A randomized clinical trial of anticaries therapies targeted according to risk assessment (caries management by risk assessment)

This randomized parallel group clinical trial assessed whether combined antibacterial and fluoride therapy benefits the balance between caries pathological and protective factors. Eligible, enrolled adults (n = 231), with 1-7 baseline cavitated teeth, attending a dental school clinic were randomly assigned to a control or intervention group. Salivary mutans streptococci (MS), lactobacilli (LB), fluoride (F) level, and resulting caries risk status (low or high) assays were determined at baseline and every 6 months. After baseline, all cavitated teeth were restored. An examiner masked to group conducted caries exams at baseline and 2 years after completing restorations. The intervention group used fluoride dentifrice (1,100 ppm F as NaF), 0.12% chlorhexidine gluconate rinse based upon bacterial challenge (MS and LB), and 0.05% NaF rinse based upon salivary F. For the primary outcome, mean caries increment, no statistically significant difference was observed (24% difference between control and intervention groups, p = 0.101). However, the supplemental adjusted zero-inflated Poisson caries increment (change in DMFS) model showed the intervention group had a statistically significantly 24% lower mean than the control group (p = 0.020). Overall, caries risk reduced significantly in intervention versus control over 2 years (baseline adjusted generalized linear mixed models odds ratio, aOR = 3.45; 95% CI: 1.67, 7.13). Change in MS bacterial challenge differed significantly between groups (aOR = 6.70; 95% CI: 2.96, 15.13) but not for LB or F. Targeted antibacterial and fluoride therapy based on salivary microbial and fluoride levels favorably altered the balance between pathological and protective caries risk factors.     

Arsenic association with circulating oxidized low-density lipoprotein in a Native American community

More than 500 abandoned uranium (U) mines within the Navajo Nation contribute U, arsenic (As) and other metals to groundwater, soil and potentially air through airborne transport. The adverse cardiovascular health effects attributed to cumulative exposure to these metals remains uncertain. The aim of this study was to examine whether environmental exposure to these metals may promote or exacerbate the oxidation of low-density lipoprotein (LDL) cholesterol in this Native American population. The correlation of cardiovascular biomarkers (oxidized LDL (oxLDL) and C-reactive protein (CRP)) from a Navajo cohort (n = 252) with mean annual As and U intakes from water and urine metals was estimated using linear regression. Proof-of-concept assays were performed to investigate whether As and U directly oxidize human LDL. Mean annual As intake from water was positively and significantly associated with oxLDL, but not CRP in this study population, while U intake estimates were negatively associated with oxLDL. In an acellular system, As, but not U, directly oxidized the apolipoprotein B-100 component of purified human LDL. Neither metal promoted lipid peroxidation of the LDL particle. Both the population and lab results are consistent with the hypothesis that As promotes oxidation of LDL, a crucial step in vascular inflammation and chronic vascular disease. Conversely, for outcomes related to U, negative associations were observed between U intake and oxLDL, and U only minimally altered human LDL in direct exposure experiments. Only urine U was correlated with CRP, whereas no other metals in water or urine were apparently reliable predictors of this inflammatory marker.     

Autoradiographic localization of quinuclidinyl benzilate binding to rat pituitary gland

The location of muscarinic receptors in the rat pituitary gland was examined with an autoradiographic technique. Slides containing 10 or 20 micron horizontal sections of tissue were incubated in a solution of 1 n M[3H]quinuclidinyl benzilate (QNB) in phosphate-buffered saline to label muscarinic receptors. Autoradiograms were produced by placing the slides into X-ray cassettes with tritium-sensitive film and processing the film 8-10 weeks later. Minimal binding occurred when sections were incubated in 1 nM[3H]QNB plus 1 microM atropine. Highest specific binding of QNB was found in the anterior and intermediate lobes along their border with the pituitary cleft. Patches of high binding were also seen penetrating the intermediate lobe and at the border between the intermediate and neural lobes. The remainder of the intermediate lobe had background density of autoradiographic grains. Moderate density of specific binding was found throughout the anterior lobe. Low specific binding occurred in the neural lobe.     

Elevated intracellular level of basic fibroblast growth factor correlates with stage of chronic lymphocytic leukemia and is associated with resistance to fludarabine

Chronic lymphocytic leukemia (CLL) is characterized by delayed senescence and slow accumulation of monoclonal, small lymphocytes. Basic fibroblast growth factor (bFGF) is a pleiotropic cytokine that plays a role in hematopoiesis and apoptosis. Elevated bFGF levels have been detected in urine from patients with a variety of neoplastic diseases including various leukemias; however, the cellular source of the bFGF has not been determined. In this study, the intracellular bFGF level in lymphocytes of 36 patients with B-CLL and 15 normal donors was determined using an enzyme-linked immunoassay. In cells derived from patients with high-risk disease, the median level of intracellular bFGF was 381.5 pg/2 x 10(5) cells, compared with a median of 90.5 pg/2 x 10(5) cells in patients with intermediate disease. In patients with low- risk disease, the median bFGF level was 4.9 pg/2 x 10(5) cells, and in normal controls, it was 6.0 pg/2 x 10(5) cells. The difference in the bFGF levels was significant for the comparison between low- and intermediate-risk (P = .00119), low- and high-risk (P < .0001), and intermediate- and high-risk disease (P = .0001). Immunofluorescent stains of peripheral blood mononuclear cells confirmed CLL lymphocytes as a cellular source of bFGF. To evaluate the potential contribution of elevated intracellular bFGF levels to the phenotype of CLL cells, leukemic cells were cultured in vitro with an apoptotic stimulus (fludarabine). CLL cells with high intracellular levels of bFGF appeared to be more resistant to fludarabine treatment. The addition of bFGF to fludarabine-treated CLL cells resulted in a delay of apoptosis and prolonged survival. These data suggest that bFGF may contribute to the resistance of CLL cells to an apoptotic stimulus.     

Uric acid excretion: quantitative assessment from spot, midmorning serum and urine samples.

Uric acid excretion can be measured in milligrams of urinary uric acid per decilitre of glomerular filtrate by obtaining the product of urinary uric acid and serum creatinine concentrations and dividing by the urine creatinine (all concentrations in mg/dL). In 29 normal adult men, the excretion rate in spot, midmorning samples was 0.4 +/- 0.1 (SD) mg of uric acid per decilitre of glomerular filtrate. Eight of 36 untreated gouty men excreted acid at a rate more than three standard deviations above normal. Excretion of uric acid is conveniently and physiologically assessed by this simple method.