Incidence of skeletal-related events over time from solid tumour bone metastases reported in randomised trials using bone-modifying agents.

AIMS: Skeletal-related events (SREs) in patients with bone metastases decrease a patient's quality of life and functional status. Although bone-modifying agents have been found to reduce the time to first on-trial SRE and decrease the total incidence of SREs in randomised clinical trials, standard practice in the management of bone metastases has changed concurrently. The purpose of this study was to investigate if advances in bone-targeted therapies have decreased the incidence of individual types of SREs and to delineate the trend of SREs. MATERIALS AND METHODS: A literature review was conducted in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials to identify phase III, randomised bisphosphonate and other bone-targeted therapy trials from 1980 to September 2011. For all studies, a mean year of enrolment ([start of enrolment + end of enrolment]/2) was calculated. The incidences of SREs were tabulated and expressed as percentages of on-trial patients. Generalised linear mixed models were used to search for the trends of SREs over time for all placebo and intervention arms. Regression coefficients were interpreted as the odds ratio, which was calculated using the exponential of the slope. Ninety-five per cent confidence intervals were also calculated. RESULTS: In total, 20 eligible studies were identified that reported SRE data from phase III trials, of which 11 were suitable for the quantitative analysis. Most of the articles included patients with breast cancer and the remaining involved patients with prostate, renal cell, bladder and lung cancer or other solid tumours. Enrolment periods for all included data ranged from 1990 to 2009. Statistically significant overall downward trends in pathological fractures and the need for surgery were seen over time. Also significant differences between intervention and placebo were seen with all SREs. CONCLUSION: The decrease in SREs over time may not only be a result of the development of new generation bone-targeted agents, but also due to better systemic management and awareness of events associated with bone metastases.

Efficacy of intracarotid propofol infusion and impact of cerebral blood flow alteration.

BACKGROUND: Intracarotid propofol infusion was studied in canines as an experimental basis for application of propofol in the Wada test. METHODS: First, efficacy and side-effects of propofol anaesthesia were studied in eight mongrel dogs that received intracarotid and i.v. propofol infusions for 30 min according to a cross-over design. Auditory evoked potentials were used to guide anaesthesia. Secondly, eight mongrel dogs received intracarotid propofol infusion during both normal and cerebral hyperperfusion states using nicardipine. Haemodynamics and clinical endpoints were compared between the two infusion conditions. RESULTS: We required 33 (7.6) mg propofol intracarotically vs 113 (17) mg propofol i.v. to achieve an anaesthetic state. The mean arterial pressure (MAP) decreased about 15-27% from the baseline during i.v. infusion. However, no obvious decrease of MAP was observed after intracarotid infusion. Administration of nicardipine increased the blood flow in the internal carotid artery by 17%. Then, the propofol dosage for achieving the anaesthetic effect increased from 7.7 (0.9) mg in the normal control to 11.3 (0.8) mg in the nicardipine group. The onset time of anaesthetic effect was prolonged and the recovery time was shortened during intracarotid infusion during cerebral hyperperfusion. CONCLUSIONS: Compared with i.v. propofol infusion, intracarotid infusion could reach and maintain the target anaesthetic depth with less dosage and without affecting MAP. In addition, increase of cerebral blood flow requires a higher propofol dose, prolongs onset, and shortens recovery time during intracarotid propofol anaesthesia, indicating that patients with a cerebral hyperperfusion state may need higher dose of anaesthetics during the Wada test.

Direct gene transfer in potato: a comparison of particle bombardment of leaf explants and PEG-mediated transformation of protoplasts.

Direct gene transfer methods in potato would facilitate the transfer of multiple genes and the manipulation of metabolic pathways in this species. In this study, up to 1.8 transformation events per shot (=0.5 per bombarded leaf) and 67.2 events per million protoplasts treated were obtained with particle bombardment and PEG-mediated direct DNA uptake, respectively. Limited disassociation of both HPT and GUS genes appeared to occur during the process of integration in only 19% of transformants. A large number of transformed potato plants with transgene expression at levels comparable to Agrobacterium-mediated transformation was obtained. High levels of GUS expression were only obtained in lines derived from PEG treatment. No correlation between the number of gene insertions and gene expression levels was found, suggesting that multiple insertions may have little or no effect on transgene expression.

Variables affecting simulated use determination of residual ethylene oxide in medical devices.

In autumn 1993, AAMI/ST/WG 63, Sterilization Residuals Working Group undertook the task of studying factors involved in determining the amount of residual ethylene oxide in medical devices after sterilization and developing a protocol for controlling the relevant variables. The protocol was evaluated by conducting a round robin study consisting of 8 participating laboratories from around the country. Results of this round robin study demonstrated the range over which results may vary despite controls placed on the time and temperature at which determinations were conducted. The data from the study suggest that small, random variations in technique during short sample extraction times can lead to variability in the results. Variables such as initial water temperature, oven temperature, weighing of sample, and length of extraction should be carefully controlled. Inherent variations in the material composition of similar devices are possible contributing factors. The efforts of this working group and the subsequent evaluation and discussion of its findings are presented.

Many parallel losses of infA from chloroplast DNA during angiosperm evolution with multiple independent transfers to the nucleus.

We used DNA sequencing and gel blot surveys to assess the integrity of the chloroplast gene infA, which codes for translation initiation factor 1, in >300 diverse angiosperms. Whereas most angiosperms appear to contain an intact chloroplast infA gene, the gene has repeatedly become defunct in approximately 24 separate lineages of angiosperms, including almost all rosid species. In four species in which chloroplast infA is defunct, transferred and expressed copies of the gene were found in the nucleus, complete with putative chloroplast transit peptide sequences. The transit peptide sequences of the nuclear infA genes from soybean and Arabidopsis were shown to be functional by their ability to target green fluorescent protein to chloroplasts in vivo. Phylogenetic analysis of infA sequences and assessment of transit peptide homology indicate that the four nuclear infA genes are probably derived from four independent gene transfers from chloroplast to nuclear DNA during angiosperm evolution. Considering this and the many separate losses of infA from chloroplast DNA, the gene has probably been transferred many more times, making infA by far the most mobile chloroplast gene known in plants.

Homeologous plastid DNA transformation in tobacco is mediated by multiple recombination events.

Efficient plastid transformation has been achieved in Nicotiana tabacum using cloned plastid DNA of Solanum nigrum carrying mutations conferring spectinomycin and streptomycin resistance. The use of the incompletely homologous (homeologous) Solanum plastid DNA as donor resulted in a Nicotiana plastid transformation frequency comparable with that of other experiments where completely homologous plastid DNA was introduced. Physical mapping and nucleotide sequence analysis of the targeted plastid DNA region in the transformants demonstrated efficient site-specific integration of the 7.8-kb Solanum plastid DNA and the exclusion of the vector DNA. The integration of the cloned Solanum plastid DNA into the Nicotiana plastid genome involved multiple recombination events as revealed by the presence of discontinuous tracts of Solanum-specific sequences that were interspersed between Nicotiana-specific markers. Marked position effects resulted in very frequent cointegration of the nonselected peripheral donor markers located adjacent to the vector DNA. Data presented here on the efficiency and features of homeologous plastid DNA recombination are consistent with the existence of an active RecA-mediated, but a diminished mismatch, recombination/repair system in higher-plant plastids.

An Arabidopsis gene encoding a chloroplast-targeted beta-amylase.

beta-Amylase is one of the most abundant starch degrading activities found in leaves and other plant organs. Despite its abundance, most if not all of this activity has been reported to be extrachloroplastic and for this reason, it has been assumed that beta-amylases are not involved in the metabolism of chloroplast-localized transitory leaf starch. However, we have identified a novel beta-amylase gene, designated ct-Bmy, which is located on chromosome IV of Arabidopsis thaliana. Ct-Bmy encodes a precursor protein which contains a typical N-terminal chloroplast import signal and is highly similar at the amino acid level to extrachloroplastic beta-amylases of higher plants. Expression of the ct-Bmy cDNA in E. coli confirmed that the encoded protein possesses beta-amylase activity. CT-BMY protein, synthesized in vitro, was efficiently imported by isolated pea chloroplasts and shown to be located in the stroma. In addition, fusions between the predicted CT-BMY transit peptide and jellyfish green fluorescent protein (GFP) or the entire CT-BMY protein and GFP showed accumulation in vivo in chloroplasts of Arabidopsis. Expression of the GUS gene fused to ct-Bmy promoter sequences was investigated in transgenic tobacco plants. GUS activity was most strongly expressed in the palisade cell layer in the leaf blade and in chlorenchyma cells associated with the vascular strands in petioles and stems. Histochemical staining of whole seedlings showed that GUS activity was largely confined to the cotyledons during the first 2 weeks of growth and appeared in the first true leaves at approximately 4 weeks.

[Quantification of female teenagers' competence of sexual cognition].

Compiling a questionnaire of sexual cognition for surveying 224 female teenagers (11 to 14 years old), the results showed that they were deficient in the knowledge of sexual physiology, mortality and law. And also, the deficiency had a high co-relationship with the age of surveyed female teenagers. It suggested that this questionnaire be valuable in the quantification of sexual cognition.

Analysis of 1.9 Mb of contiguous sequence from chromosome 4 of Arabidopsis thaliana.

The plant Arabidopsis thaliana (Arabidopsis) has become an important model species for the study of many aspects of plant biology. The relatively small size of the nuclear genome and the availability of extensive physical maps of the five chromosomes provide a feasible basis for initiating sequencing of the five chromosomes. The YAC (yeast artificial chromosome)-based physical map of chromosome 4 was used to construct a sequence-ready map of cosmid and BAC (bacterial artificial chromosome) clones covering a 1.9-megabase (Mb) contiguous region, and the sequence of this region is reported here. Analysis of the sequence revealed an average gene density of one gene every 4.8 kilobases (kb), and 54% of the predicted genes had significant similarity to known genes. Other interesting features were found, such as the sequence of a disease-resistance gene locus, the distribution of retroelements, the frequent occurrence of clustered gene families, and the sequence of several classes of genes not previously encountered in plants.

Interlaboratory comparison of analytical methods for residual ethylene oxide at low concentration levels in medical device materials.

An interlaboratory comparison of two extraction methods and one thermal desorption test method for the quantification of ethylene oxide (EO) by gas chromatography in two common medical device materials, high density polyethylene (HDPE) and plasticized polyvinyl chloride (PVC), was conducted by 15 laboratories. The three procedures included extraction with water, extraction with acetone, and headspace gas analysis, respectively. Materials were processed through an industrial EO cycle and aerated for various periods to achieve target levels of a low (5 micrograms/g), medium (10 micrograms/g), and high (25 micrograms/g) residual determination following extraction or thermal desorption. The results of this study, using only the data from the laboratories that did not deviate from the procedure, showed that the average estimated total coefficient of variation ranged from 3.63 to 12.42% for the three different methods. Each of the methods is suitable for use as a reference test method for determining residual EO in polymeric materials in the concentration range 2.8-42.3 micrograms/g.

Residual ethylene oxide determination in polymethyl methacrylate disks and intraocular lenses by headspace gas analysis and N,N-dimethylformamide extraction.

The residue in an ethylene oxide (EO)-exposed polymethyl methacrylate (PMMA) material [flat disk and intraocular lens (IOL)] was determined using three methods: semiautomatic and manual headspace methods and N,N-dimethylformamide (DMF) solvent extraction. Results from the analysis of three different sample configurations at three different EO concentrations are compared. Results from the DMF extraction of PMMA indicate that the headspace methods at 100 degrees C are not exhaustive with respect to recovery of total residual ethylene oxide. Furthermore, the manual headspace method appears to be slightly more effective than the semiautomatic injection headspace method. Sorption of EO and subsequent extraction is related to the surface area-to-volume ratio of the sample, with higher concentrations observed in samples with the high ratio.

Interlaboratory comparison of analytical methods for residual ethylene oxide in medical device materials.

An interlaboratory comparison of four gas chromatographic test procedures for the quantification of ethylene oxide in an acrylic polymer was conducted by thirteen laboratories. The procedures included extractions with water, acetone, and N,N-dimethylformamide, and headspace gas analysis. The results of this study, using only the data from the labs that did not deviate from the procedure, showed that the average estimated total coefficient of variation ranged from 8 to 22% for the four different methods. Each of the methods is suitable for use as a reference test method for determining residual ethylene oxide in polymeric materials.