Acquired or inherent drug resistance is the major problem in achieving successful cancer treatment. However, the mechanism(s) of pleiotropic drug resistance remains obscure. We have identified and characterized a cellular metabolic strategy that differentiates drug-resistant cells from drug-sensitive cells. This strategy may serve to protect drug-resistant cells from damage caused by chemotherapeutic agents and radiation. We show that drug-resistant cells have low mitochondrial membrane potential, use nonglucose carbon sources (fatty acids) for mitochondrial oxygen consumption when glucose becomes limited, and are protected from exogenous stress such as radiation. In addition, drug-resistant cells express high levels of mitochondrial uncoupling protein 2 (UCP2). The discovery of this metabolic strategy potentially facilitates the design of novel therapeutic approaches to drug resistance.

Purpose:The optimal technique to manage the airway in patients presenting with a potential or documented cervical spine (C-spine) injury remains unresolved. Using fluoroscopic video assessment, C-spine motion during laryngoscopy with a Shikani Optical Stylet® (SOS) was compared to C-spine motion during intubation using a Macintosh blade.Methods: Twenty-four healthy surgical patients gave written consent to participate in a crossover randomized controlled trial; all patients were subjected to both Macintosh and Shikani laryngoscopy with manual inline stabilization following induction of anesthesia. The C-spine motion was examined at four areas: the occiput-C1 junction, C1-C2 junction, C2-C5 motion segment, and C5-thoracic motion segment. The time required for laryngoscopy was also measured (duration > 120 sec was deemed a failure of the laryngoscopy technique). Results:On average, C-spine motion was 52% less (P < 0.02) at three of the motion segments studied, occiput-C1, C2-C5, and C5-thoracic when comparing SOS vs Macintosh laryngoscopy. There was no difference between techniques at the C1-C2 segment. Laryngoscopy with SOS (28 ± 17 sec) took longer than with Macintosh blade (17 ± 7 sec), P < 0.01. There were two failures out of 23 using the SOS, vs none with the Macintosh blade. Conclusion:For patients in whom C-spine movement is undesirable, use of the SOS may limit neck movement, while modestly increasing the time required to intubate, and/or the risk of procedure failure.

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Biopsy using the developed needle guidance system is feasible and its use decreases procedure time and decreases needle motion; thus, it has the potential to reduce patient morbidity. Moreover, less operator experience is required for a successful breast biopsy using the needle guidance system than using the freehand technique.

Image-guided needle biopsies are currently used to provide a definitive diagnosis of breast cancer; however, difficulties in tumor targeting exist as the ultrasound (US) scan plane and biopsy needle must remain coplanar throughout the procedure to display the actual needle tip position. The additional time associated with aligning and maintaining this coplanar relationship results in increased patient discomfort. Biopsy procedural efficiency is further hindered since needle pathway interpretation is often difficult, especially for needle insertions at large depths that usually require multiple reinsertions. The authors developed a system that would increase the speed and accuracy of current breast biopsy procedures using readily available two-dimensional (2D) US technology. This system is composed of a passive articulated mechanical arm that attaches to a 2D US transducer. The arm is connected to a computer through custom electronics and software, which were developed as an interface for tracking the positioning of the mechanical components in real time. The arm couples to the biopsy needle and provides visual guidance for the physician performing the procedure in the form of a real-time projected needle pathway overlay on an US image of the breast. An agar test phantom, with stainless steel targets interspersed randomly throughout, was used to validate needle trajectory positioning accuracy. The biopsy needle was guided by both the software and hardware components to the targets. The phantom, with the needle inserted and device decoupled, was placed in an x-ray stereotactic mammography (SM) machine. The needle trajectory and bead target locations were determined in three dimensions from the SM images. Results indicated a mean needle trajectory accuracy error of 0.75 +/- 0.42 mm. This is adequate to sample lesions that are < 2 mm in diameter. Chicken tissue test phantoms were used to compare core needle biopsy procedure times between experienced radiologists and inexperienced resident radiologists using free-hand US and the needle guidance system. Cylindrical polyvinyl alcohol cryogel lesions, colored blue, were embedded in chicken tissue. Radiologists identified the lesions, visible as hypoechoic masses in the US images, and performed biopsy using a 14-gauge needle. Procedure times were compared based on experience and the technique performed. Using a pair-wise t test, lower biopsy procedure times were observed when using the guidance system versus the free-hand technique (t = 12.59, p < 0.001). The authors believe that with this improved biopsy guidance they will be able to reduce the "false negative" rate of biopsies, especially in the hands of less experienced physicians.