An exploratory survival analysis of anti-angiogenic therapy for recurrent malignant glioma

Recent clinical trial results suggest that anti-angiogenic therapy may be effective against recurrent malignant glioma. Though these treatments prolong progression-free survival, the extent to which they prolong overall survival is unknown. We pooled data from 34 patients treated at a single institution on phase II clinical trials of bevacizumab and cediranib, and we compared these data to 18 patients treated on clinical trials of cytotoxic chemotherapies. In univariate and multivariate analyses, treatment group was a significant predictor of progression-free but not overall survival. Median progression-free survival was 8 vs. 22 weeks in patients treated with cytotoxic as compared to anti-angiogenic therapy (P = 0.01). Median overall survival was nearly identical in the two groups (39 vs. 37 weeks). The results of this exploratory analysis suggest that anti-angiogenic therapy may fail to prolong overall survival in patients with recurrent malignant glioma. If this conclusion proves correct, progression-free survival may be an inappropriate endpoint for phase II trials of anti-angiogenic therapies.     

New South Wales population-based birthweight percentile charts

Objective : To derive newborn percentile charts using NSW population and hospital-based data.
Methodology : Birthweight data for liveborn singleton infants were obtained from the New South Wales Midwives Data Collection (MDC) from 1990 to 1994 inclusive ( n = 422139). Data were also collected from King George V Hospital (KGV) for liveborn singleton infants less than 35 weeks of gestation for 1982-89 inclusive, and for all gestations for 1990-95 inclusive ( n = 30 610). Birthweight percentiles were derived using the MDC data separately for mates and females. Head circumference ( n = 29 090) and birth length percentiles ( n = 26 973) were derived from the KGV data.
Results : The charts derived from MDC data had generally higher percentiles than previously published charts. These represent the largest Australian population-based study published to date.
Conclusions : Periodic review of newborn growth charts is recommended because of changing ethnic and socio-economic factors.     

Double-positive thymocytes resistant to antigen-MHC-induced negative selection lack active caspase

Thymocytes bearing autoreactive TCR are eliminated from the organism by a process termed negative selection. The molecular basis of this deletion has been recently shown to be a consequence of TCR-triggered activation of a caspase by certain peptide-MHC ligands in the immature CD4+CD8+ double-positive (DP) thymocyte subpopulation. Of note, the numerically minor TCRhigh DP thymocyte subpopulation, unlike the major TCRlow DP subset, is resistant to negative selection. Despite exposure to cognate peptide, TCRhigh DP thymocytes mature into single-positive thymocytes and are exported into the periphery. Here we investigated the mechanism by which these thymocytes escape negative selection. Using a cytochemical assay in conjunction with a caspase-specific affinity ligand, we demonstrate that the resistance of the TCRhigh DP thymocytes to negative selection correlates with the disappearance of TCR-triggered caspase activity in these cells. Thus thymocytes which have presumably begun the positive selection process inactivate the thymic caspase pathway and are no longer susceptible to negative selection.      

Relative mutagenicities of gaseous nitrogen oxides in the supF gene of pSP189

Gaseous nitric oxide (NO), an environmental pollutant found in cigarette smoke and diesel exhaust, has been shown to generate mutations in aerobic in vitro assays. The objective of this study was to identify which oxides of nitrogen, formed in the gaseous phase from NO, possess mutagenic activity. Samples of the plasmid pSP189, in 1 M HEPES buffer, pH 7.4, were exposed to preparations of nitrogen dioxide (NO2), dinitrogen trioxide (N2O3) or an air control. The gas mixtures were formed in a gas-tight syringe and were then introduced into 1 l flasks. The plasmid solution was introduced immediately afterwards. Transformation of Escherichia coli strain MBM7070 with the treated plasmids allowed analysis of mutation frequencies and the types of mutations induced in the target supF gene. The mutation frequency resulting from NO2 exposure was not different from that of the control. However, N2O3 produced a substantial number of mutations. The mutation frequency and the types of mutations were found to depend on the length of time that the gases were allowed to incubate in the syringe prior to introduction into the 1 l flasks (mutation frequency was maximal at approximately 2 min). The most prevalent mutations were AT-->GC transitions (68%), followed by GC-->AT transitions (30%), similar to previous findings when pure NO was bubbled through pSP189 solutions. These results suggest that it is N2O3, rather than NO2, that is the most likely source of mutagenic potential from gaseous nitrogen oxides.      

Comparison of the rehabilitation status of continuous ambulatory peritoneal dialysis and in-centre haemodialysis in Chinese patients

Summary: In Hong Kong, dialysis treatment has become more accessible in recent years. Due to a shortage of kidney donors patients are required to stay on dialysis for longer periods. the rehabilitation status of 181 end-stage renal failure (ESRF) patients on dialysis, 34 on in-centre haemodialysis (ICHD) and 147 on continuous ambulatory peritoneal dialysis (CAPD), at the Prince of Wales Hospital was studied. There was no statistically significant difference in physical functioning due to treatment type; however, CAPD patients were shown to be more socially active and had a better family life than ICHD patients (P < 0.01). There were no statistically significant correlations between physical functioning, social life or family life and the duration of dialysis in both ICHD and CAPD patients. In both groups of patients 52.9% of ICHD and 52.4% of CAPD patients had decreased employment status. All the patients were assessed by doctors-in-charge on their physical fitness for employment, 85.7% (n= 6) of the unemployed ICHD patients and 71% (n= 44) of the unemployed CAPD patients were considered to be physically fit to work. Due to the ageing of the general population and greater availability of dialysis treatment and higher survival rate of the chronically ill have led to an increase in the number of elderly patients on dialysis (aged 60 years and over). the proportion of elderly dialysis patients in our renal centre increased from 7–23% in the past 5 years. Continuous ambulatory peritoneal dialysis patients aged less than 60 years were found to be significantly more physically active and socially active than CAPD patients aged over 60 years (P < 0.01). In the aspect of a better family life for these patients, no statistically significant difference was found between the two groups. Rehabilitation of ESRF patients can be achieved by renal replacement therapy. It is concluded that CAPD patients have better adaptation in social life and family life than ICHD patients.     

Intracellular localization of 12-O-3-N-dansylamino TPA in C3H/10T1/2 mouse cell line

The fluorescent 12-O-tetradecanoylphorbol-13-acetate (TPA) analoguedansyl-TPA allowed the distribution of fluorescent moleculesto be visualized in living mouse fibroblasts. The entry of dansyl-TPAinto cells occurred within millisecond time scale and was foundlargely energy independent. Dansyl-TPA was shown to stain theendoplasmic reticulum, Golgi apparatus, mitochondria and nuclearmembrane. In addition, dansyl-TPA fluorescence was found toparallel that obtained with rhodamine-conjugated anti- tubulin.The intracellular location of the dansyl-TPA fluorescence canbe taken into account to explain the pleiotropic action of TPAin the cells.     

Characterizations of adenovirus type 41 isolates from children with acute gastroenteritis in Japan, Vietnam, and Korea

Genetic and antigenic characterizations of 70 strains of adenovirus type 41 (Ad41), isolated between 1998 and 2001 from children in Japan, Vietnam, and Korea, were done by DNA restriction enzyme (RE) analysis, sequencing analysis, and monoclonal antibody (MAb)-based enzyme-linked immunosorbent assay (ELISA). Eight genome types were observed in the present study, among which D25, D26, D27, and D28 were novel genome types. These eight genome types were divided into two genome-type clusters (GTCs) based on phylogenetic analysis of the hypervariable regions (HVRs) of the hexon. GTC1 includes D1, D25, D26, D27, and D28, and the GTC2 contains D4, D12, and D22. The amino acid homologies among the members within a GTC were 97 to 100%, whereas between the members of different GTCs the homologies were 92 to 94%. The specificity of the GTC classification was confirmed by ELISA with MAb 1F, which was selected by the Ad41 prototype Tak strain. It was found that only the isolates of GTC1 but not of GTC2 reacted with MAb 1F. These results suggest that Ad41 isolates from the three countries should be classified into two subtypes. The accumulation of amino acid mutations located in HVRs of hexon are indicative for the classification of Ad41 subtype.