Genetic factors associated with intestinal metaplasia in a high risk Singapore-Chinese population: a cohort study

Background: Intestinal metaplasia (IM) is an important precursor lesion in the development of gastric cancer ( GC). The aim of this study was to investigate genetic factors previously linked to GC risk for their possible association with IM. A total of 18 polymorphisms in 14 candidate genes were evaluated in a Singapore-Chinese population at high risk of developing GC.

Contribution of process variables to the entrapment efficiency of propranolol hydrochloride within ethylcellulose microspheres prepared by the solvent evaporation method as evaluated using a factorial design

The effects of the process variables, pH of aqueous phase, rate of addition of organic, polymeric, drug-containing phase to aqueous phase, organic:aqueous phase volume ratio and aqueous phase temperature on the entrapment of propranolol hydrochloride in ethylcellulose (N4) microspheres prepared by the solvent evaporation method were examined using a factorial design. The observed range of drug entrapment was 1.43 +/- 0.02%w/w (pH 6, 25 degrees C, phase volume ratio 1:10, fast rate of addition) to 16.63 +/- 0.92%w/w (pH 9, 33 degrees C, phase volume ratio 1:10, slow rate of addition) which corresponded to mean entrapment efficiencies of 2.86 and 33.26, respectively. Increased pH, increased temperature and decreased rate of addition significantly enhanced entrapment efficiency. However, organic:aqueous phase volume ratio did not significantly affect drug entrapment. Statistical interactions were observed between pH and rate of addition, pH and temperature, and temperature and rate of addition. The observed interactions involving pH are suggested to be due to the abilities of increased temperature and slow rate of addition to sufficiently enhance the solubility of dichloromethane in the aqueous phase, which at pH 9, but not pH 6, allows partial polymer precipitation prior to drug partitioning into the aqueous phase. The interaction between temperature and rate of addition is due to the relative lack of effect of increased temperature on drug entrapment following slow rate of addition of the organic phase. In comparison to the effects of pH on drug entrapment, the contributions of the other physical factors examined were limited.

Factors influencing the activity of taurolidine against spores of Bacillus subtilis (NCTC 10073)

The cidal activities of aqueous taurolidine (2.0% w/v containing 5.0% wlv polyvinylpyrrolidone as a solubilising agent) and alcoholic taurolidine (2.0% w/v dissolved in Isopropyl alcohol 50% v/v) against spores of Bacillus subtilis NCTC 10073 were evaluated at 20 degrees C, 37 degrees C, 45 degrees C and 55 degrees C. Increased temperature increased both the rate and extent of sporicidal activity of both solutions. Total spore kill was not observed in either solution type over the range of temperatures and contact times examined. There were no observed differences between the sporicidal activities of aqueous and alcoholic taurolidine solutions at all temperatures examined. Ultrasonic energy (50 Hz operating frequency in a 150 W ultrasonic bath in conjunction with increasing temperature allowed to rise naturally from ambient temperature to 41 degrees C over 4 h) enhanced the sporicidal activities of both solution types. However, the difference in activity between the two solution types was not significant. Compared to normal spores, alteration of spore coat layers (hydrogen-form spores) did not alter spore susceptibility to aqueous taurolidine at elevated temperatures of 37 degrees C and 55 degrees C.

Genetic risk factors affecting mitochondrial function are associated with kidney disease in people with Type 1 diabetes

AIM: To evaluate the association with diabetic kidney disease of single nucleotide polymorphisms (SNPs) that may contribute to mitochondrial dysfunction.

METHODS: The mitochondrial genome and 1039 nuclear genes that are integral to mitochondrial function were investigated using a case (n=823 individuals with diabetic kidney disease) vs. control (n=903 individuals with diabetes and no renal disease) approach. All people included in the analysis were of white European origin and were diagnosed with Type 1 diabetes before the age of 31 years. Replication was conducted in 5093 people with similar phenotypes to those of the discovery collection. Association analyses were performed using the plink genetic analysis toolset, with adjustment for relevant covariates.

RESULTS: A total of 25 SNPs were evaluated in the mitochondrial genome, but none were significantly associated with diabetic kidney disease or end-stage renal disease. A total of 38 SNPs in nuclear genes influencing mitochondrial function were nominally associated with diabetic kidney disease and 16 SNPS were associated with end-stage renal disease, secondary to diabetic kidney disease, with meta-analyses confirming the same direction of effect. Three independent signals (seven SNPs) were common to the replication data for both phenotypes with Type 1 diabetes and persistent proteinuria or end-stage renal disease.

CONCLUSIONS: Our results suggest that SNPs in nuclear genes that influence mitochondrial function are significantly associated with diabetic kidney disease in a white European population

Predictive Factors for Local Control in Primary and Metastatic Lung Tumours after Four to Five Fraction Stereotactic Ablative Body Radiotherapy: A Single Institution's Comprehensive Experience

AIMS: We report the outcomes of a large lung stereotactic ablative body radiotherapy (SABR) programme for primary non-small cell lung cancer (NSCLC) and pulmonary metastases. The primary study aim was to identify factors predictive for local control.

MATERIALS AND METHODS: In total, 311 pulmonary tumours in 254 patients were treated between 2008 and 2011 with SABR using 48-60 Gy in four to five fractions. Local, regional and distant failure data were collected prospectively, whereas other end points were collected retrospectively. Potential clinical and dosimetric predictors of local control were evaluated using univariate and multivariate analyses.

RESULTS: Of the 311 tumours, 240 were NSCLC and 71 were other histologies. The 2 year local control rate was 96% in stage I NSCLC, 76% in colorectal cancer (CRC) metastases and 91% in non-lung/non-CRC metastases. Predictors of better local control on multivariate analysis were non-CRC tumours and a larger proportion of the planning target volume (PTV) receiving ≥100% of the prescribed dose (higher PTV V100). Among the 45 CRC metastases, a higher PTV V100 and previous chemotherapy predicted for better local control.

CONCLUSIONS: Lung SABR of 48-60 Gy/four to five fractions resulted in high local control rates for all tumours except CRC metastases. Covering more of the PTV with the prescription dose (a higher PTV V100) also resulted in superior local control.