bluuebunny/crossref_metadata_2025 huggingface dataset:
Zoledronic Acid Prevents Cancer Treatment–Induced Bone Loss in Premenopausal Women Receiving Adjuvant Endocrine Therapy for Hormone-Responsive Breast Cancer: A Report From the Austrian Breast and Colorectal Cancer Study Group
Authors: Gnant Michael F.X. , Mlineritsch Brigitte , Luschin-Ebengreuth Gero , Grampp Stephan , Kaessmann Helmut , Schmid Marianne , Menzel Christian , Piswanger-Soelkner Jutta Claudia , Galid Arik , Mittlboeck Martina , Hausmaninger Hubert , Jakesz Raimund
Published: December 2006

Purpose

Adjuvant therapy for breast cancer can be associated with decreased bone mineral density (BMD) that may lead to skeletal morbidity. This study examined whether zoledronic acid can prevent bone loss associated with adjuvant endocrine therapy in premenopausal patients.

Patients and Methods

This study is a randomized, open-label, phase III, four-arm trial comparing tamoxifen (20 mg/d orally) and goserelin (3.6 mg every 28 days subcutaneously) ± zoledronic acid (4 mg intravenously every 6 months) versus anastrozole (1 mg/d orally) and goserelin ± zoledronic acid for 3 years in premenopausal women with hormone-responsive breast cancer. In a BMD subprotocol at three trial centers, patients underwent serial BMD measurements at 0, 6, 12, 24, and 36 months.

Results

Four hundred one patients were included in the BMD subprotocol. Endocrine treatment without zoledronic acid led to significant (P < .001) overall bone loss after 3 years of treatment (BMD, −14.4% after 36 months; mean T score reduction, −1.4). Overall bone loss was significantly more severe in patients receiving anastrozole/goserelin (BMD, −17.3%; mean T score reduction, −2.6) compared with patients receiving tamoxifen/goserelin (BMD, −11.6%; mean T score reduction, −1.1). In contrast, BMD remained stable in zoledronic acid–treated patients (P < .0001 compared with endocrine therapy alone). No interactions with age or other risk factors were noted.

Conclusion

Endocrine therapy caused significant bone loss that increased with treatment duration in premenopausal women with breast cancer. Zoledronic acid 4 mg every 6 months effectively inhibited bone loss. Regular BMD measurements and initiation of concomitant bisphosphonate therapy on evidence of bone loss should be considered for patients undergoing endocrine therapy.
Adjuvant Chemotherapy Followed By Goserelin Compared With Either Modality Alone: The Impact on Amenorrhea, Hot Flashes, and Quality of Life in Premenopausal Patients—The International Breast Cancer Study Group Trial VIII
Authors: Bernhard Jürg , Zahrieh David , Castiglione-Gertsch Monica , Hürny Christoph , Gelber Richard D. , Forbes John F. , Murray Elizabeth , Collins John , Aebi Stefan , Thürlimann Beat , Price Karen N. , Goldhirsch Aron , Coates Alan S.
Published: December 2006

Purpose

The purpose of this article is to compare quality of life (QOL) and menopausal symptoms among premenopausal patients with lymph node-negative breast cancer receiving chemotherapy, goserelin, or their sequential combination, and to investigate differential effects by age.

Patients and Methods

We evaluated QOL data from 874 pre- and perimenopausal women with lymph node-negative breast cancer who were randomly assigned to receive six courses of classical cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy, ovarian suppression with goserelin for 24 months, or six courses of classical CMF followed by 18 months of goserelin. We report QOL data collected during 3 years after random assignment in patients without disease recurrence.

Results

Overall, patients receiving goserelin alone showed a marked improvement or less deterioration in QOL measures over the first 6 months than those patients treated with CMF. There were no differences at 3 years after random assignment according to treatment except for hot flashes. As reflected in the hot flashes scores, patients in all three treatment groups experienced induced amenorrhea, but the onset of ovarian function suppression was slightly delayed for patients receiving chemotherapy. Younger patients (< 40 years) who received goserelin alone returned to their premenopausal status at 6 months after the cessation of therapy, while those who received CMF showed marginal changes from their baseline hot flashes scores.

Conclusion

Age-adjusted risk profiles that consider patient-reported outcomes enable patients to adapt to their disease and treatment, such as considering the trade-offs between delayed endocrine symptoms, but higher risk of permanent menopause with chemotherapy, and immediate but reversible endocrine symptoms with goserelin, in younger premenopausal patients.
Zoledronic Acid Inhibits Adjuvant Letrozole–Induced Bone Loss in Postmenopausal Women With Early Breast Cancer
Authors: Brufsky Adam , Harker W. Graydon , Beck J. Thaddeus , Carroll Robert , Tan-Chiu Elizabeth , Seidler Christopher , Hohneker John , Lacerna Leo , Petrone Stephanie , Perez Edith A.
Published: December 2006

Purpose

Treatment with aromatase inhibitors decreases bone mineral density (BMD) and may increase the risk of fractures in postmenopausal women with early-stage breast cancer. The addition of zoledronic acid to adjuvant letrozole therapy may protect against bone loss.

Patients and Methods

Patients receiving adjuvant letrozole were randomly assigned to receive either upfront or delayed-start zoledronic acid (4 mg intravenously every 6 months). The delayed group received zoledronic acid when lumbar spine (LS) or total hip (TH) T score decreased to less than −2.0 or when a nontraumatic fracture occurred. The primary end point of this study was to compare the change in LS BMD at month 12 between the groups. Secondary end points included change in TH BMD and changes in serum bone turnover markers at month 12.

Results

The upfront and delayed groups each included 301 patients. At month 12, LS BMD was 4.4% higher in the upfront group than in the delayed group (95% CI, 3.7% to 5.0%; P < .0001), and TH BMD was 3.3% higher (95% CI, 2.8% to 3.8%; P < .0001). In the upfront group, mean serum N-telopeptide and bone-specific alkaline phosphatase concentrations decreased by 15.1% (P < .0001) and 8.8% (P = .0006), respectively, at month 12, whereas concentrations increased significantly in the delayed group by 19.9% (P = .013) and 24.3% (P < .0001), respectively.

Conclusion

With 1 year of follow-up, results of the primary end point of the Zometa-Femara Adjuvant Synergy Trial (Z-FAST) indicate that upfront zoledronic acid therapy prevents bone loss in the LS in postmenopausal women receiving adjuvant letrozole for early-stage breast cancer.
Quality of Life After Contralateral Prophylactic Mastectomy in Newly Diagnosed High-Risk Breast Cancer Patients Who Underwent BRCA1/2 Gene Testing
Authors: Tercyak Kenneth P. , Peshkin Beth N. , Brogan Barbara M. , DeMarco Tiffani , Pennanen Marie F. , Willey Shawna C. , Magnant Colette M. , Rogers Sarah , Isaacs Claudine , Schwartz Marc D.
Published: December 2006

Purpose

Recent studies indicate that high-risk breast cancer patients (ie, women who carry mutations in BRCA1/2 genes) who opt for contralateral prophylactic mastectomy (CPM) have a substantially reduced risk of developing contralateral breast cancer. However, the immediate and long-term impact of this decision on women's quality of life and psychosocial functioning is largely unknown. In this study, we compared the impact of BRCA1/2 genetic test result and CPM on these outcomes among newly diagnosed breast cancer patients who opted for CPM at the time of their definitive surgical treatment versus patients who did not.

Patients and Methods

Participants were 149 high-risk women who underwent genetic counseling and testing for alterations in the BRCA1/2 genes. We measured self-reported quality of life, cancer-specific distress, and genetic testing–specific distress using standardized instruments before receipt of genetic test results and again 1 and 12 months later.

Results

Compared with patients who chose breast conservation or unilateral mastectomy, those who chose mastectomy of the affected breast and CPM of the unaffected breast did not report diminished quality of life or elevated distress.

Conclusion

With respect to quality of life and distress, patients who choose CPM fare as well as those who do not in the first year after surgery.
Projections ofDrosophilamultidendritic neurons in the central nervous system: links with peripheral dendrite morphology
Authors: Grueber Wesley B. , Ye Bing , Yang Chung-Hui , Younger Susan , Borden Kelly , Jan Lily Y. , Jan Yuh-Nung
Published: December 2006

Neurons establish diverse dendritic morphologies during development, and a major challenge is to understand how these distinct developmental programs might relate to, and influence, neuronal function. Drosophiladendritic arborization (da) sensory neurons display class-specific dendritic morphology with extensive coverage of the body wall. To begin to build a basis for linking dendrite structure and function in this genetic system, we analyzed da neuron axon projections in embryonic and larval stages. We found that multiple parameters of axon morphology, including dorsoventral position,midline crossing and collateral branching, correlate with dendritic morphological class. We have identified a class-specific medial-lateral layering of axons in the central nervous system formed during embryonic development, which could allow different classes of da neurons to develop differential connectivity to second-order neurons. We have examined the effect of Robo family members on class-specific axon lamination, and have also taken a forward genetic approach to identify new genes involved in axon and dendrite development. For the latter, we screened the third chromosome at high resolution in vivo for mutations that affect class IV da neuron morphology. Several known loci, as well as putative novel mutations, were identified that contribute to sensory dendrite and/or axon patterning. This collection of mutants, together with anatomical data on dendrites and axons, should begin to permit studies of dendrite diversity in a combined developmental and functional context, and also provide a foundation for understanding shared and distinct mechanisms that control axon and dendrite morphology.
Infertility caused by retardation of follicular development in mice with oocyte-specific expression of Foxo3a
Authors: Liu Lian , Rajareddy Singareddy , Reddy Pradeep , Du Chun , Jagarlamudi Krishna , Shen Yan , Gunnarsson David , Selstam Gunnar , Boman Karin , Liu Kui
Published: December 2006

In recent years, mammalian oocytes have been proposed to have important roles in the orchestration of ovarian follicular development and fertility. To determine whether intra-oocyte Foxo3a, a component of the phosphatidylinositol 3-kinase (PI3K) signaling pathway, influences follicular development and female fertility, a transgenic mouse model was generated with constitutively active Foxo3a expressed in oocytes. We found that the female transgenic mice were infertile, which was caused by retarded oocyte growth and follicular development, and anovulation. Further mechanistic studies revealed that the constitutively active Foxo3a in oocytes caused a dramatic reduction in the expression of bone morphogenic protein 15 (Bmp15), connexin 37 and connexin 43, which are important molecules for the establishment of paracrine and gap junction communications in follicles. Foxo3a was also found to facilitate the nuclear localization of p27kip1 in oocytes, a cyclin-dependent kinase (Cdk) inhibitor that may serve to inhibit oocyte growth. The results from the current study indicate that Foxo3a is an important intra-oocyte signaling molecule that negatively regulates oocyte growth and follicular development. Our study may therefore give some insight into oocyte-borne genetic aberrations that cause defects in follicular development and anovulation in human diseases, such as premature ovarian failure.
Histone methylation is required for oogenesis inDrosophila
Authors: Clough Emily , Moon Woongjoon , Wang Shengxian , Smith Kathleen , Hazelrigg Tulle
Published: December 2006

SET domain proteins are histone lysine methyltransferases (HMTs) that play essential roles in development. Here we show for the first time that histone methylation occurs in both the germ cells and somatic cells of the Drosophila ovary, and demonstrate in vivo that an HMT, the product of the eggless (egg) gene, is required for oogenesis. Egg is a SET domain protein that is similar to the human protein SETDB1 and its mouse ortholog ESET. These proteins are members of a small family of HMTs that contain bifurcated SET domains. Because depletion of SETDB1 in tissue culture cells is cell-lethal, and an ESET mutation causes very early periimplantation embryonic arrest, the role of SETDB1/ESET in development has proven difficult to address. We show that egg is required in the Drosophilaovary for trimethylation of histone H3 at its K9 residue. In females bearing an egg allele that deletes the SET domain, oogenesis arrests at early stages. This arrest is accompanied by reduced proliferation of somatic cells required for egg chamber formation, and by apoptosis in both germ and somatic cell populations. We propose that other closely related SET domain proteins may function similarly in gametogenesis in other species.
The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1
Authors: Ramsey Victoria G. , Doherty Jason M. , Chen Christopher C. , Stappenbeck Thaddeus S. , Konieczny Stephen F. , Mills Jason C.
Published: December 2006

Continuous regeneration of digestive enzyme (zymogen)-secreting chief cells is a normal aspect of stomach function that is disrupted in precancerous lesions (e.g. metaplasias, chronic atrophy). The cellular and genetic pathways that underlie zymogenic cell (ZC) differentiation are poorly understood. Here,we describe a gene expression analysis of laser capture microdissection purified gastric cell populations that identified the bHLH transcription factor Mist1 as a potential ZC regulatory factor. Our molecular and ultrastructural analysis of proliferation, migration and differentiation of the gastric unit in Mist1-/- and control mice supports a model whereby wild-type ZC progenitors arise as neck cells in the proliferative (isthmal) zone of the gastric unit and become transitional cells(TCs) with molecular and ultrastructural characteristics of both enzyme-secreting ZCs and mucus-secreting neck cells as they migrate to the neck-base zone interface. Thereafter, they rapidly differentiate into mature ZCs as they enter the base. By contrast, Mist1-/- neck cells differentiate normally, but ZCs in the mature, basal portion of the gastric unit uniformly exhibit multiple apical cytoplasmic structural abnormalities. This defect in terminal ZC differentiation is also associated with markedly increased abundance of TCs, especially in late-stage TCs that predominantly have features of immature ZCs. Thus, we present an in vivo system for analysis of ZC differentiation, present molecular evidence that ZCs differentiate from neck cell progenitors and identify Mist1 as the first gene with a role in this clinically important process.
Dusp6(Mkp3) is a negative feedback regulator of FGF-stimulated ERK signaling during mouse development
Authors: Li Chaoying , Scott Daryl A. , Hatch Ekaterina , Tian Xiaoyan , Mansour Suzanne L.
Published: December 2006

Mitogen-activated protein kinase (MAPK) pathways are major mediators of extracellular signals that are transduced to the nucleus. MAPK signaling is attenuated at several levels, and one class of dual-specificity phosphatases,the MAPK phosphatases (MKPs), inhibit MAPK signaling by dephosphorylating activated MAPKs. Several of the MKPs are themselves induced by the signaling pathways they regulate, forming negative feedback loops that attenuate the signals. We show here that in mouse embryos, Fibroblast growth factor receptors (FGFRs) are required for transcription of Dusp6, which encodes MKP3, an extracellular signal-regulated kinase (ERK)-specific MKP. Targeted inactivation of Dusp6 increases levels of phosphorylated ERK, as well as the pERK target, Erm, and transcripts initiated from the Dusp6 promoter itself. Finally, the Dusp6 mutant allele causes variably penetrant, dominant postnatal lethality, skeletal dwarfism,coronal craniosynostosis and hearing loss; phenotypes that are also characteristic of mutations that activate FGFRs inappropriately. Taken together, these results show that DUSP6 serves in vivo as a negative feedback regulator of FGFR signaling and suggest that mutations in DUSP6 or related genes are candidates for causing or modifying unexplained cases of FGFR-like syndromes.
Homeobox geneDlx3is regulated by p63 during ectoderm development: relevance in the pathogenesis of ectodermal dysplasias
Authors: Radoja Nadezda , Guerrini Luisa , Lo Iacono Nadia , Merlo Giorgio R. , Costanzo Antonio , Weinberg Wendy C. , La Mantia Girolama , Calabrò Viola , Morasso Maria I.
Published: December 2006

Ectodermal dysplasias (EDs) are a group of human pathological conditions characterized by anomalies in organs derived from epithelial-mesenchymal interactions during development. Dlx3 and p63 act as part of the transcriptional regulatory pathways relevant in ectoderm derivatives, and autosomal mutations in either of these genes are associated with human EDs. However, the functional relationship between both proteins is unknown. Here,we demonstrate that Dlx3 is a downstream target of p63. Moreover, we show that transcription of Dlx3 is abrogated by mutations in the sterile α-motif (SAM) domain of p63 that are associated with ankyloblepharon-ectodermal dysplasia-clefting (AEC) dysplasias, but not by mutations found in ectrodactylyectodermal dysplasia-cleft lip/palate (EEC),Limb-mammary syndrome (LMS) and split hand-foot malformation (SHFM)dysplasias. Our results unravel aspects of the transcriptional cascade of events that contribute to ectoderm development and pathogenesis associated with p63 mutations.
Patterning the zebrafish diencephalon by the conserved zinc-finger protein Fezl
Authors: Jeong Jae-Yeon , Einhorn Zev , Mathur Priya , Chen Lishan , Lee Susie , Kawakami Koichi , Guo Su
Published: December 2006

The forebrain constitutes the most anterior part of the central nervous system, and is functionally crucial and structurally conserved in all vertebrates. It includes the dorsally positioned telencephalon and eyes, the ventrally positioned hypothalamus, and the more caudally located diencephalon[from rostral to caudal: the prethalamus, the zona limitans intrathalamica(ZLI), the thalamus and the pretectum]. Although antagonizing Wnt proteins are known to establish the identity of the telencephalon and eyes, it is unclear how various subdivisions are established within the diencephalon - a complex integration center and relay station of the vertebrate brain. The conserved forebrain-specific zinc-finger-containing protein Fezl plays a crucial role in regulating neuronal differentiation in the vertebrate forebrain. Here, we report a new and essential role of zebrafish Fezl in establishing regional subdivisions within the diencephalon. First, reduced activity of fezlresults in a deficit of the prethalamus and a corresponding expansion of the ZLI. Second, Gal4-UAS-mediated fezl overexpression in late gastrula is capable of expanding the prethalamus telencephalon and hypothalamus at the expense of the ZLI and other fore- and/or mid-brain regions. Such altered brain regionalization is preceded by the early downregulation of wntexpression in the prospective diencephalon. Finally, fezloverexpression is able to restore the anterior forebrain and downregulate wnt expression in Headless- and/or Tcf3 (also known as Tcf7l1a)-deficient embryos. Our findings reveal that Fezl is crucial for establishing regional subdivisions within the diencephalon and may also play a role in the development of the telencephalon and hypothalamus.
Cyp26 enzymes generate the retinoic acid response pattern necessary for hindbrain development
Authors: Hernandez Rafael E. , Putzke Aaron P. , Myers Jonathan P. , Margaretha Lilyana , Moens Cecilia B.
Published: December 2006

Retinoic acid (RA) is essential for normal vertebrate development,including the patterning of the central nervous system. During early embryogenesis, RA is produced in the trunk mesoderm through the metabolism of vitamin A derived from the maternal diet and behaves as a morphogen in the developing hindbrain where it specifies nested domains of Hox gene expression. The loss of endogenous sources of RA can be rescued by treatment with a uniform concentration of exogenous RA, indicating that domains of RA responsiveness can be shaped by mechanisms other than the simple diffusion of RA from a localized posterior source. Here, we show that the cytochrome p450 enzymes of the Cyp26 class, which metabolize RA into polar derivatives,function redundantly to shape RA-dependent gene-expression domains during hindbrain development. In zebrafish embryos depleted of the orthologs of the three mammalian CYP26 genes CYP26A1, CYP26B1 and CYP26C1, the entire hindbrain expresses RA-responsive genes that are normally restricted to nested domains in the posterior hindbrain. Furthermore,we show that Cyp26 enzymes are essential for exogenous RA to rescue hindbrain patterning in RA-depleted embryos. We present a `gradient-free' model for hindbrain patterning in which differential RA responsiveness along the hindbrain anterior-posterior axis is shaped primarily by the dynamic expression of RA-degrading enzymes.
An evaluation of post-sclerotherapy laser compression and its efficacy in the treatment of leg telangiectasias
Authors: Sadick N S , Sorhaindo L
Published: December 2006

Objective: The use of graduated compression stockings is presently indicated in both surgical and non-surgical treatment of varicose veins. The role that it plays in therapeutic efficacy or the complication profile is yet to be determined. The present study examined the role of compression in the treatment of class I–II venulectasia, utilizing the Pulsed Dye Laser.

Methods: Thirteen patients with leg vein size 0.5–1.0 mm in diameter were treated with the Long-Pulse Tuneable Dye Laser (Vbeam®). A surface area of 5 cm2 of vessels on bilaterally symmetric thighs was treated. Class II compression hose was applied immediately following treatment to the left thigh only and were left on during waking hours for a period of 7 days. Post-sclerotherapy results and complication profiles were analysed and graded after one treatment session by two independent blinded observers.

Results: There was no significant difference in treatment-clearing parameters or side-effect profiles in the compressed versus non-compressed or control groups ( P≤0.05).

Conclusion: Preliminary studies suggest that compression does not alter the therapeutic efficacy or complication profile of Pulsed Dye Laser treatment of class I–II venulectasia. Further studies on a larger patient population are in progress.
Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs – UIP Consensus Document. Part I: Basic principles
Authors: Coleridge-Smith P , Labropoulos N , Partsch H , Myers K , Nicolaides A , Cavezzi A
Published: December 2006

Objectives: Duplex ultrasound investigation has become the reference standard in assessing the morphology and haemodynamics of the lower limb veins. The project described in this paper was an initiative of the Union Internationale de Phlébologie (UIP). The aim was to obtain a consensus of international experts on the methodology to be used for assessment of veins in the lower limb by ultrasound imaging.

Design: Consensus conference leading to a consensus document.

Methods: The authors invited a group of experts from a wide range of countries to participate in this project. Electronic submissions from the experts were made available to all participants via the UIP website. The authors prepared a draft document for discussion at a UIP Chapter meeting held in San Diego, USA, in August 2003. Following this meeting, a revised manuscript was circulated to all participants, and further comments were received by the authors and included in subsequent versions of the manuscript. Eventually, all participants agreed on a final version of the paper.

Results: The experts have made detailed recommendations concerning the methods to be used for duplex ultrasound examination, as well as the interpretation of images and measurements obtained. This document suggests a methodology for complete assessment of the superficial and perforating veins of the lower limbs, including recommendations on reporting results and training of personnel involved in these investigations.

Conclusions: The authors and a large group of experts have agreed a methodology for the investigation of the lower limbs venous system by duplex ultrasonography.
Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs – UIP Consensus Document. Part II: Anatomy
Authors: Cavezzi A , Labropoulos N , Partsch H , Ricci S , Caggiati A , Myers K , Nicolaides A , Coleridge-Smith P
Published: December 2006

Objectives: Duplex ultrasound investigation has become the reference standard in assessing the morphology and haemodynamics of the lower limb veins. The project described in this paper was an initiative of the Union Internationale de Phlébologie (UIP). The aim was to obtain a consensus of international experts on the methodology to be used for assessment of the anatomy of superficial and perforating veins in the lower limb by ultrasound imaging.

Design: Consensus conference leading to a consensus document.

Methods: The authors performed a systematic review of the published literature on duplex anatomy of the superficial and perforating veins of the lower limbs. Afterwards, they invited a group of experts from a wide range of countries to participate in this project. Electronic submissions from the authors and the experts (text and images) were made available to all participants via the UIP website. The authors prepared a draft document for discussion at the UIP Chapter meeting held in San Diego, USA, in August 2003. Following this meeting, a revised manuscript was circulated to all participants and further comments were received by the authors and included in subsequent versions of the manuscript. Eventually, all participants agreed on the final version of the paper.

Results: The experts have made detailed recommendations concerning the methods to be used for duplex ultrasound examination as well as the interpretation of images and measurements obtained. This document provides a detailed methodology for complete ultrasound assessment of the anatomy of the superficial and perforating veins in the lower limbs.

Conclusions: The authors and a large group of experts have agreed on a methodology for the investigation of the lower limbs venous system, by duplex ultrasonography, with specific reference to the anatomy of the main superficial veins and perforators of the lower limbs in healthy and varicose subjects.
Varisolve® polidocanol microfoam compared with surgery or sclerotherapy in the management of varicose veins in the presence of trunk vein incompetence: European randomized controlled trial
Authors: Wright D , Gobin J P , Bradbury A W , Coleridge-Smith P , Spoelstra H , Berridge D , Wittens C H A , Sommer A , Nelzen O , Chanter D ,   The Varisolve® European Phase III Investigators Group
Published: December 2006

Objective: To compare the safety and efficacy of Varisolve® 1% polidocanol microfoam sclerosant with alternative treatments for patients with varicose veins and trunk vein incompetence.

Methods: An open-label, multicentre, prospective trial of 710 patients randomized to receive either Varisolve® or alternative treatment (surgery or sclerotherapy). The endpoint was ultrasound-determined occlusion of trunk vein(s) and elimination of reflux, analysed against a non-inferiority hypothesis.

Results: Overall, non-inferiority was demonstrated with 83.4% efficacy for Varisolve® compared with 88.1% for alternative treatment at three months, and the corresponding magnitudes were 78.9 and 80.4% at 12 months. Surgery was superior to Varisolve®, but the success rate of 68.2% for Varisolve® (surgery 87.2%) was poor compared with 93.8% success for Varisolve® achieved in those randomized to Varisolve® or sclerotherapy. Varisolve® was superior to sclerotherapy at 12 months ( P = 0.001). Deep vein thrombosis occurred in 11/437 (2.5%) after Varisolve®, in 1/125 (0.8%) after sclerotherapy and in none after surgery. No pulmonary emboli were detected.

Conclusion: Overall, Varisolve® was non-inferior to alternative treatment. Surgery was more efficacious, but Varisolve® caused less pain and patients returned to normal more quickly. The Varisolve® technique is a useful additional treatment for varicose veins and trunk vein incompetence.
Identification of a sequence motif critical for editing of a tobacco chloroplast transcript
Authors: Hayes Michael L. , Hanson Maureen R.
Published: December 2006

Nucleotides are specifically and efficiently targeted for modification from C to U within transcripts of chloroplasts in higher plants. Although the enzymatic apparatus responsible for altering C to U has not been identified, the sequences surrounding editing sites are known to contain information essential for efficient editing. We set out to determine the nucleotides that are critical for editing of a particular C, NTpsbE C214, in chloroplast transcripts in tobacco. Assay of editing of substrates with different lengths of 5′ and 3′ sequence around the target C was carried out to delimit the region of sequence critical for editing in vitro. Mutated substrates were then constructed with an altered nucleotide at each position within the previously defined region around NTpsbE C214. In individual nucleotides, both 5′ and 3′ of the edited nucleotide were found to be important for editing. The sequence GCCGUU, which occurs 5′ of the editing site, was discovered to be critical for editing. Editing substrates mutated to alter the distance between the GCCGUU sequence and NTpsbE C214 resulted in the generation of a new editing target, the 3′ adjacent nucleotide. These data are consistent with a model in which the selection of the C target for editing is determined by its distance from a crucial 5′ sequence.
Minimally-invasive treatment of intra-articular fractures of the calcaneum
Authors: Stulik J. , Stehlik J. , Rysavy M. , Wozniak A.
Published: December 2006

We describe the results of 287 intra-articular fractures of the calcaneum in 247 patients treated by minimally-invasive reduction and K-wire fixation between 1994 and 2003. There were 210 men (85%) and 37 women (15%). The most common cause of injury was a fall from a height in 237 patients (96%). Fracture classification was based on the method described by Sanders and Essex-Lopresti. All patients were operated on within 21 days of injury and 89% (220) within 48 hours. The reduction was graded as nearly anatomical (less than 2 mm residual articular displacement and satisfactory overall alignment) in 212 (73.9%) fractures.

There were 20 cases (7%) of superficial pin-track infection and five (1.7%) of deep infection. All healed at a mean of 6 weeks (3 to 19). Loss of reduction was observed in 13 fractures (4.5%) and a musculocutaneous flap was needed in three (1%).

The results were evaluated in 176 patients (205 fractures) with a mean age of 44.3 years (13 to 67), available for follow-up at a mean of 43.4 months (25 to 87) using the Creighton-Nebraska Health Foundation Assessment score. The mean score was 83.9 points (63 to 100). There were 29 (16.5%) excellent, 98 (55.7%) good, 26 (14.8%) fair and 23 (13%) poor results. A total of 130 patients (73.9%) were able to return to their original occupation at a mean of 5.6 months (3.2 to 12.5) after the injury.

Semi-open reduction and percutaneous fixation is an effective treatment for displaced intra-articular fractures of the calcaneum.
Neurolysis is not required for young patients with a spontaneous palsy of the anterior interosseous nerve
Authors: Seki M. , Nakamura H. , Kono H.
Published: December 2006

We studied 21 patients with a spontaneous palsy of the anterior interosseous nerve. There were 11 men and 10 women with a mean age at onset of 39 years (17 to 65).

Pain around the elbow or another region (forearm, shoulder, upper arm, systemic arthralgia) was present in 17 patients and typically lasted for two to three weeks. It had settled within six weeks in every case. In ten cases the palsy developed as the pain settled. A complete palsy of flexor pollicis longus and flexor digitorum profundus to the index finger was seen in 13 cases and an isolated palsy of flexor pollicis longus in five. All patients were treated without operation. The mean time to initial muscle contraction was nine months (2 to 18) in palsy of the flexor digitorum profundus to the index finger, and ten months (1 to 24) for a complete palsy of flexor pollicis longus. An improvement in muscle strength to British Medical Research Council grade 4 or better was seen in all 15 patients with a complete palsy of the flexor digitorum profundus and in 16 of 18 with a complete palsy of flexor pollicis longus.

There was no significant correlation between the duration of pain and either the time to initial muscle contraction or final muscle strength. Prolonged pain was not always associated with a poor outcome but the age of the patient when the palsy developed was strongly correlated. Recovery occurred within 12 months in patients under the age of 40 years who achieved a final British Medical Research Council grade of 4 or better. Surgical decompression does not appear to be indicated for young patients with this condition.
The undiagnosed Essex-Lopresti injury
Authors: Jungbluth P. , Frangen T. M. , Arens S. , Muhr G. , Kälicke T.
Published: December 2006

The Essex-Lopresti injury is rare. It consists of fracture of the head of the radius, rupture of the interosseous membrane and disruption of the distal radioulnar joint. The injury is often missed because attention is directed towards the fracture of the head of the radius. We present a series of 12 patients with a mean age of 44.9 years (26 to 54), 11 of whom were treated surgically at a mean of 4.6 months (1 to 16) after injury and the other after 18 years. They were followed up for a mean of 29.2 months (2 to 69). Ten patients had additional injuries to the forearm or wrist, which made diagnosis more difficult. Replacement of the head of the radius was carried out in ten patients and the Sauve-Kapandji procedure in three. Patients were assessed using standard outcome scores. The mean post-operative Disabilities of the Arm, Shoulder and Hand score was 55 (37 to 83), the mean Morrey Elbow Performance score was 72.2 (39 to 92) and the mean Mayo wrist score was 61.3 (35 to 80). The mean grip strength was 68.5% (39.6% to 91.3%) of the unaffected wrist.

Most of the patients (10 of 12) were satisfied with their operation and in 11 the pain was relieved. When treating the chronic Essex-Lopresti injury, we recommend accurate realignment of the radius and ulna and replacement of the head of the radius. If this fails a Sauve-Kapandji procedure to arthrodese the distal radioulnar joint should be undertaken to stabilise the forearm while maintaining mobility.
Long-term survival of a cemented titanium-aluminium-vanadium alloy straight-stem femoral component
Authors: Kovac S. , Trebse R. , Milosev I. , Pavlovcic V. , Pisot V.
Published: December 2006

We present a retrospective series of 170 cemented titanium straight-stem femoral components combined with two types of femoral head: cobalt-chromium (CoCr) alloy (114 heads) and alumina ceramic (50 heads). Of the study group, 55 patients (55 stems) had died and six (six stems) were lost to follow-up. At a mean of 13.1 years (3 to 15.3) 26 stems had been revised for aseptic loosening. The mean follow-up time for stable stems was 15.1 years (12.1 to 16.6).

Survival of the stem at 15 years was 75.4% (95% confidence interval (CI) 67.3 to 83.5) with aseptic failure (including radiological failure) as the end-point, irrespective of the nature of the head and the quality of the cement mantle. Survival of the stem at 15 years was 79.1% (95% CI 69.8 to 88.4) and 67.1% (95% CI 51.3 to 82.9) with the CoCr alloy and ceramic heads, respectively. The quality of the cement mantle was graded as a function of stem coverage: stems with complete tip coverage (type 1) had an 84.9% (95% CI 77.6 to 92.2) survival at 15 years, compared with those with a poor tip coverage (type 2) which had a survival of only 22.4% (95% CI 2.4 to 42.4). The poor quality of the cement mantle and the implantation of an alumina head substantially lowered the survival of the stem.

In our opinion, further use of the cemented titanium alloy straight-stem femoral components used in our series is undesirable.
A ceramic prosthesis for the treatment of tumours of the distal radius
Authors: Hatano H. , Morita T. , Kobayashi H. , Otsuka H.
Published: December 2006

Despite extensive experience with prosthetic replacement for the reconstruction of limbs following juxta-articular resection of tumours, there are few reports of prosthetic replacement of the distal radius. We present two cases of massive bone defects of the distal radius in which alumina ceramic prosthetic replacements were used. We evaluated the patients more than ten years after the procedure. Both patients had degenerative changes to the wrist. This, however, was not associated with pain or decreased function, and both had returned to their previous occupation after surgery.

When a patient has a massive defect of the distal radius, reconstruction using a ceramic prosthesis is a reasonable alternative to using autograft. This method of treatment results in little pain, a moderate range of movement and satisfactory function.
Topographical variation in glycosaminoglycan content in human articular cartilage
Authors: Rogers B. A. , Murphy C. L. , Cannon S. R. , Briggs T. W. R.
Published: December 2006

The weight-bearing status of articular cartilage has been shown to affect its biochemical composition. We have investigated the topographical variation of sulphated glycosaminoglycan (GAG) relative to the DNA content of the chondrocyte in human distal femoral articular cartilage.

Paired specimens of distal femoral articular cartilage, from weight-bearing and non-weight-bearing regions, were obtained from 13 patients undergoing above-knee amputation. After papain enzyme digestion, spectrophotometric GAG and fluorometric DNA assays assessed the biochemical composition of the samples. The results were analysed using a paired t-test.

Although there were no significant differences in cell density between the regions, the weight-bearing areas showed a significantly higher concentration of GAG relative to DNA when compared with non-weight-bearing areas (p = 0.02).

We conclude that chondrocytes are sensitive to their mechanical environment, and that local loading conditions influence the metabolism of the cells and hence the biochemical structure of the tissue.
The consequences of meniscectomy
Authors: McDermott I. D. , Amis A. A.
Published: December 2006

The menisci of the knee have an important role in load-bearing and shock absorption within the joint. They may also function as secondary stabilisers, have a proprioceptive role, and aid the lubrication and nutrition of the articular cartilage. Complete or partial loss of a meniscus can have damaging effects on a knee, leading to serious long-term sequelae.

This paper reviews the consequences of meniscectomy and summarises the body of evidence in the literature regarding those factors most relevant to long-term outcome.
Fracture of the stem of the femoral component after resurfacing arthroplasty of the hip
Authors: Bowman N. K. , Bucher T. A. , Bassily A. A.
Published: December 2006

Resurfacing arthroplasties of the hip are being undertaken with increasing frequency and the complications associated with this procedure are well documented. We have encountered a further problem with a fracture of the centralising peg of the femoral component in a prosthesis which had been in situ for three years.
Simultaneous in vitro measurement of patellofemoral kinematics and forces following Oxford medial unicompartmental knee replacement
Authors: Price A. J. , Oppold P. T. , Murray D. W. , Zavatsky A. B.
Published: December 2006

The Oxford medial unicompartmental knee replacement was designed to reproduce normal mobility and forces in the knee, but its detailed effect on the patellofemoral joint has not been studied previously. We have examined the effect on patellofemoral mechanics of the knee by simultaneously measuring patellofemoral kinematics and forces in 11 cadaver knee specimens in a supine leg-extension rig. Comparison was made between the intact normal knee and sequential unicompartmental and total knee replacement. Following medial mobile-bearing unicompartmental replacement in 11 knees, patellofemoral kinematics and forces did not change significantly from those in the intact knee across any measured parameter. In contrast, following posterior cruciate ligament retaining total knee replacement in eight knees, there were significant changes in patellofemoral movement and forces.

The Oxford device appears to produce near-normal patellofemoral mechanics, which may partly explain the low incidence of complications with the extensor mechanism associated with clinical use.
Arthroscopic surgery of the hip
Authors: Khanduja V. , Villar R. N.
Published: December 2006

This review describes the development of arthroscopy of the hip over the past 15 years with reference to patient assessment and selection, the technique, the conditions for which it is likely to prove useful, the contraindications and complications related to the procedure and, finally, to discuss possible developments in the future.
Predicting global and topic‐specific certainty beliefs: Domain‐specificity and the role of the academic environment
Authors: Trautwein Ulrich. , Lüdtke Oliver.
Published: December 2006

Background. Epistemological beliefs are subjective theories of the structure and acquisition of knowledge. The instruments used to measure epistemological beliefs in educational psychology (see Duell & Schommer‐Aikins, 2001) typically consist of questionnaires tapping general, decontextualized beliefs about knowledge or knowledge acquisition in a specific field or in general.

Aims. Using specific theories as stimuli, we determine the degree of topic‐specificity of certainty beliefs as well as the association between certainty beliefs and the learning environment.

Sample. Participants were 662 upper secondary school students (Study 1) and 211 college students (Study 2).

Method. A global instrument and a topic‐specific instrument were used to collect responses to up to 10 stimulus theories. Factor analysis, multiple regression analysis and multi‐level modelling were carried out.

Results. Students' topic‐specific certainty beliefs varied markedly across the stimulus theories. Furthermore, students in different academic environments differed more strongly on global certainty beliefs than on topic‐specific certainty beliefs, and global certainty beliefs were only loosely connected to topic‐specific certainty beliefs.

Conclusion. Researchers should critically assess the validity of decontextualized global questionnaires for assessing certainty beliefs. If possible, global measures should be complemented by topic‐specific measures.
Congruence between reasons for depression and motivations for specific interventions
Authors: Meyer Björn , Garcia‐Roberts Lilian
Published: December 2006

The reasons depressed clients report for their depression are thought to be important predictors of therapy process and outcome, but few studies have so far examined whether particular reasons are systematically associated with client motivations to engage with reason‐matching interventions. We hypothesized that the congruence between reasons and interventions would predict higher levels of treatment motivation. Ninety‐seven adult out‐patients from the UK completed the Reasons for Depression (RFD) questionnaire (Addis, Truax, & Jacobson, 1995) and a newly developed Motivations for Interventions questionnaire that examined the extent to which patients would prefer to receive a type of therapy that targets their perceived reasons for depression. The results generally supported the reasons‐interventions congruence hypothesis, but more so for certain specific reasons. For example, clients who believed that their depression was caused primarily by unresolved childhood issues or by biological predispositions were relatively specifically motivated to engage with treatments that target these domains. In general, clients who endorsed interpersonal reasons tended to be specifically motivated for interpersonally orientated interventions, and those who endorsed autonomous depression reasons tended to be specifically motivated to engage with autonomy‐facilitative interventions. The study also introduces a new subscale for the RFD questionnaire ‐ the cognitive reasons scale. Implications for theory development and treatment planning are discussed.
Micro-Deval Test for the Assessment of Bituminous Aggregate Durability
Authors: Jayawickrama PW , Hossain MS , Phillips F
Published: December 2006

Bituminous aggregates from a total of 52 sources located in Texas, Oklahoma, Arkansas, New Mexico, and Missouri were evaluated using both Micro-Deval and magnesium sulfate soundness tests. Each aggregate was also characterized using petrography, absorption, and specific gravity. Findings showed that Micro-Deval test is a more repeatable test than the soundness test. Micro-Deval showed a fair to good correlation with soundness and an improved correlation was observed when used along with aggregate absorption values. It is concluded that further research is needed to completely replace soundness tests but the Micro-Deval test could be used as a good quality indicator tool.
Six Trophies and a Funeral: Performance and Football in the City of Valletta
Authors: ARMSTRONG GARY , MITCHELL JON
Published: December 2006

This paper examines the elaborate celebrations organized by the fans of Valletta City football (soccer) club, Malta, when they win the Maltese football league. It argues that these celebrations constitute a continuation of the carnivalesque. Valletta fans have a reputation for their fanatical support, and are renowned as tough‐guys. Their celebrations are moments of drunken excess, which celebrate this “diamond‐in‐the‐rough” authenticity, and satirize their opponents, which they see as inauthentic “pretenders.” The celebrations use symbolism drawn from an earlier carnival tradition—particularly the symbolism of death, and the re‐enactment of funereal performance. The paper therefore argues that contemporary football celebration has replaced the carnival as a cultural form through which social antagonisms—of locality and social class—are manifest. The paper also examines the relationship between these spontaneous celebrations, and state‐sponsored pageants—including the modern carnival—which are primarily aimed at tourists. [Football Celebration, Valletta, Carnival, Nostalgia, Class].
Cosmopolitanism and Nationalism in Shanghai Sports
Authors: LOZADA ERIBERTO P.
Published: December 2006

As the symbolic centerpiece of the “New China” and the dramatic transformation of a socialist economy to a market‐driven one, Shanghai holds a special place in the Chinese social imaginary of modernity and the good life. This Shanghai modernity, however, is marked by a tension between competing claims of cosmopolitanism and nationalism that are present in everyday cultural practices. Looking at Shanghai fans' consumption of sports reveals how competing claims of cosmopolitanism and nationalism play out in this global city, showing how these seemingly paradoxical ideas are resolved in popular culture through the process of localization. [Shanghai, China, cosmopolitanism, nationalism, sports, popular culture]