Miniaturized, biopsy-implantable chemical sensor with wireless, magnetic resonance readout.

Biopsy is an important diagnostic tool for a broad range of conditions. Cancer diagnoses, for example, are confirmed using tissue explanted with biopsy. Here we demonstrate a miniaturized wireless sensor that can be implanted during a biopsy procedure and return chemical information from within the body. Power and readout are wireless via weak magnetic resonant coupling to an external reader. The sensor is filled with responsive nuclear magnetic resonance (NMR) contrast agents for chemical sensitivity, and on-board circuitry constrains the NMR measurement to the contents. This sensor enables longitudinal monitoring of the same location, and its simple readout mechanism is ideal for applications not requiring the spatial information available through imaging techniques. We demonstrated the operation of this sensor by measuring two metabolic markers, both in vitro and in vivo: pH in flowing fluid for over 25 days and in a xenograft tumor model in mice, and oxygen in flowing gas and in a rat hind-limb constriction experiment. The results suggest that this in vivo sensing platform is generalizable to other available NMR contrast agents. These sensors have potential for use in biomedicine, environmental monitoring and quality control applications.

Two phase II trials of temozolomide with interferon-alpha2b (pegylated and non-pegylated) in patients with recurrent glioblastoma multiforme.

BACKGROUND: Because of the poor outcomes for patients with recurrent glioblastoma multiforme (GBM), and some laboratory and clinical evidence of efficacy using interferon in GBM, we assessed the toxicity and efficacy of temozolomide (TMZ) combined with either short-acting (IFN) or long-acting (pegylated) interferon alpha2b (PEG) in two single-arm phase II studies, and compared the results to 6-month progression-free survival (PFS-6) data from historical controls. METHODS: Two single-arm phase II studies were carried out in adults with GBM. Patients were treated with the standard regimen of TMZ (150-200 mg m(-2) per day x 5 days every month) combined with either 4 million units per m(2) subcutaneously (SQ) three times weekly of IFN or 0.5 microg kg(-1) SQ weekly of PEG. Physical exams and imaging evaluations were carried out every 8 weeks. RESULTS: On the IFN study, 34 adults (74% men) were enrolled, and 29 adults (55% men) on the PEG study; median Karnofsky performance status was 80 and 90 for the IFN and PEG studies, respectively. Grade 3 or 4 toxicities were common, leucopoenia and thrombocytopoenia occurring in 35-38% and 18-21% of patients, respectively. Grade 3 or 4 fatigue occurred in 18% of patients on both studies. Lymphopoenia was infrequent. PFS-6 was 31% for 29 evaluable patients in the IFN study and 38% for 26 evaluable patients in the PEG study. CONCLUSION: In recurrent GBM patients, both studies of standard dose TMZ with either IFN or PEG showed improved efficacy when compared to historical controls, or reports using TMZ alone. Even though the TMZ+PEG study met criteria for further study, the results of both of these studies must be considered in light of the standard of care (TMZ plus radiotherapy) for newly diagnosed GBM, which has evolved since the inception of these studies. Despite the results of the current studies being eclipsed by the new GBM standard of care, these results can still inform the development of newer approaches for GBM, either in an earlier, upfront setting, or by extrapolation of the results and consideration of the use of PEG or IFN in conjunction with other antiglioma strategies.

An in vitro investigation of a poly(vinyl phosphonic acid) based cement with four conventional glass-ionomer cements. Part 1: Flexural strength and fluoride release.

OBJECTIVE: To investigate the flexural strength and fluoride release of four conventional glass-ionomer cements: Ketac-Molar (KM), HiFi (HF), Vivaglass Fil (VF), Ketac-Fil (KF) and a newly developed glass polyphosphonate cement, Diamond Carve (DC). METHOD: Disc specimens (10 mm diameter, 1 mm thick) were prepared and mould stored at 37 degrees C. After one hour, the specimens were removed from their mould and immersed in 20 ml of deionised water until required for testing. Biaxial flexural strength was determined at 1 hour and at 1, 7, 30 and 90 days after the start of mixing. Measurements of fluoride release from the specimens were carried out at 2 hours and at 1, 3, 7, 14, 30, 60 and 90 days after the start of mixing using a fluoride ion selective electrode. The results were analysed using ANOVA and student 't' tests. RESULTS: All the materials displayed different flexural strength patterns. KM and DC became stronger whilst KF and VF plateaued in strength with time. HF peaked in strength and then became weaker. At 90 days, the mean flexural strengths in decreasing order was as follows: KM > or = VF > or = DC > or = HF > KF. An initial fast rate of fluoride release followed by a slower but steady release of fluoride was observed in each of the materials. The mean cumulative fluoride release in decreasing order was as follows: VF > KF > or = HF > DC > KM. VF released significantly higher level and KM significantly lower level of fluoride than the other materials. CONCLUSIONS: The acid used to form the cement could not be used to predict changes in cement strength behaviour with respect to time. DC increased in strength with time and its flexural strength at 90 days was comparable to that of HF and VF. The cumulative and rate of fluoride release varied for the materials. DC had a low fluoride release consistent with a fast setting material with good early resistance to water.

An in vitro investigation of a poly (vinyl phosphonic acid) based cement with four conventional glass-ionomer cements Part 2: Maturation in relation to surface hardness.

OBJECTIVE: To investigate the surface hardness of four conventional glass-ionomer cements: Ketac-Molar (KM), HiFi (HF), Vivaglass Fil (VF), Ketac-Fil (KF) and a newly developed glass polyphosphonate based cement, Diamond Carve (DC) at different maturation times in water and to investigate the effects of early water exposure on their surface hardness. METHOD: Disc specimens (10 mm diameter, 1 mm thick) were prepared and mould stored at 37 degrees C. The effect of different maturation times (15, 30 and 60 min) and storage in water over 24 h after those maturation times on surface hardness was determined using a microindentor with a Vickers diamond indentor. The results of the surface hardness tests were analysed using Mann-Whitney non-parameteric statistics (p < or = 0.05). The working (WT) and setting (ST) times of the cements were also measured using a modified Wilson oscillating rheometer. RESULTS: All the materials became harder after 24 h immersion in water. HF, VF and DC showed initial sensitivity to a short maturation time, but only HF was adversely affected by early moisture exposure. KF and KM were least sensitive to short maturation time or early water exposure. DC had the shortest and HF the longest WT and ST. HF and VF had a high WT:ST ratio of 1:7 and 1:9, respectively. CONCLUSIONS: A short maturation time (of 15 min) and early exposure to water did not adversely affect the surface hardness of KF, KM, VF and DC. DC, based on poly(vinyl phosphonic acid), had the shortest WT and ST. Poly(acrylic acid) based HF and VF had a long ST in relation to their WT.