来自日本旭川医科大学泌尿外科的 Seiji Matsumotoa 等关于氢气水治疗膀胱炎的研究在线发表在 Urology 上，这是目前关于氢水临床研究第 8 种疾病的报道。去年我曾经对这一研究的临床注册信息介绍过。 虽然本次研究的结果并没有显示氢气水对这一疾病具有治疗作用，但是结果显示出非常明显的对抗疼痛的效果(安慰剂对照组也出现疼痛的缓解作用,效果不如氢气水,但两组差别11%不具有统计学差异)。 实验设计 Effect of Supplementation With Hydrogen-rich Water in Patients With Interstitial.pdf 过去日本学者曾经报道过氢气在糖尿病、代谢综合征、类风湿关节炎、脑干缺血、皮肤红斑、肝癌放射治疗生活质量、血液透析不良作用等的临床研究。关于氢气相关的临床研究目前大部分都支持氢气具有一定治疗效果，但是这些临床研究的病例数量都比较少（没有超过 100 例的报道），而且有些缺乏非常严格的对照，不足以获得非常明确的有效性证据。因此，关于氢气的临床研究仍需要大规模多中心的双盲对照研究。至少从文字描述上分析，这一研究可能是目前设计上最具有可信度的研究。不过本次研究只有患者 30 名，其中治疗组 20 名，安慰剂组 10 名，而且有 2 名患者中途退出实验。因此观察的数量比较少，结论尚无法最终确认。 疼痛效应结果 间质性膀胱炎（ IC Interstitial cystitis ）一种慢性盆腔疼痛综合症，是一种导致膀胱和盆腔周围不适或疼痛的疾病，女性患者要多于男性，在美国估计有超过 70 万患者， 90% 为女性。正在研究的一种理论认为 IC 是继发于膀胱感染后的自身免疫反应。另一种理论认为细菌存在膀胱细胞内，但常规尿液检查不能发现。间质性膀胱炎患者的个体症状差异较大，即使在同一患者，也可出现不同的症状。患者可以有膀胱和盆腔周围的轻度不适、压迫感、压痛，或剧烈疼痛。症状可能包括急迫排尿（尿急），频繁排尿（尿频），或者这些同时存在。在膀胱充满尿液时这些症状会加重，也可能在空虚时加重。 目前还没有一种可治愈该疾病的方法，因此也不能预测谁将对那种治疗反应最好。没有扩张、或碰巧饮食改变、或经过治疗，症状都可能消失。尽管症状消失，但经过几天、几周、几年，症状也许又出现。因此这一疾病在研究上也非常困难，患者数量太少很难判断治疗效果。 许多人担心如果出现阴性结果，似乎难以发表论文，其实象这一明显“阴性”的研究仍可以在比较好的杂志上发表，而且对人们正确认识疾病规律，认识客观现象有很正面的帮助。相信这一研究仍会受到氢气分子医学研究的关注，建议发现阴性结果的研究仍进行大胆报道，特别是具有新意的重要资料和证据。 Effect of Supplementation With Hydrogen-rich Water in Patients With Interstitial Cystitis/Painful Bladder Syndrome Seiji Matsumotoa, , , Tomohiro Uedab, Hidehiro Kakizakia a Department of Renal and Urologic Surgery, Asahikawa Medical University, Hokkaido, Japan b Department of Urology, Kyoto City Hospital, Kyoto, Japan Reprint requests: Seiji Matsumoto, M.D., Ph.D., Department of Renal and Urologic Surgery, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 Japan. Received 24 August 2012Accepted 15 October 2012Available online 30 January 2013 http://dx.doi.org/10.1016/j.urology.2012.10.026, How to Cite or Link Using DOIPermissions Reprints -------------------------------------------------------------------------------- Objective To investigate the efficacy of hydrogen-rich water for the treatment of patients with interstitial cystitis/painful bladder syndrome (IC/PBS). Methods We conducted a prospective, randomized, double-blind, placebo-controlled clinical trial of hydrogen-rich water in patients with IC/PBS. Inclusion criteria were stable symptoms of IC/PBS for ≥ 12 weeks after bladder hydrodistension, Interstitial Cystitis Symptom Index score of ≥ 7 and bladder pain (question 4 on Interstitial Cystitis Symptom Index) of ≥ 4. They were randomized by a 2:1 ratio to receive hydrogen-rich water or placebo water for 8 weeks. The symptoms were assessed using the Interstitial Cystitis Symptom Index, Interstitial Cystitis Problem Index, Parsons’ Pelvic Pain and Urgency/Frequency Patient Symptom Scale, visual analog scale bladder pain scores, and a standard 3-day voiding diary. The primary outcome was improvement of patient-reported symptoms evaluated after treatment. Results A total of 30 participants (29 women and 1 man, age 64.0 ± 14.8 years) were enrolled in the present study, and 2 patients (both women) were withdrawn from the study. The score of bladder pain was significantly reduced in both groups. However, the effect of hydrogen-rich water on symptoms was not significantly different from that of placebo, although supplementation with hydrogen-rich water was extremely effective in improving the bladder pain score in 11% of the patients. Conclusion The results of the present study do not support the use of supplementation with hydrogen-rich water for treating patients with IC/PBS. Patients with interstitial cystitis/painful bladder syndrome (IC/PBS) present with a constellation of symptoms, including bladder pain, frequency, and urgency. The proposed etiology for the symptoms of IC/PBS includes bladder ischemia and reperfusion injury. Previous reports showed pathologic findings of IC/PBS focusing on ischemia and a reduction in bladder capacity owing to fibrosis of the bladder wall.1, 2 and 3 Hyperbaric oxygen therapy has been reported to be effective in patients with IC/PBS resistant to conventional treatment.4 and 5 Oxidative stress due to free radicals, which are formed by reperfusion after bladder ischemia, can cause bladder damage. Reperfusion injury is more harmful than the damage caused by ischemia alone.6 Previous studies using an experimental cystitis animal model revealed that free radical-mediated tissue damage is also involved in the pathogenesis.7 and 8 Recently, several investigators have shown that hydrogen has potential as an antioxidant in preventive and therapeutic applications. Ohsawa et al9 reported that hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. These findings led us to consider the possibility that hydrogen-rich water might be useful as a therapeutic supplement for IC/PBS. We hypothesized that oxidative stress could be one of the causes of IC/PBS, because the disturbance of bladder blood flow has been suggested in IC/PBS. However, to our knowledge, no clinical data are available to prove the efficacy of hydrogen in patients with IC/PBS. In the present study, we assessed whether supplementation with hydrogen-rich water had beneficial effects on the symptoms in patients with IC/PBS. Table1. Summary of measured variables at baseline and after 8 weeks of hydrogen-rich water or placebo Hydrogen-rich Water Placebo Water Variable Before After P Value Before After P Value Subjects randomized 18 10 Sex Male 0 1 Female 18 9 Age (y) 65.2 ± 7.9 64.5 ± 4.5 VAS (0-10) 6.0 (1.9) 4.9 (2.8) .186 6.3 (1.5) 5.1 (2.4) .182 24-h Voiding frequency 13.0 (3.9) 14.3 (5.4) .402 13.1 (3.6) 12.5 (4.2) .736 Voiding volume 124.0 (36.4) 138.7 (54.0) .346 142.3 (27.3) 160.6 (48.7) .313 ICSI (0-20) 13.2 (3.3) 11.4 (5.0) .217 13.3 (2.0) 11.2 (3.8) .141 Pain score (Q4; ICSI, 0-5) 4.3 (0.5) 3.1 (1.3) .001 ∗ 4.4 (0.5) 3.2 (1.3) .047 ∗ ICPI (0-12) 10.1 (3.3) 9.4 (3.4) .448 10.3 (2.6) 9.6 (3.2) .595 PUF total score (0-33) 18.4 (4.1) 16.7 (5.8) .298 19.4 (5.2) 15.9 (5.7) .168 PUF symptom score (0-21) 12.4 (2.5) 11.6 (3.9) .480 12.1 (2.8) 10.2 (3.2) .177 PUF problem score (0-12) 6.1 (1.9) 5.0 (2.3) .163 7.3 (2.6) 5.7 (2.8) .203 Urgency score: Q8a in PUF (0-3) 1.7 (0.7) 1.7 (0.7) .986 1.9 (0.7) 1.6 (1.0) .493 ICPI, Interstitial Cystitis Problem Index; ICSI, Interstitial Cystitis Symptom Index; PUF, Pelvic Pain and Urgency/Frequency; VAS, visual analog scale. ∗ P .05. Full-size table
【这是新闻发布会前和朋友的通信：附上AUA年会3年结果（先不要对外透漏)。专业数据非常好，比预期的还好。另外，你们结合UROLOGY Times的报道，就会明白美国的手术难度比中国大得多，其中4个人做了神经移植。术前我就对美方和美国病人讲：你们3个做过宫内手术的都需做神经移植，成功的可能最多30%（好了1个半：一个homerun，另一个大便好了），这位37岁的脊髓膨出病人膀胱本来就发育不好，又受损太久，效果难定，其余6位有把握。现在的结果完全如我所料：总共7人自主排尿，8人自主大便。 另外：肖氏反射弧“消失”及其重要科学意义: 和截瘫不同，在脊膜膨出患者，我在最初20例就观察患儿到最后都无须利用肖氏反射弧排尿，都能像正常人一样意识控制排尿，这我在J.UROL2005文章中已经报告。其实这是肖氏反射弧一个非常重要的科学现象，证明了异类周围神经再生形成肖氏反射弧后能刺激、导致中枢包括大脑的功能重组。我973项目的一项重要内容就是证明这个重组。我已经在20多个SB病人完成了术前和术后获得排尿功能后fMRI研究，证明了这类患者术后在PONS新建立了一个排尿中枢，其位置与正常人不同！中枢的TAKEOVER非常有意思！我在SIU讲座时略微带了一下（你可去看看那视频）。已成文。这项研究非常辛苦不易，历经6-7年 。】 美国泌尿外科学会（AUA）报告美国肖氏手术三年结果 Tuesday, May 17, 2011 华盛顿 D.C 背景和目标 ：通过显微神经手术吻合腰-骶神经运动支，从而建立皮肤-中枢-膀胱反射弧来重建先天脊柱裂脊膜膨出病人膀胱和肠道功能的理论和手术是肖传国发明的。我们应用此创新手术已3年，现报告结果。 方法 ：这项为期3年的临床研究计划共收治9位病人（3男6女）平均年龄8岁（6-37岁）。本计划得到伦理委员会批准。经过详尽的术前检查和评估后，为每个病人在神经电生理监控下施行了腰-骶神经通路重建手术（即肖氏反射弧手术---译者注）。术后评估包括随访问卷，尿流动力学测定，排尿日记，肾功能研究和大肠功能评估。 结果 ：9个病人中，5个曾在出生后24小时内做过脊膜膨出修补手术，3个则在胎儿期用内窥镜作了子宫内脊髓膜膨出修补术，仅一人无手术史。手术平均时间为183分钟（127-278分钟），无任何术中并发症。术后有一个病人发生左足下垂，8个病人出现暂时性小腿肌肉力量减弱（均在6个月左右恢复至术前肌力—译者注：见术后一年报告J.Urol，Peters）。在术后12个月，9个病人中有7个经检测证实已建立皮肤-膀胱反射弧（即肖氏反射弧-译者注）在进行术后第3年随访时，有2位病人没能回访，暂列为失随访。其余7位病人术后3年结果如下：尿流动力学检查证实：膀胱平均容量从210毫升增加到293毫升。7个病人中术前有4个是高反射膀胱，现仅一位还有高反射。平均膀胱顺应性从术前12.2 ml/H2O改善为28.4 ml/H2O，其中3位术前顺应性低于10者（表示逼尿肌基本无功能-译者注）术后变成正常（从7到34.3, 从9.4到21.2, 从8.3到28.4）。 7个病人中，术前仅2人能排出平均23毫升尿，现6人已完全不需导尿管自行排尿，6个病人自己记录每次可排出平均156毫升尿，但尿流率测定证实每次平均排出高达248毫升，残余尿93毫升，有效排尿率为73% 所有6个病人都能排空至少超过59%的膀胱容量。7个病人中，5个需借助些许腹压排尿；7个病人中一个已无尿失禁，6个仍有压力性尿失禁（即打喷嚏或剧烈咳嗽时滴尿，因为尿道括约肌还较弱所致-译者注）：其中3个仅偶有滴尿，3个较易滴尿。7个病人中，3个在术前认为自己肠道功能正常，一个没有大便失禁。在术后3年随访时，6个报告肠道功能已正常，4个已无大便失禁。除一位还有高反射膀胱的病人外，其余所有病人都不再需要服用抗胆碱能药物。肾脏B超检查和血肌酐均正常。所有病人均无长期并发症。7个病人中有6个很高兴自己作了本手术。 结论： 腰-骶神经改道重建手术（即肖氏反射弧手术-译者注）能够改善先天性脊柱裂脊膜膨出并发神经性膀胱病人的大小便功能。 Tuesday, May 17, 2011 8:00 AM-10:00 AM Urodynamics/Incontinence/Female Urology: Neurogenic Voiding Dysfunction Moderated Poster Source of Funding: Ministrelli Program for Urology Research and Education (MPURE) 1502: THREE-YEAR CLINICAL OUTCOMES WITH LUMBAR TO SACRAL NERVE REROUTING IN SPINA BIFIDA Kenneth Peters，Kevin Feber， Benjamin Girdler， William Nantau， Evan Kass， Jose Gonzalez， Gary Trock ，Ananias Diokno，Royal Oak, MI INTRODUCTION AND OBJECTIVES: The concept of restoring bladder and bowel function inspina bifida by the creation of a skin-CNS-bladder reflex arc by an intradural lumbar to sacral motor root microanastomosis was introduced by Xiao. We report our three-year experience with the novel procedure. METHODS: Nine patients (3 males, 6 females) with median age of 8 (range 6 to 37) years enrolled in this institutional review board approved protocol. After extensive preoperative evaluation, lumbar to sacral nerve rerouting was performed using intraoperative neurophysiological monitoring. Postoperative evaluation included follow-up questionnaires,urodynamic testing (UDT), voiding diaries, renal function studies and bowel assessment. RESULTS: Of the 9 patients, 5 patients had defect closure within 24 hours of birth, 3 had intrauterine closure and 1 had no prior surgery. Mean operative time was 183 (range 127-278) minutes. No intraoperative complications occurred. One patient developed permanent foot drop and 8 had transient lower extremity weakness. By 12 months, 7 of 9 had a documented cutaneous to bladder reflex. At 3 years, 2 patients did not return for follow-up and were considered non-responders. Seven patients returned for 36-month evaluation. On UDT, maximum cystometric capacity improved from mean 210 cc to 293 cc. At baseline 4/7 had neurogenic detrusor overactivity (NDO); at 36 months 1/7 had NDO. Median compliance improved from 12.2 ml/H20 to 28.4 ml/H2O and 3 with a baseline compliance of less than 10 had normalization (7 to 34.3, 9.4 to 21.2, and 8.3 to 28.4). At baseline, 2/7 were able to void with an average void of 23 cc. At 36 months, 6/7 no longer required catheterization and 6/7 reported mean voided volume of 156cc on voiding diaries. Uroflow demonstrated a mean voided volume of 248 cc with a 93 cc post void residual and a voiding efficiency of 73%. All 6 patients were voiding 59% of their bladder capacity. 5 of 7 require some valsalva to void. 6/7 subjects had persistent stress incontinence with 1 subject dry, 3 with occasional leak, 3 frequent leaks. At baseline, 3/7 considered their bowels normal and 1/7 were continent of stool. At 36-months 6/7 considered bowels normal and 4/7 continent of stool. Antimuscarinics were stopped in all subjects except the 1 with persistent NDO. Renal ultrasounds and serum creatinines remained stable. No long-term complications were identified and 6/7 would undergo the procedure again. CONCLUSIONS: Lumbar to sacral nerve rerouting can improve bladder and bowel function in patients withneurogenic bladder associated with spina bifida.
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