Repeated mutKRAS ctDNA measurements represent a novel and promising tool for early response prediction and therapy monitoring in advanced pancreatic cancer.

Background: The presence of mutated KRAS (mutKRAS ctDNA) in plasma samples has been consistently shown to be a negative prognostic indicator in pancreatic cancer (PC). Only small pilot studies have evaluated the value of serial mutKRAS ctDNA-measurements in PC. Patients and methods: The aim of the present study was to explore the potential of repeated mutKRAS ctDNA measurements for response prediction and therapy monitoring in advanced PC patients. We used the BEAMing technology to determine levels of mutKRAS ctDNA, CA 19-9, CEA and CYFRA 21-1 in 284 plasma samples of 54 patients with advanced PC receiving gemcitabine-based chemotherapy. Absolute levels and kinetics of mutKRAS ctDNA, CA 19-9, CEA and CYFRA 21-1 were correlated to radiological response, progression-free and overall survival. Results: mutKRAS ctDNA was present in a majority of advanced PC patients (n = 36/54, 67%) and indicated tissue KRAS mutation status with a high sensitivity (75%) and specificity (100%). The presence of mutKRAS ctDNA, as well as higher levels of CA 19-9, CEA and CYFRA 21-1 before initiation of the first-line chemotherapy, was significantly correlated to an adverse overall survival. During therapy, changes in mutKRAS ctDNA levels were more rapid and pronounced than changes in protein-based tumor markers. A decrease in mutKRAS ctDNA levels during therapy was an early indicator of response to therapy, while there was no significant correlation between kinetics of CA 19-9, CEA or CYFRA 21-1 and response to chemotherapy during the first four weeks of treatment. Repeated mutKRAS ctDNA measurements during follow-up appeared to be superior to protein-based tumor markers in detecting progressive disease (sensitivity: 83%, specificity: 100%). Conclusion: mutKRAS ctDNA kinetics appear to be a powerful and highly specific tool in early response prediction and therapy monitoring of advanced PC patients receiving chemotherapy.

[Neurofeedback in the Treatment of Anorexia Nervosa: a Case Report]. / Der Einsatz von Neurofeedback bei Anorexia nervosa: ein Fallbeispiel.

Anorexia nervosa has been related to alterations in brain activity in terms of hyperactive EEG patterns. This case report illustrates the principles and results of a five-week neurofeedback treatment in a 29-year-old woman suffering from anorexia nervosa. A neurofeedback protocol to enhance alpha activity (8 - 12 Hz) was developed and conducted additionally to the standardized treatment for eating disorders in training sessions twice a week. Pre- and post-test measurements included resting state EEG measurements and a psychological test battery. The results show improvements from pre- to post-test in eating disorder psychopathology including psychological wellbeing, emotional competence, and eating behavior traits. In addition, a decrease in theta power (4 - 7 Hz), a well-known trait marker of anorexia nervosa, was measured. However, our data should be interpreted with caution because this is a single case study. Nevertheless, this report documents the practicability and method of neurofeedback as treatment adjunct in eating disorders from the clinical perspective. Although the use of neurofeedback in the treatment of anorexia nervosa is recommended in literature, empirical studies are still lacking. Randomized controlled trials to evaluate short- and long-term effects of neurofeedback are needed.

Abdominal obesity is associated with impaired cognitive function in euthymic bipolar individuals.

OBJECTIVES: Overweight/obesity has been implicated to play a role in cognitive deficits in bipolar disorder (BD). This study aims to identify the relationship between body fat distribution and different domains of cognition in BD during euthymia. METHODS: A sample of 100 euthymic individuals with BD was measured with a cognitive test battery (i.e., Trail Making Test-A-B/TM-A/B, d2 Test of Attention, Stroop test, California Verbal Learning Test/CVLT) and an anthropometric measures set (body mass index, waist circumference, hip circumference, waist-to-hip-ratio, waist-to-height-ratio, and lipometry). Patient data were compared with a healthy control group (n = 64). RESULTS: Results show that overweight patients with BD exhibit lower performance in the TMT-A/B as well as in the free recall performance of the CVLT compared to normal-weight patients with BD and controls. In bipolar individuals, (abdominal) obesity was significantly associated with a poor cognitive performance. In bipolar females, associations with measures of verbal learning and memory were found; in bipolar males, associations with poor performance in the TMT-A/B and in the Stroop interference task were demonstrated. In controls, no associations were found. CONCLUSIONS: There are several possible pathways moderating the association between obesity and cognition in BD. Anthropometric and lipometry data underline the substantial mediating impact of body fat distribution on cognition in BD.

Peripheral markers of oxidative stress and antioxidative defense in euthymia of bipolar disorder--Gender and obesity effects.

INTRODUCTION: Oxidative and nitrosative stress are implicated in the pathogenesis of uni- and bipolar disorder. Herein we primarily sought to characterize markers of oxidative/nitrosative stress during euthymia in adults with bipolar disorder (BD). Oxidative markers were further evaluated in this BD sample in synopsis with excess overweight or obesity and/or comorbid metabolic syndrome (MetS). METHODS: Peripheral markers of oxidative stress [i.e. thiobarbituric acid reactive substance, (TBARS), malondialdehyde (MDA), and carbonyl proteins] and antioxidant markers [e.g. total antioxidative capacity (TAC), superoxide dismutase (SOD), glutathione S-transferase (GST)] were obtained in a cohort of euthymic adults with BD (N=113) and compared to healthy controls (CG) (N=78). Additionally, anthropometric measures included the body mass index (BMI) [kg/m(2)], waist and hip circumference [cm], waist-to-hip-ratio (WHR), waist to height ratio (WtHR) as well as the IDF-defined MetS. RESULTS: The major finding was a significantly decreased TAC in BD compared to the CG (p<0.01; BD: M 1.18, SD 0.47; CG: M 1.39, SD 0.49). MDA was significantly and TBARS by trend higher in the CG compared to the euthymic bipolar test persons (MDA: p<0.01, BD: M 0.70, SD 0.18; CG: M 0.81, SD 0.25; TBARS: p<0.1, BD: M 0.78, SD 0.28; CG: M 0.76, SD 0.30). The antioxidative enzyme GST was significantly elevated in both patients and controls (BD: M 298.24, SD 133.02; CG: M 307.27 SD 118.18). Subgroup analysis revealed that the CG with concurrent MetS and obesity had significantly elevated TAC when compared to CG without concurrent MetS (p<0.05, no MetS: M 1.33, SD 0.50; MetS: M 1.67, SD 0.32), as well as persons with BD with or without current MetS (no MetS: M 1.18, SD 0.44; MetS: M 1.15, SD 0.49). Significant correlations between GST and anthropometric variables were found in male study participants. Multivariate analysis indicated a significant gender effect concerning TBARS values in all patients and CG (p<0.01, females: M 0.73, SD 0.29; males: M 0.83, SD 0.28). CONCLUSION: Euthymic bipolar adults exhibit peripheral evidence of a disturbed biosignature of oxidative stress and antioxidative defense. Male test persons showed significantly higher peripheral markers of oxidative stress than women- female sex may exert protective effects. Furthermore, the biosignature of oxidative stress obtained herein was more pronounced in males with concurrent metabolic disorders. Our results further extend knowledge by introducing the moderating influence of gender and obesity on oxidative stress and BD.

Primary epiploic appendagitis and fructose malabsorption.

Primary epiploic appendagitis (PEA) is a rare cause of abdominal acute or subacute complaints. Diagnosis of PEA is made when computed tomography (CT) reveals a characteristic lesion. We report on contrast-enhanced CT images of a patient with PEA and regression of inflammation and the reduction in size of the inflamed appendage over the time period of 4 months. Patients with PEA usually recover without medication or surgical treatment within a few weeks. However, due to continuing bloating and irregular bowel movements we investigated carbohydrate malabsorption and diagnosed a fructose malabsorption. Bloating and irregular bowel movements in this patient with PEA were correlated to carbohydrate malabsorption and were treated successfully with a diet free of culprit carbohydrates.

Smoking denial in cardiovascular disease studies.

Assessment of self-reported smoking behavior in cardiovascular studies may lead to inaccurate measures of nicotine exposure. A more objective measurement of nicotine exposure can be done by measurement of plasma cotinine levels. The aim of the present study was to define the rate of discordance between the self-reported smoking behavior and biochemically defined smoking status. Data from 3,316 patients hospitalized for coronary angiography, who completed a questionnaire on smoking behavior, were analyzed. As a biochemical assessment of smoking status we used a cut-off serum cotinine level of 15 µg/l. Smoking denial, defined as a discrepancy between high cotinine levels and self-reported never- or ex-smoking status, was observed in 3.7 % of the study participants. In a logistic regression analysis with a step-wise inclusion of sex, age, CAD, previous MI, and educational level, only male sex (odds ratio male/female: 2.00, 95 % CI 1.22-3.33; p = 0.007) and age (odds ratio per year: 0.79, 95 % confidence interval 0.66-0.94, p = 0.008) were associated with smoking denial. In conclusion, a misclassification rate of 3.7 % in the evaluation of such an important risk factor may lead to blurred effects and favor false negative results. The results of the present study substantiate the importance of biochemical markers for smoking assessment in cardiovascular studies.

In-vitro study of resin-modified glass ionomer cements for cementation of orthodontic bands. Isolation, surplus removal and humidity as factors influencing the bond strength between enamel, cement and metal.

The aim of this in vitro study was to investigate different light-cured and chemically cured resin-modified glass ionomer cements used for the cementation of orthodontic bands and to analyze various factors influencing the adhesive strength between enamel, cement and stainless steel. Four resin-modified glass ionomers (Fuji Ortho LC/GC, Fuji Duet/GC, Unitek Multi-Cure Glass Ionomer Orthodontic Band Cement/3M Unitek, Vitremer/3M) and 1 compomer (Band-Lok/Reliance) were examined. Flattened and polished bovine teeth embedded in polyurethane resin were used as enamel specimens. Before cementation, 50% of the specimens were moistened with the aerosol of an inhalation device, while the rest were dried with compressed air. Stainless steel cylinders (CrNi 18 10) were perpendicularly bonded onto the polished enamel using a custom-made cementation device and immediately topped with a pressure of 0.25 MPa. The cement was isolated with either Ketac Glaze/ESPE, Fuji Coat/GC, Cacao Butter/GC, Dryfoil/Jalenko or Final Varnish/VOCO, or was left uncoated. Eight minutes after the beginning of mixing, either the surplus cement was removed with a scalpel or surplus removal was simulated with ultrasound. After 24 hours storage in a water bath at 37 degrees C and 1,000 thermocycles the shear bond strength was determined. Significant differences with respect to the shear bond strength were found among the following cements, ranking from highest to lowest: Fuji Duet, Unitek cement > Fuji Ortho LC > Vitremer > Band-Lok. The application of a barrier coating significantly increased the shear bond strength of all cements except Fuji Ortho LC. The light-cured resin Ketac Glaze proved to be the most effective barrier coating. A dry enamel surface increased the bond strength of all investigated cements except Unitek cement. The use of ultrasound led to no significant reduction in shear bond strength in comparison with surplus removal with a scalpel.

Noise exposure-induced audiogenic seizure susceptibility in Sprague-Dawley rats.

Parameters were evaluated for the optimum induction of audiogenic seizure susceptibility in Sprague-Dawley (SD) rats by noise exposure. The effect of maturation on this susceptibility was also examined. It was found that SD rats are most inducible between neonatal days 13 and 15 and that susceptibility requires a minimum of 2 days to develop. Noise exposure on day 14 results in universal susceptibility by day 20, but seizure severity is not maximal until days 32-36. Although susceptibility persists at high levels into adulthood, seizures in older rats revert to the wild-running-only type. Seizure latency (from stimulus onset to onset of wild running) becomes increasingly shorter during the prepubescent period (days 16-24) but is stable at older ages. The mean shortness of latency in adult seizures depends somewhat on the age when initial noise exposure occurred; day-14 noise exposures result in seizures with shortest latencies. Ontogenetic comparisons were made of susceptibility in these noise exposure-induced rats, genetically epilepsy prone rats (GEPRs, which are SD substrains)29 and noise exposure-induced Wistar (WI) rats28. It appears that epileptogenesis begins at virtually the same age in all four groups of rats but that considerable differences characterize the absolute severity of seizures and the age dependence of maximum seizure severity among the strains.

[Peptic ulcer and the liver]. / Peptisches Geschwür und Leber

The interorganic relations between liver and stomach are explained from the point of view of the primary diseases of each organ and the higher mechanism is also discussed. The at present well-known and partly hypothetic pathophysiological mechanisms are treated within the subject. On own combined histologo-biochemical examinations of the liver punctate is generally explained the too little regarded role of the peptic ulcer for the induction of so-called latent hepatopathies. In this respect in operations of the stomach the vagotomy as the method of choice serves the preference compared with resections of the stomach.