The use of radiation dose-reduction techniques in the practices of dental faculty members

X-ray exposure to dental patients has been significantly reduced by the introduction of speed group E intraoral film, rectangular beam limitation, long position indicating devices (PIDs), and rare-earth intensifying screens for extraoral radiography. Research indicates that many dentists do not use these techniques. However, schools of dentistry have implemented them to varying degrees for many years, so this investigation was conducted to determine the extent to which dental school faculty members use these materials and techniques in their own practices. Comparisons were made between full- and part-time instructors, those in practice for fifteen years or less and those in practice for more than fifteen years, and those with postgraduate education versus those with no formal education beyond dental school. The significance of differences was measured with chi-square analysis. The results indicate that dentists with faculty appointments utilize dose-reducing techniques to degrees that are comparable to or greater than reported usage by non-dental faculty practitioners. Faculty dentists in practice fifteen years or less are more likely than their older colleagues to use E-speed film (p = 0.001), whereas those in practice more than fifteen years are more likely to use longer PIDs (p = 0.049). Greater acceptance of these practices by faculty may lead to reinforcement of their use in the clinical education of dental students.     

Inverse relationship between six week postvaccination varicella antibody response to vaccine and likelihood of long term breakthrough infection

BACKGROUND: We used the large clinical database that supported the development of Oka/ Merck varicella vaccine to study the relationship between the primary varicella antibody response, as determined by gpELISA, an enzyme-linked immunosorbent assay that detects antibodies to varicella-zoster virus (VZV) glycoprotein, and the subsequent risk of postvaccination breakthrough varicella. METHODS: We vaccinated 1,164 healthy children with a single dose of varicella vaccine containing 2900 to 9000 plaque-forming units/dose. The primary immune response to vaccination was determined by gpELISA 6 weeks after vaccination. Subjects were followed annually for 7 years to ascertain cases of breakthrough varicella. RESULTS: The estimated vaccine efficacy among children with a 6-week postvaccination antibody titer of > or = 5 gpELISA units was 95.5% (95% confidence interval, 94.2%, 96.8%) compared with 83.5% (95% confidence interval, 76.9%, 89.5%) for subjects with a titer of <5 gpELISA units. Children with a 6-week postvaccination antibody titer of <5 gpELISA units were 3.5 times more likely than those with a titer of > or = 5 gpELISA units to develop breakthrough varicella. CONCLUSIONS: We identified a 6-week postvaccination antibody titer of > or = 5 gpELISA units as an approximate correlate of protection. In addition we established an accelerated failure time model based on log normal hazard that predicted varicella breakthrough rates based on the distribution of 6-week postvaccination varicella antibody titers.     

Pharmacogenetics of hypertension treatment: a structured review

The extent of blood pressure lowering by anti-hypertensive agents is difficult to predict for individual patients, even when evaluated in the context of biochemical or demographic information. Genetic predictors (mainly single nucleotide polymorphisms, SNPs) have been the focus of several recent studies and are gaining much attention. We have conducted a literature search for studies in which the lowering of ambient blood pressure by specific drugs or drug classes in humans was related to specific genotypes. Twenty-eight studies were identified, of which six had a single-dose design, and the remaining 22 studied drug effects after more than 4 weeks of drug administration. Virtually all were association studies. Prospective trials that compared the prognostic value of genetic methods to routine clinical practice were not identified. Almost all studies used a candidate-gene design, usually with a very small number of SNPs (typically one). Gene-gene and gene-environment interactions were studied only rarely. Only one study targeted genes involved in drug metabolism. Most candidate-genes were part of the renin-angiotensin system. By far the most extensively studied has been the angiotensin-converting enzyme insertion/deletion polymorphism (15 studies) but, to date, no clear picture has emerged for this or other genetic variants. Thus, the potential for utility of genetic characterization of individual patients as a predictor of anti-hypertensive response has yet to be realized.     

Effects of blocking platelet-derived growth factor-receptor signaling in a mouse model of experimental prostate cancer bone metastases

BACKGROUND: Expression of platelet-derived growth factor (PDGF) and activation (by autophosphorylation) of its receptor (PDGF-R), a tyrosine kinase, are associated with the growth of metastatic prostate tumor cells in the bone parenchyma. The tyrosine kinase inhibitor STI571 blocks the PDGF signaling pathway by inhibiting PDGF-R autophosphorylation. We examined the effects of STI571, given alone or with paclitaxel (Taxol), on tumor growth in a mouse model of prostate cancer metastasis. METHODS: Human prostate cancer PC-3MM2 cells were injected into the tibias of male nude mice. Three days later the mice (20 per group) were randomly assigned to 5 weeks of treatment with oral and injected water (control), daily oral STI571, weekly injected paclitaxel, or STI571 plus paclitaxel. Lesions in bone and the surrounding muscles were then harvested and analyzed by histology, western blotting (for PDGF-R phosphorylation), immunohistochemistry (for expression of proangiogenic molecules), and double immunofluorescence (to identify endothelial cells and apoptotic tumor cells). Growth of bone lesions was monitored by digital radiography. Bone lesions from control mice were used to establish short-term cell cultures for analysis of PDGF-R phosphorylation. All statistical tests were two-sided. RESULTS: PC-3MM2 cells cultured from bone lesions and treated in vitro with STI571 had less phosphorylated PDGF-R than untreated cells. In control mice, bone lesions expressed high levels of PDGF and activated (i.e., phosphorylated) PDGF-R, whereas lesions in the adjacent musculature did not. Activated PDGF-R was present on the surface of endothelial cells within the bone lesions but not in endothelial cells of uninjected bone. Mice treated with STI571 or STI571 plus paclitaxel had a lower tumor incidence, smaller tumors, and less bone lysis and lymph node metastasis than mice treated with water or paclitaxel alone (P<.001 for all). Mice treated with STI571 or STI571 plus paclitaxel had less phosphorylated PDGF-R on tumor cells and tumor-associated endothelial cells, less tumor cell proliferation, statistically significantly more apoptotic tumor cells (all P<.001), and fewer tumor-associated endothelial cells (P<.001) than control mice. CONCLUSIONS: Endothelial cells appear to express phosphorylated PDGF-R when they are exposed to tumor cells that express PDGF. Using STI571 to inhibit PDGF-R phosphorylation may, especially in combination with paclitaxel, produce substantial therapeutic effects against prostate cancer bone metastasis.     

Family-based association analysis of alcohol dependence in the COGA sample and replication in the Australian twin-family study

Family, twin, and adoption studies have indicated that genetic and environmental factors contribute to the development of alcohol dependence (AD). We conducted a low-density genome-wide association analysis to identify genetic variants influencing AD. We used 11,120 SNPs from the Affymetrix 10K Genechips genotyped in 116 Caucasian pedigrees (272 nuclear families) from Genetic Analysis Workshop 14, a subset from the Collaborative Study on the Genetics of Alcoholism (COGA). Family-based association analyses for AD were performed by the PBAT program for autosomal SNPs and by the FBAT program for X-chromosome SNPs. We identified 37 SNPs associated with AD (P < 10⁻³), thirteen of which were located in known genes. The most significant association with AD was observed with SNP rs1986644 (P = 8.51 × 10⁻⁶) at 13q22 near EDNRB gene. The next best signal was at 1q41 in USH2A (rs532342, P = 1.07 × 10⁻⁵) and the third region was at 3q25.31 in TIPARP (rs1367311, P = 2.31 × 10⁻⁵). Furthermore, we found support for association of MAOA gene (P = 4.14 × 10⁻⁴ for rs979606). Six of the 37 AD associated SNPs were confirmed to be associated with AD in Australian twin-family study sample (P < 0.05). Interestingly, four SNPs in DSCAML1 at 11q23 reached the genome-wide significance (the top SNP is rs10892169 with P = 5.31 × 10⁻⁹), while rs637547 in NKAIN2 at 6q21 showed strong association with AD (P = 5.11 × 10⁻⁷) in the replication sample. These findings offer the potential for new insights into the pathogenesis of AD and will serve as a resource for replication in other populations to elucidate the potential role of these genetic variants in AD.