Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of magnetic resonance tomography (MRI) for the diagnosis of chondral lesions of the knee joint is still unclear. The sensitivity of the method ranges from 15% to 96%. The scope of our daily experiences showed that there were considerable deviations between the tomographical and arthroscopical results, which vary from the results of experimental studies. Therefore we have conducted a prospective study to investigate the question of how MRI can replace arthroscopy (ASC) in the diagnosis of cartilage damages in the scope of daily routine. All 195 patients included in this study received a magnetic resonance tomography followed by an arthroscopy. A clear diagnosis of supposition had to be determined before the magnetic resonance tomography. The patients were divided into 3 Groups. Group A (n=86) received a standard Military Hospital Ulm (MH) MRI--sagittal STIR TSE and PD TSE, coronal and transversal T2 FFE (TR=660 ms, TE=18 ms, FA=30 degrees, 512 matrix). In addition, one sub-Group, AK (n=21) was examined with a special cartilage sequence of the cartilage fs T1 W FFE. Neither patients in Group AK nor in Group A as a whole received any contrast medium. Group B (n=88) was examined with an alternate MRI protocol (Radiological Joint Practice, Neu-Ulm--sagittal T1 SE, T2 SE and T2 FLASH (TR=608 ms, TE=18 ms, FA=20 degrees, 256 matrix), coronal PD fs), employing gadolinium as a contrast medium. 156 cartilage lesions were found arthroscopically. In Group A the sensitivity was 33%, the specificity 99%, and the positive and negative prediction values 75% and 98% respectively. Group B reached a sensitivity of 53% and a specificity of 98%. The positive prediction value was 48% and the negative was 98%. Group AK showed a sensitivity of 38% and specificity of 98%; the positive and negative prediction values came to 50% and 97% respectively. In conclusion, our results indicate that the MRI examination techniques recommended in the literature at present are not able to replace the ASC for the diagnosis of cartilage damages of the knee joint. In view of the high specificity (97%-99%) and the high negative prediction value (97%-98%), MRI is suitable for the exclusion of cartilage lesions. For a negative MRI associated with a cartilage injury, a cautious attitude towards an operative cartilage treatment is therefore justified. Because the MRI can not replace the ASC for diagnostic of cartilage damage, the ASC still has to be seen as the method of choice for the evaluation of cartilage damage.
 ...
PMID:Diagnosis of chondral lesions of the knee joint: can MRI replace arthroscopy? A prospective study. 1290 42

We present a rare case of central nervous system lymphoma that occurred in a patient who had essential thrombocythemia for 17 years. MRI examinations disclosed multiple ring-enhanced lesions that had shown bilateral spreading in the different period. Pathological examinations confirmed CD30/Ki-1-positive ALK negative anaplastic large cell lymphoma. The possible pathogenic mechanisms of this disease are discussed.
 ...
PMID:Primary CD30/Ki-1 positive anaplastic large cell lymphoma of the central nervous system occurring in a patient with a seventeen-year history of essential thrombocythemia. 1291 80

Intra-articular ganglia and cysts of the knee joint are rare and mostly incidental findings in MRI and arthroscopy. During a period of 15 years, nearly 8000 knees were arthroscopically examined. In total, 85 intra-articular soft tissue masses were found within the knee cavity. Of these, 76 were incidental and asymptomatic findings in arthroscopy performed for treatment of osteoarthritic symptoms. Several repeated minor knee traumata were reported in this group but no histories of serious traumatic events. Nine ganglion cysts were obviously solely responsible for the intermittent or chronic non-specific knee discomfort, and classified as symptomatic. There were no histories of previous injury to the knees, no clinical signs of instabilities or meniscal and femoropatellar pathologies, and no associated further intra-articular lesions in arthroscopy. Forty-nine cystic masses originated from the ACL, 16 from the PCL, 12 from the anterior (eight medial, four lateral) and three from the posterior horn of the menisci (two medial, one lateral). Three were located in the infrapatellar fat pad, one arose from a medial plica and one from a subchondral bone cyst. All ganglion cysts were successfully resected or excised using arthroscopic technique. A review of the literature is given and compared with the findings and data of this study.
 ...
PMID:Intra-articular ganglion cysts of the knee joint: a report of 85 cases and review of the literature. 1450 17

Assessment of tumour vascularity may characterize malignancy as well as predict responsiveness to anti-angiogenic therapy. Non-invasive measurement of tumour perfusion and blood vessel permeability assessed as the transfer constant, K(trans), can be provided by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Using the orthotopic murine tumour model B16/BL6 melanoma, the small contrast agent GdDOTA (DOTAREM(R); Guerbet, Paris) was applied to assess the vascular transfer constant, K(trans), and interstitial leakage space, whereas intravascular iron oxide nanoparticles (Endorem(R); Guerbet, Paris) were used to detect relative tumour blood volume (rTBV), and in one experiment blood flow index (BFI). No correlations were observed between these four parameters (r(2) always <0.05). The B16/BL6 primary tumour and lymph-node cervical (neck) metastases produced high levels of the permeability/growth factor, VEGF. To probe the model, the novel VEGF receptor (VEGF-R) tyrosine kinase inhibitor, PTK787/ZK222584 (PTK/ZK) was tested for anti-tumour efficacy and its effects on DCE-MRI measured parameters of tumour vascularity. Data from the non-invasive measure of tumour vascularity were compared with a histological measurement of vasculature using the DNA-staining dye H33342. PTK/ZK inhibited growth of the primary and, particularly, cervical tumour metastases following chronic treatment for 2 weeks (50 or 100 mg/kg daily) of 1-week-old tumours, or with 1 week of treatment against more established (2-week-old) tumours. After chronic treatment with PTK/ZK, DCE-MRI detected significant decreases in K(trans) and interstitial leakage space, but not rTBV of both primary tumours and cervical metastases. Histological data at this time-point showed a significant decrease in blood vessel density of the cervical metastases but not the primary tumours. However, in the cervical metastases, the mean blood vessel width was increased by 38%, suggesting overall no marked change in blood volume. After acute (2-4 day) treatment, DCE-MRI of the cervical metastases demonstrated a significant decrease in K(trans) and interstitial leakage space and also in the initial area under the enhancement curve for GdDOTA (IAUC), but no change in the rTBV or BFI. Thus, significant changes could be detected in the DCE-MRI measurement of tumour uptake of a small contrast agent prior to changes in tumour size, which suggests that DCE-MRI could be applied in the clinic as a rapid and sensitive biomarker for the effects of VEGF-R inhibition on tumour blood vessel permeability and thus may provide an early marker for eventual tumour response.
 ...
PMID:PTK787/ZK222584, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor, reduces uptake of the contrast agent GdDOTA by murine orthotopic B16/BL6 melanoma tumours and inhibits their growth in vivo. 1591 78

The family of VEGF receptors are important mediators of angiogenesis, which is essential for tumour growth and metastasis. PTK/ZK is a multiple VEGF receptor inhibitor that blocks the activity of all known VEGF receptor tyrosine kinases. This phase I/II trial evaluated the safety, pharmacokinetics and efficacy of PTK/ZK in patients with liver metastases from solid tumours. Patients were administered oral PTK/ZK monotherapy once daily at doses of 300-1200 mg/day in 28-day cycles until unacceptable toxicity or tumour progression occurred. Twenty-seven patients were enrolled and treatment with PTK/ZK was generally well tolerated. The most frequently reported adverse events were fatigue, nausea, dizziness, and vomiting (mostly National Cancer Institute Common Toxicity Criteria grade 1 or 2). The area under the concentration-time curve (AUC) of PTK/ZK increased between 300 and 1000 mg/day with no further increase from 1000 to 1200 mg/day; the AUC decreased by 50% between day 1 and day 15. The DCE-MRI showed a statistically significant early reduction of tumour blood supply (measured as Ki) at day 2 at doses > or = 750 mg/day. Disease progression was significantly correlated with percent change from baseline Ki. Thirteen patients had stable disease for at least two cycles (56 days). Median overall survival was 11.8 months (95% CI = 6.6, 17.1 months). Long-term therapy with PTK/ZK demonstrated predictable pharmacokinetics, was safe and feasible in patients with metastatic disease, and showed promising clinical activity. The minimum biologically active dose was established at 750 mg/day whereas the recommended dose for phase III studies is 1200 mg/day.
 ...
PMID:Phase I clinical and pharmacokinetic study of PTK/ZK, a multiple VEGF receptor inhibitor, in patients with liver metastases from solid tumours. 1593 65

We have developed an analysis toolbox called NUTMEG (Neurodynamic Utility Toolbox for Magnetoencephalography) for reconstructing the spatiotemporal dynamics of neural activations and overlaying them onto structural MR images. The toolbox runs under MATLAB in conjunction with SPM2 and can be used with the Linux/UNIX, Mac OS X, and even Windows platforms. Currently, evoked magnetic field data from 4-D Neuroimaging, CTF, and KIT systems can be imported to the toolbox for analysis. NUTMEG uses an eigenspace vector beamforming algorithm to generate a tomographic reconstruction of spatiotemporal magnetic source activity over selected time intervals and spatial regions. The MEG coordinate frame is coregistered with an anatomical MR image using fiducial locations and, optionally, head shape information. This allows the reconstruction to be superimposed onto an MRI to provide a convenient visual correspondence to neuroanatomy. Navigating through the MR volume automatically updates the displayed time series of activation for the selected voxel. Animations can also be generated to view the evolution of neural activity over time. Since NUTMEG displays activations using SPM2's engine, certain SPM functions such as brain rendering and spatial normalization may be applied as well. Finally, as a MATLAB package, the end user can easily add customized functions. Source code is available at http://bil.ucsf.edu/ and distributed under a BSD-style license.
 ...
PMID:NUTMEG: a neuromagnetic source reconstruction toolbox. 1601 26

PTK/ZK is a novel, oral angiogenesis inhibitor that specifically targets all 3 vascular endothelial growth factor (VEGF) receptor tyrosine kinases and is currently in phase III clinical trials. In early clinical trials, PTK/ZK demonstrated a dose-dependent reduction in tumor vascular parameters as measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and an acute increase in plasma VEGF levels. The reduction in tumor vascularity was significantly correlated with improved clinical outcome in patients with advanced colorectal cancer and liver metastases. To assess the predictive value of a mouse model of tumor metastases, comparisons were performed for the biological activity of PTK/ZK in the mouse model and in patients with liver metastases in the clinical phase I trials. An orthotopic, syngeneic mouse model was used: C57BL/6 mice injected in the ear with murine B16/BL6 melanoma cells which metastases to the cervical lymph-nodes. The primary tumor and spontaneous metastases express VEGF and VEGF receptors and respond to treatment with VEGFR tyrosine kinase inhibitors. PTK/ZK was administered orally, with assessments by DCE-MRI of the metastases and plasma VEGF taken predose and at 3 days posttreatment and efficacy determined at 7 days posttreatment. Dose-ranging studies in naive mice provided preclinical pharmacokinetic data, while two dose-escalation phase I studies provided clinical pharmacokinetic data. An exposure-response relationship was observed both for mouse metastases (measured as % tumor weight treated/control) and for human liver metastases (measured as % regression). In the B16/BL6 model, the active dose of 50 mg/kg PTK/ZK yielded 62.4 (+/- 16.0) h microM plasma exposure, which is comparable to the plasma area under the concentration time curve (AUC) achieved by the 1000 mg dose of PTK/ZK used in clinical trials. At this exposure level in clinical trials, DCE-MRI showed a reduction in the area under the enhancement curve (IAUC) to 47% of baseline. At a similar exposure in the PTK/ZK-treated mice, a reduction in IAUC to 75% of baseline was observed. Furthermore, at doses of 50 mg/kg PTK/ZK and above, an increase in plasma VEGF level 10 h after drug administration was observed in mice which was consistent with findings from the clinical trials. In conclusion, the preclinical pharmacodynamics of PTK/ZK correlate well with clinical activity in phase I trials over comparable exposures to the drug. Thus, data from this preclinical model proved to be consistent with and thus predictive of the biologic effects of PTK/ZK in phase I/II clinical trials.
 ...
PMID:Biomarkers for assessment of pharmacologic activity for a vascular endothelial growth factor (VEGF) receptor inhibitor, PTK787/ZK 222584 (PTK/ZK): translation of biological activity in a mouse melanoma metastasis model to phase I studies in patients with advanced colorectal cancer with liver metastases. 1617 7

Pantibial ligamentous injury including knee dislocation and tibiotalar joint subluxation is an uncommon severe rotational injury. A 21-year-old male injured his right knee falling from a motorcycle. Physical examination revealed effusion on the right knee and ankle, and posterior translation of the tibia as well. The MRI of the right knee and ankle demonstrated the following findings: a complete disruption of cruciate ligaments, the medial collateral ligament, posteromedial corner injury together with a peripheric tear in the medial meniscus, the ruptured deltoid ligament, ankle syndesmosis space widening (>5 mm) and lateral subluxation of talus. Deltoid ligament of the right ankle was repaired and ankle syndesmosis was fixed with a cortical screw. The PCL and ACL were reconstructed arthroscopically with autogeneous bone-patellar tendon-bone graft. The midsubstance tear of MCL, posteromedial corner and medial meniscus tear were primarily repaired with nonabsorbable sutures. 3 years after the surgery, the patient was called for the final examination. MRI and X-ray findings of the knee and ankle joint demonstrated the continuity of ACL, PCL, MCL, and deltoid ligament. The patient, who is a farmer, can go back to his job and perform his daily activities. We presented a previously unreported case that involves both simultaneous occurrence of knee dislocation and tibiotalar joint subluxation. We used the term "Pantibial ligamentous injury" for this case.
 ...
PMID:An unusual rotational injury: Pantibial ligamentous injury. 1618 54

SU5416 (Z-3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]-2-indolinone; semaxanib) is a small molecule inhibitor of the vascular endothelial growth factor receptor (VEGFR2). A Phase I dose escalation study was performed. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used as a pharmacodynamic assessment tool. In all, 27 patients were recruited. SU5416 was administered twice weekly by fixed rate intravenous infusion. Patients were treated in sequential cohorts of three patients at 48, 65, 85 110 and 145 mg m-2. A further dose level of 190 mg m-2 after a 2-week lead in period at a lower dose was completed; thereafter, the cohort at 145 mg m-2 was expanded. SU5416 showed linear pharmacokinetics to 145 mg m-2 with a large volume of distribution and rapid clearance. A significant degree of interpatient variability was seen. SU5416 was well tolerated, by definition a maximum-tolerated dose was not defined. No reproducible changes were seen in DCE-MRI end points. Serial assessments of VEGF in a cohort of patients treated at 145 mg m-2 did not show a statistically significant treatment-related change. Parallel assessments of the impact of SU5416 on coagulation profiles in six patients showed a transient effect within the fibrinolytic pathway. Clinical experience showed that patients who had breaks of therapy longer than a week could not have treatment reinitiated at a dose of 190 mg m-2 without unacceptable toxicity. The 145 mg m-2 dose level is thus the recommended dose for future study.
 ...
PMID:A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points. 1622 21

We present the fourth case of a primary pancreatic anaplastic large cell lymphoma (ALCL), ALK-. An 80-year-old man was admitted to our clinic for further investigation of a fever of unknown origin. He noted anorexia, weight loss and fatigue. His laboratory tests showed anemia and a great elevation of ESR, LDH, and beta (2) microglobulin. In CT and MRI scan, a soft tissue mass in the pancreas was observed. A repeated endoscopy after his admission revealed an ulcerated mass-like deformity of the duodenal bulb. Explorative laparotomy confirmed a diffuse spread of an unresectable malignant pancreatic mass extending to the adjacent organs. Duodenal and surgical biopsies identified an ALCL of T-cell lineage, ALK-. The patient died in the Intensive Care Unit due to hemodynamic instability. Our case is the first one indicating that primary pancreatic lymphoma should be suspected in a patient with pancreatic mass and elevated serum LDH and beta(2) microglobulin.
 ...
PMID:Primary pancreatic anaplastic large cell lymphoma, ALK negative: a case report. 1627 56


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>