犬自体原位全小肠移植模型建立和手术技术的改进

目的 通过手术技术的改进成功建立犬自体原位全小肠移植模型。方法 家犬8只，将全小肠及其系膜游离后进行在体和离体灌注，然后将全小肠原位植入。血管对端缝合，肠管一期吻合。结果 8只受试犬中5只术后存活超过90d（62．5％），3只分别死于淋巴瘘、肠系膜上静脉血栓形成和麻醉意外。结论 良好的麻醉、术中监护是手术成功的基础。仔细的组织分离以及高质量的血管吻合是手术成功的关键。围手术期护理和治疗对于动物存活也至关重要。     

远交系大鼠小肠移植的实验研究：Ⅰ.移植免疫反应初探

使用显微外科技术建立大鼠全小肠移植模型。原位移植和异位移植的手术成功率分别为８０．００％和８５．７１％，原位移植，异位移植及环孢素Ａ治疗组大鼠术后平均生存天数有显著性差异。异位小肠移植大鼠的组织病理研究证实，不同品系远交系大鼠间小肠移植后排斥反应的发生时间不同，组织相容性抗原差异愈大排斥反应愈迅速；     

改良术式的大鼠小肠移植模型

目的；利用远交系大鼠进行小肠移植研究，提供排斥反应的阴性对照。方法：采用肠系膜血管吻合方法建立大鼠小肠移植模型，并与经典术式进行对照。结果：共２０３只大鼠施小肠移植手术。（１）模型稳定后改良术式和经典术式的手术成功率分别为７８．４３和８３．６４％。（２）模型稳定后，改良术式组手术操作时间较模型稳定前缩短，改良术式手术耗时较经典术式明显延长。（３）手术失败的主要原因为血管吻合操作失误。结论：改良术式     

小肠息肉引起肠套叠21例临床分析

目的：探讨小肠息肉引起肠套叠患者临床表现、诊断及手术治疗效果。方法21例由小肠息肉引起肠套叠患者,对其实施小肠息肉局部切除或者小肠部分切除术,观察治疗效果。结果本组共21例患者,其中1例术后第7天出现炎性肠梗阻,保守治疗后缓解,2例切口感染,其他患者术后恢复良好,顺利出院。21例患者均随访3~5年未见复发。结论手术治疗是小肠息肉引起肠套叠的有效方法。     

肝肾联合移植1例报告

目的 探讨肝肾联合移植的手术技术、临床治疗经验及疗效.方法 对1例32岁的肝硬化并慢性肾功能不全(尿毒症期)受体施行一期同种异体肝肾联合移植.供受体血型等组织配型相匹配.肝移植采用经典的原位移植技术.肾移植采用常规手术方法,将移植肾置于右髂窝.术前予以赛尼哌行免抑诱导,术后免疫抑制剂采用他克莫司 吗替麦考酚酯 甲强龙三联.结果 受体移植后肝肾立即发挥作用,小后无严重手术并发症发生,移植肝肾功能恢复良好.结论 肝肾联合移植是治疗肝肾同时衰竭的有效方法,良好的组织配型、完善的手术技术、免疫抑制剂的合理使用、术后并发症的正确处理是成功的关键.     

肝移植大鼠胃肠动力改变及机制

目的 探讨大鼠肝移植后早期胃肠动力改变及机制.方法 40只SD大鼠随机分为肝移植组10对、全肝血流阻断组及对照组各10只.移植组采用改良的两袖套法行原位肝移植;全肝血流阻断组参照移植组受体的手术步骤,控制无肝期时间与移植组相同;对照组仅开腹.术后1h测小肠推进率、血浆内毒素含量,肠组织匀浆测Ca2 -ATPase、丙二醛(MDA).结果 与全肝血流阻断组和对照组相比,移植组术后小肠推进率低,血内毒素水平升高、肠组织内Ca2 -ATPase活性降低、MDA升高.结论 大鼠肝移植早期,胃肠动力显著降低,与肠道能量代谢障碍、缺血再灌注损伤、内毒素移位及其它因素有关.     

大鼠原位肝移植与异位阶段性小肠移植细胞凋亡的差异

目的：将具有免疫特穗性质的移植肝脏与免疫排斥最强度的移植小肠相比较,探讨肝脏移植的特点,方法：对接受肝移植和小肠移植大鼠移植物内凋亡细胞进行观察。结果：移植肝脏内以间质细胞凋亡为主,移植小肠内以实验质细胞凋亡为主,结论：小肠腺上皮调亡在小肠排斥反应中起重要作用。移植肝脏通过浸润细胞凋亡得到保护。     

Th1和Th2细胞因子在诱导肝肠联合移植免疫耐受中的作用

目的探索肝肠联合移植时移植肝对移植小肠是否具有免疫保护作用及其部分相关机制。方法选用封闭群SD大鼠和近交系Wistar大鼠配对分3组实验：同基因小肠移植组（Wistar→Wistar，Ⅰ组）；异基因小肠移植组（SD-Wistar，Ⅱ组）；肝肠联合移植组（SD→Wistar，Ⅲ组）。各组术后均未用免疫抑制剂。术后5、7、14d从3组中随机取出4只大鼠，取静脉血进行血清Th1细胞因子IL-2、IFN-γ和Th2细胞因子IL-4、IL-10含量测定，取移植小肠标本进行组织病理学检查。结果Ⅰ组术后仅表现缺血-再灌注损伤的组织学改变；Ⅱ组术后5、7、14d分别表现为轻度、中度和重度排斥；而Ⅲ组术后5、7、14d分别表现为轻度和中度排斥。Ⅰ组血清中四种细胞因子浓度随术后时间延长而递减；Ⅱ组血清中上述四种细胞因子浓度逐渐增加，术后各时间段与同基因组比较均有显著性差异；Ⅲ组术后第5天时上述四种细胞因子浓度最高，术后14d时IL-2、IFN-γ浓度显著低于Ⅱ组。结论肝肠联合移植时移植肝可通过抑制Th1细胞因子的表达而发挥对移植小肠的免疫保护作用.     

新型人工复合皮的构建及临床初步应用

目的 探讨以小肠黏膜下层(SIS)为真皮替代物构建复合皮的可行性。方法 制取家猪小肠黏膜下层为真皮替代物。致密层表面种植呈指数分裂状态的自体表皮细胞。继续体外培养2周，获得人工复合皮。移植复合皮修复26例皮肤全层缺损创面；观察复合皮早期存活质量。并分别于培养第1周、第2周和移植后第1周、第2周取复合皮标本作组织学观察。结果 表皮细胞在SIS表面定位、生长。21例移植的复合皮早期成活良好。SIS内新生血管形成。炎性细胞浸润。无移植排斥反应。结论 以SIS为真皮替代物构建的复合皮，移植修复体表创面切实可行。     

直肠癌经腹会阴联合切除股薄肌移植括约肌成形术的术中配合及术后护理体会

目的探讨直肠癌经腹会阴联合切除股薄肌移植括约肌成形术的术中、术后护理的最佳方法。方法通过对46例直肠癌患者经腹会阴联合切除股薄肌移植括约肌成形的术中、术后临床资料进行全面分析,总结出术中配合和术后护理的最佳方法。结果46例手术均顺利完成,术后护理效果良好。结论手术护士熟练掌握手术步骤、手术风险的预见性及周密细致的护理是手术成功的关键。     

Comparison of cyclosporin A and tacrolimus concentrations in whole blood between jejunal and ileal transplanted rats.

Most immunosuppresive drugs are absorbed from the intestine after oral administration, although there is some difference of bioavailability between ileum and jejunum. Using an orthotopic segmental small bowel transplantation (SBT) model in rats, we studied the pharmacokinetic profiles of cyclosporin A and tacrolimus concentrations after oral intake, comparing jejunal and ileal transplanted rats. Two types of segmental SBT (jejunal and ileal SBT) in a syngeneic combination were performed. After oral administration of cyclosporin A (10mgkg(-1) or tacrolimus (5 mg kg(-1)), pharmacokinetic data were obtained from the long-surviving rats transplanted with segmental SBT. To determine the effect of additional bile on cyclosporin absorption, an emulsion of cyclosporin A with fresh bile juice was re-challenged on segmental SBT rats before killing. A histological study was also performed by use of the intestinal grafts from the killed SBT rats. A higher concentration of cyclosporin A was observed in the ileum-grafted rats than in the rats which received the jejunal grafts. Oral bioavailability of cyclosporin A in ileal SBT rats tended to be increased by addition of fresh bile juice, but that in jejunal SBT rats did not change. On the other hand, there was no significant difference of tacrolimus concentration between jejunum- and ileum-transplanted rats. Histological studies showed that the superficial mucosal layer of both grafts, but especially the ileal graft, was markedly elongated compared with that of normal intestine. The present study showed that cyclosporin A was more actively absorbed from ileum than from jejunum in SBT, but tacrolimus was absorbed equally from both sites. These data suggest that cyclosporin A concentration is satisfactorily controlled in the segmental ileal graft, while there is no difference of tacrolimus absorption between ileal and jejunal graft.     

Clinical experience with chemotherapy using sulbactam/cefoperazone for severe infections accompanying malignant hematological disorders

Clinical and bacteriological efficacies of sulbactam/cefoperazone (SBT/CPZ) were studied in 44 patients with serious infections associated with hematological malignancy. 1. SBT/CPZ was clinically effective in 33 cases (76.7%). Excellent effects were obtained in 23 cases, good effects in 10 cases and fairly good effects in 7 cases. Clinical effectiveness of SBT/CPZ was not dependent on neutrophil number in peripheral blood. 2. Bacteriologically SBT/CPZ was effective against all of the isolated organisms from 21 cases. 3. Adverse reactions were not significant except one case with eruption, 2 cases with abnormalities in hepatic function tests and 3 cases with abnormalities in renal function tests.     

Cerebrospinal fluid levels of sulbactam/ampicillin in rabbits with staphylococcal meningitis

Concentrations of sulbactam (SBT) and ampicillin (ABPC) in the blood and cerebrospinal fluid (CSF) following an intravenous administration of SBT/ABPC at a dose of 150 mg/kg (SBT/ABPC = 1:2) were determined in 12 rabbits with staphylococcal meningitis. Drug concentrations were measured 9 times, 6 times each with intervals of 15 minutes and thereafter with intervals of 30 minutes. The results were compared with those of a group of 9 rabbits given 100 mg/kg of ABPC alone. 1. The maximum concentration of SBT in the CSF and the percentages of both the maximum concentration and the area under the concentration-time curve (AUC) of SBT in CSF vs. those in serum of the SBT/ABPC group were higher than those of ABPC and the half-life of SBT in the CSF was also longer than that of ABPC, all with significant difference. When these parameters for SBT of SBT/ABPC groups were compared with those of ABPC of the ABPC group, not much differences existed between the 2 groups except that the CSF half-life of SBT was much longer than that of ABPC. 2. The percentages of both the maximum concentration and AUC of ABPC in CSF vs. those in serum of the SBT/ABPC group were significantly lower than those of ABPC of the ABPC group. The CSF half-life of ABPC of the former group was longer than that of the latter. 3. The above results suggest that when SBT and ABPC are administered simultaneously, the penetration of ABPC into the CSF is inhibited.     

Antidotal Sodium Bicarbonate Therapy: Delayed QTc Prolongation and Cardiovascular Events

BackgroundSodium bicarbonate therapy (SBT) is currently indicated for the management of a variety of acute drug poisonings. However, SBT effects on serum potassium concentrations may lead to delayed QTc prolongation (DQTP), and subsequent risk of adverse cardiovascular events (ACVE), including death. Emergency department (ED)–based studies evaluating associations between SBT and ACVE are limited; thus, we aimed to investigate the association between antidotal SBT, ECG changes, and ACVE.MethodsThis was a secondary data analysis of a consecutive cohort of ED patients with acute drug overdose over 3 years. Demographic and clinical data as well as SBT bolus dosage and infusion duration were collected, and outcomes were compared with an unmatched consecutive cohort of patients with potential indications for SBT but who did not receive SBT. The primary outcome was the occurrence of ACVE, and secondary outcomes were delayed QTc (Bazett) prolongation (DQTP), and death. Propensity score and multivariable adjusted analyses were conducted to evaluate associations between adverse outcomes and SBT administration. Planned subgroup analysis was performed for salicylates, wide QRS (> 100 ms), and acidosis (pH < 7.2).ResultsOut of 2365 patients screened, 369 patients had potential indications for SBT, of whom 31 (8.4%) actually received SBT. In adjusted analyses, SBT was found to be a significant predictor of ACVE (aOR 9.35, CI 3.6–24.1), DQTP (aOR 126.7, CI 9.8–1646.2), and death (aOR 11.9, CI 2.4–58.9). Using a propensity score model, SBT administration was associated with ACVE (OR 5.07, CI 1.8–14.0). Associations between SBT and ACVE were maintained in subgroup analyses of specific indications for sodium channel blockade (OR 21.03, CI 7.16–61.77) and metabolic acidosis (OR: 6.42, 95% CI: 1.20, 34.19).ConclusionIn ED patients with acute drug overdose and potential indications for SBT, administration of SBT as part of routine clinical care was an independent, dose-dependent, predictor of ACVE, DQTP, and death. This study was not designed to determine whether the SBT or acute overdose itself was causative of ACVE; however, these data suggest that poisoned patients receiving antidotal SBT require close cardiovascular monitoring.     

Pharmacokinetic and clinical studies on sulbactam/ampicillin in the pediatric field

Pharmacokinetic and clinical studies of sulbactam/ampicillin (SBT/ABPC) were conducted and the obtained results are summarized as follows. For pharmacokinetic investigation, SBT/ABPC at 30 or 60 mg/kg was administered by intravenous drip infusion over 30 minutes. The maximum blood concentration was reached just after the completion of the drip infusion in both groups. The mean peak serum concentrations of SBT and ABPC were 22.4 +/- 0.8 micrograms/ml and 32.8 +/- 1.0 micrograms/ml, respectively, in the 30 mg/kg group, and they were 54.2 micrograms/ml and 93.8 micrograms/ml, respectively, in the 60 mg/kg group. The concentrations were dose-related. The mean half-lives of SBT and ABPC following 30 mg/kg SBT/ABPC administration were 0.91 +/- 0.04 hour and 0.90 +/- 0.05 hour, respectively, and those following 60 mg/kg SBT/ABPC were 1.08 hours and 0.84 hour, respectively. The highest urinary concentration occurred 0-2 hours after the 30 minutes drip infusion. Mean urinary excretion rate of SBT and ABPC over 6 hours were 71.4 +/- 2.5% and 54.6 +/- 3.3%, respectively, in the 30 mg/kg group, and they were 80.0% and 63.7%, respectively, in the 60 mg/kg group. In the clinical investigation conducted with a total of 24 patients (15 with respiratory tract infections, 3 with urinary tract infections, 2 with lymphadenitis, and others), SBT/ABPC was found to be excellent in 14 cases, good in 9, fair in 1. The efficacy rate was, therefore, 95.8%. In the bacteriological evaluation, 9 out of 11 clinically isolated strains were eradicated, 1 unchanged and 1 unknown. The elimination rate was 90.0%. Regarding side effects, no abnormal clinical symptoms were observed. As abnormal laboratory values, a slight elevation of GOT was observed.     

Bacteriological, pharmacokinetic and clinical studies on sulbactam/cefoperazone in the pediatric field

Bacteriological and clinical effect of a newly developed SBT/CPZ in the treatment for pediatric patients was assessed by a study group consisting of 15 institutions. The results were as follows. Antibacterial effect Susceptibility studies were performed with 93 clinical isolates. The MIC of SBT/CPZ was one-tube inferior or almost similar to that of CPZ in susceptible organisms. In CPZ-resistant organisms at the inoculum of 10(8) cells/ml, however, SBT/CPZ was much superior to CPZ on the basis of the MIC. When the MIC of SBT/CPZ was compared to that of CPZ in 27 strains which have high beta-lactamase-producing activity, it was found that many of CPZ-resistant organisms were susceptible to SBT/CPZ. Serum concentration and urinary excretion The serum concentrations of SBT and CPZ were 33.2 micrograms/ml, respectively at 15 minutes after 20 mg/kg SBT/CPZ was administered by intravenous bolus injection, and those of SBT and CPZ, 51.0 micrograms/ml and 108.3 micrograms/ml, respectively following 40 mg/kg SBT/CPZ therapy. The serum concentrations of CPZ were 2.1-2.4 times as high as those of SBT. The concentrations were dose-related. The half-lives of SBT and CPZ following 20 mg/kg SBT/CPZ administration were 0.94 hour and 1.50 hours, respectively, and those following 40 mg/kg SBT/CPZ were 0.95 hour and 1.53 hours, respectively. There was no significant difference between 20 mg/kg and 40 mg/kg administrations. When compared between SBT and CPZ, CPZ had slightly longer half-lives. At the termination of 1 hour drip infusion of 20 mg/kg SBT/CPZ, the serum concentrations of SBT and CPZ were 16.7 micrograms/ml and 40.1 micrograms/ml, respectively. In the case of 40 mg/kg, the levels of SBT and CPZ were 38.6 micrograms/ml and 94.9 micrograms/ml, respectively. The concentrations were found to be dose-related as were following intravenous bolus injections. The SBT half-lives obtained after 20 mg/kg and 40 mg/kg SBT/CPZ administrations were 1.39 hours and 0.89 hour, respectively; those of CPZ, 2.00 hours and 1.44 hours, respectively. The highest urinary concentration occurred 0-2 hours after intravenous bolus injections of 20 mg/kg or 40 mg/kg SBT/CPZ. Urinary excretion of SBT over 6 hours was 60.0% and 67.7%, and that of CPZ, 21.2% and 25.0%, indicating higher urinary excretion for SBT. When 20 mg/kg SBT/CPZ or 40 mg/kg was administered over 1 hour by drip infusion, urinary excretion became the highest at 1-3 hours after administration. Urinary excretion of SBT over 7 hours following 20 mg/kg and 40 mg/kg SBT/CPZ was 68.8% and 80.3%, respectively, and that of CPZ, 24.4% and 27.3%. The results were similar to those observed following intravenous bolus injections.     

Safety and healing efficacy of Sea buckthorn (Hippophae rhamnoides L.) seed oil on burn wounds in rats

The present investigation was undertaken to determine the safety and efficacy of supercritical CO₂-extracted Hippophae rhamnoides L. (Sea buckthorn) (SBT) seed oil on burn wound model. SBT seed oil was co-administered by two routes at a dose of 2.5 ml/kg body weight (p.o.) and 200 μl (topical) for 7 days on experimental burn wounds in rats. The SBT seed oil augmented the wound healing process as indicated by significant increase in wound contraction, hydroxyproline, hexosamine, DNA and total protein contents in comparison to control and reference control treated with silver sulfadiazine (SS) ointment. Histopathological findings further confirmed the healing potential of SBT seed oil. SBT seed oil treatment up-regulated the expression of matrix metalloproteinases (MMP-2 and 9), collagen type-III and VEGF in granulation tissue. It was observed that SBT seed oil also possesses antioxidant properties as evidenced by significant increase in reduced glutathione (GSH) level and reduced production of reactive oxygen species (ROS) in wound granulation tissue. In acute and sub-acute oral toxicity studies, no adverse effects were observed in any of the groups administered with SBT seed oil. These results suggest that the supercritical CO₂-extracted Sea buckthorn seed oil possesses significant wound healing activity and have no associated toxicity or side effects.     

Pharmacokinetic and bacteriological studies on sulbactam/ampicillin in the field of pediatrics

Pharmacokinetic and bacteriological studies were carried out on sulbactam/ampicillin (SBT/ABPC) in the field of pediatrics. The results obtained are summarized as follows: 1. A total of 248 clinical isolates were employed to determine minimum inhibitory concentrations (MIC) of SBT/ABPC against various bacterial species. SBT/ABPC showed stronger antibacterial activity against Gram-positive organisms than against Gram-negative rods. 2. The peak serum level of ABPC was about twice as high as that of SBT, and serum levels of ABPC and SBT declined with time. Both drugs showed almost the same trend of changes in concentrations. The half-lives of both drugs were about 1 hour. 3. The urinary recovery rates over 6 hours after administration were 52-80% for ABPC and 70-73% for SBT. 4. The effect of SBT/ABPC on coagulation system was examined. No case showed changes in PT, APTT, TT and HPT before and after administration of SBT/ABPC. Platelet aggregation during administration of SBT/ABPC was slightly faster than that before administration, suggesting that SBT/ABPC had no effect on platelet aggregation. Generally speaking, it seemed that SBT/ABPC was a safe antibiotic for bleeding. 5. The effect of SBT/ABPC on the intestinal bacterial flora in experimental animals was examined. Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve were reduced after administration of SBT/ABPC, suggesting that the intestinal bacterial flora was affected by the administration of SBT/ABPC more greatly than by the administration of ABPC alone. In a similar investigation being made with clinical cases, both aerobes and anaerobes showed great changes. Concentrations of the drugs in feces increased with increasing dosage, resulting in greater changes of the intestinal bacterial flora. Thus, the total number of aerobes and anaerobes was reduced. No diarrhea was observed in any subjects examined. From the above results, it appeared that SBT/ABPC was a safe and useful antibiotic for various bacterial infections in the field of pediatrics.     

Comparison of the effects of prophylactic antibiotic therapy and cost-effectiveness between cefazolin (CEZ) and Sulbactam/Ampicillin (SBT/ABPC) in gastric cancer surgery employing clinical pathway

The present study was designed to investigate the effects of prophylactic antibiotic therapy and the cost-effectiveness of Cefazolin (CEZ) and Sulbactam/Ampicillin (SBT/ABPC) in gastric cancer surgery employing clinical pathway. 157 patients (62 in the CEZ group and 95 in the SBT/ABPC group), who underwent surgery for gastric cancer at the First Department of Surgery of our hospital, were investigated. There was no significant difference between the groups with regard to sex, age, incidence of complication, stage of cancer, surgical method, operative time and blood loss, length of hospitalization, the appearance of systemic inflammatory response syndrome (SIRS), changes body temperature, white blood cell count (WBC), C-reactive protein (CRP), or clinical outcome of postoperative care by a nurse during post-operation for 7 days. The prophylactic effect of infection was also no different between the CEZ (69.4%) and SBT/ABPC (69.5%) groups. In contrast, decision analysis strongly indicated that the anticipate cost of antibiotics was higher in the latter group (yen 20402) than in the CEZ group (yen 15556), suggesting that the prophylactic effect of CEZ may be more cost-effective. Thus, evaluations of pharmacotherapy from the aspect of cost may be one of the important responsibility of hospital pharmacists in the future.     

Anti-inflammatory activity of Seabuckthorn (Hippophae rhamnoides) leaves

Immunomodulatory activity of Seabuckthorn (SBT) leaf extract was evaluated in adjuvant induced arthritis (AIA) rat model. Inflammation was induced by injecting Complete Freund's Adjuvant (CFA) in the right hind paw of rats. SBT extract was administered intraperitoneally to treat the inflammation. The extent of inflammation and treatment response was evaluated by clinical analysis, scintigraphic visualization using technitium-99m-glutathione (Tc99m-GSH) and lymphocyte proliferation. Serial evaluation was carried out on days 1, 7, 14, 21 and 28 after creation of inflammation. The Tc99m-GSH uptake in the inflamed leg was compared with the normal contralateral leg of the same animal. The measurements were done by obtaining scintigraphic images using gamma camera and an online computer. Both qualitative and quantitative evaluation of radiotracer accumulation was considered to evaluate the anti-inflammatory response. The lymphocyte proliferation study revealed cellular immunosuppression during the early phase of the disease. Administration of SBT extract on the same day or 5 days prior to inflammatory insult into the joint, significantly reduced the inflammation as compared to the untreated animals in a dose dependent manner. These observations suggest that the SBT leaf extract has a significant anti-inflammatory activity and has the potential for the treatment of arthritis.