Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preliminary reports have shown a close correlation between the anatomic location of evoked magnetic somatosensory fields and intraoperative evoked somatosensory potentials in patients with mass lesions. We have performed magnetic source imaging (MSI) of sensory and motor (MER) evoked responses or fields on 4 patients with frontal convexity epileptic foci. The method involves (1) graphic overlaying of magnetoencephalography evoked field data and three-dimensional (3D) phase contrast magnetic resonance angiographic data on 3D MRI surface cortical renderings, and (2) correlating these data with intraoperative stimulation-mapped sensory and/or motor responses and local cortical venous anatomy. Our initial results indicate that the location of MSI evoked sensory data correlates closely with the results of intraoperative stimulation mapping. MSI MERs have tended to show a less discrete spatial topography, involving areas of cortex extending beyond the motor strip.
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PMID:Multichannel magnetoencephalographic mapping of sensorimotor cortex for epilepsy surgery. 763 Oct 76

This study was performed to make a normal standard by analyzing normal knee movement in detail. An open low-field unit was used for 23 healthy knee joints. With three-dimensional Fourier transformation (3DFT) gradient echo sequence, 50 sagittal slices of 4.5 mm in thickness were obtained at four flexion angles: 0, 30, 60, and 90 degrees (lateral position). Although the tension ratio of the anterior and posterior cruciate ligaments (ACL, PCL) increased during knee flexion, the change in the tension ratio was significantly different between the ACL and PCL. The femur-ACL angle and femur-PCL angle were parallel with the knee flexion angle, but the tibia-ACL angle and tibia PCL angle changed complexly. The lateral and medial condyles rolled and slid during knee flexion, and the medial side moved more than the lateral side, consistent with rotation of the lower thigh. The difference in backward movement distance on the tibia between the two condyles was significantly larger in females than in males. This might explain the dominance of knee osteoarthritis in women. Although the lateral position is not completely physiological, we could show initial cinematic data of up to 90 degrees of knee flexion using open-type MRI, which is impossible with high- and middle-field machines.
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PMID:Analysis of knee movement with low-field MR equipment--a normal volunteer study. 780 8

The aim of this paper was to evaluate the outcome and the factors predictive for a good prognosis of resective surgery for intractable partial epilepsy guided by subdural electrode arrays (SEA's) and operative electrocorticography. Sixty-four patients, aged 8-52 years, were evaluated with chronic SEAs in order to record interictal and ictal activity and delineate speech and motor areas by functionally mapping. Resection were individualized to each patient's SEA recorded electrocorticogram and operative electrocorticogram and functional mapping results (tailored resection). The follow-up time was a minimum of one year. Good seizure outcome was defined as seizure free from complex partial and secondary generalized seizures. After one year 70% of the patients with a temporal ictal focus was seizure free compared to 55% of the patients with an extra-temporal focus. Complete resection of interictal or ictal fields as mapped with SEAs, gave better prognosis than partial resection. Patients with no postresection spikes had a better prognosis than patients with residual postresection spikes evaluated with operative electrocorticography. Sex, age, duration of epilepsy prior to surgery, extent of temporal lobe resection and structural abnormalities determined by MRI were not associated with a favorable seizure outcome after surgery. We conclude that complete resection of the interictal and ictal field mapped with SEA's and absence of postresection spikes on operative electrocorticography are associated with an excellent seizure outcome.
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PMID:Outcome of resective surgery for intractable partial epilepsy guided by subdural electrode arrays. 835 70

Because SRS identifies 90% of hepatic metastatic disease and the addition of other studies (ultrasonography, C.T. MRI, and selective mesenteric angiography) identities only 4% more, the identification of a primary lesion with SRS obviates for the most part the use of further investigations. If SRS is negative, additional studies should only be undertaken if surgery is contemplated. Because SRS may only localize 60%-70% of primary gut NETs, an additional 10%-15% may be identified by undertaking additional studies. The most sensitive test, STIR-MRI, should be undertaken next, but because it is not widely available, pancreatic protocol CT scan is almost as effective in identification of a primary lesion. If a primary gastrinoma cannot be identified by SRS or STIR-MRI, endoscopic ultrasonography should be undertaken because duodenal gastrinomas are often minute and multicentric. A similar strategy applies for insulinomas because up to 40% cannot be located by SRS and the majority are located in the pancreatic head. Thus, STIR-MRI followed by endoscopic ultrasonography is the most appropriate course. Although calcium provocation-angiography is highly effective in the identification of insulinomas, it is significantly more invasive and should be used only as a last resort. Of particular interest is the observation that in the study of gastrinomas, SRS altered clinical management in almost 50% of patients. This reflected the ability of SRS not only to identify the primary tumor location but clarify equivocal localization results generated by conventional imaging studies. It thus seems that the simplicity, superior sensitivity, high specificity, and cost-effectiveness of SRS mandate that it be the imaging modality in patients with gastrinomas. Because the cost of an SRS is $1800 and may obviate the need for multiple other topographic studies that are at least as expensive, the fiscal dictates further warrant the use of this study as the initial topographic investigation. These observations are probably applicable to all gut NETs, although the likelihood of primary identification in the instance of insulinoma patients may be somewhat less. The timely and cost-effective establishment of the type of NET, its primary site, and the detection metastatic spread will enable determination of the appropriate management strategy.
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PMID:Approaches to the diagnosis of gut neuroendocrine tumors: the last word (today). 902 13

The extent and distribution of myocardial edema induced by perfusion with cardioprotective solutions is of great interest. Domestic pig hearts (n = 12) were perfused in situ after aortic cross clamping either with Bretschneider's cardioplegic solution (HTK, 4 degrees C, n = 3), with a heparinized Krebs-Henseleit solution containing 30 mmol/L 2,3 Butanedionemonoxime (BDM, 4 degrees C, n = 3) or with heparinized pig blood (HPB, 24 degrees C, n = 3). After a three-hours storage period, magnetic resonance tomography (MRI) was carried out. The acquired T1-weighted data were used for the subsequent three-dimensional reconstruction based on the "Heidelberg ray-tracing technique". The small myocardial tissue blocks (n = 216) were excised from these hearts for dry weight measurements for 9 preselected regions in duplicate including ventricular papillary muscle, ventricular free wall, ventricular septum, apex, and atrial tissue. In control hearts (n = 3), dry weight was measured immediately after explantation (no MRI). The results of dry-weight measurements and three dimensional visualization were compared. Dry-weight measurements revealed that considerable myocardial edema is induced by any of the experimental procedures. The effects were most pronounced after BDM perfusion. Regardless how the edema was induced, there were significant differences of the water content within the heart: the water content in the heads of the papillary muscles and in the interventricular septum was always smaller than that of the free left- and right-ventricular walls. The heterogeneity of myocardial edema and its spatial distribution pattern could be qualitatively visualized. The experimental data (biophysical data and 3D visualization) clearly show a heterogeneity of myocardial edema induced by different types of cardioprotective solutions. As the presence of myocardial edema represents one of the crucial events in the pathophysiology of myocardial dysfunction occurring during myocardial infarction, ischemia, heart transplantation, and extracorporeal circulation, the present study represents an interesting contribution towards intravital detection and distribution of myocardial edema.
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PMID:Heterogeneity of myocardial edema in isolated pig hearts after perfusion with different types of cardioprotective solutions. 988 20

In addition to minimizing graft site morbidity, providing stable fixation, and enabling early progressive rehabilitation, the ideal PCL reconstruction would closely simulate natural ligament function. This study retrospectively examined the 2-year postoperative outcomes of 19 athletically active patients referred with clinically symptomatic PCL-deficient knees. Preoperatively 18 patients had severely abnormal knee ligament examination scores, and one had an abnormal score (IKDC). All but one patient was confirmed negative for observable posterolateral corner injury via MRI. Eighteen patients had clinical evidence of posterolateral instability. All patients underwent double-bundle PCL reconstruction (using allograft tissue) without concomitant posterolateral corner reconstruction. Two years after surgery 100% of patients had normal ( n=18) or near normal ( n=1) passive knee joint motion. The results were: one-leg hop test, 58% normal, 37% nearly normal, 5% abnormal; knee ligament examination, 47% normal, 42% nearly normal, 5% abnormal, 5% severely abnormal; knee arthrometry, 2.4+/-2 mm posterior tibial displacement; IKDC subjective assessment section, 47% normal, 42% nearly normal, 5% abnormal, 5% severely abnormal; IKDC symptom-activity level section, 47% normal, 42% nearly normal, 5% abnormal, 5% severely abnormal; final knee ligament evaluation, 47% normal, 42% nearly normal, 5% abnormal, 5% severely abnormal; Lysholm knee scoring scale, 63% excellent, 27% good, 5% fair and 5% poor. Improved stability with clinical ligamentous laxity tests and good IKDC subjective and symptom-activity results 2 years after surgery suggest that for patients with PCL rupture and grade I or II posterolateral instability the double-bundle procedure alone sufficiently restores PCL function through a greater range of knee motion than traditional single-bundle techniques.
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PMID:Double-bundle posterior cruciate ligament reconstruction with allograft tissue: 2-year postoperative outcomes. 1235

The natural history and survival of breast cancer are extremely variable although the advances and improvement in treatment in recent years led to a lower mortality. In fact, in spite of the administration of systemic adjuvant therapy, women with metastatic lymph nodes at diagnosis have a risk of disease progression at 5 years of 40-50%. The disease heterogeneity and the intrinsic tumor cell resistance to therapies are determining factors of the problem. The role of parameters as tumor size, grading, vascular spread, axillary lymph node status, are well defined. However the increasingly early diagnosis and changes in clinical practice have led to the need for non morphologic parameters as estrogen and progesteron receptors, cell proliferation index, labelling index, growth factors tumor-dependent genes (p53, HER2), cell cycle regulators (cyclins). Specific cellular and molecular alterations are studied to identify diagnosticoinstrumental images (MRI) of tumor angiogenesis, the cause of the different tumor aggressiveness. In the surgical and consequently clinico-oncologic approach there is the problem of the interpretation and prognostic role of sentinel lymph node when it is positive for micrometastasis only, if diagnosed by immunohistochemistry.
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PMID:Biological factors and therapeutic modulation in breast cancer radiotherapy. 1269 49

Hypochondroplasia (HCH) and Muenke syndrome (MS) are caused by mutations on FGFR3 gene. FGFR3 is known to play a role in controlling nervous system development. We describe the clinical and neuroradiological findings of the first two patients, to our knowledge, affected by HCH and MS, respectively, in whom bilateral dysgenesis of the medial temporal lobe structures has been observed. In both patients diagnosis was confirmed by molecular analysis. They were mentally normal and showed similarities in early-onset temporal lobe-related seizures. In both patients EEG recorded bilateral temporal region discharges. MRI detected temporal lobe anomalies with inadequate differentiation between white and gray matter, defective gyri, and abnormally shaped hippocampus.
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PMID:Medial temporal lobe dysgenesis in Muenke syndrome and hypochondroplasia. 1279 98

PTK787/ZK 222584 (PTK/ZK) is an oral potent and selective inhibitor of the vascular endothelial growth factor (VEGF)-mediated Flt-1 and KDR receptor tyrosine kinases. PTK/ZK has been shown to reduce growth and microvasculature in subcutaneously implanted human tumor xenografts in nude mice. A clinical difficulty in evaluating angiogenesis inhibitors has been the usefulness of conventional study endpoints. Therefore, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been studied as a pharmacodynamic marker of efficacy of PTK/ZK. Phase I studies are under way evaluating the optimum dose and schedule of oral PTK/ZK administered continuously to patients with advanced cancers of types known to overexpress VEGF. To date, particularly in patients with liver metastases from colorectal cancer treated with PTK/ZK, DCE-MRI has been a useful predictor of the biological response of VEGF-receptor inhibition. Toxicities have been manageable and have included lightheadedness, ataxia, nausea, vomiting, and hypertension. Stabilization of disease for >/= 6 months has been seen in heavily pretreated patients receiving PTK/ZK at higher doses. Preliminary data suggest that PTK/ZK can be administered safely on a continuous daily dosing schedule, efficacy data look promising, and DCE-MRI correlates with biological response. DCE-MRI will be used to guide dose optimization of PTK/ZK and perhaps of other angiogenesis inhibitors in future studies.
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PMID:Vascular endothelial growth factor receptor tyrosine kinase inhibitors: PTK787/ZK 222584. 1280 93

Antiangiogenic therapy is a promising new strategy to inhibit tumor growth and formation of metastases. VEGF (vascular endothelial growth factor) is known to be the most important proangiogenic factor, necessary for the development of new tumor vessels. Specific inhibitors of the VEGF receptor tyrosine kinases, like PTK787/ZK222584 (PTK/ZK), have shown antitumoral and antiangiogenic activity in several animal models. Ongoing early clinical trials with antiangiogenic compounds reveal the need for diagnostic methods to detect their biological activity. Pro-angiogenic growth factors like VEGF and bFGF (basic fibroblast growth factor), soluble variants of proangiogenic receptors like sFLT-1 and sTIE-2, as well as endothelial activation markers like sE-Selectin, can be measured in the serum and plasma of patients by the ELISA technique. They were detected in various malignant diseases to assess their use as surrogate markers in tumor angiogenesis. In different clinical Phase I trials with antiangiogenic compounds, these soluble markers were used to detect dose levels for biological activity. Soluble markers of tumor angiogenesis can be used as prognostic markers in various malignancies like colon cancer or multiple myeloma. Furthermore, they correlated with disease activity, prognosis and imaging techniques for the detection of vascular changes. In clinical Phase I trials with specific inhibitors of the VEGF receptor tyrosine kinases, VEGF serum levels increased in patients treated with higher doses, indicating increasing tumor hypoxia. Taking results from imaging techniques such as dynamic enhanced MRI into account, optimal doses for biological activity could be concluded. New biological treatment techniques will need new diagnostic methods to assess their specific biological activity in patients. Soluble markers and imaging techniques are useful tools for the detection of hypoxia under antiangiogenic treatment. Nevertheless, these techniques are still experimental. Therefore, further clinical evaluation is necessary.
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PMID:Soluble markers for the detection of hypoxia under antiangiogenic treatment. 1282 Mar 65


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