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Background and Objective: Psychotropic drugs are among the most widely prescribed drugs. We aimed to systematically analyze the use of psychotropic drugs among inhospital patients in a large university department of internal medicine., Methods: All discharge letters from the Department of Internal Medicine III, University Hospital Jena, Germany, in the year 2010 were retrospectively screened for the use of psychotropic drugs. Metabolic parameters, blood pressure and blood counts were compared to those of a control group; psychiatric diagnoses and consultation of a psychiatrist were noted., Results: Data from 2160 patients were examined (54.5% female, 45,5% male). In 371 patients (17.2%, 63.3% female, 36.4% male) the prescription of psychotropic drugs was recorded. The remaining 1789 patients without psychotropic drugs were used as control group. Patients with psychotropic drugs were significantly older (median 69 vs. 61 years) and more frequently female (p < 0.001). The most frequently used drug group were antidepressants. Both obesity (43.3 vs. 32.3%) and cachexia (9.1 vs. 2.8%) were significantly more common in the psychotropic drug group (p < 0.001). There were also more patients with diabetes (p < 0.001), but their HbA1c levels were not different from the control group. In 44.5% of the patients no psychiatric diagnosis was noted, in only 14.5% a psychiatrist had been consulted. Rather frequently (10% of patients) therapy with benzodiazepine receptor agonists or benzodiazepines was mentioned in the discharge letters., Conclusion: The indication for psychotropic drug use could not be reproduced exactly in each case. Psychiatric diagnoses lacked in a substantial part of cases. As to the rest, affective disorders and organic mental disorders were rather frequent indications. Closer interdisciplinary cooperation between internists and psychiatrists is recommended to improve psychotropic drug therapy in older, often multimorbid patients in internal medical wards., (© Georg Thieme Verlag KG Stuttgart · New York.)

The causes of idiopathic sudden sensorineural hearing loss (SSNHL) are still unclear while SSNHL seems to be a multicausal disease. To date limited information about autonomic regulation and, especially, cardiovascular coupling (CVC) are available for those patients. The objective of this study was to characterize short-term (30 min) CVC in 23 SSNHL patients in comparison to 23 healthy age and gender matched normal hearing control subjects (CON). Further on, the results from CVC should be compared with those from standard heart rate variability (HRV) and blood pressure variability (BPV) analyses. The results showed that HRV is not affected by the disease whereas BPV analysis revealed significant differences between both groups (p<0.01) whereby SSNHL exhibit a decreased short-term BPV. Results from CVC analysis demonstrated that especially the applied nonlinear methods exhibit an increased short-term CVC in SSNHL patients (p<0.01) indicating more complex interactions of short-term HR and BP regulatory processes. In conclusion, this study was the first to show a changed and decreased short-term BPV and increased nonlinear CVC in SSNHL patients. Our findings might help to improve diagnostic strategies for hearing loss caused by vascular factors.

The perception and processing of pain is disturbed in many psychiatric diseases. Some diseases are known to show decreased perception of pain (e.g. borderline personality disorder), while others are associated with augmented pain perception (e.g. alcohol and drug dependence). The close relationship between psychiatric diseases and pain is most probably caused by aberrant processing of pain in brain structures, known to be involved in psychiatric disorders as well. Aberrant perception and processing of pain in patients with anorexia nervosa (AN) will be used to demonstrate this close relationship. Dysfunction within the insula has been suggested to account for many features of AN and might contribute to reduced pain perception. Moreover, it might lead to increased adrenergic descending inhibition associated with increased sympathetic modulation. Thus, pain research might be able to alter our view on autonomic regulation, which is putatively associated with increased cardiac mortality of the disease.

Background: The scheduled update to the German S3 guidelines on fibromyalgia syndrome (FMS) by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF; registration number 041/004) was planned starting in March 2011., Materials and Methods: The development of the guidelines was coordinated by the German Interdisciplinary Association for Pain Therapy ("Deutsche Interdisziplinären Vereinigung für Schmerztherapie", DIVS), 9 scientific medical societies and 2 patient self-help organizations. Eight working groups with a total of 50 members were evenly balanced in terms of gender, medical field, potential conflicts of interest and hierarchical position in the medical and scientific fields. Literature searches were performed using the Medline, PsycInfo, Scopus and Cochrane Library databases (until December 2010). The grading of the strength of the evidence followed the scheme of the Oxford Centre for Evidence-Based Medicine. The recommendations were based on level of evidence, efficacy (meta-analysis of the outcomes pain, sleep, fatigue and health-related quality of life), acceptability (total dropout rate), risks (adverse events) and applicability of treatment modalities in the German health care system. The formulation and grading of recommendations was accomplished using a multi-step, formal consensus process. The guidelines were reviewed by the boards of the participating scientific medical societies., Results and Conclusion: Amitriptyline and-in case of comorbid depressive disorder or generalized anxiety disorder-duloxetine are recommended. Off-label use of duloxetine and pregabalin can be considered in case of no comorbid mental disorder. Strong opioids are not recommended. The English full-text version of this article is available at SpringerLink (under "Supplemental").

Schizophrenia is associated with a cardiac autonomic dysregulation which is characterized by a decreased vagal modulation. Nevertheless, there are less information about the interrelationships of the cardiovascular and respiratory systems in schizophrenia.

AMPK is an ubiquitously distributed multienzyme complex. It is an important energy sensor and regulator of cellular metabolic activity. In this study we analyzed for the first time the cellular distribution of the catalytically active subunits AMPKα1 and α2 in different human tissues by immunohistochemistry. We found different expression patterns for both isoforms. AMPKα2 expression clearly dominates in skeletal myocytes and cardiomyocytes, whereas AMPKα1 dominates in a number of secreting cells, like mammary glands, islets of langerhans and cells of the colon crypts.

We report a patient with early-onset autosomal dominant dementia. The CSF showed increased levels of tau protein and decreased amyloid beta (ratio 42:40) typical for Alzheimer's disease. Cerebral MRI revealed vascular lesions and white-matter changes around the posterior horns of the ventricles with only moderate atrophy of the brain. Susceptibility-weighted imaging detected multiple small hemorrhagic changes. Gene analysis revealed amyloid precursor protein (APP) locus duplication as the cause of hereditary Alzheimer's dementia. The co-occurrence of CSF changes typical for Alzheimer's disease and MRI findings of cerebral amyloid angiopathy is remarkable, as it is also described for APP locus duplication. In conjunction with a family history suggestive of hereditary dementia, such a constellation should lead to enhanced gene analysis.

A major technical problem in the processing of resin-embedded tissues is the adhesion of the tissue sample on glass slides for immunohistochemical labelling. We therefore established a novel protocol for processing such specimens with improved attachment of the tissue sample during resin removal (deplastification). In order to demonstrate the feasibility of the procedure we employed a panel of smooth muscle cell maturation markers. The technique makes use of a silicone glue (Elastosil E41; Wacker Chemie, München, Germany) to attach the tissue samples to the glass slides. This allows resin dissolution in xylene/2-methoxyethylacetate without detachment of the sample from the slide. Our results demonstrate successful immunohistochemical labelling with primary antibodies directed against: smooth muscle actin, smooth muscle myosin, h-caldesmon, desmin, vimentin and von Willebrand factor. In conclusion, we have established a new and successful method for resin-embedded sample adhesion on glass slides. The developed protocol is feasible for investigation of cells which are involved in intimal proliferation following stent implantation.

Trimeric autotransporter adhesins (TAAs) are a major class of proteins by which pathogenic proteobacteria adhere to their hosts. Prominent examples include Yersinia YadA, Haemophilus Hia and Hsf, Moraxella UspA1 and A2, and Neisseria NadA. TAAs also occur in symbiotic and environmental species and presumably represent a general solution to the problem of adhesion in proteobacteria. The general structure of TAAs follows a head-stalk-anchor architecture, where the heads are the primary mediators of attachment and autoagglutination. In the major adhesin of Bartonella henselae, BadA, the head consists of three domains, the N-terminal of which shows strong sequence similarity to the head of Yersinia YadA. The two other domains were not recognizably similar to any protein of known structure. We therefore determined their crystal structure to a resolution of 1.1 A. Both domains are beta-prisms, the N-terminal one formed by interleaved, five-stranded beta-meanders parallel to the trimer axis and the C-terminal one by five-stranded beta-meanders orthogonal to the axis. Despite the absence of statistically significant sequence similarity, the two domains are structurally similar to domains from Haemophilus Hia, albeit in permuted order. Thus, the BadA head appears to be a chimera of domains seen in two other TAAs, YadA and Hia, highlighting the combinatorial evolutionary strategy taken by pathogens.

To investigate the effect of depression and medication on the autonomic nervous system (ANS) we compared 25 patients suffering from depression with 72 matched control subjects (CON). From every patient three times ECG and non-invasive blood pressure were recorded in: acute non-mediated state (T1), medicated state (T2) and clinical recovered state (T3). Cardiac autonomic regulation was evaluated by linear and nonlinear analysis methods. The results show that non-medicated depressed patients differ significantly from CON (p0.05). In the medicated state considerably high significant differences between depressed patient and CON were found (p0.0001). After an 18 months follow-up a normalization of autonomic parameters was achieved in depressed patients. These results show that depression influences autonomic parameters significantly and that medical treated clinical recovered patients approximate to healthy controls in autonomic regulation.

An increased heart rate has been reported in schizophrenia. It is unclear whether this is due to disease-related autonomic nervous system changes or a side effect of antipsychotic medication. Altered cardiac autonomic function might to some extent account for the elevated cardiovascular mortality rate of schizophrenic patients. We assessed heart rate variability (HRV) in 30 acute unmedicated schizophrenic patients and matched controls. Patients were re-investigated 2--4 days after initiation of treatment to assess effects of medication. Our study demonstrates that non-medicated schizophrenic patients were significantly different in heart rate (increase) and parasympathetic parameters (loss of efferent vagal activity) at rest and during deep respiration. No significant effect was found after initiation of neuroleptic therapy. We found a correlation between duration of disease and parasympathetic parameters as well as very low frequency power (VLF) and delusion (SAPS subscale). These data suggest that schizophrenia is accompanied by a loss of vagal efferent activity, probably due to disturbed cortical-subcortical circuits modulating the autonomic nervous system in acute psychosis. The definite mechanisms by which vagal activity might be suppressed in schizophrenia are unknown. Parasympathetic hypoactivity might increase the risk for sudden cardiac death and arrhythmias in this disease. Future studies are warranted to investigate the interaction between cardiac autonomic function and schizophrenia and to identify patients on risk.

This is a report about an inadvertent intravenous infusion of 380 mg ropivacaine in a 84-year-old patient over a period of 1.75 h. The level of serum ropivacaine measured immediately after the end of the infusion as well as 2 h and 7 h later, was initially in the lower toxic range (free concentration of 0.48 micro g/ml). The patient showed no symptoms of intoxication neither clinically nor during the technical examinations (EEG, ECG). This case confirms the wide therapeutic range of ropivacaine.

Increased incidence of clinical pain complaints from patients with major depression, as well as increased experimental pain thresholds have been reported. The basis of this phenomenon remains unclear, as well as its relation to medication, clinical recovery, gender and lateralization of hemispheric function. We aimed to further elucidate heat pain perception in depression applying a testing battery including assessment (on both arms) of warmth perception, heat pain perception and heat pain tolerance, and the jaw opening reflex (duration of ES2 component) as a putative indicator of descending pain inhibition. The battery was applied to 20 patients and 20 age- and sex-matched controls. Patients were assessed: on admission (acutely depressed, off-medication), few days after admission (depressed, on medication), and after clinical recovery (mostly on medication), and controls at corresponding intervals. Significant elevated heat pain thresholds were found off and on medication in the acute stage (mainly in women) and after recovery on the right arm only. Elevated heat pain tolerance (on the right arm only) was seen in medicated patients in the acute and recovered stage. Significant prolongation of ES2 duration was only found in acutely depressed patients off medication. While confirming hypalgesia to heat pain in major depression, our findings demonstrate a close relation to gender and strong influence of lateralization after recovery. Altered pain processing at brain stem level might only partially be responsible for the observed finding.

Increasing evidence suggests an interaction of oxidative stress and the formation of advanced glycation end products (AGE) in the onset and progression of Alzheimer's disease. We studied levels of pentosidine and N(epsilon)-(carboxymethyl)-lysine (CML) in serum and cerebrospinal fluid (CSF) of 15 patients with probable Alzheimer's disease (AD), 20 patients with vascular dementia (VD), and 31 control subjects (14 matched for age, and 17 younger patients). AGE protein concentrations in CSF did not differ within controls when divided into two subgroups by age. We found significantly elevated levels of CML in CSF of AD patients and of pentosidine in CSF of patients suffering from vascular dementia when compared to controls. The concentrations of pentosidine and CML in serum apparently did not relate directly to CSF values, suggesting influence of extra-cerebral factors in serum samples. It is concluded that AGE proteins are differentially affected in these types of dementia, depending on the specific neuropathology. Furthermore, measurements of AGE products in vivo should rely on CSF rather than blood samples.

220 of 268 polytraumatized patients (82.1%) presented an additional head injury, which increased the mortality significantly. By the Hannover Polytrauma Score we could demonstrate that the severity of the polytrauma and the prognosis depended on the extent of the brain injury. Important risk factors were skull fractures and shock on arrival. 66.7% of the patients with a severe brain trauma and a skull fracture died; without this fracture, only 36.8% died. 76.1% of the children with a systolic blood pressure (SBP) > 80 mm Hg survived, but only 31.2% with a SBF < or = 80 mm Hg did not die. For all polytraumatized children we recommend a computer tomography of the head. In spite of a negative initial CT a follow up CCT should be performed.

Prostaglandins (PGs) are local mediators of several functions in the CNS. Both primary afferent neurons and intrinsic cells in the spinal cord produce PGs, with a marked upregulation during peripheral inflammation. Therefore, the significance of spinal PGs in the neuronal processing of mechanosensory information was herein investigated. In anesthetized rats, the discharges of spinal nociceptive neurons with input from the knee joint were extracellularly recorded. Topical administration of prostaglandin E(2) (PGE(2)) to the spinal cord facilitated the discharges and expanded the receptive field of dorsal horn neurons to innocuous and noxious pressure applied to the knee joint, the ankle, and the paw, thus mimicking inflammation-induced central sensitization. Conversely, topical administration of the PG synthesis inhibitor indomethacin to the spinal cord before and during development of knee joint inflammation attenuated the generation of inflammation-induced spinal neuronal hyperexcitability. However, after development of inflammation, the responses of spinal neurons to mechanical stimuli were only reduced by systemic indomethacin but not by indomethacin applied to the spinal cord. Thus, spinal PG synthesis is important for the induction and initial expression but not for the maintenance of spinal cord hyperexcitability. Spinal PGE(2) application facilitated dorsal horn neuronal firing elicited by ionophoretic delivery of NMDA, suggesting that an interaction of PGs and NMDA receptors may contribute to inflammation-induced central sensitization. However, after development of inflammation, spinal indomethacin failed to reduce responses to ionophoretic delivery of NMDA or AMPA, suggesting that such an interaction is not required for the maintenance of central sensitization.

Objectives: To explore subclinical disturbances in the motor cortex of patients with Alzheimer's disease (AD)., Methods: We used transcranial magnetic stimulation in a paired pulse technique to test intracortical inhibition (ICI) and intracortical facilitation in mildly to moderately demented AD patients with a normal neurological examination. Patients were studied before and during treatment with the cholinesterase inhibitor donepezil., Results: AD patients had a reduced ICI compared to an age-matched control group. The amount of disinhibition correlated with the severity of dementia. Treatment with 10 mg donepezil daily was associated with an increase of ICI., Conclusions: The subclinical motor cortex disinhibition in AD patients indicates a functional disturbance, and is probably associated with a cholinergic deficit.

The aim of this study was to develop a biomechanical experimental set-up to quantify motion of ventrally inserted spinal implants at the implant/bone interface. The model we used was the vertebral column of the calf. Lumbar vertebrae L2 to L4 were "instrumented" with a screw-rod system. The adjacent vertebrae L1 and L5 were connected to a servohydraulic testing machine and axial compression applied. Shortening of the specimen and three-dimensional movement of the most cranial implant relative to the bone was recorded using 3 electromagnetic transducers. 100,000 cycles of axial loading varying between -0.5 kN and -1 kN were applied. Static shortening of the specimen of 8.5 mm and an elastic movement of 180 to 280 microns were measured. The greatest amplitude of single-plane motion was recorded in the sagittal plane in both static and elastic modes. Implant motion within each cycle was recorded accurately as load-displacement curves within a range of 1.35 to 30 microns. With this test set-up, primary stability of different spinal implant systems can be compared. The use of electromagnetic transducers permits three-dimensional implant motion analysis even when only a mono-axial servohydraulic testing machine is available.

Background & Aims: Glial cell line-derived neurotrophic factor (GDNF) signals through the product of the ret proto-oncogene, which is known to be mutated in Hirschsprung's disease and other conditions with gut dysmotility. The aim of this study was to determine the presence of GDNF and its receptor component (RET) in human adult and developing intestine and to evaluate their distribution pattern in Hirschsprung's disease., Methods: GDNF and RET were detected immunohistochemically, and GDNF was quantified by immunoassay in specimens of human adult and fetal colon and Hirschsprung's disease intestine., Results: GDNF-like immunoreactivity was detected in all specimens. Immunostaining of GDNF was restricted to neural fiber-like structures across the gut wall and was similar to staining with markers of glia and Schwann cells. In contrast, RET immunoreactivity was found only in neural cell bodies. GDNF levels determined by immunoassay were higher in muscle than mucosal gut layers, and there was no difference between affected and unaffected segments of Hirschsprung's disease., Conclusions: GDNF is present in adult and fetal human gut, where it may play a neurotrophic role. Its staining pattern suggests that it is localized in glia or Schwann cells. There seems to be no difference of GDNF levels between affected and unaffected intestinal segments in Hirschsprung's disease.