[The role of Integrating the Healthcare Enterprise (IHE) in telemedicine]. / Die Rolle von Integrating the Healtcare Enterprise (IHE) in der Telemedizin.

BACKGROUND: Telemedicine systems are today already used in a variety of areas to improve patient care. The lack of standardization in those solutions creates a lack of interoperability of the systems. Internationally accepted standards can help to solve the lack of system interoperability. With Integrating the Healthcare Enterprise (IHE), a worldwide initiative of users and vendors is working on the use of defined standards for specific use cases by describing those use cases in so called IHE Profiles. OBJECTIVES: The aim of this work is to determine how telemedicine applications can be implemented using IHE profiles. METHODS: Based on a literature review, exemplary telemedicine applications are described and technical abilities of IHE Profiles are evaluated. These IHE Profiles are examined for their usability and are then evaluated in exemplary telemedicine application architectures. RESULTS: There are IHE Profiles which can be identified as being useful for intersectoral patient records (e.g. PEHR at Heidelberg), as well as for point to point communication where no patient record is involved. In the area of patient records, the IHE Profile "Cross-Enterprise Document Sharing (XDS)" is often used. The point to point communication can be supported using the IHE "Cross-Enterprise Document Media Interchange (XDM)". IHE-based telemedicine applications offer caregivers the possibility to be informed about their patients using data from intersectoral patient records, but also there are possible savings by reusing the standardized interfaces in other scenarios.

Tentorial Venous Anatomy: Variation in the Healthy Population.

BACKGROUND AND PURPOSE: A new transtentorial venous system consisting of medial, intermediate, and lateral tentorial veins, connecting infra- and supratentorial compartments, was recently shown in 2 cadaver dissections and 2 patient scans. We sought to characterize the venous patterns within the tentorium and their relation to measures of skull development in a cohort of healthy adults. MATERIALS AND METHODS: We retrospectively reviewed tentorial venous anatomy of the head using CTA/CTV performed for routine care or research purposes in 238 patients. Included studies had adequate contrast opacification of venous structures and a section thickness of ≤2 mm; we excluded cases with space-occupying lesions and vascular pathologies. Tentorial angle, dural sinus configurations, and measures of skull base development were assessed as predictors of tentorial venous anatomy variation via Cramér V association, the binary encoded Pearson correlation, and nearest-point algorithm with the Euclidean distance metric for clustering. RESULTS: Tentorial vein development was related to the ringed configuration of the tentorial sinuses (P < .005). There were 3 configurations. Groups 1A and 1B (n = 50/238) had ringed configuration, while group 2 did not (n = 188/238). Group 1A (n = 38/50) had a medialized ringed configuration, and group 1B had a lateralized ringed configuration (n = 12/50). Measurements of skull base development were predictive of these groups. The ringed configuration of group 1 was related to the presence of a split confluens, which correlated with a decreased internal auditory canal-petroclival fissure angle. Configuration 1A was related to the degree of petrous apex pneumatization (P value = .010). CONCLUSIONS: Variations in the transtentorial venous system directly correlate with cranial development.

Mechanism of dexamethasone suppression of brain tumor-associated vascular permeability in rats. Involvement of the glucocorticoid receptor and vascular permeability factor.

Brain tumor-associated cerebral edema arises because tumor capillaries lack normal blood-brain barrier function; vascular permeability factor (VPF, also known as vascular endothelial growth factor, VEGF) is a likely mediator of this phenomenon. Clinically, dexamethasone reduces brain tumor-associated vascular permeability through poorly understood mechanisms. Our goals were to determine if suppression of permeability by dexamethasone might involve inhibition of VPF action or expression, and if dexamethasone effects in this setting are mediated by the glucocorticoid receptor (GR). In two rat models of permeability (peripheral vascular permeability induced by intradermal injection of 9L glioma cell-conditioned medium or purified VPF, and intracerebral vascular permeability induced by implanted 9L glioma), dexamethasone suppressed permeability in a dose-dependent manner. Since 80% of the permeability-inducing activity in 9L-conditioned medium was removed by anti-VPF antibodies, we examined dexamethasone effects of VPF expression in 9L cells. Dexamethasone inhibited FCS- and PDGF-dependent induction of VPF expression. At all levels (intradermal, intracranial, and cell culture), dexamethasone effects were reversed by the GR antagonist mifepristone (RU486). Dexamethasone may decrease brain tumor-associated vascular permeability by two GR-dependent mechanisms: reduction of the response of the vasculature to tumor-derived permeability factors (including VPF), and reduction of VPF expression by tumor cells.

Phase II trial of chemotherapy alone for primary CNS and intraocular lymphoma.

PURPOSE: Primary CNS lymphoma (PCNSL) and primary intraocular lymphoma (IOL) are usually treated with radiation therapy alone or in combination with chemotherapy. The neurotoxicity of these treatments can be substantial. This study attempts to define the toxicity and efficacy of the treatment of this disease with chemotherapy alone. PATIENTS AND METHODS: Fourteen nonimmunocompromised patients were accrued to a chemotherapy regimen that incorporated a 24-hour infusion of high-dose methotrexate total dose of 8.4 g/m2 with leucovorin rescue; thiotepa 35 mg/m2; vincristine 1.4 mg/m2; dexamethasone; and intrathecal cytarabine (Ara-C) and methotrexate (MTV) administered in 21-day cycles. Seven patients were prospectively followed up with formal neuropsychologic assessments for evidence of CNS toxicity. RESULTS: The response rate was 100% with 11 (79%) complete responses and three (21%) partial responses. Cumulative survival and progression-free survival rates at more than 4.5 years were 68.8% and 34.3%, respectively. Median survival has not been reached, and median progression-free survival was 16.5 months. Toxicity included severe leukoencephalopathy that was clearly attributable to chemotherapy (two patients), grade 3 or 4 neutropenia in 50% of the cycles administered, ileus (one patient), and seizures (two patients). Mucositis and renal and hepatic toxicity were mild and not therapy limiting. CONCLUSION: The MTV regimen is generally well tolerated and produces a high complete response rate. Chemotherapy alone should be investigated further in this disease to assess the necessity of initial radiation therapy, either alone or in combined modality regimens, for the achievement of optimal response and survival.

Vascular endothelial growth factor (VEGF) modulates vascular permeability and inflammation in rat brain.

Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that also induces vascular permeability and macrophage migration. VEGF expression is weak in normal adult brain, but is strongly upregulated in glioma cells and reactive astrocytes, suggesting that chronic overexpression of VEGF in the brain contributes to blood-brain barrier (BBB) breakdown. We examined the effects of chronic VEGF overexposure on the integrity of the BBB using the following approaches: 1) continuous intracerebral infusion of VEGF via miniosmotic pump; and 2) intracerebral injection of an adenoviral vector encoding the VEGF165 gene (AdCMV.VEGF). After 6 days both treatments produced approximately 10-fold breakdown of the BBB (as measured by transport of 14C-aminoisobutyric acid (AIB) from blood into brain) compared with the respective controls (albumin infusion or AdCMV.beta gal virus). BBB disruption in AdCMV.VEGF-treated brains was accompanied by a severe inflammatory response not observed in brains receiving AdCMV.beta gal or VEGF protein infusion, indicating that neither VEGF nor viral particles alone were responsible for the inflammatory response. However, injection of AdCMV.beta gal followed by VEGF infusion to the same site also elicited inflammation. Chronic overexposure of normal brain to VEGF also increased intercellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex (MHC) class I and II expression. Although VEGF itself is not inflammatory, VEGF may modulate immune responses in the central nervous system (CNS) by opening the BBB, altering the immunoprivileged status of the brain, and allowing contact between normally sequestered CNS antigens and blood-borne immune mediators.

Tumor devascularization by intratumoral ethanol injection during surgery. Technical note.

Preoperative reduction in tumor vascularity has been accomplished previously by selective catheterization of tumor vessels and delivery of occlusive materials. The results of percutaneous infusion of vertebral hemangiomas and other vascular lesions led the authors to speculate that rapid devascularization of tumors by direct injection of ethanol (ETOH) could be used to reduce bleeding and facilitate resection during surgery. Thus, the use of intratumoral injection of ETOH and its effects on tumor hemostasis and resectability were examined. Four patients received direct injection of ETOH into either a spinal epidural (two renal cell carcinomas and one rhabdomyosarcoma) or a large cerebellar neoplasm (hemangioblastoma). Intraoperative perfusion of the tumors with ETOH produced immediate blanching and devascularization and enhanced visualization and resection. Incremental tumor devascularization is achieved by careful injection of small amounts of ETOH directly into the lesion, producing immediate and complete regional tumor devascularization. Use of this technique reduces intratumoral bleeding and enhances the ease and effectiveness of resection.

In vivo transfer of the human interleukin-2 gene: negative tumoricidal results in experimental brain tumors.

The authors have recently shown the feasibility of eradicating brain tumors using in vivo retroviral-mediated transduction of tumors with the herpes simplex thymidine kinase (HStk) gene and ganciclovir therapy. However, thymidine kinase-transduced subcutaneous tumors in immunocompromised (athymic) mice were less responsive to this therapy than in immunocompetent animals, suggesting a role of the immune system in the process of tumor eradication. Broad suppression of humoral and cell-mediated immunity is found in patients with malignant gliomas. Interleukin-2 (IL-2) production and IL-2 receptor expression are decreased in gliomas patients. These findings and the proposed association between lymphocytic infiltration of brain tumors and survival suggest that immune response modifiers may be useful in treating glioma patients. To evaluate the role of local cytokine expression by tumor cells, alone or combined with HStk gene transfer and ganciclovir therapy, the authors investigated the efficacy of tumor (9L gliosarcoma) eradication in Fischer rats by in vitro and in vivo tumor transduction with the IL-2 gene alone or with a combined vector carrying both the HStk and IL-2 genes. Tumors injected with HStk vector-producer cells alone, with or without ganciclovir, and rats inoculated in the brain and subcutaneously with 9L cells that had previously been transduced in vitro served as controls. Murine vector-producer cells (3 x 10(6)/50 microliters) were injected into the brain tumors 7 days after tumor inoculation. Ganciclovir (15 mg/kg) was administered intraperitoneally twice daily for 10 days to animals that received HStk with or without IL-2 vector-producer cells, starting 5 days after producer-cell injection. The experiment was repeated with continuous daily treatment of all rats with oral dexamethasone (0.5 mg/kg). Rats were sacrificed 21 days after tumor inoculation, and the brains were removed for histological and immunohistochemical analysis for IL-2. Within each experimental group, tumors were found in a similar proportion in the dexamethasone-treated and untreated rats. Large brain tumors developed in all 10 rats that had been inoculated with 9L cells which had been pretransduced in vitro with the IL-2 gene, whereas only three of eight rats receiving subcutaneous inoculation of similar cells developed palpable tumors. No enhancement of tumor eradication was observed by adding the IL-2 gene in the HStk vector construct compared to the use of the vector with HStk alone. Lymphocytic infiltration was absent in all dexamethasone-treated rats but was observed in all treatment groups not receiving steroids.(ABSTRACT TRUNCATED AT 400 WORDS)

Spinal cord swelling preceding syrinx development. Case report.

The pathophysiology of syrinx development is controversial. The authors report on a patient with progressive cervical myelopathy and a Chiari I malformation in whom spinal cord swelling preceded, by a few months, the development of a syrinx in the same location. The patient underwent a craniocervical decompressive procedure and duraplasty, and complete resolution of cord swelling and syringomyelia was achieved. This report is consistent with the theory that patients with Chiari I malformation have increased transmural flow of cerebrospinal fluid, which causes spinal cord swelling that later coalesces into a syrinx. The pathophysiology of syrinx development from spinal cord edema and the success of surgical decompressive treatments that do not invade the central nervous system support the prompt treatment of patients with spinal cord edema who are at risk for the development of a syrinx.

Elucidating the pathophysiology of syringomyelia.

OBJECT: Syringomyelia causes progressive myelopathy. Most patients with syringomyelia have a Chiari I malformation of the cerebellar tonsils. Determination of the pathophysiological mechanisms underlying the progression of syringomyelia associated with the Chiari I malformation should improve strategies to halt progression of myelopathy. METHODS: The authors prospectively studied 20 adult patients with both Chiari I malformation and symptomatic syringomyelia. Testing before surgery included the following: clinical examination; evaluation of anatomy by using T1-weighted magnetic resonance (MR) imaging; evaluation of the syrinx and cerebrospinal fluid (CSF) velocity and flow by using phase-contrast cine MR imaging; and evaluation of lumbar and cervical subarachnoid pressure at rest, during the Valsalva maneuver, during jugular compression, and following removal of CSF (CSF compliance measurement). During surgery, cardiac-gated ultrasonography and pressure measurements were obtained from the intracranial, cervical subarachnoid, and lumbar intrathecal spaces and syrinx. Six months after surgery, clinical examinations, MR imaging studies, and CSF pressure recordings were repeated. Clinical examinations and MR imaging studies were repeated annually. For comparison, 18 healthy volunteers underwent T1-weighted MR imaging, cine MR imaging, and cervical and lumbar subarachnoid pressure testing. Compared with healthy volunteers, before surgery, the patients had decreased anteroposterior diameters of the ventral and dorsal CSF spaces at the foramen magnum. In patients, CSF velocity at the foramen magnum was increased, but CSF flow was reduced. Transmission of intracranial pressure across the foramen magnum to the spinal subarachnoid space in response to jugular compression was partially obstructed. Spinal CSF compliance was reduced, whereas cervical subarachnoid pressure and pulse pressure were increased. Syrinx fluid flowed inferiorly during systole and superiorly during diastole on cine MR imaging. At surgery, the cerebellar tonsils abruptly descended during systole and ascended during diastole, and the upper pole of the syrinx contracted in a manner synchronous with tonsillar descent and with the peak systolic cervical subarachnoid pressure wave. Following surgery, the diameter of the CSF passages at the foramen magnum increased compared with preoperative values, and the maximum flow rate of CSF across the foramen magnum during systole increased. Transmission of pressure across the foramen magnum to the spinal subarachnoid space in response to jugular compression was normal and cervical subarachnoid mean pressure and pulse pressure decreased to normal. The maximum syrinx diameter decreased on MR imaging in all patients. Cine MR imaging documented reduced velocity and flow of the syrinx fluid. Clinical symptoms and signs improved or remained stable in all patients, and the tonsils resumed a normal shape. CONCLUSIONS: The progression of syringomyelia associated with Chiari I malformation is produced by the action of the cerebellar tonsils, which partially occlude the subarachnoid space at the foramen magnum and act as a piston on the partially enclosed spinal subarachnoid space. This creates enlarged cervical subarachnoid pressure waves that compress the spinal cord from without, not from within, and propagate syrinx fluid caudally with each heartbeat, which leads to syrinx progression. The disappearance of the abnormal shape and position of the tonsils after simple decompressive extraarachnoidal surgery suggests that the Chiari I malformation of the cerebellar tonsils is acquired, not congenital. Surgery limited to suboccipital craniectomy, C-I laminectomy, and duraplasty eliminates this mechanism and eliminates syringomyelia and its progression without the risk of more invasive procedures.

Root and spinal cord compression from methylmethacrylate vertebroplasty.

STUDY DESIGN: Case report and literature review. OBJECTIVES: Clinicians use methylmethacrylate vertebroplasty to treat vertebral hemangiomas, metastases, and osteoporotic fractures. Cement may leak out of the vertebral body and compress the adjacent spinal cord and nerve roots. We review a case of nerve-root and cord compression from methylmethacrylate extrusion during vertebroplasty. SUMMARY OF BACKGROUND DATA: A 50-year-old female presented with disabling thoracic back pain. A metastasis to T1 was discovered, with collapse of the vertebral body but without cord compression. Methylmethacrylate vertebroplasty was performed. After injection, portable computed tomography (CT) showed a leakage of methylmethacrylate into the C8 and T1 foramina and spinal canal. Radiculopathy and myelopathy developed. Surgical decompression using the anterior approach was necessary. METHODS: Case report. RESULTS: Early surgical intervention decompressed the neural elements and relieved the neurological deficits. CONCLUSIONS: Neurologic complications of methylmethacrylate vertebroplasty necessitate active involvement of spine surgeons in patient evaluation and management.

[Dynamic MRI of the bone marrow for monitoring multiple myeloma during treatment with thalidomide as monotherapy or in combination with CED chemotherapy]. / Dynamische MRT des Knochenmarks zum Monitoring des Multiplen Myeloms unter Thalidomid-Monotherapie oder Kombination mit CED-Chemotherapie.

PURPOSE: To quantify changes of bone marrow microcirculation in multiple myeloma (MM) using contrast enhanced dynamic MRI (dMRI) during thalidomide as antiangiogenic monotherapy or in combination with chemotherapy (cyclophosphamide, etoposide, dexamethasone). MATERIALS AND METHODS: The study includes 63 patients with refractory or relapsed MM, who underwent dMRI with high temporal resolution (T1w-turboFLASH) of the lumbar spine before and following treatment. The contrast uptake was quantified using a two compartment model with the output parameters amplitude and k (ep) (exchange rate constant). The evaluation considered the initial dMRI finding (pathological or non-pathological) and the clinical therapeutic response (response or no response). RESULTS: During monotherapy with thalidomide (n = 38), no significant changes of the dMRI parameters were found, even when considering the initial dMRI finding (positive n = 22) and the therapeutic response (responder n = 14). The combination with chemotherapy (n = 25) had a significant reduction of k (ep) (p = 0.01) in 18 patients with positive initial dMRI finding and therapeutic response. Reduction of the amplitude was seen in most cases, but in the end without any significance (p = 0.09). CONCLUSION: dMRI can quantify significant changes of bone marrow microcirculation solely during treatment with thalidomide combined with chemotherapy, not with thalidomide alone.

Retrospective analysis of surgical treatment outcomes for gelastic seizures: a review of the literature.

Gelastic seizures are known to be refractory to medical treatment and to date surgical therapy has yet to pinpoint the best treatment for these refractory seizures. There has been a multitude of case reports published on gelastic seizures and different surgical treatments, thus we performed a review of the literature on gelastic seizures and surgical treatments to elucidate the best surgical approaches for medically refractory gelastic seizures.

Leucocyte aggregation in burned patients.

Leucocyte aggregation describes one type of biophysical behaviour of white cells. To test whether this parameter is changed in burned patients, 15 burn victims were investigated immediately after admission into hospital. Cell counts and aggregation were measured and related to the prognosis of the injury. Compared with normal controls, burning injury is associated with higher white cell counts and enhanced leucocyte aggregation. Fatal injuries showed a (non-significant) tendency for higher aggregation values than survivors. There are significant positive correlations between white cell counts, maximal aggregation values and the burned body surface area. The results suggest that leucocyte aggregation is pathologically enhanced in response to burns. Possibly this alteration is of prognostic importance.

Polysomnographic pattern recognition for automated classification of sleep-waking states in infants.

A robust, automated pattern recognition system for polysomnography data targeted to the sleep-waking state and stage identification is presented. Five patterns were searched for: slow-delta and theta wave predominance in the background electro-encephalogram (EEG) activity; presence of sleep spindles in the EEG; presence of rapid eye movements in an electro-oculogram; and presence of muscle tone in an electromyogram. The performance of the automated system was measured indirectly by evaluating sleep staging, based on the experts' accepted methodology, to relate the detected patterns in infants over four months of post-term age. The set of sleep-waking classes included wakefulness, REM sleep and non-REM sleep stages I, II, and III-IV. Several noise and artifact rejection methods were implemented, including filters, fuzzy quality indices, windows of variable sizes and detectors of limb movements and wakefulness. Eleven polysomnographic recordings of healthy infants were studied. The ages of the subjects ranged from 6 to 13 months old. Six recordings counting 2665 epochs were included in the training set. Results on a test set (2,369 epochs from five recordings) show an overall agreement of 87.7% (kappa 0.840) between the automated system and the human expert. These results show significant improvements compared with previous work.

"Hidden" bone metastasis from thyroid carcinoma: a clinical note.

The (131)I-iodide ((131)I) whole-body scan, for thyroid carcinoma is at times difficult to interpret. In a diagnostic whole body (131)I scan of a patient with follicular carcinoma, a posterior skull lesion was partially hidden by overlapping facial structures. On lateral head view, the abnormality was clearly evident. SPECT/CT and MRI showed the lesion originated in the occipital bone and had enlarged into the posterior fossa. The mass was surgically removed and the patient received (131)I therapy for residual tissue. The study demonstrates a pitfall in the reading of two dimensional radioiodine images which can be overcome by SPECT or lateral imaging.