bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Bis-2,3-dihydroquinazolin-4(1H)-ones and 2,3-Dihydroquinazolin-4(1H)-ones Derivatives with the Aid of Silica-Supported Preyssler Nanoparticles
Authors: Gharib Ali , Hashemipour Khorasani Bibi Robabeh , Jahangir Manouchehr , Roshani Mina , Safaee Reza
Published: September 2013

One-pot three-component condensation of isatoic anhydride with primary amines or ammonium carbonate and aromatic aldehydes in refluxing ethanol in the presence of catalytic amounts of silica-supported preyssler nanoparticles (SPNP) afforded the corresponding 2,3-dihydroquinazolin-4(1H)-ones in high yields, and bis-dihydroquinazolinones were synthesized for the first time by a novel pseudo-five-component condensation of isatoic anhydride, a primary amine, and a dialdehyde in water. The catalyst is reusable and can be applied several times without any decrease in product yield.
Repeated-Doses Toxicity Study of the Essential Oil ofHyptis martiusiiBenth. (Lamiaceae) in Swiss Mice
Authors: Freire Rocha Caldas Germana , Araújo Alice Valença , Albuquerque Giwellington Silva , Silva-Neto Jacinto da Costa , Costa-Silva João Henrique , de Menezes Irwin Rose Alencar , Leite Ana Cristina Lima , da Costa José Galberto Martins , Wanderley Almir Gonçalves
Published: September 2013

Hyptis martiusiiBenth. (Lamiaceae) is found in abundance in Northeastern Brazil where it is used in traditional medicine to treat gastric disorders. Since there are no studies reporting the toxicity and safety profile of this species, we investigated repeated-doses toxicity of the essential oil ofHyptis martiusii(EOHM). Swiss mice of both sexes were orally treated with EOHM (100 and 500 mg/kg) for 30 days, and biochemical, hematological, and morphological parameters were determined. No toxicity signs or deaths were recorded during the treatment with EOHM. The body weight gain was not affected, but there was an occasional variation in water and food consumption among mice of both sexes treated with both doses. The hematological and biochemical profiles did not show significant differences except for a decrease in the MCV and an increase in albumin, but these variations are within the limits described for the species. The microscopic analysis showed changes in liver, kidneys, lungs, and spleen; however, these changes do not have clinical relevance since they varied among the groups, including the control group. The results indicate that the treatment of repeated-doses with the essential oil ofHyptis martiusiishowed low toxicity in mice.
Inequalities Similar to Hilbert's Inequality
Authors: Zhao Chang-Jian
Published: September 2013

In the present paper, we establish some new inequalities similar to Hilbert’s type inequalities. Our results provide some new estimates to these types of inequalities.
Research of Hydrogen Preparation with Catalytic Steam-Carbon Reaction Driven by Photo-Thermochemistry Process
Authors: Zhang Xiaoqing , Xu Bingqing , Xu Yan , Shang Shuyong , Yin Yongxiang
Published: September 2013

An experiment of hydrogen preparation from steam-carbon reaction catalyzed by K2CO3was carried out at 700°C, which was driven by the solar reaction system simulated with Xenon lamp. It can be found that the rate of reaction with catalyst is 10 times more than that without catalyst. However, for the catalytic reaction, there is no obvious change for the rate of hydrogen generation with catalyst content range from 10% to 20%. Besides, the conversion efficiency of solar energy to chemical energy is more than 13.1% over that by photovoltaic-electrolysis route. An analysis to the mechanism of catalytic steam-carbon reaction with K2CO3is given, and an explanation to the nonbalanced [H2]/[CO + 2CO2] is presented, which is a phenomenon usually observed in experiment.
Effect of UV Irradiation on Interactions ofα-Lipoic Acid with Free Radicals
Authors: Ramos Paweł , Pepliński Piotr , Pilawa Barbara
Published: September 2013

Changes of antioxidant properties ofα-lipoic acid (LA) after UV irradiation were studied. LA is the typical drug used in diabetic neuropathy. Quenching of free radicals is an important factor of therapy by using this substance.α-Lipoic acid is exposed to UV irradiation during the storage. The aim of our studies was to examine the effect of UV irradiation on the interactions of LA with free radicals. Theα-lipoic acid was irradiated by UVA 315–400 nm light during 10 to 110 minutes by intervals of 10 minutes. The electron paramagnetic resonance spectroscopy was used as the experimental technique. The antioxidant properties of LA were spectroscopically confirmed. The strong effect of UV irradiation on interactions ofα-lipoic acid with free radicals was observed. It was pointed out that interactions of LA with free radicals decrease after its exposition on UV. The interactions of LA with free radicals were higher after the sample irradiation during 10 minutes than for the samples irradiated longer (20–110 minutes). The results are important for problems connected with photomedicine; they pointed out thatα-lipoic acid should not be stored on UV exposition. Application of electron paramagnetic resonance spectroscopy to characterize interactions of pharmacological substance with free radicals was confirmed.
Comparative Analyses of Response Surface Methodology and Artificial Neural Network on Medium Optimization for Tetraselmis sp. FTC209 Grown under Mixotrophic Condition
Authors: Mohamed Mohd Shamzi , Tan Joo Shun , Mohamad Rosfarizan , Mokhtar Mohd Noriznan , Ariff Arbakariya B.
Published: September 2013

Mixotrophic metabolism was evaluated as an option to augment the growth and lipid production of marine microalga Tetraselmis sp. FTC 209. In this study, a five‐level three‐factor central composite design (CCD) was implemented in order to enrich the W‐30 algal growth medium. Response surface methodology (RSM) was employed to model the effect of three medium variables, that is, glucose (organic C source), NaNO3 (primary N source), and yeast extract (supplementary N, amino acids, and vitamins) on biomass concentration, Xmax, and lipid yield, Pmax/Xmax. RSM capability was also weighed against an artificial neural network (ANN) approach for predicting a composition that would result in maximum lipid productivity, Prlipid. A quadratic regression from RSM and a Levenberg‐Marquardt trained ANN network composed of 10 hidden neurons eventually produced comparable results, albeit ANN formulation was observed to yield higher values of response outputs. Finalized glucose (24.05 g/L), NaNO3 (4.70 g/L), and yeast extract (0.93 g/L) concentration, affected an increase of Xmax to 12.38 g/L and lipid a accumulation of 195.77 mg/g dcw. This contributed to a lipid productivity of 173.11 mg/L per day in the course of two‐week cultivation.
Studies on a Novel Bioreactor Design for Chondrocyte Culture
Authors: Patil Harshad , Chandel Ishan Saurav , Rastogi Amit K. , Srivastava Pradeep
Published: September 2013

A bioreactor system plays an important role in tissue engineering and enables reproduction and controlled changes in the environmental factor. The bioreactor provides technical means to perform controlled processes in safe and reduced reproducible generation of time. Cartilage cells were grown in vitro by mimicking the in vivo condition. The basic unit of cartilage, that is, chondrocyte, requires sufficient shear, strain, and hydrodynamic pressure for regular growth as it is nonvascular tissue. An attempt has been made to design a novel airlift reactor for chondrocyte culture, and the reactor has been evaluated for its performance. The design includes internal loop wavy riser airlift reactor for chondrocyte culture with 5% CO2 sparging which gives a good yield of chondrocyte after 28 days. The wavy riser provides more surfaces for collision of fluid flow so to create the turbulence. Also, the horizontal semicircular baffles create an angle of 180° which helps in high shear rate. The optimized L/D ratio of the designed airlift reactor (for chondrocyte culture) is 5.67, and it also exhibits good mixing performance.
Soft Schemes for Earthquake-Geotechnical Dilemmas
Authors: García Silvia
Published: September 2013

Models of real systems are of fundamental importance in virtually all disciplines because they can be useful for gaining a better understanding of the organism. Models make it possible to predict or simulate a system’s behavior; in earthquake geotechnical engineering, they are required for the design of new constructions and for the analysis of those that exist. Since the quality of the model typically determines an upper bound on the quality of the final problem solution, modeling is often the bottleneck in the development of the whole system. As a consequence, a strong demand for advanced modeling and identification schemes arises. During the past years, soft computing techniques have been used for developing unconventional procedures to study earthquake geotechnical problems. Considering the strengths and weaknesses of the algorithms, in this work a criterion to leverage the best features to develop efficient hybrid models is presented. Via the development of schemes for integrating data-driven and theoretical procedures, the soft computing tools are presented as reliable earthquake geotechnical models. This assertion is buttressed using a broad history of seismic events and monitored responses in complicated soils systems. Combining the versatility of fuzzy logic to represent qualitative knowledge, the data-driven efficiency of neural networks to provide fine-tuned adjustments via local search, and the ability of genetic algorithms to perform efficient coarse-granule global search, the earthquake geotechnical problems are observed, analyzed, and solved under a holistic approach.
Neuromodulation of Vegetative State through Spinal Cord Stimulation: Where Are We Now and Where Are We Going?
Authors: Della Pepa Giuseppe Maria , Fukaya Chikashi , La Rocca Giuseppe , Zhong Jun , Visocchi Massimiliano
Published: September 2013

Background: Vegetative state (VS) is a complex condition that represents a challenging frontier for medicine and neuroscience research. Nowadays there is no scientifically validated treatment for VS patients, and their chronic long-term assistance is very demanding for healthcare systems worldwide. Objectives: The present paper is a systematic review of the role of spinal cord stimulation (SCS) as a treatment of patients with VS. Methods: Published literature on this topic was analyzed systematically. Clinical and epidemiological characteristics of VS, present therapeutic options and social costs of VS were also evaluated. Results: Only 10 papers have been published since 1988, and overall 308 VS patients have been treated with SCS worldwide; 51.6% displayed a clinical improvement and an amelioration of the environmental interaction. These effects are probably mediated by the stimulation of the reticular formation-thalamus-cortex pathway and by cerebral blood flow augmentation induced by SCS. Conclusions: The experience on this topic is still very limited, and on this basis it is still hard to make any rigorous assessment. However, the most recent experiments represent significant progress in the research on this topic and display SCS as a possible therapeutic tool in the treatment of VS.
A Comparison of Schemas, Schema Modes and Childhood Traumas in Obsessive-Compulsive Disorder, Chronic Pain Disorder and Eating Disorders
Authors: Voderholzer Ulrich , Schwartz Caroline , Thiel Nicola , Kuelz Anne Katrin , Hartmann Armin , Scheidt Carl Eduard , Schlegl Sandra , Zeeck Almut
Published: September 2013

Background: In this study, we investigated early maladaptive schemas (EMS), schema modes and childhood traumas in patients suffering from obsessive-compulsive disorder (OCD) in contrast to patients with other Axis I disorders. Based on cognitive theories on OCD, our main research question was whether schemas belonging to the domain of ‘impaired autonomy and performance' are more prevalent in OCD than in both eating disorders (ED) and chronic pain disorder (CPD). Sampling and Methods: EMS, schema modes and traumatic childhood experiences were measured in 60 patients with OCD, 41 with ED, 40 with CPD and 142 healthy controls. To analyze differences between the groups, MANCOVAs were conducted followed by deviation contrasts. Depression level, age and gender were considered as possible covariates. Results: OCD patients scored higher on 4 EMS, 2 of which belong to the domain ‘impaired autonomy and performance'. ED patients had higher scores in the EMS ‘emotional inhibition' and CPD patients on the Childhood Trauma Questionnaire subscale ‘physical neglect'. Conclusions: These results suggest that there might be typical schema patterns associated with OCD and ED. We can also conclude that a higher prevalence of traumatic experiences does not necessarily coincide with more EMS and schema modes.
Maternal and Paternal Body Mass Index and Offspring Obesity: A Systematic Review
Authors: Patro Bernadeta , Liber Anna , Zalewski Bartlomiej , Poston Lucilla , Szajewska Hania , Koletzko Berthold
Published: September 2013

Background/Aims: It has been hypothesized that the intrauterine environment is an independent factor in obesity development. If so, the maternal effect is likely to be a stronger influencing factor (‘fetal overnutrition hypothesis'). We aimed to systematically evaluate the associations of offspring body mass index (BMI, or adiposity) with pre-pregnancy BMI (or adiposity) of the mother and the father. Methods: The Medline, Embase and Cochrane Library databases were searched in March 2012. Results: Seven cohort studies were eligible for the analysis. Among these, 2 groups of trials presented different data from the same parent-offspring cohorts (the Avon Longitudinal Study of Parents and Children, ALSPAC, and the Mater-University Study of Pregnancy, MUSP). In total, 3 large birth cohorts and 1 additional small study were identified. Three studies provided a direct comparison of parent-offspring associations, with a statistically stronger maternal influence found only in the MUSP cohort. Equivocal results were obtained from all studies describing the ALSPAC cohort. The parental effect (indirectly estimated based on the presented odds ratio) was similar in the Finnish cohort. In 1 additional small study, maternal BMI was found to be a strong predictor of childhood obesity. Conclusions: There is only limited evidence to support the ‘fetal overnutrition hypothesis'.
Padma 28 - eine sinnvolle Ergänzung zur Behandlung der peripheren arteriellen Verschlusskrankheit im Stadium IIa und IIb
Authors: Regli Christian , Groechenig Ernst
Published: September 2013

Die periphere arterielle Verschlusskrankheit (PAVK) ist zu über 90% durch Atherosklerose bedingt. Da diese alle Arterien des Körpers betreffen kann, gilt die PAVK als wichtiger Indikator für kardiovaskuläre Ereignisse wie Herzinfarkt oder Schlaganfall und somit für die häufigste Todesursache in der westlichen Welt. Mit der ABI-Messung (Knöchel/Arm-Druck-Messung) kann die Krankheit auf eine im Praxisalltag gut durchführbare Weise diagnostiziert werden. Die Grundlage der Behandlung der Atherosklerose beinhaltet neben der Lifestyle-Änderung eine medikamentöse Behandlung der bekannten Risikofaktoren. Liegt eine schwere Durchblutungsstörung mit kritischer Ischämie vor, ist eine kathetertechnische oder chirurgische Revaskularisation zwingend. Von einer Schaufensterkrankheit sprechen wir, wenn aufgrund der PAVK die Gehstrecke limitiert ist. Hier kann neben interventionellen Behandlungen (perkutane transluminale Angioplastie (PTA) / Chirurgie) auch ein konservatives Gehtraining durchgeführt werden. Der supportive Einsatz von Padma 28 bei der konservativen Behandlung zeigt einen messbaren Effekt mit einer deutlichen Verlängerung der maximalen Gehstrecke und ist als additive Therapie eine zu prüfende Behandlungsoption.
Padma 28 bei Zytostatika-induzierten Dysästhesien und Ödemen der Hände - ein Fall aus der Praxis
Authors: Kneip Bettina
Published: September 2013

Hintergrund: Die pflanzliche Komplexformel Padma 28 wird vor allem bei durchblutungsbedingten Parästhe-sien, Schwere- und Spannungsgefühl in den Beinen und Armen und beim Einschlafen von Händen und Füßen eingesetzt. Fallbericht: Im vorgestellten Fall einer Patientin mit Mammakarzinom, Status nach vollständiger Mastektomie, traten starke, Zytostatika-induzierte Dysästhesien und Ödeme beider Hände auf. Diese machten einfache, tägliche Verrichtungen unmöglich. Eine Therapie mit hochdosiertem Vitamin B6 blieb erfolglos. Mit dem Ziel, die Mikrozirkulation zu verbessern und so die empfindlichen Nervenendigungen zu schützen, wurde Padma 28 eingesetzt. Diese Behandlung zeigte trotz fortdauernder Chemotherapie bereits nach 2 Wochen eine Verbesserung der Dysästhesien; nach 5 Wochen waren die Empfindungsstörungen und Ödeme der Hände völlig verschwunden. Schlussfolgerung: Padma 28 scheint somit geeignet zur adjuvanten Anwendung bei Parästhe-sien und Schwellungen, die im Rahmen einer Chemotherapie durch Zytostatika hervorgerufen wurden.
Indeterminate Pediatric Thyroid Fine Needle Aspirations: A Study of 68 Cases
Authors: Smith Matthew , Pantanowitz Liron , Khalbuss Walid E. , Benkovich Vanessa A. , Monaco Sara E.
Published: September 2013

Objective: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) provides a reporting scheme for thyroid fine needle aspiration (FNA) and includes three indeterminate categories with different management strategies. This study analyzes indeterminate thyroid FNAs in children, and correlates these findings with the histological features. Methods: A total of 179 thyroid FNA specimens were retrieved from children. Cases were categorized by TBSRTC. Only cases diagnosed as atypia (AUS)/follicular lesion of undetermined significance (FLUS), suspicious for follicular or oncocytic neoplasm (SFON), or suspicious for malignancy (SM) were selected and correlated with the nodule size and histological follow-up. Results: Sixty-eight cases were identified, including 43 (63%) AUS/FLUS diagnoses, 19 (28%) SFON, and 6 (9%) SM. On follow-up, 48% were malignant, including 28% AUS/FLUS cases, 58% SFON, and 100% SM. The average size of the malignant lesions diagnosed preoperatively as AUS/FLUS was 1.5 cm (range 0.7-4.5), compared to 3.3 cm (range 1.2-6.6) in SFON and 2.8 cm (range 0.7-3.8) in SM. Malignancies included 92% papillary thyroid carcinoma (PTC), 77% of which were the follicular variant of PTC (FVPTC) and 8% follicular carcinomas. The AUS/FLUS cases were largely due to compromised specimens (49%) and the highest malignancy rate occurred in those with cytological atypia (50%). Conclusions: This study shows an incremental risk of malignancy within the indeterminate categories using TBSRTC in children. Malignant nodules with a preoperative AUS/FLUS diagnosis tended to be smaller than those with a SFON or SM diagnosis, and the vast majority of malignancies were PTC, with a high proportion being FVPTC.
Indeterminate and Erroneous Fine-Needle Aspirates of Breast with Focus on the ‘True Gray Zone': A Review
Authors: Shabb Nina S. , Boulos Fouad I. , Abdul-Karim Fadi W.
Published: September 2013

Objective: To review our experience and the literature on inconclusive/erroneous fine-needle aspirates (FNAs) of breast with the focus on the ‘true gray zone'. To describe the cytology, differential diagnosis, pitfalls and limitations of common and rare lesions. Study Design: We conducted a literature search focusing on breast FNAs with statistical data of C3 and C4 categories including false-positive and false-negative cases. Similar data from 2003 to 2009 was obtained from our institution. Results: C3 and C4 categories account for 3-17% of breast FNAs. Contributing factors are technical difficulties, inexperienced pathologists interpreting FNAs of breast and overlap of cytologic features of certain benign and malignant conditions; this last, ‘true gray zone' accounts for 2% of cases. Fibroadenoma, proliferative breast lesions, gynecomastia, infiltrating and in situ low-grade adenocarcinomas and tubular, cribriform, lobular and mucinous carcinomas are the most common problematic lesions. Granular cell tumor, adenomyoepithelioma, pregnancy-related lesions, fat necrosis, inflammatory and radiation changes, adenoid cystic carcinoma, spindle-cell lesions and Phyllodes tumor are less common. Conclusion: Inconclusive/erroneous FNAs of breast due to the ‘true gray zone' are rare. Most are due to the overlapping cytologic features of some benign and malignant conditions. Practical features that may help arrive at the correct diagnoses are elucidated.
Adenoviral-Mediated Gene Transfer into Bone Marrow: An Effective Surgical Technique in Rat
Authors: Rodriguez-Lecompte J.C. , Romero-Perez G.A. , Ramirez-Yañez G. , Ask K. , Gauldie J.
Published: September 2013

Background: The role of transforming growth factor-beta 1 (TGF-β1) in the onset of bone marrow fibrosis has been confirmed in some animal models. To further understand the genetic expression of some myeloproliferative disorders affecting marrow stem cells, however, it is necessary to develop a specific and reliable procedure to deliver modified adenoviral vectors into the bone marrow cavity. The aim of this paper is to report a surgical technique designed to deliver an adenoviral vector-mediated gene expressing TGF-β1 into the bone marrow of rat femurs. Methods: Forty-two Sprague-Dawley rats were used in the study. Rat femurs were exposed and the compact and trabecular bones at the proximal head removed. An intrabone marrow injection of a mutated TGF-β1 adenoviral vector, a null adenoviral vector, or PBS was delivered into the bone. Three groups were accounted (n = 14 per group): fibrogenic and positive and negative controls. The quality of the surgical entrance was assessed by means of computerized tomography and histological changes were assessed by histochemistry. The concentration of TGF-β1 in the bone marrow was determined by ELISA. Results: The surgical technique was conducted under ideal timing (approx. 10 min) and no surgical or postsurgical complications were observed. Computerized tomography revealed no changes in the bone tissue and a clean entrance was delimited through the bone to the bone marrow. HE and Masson's trichrome staining indicated highly fibrotic areas in the profibrotic group and bone marrow lavage reported a significantly higher concentration of TGF-β1 (p < 0.05) in that same group. Conclusions: The present study confirmed that the proposed surgical technique is an effective method to deliver adenoviral vectors into the femoral bone marrow to investigate the physiopathology of bone marrow fibrosis in rats.
Thymoglobulin and Its Use in Renal Transplantation: A Review
Authors: Thiyagarajan Umasankar Mathuram , Ponnuswamy Amirthavarshini , Bagul Atul
Published: September 2013

Thymoglobulin (Thymoglobulin®; Genzyme, Cambridge, Mass., USA) is a polyclonal antibody which has been used in the field of transplantation over the last four decades. With an initial hesitancy, it is widely used now in the prevention and treatment of rejection following renal transplantation. Thymoglobulin's lack of nephrotoxic properties (unlike calcineurin inhibitors) may potentiate it to be a very useful induction therapy during the early days following transplantation, particularly in a donation after circulatory death programme. More recently its role in conjunction with inhibitors of terminal complement activation has been shown to be beneficial in cross-match-positive transplantation. This review article consolidates up-to-date available evidence to address the therapeutic role of thymoglobulin in immunological tolerance, ischemia perfusion, live donor transplantation, delayed graft function, prevention and treatment of rejection, graft survival and post-transplant lymphoproliferative disorder following renal transplantation.
Caregiver Burden in Frontotemporal Degeneration and Corticobasal Syndrome
Authors: Armstrong Nicole , Schupf Nicole , Grafman Jordan , Huey Edward D.
Published: September 2013

Background and Aims: Caregiver stress is often a serious problem when caring for a patient with frontal lobe dysfunction. Methods: A total of 102 caregivers of both patients with frontotemporal degeneration and corticobasal syndrome completed the Frontal Systems Behavior Scale (FrSBe) and the Zarit Burden Interview (ZBI). To analyze the association between apathy or disinhibition (or both) and caregiver burden, the effects of the total FrSBe and the apathy and disinhibition subscales of the FrSBE on the total ZBI score were assessed with logistic regressions and t tests. Results: Total FrSBE score and the apathy FrSBE subscore predicted caregiver burden. Apathy occurred without disinhibition, and the two occurred together, but disinhibition without apathy was very rare. Conclusions: Disinhibition without apathy occurred very rarely. Apathy was more associated with caregiver burden than disinhibition.
Klinische Studien bei peripherer arterieller Verschlusskrankheit: Update unter den Aspekten eines meta-narrativen Reviews
Authors: Melzer Jörg , Saller Reinhard
Published: September 2013

Hintergrund: Atherosklerose ist eine Systemerkrankung. Die Assoziation mit dem metabolischen Syndrom bedingt ein multimodales Therapie-Setting zur Symptomlinderung sowie zur Primär- und Sekundärprävention. In der Therapieplanung sind Informationen zur Evidenz der Interventionen und eine logische Grundlage für eine sinnvolle Kombination wichtig. Methode: Für einen meta-narrativen Review (MNR) zur Evidenz komplementärmedizinischer und konventioneller Pharmakotherapien bei peripherer arterieller Verschlusskrankheit (PAVK) wurden mittels systematischer Literaturrecherche (Datenbanken z.B. MEDLINE; Suchbegriffe z.B. Pharmakotherapie) bis September 2012 Meta-Analysen randomisierter kontrollierter Studien (RCTs) unter den Aspekten Netzwerkpharmakologie und Forschungsparameter evaluiert. Ergebnisse: Es wurden 4 verwertbare Meta-Analysen gefunden. Gegenüber Placebo bewirken die Vera eine signifikante Zunahme der maximalen Gehstrecke um 63,5 m (95% Konfidenzintervall (CI) 27,11-99,91 m; Padma 28, Tibetische Rezeptur), 41,3 m (95% CI -7,1-89,7 m; Cilostazol, Phosphodiesterase-IIl-Hemmer), 43,8 m (95% CI 14,1-73,6 m; Pentoxifyllin, Rheologikum) und 71,2 m (95% CI 13,3-129,0 m; Naftidrofuryl, Rheologikum). Einzig für Padma 28 wurde die klinische Relevanz, definiert als Verlängerung der maximalen Gehstrecke um >100 m, analysiert und unter Verum von 18,2% der Patienten gegenüber 2,1% unter Placebo erreicht (Odds Ratio 10; 95% CI 3,03-33,33). Je 1 konventionelles und komplementärmedizinisches Arzneimittel zeigten außerdem signifikante pleiotrope Effekte (Padma 28 und Cilostazol (z.B. Reduktion der Triglyceride)). Schlussfolgerungen: Der MNR zeigt, dass gemäß meta-analytischer Evidenz Naftidrofuryl und Padma 28 zur Therapie früher Stadien der PAVK klinisch relevant wirksam sind. Inwiefern die theoretische Kombinierbarkeit von Pharmaka zur Verbesserung der Systemerkrankung nach netzwerkpharmakologischen Aspekten (z.B. Synergien pleiotroper Effekte, Reduktion von Nebenwirkungen durch niedrigere Tagesdosen) zur klinischen Wirksamkeit beiträgt, muss in einer mehrarmigen RCT evaluiert werden.
Cardiovascular Burden Associated with Uremic Toxins in Patients with Chronic Kidney Disease
Authors: Moradi Hamid , Sica Domenic A. , Kalantar-Zadeh Kamyar
Published: September 2013

Background: Retention of uremic toxins in patients with chronic kidney disease (CKD) negatively affects multiple organ systems, including the cardiovascular system, resulting in significant morbidity and mortality. Alleviation of the adverse effects of uremic toxins is an important priority in the management of CKD. Scope: This review focuses on the evidence for the influence of uremic toxins on cardiovascular morbidity and mortality among patients with CKD and slowly developing uremia. The cardiovascular effects of acute kidney injury and rapidly developing azotemia are beyond the scope of this review and will not be discussed. Data on potential treatment options aimed at ameliorating the toxic effects of uremic toxins are summarized. Findings: Uremic toxins are associated with significant cardiovascular morbidity and mortality in patients with CKD. While a number of preclinical studies have detailed these effects, clinical studies directly evaluating cardiovascular outcomes consequent to the presence of uremic toxins have only recently become available. Conclusion: Uremic toxins play an important role in the progression of cardiovascular disease in patients with CKD. Further studies are needed to better characterize the impact of these compounds on cardiovascular outcomes. Beneficial treatments are currently available that, in preliminary studies, appear to neutralize some of the adverse effects of uremic toxins. Large randomized clinical trials are needed to further determine the utility of these varied therapeutic agents.
Effects of Auto-Servo Ventilation on Patients with Sleep-Disordered Breathing, Stable Systolic Heart Failure and Concomitant Diastolic Dysfunction: Subanalysis of a Randomized Controlled Trial
Authors: Birner Christoph , Series Frederic , Lewis Keir , Benjamin Amit , Wunderlich Silke , Escourrou Pierre , Zeman Florian , Luigart Ruth , Pfeifer Michael , Arzt Michael
Published: September 2013

Background: Systolic heart failure (HF) is frequently accompanied by diastolic dysfunction and sleep-disordered breathing (SDB). Objectives: The objective of this subset analysis was to determine effect sizes of auto-servo ventilation (ASV and biphasic positive airway pressure ASV) on echocardiographic measures of diastolic function in patients with systolic HF and SDB. Methods: Thirty-two patients with stable systolic HF, concomitant diastolic dysfunction [age 66 ± 9 years old, left ventricular (LV) ejection fraction: 30 ± 7% and New York Heart Association class II: 72%] and SDB (apnea-hypopnea index, AHI: 48 ± 19/h; 53% had predominantly obstructive sleep apnea) receiving either ASV (n = 19) or optimal medical treatment (control, n = 13) were analyzed in a randomized controlled clinical trial. Polysomnographic and echocardiographic measurements were obtained at baseline and after 12 weeks. Results: AHI significantly improved in the ASV group compared to the control group (-39 ± 18 vs. -0.2 ± 13.2/h, p < 0.001). At baseline, 24 (75%) patients had impaired LV relaxation, and 8 (25%) had a pseudo-normalized filling pattern. At the 12-week control visit, diastolic function assessed by the isovolumetric relaxation time (-10.3 ± 26.1 vs. 9.3 ± 49.1, p = 0.48) and deceleration time (-43.9 ± 88.8 vs. 12.4 ± 68.8, p = 0.40) tended to improve after ASV treatment, but did not reach statistical significance. Likewise, the proportion of patients whose diastolic dysfunction improved was nonsignificantly higher in the ASV than in the control group, respectively (37 vs. 15%, p = 0.25). Conclusions: ASV treatment efficiently abolishes SDB in patients with stable systolic HF and concomitant diastolic dysfunction, and was associated with a statistically nonsignificant improvement in measures of diastolic dysfunction. Thus, these data provide estimates of effect size and justify the evaluation of the effects of ASV on diastolic function in larger randomized controlled trials.
GLUT1 Regulation of the Pro-Sclerotic Mediators of Diabetic Nephropathy
Authors: Heilig Charles W. , Deb Dilip K. , Abdul Afu , Riaz Hasan , James Leighton R. , Salameh Jamal , Nahman Jr. N. Stanley
Published: September 2013

Diabetic glomerulosclerosis is characterized by accumulation of extracellular matrix proteins, mesangial expansion, and tubulointerstitial fibrosis. Hyperglycemia accelerates development of the disease, a direct result of increased intracellular glucose availability. The facilitative glucose transporter GLUT1 mediates mesangial cell glucose flux which leads to activation of signaling cascades favoring glomerulosclerosis, including pathways mediated by angiotensin II (Ang II), transforming growth factor β (TGF-β), connective tissue growth factor (CTGF), and vascular endothelial growth factor (VEGF). Ang II has both hemodynamic and metabolic effects directly inducing GLUT1 and/or matrix protein synthesis through diacyl glycerol (DAG) or protein kinase C (PKC) induction, mesangial cell stretch, and/or through transactivation of the epidermal growth factor receptor, the platelet-derived growth factor receptor, and the insulin-like growth factor-1 receptor, all of which may stimulate GLUT1 synthesis via an ERK-mediated pathway. Conversely, inhibition of Ang II effects suppresses GLUT1 and cellular glucose uptake. GLUT1-mediated glucose flux leads to metabolism of glucose via glycolysis, with induction of DAG, PKC, TGF-β1, CTGF and VEGF. VEGF in turn triggers both GLUT1 and matrix synthesis. New roles for GLUT1-mTOR and GLUT1-mechano-growth factor interactions in diabetic glomerulosclerosis have also recently been suggested. Recent mouse models confirmed roles for GLUT1 in vivo in stimulating glomerular growth factor expression, growth factor receptors and development of glomerulosclerosis. GLUT1 may therefore act in concert with cytokines and growth factors to induce diabetic glomerulosclerosis. Further clarification of the pathways involved may prove useful for the therapy of diabetic nephropathy. New directions for investigation are discussed.
The Neurology of Aretaeus: Radix Pedis Neurologia
Authors: Pearce J.M.S.
Published: September 2013

Aretaeus (Aretaios) was a physician born in Cappadocia in about the 2nd century AD, a student of medicine and physician in Alexandria. His works are found in eight books which espoused the physiological and pathological views of the Hippocratic principles derived from the pneumatists and the eclectic schools. Though he has been called the forgotten physician, it has been said that: ‘after Hippocrates no single Greek author has equalled Aretaios'. In order to give an indication of his neurological legacy, this paper offers a summary of and quotations from his principal neurological contributions: migraine, vertigo, tetanus, epilepsy, melancholia, strokes and paralysis. One of his most important discoveries was the notion that the pyramidal tract decussates.
The Gap between Trial Data and Clinical Practice - An Analysis of Case Reports on Bleeding Complications Occurring under Dabigatran and Rivaroxaban Anticoagulation
Authors: Pfeilschifter Waltraud , Luger Sebastian , Brunkhorst Robert , Lindhoff-Last Edelgard , Foerch Christian
Published: September 2013

Background: The novel direct oral anticoagulants (NOA), dabigatran (a thrombin inhibitor), rivaroxaban and apixaban (factor Xa inhibitors) have shown at least noninferiority compared to warfarin concerning the prevention of stroke and systemic embolism as well as the risk of hemorrhagic complications in large phase III trials in patients with atrial fibrillation (AF). These results have been obtained under regular monitoring of side effects and reinforcement of medication adherence in carefully controlled clinical trials. To what extent they translate into clinical practice is a matter of ongoing research. While postmarketing registers, most prominently the GLORIA-AF registry, are currently recruiting and will not report data for several years, we aimed at extracting risk factors for hemorrhagic complications under NOA from all available case reports and single case series published to date. Methods: To identify risk factors which increase the risk of hemorrhage under NOA, we performed a PubMed search for both dabigatran and rivaroxaban, as well as three search terms for hemorrhagic complications. The cases of hemorrhagic complications were analyzed for the presence of the following four factors: ‘prescriber errors', ‘unfavorable comedications', ‘renal impairment' and ‘prescription of NOA in the frail elderly'. Results and Discussion: We found a discrepancy in the frequency of case reports on hemorrhagic complications to the disadvantage of dabigatran which can hardly be attributed to the earlier marketing time of dabigatran alone. As risk factors, we identified prescriber errors, impaired renal function, comedication with antiplatelet drugs or p-glycoprotein inhibitors, old age and low body weight. Strikingly, the majority of the bleeding complications reported in this compilation of case reports showed at least one and in most cases several risk factors. Conclusions: We should, therefore, carefully select our patients for treatment with the NOA with an emphasis on age, body weight, renal function and comedications and follow them faithfully concerning their medication adherence and eventual side effects.
A Review of Cord Blood Concentrations of Iron Status Parameters to Define Reference Ranges for Preterm Infants
Authors: Lorenz Laila , Peter Andreas , Poets Christian F. , Franz Axel R.
Published: September 2013

Background: Iron plays an essential role in various tissue functions, and hence the reliable assessment of iron nutrition status of preterm infants appears to be mandatory. Objectives: To summarize available data on cord blood concentrations of iron status parameters as surrogate reference ranges for preterm infants until term-equivalent age. Methods: Review of the literature searching PubMed for cord blood values of hemoglobin, mean corpuscular volume, ferritin, soluble transferrin receptor, ferritin index, transferrin saturation, reticulocyte hemoglobin content, zinc protoporphyrin/heme ratio, and hepcidin and comparison with reference ranges established for adults. Results: Gestational age-specific cord blood concentration ranges at term were computed as weighted mean for hemoglobin [15.9 g/dl (13.3-18.4)], mean corpuscular volume [108.1 fl (97.8-118.5)] and transferrin saturation [61.2% (31.5-90.9)] and listed for ferritin, soluble transferrin receptor, ferritin index, zinc protoporphyrin/heme ratio, reticulocyte hemoglobin content and hepcidin. These surrogate reference ranges were markedly different from adult values. Conclusion: Reference ranges of iron status parameters established for adults are probably not suitable to define iron status in preterm infants. If iron supplementation in preterm infants should be individually adjusted based on iron status parameters, it may be necessary to aim for cord blood concentration ranges to enable optimal growth and development.
Births in Captive Stump-Tailed Macaques (Macaca arctoides)
Authors: Solanki G.S. , Zothansiama
Published: September 2013

In this report, nighttime births of 3 stump-tailed macaques observed at the Aizawl Zoological Park, India, are described. Continuous focal observations were collected along with video and still photographs, on the 3 parturitions, from the first observed onset of labour. The average time taken for infant birth, beginning with visibility of the head at the vaginal opening, was 45 s. The births observed were similar in many respects, regardless of parity and social context. The average time taken for consuming the placenta was 4 min 4 s and the average number of contractions was 6.3. In all cases births occurred with the infant emerging in the occiput posterior position, assisted by the mother. Individual variations existed in the number of contractions, intercontraction intervals, self-examination of the anogenital region, duration of labour and the interval between infant birth and the delivery of the placenta. Each mother ingested the placenta completely, while holding her neonate, but without paying much attention to the neonate during placentophagia. Placentophagia appears to provide nutrition to the mothers. Detailed data on parturition in non-human primates, and particularly for Macaca arctoides, are still scarce. Data, such as those presented here, contribute to our understanding of primate birth and the adaptive pressures that shape parturition behaviour and reproductive success.
Systematic Review of the Epidemiology of Urinary Incontinence and Detrusor Overactivity among Patients with Neurogenic Overactive Bladder
Authors: Ruffion Alain , Castro-Diaz David , Patel Hetal , Khalaf Kristin , Onyenwenyi Ahunna , Globe Denise , LeReun Corinne , Teneishvili Mamuka , Edwards Meredith
Published: September 2013

Background: The prevalence and incidence of neurogenic overactive bladder (nOAB) are poorly defined. This systematic literature review identified nOAB epidemiological data and estimated the incidence and prevalence of urinary incontinence (UI) and detrusor overactivity (DO) in patients with multiple sclerosis (MS), spinal cord injury (SCI), Parkinson's disease (PD), stroke and spina bifida. An initial search of MEDLINE, Embase, PubMed, and the Cochrane library was supplemented by an internet search for grey literature and manual searching of the bibliographies of retrieved articles. Additional study selection identified comparable studies for statistical analysis. A descriptive statistical analysis, single-arm meta-analysis and stratified analysis were conducted using predefined criteria. Summary: Initial selection identified 189 articles containing prevalence data. Secondary selection for statistical analysis identified 39 and 52 articles with prevalence of UI and DO, respectively. Random-effect meta-analysis found the prevalence of UI was 50.9% in patients with MS, 52.3% with SCI, 33.1% with PD and 23.6% with stroke. Spina bifida was excluded due to insufficient data. The prevalence of DO may be biased and artificially elevated because it can only be measured with urodynamic investigations. Key Messages: A substantial proportion of patients with neurological conditions develop UI that may be attributable to nOAB.
Laboratory Coagulation Parameters in Extremely Premature Infants Born Earlier than 27 Gestational Weeks upon Admission to a Neonatal Intensive Care Unit
Authors: Neary Elaine , Okafor Ike , Al-Awaysheh Faten , Kirkham Colin , Sheehan Katie , Mooney Ciaran , Foran Adrienne , Corcoran J.D. , Ni Ainle Fionnuala , Cotter Melanie , McCallion Naomi
Published: September 2013

Background: Few published data exist to guide interpretation of coagulation times in extremely premature infants. Objective: To determine coagulation reference ranges on day 1 of life in extremely premature infants. Methods: A retrospective review of day 1 coagulation tests was performed in 144 infants <27 weeks' gestation between 2004 and 2010 in a tertiary neonatal unit. Samples were drawn through a non-heparinized umbilical or peripheral venous catheter as part of routine clinical care. Results: Mean (SD) and median (range) prothrombin times (PT) of 21.5 (5.3) and 20.2 (13.3-39) s, respectively, activated partial thromboplastin times (APTT) of 75.2 (27.8) and 67.4 (34.9-191.6) s, respectively, and plasma fibrinogen levels of 1.9 (1.1) and 1.4 (0.5-4.8) g/l, respectively, were reported. Using reference intervals derived from the 2.5th to 97.5th centiles, ranges of 14.4-36.7 s, 40.5-158.5 s and 0.7-4.8 g/l were determined for PT, APTT and plasma fibrinogen levels, respectively. In a subcohort with grade 0-2 intraventricular haemorrhage (n = 92), mean PT and APTT were 20.9 and 71.3 s, respectively, versus mean PT and APTT of 23.1 and 88.4 s (p = 0.06 and p = 0.03), respectively for those with grade 3-4 intraventricular haemorrhage. Mean PT and APTT in a cohort of infants defined to be small for gestational age were 22 and 76.8 s. These results did not differ significantly from non-small for gestational age infants, with a mean PT and APTT of 19.5 and 73.4 s (p = 0.09 and p = 0.7). Conclusions: Reference ranges based on retrospective data were determined for PT, APTT and fibrinogen in a large cohort of extremely preterm infants.
Review of Emotion Recognition in Stroke Patients
Authors: Yuvaraj Rajamanickam , Murugappan Murugappan , Norlinah Mohamed Ibrahim , Sundaraj Kenneth , Khairiyah Mohamad
Published: September 2013

Objective: Patients suffering from stroke have a diminished ability to recognize emotions. This paper presents a review of neuropsychological studies that investigated the basic emotion processing deficits involved in individuals with interhemispheric brain (right, left) damage and normal controls, including processing mode (perception) and communication channels (facial, prosodic-intonational, lexical-verbal). Methods: An electronic search was conducted using specific keywords for studies investigating emotion recognition in brain damage patients. The PubMed database was searched until March 2012 as well as citations and reference lists. 92 potential articles were identified. Results: The findings showed that deficits in emotion perception were more frequently observed in individuals with right brain damage than those with left brain damage when processing facial, prosodic and lexical emotional stimuli. Conclusion: These findings suggest that the right hemisphere has a unique contribution in emotional processing and provide support for the right hemisphere emotion hypothesis. Significance: This robust deficit in emotion recognition has clinical significance. The extent of emotion recognition deficit in brain damage patients appears to be correlated with a variety of interpersonal difficulties such as complaints of frustration in social relations, feelings of social discomfort, desire to connect with others, feelings of social disconnection and use of controlling behaviors.
Neonatal Non-Invasive Respiratory Support: Synchronised NIPPV, Non-Synchronised NIPPV or Bi-Level CPAP: What Is the Evidence in 2013?
Authors: Roberts C.T. , Davis P.G. , Owen L.S.
Published: September 2013

Nasal continuous positive airway pressure (NCPAP) has proven to be an effective mode of non-invasive respiratory support in preterm infants; however, many infants still require endotracheal ventilation, placing them at an increased risk of morbidities such as bronchopulmonary dysplasia. Several other modes of non-invasive respiratory support beyond NCPAP, including synchronised and non-synchronised nasal intermittent positive pressure ventilation (SNIPPV and nsNIPPV) and bi-level positive airway pressure (BiPAP) are now also available. These techniques require different approaches, and the exact mechanisms by which they act remain unclear. SNIPPV has been shown to reduce the rate of reintubation in comparison to NCPAP when used as post-extubation support, but the evidence for nsNIPPV and BiPAP in this context is less convincing. There is some evidence that NIPPV (whether synchronised or non-synchronised) used as primary respiratory support is beneficial, but the variation in study methodology makes this hard to translate confidently into clinical practice. There is currently no evidence to suggest a reduction in mortality or important morbidities such as bronchopulmonary dysplasia, with NIPPV or BiPAP in comparison to NCPAP, and there is a lack of appropriately designed studies in this area. This review discusses the different approaches and proposed mechanisms of action of SNIPPV, nsNIPPV and BiPAP, the challenges of applying the available evidence for these distinct modalities of non-invasive respiratory support to clinical practice, and possible areas of future research.
Surgical Management of Parapharyngeal Ganglioneuroma: Case Report and Review of the Literature
Authors: Albuquerque Bruno Sousa , Farias Terence Pires , Dias Fernando Luiz , Torman Danice
Published: September 2013

Parapharyngeal ganglioneuroma is a rare benign tumor, with fewer than 40 cases having been reported in the literature. We report a case of parapharyngeal ganglioneuroma in a child, including the presentation, diagnostic testing, treatment, outcome and a review of the literature. The patient presented with a large cervical mass arising from the cervical sympathetic chain. Complete excision of the ganglioneuroma was possible via a transcervical dissection approach without mandibulotomy. Clinical follow-up was conducted, and no recurrence has been observed to date.