Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.     

Case of a palatal tic resembling palatal tremor in a patient with Tourette syndrome.

We describe a case of a palatal tic resembling palatal tremor (PT) in a young female patient with a previously unrecognized mild Tourette syndrome. At the time of her visit, the patient complained about ear clicks that were audible to others. We discuss the differential diagnoses of hyperkinetic palatal movements emphasizing the ongoing discussion about essential PT representing a more heterogeneous disorder than previously thought.     

Pharmacokinetics of the anxiolytic beta-carboline derivative abecarnil in the mouse, rat, rabbit, dog, cynomolgus monkey and baboon. Studies on species differences

The pharmacokinetics of abecarnil (isopropyl 6-(benzyloxy)-4-(methoxymethyl)-9H-pyrido [3,4-b] indole-3-carboxylate, ZK 112 119) were studied in the mouse, rat, rabbit, dog, cynomolgus monkey and baboon using 14C-labeled drug and HPLC with fluorescence detection for measurement of unchanged drug. Abecarnil was rapidly and completely absorbed after oral doses of 10 mg/kg. At higher doses, absorption was prolonged and incomplete in the cynomolgus monkey. The bioavailability of abecarnil was 20-30% in all the species investigated. The terminal half-life of the unchanged drug in plasma was relatively similar in all species (0.6-1.7 h). Abecarnil was able to pass the blood-brain barrier achieving concentrations in the brain similar to those in plasma. Tissue distribution of labeled compounds was rapid with highest concentrations in the liver, adrenals, kidneys and pancreas followed by the bone marrow, lungs, heart, fat, spleen, ovaries and thyroid gland. Excretion of radiolabeled compounds proceeded predominantly in the feces of the rat, the rabbit and the cynomolgus monkey.     

Ein Fragebogen zur infertilitätsbedingten Belastung andrologischer Patienten

The infertility distress scale (IBS) has been designed to assess the stress perceived by andrological patients resulting from infertility. This review presents findings from different studies with a total of 769 patients. The scale consists of eight items. The stability of scores is very high even for a mean follow-up of 2 years. The scale correlates highly with an already validated measure of infertility distress. Correlations with measures of depressiveness are in the low to medium range. All in all, the psychometric results indicate that the IBS is a factor-stable, reliable and valid instrument for assessing chronic infertility distress in andrological patients. After the presentation of normative data, the usefulness of the IBS as a screening instrument for identifying highly distressed patients is discussed. Findings supporting the scale's sensitivity to change are also presented. The scale is a useful tool in clinical practice as well as in research.     

Beobachtungen über Stoffaustausch im Capillargebiet mit Hilfe der intravitalen Fluorescenzmikroskopie

Research in Experimental Medicine - An Kaulquappen von Rana und Bufo und Mesenterien erwachsener Frösche wird nach Injektion fluorescierender Farbstoffe (Natriumfluorescein und Aesculin) unter...     

THE EFFECT OF HYPERTENSIVE EPISODES AND CARDIAC HYPERTROPHY ON THE CANINE CARDIAC BAROREFLEX

1. Left ventricular (LV) hypertrophy has been implicated in the reduction of baroreflex sensitivity present in hypertension. The aim of the current study was to investigate the mean arterial pressure-heart rate reflex (MAP-HR) in a model which induced left ventricular hypertrophy but no sustained blood pressure elevation. 2. Five mongrel dogs were exposed to transient blood pressure elevation of between 20 and 30 mmHg, through hindlimb compression using a pneumatic pressure suit, for 7 h per day, 6 days per week for 6 weeks. Resting blood pressure was not altered by the 6 week hindlimb compression intervention. 3. Echocardiographically determined LV mass (mean ± s.e.m.) was 116.0 ± 7.4 g prior to hindlimb compression (baseline) and elevated to 125.4 ± 8.1 g (P= 0.003) after 6 weeks of compression. A reduction in the early (E) to late (A) transmitral diastolic flow ratio (E/A) from 1.80 ± 0.06 at baseline to 1.54 ± 0.09 (P = 0.037) after the 6 week intervention suggested that cardiac compliance was reduced. 4. The maximum gain of the MAP-HR reflex, studied using the ‘steady-state’ drug technique, when blood pressure was normal, showed a trend for reduction from 3.85 ± 0.43 beats/min per mmHg at baseline to 3.10 ± 0.45 beats/min per mmHg (P= 0.067) after 6 weeks of compression. This gain reduction became significant after β-adrenoceptor blockade with propranolol (3.13 ± 0.55 vs 2.32 ± 0.25 beats/min per mmHg; P= 0.039). Covariant analysis showed a significant inverse correlation between LV mass and maximum gain (r= 0.96; P<0.001) during the 6 week compression period. 5. The MAP-HR reflex changes in this model mimic those present in hypertension and implicate cardiac hypertrophy as one possible mediator.     

Risk of acquiring influenza A in a nursing home from a culture-positive roommate.

Influenza A was cultured in 62 double rooms. The roommate was infected in 12 (19.4%). During 3,294 resident-seasons, influenza was cultured in 208 single rooms (6.3%). Those who lived in double rooms with a culture-positive roommate had a 3.07 relative risk (CI95, 1.61-5.78) of acquiring influenza.