[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.

[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.

[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.

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.

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.

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.

The small heat-shock chaperone protein, alpha-crystallin, does not recognize stable molten globule states of cytosolic proteins.

The small heat-shock protein (sHsp), alpha-crystallin, acts as a molecular chaperone by interacting with destabilized 'substrate' proteins to prevent their precipitation from solution under conditions of stress. alpha-Crystallin and all sHsps are intracellular proteins. Similarly to other chaperones, the 'substrate' protein is in an intermediately folded, partly structured molten globule state when it interacts and complexes with alpha-crystallin. In this study, stable molten globule states of the cytosolic proteins, gamma-crystallin and myoglobin, have been prepared. Within the lens, gamma-crystallin naturally interacts with alpha-crystallin and myoglobin and alpha-crystallin are present together in muscle tissue. The molten globule states of gamma-crystallin and myoglobin were prepared by reacting gamma-crystallin with glucose 6-phosphate and by removing the haem group of myoglobin. Following spectroscopic characterisation of these modified proteins, their interaction with alpha-crystallin was examined by a variety of spectroscopic and protein chemical techniques. In both cases, there was no interaction with alpha-crystallin that led to complexation. It is concluded that alpha-crystallin does not recognise stable molten globule states of cytosolic 'substrate' proteins and only interacts with molten globule states of proteins that are on the irreversible pathway towards an aggregated and precipitated form.

Non-oxidative modification of lens crystallins by kynurenine: a novel post-translational protein modification with possible relevance to ageing and cataract.

In humans, the crystallin proteins of the ocular lens become yellow-coloured and fluorescent with ageing. With the development of senile nuclear cataract, the crystallins become brown and additional fluorophores are formed. The mechanism underlying crystallin colouration is not known but may involve interaction with kynurenine-derived UV filter compounds. We have recently identified a sulphur-linked glutathionyl-3-hydroxykynurenine glucoside adduct in the lens and speculated that kynurenine may also form adducts with GSH and possibly with nucleophilic amino acids of the crystallins (e.g. Cys). Here we show that kynurenine modifies calf lens crystallins non-oxidatively to yield coloured (365 nm absorbing), fluorescent (Ex 380 nm/Em 450-490 nm) protein adducts. Carboxymethylation and succinylation of crystallins inhibited kynurenine-mediated modification by approx. 90%, suggesting that Cys, Lys and possibly His residues may be involved. This was confirmed by showing that kynurenine formed adducts with GSH as well as with poly-His and poly-Lys. NMR studies revealed that the novel poly-Lys-kynurenine covalent linkage was via the epsilon-amino group of the Lys side chain and the betaC of the kynurenine side chain. Analysis of tryptic peptides of kynurenine-modified crystallins revealed that all of the coloured peptides contained either His, Cys or an internal Lys residue. We propose a novel mechanism of kynurenine-mediated crystallin modification which does not require UV light or oxidative conditions as catalysts. Rather, we suggest that the side chain of kynurenine-derived lens UV filters becomes deaminated to yield an alpha,beta-unsaturated carbonyl which is highly susceptible to attack by nucleophilic amino acid residues of the crystallins. The inability of the lens fibre cells to metabolise their constituent proteins results in the accumulation of coloured/fluorescent crystallins with age.

Formation of betaA3/betaB2-crystallin mixed complexes: involvement of N- and C-terminal extensions.

The sequence extensions of the beta-crystallin subunits have been suggested to play an important role in the oligomerization of these eye lens proteins. This, in turn, may contribute to maintaining lens transparency and proper light refraction. In homo-dimers of the betaA3- and betaB2-crystallin subunits, these extensions have been shown by (1)H-NMR spectroscopy to be solvent-exposed and highly flexible. In this study, we show that betaA3- and betaB2-crystallins spontaneously form mixed betaA3/betaB2-crystallin complexes, which, from analytical ultracentrifugation experiments, are dimeric at low concentrations (<1 mg ml(-1)) and tetrameric at higher protein concentrations. (1)H-NMR spectroscopy reveals that in the betaA3/betaB2-crystallin tetramer, the N-terminal extensions of betaA3-crystallin remain water-exposed and flexible, whereas both N- and C-terminal extensions of betaB2-crystallin lose their flexibility. We conclude that both extensions of betaB2-crystallin are involved in protein-protein interactions in the betaA3/betaB2-crystallin hetero-tetramer. The extensions may stabilize and perhaps promote the formation of this mixed complex.

Alterations of hypothalamic catecholamines in the newborn offspring of gestational diabetic mother rats.

Catecholamines are essential organizers of the developing brain. Throughout life, they are involved, e.g., in the regulation of body weight and metabolism by specific hypothalamic nuclei, which are suggested to be highly vulnerable to maternal gestational hyperglycemia. By application of streptozotocin (30 mg/kg, i.p.) gestational diabetes (GD) was induced in female rats. On the 1st day of life, male GD offspring were underweight (P<0.05) and hyperglycemic (P<0.05), while on the 21st day of life decreased body weight (P<0.001) and elevated pancreatic insulin (P<0.01) were observed. Using HPLC with electrochemical detection, hypothalamic catecholamines were determined in the newborns, and quantitative immunocytochemistry for tyrosine hydroxylase (TH) was performed. At birth, a tendency towards increased levels of norepinephrine (NE) and dopamine (DA) in the whole hypothalami of GD offspring was observed. In the 21-day-old offspring of GD mothers, NE was significantly increased in the ventromedial hypothalamic nucleus (VMN; P<0.05) and the lateral hypothalamic area (LHA; P<0.05), while DA was significantly elevated in the paraventricular hypothalamic nucleus (PVN; P<0.05) and the LHA (P<0.05). The NE/DA-ratio was found to be decreased in the PVN of GD offspring (P<0.01). Moreover, numerical density of TH-positive neurons was clearly increased within the parvocellular division of the PVN (P<0.0001) as well as in the periventricular hypothalamic area (PER; P<0.05). These data suggest specific alterations of catecholaminergic systems within hypothalamic regulators of body weight and metabolism during early development in the offspring of gestational diabetic mother rats.

Effects of dextran on the self-association of human spectrin.

The self-association of human spectrin is enhanced in the presence of dextran. The equilibrium constant for association of two heterodimers to form a tetramer is increased by an order of magnitude in the presence of 20% dextran. The rate constant for association is also enhanced, while the rate constant for dissociation is almost independent of dextran concentration. The degree of enhancement of association is dependent only on the mass concentration of dextran; for a given mass concentration of dextran the effect is independent of dextran molecular weight. These effects are believed to be due to excluded volume phenomena, and a model is presented that realistically accounts for the effects. These results imply that the association of spectrin within the erythrocyte will be enhanced by the presence of hemoglobin.

Macromolecular crowding: effects on actin polymerisation.

Dextran has been found to enhance the polymerisation of actin. This enhancement increases exponentially with increasing mass concentrations of dextran, in a manner that is consistent with excluded volume theory. Mathematical prediction of experimental results is difficult due to the fact that all participating species, namely F-actin, G-actin and dextran are best represented by differently shaped hard particles. Modelling dextran as a sphere of radius defined by an effective thermodynamic radius (Reff), we have predicted our experimental results to an acceptable degree, given the relative crudity of the model. The results imply that the highly crowded cellular environment may help to stabilise the filamentous actin network in vivo.

Characterisation of genotoxic properties of 2',2'-difluorodeoxycytidine.

The genotoxic properties of 2',2'-difluorodeoxycytidine (dFdC) were characterised using diploid, mortal low-passage fibroblasts (LPF cells) and the spontaneously transformed fibroblast cell line V79. In both cell types, incorporation of dFdC into the DNA led to an increase of DNA single-strand breaks evaluated by an in situ nick translation assay and to an accumulation of cells in the S-phase of the cell cycle. At concentrations below those leading to cell cycle arrest, dFdC neither induced sister chromatid exchange (SCE) nor structural chromosome aberrations in LPF cells, whereas V79 cells accumulated SCEs as well as chromosome breaks over a broad dose range. In LPF cells treated with dFdC, chromosomal alterations were detected by the micronucleus assay within a narrow concentration range, whereas in V79 cells, a dose-dependent increase in the appearance of micronuclei was seen up to cytotoxic concentrations. In addition, V79 cells went into apoptosis, as evaluated by nuclear fragmentation and condensation, whereas this phenomenon was not detectable in LPF cells.

Stabilizing and directional selection on facial paedomorphosis : Averageness or juvenilization?

Averageness is purportedly the result of stabilizing selection maintaining the population mean, whereas facial paedomorphosis is a product of directional selection driving the population mean towards an increasingly juvenile appearance. If selection is predominantly stabilizing, intermediate phenotypes reflect high genetic quality and mathematically average faces should be found attractive. If, on the other hand, directional selection is strong enough, extreme phenotypes reflect high genetic quality and juvenilized faces will be found attractive. To compare the effects of stabilizing and directional selection on facial paedomorphosis (juvenilization), graphic morphing and editing techniques were used to alter the appearance of composite faces to make them appear more or less juvenile. Both facial models and judges of attractiveness were from the CSU-Long Beach campus. Although effect sizes for both preferences were large, the effect for averageness was nearly twice that found for juvenilization, an indication that stabilizing selection influences preferences for facial paedomorphosis more so than directional selection in contemporary humans.

[Importance of MR tomography for the diagnosis of bone marrow diseases in childhood]. / Bedeutung der Kernspintomographie für die Diagnostik von Knochenmarkserkrankungen im Kindesalter.

As a diagnostic and follow-up method of bone marrow diseases in children, magnetic resonance imaging (MRI) possesses special importance. It is characterised by high sensitivity in detecting bone marrow lesions, high soft tissue--bone tissue contrast, sharp demarcation of intraosseous lesions and visualisation of vascular structures without application of contrast medium. Thus it is able above all to take on the findings of radionuclide bone scanning, computed tomography and angiography. In the detection of pathophysiological alterations of the corticalis and of calcifications it is less reliable than x-ray images and CT.

A cytogenetic study on the teaching staff of a polluted school with a questionable increased incidence of malignancies.

Exposure to pollutants, in particular polychlorinated biphenyls (PCB), was established at a school built in 1966. Because of a statistically conspicuous increased frequency of breast cancer observed in the teachers of the school this study was performed to ascertain whether the teachers in the polluted school have an increased level of micronucleated cells (MN) or sister chromatid exchanges (SCE) as an expression of a raised cytogenetic risk. Teachers in a directly adjacent school served as one control group and those from a school about 30 km away as a second one. Each teacher had to answer a questionnaire and after venous blood samples had been taken, the number of MN and SCE in peripheral lymphocytes were determined. For the teachers in the polluted school, in addition, the length of stay in the building during the last month and year was recorded. Thereby no correlation with the number of MN and SCE was proven. In comparison with the two control groups, neither the number of MN nor SCE was increased in the teachers of the polluted school. Even if their predictive value for cancer risk assessment is disputed, MN and SCE have a high rating as standard procedures in the proof of an exposure to genotoxic agents. This study thus does not provide any evidence that, for the teachers in the polluted school, a relevant exposure to genotoxic agents exists.

NMR spectroscopy of alpha-crystallin. Insights into the structure, interactions and chaperone action of small heat-shock proteins.

The subunit molecular mass of alpha-crystallin, like many small heat-shock proteins (sHsps), is around 20 kDa although the protein exists as a large aggregate of average mass around 800 kDa. Despite this large size, a well-resolved 1H NMR spectrum is observed for alpha-crystallin which arises from short, polar, highly-flexible and solvent-exposed C-terminal extensions in each of the subunits, alpha A- and alpha B-crystallin. These extensions are not involved in interactions with other proteins (e.g. beta- and gamma-crystallins) under non-chaperone conditions. As determined by NMR studies on mutants of alpha A-crystallin with alterations in its C-terminal extension, the extensions have an important role in acting as solubilising agents for the relatively-hydrophobic alpha-crystallin molecule and the high-molecular-weight (HMW) complex that forms during the chaperone action. The related sHsp, Hsp25, also exhibits a flexible C-terminal extension. Under chaperone conditions, and in the HMW complex isolated from old lenses, the C-terminal extension of the alpha A-crystallin subunit maintains its flexibility whereas the alpha B-crystallin subunit loses, at least partially, its flexibility, implying that it is involved in interaction with the 'substrate' protein. The conformation of 'substrate' proteins when they interact with alpha-crystallin has been probed by 1H NMR spectroscopy and it is concluded that alpha-crystallin interacts with 'substrate' proteins that are in a disordered molten globule state, but only when this state is on its way to large-scale aggregation and precipitation. By monitoring the 1H and 31P NMR spectra of alpha-crystallin in the presence of increasing concentrations of urea, it is proposed that alpha-crystallin adopts a two-domain structure with the larger C-terminal domain unfolding first in the presence of denaturant. All these data have been combined into a model for the quaternary structure of alpha-crystallin. The model has two layers each of approximately 40 subunits arranged in an annulus or toroid. A large central cavity is present whose entrance is ringed by the flexible C-terminal extensions. A large hydrophobic region in the aggregate is exposed to solution and is available for interaction with 'substrate' proteins during the chaperone action.