bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-tesla magnetic resonance imaging of the meniscus of the knee: What about equivocal errors?
Authors: Van Dyck Pieter , Vanhoenacker Filip M. , Gielen Jan L. , Dossche Lieven , Weyler Joost , Parizel Paul M.
Published: January 2010

Background: The significance of borderline magnetic resonance (MR) findings that are equivocal for a tear of the knee meniscus remains uncertain. Given their higher signal-to-noise ratio (SNR) and greater spatial resolution, these equivocal meniscal tears could be expected to be less frequent using a 3.0T MR system.

Purpose: To investigate the prevalence of equivocal meniscal tears using 3.0T MR, and to study their impact on MR accuracy compared with arthroscopy in the detection of meniscal tears.

Material and Methods: The medical records of 100 patients who underwent 3.0T MR imaging and subsequent arthroscopy of the knee were retrospectively reviewed. Two observers interpreted MR images in consensus, and menisci were diagnosed as torn (abnormality on two or more images), equivocal for a tear (abnormality on one image), or intact, using arthroscopy as the standard of reference. The prevalence of equivocal meniscal tears was assessed, and MR accuracy was calculated as follows: first, considering both torn menisci and equivocal diagnoses as positive for a tear; and second, considering only torn menisci as positive for a tear.

Results: Evidence of meniscal tears on MR images was equivocal in 12 medial (12%) and three lateral (3%) menisci. Of these equivocal MR diagnoses, tears were found at arthroscopy in eight medial and one lateral meniscus. In our study, the specificity and positive predictive value increased for both the medial and lateral meniscus when only menisci with two or more abnormal images were considered to be torn: from 80% and 89% to 91% and 94% for the medial meniscus, and from 91% and 73% to 93% and 78% for the lateral meniscus, respectively.

Conclusion: Subtle findings that are equivocal for a tear of the knee meniscus still make MR diagnosis difficult, even at 3.0T. We recommend that radiologists should rather be descriptive in reporting subtle or equivocal MR findings, alerting the clinician of possible meniscal tear.
Breast tomosynthesis: Accuracy of tumor measurement compared with digital mammography and ultrasonography
Authors: Förnvik Daniel , Zackrisson Sophia , Ljungberg Otto , Svahn Tony , Timberg Pontus , Tingberg Anders , Andersson Ingvar
Published: January 2010

Background: Mammographic tumor size measurement can be difficult because breast structures are superimposed onto a two-dimensional (2D) plane, potentially obscuring the tumor outline. Breast tomosynthesis (BT) is a 3D X-ray imaging technique in which low-dose images are acquired over a limited angular range at a total dose comparable to digital mammography (DM). These low-dose images are used to mathematically reconstruct a 3D image volume of the breast, thus reducing the problem of superimposed tissue.

Purpose: To investigate whether breast cancer size can be more accurately assessed with breast tomosynthesis than with digital mammography and ultrasonography (US), by reducing the disturbance effect of the projected anatomy.

Material and Methods: A prototype BT system was used. The main inclusion criterion for BT examination was subtle but suspicious findings of breast cancer on 2D mammography. Sixty-two women with 73 breast cancers were included. BT, DM, and US sizes were measured independently by experienced radiologists without knowledge of the pathology results, which were used as reference.

Results: The tumor outline could be determined in significantly more cases with BT (63) and US (60) than DM (49). BT and US size correlated well with pathology ( R=0.86 and R=0.85, respectively), and significantly better than DM size ( R=0.71). Accordingly, staging was significantly more accurate with BT than with DM.

Conclusion: The study indicates that BT is superior to DM in the assessment of breast tumor size and stage.
Quantifying Information Content in Survey Data by Entropy
Authors: Dahl Fredrik A. , Østerås Nina
Published: January 2010

We apply Shannon entropy as a measure of information content in survey data, and define information efficiency as the empirical entropy divided by the maximum attainable entropy. In a case study of the Norwegian Function Assessment Scale, entropy calculations show that the 5-point response version has higher information efficiency than the 4-point version.
Decentralized Energy from Waste Systems
Authors: Antizar-Ladislao Blanca , Turrion-Gomez Juan L.
Published: January 2010

In the last five years or so, biofuels have been given notable consideration worldwide as an alternative to fossil fuels, due to their potential to reduce greenhouse gas emissions by partial replacement of oil as a transport fuel. The production of biofuels using a sustainable approach, should consider local production of biofuels, obtained from local feedstocks and adapted to the socio-economical and environmental characteristics of the particular region where they are developed. Thus, decentralized energy from waste systems will exploit local biomass to optimize their production and consumption. Waste streams such as agricultural and wood residues, municipal solid waste, vegetable oils, and algae residues can all be integrated in energy from waste systems. An integral optimization of decentralized energy from waste systems should not be based on the optimization of each single process, but the overall optimization of the whole process. This is by obtaining optimal energy and environmental benefits, as well as collateral beneficial co-products such as soil fertilizers which will result in a higher food crop production and carbon dioxide fixation which will abate climate change.
Electrostatic Interactions of Fluorescent Molecules with Dielectric Interfaces Studied by Total Internal Reflection Fluorescence Correlation Spectroscopy
Authors: Blom Hans , Hassler Kai , Chmyrov Andriy , Widengren Jerker
Published: January 2010

Electrostatic interactions between dielectric surfaces and different fluorophores used in ultrasensitive fluorescence microscopy are investigated using objective-based Total Internal Reflection Fluorescence Correlation Spectroscopy (TIR-FCS). The interfacial dynamics of cationic rhodamine 123 and rhodamine 6G, anionic/dianionic fluorescein, zwitterionic rhodamine 110 and neutral ATTO 488 are monitored at various ionic strengths at physiological pH. As analyzed by means of the amplitude and time-evolution of the autocorrelation function, the fluorescent molecules experience electrostatic attraction or repulsion at the glass surface depending on their charges. Influences of the electrostatic interactions are also monitored through the triplet-state population and triplet relaxation time, including the amount of detected fluorescence or the count-rate-per-molecule parameter. These TIR-FCS results provide an increased understanding of how fluorophores are influenced by the microenvironment of a glass surface, and show a promising approach for characterizing electrostatic interactions at interfaces.
The Fibrillar Collagen Family
Authors: Exposito Jean-Yves , Valcourt Ulrich , Cluzel Caroline , Lethias Claire
Published: January 2010

Collagens, or more precisely collagen-based extracellular matrices, are often considered as a metazoan hallmark. Among the collagens, fibrillar collagens are present from sponges to humans, and are involved in the formation of the well-known striated fibrils. In this review we discuss the different steps in the evolution of this protein family, from the formation of an ancestral fibrillar collagen gene to the formation of different clades. Genomic data from the choanoflagellate (sister group of Metazoa) Monosiga brevicollis, and from diploblast animals, have suggested that the formation of an ancestral α chain occurred before the metazoan radiation. Phylogenetic studies have suggested an early emergence of the three clades that were first described in mammals. Hence the duplication events leading to the formation of the A, B and C clades occurred before the eumetazoan radiation. Another important event has been the two rounds of “whole genome duplication” leading to the amplification of fibrillar collagen gene numbers, and the importance of this diversification in developmental processes. We will also discuss some other aspects of fibrillar collagen evolution such as the development of the molecular mechanisms involved in the formation of procollagen molecules and of striated fibrils.
Recent Developments in Fluorescence Correlation Spectroscopy for Diffusion Measurements in Planar Lipid Membranes
Authors: Macháň Radek , Hof Martin
Published: January 2010

Fluorescence correlation spectroscopy (FCS) is a single molecule technique used mainly for determination of mobility and local concentration of molecules. This review describes the specific problems of FCS in planar systems and reviews the state of the art experimental approaches such as 2-focus, Z-scan or scanning FCS, which overcome most of the artefacts and limitations of standard FCS. We focus on diffusion measurements of lipids and proteins in planar lipid membranes and review the contributions of FCS to elucidating membrane dynamics and the factors influencing it, such as membrane composition, ionic strength, presence of membrane proteins or frictional coupling with solid support.
Stability of Nanocrystalline Spark Plasma Sintered 3Y-TZP
Authors: Chintapalli Ravikiran , Mestra Alvaro , García Marro Fernando , Yan Haixue , Reece Michael , Anglada Marc
Published: January 2010

Spark plasma sintered 3Y-TZP has been investigated with respect to hydrothermal ageing and grinding. The sintering was performed between the temperatures of 1,100 and 1,600 °C for a soaking time of 5 minutes and the resulting materials were obtained with grain sizes between 65 to 800 nm and relative densities between 88.5 to 98.8%. Experiments on hydrothermal ageing in water vapour at 131 °C, 2 bars during 60 hours shows that phase stability is retained, elastic modulus and hardness of near surface region measured by nanoindentation does not change in fine grain (
Palladium-Catalyzed Heck Coupling Reaction of Aryl Bromides in Aqueous Media Using Tetrahydropyrimidinium Salts as Carbene Ligands
Authors: Yaşar Sedat , Özcan Emine Özge , Gürbüz Nevin , Çetinkaya Bekir , Özdemir İsmail
Published: January 2010

An efficient and stereoselective catalytic system for the Heck cross coupling reaction using novel 1,3-dialkyl-3,4,5,6-tetrahydropyrimidinium salts (1, LHX) and Pd(OAc)2 loading has been reported. The palladium complexes derived from the salts 1a-f prepared in situ exhibit good catalytic activity in the Heck coupling reaction of aryl bromides under mild conditions.
Antileishmanial, Antimicrobial and Antifungal Activities of Some New Aryl Azomethines
Authors: Al-Kahraman Yasser M.S.A. , Madkour Hassan. M.F. , Ali Dildar , Yasinzai Masoom
Published: January 2010

A series of eighteen azomethines has been synthesized by the reaction of appropriate primary aromatic amines with aryl and/or heteroaryl carboxaldehydes. The synthesized azomethines have been evaluated for their in vitro antileishmanial, antibacterial and antifungal activities. The results revealed some antifungal activity of most of the synthesized compounds, whereas the antileishmaniasis activity results highlighted that all synthesized azomethines inhibited parasite growth and most of them showed highly potent action towards Leishmania major promastigotes. No remarkable bactericidal activities were observed.
Assessment of Information to Substantiate a Health Claim on the Prevention of Prostate Cancer by Lignans
Authors: Saarinen Niina M. , Tuominen Juhani , Pylkkänen Liisa , Santti Risto
Published: January 2010

Lignans and their in vivo metabolites, especially enterolactone (ENL), have attracted substantial interest as potential chemopreventive agents for prostate cancer. Preclinical and clinical interventions performed with lignan-rich flaxseed that use surrogate biomarkers as endpoints suggest that lignans may attenuate prostate carcinogenesis in individuals with increased risk or with diagnosed cancer. No unequivocal prostate cancer risk reduction has been found for lignans in epidemiological studies, suggesting that lignan concentrations found in populations consuming a regular non-supplemented diet are not chemopreventive in prostate cancer. Presumably, the main obstacles in assessing the efficacy of food lignans is limited knowledge of the serum and tissue lignan concentrations required for the putative prevention. Further clinical studies performed with the purified compounds are required to substantiate a health claim.
Oromucosal Administration of Interferon to Humans
Authors: Beilharz Manfred W. , Cummins Martin J. , Bennett Alayne L. , Cummins Joseph M.
Published: January 2010

The prevailing dogma is that, to be systemically effective, interferon-alpha (IFNα) must be administered in sufficiently high doses to yield functional blood concentrations. Such an approach to IFNa therapy has proven effective in some instances, but high-dose parenteral IFNα therapy has the disadvantage of causing significant adverse events. Mounting evidence suggests that IFNα delivered into the oral cavity in low doses interacts with the oral mucosa in a unique manner to induce systemic host defense mechanisms without IFNα actually entering the circulation, thus reducing the potential for toxic side effects. A better understanding of the applications and potential benefits of this treatment modality are under active investigation. This paper provides a review of the relevant literature on the clinical use of the oromucosal route of administration of interferon, with an emphasis on the treatment of influenza.
Olesoxime (TRO19622): A Novel Mitochondrial-Targeted Neuroprotective Compound
Authors: Bordet Thierry , Berna Patrick , Abitbol Jean-Louis , Pruss Rebecca M.
Published: January 2010

Olesoxime (TRO19622) is a novel mitochondrial-targeted neuroprotective compound undergoing a pivotal clinical efficacy study in Amyotrophic Lateral Sclerosis (ALS) and also in development for Spinal Muscular Atrophy (SMA). It belongs to a new family of cholesterol-oximes identified for its survival-promoting activity on purified motor neurons deprived of neurotrophic factors. Olesoxime targets proteins of the outer mitochondrial membrane, concentrates at the mitochondria and prevents permeability transition pore opening mediated by, among other things, oxidative stress. Olesoxime has been shown to exert a potent neuroprotective effect in various in vitro and in vivo models. In particular olesoxime provided significant protection in experimental animal models of motor neuron disorders and more particularly ALS. Olesoxime is orally active, crosses the blood brain barrier, and is well tolerated. Collectively, its pharmacological properties designate olesoxime as a promising drug candidate for motor neuron diseases.
Escherichia coli Subtilase Cytotoxin
Authors: Paton Adrienne W. , Paton James C.
Published: January 2010

Subtilase cytotoxin (SubAB) is the prototype of a new AB5 toxin family produced by a subset of Shiga toxigenic Escherichia coli (STEC) strains. Its A subunit is a subtilase-like serine protease and cytotoxicity for eukaryotic cells is due to a highly specific, single-site cleavage of BiP/GRP78, an essential Hsp70 family chaperone located in the endoplasmic reticulum (ER). This cleavage triggers a severe and unresolved ER stress response, ultimately triggering apoptosis. The B subunit has specificity for glycans terminating in the sialic acid N-glycolylneuraminic acid. Although its actual role in human disease pathogenesis is yet to be established, SubAB is lethal for mice and induces pathological features overlapping those seen in the haemolytic uraemic syndrome, a life-threatening complication of STEC infection. The toxin is also proving to be a useful tool for probing the role of BiP and ER stress in a variety of cellular functions.
The Role of Nucleotide Excision by Reverse Transcriptase in HIV Drug Resistance
Authors: Acosta-Hoyos Antonio J. , Scott Walter A.
Published: January 2010

Nucleoside reverse transcriptase (RT) inhibitors of HIV block viral replication through the ability of HIV RT to incorporate chain-terminating nucleotide analogs during viral DNA synthesis. Once incorporated, the chain-terminating residue must be removed before DNA synthesis can continue. Removal can be accomplished by the excision activity of HIV RT, which catalyzes the transfer of the 3'-terminal residue on the blocked DNA chain to an acceptor substrate, probably ATP in most infected cells. Mutations of RT that enhance excision activity are the most common cause of resistance to 3'-azido-3'-deoxythymidine (AZT) and exhibit low-level cross-resistance to most other nucleoside RT inhibitors. The resistance to AZT is suppressed by a number of additional mutations in RT, most of which were identified because they conferred resistance to other RT inhibitors. Here we review current understanding of the biochemical mechanisms responsible for increased or decreased excision activity due to these mutations.
Microrna Let-7: An Emerging Next-Generation Cancer Therapeutic
Authors: Barh D. , Malhotra R. , Ravi B. , Sindhurani P.
Published: January 2010

In recent years, various rna-based technologies have been under evaluation as potential next-generation cancer therapeutics. MicroRNAS (miRNAS), known to regulate the cell cycle and development, are deregulated in various cancers. Thus, they might serve as good targets or candidates in an exploration of anticancer therapeutics. One attractive candidate for this purpose is let-7 (“lethal-7”). Let-7 is underexpressed in various cancers, and restoration of its normal expression is found to inhibit cancer growth by targeting various oncogenes and inhibiting key regulators of several mitogenic pathways. In vivo, let-7 administration was found effective against mouse-model lung and breast cancers, and our computational prediction supports the possible effectiveness of let-7 in estrogen receptor (ER)–positive metastatic breast cancer. Data also suggest that let-7 regulates apoptosis and cancer stem cell (CSC) differentiation and can therefore be tested as a potential therapeutic in cancer treatment. However, the exact role of let-7 in cancer is not yet fully understood. There is a need to understand the causative molecular basis of let-7 alterations in cancer and to develop proper delivery systems before proceeding to therapeutic applications. This article attempts to highlight certain critical aspects of let-7’s therapeutic potential in cancer.
Application of Machine Learning Methodology for Pet-Based Definition of Lung Cancer
Authors: Kerhet A. , Small C. , Quon H. , Riauka T. , Schrader L. , Greiner R. , Yee D. , McEwan A. , Roa W.
Published: January 2010

We applied a learning methodology framework to assist in the threshold-based segmentation of non-small-cell lung cancer (NSCLC) tumours in positron-emission tomography–computed tomography (PET–CT) imaging for use in radiotherapy planning. Gated and standard free-breathing studies of two patients were independently analysed (four studies in total). Each study had a PET–CT and a treatment-planning CT image. The reference gross tumour volume (GTV) was identified by two experienced radiation oncologists who also determined reference standardized uptake value (SUV) thresholds that most closely approximated the GTV contour on each slice. A set of uptake distribution-related attributes was calculated for each PET slice. A machine learning algorithm was trained on a subset of the PET slices to cope with slice-to-slice variation in the optimal SUV threshold: that is, to predict the most appropriate SUV threshold from the calculated attributes for each slice. The algorithm’s performance was evaluated using the remainder of the PET slices. A high degree of geometric similarity was achieved between the areas outlined by the predicted and the reference SUV thresholds (Jaccard index exceeding 0.82). No significant difference was found between the gated and the free-breathing results in the same patient. In this preliminary work, we demonstrated the potential applicability of a machine learning methodology as an auxiliary tool for radiation treatment planning in NSCLC.
Cost-Effectiveness of Oxaliplatin in the Adjuvant Treatment of Colon Cancer in Canada
Authors: Attard C. L. , Maroun J. A. , Alloul K. , Grima D. T. , Bernard L. M.
Published: January 2010

Objective: The cost-effectiveness of oxaliplatin in combination with 5-fluorouracil/leucovorin (5FU/LV)—the FOLFOX regimen—was compared with that of 5FU/LV alone as adjuvant therapy for patients with stage III colon cancer, from the perspective of the Cancer Care Ontario New Drug Funding Program. In the MOSAIC (Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer) trial, the FOLFOX regimen significantly improved disease-free survival. The MOSAIC trial formed the basis of the present analysis. Methodology: Extrapolated patient-level data from the MOSAIC trial were used to model patient outcomes from treatment until death. Utilities were obtained from the literature. Resource utilization data were derived from the MOSAIC trial and supplemented with data from the literature. Unit costs were obtained from the Ontario Ministry of Health and Long-Term Care, the London Health Sciences Centre, and the literature. Results: Lifetime incremental cost-effectiveness ratios for FOLFOX compared with 5FU/LV were CA$14,266 per disease-free year, CA$23,598 per life-year saved, and CA$24,104 per quality adjusted life-year (QALY) gained, discounting costs and outcomes at 5% per annum. These results were stable for a wide range of inputs; only utility values associated with relapse seemed to influence the cost-effectiveness ratios observed. Conclusions: With an incremental cost of CA$24,104 per QALY gained, FOLFOX is a cost-effective adjuvant treatment for stage III colon cancer. Compared with 5FU/LV alone, this regimen offers better clinical outcomes and provides good value for money.
Cost Effectiveness of tac versus fac in Adjuvant Treatment of Node-Positive Breast Cancer
Authors: Mittmann N. , Verma S. , Koo M. , Alloul K. , Trudeau M.
Published: January 2010

Background: This economic analysis aimed to determine, from the perspective of a Canadian provincial government payer, the cost-effectiveness of docetaxel (Taxotere: Sanofi–Aventis, Laval, QC) in combination with doxorubicin and cyclophosphamide (TAC) compared with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) following primary surgery for breast cancer in women with operable, axillary lymph node–positive breast cancer. Methods: A Markov model looking at two time phases—5-year treatment and long-term follow-up—was constructed. Clinical events included clinical response (based on disease-free survival and overall survival) and rates of febrile neutropenia, stomatitis, diarrhea, and infections. Health states were “no recurrence,” “locoregional recurrence,” “distant recurrence,” and “death.” Costs were based on published sources and are presented in 2006 Canadian dollars. Model inputs included chemotherapy drug acquisition costs, chemotherapy administration costs, relapse and follow-up costs, costs for management of adverse events, and costs for granulocyte colony-stimulating factor (G-CSF) prophylaxis. A 5% discount rate was applied to costs and outcomes alike. Health utilities were obtained from published sources. Results: For TAC as compared with FAC, the incremental cost was $6921 per life-year (LY) gained and $6,848 per quality-adjusted life-year (QALY) gained. The model was robust to changes in input variables (for example, febrile neutropenia rate, utility). When G-CSF and antibiotics were given prophylactically before every cycle, the incremental ratios increased to $13,183 and $13,044 respectively. Conclusions: Compared with FAC, TAC offered improved response at a higher cost. The cost-effectiveness ratios were low, indicating good economic value in the adjuvant setting of node-positive breast cancer patients.
Primary Epithelioid Angiosarcoma of the Breast Masquerading as Carcinoma
Authors: Muzumder S. , Das P. , Kumar M. , Bhasker S. , Sarkar C. , Medhi K. , Iyer V. K. , Rath G. K.
Published: January 2010

Here we report a case of primary epithelioid angiosarcoma (EAS) of the breast occurring in a 30-year-old woman. Following fine-needle asspiration cytology (FNAC) and tru-cut biopsy, the patient was initially diagnosed with mammary carcinoma and thereafter underwent modified radical mastectomy. Postoperative histopathologic examination and immunohistochemistry revealed a diagnosis of primary epithelioid angiosarcoma of the breast. The patient received postoperative radiotherapy to the chest wall and was started on adjuvant thalidomide. Preoperatively, EAS can be mistaken for carcinoma because it is difficult to appreciate the typical morphology on FNAC or tru-cut biopsy. Indeed, this is an area of potential diagnostic error because, nowadays, neoadjuvant therapy is often instituted after core biopsy of a breast mass. This case is being reported not only for its diagnostic difficulty, but also because of its rarity in English literature.
Knowledge and Utilization of Palliative Radiotherapy by Pediatric Oncologists
Authors: Tucker T. L. , Samant R. S. , Fitzgibbon E. J.
Published: January 2010

Background and Purpose: Palliative radiotherapy (PRT) is a routine part of oncology care in adult patients, but it is used much less frequently among children with incurable cancer. We surveyed Canadian pediatric oncologists to learn about their knowledge and use of PRT and to identify potential barriers to referral. Methods: A 13-item questionnaire assessing PRT knowledge and utilization was sent to 80 Canadian pediatric oncologists. Results: The survey completion rate was 80%, with most respondents being providers of palliative care for children and making referrals for PRT. Although 62% had received training in radiation oncology, only 28% had received formal palliative care training. Respondents with palliative care training were found to be significantly more knowledgeable about PRT and were more likely to refer children for PRT (p < 0.01). Only 59% of respondents thought that they had adequate knowledge about the indications for PRT. A positive correlation was found between knowledge about the indications for PRT and referral for treatment (p < 0.01). Among survey respondents, 51% believed that PRT was underutilized, and the perceived barriers to prt referral included patient or family reluctance, distance to the cancer centre, belief that PRT has little impact on quality of life, and concerns about toxicity. Conclusions: Palliative radiotherapy is considered to be underutilized among children. This situation appears to be related, in part, to inadequate knowledge and training among pediatric oncologists, suggesting that more emphasis needs to be placed on pediatric palliative care education.
Inter-Institutional Pathology Consultations for Breast Cancer: Impact on Clinical Oncology Therapy Recommendations
Authors: Price J. A. , Grunfeld E. , Barnes P. J. , Rheaume D. E. , Rayson D.
Published: January 2010

Background: Despite recommendations favouring review of cancer pathology specimens for patients being treated at an institution other than the one that produced the initial pathology report, data regarding discordance rates and their potential clinical impact remain limited, particularly for breast cancer. At the QEII Health Sciences Centre in Halifax, Nova Scotia, it was routine practice to review histopathology when patients referred for adjuvant therapy had undergone their breast cancer surgery and pathology reporting at another institution. The aim of the present study was to determine the rate and clinical impact of discordance in inter-institutional pathology consultations for breast cancer in Nova Scotia. Methods: We conducted a retrospective review of 100 randomly selected inter-institutional pathology consultations for breast cancer patients referred to the QEII in 2004. Cases were categorized as having either no discordance, discordance with no clinical impact, or discordance with potential for clinical impact. Cases with potential clinical impact were independently reviewed by 2 medical oncologists and 2 radiation oncologists, and the discordances were rated as having high, medium, or no clinical impact. Results: The study cohort consisted of 93 cases that met the inclusion criteria. Of these 93 cases, 6 had no discordance, 7 had discordance with no clinical impact, and 80 had discordance with potential for clinical impact. Overall, 10 cases (11%) were rated as having either high or medium clinical impact, with agreement on the clinical impact ratings by oncologist reviewers in the same specialty. The remaining cases had either no clinical impact or disagreement on the clinical impact rating. Conclusions: Inter-institutional pathology consultations for breast cancer in Nova Scotia identified discordant findings with potential clinical impact as determined by oncologist reviewers. Further evaluation of inter-institutional pathology consultations and the impact on clinical decision-making is warranted.
egfr Overexpression in Squamous Cell Carcinoma of the Penis
Authors: Lavens N. , Gupta R. , Wood L. A.
Published: January 2010

Penile cancer is a rare cancer in developed countries, but it has a higher incidence in developing countries such as Asia, Africa, and South America [...]
Management of Aromatase Inhibitor–Induced Arthralgia
Authors: Younus J. , Kligman L.
Published: January 2010

Aromatase inhibitors (AIS) are commonly used as adjuvant treatment in postmenopausal women with hormone receptor–positive early breast cancer. With both steroidal and nonsteroidal AIS, AI-induced arthralgia is frequently observed. The mechanism of AI-induced arthralgia remains unknown, and the data available from clinical trails using AIS are limited. We review the pertinent information from a clinical perspective, including an algorithm to treat AI-induced arthralgia.
Causes and Predictive Factors of Mortality in a Cohort of Patients with Hepatitis C Virus-related Cryoglobulinemic Vasculitis Treated with Antiviral Therapy
Authors: LANDAU DAN-AVI , SCERRA SAMY , SENE DAMIEN , RESCHE-RIGON MATHIEU , SAADOUN DAVID , CACOUB PATRICE
Published: January 2010

Objective.

Hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) vasculitis is an autoimmune disorder with significant morbidity and mortality. Renal involvement was associated with an increased mortality, and was the most common cause of death; these data were obtained before effective antiviral treatment was available. We studied causes of death and predictive factors in patients with HCV-associated MC vasculitis treated with antivirals.

Methods.

Case histories of 85 patients with HCV-associated MC vasculitis treated in a single center between 1990 and 2006 were retrospectively reviewed. Prognostic factors affecting mortality were studied by comparing 23 patients who died with 62 survivors, using the Cox model regression analysis.

Results.

The most common cause of death was infection, accounting for 34.7%, followed by endstage liver disease in 30.4% (including 4 patients with hepatocellular carcinoma), and cardiovascular disease in 17.4% of patients. Endstage renal disease accounted for only 8.7% of deaths, as did central nervous system vasculitis and nonhepatic malignancy. Increased mortality was strongly associated with immunosuppressive treatment [hazard ratio (HR) 6.51, 95% CI 2.75–15.37], cutaneous ulcers (HR 5.37, 95% CI 1.79–16.14), and renal insufficiency (HR 3.25, 95% CI 1.37–7.72). A 2 log10 decrease in HCV viral load at month 3 after starting antiviral treatment was associated with decreased mortality (HR 0.39, 95% CI 0.16–0.95).

Conclusion.

While renal involvement is still associated with poorer prognosis, infectious processes are now the most common cause of death in HCV cryoglobulinemia vasculitis. Immunosuppressive treatment is associated with an increased risk of death, independently from disease severity. Response to antiviral treatment is associated with significantly reduced mortality risk.
Prevalence of Autoantibodies in SAPHO Syndrome: A Single-center Study of 90 Patients
Authors: GROSJEAN CÉLINE , HURTADO-NEDELEC MARGARITA , NICAISE-ROLAND PASCALE , FERREYRA-DILLON RODRIGO , BOLLET CAROLINE , QUINTIN EMILIE , DIEUDE PHILIPPE , PALAZZO ELISABETH , WATTIAUX MARIE-JOSÉ , KAHN MARCEL-FRANCIS , MEYER OLIVIER , CHOLLET-MARTIN SYLVIE , HAYEM GILLES
Published: January 2010

Objective.

To determine the prevalence of the most often tested autoantibodies in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.

Methods.

We identified 90 patients seen in our unit between June 2002 and June 2009, and diagnosed according to the proposed criteria for SAPHO syndrome. Demographic and clinical data were collected as well as immunological results, including antinuclear, antithyroid peroxydase (TPO), antithyroid globulin (Tg), antigastric parietal cell, antismooth muscle, antimitochondria, and anti-liver-kidney microsome (LKM) antibodies. Anticyclic citrullinated peptide (CCP) antibodies were analyzed in 69 patients, antibodies to soluble extractable nuclear antigens in 43, anti-double-stranded DNA (dsDNA) antibodies in 22 [depending on the type of fluorescence of antinuclear antibody (ANA)], and antiendomysium antibodies in 55.

Results

Autoantibodies were found in 20 patients (22.2%): 14 patients (15.5%) had positive ANA (titer ≥ 1/160); among them, 10 (11%) patients never took a lupus-inducing drug. Antithyroid antibodies (anti-TPO and/or anti-Tg antibodies) were found in only 3 patients (3.3%). Three patients (3.3%) were positive for antigastric parietal cell antibodies and 4 (4.4%) were weakly positive for antismooth muscle antibodies. Antimitochondria and LKM antibodies were negative in all 90 patients. Anti-CCP and anti-dsDNA antibodies were negative in the 69 and 22 patients tested, respectively. One out of 43 patients (2.3%) had anti-SSA antibodies. Antiendomysium antibodies were negative in the 55 patients tested.

Conclusion.

Our study indicates an increased prevalence of autoantibodies in SAPHO syndrome, with no specific profile. We failed to confirm the reports of an increased prevalence of antithyroid antibodies. These results tend to support a link between autoimmunity and SAPHO syndrome.
Elevated Cardiac Troponin I and Functional Recovery and Disability in Patients After Aneurysmal Subarachnoid Hemorrhage
Authors: Miketic Joyce K. , Hravnak Marilyn , Sereika Susan M. , Crago Elizabeth A.
Published: January 2010

Background

Patients with aneurysmal subarachnoid hemorrhage experience myocardial injury at the time of rupture, but its effect on functional recovery and disability is unclear.

Objective

To describe the prevalence of myocardial injury, as indicated by high serum levels of cardiac troponin I (≥0.3 ng/mL), within the first 5 days after aneurysmal subarachnoid hemorrhage and the effect of the injury on 3-month functional recovery and disability.

Methods

In a prospective longitudinal study, 239 patients with Hunt/Hess grade 3 or greater and/or Fisher grade 2 or greater at admission had serum level of troponin I measured on days 0 to 5. Patients were interviewed at 3 months to evaluate functional recovery (Glasgow Outcome Scale) and functional disability (Modified Rankin Scale). Statistics included χ2 analysis, t tests, and binary logistic regression.

Results

Troponin values were elevated in 33.5% of the patients, and few patients in either group had a history of coronary artery disease (7.4% with troponin levels ≤ 0.3 ng/mL vs 2.7% with levels <0.3 ng/mL, P = .12). Higher troponin levels were significantly related to age and Hunt/Hess and Fisher grades, but not race, and were significantly associated with poorer functional recovery (P < .001) and more functional disability (P < .001). Even after controls for age, race, and more severe Hunt/Hess grades, higher levels remained a significant predictor of poorer functional recovery (P = .04) and disability (P = .01).

Conclusion

Elevated levels of cardiac troponin I after aneurysmal subarachnoid hemorrhage are common in patients with no cardiac history, are associated with severity of the hemorrhage, and are independently predictive of poorer functional recovery and increased disability.
Synthetic Cationic Peptide IDR-1002 Provides Protection against Bacterial Infections through Chemokine Induction and Enhanced Leukocyte Recruitment
Authors: Nijnik Anastasia , Madera Laurence , Ma Shuhua , Waldbrook Matthew , Elliott Melissa R. , Easton Donna M. , Mayer Matthew L. , Mullaly Sarah C. , Kindrachuk Jason , Jenssen Håvard , Hancock Robert E. W.
Published: January 2010

With the rapid rise in the incidence of multidrug resistant infections, there is substantial interest in host defense peptides as templates for production of new antimicrobial therapeutics. Natural peptides are multifunctional mediators of the innate immune response, with some direct antimicrobial activity and diverse immunomodulatory properties. We have previously developed an innate defense regulator (IDR) 1, with protective activity against bacterial infection mediated entirely through its effects on the immunity of the host, as a novel approach to anti-infective therapy. In this study, an immunomodulatory peptide IDR-1002 was selected from a library of bactenecin derivatives based on its substantially more potent ability to induce chemokines in human PBMCs. The enhanced chemokine induction activity of the peptide in vitro correlated with stronger protective activity in vivo in the Staphylococcus aureus-invasive infection model, with a >5-fold reduction in the protective dose in direct comparison with IDR-1. IDR-1002 also afforded protection against the Gram-negative bacterial pathogen Escherichia coli. Chemokine induction by IDR-1002 was found to be mediated through a Gi-coupled receptor and the PI3K, NF-κB, and MAPK signaling pathways. The protective activity of the peptide was associated with in vivo augmentation of chemokine production and recruitment of neutrophils and monocytes to the site of infection. These results highlight the importance of the chemokine induction activity of host defense peptides and demonstrate that the optimization of the ex vivo chemokine-induction properties of peptides is a promising method for the rational development of immunomodulatory IDR peptides with enhanced anti-infective activity.
Increasing Incidence, but Lack of Seasonality, of Elevated TSH Levels, on Newborn Screening, in the North of England
Authors: Pearce Mark S. , Korada Murthy , Day Julie , Turner Steve , Allison David , Kibirige Mohammed , Cheetham Tim D.
Published: January 2010

Previous studies of congenital hypothyroidism have suggested an increasing incidence and seasonal variation in incidence, which may suggest nongenetic factors involved in aetiology. This study describes the incidence of elevated thyroid stimulating hormone (TSH) values in newborns, a surrogate for congenital hypothyroidism, measured as part of the screening programme for congenital hypothyroidism, over an eleven-year period (1994–2005), and assesses whether seasonal variation exists. All infants born in the Northern Region of England are screened by measuring levels of circulating TSH using a blood spot assay. Data on all 213 cases born from 1994 to 2005 inclusive were available. Annual incidence increased significantly from 37 per 100,000 in 1994 to a peak of 92.8 per 100,000 in 2003. There was no evidence of seasonal variation in incidence. The reasons for the increasing incidence are unclear, but do not appear to involve increasing exposure to seasonally varying factors or changes in measurements methods.
RAPID3 (Routine Assessment of Patient Index Data) on an MDHAQ (Multidimensional Health Assessment Questionnaire): Agreement with DAS28 (Disease Activity Score) and CDAI (Clinical Disease Activity Index) activity categories, scored in five versus more than ninety seconds
Authors: Pincus Theodore , Swearingen Christopher J. , Bergman Martin J. , Colglazier C. Lee , Kaell Alan T. , Kunath Arthur M. , Siegel Evan L. , Yazici Yusuf
Published: January 2010

Objective

To compare the Routine Assessment of Patient Index Data 3 (RAPID3) on a Multidimensional Health Assessment Questionnaire (MDHAQ) with the Disease Activity Score (DAS28), Clinical Disease Activity Index (CDAI), and individual core data set measures for correlations, agreement of activity levels, and time to score.

Methods

Four rheumatologists each assessed 50 patients with rheumatoid arthritis in “real‐time” clinical care. Patients completed an MDHAQ. The rheumatologist then calculated RAPID3 (physical function, pain, patient global estimate), performed a 28‐joint count, assigned a physician global estimate, and scored a CDAI, each timed by an observer. Erythrocyte sedimentation rate (ESR) was tested on the same date, and the DAS28‐ESR was computed later, again timed by an observer. Spearman's rank‐order correlations and comparisons of patients classified as high activity, moderate activity, low activity, and remission according to the DAS28, CDAI, and RAPID3 were computed and compared with kappa statistics. A second study of 25 “paper patients” was also performed to compare time to score the DAS28, CDAI, and RAPID3 on a 0–10 versus 0–30 scale. Mean and median times to score each index were computed.

Results

The 3 indices were correlated significantly, including agreement for >80% of patients for high/moderate activity. The mean time to perform a 28‐joint count was 94 seconds, and the mean times to score the DAS28, CDAI, RAPID3 on a 0–10 scale, and RAPID3 on a 0–30 scale were 114, 106, 9.6, and 4.6 seconds, respectively.

Conclusion

RAPID3 scores provide similar quantitative information to DAS28 and CDAI, while calculated on a 0–30 scale in about 5% of the time.
Low physical activity is associated with proinflammatory high‐density lipoprotein and increased subclinical atherosclerosis in women with systemic lupus erythematosus
Authors: Volkmann Elizabeth R. , Grossman Jennifer M. , Sahakian Lori J. , Skaggs Brian J. , FitzGerald John , Ragavendra Nagesh , Charles‐Schoeman Christina , Chen Weiling , Gorn Alan , Karpouzas George , Weisman Michael , Wallace Daniel J. , Hahn Bevra H. , McMahon Maureen
Published: January 2010

Objective

To investigate the association between physical activity, functional activity of high‐density lipoprotein (HDL), and subclinical cardiovascular disease in patients with systemic lupus erythematosus (SLE).

Methods

A total of 242 SLE patients (all women) participated in this cross‐sectional study from February 2004 to February 2008. Carotid plaque and intima‐media thickness (IMT), antioxidant function of HDL, and traditional cardiac risk factors were measured. Physical activity was assessed from self‐reports by calculating the metabolic equivalents (METS) per week and by the physical function domain of the Medical Outcomes Study Short Form 36 (SF‐36). Data were analyzed using bivariate and multivariate regression analyses.

Results

Number of METS per week spent performing strenuous exercise was negatively correlated with IMT (r = −0.4, P = 0.002) and number of plaques (r = −0.30, P = 0.0001). Physical function as assessed by the SF‐36 was also negatively correlated with IMT (r = −0.14, P = 0.03) and number of plaques (r = −0.14, P = 0.04). In multivariate analyses, number of strenuous exercise METS was significantly associated with IMT (t = −2.2, P = 0.028) and number of plaques (t = −2.5, P = 0.014) when controlling for markers of SLE disease activity and damage, but not after controlling for traditional cardiac risk factors. Low physical activity, defined as <225 total METS per week, was associated with the presence of proinflammatory HDL (P = 0.03).

Conclusion

Low physical activity is associated with increased subclinical atherosclerosis and proinflammatory HDL in patients with SLE. Increased strenuous exercise may reduce the risk of atherosclerosis in SLE.
Incidence of chronic cutaneous lupus erythematosus in French Guiana: A retrospective population‐based study
Authors: Deligny Christophe , Clyti Emmanuel , Sainte‐Marie Dominique , Couppie Pierre , Huong Du Lê Thi , Piette Jean Charles , Arfi Serge , Pradinaud Roger
Published: January 2010

Objective

To retrospectively study the incidence of chronic cutaneous lupus erythematosus (CCLE) in French Guiana (FG), South America, during the period 1995–1999.

Methods

Private and public physicians specializing in dermatology, rheumatology, and internal medicine were asked during the year 2000 about lupus cases. We reviewed hospitals' files in data‐processing departments.

Results

Twenty new cases of CCLE, mostly discoid form, were identified during this 5‐year period in this population of predominantly African descent. The average annual incidence of the disease was 2.59 per 100,000 inhabitants (95% confidence interval 1.5–4). However, our methodology could introduce underestimation of the incidence of the disease.

Conclusion

The average annual incidence of CCLE in FG appears to be low in this retrospective study, but is very similar to the only previously published data in the US.
IgG4‐related systemic disease accounts for a significant proportion of thoracic lymphoplasmacytic aortitis cases
Authors: Stone John H. , Khosroshahi Arezou , Deshpande Vikram , Stone James R.
Published: January 2010

Objective

IgG4‐related systemic disease, a disorder recognized only recently, can cause lymphoplasmacytic inflammation in the thoracic aorta. The percentage of cases caused by IgG4‐related systemic disease is not known. We aimed to determine the percentage of noninfectious thoracic aortitis cases that are associated with IgG4‐related systemic disease and to establish pathologic criteria for identifying involvement of the thoracic aorta by this disorder.

Methods

We searched our Pathology Service database to identify patients with noninfectious thoracic aortitis who underwent resection over a 5‐year time span. The histologic features of these cases were reviewed. All cases of lymphoplasmacytic aortitis and representative cases of giant cell aortitis and atherosclerosis were stained by immunohistochemistry for IgG4 and for the plasma cell marker CD138. We determined the fraction of plasma cells that stained for IgG4.

Results

Of 638 resected thoracic aortas, 33 (5.2%) contained noninfectious aortitis. Four of these cases (12% of all patients with noninfectious aortitis) had histologic features of lymphoplasmacytic aortitis. Three of those 4 cases (9% of the noninfectious aortitis cases) demonstrated pathologic involvement by IgG4‐related systemic disease, with an elevated proportion of plasma cells staining for IgG4 (mean ± SD 0.82 ± 0.08) compared with cases of giant cell aortitis (0.18 ± 0.13) and atherosclerosis (0.19 ± 0.08; P < 0.00001).

Conclusion

IgG4‐related systemic disease accounted for 75% of lymphoplasmacytic aortitis cases and 9% of all cases of noninfectious thoracic aortitis in our institution during a 5‐year period. Immunohistochemical assessment of the percentage of plasma cells that stained for IgG4 in resected aortas was helpful in identifying patients with IgG4‐related systemic disease.