bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the aspartic acid (D) repeat of asporin as a risk factor for osteoarthritis in a UK Caucasian population
Authors: Mustafa Zehra , Dowling Barbara , Chapman Kay , Sinsheimer Janet S. , Carr Andrew , Loughlin John 
Published: October 2005

AbstractObjectiveA compelling genetic association with osteoarthritis (OA) of 2 functional alleles in the aspartic acid (D) repeat of the asporin gene was recently reported in a Japanese population. Allele D13 of the repeat encoded OA protection, whereas allele D14 encoded OA susceptibility. The 2 alleles mediate differences in the capacity of asporin to inhibit the cartilage growth factor transforming growth factor β, with the D14 allele being a particularly potent inhibitor. Our objective was to assess whether the D repeat is associated with OA in UK Caucasians.MethodsThe repeat was genotyped in 1,247 patients who had undergone elective joint replacement of the hip or the knee due to end‐stage primary OA and in 748 age‐matched controls.ResultsThe D13 allele was more common in controls, and the D14 allele was more common in patients. However, this trend was significant only for men who had undergone hip replacement (P = 0.016, odds ratio 1.48, 95% confidence interval 1.09–2.01).ConclusionOur data suggest that the asporin polymorphism is not a major influence on OA etiology in Caucasians. The results of our study do not question the veracity of the Japanese report. Instead, our study highlights the complex, heterogeneous nature of OA genetic susceptibility.
Circadian pattern of spontaneous behavior in monarthritic rats: A novel global approach to evaluation of chronic pain and treatment effectiveness
Authors: Millecamps Magali , Jourdan Didier , Leger Sabine , Etienne Monique , Eschalier Alain , Ardid Denis 
Published: October 2005

AbstractObjectivePreclinical evaluation is an essential step in the assessment of new antiinflammatory or analgesic drugs. This study was undertaken to develop a new mode of evaluation of drug effectiveness based on behavior indicating well‐being in a rat model of chronic inflammatory pain. We chose to examine the circadian pattern of spontaneous behavior.MethodsThe work was performed with a model of chronic monarthritis induced by Freund's complete adjuvant. Variations in behavioral patterns during the time course of arthritis were analyzed. In a second phase, the impact of acetaminophen and 2 nonsteroidal antiinflammatory drugs (aspirin and celecoxib), which are currently used in clinical practice to treat chronic inflammation, was studied after 7 days of treatment.ResultsThe nocturnal pattern of activity of healthy rats comprised 3 main bursts. Chronic painful monarthritis altered this spontaneous pattern of nocturnal behavior (normal period of activity). Monarthritic rats showed a decrease in the total time spent in activity during the night, and lost their pattern of activity. These behavioral disturbances were reversed after long‐term treatment with acetaminophen or celecoxib, with celecoxib appearing to be more effective. Aspirin was ineffective.ConclusionThese results enabled us to test this new procedure as a means of assessing well‐being or ill‐ being during stages of chronic inflammatory pain in rats, and the effectiveness of repeated pharmacologic treatments.
Characterization and consequences of pain variability in individuals with fibromyalgia
Authors: Harris Richard E. , Williams David A. , McLean Samuel A. , Sen Ananda , Hufford Michael , Gendreau R. Michael , Gracely Richard H. , Clauw Daniel J. 
Published: October 2005

AbstractObjectiveA growing body of evidence suggests that real‐time electronic assessments of pain are preferable to traditional paper‐and‐pencil measures. We used electronic assessment data derived from a study of patients with fibromyalgia (FM) to examine variability of pain over time and to investigate the implications of pain fluctuation in the context of a clinical trial.MethodsThe study group comprised 125 patients with FM who were enrolled in a randomized, placebo‐controlled trial of milnacipran. Pain intensity levels were captured in real time by participants using electronic diaries. Variability in pain was assessed as the standard deviation of pain entries over time (pain variability index [PVI]).ResultsSubstantial between‐subject differences in pain variability were observed (mean ± SD PVI 1.61 ± 0.656 [range 0.27–4.05]). The fluctuation in pain report was constant over time within individuals (r = 0.664, P < 0.001). Individuals with greater variability were more likely to be classified as responders in a drug trial (odds ratio 6.14, P = 0.006); however, this association was primarily attributable to a greater change in pain scores in individuals receiving placebo (r = 0.460, P = 0.02) rather than active drug (r = 0.09, P > 0.10).ConclusionAmong individuals with FM, there were large between‐subject differences in real‐time pain reports. Pain variability was relatively constant over time within individuals. Perhaps the most important finding is that individuals with larger pain fluctuations were more likely to respond to placebo. It is not clear whether these findings are applicable only to patients with FM or whether they may also be seen in patients with other chronic pain conditions.
MEFV analysis is of particularly weak diagnostic value for recurrent fevers in Western European Caucasian patients
Authors: Tchernitchko D. , Moutereau S. , Legendre M. , Delahaye A. , Cazeneuve C. , Lacombe C. , Grateau G. , Amselem S. 
Published: October 2005

AbstractObjectiveFamilial Mediterranean fever (FMF) is an autosomal‐recessive disorder characterized by recurrent attacks of fever, with abdominal, thoracic, or articular pain. FMF is particularly common in Mediterranean populations, while other populations are rarely affected. MEFV gene analysis provides the only objective diagnostic criterion for FMF. However, the spectrum of MEFV mutations, which was first established in classically affected populations, remains insufficiently studied in other populations. The purpose of this study was to assess involvement of MEFV in the phenotype of western European Caucasian patients with a clinical diagnosis of FMF.MethodsMutation analysis was performed in 208 Caucasian patients from western Europe, by screening for the most common MEFV mutations in exons 2, 3, 5, and 10, and by sequencing the promoter region and the whole MEFV coding sequence in 21 of these patients.ResultsNone of the patients carried 2 mutated alleles. Only 2 patients carried 1 mutated allele.ConclusionFMF‐like syndromes in western European Caucasian populations cannot be explained by MEFV mutations. These results should be helpful in avoiding laborious and costly MEFV molecular analyses that, at the population level, seem to be of poor diagnostic value in the case of western European Caucasian patients, and rather should prompt a search for other causes in those patients.
Cat‐scratch disease–associated arthropathy
Authors: Giladi Michael , Maman Eran , Paran Daphna , Bickels Jacob , Comaneshter Doron , Avidor Boaz , Varon‐Graidy Merav , Ephros Moshe , Wientroub Shlomo 
Published: October 2005

AbstractObjectiveTo characterize the articular manifestations of cat‐scratch disease (CSD) and to evaluate the long‐term clinical outcome of those manifestations.MethodsA community‐ and hospital‐based surveillance study of CSD was conducted in Israel between 1991 and 2002. CSD was defined as present in a patient when a compatible clinical syndrome and a positive confirmatory finding of Bartonella henselae (by serology and/or polymerase chain reaction) were identified. CSD patients with arthropathy (arthritis/arthralgia) that limited or precluded usual activities of daily living constituted the study group. Patients were followed up until ≥6 weeks after resolution of symptoms, or if symptoms persisted, for ≥12 months. CSD patients without arthropathy served as controls.ResultsAmong 841 CSD patients, 24 (2.9%) had rheumatoid factor–negative arthropathy that was often severe and disabling. Both univariate and multivariate analyses identified female sex (67% of arthropathy patients versus 40% of controls; relative risk [RR] 2.5, P = 0.047), age older than 20 years (100% of arthropathy patients versus 43% of controls; RR 4.9, P = 0.001), and erythema nodosum (21% of arthropathy patients versus 2% of controls; RR 7.9, P = 0.001) as variables significantly associated with arthropathy. Knee, wrist, ankle, and elbow joints were most frequently affected. Ten patients (42%) had severe arthropathy in the weight‐bearing joints, which substantially limited their ability to walk, and 4 of these patients were hospitalized. All of the patients had regional lymphadenopathy, 37.5% had nocturnal joint pain, and 25% had morning stiffness. Nineteen patients (79.2%) recovered after a median duration of 6 weeks (range 1–24 weeks), whereas 5 patients (20.8%) developed chronic disease persisting 16–53 months (median 30 months) after the onset of arthropathy.ConclusionThis is the first comprehensive study of arthropathy in CSD. CSD‐associated arthropathy is an uncommon syndrome affecting mostly young and middle‐age women. It is often severe and disabling, and may take a chronic course.
Positive effects of moderate exercise on glycosaminoglycan content in knee cartilage: A four‐month, randomized, controlled trial in patients at risk of osteoarthritis
Authors: Roos Ewa M. , Dahlberg Leif 
Published: October 2005

AbstractObjectiveTo evaluate the effects of moderate exercise on glycosaminoglycan (GAG) content in knee cartilage in subjects at high risk of knee osteoarthritis (OA).MethodsForty‐five subjects (16 women, mean age 46 years, mean body mass index 26.6 kg/m2) who underwent partial medial meniscus resection 3–5 years previously were randomized to undergo a regimen of supervised exercise 3 times weekly for 4 months or to a nonintervention control group. Cartilage GAG content, an important aspect of the biomechanical properties of cartilage, was estimated by delayed gadolinium‐enhanced magnetic resonance imaging of cartilage (dGEMRIC), with results expressed as the change in the T1 relaxation time in the presence of Gd‐DTPA (T1[Gd]).ResultsThirty of 45 patients were examined by dGEMRIC at baseline and followup. The exercise group (n = 16) showed an improvement in the T1(Gd) compared with the control group (n = 14) (15 msec versus −15 msec; P = 0.036). To study the dose response, change in the T1(Gd) was assessed for correlation with self‐reported change in physical activity level, and a strong correlation was found in the exercise group (n = 16, rS = 0.70, 95% confidence interval [95% CI] 0.31–0.89) and in the pooled group of all subjects (n = 30, rS = 0.74, 95% CI 0.52–0.87).ConclusionThis in vivo cartilage monitoring study in patients at risk of knee OA who begin exercising indicates that adult human articular cartilage has a potential to adapt to loading change. Moderate exercise may be a good treatment not only to improve joint symptoms and function, but also to improve the knee cartilage GAG content in patients at high risk of developing OA.
Assessing bone loss on radiographs of the knee in osteoarthritis: A cross‐sectional study
Authors: Dieppe Paul A. , Reichenbach Stephan , Williams Susan , Gregg Paul , Watt Iain , Jüni Peter 
Published: October 2005

AbstractObjectiveThe only established system to grade subchondral bone attrition in knee osteoarthritis (OA) has low interobserver reliability. In this study, our aim was to convert this system into a reliable tool for the assessment of subchondral bone loss in knee OA.MethodsTemplates that were designed to outline the normal contours of the knee were overlaid onto conventional radiographs of a random sample of 100 knees of OA patients who were awaiting total knee replacement (TKR). Seventy‐five films from individuals with chronic knee pain who were not awaiting TKR and 75 films from asymptomatic control subjects were also assessed. Bone loss was graded from 0 (no attrition) to 3 (severe attrition of >10 mm); other established radiologic features were also graded. Spearman's rho was used to determine the correlation of attrition scores with other features, and logistic regression was used to explore whether definite bone attrition was associated with night pain.ResultsThe inter‐ and intraobserver reliability values were high for attrition scores and for the presence of definite attrition (score ≥2). Bone attrition was evident in 62% of films from patients awaiting TKR, in 9% of films from individuals with chronic knee pain who were not awaiting TKR, and in 1% of films from controls. In all groups, the correlation between attrition and other features was weak to moderate. There was a nonsignificant association between definite bone attrition and night pain.ConclusionBone attrition is an additional dimension of knee OA that can be measured reliably. Definite attrition may be associated with night pain.
Determination of the baculovirus transducing titer in mammalian cells
Authors: Chan Zun‐Ren , Lai Chia‐Wei , Lee Hsiao‐Ping , Chen Huang‐Chi , Hu Yu‐Chen 
Published: October 2005

AbstractBaculovirus has emerged as a promising vector for in vivo or ex vivo gene therapy. To date, the infectious titer and multiplicity of infection (MOI) based on the ability of baculovirus to infect insect cells are commonly adopted to indicate the virus dosage. However, the infectious titer and MOI do not reliably represent the baculovirus transducing ability, making the comparison of baculovirus‐mediated gene transfer difficult. To determine the baculovirus transducing ability more rapidly and reliably, we developed a protocol to evaluate the transducing titers of baculovirus stocks. The virus was diluted twofold serially and used to transduce HeLa cells. The resultant transduction efficiencies were measured by flow cytometry for the calculation of transducing titers. Compared to the infectious titer, the determination of transducing titer is more reproducible as the standard deviations among measurements are smaller. Also, the transducing titers can be obtained in 24 h, which is significantly faster as opposed to 4–7 days to obtain the infectious titer. More importantly, we demonstrated that baculoviruses with higher transducing titers could transduce cells at higher efficiency and yield stronger and longer transgene expression, confirming that the transducing titer was representative of the baculovirus transducing ability. This finding is particularly significant for ex vivo gene delivery whereby unconcentrated viruses are used for transduction and long‐term transgene expression is desired. In this regard, our titration protocol provides a simple, fast, and reliable measure to evaluate the quality of virus stocks during virus production and purification, and is helpful to predict the performance of vector supernatants and ensure reproducible gene delivery experiments. © 2005 Wiley Periodicals, Inc.
Neurenteric cyst: Case report and a review of the potential dysembryology
Authors: Tubbs R. Shane , Salter E. George , Oakes W. Jerry 
Published: October 2005

AbstractWe report a 13‐year‐old female who presented to an outside emergency room following blunt trauma to the head. As part of her evaluation, an unenhanced CT of the face and radiographs of the cervical spine were performed. She was referred to our clinic with “abnormal” imaging. Radiographs revealed dysmorphic cervical spine and ventral clefting of the vertebral bodies from C7‐T2. A subsequent MRI was obtained that demonstrated a large spinal cord mass. MRI demonstrated an unenhanced intramedullary mass of the cervicothoracic spinal cord measuring approximately 1.5 cm in greatest axial diameter. Surgical exploration of her intraspinal mass revealed a neurenteric cyst. Spinal neurenteric cysts are categorized in the spectra of occult spinal dysraphism and most likely arise from incomplete separation of the developing notochord and foregut in the embryo. We discuss potential etiologies for the formation of such cysts. The clinician should consider neurenteric cysts in their differential diagnosis of patients with spinal dysraphism and/or intraspinal masses. Clin Anat. 19:669–672, 2006 © 2005 Wiley‐Liss, Inc.
The molecular genetics of gastroenteropancreatic neuroendocrine tumors
Authors: Zikusoka Michelle N. , Kidd Mark , Eick Geeta , Latich Igor , Modlin Irvin M. 
Published: October 2005

AbstractThe pathobiology of neuroendocrine tumors (NETs) is hampered by the lack of scientific tools that define their mechanisms of secretion, proliferation, and metastasis; and, currently, there are no accurate means to assess tumor behavior and disease prognosis. Molecular biologic techniques and genetic analysis may facilitate the delineation of the molecular pathology of NETs and provide novel insights into their cellular mechanisms. The current status and recent advances in assessment of the molecular basis of tumorigenesis of gastroenteropancreatic neuroendocrine tumors (GEP‐NETs) were reviewed (1981–2004). The objectives of this retrospective study were to provide a cohesive overview of the current state of knowledge and to develop a molecular understanding of these rare tumor entities to facilitate the establishment of therapeutic targets and rational management strategies. Multiple differences in chromosomal aberration patterns were noted between gastrointestinal (GI) neuroendocrine and pancreatic endocrine tumors (PETs). Divergence in gene expression patterns in the development of GI carcinoids and PETs was identified, whereas examination of the PET and GI carcinoid data demonstrated only few areas of overlap in the accumulation of genetic aberrations. These data suggest that the recent World Health Organization classification of GEP‐NETs may require updating. In addition, previous assumptions of tumor similarity (pancreatic vs. GI) may be unfounded when they are examined at a molecular level. On the basis of the evolution of genetic information, enteric neuroendocrine lesions (carcinoids) and PETs may need to be classified as two distinct entities rather than grouped together as the single entity “GEP‐NETs.” Cancer 2005. © 2005 American Cancer Society.
Phase II study of pemetrexed in combination with carboplatin in the first‐line treatment of advanced nonsmall cell lung cancer
Authors: Zinner Ralph G. , Fossella Frank V. , Gladish Gregory W. , Glisson Bonnie S. , Blumenschein George R. , Papadimitrakopoulou Vassiliki A. , Pisters Katherine M.W. , Kim Edward S. , Oh Yun W. , Peeples Beverly O. , Ye Zhishen , Curiel Rafael E. , Obasaju Coleman K. , Hong Waun K. , Herbst Roy S. 
Published: October 2005

AbstractBACKGROUNDThe primary objectives of this study were to determine the efficacy and tolerability of a pemetrexed‐carboplatin combination as first‐line therapy in patients with advanced nonsmall cell lung cancer.METHODSEligibility criteria included Zubrod performance status of 0 or 1, Stage IIIB (malignant effusion) or IV disease, and no prior chemotherapy. Treatment was pemetrexed 500 mg/m2 given intravenously and carboplatin area under the serum concentration–time curve = 6 given intravenously on Day 1 every 3 weeks for six cycles; patients could receive additional cycles at the discretion of the treating physician and patient. All patients received folic acid, vitamin B12, and dexamethasone prophylaxis.RESULTSFifty patients (31 men and 19 women) were treated. The median age was 62 years. Ninety‐six percent of patients had Stage IV disease, and 88% had a performance status of 1. The median number of cycles was 6; 15 patients received 8 or more cycles. There was Grade 3/4 neutropenia in 11 (22%) and 2 (4%) patients, respectively; Grade 3/4 thrombocytopenia in 1 (2%) and 0 patients, respectively. Three patients (6%) experienced Grade 3 nonhematologic side effects (diarrhea, neutropenic pneumonia, and fatigue). No patients had sensory neuropathy or alopecia >Grade 1. The partial response rate was 24%, median time to progression 5.4 months, 1‐year survival 56.0%, and median survival 13.5 months.CONCLUSIONSThis is an active, very well‐tolerated regimen. Trials focused on how to integrate this doublet with novel agents are warranted. Cancer 2005. © 2005 American Cancer Society.
Postnatal phenotype and localization of spinal cord V1 derived interneurons
Authors: Alvarez Francisco J. , Jonas Philip C. , Sapir Tamar , Hartley Robert , Berrocal Maria C. , Geiman Eric J. , Todd Andrew J. , Goulding Martyn 
Published: October 2005

AbstractDevelopmental studies identified four classes (V0, V1, V2, V3) of embryonic interneurons in the ventral spinal cord. Very little is known, however, about their adult phenotypes. Therefore, we characterized the location, neurotransmitter phenotype, calcium‐buffering protein expression, and axon distributions of V1‐derived neurons in the adult mouse spinal cord. In the mature (P20 and older) spinal cord, most V1‐derived neurons are located in lateral LVII and in LIX, few in medial LVII, and none in LVIII. Approximately 40% express calbindin and/or parvalbumin, while few express calretinin. Of seven groups of ventral interneurons identified according to calcium‐buffering protein expression, two groups (1 and 4) correspond with V1‐derived neurons. Group 1 are Renshaw cells and intensely express calbindin and coexpress parvalbumin and calretinin. They represent 9% of the V1 population. Group 4 express only parvalbumin and represent 27% of V1‐derived neurons. V1‐derived Group 4 neurons receive contacts from primary sensory afferents and are therefore proprioceptive interneurons. The most ventral neurons in this group receive convergent calbindin‐IR Renshaw cell inputs. This subgroup resembles Ia inhibitory interneurons (IaINs) and represents 13% of V1‐derived neurons. Adult V1‐interneuron axons target LIX and LVII and some enter the deep dorsal horn. V1 axons do not cross the midline. V1‐derived axonal varicosities were mostly (>80%) glycinergic and a third were GABAergic. None were glutamatergic or cholinergic. In summary, V1 interneurons develop into ipsilaterally projecting, inhibitory interneurons that include Renshaw cells, Ia inhibitory interneurons, and other unidentified proprioceptive interneurons. J. Comp. Neurol. 493:177–192, 2005. © 2005 Wiley‐Liss, Inc.