沙立度胺联合MP化疗方案治疗初治多发性骨髓瘤27例疗效观察

目的:观察沙立度胺联合MP方案,即马法兰加泼尼松治疗多发性骨髓瘤的疗效及其不良反应。方法:确诊的多发性骨髓瘤患者27例。沙立度胺加MP方案:沙立度胺自MP方案开始持续给药,剂量从每天50~200mg开始,每周日剂量递增50mg,至患者不能耐受或最高至每天400mg,MP方案每月1个疗程。结果:初治患者27例部分缓解16例(59.3%),进步6例(22.2%),总有效率为22/27(81.5%)。结论:沙立度胺加MP方案可作为治疗多发性骨髓瘤的治疗选择。不良反应可耐受。     

地塞米松联合沙立度胺治疗多发性骨髓瘤临床观察

目的:观察大剂量地塞米松联合低剂量沙立度胺治疗多发性骨髓瘤的临床疗效.方法:10例多发性骨髓瘤患者,包括3例髓外浆细胞瘤患者.其中沙立度胺剂量50～200 mg/d口服,同时联合大剂量地塞米松40 mg静脉滴注,连续4 d,间隙5 d,治疗3个月.结果:完全缓解(CR)2例,部分缓解(PR)2例,进步2例,无效4例,其中3例为髓外浆细胞瘤患者;不良反应可耐受,轻度便秘多见.结论:大剂量地塞米松联合低剂量沙立度胺治疗多发性骨髓瘤短期内安全有效,而对髓外浆细胞瘤患者效果不佳.     

盐酸小檗碱致肾移植受者环孢素血药水平升高1例

患者女,50岁,于6 a前行同种异体肾移植术,术后采用环孢素(CsA) 泼尼松 硫唑嘌呤(Aza)三联免疫抑制方案,具体方法:术中及术后第1、2天各静滴甲基泼尼松0.5g,术后第3天改泼尼松80 mg/d口服,每天递减10 mg至20mg维持,0.5～1 a后改为15 mg/d,维持剂量为10 mg/d;术后第2天开始口服CsA,8 mg/(kg·d)、2次/d,第2个月减至5～7 mg/(kg·d),第3个月减至4～6 mg/(kg·d),其后调整至维持剂量3～5 mg/(kg·d);术前1 d及术日分别顿服Aza 200、100 mg,术后第3天改为50 mg/d口服维持.     

地西他滨联合亚砷酸诱导治疗中高危骨髓增生异常综合征及慢性粒单核细胞白血病47例临床研究

目的探讨地西他滨联合亚砷酸方案诱导治疗中高危骨髓增生异常综合征(MDS)及慢性粒单核细胞白血病(CMML)的临床疗效。方法收集2016年4月至2018年12月中国贫血东部协作组接受地西他滨联合亚砷酸治疗的中高危MDS患者39例及CMML患者8例。地西他滨20 mg/(m~2·d)联合亚砷酸0.15 mg/(m~2·d),治疗5 d,4～6周1个疗程,完全缓解(CR)或部分缓解(PR)者进入巩固周期,分析疗效及影响因素。结果中位疗程为2个疗程(1～12个疗程),31例(66.0%)获得了临床反应,中位疗效持续时间16周(2～52周)。CR 8例(17.0%),PR 10例(21.3%),血液学改善12例(25.5%),骨髓CR 1例(2.1%),疾病稳定8例(17.0%),疾病进展1例(2.1%)。二代测序基因检测中,33例发现25个基因突变70次。表观遗传学基因突变率(57.6%)高于剪接子复合物(33.5%)、转录因子和激酶系统(54.5%)和TP53组(21.2%),差异有统计学意义(P0.01),但疗效差异无统计学意义(分别为47.4%、54.5%、50.0%和85.7%,P=0.977)。治疗有效患者等位基因突变频率(VAF)显著下降(16.67%对10.26%,P=0.014)。结论地西他滨联合亚砷酸方案诱导治疗中高危MDS及CMML的疗效佳,且不良反应少。二代基因突变检测结果可能与疗效反应有关。     

硼替佐米治疗难治/复发性多发性骨髓瘤的疗效观察

目的:了解硼替佐米对难治/复发性多发性骨髓瘤的疗效及不良反应。方法:采用VATD方案(硼替佐米1.3mg/m2,d1,4,8,11;表阿霉素10mg/d,d1~4;甲泼尼龙240~500mg/d,d1~4,8~11;沙立度胺100~200mg/d,d1~11;或VD方案(硼替佐米1.3mg/m2,d1,4,8,11;甲泼尼龙240~500mg/d,d1~4,8~11)治疗11例难治/复发性多发性骨髓瘤。结果:11例患者中,完全/接近完全缓解(CR)率:9.1%(1/11),部分缓解(PR)率:36.4%(4/11);总有效率(CR加PR)为45.5%(5/11)。不良反应主要有末梢神经炎,胃肠道反应,血小板减少等,均可耐受。结论:硼替佐米对部分已对化疗耐药的难治/复发性多发性骨髓瘤仍然有效,并且效果显著;与化疗无交叉耐药,并能延长患者生存期;为多发性骨髓瘤的治疗提供了一种全新的方法。虽然有一些不良反应但都可耐受。     

亚砷酸治疗老年恶性血液病的初步观察

目的探讨亚砷酸治疗老年恶性血液病的临床疗效及不良反应。方法对40例≥60岁的恶性血液病患者,应用亚砷酸治疗(10mg/d,静脉滴注,28d为1疗程,如不良反应明显则改为14d短疗程,间隔14d后再用14d,2次为1疗程)。观察其临床疗效及不良反应。结果急性早幼粒细胞白血病(APL)完全缓解(CR)8例,其他急性非淋巴细胞白血病(ANLL)CR1例,部分缓解(PR)1例,未缓解(NR)6例;慢性粒细胞白血病(CML)PR4例,NR2例;慢性淋巴细胞白血病(CLL)CR1例,PR1例;B细胞非霍奇金淋巴瘤(NHL)CR1例,PR2例,进步1例,无效1例;骨髓增生异常综合征(MDS)PR2例,进步2例,无效1例;慢性粒单细胞白血病(CMML)CR2例,PR2例;多发性骨髓瘤(MM)PR1例,进步1例。所有病例总有效率为75%。仅2例因严重肝损害、骨髓抑制而停药,无用亚砷酸相关死亡病例。结论对不能耐受强化疗的老年难治、复发的血液肿瘤患者,亚砷酸具有一定的治疗效果,且不良反应相对较低。     

硼替佐米及沙利度胺联合VAD方案治疗难治复发性多发性骨髓瘤疗效观察

目的:观察硼替佐米、沙利度胺联合VAD方案治疗难治复发性多发性骨髓瘤(MM)的临床疗效和不良反应。方法:9例难治复发性MM患者均采用硼替佐米、沙利度胺联合VAD方案治疗。其中,长春新碱0.4mg/d,d1～4;阿霉素10mg/d,d1～4;地塞米松40mg/次,d1～4,d9～12,d17～20;硼替佐米2mg/d,d1,4,8,11;沙利度胺,起始量100mg/d,根据患者情况,逐渐加量至200mg/d,每晚顿服,治疗2个周期。观察疗效,并按WHO不良反应分级标准判断不良反应。结果:9例患者,3例完全缓解/接近完全缓解(CR/nCR),4例部分缓解(PR),1例进步,1例无效,CR加PR率达77.8%,总有效率88.9%。不良反应主要有乏力、便秘、皮疹、胃肠道反应及末梢神经炎,均可耐受。结论:硼替佐米、沙利度胺联合VAD方案治疗难治复发性MM近期疗效显著,耐受性好,是一种新的治疗选择。     

地西他滨联合减量MA方案治疗老年急性髓系白血病的临床观察

目的观察地西他滨联合减量米托蒽醌加阿糖胞苷(MA)方案治疗老年急性髓系白血病(AML)病人的疗效及安全性。方法收集16例老年AML病人,予以地西他滨联合减量MA方案[地西他滨20 mg/(m~2·d),d 1～5;米托蒽醌8～12 mg/(m~2·d),d 6～8;阿糖胞苷100 mg/(m~2·d),d 6～8],观察病人临床疗效及不良反应。结果 16例病人中完全缓解(CR) 8例(50. 0%),部分缓解(PR) 3例(18. 8%),总有效率(ORR)为68. 8%。细胞遗传学总有效率为42. 9%。不良反应主要为骨髓抑制及继发感染,病人经过输血和抗感染等支持治疗均可以耐受。结论地西他滨联合减量MA方案治疗老年AML在血液学及细胞遗传学上均可以获得较好疗效,且不良反应较轻,耐受性良好。     

前瞻性比较普乐可复与环磷酰胺诱导治疗Ⅴ型伴Ⅳ型狼疮性肾炎的疗效

目的前瞻性比较普乐可复(FK506)与环磷酰胺(CTX)联合激素诱导治疗Ⅴ型合并Ⅳ型(Ⅴ+Ⅳ型)狼疮性肾炎LN)的临床疗效.方法经肾活检诊断为Ⅴ+Ⅳ型活动性、女性LN患者37例,平均年龄(30.0±9.8)岁,尿蛋白定量≥2.0 g/d,血清白蛋白＜3.0 g/dl,随机分为两组,分别给予口服FK506[FK506组,n=19,起始剂量0.1mg/(kg·d)]或CTX静脉冲击治疗(CTX组,n=18)(0.5～1.0g/m2 BSA,1/月×6月),同时口服泼尼松[起始剂量0.6 mg/(kg·d)],其中17例接受甲基泼尼松龙静脉冲击治疗.主要评价指标为治疗6个月完全缓解率(CR,定义为尿蛋白定量＜0.4 g/24h,尿红细胞正常范围,无管型尿及白细胞尿,血清白蛋白≥3.5 g/dl,SCr正常或上升不超过正常范围15%,无肾外狼疮活动),次要观察指标为治疗6个月部分缓解率(PR)和有效率(CR+PR).结果(1)临床疗效有31例患者完成6个月诱导期治疗,其中FK506组15例,CTX组16例;6例退出治疗,CTX组2例,FK506组4例.FK506组4例患者获得CR(26.7%),10例患者PR(66.7%),而CTX组仅1例CR(6.3%)、7例PR(43.8%).FK506组治疗有效率明显高于CTX组(93.3% vs 50%,P=0.015).两组患者治疗后SLE-DAI、血清白蛋白、补体较前有显著改善,但血尿及抗dsDNA抗体的阳性率无明显改变;FK506组平均尿蛋白较治疗前显著减少,而CTX组较治疗前无明显下降;(2)FK506剂量浓度与不良反应FK506诱导治疗剂量在0.086～0.091 mg/(kg·d),平均谷浓度水平为6.6～8.1 ng/ml.4例获得CR的患者FK506浓度在6.9～10.2 ng/ml,10例PR患者血药浓度平均为(8.1±3.3)ng/ml.在此剂量下治疗6个月,未见肾小管间质损害.FK506组不良反应的发生率(肝酶升高、上消化道不适、白细胞减少、感染、脱发、月经紊乱等)低于CTX组,尤其是月经紊乱的发生率显著低于CTX组(5.6% vs 38.9%,P=0.041);虽然血压升高、糖代谢异常等并发症高于CTX组,但两组间无统计学差异.结论FK506诱导治疗Ⅴ型合并Ⅳ型病变的LN疗效明显优于CTX治疗,不良反应小.     

间歇静脉输注去铁胺治疗老年人继发性铁过载的临床研究

目的:观察间歇静脉输注去铁胺治疗老年人继发性铁过载的效果及安全性。方法:20例老年继发性铁过载患者应用去铁胺20~50mg/(kg·d),最大剂量用至2000mg/d,加入0.9%氯化钠500ml中,持续静脉滴注6h,每4~5周连续应用5~6d。结果:治疗9个月后,血清铁蛋白从治疗前(2 977.57±506.63)μg/L下降到(2 676.57±532.26)μg/L(P0.01),去铁治疗的反应率为57.1%。结论:间歇静脉输注去铁胺治疗老年人继发性铁过载能显著降低血清铁蛋白,且无明显不良反应。     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

治疗高血压药物的经济学评价

重视高血压治疗中的经济学评价,对利用我国有限的卫生资源来遏制高血压对人民群众的危害有着重要的现实意义。药物经济学对于药物治疗的成本和治疗的结果给予同样的关注。因为治疗高血压的费用,不仅涉及药物价格,还包括患者的危险水平,降压疗效和对临床终点事件的影响,以及治疗的依从性和安全性。因此药物经济学更强调整体成本和价-效比。低危病人,若非药价低廉,治疗的价-效比不够理想。而在高危的患者,价-效比越小越经济而不是药费越便宜越好。