Reversal of multidrug resistance by two novel indole derivatives.

Two new fused indoles were found to overcome multidrug resistance in P388/Adr cells in vitro. These agents potentiated the cytotoxicity of the antitumor drugs Adriamycin, vinblastine, and vincristine in multidrug-resistant cells with no effect on drug-sensitive parent P388 cells. They significantly increased the ATP-dependent accumulation of [3H]-vinblastine and inhibited efflux of the labeled drug from resistant cells. These compounds also inhibited photoaffinity labeling of P-glycoprotein by [3H]azidopine in P388/Adr cells and membranes isolated from these cells. In addition, the calcium antagonist activity of these compounds was very weak compared with that of verapamil. These data suggest that the compounds reported here may specifically overcome multidrug resistance without the serious hypotensive effects associated with calcium antagonists and that this activity may be independent of their ability to block calcium transport.     

Evaluation of a resorbable, in situ setting bone substitute in a sheep model

The gold standard for bone substitution is the autologous bone graft, but because of its limited supply and the associated morbidity, the search for synthetic alternatives is necessary. A new in situ setting tricalcium phosphate cement was implanted in a trepanation defect (9.4 mm diameter, 10 mm depth) in the distal femoral epiphysis of sheep. Empty cavities and autologous bone graft were used as controls. Histologic and histomorphometric examinations were carried out after 12 weeks. Nearly 90% of the implanted cement was resorbed and replaced by ingrown bone with close contact between surrounding bone, new bone, and remaining cement particles. The amount of bone in the defect area was significantly higher in defects filled with cement relative to defects filled with autologous bone graft (mean 27 vs. 21%, 95% confidence intervals 23 to 31 and 18 to 23, p = 0.026). In conclusion, this new in situ setting cement is bioactive, resorbable, and osteoconductive. It will be useful as an alternative to autologous bone graft to fill stable defects.     

Removal of orbital apex hemangioma using new transorbital craniotomy through suprabrow approach.

PURPOSE: To describe a technique combining the expertise of the oculoplastic orbital surgeon and the neurosurgeon which allows access to the posterior orbit, anterior fossa, cavernous sinus and suprasellar region with minimal brain manipulation. METHODS: A transorbital craniotomy through a suprabrow incision is performed removing part of the frontal bone and orbital roof as a single piece. This allows wide access with only minimal, if any, brain retraction. The superior, lateral and medial orbit is clearly visualized, as well as the apex of the orbit. The bone flap is replaced at the end of the case with Tantalum plates. RESULTS: A cavernous hemangioma at the orbital apex was removed without complications. The exposure was superb and allowed identification and preservation of orbital structures. CONCLUSIONS: Transorbital craniotomy allows for wide access to the posterior orbit and parasellar region and anterior fossa of the brain with minimal brain manipulation. The use of a suprabrow incision results in an excellent cosmetic result. There is minimal postoperative morbidity, which decreases hospitalization time.     

CARs in the Lead Against Multiple Myeloma

The recent clinical success of CD19-directed chimeric antigen receptor (CAR) T cell therapy in chronic and acute leukemia has led to increased interest in broadening this technology to other hematological malignancies and solid tumors. Now, advances are being made using CAR T cell technology to target myeloma antigens such as B cell maturation antigen (BCMA), CD138, and kappa-light chain as well as CD19 on putative myeloma stem cells. To date, only a limited number of multiple myeloma patients have received CAR T cell therapy but preliminary results have been encouraging. In this review, we summarize the recently reported results of clinical trials conducted utilizing CAR T cell therapy in multiple myeloma (MM).     

Web-Based Immersive Virtual Patient Simulators: Positive Effect on Clinical Reasoning in Medical Education

Background

Clinical reasoning is based on the declarative and procedural knowledge of workflows in clinical medicine. Educational approaches such as problem-based learning or mannequin simulators support learning of procedural knowledge. Immersive patient simulators (IPSs) go one step further as they allow an illusionary immersion into a synthetic world. Students can freely navigate an avatar through a three-dimensional environment, interact with the virtual surroundings, and treat virtual patients. By playful learning with IPS, medical workflows can be repetitively trained and internalized. As there are only a few university-driven IPS with a profound amount of medical knowledge available, we developed a university-based IPS framework. Our simulator is free to use and combines a high degree of immersion with in-depth medical content. By adding disease-specific content modules, the simulator framework can be expanded depending on the curricular demands. However, these new educational tools compete with the traditional teaching

Objective

It was our aim to develop an educational content module that teaches clinical and therapeutic workflows in surgical oncology. Furthermore, we wanted to examine how the use of this module affects student performance.

Methods

The new module was based on the declarative and procedural learning targets of the official German medical examination regulations. The module was added to our custom-made IPS named ALICE (Artificial Learning Interface for Clinical Education). ALICE was evaluated on 62 third-year students.

Results

Students showed a high degree of motivation when using the simulator as most of them had fun using it. ALICE showed positive impact on clinical reasoning as there was a significant improvement in determining the correct therapy after using the simulator. ALICE positively impacted the rise in declarative knowledge as there was improvement in answering multiple-choice questions before and after simulator use.

Conclusions

ALICE has a positive effect on knowledge gain and raises students’ motivation. It is a suitable tool for supporting clinical education in the blended learning context.     

Elektromagnetische Navigation transpedikulärer Punktionen

Aim

Before clinical implementation of an approved electromagnetic tracking system (CAPPA IRAD EMT) an experimental trial was performed to investigate the accuracy of the system and its safety in application for transpedicular vertebral punctures in comparison to the classical fluoroscopic method.

Material and methods

A total of 110 transpedicular punctures were performed bilaterally using 11 vertebrae of 5 realistic artificial phantoms and 1 pedicle was punctured with the conventional technique using c-arm fluoroscopy and the other with the electromagnetic tracking system. As a target a radiopaque non-ferromagnetic marker was implanted bilaterally in the anterior wall of the vertebrae. For evaluation of the precision the distance from the end of the puncture to the target and the gradual deviation of the actual channel from the ideal trajectory were assessed in three-dimensional computer tomography. Calculations and statistical analysis were performed according to the Wilcoxon test by means of SPSS 16.0.1 for Windows.

Results

The mean distance from the target was 6.6 mm (±3.9 mm standard deviation SD) with electromagnetic navigation compared to 3.2 mm (±2.8 mm SD) with fluoroscopic assistance and the mean aberration from the ideal trajectory was 18.4° (±4.6° SD) compared to 6.5° (±3.5° SD), respectively. The difference of accuracy was highly significant regarding both parameters (p?<?0.001).

Conclusions

The minimum requirement for accuracy of transpedicular punctures could not be achieved with electromagnetic navigation. Unless proven otherwise, the lack of accuracy is attributed to unstable referencing. Despite evidence of successful employment for soft tissue punctures the system cannot currently be recommended for osseous applications of the spine.