Social deprivation and survival on renal replacement therapy in England and Wales

This study examines the association between social deprivation and patient characteristics and outcomes in a nationally representative cohort of incident renal replacement therapy (RRT) patients. All Caucasian patients reported to the UK Renal Registry between 1997 and 2004 by centers in England and Wales with high data completeness were included. Social deprivation was assessed using the Townsend index. Socially deprived patients were more likely to be referred late. They were less likely to receive peritoneal dialysis (25.1 vs 34.8% on day 1, P trend <0.0001) or a renal transplant (5.3 vs 12.4% at 1 year, P trend <0.0001), and were less likely to attain UK Renal Association standards for hemoglobin and phosphate at 1 year. Crude survival decreased significantly with increasing deprivation for patients under the age of 65 years, but not for those aged 65 years and above (likelihood ratio for age-social deprivation interaction P<0.0001). Social deprivation was significantly associated with poorer survival after adjustment for age, gender, and cause of renal failure. After adjusting for baseline co-morbidity, social deprivation was no longer associated with poorer survival. Baseline differences in co-morbidity seem to explain poorer crude survival in incident Caucasian RRT patients from socially deprived areas in England and Wales. Differences also exist in some processes of care and intermediate outcomes, which may be amenable to intervention.     

Amplification versus mutation as a mechanism for reversion of anHGPRT mutation

We have used a cloned cDNA for hypoxanthine-guanine phosphoribosyltransferase (HGPRT) to analyze the HGPRTgene and mRNA in an HGPRT-deficient mutant of Chinese hamster cells (RJK10) and its HGPRT-positive revertants. By Southern blot analysis, no DNA rearrangements were detected within the genes from any of the cell lines examined. However, four of five spontaneous revertants each contained 10-to 20-fold more copies of the HGPRTgene than did RJK10 or wild-type cells. In contrast, the gene was not amplified in four mutagen-induced revertants. The RJK10 mutation did not alter the size or concentration of HGPRT mRNA and representatives of the revertants contained the mRNA in amounts proportional to the number of genes they carried. Examples of clones with either stable or unstable gene amplification were identified and their HGPRT-positive phenotypes were shown to be dependent on the gene amplification. In a stably amplified revertant, the extra genes were found to be syntenic with the X chromosome marker glucose-6-phosphate dehydrogenase. In an unstable revertant only one of the 10 to 20 copies of the gene could be shown to be X linked. Thus, we found that RJK10 can revert by at least two distinct mechanisms: amplification of the HGPRTgene, which occurred spontaneously, or point mutation, which predominated after exposure to mutagens.     

Adolescents anticipated experience of screening for genital herpes

Screening asymptomatic adolescents for genital herpes will require sensitivity to adolescents' developmental needs. Twenty-four adolescents (age range 1619 years) were interviewed to explore their perceptions of screening. In general, adolescents thought screening for genital herpes would be viewed as taking care of themselves, although there were concerns that their peers might view getting screened as implying that the adolescent was infected or sexually promiscuous. Most adolescents expected their parents to respond positively, but typically thought that younger adolescents should obtain parental consent for screening, and that adolescents should inform their parents of positive test results. Adolescents wanted to be screened in settings that provided confidentiality and by non-judgemental care providers, but they differed on the setting which they believed would accomplish this. Some recommended mass screening (for example, screening all of those in a certain year at school), presumably as a way to reduce embarrassment and/or stigma. Screening programmes that are adolescent-friendly and accessible, and address adolescents' specific concerns regarding managing the information, can be created.     

Alu-primed polymerase chain reaction for regional assignment of 110 yeast artificial chromosome clones from the human X chromosome: identification of clones associated with a disease locus.

Over 400 yeast artificial chromosome (YAC) clones were isolated from the human X chromosome, and 110 of these were assigned to regions defined by chromosome translocation and deletion breakpoints. Polymerase chain reaction using Alu primers was applied to YAC clones in order to generate probes, to identify overlapping clones, and to derive "fingerprints" and sequence data directly from total yeast DNA. Several clones were identified in regions of medical interest. One set of three overlapping clones was found to cross a chromosomal translocation implicated in Lowe syndrome. The regional assignment of groups of YAC clones provides initiation points for further attempts to develop large cloned contiguous sequences, as well as material for investigation of regions involved in genetic diseases.     

Efficient adenoviral-mediated ornithine transcarbamylase expression in deficient mouse and human hepatocytes.

100% of primary human hepatocytes infected with an adenoviral vector carrying beta-galactosidase expressed the exogenous gene. Expression was also achieved in > 40% of adult mouse hepatocytes in vivo. Normal levels of activity were achieved in mouse ornithine transcarbamylase (OTC)-deficient primary hepatocytes using another adenoviral vector carrying human OTC cDNA. Study of OTC-deficient primary human hepatocytes from a single patient confirmed the utility of adenoviral delivery of OTC. We describe adenoviral-mediated exogenous gene expression in human and mouse hepatocytes in vitro and in mouse liver in vivo. Data suggest that adenoviral vectors may be useful for correcting OTC deficiency.     

Peptide Chain Termination, VII. The Ribosomal and Release Factor Requirements for Peptide Release

Release factors participate in release of fMet from fMet-tRNA · AUG · ribosome intermediates upon binding to ribosomes. This release requires R factor and occurs in the absence of terminator codon in reactions containing 20 per cent ethanol. Release occurs only when both 30S and 50S ribosomal subunits are present and when fMet-tRNA is located in the ribosomal P site. Release factor-dependent deacylation of fMet-tRNA is inhibited by sparsomycin, amicetin, lincocin, and chloramphenicol, antibiotics which have little effect on binding of R factor to ribosomes. The possible role of peptidyl transferase in the release reaction is discussed.     

Three-dimensional measurement of essential tremor.

A mechanical linkage device was used to measure the three-dimensional position of the fingertip during a postural task. Thirty patients with essential tremor were tested simultaneously with the device, uniaxial accelerometry, and clinical tremor measures. Eighteen patients were tested again 16+/-4 days later. The device accurately recorded the three-dimensional behavior of essential tremor. Measures from the device included mean three-dimensional velocity, mean three-dimensional dispersion, and power of the three-dimensional acceleration. The logarithms of these measures were strongly correlated (r = .841-.984) with all clinical measures including self-reported tremor disability. The device measures were reliable within and between testing sessions (intraclass correlation coefficients = .971-.977). The performance of the device was superior to uniaxial accelerometry, most likely as a result of the three-dimensional nature of the measurements. We conclude that essential tremor can be validly and reliably quantified during a postural task providing the recording device records movement in three dimensions and the measurements are logarithmically transformed.