[Biased objectivity--images of women in 19th century German neuroscience]. / Tendenziöse Objektivität - Frauenbilder in der deutschen Neurowissenschaft des 19. Jahrhunderts.

At the beginning of the 19 (th) century German scholars wanted to differentiate men and women on the basis of anatomic brain or cerebrum particularities. With the help of scientific criteria such as the weight of the brain they aimed not only to prove pre-postulated intellectual differences, but also to find scientific justification for the inferiority of women in general and their inferior position and treatment in society. This paper presents insights into and excerpts from studies written by renowned scientists such as S. T. von Soemmerring, J. F. Ackermann, K. F. Burdach, F. Tiedemann, E. Huschke, H. Schaaffhausen, or P. J. Möbius. Covering the years from 1780 to 1900, these materials show how at the beginning the interest was primarily in comparative anatomic studies and results, but was soon mingled with sociological intentions. Hence this study gives insights into the history of modern gender studies of neurosciences.

Hemorrhagic complications after systemic thrombolysis in acute stroke patients with abnormal baseline coagulation.

BACKGROUND AND PURPOSE: As patients with abnormal baseline coagulation were excluded from the large randomized trials, the safety of intravenous thrombolysis after ischaemic stroke in this patient population remains controversial. METHODS: We assessed the risk of symptomatic intracerebral hemorrhage (SICH) after systemic thrombolysis in patients with elevated baseline international normalized ratios (INRs) (≥1.3) or activated partial thromboplastin times (aPTT) (>37 s) using a prospectively recorded database from 2006 to 2010. An intracerebral hemorrhage leading to a deterioration of ≥4 points on the National Institutes of Health Stroke scale (NIHSS) was classified as symptomatic. RESULTS: Amongst 688 patients (mean age, 72 years; median NIHSS, 11, median onset-to-treatment time, 135 min), 36 patients (5%) had an abnormal baseline coagulation. Twenty-nine of these patients had taken oral anticoagulants leading to elevated baseline INRs (median INR: 1.5; IQR 1.4-1.9), whereas seven patients had elevated aPTTs because of heparin therapy (n = 2), a coagulation disorder (n = 2), or for unknown reasons (n = 3). The rate of SICH did not differ significantly between patients with abnormal and normal baseline coagulation (4.4% vs. 0%; P = 0.6). Moreover, the in-hospital mortality was not significantly different between both treatment groups (8.3% in patients with abnormal baseline coagulation vs. 8.7% in patients with normal baseline coagulation, P = 1.0). CONCLUSIONS: The risk of SICH following intravenous thrombolysis after ischaemic stroke does not appear to be increased in patients with abnormal baseline coagulation.

Game theoretical modelling of survival strategies of Candida albicans inside macrophages.

The polymorphic fungus Candida albicans can live as an aggressive pathogen that causes a wide variety of diseases in humans. Host resistance against these infections is mediated predominantly by phagocytes, namely neutrophils and macrophages. This report provides two game theoretical models of ingested C. albicans cells in macrophages. Two strategies are available for each pathogenic yeast cell: avoiding lysis transiently (called silencing) or forming hyphae and escaping (called piercing because the macrophage is pierced from inside). In dependence on parameter values, two different outcomes can be derived from the model: when the difference of the costs of the two strategies is low, all fungal cells inside a macrophage will play the piercing strategy, while in the high-cost case, a mixed population of piercing and silencing cells is the only stable solution. Further, the role of the SAP gene family encoding secreted proteinases and the Sap proteins is investigated with the help of known studies and is put in relation to the costs of the strategies, the most important parameter of this model. Our results are in agreement with wet-lab results presented by other groups and the model parameters can be estimated from experimental data.

Long-term experience with setup and implementation of an IHE-based image management and distribution system in intersectoral clinical routine.

PURPOSE: Sharing of medical data is crucial for the proper treatment of patients as it could reduce the risk of duplicated medical tests and speed up the care process if all documents are readily available. Despite great technical progress, sharing patient data while maintaining full control over the process in an intersectoral (in Germany, this describes the different actors in the healthcare system consisting of clinic, ambulatory care, etc.) setting remains a particular challenge. This paper focuses on the successful implementation of a privacy compliant, standards-based image-management component of a personal electronic health record. METHODS: Over a 5-year period, a sharing system based on readily available IHE profiles constructed around XDS has been built. It was necessary to create interfaces for the existing hospital sub-systems to become part of the network. Specifically, the imaging workflow had to be adapted to allow for fast and easy access to DICOM images utilizing a flexible web-based image viewer. In addition to the standard XDS workflow, an Imaging Cache was established which combines the Imaging Document Source and Consumer to guarantee fast and streaming-based access to all images in the network observing the high security standards of the hospital network. RESULTS: The authors of this paper have proven that it is possible to build a fast and reliable sharing system based on IHE profiles using most of the transactions of XDS-I with some adaptions to the clinical workflow. Primary hospital systems were enabled by building adapters to overcome lack of IHE compatibility. The established system embraces the existing security mechanisms in hospital networks while connecting patients and referring physicians from outside in a secure and convenient manner. CONCLUSIONS: A state-of-the-art sharing system that is used in a productive clinical environment has been established and is ready to grow with more partners. The system is the basis for an elaborated interdisciplinary collaboration where data, and in particular images, can now be shared between medical professionals.

Isolation and characterization of coenzyme A glutathione disulfide as a parathyroid-derived vasoconstrictive factor.

BACKGROUND: Coenzyme A glutathione disulfide (CoA-SSG) was recently isolated from bovine adrenal glands and was shown to be a renal vasoconstrictor. The identification of CoA-SSG in human parathyroid glands and its action on cultured vascular smooth muscle cells (VSMCs) are described here. METHODS AND RESULTS: After purification to homogeneity by several chromatographic steps, CoA-SSG was identified by matrix-assisted laser desorption/ionization mass spectrometry and enzymatic analysis. The dose-dependent growth-stimulating effect of CoA-SSG on VSMCs, measured by the [(3)H]thymidine method, is characterized by a threshold of 10(-)(8) mol/L and a maximum effect of 10 micromol/L, increasing VSMC proliferation 254+/-21% above control. A dose of 10 micromol/L methylmalonyl-CoA and 10 micromol/L CoA increased the rate of proliferation of VSMCs only by 178+/-43% and 50+/-42% above control, respectively. Glutathione has no proliferative effect on VSMCs. The growth-stimulating effect of CoA-SSG (1 micromol/L) was decreased by the antagonists 3,7-dimethyl-1-propargylxanthine (DMPX; 11 micromol/L) (38% compared with CoA-SSG without antagonist) and pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid (PPADS; 10 micromol/L) (48% compared with CoA-SSG without antagonist; each P:<0. 05 versus control), indicating that the effect is mediated partly via A(2) and partly via P(2)Y(1) and/or P(2)Y(4) receptor. CONCLUSIONS: CoA-SSG may play a regulatory role in VSMC growth as a progression factor and thereby could play an important role in development of hypertension.

[Teleradiology with DICOM e-mail: recommendations of @GIT]. / Teleradiologie mit DICOM E-mail: Empfehlungen der @GIT.

E-mail is ideal for ad-hoc connections in teleradiology. The DICOM standard offers the possibility to append DICOM data types as a MIME attachment to any e-mail, thus ensuring the transmission of the original DICOM data. Nevertheless, there are additional requirements (e.g. protection of data privacy) which must be obeyed. Because of the lack of given standards which would grant interoperability as well as manufacturer independence, teleradiology has not been established in Germany until today. Therefore, the IT-Team (Arbeitsgemeinschaft fur Informationstechnologie, @GIT) of the Radiological Society of Germany (Deutsche Rontgengesellschaft, DRG) set up an initiative to standardise telemedicine by using e-mail. Its members agreed that an e-mail-based variant would be the most practicable way to a communication solution -- as easy to implement as to use. In their opinion, e-mail represents the smallest common denominator for a safe data interchange that would fulfill the legal advantages for telemedicine in Germany.

Magnetic resonance imaging in the clinical diagnosis of Creutzfeldt-Jakob disease.

OBJECTIVE: To evaluate the diagnostic usefulness of magnetic resonance imaging (MRI) in the clinical diagnosis of Creutzfeldt-Jakob disease (CJD). BACKGROUND: Creutzfeldt-Jakob disease is a rare neurodegenerative disease that belongs to the group of human spongiform encephalopathies and usually affects elderly people. It is clinically characterized by rapidly progressive dementia and development of neurological symptoms, such as myoclonus or ataxia. Until now, neuroradiologic investigations have only played a minor role in establishing the clinical diagnosis of CJD, and they are often performed to exclude differential diagnoses. SETTING: A university hospital, base of the German National Creutzfeldt-Jakob Disease Surveillance Study. METHODS AND PATIENTS: In this study, MRIs from suspected cases of CJD were examined by one investigator blinded to the diagnosis. Patients were classified according to the established clinical and neuropathological criteria. RESULTS: Bilateral symmetric, high signal intensities on T2-weighted MRIs were present in the basal ganglia of 109 (67%) of 162 patients with CJD. In the control group, which consisted of non-CJD dementia patients, these abnormalities on T2-weighted MRIs were found in 4 (7%) of 58 patients. This corresponds to a high specificity in the differential diagnosis of CJD. CONCLUSION: These results indicate that MRI is a useful and valuable tool with reasonable sensitivity (67%) and high specificity (93%) and should be considered as an additional cornerstone in the clinical diagnosis of CJD.

Decreased beta-amyloid1-42 in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.

OBJECTIVES: Decreased levels of Abeta1-42 are found in CSF of patients with AD. Because early stages of Creutzfeldt-Jakob disease (CJD) and AD share several clinical features, we investigated Abeta1-42 levels in CSF of these groups, inferring that this might give additional help in differentiating patients with CJD from AD patients. METHODS: We investigated 27 patients with CJD, 14 patients with AD, 19 patients with other dementias, and 20 nondemented controls (NDC) for Abeta1-42 in CSF. Twenty-four of the 27 CJD patients were neuropathologically verified. All the neuropathologically verified patients presented with a type 1 prion protein pattern. CJD patients were all homozygous for methionine at codon 129. Except in five CJD patients, no beta-amyloid plaques were seen. Additionally, APOE status was determined in patients with CJD. RESULTS: Levels of Abeta1-42 in CSF were decreased in patients with AD as well as in CJD. Levels of Abeta1-42 in CSF of patients with CJD and AD were significantly different from the other dementia and NDC groups. There was no substantial difference between the CJD and AD groups (p = 0.66). Decreased levels of Abeta1-42 did not correlate with the APOE epsilon4 load in patients with CJD. CONCLUSION: Low levels of Abeta1-42 in CSF do not exclude a diagnosis of CJD. Decreased levels of Abeta1-42 in CSF can occur without beta-amyloid plaque formation in the brain. However, the underlying mechanism of this phenomenon must be elucidated.

Clinical and biological findings in a case with 48-hour bipolar ultrarapid cycling before and during valproate treatment.

BACKGROUND: The rare cases of patients with 48-hour ultrarapid cycling allow close investigation of mood cycles in affective disorders, because rhythmic changes in psychopathologic state and biological parameters happen very precisely. METHOD: A 67-year-old white man who had experienced bipolar 48-hour ultrarapid cycling (DSM-IV 296.80) for several years was studied without any medication and then again studied 4 weeks later during treatment with valproate (1800 mg/day). RESULTS: Objective and self ratings revealed pronounced manic states 1 day and depressed states the following day, which were found to be accompanied by rhythmic fluctuations in behavior and electroencephalographic parameters, blood cortisol and growth hormone levels (both elevated on depressive days), and urinary metanephrine (dopamine metabolite) and norepinephrine levels (both elevated on manic days). Using single photon emission computed tomography, regional blood flow in the left thalamus was lower than in the right thalamus on the manic day, while symmetric perfusion of the thalamus was found on the depressive day. Under valproate treatment, the patient remitted completely, and significant rhythmic changes in most of the biological parameters were no longer detectable. CONCLUSION: The biological findings in this patient with bipolar 48-hour ultrarapid cycling, which correspond to those in other types of affective disorders, suggest that disturbances in the diencephalon-pituitary axis may be especially correlated to pathologic changes of mood.

Digitized analysis of abnormal hand-motor performance in schizophrenic patients.

Many studies have shown a high prevalence of discrete neuromotor disturbances in schizophrenic patients. It was hypothesized that these disturbances are lateralized and reflect a neurodevelopmental disorder underlying schizophrenia. A new method for assessing subtle motor dysfunction and hemispheric asymmetries is the registration of hand movements with a digitizing tablet. Using this method, we studied hand-motor dysfunction and its lateralization in schizophrenics, as compared with healthy controls. All subjects (27 schizophrenic patients, 13 of them without neuroleptic medication, the others under neuroleptics; 31 healthy controls) drew super-imposed concentric circles. We computed kinematic parameters reflecting velocity and automatization to quantify neurological soft signs (NSS). The patients had significant impairments of regularity of repetitive hand movements, as compared with the healthy controls (F> or =5.35; p< or =0.024(*)). Comparing differences of left- and right-hand performance between patients and controls, we found longer stroke duration (F=(15,98); p=0.000***) and decreased automatization (F=18,14; p=0.000***), especially on the left side in schizophrenic patients. Measuring hand movements with a digitizing tablet is a sensitive method for assessing subtle motor dysfunction in schizophrenic patients, not reflected in the scores of clinical scales. Our findings show NSS in schizophrenic patients, independently of neuroleptics. Further, the hypothesis of lateralization of cerebral structures generating NSS towards the right hemisphere in schizophrenia is supported.

6-phosphofructo-1-kinase from the lipid accumulating, non-fermentative, red yeast Rhodotorula glutinis.

6-Phosphofructo-1-kinase (PFK, EC 2.7.1.11) activity was detected in extracts of Rhodotorula glutinis grown on different nitrogen and carbon sources. The activity of PFK varied depending on the composition of the culture medium and on the state of growth. Using a carbon-limited medium containing glucose and a mixed organic/inorganic nitrogen source, maximal yield, activity and stability of PFK were found under aerobic conditions at the end of the exponential growth phase. Native Rhodotorula-PFK could be separated by polyacrylamide gel electrophoresis. Applying this method for molecular mass estimation a value of 450 +/- 90 kDa was calculated. Taking into account a molecular mass of 130 +/- 5 kDa for the subunit, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis following immunoblotting, a tetrameric structure of the native PFK is likely. Polyclonal antibodies, raised against PFK from Saccharomyces cerevisiae, were able to cross-react with Rhodotorula-PFK. Therefore, there are similarities in the primary structure of both enzymes. Fructose 2,6-bisphosphate was identified as a significant activator of Rhodotorula-PFK leading to a 10-fold activation of the enzyme: maximal activation was achieved with 5 microM fructose 2,6-bisphosphate.

Digitized analysis of handwriting and drawing movements in healthy subjects: methods, results and perspectives.

The diagnosis of movement disorders and the distinction between their possible generation by drug-treatment or illness can be done more objectively by using digitized analyses of hand movements. The aim of this study was to define this method, that is to identify its reliability and the influence of several covariables upon measurements, in healthy subjects. Simple writing and drawing tests were administered, using a digitizing tablet, transmitting signals to a computer for processing. The kinematic parameters identified in this way provided objective, reliable and valid measures for the dynamics and the degree of automation of hand movements. Analysis of the data showed that younger subjects write faster and with a higher degree of automation than older subjects. Other moderating variables, such as verbal intelligence and customary motor activity in everyday life (motoric practice) could be identified, whereas personality and gender were found to have little influence. There were no significant differences between left-handers and right-handers in hand movements. The movement parameters had a high test retest stability. The results of this study in healthy subjects indicate that age, verbal intelligence and motor practice should be considered when evaluating the effects of drug-treatment or psychiatric illness upon hand-movement in patients.

Alloplastic spermatocele: insemination from epididymal reservoir.

Insemination with the sperm of an epididymal reservoir three days after implantation of the prosthesis led to a successful pregnancy with subsequent delivery of five healthy sucklings. Alloplastic spermatocele can function longer than four months as proved by a successful pregnancy.

Unaltered apoptotic behaviour of mononuclear cells from patients with sporadic Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) belongs to the group of transmissible spongiform encephalopathies. It is suspected that a pathologically altered form of the prion protein (PrPSc) is the decisive trigger of the disease. Data from animal experiments suggest an involvement of the lymphatic system in the intracorporal transport of PrPSc. However, it has not so far been possible to detect PrPSc on mononuclear cells (MNCs) either in the sporadic form of CJD or in the new variant of CJD (vCJD). In order to determine a possible alteration of MNCs in CJD, we investigated the natural and induced apoptotic behaviour of these cells. MNCs from 19 patients with sporadic CJD and from 20 patients with other neurological disorders were used. The cells were analysed by fluorescence cytometry with and without apoptosis induction by xanthine oxidase and hypoxanthine. The apoptosis rate was quantified using the stain 7-amino-actinomycin D (7-AAD). In the morphological investigation of the cells before apoptosis induction, there were no significant differences between the groups with regard to cell size and granularity of the MNCs. After apoptosis induction, the typical significant decrease in cell size and increase in granularity of the cells occurred in both groups. Significant differences between the patient populations were not found. For the first time, our investigation has demonstrated that a functional impairment of MNCs with regard to their apoptotic behaviour does not occur in sporadic CJD. It remains open to question whether this mechanism plays an important role in forms of transmissible encephalopathy other than sporadic CJD, especially after oral transmission.

Modes of allosteric interactions with free and [3H]N-methylscopolamine-occupied muscarinic M2 receptors as deduced from buffer-dependent potency shifts.

Muscarinic M2 acetylcholine receptors contain an allosteric site that is probably located at the entrance of the ligand binding pocket above the orthosteric binding site. With the orthosteric area not occupied, allosteric agents might gain access to this site. The interaction of allosteric agents with orthoster-occupied receptors is known to depend on the buffer conditions in an alloster-specific fashion. Utilizing the buffer-dependent potency shift as an indicator, we aimed to find out for two rod-like shaped and flexible allosteric agents whether or not there is evidence for a switch in the site of attachment in free compared with [3H]N-methylscopolamine ([3H]NMS)-occupied porcine heart M2 receptors. These agents are the bispyridinium compounds WDuo3 (1,3-bis[4-(phthalimidomethoxyimino-methyl)-pyridinium-1-yl] propane dibromide) and Duo3 (4,4'-bis-[(2,6-dichloro-benzyloxy-imino)-methyl]-1,1'-propane-1,3-diyl-bis-pyridinium dibromide). The prototype allosteric agents gallamine and alcuronium were included. Inhibition of [3H]NMS association was taken to reflect alloster interaction with free receptors, inhibition of [3H]NMS dissociation indicated binding to [3H]NMS-occupied receptors. In Na,K,Pi buffer (4 mM Na2HPO4, 1 mM KH2PO4, pH 7.4 at 23 degrees C) compared with Mg,Tris,Cl,Pi buffer (45 mM Tris-HCl, 2.6 mM MgHPO4, pH 7.3 at 37 degrees C) WDuo3 underwent the same loss of potency for the interaction with either free or [3H]NMS-liganded receptors. The loss of potency was quantified by a potency ratio (PR), i.e. the ratio between the concentrations of the modulator leading to a half-maximal delay of [3H]NMS association or dissociation, respectively, in Mg,Tris,Cl,Pi compared with Na,K,Pi. For WDuo3 the ratios were PRass=27 and PRdiss=22, respectively. For Duo3, the interaction with free and [3H]NMS-occupied receptors only slightly depended on the composition of the incubation medium: PRass=1.3, PRdiss=2.8. In contrast to the other agents, the concentration-effect curves of which had slope factors nH not different from unity, the curves of Duo3 were steep (nH about -1.6). For alcuronium the shift factors amounted to PRass=29 and PRdiss=25, for gallamine to PRass=216 and PRdiss=159. In conclusion, there was a wide variation between the allosteric agents with regard to the respective buffer dependence of action. Yet, for a given allosteric agent, the interaction with either free or [3H]NMS-occupied receptors was always characterized by the same buffer-dependent shift. Thus, even the applied rod-shaped allosteric agents do not appear to switch to the orthosteric site in free compared with orthoster-occupied M2 receptors.

The integration of medical images with the electronic patient record and their web-based distribution.

Medical images are currently created digitally and stored in the radiology department's picture archiving and communication system. Reports are usually stored in the electronic patient record of other information systems, such as the radiology information system (RIS) and the hospital information system (HIS). But high-quality services can only be provided if electronic patient record data is integrated with digital images in picture archiving and communication systems. Clinicians should be able to access both systems' data in an integrated and consistent way as part of their regular working environment, whether HIS or RIS. Also, this system should allow for teleconferencing with other users, eg, for consultation with a specialist in the radiology department. This article describes a web-based solution that integrates the digital images of picture archiving and communication systems with electronic patient record/HIS/RIS data and has built-in teleconferencing functionality. This integration has been successfully tested using three different commercial RIS and HIS products.

The German teleradiology system MEDICUS: system description and experiences in a German field test.

MEDICUS is a teleradiology system which has been developed in a joint project of the German Cancer Research Center (Deutsches Krebsforschungszentrum) and the Transfer Center Medical Informatics (Steinbeis-Transferzentrum Medizinische Informatik) in Heidelberg, Germany. The system is designed to work on ISDN lines as well as in a local area network. Special attention has been given to the design of the user interface and data security, integrity, and authentication. The software is in use in 13 radiology departments in university clinics, small hospitals, private practices, and research institutes. More than 25 thousand images have been processed in 6 months. The system is in use in six different application scenarios. MEDICUS is running under the UNIX operating system. The connection of the modalities could in most cases not be realized with the DICOM protocol as older machines were not equipped with this standard protocol. Clinical experiences show that the MEDICUS system provides a very high degree of functionality. The system has an efficient and user friendly graphical user interface. The result of a comparison with other systems shows that MEDICUS is currently the best known teleradiology system. Cost reductions are already obvious, but additional research has to be performed in this field. An even more powerful commercial successor is currently under construction at the Steinbeis-Transferzentrum Medizinische Informatik in Heidelberg.

A three-generation model for teleradiology.

This paper proceeds from the definition of teleradiology. It identifies three different generations of teleradiology systems and includes those systems that are not regarded as teleradiology systems by the authors. A list of requirements pertinent to users of first-generation teleradiology systems is introduced. Most of the requirements have been realized in a new generation teleradiology system called CHILI.

Extending a teleradiology system by tools for visualization and volumetric analysis through a plug-in mechanism.

This paper describes ongoing research concerning interactive volume visualization coupled with tools for volumetric analysis. To establish an easy to use application, the three-dimensional-visualization has been embedded in a state of the art teleradiology system, where additional functionality is often desired beyond basic image transfer and management. Major clinical requirements for deriving spatial measures are covered by the tools, in order to realize extended diagnosis support and therapy planning. Introducing a general plug-in mechanism, this work exemplarily describes the useful extension of an approved application. Interactive visualization was achieved by a hybrid approach taking advantage of both the precise volume visualization based on the Heidelberg ray-tracing model and the graphics acceleration capabilities of modern workstations. Several tools for volumetric analysis extend the three-dimensional-viewing. They are controlled by adequate input devices to select locations in the data volume, measure anatomical structures or initiate a segmentation process. Moreover, a haptic interface can be connected to provide a more realistic feedback while navigating within the three-dimensional-reconstruction. The work is closely related to research in the field of heart, liver and head surgery. In cooperation with our medical partners the development of tools as presented facilitates the integration of image analysis into the clinical routine.

The HELIOS Medical Connection Services.

This paper presents the design and implementation of the HELIOS software component that deals with integration of medical applications in health information networks. The problem of interoperability between health information systems based on different data exchange syntaxes is first discussed. A meta-model, relying on CEN TC251 recommendations, is then presented as a possible solution to this problem and a message description language including these recommendations is proposed. Using this meta-model, the Medical Connection Services that comprises a generic message processing automaton, a resource manager and a mapper is able either to interpret messages expressed in a given syntax (e.g., EDIFACT, ASTM) and map them to the application objects or to automate the translation of the messages in another syntax. Special focus is given on the position of the Medical Connection Services within the HELIOS integration strategy (i.e., through data, presentation and communication). The problem of semantic heterogeneity is then discussed.