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.

Neuronal repair. Asynchronous therapy restores motor control by rewiring of the rat corticospinal tract after stroke.

The brain exhibits limited capacity for spontaneous restoration of lost motor functions after stroke. Rehabilitation is the prevailing clinical approach to augment functional recovery, but the scientific basis is poorly understood. Here, we show nearly full recovery of skilled forelimb functions in rats with large strokes when a growth-promoting immunotherapy against a neurite growth-inhibitory protein was applied to boost the sprouting of new fibers, before stabilizing the newly formed circuits by intensive training. In contrast, early high-intensity training during the growth phase destroyed the effect and led to aberrant fiber patterns. Pharmacogenetic experiments identified a subset of corticospinal fibers originating in the intact half of the forebrain, side-switching in the spinal cord to newly innervate the impaired limb and restore skilled motor function.

[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.

High-dose corticosteroids after spinal cord injury reduce neural progenitor cell proliferation.

We assessed whether a clinical dose of the anti-inflammatory drug methylprednisolone (MP) given to adult mice acutely after spinal cord injury (SCI) influences spinal cord or hippocampal progenitor cells. Mice underwent a thoracic dorsal hemisection of the spinal cord and received 30 mg/kg MP immediately and 24 h post-lesion. 5-Bromo-2-deoxyuridine (BrdU) was administered after lesion either acutely (1-6 days) or late (22-27 days) to label proliferating cells. Reaction of microglia/macrophages was quantified 7 days post-lesion and proliferation as well as differentiation of neural progenitor cells (NPCs) was analyzed after two survival times (7 days and 28 days). We also tested the influence of MP on microglia and adult NPCs in vitro. MP treatment reduced the number of cells proliferating acutely after SCI in the spinal cord and hippocampus. Besides reducing activation and proliferation of microglia/macrophages in the spinal cord, MP also decreased the number of oligodendrocyte progenitor cells (OPCs). Analysis of acutely BrdU-labeled cells at 28 days post-lesion suggests that proliferation and number of OPCs were changed chronically. Late proliferating cells were no longer influenced by the glucocorticoid regimen. In vitro experiments showed an inhibitory effect of MP on adult spinal cord and hippocampal progenitor cell proliferation. Both cell types express the glucocorticoid and mineralocorticoid receptors allowing a direct effect of MP. Our results show that MP reduces OPC proliferation after SCI either by affecting progenitor cells directly or via its anti-inflammatory effects. These findings open the question to which extent MP treatment limits the repair capacity of endogenous progenitor cells after CNS injury.

Teleradiology applications with DICOM-e-mail.

For the connection of several partners to a Dicom-e-mail based teleradiology network concepts were developed to allow the integration of different teleradiology applications. The organisational and technical needs for such an integration were analysed. More than 60 institutions including 23 hospitals in the Rhein-Neckar-Region, Germany were connected. The needed functionality was grouped in six teleradiology applications (emergency consultation, tele-guided examinations, expert consultations, cooperative work, scientific cooperations and homework with on call services) and their technical and organisational needs according to availability, speed of transfer, workflow definitions and data security needs was analysed. For the local integration of teleradiology services the setup and workflow is presented for a standalone teleradiology workstation and a server based teleradiology gateway. The line type needed for different groups of applications and users is defined. The security concept and fallback strategies are laid out, potential security problems and sources of errors are discussed. The specialties for the emergency teleradiology application are presented. The DICOM-e-mail protocol is a flexible and powerful protocol that can be used for a variety of teleradiology applications. It can meet the conditions for emergency applications but is limited if synchronous applications like teleconferences are needed.

Standardization of teleradiology using Dicom e-mail: recommendations of the German Radiology Society.

Until recently there has been no standard for an interoperable and manufacturer-independent protocol for secure teleradiology connections. This was one of the main reasons for the limited use of teleradiology in Germany. Various teleradiology solutions have been developed in the past, but the vast majority have not been interoperable. Therefore an ad hoc teleradiology connection was impossible even between partners who were already equipped with teleradiology workstations. Based on the evaluation of vendor-independent protocols in recent years the IT Working Group (AGIT) of the German Radiology Society set up an initiative to standardize basic teleradiology. An e-mail based solution using the Dicom standard for e-mail attachments with additional encryption according to the OpenPGP standard was found to be the common denominator. This protocol is easy to implement and safe for personalized patient data and fulfills the legal requirements for teleradiology in Germany and other countries. The first version of the recommendation was presented at the 85th German Radiology Convention in 2004. Eight commercial and three open-source implementations of the protocol are currently available; the protocol is in daily use in over 50 hospitals and institutions.

[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.

Whipple's disease presenting as an isolated lesion of the cervical spinal cord.

Chronic myelitis from Whipple's disease of the spinal cord is extremely rare. The differential diagnosis includes chronic inflammatory lesions, viral or bacterial infections, and tumours of the spinal cord. Here we present a 50-year-old man with mild sensory deficits because of a large lesion of the cervical spinal cord who markedly showed improvement during probatory antibiotic therapy. PCR and jejunal biopsy were initially negative and only later confirmed the diagnosis of Whipple's disease. Clinical and neuroradiological criteria are suggested which may be of help in the early diagnosis of spinal Whipple's disease before confirmation by molecular biology or histology.

Sporadic Creutzfeldt-Jakob disease: magnetic resonance imaging and clinical findings.

OBJECTIVE: To assess if clinical features, prion protein codon 129, and molecular subtype correlate with MRI basal ganglia hyperintensity in sporadic Creutzfeldt-Jakob disease (CJD). METHODS: The authors studied 219 patients including 153 confirmed CJD cases for their neurologic symptoms and MRI findings. The MRI was assessed by a blinded investigator for the presence of high signal intensity on T2-weighted images in the basal ganglia. RESULTS: Patients with basal ganglia high signal on T2-weighted images were more likely to present with rapid progressive dementia in an early stage and shorter disease duration (median 6.7 months and 8.6 months). Surprisingly, among the CJD cases, patients without signal increase of the basal ganglia were shown to have a higher frequency of extrapyramidal disturbances (82% vs 70%). More striking differences were found for symptoms such as depression and sensory disturbances, which were more frequent among cases without signal increase. MRI was more likely to be diagnostic in patients with MV2 molecular subtype. CONCLUSIONS: Selected clinical and pathologic features correlate with the presence of basal ganglia high signal on T2-weighted MRI in patients with definite or probable CJD.

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.

Kinematical analysis of handwriting movements in depressed patients.

OBJECTIVE: Motor disturbances are a relevant aspect of depression. Kinematical analysis of movements can be applied to explore which type of motor dysfunction is associated with depression. We hypothesized that depressed patients draw and write significantly slower than controls and that motor disturbances become more pronounced under bi-manual demands. METHOD: We examined 37 depressed patients and 37 healthy controls using a digitizing graphic tablet and subsequent kinematical analysis of handwriting and rapid drawing movements. RESULTS: Depressed patients performed drawing with significantly less regular velocity than controls (P < 0.001), but normal velocity. Motor differences between patients and controls did not increase under bi-manual demands. Handwriting of patients was abnormally slow (P = 0.04). CONCLUSION: Irregular patterns of velocity peaks in depressed patients point to basal ganglia dysfunction and/or deficient activity of the sensorimotor cortex and the supplementary motor area as a possible substrate of hand-motor disturbances in depression.

CSF lactate dehydrogenase activity in patients with Creutzfeldt-Jakob disease exceeds that in other dementias.

The diagnosis of Creutzfeldt-Jakob disease (CJD) is still made by exclusion of other dementias. We now evaluated lactate dehydrogenase (LDH) in the cerebrospinal fluid (CSF) as a possible additional diagnostic tool. CSF LDH levels of patients with CJD (n = 26) were compared with those in other dementias (n = 28). LDH isoenzymes were determined in a subset (n = 9). Total LDH and isoenzyme LDH-1 were significantly higher, whereas the fractions of LDH-2 and LDH-3 were significantly lower in CJD patients. We conclude that in addition to established CSF parameters, LDH and its isoenzymes might serve as a further help to discriminate between CJD and other dementias.

Long-term inter-episode stability of syndromes underlying mania.

OBJECTIVE: To explore the stability of diverse manic presentations across manic recurrences. METHOD: A total of 253 bipolar patients who experienced two or more hospitalizations, because of consecutive manic (or mixed) episodes, during a 20-year period were included. All patients had second hospitalizations with an mean interval of 773 days, while 126 and 91 patients had third and fourth hospitalizations with mean intervals of 1559 and 2237 days from the index hospitalization, respectively. Seven symptom scores, previously factor-validated, were calculated. RESULTS: Depressive mood, irritable aggression, psychomotor/thought inhibition, mania, emotional lability/agitation and psychosis were moderately correlated across the index and subsequent hospitalizations. CONCLUSION: A majority of diverse manic presentations were stable across manic recurrences. The stability was not restricted to two consecutive recurrences but appeared widespread over the long-term course of bipolar disorder. The finding may serve for the development of more effective long-term treatment strategies and a clinically more reasonable subtyping of mania.

Frequency of manic symptoms during a depressive episode and unipolar 'depressive mixed state' as bipolar spectrum.

OBJECTIVE: To report the frequency of intra-episode manic symptoms in depressive episodes, and to evaluate unipolar depressive mixed state (DMS) as bipolar spectrum. METHOD: A total of 958 (863 unipolar, 25 bipolar II, and 70 bipolar I) depressive in-patients were assessed in terms of manic symptoms at admission, and several clinical variables using standardized methods. RESULTS: The frequency of manic symptoms (flight of idea, logorrhea, aggression, excessive social contact, increased drive, irritability, racing thoughts, and distractibility) was significantly higher in bipolar depressives than in unipolar depressives. Unipolar depressives with DMS - defined as having two or more manic symptoms - had more similarities to bipolar depressives than to other unipolar depressives in clinical variables such as onset age, family history of bipolar disorder, and possibly suicidality. CONCLUSION: Depressive mixed state is frequent, particular in bipolar depressives. Unipolar depressives with DMS may be better classified into bipolar spectrum.

Kinematic analysis of handwriting movements in patients with Alzheimer's disease, mild cognitive impairment, depression and healthy subjects.

A variety of studies have demonstrated that motor disorders, parkinsonism and extrapyramidal motor symptoms (EPMS) are common in patients with Alzheimer's disease (AD). Several studies have reported an association of EPMS with severity, progression and poor prognosis of AD. The majority of these studies used clinical assessments for the rating of EPMS. In this study, kinematic handwriting analysis was used to quantify differences in fine hand motor function in patients with probable AD and mild cognitive impairment (MCI, as an assumed initial stage of AD) compared to depressed patients and healthy controls. Both patients with MCI and patients with probable AD exhibited loss of fine motor performance. Movements of AD patients were significantly less regular than those of healthy controls.

[Evaluation of CHILI teleradiology network 4 years after clinical implementation]. / Evaluation des CHILI-Teleradiologienetzwerks nach 4 Jahren im klinischen Einsatz.

The CHILI teleradiology network has more than 60 installations in Germany and the USA. Radiological images and cardiological multiframe series are exchanged in clinical routine. This article investigates in what way and how often the system is used. This is done by means of accounting files that are produced automatically by the system. User functions, transmission protocols, data quantity, frequencies and time of data transmission and teleconferences are evaluated and discussed in this paper. Different application scenarios have been identified and are described and analyzed as well. An important result is, that the system is not merely an emergency system. Instead, it is used in daily routine as a multifunctional, multimodality workstation with advanced features for teleradiology and telecardiology.

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.