bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical relevance of positron emission tomography/computed tomography‐positive inguinal nodes in rectal cancer after neoadjuvant chemoradiation
Authors: Perez R. O. , Habr‐Gama A. , São Julião G. P. , Proscurshim I. , Ono C. R. , Lynn P. , Bailão Aguilar P. , Nahas S. C. , Gama‐Rodrigues J. , Buchpiguel C. A.
Published: February 2013

Aim

Inguinal nodes may be a possible route for lymphatic spread in patients with distal rectal cancer. The outcome was examined for patients with distal rectal cancer undergoing neoadjuvant chemoradiation (CRT) and having 2‐fluorine‐18‐fluoro‐2‐deoxy‐d‐glucose (FDG)‐avid inguinal nodes using positron emission tomography/computed tomography (PET/CT) imaging.

Method

Ninety‐nine consecutive patients with cT2‐4N0‐2M0 distal rectal adenocarcinoma were enrolled in a clinical trial (NCT00254683) and underwent baseline PET/CT followed by 54 Gy and 5‐fluorouracil‐based CRT. After CRT, patients underwent 6‐ and 12‐week PET/CT. Patients with positive inguinal node uptake were compared with patients with negative uptake. The inguinal region was not included in the field of radiation therapy.

Results

Seventeen (17%) patients had baseline positive inguinal node FDG uptake. They were more likely to have the tumour closer to the anal verge (2.0 vs 4.2 cm; P = 0.001). Of these, eight (47%) demonstrated a positive inguinal uptake at PET/CT after 12 weeks from CRT. Patients with inguinal node FDG uptake after CRT (positive PET at baseline and 12 weeks) had a significantly worse 3‐year overall and disease‐free survival (P = 0.02 and P = 0.03). After a median follow‐up period of 22 months, none of these patients had developed inguinal recurrence.

Conclusion

Uptake of inguinal nodes at PET/CT may be present in up to 17% of patients with distal rectal cancer, particularly with ultra‐low tumours. Nearly half of these nodes no longer show uptake after CRT despite the groin area not being included in the radiation field. Persistence of inguinal node uptake 12 weeks after CRT completion may be a marker for worse oncological outcome.
Use of the high dependency unit, increased consultant involvement and reduction in adverse events in patients who die after colorectal cancer surgery
Authors: Young J. A. , Waugh L. , McPhillips G. , Steele R. J. C. , Thompson A. M.
Published: February 2013

Aim

We prospectively audited adverse events for surgical patients with colorectal cancer who died under surgical care to test the hypothesis that increased critical care and consultant input could be associated with a reduction in adverse events.

Method

Patients with a diagnosis of colorectal cancer who died under surgical care in Scotland from 1996 to 2005 underwent peer review audit using established methodologies through the Scottish Audit of Surgical Mortality.

Results

In the 10‐year study period, 3029 patients with colorectal cancer, mean age 76 (13–105) years, died under surgical care, of whom 80% had presented as an emergency admission. Operative intervention was performed in 1557 (51%) patients of whom 1030 (34%) patients had a resection of the cancer. The annual number of patients dying after a cancer resection decreased significantly (P = 0.009). Significant decreases in adverse events were noted over time with a 67% fall in adverse events relating to critical care (P = 0.009), a 37% fall for surgical care (P = 0.04) and a significant increase in consultant anaesthetist and consultant surgeon input, but there was a 9% increase in delay as an adverse event (P = 0.006). The documented anastomotic leakage rate in patients who died increased from 8% in 1996 to 19% in 2005 (P = 0.016).

Conclusion

The number of patients dying with colorectal cancer after surgery has decreased in recent years. Adverse events in these patients have significantly reduced over a decade with increased consultant involvement although there is the potential for further improvement.
Clinical course and rebleeding predictors of acute haemorrhagic rectal ulcer: 5‐year experience and review of the literature
Authors: Matsumoto T. , Inokuma T.
Published: February 2013

Aim

This study was carried out to clarify the clinical features of acute haemorrhagic rectal ulcer (AHRU) and to determine the risks and predictors of AHRU rebleeding.

Method

Forty patients with AHRU were retrospectively analysed. Patient characteristics, endoscopic features and clinical course were investigated and predictors of AHRU rebleeding were analysed.

Results

All patients were in a bedridden state as a result of various diseases, and many patients had atherosclerosis‐related comorbidities such as hypertension (67.4%), diabetes mellitus (40.0%) and chronic kidney disease (42.5%). All patients had hypoalbuminaemia, 75% of patients were using antithrombotic drugs and 25% of patients were using systemic corticosteroids. Based on colonoscopy, all patients developed ulcers in the distal rectum just above the dentate line and 30% of patients developed whole circumferential ulcers. The median interval between the onset of the bedridden state and the first massive haematochezia was 16 days and 50% of all patients developed rebleeding regardless of the presence or absence of haemostatic therapy. The median time from initial haemostasis to rebleeding was 6 days. Univariate analysis and stepwise multivariate analysis revealed that whole circumferential ulcer (P = 0.036) was a significant independent predictor of AHRU rebleeding.

Conclusion

In the present study, we elucidated the clinical features of AHRU in detail and reviewed previous reports of AHRU. Rebleeding of AHRU occurred at a high rate and whole circumferential ulcer was a significant independent predictor of AHRU rebleeding.
Dysglycaemia in the critically ill – significance and management
Authors: Deane A. M. , Horowitz M.
Published: February 2013

Hyperglycaemia frequently occurs in the critically ill, in patients with diabetes, as well as those who were previously glucose‐tolerant. The terminology ‘stress hyperglycaemia’ reflects the pathogenesis of the latter group, which may comprise up to 40% of critically ill patients. For comparable glucose concentrations during acute illness outcomes in stress hyperglycaemia appear to be worse than those in patients with type 2 diabetes. While several studies have evaluated the optimum glycaemic range in the critically ill, their interpretation in relation to clinical recommendations is somewhat limited, at least in part because patients with stress hyperglycaemia and known diabetes were grouped together, and the optimum glycaemic range was regarded as static, rather than dynamic, phenomenon. In addition to hyperglycaemia, there is increasing evidence that hypoglycaemia and glycaemic variability influence outcomes in the critically ill adversely. These three categories of disordered glucose metabolism can be referred to as dysglycaemia. While stress hyperglycaemia is most frequently managed by administration of short‐acting insulin, guided by simple algorithms, this does not treat all dysglycaemic categories; rather the use of insulin increases the risk of hypoglycaemia and may exacerbate variability. The pathogenesis of stress hyperglycaemia is complex, but hyperglucagonaemia, relative insulin deficiency and insulin resistance appear to be important. Accordingly, novel agents that have a pathophysiological rationale and treat hyperglycaemia, but do not cause hypoglycaemia and limit glycaemic variability, are appealing. The potential use of glucagon‐like peptide‐1 (or its agonists) and dipeptyl‐peptidase‐4 inhibitors is reviewed.
Yohimbine anxiogenesis in the elevated plus maze requires hindbrain noradrenergic neurons that target the anterior ventrolateral bed nucleus of the stria terminalis
Authors: Zheng Huiyuan , Rinaman Linda
Published: February 2013

The α2 adrenergic receptor antagonist yohimbine (YO) increases transmitter release from noradrenergic (NA) terminals in cortical and subcortical brain regions, including the bed nucleus of the stria terminalis (BST). YO activates the hypothalamic–pituitary–adrenal (HPA) stress axis and is potently anxiogenic in rats and humans. We previously reported that hindbrain NA neurons within the caudal nucleus of the solitary tract (NST‐A2/C2) and ventrolateral medulla (VLM‐A1/C1) that innervate the anterior ventrolateral (vl)BST contribute to the ability of YO to activate the HPA stress axis in rats. To determine whether the same NA pathway also contributes to YO‐induced anxiogenesis in the elevated plus maze (EPMZ), a selective saporin ribotoxin conjugate (dopamine beta hydroxylase conjugated to saporin toxin, DSAP) was microinjected bilaterally into the anterior vlBST to destroy its NA inputs. Sham‐lesioned controls were microinjected with vehicle. Two experiments were conducted to determine DSAP lesion effects on EPMZ behavior. DSAP lesions did not alter maze behavior in rats after intraperitoneal saline, and did not alter the significant effect of prior maze experience to reduce exploratory and open arm maze activities. However, in maze‐naïve rats, DSAP lesions abolished YO anxiogenesis in the EPMZ. Post‐mortem immunocytochemical analyses confirmed that DSAP consistently ablated caudal NST‐A2/C2 and VLM‐A1/C1 neurons that innervate the anterior vlBST. DSAP lesions did not destroy non‐NA inputs to the anterior vlBST, and produced inconsistent cell loss within the pontine locus coeruleus (A6 cell group) that was unrelated to YO anxiogenesis. Thus, the ability of YO to increase anxiety‐like behavior in the EPMZ depends on hindbrain NA neurons that target the anterior vlBST.
Interobserver agreement of the old and the newly proposed ILAE epilepsy classification in children
Authors: van Campen Jolien S. , Jansen Floor E. , Brouwer Oebele F. , Nicolai Joost , Braun Kees P. J.
Published: February 2013

Purpose

Accurate classification of epileptic seizures, epilepsies, and epilepsy syndromes is mandatory in both clinical practice and epilepsy research. In 2010, the International League Against Epilepsy (ILAE) proposed a new classification scheme. The aim of this study is to determine whether application of this new classification for epileptic seizures and epilepsies has improved interobserver agreement compared to the classification schemes used previously.

Methods

Three pediatric neurologists working in different university hospitals retrospectively classified seizures and epilepsies of 80 children (165 seizures) referred to the University Center Utrecht, based on anonymized data, according to the newly proposed (2010) as well as the old (1981/1989) ILAE classification schemes. We determined interobserver agreement of the application of both ILAE classifications with kappa statistics.

Key Findings

Interobserver agreement of the new classification for seizures and epilepsies is comparable to that of previous classifications. There is substantial agreement on the newly introduced etiologic axis.

Significance

Introduction of the new epilepsy classification has not substantially improved interobserver agreement. This study shows which items cause considerable interobserver disagreement and therefore need specification.
Border Children: Interpreting Autism Spectrum Disorder in South Korea
Authors: Grinker Roy Richard , Cho Kyungjin
Published: February 2013

In this article, we describe reluctant mothers on the brink of accepting autism spectrum disorder (ASD) as a diagnosis for their children, but caught in a web of social meanings that push them to resist it. We argue that several tensions underlie this resistance: (1) an opposition between homogeneity and heterogeneity, in which mothers aim to define their child as “normal”; (2) a distinction between social and intellectual domains of child development, in which mothers localize their children's problems as deficits in a discrete area of development, rather than as a global or pervasive impairment; and (3) an opposition between chronicity and recovery, in which mothers reject a label they fear will index a permanent condition. These oppositions help to define the interaction between a diagnosis new to Koreans (ASD) and a particular condition (the child who has the symptoms of ASD but is academically successful) to form a new kind of child that mothers and teachers increasingly call “border children” (gyonggye‐seon aideul). This specific ethnographic inquiry informs debates over the ontological bases for psychiatric diagnoses in children, and the processes through which local institutions, classificatory schemes, expertise, and child behavior shape conceptions of child development. [autism, Korea, child development, child psychiatry, border children]
“We Want to See Our King”: Apparitions in Messianic Habad
Authors: Bilu Yoram
Published: February 2013

Reports of apparitions of the late Rabbi Menachem Mendel Schneerson, the last leader of the Habad Hasidic movement, have been spreading among the radically messianic Hasidim (meshichistim) in Israel, who maintain that the Rabbi, the designated Messiah, has not died. Expanding on the cognitive model of source misattribution, I seek to account for the apparitions by unpacking the messianic ecology cultivated by the meshichistim to make the absent Rabbi present. Habad's dialectical mysticism and anguish over the Rabbi's disappearance are likely to provide the mindset and motivation for sightings, but it is the rich array of icons and traces of the Rabbi, and mimetic practices in which they are embedded, that constitute the perceptual field where he can be seen. This cultural décor is particularly evident for apparitions in ritual arenas, while apparitions in mundane settings are often triggered by acute distress. Comparing the apparitions to visions in Christianity, I account for the lingering ambivalence toward apparitions in messianic Habad by highlighting the epistemological constraints imposed on them by the denial of the Rabbi's death. [apparitions, Habad Hasidism, signal detection theory, messianic ecology, Rabbi Menachem Mendel Schneeerson]
Respiratory diseases and their effects on respiratory function and exercise capacity
Authors: Van Erck‐Westergren E. , Franklin S. H. , Bayly W. M.
Published: February 2013

Given that aerobic metabolism is the predominant energy pathway for most sports, the respiratory system can be a rate‐limiting factor in the exercise capacity of fit and healthy horses. Consequently, respiratory diseases, even in mild forms, are potentially deleterious to any athletic performance. The functional impairment associated with a respiratory condition depends on the degree of severity of the disease and the equestrian discipline involved. Respiratory abnormalities generally result in an increase in respiratory impedance and work of breathing and a reduced level of ventilation that can be detected objectively by deterioration in breathing mechanics and arterial blood gas tensions and/or lactataemia. The overall prevalence of airway diseases is comparatively high in equine athletes and may affect the upper airways, lower airways or both. Diseases of the airways have been associated with a wide variety of anatomical and/or inflammatory conditions. In some instances, the diagnosis is challenging because conditions can be subclinical in horses at rest and become clinically relevant only during exercise. In such cases, an exercise test may be warranted in the evaluation of the patient. The design of the exercise test is critical to inducing the clinical signs of the problem and establishing an accurate diagnosis. Additional diagnostic techniques, such as airway sampling, can be valuable in the diagnosis of subclinical lower airway problems that have the capacity to impair performance. As all these techniques become more widely used in practice, they should inevitably enhance veterinarians' diagnostic capabilities and improve their assessment of treatment effectiveness and the long‐term management of equine athletes.
Synstatin: a selective inhibitor of the syndecan‐1‐coupled IGF1R–αvβ3 integrin complex in tumorigenesis and angiogenesis
Authors: Rapraeger Alan C.
Published: February 2013

The syndecans are a family of heparan sulfate‐decorated cell‐surface proteoglycans: matrix receptors with roles in cell adhesion and growth factor signaling. Their heparan sulfate chains recognize ‘heparin‐binding’ motifs that are ubiquitously present in the extracellular matrix, providing the means for syndecans to constitutively bind and cluster to sites of cell–matrix adhesion. Emerging evidence suggests that specialized docking sites in the syndecan extracellular domains may serve to localize other receptors to these sites as well, including integrins and growth factor receptor tyrosine kinases. A prototype of this mechanism is capture of the αvβ3 integrin and insulin‐like growth factor 1 receptor (IGF1R) by syndecan‐1 (Sdc1), forming a ternary receptor complex in which signaling downstream of IGF1R activates the integrin. This Sdc1‐coupled ternary receptor complex is especially prevalent on tumor cells and activated endothelial cells undergoing angiogenesis, reflecting the up‐regulated expression of αvβ3 integrin in such cells. As such, much effort has focused on developing therapeutic agents that target this integrin in various cancers. Along these lines, the site in the Sdc1 ectodomain that is responsible for capture and activation of the αvβ3 or αvβ5 integrins by IGF1R can be mimicked by a short peptide called ‘synstatin’, which competitively displaces the integrin and IGF1R kinase from the syndecan and inactivates the complex. This review summarizes our current knowledge of the Sdc1‐coupled ternary receptor complex and the efficacy of synstatin as an emerging therapeutic agent to target this signaling mechanism.
Imatinib as a key inhibitor of the platelet‐derived growth factor receptor mediated expression of cell surface heparan sulfate proteoglycans and functional properties of breast cancer cells
Authors: Malavaki Christina J. , Roussidis Andreas E. , Gialeli Chrisostomi , Kletsas Dimitris , Tsegenidis Theodore , Theocharis Achileas D. , Tzanakakis George N. , Karamanos Nikos K.
Published: February 2013

Cell surface heparan sulfate proteoglycans (HSPGs), syndecans and glypicans, play crucial roles in the functional properties of cancer cells, such as proliferation, adhesion, migration and invasion. Platelet‐derived growth factor (PDGF)/PDGF receptor (PDGF‐R) mediated signaling, on the other hand, is highly associated with cancer progression. Specifically, PDGF‐Rα and PDGF‐Rβ expressions documented in breast cancer tissue specimens as well as breast cancer cell lines are correlated with tumor aggressiveness and metastasis. Imatinib (Glivec®) is a tyrosine kinase inhibitor specific for PDGF‐Rs, c‐ΚΙΤ and BCR‐ABL. In this study we evaluated the effects of imatinib on the properties of breast cancer cells as well as on the expression of HSPGs in the presence and absence of PDGF‐BB. These studies have been conducted in a panel of three breast cancer cell lines of low and high metastatic potential. Our results indicate that imatinib exerts a significant inhibitory effect on breast cancer cell proliferation, invasion and migration as well as on the cell surface expression of HSPGs even after exposure of PDGF. These effects depend on the aggressiveness of breast cancer cells and the type of HSPG. It is suggested that imatinib may be of potential therapeutic usefulness in breast cancer regimes.
Endorepellin laminin‐like globular 1/2 domains bind Ig3–5 of vascular endothelial growth factor (VEGF) receptor 2 and block pro‐angiogenic signaling by VEGFA in endothelial cells
Authors: Willis Chris D. , Poluzzi Chiara , Mongiat Maurizio , Iozzo Renato V.
Published: February 2013

Endorepellin, a processed fragment of perlecan protein core, possesses anti‐angiogenic activity by antagonizing endothelial cells. Endorepellin contains three laminin G‐like (LG) domains and binds simultaneously to vascular endothelial growth factor receptor 2 (VEGFR2) and α2β1 integrin, resulting in dual receptor antagonism. Treatment of endothelial cells with endorepellin inhibits transcription of VEGFA, the natural ligand for VEGFR2, attenuating the pro‐survival and migratory activities of VEGFA/VEGFR2 signaling cascade. Here, we investigated the specific binding site of endorepellin within the ectodomain of VEGFR2. Full‐length endorepellin was not capable of displacing VEGFA binding from VEGFR2 and LG3 domain alone did not bind VEGFR2. This suggested different binding mechanisms of the extracellular Ig domains of VEGFR2. Therefore, we hypothesized that endorepellin would bind through its proximal LG1/2 domains to VEGFR2 in a different region than VEGFA. Indeed, we found that LG1/2 did not bind Ig1–3, but did bind with high affinity to Ig3–5, distal to the known VEGFA binding site, i.e. Ig2–3. These results support a role for endorepellin as an allosteric inhibitor of VEGFR2. Moreover, we found that LG1/2 blocked the rapid VEGFA activation of VEGFR2 at Tyr1175 in endothelial cells. In contrast, LG1/2 did not result in actin cytoskeletal disassembly in endothelial cells whereas LG3 alone did induce cytoskeletal collapse. However, LG1/2 did inhibit VEGFA‐dependent endothelial migration through fibrillar collagen I. These studies provide a mechanistic understanding of how the different LG domains of endorepellin signal in endothelial cells while serving as a template for protein design of receptor tyrosine kinase antagonists.

Structured digital abstract

Ig1-3 of VEGFR2 binds to VEGFA by filter binding (View interaction)

Ig3-5 of VEGFR2 binds to Endorepellin LG1/2 by enzyme linked immunosorbent assay (View interaction)

Ig1-3 of VEGFR2 binds to Endorepellin LG1/2 by filter binding (View Interaction: 1, 2)

Endorepellin LG1/2 binds to Ig3-5 of VEGFR2 by anti bait coimmunoprecipitation (View interaction)

[Structured digital abstract was added on 3 May 2013 after original online publication]
Interannual variability of net ecosystem productivity in forests is explained by carbon flux phenology in autumn
Authors: Wu Chaoyang , Chen Jing M. , Black T. Andrew , Price David T. , Kurz Werner A. , Desai Ankur R. , Gonsamo Alemu , Jassal Rachhpal S. , Gough Christopher M. , Bohrer Gil , Dragoni Danilo , Herbst Mathias , Gielen Bert , Berninger Frank , Vesala Timo , Mammarella Ivan , Pilegaard Kim , Blanken Peter D.
Published: February 2013

Aim

To investigate the importance of autumn phenology in controlling interannual variability of forest net ecosystem productivity (NEP) and to derive new phenological metrics to explain the interannual variability of NEP.

Location

North America and Europe.

Method

Flux data from nine deciduous broadleaf forests (DBF) and 13 evergreen needleleaf forests (ENF) across North America and Europe (212 site‐years) were used to explore the relationships between the yearly anomalies of annual NEP and several carbon flux based phenological indicators, including the onset/end of the growing season, onset/end of the carbon uptake period, the spring lag (time interval between the onset of growing season and carbon uptake period) and the autumn lag (time interval between the end of the carbon uptake period and the growing season). Meteorological variables, including global shortwave radiation, air temperature, soil temperature, soil water content and precipitation, were also used to explain the phenological variations.

Results

We found that interannual variability of NEP can be largely explained by autumn phenology, i.e. the autumn lag. While variation in neither annual gross primary productivity (GPP) nor in annual ecosystem respiration (Re) alone could explain this variability, the negative relationship between annual NEP and autumn lag was due to a larger Re/GPP ratio in years with a prolonged autumn lag. For DBF sites, a longer autumn lag coincided with a significant decrease in annual GPP but showed no correlation with annual Re. However, annual GPP was insensitive to a longer autumn lag in ENF sites but annual Re increased significantly.

Main conclusions

These results demonstrate that autumn phenology plays a more direct role than spring phenology in regulating interannual variability of annual NEP. In particular, the importance of respiration may be potentially underestimated in deriving phenological indicators.
Comparison of near infrared reflectance spectroscopy calibration strategies for the botanical composition of grass‐clover mixtures
Authors: Cougnon M. , Van Waes C. , Dardenne P. , Baert J. , Reheul D.
Published: February 2013

Predicting species composition in mixed swards by near infrared reflectance spectroscopy (NIRS) can save labour in grassland research, provided equations are available. This study compares calibration strategies to predict species composition in swards with tall fescue (Festuca arundinacea), perennial ryegrass (Lolium perenne) and white clover (Trifolium repens). The compared calibration strategies were based on either real or artificial samples. Real samples are samples taken from multispecies swards; the species composition is known by hand separating; after separating, the original samples are recomposed. Artificial samples are samples obtained by mixing single species grown in pure stands in known proportions. The performance of the equation based on real samples was significantly better than the performance of the equation based on artificial samples. We hypothesized that the weak performance of the equation based on artificial samples was due to a lack of environmental variation in the spectra of the artificial samples. The hypothesis was supported by the good performance of a novel calibration strategy based on the spectra of the artificial samples with added variation. According to the obtained results, a calibration strategy based on few but diverse calibration samples is discussed.
Characterization of Flow Dynamics and Vulnerability in a Coastal Aquifer System
Authors: Murgulet Dorina , Tick Geoffrey R.
Published: February 2013

Traditional aquifer vulnerability techniques primarily rely on spatial property data for a region and are limited by their ability to directly or indirectly assess flow and transport processes occurring from the surface to depth within an aquifer system. The main objective of this study was to investigate groundwater vulnerability in terms of aquifer interconnectivity and flow dynamics. A combination of stable isotopes, groundwater age‐dating (radiocarbon), and geomorphic/geogenic spatial analyses was applied to a regional, highly developed coastal aquifer to explain the presence of nitrate at depth. The average δ13C value (−17.3 ± 2‰ VPDB, n = 27) is characteristic of groundwater originating from locally infiltrated precipitation through extensively cultivated soils. The average δ18O and δD values (−4.0 ± 0.1‰ VSMOW, n = 27; δD: −19.3 ± 1‰ VSMOW, n = 27, respectively) are similar to precipitation water derived from maritime sources feeding the region's surface water and groundwater. Stable and radioactive isotopes reveal significant mixing between shallow and deep aquifers due to high velocities, hydraulic connection, and input of local recharge water to depths. Groundwater overdevelopment enhances deeper and faster modern water downward flux, amplifying aquifer vulnerability. Therefore, aquifer vulnerability is a variable, dependent on the type and degree of stress conditions experienced by a groundwater system as well as the geospatial properties at the near surface.
Enhanced cross‐priming of naive CD8+T cells by dendritic cells treated by the IMiDs® immunomodulatory compounds lenalidomide and pomalidomide
Authors: Henry Jake Y. , Labarthe Marie‐Christine , Meyer Brendan , Dasgupta Prokar , Dalgleish Angus G. , Galustian Christine
Published: February 2013

The IMiDs® immunomodulatory compounds lenalidomide and pomalidomide are agents with anti‐inflammatory, immunomodulatory and anti‐cancer activity. An excellent success rate has been shown for multiple myeloma in phase I/II clinical trials leading to Food and Drug Administration approval of lenalidomide. One mechanism by which these drugs could enhance anti‐tumour immunity may be through enhanced dendritic cell (DC) function. Thalidomide, a compound structurally related to lenalidomide and pomalidomide, is known to enhance DC function, and we have investigated whether its analogues, pomalidomide and lenalidomide, also have functional effects on DCs. We used mouse bone marrow‐derived DCs treated with 5 or 10 μm pomalidomide, or lenalidomide from day 1 of culture. Treatment with IMiD® immunomodulatory compounds increased expression of Class I (H2‐Kb), CD86, and pomalidomide also increased Class II (I‐Ab) expression in bone marrow‐derived DCs, as measured by flow cytometry. Fluorescent bead uptake was increased by up to 45% when DCs were treated with 5 or 10 μm pomalidomide or lenalidomide compared with non‐treated DCs. Antigen presentation assays using DCs primed with ovalbumin, and syngeneic T cells from transgenic OTI and OTII mice (containing MHC restricted, ovalbumin‐specific, T cells) showed that both pomalidomide and lenalidomide effectively increased CD8+ T‐cell cross‐priming (by up to 47%) and that pomalidomide alone was effective in increasing CD4+ T‐cell priming (by 30%). Our observations suggest that pomalidomide and lenalidomide enhance tumour antigen uptake by DCs with an increased efficacy of antigen presentation, indicating a possible use of these drugs in DC vaccine therapies.
Older Methadone Patients Achieve Greater Durations of Cocaine Abstinence with Contingency Management Than Younger Patients
Authors: Weiss Lindsay , Petry Nancy M.
Published: February 2013

Background and Objectives

Contingency management (CM) interventions are efficacious in treating cocaine abusing methadone patients, but few studies have examined the effect of age on treatment outcomes in this population. This study evaluated the impact of age on treatment outcomes in cocaine abusing methadone patients.

Methods

Data were analyzed from 189 patients enrolled in one of three randomized studies that evaluated the efficacy of CM versus standard care (SC) treatment.

Results

Age was associated with some demographics and drug use characteristics including racial composition, education, and methadone dose. Primary drug abuse treatment outcomes did not vary across age groups, but CM had a greater benefit for engendering longer durations of abstinence in the middle/older and older age groups compared to the younger age groups. At the 6‐month follow‐up, submission of a cocaine positive urine sample was predicted by submission of a cocaine positive sample at intake, higher methadone doses, and assignment to SC rather than CM treatment.

Conclusions and Scientific Significance

As substance abusers are living longer, examination of the efficacy of pharmacological and psychosocial treatments specifically within older age groups may lead to a better understanding of subpopulations for whom enhanced treatments such as CM are warranted. (Am J Addict 2013;22:119‐126)
Performance‐Enhancing Drugs on the Web: A Growing Public‐Health Issue
Authors: Brennan Brian P. , Kanayama Gen , Pope Harrison G.
Published: February 2013

Background and Objectives

Today's Internet provides extensive “underground” guidelines for obtaining and using illicit substances, including especially anabolic‐androgenic steroids (AAS) and other appearance‐ and performance‐enhancing drugs (APEDs). We attempted to qualitatively characterize APED‐related Internet sites.

Methods

We used relevant Internet search terms (eg, “steroids bodybuilding” and “buy steroids online”) to assess (i) the numbers of site visitors; (ii) offers of drugs for sale; and (iii) the quality of online medical information. We also chose the examples of (iv) “site‐enhancing oils” and (v) “cattle implants” to illustrate the volume of available Internet information as compared with that in the medical literature.

Results

We found thousands of sites involving AAS and other APEDs. Most sites presented an unabashedly pro‐drug position, often openly questioning the qualifications and motivations of mainstream medical practitioners. Offers of AAS and other APEDs for sale, together with medical advice of varying legitimacy, was widespread across sites. Importantly, many sites provided detailed guidelines for exotic forms of APED use, some likely associated with serious health risks, which are probably unknown to most practicing clinicians.

Conclusions and Scientific Significance

It seems important for practitioners to be aware of the extent of this “underground literature,” which may strongly influence their patients' decisions about use and abuse of APEDs. (Am J Addict 2013;22:158‐161)
Experimental and Clinical Evaluation of Transperitoneal Laparoscopic Ureteronephrectomy in Dogs
Authors: Mayhew Philipp D. , Mehler Stephen J. , Mayhew Kelli N. , Steffey Michele A. , Culp William T. N.
Published: February 2013

Objective

To report a surgical technique for transperitoneal laparoscopic ureteronephrectomy (TLU) in dogs and describe complications and outcome in a cohort of dogs.

Study Design

Experimental study and case series.

Animals

Purpose‐bred research dogs (n = 3) and canine clinical cases (9).

Methods

In 11 of 12 dogs, a 3 port laparoscopic approach was used and in 1 dog a 4‐port approach was used. Incision through the retroperitoneal space was followed by early dissection of the ureter to aid retraction and elevation of the renal hilus. Dissection was performed principally by use of a vessel‐sealing device. Ligation of the renal hilar vessels was accomplished using laparoscopic hemoclips. Experimental dogs were euthanatized and necropsied.

Results

In 3 experimental dogs, no intraoperative complications occurred and conversion to an open approach was unnecessary. Of 9 clinical cases, conversion to an open approach was required in 2 dogs, because of severe hydroureter obscuring observation in 1, and uncontrollable retroperitoneal hemorrhage in the other dog. In 1 dog hemorrhage from the renal capsule and renal vein was controlled laparoscopically. No other major complications occurred. All dogs were discharged.

Conclusions

Transperitoneal laparoscopic ureteronephrectomy is feasible in dogs although conversion to an open approach should be considered when uncontrollable hemorrhage is encountered or the view is obscured by anatomic alteration.
A Single Caudally Based Frontonasal Bone Flap for Treatment of Bilateral Mucocele in the Paranasal Sinuses of an American Miniature Horse
Authors: Easley Jeremiah T. , Freeman David E.
Published: February 2013

Objective

To describe successful surgical treatment of bilateral mucocele in an American Miniature horse using a single bone flap to approach right and left paranasal sinuses simultaneously.

Study Design

Clinical report.

Animal

A castrated 6‐year‐old American Miniature Horse with a bilateral mucocele of the paranasal sinuses.

Methods

A single bilateral frontonasal sinus flap was used in a standing procedure to access the left and right conchofrontal sinuses simultaneously to remove the mucous contents and to establish permanent drainage into the nasal cavities.

Results

The novel procedure used in this horse allowed excellent access to right and left paranasal sinuses simultaneously and completely resolved nasal discharge and difficulty breathing.

Conclusions

A single, bilateral frontonasal sinus flap can be used successfully as a standing procedure to treat bilateral sinonasal disease in horses.
Optimal Tension, Position, and Number of Prostheses Required for Maximum Rima Glottidis Area After Laryngoplasty
Authors: Bischofberger Andrea S. , Wereszka Marta M. , Hadidane Ines , Perkins Nigel R. , Jeffcott Leo B. , Dart Andrew J.
Published: February 2013

Objectives

To evaluate the effect of 3 laryngeal prostheses alone or in combination on rima glottidis area in horses.

Study Design

Experimental randomized design.

Sample Population

Cadaveric equine larynges (n = 22).

Methods

Three prostheses were preplaced in each of 14 larynges. Rima glottidis area was measured after loading each suture in 5 Newton (N) increments from 0 N to 35 N. In 8 larynges, the 3 prostheses were tied alone or in combination at a fixed load of 15 N and rima glottidis area measured.

Results

Rima glottidis cross‐sectional area increased as the load on each prosthesis increased with maximum area reached at 20 N for each prosthesis. At a fixed load of 15 N, tying 2 and 3 prostheses in combination resulted in a larger rima glottidis cross‐sectional area than achieved with each prosthesis alone.

Conclusions

A combination of 2 or 3 prostheses tied at a fixed load of 15 N optimized rima glottidis cross‐sectional area irrespective of the anatomic location of the prosthesis.
Diagnostic Accuracy of Tissue Impedance Measurement Interpretation for Correct Veress Needle Placement in Canine Cadavers
Authors: Whittemore Jacqueline C. , Mitchell Amanda , Hyink Sara , Reed Ann
Published: February 2013

Objective

To establish the diagnostic accuracy of tissue impedance measurement interpretation (TIMI) for determining correct versus incorrect Veress needle placement.

Study Design

Prospective, randomized, blinded trial.

Study Population

Canine cadavers (n = 20).

Methods

Two laparoscopists (1 experienced, 1 novice), blinded to tissue impedance measurement results, placed reusable Veress needles in canine cadavers in a randomized order. A 3rd individual interpreted impedance measurements as consistent with correct or incorrect Veress needle placement. Veress needle tip locations were marked by injecting contrasting colors of India ink. Tissue dissection was performed to localize ink. Sensitivity, specificity, accuracy, precision, and kappa statistics for TIMI for placements by the experienced and novice laparoscopist were determined. P < .05 was considered significant.

Results

TIMI identified 29/33 correct and 7/7 incorrect placements, respectively. Impedance measurement interpretation had 87.9% sensitivity, 100% specificity, 90% accuracy, and 100% precision overall. Agreement between TIMI and Veress needle location was moderate (kappa 0.50, P = .01) for placements by the experienced laparoscopist and very high (kappa 0.88, P < .01) for the novice laparoscopist.

Conclusions

Diagnostic accuracy of TIMI for Veress needle placement was higher than has been reported for other tests, and TIMI had a shallow learning curve. TIMI successfully detected all incorrect Veress needle placements. Further prospective evaluation of Veress needle placement with and without TIMI is warranted to determine if its use increases operator detection of inappropriate Veress needle placements or decreases installment phase complication rates.
Women's Attitudes Toward Their Partners’ Involvement in Antenatal Care and Prevention of Mother‐to‐Child Transmission of HIV in Cameroon, Africa
Authors: Nkuoh Godlove N. , Meyer Dorothy J. , Nshom Emmanuel M.
Published: February 2013

Introduction: Although the HIV epidemic has stabilized worldwide, it remains a public health challenge in sub‐Saharan Africa. The key strategy to prevention and control of HIV remains voluntary counseling and testing. In sub‐Saharan Africa, 76% of pregnant women have at least one antenatal visit. Therefore, antenatal care is a venue through which women can access HIV testing, and, if infected, obtain care for prevention of mother‐to‐child transmission (PMTCT). Public health organizations have promoted increasing HIV testing of men by incorporating partner testing into antenatal care. Recent studies have shown that African women may not be receptive to their partner's involvement in obstetric care secondary to cultural attitudes and traditional beliefs.

Methods: A quality improvement project surveyed women to identify their attitudes and beliefs concerning antenatal care, PMTCT, and partner's participation in antenatal care and testing.

Results: Women viewed antenatal care as important to having a positive pregnancy outcome and the primary venue through which they accessed HIV testing. Most women (83.8%) were receptive to their partners’ involvement in antenatal care and identified increased partner participation over the past 5 years. Women (98.2%) said men's primary role was payment for obstetric care. Cultural and gender‐based attitudes and beliefs were identified as barriers to HIV testing of men.

Discussion: Women viewed antenatal care as important to a positive pregnancy outcome with access dependent on their families’ finances and their partners’ ability and willingness to pay for their care. Although pregnancy has traditionally been viewed as a women's affair, the majority of women wanted their partners to participate in their care, including receiving HIV counseling and testing. Women identified men's involvement as an individual belief, saying that many in their community were not supportive of male participation in antenatal care. Multiple options, including couples testing in antenatal clinics, should be available to increase HIV testing in men.
Childhood Abuse History, Posttraumatic Stress Disorder, Postpartum Mental Health, and Bonding: A Prospective Cohort Study
Authors: Seng Julia S. , Sperlich Mickey , Low Lisa Kane , Ronis David L. , Muzik Maria , Liberzon Israel
Published: February 2013

Introduction: Research is needed that prospectively characterizes the intergenerational pattern of effects of childhood maltreatment and lifetime posttraumatic stress disorder (PTSD) on women's mental health in pregnancy and on postpartum mental health and bonding outcomes. This prospective study included 566 nulliparous women in 3 cohorts: PTSD‐positive, trauma‐exposed resilient, and not exposed to trauma.

Methods: Trauma history, PTSD diagnosis, and depression diagnosis were ascertained using standardized telephone interviews with women who were pregnant at less than 28 gestational weeks. A 6‐week‐postpartum interview reassessed interim trauma, labor experience, PTSD, depression, and bonding outcomes.

Results: Regression modeling indicates that posttraumatic stress in pregnancy, alone, or comorbid with depression is associated with postpartum depression (R2= .204; P < .001). Postpartum depression alone or comorbid with posttraumatic stress was associated with impaired bonding (R2= .195; P < .001). In both models, higher quality of life ratings in pregnancy were associated with better outcomes, while reported dissociation in labor was a risk for worse outcomes. The effect of a history of childhood maltreatment on both postpartum mental health and bonding outcomes was mediated by preexisting mental health status.

Discussion: Pregnancy represents an opportune time to interrupt the pattern of intergenerational transmission of abuse and psychiatric vulnerability. Further dyadic research is warranted beyond 6 weeks postpartum. Trauma‐informed interventions for women who enter care with abuse‐related PTSD or depression should be developed and tested.
Italian Multicenter Study on Low‐Density Lipoprotein Apheresis Working Group 2009 Survey
Authors: Stefanutti Claudia , Morozzi Claudia , Di Giacomo Serafina ,   the Italian Multicenter Study on Low‐Density Lipoprotein Apheresis Working Group
Published: February 2013

We present results of the second survey of the Italian Multicenter Study on Low‐Density Lipoprotein Apheresis (IMSLDLa‐WG/2). The study involved 18 centers in 2009, treating 66 males and 35 females, mean age 47 ± 18 years. Mean age for initiation of drug treatment before low‐density lipoprotein apheresis (LDLa) was 31 ± 18 years, mean age to the first LDLa was 37 ± 20 years and average duration of treatment was 9 ± 6 years. The techniques used included direct adsorption of lipids, dextran sulfate cellulose adsorption, heparin‐mediated low‐density lipoprotein (LDL) precipitation, cascade filtration, and plasma exchange. The mean treated plasma/blood volumes/session were 3127 ± 518 mL and 8666 ± 1384 mL, respectively. The average plasma volume substituted was 3500 ± 300 mL. Lipid therapy before LDLa included ezetimibe, statins, ω‐3 fatty acids and fenofibrate. Baseline mean LDL cholesterol (LDLC) levels were 386 ± 223 mg/dL. The mean before/after apheresis LDLC level decreased by 67% from 250 ± 108 mg/dL (P = 0.05 vs. baseline) to 83 ± 37 mg/dL (P = 0.001 vs. before). Baseline mean Lipoprotein(a) [Lp(a)] level was 179 ± 136 mg/dL. Mean before/after apheresis Lp(a) level decreased by 71% from 133 ± 120 mg/dL (P = 0.05 vs. baseline) to 39 ± 44 mg/dL (P = 0.001 vs. before). Major and minor side effects occurred in 27 and 62 patients, respectively. Among patients with coronary artery disease (CAD), 62.3% had coronary angiography and 50.4% coronary revascularization before LDLa. Single vessel, double vessel and triple vessel CAD occurred in 19 (30.1%), 15 (23.8%) and 29 (46%) patients, respectively. Both CAD and extra‐CAD occurred in 41.5%, 39% had hypertension, 9.9% were smokers, 9.9% consumed alcohol and 42% were physically active. Ischemic cardiovascular events were not observed in any patient over 9 ± 6 years of treatment. Two centers have also treated 34 patients (females: 17/males 17; no. sessions: 36; average plasma volume treated: 3000 mL) for sudden hearing loss (SHL). Relief of symptoms was obtained, independently of the system used (HELP; cascade‐filtration).
Infectious bovine keratoconjunctivitis: seasonal variation in cultural, biochemical and immunoreactive properties of Moraxella bovis isolated from the eyes of cattle
Authors: LEPPER A W D , BARTON I J
Published: February 2013

SUMMARY: The eyes of 20 young cattle were examined over an 18 month period in which 12 members of the group contracted infectious bovine keratoconjunctivitis (IBK). On each of 23 occasions cultural, biochemical and immunoreactive properties of up to 6 isolates of Moraxella bovis derived from each eye were determined. Relationships between the clinical response of eyes, phenotypic properties of M. bovis and annual variations in the level of solar ultraviolet radiation of 280 to 320nm wavelength were examined.

M. bovis was isolated from all IBK‐affected and some unaffected eyes less than one month after the maximum annual level of the mean weekly UV radiation (2,840 mWh.m−2.nm−1) was recorded. A high proportion of M. bovis from IBK lesions were simultaneously active In haemolysis, agar corrosion, gelatin liquefaction and litmus milk peptonisation. Some of these characteristics showed marked dissociation despite consistent reactivity in the fluorescent antibody test, which had a sensitivity and specificity of 95%. Fall in the mean weekly level of UV radiation below 1,438 mWh.m−2.nm−1 in autumn was accompanied by healing of ulcers, persistent scar formation and a decline in the number of M. bovis isolated from affected eyes. A slower decline in the number of M. bovis isolated from apparently healthy eyes occurred in the winter and occasional fresh IBK lesions occurred. In spring, the rise in UV radiation above 1,438 mWh.m−2.nm−1 was accompanied by an increased frequency of isolation of M. bovis with all 4 characteristics, initially from scarred eyes, and later from those showing fresh ulcers. During late spring and the following summer, when mean weekly solar UV levels were in excess of 2,500 mWh.m−2.nm−1, increasing numbers of non‐haemolytic M. bovis were isolated, which were agar‐corroding and proteolytic, but were not associated with disease. Establishment, or re‐establishment, of M. bovis in the eye was associated with smooth colony morphology, followed by a gradual change to about 50% rough colony variants. This trend continued though winter, but as UV levels rose above 1,500 mWh.m−2.nm−1 during the second summer, smooth colony, non‐haemolytic types predominated. The possible use of such information in vaccination strategy against IBK is discussed.