bluuebunny/crossref_metadata_2025 huggingface dataset:
Total Intra‐Uterine Volume and Symphysis Fundus Height
Authors: Geirsson Reynir T. , Agustsson Pall
Published: December 2007

The concordance between measurements of total intra‐uterine volume (parallel planimetric area method) and symphysis fundus height and the efficacy of these measurements in predicting birthweight by centile range was prospectively investigated in a blind study of 81 measurement sets in 74 women in the third trimester of pregnancy. Gestational length was determined by early ultrasound scans in all cases. Reference curves were from separate populations. Correlation between the measurements was significant, both at 32 weeks (p = 0.015) and 36 weeks (p < 0.001), but only 21% of the variation in intra‐uterine volume at 32 weeks and 63% at 36 weeks' gestation was attributable to changes in fundal height. Intra‐uterine volume was therefore not accurately reflected by fundal height. Fundal height and intra‐uterine volume were in the same centile range in 34% of cases. Maternal height and weight did not correlate with intrauterine volume, but there were significant relations with fundal height, particularly at 36 weeks. Birthweight correlated better with volume (r = 0.665) than with fundal height (r = 0.461) at 32 weeks, while at 36 weeks there was little difference (r = 0.691 and 0.794). In 54% of volume and 47% of symphysis fundus measurements there was agreement with the same centile range of birthweight. Predictive capacity of volume measurements appeared better for the lower birthweight ranges.
Growth and Function of Human Fetal Heart in Normal, Hypertensive and Diabetic Pregnancy
Authors: Räsänen Juha , Kirkinen Pertti
Published: December 2007

Fetal cardiac left and right ventricular dimensions and contractility were measured by echocardiography in late pregnancy in 51 normal, 26 hypertensive and 18 diabetic pregnancies. In relationship with the fetal size, both of the ventricular dimensions, the contractility and left ventricular output were decreased in diabetic cases. In hypertensive pregnancy the relative size of the right ventricle was increased and its contractility decreased, but the function of the left ventricle was no different from normal. These findings may reflect biochemical changes in diabetic myocardium and increased peripheral fetal and placental resistance in hypertensive pregnancy.
Serum Sex Hormone Binding Globulin (SHBG), Testosterone/SHBG Index, Endometrial Pathology and Bone Mineral Density in Postmenopausal Women
Authors: Brody Sam , Carlström Kjell , Lagrelius Anders , Lunell Nils‐Olov , Mollerstrom Gunnar , Pousette Åke
Published: December 2007

Serum levels of sex hormone binding globulin (SHBG) and testosterone (T) and bone mineral density (BMC) in the non‐dominant forearm were determined in 28 postmenopausal women aged 44‐62 years. Significant correlations (Spearman's rank correlation test) were found between BMC and SHBG (negative) and between BMC and the T/SHBG index on biologically active androgen (positive). Significant correlations were also found between endometrial pathology (Kruskal‐Wallis test; 0 = atrophic, 1 = hyperplasia, 2 = cancer) and SHBG (negative) and the T/SHBG index (positive). It is suggested that SHBG may act as one common denominator in the pathogenesis of postmenopausal osteoporosis and endometrial disease by regulating the levels of unbound, biologically active androgens and estrogens.
C‐Reactive Protein: An Early Marker for Neonatal Bacterial Infection Due to Prolonged Rupture of Amniotic Membranes And/Or Amnionitis
Authors: Salzer H. R. , Genger H. , Muhar U. , Lischka A. , Schatten Chr. , Pollak A.
Published: December 2007

The C‐reactive protein (CRP) concentration was determined in 25 infants whose mothers had presented with prolonged rupture of amniotic membranes (PROM) and/or amnionitis. CRP was positive (i.e ≥ 6 mg/1) within the first 6 hrs of life in 10 and negative in 15 infants. Clinically, all infants with positive CRP developed symptoms suggesting bacterial infection and both the absolute immature neutrophil counts as well as the ratio immature/total neutrophils were significantly higher in them on day 2 of life than in infants with negative CRP. Blood cultures were only positive in infants with positive CRP. Thus CRP can be regarded as an early marker for neonatal bacterial infection due to PROM and/or amnionitis.
Pad Test with Fixed Bladder Volume in Urinary Stress Incontinence
Authors: Kinn Anne‐Charlotte , Larsson Barbro
Published: December 2007

A pad‐weighing test of urinary stress incontinence during a set program of physical exercises is presented. The test was begun at a fixed bladder volume (75% of maximum capacity) and was repeated once. The duration of the exercises was approx. 15 min. Leakage was greater in the second test, but statistical analysis showed highly significant intra‐individual correlation between the two amounts. Degree of leakage was not correlated to subjective assessment of incontinence. The test can be done as part of a routine urody‐namic investigation.
Pregnancy After Gamete Intrafallopian Transfer
Authors: Henriksen Tore , Åbyholm Thomas
Published: December 2007

A couple with a history of 6 years' unexplained infertility was treated by gamete intrafallopian transfer (GIFT). Thus, oocytes were obtained by laparoscopy and immediately placed in a transfer catheter together with sperms. The oocyte/sperm preparation was injected into the Fallopian tube via a separate trochar under laparoscopic direction. Four weeks later pregnancy was confirmed by ultrasound.
Immature Cervical Teratoma Arising in One Fetus of A Twin Pregnancy: Case report and reveiw of the literature
Authors: Hitchcock Andrew , Sears Richard T. , O'neill Thomas
Published: December 2007

This is the first recorded case of an immature cervical teratoma arising in one fetus of a twin pregnancy. Although real‐time ultrasound detected the presence of an abnormality, its true nature was not established until after histological examination. Extra‐amniotic prostaglandin pregnancy termination was performed at 20 weeks' gestation due to the onset of acute hydramnios and the rapid increase in tumor size. Delivery of both fetuses was performed under general anesthesia. Extraction of the abnormal twin was only possible after the tumor was separated off from the fetal neck in utero.
Spying on Terrorists: Germany in Comparative Perspective
Authors: McAdams A. James
Published: December 2007

Intelligence and law enforcement agencies in western democracies are turning increasingly to electronic surveillance tools in their efforts to identify and combat new terrorist threats. But this does not mean that they are equally equipped to undertake these measures. As the author shows by comparing surveillance activities in three countries—Great Britain, the United States, and Germany—the Federal Republic's more restrictive legal norms and institutions provide its government with much less freedom of maneuver than its allies.
Inside Front Cover: Polymer–Silicon Flexible Structures for Fast Chemical Vapor Detection (Adv. Mater. 23/2007)
Authors: Singamaneni S. , McConney M. E. , LeMieux M. C. , Jiang H. , Enlow J. O. , Bunning T. J. , Naik R. R. , Tsukruk V. V.
Published: November 2007

Vladimir Tsukruk and co‐workers demonstrate on p. 4248 the application of plasma‐polymerized organic/silicon bimaterial structures as highly sensitive and agile chemical sensors. Owing to their unique nanoscale topology, highly crosslinked structure, and precise choice of the precursors, polymer films coated on microcantilevers exhibited record sensitivity to water vapor and other volatile organic compounds in conjunction with fast response times. The inside cover image by Brian Schrank shows the bimaterial structure deflection in the presence of a stimuli vapor.
Involvement of protein kinase Cζ in interleukin‐1β induction of ADAMTS‐4 and type 2 nitric oxide synthase via NF‐κB signaling in primary human osteoarthritic chondrocytes
Authors: Chockalingam Priya S. , Varadarajan Usha , Sheldon Richard , Fortier Eric , LaVallie Edward R. , Morris Elisabeth A. , Yaworsky Paul J. , Majumdar Manas K.
Published: November 2007

Objective

Protein kinase Cζ (PKCζ), an atypical PKC, has been found to be transcriptionally up‐regulated in human osteoarthritic (OA) articular cartilage. This study was undertaken to examine the role of PKCζ in interleukin‐1β (IL‐1β)–induced NF‐κB signaling in human OA chondrocytes, and ultimately to better understand its function in the regulation of downstream mediators of cartilage matrix degradation.

Methods

Pharmacologic inhibitors or genetic knockdown techniques were used to investigate the role of PKCζ. Western blot analysis was used to evaluate phosphorylation of PKCζ and NF‐κB. Quantitative polymerase chain reaction (PCR) and activity assays were used to evaluate ADAMTS‐4 expression and aggrecanase activity, respectively. Quantitative PCR, biochemical identification, and Western blot analysis were used to evaluate type 2 nitric oxide synthase (NOS2) and NO production.

Results

Phosphorylation of PKCζ and NF‐κB was induced by IL‐1β treatment in a time‐dependent manner, and was specifically inhibited by inhibitors of atypical PKCs. Inhibition of PKCζ suppressed IL‐1β–induced up‐regulation of ADAMTS‐4 messenger RNA (mRNA) and aggrecanase activity. Inhibitors of atypical PKCs also inhibited IL‐1β–induced NO production and NOS2 mRNA expression, demonstrating a novel link between PKCζ and NO production. Furthermore, small interfering RNA– or short hairpin RNA–mediated knockdown of PKCζ mRNA resulted in significant repression of both ADAMTS‐4 and NOS2 mRNA expression.

Conclusion

Our results show that PKCζ is involved in the regulation of IL‐1β–induced NF‐κB signaling in human OA chondrocytes, which in turn regulates downstream expression of ADAMTS‐4 and NOS2. Therefore, inhibition of PKCζ could potentially regulate the production of matrix‐degrading enzymes as well as NO production and have a profound effect on disease progression in OA.
Adalimumab significantly reduces both spinal and sacroiliac joint inflammation in patients with ankylosing spondylitis: A multicenter, randomized, double‐blind, placebo‐controlled study
Authors: Lambert Robert G. W. , Salonen David , Rahman Proton , Inman Robert D. , Wong Robert L. , Einstein Steven G. , Thomson Glen T. D. , Beaulieu Andre , Choquette Denis , Maksymowych Walter P.
Published: November 2007

Objective

To compare the efficacy of adalimumab versus placebo in reducing spinal and sacroiliac (SI) joint inflammation, by magnetic resonance imaging (MRI) in patients with active ankylosing spondylitis (AS).

Methods

This was a randomized, multicenter, double‐blind, placebo‐controlled study. Patients (n = 82) received 40 mg adalimumab or placebo every other week during an initial 24‐week double‐blind period. MRIs of both the spine and SI joints were obtained at baseline, week 12, and week 52. Spinal and SI joint inflammation were measured using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index.

Results

The spine SPARCC score in placebo‐treated patients increased by a mean of 9.4% from baseline, compared with a mean decrease of 53.6% in adalimumab‐treated patients (P < 0.001); the SI joint SPARCC score decreased by a mean of 12.7% from baseline in placebo‐treated patients and by 52.9% in adalimumab‐treated patients (P = 0.017). The response in adalimumab‐treated patients was maintained at week 52. Placebo‐treated patients were switched to open‐label adalimumab treatment at week 24 and experienced similar reductions in spinal and SI joint inflammation by week 52. Similar large reductions in the spine and SI joint SPARCC scores were noted, even in patients who failed to meet the ASsessment in Ankylosing Spondylitis (International Working Group) criteria (nonresponders) at 12 weeks. In adalimumab‐treated patients, a reduced C‐reactive protein concentration at week 12 was significantly associated with improvement in the spine SPARCC score (P = 0.018).

Conclusion

Adalimumab significantly reduced both spinal and SI joint inflammation in patients with active AS after 12 weeks of treatment, and these improvements were maintained for up to 52 weeks.
Treatment of early rheumatoid arthritis: A randomized magnetic resonance imaging study comparing the effects of methotrexate alone, methotrexate in combination with infliximab, and methotrexate in combination with intravenous pulse methylprednisolone
Authors: Durez Patrick , Malghem Jacques , Toukap Adrien Nzeusseu , Depresseux Geneviève , Lauwerys Bernard R. , Westhovens René , Luyten Frank P. , Corluy Luc , Houssiau Frédéric A. , Verschueren Patrick
Published: November 2007

Objective

To compare the effects of methotrexate (MTX), alone or in combination with intravenous (IV) methylprednisolone (MP) or infliximab, on magnetic resonance imaging (MRI)–detected synovitis, bone edema, and erosive changes in patients with early rheumatoid arthritis (RA).

Methods

Forty‐four patients with early RA were randomized to receive MTX alone (MTX group), MTX plus IV MP (IV MP group), or MTX plus infliximab (infliximab group), infused on day 0 and weeks 2, 6, 14, 22, 30, 38, and 46. Gadolinium‐enhanced MRI scans of the metacarpophalangeal joints, wrists, and metatarsophalangeal joints were performed at baseline, week 18, and week 52.

Results

Scores for MRI‐detected synovitis and bone edema improved over time in the 3 groups, with significantly lower synovitis scores in the infliximab group compared with the MTX group and significantly lower bone edema scores in the infliximab group compared with the MTX and the IV MP groups. Scores for MRI‐detected erosion significantly increased over time in all groups. There were no differences in erosion scores between the MTX group and the other groups. It is of note that patients treated with IV MP showed more significant progression in MRI‐detected erosions compared with patients treated with infliximab. At week 22, response rates according to the American College of Rheumatology 20% improvement criteria (ACR20), the ACR50, and the ACR70 were significantly higher in both the IV MP group and the infliximab group compared with the MTX group. At week 52, remission was achieved in 40% of patients in the MTX group and in 70% of patients in the IV MP and infliximab groups. Health Assessment Questionnaire scores improved significantly over time in all groups, with patients receiving IV MP experiencing significantly more improvement compared with patients treated with MTX alone. No severe side effects were observed, except 1 case of MTX‐related pneumonitis.

Conclusion

The combination of MTX and infliximab is superior to MTX alone for reducing MRI‐detected signs of synovitis and bone edema in patients with early RA. Progression of MRI‐detected erosion was greater in patients treated with MTX plus IV MP compared with that in patients who received MTX plus infliximab.
Role of hypoxia and cAMP in the transdifferentiation of human fetal cardiac fibroblasts: Implications for progression to scarring in autoimmune‐associated congenital heart block
Authors: Clancy Robert M. , Zheng Ping , O'Mahony Marguerita , Izmirly Peter , Zavadil Jiri , Gardner Lawrence , Buyon Jill P.
Published: November 2007

Objective

Identification of isolated congenital heart block (CHB) predicts, with near certainty, the presence of maternal anti‐SSA/Ro antibodies; however, the 2% incidence of CHB in first offspring of anti‐SSA/Ro+ mothers, 20% recurrence in subsequent pregnancies, and discordance in identical twins suggest that an environmental factor amplifies the effect of the antibody. Accordingly, this study was carried out to explore the hypothesis that hypoxia potentiates a profibrosing phenotype of the fetal cardiac fibroblast.

Methods

Evidence of an effect of hypoxia was sought by immunohistologic evaluation of CHB‐affected fetal heart tissue and by determination of erythropoietin levels in cord blood. The in vitro effect of hypoxia on gene expression and phenotype in fibroblasts derived from fetal hearts and lungs was investigated by Affymetrix arrays, quantitative polymerase chain reaction (PCR), immunofluorescence, and immunoblotting.

Results

In vivo hypoxic exposure was supported by the prominent intracellular fibroblast expression of hypoxia‐inducible factor 1α in conduction tissue from 2 fetuses in whom CHB led to death. The possibility that hypoxia was sustained was suggested by significantly elevated erythropoietin levels in cord blood from CHB‐affected, as compared with unaffected, anti‐SSA/Ro–exposed neonates. In vitro exposure of cardiac fibroblasts to hypoxia resulted in transdifferentiation to myofibroblasts (a scarring phenotype), as demonstrated on immunoblots and immunofluorescence by increased expression of smooth muscle actin (SMA), an effect not seen in lung fibroblasts. Hypoxia‐exposed cardiac fibroblasts expressed adrenomedullin at 4‐fold increased levels, as determined by Affymetrix array, quantitative PCR, and immunofluorescence, thus focusing attention on cAMP as a modulator of fibrosis. MDL12,330A, an adenylate cyclase inhibitor that lowers the levels of cAMP, increased expression of fibrosis‐related proteins (mammalian target of rapamycin, SMA, plasminogen activator inhibitor type 1, and type I collagen), while the cAMP activator forskolin attenuated transforming growth factor β–elicited fibrosing end points in the cardiac fibroblasts.

Conclusion

These findings provide evidence that hypoxia may amplify the injurious effects of anti‐SSA/Ro antibodies. Modulation of cAMP may be a key component in the scarring phenotype. Further assessment of the susceptibility of cardiac fibroblasts to cAMP modulation offers a new research direction in CHB.
Effect of meniscal damage on the development of frequent knee pain, aching, or stiffness
Authors: Englund M. , Niu J. , Guermazi A. , Roemer F. W. , Hunter D. J. , Lynch J. A. , Lewis C. E. , Torner J. , Nevitt M. C. , Zhang Y. Q. , Felson D. T.
Published: November 2007

Objective

To evaluate the effect of meniscal damage on the development of frequent knee pain, aching, or stiffness in middle‐aged and older adults.

Methods

The Multicenter Osteoarthritis Study is a prospective study of 3,026 individuals 50 years of age or older who have or are at high risk of developing knee osteoarthritis (OA). We investigated knees at baseline and at 15 months. Case knees (n = 110) were those with no pain, aching, or stiffness on most days at baseline, but that had developed frequent pain, aching, or stiffness at 15 months. Control knees (n = 220) were drawn randomly from knees with no frequent symptoms at baseline that did not become case knees. Using 1.0T magnetic resonance imaging performed at baseline and at followup, 2 musculoskeletal radiologists blinded to the case–control status assessed the meniscal damage using the following scale: 0 = intact, 1 = minor tear, 2 = nondisplaced tear or prior surgical repair, and 3 = displaced tear, resection, maceration, or destruction. The effect of meniscal damage was analyzed by contingency tables and logistic regression.

Results

Meniscal damage was common at baseline both in case knees (38%) and in control knees (29%). Although there was a modest association between the meniscal damage score (range 0–3) and the development of frequent knee pain, aching, or stiffness (odds ratio [OR] 1.21, 95% confidence interval [95% CI] 0.96–1.51, adjusted for age, sex, and body mass index), meniscal damage was mostly present in knees with OA. When considering the co‐occurrence of OA, we found no independent association between meniscal damage and the development of frequent knee symptoms (OR 1.05, 95% CI 0.80–1.37).

Conclusion

In middle‐aged and older adults, any association between meniscal damage and the development of frequent knee pain seems to be present because both pain and meniscal damage are related to OA and not because of a direct link between the two.
Persistence of abnormal bronchoalveolar lavage findings after cyclophosphamide treatment in scleroderma patients with interstitial lung disease
Authors: Mittoo Shikha , Wigley Fredrick M. , Wise Robert , Xiao Huiqing , Hummers Laura
Published: November 2007

Objective

Bronchoalveolar lavage (BAL) is a procedure for sampling the terminal airspace cell population to diagnose alveolitis, a condition that predicts changes in lung function in scleroderma patients. Cyclophosphamide (CYC) stabilizes the progression of lung disease in some, but not all, patients with active alveolitis. However, it is unknown whether the BAL fluid cell count obtained after CYC treatment of alveolitis predicts long‐term lung function outcomes and can therefore be used to assist in therapeutic decision‐making. The purpose of this study was to determine whether CYC therapy for active lung disease alters BAL fluid neutrophil and eosinophil counts and whether the persistence of abnormal BAL findings after CYC therapy predicts a decline in lung function in patients with scleroderma and interstitial lung disease (ILD).

Methods

We systematically reviewed the records of scleroderma patients who had active ILD, as evidenced by neutrophilia or eosinophilia on BAL fluid analysis before CYC therapy and on repeat analysis after completion of CYC. Pulmonary function tests (PFTs) were performed before initiation of therapy, at completion of therapy, and during long‐term followup (mean ± SD 3.6 ± 1.94 years).

Results

Of the 25 study patients, in only 6 did the BAL fluid cell counts normalize after CYC therapy. No significant differences were observed between the proportions of patients who had a ≥10% decline in the % predicted DLCO or FVC on the second set of PFTs and had abnormal findings on followup BAL fluid analysis. During long‐term followup, patients with persistent alveolitis had a decline in lung function (mean ± SD change in % predicted FVC −0.6 ± 10.8 liters and mean ± SD change in % predicted DLCO −4.7 ± 21.43 ml/minute/mm Hg), but their lung function did not significantly differ from that in patients whose BAL fluid cell counts had normalized (P = 0.70 and P = 0.62, respectively).

Conclusion

Persistently abnormal results on BAL fluid analysis following CYC treatment is a common finding and does not predict a subsequent decline in lung function.
Case management of arthritis patients in primary care: A cluster‐randomized controlled trial
Authors: Rosemann Thomas , Joos Stefanie , Laux Gunter , Gensichen Jochen , Szecsenyi Joachim
Published: November 2007

Objective

To assess whether providing information on arthritis self‐management through general practitioners (GPs) increases the quality of life in patients with osteoarthritis and whether additional case management provided by practice nurses shows better results.

Methods

We conducted a pragmatic, cluster‐randomized, controlled, 3‐arm trial that included 1,021 patients from 75 primary care practices in Germany. GPs were randomized to intervention group I, group II, or a control group. GPs of both intervention groups participated in 2 peer group meetings. In intervention group II, additional case management was conducted via telephone by a practice nurse. The primary outcome was change in quality of life, assessed by the German version of the Arthritis Impact Measurement Scales Short Form (AIMS2‐SF). Secondary outcomes were health service utilization, prescriptions, and physical activity. Data were controlled for depression using the Patient Health Questionnaire 9 as a potential confounder.

Results

Of 1,125 administered questionnaires, 1,021 were analyzed. Compared with the control group, no significant changes occurred in intervention group I with respect to the primary outcome. Performed radiographs decreased significantly (P = 0.050), whereas prescriptions of acetaminophen increased significantly (P < 0.001). In intervention group II, significant changes in the AIMS2‐SF dimensions social (P < 0.001), symptom (P = 0.048), and lower body (P = 0.049) were identified. Radiographs (P = 0.031) and orthopedic referrals (P = 0.044) decreased whereas prescriptions of pain relievers increased significantly.

Conclusion

Improving the quality of life in patients with arthritis using arthritis self‐management seems challenging. Simply providing this information through GPs is not sufficient but combining it with case management seems to be a promising approach.
Delay in consultation with specialists for persons with suspected new‐onset rheumatoid arthritis: A population‐based study
Authors: Feldman Debbie Ehrmann , Bernatsky Sasha , Haggerty Jeannie , Leffondré Karen , Tousignant Pierre , Roy Yves , Xiao Yongling , Zummer Michel , Abrahamowicz Michal
Published: November 2007

Objective

Care in rheumatoid arthritis (RA) is optimized by involvement of rheumatologists. We wished to determine whether patients suspected of having new‐onset RA in Québec consulted with a rheumatologist, to document any delay in these consultations, and to determine factors associated with prompt consultation.

Methods

Physician reimbursement administrative data were obtained for all adults in Québec. Suspected new‐onset cases of RA in the year 2000 were defined operationally as a physician visit for RA (based on the International Classification of Diseases, Ninth Revision diagnostic codes), where there had been no prior visit code to any physician for RA in the preceding 3 years. For those patients who were first diagnosed by a nonrheumatologist, Cox regression modeling was used to identify patient and physician characteristics associated with time to consultation with a rheumatologist.

Results

Of the 10,001 persons coded as incident RA by a nonrheumatologist, only 27.3% consulted a rheumatologist within the next 2.5–3.5 years. Of those who consulted, the median time from initial visit to a physician for RA to consultation with a rheumatologist was 79 days. The strongest predictors of shorter time to consultation were female sex, younger age, being in a higher socioeconomic class, and having greater comorbidity.

Conclusion

Our data suggest that the vast majority of patients suspected of having new‐onset RA do not receive rheumatology care. Further action should focus on this issue so that outcomes in RA may be optimized.
Reliability of exercise testing and functional activity questionnaires in children with juvenile arthritis
Authors: Stephens Samantha , Singh‐Grewal Davinder , Bar‐Or Oded , Beyene Joseph , Cameron Bonnie , Leblanc Claire M. A. , Schneider Rayfel , Schneiderman‐Walker Jane , Selvadurai Hiran , Silverman Earl , Spiegel Lynn , Tse Shirley M. L. , Wright Virginia , Feldman Brian M.
Published: November 2007

Objective

To determine the reliability of formal exercise testing and the reliability of functional and activity questionnaires in children with juvenile idiopathic arthritis (JIA).

Methods

Children with JIA of any subtype ages 8–16 years who were recruited to a randomized trial comparing different exercise therapies participated in 2 preintervention sessions of exercise testing 2–6 weeks apart. Exercise testing included 1) submaximal oxygen uptake (VO2submax), 2) peak VO2 (VO2peak), and 3) anaerobic power using modified Wingate tests (Want). Two physical function questionnaires (the Childhood Health Assessment Questionnaire [C‐HAQ] and Revised Activity Scale for Kids [ASK]) and 1 daily physical activity questionnaire (the Habitual Activity Estimation Scale [HAES]) were also completed at these times. Test–retest reliability was assessed using type 3, intrarater intraclass correlation coefficient (ICC3,1) and Bland and Altman plots were used to determine limits of agreement.

Results

Data were available for 74 patients (58 girls). VO2submax, VO2peak, and Want demonstrated high reliability (ICC3,1 0.82, 0.91, and 0.94, respectively). C‐HAQ and ASK questionnaires also had very high reliability (ICC3,1 0.82 and 0.91, respectively). The HAES demonstrated low reliability for total activity score (ICC3,1 0.15) and moderate reliability when the number of very active hours was analyzed separately (ICC3,1 0.59).

Conclusion

Results of this investigation suggest that exercise testing and functional questionnaires in children with JIA are consistent and reliable. Reliability of the HAES total score was poor, but moderate when the very active hours subscale score was used.
Osteoporosis disease management for fragility fracture patients: New understandings based on three years' experience with an osteoporosis care service
Authors: Harrington J. Timothy , Lease JoEllen
Published: November 2007

Objective

To review the 3‐year performance of an established osteoporosis care service and consider further improvements in an effort to reduce fragility fractures.

Methods

Osteoporosis care has been coordinated for all willing and able patients with orthopedic fragility fractures in our health system by a nurse and medical director since 2003, using a guideline‐based care algorithm and task management software. Patients were followed by telephone for 2 years to monitor their status and optimize adherence to treatment. Demographics, management recommendations, clinical data, and adherence to treatment were reviewed for the 2003–2005 patient population.

Results

Of 1,019 patients with fragility fractures, 61% underwent osteoporosis evaluation and treatment. The remainder included 15% who refused to participate and 24% who were unable to participate for various logistical and health reasons. More patients age >80 years were unwilling or unable to participate. Bone densities (dual x‐ray absorptiometry [DXA]) were normal, low, or osteoporotic in 24%, 55%, and 21% of patients, respectively, and 60% of the osteoporotic group had ≥1 abnormal metabolic bone laboratory result. Only 17% of the total reported a previous fracture, and 47% had ever undergone DXA. Few experienced bone loss, a new fracture, or bisphosphonate intolerance during treatment.

Conclusion

An osteoporosis care service has coordinated care for every willing and able fragility fracture patient with positive outcomes. In addition, the results suggest a high priority for earlier proactive diagnosis and intervention of the at‐risk population if fractures are to be reduced.
Treatment of refractory polymyalgia rheumatica with etanercept: An open pilot study
Authors: Catanoso Maria Grazia , Macchioni Pierluigi , Boiardi Luigi , Pipitone Nicolò , Salvarani Carlo
Published: November 2007

Objective

To investigate whether etanercept has a steroid‐sparing effect in the treatment of patients with relapsing polymyalgia rheumatica (PMR).

Methods

The study group comprised patients with relapsing PMR who were not able to reduce their prednisone dosage below 7.5–10 mg/day and who had experienced corticosteroid‐related side effects. Patients received injections of etanercept 25 mg twice weekly for 24 weeks, and were followed up for 3 additional months after treatment withdrawal. Patients regularly underwent clinical assessment, measurement of erythrocyte sedimentation rate and C‐reactive protein level, and ultrasound (US) examination of the shoulders during the 9 months of the followup period.

Results

All 6 enrolled patients responded to etanercept with sustained remission (improvement of at least 70% according to European League Against Rheumatism response criteria for PMR in 4 patients and at least 50% in 2 patients) and were able to significantly reduce their median prednisone daily dosage without experiencing a disease relapse (8.75 mg versus 2.5 mg; P = 0.026) at the end of the 9‐month study period. US shoulder examination performed at the end of followup demonstrated a parallel reduction of glenohumeral and periarticular inflammation. A significant reduction in the cumulative prednisone dose 9 months before versus the 9‐month study period was observed (mean ± SD 1,767 ± 524 mg versus 730 ± 182 mg; P = 0.028). Three patients developed nonsevere side effects: bacterial cystitis in 2 and influenza in 1.

Conclusion

These results, which should be confirmed in a controlled study, suggest that etanercept may be a safe and useful corticosteroid‐sparing agent in relapsing PMR.
General and specific factors associated with severity of cognitive impairment in systemic lupus erythematosus
Authors: Tomietto P. , Annese V. , D'agostini S. , Venturini P. , La Torre G. , De Vita S. , Ferraccioli G. F.
Published: November 2007

Objective

To determine factors affecting the severity of cognitive impairment in systemic lupus erythematosus (SLE) and to analyze its anatomic location.

Methods

Fifteen cognitive functions grouped into 8 domains were evaluated in 52 patients with SLE and 20 with rheumatoid arthritis. Patients were classified according to severity of impairment as normal, mild, or moderate/severe. Multivariate analysis was performed to identify the main factors affecting severity of cognitive deficits. The most likely anatomic site of damage according to neuropsychological performance was compared with the lesion's location on magnetic resonance imaging (MRI).

Results

In SLE patients, a stepwise regression analysis showed that the number of impaired functions (dependent variable) was associated with antiphospholipid antibody positivity (aPL+; P = 0.04), the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI; P = 0.001), hypertension (P = 0.032), and was inversely related to educational level (P = 0.021). Including MRI, the number of impaired functions was associated with severity of MRI (P < 0.001), the SDI (P = 0.013), and the presence of Raynaud's phenomenon (P = 0.04). The contemporary presence of aPL+ and Raynaud's phenomenon resulted in a higher probability to develop moderate/severe cognitive deficits (P = 0.015). Two logistic multiple regression analyses identified hypertension (P < 0.05), the SDI (P < 0.01), and moderate/severe MRI findings as main predictors of moderate/severe impairment (dependent variable). The damage site hypothesized through neuropsychological testing corresponded with MRI findings in 71.7% of SLE patients K = 0.42, P = 0.005).

Conclusion

Hypertension, aPL+, accumulated damage, and MRI lesions are the main factors affecting severity of cognitive impairment in SLE. The hypothesized sites of central nervous system involvement according to neuropsychological testing correlated with MRI findings in most patients.
Measurement of fatigue in systemic lupus erythematosus: A systematic review
Authors:   Ad Hoc Committee on Systemic Lupus Erythematosus Response Criteria for Fatigue
Published: November 2007

Objective

To systematically review fatigue instruments used in patients with systemic lupus erythematosus (SLE) and to seek consensus on which instruments should be recommended for future studies and which data on comorbid conditions should be reported when evaluating fatigue in patients with SLE.

Methods

We used data from Medline and EMBase databases (from January 1970 to June 2006), clinical experts, and bibliographies. Data were extracted independently by 4 authors and reviewed by a working group and larger expert panel to produce a recommendation. Instruments were examined for construct validity, reliability, and responsiveness to change. Correlations between fatigue and some components of the Medical Outcomes Study Short Form 36 (SF‐36), disease activity, and comorbidities were reviewed.

Results

We identified 34 studies that used 15 fatigue instruments in patients with SLE. The Fatigue Severity Scale (FSS) was used in 56% of the studies. The Systemic Lupus Activity Measure was significantly correlated with fatigue, but the Systemic Lupus Erythematosus Disease Activity Index was not. Fatigue was also correlated with pain, poor quality of sleep, depression, and with each subscale of the SF‐36.

Conclusion

The working group and expert panel recommend the 9‐item FSS for evaluating fatigue in SLE patients. Responsiveness to change of fatigue instruments has not been well established in SLE and needs further study. The panel suggested that an important improvement or response could be a 15% decrease in the FSS. The effect of several important confounding factors of fatigue such as sleep disorders, depression, fibromyalgia, and anemia needs to be collected and reported.
Atherosclerosis in patients with biopsy‐proven giant cell arteritis
Authors: Gonzalez‐Juanatey Carlos , Lopez‐Diaz Maria J. , Martin Javier , Llorca Javier , Gonzalez‐Gay Miguel A.
Published: November 2007

Objective

To examine the presence of atherosclerosis in a series of giant cell arteritis (GCA) patients attended to in a community hospital and to determine whether clinical features or steroid therapy might be associated with the development of atherosclerotic disease.

Methods

Forty consecutive patients diagnosed with biopsy‐proven GCA, periodically followed at the rheumatology outpatient clinic of Hospital Xeral‐Calde, Lugo (Spain), who had ended steroid therapy and had at least 3 years of followup were assessed for the presence of atherosclerosis by determination of the carotid intima‐media thickness (IMT) and carotid plaques using high‐resolution B‐mode ultrasound. Forty matched controls were also studied.

Results

GCA patients exhibited less carotid artery IMT than did matched controls (mean ± SD 1.01 ± 0.16 mm versus 1.13 ± 0.20 mm; P = 0.005; difference in means 0.12, 95% confidence interval 0.04–0.20). Patients who required steroid therapy for >2 years had greater mean ± SD carotid IMT (1.04 ± 0.17 mm versus 0.95 ± 0.15 mm) but the difference was not statistically significant (P = 0.10). A positive correlation between age at the time of the study and the carotid artery IMT in GCA patients was observed (r = 0.673, P < 0.001). However, adjusting for age, sex, and classic atherosclerosis risk factors, no significant correlation between carotid IMT and the routine laboratory markers of inflammation assessed at the time of disease diagnosis, disease duration, or cumulative prednisone dose was found.

Conclusion

The present study demonstrates that atherosclerotic macrovascular disease is not increased in patients with GCA.
Antibody responses to Borrelia burgdorferi in patients with antibiotic‐refractory, antibiotic‐responsive, or non–antibiotic‐treated lyme arthritis
Authors: Kannian Priya , McHugh Gail , Johnson Barbara J. B. , Bacon Rendi M. , Glickstein Lisa J. , Steere Allen C.
Published: November 2007

Objective

To compare the pattern of antibody responses to Borrelia burgdorferi in patients with antibiotic‐refractory, antibiotic‐responsive, or non–antibiotic‐treated Lyme arthritis as an indirect measure of spirochetal persistence or eradication.

Methods

At least 3 serial serum samples from 41 patients with antibiotic‐refractory arthritis and 23 patients with antibiotic‐responsive arthritis, and samples from 10 non–antibiotic‐treated, historical control patients were tested for IgG reactivity with B burgdorferi sonicate and 4 differentially expressed outer surface lipoproteins of the spirochete, by enzyme‐linked immunosorbent assay.

Results

Among non–antibiotic‐treated patients, antibody titers to B burgdorferi antigens remained high throughout a 2–5‐year period of arthritis. In contrast, in patients with antibiotic‐responsive arthritis, in whom joint swelling usually resolved during a 1‐month course of oral antibiotic therapy, the median antibody titers to most of the spirochetal antigens remained steady or decreased during the first 1–3 months after starting antibiotic therapy. In patients with antibiotic‐refractory arthritis, who had persistent joint swelling for a median duration of 10 months despite 2–3 months of oral or intravenous antibiotics, the median titers to most antigens increased slightly during the first 1–3 months. However, by 4–6 months after starting antibiotic therapy, reactivity with all antigens declined similarly in both antibiotic‐treated groups.

Conclusion

Whereas the antibody titers to B burgdorferi remained high in non–antibiotic‐treated patients, the titers declined similarly 4–6 months after starting therapy in patients with antibiotic‐responsive or antibiotic‐refractory arthritis, suggesting that synovial inflammation persisted in patients with antibiotic‐refractory arthritis after the period of infection.
Hypoxia‐inducible factor 1α is involved in the prostaglandin metabolism of osteoarthritic cartilage through up‐regulation of microsomal prostaglandin E synthase 1 in articular chondrocytes
Authors: Grimmer C. , Pfander D. , Swoboda B. , Aigner T. , Mueller L. , Hennig F. F. , Gelse K.
Published: November 2007

Objective

To investigate crosslinks between catabolic and anabolic pathways in articular cartilage by examining the synthesis and distribution pattern of microsomal prostaglandin E synthase 1 (mPGES‐1) in healthy and osteoarthritic (OA) cartilage and analyzing its functional relationship to hypoxia‐inducible factor 1α (HIF‐1α) in primary articular chondrocytes.

Methods

Normal cartilage and OA cartilage were subjected to immunohistochemical staining for mPGES‐1 and HIF‐1α. Isolated chondrocytes were cultivated under 21% or 1% O2. Microarray analysis and quantitative reverse transcriptase–polymerase chain reaction were used to detect genes differentially expressed in chondrocytes cultured under normoxic compared with hypoxic conditions. Immunoblotting was conducted to evaluate intracellular protein levels of mPGES and nuclear accumulation of HIF‐1α under different oxygen tension levels and with different stimulatory or inhibitory chemical agents.

Results

We found enhanced levels of expression of the mPGES‐1 gene and an increased number of OA chondrocytes showing staining for mPGES‐1 in OA cartilage. Microarray analysis demonstrated that mPGES‐1 was among the genes that were up‐regulated to the greatest degree in primary chondrocytes exposed to 1% O2. In vitro, hypoxia led to an enhanced synthesis of mPGES‐1, coinciding with a nuclear accumulation of the transcription factor HIF‐1α. In chondrocyte culture, stimulation with dimethyloxaloylglycine promoted the expression of mPGES‐1, phosphoglycerate kinase 1, and cyclooxygenase 2 (COX‐2) by stabilizing HIF‐1α protein levels. A reduction of mPGES‐1 synthesis was detected after treatment with 2‐methoxyestradiol, correlating with lower HIF‐1α activity. In contrast, synthesis of mPGES‐1 was not influenced by treatment with the specific COX‐2 inhibitor NS398.

Conclusion

These findings suggest that the transcription factor HIF‐1α is involved in the up‐regulation of mPGES‐1 and may therefore play an important role in the metabolism of OA cartilage.
Articular cartilage and biomechanical properties of the long bones in Frzb‐knockout mice
Authors: Lories Rik J. U. , Peeters Jenny , Bakker Astrid , Tylzanowski Przemko , Derese Inge , Schrooten Jan , Thomas J. Terrig , Luyten Frank P.
Published: November 2007

Objective

Ligands and antagonists of the WNT pathway are linked to osteoporosis and osteoarthritis. In particular, polymorphisms in the FRZB gene, a secreted WNT antagonist, have been associated with osteoarthritis. The aim of this study was to examine cartilage and bone in Frzb−/− mice.

Methods

The Frzb gene in mice was inactivated using a Cre/loxP strategy. Three models of osteoarthritis were used: collagenase, papain, and methylated bovine serum albumin induced. Bone biology was studied using density measurements and microfocal computed tomography. Bone stiffness and mechanical loading–induced bone adaptation were studied by compression of the ulnae.

Results

Targeted deletion of the Frzb gene in mice increased articular cartilage loss during arthritis triggered by instability, enzymatic injury, or inflammation. Cartilage damage in Frzb−/− mice was associated with increased WNT signaling and matrix metalloproteinase 3 (MMP‐3) expression and activity. Frzb−/− mice had increased cortical bone thickness and density, resulting in stiffer bones, as demonstrated by stress–strain relationship analyses. Moreover, Frzb−/− mice had an increased periosteal anabolic response to mechanical loading as compared with wild‐type mice.

Conclusion

The genetic association between osteoarthritis and FRZB polymorphisms is corroborated by increased cartilage proteoglycan loss in 3 different models of arthritis in Frzb−/− mice. Loss of Frzb may contribute to cartilage damage by increasing the expression and activity of MMPs, in a WNT‐dependent and WNT‐independent manner. FRZB deficiency also resulted in thicker cortical bone, with increased stiffness and higher cortical appositional bone formation after loading. This may contribute to the development of osteoarthritis by producing increased strain on the articular cartilage during normal locomotion but may protect against osteoporotic fractures.
Treg cells suppress osteoclast formation: A new link between the immune system and bone
Authors: Zaiss Mario M. , Axmann Roland , Zwerina Jochen , Polzer Karin , Gückel Eva , Skapenko Alla , Schulze‐Koops Hendrik , Horwood Nikki , Cope Andrew , Schett Georg
Published: November 2007

Objective

To investigate whether Treg cells can suppress osteoclast differentiation, and to define a new potential link between the immune system and the skeleton.

Methods

Regulatory CD4+,CD25+,Foxp3+ T cells were isolated and purified from the spleen and cocultured with CD11b+ osteoclast precursor cells isolated from bone marrow. Osteoclastogenesis and bone erosion were assessed by tartrate‐resistant acid phosphatase staining and pit resorption assay, respectively. In addition, Transwell experiments and cytokine‐blocking experiments were performed to define the mechanisms of interaction between Treg cells and osteoclasts.

Results

CD4+,CD25+,Foxp3+ T cells, but not CD4+,CD25− T cells, dose dependently inhibited macrophage colony‐stimulating factor– and RANKL‐dependent osteoclast formation. Pit formation was inhibited by up to 80% when Treg cells were added. The blockade of osteoclast formation was not based on the alteration of RANKL/osteoprotegerin balance but was essentially dependent on direct cell–cell contact via CTLA‐4. Treg cell–mediated expression of transforming growth factor β, interleukin‐4 (IL‐4), and IL‐10 contributed but was not essential to the inhibitory effect on osteoclastogenesis.

Conclusion

These data show that CD4+,CD25+,Foxp3+ Treg cells suppress osteoclast formation, provide a new link between the immune system and bone, and extend our knowledge on regulation of bone homeostasis by the immune system.
Reflections on training in child abuse and neglect prevention: Experiences in Brazil
Authors: Lidchi Victoria Gabrielle
Published: November 2007

In cooperation with an international partner, Brazilian professionals based in Rio de Janeiro designed a training programme in child protection to respond to the particular challenges to effective practice posed by the local environment and to address obstacles to its achievement in the existing child protection system. Training participants used a structured process to identify and address such external challenges and internal obstacles. The use of the framework included an exploration of beliefs held by Brazilian child protection professionals. The training was itself envisaged as an intervention opportunity for participants to promote ‘bottom up’ processes of local systemic change. The programme aimed to provide training that accessed the experience of the international partner's ‘community of expertise’, but mitigated the risk to effectiveness of a ‘transplant’ programme that fails to engage with the surrounding social reality and culture. As part of a nine‐country international training project initiative (ITPI, International Training Project Initiative by ISPCAN) sponsored by the International Society for the Prevention of Child Abuse and Neglect (ISPCAN), standardised tools were adopted to monitor and evaluate the training process. Copyright © 2007 John Wiley & Sons, Ltd.