment to dissociate neurons for culture. In addition, dissociated human DRG neurons were placed in a specially designed axon expansion chamber that induces continuous mechanical tension on axon fascicles spanning 2 populations of neurons originally plated ∼ 100 μm apart.

Results

The adult human DRG neurons, positively identified by neuronal markers, survived at least 3 months in culture while maintaining the ability to generate action potentials. Stretch-growth of axon fascicles in the expansion chamber occurred at the rate of 1 mm/day to a length of 1 cm, creating the first engineered living human nervous tissue constructs.

Conclusions

These data demonstrate the promise of adult human DRG neurons as an alternative transplant material due to their availability, viability, and capacity to be engineered. Also, these data show the feasibility of harvesting DRGs from living patients as a source of neurons for autologous transplant as well as from organ donors to serve as an allograft source of neurons.
Stent placement for management of a small parasagittal meningioma
Authors: Ganesan Dharmendra , Higgins J. Nicholas P. , Harrower Timothy , Burnet Neil G. , Sarkies Nicholas J. C. , Manford Mark , Pickard John D.
Published: February 2008

✓ The patient in this report had a parasagittal meningioma with an intrasinus extension that presented with features of benign intracranial hypertension and no focal neurological deficit or seizure. The meningioma was managed with a combination of endovascular stent placement and radiotherapy. The authors describe the investigation and technical aspects of stent placement for the stenosed sinus. Good symptomatic relief in the patient was achieved.
Virtual reality system for planning minimally invasive neurosurgery
Authors: Stadie Axel Thomas , Kockro Ralf Alfons , Reisch Robert , Tropine Andrei , Boor Stephan , Stoeter Peter , Perneczky Axel
Published: February 2008

Object

The authors report on their experience with a 3D virtual reality system for planning minimally invasive neurosurgical procedures.

Methods

Between October 2002 and April 2006, the authors used the Dextroscope (Volume Interactions, Ltd.) to plan neurosurgical procedures in 106 patients, including 100 with intracranial and 6 with spinal lesions. The planning was performed 1 to 3 days preoperatively, and in 12 cases, 3D prints of the planning procedure were taken into the operating room. A questionnaire was completed by the neurosurgeon after the planning procedure.

Results

After a short period of acclimatization, the system proved easy to operate and is currently used routinely for preoperative planning of difficult cases at the authors' institution. It was felt that working with a virtual reality multimodal model of the patient significantly improved surgical planning. The pathoanatomy in individual patients could easily be understood in great detail, enabling the authors to determine the surgical trajectory precisely and in the most minimally invasive way.

Conclusions

The authors found the preoperative 3D model to be in high concordance with intraoperative conditions; the resulting intraoperative “déjà-vu” feeling enhanced surgical confidence. In all procedures planned with the Dextroscope, the chosen surgical strategy proved to be the correct choice.

Three-dimensional virtual reality models of a patient allow quick and easy understanding of complex intracranial lesions.
Association of the HLA–DRB1 gene with premature death, particularly from cardiovascular disease, in patients with rheumatoid arthritis and inflammatory polyarthritis
Authors: Farragher Tracey M. , Goodson Nicola J. , Naseem Haris , Silman Alan J. , Thomson Wendy , Symmons Deborah , Barton Anne
Published: January 2008

Objective

To examine the role of the variants of the PTPN22 and HLA–DRB1 genes as predictors of mortality in inflammatory polyarthritis (IP) and rheumatoid arthritis (RA).

Methods

Patients were recruited from a primary care–based inception cohort of patients with IP and were followed up prospectively. For patients who died, the cause and date of death was obtained. Cox proportional hazards regression models were used to assess the association of the HLA–DRB1 (including the shared epitope [SE]) and PTPN22 genes with the risk of death from all causes and from cardiovascular disease (CVD) and to assess the interactions between SE, smoking, and anti–cyclic citrullinated peptide (anti‐CCP) status, adjusted by age at symptom onset and sex.

Results

DNA samples were available from 1,022 IP patients. During followup, 751 of them (74%) satisfied the American College of Rheumatology 1987 criteria for RA, and 242 of them (24%) died. Carriage of 2 copies of SE alleles predicted death from all causes (hazard ratio [HR] 1.57 [95% confidence interval (95% CI) 1.1–2.2]) and from CVD (HR 1.68 [95% CI 1.1–2.7]). This effect was most marked for individuals with the HLA–DRB1*01/*04 combination. An interaction of smoking, SE alleles, and anti‐CCP antibodies was observed and was associated with the greatest risk of death from CVD (HR 7.81 [95% CI 2.6–23.2]). No association of the PTPN22 gene with mortality was detected.

Conclusion

SE alleles, particularly compound heterozygotes, are associated with death from all causes and from CVD, independently of autoantibody status. However, the combination of SE, smoking, and anti‐CCP antibodies is associated with a high risk of premature death in patients with IP and RA, which raises the possibility of a targeted strategy to prevent CVD in these patients.
Haplotypes of the HRES‐1 endogenous retrovirus are associated with development and disease manifestations of systemic lupus erythematosus
Authors: Pullmann Rudolf , Bonilla Eduardo , Phillips Paul E. , Middleton Frank A. , Perl Andras
Published: January 2008

Objective

Endogenous retroviral sequences represent a link between viral and genetic factors that may influence the development of systemic lupus erythematosus (SLE). The HRES‐1 human endogenous retroviral sequence is centrally located at the 1q42 chromosomal region relative to microsatellites previously associated with SLE. We therefore undertook the present study to determine the haplotypes of the HRES‐1 locus and their linkage to SLE.

Methods

One hundred six patients with SLE, 82 unrelated healthy Caucasian individuals, and 70 healthy members of 34 lupus families were examined. HRES‐1 was amplified by polymerase chain reaction (PCR) and analyzed by sequencing and restriction enzyme mapping. Microsatellites were analyzed by PCR. Haplotype construction and transmission disequilibrium testing (TDT) were performed in lupus families.

Results

Based on 4 single‐nucleotide polymorphisms (SNPs) within a 935‐base interval, we detected 6 HRES‐1 haplotypes that were differentially segregated in unrelated Caucasian patients and control subjects (χ2 = 16.86, P = 0.0048) and were in linkage disequilibrium (LD) with the D1S225 microsatellite (P = 0.0002). The microsatellites D1S225, D1S235, and D1S2785 (but not D1S229) were linked to SLE by TDT. Interestingly, LD between HRES‐1 SNPs at bases 653 and 1259 was reduced in patients with SLE (P = 0.048). The HRES‐1 653C/1259C–harboring alleles were associated with the presence of renal disease (P = 0.0021) and with the absence of lung disease (P = 0.0323), while the 956A allele was associated with the antiphospholipid syndrome in patients with SLE (P = 0.0036).

Conclusion

The HRES‐1 locus represents a recombination hot spot at the 1q42 chromosomal region that influences the development and disease manifestations of SLE.
Hsp60 in inflamed muscle tissue is the target of regulatory autoreactive T cells in patients with juvenile dermatomyositis
Authors: Elst Elisabeth F. , Klein Mark , de Jager Wilco , Kamphuis Sylvia , Wedderburn Lucy R. , van der Zee Ruurd , Albani Salvatore , Kuis Wietse , Prakken Berent J.
Published: January 2008

Objective

Juvenile dermatomyositis (DM) is an autoimmune disease of unknown origin characterized by muscle weakness and skin manifestations. No definite autoantigen has yet been identified. Heat‐shock proteins (HSPs) can be up‐regulated at sites of inflammation, and immune reactivity to Hsp60 is suggested to play a regulatory role in various chronic inflammatory diseases. The purpose of this study was to determine whether Hsp60 could serve as an autoantigen in juvenile DM.

Methods

Muscle tissue from 4 patients with juvenile DM and 1 healthy control subject without evidence of muscle disease was stained for Hsp60. Peripheral blood mononuclear cells (PBMCs) from 22 patients and 10 healthy control subjects were tested for T cell proliferation induced by human and microbial Hsp60. Cytokine production in response to Hsp60 was examined in 15 patients and 6 healthy controls. T cell reactivity to Hsp60 was determined in muscle biopsy samples from 2 patients.

Results

We found significantly increased T cell proliferation to human Hsp60 in PBMCs from juvenile DM patients, which was higher during disease remission. Following in vitro activation with Hsp60, significant amounts of tumor necrosis factor α, interleukin‐1β (IL‐1β), and IL‐10 were produced. In contrast to muscle biopsy samples from healthy controls, samples from juvenile DM patients showed up‐regulation of Hsp60, induction of T cell proliferation, and production of cytokines. Production of proinflammatory cytokines by muscle‐derived cells in response to Hsp60 was associated with a poor clinical prognosis, whereas human Hsp60–specific induction of IL‐10 was followed by clinical remission.

Conclusion

These findings suggest that human (self) Hsp60 is a disease‐relevant autoantigen in juvenile DM. The difference in T cell response with regard to disease activity indicates an immune regulatory effect of Hsp60‐specific T cells, opening up perspectives for antigen‐specific immunotherapy.
A six‐month randomized controlled trial of exercise and pyridostigmine in the treatment of fibromyalgia
Authors: Jones K. D. , Burckhardt C. S. , Deodhar A. A. , Perrin N. A. , Hanson G. C. , Bennett R. M.
Published: January 2008

Objective

A subset of fibromyalgia (FM) patients have a dysfunctional hypothalamic–pituitary–insulin‐like growth factor 1 (IGF‐1) axis, as evidenced by low serum levels of IGF‐1 and a reduced growth hormone (GH) response to physiologic stimuli. There is evidence that pyridostigmine (PYD) improves the acute response of GH to exercise in FM patients. The purpose of this study was to evaluate the clinical effectiveness of 6 months of PYD and group exercise on FM symptoms.

Methods

FM patients were randomized to 1 of the following 4 groups: PYD plus exercise, PYD plus diet recall but no exercise, placebo plus exercise, and placebo plus diet recall but no exercise. The primary outcome measures were the visual analog scale (VAS) score for pain, tender point count, and total myalgic score. Secondary outcome measures were the total score on the Fibromyalgia Impact Questionnaire (FIQ) and FIQ VAS scores for individual symptoms (fatigue, poor sleep, stiffness, and anxiety), as well as quality of life (QOL) and physical fitness (lower body strength/endurance, upper and lower body flexibility, balance, and time on the treadmill).

Results

A total of 165 FM patients completed baseline measurements; 154 (93.3%) completed the study. The combination of PYD and exercise did not improve pain scores. PYD groups showed a significant improvement in sleep and anxiety in those who completed the study and in QOL in those who complied with the therapeutic regimen as compared with the placebo groups. Compared with the nonexercise groups, the 2 exercise groups demonstrated improvement in fatigue and fitness. PYD was generally well tolerated.

Conclusion

Neither the combination of PYD plus supervised exercise nor either treatment alone yielded improvement in most FM symptoms. However, PYD did improve anxiety and sleep, and exercise improved fatigue and fitness. We speculate that PYD may have improved vagal tone, thus benefiting sleep and anxiety; this notion warrants further study.
Increased proliferation of human synovial mesenchymal stem cells with autologous human serum: Comparisons with bone marrow mesenchymal stem cells and with fetal bovine serum
Authors: Nimura Akimoto , Muneta Takeshi , Koga Hideyuki , Mochizuki Tomoyuki , Suzuki Koji , Makino Hatsune , Umezawa Akihiro , Sekiya Ichiro
Published: January 2008

Objective

Synovial mesenchymal stem cells (MSCs) are a promising cell source for cartilage regeneration due to their high chondrogenic potential. For clinical safety, autologous human serum should be used instead of fetal bovine serum (FBS). We undertook this study to compare the 2 types of serum for their enhancement of the proliferation and chondrogenic potentials of synovial MSCs and to investigate the mechanisms of the differences. Since effectiveness of the sera might depend on the origin of the MSCs, we also examined bone marrow MSCs.

Methods

Synovium, bone marrow, and peripheral blood were obtained from 18 donors. Synovial and bone marrow MSCs were cultured with autologous human serum or FBS and analyzed. In addition, rabbit synovial MSCs cultured with autologous serum or FBS were transplanted into full‐thickness cartilage defects of the knees of the same rabbits.

Results

Human synovial MSCs expanded more in human serum than in FBS, and the opposite results were obtained with bone marrow MSCs. Hierarchical clustering analysis showed that the cell source, rather than the type of serum, affected the gene expression profile. Human serum contained high levels of platelet‐derived growth factor (PDGF), synovial MSCs expressed higher levels of PDGF receptor α than did bone marrow MSCs, and neutralizing PDGF decreased the proliferation of synovial MSCs with autologous human serum. Although the in vitro chondrogenic potential of human synovial MSCs was affected by the serum source, the in vivo chondrogenic potential of rabbit synovial MSCs was similar in autologous serum and FBS groups.

Conclusion

Autologous serum predominates in increasing the proliferation of synovial MSCs with chondrogenic potential through PDGF signaling.
Cathepsin K deficiency partially inhibits, but does not prevent, bone destruction in human tumor necrosis factor–transgenic mice
Authors: Schurigt Uta , Hummel Klaus M. , Petrow Peter K. , Gajda Mieczyslaw , Stöckigt Renate , Middel Peter , Zwerina Jochen , Janik Tobias , Bernhardt Ricardo , Schüler Susann , Scharnweber Dieter , Beckmann Felix , Saftig Paul , Kollias George , Schett Georg , Wiederanders Bernd , Bräuer Rolf
Published: January 2008

Objective

Cathepsin K is believed to have an eminent role in the pathologic resorption of bone. However, several studies have shown that other proteinases also participate in this process. In order to clarify the contribution of cathepsin K to the destruction of arthritic bone, we applied the human tumor necrosis factor (hTNF)–transgenic mouse model, in which severe polyarthritis characterized by strong osteoclast‐mediated bone destruction develops spontaneously.

Methods

Arthritis was evaluated in hTNF‐transgenic mice that were either wild‐type for cathepsin K (CK+/+), heterozygous for cathepsin K (CK+/−), or deficient in cathepsin K (CK−/−). Arthritic knee joints were prepared for standard histologic assessment aimed at establishing a semiquantitative score for joint destruction and quantification of the area of bone erosion. Additionally, microfocal computed tomography was performed to visualize bone destruction in mice with the different CK genotypes. CK+/+ and CK−/− osteoclasts were generated in vitro, and their proteinase expression profiles were compared by complementary DNA array analysis, real‐time polymerase chain reaction, and activity assays.

Results

Although the area of bone erosion was significantly reduced in hTNF‐transgenic CK−/− mice, the absence of cathepsin K did not completely protect against inflammatory bone lesions. Several matrix metalloproteinases (MMPs) and cathepsins were expressed by in vitro–generated CK−/− osteoclasts, without marked differences from CK+/+ osteoclasts. MMP activity was detected in CK−/− osteoclasts, and MMP‐14 was localized by immunohistochemistry in inflammatory bone erosions in hTNF‐transgenic CK−/− mice, suggesting MMPs as potential contributors to bone destruction. Additionally, we detected a reduction in osteoclast formation in cathepsin K–deficient mice, both in vitro and in vivo.

Conclusion

The results of our experiments raise doubts about a crucial role of cathepsin K in arthritic bone destruction.
Persistent association of nailfold capillaroscopy changes and skin involvement over thirty‐six months with duration of untreated disease in patients with juvenile dermatomyositis
Authors: Christen‐Zaech Stéphanie , Seshadri Roopa , Sundberg Joyce , Paller Amy S. , Pachman Lauren M.
Published: January 2008

Objective

To determine the association of changes on nailfold capillaroscopy with clinical findings and genotype in children with juvenile dermatomyositis (DM), in order to identify potential differences in disease course over 36 months.

Methods

At diagnosis of juvenile DM in 61 children prior to the initiation of treatment, tumor necrosis factor α (TNFα) −308 allele and DQA1*0501 status was determined, juvenile DM Disease Activity Scores (DAS) were obtained, and nailfold capillaroscopy was performed. The disease course was monitored for 36 months. Variations within and between patients were assessed by regression analysis.

Results

At diagnosis, shorter duration of untreated disease (P = 0.05) and a lower juvenile DM skin DAS (P = 0.035) were associated with a unicyclic disease course. Over 36 months, end‐row loop (ERL) regeneration was associated with lower skin DAS (P < 0.001) but not muscle DAS (P = 0.98); ERL regeneration and decreased bushy loops were associated with a shorter duration of untreated disease (P = 0.04 for both). At 36 months, increased ERL regeneration (P = 0.007) and improvement of skin DAS (P < 0.001) and muscle DAS (P = 0.025) were associated with a unicyclic disease course.

Conclusion

Early treatment of juvenile DM may lead to a unicyclic disease course. The non‐unicyclic disease course usually involves continuing skin manifestations with persistent nailfold capillaroscopy changes. The correlation of nailfold capillaroscopy results with cutaneous but not with musculoskeletal signs of juvenile DM over a 36‐month period suggests that the cutaneous and muscle vasculopathies have different pathophysiologic mechanisms. These findings indicate that efforts to identify the optimal treatment of cutaneous features in juvenile DM require greater attention.
Association between treatment with central nervous system stimulants and Raynaud's syndrome in children: A retrospective case–control study of rheumatology patients
Authors: Goldman William , Seltzer Ryan , Reuman Peter
Published: January 2008

Objective

To investigate whether central nervous system (CNS) stimulants used for the treatment of attention deficit hyperactivity disorder (ADHD) are associated with the development of Raynaud's syndrome (RS).

Methods

A case–control design was used for this study. All patients seen in a pediatric rheumatology practice during a 5‐year period who had signs and symptoms of RS and met diagnostic criteria for RS as determined by pulse volume recording were studied as cases. Controls were randomly selected patients at the same clinic who did not have signs or symptoms of RS. They were matched to the cases for age, sex, and time of presentation. We tested for associations between various CNS medications and presence of RS. We also evaluated differences in laboratory test results between RS cases and matched controls.

Results

Sixty‐four patients were enrolled in the study (32 cases with RS [23 female, 9 male] and 32 control patients). McNemar's test showed a significant association between the presence of RS and past or current use of ADHD stimulants (methylphenidate and dextroamphetamine) (χ2 = 5.00, P = 0.01). The use of other CNS medications was not found to be significantly associated with RS (χ2 = 1.33, P = 0.25 by McNemar's test). C‐reactive protein levels and erythrocyte sedimentation rates were significantly higher in controls than in cases.

Conclusion

The results of this study indicate that there is a significant association between development of RS and therapy with CNS stimulants used for the treatment of ADHD. Although this was a small study, these findings provide preliminary evidence of an adverse effect of CNS stimulant medications in patients seen in rheumatology practice.
Immunosuppressive therapy in lupus‐ and mixed connective tissue disease–associated pulmonary arterial hypertension: A retrospective analysis of twenty‐three cases
Authors: Jais Xavier , Launay David , Yaici Azzedine , Le Pavec Jérôme , Tchérakian Colas , Sitbon Olivier , Simonneau Gérald , Humbert Marc
Published: January 2008

Objective

To describe the response to first‐line immunosuppressive therapy with or without pulmonary vasodilators in pulmonary arterial hypertension (PAH) associated with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MCTD).

Methods

Twenty‐three consecutive patients with SLE‐ or MCTD‐associated PAH treated with first‐line immunosuppressive therapy either alone (n = 16) or in combination with pulmonary vasodilators (n = 7) were evaluated according to clinical and hemodynamic criteria before and after immunosuppressive therapy. Responders were defined as patients in New York Heart Association (NYHA) functional class I or II with hemodynamic improvement after the last pulse of cyclophosphamide.

Results

Among the 16 patients treated with first‐line immunosuppressive therapy alone, 8 (50%) were responders. These patients had a significantly improved NYHA functional class, 6‐minute walking distance, and mean pulmonary artery pressure. Patients in NYHA functional class I or II and/or a cardiac index >3.1 liters/minute/m2 at baseline were more likely to benefit from immunosuppressive therapy. Six of the 8 nonresponders subsequently improved with pulmonary vasodilators. Among the 7 patients who were initially treated with immunosuppressive therapy and pulmonary vasodilators, 4 (57.1%) were responders.

Conclusion

PAH associated with SLE or MCTD may respond to a treatment combining cyclophosphamide and glucocorticoids. Patients who could benefit from this immunosuppressive therapy could be those who have less severe disease at baseline. For patients with more severe disease, pulmonary vasodilators should be started, possibly in combination with immunosuppressants. In any case, clinical and hemodynamic evaluations are mandatory to monitor the response and adapt the treatment. These retrospective and uncontrolled data need to be confirmed by randomized controlled trials.
AUF1, the regulator of tumor necrosis factor α messenger RNA decay, is targeted by autoantibodies of patients with systemic rheumatic diseases
Authors: Skriner Karl , Hueber Wolfgang , Süleymanoglu Erhan , Höfler Elisabeth , Krenn Veit , Smolen Josef , Steiner Günter
Published: January 2008

Objective

To investigate which members of the heterogeneous nuclear RNP (hnRNP) family are targeted by autoantibodies from patients with systemic rheumatic diseases.

Methods

Using a semipurified preparation of natural hnRNP proteins, 365 sera from patients with rheumatic diseases and control subjects were screened by immunoblotting for the presence of autoantibodies. Bacterially expressed recombinant hnRNP D (AUF1) proteins were used for confirming the data obtained. Binding of RNA and autoantibody to AUF1 was investigated by gel retardation assays. Expression of AUF1 in cultivated cells and synovial tissue was analyzed by indirect immunofluorescence and immunohistochemistry.

Results

Autoantibodies to AUF1 proteins were detected in 33% of patients with systemic lupus erythematosus, 20% of patients with rheumatoid arthritis, 17% of patients with mixed connective tissue disease, and <10% of patients with other rheumatic disorders. Epitope mapping studies showed the autoantibodies to be directed to conformational epitopes in the N‐terminal RNA‐binding part of AUF1. However, autoantibody binding did not interfere with RNA binding as assessed by gel‐shift assays. Immunohistochemical studies revealed AUF1 to be expressed in the cytoplasm of RA synovial tissue as compared with nuclear staining in osteoarthritis and normal synovium, particularly in macrophages of the lining layer and in fibroblasts of the sublining areas.

Conclusion

These data identify AUF1 proteins as novel autoantigens in SLE and related autoimmune disorders. Because AUF1 proteins are major components of messenger RNA stability complexes, our findings suggest that these complexes form a novel macromolecular target structure for autoantibodies in rheumatic autoimmune diseases.
Factors influencing surgeons' decisions in the indication for total joint replacement in hip osteoarthritis in real life
Authors: Maillefert Jean Francis , Roy Carine , Cadet Christian , Nizard Rémy , Berdah Laurent , Ravaud Philippe
Published: January 2008

Objective

To evaluate factors influencing orthopedic surgeons' decision in daily practice to recommend or not recommend total hip arthroplasty (THA) in patients with hip osteoarthritis (OA).

Methods

General practitioners and rheumatologists were asked to prospectively include 1 patient with hip OA for whom a consultation with an orthopedic surgeon was planned to determine whether or not THA was indicated. The following variables were obtained: age, sex, occupational status, body mass index, comorbidities, duration of hip OA, patient's global assessment, Western Ontario and McMaster Universities Osteoarthritis Index pain and functioning subscale scores, New Zealand score, quality of life, and structural parameters on radiographs. The surgeon's decision was obtained by followup questionnaires. Statistical analysis evaluated potential predictors of the surgeon's decision (indication for THA within the next 6 months, yes or no) using univariate and multivariate analysis.

Results

A total of 558 patients were included (249 men, 300 women, mean age 68.4 years, mean disease duration 4.9 years). The surgeon's decision, available for 486 patients, was to prescribe THA in 60.7% of patients. On multivariate analysis, the variables related to the surgeon's decision were the presence or absence of severe cardiovascular disease, Short Form 12 physical subscale score, and amount of joint space narrowing.

Conclusion

While the amount of structural degradation is only slightly or not at all taken into account in numerous criteria and/or recommendations on indications for THA, it is an independent predictor of the surgeon's decision in daily practice. Such a discrepancy should be evaluated and understood in further studies.
Association of health‐related quality of life with dual use of prescription and over‐the‐counter nonsteroidal antiinflammatory drugs
Authors: Kovac Stacey H. , Saag Kenneth G. , Curtis Jeffrey R. , Allison Jeroan
Published: January 2008

Objective

Inadequate prescription therapy pain management, lack of doctor‐patient communication about over‐the‐counter (OTC) medications, and easy accessibility of OTC medications may contribute to patients using more than 1 medication to manage pain. It is well established that taking multiple nonsteroidal antiinflammatory drugs (NSAIDs) can lead to serious gastrointestinal problems. Little is known about whether use of more than 1 NSAID (i.e., dual use) is related to patient self‐reported outcomes, specifically health‐related quality of life (HRQOL). We hypothesized that dual use of NSAIDs would be associated with reduced HRQOL.

Methods

Patients from a managed care organization who filled ≥1 NSAID prescription over a 6‐month period were eligible for a telephone interview focusing on NSAID use, which included the Short Form 12 (SF‐12) Health Survey. Dual use was defined as taking 2 NSAIDs, either prescription or OTC, at least twice weekly during the past month. A multivariable linear regression model examined the association between dual use and the Physical Component Summary score (PCS‐12) from the SF‐12.

Results

Dual use was associated with lower PCS‐12 scores indicating poorer HRQOL, after controlling for clinical and demographic factors.

Conclusion

Patients may self‐manage their pain to improve their daily activities by taking more than 1 NSAID. However, by attempting to obtain symptom relief, patients may be putting themselves at risk for complications. Providers are likely unaware of patients' risk. Future research should evaluate the causal factors contributing to dual use.
Performance of the polymyalgia rheumatica activity score for diagnosing disease flares
Authors: Binard Aymeric , de Bandt Michel , Berthelot Jean‐Marie , Saraux Alain ,   Inflammatory Joint Disease Working Group of the French Society for Rheumatology
Published: January 2008

Objective

To evaluate the effectiveness of the polymyalgia rheumatica activity score (PMR‐AS) in diagnosing disease flares.

Methods

Rheumatologists prospectively included 89 patients with PMR (mean ± SD age 74.6 ± 6.2 years, mean ± SD disease duration 1.6 ± 2.2 years). At each visit, the rheumatologist assessed disease activity using a visual analog scale (VAS) and recorded whether a disease flare was diagnosed and/or the glucocorticoid dose changed. Overall, 137 visits including 49 pairs (allowing intraindividual comparisons) were available; a disease flare was diagnosed at 32 visits. We evaluated statistical associations linking flare diagnosis to the PMR‐AS, each of its components (VAS, VAS for pain, C‐reactive protein, morning stiffness, and elevation of upper limbs), and changes in these parameters between 2 visits.

Results

Associations with disease flare diagnosis were strongest for PMR‐AS scores ≥9.35 (agreement 92%, 95% confidence interval [95% CI] 85.8–95.7%, κ = 0.78; sensitivity 96.6%, 95% CI 80.4–99.8; specificity 90.7%, 95% CI 83.2–95.2) and for ΔPMR‐AS scores ≥6.6 (agreement 98%, 95% CI 88.0–99.9%, κ = 0.95; sensitivity 100%, 95% CI 74.7–100; specificity 97.1%, 95% CI 82.9–99.8). Other parameters showed weaker diagnostic performance.

Conclusion

This study supplies new evidence that the PMR‐AS is useful for monitoring PMR activity in everyday practice and for managing glucocorticoid tapering. PMR activity changes seem even more relevant than absolute values.
Preliminary validation and clinical meaning of the cutaneous assessment tool in juvenile dermatomyositis
Authors: Huber Adam M. , Dugan Elizabeth M. , Lachenbruch Peter A. , Feldman Brian M. , Perez Maria D. , Zemel Lawrence S. , Lindsley Carol B. , Rennebohm Robert M. , Wallace Carol A. , Passo Murray H. , Reed Ann M. , Bowyer Suzanne L. , Ballinger Susan H. , Miller Frederick W. , Rider Lisa G. ,   Juvenile Dermatomyositis Disease Activity Collaborative Study Group
Published: January 2008

Objective

To provide preliminary validation of the Cutaneous Assessment Tool (CAT), a new tool to assess cutaneous manifestations of juvenile dermatomyositis (DM), and to explore the clinical meaning of CAT scores.

Methods

Children with juvenile DM (n = 113) were assessed at baseline and 7–9 months later (n = 94). Internal consistency, redundancy, construct validity, and responsiveness of the CAT were examined. CAT scores corresponding to ordinal global assessments were determined.

Results

Item‐total correlations ranged from 0.27–0.67 for activity lesions present in ≥10% of patients; item‐domain and domain‐total correlations ranged from 0.25–0.99. Cronbach's alpha was 0.79 for the CAT activity score and 0.74 for the CAT damage score. As predicted, the CAT activity score correlated strongly with both global disease activity and skin disease activity and moderately with the Childhood Myositis Assessment Scale, whereas the CAT damage score correlated moderately with the physician global disease and skin disease damage scores. Median CAT activity scores of 1, 7, 13, 18, and 31 corresponded to absent, mild, moderate, severe, and extremely severe skin disease activity, respectively. Median CAT damage scores of 0, 1, 2, and 5 correlated with the same descriptions of damage (severe and extremely severe combined).

Conclusion

Preliminary validation of the CAT demonstrated good internal consistency, nonredundancy, good construct validity, and appropriate responsiveness. The CAT is a comprehensive, semiquantitative assessment tool for skin disease in juvenile DM.
Development and validation of a patient‐based disease activity score in rheumatoid arthritis that can be used in clinical trials and routine practice
Authors: Choy Ernest H. , Khoshaba Bernadette , Cooper Derek , MacGregor Alex , Scott David L.
Published: January 2008

Objective

Assessor‐based disease activity measures such as the Disease Activity Score in 28 joints (DAS28), although widely used in rheumatoid arthritis (RA), have high interobserver variability. We developed and validated a patient‐based disease activity score (PDAS) as an alternative assessment.

Methods

Patients' assessments of swollen or tender joints, visual analog scales for pain and general health, the Health Assessment Questionnaire, and erythrocyte sedimentation rate (ESR) were used to develop the PDAS. In a developmental cohort (204 patients), regression analyses determined the best fit with the DAS28. A validation cohort (322 patients) subsequently evaluated criterion and construct validity against a range of outcome measures, including the Nottingham Health Profile (NHP) and Short Form 36 (SF‐36). Sensitivity to change was assessed in 56 patients after 6 months of treatment with disease‐modifying antirheumatic drugs or biologics.

Results

In the developmental cohort, the PDAS with ESR (PDAS1) and without ESR (PDAS2) achieved excellent fit with the DAS28 (r = 0.88 and 0.74, respectively). In the validation cohort, the PDAS showed high criterion validity by correlation with the DAS28 (PDAS1: r = 0.89, PDAS2: r = 0.76). Construct validity was demonstrated by high correlations with a range of disease activity measures (r ≥ 0.45), whereas low correlations (r < 0.45) with mental and social components of the SF‐36 and NHP indicated divergent validity. The PDAS and DAS28 had similar sensitivity to change, determined using effect sizes (DAS28 = 1.03, PDAS1 = 1.02, PDAS2 = 0.77) or standardized response means (DAS28 = 0.79, PDAS1 = 0.77, PDAS2 = 0.73).

Conclusion

The PDAS1 and PDAS2 are valid and sensitive tools to assess disease activity in RA. They appear suitable for clinical decision making, epidemiologic research, and clinical trials.
Recent corticosteroid use and recent disease activity: Independent determinants of coronary heart disease risk factors in systemic lupus erythematosus?
Authors: Karp Igor , Abrahamowicz Michal , Fortin Paul R. , Pilote Louise , Neville Carolyn , Pineau Christian A. , Esdaile John M.
Published: January 2008

Objective

Systemic lupus erythematosus (SLE) is characterized by a markedly elevated risk for coronary heart disease (CHD), the exact pathogenesis of which is unknown. In particular, the causal roles of corticosteroid therapy and SLE disease activity, and whether their putative effects are mediated through conventional risk factors, remain unclear.

Methods

Data abstracted retrospectively from the charts at 11,359 clinic visits for 310 patients with SLE to the Montreal General Hospital were used to investigate the associations of recent corticosteroid dose and recent Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score with 8 CHD risk factors (total serum cholesterol, high‐density lipoprotein [HDL] cholesterol, low‐density lipoprotein cholesterol, apolipoprotein B [Apo B], triglycerides, systolic blood pressure [BP], body mass index, and blood glucose) and the aggregate estimate of 2‐year CHD risk. Separate multivariable linear regression models estimated the mutually‐adjusted effects of average daily corticosteroid dose and average SLEDAI score within the past year on the current level of each risk factor while adjusting for age, sex, cumulative damage score, disease duration, and, where appropriate, use of relevant medications.

Results

Higher past‐year corticosteroid dose was independently associated with significantly higher overall 2‐year CHD risk and with higher levels of all 8 individual risk factors. Higher past‐year lupus disease activity was independently associated with higher overall 2‐year CHD risk, lower HDL cholesterol, and higher values of systolic BP, Apo B, triglycerides, and blood glucose.

Conclusion

In SLE, both recent use of corticosteroids and recent lupus activity are independently associated with higher values of several well‐recognized CHD risk factors and overall 2‐year CHD risk.
Enhanced systemic availability of methotrexate in the presence of morin in rats
Authors: Hong Soon Sun , Jin Ming‐Ji , Han Hyo‐Kyung
Published: January 2008

The present study aimed to investigate the effect of morin on the pharmacokinetics of methotrexate (MTX) in rats. Pharmacokinetic parameters of MTX were determined in rats following an intravenous administration of MTX (2 mg/kg) in the presence and absence of morin (25 mg/kg, p.o.). The cellular accumulation of MTX was also examined by using MDCK cells stably overexpressing hOAT1 or hOAT3. Compared with the control given MTX alone, pretreatment with morin 15 min prior to MTX administration significantly altered the pharmacokinetics of MTX in rats. Renal clearance and total clearance of MTX were reduced by 42% and 58%, respectively, in the presence of morin. Accordingly, the systemic exposure of MTX in the rats pretreated with morin was significantly higher than that from the control group. The mean residence time (MRT) and terminal plasma half‐life of MTX were prolonged by 3.3‐ and 2.4‐fold, respectively, by the concurrent use of morin. The cellular uptake of MTX (20 µM) was significantly reduced by the co‐incubation with morin (100 µM) in MDCK‐hOAT1 cells but not in MDCK‐hOAT3 cells. Taken together, morin appeared to be effective in altering the pharmacokinetics of MTX in rats, likely by the inhibition of OAT1‐mediated renal excretion. Copyright © 2008 John Wiley & Sons, Ltd.
Future‐biased search: the quest for the ideal
Authors: Shu Suzanne B.
Published: February 2008

Decision‐makers with ideal candidates already in mind often extend search beyond optimal endpoints when searching for the best option among a sequential list of alternatives. Extended search is investigated here using three laboratory experiments; individuals in these tasks exhibit future‐bias, delaying choice beyond normative benchmarks. Searchers' behavior is consistent with setting high thresholds based on a focal ideal outcome without full attention to its probability or the value of second‐best alternatives; the behavior is partially debiased by manipulating which outcomes are in the searchers' focal set. Documenting future‐bias in sequential search tasks offers new insights for understanding self‐control and intertemporal choice by providing a situation in which thresholds may be set too high and myopic behavior does not prevail. Copyright © 2008 John Wiley & Sons, Ltd.
Antioxidant and free radical scavenging activities of an exopolysaccharide from a probiotic bacterium
Authors: Kodali Vidya Prabhakar , Sen Ramkrishna
Published: February 2008

Probiotic bacteria synthesize extracellular polysaccharides (EPSs) with commercially significant physiological and therapeutic activities. This important class of biomolecules is also characterized by their ability to remove reactive oxygen species (ROS) that are formed in the intestine by various metabolic reactions; hence, they exhibit antioxidant activities. Our probiotic bacterium, Bacillus coagulans RK‐02, produces an EPS during the exponential and stationary growth phases when grown in a glucose mineral salts medium. The time course of EPS synthesis was studied with respect to biomass growth. The antioxidant and free radical scavenging potential of isolated EPS were studied by various methods, including the β‐carotene‐linoleic acid model system, a superoxide radical scavenging assay using the PMS‐NADH‐nitroblue tetrazolium system, the 1,1‐diphenyl‐2‐picrylhydrazyl radical scavenging activity, a hydroxyl radical scavenging assay using the ascorbic acid‐Cu2+‐cytochrome c system and an in vitro microsome peroxidation inhibition study using a thiobarbituric acid assay. The antioxidant activities were compared to known antioxidants vitamin C and E, which were used as reference standards. The results showed that the EPS, which is a heteropolymer composed of four monosaccharides, produced by B. coagulans RK‐02 had significant antioxidant and free radical scavenging activities.
Monitoring of native chemical ligation on solid substrate by surface plasmon resonance
Authors: Wieczerzak Ewa , Hamel Raymond , Chabot Vincent , Aimez Vincent , Grandbois Michel , Charette Paul G. , Escher Emanuel
Published: January 2008

During the last years native chemical ligation (NCL) gained in popularity as a method allowing the chemical synthesis of large peptides and entire proteins. NCL is particularly well‐suited for chemoselective and nondenaturing attachment of biomolecules on solid substrates. In the present work, we show the feasibility of monitoring of peptide synthesis, NCL and its catalysis on silicon oxide modified gold surfaces by surface plasmon resonance (SPR). NCL of a model peptide—bradykinin thioester—was carried out and monitored with a custom‐built SPR apparatus. Solid‐phase produced bradykinin thioester was ligated to the surface in the presence of variable concentrations of 4‐mercaptophenylacetic acid as transthioesterification catalyst. At catalyst concentration of 48 mM and above, the NCL reaction was maximal and identical to the reaction of the purified peptide‐mercaptophenylacetic acid thioester. SPR curves indicate typical first‐order kinetics with t1/2 of 81 s for this aryl thioester, but of 104 min for the primary alkyl thioester. © 2008 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90: 415–420, 2008.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
A powerful and versatile educational software to simulate transient heat transfer processes in simple fins
Authors: Del Cerro Velázquez F. , Gómez‐Lopera S. A. , Alhama F.
Published: February 2008

Based on the network simulation method and using commercial computer codes, educational software has been developed for numerically solving and simulating lineal and non‐lineal problems of unsteady heat transfer in simple extended 1D surfaces, assuming convection and/or radiation as boundary conditions. Interface communication with the user is pleasant and immediate through the window ambient created in visual C++ source code. After introduction of the data, which includes reticulation parameters, a network model is generated whose finite difference differential equations are formally equivalent to those of the problem. Time remains a continuous variable in the model. The file is numerically run using a network simulation code, providing the transient temperature fields and heat fluxes in the whole medium. The results are shown by graphics or as tables. The program can be used as a low cost laboratory tool for teaching heat transfer or even for the design of simple fins. Students can easily determine the influence of physical parameters, such as thermal conductivity, specific heat, heat transfer coefficient, emissivity, reference temperatures, etc., in the problem. © 2008 Wiley Periodicals, Inc. Comput Appl Eng Educ 16: 72–82, 2008; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.20159