Disposition Characteristics of Macromolecules in Tumor-Bearing Mice

As part of the strategy for the design of macromolecular carriers for drug targeting, the disposition characteristics of macromolecules were studied in mice bearing tumors that served as target tissues. Eight kinds of macromolecules including four polysaccharides and four proteins with different molecular weights and electric charges were used; tissue distribution and tumor localization after intravenous injection were studied. Pharmacokinetic analysis revealed that the tissue radioactivity uptake rate index calculated in terms of clearance was different among the tested compounds; especially, the urinary radioactivity excretion clearances and the total hepatic radioactivity uptake clearances varied widely. Compounds with low molecular weights (approximately 10 kD) or positive charges showed lower tumor radioactivity accumulation; radioactivity was rapidly eliminated from the plasma via rapid urinary excretion or extensive hepatic uptake, respectively. On the other hand, large and negatively charged compounds, carboxymethyl dextran, bovine serum albumin, and mouse immunoglobulin G, showed higher radioactivity accumulation in the tumor (calculated total amounts were 15.6, 10.8, and 20.8% of the dose, respectively) and prolonged retention in the circulation. These results demonstrated that the total systemic exposure rather than the uptake rate index was correlated with total tumor uptake. Molecular weight and electric charge of the macromolecules significantly affected their disposition characteristics and, consequently, determined radioactivity accumulation in the tumor. It was concluded that a drug–carrier complex designed for systemic tumor targeting should be polyanionic in nature and larger than 70,000 in molecular weight.     

下尿路梗阻性肾积水患者逼尿肌功能变化

目的：探讨下尿路梗阻性肾积水患者逼尿肌功能变化。方法：对20例（3．5－73岁）下尿路梗阻导致的肾积水组和10例（13－67岁）无肾积水的对照组进行膀胱压力容积测定与压力－流率测定，并记录不同膀胱灌注量的逼尿肌基础压力。结果：下尿路梗阻性肾积水组逼尿肌－括约肌协同失调（DSD）11例（55％），逼尿肌功能过度活跃5例；而对照组仅发现1例（10％）DSD，未发现有逼尿肌功能过度活跃。下尿路梗阻性肾积水组平均膀胱顺应性显著低于对照组（P＜0．05），而下尿路梗阻性肾积水组平均逼尿肌基础压力，平均逼尿肌最大收缩压和残余尿量均显著高于对照组（P＜0．05），且下尿路梗阻性肾积水组在灌注量逐渐增加时高逼尿肌基础压力发生率逐渐增加。结论：下尿路梗阻性肾积水多伴有逼尿肌功能异常，提示膀胱逼尿肌功能改变与下尿路梗阻性肾积水的形成及发展有一定的相关性。     

One month maximal electrostimulation for genuine stress incontinence in women

While awaiting surgery for genuine urinary stress incontinence, 51 women with were treated at home for 1 month with vaginal maximal electrostimulation. They were evaluated subjectively, urodynamically, and with two different pad tests. Six patients (12%) were cured and 17 (33%) were much improved, subjectively and objectively. Statistically significant improvement was observed for both pad tests. Successful treatment was significantly more likely in women with milder degrees of incontinence but was unrelated to age or urethral pressure. Patient acceptance was excellent and apart from some vaginal soreness no complications were seen. Sixteen patients (31%) elected not to be operated on. These 16 patients were reevaluated after 1 year and 13 (81%) had maintained their improvement. Three had disimproved but were still better than before treatment; 2 again refused surgery and 1 opted for surgery. Therefore, 15 of 51 (29%) operations were saved after 1 year. This conservative treatment for stress incontinence is safe, simple, inexpensive, and reasonably successful. © 1994 Wiley-Liss, Inc.     

哈乐在良性前列腺增生伴急性尿潴留中的应用

目的 :探讨α1A肾上腺素能受体阻滞剂哈乐 (tamsulosin)对良性前列腺增生 (BPH)伴急性尿潴留病人的治疗作用。方法 :对 72例BPH伴急性尿潴留病人采用随机、对照研究 ,分为治疗组和对照组。病人均行保留导尿 ,口服抗生素治疗。治疗组加用哈乐 0 .4mg ,1次 /d ,连续服用 3次。 72h后拔除导尿管。　结果 :拔除导尿管后 4 4 % (32 / 72 )的病人能自行排尿。有效率治疗组为 6 1% (2 2 / 36 ) ,对照组为 2 8% (10 / 36 ) ,两组比较差异有显著性 (P <0 .0 1)。　结论 :对BPH伴急性尿潴留应用哈乐治疗 ,可提高早期拔除导尿管后病人自行排尿的成功率 ,且疗效与前列腺体积大小无关。     

无张力阴道吊带术治疗女性压力性尿失禁

目的：探讨无张力阴道吊带术(TVT)治疗女性压力性尿失禁的初步疗效和手术安全性。方法：对20例经过临床和尿动力学检查诊断为压力性或混合性尿失禁的女性患者进行TVT手术治疗，并对手术效果和并发症进行初步的随访研究。结果：平均手术时间40min(25—100min)，平均术后住院3．2d(1—28d)。18例单纯性压力性尿失禁患者16例治愈，治愈率为88．89％(16／18)，另2例显效(11．1％)。2例混合性尿失禁患者中1例显效，另1例无效。术后发生尿潴留3例，2例作松解术，1例延长导尿管留置时间后缓解。发生局部血肿1例经保守治疗后康复。结论：TVT手术是一种治疗压力性尿失禁的安全有效的方法，具有手术简单、创伤小、并发症少、患者康复快等优点。     

无张力阴道吊带术治疗女性压力性尿失禁(附20例报告)

目的 评价无张力阴道吊带术(tension-free vaginal tape，TVT)治疗女性压力性尿失禁的疗效。方法 总结采用TVT术治疗女性压力性尿失禁20例的临床资料。结果 平均手术时间26.5min。拔除尿管后，19例病人控尿满意，1例仍有轻微尿失禁。术后平均随访12(3-24)个月，20例病人均无尿失禁。合并症有1例膀胱穿孔，1例术后轻度排尿不畅，2例尿频尿急。结论 TVT术操作简便快捷，创伤小，合并症少，术后康复快，是一种治疗女性压力性尿失禁的理想方法。     

胃管作尿道支撑引流管在尿道下裂中的应用

目的 评价单纯用胃管兼作尿道支撑管和引流管在尿道下裂尿道成形术中的作用。方法 回顾性分析新华医院1997年12月～2004年12月间收治的先天性尿道下裂患者，在做尿道成形手术中单纯应用胃管作尿道支撑引流管1176例，年龄6个月-20岁。未进行膀胱造瘘等尿液改道引流方法。结果 术后因发生尿瘘而需再次尿道成形术的113例（9．6％），尿道狭窄需再次手术成形的8例（0．7％），尿道裂开需尿道再成形的5例（0．4％）。结论 在尿道下裂尿道成形术中单纯用胃管兼作尿道支撑管和引流管引流尿液是充分有效的，无须另行尿流改道。     

An effective treatment for functional urinary incoordination

Twenty women diagnosed with functional urinary incoordination were randomly assigned to one of two treatment groups: biofeedback or progressive muscle relaxation. Ten subjects who were placed on a waiting list prior to treatment allocation served as a comparison group. The biofeedback intervention focused specifically on retraining of pelvic floor musculature (PFM). Patients were assessed pretreatment, posttreatment, and at 2-month follow-up. Outcome measures included self-reported symptomatology, psychological functioning, psychophysiological assessment of the PFM, and urologist ratings of problem severity and treatment efficacy. Both treatment approaches proved effective in improving symptomatology and psychological state. Subjects on the waiting list demonstrated no change in urological difficulties. No differences were found between the two treatment groups on any of the outcome measures. Theoretical and practical implications of the results are discussed.     

Prejunctional effects of muscarinic agonists on 3H-acetylcholine release in the rat urinary bladder strip

Summary The inhibitory effects of some muscarinic agonists on tritiated acetylcholine release evoked by field stimulation were investigated in the rat urinary bladder strip. The acetylcholine stores of the preparation were labelled with ³H-choline. Electrical field stimulation caused an outflow of tritium, reflecting the release of ³H-acetylcholine. The release of ³H-acetylcholine was decreased in a concentration-dependent manner by all the agonists tested: oxotremorine, muscarone, muscarine, carbachol and methylfurtrethonium. On the contrary, only muscarine and muscarone enhanced the basal efflux of tritium in a concentration-dependent fashion. Concentration-response curves were determined both at 2 Hz and at 1 Hz by using intermittent administration of the drugs. Maximal depression in release (by 78 – 82%) was observed in experiments at 1 Hz. A similar inhibition was obtained at 2 Hz frequency only when a low concentration of calcium (0.6 mM) in the medium was used. Oxotremorine was the most potent among the tested compounds with the same intrinsic activity as the other drugs. In contrast to the other agonists investigated, oxotremorine showed in about 10-fold greater potency at pre- than at postjunctional muscarine receptors in the rat urinary bladder. This difference might depend either on heterogeneity of muscarine receptors or on different mechanism(s) relating to the transducing properties of receptors at the pre- and postjunctional level. A comparison between the relative prejunctional potencies in the rat urinary bladder and in the guinea pig myenteric plexus (data from the literature) suggests that prejunctional muscarine receptors are similar in these tissues. Furthermore, the findings obtained with a low concentration of calcium in the medium may support the view that intraneuronal availability of calcium plays a significant role in modulating the prejunctional negative feed-back mechanism in the rat urinary bladder.Send offprint requests to Dr. G. D'Agostino at the above address     

Is it time to reconsider initial antibiotic treatment strategies for severe urinary tract infections in Europe?

Until recently, most reported cases of bacteraemia caused by multidrug-resistant strains of Enterobacteriacae producing an extended-spectrum beta-lactamase (ESBL) in Europe have been nosocomial in origin. However, increasing numbers of reports of community-acquired bacteraemia and urinary tract infection caused by ESBL-producing microorganisms suggest that the geographical origin of patients should be taken into account as a risk-factor for possible ESBL production. Early identification of patients at high-risk of infection with ESBL-producing microorganisms, based on their geographical origin and travel history, should help to optimise initial antibiotic treatment strategies for severe urinary tract infections in Europe.