bluuebunny/crossref_metadata_2025 huggingface dataset:
Mycobacterial immune reconstitution inflammatory syndrome in HIV-1 infection after antiretroviral therapy is associated with deregulated specific T-cell responses: Beneficial effect of IL-2 and GM-CSF immunotherapy
Authors: Pires A , Nelson M , Pozniak AL , Fisher M , Gazzard B , Gotch F , Imami N
Published: September 2005

Background

With the advent of antiretroviral therapy (ART) cases of immune reconstitution inflammatory syndrome (IRIS) have increasingly been reported. IRIS usually occurs in individuals with a rapidly rising CD4 T-cell count or percentage upon initiation of ART, who develop a deregulated immune response to infection with or without reactivation of opportunistic organisms. Here, we evaluated rises in absolute CD4 T-cells, and specific CD4 T-cell responses in 4 HIV-1+ individuals presenting with mycobacterial associated IRIS who received in conjunction with ART, IL-2 plus GM-CSF immunotherapy.

Methods

We assessed CD4 T-cell counts, HIV-1 RNA loads, phenotype for naïve and activation markers, and in vitro proliferative responses. Results were compared with those observed in 11 matched, successfully treated asymptomatic clinical progressors (CP) with no evidence of opportunistic infections, and uninfected controls.

Results

Median CD4 T-cell counts in IRIS patients rose from 22 cells/μl before initiation of ART, to 70 cells/μl after 8 months of therapy (median 6.5 fold increase). This coincided with IRIS diagnosis, lower levels of naïve CD4 T-cells, increased expression of immune activation markers, and weak CD4 T-cell responses. In contrast, CP had a median CD4 T-cell counts of 76 cells/μl at baseline, which rose to 249 cells/μl 6 months post ART, when strong T-cell responses were seen in > 80% of patients. Higher levels of expression of immune activation markers were seen in IRIS patients compared to CP and UC (IRIS > CP > UC). Immunotherapy with IL-2 and GM-CSF paralleled clinical recovery.

Conclusion

These data suggest that mycobacterial IRIS is associated with inadequate immune reconstitution rather than vigorous specific T-cell responses, and concomitant administration of IL-2 and GM-CSF immunotherapy with effective ART may correct/augment T-cell immunity in such setting resulting in clinical benefit.
Selection of gonadotrophin surge attenuating factor phage antibodies by bioassay
Authors: Sorsa-Leslie Tarja , Mason Helen D , Harris William J , Fowler Paul A
Published: September 2005

Background

We aimed to combine the generation of "artificial" antibodies with a rat pituitary bioassay as a new strategy to overcome 20 years of difficulties in the purification of gonadotrophin surge-attenuating factor (GnSAF).

Methods

A synthetic single-chain antibody (Tomlinson J) phage display library was bio-panned with partially purified GnSAF produced by cultured human granulosa/luteal cells. The initial screening with a simple binding immunoassay resulted in 8 clones that were further screened using our in-vitro rat monolayer bioassay for GnSAF. Initially the antibodies were screened as pooled phage forms and subsequently as individual, soluble, single-chain antibody (scAbs) forms. Then, in order to improve the stability of the scAbs for immunopurification purposes, and to widen the range of labelled secondary antibodies available, these were engineered into full-length human immunoglobulins. The immunoglobulin with the highest affinity for GnSAF and a previously described rat anti-GnSAF polyclonal antiserum was then used to immunopurify bioactive GnSAF protein. The two purified preparations were electrophoresed on 1-D gels and on 7 cm 2-D gels (pH 4–7). The candidate GnSAF protein bands and spots were then excised for peptide mass mapping.

Results

Three of the scAbs recognised GnSAF bioactivity and subsequently one clone of the purified scAb-derived immunoglobulin demonstrated high affinity for GnSAF bioactivity, also binding the molecule in such as way as to block its bioactivity. When used for repeated immunopurification cycles and then Western blot, this antibody enabled the isolation of a GnSAF-bioactive protein band at around 66 kDa. Similar results were achieved using the rat anti-GnSAF polyclonal antiserum. The main candidate molecules identified from the immunopurified material by excision of 2-D gel protein spots was human serum albumin precursor and variants.

Conclusion

This study demonstrates that the combination of bioassay and phage display technologies is a powerful tool in the study of uncharacterised proteins that defy conventional approaches. In addition, we conclude that these data support suggestions that GnSAF may be structurally related to serum albumin or very tightly bound to serum albumin.
Quelque chose … de remarquable in English-French acquisition: mandatory, informationally encapsulated computations in second language interpretation
Authors: Dekydtspotter Laurent , Hathorn Jon C.
Published: September 2005

We discuss the results of an experiment that investigates English-French learners’ interpretation of quantifiers with detachable restrictions. Such quantifiers are ungrammatical in English. We investigate aspects of interpretation that rely on a highly idiosyncratic interface between grammar and general principles of conversational cooperation in native French. We show that a learning-theoretic challenge of the most severe kind arises in English-French acquisition unless second language acquisition is constrained by very specific relations between syntactic, semantic and pragmatic modules. We therefore argue that the emergence of knowledge of interpretation in English-French interlanguage suggests mandatory, informationally encapsulated computations. This supports Schwartz’s (1986; 1987; 1999) contention that inter-language knowledge is constrained by a mental organization in which Universal Grammar provides the contents of a largely universal processor devoted to language.
The perception of word boundaries in a second language
Authors: Altenberg Evelyn P.
Published: September 2005

Adult Spanish second language (L2) learners of English and native speakers of English participated in an English perception task designed to investigate their ability to use L2 acoustic-phonetic cues, e.g., aspiration, to segment the stream of speech into words. Subjects listened to a phrase and indicated whether they heard, e.g., keep sparking or keeps parking. The results indicate that learners are significantly worse than native speakers at using acoustic-phonetic cues, and that some types of stimuli are easier for learners to segment than others. The findings suggest that various factors, including transfer and markedness, may be relevant to success in L2 segmentation.
A further note on simulating word association behaviour in a second language
Authors: Wilks Clarissa , Meara Paul , Wolter Brent
Published: September 2005

This article explores some critical methodological and theoretical issues that emerge from recent research into word association behaviour in second language (L2) learners. The studies that we discuss here all use computer simulations as a tool to investigate L2 lexical networks, and to compare these networks with those of first language (L1) speakers. This article broaches some previously unacknowledged complexities in this kind of research, and draws attention to the importance of which assumptions are built into simulation models. The article queries some of the assumptions of our 2002 article (Wilks and Meara, 2002), and provides a reinterpretation of some of the data that we presented there. The article argues that simulation modelling forces us to make critical analyses of assumptions in a way that is not always necessary in less exacting experimental environments.
Interlanguage corpora and second language acquisition research
Authors: Myles Florence
Published: September 2005

This article presents a selective review of the work carried out recently in second language acquisition (SLA) research which makes use of oral learner corpora and computer technologies. In the first part, the reasons why the field of SLA needs corpora for addressing current theoretical issues are briefly reviewed. In the second part, recent literature on corpora and SLA is presented, as well as corpora currently available. The final part of the article demonstrates the way in which computerized methodologies can be used, by presenting a case study of a project whose aim was to construct a database of French Learner Oral Corpora, and by illustrating how the CHILDES tools have assisted in addressing a specific research agenda.
Theories of second language acquisition: three sides, three angles, three points
Authors: Thomas Margaret
Published: September 2005

Three recent books take up different positions in the on-going debate about how, and out of what, to construct a theory of second language (L2) acquisition. Johnson (2004) advocates a ‘dialogically based approach’, inspired by Vygotsky’s sociocultural theory and Bakhtin’s ‘dialogized heteroglossia’, with which she would replace what she views as a prevailing ‘cognitive bias’ in the field. Block (2003) similarly supports a ‘more interdisciplinary and socially informed orientation’ to second language acquisition. But Block wants to reform rather than replace certain assumptions of what he represents as the best existing theory of second language acquisition, namely, Susan Gass’ Input-Interaction-Output model (IIO model). Jordan (2004), on the other hand, argues forcefully that theorizing about second language acquisition must be based on a rationalist epistemology. He provides a set of ‘Guidelines’ for theory construction, including six assumptions foundational to rationalist inquiry in general, and a five-point evaluation metric against which rival theories can be judged. He also passes on a list of six ‘practices to be avoided’. Jordan encourages the cultivation of many, varied, theories so long as they observe the rationalist Guidelines. He goes on to criticize a broad sample of L2 research, commenting on whether specific proposals do or do not adhere to the Guidelines. This article reviews all three scholars’ positions in this important debate, which has the potential to sharpen second language theorists’ sense of what they are doing and how they should do it.
Tositumomab and Iodine-131 Tositumomab Produces Durable Complete Remissions in a Subset of Heavily Pretreated Patients With Low-Grade and Transformed Non-Hodgkin’s Lymphomas
Authors: Fisher Richard I. , Kaminski Mark S. , Wahl Richard L. , Knox Susan J. , Zelenetz Andrew D. , Vose Julie M. , Leonard John P. , Kroll Stewart , Goldsmith Stanley J. , Coleman Morton
Published: September 2005

Purpose

This study is an integrated efficacy analysis of the five clinical trials of tositumomab and iodine-131 tositumomab in patients with relapsed or refractory low-grade, follicular, or transformed low-grade non-Hodgkin’s lymphoma (NHL) that resulted in the regulatory approval of the iodine-131 tositumomab by the US Food and Drug Administration.

Patients and Methods

This integrated analysis included 250 patients. Patients received a single course of iodine-131 tositumomab. Responses were assessed by an independent panel of radiologists and oncologists.

Results

Response rates in the five trials ranged from 47% to 68%; complete response rates ranged from 20% to 38%. With a median follow-up of 5.3 years, the 5-year progression-free survival was 17%. Eighty-one (32%) of 250 patients had a time to progression of ≥ 1 year (termed durable response population). For the durable response population, 44% had not progressed at ≥ 2.5 to ≥ 9.5 years and had a median duration of response of 45.8 months. The median duration of complete response was not reached. The durable response population had many poor prognostic characteristics, including bone marrow involvement (41%), bulky disease ≥ 5 cm (49%), and transformed histology (23%). Forty-three percent of the patients had been treated with more than four prior therapies and 36% had not responded to their most recent therapy.

Conclusion

The tositumomab and iodine-131 tositumomab therapeutic regimen produces high response rates in patients with relapsed or refractory low-grade, follicular, and transformed low-grade NHL, with a sizable subgroup of patients achieving long-term durable responses.
Prognostic Factors and Life Expectancy in Myelodysplastic Syndromes Classified According to WHO Criteria: A Basis for Clinical Decision Making
Authors: Malcovati Luca , Porta Matteo Giovanni Della , Pascutto Cristiana , Invernizzi Rosangela , Boni Marina , Travaglino Erica , Passamonti Francesco , Arcaini Luca , Maffioli Margherita , Bernasconi Paolo , Lazzarino Mario , Cazzola Mario
Published: September 2005

Purpose

The aim of this study was to evaluate the prognostic value of the WHO proposal, to assess the role of the main prognostic factors in myelodysplastic syndromes (MDSs) classified into WHO subgroups, and to estimate mortality (standardized mortality ratio [SMR]) and life expectancy in these groups as a basis for clinical decision making.

Patients and Methods

Four hundred sixty-seven patients who were diagnosed as having de novo MDS at the Division of Hematology, University of Pavia (Pavia, Italy), between 1992 and 2002, were evaluated retrospectively for clinical and hematologic features at diagnosis, overall survival (OS), and progression to leukemia (leukemia-free survival).

Results

Significant differences in survival were noted between patients with refractory anemia (RA), refractory cytopenia with multilineage dysplasia, RA with excess blasts, type 1 (RAEB-1), and RAEB-2. The effect of demographic factors on OS was observed in MDS patients without excess blasts (age, P = .001; sex, P = .006), as in the general population. The mortality of RA patients 70 years or older did not differ significantly from that of the general population (SMR, 1.62; P = .06). Cytogenetics was the only International Prognostic Scoring System variable showing a prognostic value in MDS classified into WHO subgroups. Transfusion-dependent patients had a significantly shorter survival than patients who did not require transfusions (P < .001). Developing a secondary iron overload significantly affected the survival of transfusion-dependent patients (P = .003).

Conclusion

These data show that the WHO classification of MDSs has a relevant prognostic value. This classification, along with cytogenetics, might be useful in decisions regarding transplantation. MDS with isolated erythroid lineage dysplasia identifies a subset of truly low-risk patients, for whom a conservative approach is advisable.
Early Allogeneic Stem-Cell Transplantation for Young Adults With Acute Myeloblastic Leukemia in First Complete Remission: An Intent-to-Treat Long-Term Analysis of the BGMT Experience
Authors: Jourdan Eric , Boiron Jean-Michel , Dastugue Nicole , Vey Norbert , Marit Gérald , Rigal-Huguet Françoise , Molina Lysiane , Fegueux Nathalie , Pigneux Arnaud , Recher Christian , Rossi Jean-François , Attal Michel , Sotto Jean-Jacques , Maraninchi Dominique , Reiffers Josy , Bardou Valerie-Jeanne , Esterni Benjamin , Blaise Didier
Published: September 2005

Purpose

We analyzed the impact of allogeneic stem-cell transplantation (alloSCT) as an early consolidation for young patients with acute myeloblastic leukemia in first complete remission (CR1) through four successive protocols.

Patients and Methods

Of the 472 patients who achieved CR1, 182 (38%) had an HLA-identical sibling (donor group), and alloSCT was performed in 171 patients (94%). Of the 290 patients without donor (no-donor group), 62% received an autologous SCT.

Results

In an intent-to-treat analysis based on donor availability, the overall 10-year survival probability was 51% v 43% (P = .11) for the donor and no-donor groups, respectively. A Cox analysis determined that four factors had independent prognostic significance for survival (initial WBC count, French-American-British subtypes, cytogenetic risk, and number of induction courses). This permitted constitution of a simple index that reclassified 21% of the patients compared with usual cytogenetic classification and identified three subpopulations with different outcome and different impact of alloSCT.

Conclusion

AlloSCT was associated with a survival advantage for an intermediate-risk group. In other groups, numbers are limited for definitive conclusion. However, early performed alloSCT does not seem to be the optimal treatment of high-risk patients or offer any advantage over intensive chemotherapy in low-risk patients.
Choice-Based Elicitation and Decomposition of Decision Weights for Gains and Losses Under Uncertainty
Authors: Abdellaoui Mohammed , Vossmann Frank , Weber Martin
Published: September 2005

This paper reports the results of an experimental parameter-free elicitation and decomposition of decision weights under uncertainty. Assuming cumulative prospect theory, utility functions were elicited for gains and losses at an individual level using the tradeoff method. Subsequently, decision weights were elicited through certainty equivalents of uncertain two-outcome prospects. Furthermore, decision weights were decomposed using observable choice instead of invoking other empirical primitives, as in previous experimental studies. The choice-based elicitation of decision weights allows for a quantitative study of their characteristics, and also allows, among other things, for the examination of the sign-dependence hypothesis for observed choice under uncertainty. Our results confirm concavity of the utility function in the gain domain and bounded subadditivity of decision weights and choice-based subjective probabilities. We also find evidence for sign dependence of decision weights.
Preferences, Identity, and Competition: Predicting Tie Strength from Demographic Data
Authors: Reagans Ray
Published: September 2005

This research examines the combined influence of three causal mechanisms shaping interpersonal dynamics. Sharing a demographic characteristic has been shown to strengthen a relationship between people. The initial explanation for this positive effect emphasized the importance of individual preferences for social contact. Similar people share common interests, which makes them more attractive as exchange partners. More recent explanations have highlighted the important role of identification and competition. Identification increases the tendency for strong ties to develop among similar people, while competition reduces that tendency. I argue that tie strength is a function of all three mechanisms: a baseline level of interpersonal attraction, a positive identification effect, and a negative competition adjustment. Identification and competition vary with the number of people sharing the focal attribute to define a predictable association between sharing the focal attribute and the strength of a network connection. Predictions are tested with tenure and tie-strength data from a small research and development firm. Analysis indicates that having the same tenure has the predicted effect on communication frequency. The implications of the findings are discussed for homophily research in particular and demography research in general.
A Partially Observed Markov Decision Process for Dynamic Pricing
Authors: Aviv Yossi , Pazgal Amit
Published: September 2005

In this paper, we develop a stylized partially observed Markov decision process (POMDP) framework to study a dynamic pricing problem faced by sellers of fashion-like goods. We consider a retailer that plans to sell a given stock of items during a finite sales season. The objective of the retailer is to dynamically price the product in a way that maximizes expected revenues. Our model brings together various types of uncertainties about the demand, some of which are resolvable through sales observations. We develop a rigorous upper bound for the seller’s optimal dynamic decision problem and use it to propose an active-learning heuristic pricing policy. We conduct a numerical study to test the performance of four different heuristic dynamic pricing policies in order to gain insight into several important managerial questions that arise in the context of revenue management.
Your Money or Your Life: A Prescriptive Model for Health, Safety, and Consumption Decisions
Authors: Smith James E. , Keeney Ralph L.
Published: September 2005

In this paper we develop a conceptual framework and model for valuing risks to an individual’s health and life and to support decision making about investments in health, quality of life, and safety. Our treatment of health risks in the model builds on the popular quality-adjusted-life-year (QALY) framework that balances health quality and length of life issues. We extend this framework to consider financial concerns as well as health quality and length of life. Our model considers uncertainty in income and health and incorporates the decision maker’s ability to adjust consumption over time in response to changes in expectations about health and income. We use this model to study the optimal tradeoffs between financial gains or losses and improvements or reductions in health or longevity and apply it in two example medical decision problems.
An Approach to the Measurement, Analysis, and Prediction of Brand Equity and Its Sources
Authors: Srinivasan V. , Park Chan Su , Chang Dae Ryun
Published: September 2005

The authors propose a new approach for measuring, analyzing, and predicting a brand’s equity in a product market. Brand equity is defined as the incremental contribution ($) per year obtained by the brand in comparison to the underlying product (or service) with no brand-building efforts. The incremental contribution is driven by the individual customer’s incremental choice probability for the brand in comparison to his choice probability for the underlying product with no brand-building efforts. The approach takes into account three sources of brand equity—brand awareness, attribute perception biases, and nonattribute preference—and reveals how much each of the three sources contributes to brand equity. This is done by taking into account not only the direct effects of these three sources on choice probabilities, but also the indirect effects through enhancing the brand’s availability. The method provides what-if analysis capabilities to predict the likely impacts of alternative strategies to enhance a brand’s equity. The survey-based results from applying the method to the digital cellular phone market in Korea show that the proposed approach has good face validity and convergent validity, with brand awareness playing the largest role, followed by nonattribute preference.
Four Score and Seven Years from Now: The Date/Delay Effect in Temporal Discounting
Authors: Read Daniel , Frederick Shane , Orsel Burcu , Rahman Juwaria
Published: September 2005

We describe a new anomaly in intertemporal choice—the “date/delay effect”: discount rates that are imputed when time is described using calendar dates (e.g., on October 17) are markedly lower than those revealed when future outcomes are described in terms of the corresponding delay (e.g., in six months). Date descriptions not only reduce discount rates, but also affect the implied shape of the discount function: When inferred from intertemporal choices between options referenced by calendar dates, the discount function appears markedly less hyperbolic. We discuss potential psychological bases of the date/delay effect, its implications, and other modes of temporal reference.
Combined diastematomyelia and hemivertebra
Authors: Leung Y. L. , Buxton N.
Published: September 2005

A combination of hemivertebrae and diastematomyelia is rare. We have identified 12 such patients seen during a period of 11 years in the orthopaedic, spinal and neurosurgical units in Nottingham and analysed their treatment and outcome.
A prospective, randomised, controlled trial of the use of drains in total hip arthroplasty
Authors: Walmsley P. J. , Kelly M. B. , Hill R. M. F. , Brenkel I.
Published: September 2005

The routine use of surgical drains in total hip arthroplasty remains controversial. They have not been shown to decrease the rate of wound infection significantly and can provide a retrograde route for it. Their use does not reduce the size or incidence of post-operative wound haematomas. This prospective, randomised study was designed to evaluate the role of drains in routine total hip arthroplasty.

We investigated 552 patients (577 hips) undergoing unilateral or bilateral total hip arthroplasty who had been randomised to either having a drain for 24 hours or not having a drain. All patients followed standardised pre-, intra-, and post-operative regimes and were independently assessed using the Harris hip score before operation and at six, 18 and 36 months follow-up.

The rate of superficial and deep infection was 2.9% and 0.4%, respectively, in the drained group and 4.8% and 0.7%, respectively in the undrained group. One patient in the undrained group had a haematoma which did not require drainage or transfusion. The rate of transfusion after operation in the drained group was significantly higher than for undrained procedures (p < 0.042). The use of a drain did not influence the post-operative levels of haemoglobin, the revision rates, Harris hip scores, the length of hospital stay or the incidence of thromboembolism. We conclude that drains provide no clear advantage at total hip arthroplasty, represent an additional cost, and expose patients to a higher risk of transfusion.
Recombinant human vascular endothelial growth factor enhances bone healing in an experimental nonunion model
Authors: Eckardt H. , Ding M. , Lind M. , Hansen E. S. , Christensen K. S. , Hvid I.
Published: September 2005

The re-establishment of vascularity is an early event in fracture healing; upregulation of angiogenesis may therefore promote the formation of bone. We have investigated the capacity of vascular endothelial growth factor (VEGF) to stimulate the formation of bone in an experimental atrophic nonunion model.

Three groups of eight rabbits underwent a standard nonunion operation. This was followed by interfragmentary deposition of 100 μg VEGF, carrier alone or autograft.

After seven weeks, torsional failure tests and callus size confirmed that VEGF-treated osteotomies had united whereas the carrier-treated osteotomies failed to unite. The biomechanical properties of the groups treated with VEGF and autograft were identical. There was no difference in bone blood flow.

We considered that VEGF stimulated the formation of competent bone in an environment deprived of its normal vascularisation and osteoprogenitor cell supply. It could be used to enhance the healing of fractures predisposed to nonunion.
Cosmetic bilateral leg lengthening
Authors: Catagni M. A. , Lovisetti L. , Guerreschi F. , Combi A. , Ottaviani G.
Published: September 2005

The Ilizarov method for leg lengthening was used for cosmetic reasons in 54 patients with constitutional short stature. A mean lengthening of 7 cm with a low rate of complications produced an excellent or good outcome in all the patients, including improvement in psychological disturbances related to short stature. Those who undergo the procedure must be highly motivated, fully informed and understand the technique and possible complications. We suggest that the Ilizarov method for cosmetic limb lengthening is a technique without major complications. However, it requires careful follow-up, and the involvement of orthopaedic surgeons who are familiar with use of the circular frame and are experienced in limb lengthening and correction of deformity for pathological conditions.
An isolated osteochondroma with underlying non-Hodgkin’s lymphoma of bone
Authors: Roy S. , Dobson P. , Henry L.
Published: September 2005

Osteochondroma is the most common benign bone tumour. The risk of sarcomatous change in an isolated lesion is approximately 1%. We report a case of an isolated osteochondroma which appeared benign on clinical and plain radiographic examination but routine histological analysis revealed non-Hodgkin’s lymphoma in the underlying bone. This association has not previously been reported and the case emphasises the importance of routine histological analysis, even if a lesion appears benign.
Fractures of distally-fixed femoral stems after revision arthroplasty
Authors: Busch C. A. , Charles M. N. , Haydon C. M. , Bourne R. B. , Rorabeck C. H. , MacDonald S. J. , McCalden R. W.
Published: September 2005

We identified five (2.3%) fractures of the stem in a series of 219 revision procedures using a cementless, cylindrical, extensively porous-coated, distally-fixed femoral stem. Factors relating to the patients, the implant and the operations were compared with those with intact stems. Finite-element analysis was performed on two of the fractured implants.

Factors associated with fracture of the stem were poor proximal bone support (type III–type IV; p = 0.001), a body mass index > 30; (p = 0.014), a smaller diameter of stem (< 13.5 mm; p = 0.007) and the use of an extended trochanteric osteotomy (ETO 4/5: p = 0.028). Finite-element analysis showed that the highest stresses on the stem occurred adjacent to the site of the fracture. The use of a strut graft wired over an extended trochanteric osteotomy in patients lacking proximal femoral cortical support decreased the stresses on the stem by 48%.

We recommend the use of a strut allograft in conjunction with an extended trochanteric osteotomy in patients with poor proximal femoral bone stock.
Safety and efficacy of the extended iliofemoral approach in the treatment of complex fractures of the acetabulum
Authors: Griffin D. B. , Beaulé P. E. , Matta J. M.
Published: September 2005

There remains uncertainty about the most effective surgical approach in the treatment of complex fractures of the acetabulum. We have reviewed the experience of a single surgeon using the extended iliofemoral approach, as described by Letournel.

A review of the database of such fractures identified 106 patients operated on using this approach with a minimum follow-up of two years. All data were collected prospectively. The fractures involved both columns in 64 (60%). Operation was undertaken in less than 21 days after injury in 71 patients (67%) and in 35 (33%) the procedure was carried out later than this. The reduction of the fracture was measured on plain radiographs taken after operation and defined as anatomical (0 to 1 mm of displacement); imperfect (2 to 3 mm) or poor (> 3 mm). The functional outcome was measured by the modified Merle d’Aubigné and Postel score. The mean follow-up was for 6.3 years (2 to 17).

All patients achieved union of the fractures. The reduction was graded as anatomical in 76 (72%) of the patients, imperfect in 23 (22%), and poor in six (6%). The mean Merle d’Aubigné and Postel score was 15 (5 to 18) with 68 patients (64%) showing good or excellent and 38 (36%) fair or poor results. Function correlated significantly with the accuracy of the reduction (p < 0.009). Significant heterotopic ossification developed in 32 patients (30%) and was associated with a worse mean Merle d’Aubigné and Postel score of 13.7.

The extended iliofemoral approach can be performed safely in selected complex acetabular fractures with an acceptable clinical outcome and rate of complications. Effective prophylaxis against heterotopic ossification should be strongly considered.
Five-year clinical, radiological and postmortem results of the Cambridge Cup in patients with displaced fractures of the neck of the femur
Authors: Field R. E. , Rushton N.
Published: September 2005

The Cambridge Cup has been designed to replace the horseshoe-shaped articular cartilage of the acetabulum and the underlying subchondral bone. It is intended to provide physiological loading with minimal resection of healthy bone.

The cup has been used in 50 women with displaced, subcapital fractures of the neck of the femur. In 24 cases, the cup was coated with hydroxyapatite. In 26, the coating was removed before implantation in order to simulate the effect of long-term resorption.

The mean Barthel index and the Charnley-modified Merle d’Aubigné scores recovered to their levels before fracture. We reviewed 30 women at two years, 21 were asymptomatic and nine reported minimal pain. The mean scores deteriorated slightly after five years reflecting the comorbidity of advancing age. Patients with the hydroxyapatite-coated components remained asymptomatic, with no wear or loosening. The uncoated components migrated after four years and three required revision. This trial shows good early results using a novel, hydroxyapatite-coated, physiological acetabular component.
Movement patterns of the C-stem femoral component
Authors: Sundberg M. , Besjakov J. , von Schewelow T. , Carlsson å.
Published: September 2005

We used roentgen stereophotogrammetric analysis to follow 33 C-stem femoral components for two years after primary total hip arthroplasty. All components migrated distally and posteriorly within the cement mantle. The mean distal migration was 1.35 mm (sd 0.62) at two years and the mean posterior migration was 1.35 mm (sd 0.69) at two years. All the femoral components rotated into retroversion with a mean rotation at two years of 1.9° (sd 1.1). For all other directions, the prosthesis was stable up to two years. Compared with other tapered prostheses, the distal migration of the C-stem is the same, but posterior rotation and posterior migration are greater.
Improvements in balance after total hip replacement
Authors: Majewski M. , Bischoff-Ferrari H. A. , Grüneberg C. , Dick W. , Allum J. H. J.
Published: September 2005

We have investigated whether control of balance is improved during stance and gait and sit-to-stand tasks after unilateral total hip replacement undertaken for osteoarthritis of the hip.

We examined 25 patients with a mean age of 67 years (sd 6.2) before and at four and 12 months after surgery and compared the findings with those of 50 healthy age-matched control subjects. For all tasks, balance was quantified using angular measurements of movement of the trunk.

Before surgery, control of balance during gait and sit-to-stand tasks was abnormal in patients with severe osteoarthritis of the hip, while balance during stance was similar to that of the healthy control group. After total hip replacement, there was a progressive improvement at four and 12 months for most gait and sit-to-stand tasks and in the time needed to complete them. By 12 months, the values approached those of the control group. However, trunk pitch (forwards-backwards) and roll (side-to-side) velocities were less stable (greater than the control) when walking over barriers as was roll for the sit-to-stand task, indicative of a residual deficit of balance.

Our data suggest that patients with symptomatic osteoarthritis of the hip have marked deficits of balance in gait tasks, which may explain the increased risk of falling which has been reported in some epidemiological studies. However, total hip replacement may help these patients to regain almost normal control of balance for some gait tasks, as we found in this study. Despite the improvement in most components of balance, however, the deficit in the control of trunk velocity during gait suggests that a cautious follow-up is required after total hip replacement regarding the risk of a fall, especially in the elderly.
Compartment syndrome and systemic hypertension
Authors: Namboothiri S.
Published: September 2005

We present two rare variations related to compartment syndrome. The first is a 69-year-old hypertensive man with compartment syndrome of the arm. The second is a 58-year-old man with compartment syndrome of the forearm with severe compensatory hypertension.
Rupture of the quadriceps tendon
Authors: Hardy J. R. W. , Chimutengwende-Gordon M. , Bakar I.
Published: September 2005

We reviewed the records of 107 consecutive patients who had undergone surgery for disruption of the knee extensor mechanism to test whether an association existed between rupture of the quadriceps tendon and the presence of a patellar spur. The available standard pre-operative lateral radiographs were examined to see if a patellar spur was an indicator for rupture of the quadriceps tendon in this group of patients. Of the 107 patients, 12 underwent repair of a ruptured patellar tendon, 59 had an open reduction and internal fixation of a patellar fracture and 36 repair of a ruptured quadriceps tendon. In the 88 available lateral radiographs, patellar spurs were present significantly more commonly (p < 0.0005) in patients operated on for rupture of the quadriceps tendon (79%) than in patients with rupture of the patellar tendon (27%) or fracture of the patella (15%). In patients presenting with failure of the extensor mechanism of the knee in the presence of a patellar spur, rupture of the quadriceps tendon should be considered as a possible diagnosis.
Correction of rotational deformity of the tibia in cerebral palsy by percutaneous supramalleolar osteotomy
Authors: Inan M. , Ferri-de Baros F. , Chan G. , Dabney K. , Miller F.
Published: September 2005

A percutaneous supramalleolar osteotomy with multiple drill holes and closed osteoclasis was used to correct rotational deformities of the tibia in patients with cerebral palsy. The technique is described and the results in 247 limbs (160 patients) are reported. The mean age at the time of surgery was 10.7 years (4 to 20). The radiographs were analysed for time to union, loss of correction, and angulation at the site of the osteotomy.

Bone healing was obtained in all patients except one in a mean period of seven weeks (5 to 12). Malunion after loss of reduction at the site of the osteotomy developed in one tibia.

Percutaneous supramalleolar osteotomy of the tibia is a safe and simple surgical procedure.
Different expression of catecholamine transporters in phaeochromocytomas from patients with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2
Authors: Huynh Thanh-Truc , Pacak Karel , Brouwers Frederieke M , Abu-Asab Mones S , Worrell Robert A , Walther MacClellan M , Elkahloun Abdel G , Goldstein David S , Cleary Susannah , Eisenhofer Graeme
Published: September 2005

Objective: Phaeochromocytomas in patients with multiple endocrine neoplasia type 2 (MEN 2) produce adrenaline, whereas those with von Hippel-Lindau (VHL) syndrome do not. This study assessed whether these distinctions relate to differences in expression of the transporters responsible for uptake and storage of catecholamines – the noradrenaline transporter and the vesicular monoamine transporters (VMAT 1 and VMAT 2).

Methods: Tumour tissue and plasma samples were obtained from 31 patients with hereditary phaeochromocytoma − 18 with VHL syndrome and 13 with MEN 2. We used quantitative PCR, Western blotting, electron microscopy, immunohistochemistry and measurements of plasma and tumour catecholamines to assess differences in expression of the transporters in noradrenaline-producing vs adrenaline-producing hereditary tumours. These differences were compared with those in a further group of 26 patients with non-syndromic phaeochromocytoma.

Results: Adrenaline-producing phaeochromocytomas in MEN 2 patients expressed more noradrenaline transporter mRNA and protein than noradrenaline-producing tumours in VHL patients. In contrast, there was greater expression of VMAT 1 in VHL than MEN 2 tumours, while expression of VMAT 2 did not differ significantly. These differences were associated with larger numbers of storage vesicles and higher tissue contents of catecholamines in MEN 2 than in VHL tumours. Differences in expression of the noradrenaline transporter were weaker, and those of VMAT 1 and VMAT 2 stronger, in noradrenaline and adrenaline-producing non-syndromic than in hereditary tumours.

Conclusions: The findings show that, in addition to differences in catecholamine biosynthesis, phaeochromocytomas in MEN 2 and VHL syndrome also differ in expression of the transporters responsible for uptake and vesicular storage of catecholamines.
Differential expression of p160 steroid receptor coactivators in the rat testis and epididymis
Authors: Igarashi-Migitaka Junko , Takeshita Akira , Koibuchi Noriyuki , Yamada Shozo , Ohtani-Kaneko Ritsuko , Hirata Kazuaki
Published: September 2005

Objective: Androgens are critical for the development and maintenance of male sexual characteristics. Their action is mediated through the androgen receptor (AR). Ligand-bound AR interacts with coactivator proteins that mediate transcriptional activation. Such coactivators include three members of the 160 kDa proteins (p160s): SRC-1, TIF2/GRIP1, and p/CIP/RAC3/ACTR/AIB1/TRAM-1. The aim of this study was to investigate the expression of the three p160 coactivators and their association with AR in testis and epididymis.

Methods: We determined the localization of these three p160 coactivators in immature and mature rat testis, and epididymis by immunohistochemistry using the specific monoclonal antibodies. We also performed double immunofluorescence staining to examine whether p160s are colocalized with AR in these tissues.

Results: In seminiferous tubules of mature rat testis, SRC-1 and TRAM-1 immunoreactivity was found predominantly in spermatogonia and spermatocytes. In contrast, TIF2 was expressed predominantly in Sertoli cells. AR was coexpressed with TIF2 in this cell type. In immature rat testis, however, all three coactivators were expressed in both germ cells and Sertoli cells. In the epididymis, SRC-1 and TIF2 immunoreactivities were localized in nuclei of epithelial cells. However, TRAM-1 immunostaining was observed in the luminal portion of the cytoplasm with greater intensity than in the nucleus, especially in the caput epididymidis.

Conclusions: The cell-type-specific expression of p160 coactivators suggests specific roles in male reproductive organs. Further, the strong cytoplasmic localization of TRAM-1 protein in epithelial cells of epididymis suggests that TRAM-1 may have additional role(s) in transcriptional regulation.
Low-dose glucose infusion after achieving critical hypoglycemia during insulin tolerance testing: effects on time of hypoglycemia, neuroendocrine stress response and patient’s discomfort in a pilot study
Authors: Borm K , Slawik M , Beuschlein F , Seiler L , Flohr F , Berg A , Koenig A , Reincke M
Published: September 2005

Objective: The insulin tolerance test (ITT) is regarded as the gold standard for the evaluation of pituitary ACTH and growth hormone reserve. However, the intended critical hypoglycemia results in considerable discomfort and requires close surveillance during the test.

Design and methods: In a pilot study, we evaluated whether the ITT could be markedly simplified, made less hazardous and more convenient by routine i.v. low-dose glucose administration after hypoglycemia has been achieved. Sixteen healthy subjects (three females, 13 males) were tested twice in a randomized, single-blinded fashion, receiving 0.15 IU insulin/kg body weight as an i.v. bolus. After hypoglycemia (serum glucose less than 2.2 mmol/l) had been achieved, 500 ml isotonic saline (protocol A (A)), or 500 ml 5% glucose solution (protocol B (B)) were infused over 30 min.

Results: Compared with saline, glucose infusion shortened the period of hypoglycemia from 31 + 14 to 17 + 6 min (P < 0.01). In addition, prolonged duration of hypoglycemia (>45 min) was reduced (6 subjects in protocol A vs none in protocol B). Despite shorter duration of hypoglycemia, all subjects had adequate stimulated cortisol (>500 nmol/l) and hGH (>5 μg/l) levels. Mean peak concentrations of plasma ACTH (24 ± 12 pmol/l (A) vs 21 ± 8 pmol/l (B)), serum cortisol (690 ± 83 nmol/l vs 634 ± 83 nmol/l) and serum hGH (26 ± 16 μg/l vs 22 ± 13 μg/l) were slightly, but not significantly lower. In contrast, glucose infusion significantly reduced peak plasma epinephrine levels at 45 min (4.96 ± 4.91 pmol/l (A) vs 1.53 ± 1.1 pmol/l (B), P < 0.05) and ameliorated discomfort, as evaluated by a visual analog scale (P < 0.05).

Conclusions: Taken together, our pilot study suggests that, while the duration of hypoglycemia is shortened and acute epinephrine response is reduced, low-dose infusion of glucose does not significantly alter peak cortisol and growth hormone responses during ITT. Studies with a larger number of subjects and patients with suspected hypopituitarism are needed to further evaluate this modified protocol.
A systematic review of drug therapy for Graves’ hyperthyroidism
Authors: Abraham Prakash , Avenell Alison , Park Christine M , Watson Wendy A , Bevan John S
Published: September 2005

We assessed the effects of dose, regimen and duration of anti-thyroid drug therapy for Graves’ thyrotoxicosis on recurrence of hyperthyroidism, course of ophthalmopathy, adverse effects, health-related quality of life and economic outcomes. We undertook a systematic review and meta-analyses of randomised controlled trials (RCTs). We identified RCTs regardless of language or publication status by searching six databases, and trial registries. Dual, blinded data abstraction and quality assessment were undertaken. Trials included provided therapy for at least 6 months with follow-up at least 1 year after drug cessation. Fixed or random effects meta-analyses were used to combine study data. Twelve trials compared a Block-Replace regimen (requiring a higher dose of anti-thyroid drug treatment) with a Titration regimen. Overall, there was no significant difference between the regimens for relapse of hyperthyroidism (relative risk (RR) = 0.93, 95% confidence interval (CI) 0.84 to 1.03). Participants were more likely to withdraw due to adverse events with a Block-Replace regimen (RR = 1.89, 95% CI 1.25 to 2.85). Prescribing replacement thyroxine, either with the anti-thyroid drug treatment, or after this was completed, had no significant effect on relapse. Limited evidence suggested 12–18 months of anti-thyroid drug treatment should be used. The titration regimen appeared as effective as the Block-Replace regimen, and was associated with fewer adverse effects. However, relapse rates over 50% and high participant drop-out rates in trials mean that the results should be interpreted with caution, and may suggest that other strategies for the management of Graves’ disease, such as radioiodine, should be considered more frequently as first-line therapy. There were no data on the course of ophthalmopathy, health-related quality of life and economic outcomes.
Analogs of GnRH-I and GnRH-II inhibit epidermal growth factor-induced signal transduction and resensitize resistant human breast cancer cells to 4OH-tamoxifen
Authors: Günthert Andreas R , Gründker Carsten , Olota Agnes , Läsche Julia , Eicke Nicola , Emons Günter
Published: September 2005

About 50–64% of human breast cancers express receptors for GnRH-I. Direct antiproliferative effects of analogs of GnRH-I on human breast cancer cell lines have been shown. They are at least in part mediated by antagonizing growth promoting effects of estradiol, epidermal growth factor (EGF) or insulin-like growth factor. Recently, expression of a putative receptor for GnRH-II in human tissues was demonstrated. Antiproliferative effects of GnRH-II in human endometrial and ovarian cancer cells were shown not to be mediated through the GnRH-I receptor. Now we demonstrate direct anti-proliferative effects of the GnRH-I analog Triptorelin and the GnRH-II analog [d-Lys6]GnRH-II in MCF-7 and T47D human breast cancer cells expressing GnRH-I receptors and putative GnRH-II receptors. Pretreatment with Triptorelin or [d-Lys6]GnRH-II blocked EGF-induced autophosphoryla-tion of EGF receptor and activation of mitogen-activated protein kinase (extracellular-signal-regulated kinase 1/2 (ERK1/2)) in these cells. In sublines of MCF-7 and T47D cells, which were developed to be resistant to 4OH-tamoxifen, HER-2/p185 was overexpressed. Pretreatment of these cell lines with Triptorelin or [d-Lys6]GnRH-II completely abolished resistance to 4OH-tamoxifen, assessed by 4OH-tamoxifen-induced apoptosis. Analogs of GnRH-I and GnRH-II counteract EGF-dependent signal transduction in human breast cancer cells with expression of receptors for GnRH-I and GnRH-II. Through this mechanism, they probably reverse acquired resistance to 4OH-tamoxifen mediated through overexpression or activation of receptors of the c-erbB family.