Buffered 1% Lidocaine With Epinephrine Can Be as Effective as Nonbuffered 2% Lidocaine With Epinephrine for Maxillary Field Block

Buffering local anesthetics with epinephrine (Epi) offers clinicians options not often considered. This study assessed outcomes for pulpal anesthesia, pain on injection, and time to midface numbness for buffered 1% lidocaine with 1:100,000 Epi versus nonbuffered 2% lidocaine with 1:100,000 Epi. In this trial with a randomized, crossover design, buffered 1% lidocaine was compared with nonbuffered 2% lidocaine. Subjects were adult volunteers who served as their own controls. The predictor variables were alternate drug formulations. The outcome variables were subjects' responses to cold and electric pulp testing (EPT) stimulation of the maxillary first molar and canine, pain levels during the injection, and time to midface numbness. After maxillary field blocks with 40 mg of buffered lidocaine or 80 mg of nonbuffered lidocaine, subjects reported pain on injection and responses of the maxillary first molar and canine after cold and EPT stimulation. Teeth were tested before field block and at 30-minute intervals until a positive response was detected. Two weeks later, subjects were tested with the alternate drug combinations. For all outcome variables, assessment of treatment difference, calculated as 1% buffered minus 2% nonbuffered, was performed with the Wilcoxon rank sum test with significance at P < .05. More of the 24 subjects were women and Caucasian. The median age was 23.5 years (interquartile range, 21, 25 years), and the median body weight was 155 lb (interquartile range, 128.5, 176.5 lb). Pain levels during the injection were significantly lower for 1% buffered lidocaine, with P = .04. Times to response after injection were not significantly different between the 2 drug formulations for the cold test on a molar, with P = .08, or the cold test on a canine, with P = .22. However, times to response were significantly longer for nonbuffered drugs for EPT on the molar and canine, both with P = .01. Buffering 1% lidocaine with 1:100,000 Epi reduces the pain on injection with a maxillary field block and results in similar lengths of pulpal anesthesia tested with a cold stimulus as compared with nonbuffered 2% lidocaine with 1:100,000 Epi

Time-dependent inhibition of oxygen radical induced lung injury

Experimental acute lung injury mediated by reactive metabolites of oxygen can be inhibited by the antioxidant enzymes catalase and Superoxide dismutase (SOD). However, the specific time interval during which these enzymes must be present in order to cause protection is not well defined. Using two experimental models of oxidant-dependent acute lung injury, one involving the intratracheal injection of glucose, glucose oxidase, and lactoperoxidase and the other involving the intravenous injection of cobra venom factor (CVF), we investigated the effects of delaying antioxidant administration on the outcome of the inflammatory response. In both cases, the protective effects of catalase and SOD were rapidly attenuated when their administration was delayed for a short period of time. For example, intratracheal catalase resulted in 98% protection when given simultaneously with the glucose oxidase and lactoperoxidase, but only 13% protection when the catalase was delayed 4 min. Likewise, in the CVF-induced lung injury model, intravenous catalase resulted in 40% protection when given simultaneously with the CVF, but only 2% protection when the catalase was delayed 20 min, even though the peak of the injury occurred hours after the initiation of the injury. A similar time dependence was seen with SOD. These results indicate that antioxidant therapy is required early in the course of oxygen radical-mediated acute lung injury for effective protection.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44504/1/10753_2004_Article_BF00914272.pd

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio