bluuebunny/crossref_metadata_2025 huggingface dataset:
rs4711751 and rs1999930 Are Not Associated with Neovascular Age-Related Macular Degeneration or Polypoidal Choroidal Vasculopathy in the Chinese Population
Authors: Huang Lvzhen , Li Mingwu , Ma Xiaoyun , Li Yingjie , Zhang Chunfang , Sun Yaoyao , Bai Yujing , Wang Bin , Yu Wenzhen , Zhao Mingwei , Khor Chiea Chuen , Li Xiaoxin
Published: September 2014

Purpose: rs1999930 and rs4711751 have recently been identified as novel variants associated with advanced age-related macular degeneration (AMD) in populations of European ancestry. We aimed to investigate whether these two single nucleotide polymorphisms (SNPs) were associated with neovascular AMD (nAMD) or with polypoidal choroidal vasculopathy (PCV), a variant of AMD in Asians, using a Chinese case-control study. Methods: A total of 900 subjects, including 300 controls, 300 cases with nAMD and 300 cases with PCV, were included in the present study. Genomic DNA was extracted from venous blood leukocytes. The allelic variants of rs1999930 and rs4711751 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The differences in allele distribution between cases and controls were tested by a χ2 test, with additional adjustments for age and gender using logistic regression. The statistical power was also calculated. Values of p < 0.05 were considered statistically significant. Results: No statistically significant association was observed between the two polymorphisms of nAMD or PCV phenotype (p > 0.05 for all comparisons). The difference remained insignificant after correction for age and gender (p > 0.05 for all comparisons). The statistical powers to detect the association between these two SNPs and nAMD or PCV range from 0.05 to 0.36, assuming conventional levels of statistical significance. Conclusions: In the present study, we could not replicate the reported association of these two SNPs and either nAMD or PCV in a Chinese population, suggesting that they are unlikely to be a major AMD and PCV susceptibility gene locus in the Chinese population. Considering the low power value, a large sample size is required to draw more reliable conclusions.
Impact of BMI on Cardiovascular Events, Renal Function, and Coronary Artery Calcification
Authors: Russo Domenico , Morrone Luigi Francesco , Errichiello Carmela , De Gregorio Maria Grazia , Imbriaco Massimo , Battaglia Yuri , Russo Luigi , Andreucci Michele , Di Iorio Biagio Raffaele
Published: September 2014

Background/Aims: High BMI increases the risk of cardiovascular events (CVEs) in the general population. Conflicting results have been reported on the role of BMI on CVEs and on decline of renal function in patients with chronic kidney disease not on dialysis (CKD). This study evaluates the impact of BMI on CVEs, dialysis initiation, and coronary artery calcification (CAC) in CKD patients. Methods: CKD patients were divided in normal-BMI and high-BMI patients. CVEs, initiation of dialysis, and extent and progression of CAC were assessed. Univariate and multivariable analysis were performed (adjustment variables: age, diabetes, hypertension, gender, CKD stage, serum concentration of hemoglobin, parathyroid hormone, calcium, phosphorus, albumin, C-reactive protein, LDL-cholesterol, total calcium score, 24-hour proteinuria). Patients were followed to the first event (CVE, dialysis) or for 2 years. Results: 471 patients were evaluated. A CVE occurred in 13.5 and 21.3% (p < 0.05) of normal-BMI and high-BMI patients, respectively. High BMI did not increase the risk for CVEs in univariate (HR: 1.86; 95% CI: 0.97-3.54; p = 0.06) or multivariable analysis (HR: 1.36; 95% CI: 0.57-3.14; p = 0.50). High BMI did not increase the risk for initiation of dialysis in univariate (HR: 0.96; 95% CI: 0.58-1.60; p = 0.9) or multivariable analysis (HR: 1.77; 95% CI: 0.82-3.81; p = 0.14). Adding the interaction term (between BMI and glomerular filtration rate) to other variables, the risk of dialysis initiation significantly increased (HR: 3.06; 95% CI: 1.31-7.18; p = 0.01) in high-BMI patients. High BMI was not a predictor of CAC extent or progression. Conclusions: High BMI was not a predictor of CVEs. High BMI increased the risk for dialysis initiation, but high BMI was not associated to CAC extent and progression. The presence of confounders may underestimate the impact of high BMI on dialysis initiation.
The Impact of Dialysis Modality on Novel Markers of Stress Reaction, Matrix Remodeling and Endothelial Damage in Children on Chronic Dialysis
Authors: Musiał Kinga , Zwolińska Danuta
Published: September 2014

Background/Aims: Dialysis triggers stress reaction, matrix remodeling and endothelial damage, but little is known about the changes it induces on selected heat shock proteins (Hsp90α), adhesion molecules (E-cadherin, sE-selectin), metalloproteinases (MMP-8) and their extracellular inducer (EMMPRIN). The aim of this study was to assess serum concentrations of the above-mentioned parameters in children on chronic dialysis. Methods: 19 patients on hemodialysis (HD), 22 children on peritoneal dialysis (PD) and 30 age-matched controls were examined. Serum concentrations of parameters were assessed by ELISA. Results: Hsp90α, MMP-8, EMMPRIN and E-cadherin concentrations were significantly increased in children on dialysis vs. controls and higher levels were in HD than PD patients. There was no difference in the level of sE-selectin between HD and PD modalities. A single HD session diminished Hsp90α, MMP-8, EMMPRIN and E-cadherin values, but had no impact on sE-selectin levels. Conclusions: Hemodialysis evokes stress reaction, matrix and endothelium destruction, to a greater extent than peritoneal dialysis. Single hemodialysis influences circulating cells rather than endothelial cells.
Clinical Application of a Tissue-Cultured Skin Autograft: An Alternative for the Treatment of Non-Healing or Slowly Healing Wounds?
Authors: Zöller Nadja , Valesky Eva , Butting Manuel , Hofmann Matthias , Kippenberger Stefan , Bereiter-Hahn Jürgen , Bernd August , Kaufmann Roland
Published: September 2014

Background: The treatment regime of non-healing or slowly healing wounds is constantly improving. One aspect is surgical defect coverage whereby mesh grafts and keratinocyte suspension are applied. Objective: Tissue-cultured skin autografts may be an alternative for the treatment of full-thickness wounds and wounds that cover large areas of the body surface. Methods: Autologous epidermal and dermal cells were isolated, expanded in vitro and seeded on collagen-elastin scaffolds. The developed autograft was immunohistochemically characterized and subsequently transplanted onto a facial chronic ulceration of a 71-year-old patient with vulnerable atrophic skin. Results: Characterization of the skin equivalent revealed comparability to healthy human skin due to the epidermal strata, differentiation and proliferation markers. Within 138 days, the skin structure at the transplantation site closely correlated with the adjacent undisturbed skin. Conclusion: The present study demonstrates the comparability of the developed organotypic skin equivalent to healthy human skin and the versatility for clinical applications.
Use of Surveillance Colonoscopy in Medicare Patients with Inflammatory Bowel Disease prior to Colorectal Cancer Diagnosis
Authors: Wang Yize R. , Cangemi John R. , Loftus,Jr. Edward V. , Picco Michael F.
Published: September 2014

Background: Patients with longstanding inflammatory bowel disease (IBD) involving large intestine proximal to rectum are considered to be at increased risk for colorectal cancer (CRC). One prior study showed low utilization of surveillance colonoscopy in patients with ≥8 years of ulcerative colitis (UC) in the USA. Aims: To study use of surveillance colonoscopy among Medicare beneficiaries with IBD in the 2-year period prior to CRC diagnosis. Data and Methods: Our study sample included Medicare beneficiaries in the SEER-Medicare-linked database who were diagnosed with CRC during 2001-2005 and had ≥3 physician visits with ICD-9 diagnosis code for IBD prior to CRC diagnosis. Medicare beneficiaries aged >85 years without Part B coverage or enrolled in HMOs were excluded. Colonoscopy performed within 6-30 months prior to CRC diagnosis was defined as surveillance colonoscopy. The χ2 test and multivariate logistic regression were used in statistical analysis. Results: Of 241 Medicare beneficiaries with IBD and diagnosed with CRC, 92 (38%) patients underwent ≥1 surveillance colonoscopy in the 2 years prior to cancer diagnosis. The use of surveillance colonoscopy was similar between Crohn's disease (28/86, 33%) and UC (64/155, 41%). In multivariate logistic regression, older age (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94-0.99) was negative associated with surveillance colonoscopy use and personal history of colon polyp (OR 2.73, 95% CI 1.09-6.87) was positively associated with surveillance colonoscopy use. Conclusions: Use of surveillance colonoscopy was low among Medicare beneficiaries with IBD in the 2 years prior to CRC diagnosis.
Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: Patient Satisfaction under Light Conscious Sedation
Authors: Jeyabalan Abiramy , Medford Andrew R.L.
Published: September 2014

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an increasingly used mediastinal sampling technique. Many centres use conscious sedation in an ambulatory setting to optimise the flow of patients, save costs and shorten recovery time. The only EBUS-TBNA patient satisfaction study published so far used deep conscious sedation with propofol. To our knowledge, ours is the largest prospective study evaluating the experience of patients undergoing EBUS-TBNA using light conscious sedation without propofol. Objectives: To evaluate the patient tolerability of EBUS-TBNA under mild conscious sedation. Methods: Eighty-two consecutive patients between January 2011 and November 2011 requiring EBUS-TBNA under light conscious sedation for either mediastinal staging of lung cancer or the diagnosis of suspected mediastinal disease due to malignancy or granulomatous disease were invited to complete a questionnaire after the intervention. The collection of data included the diagnostic yield, the number and size of nodes sampled and the dose of sedative medication administered. Results: The average dose of sedative agents administered was 59.4 μg fentanyl and 3.2 mg midazolam. The sensitivity of EBUS-TBNA for the cancer staging, cancer diagnosis and granulomatous disease cohorts was 90.0, 94.1 and 87.5%, respectively. The most commonly reported symptom was a cough in 65 (93%) patients. Of these patients, 46 (71%) described the severity as being mild. All but 9 patients (61/70 or 87%) stated that they would definitely or probably undergo a repeat EBUS-TBNA. Conclusions: This single-centre UK study confirms that EBUS-TBNA under light conscious sedation is a well-tolerated procedure maintaining the expected diagnostic performance, with patients reporting a high degree of satisfaction with both the test and the information received beforehand.
Coping with Delusions in Schizophrenia and Affective Disorder with Psychotic Symptoms: The Relationship between Coping Strategies and Dimensions of Delusion
Authors: Rückl Sarah , Gentner Nana Christina , Büche Liesa , Backenstrass Matthias , Barthel Andreas , Vedder Helmut , Bürgy Martin , Kronmüller Klaus-Thomas
Published: September 2014

Background: Self-generated coping strategies and the enhancement of coping strategies are effective in the treatment of psychotic symptoms. Evaluating these strategies can be of clinical interest to develop better coping enhancement therapies. Cognitive models consider delusions as multidimensional phenomena. Using a psychometric approach, the relationship between coping and the dimensions of delusion were examined. Methods: Thirty schizophrenia spectrum patients with delusions and 29 patients with affective disorder with psychotic symptoms were interviewed using the Heidelberg Coping Scales for Delusions and the Heidelberg Profile of Delusional Experience. Analyses of variance were conducted to investigate differences between the groups, and Spearman's rank-based correlations were used to examine the correlations between coping factors and the dimensions of delusion. Results: Schizophrenia spectrum patients used more medical care and symptomatic coping, whereas patients with affective disorder engaged in more depressive coping. In the schizophrenia spectrum sample, the action-oriented, the cognitive, and the emotional dimensions of delusion were related to coping factors. In patients with affective disorder, only the action-oriented dimension was related to coping factors. Conclusion: Patients with schizophrenia and affective disorder cope differently with delusions. The dimensions of delusion are related to coping and should be regarded when using cognitive therapy approaches to enhance coping strategies.
Natural Killer Cells: A Coherent Model for Their Functional Role in Mycobacterium tuberculosis Infection
Authors: Esin Semih , Batoni Giovanna
Published: September 2014

Tuberculosis is still a leading cause of bacterial infection worldwide, with an estimate of over two billion people latently infected with Mycobacterium tuberculosis (MTB). A delicate interplay between MTB and the host's innate and acquired immune system can influence the outcome of the infection, which ranges from pathogen elimination to the establishment of a latent infection or a progressive disease. Although the host cell-mediated adaptive immune response is of vital importance in the control of MTB infection, growing evidence indicates that innate immune cells may greatly influence the outcome of the interaction between the bacterium and the host. Among the cell populations likely to play a role in the host immune response to MTB, natural killer (NK) cells have recently attracted considerable interest. This review is dedicated to dissecting the role of NK cells in immunity to tuberculosis, reporting the most relevant findings and providing a working model of the possible contribution of NK cells in early and late events associated with MTB infection.
Die Rolle des endobronchialen und endoskopischen Ultraschalls in der Pneumologie
Authors: Gompelmann Daniela , Herth Felix J.F.
Published: September 2014

In den letzten 10 Jahren hat sich der endobronchiale Ultraschall (EBUS) zu einem wichtigen Instrument der diagnostischen Bronchoskopie in der täglichen Praxis entwickelt. Der EBUS hat sich als Standard für die Diagnose der hilären und mediastinalen Lymphadenopathie ebenso etabliert wie als Führungstechnik bei peripheren Lungenläsionen sowie zur Beurteilung des Tumorbefalls der Tracheobronchialwand und des Mediastinums. Heute spielt der EBUS außerdem eine bedeutende Rolle beim mediastinalen Staging des Lungenkarzinoms. Aber der EBUS ist nicht nur für die Diagnose maligner Erkrankungen von Bedeutung, sondern auch für die Diagnose gutartiger Krankheiten.
Die notfallmäßige Thoraxsonographie
Authors: Kreuter Michael , Mathis Gebhard
Published: September 2014

Der Thoraxsonograph ist ein nichtinvasives und portables diagnostisches Instrument, das für die initiale Diagnostik bei thorakalen Notfällen in hohem Maße indiziert ist. Ein Verdacht auf Pneumothorax, Pneumonie, Lungenembolie oder Lungenkontusion nach einem Trauma lässt sich mit diesem Verfahren rasch abklären. Die Hauptvorteile der Thoraxsonographie sind ihre gute Verfügbarkeit und die steile Lernkurve. Weitere Vorteile dieser schnellen, symptombasierten Untersuchung sind ihre hohe Sensitivität und Spezifität. Allerdings hat die Thoraxsonographie den Nachteil, dass sie nur solche Läsionen darstellen kann, die pleuraständig oder über ein Schallfenster sichtbar sind (z.B. Pleuraergüsse oder subpleurale Konsolidierungen).
Ayurvedische Medizin und die Lunge
Authors: Lim Chiao Yuen , Takano Angela , Yang Steve , Lee Pyng
Published: September 2014

Eine indische Frau mittleren Alters mit Schmerzen im Kniegelenk hatte seit 6 Monaten täglich ayurvedische Medikamente (Ostolief®- und Arthrella®-Tabletten) eingenommen. Sie stellte sich mit einer sich verschlechternden Dyspnoe, mit Husten und einem seit 2 Monaten fortschreitenden Gewichtsverlust in der pneumologischen Klinik vor. Sie war Hausfrau, hatte nie geraucht und hielt keine Vögel. Die körperliche Untersuchung ergab feine Rasselgeräusche beim Einatmen. Trommelschlägelfinger, Gelenkdeformitäten oder -schwellungen, Hautläsionen oder eine Lymphadenopathie mit vergrößerten zervikalen Lymphknoten lagen nicht vor. In der hochauflösenden Computertomographie waren diffuse zentrilobuläre Knoten mit Milchglastrübung zu erkennen. In der Spirometrie wurde eine restriktive Ventilationsstörung festgestellt (FVC 44% des Sollwerts, FEV1/FVC-Quotient 93%), und das Autoimmun-Screening war negativ. In der bronchoalveolären Lavage wurde eine Lymphozytose mit erhöhtem CD4/CD8-Verhältnis (T-Helfer-/T-Suppressorzellen) entdeckt. Kulturen für Bakterien, Mykobakterien, Pilze, Viren und Pneumocystis carinii waren negativ. In der bronchoskopischen Lungenbiopsie wurden eine Alveolitis mit lymphozytärer Infiltration des Interstitiums sowie peribronchioläre, nichtverkäsende Granulome festgestellt. Die Diagnose «Hypersensitivitätspneumonitis infolge ayurvedischer Medikation» wurde gestellt. Der Patientin wurde geraten, die auslösenden Medikamente abzusetzen; eine Behandlung mit hochdosierten Steroiden und prophylaktisch verabreichtem Bactrim® wurde eingeleitet und über 3 Monate wieder ausgeschlichen; sie schlug gut an, und die radiologische Bildgebung zeigte eine vollständige Abheilung. Die Patientin wurde 1 Jahr nachbeobachtet; ein Rückfall trat nicht auf.
Giant Chorioangiomas: Perinatal Outcomes and Techniques in Fetoscopic Devascularization
Authors: Lim Foong-Yen , Coleman Alan , Polzin William , Jaekle Ronald , Habli Mounira , Van Hook James , Lewis David , Crombleholme Timothy
Published: September 2014

Objective: To evaluate the intrauterine management and perinatal outcome of pregnancies complicated by giant placental chorioangioma (>4 cm) and elaborate on various devascularization techniques. Materials and Methods: Retrospective review of 10 cases of giant placental chorioangioma evaluated between January 2005 and August 2012. Maternal demographics, prenatal imaging, response to fetoscopic treatment, obstetrical complications, and perinatal outcomes were evaluated. Results: Overall survival was 80%. Seven (70%) cases were associated with obstetrical complications, including polyhydramnios (n = 7), non-immune hydrops (n = 3), and high cardiac output state (n = 5). Five patients underwent fetoscopic devascularization at a mean gestational age of 24.03 weeks with 80% survival. The tumors were devascularized by bipolar coagulation (n = 1), combination of bipolar and diode laser (n = 2), bipolar and radiofrequency ablation (n = 1), and surgical clip application (n = 1). Postoperatively, all survivors had resolution of hydrops and high cardiac output states with survival beyond 60 days of life. Discussion: Fetoscopic devascularization is indicated for high cardiac output states or non-immune hydrops and may require multiple techniques including bipolar coagulation, clip application, and/or laser to interrupt arterial inflow and devascularize the mass.
Differential Effects of Prenatal Stress in Female 5-Htt-Deficient Mice: Towards Molecular Mechanisms of Resilience
Authors: Jakob Sissi , Schraut Karla-Gerlinde , Schmitt Angelika G. , Scholz Claus-Jürgen , Ortega Gabriela , Steinbusch Harry W. , Lesch Klaus-Peter , van den Hove Daniel L.A.
Published: September 2014

Prenatal stress (PS) exposure is known to increase the risk of developing emotional disorders like major depression in later life. However, some individuals do not succumb to adversity following developmental stress exposure, a phenomenon referred to as resilience. To date, the molecular mechanisms explaining why some subjects are vulnerable and others more resilient to PS are far from understood. Recently, we have shown that the serotonin transporter (5-HTT) gene may play a modulating role in rendering individuals susceptible or resilient to PS. However, it is not clear which molecular players are mediating the interaction between PS and the 5-Htt genotype in the context of vulnerability and resilience to PS. For this purpose, we performed a microarray study with the help of Affymetrix GeneChip® Mouse Genome 430 2.0 Array, in which we separated wild-type and heterozygous 5-Htt-deficient (5-Htt+/-) PS offspring into susceptible and resilient offspring according to their performance in the forced swim test. Performance-oriented LIMMA analysis on the mRNA expression microarray data was followed by subsequent Spearman's correlation analysis linking the individual qRT-PCR mRNA expression data to various anxiety- and depression-related behavioral and neuroendocrine measures. Results indicate that, amongst others, Fos-induced growth factor (Figf), galanin receptor 3 (Galr3), growth hormone (Gh) and prolactin (Prl) were differentially expressed specifically in resilient offspring when compared to controls, and that the hippocampal expression of these genes showed several strong correlations with various measures of the hypothalamus-pituitary-adrenal axis (re)activity. In conclusion, there seems to be an intricate interplay between the expression of Figf, Galr3, Gh and Prl and neuroendocrine regulation, which may be critical in mediating resilience to PS exposure. More insight into the exact role of these molecular players may significantly enhance the development of new treatment strategies for stress-related emotional disorders.
Hydrocephalus after Decompressive Craniotomy: A Case Series
Authors: Wani Abrar A. , Ramzan Altaf U. , Tanki Humam , Malik Nayil K. , Dar Bashir A.
Published: September 2014

Background: Post-craniectomy hydrocephalus in patients with intracranial hypertension is becoming a major concern for neurosurgeons because of the increasing number of hospital admissions for head trauma, stroke and other lesions which may lead to severe brain oedema requiring decompressive craniectomy. Methods: We collected records of all the paediatric patients who developed hydrocephalus following decompressive craniotomy from October 2011 to October 2013 and analysed their clinical profiles. Results: We had 3 patients in this group, ranging in age from 6 to 18 years; 1 patient died and the other 2 patients continue to remain in follow-up. Conclusion: Post-traumatic hydrocephalus is one of the rare complications of decompressive craniotomy; CSF diversion remains the only option for improvement in neurological status.
Serial Ultrasonographic Examination of the Fetal Thymus in the Prediction of Early Neonatal Sepsis in Preterm Premature Rupture of Membranes
Authors: Cetin Orkun , Dokurel Cetin Ipek , Uludag Seyfettin , Sen Cihat , Verit Fatma Ferda , Guralp Onur
Published: September 2014

Background/Aims: To evaluate the diagnostic accuracy of fetal thymus transverse diameter (FTTD) in predicting fetal infection in preterm premature rupture of membranes (PPROM) and compare its accuracy with cord blood tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Methods: Forty consecutive pregnancies complicated with PPROM between 261/7 and 366/7 gestational weeks were evaluated prospectively. Serial fetal ultrasonography follow-ups with 3-day intervals were performed beginning on the admission day. The FTTD was recorded on every ultrasonographic examination. Cord blood TNF-α and IL-6 values were measured after delivery. Results: FTTD was decreased below 5% according to nomograms compared to the initial measurement in 45% of all PPROM cases. Decreased FTTD had a sensitivity of 100%, specificity of 73%, positive predictive value of 55%, and negative predictive value of 100% in predicting early neonatal sepsis. Cord blood TNF-α had a sensitivity of 80% and specificity of 90%, whereas IL-6 had a sensitivity of 90% and specificity of 63.3% in predicting early neonatal sepsis. Conclusions: Assessment of the decrease in FTTD by serial ultrasonographic examinations is a promising ‘prenatal' method for the early detection of early neonatal sepsis.
Comparison of Three Cough-Augmentation Techniques in Neuromuscular Patients: Mechanical Insufflation Combined with Manually Assisted Cough, Insufflation-Exsufflation Alone and Insufflation-Exsufflation Combined with Manually Assisted Cough
Authors: Lacombe Matthieu , Del Amo Castrillo Lorena , Boré Aurélien , Chapeau David , Horvat Eric , Vaugier Isabelle , Lejaille Michelle , Orlikowski David , Prigent Hélène , Lofaso Frédéric
Published: September 2014

Background: Mechanical insufflation-exsufflation (MI-E), more commonly known as ‘cough assist therapy', is a method which produces inspiratory and expiratory assistance to improve cough performances. However, other alternatives or combinations are possible. Objective: The objective was to compare the effects of mechanical insufflation combined with manually assisted coughing (MAC), insufflation-exsufflation alone and insufflation-exsufflation combined with MAC in neuromuscular patients requiring cough assistance. Methods: Eighteen neuromuscular patients with severe respiratory muscle dysfunction and peak cough flow (PCF) lower than 3 liters/s or maximal expiratory pressure (MEP) lower than +45 cm H2O were studied. Patients were studied under three cough-assisted conditions, which were used in random order: insufflation by intermittent positive-pressure breathing (IPPB) combined with MAC, MI-E and MI-E + MAC. Results: Overall, PCF was higher with IPPB + MAC than with MI-E + MAC or MI-E alone. Among the 12 patients who had higher PCF values with IPPB + MAC than with the two other techniques, 9 exhibited mask pressure swings during MI-E exsufflation, with a transient positive-pressure value due to the expiratory flow produced by the combined patient cough effort and MAC. Each of these 9 patients had higher PCF values (>5 liters/s) than did the other 9 patients when using IPPB + MAC. Conclusion: Our results indicate that adding the MI-E device to MAC is unhelpful in patients whose PCF with an insufflation technique and MAC exceeds 5 liters/s. This is because the expiratory flow produced by the patient's effort and MAC transitorily exceeds the vacuum capacity of the MI-E device, which therefore becomes a transient load against the PCF.
Low Cognitive Status Is Associated with a Lower Ability to Maintain Standing Balance in Elderly Outpatients
Authors: Stijntjes Marjon , Pasma Jantsje H. , van Vuuren Marjet , Blauw Gerard Jan , Meskers Carel G.M. , Maier Andrea B.
Published: September 2014

Background: Evidence is emerging that cognitive performance is involved in maintaining balance and thereby involved in falls in the elderly. Objective: To investigate the association of cognitive status with measures of standing balance in elderly outpatients. Methods: In a cross-sectional study, 197 community-dwelling elderly [mean age (SD) 81.9 (7.1) years] referred to a geriatric outpatient clinic were included and subsequently dichotomized into a group with low and normal cognitive status based on cut-off values of the Mini-Mental State Examination, Montreal Cognitive Assessment and Visual Association Test. The ability to maintain standing balance as well as the center of pressure (CoP) movement were assessed during 10 s of side-by-side, semi-tandem and tandem stance with eyes open and eyes closed. Logistic and linear regression were used to examine the association between cognitive status and measures of standing balance adjusted for age, gender and highest completed education. Results: Low cognitive status in elderly outpatients was associated with a lower ability to maintain 10 s of balance in side-by-side stance with eyes closed [OR (95% CI): 3.57 (1.60; 7.97)] and in semi-tandem stance with eyes open and eyes closed [OR (95% CI): 3.93 (1.71; 9.00) and OR (95% CI): 2.32 (1.11; 4.82), respectively]. Cognitive status was not associated with CoP movement. Conclusion: Low cognitive status associates with a lower ability to maintain standing balance in more demanding standing conditions in elderly outpatients. This may have implications for routine geriatric screening strategies and interpretation of results of either standing balance or cognitive tests.
Role of the Natriuretic Peptide System in Normal Growth and Growth Disorders
Authors: Vasques Gabriela A. , Arnhold Ivo J.P. , Jorge Alexander A.L.
Published: September 2014

The C-type natriuretic peptide (CNP) and its receptor (NPR-B) are recognized as important regulators of longitudinal growth. Animal models involving CNP or NPR-B genes (Nppc or Npr2) support the fundamental role of CNP/NPR-B for endochondral ossification. Studies with these animals allow the development of potential drug therapies for dwarfism. Polymorphisms in two genes related to the CNP pathway have been implicated in height variability in healthy individuals. Biallelic loss-of-function mutations in NPR-B gene (NPR2) cause acromesomelic dysplasia type Maroteux, a skeletal dysplasia with extremely short stature. Heterozygous mutations in NPR2 are responsible for nonsyndromic familial short stature. Conversely, heterozygous gain-of-function mutations in NPR2 cause tall stature, with a variable phenotype. A phase 2 multicenter and multinational trial is being developed to evaluate a CNP analog treatment for achondroplasia. Pediatricians and endocrinologists must be aware of growth disorders related to natriuretic peptides, although there is still much to be learned about its diagnostic and therapeutic use.
Prediction of Survival by Tumor Area on Endosonography after Definitive Chemoradiotherapy for Locally Advanced Squamous Cell Carcinoma of the Esophagus
Authors: Shim Choong Nam , Song Mi Kyung , Lee Hye Sun , Chung Hyunsoo , Lee Hyuk , Shin Sung Kwan , Lee Sang Kil , Lee Yong Chan , Park Jun Chul
Published: September 2014

Background: Definitive chemoradiotherapy (CRT) is a reasonable approach for patients with locally advanced esophageal cancer who are not surgical candidates. This study was performed to investigate whether endosonography (EUS) assessment of tumor area response is a useful prognostic marker in patients with squamous cell carcinoma (SCC) of the esophagus who receive definitive CRT. Methods: A total of 33 patients who received definitive CRT for locally advanced esophageal SCC were enrolled. The maximal transverse cross-sectional area of the tumor was measured before and after definitive therapy. EUS response was defined as a ≥50% reduction of the tumor area after definitive CRT. Results: Based on EUS evaluation, there were 20 nonresponders (60.6%) and 13 responders (39.4%). The median progression-free survival (PFS) was significantly longer in EUS responders than EUS nonresponders (p = 0.005). However, there was no statistical significance in overall survival according to EUS response (p = 0.120). During multivariate analysis, EUS response to definitive CRT was the only significant factor associated with PFS (p = 0.045), whereas EUS response to definitive CRT was not associated with overall survival (p = 0.221). Conclusions: A reduction of the maximal cross-sectional tumor area measured by EUS correlates with a superior prognosis in patients with locally advanced SCC of the esophagus after definitive CRT.
Preimplantational Genetic Diagnosis and Mutation Detection in a Family with Duplication Mutation of DMD Gene
Authors: Ye Yinghui , Yu Ping , Yong Jing , Zhang Ting , Wei Xiaoming , Qi Ming , Jin Fan
Published: September 2014

Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disease caused by mutation in the DMD gene. A 38-year-old woman was referred to our hospital with her son who was diagnosed with DMD. Multiplex PCR failed to detect DMD mutations in the affected child. The female carrier underwent preimplantation genetic diagnosis by linkage analysis and gender determination. Eight embryos were biopsied after in vitro fertilization. Two healthy embryos determined both as females (E1 and E3) were transferred. Although the paternal allele was absent in E3, it was considered to be a result of allele dropout for the STR-49 marker. Surprisingly, a female and a male baby were delivered at 38 gestational weeks, suggesting that E3 was a male embryo with the allele dropout occurring at the SRY gene. Exon 2 duplication was detected in the DMD patient and the carrier mother using next-generation sequencing and multiple ligation-dependent probe amplification. Next, we verified the duplication of exon 2 by real-time PCR, using a special primer at 3′ of intron 1, very close to exon 2. Finally, we confirmed that both newborns inherited the normal allele, using quantitative real-time PCR and linkage analysis.
Well-Differentiated Neuroendocrine Neoplasia: Relapse-Free Survival and Predictors of Recurrence after Curative Intended Resections
Authors: Dieckhoff P. , Runkel H. , Daniel H. , Wiese D. , Koenig A. , Fendrich V. , Bartsch D.K. , Moll R. , Müller D. , Arnold R. , Gress T. , Rinke A.
Published: September 2014

Background: Resection with curative intention is the cornerstone of treatment in patients with neuroendocrine tumors. A proportion of patients will relapse after R0 resection, but the factors predictive of recurrence are not well understood. Methods: A database established 1998 at the University Hospital Marburg was queried for all patients with documented R0 resection. Recurrence-free survival and overall survival were estimated using the Kaplan-Meier method. Uni- and multivariate analyses were performed. Results: 180 patients with a median age of 52 years entered the analysis. We observed 77 recurrences after a median time of 2.9 years. 24% of the recurrences occurred later than 5 years after operation. Median recurrence-free survival of the whole cohort was 101 months. In univariate analysis grade by Ki-67, stage, high lymph node ratio and microangioinvasion were significant predictors of recurrence. On multivariate analysis these parameters were confirmed as independent prognostic parameters with stage and microangioinvasion being the most important predictors. Conclusions: After R0 resection of neuroendocrine tumors, postoperative surveillance should be extended to at least 10 years. Patients with distant metastases and microangioinvasion are at high risk of recurrence. Clinical trials of adjuvant treatment protocols are indicated in these patients.
The Role of Pericyte Detachment in Vascular Rarefaction
Authors: Schrimpf Claudia , Teebken Omke E. , Wilhelmi Mathias , Duffield Jeremy S.
Published: September 2014

Background: Pericytes surround endothelial cells at the perivascular interface. Signaling between endothelial cells and pericytes is crucial for capillary homeostasis, as pericytes stabilize vessels and regulate many microvascular functions. Recently it has been shown that pericytes are able to detach from the vascular wall and contribute to fibrosis by becoming scar-forming myofibroblasts in many organs including the kidney. At the same time, the loss of pericytes within the perivascular compartment results in vulnerable capillaries which are prone to instability, pathological angiogenesis, and, ultimately, rarefaction. Aims: This review will give an overview of pericyte-endothelial cell interactions, summarize the signaling pathways that have been identified to be involved in pericyte detachment from the vascular wall, and present pathological endothelial responses in the context of disease of the kidney.
Implication of Microscopic and Macroscopic Vascular Invasion for Liver Resection in Patients with Hepatocellular Carcinoma
Authors: Faber Wladimir , Stockmann Martin , Kruschke Johannes Eberhard , Denecke Timm , Bahra Marcus , Seehofer Daniel
Published: September 2014

Background and Aim: Long-term data after liver resection for hepatocellular carcinoma (HCC) with vascular invasion are rare for non-Asian patients. The aim of the present study was to analyze the long-term outcome of liver resection for HCC with vascular invasion and to compare the results of subgroups with micro- and macrovascular invasion. Methods: From January 2000 to September 2010, 288 patients without extrahepatic metastases underwent liver resection for HCC. In 107 out of 288 patients (37%), vascular invasion was found in the final pathological analysis. The long-term outcome as well as the perioperative course of these patients was analyzed using a prospective database. Results: The 1-, 3- and 5-year cumulative survival rate of HCC patients with vascular invasion was 64.3, 41.4 and 23.9%, respectively. The median survival was 19 months. In the multivariate analysis, the overall survival was not influenced by the type of vascular invasion (micro- vs. macrovascular invasion), however overall survival was significantly impaired in case of lymphatic vessel invasion, intraoperative blood transfusions, need of fresh frozen plasma application, prolonged ICU stay and elevated preoperative bilirubin levels. Conclusions: Acceptable survival rates can be achieved in selected patients with macrovascular invasion after surgical resection, which is not markedly different from those with microvascular invasion. In view of an otherwise poor prognosis, liver resection seems to be justified for selected HCC patients with macrovascular invasion, although this stands in contrast with the BCLC recommendations. However, it is in accordance for example with the guidelines of the Asia-Pacific Association for the Study of the Liver.
Changes in the Small Bowel of Symptomatic Kidney Transplant Recipients Converted from Mycophenolate Mofetil to Enteric-Coated Mycophenolate Sodium
Authors: Bunnapradist Suphamai , Sampaio Marcelo S. , Wilkinson Alan H. , Pham Phuong-Thu , Huang Edmund , Kuo Hung-Tien , Anastasi Bishoy , Danovitch Gabriel M. , Lo Simon K.
Published: September 2014

Background/Aims: Gastrointestinal (GI) symptoms in renal transplant recipients may be caused due to mycophenolic acid (MPA) toxicity. Using small bowel capsule endoscopy (SBCE) we examined the impact of conversion from Mycophenolate Mofetil (MMF) to enteric-coated formulation of Mycophenolate Sodium (EC-MPS) given to treat GI mucosal lesions. Methods: Adult kidney-only recipients at least 30 days after transplant, presenting with GI symptoms while receiving MMF completed a Gastrointestinal Symptom Rating Scale (GSRS) questionnaire, underwent SBCE, and had MMF substituted by EC-MPS. After 30 days, GSRS and SBCE were repeated and findings were compared to baseline values. Patients who were still on EC-MPS 6-24 months post-conversion were contacted for completing a follow-up GSRS questionnaire and SBCE. Results: Eighteen out of 23 subjects completed the first part of the study. Subjects' median ages and post-transplant time were 47.5 years old and 4.5 months, respectively. Tacrolimus, MMF and prednisone was the main regimen (94%), with a median MMF dose of 750 mg BID. The average baseline GSRS was 2.99 ± 0.81; it significantly decreased to 2.19 ± 0.8 at 30 days post-conversion. At baseline, 50 had gastric and 89% had small bowel lesions. At 30 days, 29 and 62% of the SBCE were still showing gastric and small bowel lesions, respectively. Of 5 patients in the study extension, 4 had abnormal SBCE findings but have been reporting improvement in their symptoms. Conclusion: Stomach and small bowel mucosal lesions are common in kidney recipients with GI symptoms when treated with MMF. Conversion to EC-MPS for 30 days significantly alleviated the GI symptoms; however, no evident correlation with SBCE findings was found.
Leukotriene Receptor Blockade as a Life-Saving Treatment in Severe Bronchopulmonary Dysplasia
Authors: Rupprecht Thomas , Rupprecht Christian , Harms Dieter , Sterlacci William , Vieth Michael , Seybold Kathrin
Published: September 2014

Background: Bronchopulmonary dysplasia (BPD) is a major cause of mortality and morbidity in infants with an extremely low birth weight. Because there is no effective therapy, the mortality of this condition in severely affected patients is high. Therapeutic blocking of the leukotriene system seems to be a logical approach due to the known pathophysiology of BPD. Objectives: The aim of this study was to examine the therapeutic effect of montelukast in preterm children suffering from severe BPD. Methods: We performed an unblinded, prospective trial including infants born between 23 and 27 weeks of gestation suffering from severe BPD. The study drug was montelukast (1 mg/kg of body weight as a single dose daily in the 1st week of therapy, increasing to 1.5 mg/kg of body weight in the 2nd week and finally to 2 mg/kg of body weight in the 3rd week). Treatment was continued until the radiological signs and the clinical symptoms of BPD disappeared or the patient was discharged from the hospital. Each patient included in this study was matched for gestational age, birth weight, and pulmonary severity score to a control. Results: Until March 2014, a total of 22 infants were enrolled into the study. The rates of the primary outcome differed significantly between the montelukast-treated group and the control group. All but 1 of the children in the treatment group survived (91%), whereas 7 of the 11 children in the control group died (survival rate 36%; p = 0.002 using Fisher's exact test). The mean mechanical ventilation time (41.2 ± 25.3 vs. 103.7 ± 90.6 days) was significantly shorter and the mean preterm complication score (3.0 ± 1.7 vs. 5.6 ± 1.4) was significantly lower in treated patients compared to the control group. (p = 0.05 for both items; Wilcoxon's matched-pairs test). Conclusion: Based on the clinical observations, the statistical results, and the relatively low risk of the study drug montelukast, we recommend using this treatment in severe cases of BPD for infants facing a high risk of death.
Patterns of Hippocampal Tau Pathology Differentiate Neurodegenerative Dementias
Authors: Milenkovic Ivan , Petrov Tatjana , Kovacs Gabor G.
Published: September 2014

Background/Aims: Deposits of phosphorylated tau protein and convergence of pathology in the hippocampus are the hallmarks of neurodegenerative tauopathies. Thus we aimed to evaluate whether regional and cellular vulnerability patterns in the hippocampus distinguish tauopathies or are influenced by their concomitant presence. Methods: We created a heat map of phospho-tau (AT8) immunoreactivity patterns in 24 hippocampal subregions/layers in individuals with Alzheimer's disease (AD)-related neurofibrillary degeneration (n = 40), Pick's disease (n = 8), progressive supranuclear palsy (n = 7), corticobasal degeneration (n = 6), argyrophilic grain disease (AGD, n = 18), globular glial tauopathy (n = 5), and tau-astrogliopathy of the elderly (n = 10). AT8 immunoreactivity patterns were compared by mathematical analysis. Results: Our study reveals disease-specific hot spots and regional selective vulnerability for these disorders. The pattern of hippocampal AD-related tau pathology is strongly influenced by concomitant AGD. Mathematical analysis reveals that hippocampal involvement in primary tauopathies is distinguishable from early-stage AD-related neurofibrillary degeneration. Conclusion: Our data demonstrate disease-specific AT8 immunoreactivity patterns and hot spots in the hippocampus even in tauopathies, which primarily do not affect the hippocampus. These hot spots can be shifted to other regions by the co-occurrence of tauopathies like AGD. Our observations support the notion that globular glial tauopathies and tau-astrogliopathy of the elderly are distinct entities.
Mechanisms of Acid Reflux and How Refluxed Acid Extends Proximally in Patients with Non-Erosive Reflux Disease
Authors: Sano Hirohito , Iwakiri Katsuhiko , Kawami Noriyuki , Tanaka Yuriko , Sakamoto Choitsu
Published: September 2014

Background/Aims: The mechanisms that cause acid reflux in patients with non-erosive reflux disease (NERD), including those that determine how acid extends proximally, are not yet clear. Methods: Concurrent esophageal manometry and pH monitoring were performed for 3 h after a meal in 13 patients with NERD, 12 with mild reflux esophagitis (RE), and 13 healthy subjects (HS). Results: Transient lower esophageal sphincter (LES) relaxation (TLESR) was the major mechanism of acid reflux in all three groups. LES pressure did not differ between the groups. At 2 cm above the LES, there were no differences between the three groups in the number of TLESR-related acid reflux episodes, rate of TLESRs and rate of acid reflux during TLESR. However, at 7 cm above the LES, the rate of acid reflux during TLESRs was significantly higher in patients with NERD (mean ± SEM 42.3 ± 4.8) than in those with mild RE (28.0 ± 3.8) and HS (10.8 ± 2.5). Conclusions: TLESRs are the sole motor events underlying acid reflux episodes in patients with NERD. Acid extends proximally more readily in patients with NERD than in HS and those with mild RE.
Oligometastatic Non-Small Cell Lung Cancer: A Significant Entity outside of Specialized Cancer Centers?
Authors: Nieder Carsten , Tollåli Terje , Reigstad Anne , Pawinski Adam , Haukland Ellinor , Dalhaug Astrid
Published: September 2014

Objective: To report the incidence, patterns of care, and outcomes of oligometastatic non-small cell lung cancer (NSCLC) in a rural practice setting in Norway. Materials and Methods: A retrospective analysis was conducted of all patients with stage IV NSCLC at the initial diagnosis who received active treatment in the central part of Nordland, a rural county in northern Norway, during the period of 2006-2012. We analyzed overall survival and prognostic factors. Results: The initial study population included 113 patients with stage IV disease who received active therapy; of these, 23 (20%) had oligometastatic spread (a maximum of 3 metastases to 1 organ). The median age was 71 years. Of the 23 patients, 16 (70%) did not receive radical or at least moderately aggressive local treatment for their thoracic disease. Of the remaining 7 patients, 4 (17.4%) did not receive systemic therapy. The median actuarial survival was 5.6 months in patients with more advanced metastases and 11.7 months in those with oligometastases (p = 0.03). Significant differences were also seen between the 2 oligometastatic patient groups with and without more intense thoracic treatment (median 19.7 vs. 7.6 months, p = 0.004). Further significant predictors of survival in patients with oligometastases were nodal stage (p = 0.028) and weight loss (p = 0.045). Trends were seen for T stage (p = 0.058) and performance status (p = 0.07). Conclusion: Oligometastatic NSCLC was diagnosed in a relevant proportion of patients; therefore, warranting prospective studies are recommended. Such studies are also needed to confirm the treatment-dependent survival differences observed in our patient population.