糖尿病足的综合治疗（四）

4．9．2下肢血供重建的原则 （1）大血管（腹主、髂动脉）病变：①腔内或搭桥或杂交手术;②不适合做干细胞移植或其他措施。（2）中等血管（股、胭动脉）病变：①首选腔内或搭桥或杂交;②有条件者可次选自体干细胞移植或其他措施。（3）小血管病变（膝下小动脉：胫前动脉、胫后动脉和腓动脉以及足部动脉）：①远端动脉流出道好,患者身体允许,可选择动脉旁路移植;②远端动脉流出道好,且患者身体差,可以选择小球囊成形;③远端动脉流出道差,可以选择小球囊或者自体干细胞移植。     

干细胞移植--治疗糖尿病缺血性下肢血管病变的新手段

缺血性下肢血管病变是引起糖尿病足溃疡、坏疽、截肢的重要因素.自体骨髓或外周血干细胞移植能促进缺血下肢的新血管生成,适用于内科疗效不佳、下肢远端动脉流出道差而无法进行下肢搭桥的患者及年老体弱或伴发其他疾病不能接受手术的患者,这种方法临床操作简单,无明显副作用,作为治疗下肢缺血性病变的新方法,具有广阔的应用前景.     

干细胞移植——治疗糖尿病缺血性下肢血管病变的新手段

缺血性下肢血管病变是引起糖尿病足溃疡、坏疽、截肢的重要因素.自体骨髓或外周血干细胞移植能促进缺血下肢的新血管生成,适用于内科疗效不佳、下肢远端动脉流出道差而无法进行下肢搭桥的患者及年老体弱或伴发其他疾病不能接受手术的患者,这种方法临床操作简单,无明显副作用,作为治疗下肢缺血性病变的新方法,具有广阔的应用前景.     

糖尿病性下肢缺血的外科治疗

目的 探讨糖尿病下肢缺血的外科治疗方法。方法 78例2型糖尿病(T2DM)患者合并下肢动脉缺血的95条肢体进行了外科手术治疗，其中动脉旁路移植术76条下肢，占80％。主要方式为股动脉-腘动脉人工血管旁路移植-单支小腿动脉自体血管旁路移植术(23．2％)和腘动脉-小腿动脉旁路移植术(21．0％)；15例患者16条下肢截肢处理，占16．8％；自体骨髓干细胞移植3例3条患肢，占3．1％。结果 75例91条下肢的移植血管在出院时均保持通畅，通畅率为100％；3例(4条下肢)于术后死亡，围手术期病死率为3．8％，手术成功率为96．2％。术后踝肱指数(ABI)为0．86～1．12，平均0．94。自体骨髓干细胞移植的3例患者，均达到避免截肢或降低截肢平面的目的。出院时足部创面愈合率39．2％。结论 糖尿病性下肢缺血可以通过外科治疗，如下肢远端动脉旁路移植、腔内血管成型术、自体骨髓干细胞移植及适当平面的截肢等方法而获得较好的疗效，外科治疗不仅可以挽救肢体或降低截肢平面，而且可为足部创面的愈合提供较好的营养环境，有利于创面的愈合和提高生活质量。     

糖尿病下肢动脉病变的外科治疗

糖尿病下肢动脉病变主要指在糖尿病的基础上发生的下肢动脉硬化闭塞或狭窄，可造成下肢远端组织的缺血。临床上主要表现为间歇性跛行、静息痛和足部溃疡或坏疽。治疗主要包括内科的扩血管、抗凝等药物治疗和外科的下肢血流重建治疗或截肢处理。其中下肢血流重建的效果最为理想，目前最常用的方法有下肢动脉的腔内介入术、动脉旁路移植术等。最近几年在国内首先开展了自体骨髓干细胞移植和由中国医学科学院血液病研究所首先开展的外周血干细胞移植术，这种方法称为“细胞架桥”，取得了一定效果。     

自体造血干细胞移植治疗糖尿病下肢血管病变临床观察

目的探讨自体造血干细胞移植（AHSCT）对糖尿病（DM）下肢血管病变的疗效及安全性。方法应用AHSCT治疗远端流出道狭窄的DM下肢血管病变患者21例（36条），术前皮下注射重组人粒细胞集落刺激因子，使术日外周血WBC计数达30．0×10^9／L后，自患者髂后上棘抽取骨髓血约200ml，分离提纯自体骨髓干细胞悬液40～50ml，在硬膜外麻醉或静脉全麻下于患肢小腿沿血管走行方向自上而下局部肌注。结果治疗3个月后，患肢麻木缓解率91．7％，冷凉缓解率86．1％，疼痛缓解率80．6％，间歇性跛行缓解率64．7％，行走间距延长率35．2％，溃疡愈合率75．0％，坏疽好转率50．0％；踝肱动脉指数改善率77．8％。治疗过程中未发现其他并发症及不良反应。结论AHSCT治疗远端流出道狭窄的DM下肢血管病变安全、有效。     

自体骨髓干细胞移植治疗糖尿病足13例报告

目的 观察自体骨髓干细胞移植治疗糖尿病足(DF)的疗效。方法 2003年3～12月，应用自体骨髓干细胞移植治疗13例DF患者。男7例，女6例；平均年龄70岁；患肢共15条，左7条和右8条。手术首先抽取自体骨髓350ml，从中分离出单个核细胞悬浊液约40ml，行下肢缺血肌肉内局部注射。结果 小腿疼痛缓解率为100％，足部疼痛改善率为84．6％。保肢率为80％。冷、凉感觉改善率为100％。1例间歇性跛行患者的行走距离由术前的50m延长到120m。7例患者的8条下肢的动脉造影，显示均有新生侧枝血管形成。踝部经皮氧分压测定，10例患者的12条下肢均高于目前临床上截肢的最低临界值20mm Hg。结论 对由于下肢远端动脉流出道差或年老体弱或伴发其他疾病等不能接受搭桥术的患者，自体骨髓干细胞移植治疗DF是一种有效的方法。     

动脉内膜剥脱自体干细胞移植治疗下肢动脉闭塞症的临床疗效观察

目的探讨患肢动脉内膜剥脱和(或)人工血管旁路术、自体骨髓干细胞动脉腔内及肌内移植对治疗下肢动脉硬化闭塞症的临床价值。方法总结185例下肢动脉闭塞症的临床资料,回顾分析其病因、临床特点、诊断方法、治疗手段及治疗效果。结果 185例经闭塞段动脉内膜剥脱、自体干细胞腔内和肌内移植,术后随访3、6、12、18、24个月,肢体血液循环改善明显,临床症状缓解。结论下肢动脉硬化闭塞症采取闭塞段内膜剥脱和(或)人工血管旁路术,辅以自体骨髓干细胞动脉腔内和肌内移植可获较好疗效。     

糖尿病下肢动脉病变的外科治疗

糖尿病下肢动脉病变主要指在糖尿病的基础上发生的下肢动脉硬化闭塞或狭窄,可造成下肢远端组织的缺血。临床上主要表现为间歇性跛行、静息痛和足部溃疡或坏疽。治疗主要包括内科的扩血管、抗凝等药物治疗和外科的下肢血流重建治疗或截肢处理。其中下肢血流重建的效果最为理想,目前最常用的方法有下肢动脉的腔内介入术、动脉旁路移植术等。最近几年在国内首先开展了自体骨髓干细胞移植和由中国医学科学院血液病研究所首先开展的外周血干细胞移植术,这种方法称为“细胞架桥”,取得了一定效果。     

下肢远端动脉旁路移植治疗糖尿病下肢缺血

目的探讨治疗糖尿病下肢缺血动脉旁路移植的方法和疗效。方法从2000年7月至2004年7月，应用下肢远端动脉旁路移植手术治疗了82例2型糖尿病病人的96条下肢。主要方式为股动脉-胭动脉人工血管＋小腿动脉自体血管旁路移植术31条（32．3％），胭动脉-小腿动脉旁路移植22条（22．9％），髂动脉支架＋股动脉-胭动脉人工血管＋小腿动脉自体血管旁路移植术12条（12．5％），股动脉-小腿动脉旁路移植10条（10．4％）。结果82例中，3例全麻手术病人（4条下肢）于术后死亡，病死率为3．7％；手术成功率为96．3％，总有效率为93．7％；救肢成功率为98．9％；足部创面愈合率37．3％。76例患者（96．2％）被随访，平均随访时间为13．5个月，移植血管通畅率为92．2％；死亡率为3．9％；总有效率为87．6％；截肢率为4．5％，保肢率为95．5％。93．8％（30／32）下肢创面分别于出院2～10个月（平均6个月）后愈合。结论糖尿病下肢缺血行远端动脉旁路移植手术，可以使大多数患者得到有效治疗，从而挽救肢体或降低截肢平面。     

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.     

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.     

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.     

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.