Microsatellite instability in oral cancer

Generalized genomic instability, detected as somatic changes in allele sizes at microsatellite loci in tumors compared to peripheral lymphocyte DNA, is a recently recognized mechanism of mutation in cancer. Such instability results from the Somatic loss of DNA mismatch repair capability. Germ-line mutations at DNA mismatch repair loci confer susceptibility to colon cancer in hereditary non-polyposis colorectal cancer. Somatic loss of DNA mismatch repair has been reported in a large variety of other tumor types. Our goal was to determine the frequency of microsatellite instability in a large series of oral tumors. Out of 91 tumors analyzed for microsatellite instability, 6 (7%) showed microsatellite instability. Instability was observed at multiple loci with a range of 50-74% of loci affected. Alterations include both increase (74%) and decrease (26%) in allele sizes. The proportion of alleles affected ranged from 30-58% of all alleles. Our data suggest that somatic genomic instability plays a role in the pathogenesis of a small subset of oral tumors. © 1995 Wiley-Liss, Inc.     

Serum androgenic hormones motivate sexual behavior in adolescent boys

In order to separate hormonal from social effects on adolescent male sexual behavior, serum hormone assays were performed and questionnaire data on sexual motivation and behavior were collected on a representative sample of 102 boys in grades 8, 9, and 10 of a public school system. Free testosterone was a strong predictor of sexual motivation and behavior, with no additional contribution of other hormones. Including measures of pubertal development and age (indexing the effects of social processes) indicated no additional effects. Free testosterone, therefore, appears to affect sexual motivation directly and does not work through the social interpretation of the accompanying pubertal development.     

Kinder and gentler: physicians and managed care, 1997-2001

Despite the managed care backlash, an overwhelming majority of U.S. physicians continue to contract with managed care health plans. In fact, according to a new Center for Studying Health System Change (HSC) study, between 1997 and 2001 physicians reported a modest increase in the proportion of practice revenue from managed care contracts and the average number of contracts. At the same time, the nature of physicians' relationships with health plans changed, with a significant decrease in plans' use of capitation, or fixed monthly payments for each patient regardless of the amount of care provided. Meanwhile, physician practices moved away from using direct financial incentives to influence doctors' clinical decision making, but did experience an increase in the overall influence of treatment guidelines and other practices commonly associated with managed care.     

SR-141716A-induced stimulation of locomotor activity. A structure-activity relationship study

The central cannabinoid receptor (CB(1)) antagonist, SR-141716A, has been used extensively to ascertain that cannabinoids interact with the CB(1) receptor. SR-141716A has been shown to produce effects opposite of cannabinoids when administered alone. It has been theorized that SR-141716A may act as an inverse agonist at the CB(1) receptor or by disinhibiting an endogenous cannabinoid tone. In an effort to ascertain the exact interaction between SR-141716A and the CB(1) receptor, we have conducted a structure-activity relationship study to compare CB(1) receptor affinity of SR-141716A analogs with their ability to produce an increase in locomotor activity. SR-141716A produced a significant increase in locomotor activity in mice within the first hour of administration. Twenty SR-141716A analogs from five different chemical series were also tested. Our data implicate particular regions of the SR-141716A molecule that may be involved in stimulation and depression of locomotor activity. When the K(I) of the analogs was plotted against the percent stimulation that each analog produced, it is evident that there is no correlation between the ability of the analogs to stimulate locomotor activity and their affinity for the CB(1) receptor. [35S]GTPgammaS binding data indicate that SR-141716A and five of the analogs are inverse agonists. However, none of the analogs demonstrating inverse agonism produce stimulation of locomotor activity. It is therefore concluded that the SR-141716A-induced stimulation in locomotor activity is not the result of inverse agonist activity at the CB(1) receptor or by disinhibition of an endogenous tone.     

Doppler sonographic findings in the long bicipital tendon sheath in patients with rheumatoid arthritis as compared with patients with degenerative diseases of the shoulder

OBJECTIVE: To compare power Doppler sonography (PDS) findings inside the bicipital tendon sheath in patients with rheumatoid arthritis (RA) and degenerative disorders of the shoulder, in order to evaluate the diagnostic value of PDS in distinguishing between inflammatory and noninflammatory shoulder pain. METHODS: The glenohumeral joints of 41 consecutive patients with shoulder pain were examined by ultrasound. Using ventral transverse and longitudinal scanning, the vascularity near and/or inside the bicipital tendon sheath was visualized by PDS. One fully trained and experienced examiner performed the sonography. Representative images were digitally stored and were read, under blinded conditions, by 2 independent investigators, who categorized the Doppler signals as being either inside or outside the tendon sheath. RESULTS: Biceps tendon sheath effusion, represented by the typical hypoechoic rim, was found in 95.8% of the RA patients (23 of 24) and in 58.8% of the patients with degenerative disorders (10 of 17). PDS signals were localized to inside the tendon sheath in 22 of the RA patients (91.7%) and in none of the patients with degenerative disorders. Although no PDS signal was found inside the tendon sheath in patients with degenerative disorders, in 9 of these patients (52.9%), signals could be localized to the environment of the tendon sheath. CONCLUSION: PDS demonstrates vascularity in the long bicipital tendon sheath of patients with RA, but not in those with degenerative shoulder disorders.     

基因-病毒载体的研制及其抗肿瘤作用的初步研究

目的：研究一种结合肿瘤基因治疗与病毒治疗优势的新型肿瘤治疗载体系统,即基因－病毒载体系统。方法：利用病毒重组技术将抗癌基因插入肿瘤细胞特异性的增殖病毒的病毒基因组中,通过细胞病理作用、荧光显微镜、免疫酶链技术及电镜等技术分别观察病毒的杀伤效应、报告基因绿色荧光蛋白、抗癌基因小鼠白细胞介素12表达量及病毒复制情况。结果构建了一种新型基因－病毒载体系统,该载体系统腺病毒E1b55000蛋白缺失,保留了腺病毒E1a蛋白。该载体系统具有肿瘤增殖病毒ONYX－015的相似功能,即它可在肿瘤细胞内复制及增殖,而在正常细胞内不能复制及增殖,从而特异性杀灭肿瘤细胞。该载体系统还可携带各种抗癌基因以进一步提高抗肿瘤的疗效。应该该载体系统携带该报告基因荧光蛋白可使绿色荧光蛋白在肿瘤细胞内高效表达,其表达量明显高于传统基因治疗的腺病毒载体系,而在正常细胞内低表达,表达量与传统腺病毒载体系统相似或更低。应用该载体系统携带抗癌基因小鼠白细胞介素12,也产生类似结果。电镜也证实该载体系统携带抗肿瘤基因小鼠白细胞介素12可在肿瘤细胞株中复制及增殖。结论：基因－病毒载体将抗癌基因插入肿瘤增殖病毒基因组,可数百倍乃至上万部提高抗癌基因的表达量,进一步提高抗肿瘤的疗效。     

Sinopulmonary complications of illicit drug use

Illicit drug use is frequently complicated by sinopulmonary illnesses. These complications fall into two major categories: (1) direct effects of drug exposure, and (2) indirect effects caused by HIV-induced immunosuppression. This article reviews the more common sinopulmonary syndromes associated with illicit drug use.     

Financial Indicators for Critical Access Hospitals

CONTEXT: There is a growing recognition of the need to measure and report hospital financial performance. However, there exists little comparative financial indicator data specifically for critical access hospitals (CAHs). CAHs differ from other hospitals on a number of dimensions that might affect appropriate indicators of performance, including differences in Medicare reimbursement, limits on bed size and average length of stay, and relaxed staffing rules. PURPOSE: To develop comparative financial indicators specifically designed for CAHs using Medicare cost report data. METHODS: A technical advisory group of individuals with extensive experience in rural hospital finance and operations provided advice to a research team from the University of North Carolina at Chapel Hill. Twenty indicators deemed appropriate for assessment of CAH financial condition were chosen and formulas determined. Issues 1 and 2 of the CAH Financial Indicators Report were mailed to the chief executive officers of 853 CAHs in the summer of 2004 and 1,092 CAHs in the summer of 2005, respectively. Each report included indicator values specifically for their CAH, indicator medians for peer groups, and an evaluation form. FINDINGS: Chief executive officers found the indicators to be useful and the underlying formulas to be appropriate. The multiple years of data provide snapshots of the industry as a whole, rather than trend data for a constant set of hospitals. CONCLUSIONS: The CAH Financial Indicators Report is a useful first step toward comparative financial indicators for CAHs.     

Nonsurgical fluoroscopically guided dacryocystoplasty of common canalicular obstructions

Purpose: To assess dacryocystoplasty in the treatment of epiphora due to obstructions of the common canaliculus. Methods: Twenty patients with severe epiphora due to partial (n = 16) or complete (n = 4) obstruction of the common canaliculus underwent fluoroscopically guided dacryocystoplasty. In all cases of incomplete obstruction balloon dilation was performed. Stent implantation was attempted in cases with complete obstruction. Dacryocystography and clinical follow-up was performed at intervals of 1 week, and 3, 6, 12, and 18 months after the procedure. The mean follow-up was 6 months (range 3–18 months). Results: Balloon dilation was technically successfully performed in all patients with incomplete obstructions (n = 16). In three of four patients with complete obstruction stent implantation was performed successfully. Subsequent to failure of stent implantation in one of these patients balloon dilation was performed instead. The long-term primary patency rate in patients with incomplete obstructions was 88% (n = 14/16). In three of four cases with complete obstruction long-term patency was achieved during follow-up. Severe complications, infections, or punctal splitting were not observed. Conclusion: Fluoroscopically guided balloon dacryocystoplasty is a feasible nonsurgical therapy in canalicular obstructions with good clinical results that may be used as an alternative to surgical procedures. In patients with complete obstructions stent placement is possible but further investigations are needed to assess the procedural and long-term results.     

Assessment of the validity of in vivo methods of measuring human macular pigment optical density.

PURPOSE: As a result of the putative protective role of lutein and zeaxanthin at the site of the retina (macular pigment [MP]), interest in the noninvasive measurement of these retinal carotenoids is increasing. In principle, any method used to measure MP in vivo should provide spectral absorption curves that match extinction spectra of MP measured ex vivo. METHODS: In this article, we assess published spectral curves with respect to this criterion. RESULTS AND DISCUSSION: Variation in derived MP measures resulting from methodological differences between techniques is noted and discussed.