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.     

靶控输注异丙酚意识消失时血浆和效应室浓度的EC50与脑电双频谱指数的关系多中心大样本临床研究

目的 研究择期手术患者靶控输注（TCI）异丙酚意识消失时血浆、效应室靶浓度的50%患者意识消失时的药物浓度（EC50）与脑电双频谱指数（BIS）的关系。方法 5家医疗中心405例择期手术患者（国人）,ASAⅠ或Ⅱ级。靶控输注异丙酚,以血浆靶浓度1．2μg/ml为起点,到达预期血浆靶浓度后每30秒递增0．3μg/ml,直至患者意识消失。采用概率单位回归分析计算患者意识消失时异丙酚血浆靶浓度、效应室靶浓度的EC05、EC50和EC95及其所对应的BIS。结果 择期手术患者TCI异丙酚意识消失时异丙酚血浆靶浓度EC05、EC50和EC95分别是2．9μg/ml、3．8μg/ml和4．8μg/ml,效应室靶浓度EC05、EC50和EC95分别是1．3μg/ml、2．2μg/ml和3．2μg/ml,50%患者意识消失的BIS是58,5%和95%患者意识消失的BIS分别是77和40。结论 择期手术患者TCI异丙酚意识消失时血浆靶浓度和效应室靶浓度EC50及95%置信区间分别是3．8μg/ml（3．8～3．9μg/ml）和2．2μg/ml（2．2～2．3μg/ml）, 50%患者意识消失的BIS用95%置信区间是58（58～59）。     

老年患者不同靶浓度罗库溴铵肌松效应的比较

目的比较老年患者不同靶浓度罗库溴铵的肌松效应。方法择期全麻老年患者100例,ASAⅡ级,随机分为4组(n=25),A组、B组和C组麻醉诱导气管插管时效应室靶浓度(Ce)为3μg/ ml,术中维持Ce分别为0.6、0.8、1.0μg/ml;D组麻醉诱导气管插管时Ce为3.3μg/ml,术中维持Ce为0_8μg/ml。记录肌松起效时间、恢复时间和恢复指数。评价气管插管条件和术中肌松程度。记录手术及TCI时间、罗库溴铵总用药量和期间用药量[总用药量,(体重×TCI时间)]。结果4组均可顺利完成气管插管,D组起效时间较A组、B组和C组缩短(P<0.05);A组肌松满意率低,B组、C组和D组均可维持满意肌松,但C组罗库溴铵用量较多,术中肌松程度较大,术后恢复时间较长(P<0.05)。结论麻醉诱导气管插管时罗库溴铵Ce为3.3μg/ml、术中麻醉维持Ce为0.8μg/ml,可产生满意的肌松条件,且有利于术后肌松恢复,是一种适用于老年患者合理的TCI给药方案。     

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 practice of forensic psychiatry in cases of homicide in Copenhagen, 1959 to 1983

During the years 1959 to 1983 a doubling in the rate of homicide took place in Copenhagen. This increase was exclusively due to an increasing number of male offenders. By comparing with another Danish material, the frequency of female homicide as well as that of homicide combined with suicide was found practically unchanged since 1946, indicating that both of these kinds of homicides seem to have a background different from those of other offences of fatal violence. During the years 1959 to 1983, the criteria of selection of the defendants for a psychiatric examination for the court were fairly consistent. Examinations were performed in practically all cases, where a charge of murder raised by the police was followed by a legal trial for homicide. Less and less of the defendants, however, were hospitalized for the examination, while more were examined in The Clinic of Forensic Psychiatry in Copenhagen.     

Drug Delivery by Phonophoresis

Phonophoresis is defined as the migration of drug molecules, contained in a contact agent, through the skin under the influence of ultrasound. Several drugs have been introduced into the body by this technique. The design of a phonophoretic drug delivery system is in developmental stages in various research laboratories. Parameters affecting the delivery of drugs by this technique and devices available for drug delivery purposes are discussed in this review.     

Effects of Polyethyleneglycol Chain Length and Phospholipid Acyl Chain Composition on the Interaction of Polyethyleneglycol-phospholipid Conjugates with Phospholipid: Implications in Liposomal Drug Delivery

Purpose. The purpose of this study was to investigate polyethyleneglycol(PEG)-phosphatidylethanolamine(PE) conjugate interaction with phospholipid bilayers, in an attempt to explain the dependence of liposome circulation time on formulation. Methods. Differential scanning calorimetry, electron microscopy, dynamic light scattering and NMR were the major methods used in the study. Results. Mixtures of PEG-phospholipid conjugates and phosphatidylcholine existed in three different physical states: a lamellar phase with components exhibiting some miscibility, a lamellar phase with components phase separated, and mixed micelles. Beyond 7 mol% of PEG(l,000–3,000)-dipalmitoyl phosphatidylethanolamine (DPPE), and 11 mol% PEG(5,000)-DPPE in dipalmitoyl phosphatidylcholine (DPPC), a strong tendency towards mixed micelle formation was observed. All concentrations of PEG(12,000)-DPPE and PEG(5,000)-DPPE beyond 8 mol% formed phase separated lamellae with phosphatidylcholine. Decreasing the acyl chain length from C_16:0 to C_14:0 caused a decrease in tendency towards micelle formation and phase separation. These tendencies increased upon increasing acyl chain length to C_18:0. Phase separation was at least partly due to PEG chain-chain interaction. This was supported by an increased fraction of PEG chains exhibiting a fast NMR transverse relaxation in DPPC/PEG(5,000)-DPPE mixtures as compared to that in distearoyl phosphatidylcholine (DSPC)/PEG(5,000)-dioleoyl-PE (DOPE). Conclusions. These phenomena are discussed in relation to both bilayer and steric stabilization of liposomes, and the lack of prolonged circulation with certain formulations is discussed.     

Oral Controlled Release Technology for Peptides: Status and Future Prospects

In spite of significant efforts in academic and commercial laboratories, major breakthroughs in oral peptide and protein formulation have not been achieved. The major barriers to developing oral formulations for peptides and proteins include poor intrinsic permeability, lumenal and cellular enzymatic degradation, rapid clearance, and chemical and conformational stability. Pharmaceutical approaches to address these barriers, which have been successful with traditional, small, organic drug molecules, have not readily translated into effective peptide and protein formulations. The success achieved by Sandoz with cyclosporin formulations remains one clear example of what can be achieved, although it is likely that effective oral formulations for peptides and proteins will remain highly compound specific. Although the challenges are significant, the potential therapeutic benefit remains high, particularly with the increasing identification of potential peptide and protein drug candidates emerging from the biotechnology arena. Successful formulations will most likely require a systematic and careful merger of formulation and design delivery systems which maximize the potential for absorption across the epithelial cell layer.     

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.     

Favorable effects of epidural analgesia on hemodynamics,oxygenation and metabolic variables in the immediate post-anesthetic period

Fourteen adult patients undergoing elective major abdominal surgery were divided into two groups. One group received epidural and general anesthesia (epidural group), and 20 ml of 0.125% bupivacaine and 2 mg of morphine were administered epidurally about 30 min before the end of the operation for post-anesthetic analgesia. The other group (control group) received general anesthesia alone with nitrous oxide, oxygen and enfiurane. Flow-directed pulmonary arterial and radial arterial catheters were inserted preoperatively, and hemodynamic, respiratory, neuroendocrine and metabolic variables were measured serially. The data were compared during anesthesia and the immediate post-anesthetic recovery period. In the control group, the plasma epinephrine level in the post-anesthetic recovery period increased about four times over the anesthetic period. Oxygen consumption was increased and mixed venous oxygen saturation was decreased significantly. There was a close linear correlation between oxygen consumption (Y) and plasma epinephrine (X) level: Y = 285.7X + 90.5 (P < 0.01, r = 0.72). On the other hand, plasma epinephrine, oxygen consumption and mixed venous oxygen saturation did not change significantly in the epidural group in the post-anesthetic recovery period. There was also a close linear correlation between oxygen consumption (Y) and oxygen delivery (X): Y = 0.22X -32.0 (P < 0.01, r = 0.89). We conclude that the surgical stress and anesthetic reversal may seriously influence neuroendocrine responses and subsequently increase plasma epinephrine. Tissue oxygenation and metabolic imbalance may occur due to the rapid increase of epinephrine in the postanesthetic recovery period. Epidural analgesia at this period may play a more important role and have a more favorable effect on the tissue metabolism.