阿米替林与二甲基亚砜治疗间质性膀胱炎的临床研究

目的探讨口服阿米替林及膀胱灌注二甲基亚砜（DMSO）治疗间质性膀胱炎的临床有效性及安全性。方法2004年7月~2008年5月,采用美国国立肾病、消化病和糖尿病研究所（NIDDK）制定的标准诊断间质性膀胱炎19例,口服阿米替林25mg／d。治疗1周效果不佳的患者加服阿米替林至50mg／d,最大不超过75mg／d。对无效或不能耐受阿米替林副作用的患者加用50％DMSO50mL膀胱灌注连续10次（其中2例用50％DMSO50mL＋1万单位低分子肝素钠灌注）,总疗程3个月。观察指标：O’Leary间质性膀胱炎症状指数、间质性膀胱炎问题指数、视觉疼痛模拟量表及排尿日记。结果19例患者均完成治疗,17例患者取得良好的效果,2例患者效果较差。结论口服阿米替林及膀胱灌注DMSO是治疗间质性膀胱炎简单有效的方法,可以缓解患者的临床症状,提高生活质量,其副作用可以被大多数患者耐受。     

阿米替林治疗间质性膀胱炎的临床研究

目的 探讨阿米替林治疗间质性膀胱炎的有效性和安全性. 方法 采用前瞻性研究.间质性膀胱炎患者54例,病程19～72个月,平均(40.7±11.6)个月.口服阿米替林治疗,起始剂量25 mg/次,每晚1次.1周后,若症状不缓解,可加量至50 mg/次;再观察1周,若症状仍不缓解,则可加量至75 mg/次;维持能够缓解症状的最小剂量,总疗程3个月.观察用药前及用药3个月后患者的临床症状(每日排尿次数、最大排尿容量、尿痛程度评分)和O'Leary-Sant间质性膀胱炎问卷表评分及生活质量评分情况.并记录不良反应发生情况. 结果 ①用药3个月后每日排尿次数明显减少,治疗前后分别为(28.5±8.4)和(15.6±3.3)次;最大排尿容量明显增加,治疗前后分别为(108.7±62.2)和(171.0±53.9)ml;尿痛程度评分明显下降,治疗前后分别为6.4±1.5和2.2±1.5,上述指标用药前后相比,差异均有统计学意义(P<0.01).②患者用药3个月后问卷评分和生活质量评分均明显减少,治疗前后分别为26.9±4.0和13.7±5.7及5.5±0.5和2.5±0.6;用药前后比较,差异有统计学意义(P<0.01).③45例在服药第1个月内有不同程度的困倦,43例1个月后自行缓解,2例由于困倦严重且不能缓解而停药.10例服药3个月后体质量增加(5.8±1.8)kg.11例有轻度便秘症状,可以耐受.9例有口干症状,可以耐受.3例出现重度排尿困难,停药后改为其他方法治疗. 结论 阿米替林口服治疗能有效缓解间质性膀胱炎患者的临床症状,改善生活质量,且耐受性及安全性好.     

膀胱扩张术联合药物治疗间质性膀胱炎患者的护理

对19例间质性膀胱炎患者行膀胱扩张术和口服阿米替林和/或二甲基亚砜膀胱灌注治疗。结果 19例患者均完成治疗,17例症状明显缓解,20例改用辣椒辣素类似物（RTX）膀胱灌注后症状缓解。患者平均尿量显著增加,24 h排尿次数、夜尿次数显著减少,VAS评分显著降低,总尿量则无明显改变。提出术前做好症状量化评估和解释工作,术后严密观察导尿管引流,做好用药护理、预防感染、心理支持及健康教育,出院做好心理疏导,妥善安排膀胱灌注及随访时间是良好效果的保证。     

膀胱扩张术联合药物治疗间质性膀胱炎患者的护理

对19例间质性膀胱炎患者行膀胱扩张术和口服阿米替林和/或二甲基亚砜膀胱灌注治疗。结果 19例患者均完成治疗,17例症状明显缓解,20例改用辣椒辣素类似物(RTX)膀胱灌注后症状缓解。患者平均尿量显著增加,24 h排尿次数、夜尿次数显著减少,VAS评分显著降低,总尿量则无明显改变。提出术前做好症状量化评估和解释工作,术后严密观察导尿管引流,做好用药护理、预防感染、心理支持及健康教育,出院做好心理疏导,妥善安排膀胱灌注及随访时间是良好效果的保证。     

间质性膀胱炎诊断及治疗

间质性膀胱炎(interstitial cystitis,IC)是一种临床常见的、慢性的、严重的膀胱壁炎症.表现为尿频、尿急和严重的下腹或会阴区疼痛.临床诊治困难.该病好发于中年,女性多于男性.对IC的认识已经历100年历史,但人们对该病的定义、病因、病理乃至流行病学等研究迄今仍尚不明了.目前主要有以下几种学说:感染因素,黏膜上皮通透性改变,肥大细胞浸润,神经源性机制和自身免疫学说等.     

阿米替林联合透明质酸钠、肝素治疗间质性膀胱炎的临床疗效评价

目的探讨口服阿米替林联合膀胱灌注透明质酸钠、肝素治疗间质性膀胱炎/膀胱疼痛综合征（interstitial cystitis/painfulbladder syndrome,IC/PBS）的临床疗效和安全性。方法 24例IC/PBS患者行口服阿米替林联合膀胱灌注透明质酸钠、肝素治疗。麻醉下膀胱镜检查及水扩张后,诊断明确所有患者即开始口服阿米替林25mg/d,最大剂量75mg/d;同采用透明质酸40mg、肝素25 000U混合液膀胱灌注、每周1次,4次后改每月1次。观察治疗前及治疗后3、6个月的排尿次数、排尿量和Oleary saint问卷表评分（OLeary-Sant patient symptom/problem index scores,ICSI/ICPI）;盆腔疼痛及尿频评分（pelvic painand urgency frequency questionnaire,PUF）;第6月复查膀胱镜。结果 22例患者完成本研究,随访3、6月时,每日排尿次数明显减少,尤其是夜尿次数,平均每次尿量明显增加,ICSI、ICPI、PUF评分明显降低,差异有统计学意义（P〈0.001）;治疗6月与治疗3月相比差异除夜尿次数及PUF评分外,其他各项指标均无统计学意义（P〉0.05）。6月复查膀胱镜检查,19例黏膜下出血点消失或减轻,3例膀胱三角区炎性改变。结论阿米替林联合透明质酸钠、肝素治疗IC/PBS安全有效。     

阿米替林联合透明质酸钠治疗膀胱疼痛综合征/间质性膀胱炎的临床研究(附58例报告)

目的:探讨联合应用阿米替林和透明质酸钠治疗膀胱疼痛综合征/间质性膀胱炎(BPS/IC)的临床疗效和安全性。方法:对58例BPS/IC患者行膀胱灌注透明质酸钠和口服阿米替林治疗。所有患者在膀胱镜检+水扩张后,病理诊断为非特异性炎症者并且统计肥大细胞数目,然后膀胱灌注透明质酸钠。第1个月每周1次,连续灌注4周,然后每月1次,直到第6个月。观察用药前及用药1、3、6个月时的临床症状情况(每日排尿次数、最大排尿容量、膀胱区疼痛程度评分)和O’Leary-Sant间质性膀胱炎问卷表评分及生活质量评分(QOL)情况。在第一次灌注透明质酸钠的同时持续口服阿米替林25mg/每晚,1周后根据患者耐受情况增加阿米替林至每日口服25mg两次,6个月。实验期间均观察患者有无不良反应。到了治疗后第6个月所有入组患者复查膀胱尿道镜检时再次膀胱黏膜随机活检,观察膀胱黏膜炎症的变化,病理上再次统计肥大细胞数目,与治疗前的肥大细胞数目相比较有无统计学的差异。结果:58例总有效率62.1%(36/58),其中完全缓解率为39.7%(23/58),部分缓解率为22.4%(13/58),治疗无效率为37.9%(22/58)。治疗前所有患者平均每日排尿次数、每次排尿量、疼痛程度、O’Leary Sant评分、生活质量评分和膀胱黏膜下肥大细胞计数与治疗后相比均存在显著改善(均P值<0.001)。结论:阿米替林联合透明质酸钠治疗BPS/IC能有效缓解患者的临床症状和改善其生活质量。     

膀胱水扩张加肝素灌注治疗女性间质性膀胱炎10例报告

目的观察膀胱水扩张加肝素灌注治疗间质性膀胱炎（IC）的疗效。方法该组10例IC患者均为女性。平均年龄36岁。平均病程30个月。所有患者在麻醉下行膀胱镜检加水扩张,次日均使用肝素钠10^5u加入无菌生理盐水20mL膀胱灌注,完成治疗后以O’Leary-Sant间质性膀胱炎症状评分（ICSI）、每日排尿次数及最大膀胱容量作为疗效评判标准,观察治疗前后患者各项指标情况。结果10例患者按照疗程治疗后随访4-12个月,平均7.5个月,症状缓解4例,症状显著缓解或消失6例;O’Leary-Sant ICSI治疗前为（12.5±4.9）分,平均治疗7个月后降为（6.5±2.3）分（P〈0.01）;治疗前患者平均排尿次数为（14.9±2.6）次／d,完成治疗后患者排尿次数减少至（7.8±2.8）次／d（P〈0.01）;膀胱最大容量治疗前为（73±10）mL,治疗后为（260±56）mL（P〈0.01）。治疗期间发生轻微肉眼血尿2例。结论膀胱水扩张联合肝素膀胱灌注治疗可有效缓解间质性膀胱炎患者症状,提高生活质量,是一种有效的治疗方法。     

临床表型分类法在间质性膀胱炎/膀胱疼痛综合征患者中的应用价值

目的 探讨临床表型6个亚型(urinary,psychosocial,organ specific,infection,ncurological/systemic and tenderness,UPOINT;泌尿、心理、器官特异性、感染、神经性和压痛)分类法在间质性膀胱炎/膀胱疼痛综合征(IC/PBS)患者中的应用价值.方法 2009年11月至2011年10月收治IC/PBS患者54例.女42例,男12例.年龄21 ～ 76岁,平均(41.0±12.4)岁.病程6～240个月,平均(63.0±59.2)个月.采用UPOINT表型分类法对患者进行分类,同时采用间质性膀胱炎症状指数(interstitial cystitis symptom index,ICSI)和盆腔疼痛、尿频尿急症状评分(pelvic pain and urgency/frequency patient symptom scale,PUF)评估患者症状,视觉模拟评分法(visual analogue scale,VAS)分别评估与膀胱有关的疼痛、尿频、尿急症状.结果 54例患者中,ICSI 9～19分,平均(15.0±1.84)分.PUF评分14～25分,平均(20.0±2.3)分.与膀胱有关的疼痛VAS评分5～ 10分,平均(7.0±1.0)分;尿频评分8～10分,平均(9.0±0.9)分;尿急评分8～10分,平均(9.0±1.3)分.54例患者中,泌尿分类项目患者占100％,器官特异性分类项目占96％,社会心理分类项目占44％,感染分类项目占33％,神经性分类项目占24％,压痛分类项目占28％.占2项分类项目者11％,占3项分类项目者38％,占4项分类项目者36％,占5项分类项目者13％,占6项分类项目者2％.患者症状持续时间与所占项目数相关(r =0.76,P＜0.01);ICSI与患者所占的分类项目阳性数相关(r =0.89,P＜0.01);PUF评分与患者所占的分类项目数无相关性;患者所占分类项目的阳性数与VAS疼痛评分呈正比,与尿频、尿急VAS评分无相关性.结论 UPOINT临床表型分类法可对IC/PBS患者临床症状进行划分,不仅可提高对IC/PBS患者的诊断率,还为制订IC/PBS患者的个体化治疗方案提供了理论基础,值得临床工作中推广     

间质性膀胱炎大鼠动物模型膀胱黏膜保护前后组胺受体变化及意义

目的 探讨透明质酸膀胱灌注治疗间质性膀胱炎(IC)后膀胱组织中组胺受体变化的意义. 方法 IC模型大鼠20只,随机分为2组,每组10只.实验组尿道灌注0.8 g/L透明质酸.对照组即时处死.HE染色计数膀胱固有层单核炎症细胞,特殊染色计数肥大细胞.免疫组化染色2组大鼠膀胱组织,IPP4.5图像分析软件计算吸光度(A)值,比较2组间的差异. 结果 实验组单核炎症细胞数和肥大细胞数分别为(12.20±2.48)、(2.90±0.87)个/视野;组胺H1～H4受体A值分别为0.015±0.007、0.006±0.001、0.007±0.004、0.061±0.026;对照组单核炎症细胞数和肥大细胞数分别为(23.90±3.07)、(7.08±1.23)个/视野;组胺H1～H4受体A值分别为0.055±0.033、0.031±0.023、0.033±0.017、0.091±0.059.2组单核炎症细胞和肥大细胞数比较差异均有统计学意义(P＜0.01);H1、H2、H3受体A值明显减小(P＜0.05);组胺H4受体A值差异无统计学意义(P＞0.05). 结论 组胺H1、H2、H3受体参与IC发生,其受体拮抗剂可能用于临床治疗IC.     

A prospective, randomized, placebo controlled, double-blind study of amitriptyline for the treatment of interstitial cystitis

PURPOSE: We conducted a prospective study to examine the safety and efficacy of the tricyclic antidepressant amitriptyline in patients with interstitial cystitis (IC). MATERIALS AND METHODS: The study comprised 44 women and 6 men who all met the symptom criteria of the National Institute of Diabetes, Digestive and Kidney Diseases for IC. The patients were randomly assigned to amitriptyline or placebo. Patients were prospectively treated for 4 months with a self-titration protocol that allowed them to escalate drug dosage in 25 mg increments in 1 week-intervals (maximum dosage 100 mg). The change from baseline in the O'Leary-Sant IC symptom and problem index was the primary outcome parameter. Changes in functional bladder capacity and frequency (48-hour voiding log), and intensity of pain and urgency (visual analog scales) were chosen as secondary outcome parameters. RESULTS: Two patients (1 on amitriptyline, 1 on placebo) dropped out of the study due to side effects. Thus, the data of 48 patients (24 patients in each group) were available for evaluation. Mean symptom score decreased from 26.9 to 18.5 in the amitriptyline group compared with 27.6 to 24.1 in the placebo group (p = 0.005). Pain and urgency intensity improved statistically significantly in the amitriptyline group compared with the placebo group (p <0.001). The frequency and functional bladder capacity improved to a much greater degree in the amitriptyline group but the differences were not statistically significant (p = 0.063, p = 0.083). Anticholinergic side effects were reported by all except 2 patients in the amitriptyline group (92%) and by 5 patients in the placebo group (21%). Mouth dryness was the most frequent side effect reported in the amitriptyline group (79%). CONCLUSIONS: Amitriptyline therapy for 4 months is safe and effective for treating IC. A statistically significant change in the symptom score and statistically significant improvement of pain and urgency intensity compared with placebo were observed. Anticholinergic side effects constitute the major drawback of amitriptyline treatment for IC.     

Evaluation of urinary and general symptoms and correlation with other clinical parameters in interstitial cystitis patients

AIMS: Interstitial cystitis (IC) has been deemed by some authors as a local manifestation of a systemic disease, particularly one of the autoimmune disorders. In order to provide an answer to the question whether IC patients do or do not indiscriminately report high scores for various somatic symptoms, we compared University of Wisconsin scores (U-W scores), including both urinary and non-urinary symptoms, for 30 IC female patients and 30 female controls. MATERIALS AND METHODS: A total of 30 female patients with IC and 30 healthy female controls were recruited for the study. All patients had to meet the symptom criteria established by the National Institute for Diabetes and Digestive and Kidney Diseases. Each patient completed a University of Wisconsin symptom scale, after translation (WICS). RESULTS: In the IC group median score was zero for all, but two of the reference symptoms: abdominal cramps and dizziness. All urinary symptoms were significantly increased in IC patients compared to controls. In the control group, the median value of urinary symptoms was zero. The duration of the disease was then related to IC symptoms in the patient group. Among the bladder-related symptoms, a good correlation was found for several specific symptoms and urinary symptoms as a whole. An association could be found between a positive potassium sensitivity test (PST) and burning bladder sensation, as well as pelvic discomfort. CONCLUSIONS: IC patients had significantly higher scores for the seven urinary symptoms compared to controls. The duration of disease was found to be correlated with the group of seven urinary symptoms.     

Long-term results of amitriptyline treatment for interstitial cystitis

Purpose:

We performed a prospective, open label study to examine the safety and efficacy of the long-term administration of the tricyclic antidepressant amitriptyline in patients with interstitial cystitis (IC).

Materials and Methods:

A total of 94 patients were stratified into 2 groups, namely a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) group of those who fulfilled NIDDK criteria for IC and a nonNIDDK group of those who presented with characteristic IC symptoms but met at least 1 NIDDK exclusion criterion. Amitriptyline was received strictly at bedtime following an established self-titration protocol without a limitation of the maximum daily dose. Patients reporting improvement in a global response assessment questionnaire were considered treatment responders. Further efficacy measures were changes in pain and urgency, functional bladder capacity and frequency. Changes in the O′Leary-Sant IC index and rating of overall satisfaction with the therapeutic outcome were also reported.

Results:

Mean study followup ± SD was 19.0 ± 12.5 months. The response rate was 64% (60 patients). The overall mean dose was 55 mg (range 12.5 to 150). Side effects occurred in 79 patients (84%), including dry mouth in 79% and weight gain in 59%. Patient overall satisfaction with the therapeutic result was excellent or good in 43 (46%). The dropout rate was 31% (29 patients) after a mean treatment period of 6 weeks at a mean dose of 70 mg. Nonresponse to treatment was the primary reason for dropout in all cases, while side effects contributed to dropout in 25 (86%). Improvement in the various IC symptoms was statistically significant compared with baseline.

Conclusions:

Long-term administration of amitriptyline is a feasible, safe and effective treatment for IC, provided that the drug is used judiciously to minimize adverse effects. The therapeutic response to amitriptyline was uniformly observed in patients fulfilling NIDDK criteria and in those with the pure clinical diagnosis of IC.     

Role of liposome in treatment of overactive bladder and interstitial cystitis

Intravesical (local) therapy of agents has been effective in delaying or preventing recurrence of superficial bladder cancer. This route of drug administration has also shown tremendous promise in the treatment of interstitial cystitis/painful bladder syndrome (IC/PBS) and overactive bladder without systemic side effects. Liposomes are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core. They can incorporate drug molecules, both hydrophilic and hydrophobic, and show greater uptake into cells via endocytosis. Intravesical liposomes have therapeutic effects on IC/PBS patients, mainly because of their ability to form a protective lipid film on the urothelial surface. Recent studies have shown the sustained efficacy and safety of intravesical instillation of botulinum toxin formulated with liposomes (lipo-BoNT) for the treatment of refractory overactive bladder This review considers the current status of intravesical liposomes or liposomal mediated drug delivery for the treatment of IC/PBS and overactive bladder.     

The cysteinyl leukotriene D4 receptor antagonist montelukast for the treatment of interstitial cystitis

PURPOSE: The presence of leukotriene D4 receptors in human detrusor myocytes and increased urinary leukotriene E4 in patients with interstitial cystitis and detrusor mastocytosis imply a role for cysteinyl containing leukotrienes as proinflammatory mediators in this disease. We examined the efficacy of the cysteinyl leukotriene 1 receptor antagonist montelukast for treating patients with interstitial cystitis and detrusor mastocytosis. MATERIALS AND METHODS: Ten women in whom interstitial cystitis was diagnosed according to National Institute of Diabetes and Digestive and Kidney Diseases criteria and who also had detrusor mastocytosis with a minimum of 28 mast cells per mm.2 muscle tissue were included in this study. Patients received a single dose of montelukast daily for 3 months. The efficacy of treatment was determined by 24-hour urinary frequency, nocturia and pain using visual analog scales. RESULTS: After 1 month of montelukast treatment there was a statistically significant decrease in 24-hour urinary frequency, nocturia and pain which persisted during the 3 months of treatment. After 3 months 24-hour urinary frequency had decreased from 17.4 to 12 voidings (p = 0.009), nocturia had decreased from 4.5 to 2.8 (p = 0.019) and pain had decreased from 46.8 to 19.6 mm. on a visual analog scale (p = 0.006). No side effects were observed during treatment. CONCLUSIONS: Montelukast treatment resulted in significant improvement in urinary frequency and pain. Its efficacy for decreasing urinary frequency and pain imply a role of leukotriene receptor antagonists for managing interstitial cystitis but further placebo controlled clinical studies are needed.     

The potassium sensitivity test: a predictor of treatment response in interstitial cystitis

OBJECTIVE: To determine whether the potassium sensitivity test (PST) can be used to predict the response to treatment with intravesical sodium hyaluronate in patients with interstitial cystitis. PATIENTS AND METHODS: Thirty-eight patients diagnosed with interstitial cystitis were recruited; each had a PST, carried out in a double-blind fashion, followed by six weekly doses of intravesical sodium hyaluronate. The patients were assessed before and after treatment using a self-administered interstitial cystitis symptom index (CSI) and problem index (PI). The clinical response was defined as none (<25% improvement in clinical symptoms), mild (>25%), moderate (50-75%) and excellent (>75%). RESULTS: The PST was positive in 23 and negative or indeterminate in 13 patients; two patients withdrew from the study. Overall 20 of 36 (55%) patients reported an improvement after six doses of intravesical sodium hyaluronate, but 17 (74%) with a positive PST improved, compared to only five (22%) with a negative test (P = 0.03). There was an improvement in the CSI after treatment in both groups, but a significant improvement in the PI only in patients with a positive PST (P = 0.01). The magnitude of change for the CSI and PI was significantly greater in the positive than in the negative group (CSI, P = 0.043; PI, P < 0.001). There were no major complications. Three patients complained of pain after the test, and two with a positive and one with a negative PST developed a urinary tract infection. CONCLUSIONS: Although the role of the PST in the diagnosis of interstitial cystitis requires further clarification, the test helps to predict the response to treatment with glycosaminoglycan-substitution therapy.