Interdisciplinary consensus on indications for transfemoral transcatheter aortic valve implantation (TF-TAVI) : Joint Consensus Document of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte e.V. (ALKK) and cooperating Cardiac Surgery Departments.

Indications for TF-TAVI (transfemoral transcatheter aortic valve implantation) are rapidly changing according to increasing evidence from randomized controlled trials. Present trials document the non-inferiority or even superiority of TF-TAVI in intermediate-risk patients (STS-Score 4-8%) as well as in low-risk patients (STS-Score < 4%). However, risk scores exhibit limitations and, as a single criterion, are unable to establish an appropriate indication of TF-TAVI vs transapical TAVI vs SAVR (surgical aortic valve replacement). The ESC (European Society of Cardiology)/EACTS (European Association for Cardio-Thoracic Surgery) guidelines 2017 and the German DGK (Deutsche Gesellschaft für Kardiologie)/DGTHG (Deutsche Gesellschaft für Thorax-, Herz- und Gefäßchirurgie) commentary 2018 offer a framework for the selection of the best therapeutic method, but the individual decision is left to the discretion of the heart teams. An interdisciplinary TAVI consensus group of interventional cardiologists of the ALKK (Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte e.V.) and cardiac surgeons has developed a detailed consensus on the indications for TF-TAVI to provide an up-to-date, evidence-based, comprehensive decision matrix for daily practice. The matrix of indication criteria includes age, risk scores, contraindications against SAVR (e.g., porcelain aorta), cardiovascular criteria pro TAVI, additional criteria pro TAVI (e.g., frailty, comorbidities, organ dysfunction), contraindications against TAVI (e.g., endocarditis) and cardiovascular criteria pro SAVR (e.g., bicuspid valve anatomy). This interdisciplinary consensus may provide orientation to heart teams for individual TAVI-indication decisions. Future adaptations according to evolving medical evidence are to be expected. Interdisciplinary consensus on indications for transfemoral transcatheter aortic valve implantation (TF-TAVI).

[Vermilion reconstruction after dog bite injuries]. / Rekonstruktion des Lippenrotes nach Hundebissverletzungen.

Dog bite injuries often concern the lips. In children, injuries of the face are most common, but also in adults so-called kissing injuries frequently happen. All-layer defects are treated by wedge excision in minor cases and by myocutaneous flaps in major cases of lower lip injuries, whereas upper lip defects are reconstructed by exchange flaps. If only the vermilion is concerned, mucosal flaps according to the von Esmarch technique yield very good aesthetic results with excellent function and without impairment of the mouth opening.

Temporal evolution of mouse striatal gene expression following MPTP injury.

The gradual loss of striatal dopamine and dopaminergic neurons residing in the substantia nigra (SN) causes parkinsonism characterized by slow, halting movements, rigidity, and resting tremor when neuronal loss exceeds a threshold of approximately 80%. It is estimated that there is extensive compensation for several years prior to symptom onset, during which vulnerable neurons asynchronously die. Recent evidence would argue that much of the compensatory response of the nigrostriatal system is multimodal including both pre-synaptic and striatal mechanisms. Although parkinsonism may have multiple causes, the classic syndrome, Parkinson's disease (PD), is frequently modeled in small animals by repeated administration of the selective neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Because the MPTP model of PD recapitulates many of the known behavioral and pathological features of human PD, we asked whether the striatal cells of mice treated with MPTP in a semi-chronic paradigm enact a transcriptional program that would help elucidate the response to dopamine denervation. Our findings reveal a time-dependent dysregulation in the striatum of a set of genes whose products may impact both the viability and ability to communicate of dopamine neurons in the SN.

[Improvement of chronic pain syndrome by free tissue transfer. Report of two cases]. / Linderung chronischer Schmerzzustände durch freien Gewebstransfer. Zwei Fallberichte.

We report on two patients with chronic pain syndrome of a lower limb due to chronic constriction after radiation therapy in one case and to popliteal entrapment in the other. The patients had been in pain therapy for years and had achieved insufficient analgesia in one case and satisfactory analgesia in another case with high doses of morphine sulphate and other medication. Surgery was indicated for limb salvage in one patient, and for pain relief in the other patient. It consisted of decompression and defect reconstruction by free latissimus dorsi flaps. In both cases, after an uncomplicated follow-up, quick and complete weaning from the analgesics was possible. One of the patients is completely free of pain.

[Influence of heart rate on image quality and detection of coronary stenoses with multislice spiral CT]. / Einfluss der Herzfrequenz auf die Bildqualität und den Nachweis von Koronarstenosen mittels 4-Zeilen-Spiral CT.

Multi-slice spiral CT (MSCT) permits the detection of coronary stenoses. We investigated the influence of the patient's heart rate (HR) during the scan on stenosis detection and the presence of motion artifacts. In 100 patients MSCT was performed and retrospectively ECG-gated cross-sectional images were reconstructed. 115 of 400 coronary arteries (29%) were unevaluable due to motion artifacts (84/115) or other reasons (31/115). In evaluable arteries, sensitivity was 91% (51/56 high grade stenoses detected), specificity was 89%. With increasing HR, the number of unevaluable arteries increased and overall sensitivity for stenosis detection decreased from 62% (HR < or = 70 bpm) to 33% (HR > 70 bpm). MSCT permits detection of coronary stenoses, but evaluability and accuracy decrease with increasing HR.

Noninvasive coronary angiography by magnetic resonance imaging, electron-beam computed tomography, and multislice computed tomography.

In recent years, several techniques for noninvasive imaging of the coronary artery lumen (noninvasive coronary angiography) have been developed. These techniques include magnetic resonance imaging, electron-beam computed tomography, and, most recently, multislice computed tomography. Each of these techniques has specific advantages and disadvantages. Currently, EBCT seems to permit the most robust coronary artery imaging. In the future, imaging modalities will have to be further improved and validated in order to define specific areas for potential clinical applications.

Rapid amplification of plasmid and phage DNA using Phi 29 DNA polymerase and multiply-primed rolling circle amplification.

We describe a simple method of using rolling circle amplification to amplify vector DNA such as M13 or plasmid DNA from single colonies or plaques. Using random primers and phi29 DNA polymerase, circular DNA templates can be amplified 10,000-fold in a few hours. This procedure removes the need for lengthy growth periods and traditional DNA isolation methods. Reaction products can be used directly for DNA sequencing after phosphatase treatment to inactivate unincorporated nucleotides. Amplified products can also be used for in vitro cloning, library construction, and other molecular biology applications.

Detection of coronary artery stenoses by contrast-enhanced, retrospectively electrocardiographically-gated, multislice spiral computed tomography.

BACKGROUND: Multislice spiral computed tomography (MSCT) with retrospectively ECG-gated image reconstruction permits coronary artery visualization. We investigated the method's ability to identify high-grade coronary artery stenoses and occlusions. METHODS AND RESULTS: A total of 64 consecutive patients were studied by MSCT (4x1 mm cross-sections, 500-ms rotation, table feed 1.5 mm/rotation, intravenous contrast agent, retrospectively ECG-gated image reconstruction). All coronary arteries and side branches with a luminal diameter >/=2.0 mm were assessed concerning evaluability and the presence of high-grade stenoses (>70% diameter stenosis) or occlusions. Results were compared with quantitative coronary angiography. Of 256 coronary arteries (left main, left anterior descending, left circumflex and right coronary artery, including their respective side branches), 174 could be evaluated (68%). In 19 patients (30%), all arteries were evaluable. Artifacts caused by coronary motion were the most frequent reason for unevaluable arteries. Overall, 32 of 58 high-grade stenoses and occlusions were detected by MSCT (58%). In evaluable arteries, 32 of 35 lesions were detected, and the absence of stenosis was correctly identified in 117 of 139 arteries (sensitivity, 91%; specificity, 84%). If analysis was extended to all stenoses with >50% diameter reduction, sensitivity was 85% (40 of 47) and specificity was 76% (96 of 127). CONCLUSIONS: MSCT with retrospective ECG gating permits the detection of coronary artery stenoses with high accuracy if image quality is sufficient, but its clinical use may presently be limited due to degraded image quality in a substantial number of cases, mainly due to rapid coronary motion.

p53 mediates bcl-2 phosphorylation and apoptosis via activation of the Cdc42/JNK1 pathway.

A member of the small G protein family, cdc42, was isolated from a screen undertaken to identify p53-inducible genes during apoptosis in primary baby rat kidney (BRK) cells transformed with E1A and a temperature-sensitive mutant p53 using a PCR-based subtractive hybridization method. Cdc42 is a GTPase that belongs to the Rho/Rac subfamily of Ras-like GTPases. In response to external stimuli, Cdc42 is known to transduce signals to regulate the organization of the actin cytoskeleton, induce DNA synthesis in quiescent fibroblasts, and promote apoptosis in neuronal and immune cells. In this study, we have demonstrated that cdc42 mRNA and protein were up-regulated in the presence of wild-type p53 in BRK cells, followed by cytoplasmic to plasma membrane translocation of Cdc42. Overexpression of Cdc42 in the presence of a dominant-negative mutant p53 induced apoptosis rapidly, indicating that Cdc42 functions downstream of p53. Furthermore, stable expression of a dominant-negative mutant of Cdc42 partially inhibited p53-mediated apoptosis. The Bcl-2 family members Bcl-xL, and the adenovirus protein E1B 19K, inhibited Cdc42-mediated apoptosis, whereas Bcl-2 did not. We provide evidence that PAK1 and JNK1 may play a role downstream of Cdc42 to transduce its apoptotic signal. Cdc42/PAK1 activates JNK1-induced phosphorylation of Bcl-2, thereby inactivating its function, and that a phosphorylation resistant mutant (Bcl-2S70,87A,T56,74A) gains the ability to inhibit Cdc42- and p53-mediated apoptosis. Thus, one mechanism by which p53 promotes apoptosis is through activation of Cdc42 and inactivation of Bcl-2.

Noninvasive coronary angiography by retrospectively ECG-gated multislice spiral CT.

BACKGROUND: We investigated the applicability and image quality of contrast-enhanced coronary artery visualization by multislice spiral CT using retrospective ECG gating. METHODS AND RESULTS: Twenty-five patients in sinus rhythm (significant coronary artery stenoses ruled out by invasive angiography) were studied with a multislice spiral CT (Siemens SOMATOM Volume Zoom). In inspiration (mean breath-hold, 37 seconds), a volume data set of the heart was acquired (intravenous contrast agent; 4 x 1-mm slice thickness; 500-ms rotation; table feed, 1.5 mm/360 degrees ). Simultaneous recording of the ECG permitted retrospective reconstruction of contiguous cross sections in intervals of 1 mm at any desired interval of the cardiac cycle. The mean duration of the image reconstruction window was 185 ms. Next to 3-dimensional reconstructions of the heart and coronary arteries, multiplanar reconstructions were rendered to determine the visualized length of the coronary arteries, the contrast-to-noise ratio, and the correlation of coronary artery diameters to quantitative coronary angiography. CONCLUSIONS: The coronary arteries could be visualized over long segments (left main, 9+/-4 mm; left anterior descending, 112+/-34 mm; left circumflex, 80+/-29 mm; right coronary artery, 116+/-33 mm). On average, 78+/-16% of these distances were visualized free of motion artifacts. The mean contrast-to-noise ratio was 9.3+/-3.3. Coronary artery diameters in multislice spiral CT showed close correlation to quantitative coronary angiography (CT, 3.3+/-1.0 mm; angiography, 3. 2+/-0.9 mm; mean difference, 0.38 mm; r=0.86). Contrast-enhanced multislice spiral CT permits visualization of the coronary artery lumen. Further studies are necessary to determine whether image quality is sufficient to reliably detect coronary artery stenoses.

Correction of the Bloom syndrome cellular phenotypes.

Bloom syndrome (BLM) is a genetic disorder associated with predisposition to cancer and chromosome instability. However, the most readily recognized clinical feature of the syndrome is growth retardation. Introduction of the previously cloned BLM gene into BLM cells yielded correction of the chromosome instability and slow growth phenotypes. Additionally, asynchronous cultures of complemented clones revealed a lower percentage of cells in S-phase than uncomplemented BLM cells. These results support the notion that BLM is a defect in which short stature, chromosome instability and cancer predisposition are all associated with an error in DNA replication.