卡培他滨致手足综合征严重程度与血浆中炎症因子含量的分析

目的 检测并分析服用卡培他滨后出现手足综合征的结直肠癌患者血浆中主要炎症因子（IL-1β、IL-6、IL-10、IL-12、IL-17、IL-23、TNF-α、IFN-γ、CPR和CCL-5）与手足综合征之间的相关性。方法 收集35例服用卡培他滨的结直肠癌患者血浆样本,根据手足综合征分级诊断标准对其轻重程度进行划分,用ELISA试剂盒检测血浆中各炎症因子的含量。结果 所有炎症因子的标准曲线呈线性（r>0.9900）,并测定了不同结直肠癌患者血浆中炎症因子的含量,其中,TNF-α 含量水平变化较为明显,且具有参考价值。结论 不同的炎症因子在不同分级的手足综合征患者血浆中浓度存在一定差异,且TNF-α 炎症因子含量水平与其发生手足综合症的轻重程度密切相关。     

An unusual case of capecitabine hyperpigmentation: Is hyperpigmentation a part of hand-foot syndrome or a separate entity?

A 59-year-old man with adenocarcinoma of stomach was prescribed capecitabine as adjuvant chemotherapy. After two cycles of therapy, patient developed hyperpigmentation on hands and feet. Examination revealed a peculiar distribution of hyperpigmentation on hands and feet and in addition, hyperpigmented spots on the dorsum of tongue. Although hand-foot syndrome (HFS) to capecitabine solely manifesting as palmoplantar hyperpigmentation has been described earlier, this is probably the first instance wherein oral pigmentation has also been found in association. In addition, this finding lends support to the growing argument of hyperpigmentation being a separate entity: different from HFS, both therefore being separate adverse effects of the same drug.     

Unilateral hand–foot syndrome: an extraordinary side effect of capecitabine

Background: Hand–foot syndrome (HFS), the most common toxicity of capecitabine, is characterized by tingling, numbness, pain, erythema, dryness, rash, swelling, increased pigmentation, and/or pruritus of the palmar and/or plantar surfaces of the hands and/or feet. HFS is usually seen in both the hands and the feet, with varying severity. We have previously published a case report of dihydropyrimidine dehydrogenase (DPD) deficiency that manifested a variant of HFS.

Case report: We report the case of a 65-year-old Turkish Cypriot male patient with advanced gastric cancer who developed pain, numbness, and reddening in his left palm and left sole 10 days after the fourth cycle of capecitabine at a dose of 1,000?mg/m²/day twice daily (BID) on days 1 to 14 every 21 days. On physical examination, he had unilaterally erythematous changes and skin scaling on his left sole and palm consistent with grade II HFS. After stopping administration of capecitabine and supportive management, the HFS resolved in a week’s time.

Conclusions: To the best of our knowledge, this is the first case of capecitabine-induced unilateral HFS. Further investigation related to this toxicity associated with capecitabine is warranted.     

化疗药物诱导的手足综合症

手足综合症（HFS）通常是由化疗药物诱导的一种皮肤毒性反应,许多化疗药物在不同程度上表现出这一不良反应。本综述介绍了HFS的临床表现、毒性分级、导致这一症状的常见化疗药物及其可能的病因、预防与治疗措施等。     

Candidate mechanisms for capecitabine-related hand-foot syndrome

AIMS

The oral fluoropyrimidine prodrug capecitabine is widely used in oncology. Capecitabine was designed to generate 5FU via the thymidine phosphorylase (TP) enzyme, preferentially expressed in tumoral tissues. Hand–foot syndrome (HFS) is a limiting toxicity of capecitabine. A pilot study on healthy volunteers was conducted in order to test the hypothesis that the occurrence of HFS could be related to tissue-specific expression of drug-metabolizing enzymes in the skin of the palm and sole. To this end, the expression of TP (activating pathway), dihydropyrimidine dehydrogenase (DPD, catabolic pathway) and cell proliferation (Ki67) were measured in the skin of the palm (target tissue for HFS) and of the lower back (control area).

METHODS

Two paired 4-mm diameter punch biopsy specimens (palm and back) were taken in 12 healthy volunteers. Immunohistochemical analyses were performed on frozen tissues.

RESULTS

Proliferation rate (Ki67 staining) was significantly higher in epidermal basal cells of the palm compared with the back (P = 0.008). Also, TP and DPD expression were significantly greater in the palm relative to the back (P = 0.039 and 0.012, respectively). TP and Ki67 expression were positively and significantly correlated in the palm.

CONCLUSIONS

The high proliferation rate of epidermal basal cells in the palm could make them more sensitive to the local action of cytotoxic drugs. TP-facilitated local production of 5FU in the palm during capecitabine treatment could explain the occurrence of HFS. This observation may support future strategies to limit the occurrence of HFS during capecitabine therapy.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Hand–foot syndrome (HFS) is a limiting toxicity of the widely used fluorouracil (5FU) prodrug capecitabine.
• The pharmacological origin of HFS has not been elucidated.
• The expression of capecitabine-metabolizing enzymes thymidine phosphorylase (TP, activating pathway) and dihydropyrimidine dehydrogenase (DPD, catabolic pathway) in the skin of the palm (target tissue for HFS) is unknown.

WHAT THIS STUDY ADDS

• This pilot study, conducted in healthy volunteers, clearly demonstrated that TP expression is significantly greater in the palm compared with the lower back (control area).
• This suggests TP-facilitated enhanced production of 5FU in the palm that could explain the occurrence of HFS.
• This result may support strategies to prevent HFS.

     

炎敌油用于希罗达治疗乳腺癌所致手足综合征的疗效观察

目的观察炎敌油用于希罗达(卡培他滨)治疗乳腺癌所致手足综合征的临床疗效。方法采用病例对照研究的方法,选择53例乳腺癌口服希罗达患者,随机分为实验组29例和对照组24例。对照组口服希罗达同时给予常规护理及口服维生素B6,实验组在常规护理的基础上同时涂抹炎敌油。观察两组手足综合征的发生情况。结果实验组手足综合征的发生率为34.5%,对照组为58.3%,两组比较差异有统计学意义(P<0.05)。结论炎敌油对防治口服希罗达所致手足综合征有一定的疗效。     

手太阴肺气证在小儿外感温热病手足太阴肺脾顺传规律过程中的临床观察

目的:观察小儿外感温热病顺传手足太阴肺脾的规律中,手太阴肺气证这一传变过程。方法:以临床观察研究为主,观察目前成都地区中医儿科临床名家治疗小儿外感温热病的辨证思路,即手足太阴肺脾顺传规律,本文主要观察小儿外感温热病手足太阴肺脾顺传规律过程中手太阴肺气证,以及影响本阶段传变的必要因素:年龄、主证轻重、主证缓解时间。结果:对所观察的患儿发生外感温热病初期时,辨证为手太阴肺卫证,或手太阴肺气证,均有相同的可能性,差异无统计意义(P>0.05);年龄、主证轻重、主证缓解时间3个因素均对本证传变产生影响,差异均有高度统计意义(P<0.01)。结论:以咳嗽为主要表现的手太阴肺气证证型确为小儿外感温热病发病的初期,临床中医儿科医师应重视本阶段的发生、发展及变化,以防传变,并尽早做好传变至下阶段后的治疗准备。     

盐酸多柔比星脂质体注射液联合注射用紫杉醇(白蛋白结合型)致严重皮肤损害1例分析

目的 提醒临床医生在联合使用多柔比星脂质体和紫杉醇(白蛋白结合型)时应密切关注用药安全.方法 分析了1例43岁女性患者联合使用多柔比星脂质体和紫杉醇(白蛋白结合型)后出现3级手足综合征和2级皮肤擦烂样皮炎的病例,文献回顾上述2种药物所致皮肤毒性的临床表现、发病机制和防治措施.结果 该患者的手足综合征很可能由多柔比星脂质...     

恩度联合卡培他滨治疗晚期乳腺癌的临床观察

目的评价重组人血管内皮抑制素注射液(恩度)联合卡培他滨治疗晚期乳腺癌的有效性和安全性。方法经病理学确定的Ⅳ期乳腺癌患者6例,其中浸润性导管癌4例,浸润性小叶癌1例,髓样癌1例,均接受恩度联合卡培他滨的治疗。恩度15 mg加生理盐水500 ml匀速缓慢静脉滴注1~14 d,间歇7 d,重复给药;卡培他滨每日2 500 mg/m2分早、晚2次口服,于饭后半小时用水吞服,1~14 d,休息7 d,21 d为一周期。按照RECIST标准评价近期疗效,参照Kamofsky评分(KPS)变化评价生活质量(QOL)。按照NCI.CTC3.0版标准评价毒性反应,用药1周期即可评价毒性,2周期后方可评价疗效。结果6例患者均可评价客观疗效和安全性。共完成26个周期,平均为4.3个周期,获得CR 1例、PR 2例、SD 2例、PD 1例。客观有效率(RR)(3/6),疾病控制率(DCR)(5/6),生活质量改善者4例、稳定1例、下降1例。C3/4级毒性主要与化疗药物有关,白细胞下降1例,血小板下降1例,恶心、呕吐1例。结论恩度联合卡培他滨治疗晚期乳腺癌具有协同作用,疗效好,毒性低,安全性好,可改善患者的生活质量,值得进一步研究观察。     

婴幼儿泄泻辨证推拿研究

目的:研究中医推拿手法治疗婴幼儿泄泻的疗效可靠性。方法:将353例婴幼儿腹泻患儿分为推拿组(205例)和对照组(148例)。推拿组经过辨证分型后,采用相应的推拿治疗手法,对照组采用常规西医方法治疗。2组均3～5 d为1个疗程,1～2个疗程后统计疗效。结果:推拿组治愈159例(占77.56%),好转35例(占17.08%),无效11例(占5.36%),总有效率为94.64%;对照组治愈70例(占47.30%),好转43例(占29.05%),无效35例(占23.65%),总有效率为76.35%。2组总有效率比较,差异有统计意义(P0.05)。结论:辨证分型后的推拿治疗方法具有高效、安全、无毒副作用,既解决了患儿服药难问题,又避免了抗生素带来的不良反应,应该大力普及推拿疗法治疗小儿腹泻适宜技术,让更多患儿享受绿色医学。     

椎体术后吉非替尼治疗肺癌合并脊髓压迫综合征1例

椎体是非小细胞肺癌(NSCLC)骨转移的常见部位,脊神经和马尾受压后会导致脊髓压迫综合征(SCCS)。SCCS是一种肿瘤急症,需要立即治疗减轻疼痛和保护神经功能。肺癌合并SCCS的患者生存期较短。本文报道1例非小细胞肺癌合并脊髓压迫导致截瘫的患者,椎体减压固定后不能耐受放化疗,口服吉非替尼(250 m.gd-1)治疗,无疾病进展期是27月,生存期达到28月。所以,对于合并SCCS的NSCLC患者,联合表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKI)的综合治疗是一个较好的选择。     

思密达与美常安对腹泻型肠易激综合征的治疗效果

目的：观察思密达与美常安联合应用对腹泻型肠易激综合征（IBS）的治疗效果。方法：60例腹泻型1BS患者随机分为三组：联合用药组21例同时服思密达3g，tid及美常安胶囊500mg，tid，另两组分别服思密达（18例）或美常安（21例），剂量同前。记录治疗前后患者的症状、大便次数、大便性状。结果：联合用药组在服药d7时症状总评分已比治疗前下降78．1％，每日大便次数、大便性状评分已接近正常，与思密达组或美常安组比较，差异有统计学意义（P〈0．05），未观察到联合用药有明显的不良反应。结论：联合应用作用机制不同的思密达与美常安能迅速、安全地缓解腹泻型IBS的病情。     

微生态制剂的进展与临床应用评价

目的:源于上世纪初的微生物理论而于近年发展的微生态制剂在临床上广泛应用,借以调整微生态失调,保持生态平衡,促进内环境的稳定,控制某些感染性、菌群生态失调、菌群定位转移所相关的多种胃肠道疾病。本文剖析此类药物的分类、作用、评价和应用原则,为临床提供较为丰厚的信息。方法:综述国内外医药学文献。结果及结论:鉴于微生态制剂上市历程尚短,对其药动学、体内过程、临床疗效等参数,迄今为止的报道甚少,尚有待于循证医学的多中心、大样本的研究结果所证实。     

阿立哌唑口崩片治疗Tourette综合征临床研究

目的：探讨阿立哌唑口崩片治疗Tourette综合征（Tourette syndrome,TS）的疗效和安全性。方法：对47例TS患者进行为期8周的阿立哌唑口崩片单一治疗,采用耶鲁抽动症状严重程度量表（YGTSS）、副反应量表（TESS）于治疗前和治疗后第2、4、8周末对患者进行评估,并作实验室监测。结果：70.2%的病人疗效显著,87.2%症状改善。有效日剂量为5～30 mg,患者治疗后第2、4、8周末YGTSS得分与治疗前相比均有明显下降,差异有极显著性（P〈0.01）,副反应少且轻微。结论：阿立哌唑能有效改善Tourette综合征的运动及发声抽动症状,且副反应轻微。     

食物不耐受在腹泻型肠易激综合征中的作用

肠易激综合征(irritable bowel syndrome,IBS)是一种以腹痛或腹部不适伴排便习惯改变为特征的慢性功能性肠道疾病,人群总患病率5%~25%,且呈逐年增加趋势[1]。在IBS的病因学研究中,食物不耐受已成为热点。本研究通过测定腹泻型肠易激综合征(IBS with diarrhea,IBS-D)患者血清中14种常见食物特异性IgG抗体(specific IgG,SIgG),探     

Current and future pharmacological treatments for diarrhea-predominant irritable bowel syndrome

Introduction: Diarrhea-predominant irritable bowel syndrome (IBS-D) affects about one-third of patients with IBS, which is observed in about 12% of people across five continents. The ultimate goal in this field is to identify the underlying cause of symptoms in order to individualize education of the patient, and to provide optimal treatment of this highly prevalent condition.

Areas covered: This review addresses the pharmacological treatments for IBS-D under three categories: drugs for IBS-D (i.e., the 5-HT₃ antagonist, alosetron); drugs approved for other indications that are used in IBS-D (e.g., opioid agonists; other 5-HT₃ antagonists; serotonergic psychoactive agents; bile acid binders; 5-ASA compounds; probiotics and non-absorbable antibiotics); as well as development of drugs that are likely to impact the management of IBS-D in the future (e.g., drug absorbents; TPH₁ inhibitors; mast cell stabilizers; centrally acting benzodiazepines). The final section addresses key findings: regulatory roadblocks; weaknesses in the current research in this field so far and opportunities to address unmet needs including restoration of normal intestinal barrier function or permeability, and suppression within the intestines of local immune activation that is thought to trigger abnormal motor, sensory and secretory functions in IBS-D.

Expert opinion: While symptomatic treatment of diarrhea is effective, there is a need for new treatments for the IBS-D complex. Greater understanding of the mechanisms in IBS-D has led to promising approaches to develop more efficacious therapies.     

连续性血液净化在多器官功能障碍综合征中的应用及护理

目的探讨连续性血液净化（CBP）治疗多器官功能障碍综合征（MODS）的效果,总结护理措施。方法选取2011年10月至2012年10月期间我院MODS患者58例,在原发病治疗的基础上同时给予CBP治疗,同时采取合理有效的护理措施。结果58例MODS患者中,经CBP治疗,治愈34例,好转10例,死亡14例,其中4例因经济问题出院而死亡,10例合并其他并发症死亡。CBP治疗后与治疗前在肌酐、尿素氮、心率、PaO2及PaO／FiO2方面比较,差异有统计学意义U）〈0．05）,在平均动脉压、PH、PaCO2和HCO3方面差异无统计学意义（P〉0．05）。结论CBP能有效缓解MODS患者的症状,合理有效的护理措施有助于提高MODS患者的生存率。     

洁白胶囊联合阿米替林治疗腹肠易激综合征的临床研究

目的 观察洁白胶囊（抗胃肠功能紊乱药）联合阿米替林治疗腹泻型肠易激综合征（D-IBS）的疗效。方法 143例D-IBS患者随机分成3组，常规治疗组（48例）：每次VI服洁白胶囊0．8g，每天3次；联合治疗组（49例）：常规治疗外，睡前加用阿米替林，第1周，每天12．5mg；第2～4周，每天25mg；对照组（46例）：服用淀粉片每次1片，每天3次，饭后服用。4周为一疗程。结果 治疗1，2，4周后，常规治疗组有效率分别为60．4％，73．9％，77．8％；联合治疗组分别为65．3％，82．6％，93．2％，均明显高于安慰剂组（P〈0．01）；而联合组明显高于常规组（P〈0．05）。结论 洁白胶囊对D-IBS有较好疗效，阿米替林能明显增加洁白胶囊的治疗效果，且病人耐受性较好。     

老年急性冠脉综合征与脂蛋白(a)及血浆纤维蛋白原的关系

目的:探讨脂蛋白(a)[Lp(a)]、血浆纤维蛋白原(FG)与急性冠脉综合征(ACS)的关系。方法:选择临床确诊老年ACS患者70例作为ACS组,选择除外老年ACS者70例作为对照组。结果:与对照组比较ACS患者LP(a)、FG均增高(P≤0.05),差异有显著性。结论:LP(a)、FG在ACS的发生和发展中起重要作用。