bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring health in patients with fibromyalgia: Content comparison of questionnaires based on the International Classification of Functioning, Disability and Health
Authors: Prodinger Birgit , Cieza Alarcos , Williams David A. , Mease Philip , Boonen Annelies , Kerschan‐Schindl Katharina , Fialka‐Moser Veronika , Smolen Josef , Stucki Gerold , Machold Klaus , Stamm Tanja
Published: April 2008

Objective

To analyze the content of outcome measures commonly used to assess health in patients with fibromyalgia (FM) by linking the items of the instruments with the International Classification of Functioning, Disability and Health (ICF) in order to evaluate the adequacy of currently used measures.

Methods

Questionnaires used in FM were identified in a structured literature search. All concepts included in the items of the questionnaires were linked to ICF categories, according to previously published linking rules, by 2 independent health professionals. The percentages of linked ICF categories addressing the different ICF components were calculated.

Results

Generic and symptom‐specific instruments were included. From the 296 items contained in all 16 instruments, 447 concepts were extracted and then linked to 52 ICF categories of the component body functions, 1 category of the component body structure, 40 categories of the component activities and participation, and 9 categories of the component environmental factors. More than half of the concepts identified were linked to body function, fewer were linked to activities and participation, and only concepts of 4 instruments were linked to the ICF component environmental factors.

Conclusion

Many concepts were linked to the categories in the ICF component body functions. While linking to the broad category, purportedly similar instruments often covered widely varying areas of function at more fine‐grained levels of detail. Some categories, such as environmental factors, were barely covered by any of the instruments and might constitute an important aspect of health deserving better coverage and future development.
Effects of glucocorticoids on weight change during the treatment of Wegener's granulomatosis
Authors: Wung Peter K. , Anderson Troy , Fontaine Kevin R. , Hoffman Gary S. , Specks Ulrich , Merkel Peter A. , Spiera Robert , Davis John C. , St.Clair E. William , McCune W. Joseph , Stone John H.
Published: April 2008

Objective

Weight gain is a side effect of glucocorticoid (GC) use, but the natural history and health implications of changes in weight that occur during the treatment of inflammatory disease are not understood.

Methods

We evaluated data from the Wegener's Granulomatosis Etanercept Trial. Patients were categorized according to clinical outcome at 1 year: remission (no disease flares), single flare, or multiple flares. Risk factors for gaining ≥10 kg were examined in multivariate models.

Results

Weights at baseline and 1 year were available for 157 (93%) of the 168 patients analyzed. During year 1, the mean cumulative prednisone dosage in the multiple flares subgroup was 7.9 gm, compared with 6.0 gm and 3.9 gm in the single flare and remission subgroups, respectively (P < 0.001). Patients in these subgroups gained an average of 2.6 kg, 4.1 kg, and 5.8 kg, respectively (P = 0.005). Weight gain did not correlate with cumulative GC dose (R = 0.10, P = 0.25). Thirty‐five patients (22.3%) gained and maintained ≥10 kg in the first year. New diagnosis of Wegener's granulomatosis at baseline was an independent predictor of gaining ≥10 kg at 1 year (odds ratio 19.7, 95% confidence interval 2.4–162.6, P = 0.006). Among the 78 patients in the remission subgroup, 40 sustained remissions through the 2‐year time point. For these 40 patients, the mean weight gained at year 1 did not regress by the end of year 2, despite the absence of continued GC use.

Conclusion

Disease control was associated with lower cumulative GC doses but greater weight gain. More than one‐fifth of patients gained >10 kg in the first year of treatment. The quantity of weight gained by patients during treatment has potential future health implications.
A primary care back pain screening tool: Identifying patient subgroups for initial treatment
Authors: Hill Jonathan C. , Dunn Kate M. , Lewis Martyn , Mullis Ricky , Main Chris J. , Foster Nadine E. , Hay Elaine M.
Published: April 2008

Objective

To develop and validate a tool that screens for back pain prognostic indicators relevant to initial decision making in primary care.

Methods

The setting was UK primary care adults with nonspecific back pain. Constructs that were independent prognostic indicators for persistence were identified from secondary analysis of 2 existing cohorts and published literature. Receiver operating characteristic curve analysis identified single screening questions for relevant constructs. Psychometric properties of the tool, including concurrent and discriminant validity, internal consistency, and repeatability, were assessed within a new development sample (n = 131) and tool score cutoffs were established to enable allocation to 3 subgroups (low, medium, and high risk). Predictive and external validity were evaluated within an independent external sample (n = 500).

Results

The tool included 9 items: referred leg pain, comorbid pain, disability (2 items), bothersomeness, catastrophizing, fear, anxiety, and depression. The latter 5 items were identified as a psychosocial subscale. The tool demonstrated good reliability and validity and was acceptable to patients and clinicians. Patients scoring 0–3 were classified as low risk, and those scoring 4 or 5 on a psychosocial subscale were classified as high risk. The remainder were classified as medium risk.

Conclusion

We validated a brief screening tool, which is a promising instrument for identifying subgroups of patients to guide the provision of early secondary prevention in primary care. Further work will establish whether allocation to treatment subgroups using the tool, linked with targeting treatment appropriately, improves patient outcomes.
Validity, reliability, and feasibility of durometer measurements of scleroderma skin disease in a multicenter treatment trial
Authors: Merkel Peter A. , Silliman Nancy P. , Denton Christopher P. , Furst Daniel E. , Khanna Dinesh , Emery Paul , Hsu Vivien M. , Streisand James B. , Polisson Richard P. , Åkesson Anita , Coppock John , van den Hoogen Frank , Herrick Ariane , Mayes Maureen D. , Veale Douglas , Seibold James R. , Black Carol M. , Korn Joseph H.
Published: April 2008

Objective

To determine the validity, reliability, and feasibility of durometer measurements of skin hardness as an outcome measure in clinical trials of scleroderma.

Methods

Skin hardness was measured during a multicenter treatment trial for scleroderma using handheld digital durometers with a continuous scale. Skin thickness was measured by modified Rodnan skin score (MRSS). Other outcome data collected included the Scleroderma Health Assessment Questionnaire. In a reliability exercise in advance of the trial, 9 investigators examined the same 5 scleroderma patients by MRSS and durometry.

Results

Forty‐three patients with early diffuse cutaneous systemic sclerosis were studied at 11 international centers (mean age 49 years [range 24–76], median disease duration 6.4 months [range 0.3–23], and median baseline MRSS 22 [range 11–38]). The reliability of durometer measurements was excellent, with high interobserver intraclass correlation coefficients (ICCs) (0.82–0.92), and each result was greater than the corresponding skin site ICCs for MRSS (0.54–0.85). Baseline durometer scores correlated well with MRSS (r = 0.69, P < 0.0001), patient self‐assessments of skin disease (r = 0.69, P < 0.0001), and Health Assessment Questionnaire (HAQ) disability scores (r = 0.34, P = 0.03). Change in durometer scores correlated with change in MRSS (r = 0.70, P < 0.0001), change in patient self‐assessments of skin disease (r = 0.52, P = 0.003), and change in HAQ disability scores (r = 0.42, P = 0.017). The effect size was greater for durometry than for MRSS or patient self‐assessment.

Conclusion

Durometer measurements of skin hardness in patients with scleroderma are reliable, simple, accurate, demonstrate good sensitivity to change compared with traditional skin scoring, and reflect patients' self‐assessments of their disease. Durometer measurements are valid, objective, and scalable, and should be considered for use as a complementary outcome measure to skin scoring in clinical trials of scleroderma.
Racial differences in expectations of joint replacement surgery outcomes
Authors: Groeneveld Peter W. , Kwoh C. Kent , Mor Maria K. , Appelt Cathleen J. , Geng Ming , Gutierrez Jennifer C. , Wessel Damaris S. , Ibrahim Said A.
Published: April 2008

Objective

Prior studies have indicated racial differences in patients' expectations for joint replacement surgery outcomes. The goal of this study was to measure these differences using a well‐validated survey instrument and to determine if the differences could be explained by racial variation in disease severity, socioeconomic factors, literacy, or trust.

Methods

Detailed demographic, clinical, psychological, and social data were collected from 909 male patients (450 African American, 459 white) ages 50–79 years with moderate or severe osteoarthritis (OA) of the hip or knee receiving primary care at 2 veterans affairs medical centers. The previously validated Joint Replacement Expectations Survey was used to assess expectations for pain relief, functional improvement, and psychological well‐being after joint replacement.

Results

Among knee OA patients (n = 627), the unadjusted mean expectation score (scale 0–76) for African American patients was 48.7 versus 53.6 for white patients (mean difference 4.9, P < 0.001). For hip OA patients (n = 282), the unadjusted mean expectation score (scale 0–72) for African Americans was 45.4 versus 51.5 for whites (mean difference 6.1, P < 0.001). Multivariable adjustment for disease severity, socioeconomic factors, education, social support, literacy, and trust reduced these racial differences to 3.8 points (95% confidence interval [95% CI] 1.2, 6.3) among knee OA patients and 4.2 points (95% CI 0.4, 8.0) among hip patients.

Conclusion

Among potential candidates for joint replacement, African American patients have significantly lower expectations for surgical outcomes than white patients. This difference is not entirely explained by racial differences in demographics, disease severity, education, income, social support, or trust.
Short‐term outcome of neuropsychiatric events in systemic lupus erythematosus upon enrollment into an international inception cohort study
Authors: Hanly J. G. , Urowitz M. B. , Su L. , Sanchez‐Guerrero J. , Bae S. C. , Gordon C. , Wallace D. J. , Isenberg D. , Alarcón G. S. , Merrill J. T. , Clarke A. , Bernatsky S. , Dooley M. A. , Fortin P. R. , Gladman D. , Steinsson K. , Petri M. , Bruce I. N. , Manzi S. , Khamashta M. , Zoma A. , Font J. , Van Vollenhoven R. , Aranow C. , Ginzler E. , Nived O. , Sturfelt G. , Ramsey‐goldman R. , Kalunian K. , Douglas J. , Qiufen Qi K. , Thompson K. , Farewell V.
Published: April 2008

Objective

To determine the short‐term outcome of neuropsychiatric (NP) events upon enrollment into an international inception cohort of patients with systemic lupus erythematosus (SLE).

Methods

The study was performed by the Systemic Lupus International Collaborating Clinics. Patients were enrolled within 15 months of SLE diagnosis and NP events were characterized using the American College of Rheumatology case definitions. Decision rules were derived to identify NP events attributable to SLE. Physician outcome scores of NP events and patient‐derived mental component summary (MCS) and physical component summary (PCS) scores of the Short Form 36 were recorded.

Results

There were 890 patients (88.7% female) with a mean ± SD age of 33.8 ± 13.4 years and mean disease duration of 5.3 ± 4.2 months. Within the enrollment window, 271 (33.5%) of 890 patients had at least 1 NP event encompassing 15 NP syndromes. NP events attributed to SLE varied from 16.5% to 33.9% using alternate attribution models and occurred in 6.0–11.5% of patients. Outcome scores for NP events attributed to SLE were significantly better than for NP events due to non‐SLE causes. Higher global disease activity was associated with worse outcomes. MCS scores were lower in patients with NP events, regardless of attribution, and were also lower in patients with diffuse and central NP events. There was a significant association between physician outcome scores and patient MCS scores only for NP events attributed to SLE.

Conclusion

In SLE patients, the short‐term outcome of NP events is determined by both the characteristics and attribution of the events.
Graded activity for workers with low back pain: Who benefits most and how does it work?
Authors: Staal J. Bart , Hlobil Hynek , Köke Albère J. A. , Twisk Jos W. R. , Smid Tjabe , van Mechelen Willem
Published: April 2008

Objective

To identify subgroups of workers absent from work due to low back pain who are more or less likely to return to work earlier as a result of a graded activity intervention, and to investigate whether this intervention is effective in reducing pain‐related fears and if so, whether these reductions in pain‐related fears mediate return to work.

Methods

A subgroup analysis was conducted on data from a previous randomized controlled trial of 134 Dutch airline workers, which found that a behaviorally‐oriented graded activity intervention was more effective than usual care in stimulating return to work. The subgroup analyses added interaction terms to a Cox regression model that described the relationship between treatment allocation and return to work over 12 months of followup. Furthermore, we studied the effects of graded activity on pain‐related fears and added variables indicating a reduction in pain‐related fears to the model in order to investigate their influence on return to work.

Results

Statistically significant interactions were found for disability, fear‐avoidance beliefs about physical activity, and fear‐avoidance beliefs about work. No indication was found that the reduction in pain‐related fears in the graded activity group mediated more favorable return‐to‐work results in this group.

Conclusion

Workers who perceive their disability to be moderate and workers with moderate scores for fear‐avoidance beliefs return to work more rapidly as a result of the graded activity intervention than workers with higher scores. The return to work of workers receiving the graded activity intervention is possibly independent from the reductions in pain‐related fears caused by this intervention.
Interstitial lung disease in polymyositis and dermatomyositis: Longitudinal evaluation by pulmonary function and radiology
Authors: Fathi Maryam , Vikgren Jenny , Boijsen Marianne , Tylen Ulf , Jorfeldt Lennart , Tornling Göran , Lundberg Ingrid E.
Published: April 2008

Objective

To estimate predictors and long‐term outcome of interstitial lung disease (ILD) in patients with polymyositis (PM) and dermatomyositis (DM).

Methods

We conducted a prospective study in which newly diagnosed PM/DM patients, regardless of clinical symptoms of pulmonary disease, were investigated with repeated chest radiography, high‐resolution computed tomography (HRCT) of the lungs, and pulmonary function test (PFT). Clinical, radiologic, and lung function outcome was based on the last followup results.

Results

Twenty‐three patients with a mean followup period of 35 months were included. Findings on radiographic examination and/or PFT compatible with ILD were recorded in 18 patients (78%). Patients with ILD had lower lung function, higher radiologic scores, and higher creatine kinase values than those without ILD. All patients were treated with high‐dose glucocorticoids and other immunosuppressive agents. Two patients died due to ILD, both with active myositis. During the followup, total lung capacity (TLC) improved in 33%, remained stable in 39%, and deteriorated in 28%. Changes in TLC correlated only partially with HRCT findings, which persisted even after normalizing for lung function.

Conclusion

ILD associated with PM/DM is in most cases mild, chronic, and has a nonprogressive course during immunosuppressive treatment. PFT can be normalized during treatment with immunosuppressive therapy, even if radiologic signs of ILD persist. The course of ILD could not be predicted on the first examination. Therefore, myositis patients with ILD need careful evaluation of clinical features as well as PFT and radiologic features during followup.
Validation of the Health Assessment Questionnaire disability index in patients with gout
Authors: Álvarez‐Hernández Everardo , Peláez‐Ballestas Ingris , Vázquez‐Mellado Janitzia , Terán‐Estrada Leobardo , Bernard‐Medina Ana Guishlaine , Espinoza Jesús , Aceves‐Avila Francisco J. , Goycochea‐Robles María V. , Garza Mario , Ventura Lucio , Burgos‐Vargas Rubén
Published: April 2008

Objective

To assess the psychometric properties of the Health Assessment Questionnaire (HAQ) disability index (DI) in patients with gout.

Methods

This study was conducted in a multicenter cohort of patients with gout whose data were collected at baseline (time 0) and 6 months later (time 6). Reliability was assessed by test–retest reliability (intraclass correlation coefficient [ICC]) and internal consistency (Cronbach's alpha coefficient). Construct validity was assessed with convergent validity (HAQ DI correlation with Short Form 36 [SF‐36]) and discriminative validity (HAQ DI correlation with clinical features). Sensitivity to change was determined by comparing HAQ DI time 0 versus HAQ DI time 6 (percentage of change, effect size, smallest real difference [SRD], and Guyatt's responsiveness index [GRI]).

Results

We included 206 patients (96.6% men, mean ± SD age and disease duration 56.3 ± 12.4 years and 9.3 ± 8.5 years, respectively). Of these, 52.4% had joint pain, 22.8% swelling, 32.5% reduced joint mobility, and 36.9% tophi. The mean HAQ DI score was 0.59 ± 0.77 (95% confidence interval [95% CI] 0.49–0.70). ICC (n = 36, evaluations at baseline and 5 days later) was 0.76. Cronbach's alphas were 0.91 (95% CI 0.88–0.92, P = 0.000) for the 20 HAQ DI items and 0.93 (95% CI 0.92–0.94, P = 0.000) for the 8 HAQ DI categories. The HAQ DI correlated in predictable ways with SF‐36 subscales and clinical variables, and discriminated between subgroups with and without any joint pain, swelling, and tophi. Concerning sensitivity to change (n = 167), the difference between HAQ DI time 0 and HAQ DI time 6 was 0.31 ± 0.58 (effect size 0.62, SRD 0.59, and GRI 1.91). ΔHAQ DI correlated with Δpain (r = 0.349, P = 0.000).

Conclusion

The HAQ DI is a valid and reliable measure of functioning in patients with gout.
Safety and usefulness of minor salivary gland biopsy: Retrospective analysis of 502 procedures performed at a single center
Authors: Caporali Roberto , Bonacci Eleonora , Epis Oscar , Bobbio‐Pallavicini Francesca , Morbini Patrizia , Montecucco Carlomaurizio
Published: April 2008

Objective

To analyze the safety of our biopsy technique and the effectiveness of minor salivary gland biopsy (MSGB) for the diagnosis of Sjögren's syndrome (SS) and amyloidosis.

Methods

We conducted a retrospective analysis of 452 patients with suspected SS and 50 with suspected amyloidosis and negative periumbilical fat aspiration analysis who underwent MSGB at a single center. Diagnostic evaluation for SS included Schirmer's test, unstimulated whole salivary flow, detection of antinuclear antibodies and anti‐SSA/SSB, erythrocyte sedimentation rate, C‐reactive protein, IgM rheumatoid factor, and serology for hepatitis C virus. For all biopsy samples, a cumulative focus score on multilevel sections was calculated. SS was diagnosed according to American‐European Consensus Group (AECG) criteria. Histologic evaluation for amyloidosis was performed using Congo red staining and polarized‐light microscopy. Adverse events were recorded on a questionnaire immediately after the procedure and 7 days, 14 days, and 6 months thereafter.

Results

Sixty‐four patients (12.7%) reported transient adverse events: 40 paresthesias lasting <7 days, 17 paresthesias lasting <14 days, 27 cases of local swelling, and 8 external hematoma. One patient has had local paresthesia for 2 years. A total of 498 (99.2%) samples provided adequate material for histologic analysis. Of 452 patients evaluated for SS, 378 were finally evaluated. Ninety‐three patients (24.5%) had a cumulative focus score ≥1, and 87 (94.5%) of 93 satisfied the AECG criteria. Classification of SS was possible for 124 (32.8%) of 378 patients. In 51 (41%) of 124, MSGB was essential to reach the number of criteria needed for classification. Of 50 patients evaluated for amyloidosis, 10 (20%) had positive Congo red staining.

Conclusion

MSGB is a simple, safe, and reliable tool for the diagnosis of SS and amyloidosis, and therefore is suitable for more extensive application.
Thinking about movement hurts: The effect of motor imagery on pain and swelling in people with chronic arm pain
Authors: Moseley G. Lorimer , Zalucki Nadia , Birklein Frank , Marinus Johan , van Hilten Jacobus J. , Luomajoki Hannu
Published: April 2008

Objective

Chronic painful disease is associated with pain on movement, which is presumed to be caused by noxious stimulation. We investigated whether motor imagery, in the absence of movement, increases symptoms in patients with chronic arm pain.

Methods

Thirty‐seven subjects performed a motor imagery task. Pain and swelling were measured before, after, and 60 minutes after the task. Electromyography findings verified no muscle activity. Patients with complex regional pain syndrome (CRPS) were compared with those with non‐CRPS pain. Secondary variables from clinical, psychophysical, and cognitive domains were related to change in symptoms using linear regression.

Results

Motor imagery increased pain and swelling. For CRPS patients, pain (measured on a 100‐mm visual analog scale) increased by a mean ± SD of 5.3 ± 3.9 mm and swelling by 8% ± 5%. For non‐CRPS patients, pain increased by 1.4 ± 4.1 mm and swelling by 3% ± 4%. There were no differences between groups (P > 0.19 for both). Increased pain and swelling related positively to duration of symptoms and performance on a left/right judgment task that interrogated the body schema, autonomic response, catastrophic thoughts about pain, and fear of movement (r > 0.42, P < 0.03 for all).

Conclusion

Motor imagery increased pain and swelling in patients with chronic painful disease of the arm. The effect increased in line with the duration of symptoms and seems to be modulated by autonomic arousal and beliefs about pain and movement. The results highlight the contribution of cortical mechanisms to pain on movement, which has implications for treatment.
Promotion Time Models with Time‐Changing Exposure and Heterogeneity: Application to Infectious Diseases
Authors: Tournoud Maud , Ecochard René
Published: April 2008

Promotion time models have been recently adapted to the context of infectious diseases to take into account discrete and multiple exposures. However, Poisson distribution of the number of pathogens transmitted at each exposure was a very strong assumption and did not allow for inter‐individual heterogeneity. Bernoulli, the negative binomial, and the compound Poisson distributions were proposed as alternatives to Poisson distribution for the promotion time model with time‐changing exposure. All were derived within the frailty model framework. All these distributions have a point mass at zero to take into account non‐infected people. Bernoulli distribution, the two‐component cure rate model, was extended to multiple exposures. Contrary to the negative binomial and the compound Poisson distributions, Bernoulli distribution did not enable to connect the number of pathogens transmitted to the delay between transmission and infection detection. Moreover, the two former distributions enable to account for inter‐individual heterogeneity. The delay to surgical site infection was an example of single exposure. The probability of infection was very low; thus, estimation of the effect of selected risk factors on that probability obtained with Bernoulli and Poisson distributions were very close. The delay to nosocomial urinary tract infection was a multiple exposure example. The probabilities of pathogen transmission during catheter placement and catheter presence were estimated. Inter‐individual heterogeneity was very high, and the fit was better with the compound Poisson and the negative binomial distributions. The proposed models proved to be also mechanistic. The negative binomial and the compound Poisson distributions were useful alternatives to account for inter‐individual heterogeneity. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Youden Index and Optimal Cut‐Point Estimated from Observations Affected by a Lower Limit of Detection
Authors: Ruopp Marcus D. , Perkins Neil J. , Whitcomb Brian W. , Schisterman Enrique F.
Published: April 2008

The receiver operating characteristic (ROC) curve is used to evaluate a biomarker's ability for classifying disease status. The Youden Index (J), the maximum potential effectiveness of a biomarker, is a common summary measure of the ROC curve. In biomarker development, levels may be unquantifiable below a limit of detection (LOD) and missing from the overall dataset. Disregarding these observations may negatively bias the ROC curve and thus J. Several correction methods have been suggested for mean estimation and testing; however, little has been written about the ROC curve or its summary measures. We adapt non‐parametric (empirical) and semi‐parametric (ROC‐GLM [generalized linear model]) methods and propose parametric methods (maximum likelihood (ML)) to estimate J and the optimal cut‐point (c *) for a biomarker affected by a LOD. We develop unbiased estimators of J and c * via ML for normally and gamma distributed biomarkers. Alpha level confidence intervals are proposed using delta and bootstrap methods for the ML, semi‐parametric, and non‐parametric approaches respectively. Simulation studies are conducted over a range of distributional scenarios and sample sizes evaluating estimators' bias, root‐mean square error, and coverage probability; the average bias was less than one percent for ML and GLM methods across scenarios and decreases with increased sample size. An example using polychlorinated biphenyl levels to classify women with and without endometriosis illustrates the potential benefits of these methods. We address the limitations and usefulness of each method in order to give researchers guidance in constructing appropriate estimates of biomarkers' true discriminating capabilities. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Regression Analysis of Multivariate Interval‐Censored Failure Time Data with Application to Tumorigenicity Experiments
Authors: Tong Xingwei , Chen Man‐Hua , Sun Jianguo
Published: April 2008

This paper discusses multivariate interval‐censored failure time data that occur when there exist several correlated survival times of interest and only interval‐censored data are available for each survival time. Such data occur in many fields. One is tumorigenicity experiments, which usually concern different types of tumors, tumors occurring in different locations of animals, or together. For regression analysis of such data, we develop a marginal inference approach using the additive hazards model and apply it to a set of bivariate interval‐censored data arising from a tumorigenicity experiment. Simulation studies are conducted for the evaluation of the presented approach and suggest that the approach performs well for practical situations. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Solid‐State Photochemical [2+2] Cycloaddition in a Hydrogen‐Bonded Metal Complex Containing Several Parallel and Crisscross CC bonds
Authors: Peedikakkal Abdul Malik Puthan , Vittal Jagadese J.
Published: April 2008

One‐dimensional hydrogen‐bonded complex [Zn(bpe)2(H2O)4](NO3)2⋅8/3 H2O⋅2/3 bpe (1, bpe=4,4′‐bipyridylethylene) containing coordination complex cations [Zn(bpe)2(H2O)4]2+ with parallel and crisscross double bonds undergoes photochemical [2+2] cycloaddition in the solid state and produces tetrakis(4‐pyridyl)cyclobutane (tpcb) in up to 100 % yield with rctt‐tpcb (2 a) as major and rtct‐tpcb (2 b) as minor product. The bpe ligands with crisscross conformation of CC bonds appear to undergo pedal‐like motion prior to photodimerization. Grinding single crystals to powder accelerates the pedal motion of crisscrossed olefins in the bpe ligands to parallel alignment and provides the rctt‐cyclobutane stereoisomer 2 a quantitatively. In addition, 100 % photodimerization of ground 1 indicates that the free bpe ligands, which are remote from each other in a pool of water, and NO3− ions moved toward each other to give a mixture of rctt‐ and rtct‐tpcb isomers.
Mesenchymal chondrosarcoma of soft tissues and bone in children, adolescents, and young adults
Authors: Dantonello Tobias M. , Int‐Veen Christoph , Leuschner Ivo , Schuck Andreas , Furtwaengler Rhoikos , Claviez Alexander , Schneider Dominik T. , Klingebiel Thomas , Bielack Stefan S. , Koscielniak Ewa
Published: April 2008

BACKGROUND.

Mesenchymal chondrosarcoma (MCS) is a rare tumor with a strong tendency toward late recurrences leading to reported 10‐year survival rates below 50%. The recommended treatment is resection with wide margins; the effectiveness of chemo‐ and radiotherapy remain poorly defined. As reports about MCS in young patients are scarce, treatment and outcomes of children/adolescents/young adults in the CWS and COSS studies were investigated.

METHODS.

Since 1977, 15 of >7000 CWS and COSS patients ≤25 years had a confirmed diagnosis of MCS.

RESULTS.

The median age was 16.6 (range, 1–25) and median follow‐up 9.6 years (range, 1–22). Four MCS were osseous and 11 extraosseous. All but 1 patient had nonmetastatic disease. Tumor sites were head/neck (n = 6), paravertebral (n = 3), pelvis (n = 3), limbs (n = 2), and kidney (n = 1). All tumors were resected, but only 8 completely. Thirteen individuals received chemotherapy, 6 were irradiated. Actuarial 10‐year event‐free and overall survival rates were 53% and 67%, respectively. Four recurrences occurred, all within 4 years from diagnosis (3 local, 1 combined; 2 of these in irradiated patients). One of these patients survived after surgery and radiation for local recurrence. Seven of 8 patients whose tumors were completely resected during primary treatment, but only 4 of 7 patients with incomplete surgery survived disease‐free.

CONCLUSIONS.

This series of 15 MCS differs from others: the median age was young, most tumors were extraosseous, most patients received chemotherapy, and the outcome was better than published. Despite long‐term follow‐up, characteristic late metastatic recurrences were not observed. Treating MCS according to standard multimodal soft tissue/bone sarcoma regimens is proposed. Cancer 2008. © 2008 American Cancer Society.
Final survival and safety results from a multicenter, open‐label, phase 3b trial of erlotinib in patients with advanced nonsmall cell lung cancer
Authors: Spigel David R. , Lin Ming , O'Neill Vincent , Hainsworth John D.
Published: April 2008

BACKGROUND.

Erlotinib is an orally available, reversible inhibitor of epidermal growth factor receptor (EGFR) with a proven survival advantage for patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) who have failed a prior chemotherapy. This phase 3b, multicenter, open‐label trial of erlotinib in patients with advanced NSCLC who had progressed after standard chemotherapy treatment was conducted to examine the efficacy and safety of erlotinib monotherapy in patients with advanced NSCLC who had developed disease progression after previous chemotherapy and to characterize the duration of survival and the response rate of erlotinib‐treated patients in subpopulations defined by other patient characteristics before U.S. Food and Drug Administration approval.

METHODS.

A total of 229 patients were enrolled and treated with the standard dose of erlotinib (150 mg once daily). The coprimary objectives were to characterize the overall response rate (ORR) and overall survival (OS) associated with erlotinib therapy in this group and in patient subsets defined by tobacco history. Secondary objectives were to assess safety, to characterize OS and ORR in patient subpopulations, and to determine duration of time on treatment. Patients could remain on study up to 9 months after approval.

RESULTS.

The ORR was 8.3% (95% confidence interval [95% CI], 5.2–2.4%). The ORR in never‐smokers, previous smokers, and current smokers was 28.6% (95% CI, 13.2–50.6%), 6.0% (95% CI, 3.0–10.4%), and 7.3% (95% CI, 2.0–19.0%), respectively. The median OS for all patients was 6.3 months (95% CI, 4.7–8.0 months). In previous and current smokers, the median survival was 5.2 months (95% CI, 4.2–7.3 months) and 6.3 months (95% CI, 3.6–9.2 months), respectively, and was not reached in never‐smokers. The median duration of treatment was 10.6 weeks. One (0.4%) interstitial lung disease‐like event was reported.

CONCLUSIONS.

No new safety signals were noted. The observed ORR and survival data are consistent with results from the pivotal trial BR.21. Cancer 2008. © 2008 American Cancer Society.
Halogen Effect on the Photodissociation Mechanism for Gas‐Phase Bromobenzene and Iodobenzene
Authors: Zhang Xiao‐Peng , Wei Zheng‐Rong , Tang Ying , Chao Ting‐Jung , Zhang Bing , Lin King‐Chuen
Published: April 2008

The velocity imaging technique combined with (2+1) resonance‐enhanced multiphoton ionization (REMPI) is used to detect the halogen fragments in the photodissociation of bromobenzene and iodobenzene at 266 nm. With the aid of potential energy curve calculations by Lunell (Y. J. Liu, P. Persson, S. Lunell, J. Phys. Chem. A 2004, 108, 2339–2345.), the Br fragmentation is proposed to stem from excitation of the lowest excited singlet ${(\pi - \pi ^\ast )}$ state followed by predissociation along a repulsive triplet ${(n - \sigma ^\ast )}$ state. The slowed dissociation rate leads to production of the isotropic Br fragments and 93 % internal energy deposition. Only the ground state Br(2P3/2) is detectable. In contrast, when iodine is substituted, the iodine effect stabilizes the repulsive states associated with the IC6H5 bond rupture and the subsequent dissociation channels become more complicated. 84 % of the iodobenzene molecules obtained follow a direct dissociation channel, while the remaining undergo a predissociative process. Both routes result in rapid dissociation with anisotropy parameters of 0.7±0.2 and 0.9±0.2 as well as 70 % and 26 % in the fractions of translational energy deposition, respectively. The relative quantum yields of I* and I are 0.35 and 0.65 and their related photodissociation pathways are discussed in detail.
Reactions of [Hg(Tab)2](PF6)2 [Tab = 4‐(trimethylammonio)benzenethiolate] with NaX (X = Cl, NO2, NO3): Isolation and Structural Characterization of a Series of Mono‐ and Binuclear Hg/Tab/X Compounds
Authors: Tang Xiao‐Yan , Chen Jin‐Xiang , Liu Guang‐Fei , Ren Zhi‐Gang , Zhang Yong , Lang Jian‐Ping
Published: April 2008

The complex [Hg(Tab)2](PF6)2 [Tab = 4‐(trimethylammonio)benzenethiolate] (1) reacts with one or two equivalents of NaCl to afford the mononuclear complex [Hg(Tab)2Cl](PF6) (2) and the dinuclear complex [{Hg(μ‐Tab)(Tab)Cl}2]Cl2·H2O (3·H2O), respectively. Similar reactions of 1 with NaCl and NaX (molar ratio = 1:1) produce the dinuclear species [{Hg(μ‐Tab)(Tab)Cl}2]X2 [X = NO2 (4), NO3 (5)], while those with NaNO2 or NaNO3 give rise to [{Hg(μ‐Tab)(Tab)X}2]X2 [X = NO2 (6), NO3 (7)]. Complexes 2–7 have been characterised by elemental analysis, IR, UV/Vis, and 1H NMR spectroscopy, and X‐ray crystallography. The Hg atom of the [Hg(Tab)2Cl]+ cation in 2 adopts a T‐shaped coordination geometry. Two [Hg(Tab)2Cl]+ cations in 3·H2O, 4, and 5 are linked by a pair of weak Hg–S bonds to form a dimeric [Hg(μ‐Tab)(Tab)Cl]22+ dication, and the centrosymmetric [Hg(μ‐Tab)(Tab)X]22+ dication in 6 and 7 consists of two [Hg(Tab)2X]+ cations linked by a couple of weak Hg–S bonds. The hydrogen‐bonding interactions in 2–7 lead to the formation of interesting 2D (5, 7) or 3D (2–4, 6) hydrogen‐bonded networks.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Borage and evening primrose oil
Authors: Eskin N. A. Michael
Published: April 2008

The paper gives a short overview about the production and composition of borage (Borago officinalis) and evening primrose (Oenothera biennis) oil considering special aspects of the production as cold‐pressed oil. Both oils are characterized by a remarkable amount of γ‐linolenic acid, which has some nutritional advantages. The fatty acid composition of evening primrose oil is dominated by linoleic acid with about 72% and about 13% γ‐linolenic acid, while borage oil consists of twice the amount of γ‐linolenic acid and only 38% linoleic acid. The amount of saturated fatty acids is higher in borage oil. The tocopherol composition of both oils is dominated by γ‐tocopherol, with borage oil containing twice the amount compared to evening primrose oil.
Simultaneous separation of eight β‐adrenergic drugs using titanium dioxide nanoparticles as additive in capillary electrophoresis
Authors: Zhou Shanshan , Wang Yanqing , De Beer Thomas , Baeyens Willy R. G. , Fei Guang Tao , Dilinuer Malike , Ouyang Jin
Published: April 2008

The analysis is described for separating seven β‐adrenergic blocking agents (atenolol, celiprolol, clorprenaline, fenoterol, metoprolol, propranolol, terbutaline) and clenbuterol (sympathomimetic β‐2 receptor stimulating agonist, decongestant and bronchodilator, illicit anabolic used in athletics) by CE with UV detection. In order to simultaneously separate all analytes, Tris‐H3PO4 solution was applied containing titanium dioxide nanoparticles (TiO2 NPs) as BGEs. The effects of important factors, such as concentration of TiO2 NPs, optimum pH, run buffer concentration, and separation voltage, were investigated so as to achieve best CE separation. The eight analytes could be well separated applying a separation voltage of 15 kV in 75 mM Tris‐H3PO4 buffer at a pH of 2.40, containing 6.0×10−6 g/mL TiO2 NPs. Under these optimal conditions, the RSDs for peak areas and for migration times were less than 2.7 and 2.3%, respectively. The detection limits were 0.1 μg/mL for celiprolol, 0.1 μg/mL for propranolol, 0.2 μg/mL for fenoterol, 1.0 μg/mL for atenolol, 1.0 μg/mL for clenbuterol, 1.0 μg/mL for clorprenaline, 1.0 μg/mL for metoprolol, and 1.0 μg/mL for terbutaline. The proposed method was successfully applied for the rapid CE determination of the frequently applied antihypertensive β‐blocking compounds atenolol, metoprolol, terbutaline, and propranolol in pharmaceutical tablets.
Fluorescence energy transfer‐labeled primers for high‐performance forensic DNA profiling
Authors: Yeung Stephanie H. I. , Seo Tae Seok , Crouse Cecelia A. , Greenspoon Susan A. , Chiesl Thomas N. , Ban Jeff D. , Mathies Richard A.
Published: April 2008

A fluorescence energy transfer (ET) dye‐labeled STR typing system (ET 16‐plex) is developed for the markers used in the commercial STR typing kit PowerPlex 16, and its performance assessed using a 96‐lane microfabricated capillary array electrophoresis (μCAE) system. The ET 16‐plex amplicons displayed 1.6–9‐fold higher fluorescence intensities compared to those produced using the single‐dye (SD)‐labeled multiplex kits. The ET multiplex delivered full STR profiles from 62.5 pg of DNA; half the input required for the SD kits while maintaining a similar heterozygote allele balance. This increased sensitivity should improve typing of poor‐quality DNA samples by making minor or imbalanced alleles more readily detectable at the low copy number (LCN) threshold. The ET 16‐plex also generated complete profiles with only 28 PCR cycles; this capability should improve LCN typing by reducing the amplification time and drop‐in allele incidence. To confirm the practical advantages of ET‐labeled primers, six previously problematic casework samples were tested and only the ET 16‐plex kit was able to capture additional allele data. The successful development and demonstration of ET primers for higher sensitivity STR typing offers a simple solution to improving current commercial multiplex typing capability. The superior spectral properties and universal compatibility with any primer sequence provided by ET cassettes will make future multiplex construction more facile and straightforward. The pairing of ET cassette technology with the μCAE system illustrates not only an enhanced STR typing platform, but a significant step toward a higher‐efficiency forensic laboratory enabled by better chemistry and microfluidics.
Cation‐selective exhaustive injection and sweeping micellar electrokinetic chromatography for analysis of morphine and its four metabolites in human urine
Authors: Lin Yi‐Hui , Chiang Jui‐Feng , Lee Maw‐Rong , Lee Ren‐Jye , Ko Wei‐Kung , Wu Shou‐Mei
Published: April 2008

A cation‐selective exhaustive injection and sweeping micellar EKC (CSEI‐Sweep‐MEKC) was established to analyze morphine and its four metabolites, including codeine, normorphine (NM), morphine‐3‐glucuronide (M3G), and morphine‐6‐glucuronide (M6G). After SPE, the urine samples were analyzed by this CE method. The phosphate buffer (75 mM, pH 2.5) containing 30% methanol was first filled into an uncoated fused‐silica capillary (40 cm, 50 μm id), then a high‐conductivity buffer (120 mM phosphate, 10.3 kPa for 99.9 s) followed. The pretreated urine sample was loaded by electrokinetic injection (10 kV, 600 s). The stacking and separation were performed by using phosphate buffer (25 mM, pH 2.5) containing 22% methanol and 100 mM SDS at −20 kV, and detected at 200 nm. During method validation, calibration plots were linear (r ≥ 0.998) over a range of 30–3000 ng/mL for morphine, NM, and codeine, 100–2000 ng/mL for M6G, and 80–3200 ng/mL for M3G. The LODs (S/N = 5, sampling 600 s at 10 kV) were 10 ng/mL for morphine, NM, and codeine, 35 ng/mL for M6G, and 25 ng/mL for M3G. This stacking CE method could increase 2500‐fold sensitivity of codeine, when comparing with CZE. Five addicts' urine specimens were analyzed. Their results were compared with those of LC‐MS‐MS, and showed good coincidence. This method could be feasible for monitoring morphine and its metabolites in forensic interest and pharmacokinetic investigations.
Enzymatic membranes for the selective transport of neutral molecules by electrophoresis
Authors: Perrin Bernard , Couturier Roger , Fiaty Koffi , Charcosset Catherine , Maïsterrena Bernard
Published: April 2008

The active and selective transport of glucose and glycerol was carried out using electrophoresis and artificial enzymatic membranes. These positively charged composite membranes carry, on the face adjacent to the donor compartment of an electrophoresis module, a specific kinase (hexokinase or glycerokinase) and, on the opposite face, an alkaline phosphatase (ALP). Phosphorylation of the neutral substrate (glucose or glycerol) on the donor side by the kinase generates a negatively charged phosphorylated substrate, whose transmembrane migration is promoted by an electric field and by the membrane's positive charge. Dephosphorylation of the phosphorylated substrate by ALP on the opposite face regenerates the neutral substrate, which accumulates in the receiver compartment of the electrophoresis module. Using an electrophoresis module specifically designed for this study, our experiments were carried out enabling glucose and glycerol to be concentrated approximately eight‐ and twelve‐fold, respectively, in 8 h.
The case for structured random codes in network capacity theorems
Authors: Nazer Bobak , Gastpar Michael
Published: April 2008

Random coding arguments are the backbone of most channel capacity achievability proofs. In this paper, we show that in their standard form, such arguments are insufficient for proving some network capacity theorems: structured coding arguments, such as random linear or lattice codes, attain higher rates. Historically, structured codes have been studied as a stepping stone to practical constructions. However, Körner and Marton demonstrated their usefulness for capacity theorems through the derivation of the optimal rate region of a distributed functional source coding problem. Here, we use multicasting over finite field and Gaussian multiple‐access networks as canonical examples to demonstrate that even if we want to send bits over a network, structured codes succeed where simple random codes fail. Beyond network coding, we also consider distributed computation over noisy channels and a special relay‐type problem. Copyright © 2008 John Wiley & Sons, Ltd.
Molecular dissection of the chromosome band 7q21 amplicon in gastroesophageal junction adenocarcinomas identifies cyclin‐dependent kinase 6 at both genomic and protein expression levels
Authors: van Dekken H. , van Marion R. , Vissers K. J. , Hop W. C. J. , Dinjens W. N. M. , Tilanus H. W. , Wink J. C. , van Duin M.
Published: April 2008

Amplification of chromosome band 7q21 has been frequently detected in various types of cancer including gastroesophageal junction (GEJ) adenocarcinomas. At present, no gene has been disclosed that can explain this frequent amplification of 7q21 in GEJ carcinomas. Therefore, a detailed genomic analysis of the 7q21 region was performed on a selected series of GEJ adenocarcinomas, i.e., 14 primary adenocarcinomas and 10 cell lines, by array comparative genomic hybridization (aCGH) with a 7q11.22‐q31.2 contig array. A distinct peak of amplification was identified at 92.1 Mb in 7q21.2, precisely comprising cyclin‐dependent kinase 6 (CDK6), a gene involved in cell cycle regulation. A smaller peak was seen at 116.2 Mb in 7q31.2, the locus of the MET proto‐oncogene. No distinct peak was detected for the hepatocyte growth factor (HGF) at 81.3 Mb in 7q21.11. An immunoprofile of HGF, CDK6 and MET revealed a strong correlation between aCGH and immunohistochemical protein expression for CDK6 (P = 0.002). Furthermore, immunohistochemistry did not show expression of CDK6 in Barrett's dysplasia and carcinoma in situ, correlating expression of CDK6 with a malignant phenotype. We conclude that high‐resolution genomic analysis and immunoprofiling identify CDK6 as the main candidate target for the recurrent amplification of 7q21 in GEJ adenocarcinomas. © 2008 Wiley‐Liss, Inc.