bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduction of arthritis severity in protease‐activated receptor–deficient mice
Authors: Yang Yuan H. , Hall Pam , Little Christopher B. , Fosang Amanda J. , Milenkovski Georgia , Santos Leilani , Xue Jin , Tipping Peter , Morand Eric F.
Published: April 2005

Objective

Protease‐activated receptor 1 (PAR‐1) is the cell surface receptor for thrombin. It is unclear whether thrombin contributes to inflammation other than by effects on coagulation. We investigated the proinflammatory participation of PAR‐1 in antigen‐induced arthritis (AIA).

Methods

Arthritis was induced by intraarticular injection of methylated bovine serum albumin (mBSA) in preimmunized PAR‐1–deficient (PAR‐1−/−) and wild‐type (WT) mice. The disease was assessed after 7 days by histologic examination of knee joints after decalcification and Safranin O/toluidine blue staining. Serum levels of anti‐mBSA IgG, interferon‐γ, and interleukin‐4 (IL‐4) were determined by enzyme‐linked immunosorbent assay. T cell proliferation response was determined by measuring the incorporation of 3H‐thymidine. Cytokine messenger RNA (mRNA) expression was detected in synovial tissues and peritoneal cells by real‐time polymerase chain reaction.

Results

Arthritis severity was significantly reduced in PAR‐1−/− mice compared with WT mice (P = 0.017). Analysis of individual aspects of joint histology revealed significant reductions in synovial exudates (P < 0.001), cartilage degradation (P < 0.01), and bone damage (P = 0.05) in PAR‐1−/− mice. Synovial IL‐1, IL‐6, and matrix metalloproteinase 13 (MMP‐13) mRNA was significantly reduced in PAR‐1−/− mice. The titers of antigen‐specific serum anti‐mBSA total IgG, IgG1, and IgG2a were significantly reduced, and serum IL‐4 was significantly increased in arthritic PAR‐1−/− mice. In contrast, no difference was observed in antigen‐induced T cell proliferation between PAR‐1−/− and WT mice. In vitro, thrombin‐induced (but not lipopolysaccharide‐induced) IL‐1, IL‐6, and MMP‐13 mRNA expression was significantly impaired in PAR‐1−/− mice compared with WT controls.

Conclusion

These data demonstrate the requirement of PAR‐1 for the expression of AIA, the development of an antigen‐specific Ig response, thrombin‐induced macrophage cytokine and MMP expression, and the inhibitory effect of PAR‐1 on serum IL‐4. We conclude that PAR‐1 plays a significant role in this model of arthritis.
Minimizing complications from nonsteroidal antiinflammatory drugs: Cost‐effectiveness of competing strategies in varying risk groups
Authors: Spiegel Brennan M. R. , Chiou Chiun‐Fang , Ofman Joshua J.
Published: April 2005

Objective

To appraise the cost‐effectiveness of competing therapeutic strategies in patient cohorts eligible for aspirin prophylaxis with varying degrees of gastrointestinal (GI) and cardiovascular risk.

Methods

Cost‐effectiveness and cost‐utility analyses were performed to evaluate 3 competing strategies for the management of chronic arthritis: 1) a generic nonselective nonsteroidal antiinflammatory drug (NSAIDNS) alone; 2) NSAIDNSplus a proton pump inhibitor (PPI); and 3) a cyclooxygenase 2‐selective inhibitor (coxib) alone. Cost estimates were from a third‐party payer perspective. The outcomes were incremental cost per ulcer complication avoided and incremental cost per quality‐adjusted life year (QALY) gained. Sensitivity analysis was performed to evaluate the impact of varying patient GI risks and aspirin use.

Results

In average‐risk patients, the NSAIDNS+ PPI strategy costs an incremental $45,350 per additional ulcer complication avoided and $309,666 per QALY gained compared with the NSAIDNSstrategy. The coxib strategy was less effective and more expensive than the NSAIDNS+ PPI strategy. Sensitivity analysis revealed that the NSAIDNS+ PPI strategy became the dominant approach in patients at high risk for an NSAID adverse event (i.e., patients taking aspirin with ≥1 risk factor for a GI complication).

Conclusion

Generic nonselective NSAIDs are most cost‐effective in patients at low risk for an adverse event. However, the addition of a PPI to a nonselective NSAID may be the preferred strategy in patients taking aspirin or otherwise at high risk for a GI or cardiovascular adverse event.
Determinants of sleep quality in women with systemic lupus erythematosus
Authors: Costa Deborah Da , Bernatsky Sasha , Dritsa Maria , Clarke Ann E. , Dasgupta Kaberi , Keshani Anahita , Pineau Christian
Published: April 2005

Objective

To characterize sleep complaints in women with systemic lupus erythematosus (SLE) and to identify correlates of sleep quality.

Methods

Sleep quality in 100 women with SLE was assessed using the Pittsburgh Sleep Quality Index (PSQI). Participants completed standardized questionnaires assessing depressed mood, leisure time physical activity, functional disability, and pain severity. A clinical examination determined disease activity, cumulative damage, and whether patients fulfilled the American College of Rheumatology criteria for fibromyalgia. A series of hierarchical multiple regressions were computed.

Results

The mean ± SD global PSQI score was 6.98 ± 4.03, with moderate to severe sleep impairment reported by 56% of the sample. The first model testing the importance of demographic factors was not statistically significant. In the disease‐related model, the use of prednisone and functional disability both contributed to poor sleep quality (P < 0.001). The addition of level of exercise participation to the demographic set significantly added to the model (P = 0.001). Depression significantly added to the demographic set, explaining 29% of the variance (P < 0.0001). When these variables, along with disease related variables, were simultaneously regressed on the PSQI Global Score, only depressed mood appeared as a significant independent determinant of global sleep quality (P < 0.001). However, the point estimates for the Beta coefficients were consistent with effects for lack of exercise and prednisone use.

Conclusion

A significant proportion of women with SLE suffer from poor sleep quality. The findings suggest that depressed mood, prednisone use, and lack of exercise contribute to decreased overall sleep quality.
Are health care professionals advising adults with arthritis to become more physically active?
Authors: Fontaine Kevin R. , Bartlett Susan J. , Heo Moonseong
Published: April 2005

Objective

To describe the proportion and characteristics of adults with self‐reported, doctor‐diagnosed arthritis who report ever having been advised by a health professional to become more physically active and to assess whether the advice was associated with recent physical activity.

Methods

Using population‐based data from the 2003 Behavioral Risk Factor Surveillance Survey, respondents were classified according to their arthritis status, whether or not they were ever advised by a health professional to increase their physical activity to help them better manage their arthritis, and whether they engaged in exercise or physical activity within the past month.

Results

Overall, 42% of respondents with arthritis reported ever being advised to increase their physical activity to help their arthritis. Respondents who were more likely to have ever received the advice were female, middle‐aged or older, African American, Hispanic, overweight or obese, sedentary or insufficiently physically active, and had higher levels of education. Persons who reported ever receiving the advice were less likely to report that they had exercised within the past month. A higher level of education was the only variable associated with recent exercise or physical activity among those advised to be more active.

Conclusion

Less than 50% of adults with arthritis report ever being advised by a health professional to become more physically active. Advice alone appears insufficient to promote increased physical activity in adults with arthritis.
Positron emission tomography (PET): Evaluation of chronic periaortitis
Authors: Salvarani Carlo , Pipitone Nicolò , Versari Annibale , Vaglio Augusto , Serafini Desiderio , Bajocchi Gianluigi , Salvo Diana , Buzio Carlo , Greco Paolo , Boiardi Luigi
Published: April 2005

Objective

To evaluate the presence and extent of large‐vessel inflammation in patients with chronic periaortitis (CP) using 18F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET).

Methods

A consecutive case series consisting of 7 patients with CP seen over a 3‐year period and a control group of 14 patients with malignancy were evaluated with FDG‐PET. For every case we selected 2 age‐ and sex‐matched controls who underwent PET imaging for malignancy. The diagnosis of CP was made by means of computed tomography. PET imaging was performed at diagnosis before therapy was started. Measurement of vascular uptake was graded using a 4‐point semiquantitative scale.

Results

All patients had evidence of grade 2+ or 3+ vascular uptake in the abdominal aorta and/or iliac artery. No controls showed vascular uptake greater than 1+. Vascular uptake in the thoracic aorta and/or in its branches was seen in 3 (43%) of 7 patients. Vascular uptake in abdominal aorta and/or iliac artery was observed in patients with CP but not in controls (100% versus 0%). There was also a significantly more frequent FDG uptake in the large thoracic arteries in case‐patients compared with controls (43% versus 0%; P = 0.03).

Conclusion

FDG‐PET scan shows in patients with CP the presence of a large‐vessel vasculitis involving abdominal aorta and common iliac arteries, which in some patients is also extended to thoracic aorta and/or its branches.
Relationship of pain‐coping strategies and pain‐specific beliefs to pain experience in children with juvenile idiopathic arthritis
Authors: Thastum Mikael , Herlin Troels , Zachariae Robert
Published: April 2005

Objective

To examine whether pain‐specific beliefs and coping strategies of patients with juvenile idiopathic arthritis (JIA) independently predict their reported pain, while controlling for relevant demographic variables, disease activity, and parent‐rated disability. To compare use of pain‐coping strategies and pain‐related beliefs of a selected subgroup of patients with high pain and low disease activity (high pain group) with the remaining patients.

Methods

Children with JIA (n = 56) completed the Pain Coping Questionnaire, a revised version of the Survey of Pain Attitudes, and a 3‐week pain diary. The parents completed the Childhood Health Assessment Questionnaire (CHAQ). Second order principal component analyses were conducted in order to reduce the number of independent variables. Regression analyses of the dependent measure were performed. The use of coping strategies and health beliefs were compared using t‐tests for independent samples. Pearson's correlation coefficients were calculated to examine the direct associations between each individual coping and belief scale, and the pain measure.

Results

Only the CHAQ and the cognitive belief composite factor score made statistically significant contribution to the prediction of pain after controlling for other variables. Significant differences were found between the scores of high pain patients and the rest of the group for the health belief subscale of disability (mean ± SD 2.0 ± 0.6 and 1.2 ± 0.7, respectively), and for the health belief subscale of harm (mean ± SD 2.7 ± 0.6 and 1.8 ± 0.7, respectively). Significant correlations were obtained between the pain measure and the pain‐coping subscale of catastrophizing, the pain belief subscales of disability, harm, solicitude (inverse), control, and medical cure.

Conclusion

These results support a model of pain experience in patients with JIA where psychological factors are strongly influential. It may be efficient to focus behavioral interventions on a subgroup of children where the pain experience seems to be in discordance with the disease activity.
The health assessment questionnaire disability index and scleroderma health assessment questionnaire in scleroderma trials: An evaluation of their measurement properties
Authors: Johnson Sindhu R. , Hawker Gillian A. , Davis Aileen M.
Published: April 2005

Objective

To evaluate the measurement properties of the Health Assessment Questionnaire (HAQ) disability index (DI) for group comparisons in scleroderma trials, and to determine if the Scleroderma Health Assessment Questionnaire (SHAQ) visual analog scales confer any measurement advantage over the HAQ DI.

Methods

A computer search for articles describing the use of the HAQ DI and SHAQ in scleroderma was performed. Evidence supporting the sensibility, reliability, validity, and responsiveness of these measures was evaluated.

Results

The SHAQ has incremental face and content validity over the HAQ DI because it addresses scleroderma‐specific manifestations that also contribute to disability. The HAQ DI has good concurrent validity, construct validity, and predictive validity. Whether SHAQ confers incremental construct, concurrent, or predictive validity over the HAQ DI is uncertain. The HAQ DI appears more reliable than the SHAQ; however, reliability studies provide insufficient data to ascertain if minimum standards have been achieved. Responsiveness of the HAQ DI subscales has been demonstrated.

Conclusion

The SHAQ has incremental face and content validity over the HAQ DI. The HAQ DI has greater reliability and demonstrated construct, concurrent, and predictive validity. Further investigation into the measurement properties of the HAQ DI and SHAQ visual analog scales, and their relation to the required standards of measurement is needed.
Comprehensive assessment of clinical outcome and quality of life after resection interposition arthroplasty of the thumb saddle joint
Authors: Angst Felix , John Michael , Goldhahn Jörg , Herren Daniel B. , Pap Géza , Aeschlimann André , Schwyzer Hans‐Kaspar , Simmen Beat R.
Published: April 2005

Objective

To explore the biometric and psychometric properties of clinical, generic, and condition‐specific instruments and to assess quantitatively the outcome after resection interposition arthroplasty (RIAP) of the thumb saddle joint.

Methods

One hundred three patients requiring 112 arthroplasties were assessed in a 4.5–7.7‐year cross‐sectional catamnesis by means of 4 widely used questionnaires and clinical and radiographic examinations.

Results

In all dimensions of the Short Form 36 (SF‐36), the outcome was equal or significantly better than expected by the norm. The Disability of the Arm, Shoulder and Hand questionnaire (DASH) revealed some small, mainly functional limitations (mean score 78.4, norm 86.4). The SF‐36, the DASH, and the Patient Related Wrist Evaluation form (PRWE) correlated highly and loaded on the same factor. The Hand Function Index was independent of the clinical measurements (range of motion, strength, etc. on the specially designed Custom Form) and of the self rating.

Conclusion

Long‐term followup of 112 RIAP patients showed excellent health and quality of life. A questionnaire set consisting of the SF‐36, the DASH (or alternatively the short PRWE), and the Custom Form is proposed for the comprehensive and specific assessment of thumb joint conditions.
Critical appraisal of femorofemoral crossover grafts
Authors: Pursell R , Sideso E , Magee T R , Galland R B
Published: April 2005

Background

The aim of this study was to determine how often femorofemoral crossover grafting for critical ischaemia or intermittent claudication gives an ideal result. An ideal result is an uncomplicated operation with primary wound healing, relief of ischaemic symptoms without recurrence and no need for further intervention.

Methods

All patients undergoing primary femorofemoral crossover grafting between January 1988 and December 2003 were studied.

Results

Some 144 operations were analysed; 51 patients had critical ischaemia and 93 claudication. There was one postoperative death (0·7 per cent). Complications occurred within 30 days in 32 patients (22·2 per cent), including graft occlusion in three (2·1 per cent); six patients (4·2 per cent) required early reoperation. Primary patency for patients with critical ischaemia was 88, 82 and 74 per cent at 1, 3 and 5 years respectively. Respective figures for those who presented with claudication were 93, 92 and 90 per cent (P = 0·034). Late symptoms included graft occlusion (20 patients), disease progression (25), ongoing ulceration (six), graft infection (nine), false aneurysm formation (two) and late donor-site stenosis (two).

Conclusion

When obtaining informed consent, simply describing patency and limb salvage rates does not provide an accurate picture of the outcome of femorofemoral grafting.
Prediction of non-sentinel lymph node status in breast cancer with a micrometastatic sentinel node
Authors: Schrenk P , Konstantiniuk P , Wölfl S , Bogner S , Haid A , Nemes C , Jagoutz-Herzlinger M , Redtenbacher S
Published: April 2005

Background

Axillary lymph node dissection (ALND) may not be necessary in women with breast cancer who have micrometastasis in a sentinel node (SN), owing to the low risk of non-SN (NSN) involvement. The aim of this study was to identify a subgroup of women with a micrometastatic SN and a negligible risk of positive NSNs in whom ALND may be avoided.

Methods

Some 237 of 241 women with a macrometastatic SN and 122 of 138 with a micrometastatic SN underwent completion ALND and were compared with respect to NSN involvement. The 122 patients with SN micrometastasis were further analysed to determine factors that could predict the risk of positive NSNs.

Results

A total of 121 (51·1 per cent) of 237 women with SN macrometastasis had positive NSNs compared with 22 (18·0 per cent) of 122 with SN micrometastasis (P < 0·001). Multivariate analysis showed that size of SN micrometastasis (odds ratio 3·49 (95 per cent confidence interval (c.i.) 1·32 to 9·23); P = 0·012) and presence of lymphovascular invasion (odds ratio 0·23 (95 per cent c.i. 0·05 to 1·00); P = 0·050) were significantly associated with positive NSNs. SN micrometastasis less than 0·5 mm in diameter combined with absence of lymphovascular invasion was associated with an 8·5 per cent risk of NSN involvement.

Conclusion

Size of micrometastasis and presence of lymphovascular invasion were significantly related to the risk of finding additional positive axillary lymph nodes when the SN contained only micrometastasis.
Assessing the technical skills of surgical trainees
Authors: Beard J D , Jolly B C , Newble D I , Thomas W E G , Donnelly J , Southgate L J
Published: April 2005

Background

The aims were to determine whether tests of technical skill on simple simulations can predict competence in the operating theatre and whether objective assessment in the operating theatre by direct observation and video recording is feasible and reliable.

Methods

Thirty-three general surgical trainees undertook five simple skill simulations (knotting, skin incision and suturing, tissue dissection, vessel ligation and small bowel anastomosis). The operative competence of each trainee was then assessed during two or three saphenofemoral disconnections (SFDs) by a single surgeon. Video recordings of the operations were also assessed by two surgeons.

Results

The inter-rater reliability between direct observation and blinded videotape assessment was high (α = 0·96 (95 per cent confidence interval 0·92 to 0·98)). Backward stepwise regression analysis revealed that the best predictors of operative competence were the number of SFDs performed previously plus the simulation scores for dissection and ligation, the key components of SFD (64 per cent of variance explained; P = 0·001).

Conclusion

Deconstruction of operations into their component parts enables trainees to practise on simple simulations representing each component, and be assessed as competent, before undertaking the actual operation. Assessment of surgical competence by direct observation and video recording is feasible and reliable; such assessments could be used for both formative and summative assessment.
Randomized clinical trial of routine preoperative duplex imaging before varicose vein surgery
Authors: Blomgren L , Johansson G , Bergqvist D
Published: April 2005

Background

Duplex imaging is used increasingly for preoperative evaluation of varicose veins, but its value in terms of the long-term results of surgery is not clear.

Methods

Patients with primary varicose veins were randomized to operation with or without preoperative duplex imaging. Reoperation rates, clinical and duplex findings were compared at 2 months and 2 years after surgery.

Results

Two hundred and ninety-three patients (343 legs) had varicose vein surgery after duplex imaging (group 1; 166 legs) or no imaging (group 2; 177 legs). In 44 legs (26·5 per cent), duplex examination suggested a different surgical procedure than had been considered on clinical grounds; the procedure was changed accordingly for 29 legs. At 2 months, incompetence was detected at the saphenofemoral or saphenopopliteal junction (or both) in 14 legs (8·8 per cent) in group 1 and in 44 legs (26·5 per cent) in group 2 (P < 0·001). At 2 years, two legs (1·4 per cent) had undergone or were awaiting reoperation in group 1, and 14 legs (9·5 per cent) in group 2 (P = 0·002). In the remainder, major incompetence was found in 19 legs (15·0 per cent) in group 1 and in 53 (41·1 per cent) in group 2 (P < 0·001).

Conclusion

Routine preoperative duplex examination led to an improvement in results 2 years after surgery for patients with primary varicose veins.
Victim‐centric diversion? The electronic monitoring of domestic violence cases
Authors: Ibarra Peter R. , Erez Edna
Published: April 2005

This article discusses the electronic monitoring of domestic violence cases as a form of diversion. The data derive from a two and a half year study of two “bilateral” electronic monitoring programs geared towards domestic violence offenders, mostly defendants, and their former or current intimate partners. Analysis consists of an examination of how the programs under study manifest the aims and tensions of diversion, and highlights how a victim‐centered approach to diversion can amplify the tensions of diversion. Copyright © 2005 John Wiley & Sons, Ltd.
From referral to disposition: case processing in seven mental health courts
Authors: Steadman Henry J. , Redlich Allison D. , Griffin Patricia , Petrila John , Monahan John
Published: April 2005

The number of mental health courts in the United States is rapidly increasing, from one in 1997 to nearly 100 in 2004. However, to date there is comparatively little research regarding these specialty courts. The present study reports data on the referral and disposition decision‐making processes of seven mental health courts. Information on all referrals to the seven courts over a three‐month period was gathered. Results show that, in comparison with individuals involved in the criminal justice system, mental health court clients are more likely to be older, White, and women than individuals in the general criminal justice system. Furthermore, this over‐representation occurs at the point of referral, rather than at the point of the court's decision to accept or reject a referral. In addition, the length of time from referral to diversion is much longer in these mental health courts than in other types of diversion programs. Implications of these findings are discussed. Copyright © 2005 John Wiley & Sons, Ltd.
Accuracy of self‐reported arrests among a forensic SPMI population
Authors: Crisanti Annette S. , Laygo Ranilo , Claypoole Keith H. , Junginger John
Published: April 2005

Self‐reports are prone to response error even in the most structured and standardized environment, but the highly stigmatizing nature of illegal behavior and the possible cognitive problems inherent to the SPMI population increase the likelihood of such error. Using administrative data as the gold standard, the validity of self‐reported arrests was examined among 85 mentally ill substance‐abusing individuals with justice involvement. The overall accuracy of self‐reported arrests during a three‐month recall period was 84.7%. Validity was higher among individuals who at the time of the follow‐up interview were either in a jail diversion program or incarcerated. Individuals with a mood disorder appeared to be somewhat less accurate in their self‐reports than subjects with schizophrenia, despite the implication of cognitive distortion accompanying this latter diagnostic category. Further research on issues such as the accuracy of self‐reports over longer recall periods, or the accuracy of self‐reported frequency of arrest, is necessary, given the reliance on self‐report methodology in outcome studies. Copyright © 2005 John Wiley & Sons, Ltd.
Evaluating the efficiency and community safety goals of the Broward County Mental Health Court
Authors: Christy Annette , Poythress Norman G. , Boothroyd Roger A. , Petrila John , Mehra Shabnam
Published: April 2005

Mental health courts have developed as one response to persons with mental illness who are involved with the criminal justice system. This study investigated the efficiency and safety goals of one such court in Broward County, FL. Mental health court (MHC) clients spent significantly fewer days in jail for the index arrest associated with study enrollment than a comparison group. MHC clients had similar survival time to re‐arrest up to one year after study enrollment. MHC clients did not significantly differ from the comparison group in self‐reported aggressive acts over an 8 month follow‐up period, while they did self‐report significantly fewer acts of violence than the comparison group at the 8 month follow‐up. These findings suggest that some of the benefits associated with the MHC reported in prior studies were not achieved at the expense of efficiency and safety. Copyright © 2005 John Wiley & Sons, Ltd.
Integrating the criminal justice system into mental health service delivery: the worcester diversion experience
Authors: Grudzinskas Albert J. , Clayfield Jonathan C. , Roy‐Bujnowski Kristen , Fisher William H. , Richardson Maurice H.
Published: April 2005

The substantial number of persons with mental illness encountered in many sectors of the criminal justice system has spurred actors from various agencies within that system to take actions aimed at reducing the growth of this population. These actions have included the development of specialty police units, jail diversion programs, and other mechanisms for channeling persons with mental illness out of the criminal justice system and into mental health treatment. The courts, too, have become involved in this effort with the recent development of the “mental health court,” the latest of the “specialty” or “problem solving courts.” These courts have not been without their critics, however, nor are they the only feasible approach to court‐based diversion. This paper identifies and explores a range of options for structuring the relationship between criminal courts and local mental health systems. Beginning with a discussion of the rationale motivating the development of mental health courts, two alternatives to this specialty court model are discussed. One involves judges dealing with defendants having mental illness and substance abuse on a case‐by‐case basis. The other takes advantages of linkages that may already exist between most courts and the mental health providers who conduct their forensic assessments, expanding the role of these providers to serve as boundary spanners between courts and the components of local mental health systems. Regardless of the model adopted, however, appropriate linkages must exist between the courts and relevant providers. A case study is provided that demonstrates how the status of a locale's linkages can be evaluated and how the information derived from such evaluation can be used to improve the linkages between police, courts, and health and human services agencies. Copyright © 2005 John Wiley & Sons, Ltd.
The role of competency to stand trial in mental health courts
Authors: Stafford Kathleen P. , Wygant Dustin B.
Published: April 2005

Concerns have been raised in the literature about the competency to stand trial and competency to make treatment decisions of defendants referred to mental health courts. However, there is little information reported about the evaluation and prevalence of incompetence, characteristics of incompetent mental health court defendants, and disposition of mentally ill defendants too disturbed to be diverted from the criminal justice system through mental health courts. This study reports on the 85 potential mental health court defendants referred for trial competency evaluations during the first three years of operation of the Akron Ohio Mental Health Court. Of the 80 defendants who could be located for evaluation, 77.5% were found incompetent, and 53% of the incompetent defendants were not restored to competence even after an average of 49 days of treatment in a state psychiatric hospital. The implications of these findings in terms of the diversion potential of mental health courts for the severely mentally ill are discussed. Copyright © 2005 John Wiley & Sons, Ltd.
Palladium(0)‐Catalyzed Tandem Cyclization of Allenenes: Direct Construction of Tricyclic Heterocycles through Aromatic CH Activation
Authors: Ohno Hiroaki , Miyamura Kumiko , Mizutani Tsuyoshi , Kadoh Yoichi , Takeoka Yusuke , Hamaguchi Hisao , Tanaka Tetsuaki
Published: April 2005

Palladium(0)‐catalyzed tandem cyclization of allenenes is described. Treatment of allenenes with an aryl halide, potassium carbonate, and catalytic [Pd(PPh3)4] in dioxane afforded tri‐ or tetracyclic heterocycles in moderate to good yields through insertion of arylpalladium(II) halide into the allenic moiety, intramolecular carbopalladation, and aromatic CH bond activation. The substituent on the olefin terminus has proven to be essential for the success of the tandem cyclization. The reaction with heterocyclic aryl halides such as iodopyrazine or 4‐bromo‐1‐methylindole afforded tri‐ or tetracyclic heteroaromatic products in good yields.
A Markov model approach shows a large variation in the length of S phase in MCF‐7 breast cancer cells
Authors: Larsson Sara , Johansson Maria , Oredsson Stina , Holst Ulla
Published: April 2005

Background

The potential doubling time of a tumor has been suggested to be a measurement of tumor aggressiveness; therefore, it is of interest to find reliable methods to estimate this time. Because of variability in length of the various cell cycle phases, stochastic modeling of the cell cycle might be a suitable approach.

Methods

The relative movement curve and the DNA synthesis time were estimated by using local polynomial regression methods. Further, the rate of nucleotide incorporation was estimated by using a Markov pure birth process with one absorbing state to model the progression of the DNA distribution through S phase.

Results

An estimate of the DNA synthesis time, with confidence intervals, was obtained from the relative movement curve. The Markov approach provided an estimate of the distribution of the time to complete S phase given the initial distribution. Using the Markov approach we also made an estimate of the mean number of active replicons during S phase.

Conclusions

A Markov pure birth process has shown to be useful to model the progression of cells through S phase and to increase knowledge about the variability in the length of S phase and a large variation is shown. © 2005 Wiley‐Liss, Inc.
Detection and quantification of circulating tumor cells in mouse models of human breast cancer using immunomagnetic enrichment and multiparameter flow cytometry
Authors: Allan Alison L. , Vantyghem Sharon A. , Tuck Alan B. , Chambers Ann F. , Chin‐Yee Ian H. , Keeney Michael
Published: April 2005

Background

Circulating tumor cells (CTCs) in the peripheral blood of breast cancer patients may be an important indicator of metastatic disease and poor prognosis. However, the use of experimental models is required to fully elucidate the functional consequences of CTCs. The purpose of this study was to optimize the sensitivity of multiparameter flow cytometry for detection of human tumor cells in mouse models of breast cancer.

Methods

MDA‐MB‐468 human breast cancer cells were serially diluted in whole mouse blood. Samples were lysed and incubated with a fluorescein isothiocyanate–conjugated anti–human leukocytic antigen antibody and a phycoerythrin‐conjugated anti‐mouse pan‐leukocyte CD45 antibody. Samples were then immunomagnetically depleted of CD45‐positive leukocytes, fixed, permeabilized, and stained with propidium iodide before flow cytometric analysis.

Results

Human breast cancer cells could be differentiated from mouse leukocytes based on increased light scatter, cell surface marker expression, and aneuploid DNA content. The method was found to have a lower sensitivity limit of 10−5 and was effective for detecting human breast cancer cells in vivo in the circulation of experimental mice carrying primary human mammary tumors.

Conclusions

This technique has the potential to be a valuable and sensitive tool for investigating the biological relevance of CTCs in experimental mouse models of breast cancer. © 2005 Wiley‐Liss, Inc.
The human β‐glucan receptor is widely expressed and functionally equivalent to murine Dectin‐1 on primary cells
Authors: Willment Janet A. , Marshall Andrew S. J. , Reid Delyth M. , Williams David L. , Wong Simon Y. C. , Gordon Siamon , Brown Gordon D.
Published: April 2005

We identified the C‐type‐lectin‐like receptor, Dectin‐1, as the major receptor for fungal β‐glucans on murine macrophages and have demonstrated that it plays a significant role in the cellular response to these carbohydrates. Using two novel, isoform‐specific mAb, we show here that human Dectin‐1, the β‐glucan receptor (βGR), is widely expressed and present on all monocyte populations as well as macrophages, DC, neutrophils and eosinophils. This receptor is also expressed on B cells and a subpopulation of T cells, demonstrating that human Dectin‐1 is not myeloid restricted. Both major functional βGR isoforms – βGR‐A and βGR‐B – were expressed by these cell populations in peripheral blood; however, only βGR‐B was significantly expressed on mature monocyte‐derived macrophages and immature DC, suggesting cell‐specific control of isoform expression. Inflammatory cells, recruited in vivo using a new skin‐window technique, demonstrated that Dectin‐1 expression was not significantly modulated on macrophages during inflammation, but is decreased on recruited granulocytes. Despite previous reports detailing the involvement of other β‐glucan receptors on mature human macrophages, we have demonstrated that Dectin‐1 acted as the major β‐glucan receptor on these cells and contributed to the inflammatory response to these carbohydrates.
Nitrosyl Ruthenium Diolato Complexes
Authors: Barth Michael , Kästele Xaver , Klüfers Peter
Published: April 2005

[mer‐(dien)(NO)Ru(AnErytH–2)]BPh4·2 H2O (1), [mer‐(dien)(NO)Ru(R,R‐ChxdH–2)]BPh4 (2), [mer‐(dien)(NO)Ru(EthdH–2)]BPh4 (3), and [mer‐(dien)(NO)Ru(Me‐β‐D‐Ribf2,3H–2)]BPh4·5.5 H2O (4) have been synthesized in the form of light pink crystals by the reaction of [mer‐(dien)(NO)RuCl2]X with the respective diol in aqueous sodium hydroxide solution (dien = diethylenetriamine, AnEryt = anhydroerythritol, Chxd = cyclohexane‐1,2‐diol, Ethd = ethanediol, Rib = ribose; X = BPh4 or PF6). The nitrosyl ligand exhibits a strong trans influence which causes the trans‐bonded oxygen atom of the diolato ligand to form a shorter bond with the Ru centre. Mean values are 2.038 for cis and 1.946 Å for trans O‐binding. Back donation is strongly supported by the diolato ligand resulting in low energies for the N–O stretch which can be observed as low as 1805 cm–1. trans‐Oxygen atoms do not act as hydrogen‐bond acceptors in any of the cases. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Adducts of Cyclotriphosphorus Complexes with Cyclopentadienyl Ruthenium Fragments: Synthesis, Solid‐State Structure and Solution Behaviour
Authors: Barbaro Pierluigi , Di Vaira Massimo , Peruzzini Maurizio , Seniori Costantini Stefano , Stoppioni Piero
Published: April 2005

Treatment of the cyclo‐P3 complexes [(triphos)M(η3‐P3)]‐[triphos = 1,1,1‐tris(diphenylphosphanylmethyl)ethane; M = Co (1), Rh (2)] with stoichiometric amounts of [CpRu‐(CH3CN)2(PR3)]PF6 [R = Ph (3), Me (4), Cy (5)] in CH2Cl2 in the presence of CH3CN yields the bimetallic adducts [{(triphos)M}(μ,η3:1‐P3){CpRu(CH3CN)(PR3)}]PF6 [M = Co; R = Ph (6), Me (7), Cy (8); M = Rh; R = Ph, (9), Me (10), Cy (11)]. The rhodium derivatives 9 and 11, upon treatment with one equivalent of PMe3, form the complexes [{(triphos)Rh}(μ,η3:1‐P3){CpRu(PMe3)(PR3}]PF6 [R = Ph (12), Cy (13)]. On standing in CH2Cl2, the rhodium complexes 9 and 10 lose acetonitrile to yield compounds with the formula [{(triphos)Rh}(μ,η3:1,1'‐P3){CpRu(PR3)}]PF6 [R = Ph (14), Me (15)]. All the compounds have been characterised by elemental analyses and, in solution, by 31P and 1H NMR spectroscopy. The 31P{1H} EXSY NMR spectroscopic data at different temperatures of 11 and 14 have highlighted the occurrence of independent dynamic processes that exchange both the triphos and the cyclo‐P3 phosphorus nuclei. An X‐ray structural investigation carried out on 6 has confirmed the occurrence of the μ,η3:1‐ligating behaviour of the cyclo‐P3 ligand. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Relationship between the Molecular Structure and the π–π* Transition Energy of a Lattice‐Framework Disilene: A DFT Study
Authors: Tanaka Hiromasa , Kwon Eunsang , Tsutsui Shinobu , Matsumoto Shigeki , Sakamoto Kenkichi
Published: April 2005

The origin of a significantly red‐shifted π–π* transitionobserved in a unique lattice‐framework disilene,2,3,4,6,7,8,2',3',4',6',7',8'‐dodeca‐tert‐butyl[5,5']bi{1,5‐di‐silatricyclo[4.2.0.01,4]octylidene}‐2,7,2',7'‐tetraene, has been elucidated by time‐dependent density functional calculations and MO energy calculations. An intramolecular through‐space interaction between the π*Si=Si orbital and the π*C=C orbitals in the lattice framework strongly stabilizes the LUMO, resulting in a small HOMO–LUMO energy gap. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
New Tris(thioimidazolyl)borate Ligands and Some Zinc Complexes Thereof
Authors: Ibrahim Mohamed M. , Shu Mouhai , Vahrenkamp Heinrich
Published: April 2005

In order to improve the encapsulation of metal ions coordinated by tris(thioimidazolyl)borate ligands, four new such ligands with o‐substituted phenyl substituents were synthesised as well as ones with p‐tolyl and cyclohexyl substituents. In order to provide a basis for their bioinorganic zinc complex chemistry, they were converted to some zinc‐halide, ‐carboxylate, ‐nitrate, ‐phenolate and ‐benzylate complexes. They form zinc‐perchlorate complexes which are productive starting materials for the attachment of alcohols and alkoxides at zinc, thereby yielding new structural models for the zinc enzyme alcohol dehydrogenase. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Screening by NMR: A New Approach for the Study of Bioactive Natural Products? The Example of Pleurotus ostreatus Hot Water Extract
Authors: Politi Matteo , Chávez María Isabel , Cañada F. Javier , Jiménez‐Barbero Jesús
Published: April 2005

Direct NMR screening of natural products obtained from hot water extracts of medicinal species is accomplished through STD and tr‐NOESY experiments on a crude mixture and a given protein receptor. It is shown, with use of a mushroom extract as model case, that this protocol may provide a fast and simple method, particularly useful in natural products chemistry, through which to detect the presence of ligands for a target receptor. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Donor–Acceptor‐Substituted Phenylacetylene Macrocycles with Threefold Symmetry
Authors: Traber Boris , Oeser Thomas , Gleiter Rolf
Published: April 2005

A stepwise synthesis of the donor–acceptor‐substituted macrocycle 5,21,37‐tris(diethylamino)‐13,29,45‐trinitro[2.2.2.2.2.2]metacyclophane‐1,9,17,25,33,42‐hexayne (1a) from 3,5‐bis(3‐iodo‐5‐nitrophenylethynyl)‐N,N‐diethylaniline (11) and 3,5‐bis([3‐diethylamino‐5‐ethynylphenyl]ethynyl)nitrobenzene (12) failed, mostly due to the low solubility of 1a. The synthesis of the 5,21,37‐tris(N,N‐di‐n‐hexylamino) congener of 1a, 1b, was achieved in a one‐pot reaction from 1,3‐diiodo‐5‐nitrobenzene (3) and 3,5‐diethynyl‐N,N‐di(n‐hexyl)aniline (16) in 23 % yield. X‐ray investigations on 1b revealed a planar π ring system with an inner diameter of 10 Å. Despite a high absorbance of 1b at 300 nm, no measurable NLO activity was found. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Free‐Radical Approach to 4‐Substituted Dipicolinates
Authors: Shelkov Rimma , Melman Artem
Published: April 2005

Dimethyl pyridine‐2,6‐dicarboxylate was selectively substituted through free‐radical reactions. The substitution involves the generation of free radicals through Fenton‐type reactions, followed by hydrogen abstraction from aldehydes or alcohols. The resultant carbon‐centered acyl, alkyl, or hydroxyalkyl free radicals regioselectively attack protonated dimethyl pyridine‐2,6‐dicarboxylate at position 4, yielding the corresponding dimethyl 4‐acyl‐, 4‐alkyl‐, and 4‐(hydroxyalkyl)pyridine‐2,6‐dicarboxylates. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
First Model Reactions towards the Synthesis of Sarain A Core Skeleton Based upon a Biogenetic Scenario
Authors: Hourcade Stéphane , Ferdenzi Antoine , Retailleau Pascal , Mons Stéphane , Marazano Christian
Published: April 2005

Sarain A is a complex macrocyclic marine alkaloid extracted from sponges of the order Haplosclerida. It is likely that this alkaloid shares a common origin with manzamine alkaloids, also extracted from sponges of the same order. In this paper, new concepts concerning this origin are presented and constitute the basis for a synthetic strategy. A preliminary evaluation of this strategy is presented and leads, as a first result, to a five‐step access to the bicyclic intermediate 43. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Diastereoselective Alkylation of (Arene)tricarbonylchromium and Ferrocene Complexes Using a Chiral, C2‐Symmetrical 1,2‐Diamine as Auxiliary
Authors: Alexakis Alexandre , Tomassini Axel , Andrey Olivier , Bernardinelli Gerald
Published: April 2005

The aminal of (benzaldehyde)tricarbonylchromium and en‐antiopure bipyrrolidine undergoes diastereoselective ortho‐metallation with butyllithium. Quenching with various electrophiles, followed by hydrolysis of the aminal, affords ortho‐substituted (benzaldehyde)tricarbonylchromium compounds with high ee (91–99 %). When quenched with Ph2PCl, a new chiral P,N‐bidentate ligand is obtained, which shows efficiency in Pd‐ and Cu‐catalysed reactions. The aminal of ferrocenecarbaldehyde could also be formed, but the ortho‐deprotonation occurs with only moderate diastereoselectivity (70 %). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Synthesis and Characterization of Phosphorus Dendrimers Containing Long, Conjugated Branches
Authors: Magro Germinal , Marchand Patrice , Sebastián Rosa‐María , Guyard‐Duhayon Carine , Caminade Anne‐Marie , Majoral Jean‐Pierre
Published: April 2005

The synthesis of a new family of phosphorus dendrimers is described up to the fifth generation (96 end‐groups). The reaction is based on the nucleophilic substitution of P(S)Cl2 end‐groups by 4‐hydroxy‐3‐methoxycinnamaldehyde, and by the condensation of CHO end‐groups with a dichlorophosphorhydrazide. The structure of the first generation has been determined by X‐ray diffraction. This structure shows that the OC6H3CH=CHCH=NNMeP(S) linkage is close to planarity, which indicates an extended conjugation of this linkage that leads to a semi‐rigid skeleton for these dendrimers. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Improved Synthesis and Conformational Analysis of anA,D‐1,10‐Phenanthroline‐Bridged Calix[6]arene
Authors: W. Eggert Jan P. , Harrowfield Jack , Lüning Ulrich , Skelton Brian W. , White Allan H. , Löffler Frank , Konrad Serge
Published: April 2005

The synthesis of the A,D‐1,10‐phenanthroline‐bridged calix[6]arene 3 is improved by applying a new strategy for the synthesis of the important intermediate 2,9‐bis(bromomethyl)‐1,10‐phenanthroline (2) and variation of the bridging conditions. Crystals were obtained from two different solvent systems. Two structures were determined by X‐ray studies. Both analyses reveal a rare conformation for A,D‐bridged calix[6]arenes (uduuuu). Calculations with different methods were performed for this and other relevant conformers, and revealed various local minima. The uduuuu conformation also explains the molecular asymmetry evident in low‐temperature NMR spectra of metal complexes of 3. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Steric Effects in Enantioselective Allylic Alkylation Catalysed by Cationic(η3‐Allyl)palladium Complexes Bearing Chiral Pyridine‐Aziridine Ligands
Authors: Ferioli Federico , Fiorelli Claudio , Martelli Gianluca , Monari Magda , Savoia Diego , Tobaldin Paolo
Published: April 2005

Enantiopure N,N′‐bidentate ligands (N,N′)*, containing substituted aziridine and aza‐aromatic rings, were prepared from imines derived from (S)‐valinol or (R)‐phenylglycinol and heteroaromatic aldehydes (2‐pyridine‐, 6‐benzyl‐2‐pyridine‐, 2‐ and 8‐quinolinecarbaldehyde) by the addition of iPrMgCl and subsequent cyclisation of the 1,2‐amino alcohol moiety to aziridine. Crystalline [(N,N′)*(η3‐allyl)Pd][SbF6] complexes were prepared from these ligands and used as catalysts in the alkylation of sodium dimethyl malonate with 1,3‐diphenyl‐2‐propenyl acetate and carbonate. By comparing the performances of two complexes bearing similar pyridine‐aziridine ligands but with a different C2‐aziridine substituent (Ph vs. iPr), a better enantioselectivity was provided by the Ph‐substituted ligand (90 % vs. 41 % ee), whereas the presence of a C6‐pyridine benzyl substituent caused inversion of the enantioselectivity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
A One‐Pot Synthesis of Doubly Unsaturated Trifluoromethyl Amines:Easy Access to CF3‐Substituted Piperidines
Authors: Magueur Guillaume , Legros Julien , Meyer Franck , Ourévitch Michèle , Crousse Benoit , Bonnet‐Delpon Danièle
Published: April 2005

A straightforward route to trifluoromethyl analogs of piperidines is described. These syntheses involve a Barbier‐type allylation reaction of trifluoroacetaldimines, followed by N‐allylation (one‐pot), and ring‐closing metathesis. An efficient asymmetric version is also reported (>98 % de). Functionalized heterobicyclic compounds can also be obtained by a Pauson–Khand reaction. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
A Chemoenzymatic, Enantioconvergent, Asymmetric Total Synthesis of(R)‐Fridamycin E
Authors: Ueberbacher Bernhard J. , Osprian Ingrid , Mayer Sandra F. , Faber Kurt
Published: April 2005

A chemoenzymatic, asymmetric total synthesis of the anti‐biotic (R)‐fridamycin E has been accomplished following a biocatalytic deracemization procotol. The key step comprises the construction of the chiral side‐chain from a functionalized rac‐2,2‐disubstituted oxirane via a kinetic resolution/stereoinversion sequence without formation of the undesiredstereoisomer. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)