Serologic test for syphilis as a surrogate marker for human immunodeficiency virus infection among United States blood donors

BACKGROUND: This study evaluated the usefulness of the serologic test for syphilis (STS) in preventing the transmission of human immunodeficiency virus (HIV), hepatitis B and C viruses, and human T- lymphotropic virus via the transfusion of seronegative, infectious window-period blood. STUDY DESIGN AND METHODS: Demographic and laboratory information on blood donations made between January 1992 and June 1994 in 18 American Red Cross regions was analyzed. It was assumed that the same proportion of HIV-positive and HIV-infectious window- period donations reacted on STS and were negative on other screening tests (hepatitis B and C viruses and human T-lymphotropic virus). This proportion multiplied by the estimated number of HIV-infectious window- period donations is the number of post-screening HIV-infectious donations removed by STS. RESULTS: Of 4,468,570 donations, 12,145 (0.27%) were STS positive and 377 (0.008%) were HIV positive. Among donations that were negative on other screening tests, STS-reactive donations were 12 times more likely to be HIV positive (odds ratio = 11.9; 95% CI = 5,26). However, of an estimated 13 infectious window- period donations, 0.2 would have been removed because of a reactive STS, at a cost of over $16 million. CONCLUSION: STS is a poor marker and a costly strategy for preventing post-screening HIV infections and other blood-borne diseases.     

The Impact of Primary Tumor Location on Long-Term Survival in Patients Undergoing Hepatic Resection for Metastatic Colon Cancer

Background

The impact of primary tumor location on overall survival (OS), recurrence-free survival (RFS), and long-term outcomes has not been well established in patients undergoing potentially curative resection of colorectal liver metastases (CRLM).

Methods

A single-institution database was queried for initial resections for CRLM 1992–2004. Primary tumor location determined by chart review (right = cecum to transverse; left = splenic flexure to sigmoid). Rectal cancer (distal 16 cm), multiple primaries, and unknown location were excluded. Kaplan–Meier and Cox regression methods were used. Cure was defined as actual 10-year survival with either no recurrence or resected recurrence with at least 3 years of disease-free follow-up.

Results

A total of 907 patients were included with a median follow-up of 11 years; 578 patients (64%) had left-sided and 329 (36%) right-sided primaries. Median OS for patients with a left-sided primary was 5.2 years (95% confidence interval [CI] 4.6–6.0) versus 3.6 years (95% CI 3.2–4.2) for right-sided (p = 0.004). On multivariable analysis, the hazard ratio for right-sided tumors was 1.22 (95% CI 1.02–1.45, p = 0.028) after adjusting for common clinicopathologic factors. Median RFS was marginally different stratified by primary location (1.3 vs. 1.7 years; p = 0.065). On multivariable analysis, location of primary was not significantly associated with RFS (p = 0.105). Observed cure rates were 22% for left-sided and 20% for right-sided tumors.

Conclusions

Among patients undergoing resection of CRLM, left-sided primary tumors were associated with improved median OS. However, long-term survival and recurrence-free survival were not significantly different stratified by primary location. Patients with left-sided primary tumors displayed a prolonged clinical course suggestive of more indolent biology.

     

Importance of collateral circulation in coronary heart disease.

AIMS: Collateral arteries are a common but inconsistent finding in coronary heart disease (CHD). We endeavoured to review the methods for coronary artery collateral assessment, the predictors and clinical importance of collateral blood flow, and the potential for therapeutic augmentation of collateral anastomoses. METHODS AND RESULTS: While many methods have been used to assess collateral blood flow only a few have been formally validated. Collateral flow index, as determined by measurement of intra-coronary pressure or flow velocity, is the most robust measure of collateral flow. These techniques have led to important advances in our understanding of collateral artery function. Coronary collateral arteries may prevent myocardial ischaemia in healthy subjects and in patients with CHD. A functional collateral circulation may lead to reduced ischaemia, preservation of ventricular function, and an improved prognosis. Recent trials have demonstrated that vascular progenitor cell therapies may improve ventricular function following acute myocardial infarction, raising the possibility of effective biological treatments to improve myocardial blood flow and prognosis in CHD. CONCLUSIONS: Coronary collateral anastomoses represent a prognostically important adaptive response in patients with CHD. Therapeutic augmentation of collaterals with emerging biological therapies represents a desirable goal for treating CHD patients.     

Conventional versus endoscopic powered adenoidectomy: A comparative study

Background: Adenoidectomy is a commonly performed ENT surgery. It is conventionally performed using the curettage method. This present article aims to evaluate endoscopic powered adenoidectomy as an alternative.     

Conventional Versus Endoscopic Powered Adenoidectomy: A Comparative Study

Background

Adenoidectomy is a commonly performed ENT surgery. It is conventionally performed using the curettage method. This present article aims to evaluate endoscopic powered adenoidectomy as an alternative.

Methods

Sixty consecutive cases requiring adenoidectomy were randomized into two groups of thirty each. Group A underwent conventional adenoidectomy using the curettage method and Group B underwent endoscopic assisted micro-debrider adenoidectomy. The parameters studied were intra-operative time, intra-operative bleeding and completeness of resection, collateral damage, post operative pain and recovery time.

Result

Sixty cases of adenoidectomy were done using conventional surgery and powered endoscopic adenoidectomy in the study period from Aug 04 to Dec 05. The time taken in Group A (conventional surgery) varied from 22–39 minutes (95% Confidence Interval (CI) −27.7 – 30.9)and in Group B (powered endoscopic surgery) from 27–55 minutes(95% CI 36.6 – 41.9) (p<0.05). The average blood loss in Group A was 21 ml (range 10–50) as compared to 31.67 ml (range 10-60) in Group B (p<0.05). The resection was invariably complete in Group B whereas seven(23%) cases had more than 50% residual adenoid tissue in Group A. Three cases in group A had collateral damage whereas in Group B, there were no added injuries. Post operative pain was studied only in cases undergoing adenoidectomy alone. Group A (n=8) demonstrated a pain score of 1.64–2.63–3.63 (95% CI) whereas Group B (n=11) demonstrated a pain score of 1.19–2.13–3.06 (95% CI). This difference was not statistically significant. In group A, the mean recovery period was 3.5 days and 2.93 days in Group B(p<0.05).

Conclusion

Endoscopic powered adenoidectomy was found to be a safe and effective tool for adenoidectomy. The study parameters where endoscopic powered adenoidectomy fared better were completeness of resection, accurate resection under vision, lesser collateral damage and faster recovery time. On the other hand, conventional adenoidectomy scored in matter of lesser operative time and intra-operative bleeding.Key Words: Adenoidectomy, Powered adenoidectomy, Endoscopic adenoidectomy     

Structure-activity and high-content imaging analyses of novel tubulysins

The synthesis and biological evaluation of three tubulysin analogs provides the first structure-activity relationship in this family of potent cytotoxic myxobacteria metabolites. Most importantly, the labile N,O-acetal at N(14) is not essential for biological activity. Further, structural simplifications are possible without abolishing biological activities. The N-terminal amino acid can be replaced with N-methylsarcosine, and the configuration at the acetoxy-bearing stereocenter at C(11) is important but not critical for almost all aspects of the biological profile. Our data encourage further development of these compounds as potential therapeutic agents in cancer treatment.     

Total synthesis and biological evaluation of C16 analogs of (-)-dictyostatin

The structure-activity relationship of the crucial C16 region of (-)-dictyostatin was established through total synthesis of analogs followed by detailed biological characterization. A versatile synthetic strategy was used to prepare milligram quantities of 16-normethyldictyostatin, 16-epi-dictyostatin, and the C16-normethyl-C15Z isomer. Along the way, a number of other E/Z isomers and epimers were prepared, and a novel lactone ring contraction to make iso-dictyostatins with 20-membered macrolactones (instead of 22-membered macrolactones) was discovered. The synthesis of 16-normethyl-15,16-dehydrodictyostatin is the first of any dictyostatin by a maximally convergent route in which three main fragments are assembled, coupled in back-to-back steps, and then processed through refunctionalization and macrolactonization. Cell-based and biochemical evaluations showed 16-normethyl-15,16-dehydrodictyostatin and 16-normethyldictyostatin to be the most potent of the new agents, only 2- and 5-fold less active than (-)-dictyostatin itself. This data and that from previously generated dictyostatin analogs are combined to produce a picture of the structure-activity relationships in this series of anticancer agents.     

Effects of dietary protein, energy and tyrosine on central and peripheral norepinephrine turnover in mice

Norepinephrine (NE) turnover rate and tyrosine concentrations were assessed in several tissues of 5-wk-old female lean mice that were fed diets of 20% protein (1.2% tyrosine), 40% protein (2.4% tyrosine) or tyrosine-supplemented diets of 40% protein with 4 or 8% tyrosine or 20% protein with 4% tyrosine for 4 d. Mice fed the 40% protein diet had significantly lower NE turnover rates in interscapular brown adipose tissue, heart and kidney (66, 64 and 49%, respectively) and nonsignificantly lower (84%) turnover rate in brain than did mice fed the 20% protein diet, but plasma and tissue tyrosine concentrations did not differ. When energy intake of the 20% protein-fed mice was restricted to 92% of the 40% protein-fed mice, tyrosine concentration in plasma and tissues was lower by half, but NE turnover rate did not differ between the two groups. Supplementation of the 40 or 20% diets with tyrosine, resulting in twofold higher plasma and tissue tyrosine concentrations, had no effect on NE turnover rate in any organ examined. We conclude that both energy intake and dietary protein concentration affect sympathetic nervous system activity in young mice. Tyrosine does not mediate or alter these changes.