bluuebunny/crossref_metadata_2025 huggingface dataset:
Supporting Mothers’ Engagement in a Community-Based Methadone Treatment Program
Authors: Letourneau Nicole , Campbell Mary Ann , Woodland Jennifer , Colpitts Jennifer
Published: May 2013

Unmanaged maternal opioid addiction poses health and social risks to both mothers and children in their care. Methadone maintenance treatment (MMT) is a targeted public health service to which nurses and other allied health professionals may refer these high risk families for support. Mothers participating in MMT to manage their addiction and their service providers were interviewed to identify resources to maximize mothers’ engagement in treatment and enhance mothers’ parenting capacity. Twelve mothers and six service providers were recruited from an outpatient Atlantic Canadian methadone treatment program. Two major barriers to engagement in MMT were identified by both mothers and service providers including (1) the lack of available and consistent childcare while mothers attended outpatient programs and (2) challenges with transportation to the treatment facility. All participants noted the potential benefits of adding supportive resources for the children of mothers involved in MMT and for mothers to learn how to communicate more effectively with their children and rebuild damaged mother-child relationships. The public health benefits of integrating parent-child ancillary supports into MMT for mothers are discussed.
GDNF–RET Signaling in ER-Positive Breast Cancers Is a Key Determinant of Response and Resistance to Aromatase Inhibitors
Authors: Morandi Andrea , Martin Lesley-Ann , Gao Qiong , Pancholi Sunil , Mackay Alan , Robertson David , Zvelebil Marketa , Dowsett Mitch , Plaza-Menacho Ivan , Isacke Clare M.
Published: May 2013

Most breast cancers at diagnosis are estrogen receptor-positive (ER+) and depend on estrogen for growth and survival. Blocking estrogen biosynthesis by aromatase inhibitors has therefore become a first-line endocrine therapy for postmenopausal women with ER+ breast cancers. Despite providing substantial improvements in patient outcome, aromatase inhibitor resistance remains a major clinical challenge. The receptor tyrosine kinase, RET, and its coreceptor, GFRα1, are upregulated in a subset of ER+ breast cancers, and the RET ligand, glial-derived neurotrophic factor (GDNF) is upregulated by inflammatory cytokines. Here, we report the findings of a multidisciplinary strategy to address the impact of GDNF–RET signaling in the response to aromatase inhibitor treatment. In breast cancer cells in two-dimensional and three-dimensional culture, GDNF-mediated RET signaling is enhanced in a model of aromatase inhibitor resistance. Furthermore, GDNF–RET signaling promoted the survival of aromatase inhibitor-resistant cells and elicited resistance in aromatase inhibitor-sensitive cells. Both these effects were selectively reverted by the RET kinase inhibitor, NVP-BBT594. Gene expression profiling in ER+ cancers defined a proliferation-independent GDNF response signature that prognosed poor patient outcome and, more importantly, predicted poor response to aromatase inhibitor treatment with the development of resistance. We validated these findings by showing increased RET protein expression levels in an independent cohort of aromatase inhibitor-resistant patient specimens. Together, our results establish GDNF–RET signaling as a rational therapeutic target to combat or delay the onset of aromatase inhibitor resistance in breast cancer. Cancer Res; 73(12); 3783–95. ©2013 AACR.
The Effects of Aerobic Exercise on Estrogen Metabolism in Healthy Premenopausal Women
Authors: Smith Alma J. , Phipps William R. , Thomas William , Schmitz Kathryn H. , Kurzer Mindy S.
Published: May 2013

Background: It is well accepted that exercise can decrease breast cancer risk. Limited clinical evidence suggests that this risk could be mediated through changes in estrogen metabolism in premenopausal women. Our objective was to investigate the effects of exercise on premenopausal estrogen metabolism pertinent to breast cancer risk.

Methods: Sedentary, healthy, young eumenorrheic women were randomized into an intervention of 30 minutes of moderate-to-vigorous aerobic exercise five times a week for approximately 16 weeks (n = 212), or into a usual-lifestyle sedentary control group (n = 179). Urinary levels of estrogens [estrone [E1], estradiol, and estriol] and nine estrogen metabolites were measured at baseline and at study end by liquid chromatography/tandem mass spectrometry. The ratios of 2-hydroxyestrone to 16α-hydroxyestrone (2-OHE1/16α-OHE1) and 2-OHE1 to 4-hydroxyestrone (2- OHE1/4-OHE1) were also calculated.

Results: The exercise intervention resulted in significant increases in aerobic fitness and lean body mass and a significant decrease in percent body fat. For exercisers who completed the study (n = 165), 2-OHE1/16α-OHE1 increased significantly (P = 0.043), whereas E1 decreased significantly (P = 0.030) in control participants (n = 153). The change from baseline in 2-OHE1/16α-OHE1 was significantly different between groups (P = 0.045), even after adjustment for baseline values.

Conclusions: The exercise intervention resulted in a significant increase in the 2-OHE1/16α-OHE1 ratio but no differences in other estrogen metabolites or ratios.

Impact: Our results suggest that changes in premenopausal estrogen metabolism may be a mechanism by which increased physical activity lowers breast cancer risk. Cancer Epidemiol Biomarkers Prev; 22(5); 756–64. ©2013 AACR.
Immunomodulatory Monoclonal Antibodies Combined with Peptide Vaccination Provide Potent Immunotherapy in an Aggressive Murine Neuroblastoma Model
Authors: Williams Emily L. , Dunn Stuart N. , James Sonya , Johnson Peter W. , Cragg Mark S. , Glennie Martin J. , Gray Juliet C.
Published: May 2013

Purpose: Neuroblastoma is one of the commonest extracranial tumors of childhood. The majority of patients present with metastatic disease for which outcome remains poor. Immunotherapy is an attractive therapeutic approach for this disease, and a number of neuroblastoma tumor antigens have been identified. Here, we examine the therapeutic potential of combining immunomodulatory monoclonal antibodies (mAb) with peptide vaccination in murine neuroblastoma models.

Experimental Design: Neuroblastoma-bearing mice were treated with mAb targeting 4-1BB, CD40, and CTLA-4 alone, or in combination with a peptide derived from the tumor antigen survivin (GWEDPPNDI). Survivin-specific immune response and therapeutic efficacy were assessed.

Results: In the Neuro2a model, treatment of established tumor with anti-4-1BB, anti-CD40, or anti-CTLA-4 mAb results in tumor regression and long-term survival in 40% to 60% of mice. This is dependent on natural killer (NK) and CD8+ T cells and is associated with tumor CD8+ lymphocyte infiltrate. Successful therapy is achieved only if mAb is given to mice once tumors are established, suggesting dependence on sufficient tumor to provide antigen. In the more aggressive AgN2a and NXS2 models, single-agent mAb therapy provides ineffective therapy. However, if mAb (anti-CTLA-4) is given in conjunction with survivin peptide vaccination, then 60% long-term survival is achieved. This is associated with the generation of survivin-specific T-cell immunity, which again is only shown in the presence of tumor antigen.

Conclusions: These data suggest that the combination of antigen and costimulatory mAb may provide effective immunotherapy against neuroblastoma and may be of particular use in the minimal residual disease setting. Clin Cancer Res; 19(13); 3545–55. ©2013 AACR.
Design of a Bioartificial Pancreas
Authors: Pareta Rajesh A. , Farney Alan C. , Opara Emmanuel C.
Published: May 2013

Islet transplantation has been shown to be a viable treatment option for patients afflicted with type 1 diabetes. However, the lack of availablity of human pancreases and the need to use risky immunosuppressive drugs to prevent transplant rejection remain two major obstacles to the routine use of islet transplantation in diabetic patients. Successful development of a bioartificial pancreas using the approach of microencapsulation with perm-selective coating of islets in hydrogels for graft immunoisolation holds tremendous promise for diabetic patients because it has great potential to overcome these two barriers. In this review article, we will discuss the need for a bioartificial pancreas, provide a detailed description of the microencapsulation process, and review the status of the technology in clinical development. We will also critically review the various factors that will need to be taken into consideration in order to achieve the ultimate goal of routine clinical application.
Cervical Myelopathy due to an Epidural Cervical Mass after Chronic Cervical Spinal Cord Stimulation
Authors: Wloch Andreas , Capelle H. Holger , Saryyeva Assel , Krauss Joachim K.
Published: May 2013

Background: Spinal cord stimulation (SCS) is an established treatment for neuropathic pain. Severe long-term complications are rare. Only recently secondary mass lesions associated with chronic stimulation were noted to occur. Objectives: To report the rare occurrence of cervical myelopathy secondary to an epidural cervical spinal mass after chronic cervical SCS. Methods: Implantation of a paddle electrode at C2-C4 for chronic neuropathic pain resulted in improvement of pain for several years but it lost its efficacy after 8 years. Myelography and postmyelographic CT detected an epidural mass surrounding the electrode and compressing the spinal cord when cervical myelopathy had developed 17 years after electrode implantation. Results: The mass which consisted of dense fibrous scar tissue was removed via hemilaminectomy. At postoperative follow-up at 8 months there was no further progression of gait disorder. Conclusion: Long-term cervical SCS in a rare case may lead to fibrous epidural mass lesions which may not only cause loss of efficacy but which may also result in new neurological deficits.
The Experience of Long-Term Opiate Maintenance Treatment and Reported Barriers to Recovery: A Qualitative Systematic Review
Authors: Notley Caitlin , Blyth Annie , Maskrey Vivienne , Craig Jean , Holland Richard
Published: May 2013

Background/Aim: To inform understanding of the experience of long-term opiate maintenance and identify barriers to recovery. Methods: A qualitative systematic review. Results: 14 studies in 17 papers, mainly from the USA (65%), met inclusion criteria, involving 1,088 participants. Studies focused on methadone prescribing. Participants reported stability; however, many disliked methadone. Barriers to full recovery were primarily ‘inward focused'. Conclusion: This is the first review of qualitative literature on long-term maintenance, finding that universal service improvements could be made to address reported barriers to recovery, including involving ex-users as positive role models, and increasing access to psychological support. Treatment policies combining harm minimisation and abstinence-orientated approaches may best support individualised recovery.
Functional Polymorphism in the Neuropeptide Y Gene Promoter (rs16147) Is Associated with Serum Leptin Levels and Waist-Hip Ratio in Women
Authors: Mutschler Jochen , Abbruzzese Elvira , Wiedemann Klaus , von der Goltz Christoph , Dinter Christina , Mobascher Arian , Thiele Holger , Diaz-Lacava Amalia , Dahmen Norbert , Gallinat Jürgen , Majic Tomislav , Petrovsky Nadine , Thuerauf Norbert , Kornhuber Johannes , Gründer Gerhard , Rademacher Lena , Brinkmeyer Juergen , Wienker Thomas , Wagner Michael , Winterer Georg , Kiefer Falk
Published: May 2013

Objective: The neuropeptide-Y (NP-Y) gene is a strong candidate gene in the pathophysiology of obesity-linked behavior, and several single-nucleotide polymorphisms of NP-Y have already been linked to body weight and appetite. However, the results from current studies remain inconclusive. The aim of the present study was to test whether a certain functional genetic variant (SNP rs16147) in the NP-Y promoter gene is associated with serum leptin levels and body fat distribution. Method: We genotyped and measured the serum leptin levels of the NP-Y rs16147 polymorphism in 1,097 Caucasian subjects in the context of a population-based, case-control multicenter study. We measured weight, height and waist circumference, from which we then calculated BMI and waist-to-hip ratio (WHR). Results: We found the CT-genotype of the SNP rs16147 to be significantly associated with lower WHRs and higher serum leptin levels in women, compared to homozygote gene carriers. No association between rs16147, WHR and serum leptin levels was found in men. Conclusion: Our results provide evidence that the functionally relevant SNP in the NP-Y promoter gene affects body fat distribution and serum leptin levels in women, pointing towards possible behavioral effects of NPY in obesity.
Anaesthetic Management of a Giant Encephalocele: Size Does Matter
Authors: Singh Neha , Rao Parnandi Bhaskar , Ambesh Sushil Prakash , Gupta Devendra
Published: May 2013

Encephalocele is a form of neural tube defect, characterized by protrusion out of the meninges and brain tissue through a bony skull defect. As per the site of origin, these encephaloceles have been classified into different types, out of which the frontoethmoidal one is exclusively common in Southeast Asia with a reported incidence of 1 in 5,000. Neurological outcome of such malformations depends on the size of the sac, neural tissue content, hydrocephalus, associated infection, and other pathologies that accompany this condition. Here we describe the anaesthetic concerns and perioperative management of a giant occipital encephalocele.
Therapeutic Strategies for Tendon Healing Based on Novel Biomaterials, Factors and Cells
Authors: Gross Gerhard , Hoffmann Andrea
Published: May 2013

The repair of tendon injuries still presents a major clinical challenge to orthopedic medicine. Tendons, like some other tissues, are poorly vascularized and heal slowly. In addition, healing often leads to the formation of fibrous tissue and scar tissue which lack flexibility and biomechanical properties. So the treatment of tendon injuries is challenging. We give an overview of the structure and composition of tendons, pathological states of tendon and natural healing, as well as therapeutic options. We focus in particular on biomaterials that have been specifically developed or suggested for the successful repair of tendon injuries. In addition, we also review factor- and cell-dependent strategies to heal tendon and ligament disorders. Although brief, we hope that this review will be helpful, particularly for those readers who are new to the field of tendon tissue engineering.
The Effects of Ezetimibe/Simvastatin versus Simvastatin Monotherapy on Platelet and Inflammatory Biomarkers in Patients with Metabolic Syndrome
Authors: Miller Michael , DiNicolantonio James J. , Can Mehmet , Grice Rachel , Damoulakis Abigail , Serebruany Victor L.
Published: May 2013

In a randomized, double-blind, crossover study of 15 aspirin-naive patients (mean age 48.8 ± 10.2 years) with the metabolic syndrome, statin monotherapy (simvastatin 40 mg daily) was compared to combination therapy (simvastatin 40 mg and ezetimibe 10 mg daily) on biomarkers of inflammation and platelet activity. The addition of ezetimibe to simvastatin over a 4-week period was associated with reduced expression of CD141 (thrombomodulin; p = 0.02), platelet endothelial cell adhesion molecule (p < 0.0001) and CD51/61 (vitronectin receptor; p = 0.048) compared to statin monotherapy. Ezetimibe added to simvastatin improves several indices of platelet reactivity beyond statin monotherapy. However, the clinical relevance of these findings await results of the IMPROVE-IT trial (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).
Long-Term Efficacy of Stereotactic Bilateral Anterior Cingulotomy and Bilateral Anterior Capsulotomy as a Treatment for Refractory Obsessive-Compulsive Disorder
Authors: Zhang Q.J. , Wang W.H. , Wei X.P.
Published: May 2013

Objective: To investigate the long-term efficacy and adverse effects of stereotactic bilateral anterior cingulotomy (BACI) and bilateral anterior capsulotomy (BACA) as a treatment for refractory obsessive-compulsive disorder (OCD) patients. Methods: Seven patients suffering from refractory OCD underwent stereotactic surgery and were followed for 12 months. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to assess the efficacy. The test was taken before and 6 and 12 months after surgery. Results: The mean Y-BOCS scores decreased signiﬁcantly from 32.9 ± 4.7 at baseline to 20.6 ± 5.3 after 12 months. Five out of the 7 patients showed a decrease of more than 35%. During the 12-month follow-up, the effective rate had increased from 28.6 to 71.4%. There were no significant adverse effects observed after surgery. Conclusions: The BACI and BACA were effective for the treatment of refractory OCD, and no significant adverse effects on long-term follow-up were found.
Perspectives on Resorbable Osteosynthesis Materials in Craniomaxillofacial Surgery
Authors: Schumann Paul , Lindhorst Daniel , Wagner Maximilian E.H. , Schramm Alexander , Gellrich Nils-Claudius , Rücker Martin
Published: May 2013

Since introduction to the clinics in the 1990s, resorbable osteosynthesis systems have undergone extensive improvements in order to establish their use as a standard treatment, especially in craniomaxillofacial surgery. However, the development of osteosynthesis systems made of poly(α-hydroxy acid) polymers has been hindered by the lack of information on the mechanical properties and biocompatibility of these materials. Moreover, magnesium-based degredable osteosynthesis materials have not yet been integrated into clinical practice owing to biocompatibility problems. Osteosynthesis systems made from nonresorbable titanium alloys have shown excellent biocompatibility, stability and individual fitting to the implant bed, so these materials are currently considered the ‘gold standard'. The procedure of plate removal has been subjected to intense scrutiny and controversy. Bioresorbable materials are indicated for special conditions, such as osteosynthesis of the growing skull or orbital floor reconstructions. This paper presents an overview of the currently available and investigated resorbable osteosynthesis materials in comparison with the nonresorbable ‘gold standard' titanium. The main problem areas such as sterilization, biocompatibility and stability are highlighted and perspectives for further improvements are provided.
Single-Domain Amnestic Mild Cognitive Impairment Identified by Cluster Analysis Predicts Alzheimer's Disease in the European Prospective DESCRIPA Study
Authors: Damian Marinella , Hausner Lucrezia , Jekel Katrin , Richter Melany , Froelich Lutz , Almkvist Ove , Boada Merce , Bullock Roger , De Deyn Peter Paul , Frisoni Giovanni B. , Hampel Harald , Jones Roy W. , Kehoe Patrick , Lenoir Hermine , Minthon Lennart , Olde Rikkert Marcel G.M. , Rodriguez Guido , Scheltens Philip , Soininen Hilkka , Spiru Luiza , Touchon Jacques , Tsolaki Magda , Vellas Bruno , Verhey Frans R.J. , Winblad Bengt , Wahlund Lars-Olof , Wilcock Gordon , Visser Pieter Jelle
Published: May 2013

Background/Aims: To identify prodromal Alzheimer's disease (AD) subjects using a data-driven approach to determine cognitive profiles in mild cognitive impairment (MCI). Methods: A total of 881 MCI subjects were recruited from 20 memory clinics and followed for up to 5 years. Outcome measures included cognitive variables, conversion to AD, and biomarkers (e.g. CSF, and MRI markers). Two hierarchical cluster analyses (HCA) were performed to identify clusters of subjects with distinct cognitive profiles. The first HCA included all subjects with complete cognitive data, whereas the second one selected subjects with very mild MCI (MMSE ≥28). ANOVAs and ANCOVAs were computed to examine whether the clusters differed with regard to conversion to AD, and to AD-specific biomarkers. Results: The HCAs identified 4-cluster solutions that best reflected the sample structure. One cluster (aMCIsingle) had a significantly higher conversion rate (19%), compared to subjective cognitive impairment (SCI, p < 0.0001), and non-amnestic MCI (naMCI, p = 0.012). This cluster was the only one showing a significantly different biomarker profile (Aβ42, t-tau, APOE ε4, and medial temporal atrophy), compared to SCI or naMCI. Conclusion: In subjects with mild MCI, the single-domain amnestic MCI profile was associated with the highest risk of conversion, even if memory impairment did not necessarily cross specific cut-off points. A cognitive profile characterized by isolated memory deficits may be sufficient to warrant applying prevention strategies in MCI, whether or not memory performance lies below specific z-scores. This is supported by our preliminary biomarker analyses. However, further analyses with bigger samples are needed to corroborate these findings.
‘Distorteidolias' - Fantastic Perceptive Distortion
Authors: Delgado Montserrat G. , Bogousslavsky Julien
Published: May 2013

The role of the thalamus in the pathogenesis of the visual and auditory hallucinations has been reported under the name of peduncular hallucinosis, usually with coexisting midbrain involvement. These hallucinations typically take the form of dreamy de novo productions (phanteidolias), less often that of transformations of perceptions into new items (such as seeing faces in clouds) called pareidolias. However, hallucinations taking the form of a complex distortion of perception is a different phenomenon, which to our knowledge has not been reported. We studied 2 patients with complex, ‘fantastic', perceptive distortion involving the visual and auditory systems after thalamic stroke limited to the region of the dorsomedial nucleus, sparing the intralaminar nuclei and the midbrain (explaining the lack of disorders of consciousness and confusional state). Our patients reported the modification of usual stimuli (face, body, voices) into unreal, fantastically distorted perceptions (monstrous change of shapes or sounds without appearance of new items). While the exact mechanism leading to such perceptive distortions remains unknown, a release phenomenon due to damage to the dorsomedial thalamus (probably affecting cholinergic system) responsible for a disinhibition of cortical function involved in familiarity of perception seems likely. We suggest that these hallucinations should be called ‘distorteidolias'.
Caries Prevalence in Non-Syndromic Patients with Cleft Lip and/or Palate: A Meta-Analysis
Authors: Antonarakis G.S. , Palaska P.-K. , Herzog G.
Published: May 2013

Aim: To evaluate caries prevalence in non-syndromic patients with cleft lip and/or palate (CLP) in comparison with a matched non-CLP population. Methods: A literature search was conducted in order to identify articles reporting on the prevalence of caries in CLP versus non-CLP individuals. The related citations function in PubMed and reference lists of retrieved articles were used to expand the search. Only studies with a suitable matched control group were included. From each included study, study and sample characteristics were extracted, as were results. The main outcome was the score given for caries prevalence in each study, using a well-defined index. The data were entered into meta-analysis software and a meta-analysis performed using the random-effects model. Results: From the 592 articles initially identified, 7 were chosen according to preset inclusion and exclusion criteria. All of the studies were cross-sectional in nature, and used the decayed, missing, and filled (DMF/dmf) indices as the final outcomes. The included studies involved a total of 474 CLP patients aged 1.5-29 years. When looking at permanent teeth, data from 5 studies suggest that CLP patients have a higher number of DMF teeth than the controls (mean difference 1.38; p = 0.003). For deciduous teeth, data from 4 studies suggest that CLP patients have a higher number of dmf teeth than the controls (mean difference 1.51; p = 0.03). Conclusion: Non-syndromic patients with CLP tend to have higher caries prevalence, both in the permanent and the deciduous dentition, in comparison with matched non-CLP controls.
In vitro Culture of Tumour-Derived Hepatocytes in Decellularised Whole-Liver Biological Scaffolds
Authors: Cheng Yuan , Wang Yan , Kang Yu Zan , Hu Peng Yun , Gao Yi , Pan Ming Xin
Published: May 2013

Background: To explore the feasibility of preparing transplantable recellularised liver grafts by preparing a decellularised whole-liver scaffold, decellularisation and recellularisation of a liver scaffold using a chemical detergent were performed on the liver cancer cell lines HepG2 and C3A. Materials and Methods: D-Hanks' solution containing sodium EDTA, gradient sodium dodecyl sulphate (SDS, 1/0.5/0.1%) and Triton X-100 were infused via the portal vein to prepare the decellularised scaffold. HepG2 and C3A cells were seeded onto the scaffold, and a circulation perfusion culture was carried out. The efficiency of the engraftment and the function of the cells in the scaffold were evaluated. Results: The decellularisation method used completely removed the intrahepatic cellular components while only components with low immunogenicity were retained, such as collagen and fibronectin. Meanwhile, the vascular structure was completely retained, which provided a structural basis for circulation bypass. The engraftment efficiencies of the HepG2 and C3A cells were 86 ± 5 and 88 ± 5%, respectively, and were not significantly different between the two groups (p > 0.05, n = 10). The cells grew well on the scaffold, and the albumin synthesis and urea secretion functions were superior to those obtained after a traditional two-dimensional culture. Conclusions: The preparation of a liver scaffold using a chemical detergent technique has good reproducibility, and the scaffold is suitable for the growth of liver tumour cell lines.
Cost Effectiveness of Neoadjuvant Chemotherapy in Locally Advanced Operable Head and Neck Cancer Followed by Surgery and Postoperative Radiotherapy: A Markov Model-Based Decision Analysis
Authors: Himmel M. , Hartmann M. , Guntinas-Lichius O.
Published: May 2013

Introduction: Head and neck carcinomas are among the most frequent tumor diseases and, because of different multimodal therapy options, cause enormous costs. For this reason, we examined whether in operable advanced head and neck carcinomas, neoadjuvant induction chemotherapy is cost effective in comparison with surgery followed by postoperative radio(chemo)therapy. Material and Methods: A Markov model was developed with paclitaxel, cisplatin and fluorouracil as induction therapy. The legal health insurance in Germany was chosen for cost perspectives, and a willingness-to-pay limit at EUR 38,000 was set. Results: Total costs for surgery with postoperative radiochemotherapy amounted to EUR 13,999. Prior induction chemotherapy raised the costs to EUR 17,377, with a higher effectiveness by 0.1 years of life. Costs per year of life gained are EUR 33,780. The incremental cost effectiveness ratio (ICER) with variations in side effects for surgery and postoperative chemotherapy amounted to between EUR 31,520 and 36,050. With variations in side effects for induction chemotherapy, the ICER amounted to EUR 30,060-37,520. The Monte Carlo simulation disclosed cost effectiveness for 55.4% of the patients; for 44.6%, there was no cost effectiveness. Conclusion: The Markov-modeled cost effectiveness analysis indicates that with operable head and neck tumors, induction therapy with paclitaxel, cisplatin and fluorouracil is cost effective.
Effect of Genetic Polymorphisms in CA6 Gene on the Expression and Catalytic Activity of Human Salivary Carbonic Anhydrase VI
Authors: Aidar M. , Marques Rocha , Valjakka J. , Mononen N. , Lehtimäki T. , Parkkila S. , de Souza A.P. , Line Peres
Published: May 2013

Carbonic anhydrase isoenzyme VI (CA VI) plays an important role in the homeostasis of oral tissues participating in the processes of taste, protection of dental tissues against the loss of minerals, caries, and possibly in the formation of dental calculus in periodontal disease. This study aimed to verify the correlation between changes in the expression and activity of human salivary carbonic anhydrase VI and genetic polymorphisms in its gene (CA6). The study population consisted of 182 healthy volunteers (female and male, aged 18-22). Samples of total saliva were assayed for CA VI concentrations using a specific time-resolved immunofluorometric assay. CA VI catalytic activity was detected by a modified protocol of Kotwica et al. [J Physiol Pharmacol 2006;57(suppl 8):107-123], adapted to CA VI in saliva. Samples of genomic DNA were genotyped for polymorphisms rs2274327 (C/T), rs2274328 (A/C) and rs2274333 (A/G) by TaqMan® SNP Genotyping Assays. The concentration and catalytic activity of the salivary CA VI obtained for the different genotypes were analyzed using the Kruskal-Wallis nonparametric test and the Dunn test. The results showed that individuals with TT genotype (rs2274327) had significantly lower CA VI concentrations than the individuals with genotypes CT or CC (p < 0.05). There was also an association between polymorphism rs2274333 and salivary CA VI concentrations. There were no associations between the three polymorphisms analyzed and variations in CA VI activity. Our results suggest that polymorphisms in the CA6 gene are associated with the concentrations of secreted CA VI.
Differential Endothelial Coverage, Response to Injury and Neointimal Integration of CX3CR1/Smooth Muscle-Like Cells after Carotid or Femoral Arterial Injury
Authors: Martin Kenneth , Kumar Arun H.S. , Klinkert Kerstin , Caplice Noel M.
Published: May 2013

Background: Previously, we established the importance of the CX3CL1/CX3CR1 axis in the promotion of myeloid cell differentiation into neointimal smooth muscle-like cells (SMLC). Methods: In this study, acute (24 h) endothelial coverage and CX3CL1 expression as well as chronic (2 weeks) vascular remodeling was examined with respect to whether myeloid CX3CR1+ SMLC number in the neointima differed between carotid and femoral artery wire injury. Results and Conclusion: Twenty-four hours after injury, CX3CL1 expression was significantly elevated in injured carotid compared to femoral arteries. In mice with CX3CR1 promoter-driven expression of green fluorescent protein, neointima formation was significantly greater (p < 0.05) 2 weeks after injury in femoral versus carotid arteries as determined by the intima/media ratio. Although the percentage of F4/80/CX3CR1+ cell integration was similar in both models, the carotid lesion had greater proportions of cells coexpressing CX3CR1 and both α-smooth muscle actin and calponin (p < 0.05). Wire injury of carotid arteries was associated with greater CX3CL1 expression in the acute phase followed by greater CX3CR1 coexpressing SMLC content in later lesions as well as less neointima formation than in femoral arteries. This may, in part, explain the variability in lesion composition after carotid versus femoral wire injury.
Risk of Metabolic Bone Disease is Increased Both during and after Weaning off Parenteral Nutrition in Pediatric Intestinal Failure
Authors: Mutanen Annika , Mäkitie Outi , Pakarinen Mikko P.
Published: May 2013

Aim: To assess bone health in pediatric intestinal failure (IF). Methods: A population-based cohort of 41 IF patients (age 9.9 years) underwent evaluation of bone mineral density (BMD), bone biochemistry, nutritional status and growth. Eleven patients remained on parenteral nutrition (PN) after 69 months. Thirty had weaned off PN 9.0 years earlier (mean), i.e. after 30 months on PN. Results: The majority of patients had lumbar spine or femoral BMD Z-score ≤-1.0 (70%), vitamin D deficiency (serum 25-hydroxyvitamin-D, S-25-OHD, <50 nmol/l, 41%) or secondary hyperparathyroidism (plasma parathyroid hormone >47 ng/l, 44%), equally during and after weaning off PN. Hyperparathyroidism was absent when S-25-OHD was >80 nmol/l. Until puberty, height (-1.4 to -0.8, age 1-12) and weight Z-scores (-1.3 to -0.5, age 1-16) were below the normal mean (p < 0.05). Small bowel length associated with S-25-OHD levels (r = 0.489, p = 0.013). In a multivariate model, time after weaning off PN (β = -0.597, p = 0.001), duration of PN (β = -0.466, p = 0.006) and calcium intake (β = -0.331, p = 0.035) predicted decreased lumbar spine BMD. Conclusions: In pediatric IF, vitamin D insufficiency, secondary hyperparathyroidism and decreased BMD are common. BMD, vitamin D, calcium and nutritional status should be closely monitored during and after weaning off PN to ensure sufficient vitamin D and mineral substitution for normal growth and bone mass attainment.
Low-Dose Furosemide Administered with Adequate Hydration Reduces Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography
Authors: Gu Guo-Qiang , Lu Rui , Cui Wei , Liu Fan , Zhang Ying , Yang Xiao-Hong , Chen Xue-Feng , Jia Wan-Ming
Published: May 2013

Objective: We investigated the effects of low-dose furosemide, administered with adequate hydration on contrast-induced nephropathy (CIN). Methods: A total of 859 patients scheduled to undergo coronary angiography or angioplasty were enrolled and randomly assigned to a furosemide treatment or control group. All patients received supplemental hydration. Immediately after surgery, patients in the furosemide group received intravenous furosemide injection (20 mg); those in the control group received no treatment. Total fluid intake and urine output were recorded. Pre- and postsurgical changes in serum creatinine levels (SCr), glomerular filtration rate (GFR) and creatinine clearance rate (CCr) were assessed, and the incidence of CIN was also evaluated between the two groups. Logistic regression analysis was used to study risk factors for CIN. Results: General baseline conditions were similar between the two groups. Patients who received furosemide had significantly less increase in SCr and a more marked increase in GFR and CCr than those who did not. The incidence of CIN was significantly higher in the control group. Logistic regression analysis revealed that female gender and angiotensin-converting enzyme inhibitor were risk factors for CIN, whereas furosemide acted as a protective agent. Conclusions: With full hydration, small doses of furosemide can reduce CIN better than hydration alone.
Molecular and Phenotypic Characterization of Ring Chromosome 22 in Two Unrelated Patients
Authors: Hannachi H. , Mougou S. , Benabdallah I. , Soayh N. , Kahloul N. , Gaddour N. , Le Lorc'h M. , Sanlaville D. , El Ghezal H. , Saad A.
Published: May 2013

We report on the cytogenetic and molecular characterization of a constitutional de novo ring chromosome 22 (r(22)) in 2 unrelated patients with emphasis on different hypotheses proposed to explain the phenotypic variability characterizing this genomic disorder. In both patients, molecular investigations using FISH and array-CGH techniques revealed a 22q terminal deletion involving the 22q13.33 critical region. The size of the deletion was estimated to at least 1.35 Mb in the first proband and to only 300 kb in the second. They both exhibited the major features of r(22) syndrome, but the first patient was more profoundly affected. He had a more severe phenotype, further complicated by behavioral anomalies, autistic-like features with abnormal EEG pattern and brain MRI profile. Haploinsufficiency of the SHANK3 gene, lying in the minimal critical region, is nowadays considered as responsible for most neurobehavioral anomalies. Nevertheless, phenotypic severity and occurrence of additional features in the first patient suggest a potential involvement of one or more specific gene(s) located proximally to SHANK3 (as PLXNB2, PANX2, ALG12 or MLC1), acting either independently of it or by regulating or promoting its expression and thus disrupting its function when deleted.
Nondialyzable Uremic Toxins
Authors: Piroddi Marta , Bartolini Desireé , Ciffolilli Silvia , Galli Francesco
Published: May 2013

Nondialyzable uremic toxins can be defined as solutes producing adverse biological effects that consequently to peculiar physicochemical features (mainly their large size and hydrophobic character) cannot leave the blood stream through a dialysis membrane. These are the subject of great interest for the scientific community, in that emerging evidence suggests that such uremic retention solutes may contribute a main role to the complex inflammatory and vascular comorbidity of the uremic syndrome. Treatments based on most efficient diffusive or convective protocols of dialysis and pharmacological therapies cannot prevent nor correct such clinical symptoms. Protein-bound solutes and other proteinaceous components present in excess in the uremic milieu are thus natural candidates for explaining the resistance of uremic toxicity to current regimens of therapy. Intense research is in progress to identify molecular species and mechanisms of toxicity, but the real challenge of our times is to develop innovative clinical protocols that may remove or prevent the formation/toxicity of nondialyzable uremic solutes. These include high-efficacy protein-leaking dialyzers, adsorption techniques, frequent dialysis, and pharmacological therapies. These aspects are examined in this review paper, paying particular attention to covalent posttranslational modifications of plasma proteins produced as a consequence of oxidative, nitrosative and carbonyl stress. These represent an emerging trait in the pathobiology of inflammatory and age-related disorders, deserving further consideration in chronic kidney disease.
Adsorption Techniques: Dialysis Sorbents and Membranes
Authors: Perego Angelo F.
Published: May 2013

Adsorption is based on the attraction between the sorbent and the solute through hydrophobic interactions, ionic or electrostatic forces, hydrogen bonding or van der Waals forces. Adsorption is the adherence of molecules by the above-mentioned forces not only to the surface of the membrane but also to its interior. Since polymethylmethacrylate membranes have a much higher inside effective exchange surface than polysulfone membranes, these membranes are able to ensure a high level of adsorption, and therefore reduce the concentration of high-molecular-weight molecules and protein-bound uremic toxins.
Matrix-Producing Carcinoma of the Breast: A Case Report
Authors: Rossi Lorenzo , Paglicci Carlo , Caprio Giuliana , Barberi Simona , Ranieri Ersilia , Zancla Serena , Rengo Mario , Pagni Paola
Published: May 2013

Matrix-producing breast cancer (MPC) is a subtype of metaplastic carcinoma of the breast. It is a very rare tumor, which constitutes less than 1% of all malignant mammary tumors. The origin of this tumor is still unclear: there are molecular studies that suggest an origin from myoepithelial cells, whereas other studies underline the neoplastic transformation of a multipotent stem cell. Even the differential diagnosis of MPC and other breast neoplasms (phyllodes tumors and real sarcomas of the breast) is not always easy. In the literature, a certain chemoresistance has been demonstrated, and a standard treatment of this tumor does not exist at this time. We report the case of a 44-year-old, premenopausal, female patient with a 6-cm breast lump. Neither imaging nor fine needle aspiration biopsy was crucial in achieving a diagnosis. The patient underwent a simple mastectomy. In consideration of the negative lymph node status, the patient was not subjected to radiotherapy or adjuvant chemotherapy. Moreover, since the receptor status was negative, hormone therapy was not necessary. The patient has been disease free for 4 years now.
Increase in the Size of an Intracardiac Thrombus during Dabigatran Therapy (110 mg b.i.d.) in an Acute Cardioembolic Stroke Patient
Authors: Tabata Emi , Yasaka Masahiro , Wakugawa Yoshiyuki , Komori Motohiro , Mori Kohta , Tsurusaki Yuichiro , Kokuba Kazuhito , Sambongi Yoshiki , Maeda Koichiro , Okada Yasushi
Published: May 2013

We report a case of atrial fibrillation in a patient in whom a mobile thrombus in the left atrial appendage increased in size after low-dose dabigatran therapy. A 74-year-old man was admitted to our hospital because of sudden onset of right hemiplasia and dysarthria. On admission, his National Institutes of Health Stroke Scale score was three. Axial diffusion-weighted magnetic resonance images and magnetic resonance angiography images showed hyperintense signals in the left front-parietal cerebral cortex without any intracranial stenotic lesions, and acute cardioembolic stroke associated with nonvalvular atrial fibrillation was diagnosed. Transesophageal echocardiography revealed a mobile thrombosis (1.0 × 2.2 cm) in the left atrial appendage, and dabigatran therapy (110 mg b.i.d.) was initiated to prevent stroke recurrence. Transesophageal echocardiography performed 6 days later revealed that the size of the thrombus had increased to 1.5 × 3.0 cm. Medication was changed to warfarin, and the thrombosis subsequently decreased in size. The patient did not have a recurrent stroke and was discharged with a National Institutes of Health Stroke Scale score of zero. This case demonstrates that low-dose dabigatran may not be effective in reducing the size of a thrombus.
Mirizzi Syndrome with Endoscopic Ultrasound Image
Authors: Rayapudi K. , Gholami P. , Olyaee M.
Published: May 2013

We describe a 66-year-old Caucasian man with type 1 Mirizzi syndrome diagnosed on endoscopic ultrasound. He presented with acute onset of jaundice, malaise, dark urine over 3-4 days, and was found to have obstructive jaundice on lab testing. CT scan of the abdomen showed intrahepatic biliary ductal dilation, a 1.5 cm common bile duct (CBD) above the pancreas, and possible stones in the CBD, but no masses. Endoscopic retrograde cholangiopancreatography (ERCP) by a community gastroenterologist failed to cannulate the CBD. At the University Center, type 1 Mirizzi syndrome was noted on endoscopic ultrasound with narrowing of the CBD with extrinsic compression from cystic duct stone. During repeat ERCP, the CBD could be cannulated over the pancreatic duct wire. A mid CBD narrowing, distal CBD stones, proximal CBD and extrahepatic duct dilation were noted, and biliary sphincterotomy was performed. A small stone in the distal CBD was removed with an extraction balloon. The cystic duct stone was moved with the biliary balloon into the CBD, mechanical basket lithotripsy was performed and stone fragments were delivered out with an extraction balloon. The patient was seen 7 weeks later in the clinic. Skin and scleral icterus had cleared up and he is scheduled for an elective cholecystectomy. Mirizzi syndrome refers to biliary obstruction resulting from impacted stone in the cystic duct or neck of the gallbladder and commonly presents with obstructive jaundice. Type 1 does not have cholecystocholedochal fistulas, but they present in types 2, 3 and 4. Surgery is the mainstay of therapy. Endoscopic treatment is effective and can also be used as a temporizing measure or definitive treatment in poor surgical risk candidates.
Polymorphic Eruption of Pregnancy Presented with Targetoid Lesions: A Report of Two Cases
Authors: Sirikudta Wararat , Silpa-archa Narumol
Published: May 2013

Background: Skin lesions in pregnant women could be caused by physiologic or pathologic changes. Polymorphic eruption of pregnancy (PEP), which manifests as various types of skin lesions, is the most common pregnancy dermatosis. Thus, PEP could mimic other skin diseases related to unfavorable maternal and fetal outcomes. Main Observations: Two PEP patients with targetoid lesions are presented here. One of them was a primigravida, whereas the other was a secundigravida. Both patients had singleton pregnancies and skin rash which started during the third trimester. The lesions began on the abdomen and then spread to the trunk and extremities. The face, palms, soles, and mucosa were not affected. Pruritus was observed but no other systemic symptoms were reported. Both patients delivered healthy, term infants without complications. Conclusion: Targetoid lesions in PEP are an uncommon presentation, and the differential diagnosis of PEP along with other dermatoses should be considered. However, the prognosis for this type of PEP is not different from that for classic PEP.
Evaluation of the Effectiveness of Antibiotics against Eosinophilic Pustular Folliculitis
Authors: Ono Sachiko , Yamamoto Yosuke , Otsuka Atsushi , Kabashima Kenji , Miyachi Yoshiki
Published: May 2013

Eosinophilic pustular folliculitis (EPF) is a chronic intractable pruritic dermatosis. Although indomethacin is generally effective against EPF and considered as a first-line therapy, quite a few patients with indomethacin still suffer from the symptoms. Among other therapeutic options, some antibiotics have been reported to be effective; however, there has been no epidemiological description regarding oral antibiotics use in patients with EPF. In this study, we investigated the frequency of antibiotics use and the effectiveness in patients with EPF.
Neurological Complications of Infective Endocarditis
Authors: García-Cabrera Emilio , Fernández-Hidalgo Nuria , Almirante Benito , Ivanova-Georgieva Radka , Noureddine Mariam , Plata Antonio , Lomas Jose M. , Gálvez-Acebal Juan , Hidalgo-Tenorio Carmen , Ruíz-Morales Josefa , Martínez-Marcos Francisco J. , Reguera Jose M. , de la Torre-Lima Javier , González Arístides de Alarcón
Published: May 2013

Background—

The purpose of this study was to assess the incidence of neurological complications in patients with infective endocarditis, the risk factors for their development, their influence on the clinical outcome, and the impact of cardiac surgery.

Methods and Results—

This was a retrospective analysis of prospectively collected data on a multicenter cohort of 1345 consecutive episodes of left-sided infective endocarditis from 8 centers in Spain. Cox regression models were developed to analyze variables predictive of neurological complications and associated mortality. Three hundred forty patients (25%) experienced such complications: 192 patients (14%) had ischemic events, 86 (6%) had encephalopathy/meningitis, 60 (4%) had hemorrhages, and 2 (1%) had brain abscesses. Independent risk factors associated with all neurological complications were vegetation size ≥3 cm (hazard ratio [HR] 1.91),
Staphylococcus aureus
as a cause (HR 2.47), mitral valve involvement (HR 1.29), and anticoagulant therapy (HR 1.31). This last variable was particularly related to a greater incidence of hemorrhagic events (HR 2.71). Overall mortality was 30%, and neurological complications had a negative impact on outcome (45% of deaths versus 24% in patients without these complications;
P
<0.01), although only moderate to severe ischemic stroke (HR 1.63) and brain hemorrhage (HR 1.73) were significantly associated with a poorer prognosis. Antimicrobial treatment reduced (by 33% to 75%) the risk of neurological complications. In patients with hemorrhage, mortality was higher when surgery was performed within 4 weeks of the hemorrhagic event (75% versus 40% in later surgery).

Conclusions—

Moderate to severe ischemic stroke and brain hemorrhage were found to have a significant negative impact on the outcome of infective endocarditis. Early appropriate antimicrobial treatment is critical, and transitory discontinuation of anticoagulant therapy should be considered.