初诊2型糖尿病胰岛素治疗与胰岛β细胞修复效果观察

目的：观察初诊2型糖尿病（T 2DM）患者胰岛素治疗后胰岛β细胞功能的修复情况。方法将初诊80例T 2DM均分为胰岛素治疗组（试验组）和口服药物治疗组（对照组）（n=40）,试验组应用胰岛素治疗,早晚餐前30 min皮下注射甘舒霖30 R,起始剂量为0.5 U/（kg·d）,根据血糖变化调整胰岛素剂量,2～3周血糖达标,空腹血糖≤6.1 mmol/L,服75 g葡萄糖后2 h血糖≤8.0 mmol/L,适当剂量胰岛素维持治疗3个月;对照组：采用口服糖适平治疗,每天1～6片,每片30 mg,通过调整药物的种类及剂量改善血糖水平。检测治疗前及治疗3个月后空腹血糖（FPG）、空腹C肽（FC-P）、服75 g葡萄糖后2 h血糖（2 hPG）及C肽（2 hC-P）、糖化血红蛋白（HbA 1c）、体质量指数（BMI）等指标。结果试验组患者治疗2～3周血糖即迅速达标。治疗3个月后,试验组患者胰岛β细胞功能有明显恢复;与对照组比较差异有统计学意义。2组治疗后血糖与治疗前比较,差异有统计学意义（P〈0.01）;HbA 1c与治疗前比较,差异有统计学意义（P〈0.01）。结论应用胰岛素治疗初诊T 2DM,既可使患者血糖尽快达标,又能显著改善患者的胰岛β细胞功能。     

Cyclosporin A as prophylaxis against graft-versus-host disease in 36 patients

Oral cyclosporin A was used as prophylaxis against graft-versus-host disease in (a) 31 patients with acute leukaemia or aplastic anaemia given transplants of HLA-matched bone marrow and (b) five patients with inborn errors of metabolism given transplants of haplotype-identical (parental) bone marrow. Twenty-six patients survived longer than two months after the operation. Despite the cyclosporin A, 31 patients (86%) suffered an acute form of graft-versus-host disease and 22 (61%) a chronic form. Nevertheless, the disease was usually treatable with immunosuppressive agents and caused the death of only one patient. Cyclosporin A caused renal toxicity in all cases; occasionally this was associated with a "capillary leak" syndrome, fatal in two patients. In children hypertension, fits, and fluid retention were common side effects. Blood concentrations of cyclosporin A correlated with blood urea values and blood pressure but did not predict the occurrence of graft-versus-host disease. Four different dose schedules were used to find the optimum way to administer this drug. Oral cyclosporin A is extremely effective at reducing the severity of graft-versus-host disease, but prevention of the disease is limited by toxicity of the drug and variable absorption. Better results might be achieved with parenteral administration or by using the drug in combination with other methods.     

FK506的药代动力学及临床研究

目的 探讨FK506血药浓度与急性排斥反应及毒副反应的关系。方法 10例肾移植术后患者,予FK506为基础的免疫抑制治疗,首次服药后进行药代动力学测定,并记录术后FK506的用药量、急性排斥反应、药物毒副反应的发生情况。结果 峰值时间t（peak）为（1.4797±1.2174）h,分布相半衰期（t1/2β beta）为（10.8065±12.0799）h,平均滞留时间（MRT）为（8.0535±4.4750）h。2例病人在术后1月内发生急性排斥反应; 2例病人在术后1月内发生糖尿病。术后1月内急性排斥反应组与非排斥反应组的FK506浓度无明显差异,术后1月内糖尿病组的FK506浓度显著高于非糖尿病组。结论 我国肾移植成人患者口服FK506药代动力学个体差异大,用药应个体化;FK506具有很强的免疫抑制效应,能很好地预防急性排斥反应;在一定的浓度范围内,FK506的血药浓度与急性排斥反应的发生没有相关性,但随着药物浓度的增加,FK506的毒副反应明显增加;小剂量低谷值浓度用药能取得良好疗效。     

Metabolic control of type I (insulin dependent) diabetes after pancreas transplantation

A study was conducted of the circadian hormonal and metabolic patterns of 10 type I (insulin dependent) uraemic diabetic patients after pancreas and renal transplantation. A single 24 hour profile was obtained in each patient following as closely as possible his or her normal daily routine two to 15 months after transplantation. None of the patients were using insulin at the time of the study. Compared with a group of six normal subjects the transplant recipients had mildly raised blood glucose concentrations, hyperinsulinaemia between meals and at night, delayed postprandial insulin peaks, mild hyperketonaemia, and normal blood lactate and plasma glucagon concentrations. The findings showed that successful pancreas transplantation results in disappearance of the need for insulin and return to normal or near normal of the metabolic abnormalities of diabetes. The minor differences observed in comparison with normal hormonal and metabolic homoeostasis were probably due to intrinsic (reduced islet mass, denervation, peripheral hormone delivery) and environmental (immunosuppression, relatively impaired renal function) factors.     

谷赖胰岛素与门冬胰岛素治疗胰岛β细胞功能衰竭2型糖尿病的疗效与安全性比较

目的探讨谷赖胰岛素与门冬胰岛素联合甘精胰岛素在治疗胰岛β细胞功能衰竭2 型糖尿病的疗效与安全性差异。方法选取2015 年12 月-2016 年6 月于吉林大学第二医院内分泌科住院及门诊治疗的胰岛β细胞功能衰竭的2 型糖尿病患者68 例。所有入选患者进行糖尿病宣传教育、饮食及运动控制,监测每日空腹、餐前、三餐后2 h及睡前血糖。入选患者随机分为两组,实验组给予谷赖胰岛素联合甘精胰岛素皮下注射降糖治疗,对照组给予门冬胰岛素联合甘精胰岛素皮下注射降糖治疗,比较两组在治疗前后空腹、餐前、三餐后2 h 睡前血糖变化、日需胰岛素剂量、糖化血红蛋白（HbA1c）变化及低血糖发生次数。结果①经过3 个月的治疗随访观察,两组在空腹、餐前、三餐后2 h、睡前血糖及糖化血红蛋白上均较治疗前有下降（P <0.05）;②两组在控制血糖达标所需日胰岛素剂量比较差异无统计学（P >0.05）;③对照组在餐前及夜间血糖控制上优于实验组（P <0.05）;④实验组在控制餐后2 h血糖上优于对照组（P <0.05）;⑤两组在糖化血红蛋白控制上差异无统计学（P >0.05）;⑥实验组的低血糖次数少于对照组,差异有统计学意义（P <0.05）。结论谷赖胰岛素联合甘精胰岛素较门冬胰岛素联合甘精胰岛素能更好控制胰岛β细胞功能衰竭2 型糖尿病的血糖,耐受好、低血糖发生次数少及降低血糖波动,减少或延缓糖尿病的各种急慢性并发症发生。     

Blood cyclosporin concentrations and renal allograft dysfunction

Forty nine renal allograft recipients taking oral cyclosporin suffered 76 episodes of renal dysfunction within six months of transplantation. These episodes were diagnosed as graft rejection or cyclosporin induced nephrotoxicity on the basis of histological findings in allograft biopsy specimens and the response to treatment. Mean predose blood cyclosporin concentrations measured by radioimmunoassay during the week before the onset of renal dysfunction were significantly higher when the cause was cyclosporin toxicity rather than graft rejection (392 v 741 nmol/l (471 v 891 ng/ml). During this period there was a significant association between both the frequency of measurements above 666 nmol/l (800 ng/ml) and the diagnosis of toxicity and the frequency of measurements below 333 nmol/l (400 ng/ml) and the diagnosis of allograft rejection. Cyclosporin measurements made at the time of biopsy and reference to the highest or lowest concentrations measured during the week preceding biopsy were of less value in distinguishing between the two groups. Despite lacking specificity for the parent compound, the radioimmunoassay used produced results which were of clinical value in optimising cyclosporin treatment.     

正极性驻极体和氮酮对环孢素A的体外透皮促渗作用

目的：研究正极性驻极体与不同浓度氮酮对环孢菌素A的经皮促渗作用,探索驻极体与化学促渗剂联合促渗的可行性及其协同促渗规律。方法：以环孢菌素A为模型药物,用电晕充电技术制备正极性驻极体,通过 Franz扩散池透皮实验和高效液相色谱技术研究正极性驻极体、不同浓度氮酮、正极性驻极体与不同浓度氮酮联用对环孢菌素A的体外促渗规律。结果：1）+500V , +1000V 和 +2000V 驻极体作用离体皮肤24h后,均对环孢菌素A具有较好的促渗效果;2）与对照组相比,1%氮酮、3%氮酮、5%氮酮分别作用于皮肤24h,对环孢菌素A的稳态透皮速率分别是对照组的6.72倍、2.11倍、1.43倍（P<0.05）;3）正极性驻极体与不同浓度的氮酮联合使用对环孢菌素A经皮促渗24h后,+1000V驻极体与1%氮酮联用组的促渗效果较好,但二者无叠加作用,即驻极体与不同浓度氮酮联用均没有表现出协同促渗作用。结论：正极性驻极体对环孢菌素A的经皮给药具有一定的促渗作用;正极性驻极体与氮酮联用对环孢菌素A未见协同促渗作用。     

自体造血干细胞移植对1型糖尿病患者血糖控制作用的对照研究

目的 对比自体造血干细胞移植和胰岛素对1型糖尿病患者血糖控制作用。方法 将40例初发1型糖尿病患者根据治疗方法分为移植组15例和胰岛素组25例,移植组采用自体造血干细胞移植治疗,胰岛素组采用常规胰岛素注射治疗,随访〉12个月,治疗12个月后采用动态血糖监测评价血糖控制情况。结果 移植组治疗后MBG、LAGE均显著低于治疗前（P〈0.05）,治疗后移植组MBG、SDBG、LAGE、MAGE均显著低于胰岛素组（P〈0.05）。移植组治疗后HbA1c较治疗前显著降低并显著低于胰岛素组（P〈0.05）,移植组2例分别在9.3、11.2个月时停用胰岛素,胰岛素平均减量（53.28±21.29）%,移植组治疗后胰岛素用量显著降低并显著低于胰岛素组（P〈0.05）,移植组治疗后血糖〈3.9 mmol/L时间百分比,血糖〉11.1 mmol/L时间百分比均较治疗前显著降低,并显著低于胰岛素组,血糖（3.9~11.1）mmol/L时间百分比较治疗前显著增加,并显著高于胰岛素组（P〈0.05）。所有患者未出现严重不良反应。结论 相比传统胰岛素注射治疗,自体造血干细胞移植能有效控制1型糖尿病患者血糖,可降低血糖波动,减少胰岛素依赖。     

Triad of markers for identifying children at high risk of developing insulin-dependent diabetes mellitus

A longitudinal investigation was conducted from 1977 to 1984 on 178 families in which one or more of the children had insulin-dependent diabetes mellitus. Of 351 nondiabetic sibs followed up for an average of 54 months, ten have, thus far, become diabetic. Eight sibs were HLA identical to their diabetic proband and nine had HLA-DR3 and/or HLA-DR4. Islet cell surface antibody and islet cell cytoplasmic antibody were found from two to 74 months before the onset of clinical diabetes in 100% and 90%, respectively, of the children. A decrease in insulin secretion was observed in all of these children on entry into the study and was detected in the absence of elevated plasma glucose concentrations. The data suggest that the triad of HLA identity, pancreatic islet cell antibodies, and depressed insulin secretion identifies those sibs who are at high risk of developing insulin-dependent diabetes mellitus.     

自体胰岛细胞移植治疗大鼠全胰十二指肠 切除术后糖尿病的研究

目的 探讨全胰十二指肠切除术后大鼠血糖变化及自体胰岛细胞移植治疗术后糖尿病的可行性和 有效性。方法 将SD 大鼠随机分成对照组、手术组和实验组（手术+ 自体胰岛移植）,每组10 只大鼠。对照组 未做任何处理;手术组和实验组均行全胰十二指肠切除术;实验组全胰切除后分离、纯化自体胰岛细胞,将胰岛 细胞通过门静脉回植入肝脏。术后各组分别监测血糖、C 肽、糖化血红蛋白,以判断单纯手术后复制模型的有 效性及实验组移植后的胰岛功能。结果 全胰切除后手术组第1 天大鼠血糖即升高为（20.58±2.00）mmol/L ; 手术组与对照组血糖比较,差异有统计学意义（P <0.05）,手术组血糖高于对照组;实验组自体胰岛细胞移植后 血糖与手术组比较,差异有统计学意义（P <0.05）,实验组血糖下降。术后持续4 个月监测血清糖化血红蛋白,第 4 个月,手术组与对照组比较,差异有统计学意义（P <0.05）,手术组升高;实验组与手术组比较,差异有统计 学意义（P <0.05）。结论 全胰十二指肠切除术是复制大鼠糖尿病模型的安全可靠途径;自体胰岛细胞移植是 治疗大鼠全胰切除术后糖尿病的有效方式。     

肾移植受者应用霉酚酸酯的合理治疗窗

目的确定肾脏移植受者应用霉酚酸酯（MMF）的合理治疗窗浓度。方法选取110例肾移植受者分别于术后1月内、2~3
个月、>4个月应用酶放大免疫分析技术测定口服MMF（分两次服用,间隔12 h）12 h后全血谷浓度（即MPA-C0）,并观察受者用
药期间急性排斥反应及药物毒副反应发生情况,对所有受者随访时间均为1年。结果统计资料显示,术后急性排斥反应发生
率为13.64%（15/110）,药物毒副反应发生率为32.73%（36/110）,其中白细胞减少症12例,MMF相关性腹泻10例,感染10例,肝
功能损害4例。发生急性排斥反应受者予甲基强的松龙冲击治疗后均成功逆转,药物毒副反应受者经治疗和（或）调整MMF剂
量后病情恢复,无死亡病例及移植肾摘除病例。通过ROC曲线计算得出,MPA-C0控制在1.40~2.80 mg/L可较好避免肾移植术
后急性排斥反应并减少受者的药物毒副反应。结论对肾移植术后服用MMF的受者进行MPA-C0监测,对MMF用量进行个体
化调整,有利于预防急性排斥反应和药物毒副反应发生,减少并发症,提高移植肾及受者的存活率。
     

胰岛素治疗新诊断的 2 型糖尿病患者血糖控制的远期效果

目的 探讨胰岛素对2型糖尿病患者血糖控制的远期疗效。方法 选择北京中医药大学东直门医院东院区2011年5月～2012年12月收治入院新诊断的2型糖尿病患者100例临床资料进行回顾性分析,观察空腹血糖、三餐后2h血糖、空腹胰岛素水平、空腹C肽及糖化血红蛋白（HbA1c）,对比胰岛素强化治疗前、治疗2个月后,治疗1年后空腹及餐后2h血糖、空腹胰岛素水平、空腹C肽及HbA1c。结果 本组100例新诊断2型患者采用胰岛素强化治疗后空腹及餐后2h血糖均有明显下降,胰岛水平及C肽有所改善。治疗2个月及1年后空腹及餐后2h血糖、空腹胰岛素水平、空腹C肽及HbA1c与治疗前比较差异均有统计学意义（P〈0．05）;所有患者均随访1年以上．患者仅需口服少量降糖药物治疗即能维持良好血糖控制。结论 强化胰岛素治疗可以显著恢复代表胰岛β细胞功能的血糖、胰岛素浓度、C肽,使患者的糖尿病回到2型糖尿病自然病程的更早期阶段,其总体疗效明显,治疗初诊2型糖尿病,能取得较好的血糖控制及预后,值得临床推广。     

Cyclosporin, a new treatment for autoimmune chronic active hepatitis

A 51-year-old man whose aggressive autoimmune chronic active hepatitis had been treated with prednisone for five years, was treated with cyclosporin for 12 months. The disease had become unresponsive to high doses of prednisone and the side-effects had become disabling. Azathioprine could not be used because of drug hypersensitivity. With cyclosporin therapy the patient's symptoms disappeared for the first time since the onset of his illness, his liver enzyme levels fell almost to normal values and virtually no side-effects occurred. We suggest that cyclosporin be used on a clinical trial basis in patients with autoimmune chronic active hepatitis that is resistant to prednisone and azathioprine therapy.     

Imatinib prevents beta cell death in vitro but does not improve islet transplantation outcome

Introduction Improving islet transplantation outcome could not only bring benefits to individual patients but also widen the patient pool to which this life-changing treatment is available. Imatinib has previously been shown to protect beta cells from apoptosis in a variety of in vitro and in vivo models. The aim of this study was to investigate whether imatinib could be used to improve islet transplantation outcome.

Methods Islets were isolated from C57Bl/6 mice and pre-cultured with imatinib prior to exposure to streptozotocin and cytokines in vitro. Cell viability and glucose-induced insulin secretion were measured. For transplantation experiments, islets were pre-cultured with imatinib for either 72?h or 24?h prior to transplantation into streptozotocin-diabetic C57Bl/6 mice. In one experimental series mice were also administered imatinib after islet transplantation.

Results Imatinib partially protected islets from beta cell death in vitro. However, pre-culturing islets in imatinib or administering the drug to the mice in the days following islet transplantation did not improve blood glucose concentrations more than control-cultured islets.

Conclusion Although imatinib protected against beta cell death from cytokines and streptozotocin in vitro, it did not significantly improve syngeneic islet transplantation outcome.     

T细胞疫苗诱导异种胰岛移植免疫耐受的实验研究

目的体外制备供体特异性T细胞疫苗（T cell vaccine）,探讨T细胞疫苗免疫（T cell vaccination）诱导异种胰岛细胞移植免疫耐受的作用。方法腹腔注射链脲佐菌素诱导建立Balb／c小鼠Ⅰ型糖尿病模型,用酶消化法和密度梯度离心法无菌分离纯化Wistar大鼠胰岛细胞。制备Balb／c小鼠针对Wistar大鼠的T细胞疫苗：实验随机分为三组,G1：糖尿病小鼠对照组;G2：胰岛细胞移植组,糖尿病小鼠＋胰岛细胞移植＋1640培养液（对照组）;G3：胰岛细胞移植加T细胞疫苗免疫组,糖尿病小鼠＋胰岛细胞＋T细胞疫苗（实验组）,于d1,d7,d14,d21实验组Balb／c小鼠接种TCV（1×107／mL）,对照组用1640替代。接种前和每次接种后第5d分别进行混合淋巴细胞反应。胰岛细胞移植：将Wistar大鼠的胰岛按1200。1500IEQ／kg经肝门静脉导入小鼠体内,移植后观测血糖和体重变化。结果异种胰岛细胞移植可以诱导I型糖尿病小鼠血糖降至正常水平且维持一段时间,对照组小鼠移植后（5．12±1．36）d即发生排斥,实验组移植物存活时间达（20．25±3．45）d。结论TCV能够有效延长异种胰岛移植物的存活时间,是一种潜在诱导异种胰岛移植免疫耐受的方法。     

大鼠胰腺导管上皮细胞体外诱导的研究

目的:观察大鼠胰腺导管上皮经四步法诱导分化为胰岛样细胞团后移植治疗糖尿病的效果?方法:采用Ⅴ型胶原酶胆管内灌注消化法,经Ficoll不连续密度梯度离心后分别获得导管上皮细胞和新鲜胰岛?导管上皮细胞经原代培养及传代后取2~6代细胞开始进行四步18天的诱导,分化为胰岛样细胞团,行免疫荧光鉴定?将链脲佐菌素造模成功的18只SD大鼠采用完全随机法均分成3组,空白对照组?新鲜胰岛组?胰岛样细胞团组进行左肾包膜下移植?分别给予RMPI1640?新鲜胰岛和胰岛样细胞团,移植后隔日固定时间监测血糖?结果:经免疫荧光鉴定,分离纯化的胰腺导管细胞具有干细胞特性,诱导后的胰岛样细胞团胰岛素?胰高血糖素染色均为阳性?移植后空白对照组血糖维持在高血糖范围?新鲜胰岛组移植后血糖逐步下降至正常水平,并在2周之内基本稳定在正常范围内但略有上升?胰岛样细胞团组移植后前2天血糖不降反升,之后有所下降但始终未能降至正常范围,然后又逐渐上升?结论:胰腺导管上皮细胞经该方案诱导后分化为胰岛样细胞团,使糖尿病大鼠血糖有一定程度的下降,但下降幅度及维持时间不能令人满意,可能与移植量不够及诱导的胰岛样细胞团功能不良有关?     

心脏移植17例随访观察

目的观察心脏移植的疗效。方法1997年6月至2009年8月行同种原位心脏移植17例,其中1例为心肾联合移植。随访接受心脏移植患者术后的劳动力、生活质量以及精神和（或）身体的并发症。结果2例围手术期死亡,原因分别为急性排斥反应和急性肾功能衰竭。另有2例分别于术后7个月和术后2年半因停服免疫抑制药物而引发急性排斥反应死亡。另1例为ABO血型不合者．在术后6个月因急性排斥反应死亡。长期生存11例,其中4例已生存10年余。心肾联合移植患者也已生存近9年。除最近1例（正在康复中）,其余11例术后半年心功能均达到Ⅰ级,并保持至今,且均已恢复工作。前9例生存达1年的患者均作冠状动脉造影,每例均表现冠状动脉变细,侧支减少,有4例于术后4、5年心肌ECT扫描显示左心室前壁或后壁局部缺血,但这些生存者临床上均无冠心病症状。2例出现糖尿病。术后早期每例均有不同程度的右心功能不全、口腔溃疡及服用环孢素后血压升高。11例均因此需长期服降压药物控制血压。第一例患者术后12年出现恶性淋巴瘤,用CHOP方案化疗2个疗程后完全缓解。结论心脏移植是治疗终末期扩张型心肌病的有效方法,但术后可能发生的并发症较多,有的影响生活质量,有的甚至可危及生命。术后密切的随访,预防并及时发现和处理并发症将有助于提高疗效。     

肾移植术后近期脑梗死危险因素分析

目的探讨肾移植术后患者近期发生脑梗死的危险因素。方法13例肾移植术后近期发生脑梗死的患者,回顾性分析其移植前及移植后第1、2、3个月的平均血压、空腹血糖、总胆固醇、甘油三酯、血肌酐水平以及环孢素(CsA)或他可莫司(FK506)浓度。结果肾移植术后患者血脂和血糖均明显升高(P<0.05),肾移植术后脑梗死患者血肌酐水平较术前明显降低(P<0.05),平均血压水平与手术后3个月比较差异无统计学意义(P>0.05)。结论影响近期肾移植术后病人发生脑梗死的主要危险因素是肾功能,空腹血糖以及血脂水平;且血糖、总胆固醇、甘油三酯水平和CsA或FK506浓度有相关性。     

Kaposi's sarcoma in a patient after renal transplantation.

A patient is described who developed the lesion of Kaposi''s sarcoma 4 months after receiving a cadaveric renal transplant. Immunosuppression had been achieved using cyclosporin A and prednisolone. The lesions spread from the hands to other areas, but later regressed when the dose of cyclosporin A was reduced to 100 mg daily. The patient remains well with no evidence of rejection 15 months later.