Germline mutations in the p73 gene do not predispose to familial prostate-brain cancer

BACKGROUND: Analysis of high-risk prostate cancer (PC) families with at least one confirmed case of primary brain cancer (BC) has identified a region of genetic linkage on chromosome 1p36 termed CAPB. The p36 region of chromosome one has been reported to have frequent loss of heterozygosity (LOH) in brain and central nervous system (CNS) tumors and epidemiological studies have shown an increased relative risk of BC and tumors of the CNS in PC families. In 1997 a reported tumor suppressor with high homology to p53, termed p73, was mapped to the p36 region of chromosome one. Here, we examine the p73 gene as a potential candidate for CAPB. METHODS: Ninety-four members from the 12 prostate-brain cancer families in which linkage was originally found were examined. The complete coding region and intron-exon boundaries of the p73 gene were analyzed for germline mutations by Single Stranded Conformational Polymorphism analysis (SSCP) and direct DNA sequencing. RESULTS: Silent nucleotide substitutions only were detected within the coding regions of the gene in affected individuals. Nucleotide changes were detected in introns 1, 6, 8, 9, and 10, but all were located >or=16 base pairs from the splice site, and are thus unlikely to be deleterious mutations. CONCLUSIONS: Germline mutations in the p73 gene are unlikely to be critical for inherited susceptibility to PC in this specified subset of families.     

Imaging studies for acute low back pain. When and when not to order them

Acute low back pain is generally a self-limited condition, and most patients recover within a few weeks without the need for imaging studies. However, physicians need to be on the lookout for red flags that point to more serious conditions, such as infection or malignancy, which require imaging. In this article, the authors identify these warning signs and discuss the appropriate use of imaging studies for a variety of symptoms and conditions.     

Nicotine reduces the frequency of anger reports in smokers and nonsmokers with high but not low hostility: an ambulatory study

Two studies were conducted to determine the anger-attenuating effects of nicotine as a function of trait hostility. The 1st study examined the effects of nicotine on diary ratings of anger during a 24-hr period in a natural setting in 30 smokers and 30 nonsmokers. Participants took part in 2 monitoring sessions involving the administration of a nicotine patch and a placebo patch. Participants were categorized as high or low on trait hostility on the basis of their scores on the Cook-Medley Hostility scale. Administration of the nicotine patch, compared with the placebo patch, resulted in a significant reduction in diary reports of anger from 24% to 13% in high-hostile participants. In low-hostile participants, nicotine had no effect on reports of anger during the day. The anger-palliative effects of nicotine were greatest among participants more frequently reporting anger on the placebo-patch day. These effects were independent of smoking status and gender. The 2nd study, which was restricted to high-hostile smokers (n = 19) and nonsmokers (n = 23), found that, compared with a placebo patch, administration of nicotine resulted in significant reductions in reports of anger in smokers and nonsmokers. The results of these 2 studies clearly link nicotine to reduced reports of anger in high-hostile individuals.     

Confirmation of prostate cancer susceptibility genes using high-risk families

Data from many types of studies support the hypothesis that strong familial components are involved in the etiology of prostate cancer. One way to access such genes is through the study of families with multiple affected family members and, in particular, families with individuals affected comparatively early in life. Several prostate cancer susceptibility loci have been described to date. Confirmation of the linkage and estimation of the proportion of families who are linked in large independent datasets is essential to understanding the significance of susceptibility genes. We explore the methodology used to perform such studies and the factors that can limit the ability to confirm linkage results. We report specifically the example of the HPC1 gene on 1q24-25.     

Neuropathic Tissue Responds Preferentially to Stimulation by Intense Focused Ultrasound

We tested the hypothesis that neuropathic tissue is more sensitive to stimulation by intense focused ultrasound (iFU) than control tissue. We created a diffusely neuropathic paw in rats via partial ligation of the sciatic nerve, whose sensitivity to iFU stimulation we compared with sham-surgery and normal control paws. We then applied increasing amounts of iFU (individual 0.2 s pulses at 1.15 MHz) to the rats' paws, assaying for their reliable withdrawal from that stimulation. Neuropathic rats preferentially withdrew their injured paw from iFU at smaller values of iFU intensity (84.2 W/cm² ± 25.5) than did sham surgery (97.7 W/cm² ± 11.9) and normal control (> 223 W/cm²) animals, with greater sensitivity and specificity (85% for neuropathic rats and 50% each of sham surgery and normal control rats). These results directly support our hypothesis as well as Gavrilov's idea that doctors may some day use iFU stimulation to diagnose patients with neuropathies.     

兔口服炔诺酮肟和炔诺酮的药代动力学

本文用高效液相色谱分离、液闪测定放射性的方法,测定了兔口服炔诺酮肟(NETO)和炔诺酮(NET)的血浓,并比较了二者的药代动力学参数。结果表明:二者吸收迅速,从血中的消除均呈快慢两个时相。NETO在兔体内一部分迅速转变为NET,另一部分则以原药形式存在,24 h内NETO与其代谢产物NET在血清中的浓度大致各占一半。兔口服NETO与NET后,血浓—时间曲线符合二室模型,NETO的达峰时间比NET短,二者有显著差异(P<0.05),其它动力学参数无明显差异(P>0.05)。     

Transdermal nicotine and smoking behavior in psychiatric patients

The authors used a double-blind crossover design to observe the effect of transdermally administered nicotine on the smoking behavior of 13 psychiatric patients who were not trying to stop smoking. The patients smoked significantly fewer cigarettes while receiving nicotine than while receiving placebo. These data suggest that transdermally administered nicotine can be a useful adjunct in treating nicotine-addicted psychiatric patients in a non-smoking environment.