Vascular PET Prostheses Surface Modification with Cyclodextrin Coating: Development of a New Drug Delivery System

PURPOSE: Cyclodextrins (CDs) are torus shaped cyclic oligosaccharides with a hydrophobic internal cavity and a hydrophilic external surface. We performed and analysed an antibiotic binding on Dacron (polyethyleneterephtalate, PET) vascular grafts, previously coated with CDs based polymers. METHODS: The CDs coating process was based on the pad-dry-cure method patented in our laboratory. The Dacron prostheses were immersed into a solution containing a polycarboxylic acid, a cyclodextrin and a catalyst, and placed into a thermofixation oven before impregnation with an antibiotic solution (Vancomycin). Biocompatibility tests were performed with L132 human epithelial cells. The antibiotic release in an aqueous medium was assessed by batch type experiments using UV spectroscopy. RESULTS: Viability tests confirmed that the CDs polymers coating the Dacron fibers were not toxic towards L132 cell. Cell proliferation was similar on coated and uncoated grafts. A linear release of Vancomycin was observed over 50 days. CONCLUSION: Our results demonstrate the feasibility of coating CDs onto vascular Dacron grafts. Biological tests show no toxicity of the different cyclodextrins coated. A linear release of antibiotics was depicted over 50 days, demonstrating that cyclodextrin grafting was an efficient drug delivery system.     

Continuous In-Line Monitoring of Oxygen Delivery to Control Artificial Heart Output

In order to evaluate the pump output control based on the oxygen delivery to peripheral tissues, arterial and mixed venous hemoglobin content ([Hb]) and oxygen saturation (SO2) were continuously monitored in three biventricular bypass animals (3-, 6-, and 40-day experiments) with fibrillating ventricles. The specially developed oxygen sensors were mounted in the outflow ports of the artificial hearts to measure [Hb] and SO2. One animal was exercised on the treadmill at 2.0 mile/h for 15 min with pump flows fixed to deliver oxygen of (a) above 13 cc/min/kg, (b) 10, and (c) 9. In (a), the mixed venous saturation (SvO2) dropped to approximately 25% with no increase in the blood lactate level. In (b) and (c), the SvO2 decreased to approximately 10-15% with increase in blood lactate levels from 4 to 10-30 mg/dl. Also, the recovery of the SvO2 in these groups following the termination of the exercise was slower in comparison to (a). The lower limit of the SvO2 level that would create oxygen debt situation in the peripheral tissues was approximately 25-30% for the exercise of 2.0 mile/h. The SvO2 reflects changes in respiratory status, pump output, hemoglobin level, and metabolism, and is thus a useful indicator to diagnose quickly the circulatory status as well as possibly to control the artificial heart output.     

The importance of vaginal mucosal folds at the urethral external meatus

We report on the vaginal mucosal folds (VMF) at the urethral external meatus. Resection of the VMF reduces the dispersed micturition and other urinary symptoms. EDITORIAL COMMENT: The investigators describe the presence of a vaginal mucosal fold (VMF) just dorsal to the urethral meatus and its relationship to voiding abnormalities. VMF were found on physical examination in 8.9% of the clinic population, all of whom complained of dispersed micturition, and 79% also experienced other voiding abnormalities. The complaint of dispersed micturition was successfully treated with excision of the VMF, and the other associated symptoms were improved. This structure should be routinely looked for on physical examination, especially in patients with voiding symptoms. Only further investigation of this newly described entity at other centers around the world will determine the incidence of the anatomic finding and the prevalence of associated voiding disturbances across different populations.     

Colonic Drug Delivery: Enhanced Release of Indomethacin from Cross-Linked Chondroitin Matrix in Rat Cecal Content

Pharmaceutical Research -     

Skilled birth attendant competence: an initial assessment in four countries, and implications for the Safe Motherhood movement.

OBJECTIVES: Percentage of deliveries assisted by a skilled birth attendant (SBA) has become a proxy indicator for reducing maternal mortality in developing countries, but there is little data on SBA competence. Our objective was to evaluate the competence of health professionals who typically attend hospital and clinic-based births in Benin, Ecuador, Jamaica, and Rwanda. Methods: We measured competence against World Health Organization's (WHO) Integrated Management of Pregnancy and Childbirth guidelines. To evaluate knowledge, we used a 49-question multiple-choice test covering seven clinical areas. To evaluate skill, we had participants perform five different procedures on anatomical models. The 166 participants came from facilities at all levels of care in their respective countries. Results: On average, providers answered 55.8% of the knowledge questions correctly and performed 48.2% of the skills steps correctly. Scores differed somewhat by country, provider type, and subtopic. Conclusion: A wide gap exists between current evidence-based standards and current levels of provider competence.     

Clinical response to local delivery of tetracycline in relation to overall and local periodontal conditions

Abstract The purpose of this study was to determine the clinical response to local delivery of tetracycline in relation to clinical and microbiological conditions of the other teeth. 4 deep pockets were monitored in 19 subjects with multiple deep periodontal lesions and high counts of P. gingivalis. In 9 patients (XT) only 2 of the selected lesions were treated by placement of tetracycline fibers (Actisite®). while the rest of the dentition was left untreated. In the other 10 patients, all teeth were supragingivally scaled and then treated by application of polymeric tetracycline HCl containing fibers, the whole dentition was subject to full mouth scaling and root planing, and the patients rinsed with 0.2% chlorhexidine (FT). A significant reduction in mean PPD was observed in all treated sites after two months. This reduction was maintained over the following 4 months. The magnitude of the effect was significantly greater in the FT group (1.74 mm) than in the LT group (0.88 mm). The mean attachment level changes were similar after 2 months in locally and fully treated subjects. A tendency of relapse was noted for treated sites in LT patients from month 2 to 6. A level of statistical significance was not reached for this effect. Data from measurements recorded at 6 sites around all teeth in the full mouth treated patients were analyzed using multiple linear regression. This analysis showed local changes in PPD and AL were significantly and strongly correlated with the baseline value of the respective parameter at the same site. In addition, more pocket depth reduction was noted if a site was not bleeding on probing at 6 months, if the location of a site was not approximal and if the tooth was not a second molar. Sites located on second molars showed also less AL gain than sites located on other teeth. Smokers showed significantly less reduction in PPD and significantly less AL gain. Furthermore, if subjects had a high % of pockets deeper than 4 mm at baseline they showed significantly less attachment gain.     

Geometric Resistance and Microvascular Network Architecture of Human Colorectal Carcinoma

Objective : To measure the geometric resistance to blood flow in human colorectal carcinoma. Although tumor blood flow is of central importance in both the detection and the treatment of cancer, the determinants of blood flow through the neoplastic circulation are poorly understood. Methods : Human colorectal carcinomas (tissue weight = 272 g ± 43 g (SD), n = 6) were perfused ex vivo with a buffered physiological salt solution of known viscosity at flow rates ranging from 2.5 to 40 ml/min and perfusion pressures from 8 to 100 mm Hg. The geometric resistance was determined from the slope of the pressure-flow curve. For examination of the principal determinant of geometric resistance, the vascular architecture, one of the tumors was perfused with Batson's No. 17 polymer and macerated in KOH to produce a positive vascular cast that was used for measurement of vascular branching patterns and dimensions. Results : The pressure-flow relationship was linear at perfusion pressures above 40 mm Hg, and the geometric resistance, z₀, was constant at approximately 6.5 ± 10⁹g/cm³. Below 40 mm Hg, z₀ increased rapidly. The architecture of the arteriolar and capillary networks of human colorectal carcinoma is similar to those of experimental rodent tumors. Capillaries in planar and nonplanar mesh-works had mean segment diameters of 11 ± 2 and 9.6 ± 2 μm, lengths of 46 ± 24 and 107 ± 40 μm, and intercapillary distances of 46 ± 13 and 74 ± 24 μm, respectively. Conclusions : The geometric flow resistance in neoplastic tissue is 1–2 orders of magnitude higher than that observed in normal tissues. A decrease in functional vascular cross-sectional area may explain the additional increase in resistance at small perfusion pressures. The observed flow resistance may be due to the specialized arteriolar and capillary network architecture, pressures exerted by proliferating cancer cells, and/or coupling between vascular and extravascular flow. These observations demonstrate that tumor vascularity alone may not be indicative of flow resistance or tumor susceptibility to blood-borne therapeutic agents.     

不同剂量瑞芬太尼复合靶控输注异丙酚对心脏瓣膜置换术病人气管插管时血液动力学反应的影响

目的 评价不同剂量瑞芬太尼复合靶控输注(TCI)异丙酚对心脏瓣膜置换术病人气管插管时血液动力学反应的影响.方法 拟行心脏瓣膜置换术的风湿性心脏病病人30例,随机分为3组(n=10):芬太尼组(Ⅰ组)、小剂量瑞芬太尼组(Ⅱ组)和大剂量瑞芬太尼组(Ⅲ组).麻醉诱导:Ⅰ组静脉注射芬太尼10 μg/kg,然后持续静脉输注芬太尼10 μg·kg-1·h-1;Ⅱ组和Ⅲ组静脉注射瑞芬太尼1μg/kg,然后分别持续静脉输注瑞芬太尼0.5、1.0 μg·kg-1·min-1.3组静脉注射芬太尼或瑞芬太尼后3min开始TCI异丙酚,初始血浆靶浓度为1.0 μg/ml,逐渐递增至2.0 μg/ml.静脉注射罗库溴铵0.6 mg/kg后气管插管.分别在麻醉诱导前(T0)、诱导期间血压最低值时(T1)、插管前即刻(T2)、插管后1 min(T3)、插管后2 min(T4)及插管后5 min(T5)时记录心率(HR)、平均动脉压(MAP)、中心静脉压(CVP)、肺毛细血管楔压(PCWP)、心脏指数(CI)、外周血管阻力指数(SVRI)及左室每搏功指数(LVSWI),并于上述时点测定混合静脉血氧饱和度(S(v)O2).记录诱导期间低血压及气管插管心血管反应的发生情况.结果 3组间麻醉诱导期间低血压及气管插管心血管反应的发生率差异无统计学意义(P＞0.05).与T0比较,各组T1,2时HR和MAP均降低,Ⅱ组T3时HR和MAP升高,Ⅲ组T4时MAP降低,Ⅰ组和Ⅱ组T2-4时S(v)O2升高(P＜0.05);3组间各时点CVP、PCWP、CI、LVSWI和S(v)O2差异无统计学意义(P＞0.05).结论 复合TCI异丙酚(血浆靶浓度2.0 μg/ml)时,静脉注射瑞芬太尼1 μg/kg负荷剂量后,持续静脉输注0.5 μg·kg-1·min-1麻醉诱导时血压和HR下降适度,可较好地抑制心脏瓣膜置换术病人气管插管时血液动力学反应.     

The use of locally-delivered chlorhexidine in the treatment of periodontitis. Clinical results*

Abstract. Since the advent of a nondegradable controlled local delivery of antibiotics in 1979, several second generation systems have been developed. Second generation systems have attempted to improve on the early system. Chlorhexidine has been used effectively for over 30 years as an antiseptic. In the early 1970s, chlorhexidine gluconate was incorporated at 0.2% into mouthrinses in Europe and in 1986 it was incorporated at 0.12%, in a mouthrinse in the United States. Since these mouthrinses were effective in reducing the supragingival flora, had a high safety margin, and had no reported bacterial resistance, chlorhexidine offered a therapeutic advantage for a local delivery system. This system was developed and studied. This report will discuss this new biodegradable system containing chlorhexidine gluconate as the active agent (PerioChip^®). Parmacokinetics of the system and a review of the multicenter studies in Europe and the United States are discussed. In these randomized clinical trials the chlorhexidine chip has been shown to enhance the effects of scaling and root planing. Chlorhexidine chip in conjunction with scaling and root planing, when compared to scaling and root planing alone, has shown significant improvement in probing pocket depth reduction, probing attachment level and bleeding on probing. This delivery system, in combination with scaling and root planing, has also resulted in significantly more probing depth reductions of 2 mm or more. The system is safe and efficacious. Placement of the chip is usually done in less than 1 min, it requires no retention system, biodegrades, and does not require a follow-up dental appointment.     

ONO—802阴道给药抗早孕50例临床效果观察

本文报告了停经56天以内的早孕妇女应用ONO-802阴道栓剂抗早孕的临床观察及效果。50例早孕妇女住院观察24小时,阴道投药1枚(1mg/枚),5枚为一疗程。用药后1周、2周、4～6周门诊随访,复查尿HCG、血红蛋白。在第二周随访时判断用药效果。临床结果:总有效率82%,其中完全流产76%,不全流产6%,失败率18%。ONO-802使用方便,副反应轻,是深受广大妇女欢迎的一种非手术终止妊娠的方法。本项试验结果通过与国内PG 联合用药的结果和研究资料对比,ONO-802如果能与丙睾、R2323、天花粉等联合应用,将会提高其抗早孕的有效率。