Standalone portable xenon-129 hyperpolariser for multicentre clinical magnetic resonance imaging of the lungs

ObjectivesDesign and build a portable xenon-129 (¹²⁹Xe) hyperpolariser for clinically accessible ¹²⁹Xe lung MRI.MethodsThe polariser system consists of six main functional components: (i) a laser diode array and optics; (ii) a B₀ coil assembly; (iii) an oven containing an optical cell; (iv) NMR and optical spectrometers; (v) a gas-handling manifold; and (vi) a cryostat within a permanent magnet. All components run without external utilities such as compressed air or three-phase electricity, and require just three mains sockets for operation. The system can be manually transported in a lightweight van and rapidly installed on a small estates footprint in a hospital setting.ResultsThe polariser routinely provides polarised ¹²⁹Xe for routine clinical lung MRI. To test the concept of portability and rapid deployment, it was transported 200 km, installed at a hospital with no previous experience with the technology and ¹²⁹Xe MR images of a diagnostic quality were acquired the day after system transport and installation.ConclusionThis portable ¹²⁹Xe hyperpolariser system could form the basis of a cost-effective platform for wider clinical dissemination and multicentre evaluation of ¹²⁹Xe lung MR imaging.Advances in knowledgeOur work successfully demonstrates the feasibility of multicentre clinical ¹²⁹Xe MRI with a portable hyperpolariser system.     

Production of justicidin B, a cytotoxic arylnaphthalene lignan from genetically transformed root cultures of Linum leonii

Callus and hairy root cultures of Linum leonii were established. The genetic transformation in hairy roots was proven by PCR analysis, which showed integration of rol A and rol C genes into the plant genome. Calli and hairy roots accumulate the arylnaphthalene lignan justicidin B as a major constituent. Hairy roots produce 5-fold higher yields of justicidin B (10.8 mg g(-1) DW) compared to calli. Justicidin B shows strong cytotoxicity on the chronic myeloid leukemia LAMA-8 and K-562 cell lines and on the chronic lymphoid leukemia SKW-3 cell line with IC(50) values of 1.11, 6.08, and 1.62 microM, respectively. Apoptotic properties of justicidin B are reported for the first time.     

Biomechanical profile of the cornea in primary congenital glaucoma

Purpose: The aim of our study was to investigate the biomechanical properties of the cornea in primary congenital glaucoma (PCG) and to identify the potential ocular determinants, which affect the corneal biomechanical metrics. Methods: Corneal hysteresis (CH), corneal resistance factor (CRF) and central corneal thickness (CCT) were measured in 26 patients with PCG (40 eyes) with the aid of ocular response analyser. In vivo laser‐scanning confocal microscopy was used for the estimation of stromal keratocyte density (KD) and the evaluation of corneal endothelium. Twenty normal subjects (40 eyes) served as controls. Student’s t‐test and Pearson’s correlation coefficients were used for statistical analysis. p Values <0.05 were considered statistically significant. Results: Corneal hysteresis, CRF and CCT were significantly reduced in patients with PCG (all p < 0.05). Corneal hysteresis and CRF negatively correlated with the corneal diameter in both groups (r₁ = ?0.53, r₂ = ?0.66, p < 0.001 for CH and r₁ = ?0.61, r₂ = ?0.69, p < 0.001 for CRF). Moreover, we identified a significant correlation between CH and CRF with CCT in both groups (r₁ = 0.51, r₂ = 0.48, p < 0.001 for CH and r₁ = 0.45, r₂ = 0.44, p < 0.001 for CRF). Mean KD was significantly reduced both in the anterior and posterior corneal stroma in patients with PCG (764 ± 162 and 362 ± 112 cells/mm², respectively) compared with controls (979 ± 208 and 581 ± 131 cells/mm², respectively) (p < 0.001). There was no significant correlation between the keratocyte density in anterior and/or posterior stroma and CH or CRF in any group (r₁ = 0.29, r₂ = 0.31, p < 0.06). Mean endothelial cell density was also significantly reduced in PCG group (2920 ± 443 cells/mm²) compared with control group (3421 ± 360 cells/mm²) (p < 0.001). Pleomorphism and polymegalism were significantly increased in corneal endothelium of patients with PCG. Conclusions: Our results showed a significant reduction in CH and CRF in PCG. Both CH and CRF were negatively correlated with corneal diameter. A significant correlation of CH and CRF with CCT was identified in both groups. Keratocyte density was decreased in PCG, but did not have a significant impact on CH and CRF. Mean endothelial density was also decreased in PCG. Our results suggest that reduced CCT and increased corneal diameter are major ocular determinants for the modified corneal biomechanical profile in PCG, while cellular alterations in corneal stroma and endothelium have no significant biomechanical impact.     

Getting the most out of your IP--patent management along its life cycle

Effectively managing and optimizing the value of the patent portfolio is a major challenge for many firms, especially those in knowledge intensive industries, such as the pharmaceutical, biotechnological and chemical industry. However, insights on effective patent portfolio strategies are rare. Therefore, in this article we investigate in detail how firms successfully manage and optimize their patent portfolios to increase their overall competitiveness. We discover that successful patent portfolio management is rooted in managing the patents along their life cycles. Based on the findings of ten case studies, we develop a holistic patent life cycle management model reflecting five distinctive phases of patent management: explore, generate, protect, optimize and decline. We conclude with how our findings can be used in practice.     

Laparoscopic management of ectopic pregnancy in the presence of a significant haemoperitoneum

Objective To assess the trend in the use of operative laparoscopy in the management of patients with ruptured ectopic pregnancy and significant haemoperitoneum. Method Four-year prospective observational study of the operative management of women with ruptured ectopic pregnancy and significant haemoperitoneum at the Whipps Cross University Hospital from January 2003 to December 2006. The inclusion criteria were patients with a clinical or laparoscopic assessment of significant haemoperitoneum (>800 ml). The amount of haemoperitoneum was determined at surgery. Results The blood loss ranged from 800 to 3,500 ml. The laparoscopic approach in this specific clinical scenario increased from 40% in 2003 to 100% in 2006. In 2003 there were five patients, two (40%) were treated by laparoscopy, one (20%) was converted from laparoscopy to laparotomy and two (40%) had laparotomy. In 2004 there were six patients, five (85%) underwent laparoscopic management and one (15%) had laparotomy. In 2005 we had 14 patients, ten (72%) had laparoscopic management, 2 (14%) were converted to laparotomy and 2 (14%) had laparotomies. There were12 patients in 2006 and all (100%) were treated by laparoscopy. Conclusion Our study demonstrates that with highly skilled anaesthetic and surgical teams, operative laparoscopy with its recognized advantages over laparotomy and is feasible in women with ruptured ectopic pregnancy and significant haemoperitoneum.     

Intraperitoneal chemotherapy for patients with advanced ovarian cancer: a review of the evidence and standards for the delivery of care

OBJECTIVES: To evaluate the role of intraperitoneal (IP) chemotherapy as part of primary treatment in patients with advanced ovarian cancer and to develop standards of care within the context of current clinical practice. METHODS: A multidisciplinary expert panel, convened to develop standards on the use of IP chemotherapy, searched the MEDLINE, EMBASE, and Cochrane Library databases up to December 2006 for randomized trials or published standards on the efficacy and/or delivery of IP chemotherapy. RESULTS: Eight randomized trials comparing IP chemotherapy versus intravenous (IV) chemotherapy were identified. Three trials reported statistically significant improvements in median survival of 8.0, 11.0, and 15.9 months with cisplatin-based IP chemotherapy. In one trial, the 15.9-month improvement in median overall survival (RR=0.75, 95% CI=0.58-0.97) represented a 25% reduction in the risk of death with IP chemotherapy. Severe adverse events and catheter-related complications were often dose limiting with IP chemotherapy. Using a consensus-based approach with a nationally representative panel, multidisciplinary care standards were developed to review medical and surgical criteria, the practice setting, volume requirements, and the institutional criteria required to safely deliver IP chemotherapy. CONCLUSION: The survival benefits with cisplatin-based IP chemotherapy may represent a significant improvement in the outlook for select patients with advanced ovarian cancer. The delivery of IP chemotherapy is more challenging than the IV route; however, severe adverse events and catheter-related complications may be offset through research defining the optimum treatment regimen, and the standardization of care. System-wide standards for the delivery of IP chemotherapy in Canada for patients with optimally debulked stage III ovarian cancer are offered.     

Strategic,feasibility, economic,and cultural aspects of phase 0 approaches: Is it time to change the drug development process in order to increase productivity?

Research conducted over the past 2 decades has enhanced the validity and expanded the applications of microdosing and other phase 0 approaches in drug development. Phase 0 approaches can accelerate drug development timelines and reduce attrition in clinical development by increasing the quality of candidates entering clinical development and by reducing the time to “go‐no‐go” decisions. This can be done by adding clinical trial data (both healthy volunteers and patients) to preclinical candidate selection, and by applying methodological and operational advantages that phase 0 have over traditional approaches. The main feature of phase 0 approaches is the limited, subtherapeutic exposure to the test article. This means a reduced risk to research volunteers, and reduced regulatory requirements, timelines, and costs of first‐in‐human (FIH) testing. Whereas many operational aspects of phase 0 approaches are similar to those of other early phase clinical development programs, they have some unique strategic, regulatory, ethical, feasibility, economic, and cultural aspects. Here, we provide a guidance to these operational aspects and include case studies to highlight their potential impact in a range of clinical development scenarios.