[Cave: interscalene catheters]. / Cave: Interskalenuskatheter.

Interscalene regional anesthesia is an established and highly effective procedure; however, it represents an increased level of risk due to the close proximity of anatomical structures, such as the cervical spinal cord and many vessels. Furthermore, due to inadvertent placement of a catheter close to the cervical spinal cord or into a vessel, as opposed to a single shot injection technique, it remains a latent danger until it is removed. This article describes seven  cases of misplaced catheters. The etiology and symptoms are discussed as well as recommendations regarding the prevention of catastrophic complications. As a result, internal practice guidelines are recommended for anesthesia departments in order to enhance the safety and quality of regional anesthesia.

[A 44 year old patient presenting with Ewing's sarcoma of the big toe]. / 44-jährige Patientin mit Ewing­Sarkom der Großzehengrundphalanx.

We present the case of a patient with osseous Ewing's sarcoma of the big toe occurring during the healing process after a fracture of the little toe, which significantly delayed diagnosis, despite striking findings on imaging. We subsequently performed further diagnostics, neoadjuvant chemotherapy, tumor resection in the form of a resection of the first ray, and adjuvant chemotherapy. This case shows that the occurrence of a secondary disease should always be considered in untypical courses of healing.

[Psychotherapy of suicidality]. / Psychotherapie der Suizidalität.

Psychotherapy is an important therapeutic option in the treatment of suicidality. Irrespective of the different treatment settings the psychotherapeutic attitudes, strategies and techniques are presented as they were developed on the basis of cognitive behavioral therapy and psychoanalysis. Starting from the common basic attitude of an active, approachable and for the patient recognizable therapist, the cognitive behavioral attitude is defined by the concept of a "team" involving patient and therapist, which fights against suicidality. The problems that led to suicidal ideation have to be exactly defined and specific behavioral strategies should aim at a modification of the behavioral repertoire and of cognitive strategies. A psychodynamic strategy starting from the analysis of the therapist's inner reaction, the countertransference comes from a primary involvement of both patient and therapist, which the therapist has to recognize and interpret to the patient in a "digestible" way. The experience of an approachable therapist who unexpectedly behaves differently than usual or feared, enables the patient to come to insights and new relational patterns which make suicidal destruction unnecessary. Finally, empirical evidence for the effectiveness of cognitive behavioral and psychodynamic treatment of suicidality is presented.

Physical distress and relationship problems: exploring the psychosocial and intrapsychic world of suicidal geriatric patients.

BACKGROUND: Suicide is a serious mental health problem in old age. Suicide ideation and life weariness are important psychopathological issues in geriatric medicine, although suicide ideation does not primarily depend on the severity of any physical disease. Despite these facts, insight into the internal psychological state of suicidal geriatric patients is still limited. MATERIAL AND METHODS: This study examines intrapsychic and psychosocial issues in suicidal geriatric inpatients. A semistructured interview concerning suicide ideation in old age was used to interview 20 randomly chosen, acutely suicidal clinically geriatric inpatients aged 60 years and older. The control group comprised 20 nonsuicidal patients. RESULTS: Hamilton Depression Scale 21 scores (HAMD 21; patient mean 17.3, control mean 6.1), suicidal ideation and psychiatric treatments differed significantly between the groups. In contrast to lifetime suicidal ideation, the discovery of a physical disease was the primary trigger for current suicidal ideation, followed by interactional conflicts. Patients would rather speak with family or friends than professionals about their suicidal ideation. CONCLUSION: Suicidal ideation should be recognised as an important psychological problem in geriatric patients with interpersonal conflicts. Specific help and training for relatives is recommended.

[Ideal types of interaction patterns of psychosomatic patients in geriatric inpatient treatment]. / Idealtypische Interaktionsmuster psychosomatischer Patienten in stationär-geriatrischer Behandlung.

BACKGROUND: Cooperation between psychosomatic and geriatric medicine is still sporadic and rarely institutionally integrated. At the same time, however, nearly half of geriatric inpatients suffer from psychopathological symptoms of clinical relevance. The patterns of interactions between patients and professionals of the geriatric team prior to a psychosomatic intervention that lead to a specific consultation are still rarely known. The aim of this paper was to identify these relational patterns, which can again occur during interaction with the psychosomatic patient. MATERIAL AND METHODS: Protocols from the consultation sessions of 76 geriatric in-patients, treated over a period of 1 year, were used as the basis data for the development of interactional patterns with the systematic, qualitative method of forming ideal types by understanding. RESULTS: Three groups with a total of 11 interactional patterns were formed: (1) "conflictuous interaction" with patients who re-enact their inner conflicts (e.g., autonomy or conflicts on power and subjugation), (2) "the problem can not be dealt with" with patients who forget or deny and repress their mental problems in other ways, and (3) "avoiding contact" with patients who have different forms of psychosocial withdrawal. CONCLUSION: Extension of the geriatric functional diagnostic approach on interactional-psychodynamic aspects is possible and fosters a differentiated view on the psychosomatic situation of geriatric patients.

[Dacryocystorhinostomy as part of the interdisciplinary treatment of lacrimal duct]. / Dakryozystorhinostomie nach West in der interdisziplinären Behandlung von Tränenwegsstenosen.

INTRODUCTION AND METHODS: Epiphora, which leads to blurry vision, is the leading symptom for intra- and/or postsaccal lacrimal duct stenosis. Due to the anatomy of the tear duct system, which lies between the fields of ophthalmology and otorhinolaryngology, and due to newly available techniques in interventional radiology to diagnose and treat patients with intra- and postsaccal lacrimal duct stenosis, various methods for diagnosis and treatment are available. We report the results of 107 patients who underwent endonasal dacryocystorhinostomy (DCR) between 2005 and 2011. RESULTS: Prior to the DCR, dacryocystography was performed in 95 of the 107 patients. In 68 of these 95 cases, balloon dilatation was unsuccessful. Histological examination of 64 patients showed chronic inflammation in 61 patients, non-Hodgkin's lymphoma was diagnosed in 2 patients and aspergilloma in1 patient. Over a follow-up time of 6 months to a maximum of 7 years we revised 15 of 107 patients, due to reocclusion after removal of the stent. None of these patients showed recurrence of epiphora. DISCUSSION: In comparison to transcutaneous DCR, endonasal DCR has certain benefits: it is less invasive, no visible scars occur because of the endonasal approach, and the function of the lacrimal pump remains uneffected. Furthermore, the possibility of co-treatment of endonasal pathologies during DCR exists. We observed no serious adverse events in our study group and the success rate was similar to other studies.

A KRAS variant is a biomarker of poor outcome, platinum chemotherapy resistance and a potential target for therapy in ovarian cancer.

Germline variants in the 3' untranslated region (3'UTR) of cancer genes disrupting microRNA (miRNA) regulation have recently been associated with cancer risk. A variant in the 3'UTR of the KRAS oncogene, referred to as the KRAS variant, is associated with both cancer risk and altered tumor biology. Here, we test the hypothesis that the KRAS variant can act as a biomarker of outcome in epithelial ovarian cancer (EOC), and investigate the cause of altered outcome in KRAS variant-positive EOC patients. As this variant seems to be associated with tumor biology, we additionally test the hypothesis that this variant can be directly targeted to impact cell survival. EOC patients with complete clinical data were genotyped for the KRAS variant and analyzed for outcome (n=536), response to neoadjuvant chemotherapy (n=125) and platinum resistance (n=306). Outcome was separately analyzed for women with known BRCA mutations (n=79). Gene expression was analyzed on a subset of tumors with available tissue. Cell lines were used to confirm altered sensitivity to chemotherapy associated with the KRAS variant. Finally, the KRAS variant was directly targeted through small-interfering RNA/miRNA oligonucleotides in cell lines and survival was measured. Postmenopausal EOC patients with the KRAS variant were significantly more likely to die of ovarian cancer by multivariate analysis (hazard ratio=1.67, 95% confidence interval: 1.09-2.57, P=0.019, n=279). Perhaps explaining this finding, EOC patients with the KRAS variant were significantly more likely to be platinum resistant (odds ratio=3.18, confidence interval: 1.31-7.72, P=0.0106, n=291). In addition, direct targeting of the KRAS variant led to a significant reduction in EOC cell growth and survival in vitro. These findings confirm the importance of the KRAS variant in EOC, and indicate that the KRAS variant is a biomarker of poor outcome in EOC likely due to platinum resistance. In addition, this study supports the hypothesis that these tumors have continued dependence on such 3'UTR lesions, and that direct targeting may be a viable future treatment approach.

[Sustentaculum tali screw placement for calcaneus fractures--different navigation procedures compared to the conventional technique]. / Sustentaculum-tali-Schraubenplatzierung bei der Versorgung von Kalkaneusfrakturen--verschiedene Navigationsverfahren im Vergleich zur konventionellen Technik.

AIM: Precise placement of the sustentaculum tali screw is essential for fixation of calcaneus fractures to achieve the best fixation strength. In the clinical practice, this procedure is demanding due to the complex anatomic configuration of the calcaneus and the limited visualisation in the intraoperative fluoroscopic images. The aim of this study was an evaluation of the accuracy for the sustentaculum tali screw placement by using different navigation procedures compared to the standard procedure. The different navigation specific workflows were evaluated and the feasibility of each procedure proven in clinical applications. METHOD: Eight sustentaculum screws per group were placed in an artifical Synbone model. Different navigation procedures were evaluated: 2D-fluoroscopy (group I), 3D-fluoroscopy (group II), fluoro-free (group III) and compared to the conventional screw placement without navigation (group IV). For each screw the time of fluoroscopy and the duration of the procedure were measured. The accuracy was evaluated postoperatively by computed tomography using axial slices and coronary as well as sagittal reformations. Furthermore, the workflow of each navigation procedure was analysed and proven in clinical applications. RESULTS: In the experimental setup, no radiation exposure was mandatory for the conventional and fluoro-free procedures, whereas mean fluoroscopy times of 17 +/- 1.03 und 66.8 +/- 0.9 were measured for 2D- and 3D-navigation procedures. In line with this, the overall mean procedure times for the screw placement were 1.26 +/- 0.05 (group IV), 3.49 +/- 0.26 (group III), 13.32 +/- 0.49 (group I) und 19.04 +/- 1.41 minutes (group II). No significant differences were observed for the accuracy of screw placement. In the clinical practice a better orientation was achieved by use of a navigation system. The fluoro-free procedure can be easily integrated into the common operation workflow, whereas the workflow of both image-based navigation procedures is technically demanding. CONCLUSION: Navigation procedures seem to be helpful for the precise placement of sustentaculum tali screws in cases of operative calcaneus fracture fixation. The kind of application to be used depends on the infrastructure of the department and the navigation-experience of the operating room team. Whereas the fluoro-free procedure is intuitive in use, the 2D-navigation does not justify the extra efforts. The 3D-procedure is the recommended application for surgeons familiar with navigation, providing the best orientation due to the slice image visualisation in all three dimensions.

Increased formation of sister chromatid exchanges, but not of micronuclei, in anaesthetists exposed to low levels of sevoflurane.

We have assessed, for the first time, genotoxicity (i.e. sister chromatid exchanges and micronuclei) in anaesthetists exposed to a single volatile anaesthetic (sevoflurane) without nitrous oxide. The anaesthetists were exposed to an 8-h time-weighted average of 0.2 parts per million sevoflurane. Internists served as non-exposed controls. Mean (SD) sister chromatid exchanges per cell were significantly higher in anaesthetists compared to internists (6.6 (0.9) vs 5.1 (0.8); p < 0.001) whereas median (IQR [range]) micronuclei per 1000 binucleated cells did not differ (9.5 (6.3-10.8 [2.0-15.5]) vs 8.5 (6.0-10.5 [3.0-25.5]), respectively). Although the anaesthetists were exposed to rather low concentrations of sevoflurane, this 30% increase of sister chromatid exchanges is in agreement with a recently reported 300% increase with a high level exposure to sevoflurane and nitrous oxide. Omitting nitrous oxide does not normalise increased rates of sister chromatid exchanges.

[Sexuality of suicidal elderly]. / Sexualität suizidaler Alterer.

Sexuality and suicidality in the elderly seem to underlie a taboo in science and in therapeutic practice. It is urgent to find an understanding about both aspects of human experience and behaviour by explorative studies. In a sample (N=67), the narratives of 56 persons (suicidal=43 and non-suicidal=23) on questions concerning their sexuality were transcribed and ideal types were developed with the systematic qualitative method of forming types by understanding. Four of these types consist of clearly more suicidal persons, in two the non-suicidals predominate, the rest is more heterogeneous in this aspect. Some of these types can be interpreted unequivocally. One type was surprisingly clearly suicidal dynamic, while others were a "female narcissistic" or a "male narcissistic" type. This explorative typology may help the interested therapist/counsellor as a landmark to relate to sexuality as an important aspect of life, even in old age, and to use the discussion of sexuality to improve the understanding of patients, especially in suicidal crisis.

Up-regulation of hypertonicity-activated myo-inositol transporter SMIT1 by the cell volume-sensitive protein kinase SGK1.

Mechanisms of regulatory cell volume increase following cell shrinkage include accumulation of organic osmolytes such as betaine, taurine, sorbitol, glycerophosphorylcholine (GPC) and myo-inositol. Myo-inositol is taken up by the sodium-myo-inositol-transporter SMIT1 (SLC5A3) expressed in a wide variety of cell types. Hypertonicity induces the transcription of the SMIT1 gene upon binding of the transcription factor tonicity enhancer binding protein (TonEBP) to tonicity responsive enhancers (TonE) in the SMIT1 promoter region. However, little is known about post-translational regulation of the carrier protein. In this study we show that SMIT1 is modulated by the serum- and glucocorticoid-inducible kinase SGK1, a protein genomically up-regulated by hypertonicity. As demonstrated by two-electrode voltage-clamp in the Xenopus oocyte expression system, SMIT1-mediated myo-inositol-induced currents are up-regulated by coexpression of wild type SGK1 and constitutively active (S422D)SGK1 but not by inactive (K127N)SGK1. The increase in SMIT1 activity is due to an elevated cell surface expression of the carrier while its kinetic properties remain unaffected. According to the decay of SMIT1 activity in the presence of brefeldin A, SGK1 stabilizes the SMIT1 protein in the plasma membrane. The SGK isoforms SGK2, SGK3 and the closely related protein kinase B (PKB) are similarly capable of activating SMIT1 activity. SMIT1-mediated currents are decreased by coexpression of the ubiquitin-ligase Nedd4-2, an effect counteracted by additional coexpression of SGK1. In conclusion, the present observations disclose SGK isoforms and protein kinase B as novel regulators of SMIT1 activity.

Regulation of the epithelial calcium channel TRPV6 by the serum and glucocorticoid-inducible kinase isoforms SGK1 and SGK3.

Epithelial calcium (re)absorption is mediated by TRPV5 and TRPV6 channels. TRPV5 is modulated by the SGK1 kinase, a process requiring the PDZ-domain containing scaffold protein NHERF2. The present study explored whether TRPV6 is similarly regulated by SGKs and the scaffold proteins NHERF1/2. In Xenopus oocytes, SGKs activate TRPV6 by increasing its plasma membrane abundance. Deletion of the putative PDZ binding motif on TRPV6 did not abolish channel activation by SGKs. Furthermore, coexpression of neither NHERF1 nor NHERF2 affected TRPV6 or potentiated the SGKs stimulating effect. The present observations disclose a novel TRPV6 regulatory mechanism which presumably participates in calcium homeostasis.

[New kinds of relationships on the internet. Virtual object relations in psychotherapy]. / Neue Beziehungsformen im Internet. Virtuelle Objektbeziehungen in der Psychotherapie.

Communication in the internet by e-mail is gaining in significance in counseling and psychotherapy of suicidal patients as well as an additional communication in face-to-face psychotherapy. E-Mail contacts during psychodynamic psychotherapy are defined as a transference offer of a virtual object relation. In two case descriptions of suicidal patients, examples of making contact with psychotherapy on the internet are presented. The concept of the virtual object is explained and its application for understanding these initial scenes and phenomena is discussed.

[Phylogenetics of the immunosystem]. / Phylogenese des Immunsystems.

The human immune system is composed of two closely cooperating entities: innate, "unspecific" immune defense on one hand and adaptive, "specific" immunity on the other. Innate immune defense mechanisms were already developed very early in the evolution of the animal kingdom. By contrast, adaptive immunity exclusively evolved in jawed vertebrates within a surprisingly short time span. New data especially from genome sequencing projects now allow first glimpses on those events that resulted in the formation of adaptive immunity.

Scanning probe microscopy for Bio & Nanotechnology onboard the ISS.

Since February 2002 Kayser-Threde GmbH, Munich (Germany) leads a study under ESA contract in order to study the technical feasibility and the applications of "Scanning Probe Microscopy for Bio & Nanotechnology onboard the ISS (SONOS)". The objective of this effort is to demonstrate the feasibility of an SPM instrument on the ISS. An appropriate breadboard model will be manufactured and tested within the present study. Its development will be based upon the developed pocket size SPM instrument by Professor W. Hecki of the Center for Crystallography and NanoScience (CeNS) at the Ludwig-Maximilians University (LMU) in Munich. Scanning probe microscopy (SPM) investigates surface structures at very high resolution and can perform nanoengineering. These techniques can be applied to non organic as well as to organic or biological materials.

The molecular chaperone, alpha-crystallin, inhibits amyloid formation by apolipoprotein C-II.

Under lipid-free conditions, human apolipoprotein C-II (apoC-II) exists in an unfolded conformation that over several days forms amyloid ribbons. We examined the influence of the molecular chaperone, alpha-crystallin, on amyloid formation by apoC-II. Time-dependent changes in apoC-II turbidity (at 0.3 mg/ml) were suppressed potently by substoichiometric subunit concentrations of alpha-crystallin (1-10 microg/ml). alpha-Crystallin also inhibits time-dependent changes in the CD spectra, thioflavin T binding, and sedimentation coefficient of apoC-II. This contrasts with stoichiometric concentrations of alpha-crystallin required to suppress the amorphous aggregation of stressed proteins such as reduced alpha-lactalbumin. Two pieces of evidence suggest that alpha-crystallin directly interacts with amyloidogenic intermediates. First, sedimentation equilibrium and velocity experiments exclude high affinity interactions between alpha-crystallin and unstructured monomeric apoC-II. Second, the addition of alpha-crystallin does not lead to the accumulation of intermediate sized apoC-II species between monomer and large aggregates as indicated by gel filtration and sedimentation velocity experiments, suggesting that alpha-crystallin does not inhibit the relatively rapid fibril elongation upon nucleation. We propose that alpha-crystallin interacts stoichiometrically with partly structured amyloidogenic precursors, inhibiting amyloid formation at nucleation rather than the elongation phase. In doing so, alpha-crystallin forms transient complexes with apoC-II, in contrast to its chaperone behavior with stressed proteins.

One-step separation of endocytic organelles, Golgi/trans-Golgi network and plasma membrane by density gradient electrophoresis.

Many different methods for the fractionation of subcellular organelles have been reported. However, no protocol for rapid separation of plasma membrane, Golgi/trans-Golgi network (TGN) and endosomes is available to date. Such a method is a prerequisite for a quantitative biochemical analysis of vesicular transport from the Golgi/TGN compartment to plasma membrane and endosomes. Here a density gradient electrophoresis protocol is described that allows the fractionation of these organelles in one step. This protocol requires only low-cost instrumentation available in most biochemical laboratories.

The molecular chaperone alpha-crystallin is in kinetic competition with aggregation to stabilize a monomeric molten-globule form of alpha-lactalbumin.

In vivo, alpha-crystallin and other small heat-shock proteins (sHsps) act as molecular chaperones to prevent the precipitation of 'substrate' proteins under stress conditions through the formation of a soluble sHsp-substrate complex. Using a range of different salt conditions, the rate and extent of precipitation of reduced alpha-lactalbumin have been altered. The interaction of alpha-crystallin with reduced alpha-lactalbumin under these various salt conditions was then studied using a range of spectroscopic techniques. Under conditions of low salt, alpha-lactalbumin aggregates but does not precipitate. alpha-Crystallin is able to prevent this aggregation, initially by stabilization of a monomeric molten-globule species of alpha-lactalbumin. It is proposed that this stabilization occurs through weak transient interactions between alpha-crystallin and alpha-lactalbumin. Eventually a stable, soluble high-molecular-mass complex is formed between the two proteins. Thus it appears that a tendency for alpha-lactalbumin to aggregate (but not necessarily precipitate) is the essential requirement for alpha-crystallin-alpha-lactalbumin interaction. In other words, alpha-crystallin interacts with a non-aggregated form of the substrate to prevent aggregation. The rate of precipitation of alpha-lactalbumin is increased significantly in the presence of Na2SO4 compared with NaCl. However, in the former case, alpha-crystallin is unable to prevent this aggregation and precipitation except in the presence of a large excess of alpha-crystallin, i.e. at mass ratios more than 10 times greater than in the presence of NaCl. It is concluded that a kinetic competition exists between aggregation and interaction of unfolding proteins with alpha-crystallin.