他克莫司切换为环孢素A对移植后糖尿病的疗效

目的观察他克莫司切换为环孢素A对移植后糖尿病的疗效。方法选取该院2015年6月—2016年3月收治的50例肾移植后新发糖尿病患者作为研究对象,按随机排列表法分成对照组和观察组,各25例,对照组行标准他克莫司治疗方案,观察组行他克莫司切换为环孢素A治疗方案,对比两组血糖改善情况和不良反应发生情况。结果观察组移植后3、6、9、12个月的空腹血糖值和糖化血红蛋白水平均低于对照组,差异有统计学意义(P0.05);两种方案的不良反应发生率分别为40.0%、48.0%,差异无统计学意义(P0.05)。结论对肾移植后糖尿病患者行他克莫司切换为环孢素A治疗方案比标准他克莫司治疗方案更能有效改善患者血糖水平,且两者安全性不相上下。     

他克莫司和霉酚酸酯分别联合激素治疗特发性膜性肾病Ⅲ期疗效比较

目的 观察不同疗程中他克莫司、霉酚酸酯分别联合激素治疗有肾病综合征表现的特发性膜性肾病Ⅲ期患者的疗效和安全性.方法 选择2010年9月～2012年7月我院肾内科收治的表现为肾病综合征的特发性膜性肾病Ⅲ期患者60例,并将60例患者分为他克莫司、霉酚酸酯分别联合激素治疗两组,每组30例,观察两组的临床疗效、他克莫司的浓度变化及两组的复发等情况.结果 他克莫司联合激素治疗组治疗6个月后完全缓解15例,部分缓解12例,无效3例;出现呼吸道感染2例,出现血糖和血压升高各3例.治疗期间他克莫司的平均血药浓度维持在4.5～7.8 μg/L;治疗结束后,复发6例.霉酚酸酯联合激素治疗组完全缓解11例,部分缓解14例,无效5例;患者出现胃肠道反应3例,血白细胞减少3例,无肝功能异常及血压升高;治疗结束后,复发10例.结论 他克莫司、霉酚酸酯分别联合激素治疗均可缓解病情,他克莫司组与霉酚酸酯组比较复发率低,病情缓解率高.     

老年患者肾移植术后他克莫司应用体会

老年患者肾移植以往采用环孢素治疗，但其影响老年血脂代谢，而新型免疫抑制药他克莫司对血脂代谢影响甚微。我院2000年9月应用他克莫司，本文对比观察老年和成年患者他克莫司用药情况。     

他克莫司治疗特发性膜性肾病的临床疗效观察

目的 观察他克莫司(Tacrolimus)治疗有肾病综合征表现的特发性膜性肾病的临床疗效和安全性,并与来氟米特(LEF)进行比较.方法 将表现为肾病综合征的特发性膜性肾病患者20例随机分为他克莫司治疗组(n=10)和LEF治疗组(n=10),分别给予他克莫司及LEF联合强的松治疗6个月,观察各组的疗效、不良反应以及他克莫司的浓度变化.结果 他克莫司治疗组治疗6个月后5例完全缓解,24h尿蛋白量和血清白蛋白的水平完全恢复到正常范围,占50%;4例部分缓解,24 h尿蛋白量在0.4-3.0 g之间,血清白蛋白＞30 g/L,占40%;1例无效,24 h尿蛋白定量＞3.0 g,占10%;治疗期间他克莫司的平均药物浓度保持在5～7 ng/ml的水平.LEF治疗组在疗程结束时,有2例病人获得完全缓解,占20%;3例获得部分缓解,占30%;5例无效,占50%.结论 与LEF相比,他克莫司治疗特发性膜性肾病,可明显缓解病情,不良反应少.     

造血干细胞移植术后环孢素A致牙龈增生2例并分析

目的:在成人器官移植中,环孢素(CsA)诱导的牙龈增生(CsA-GO)发生率高达70%以上,目前报道主要集中为肾移植病例,在骨髓造血干细胞移植术后CsA-GO尚属罕见,尚未见报道。本文就2例造血干细胞移植术后CsA-GO的治疗进行了探索,期望为CsA-GO的治疗提供新的思路。方法:2例患者在我院行造血干细胞移植后,使用CsA抗GVHD过程中发生CsA-GO,予以停用CsA、他克莫司替代治疗。结果:2例患者他克莫司替代治疗7d后牙龈增生均迅速消失。结论:他克莫司替代CsA抗GVHD治疗,是目前治疗外周血造血干细胞移植术后CsA-GO的简单、有效的方案。     

肾移植患者神经钙蛋白阻滞药的肾毒性研究分析

目的探讨神经钙蛋白阻滞药的减量或停用对肾移植后慢性移植物肾病患者肾功能的影响。方法将105例肾移植后慢性移植物肾病患者根据是否将环孢素A或他克莫司减量或停用分为实验组和对照组。将药物调整3 a后患者的肾功能情况进行比较。结果与对照组比较,实验组肾功能稳定及好转人数增加,内生肌酐清除率减损量降低,24 h尿蛋白定量降低（P均〈0.05）。结论肾移植后慢性移植物肾病患者减量或停用环孢素A或他克莫司可以延缓患者的肾功能恶化。     

他克莫司在心脏移植患者体内的临床药动学

目的 :了解他克莫司在心脏移植患者体内的药代动力学特征 ,为患者实施用药的个体化。方法 :采集 4例心脏移植患者稳态时一个用药间隔 （τ）内 9个不同时间点血样 ,以微粒子酶标免疫分析法 （MEIA）测定全血中他克莫司的浓度 ,计算他克莫司在个体患者体内的药动学参数 ,并以此参数为依据实施用药的个体化。以他克莫司谷浓度结合患者临床疗效及不良反应的情况 ,总结他克莫司在心脏移植术后的治疗窗。结果 :患者口服他克莫司 （4～ 5mg/ 8h）后 ,其体内处置为一室开放模型 ,平均药动学参数 Tm ax,Cmax,T1 /2 ke和 AUC依次分别为 1.2± 0 .4h,2 9± 7m g· L- 1 ,7.6± 1.2 h和 2 75± 10 8mg· h- 1 · L- 1 。术后 1年来他克莫司谷浓度控制在 2 5～ 5 m g· L- 1 ,患者未出现严重的排斥或中毒反应。结论 :他克莫司药动学的个体差异较大 ,应加强全血谷浓度监测 ,确保用药的安全有效。他克莫司在心脏移植的治疗窗 （谷浓度 ）为 :0～ 1个月 15～ 2 0 mg· L- 1 ,1～ 3个月 10～ 15 mg· L- 1 ,3～ 6个月8～ 12 m g· L- 1 ,6个月后 5～ 8mg· L- 1 ,此浓度范围即可有满意的免疫抑制效果 ,又可减少他克莫司不良反应。     

他克莫司联合小剂量激素治疗特发性膜性肾病的疗效观察

目的 观察不同疗程中他克莫司治疗有肾病综合征表现的特发性膜性肾病的疗效和安全性.方法 将2004年3月至2007年8月吉林大学第二医院收治的表现为肾病综合征的特发性膜性肾病患者20例随机分为短疗程组10例和长疗程组10例,短疗程组给予他克莫司联合口服泼尼松治疗6个月,长疗程组治疗24个月,观察各组的疗效、他克莫司的浓度变化及复发等情况.结果 短疗程组治疗6个月后5例完全缓解,4倒部分缓解,1例无效;治疗期间他克莫司的平均血药浓度保持在5～7μg/L;治疗结束后,6例复发.长疗程组治疗24个月后6例患者获得完全缓解,3例获得部分缓解,1例无效;长疗程组他克莫司的浓度在6个月内波动于5～8μg/L,12个月时保持在3.38～4.36μg/L;疗程结束时,无复发.结论 短疗程和长疗程他克莫司治疗特发性膜性肾病,均可明显缓解病情;长疗程组可以用较低浓度的他克莫司使病情得到持续缓解,且复发率低.     

他克莫司替换环孢素A治疗肾移植后肝、肾功能损害的临床观察

19例用环孢素A(CsA)并相继出现肝和(或)肾功能损害的肾移植患者，用他克莫司(FK506)替换CsA治疗，取得了明显疗效，平均随访观察6个月，疗效稳定。     

肾移植术后应用他克莫司诱发急性胰腺炎1例

药物性胰腺炎是AP的一种罕见病因, 占所有AP病例的2%～5%。他克莫司是器官移植术后患者应用的一种免疫抑制剂, 目前, 肾移植术后应用他克莫司导致AP的报道很少。本文报道1例肾移植术后他克莫司导致AP的病例, 以供临床参考。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.