4-烷硫基-4-脱氧-4′-去甲表鬼臼毒素的合成和抗肿瘤活性

对4’-去甲表鬼臼毒素的C₄位进行化学修饰,合成和筛选了10个4-烷硫基-4-脱氧-4’-去甲表鬼臼毒素衍生物以进一步研究C₄位不同的原子和取代基与活性之间的关系及寻找结构简单、活性更强的抗肿瘤新药。4’-去甲表鬼臼毒素与硫醇在三氟化硼·乙醚或三氟乙酸存在下生成相应的硫醚,也可用硫醇与4β-溴-4-脱氧-4’-去甲表鬼臼毒素反应生成相应的硫醚。在体外筛选中,化合物10和12抑制L1210白血病细胞的活性与依托泊甙相当或更强,化合物9,10,12和15抑制KB细胞的活性与依托泊甙相当或更强。     

Modeling preclinical cardiovascular risk for use in epidemiologic studies: Miami community health study

To develop a method for assessing preclinical cardiovascular disease risk, models of resting cardiovascular regulation and of insulin metabolic syndrome were derived from information collected from 1991 to 1996 in a culturally heterogeneous sample of 319 healthy men and women (aged 25-44 years) from Miami-Dade County, Florida. The model of resting cardiovascular regulation used 8 noninvasive measures of autonomic and cardiovascular function. Three factors were derived: 1) parasympathetic, 2) inotropy, and 3) systemic vascular resistance. The model of insulin metabolic syndrome used 12 measures assessing body mass, insulin, glucose, and lipid metabolism. Four factors were derived: 1) body mass and fat distribution, 2) glucose level and regulation, 3) insulin level and regulation, and 4) plasma lipid levels. Analyses of the association of the two models revealed that subjects with lower cardiac contractility had greater body mass, higher fasting and postload insulin and glucose levels, and lower insulin sensitivity. Subjects with greater vascular resistance had greater body mass, higher total cholesterol and triglyceride levels, and lower high density lipoprotein cholesterol levels. These findings indicate that preclinical cardiovascular disease risk may involve pathophysiologic processes in which cardiac inotropic and vasodilatory functions are linked to specific aspects of insulin metabolic syndrome.     

Design of a phantom for the quality control of high dose rate 192Ir source used in brachytherapy.

BACKGROUND AND PURPOSE: A new phantom is proposed for measuring the strength of 192Ir high dose rate sources and for verification of the dose calculated by the treatment planning system. The complete formalism and measurement procedure for this phantom is described, as well as the preliminary results obtained in a number of centers around Brazil. MATERIALS AND METHODS: The measurements are performed using powder thermoluminescent dosimeter capsules; the source strength is measured in air and the verification of the dose calculation algorithm in water phantom. The correction factors required to take into account the specificities related to the geometry and the phantom materials have been assessed using the PENELOPE Monte Carlo code and experimental methods. The dedicated phantom, constructed to use as part of a QA program, in this case specifically for high dose rate 192Ir brachytherapy sources, allows simultaneous irradiation of three thermoluminescent dosimeter capsules, requiring only one source stop (dwell positions). RESULTS: The phantom was mailed to seven radiotherapy institutions in Brazil, and the results show its usefulness in verifying the source air kerma and correctness of treatment planning dose calculation in water phantom. CONCLUSIONS: The comparison made between the phantom measurements, the well-type ionization chamber, and source specifications stated by the hospital (most of the times provided by the source manufacturer) agreed within 3% showing the quality in the HDR dose delivery in Brazilian radiotherapy centers.     

Laparoscopic cecal ligation and puncture in the rat

Background: We describe a technique of laparoscopic cecal ligation and puncture (CLP) in the rat analogous to open CLP which may facilitate the study of minimally invasive surgery (MIS) and peritonitis. Methods: Forty-four rats were randomized to either laparoscopic or open CLP and their 3-day mortality was recorded. Autopsies were performed for peritoneal fluid cultures, measurement of the length of ligated cecum, and scoring of the degree of cecal necrosis. Results: Laparoscopic CLP required slightly longer operating times compared to open CLP (average 15.6 vs 13.1 min, p= 0.002). Three-day postoperative mortality was 36.4% and 22.7% for open and laparoscopic CLP, respectively (p= NS). There were no differences in the length of ligated cecum or the cecal necrosis score between the open and laparoscopic CLP groups. Conclusion: Laparoscopic CLP is feasible and produces a fecal peritonitis with similar characteristics to those of traditional open CLP. Received: 3 July 1996/Accepted: 7 January 1997     

Temporal trends in primary total hip and knee arthroplasty surgery: results from a UK regional joint register, 1991�C2004

INTRODUCTION

The aim of this study was to evaluate temporal trends in the prevalence of primary total hip and knee replacements (THRs and TKRs) throughout the Trent region from 1991 to 2004.

PATIENTS AND METHODS

The Trent Regional Arthroplasty Study records details of primary THR and TKR prospectively and data from the register were examined. Age and gender population data were provided by the Office for National Statistics.

RESULTS

A total of 26,281 THRs and 23,606 TKRs were recorded during this period. Analysis showed that females had an increased incidence rate ratio (IRR) for both primary THR (IRR = 1.29; 95% CI 1.26–1.33; P < 0.001) and TKR (IRR = 1.17; 95% CI 1.14–1.20; P < 0.001). Patients aged 74–85 years had the largest IRR for both primary THR (IRR = 6.7; 95% CI 6.4–7.0; P < 0.001) and TKR (IRR = 15.3; 95% CI 14.4–16.3; P < 0.001).

CONCLUSIONS

The prevalence of primary TKR increased significantly over time whereas THR remained steady in the Trent region between 1991 and 2004.     

Cardiac morbidity and mortality after breast conservation treatment in patients with early-stage breast cancer and preexisting cardiac disease

BackgroundThis study was undertaken to determine the risk of late cardiac morbidity and mortality in patients with preexisting cardiac disease treated with contemporary radiation techniques for early-stage breast cancer.Patients and MethodsMedical records were reviewed for 41 patients with early-stage breast cancer and a history of myocardial infarction, congestive heart failure (CHF), and/or coronary artery disease before radiation therapy. Data were recorded on baseline cardiac disease and tumor characteristics, cardiac morbidity during and after treatment, and survival status of each patient. Patients were stratified for right-versus left-sided breast cancer and compared.ResultsThere was no significant difference in overall survival (OS) between the right-and left-sided groups (log-rank test; P = .19). The left-sided group had a higher incidence of cardiac deaths (right side, 2 of 26 [9%]; left side, 4 of 15 [27%]; hazard ratio, 4.2; P = .08) 10 years after treatment, including deaths secondary to myocardial infarction, CHF, or coronary artery disease. On the other hand, the right-sided group had a higher proportion of deaths secondary to breast cancer (right, 8 of 26 [31%]; left, 2 of 15 [13%]) and non–breast cancer/noncardiac causes (right, 7 of 26 [27%]; left, 1 of 15 [7%]).ConclusionAlthough OS was similar in both groups, radiation was associated with a higher incidence of cardiac death in patients with left-sided breast cancer. Efforts should be made to minimize cardiac exposure and also to promote more vigilant risk factor modification in this group of women.     

Glycoproteins present in human follicular fluid that inhibit the zona- binding capacity of spermatozoa

Previous studies have suggested that human follicular fluid contains factors that reduce the zona-binding capacity of spermatozoa. The present study provides further evidence of the existence of such factors. Using the hemizona binding assay (HZA), we have shown that the inhibitory effect of human follicular fluid on the zona-binding capacity of spermatozoa is concentration-dependent, an inhibitory effect being detected when the concentration of human follicular fluid was > or = 10%. A 1% concentration of human follicular fluid did not possess this inhibitory activity. Heating human follicular fluid at 56 degrees C for 30 min did not affect its inhibitory properties; treatment with proteinase-K abolished such inhibition. Human follicular fluid was fractionated sequentially by concanavalin-A affinity chromatography, Mono Q ion-exchange chromatography and Superose-12 gel filtration. The zona binding inhibitory activity resided in the fraction which bound to the lectin and Mono Q column and contained molecules with native molecular weights of 32 and 192 kDa. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis suggested that the 192 kDa glycoprotein was a tetramer, while the 32 kDa glycoprotein remained as a single molecular species under denaturing conditions. We conclude that two glycoproteins were responsible for the zona binding inhibitory activity of human follicular fluid. The physiological role of these factors remains unclear.      

血管细胞粘附分子调控造血的研究进展

本文简述了血管细胞粘附分子 (Vascularcelladhesionmolecule 1,VCAM 1)的结构和生物学功能 ,总结了VCAM 1在恶性血液病骨髓基质中的表达和意义 ,探讨了VCAM 1在造血干细胞动员和归巢中的作用 ,指出VCAM 1作用机制的深入研究将对恶性血液病的治疗提供更为有效的方法。     

An immediate generalized reaction to iopamidol

Intravascularly administered lower-osmolality contrast media cause fewer adverse effects than do higher-osmolality media. Immediate generalized reactions such as acute urticaria or bronchospasm have been documented occasionally in patients receiving lower-osmolality contrast media. To our knowledge, this is the first reported case of an immediate generalized reaction to a lower-osmolality contrast medium in which significant hypotension also occurred. During cardiac catheterization, in a patient who had never been exposed to a contrast medium, a 69-year old man developed chest tightness, periorbital and facial edema, slight uvular edema, and a decline in blood pressure from 150/71 to 97/67 mm Hg. Epinephrine hydrochloride, diphenhydramine hydrochloride, and hydrocortisone were administered. The lack of absolute safety of lower-osmolality contrast media emphasizes the need for clinical awareness and availability of emergency therapy when these agents are utilized.