抗生素对肝脏和胰腺组织穿透能力及杀菌效力的实验研究

目的 测定７种抗生素对肝脏和胰腺组织的穿透能力，为临床选择用药提供参考。方法 小鼠静脉注射或灌服抗生素后不同时间点采集血清及肝、胰组织标本，按微生物琼脂扩散法测定抗生素浓度。测定抗生素对６种常 病原菌的最小抑菌浓度。计算出抗生素对组织的穿透率及在组织中的钉菌指数。结果 抗生素对肝、胰组织的穿透率分别是：氨曲南４７２．９％和８２．７％，头孢唑肟９９．０％和４４．６％，头孢三嗪９２．４％和２２．０％     

套入空肠段肠粘膜破坏对胰肠吻合口愈合的影响

目的：从术后胰漏的发生率和组织病理学角度,比较胰套入空肠段粘膜破坏与否对吻合口愈合的影响。方法：①１０只健康杂种犬分为２组,均行胰尾切除空肠单层套入吻合。一组行套入段肠粘膜全层电灼破坏,另一组不破坏肠粘膜。术后取胰肠吻合口标本行组织病理学检查;②统计分析本院１９８９年１月～２０００年５月行胰肠套入吻合病例中,套入段肠粘膜破坏组与不破坏组的胰漏发生率。结果：两组犬吻合口组织病理学检查显示,肠粘膜破坏组套入段肠壁与胰腺包膜愈合佳,而肠粘膜不破坏组套入段肠壁与胰腺包膜愈合不完全。临床分析显示,肠粘膜破坏组胰漏发生率为２．７％,不破坏组为１６．４％,两组差异显著（Ｐ＜０．０５）。结论：胰套入段空肠粘膜破坏,使肠壁失去分泌功能,与胰腺包膜较可靠地愈合,可减少胰漏发生率。     

中药清胰汤对犬急性坏死性胰腺炎肠粘膜损伤修复的影响

为观察中药清胰腺对急性坏死性胰腺炎（ＡＮＰ）犬肠粘膜损伤修复的作用，经主胰管注入牛磺胆酸钠和胰蛋白酶复制犬ＡＮＰ模型，观察ＡＮＰ时及中药清胰汤治疗后肠粘膜组织结构的变化，肠组织蛋白、丙二醛（ＭＤＡ）含量及二胺氧化酶活性（ＤＡＯ）改变，肠通透性变化，检测血中内毒素水平，并做脏器细胞培养。结果发现，经中药清胰汤治疗后，ＡＮＰ犬的肠粘膜损害明显减轻，肠粘膜绒毛宽度、高度和面积显著增加，肠组织蛋白含量增加，肠通透性显著下降，血中内毒素水平下降１～２倍，脏器细菌移位率减少５０％。本实验结果提示：中药清胰汤能显著减轻犬ＡＮＰ时肠粘膜的损伤，保护肠屏障功能，减少肠道内毒素和细菌移位     

莫匹罗星（百多邦）：全新的外用抗生素——对多种抗生素耐药的细菌有效

作者ｌｅｙｄｅｎ从常见的对多种抗生素耐药的感染性湿疹患者皮损处得到的１５３株金黄色葡萄球菌，并测定它对各种抗生素的敏感性。结果表明：青霉素和氨苄青霉素耐药性最高。苯唑青霉素和甲氧西林均为１３．７％，红霉素和四环素分别为１６．４％和１５．６％，莫匹罗星几乎无耐药性。     

结扎法建立犬胰管扩张模型的实验研究

胰瘘是胰十二指肠切除术后最常见和最严重的并发症之一,其治疗困难,死亡率较高,发生率在4％～30％不等[1].本实验旨在建立犬胰管扩张模型,适于胰肠吻合时放置内或外胰管支架管,以探求能有效减少胰瘘发生的新胰肠吻合方式.     

胰十二指肠切除术后胰瘘合并腹腔感染的病原菌分析及诊治

目的 探讨胰十二指肠切除术后胰瘘合并腹腔感染患者的主要病原菌分布、耐药性特点及诊断和治疗方法.方法 回顾性分析解放军总医院2010年1月-2012年12月386例行胰十二指肠切除术患者的临床资料,其中术后发生胰瘘患者84例,胰瘘发病率为21.8％,胰瘘合并有腹腔感染患者32例.对于临床上怀疑胰瘘合并腹腔感染的患者血液及引流液行需氧菌、厌氧菌和真菌培养及药敏实验,并进一步行腹部B超或CT平扫等检查,一经确诊,即给予充分引流、抗生素等综合治疗措施,对送检标本中分离出的病原菌的分布及耐药性情况进行分析.结果 32例胰瘘合并腹腔感染的患者中,共培养出阳性菌53例次,分离出的53株病原菌包括41株细菌和12株真菌,包括革兰阳性球菌23株（43.4％）、革兰阴性杆菌18株（40.0％）、真菌12株（16.6％）,其中常见的细菌主要有屎肠球菌（24.5％）、鲍曼不动杆菌（13.2％）、凝固酶阴性葡萄球菌（11.3％）,最常见的真菌主要是白假丝酵母菌（7.5％）.病原菌耐药性较高,其中,头孢哌酮/舒巴坦是治疗革兰阴性杆菌最有效的抗生素,万古霉素和替考拉宁对于革兰阳性球菌具有较好的治疗作用,氟康唑是治疗真菌感染最有效的抗生素.32例患者经充分引流和调整抗生素治疗后好转,无患者死亡.结论 胰瘘合并腹腔感染是胰十二指肠切除术后主要并发症之一,其病原菌呈多重耐药性,有效预防与早期治疗是控制感染的关键,对于胰瘘合并腹腔感染的患者,影像学检查及病原学检查尤为重要,保持充分引流和应用敏感抗生素是治疗的有效措施.     

青霉素及克林霉素在兔椎间盘中的渗透性研究

目的：观察青霉素和克林霉素渗透兔椎间盘的情况，分析其渗透性差异的原因。方法：雄性成年新西兰大白兔14只，随机分成两组，每组7只，分别经兔耳缘静脉注射青霉素（A组）和克林霉素（B组）。A组每只每次静脉注射青霉素钠4．8mg，每隔0．5h一次，共给药5次；B组每只每次静脉注射克林霉素磷酸酯9mg，每隔2h一次，共给药5次。A、B组分别于末次给药后0．5h、2h抽取血样，1ml／只，随后立即处死，取出L4/5髓核。将所有血样和髓核采用高效液相色谱法（HPLC）检测药物浓度，计算药物在髓核中的渗透率（髓核药物浓度／血药浓度×100％）。结果：克林霉素渗透椎间盘髓核的渗透率为38．7％～49．0％，平均为（43．3±3．9）％：青霉素的渗透率为0～1．2％．平均（0．7±0．5）％，两者比较有显著性差异（P〈0．0001）。结论：克林霉素渗透椎间盘髓核的能力比青霉素强。     

0.25%5—氟脲嘧啶胰被膜下灌注抑制胰腺外分泌的研究

通过动物模型的制作探讨了在急性出血坏死性胰腺炎时,清除坏死胰组织后,在胰被膜下局部灌注抗代谢药5-FU与静脉滴注5-FU,对抑制胰腺外分泌淀粉酶含量的动态变化。结果表明,胰被膜下局部灌注5-FU犬组(A组)在48小时末血清淀粉酶和主胰管插管胰液淀粉酶的含量分别降至49±13、189±31苏氏单位;静脉滴注5-FU犬组(B组)在48小时末分别降至46±28、198±28苏氏单位(P>0.05),提示胰被膜下局部灌注5-FU使之与有生机的胰组织直接接触,抑制胰腺外分泌同样能达到静脉途径给药的目的。     

肌肉骨骼系统感染的抗生素治疗

根据不同的作用机制,抗生素可分为干扰细菌细胞壁合成的抗生素、作用于细菌核糖体而影响蛋白质合成的抗生素、作用于细菌RNA和DNA的抗生素、抑制细菌代谢和合成的抗生素等。 1 干扰细菌细胞壁合成的抗生素 1.1 青霉素类 青霉素类抗生素经常用于治疗肌肉骨骼系统感染。矫形外科医生最感兴趣的主要几类青霉素包括:天然青霉素、氨基青霉素、耐酶青霉素、抗假单胞青霉素及衍生青霉素。各种类间有相互的重叠,不同点在于药理学差异。所有青霉素类抗生素主要的不良反应是过敏反应。     

犬胰和十二指肠的血供

通过动脉灌注，在４１例标本上研究犬胰和十二指肠的血供。犬胰的血供分为四组：胰械叶由胃十二指肠动脉、脾动脉主干及其尾侧干的胰支供应；胰角由胃十二指肠动脉和胃网膜右动脉的胰支供应；胰右叶头侧头由胰十二指肠头侧动脉的胰支供应；胰右叶属侧部由胰十二指肠头，尾侧动脉的胰动供应。十二指肠主要由十二指肠上动脉和胰十二指肠头，尾侧动脉的十二指肠支供应。本研究对犬的胰腺切除术及胰腺移植术提供了解剖学资料。     

Pathogenesis and prevention of early pancreatic infection in experimental acute necrotizing pancreatitis.

OBJECTIVE: The authors test antibiotic strategies aimed at either mitigating bacterial translocation from the gut or delivering antibiotics specifically concentrated by the pancreas for prevention of early secondary infection after acute necrotizing pancreatitis. BACKGROUND: Infection currently is the principal cause of death after severe pancreatitis. The authors have shown that the risk of bacterial infection correlates directly with the degree of tissue injury in a rodent model of pancreatitis. Bacteria most likely arrive by translocation from the colon. METHODS: Severe acute necrotizing pancreatitis was induced in rats by a combination of low-dose controlled intraductal infusion of glycodeoxycholic acid superimposed on intravenous cerulein hyperstimulation. At 6 hours, animals were randomly allocated to five treatment groups: controls, selective gut decontamination (oral antibiotics and cefotaxime), oral antibiotics alone, cefotaxime alone, or imipenem. At 96 hours, surviving animals were killed for quantitative bacterial study of the cecum, pancreas, and kidney. RESULTS: The 96-hour mortality (35%) was unaffected by any treatment regimen. Cecal gram-negative bacteria were significantly reduced only by the oral antibiotics. Pancreatic infection was significantly reduced by full-gut decontamination and by imipenem, but not by oral antibiotics or by cefotaxime alone. Renal infection was reduced by both intravenous antibiotics. CONCLUSIONS: Early pancreatic infection after acute necrotizing pancreatitis can be reduced with a full-gut decontamination regimen or with an antibiotic concentrated by the pancreas (imipenem) but not by unconcentrated antibiotics of similar spectrum (cefotaxime) or by oral antibiotics alone. These findings suggest that 1) both direct bacterial translocation from the gut and hematogenous seeding interplay in pancreatic infection while hematogenous seeding is dominant at extrapancreatic sites and 2) imipenem may be useful in clinical pancreatitis.     

区域动脉灌注治疗重症急性胰腺炎116例报告

目的为探讨提高重症急性胰腺炎的疗效。方法应用Ｓｅｌｄｉｎｇｅｒ法,置导管于胰腺病变供血动脉内,灌注抑酶制剂和抗生素,以提高进入胰腺组织内的药物浓度,达到控制胰腺病变和预防继发性感染的目的。结果通过１１６例区域动脉灌注的方法和综合疗法,明显减少了坏死胰腺组织的感染,降低了死亡率。结论该法是治疗重症急性胰腺炎的新疗法,特别适合于胰腺早期病变的治疗。     

环丙沙星和头孢哌酮透入人类胰液的研究

通过7例胰十二指肠切除术后患者胰管内置管获得的纯胰液，用高效液相色谱法测定环丙沙星和头孢哌酮在血清及胰液中的浓度。结果显示：环丙沙星和头孢哌酮的平均胰液渗透率分别为43％和16％，两药在胰液中的浓度均在大多数胰腺感染致病菌的MIC－90以上。     

SIRS发展在胰腺坏死、继发感染致胰腺炎病变加重中的作用

目的 探讨全身炎症反应综合征（SIRS）在胰腺坏死、继发感染致胰腺炎病变加重中的作用.方法 健康雄性SD大鼠46只,随机分为四组：SO组仅翻动胰腺,Ⅰ、Ⅱ、Ⅲ组经胰管逆行注射1％、3％、5％牛磺胆酸钠＋104/mL大肠杆菌混合液.8 h后处死大鼠,检测胰腺组织细菌培养、脂肪酶、磷脂酶A2、c反应蛋白、TNF-α、IL-1β、IL-6水平,进行胰腺组织病理学检查及Schmidt评分.结果 ①SO、Ⅰ、Ⅱ、Ⅲ组胰腺组织细菌培养阳性率分别为0 （0/10）、0（0/12）、25％ （3/12）、90％ （9/10）,其中Ⅲ组与SO、Ⅰ、Ⅱ组比较有统计学差异（P＜ 0.01）.②SO、Ⅰ、Ⅱ、Ⅲ组血清脂肪酶、C反应蛋白、TNF-α、IL-1β、IL-6、Schmidt评分逐渐升高,各组间差别有统计学意义（P＜0.05）.③Ⅰ、Ⅱ、Ⅲ组血清磷脂酶A2水平较SO组有显著性升高（P＜0.01）,Ⅲ、Ⅱ组比Ⅰ组亦有显著性升高（P＜0.01）.④病理学检查结果：SO组未见明显病变;Ⅰ组可见胰腺水肿,炎性细胞浸润;Ⅱ组腺泡水肿,炎性细胞浸润,血管内充血,散在坏死灶与出血点;Ⅲ组可见凝固性坏死灶,大量炎性细胞浸润,微血管破裂,片状出血,甚至可见微脓肿.结论 ①胰腺坏死程度越重,其继发感染的概率越大;②SIRS可能是胰腺坏死、继发感染致胰腺炎病变加重的共同机制,抑制SIRS有助于SAP的治疗.     

Microcirculatory derangement and ischemia of the pancreas]

We present a review of the microvascular morphology of the pancreas and microstructure of the pancreatic lobule, and introduce our experimental results on pancreatic microcirculation following acute pancreatitis. Impairment of pancreatic microcirculation in the early phase of acute pancreatitis may play a key role in the progression of this disease. Possible contributory mechanisms include increased vascular permeability, reduced blood flow, leukocyte-endothelial cell interaction, and intravascular thrombus formation. We achieved direct-visualization and quantification of changes in microvascular permeability and leukocyte behavior in the pancreas with acute pancreatitis using an in vivo microscope system and off-line computer analysis. Bradykinin and oxygen radicals have been demonstrated to be involved in the increased vascular permeability in the early stage of cerulein pancreatitis. Gabexate mesilate (FOY) prevents the increase in vascular permeability, resulting in a decreased number of rolling leukocytes. Leukocyte adherence to the pancreatic microcirculation is a secondary event following permeability changes in acute pancreatitis. Leukocyte infiltration during aggravation of acute pancreatitis is mediated by leukocyte-endothelial cell interaction via leukocyte integrin CD11b/18. The diamino-pyridine derivative IS-741 inhibits the progression of pancreatic inflammation by down-regulating the expression of CD11b/18.     

Pancreatic microcirculation in acute pancreatitis

We present a review of the microvascular morphology of the pancreas and microstructure of the pancreatic lobule, and report our experimental results of the investigation of pancreatic microcirculation following acute pancreatitis. Impairment of pancreatic microcirculation in the early phase of acute pancreatitis may play a key role in the progression of this disease. Possible contributory mechanisms include increased vascular permeability, reduced blood flow, leukocyte-endothelial cell interaction and intravascular thrombus formation. Using an in-vivo microscope system and off-line computer analysis, we achieved direct visualization and quantification of changes in microvascular permeability and leukocyte behavior in pancreas with acute pancreatitis. Bradykinin and oxygen radicals have been demonstrated to be involved in the increase of vascular permeability in the early stage of caerulein pancreatitis. Leukocyte adherence to the vessels in the pancreatic microcirculation is a secondary event following permeability changes in acute pancreatitis. Leukocyte infiltration during exacerbation of acute pancreatitis is mediated by leukocyte-endothelial cell interaction via leukocyte integrin CD11b/18. Received for publication on Jan. 29, 1997; accepted on April 24, 1997     

Fungal infection but not type of bacterial infection is associated with a high mortality in primary and secondary infected pancreatic necrosis

INTRODUCTION: Knowledge of microbiology in the prognosis of patients with necrotizing pancreatitis is incomplete. AIM: This study compared outcomes based on primary and secondary infection after surgery for pancreatic necrosis. METHOD: From a limited prospective database of pancreatic necrosectomy, a retrospective case note review was performed (October 1996 to April 2003). RESULTS: 55 of 73 patients had infected pancreatic necrosis at the first necrosectomy. 25 of 47 patients had resistant bacteria to prophylactic antibiotics (n = 21) or did not receive prophylactic antibiotics (n = 4), but this was not associated with a higher mortality (9 of 25) compared to those with sensitive organisms (4 of 22). Patients with fungal infection (n = 6) had a higher initial median (95% CI) APACHE II score compared to those without (11 (9-13) verus 8.5 (7-10), p = 0.027). Five of six patients with fungal infection died compared to 13 of 47 who did not (p = 0.014). With the inclusion of secondary infections 21 (32%) of 66 patients had fungal infection with 10 (48%) deaths compared to 11 (24%) of 45 patients without fungal infection (p = 0.047). CONCLUSION: Whether associated with primary or secondary infected pancreatic necrosis, fungal but not bacterial infection was associated with a high mortality.     

Ectopic pancreas presenting as ampulla of Vater tumor

Ectopic pancreas is relatively rare and is defined as pancreatic tissue that is situated abnormally, has no contact with the normal pancreas, and has its own ductal system and blood supply. It is usually an incidental finding in clinical practice. Most patients with an ectopic pancreas are asymptomatic, and, if present, symptoms are nonspecific and depend on the site of the lesion and the different complications encountered. Heterotopic pancreatic tissue has been found in several abdominal and intrathoracic locations, most frequently in the stomach (25%-60%) or the duodenum (25%-35%). Herein, we report a patient presenting with symptoms of ampullary tumor with obstructive jaundice, but the imaging study did not suggest the possibility of ectopic pancreas preoperatively.     

Prophylactic antibiotics alter the bacteriology of infected necrosis in severe acute pancreatitis

BACKGROUND: Use of appropriate prophylactic antibiotics has been shown to decrease infectious complications and mortality rate in patients with severe acute pancreatitis, but its influence on the bacteriology of secondary pancreatic infection is poorly defined. STUDY DESIGN: Operative cultures from 61 consecutive patients with pancreatic necrosis treated during routine prophylactic antibiotic use (1993-2001) were compared with 34 consecutive patients with necrosis treated before routine antibiotic use (1977-1992). RESULTS: The two groups of patients were similar in demographics, etiology of pancreatitis, and severity of illness. All patients in the antibiotic group received prophylactic antibiotics compared with only 38% (13 of 34) in the control group. Routine broad-spectrum prophylactic antibiotics altered the bacteriology of secondary pancreatic infection in severe acute pancreatitis from predominantly gram-negative coliforms (56% versus 26%, p = 0.005) to predominately gram-positive organisms (23% versus 52%, p = 0.009) without a significant increase in either the rate of beta-lactam resistance or fungal infections. The overall hospital stay in patients treated with prophylactic antibiotics was significantly reduced (61 +/- 24 days versus 41 +/- 28 days, p = 0.002), and there was a trend toward a decline in mortality rate in the antibiotic treatment group. CONCLUSION: Routine broad-spectrum prophylactic antibiotic use has altered the bacteriology of secondary pancreatic infection in severe acute pancreatitis from predominantly gram-negative coliforms to predominantly gram-positive organisms without altering the rate of beta-lactam resistance or fungal superinfection.     

内源性一氧化氮对急性胰腺炎大鼠胰腺微血管通透性的影响

目的 探讨内源性一氧化氮（NO）对急性坏死性胰腺炎大鼠胰腺炎大鼠胰腺微血管通透性的影响。方法 以5%牛磺胆酸钠溶液胰胆管注射（1ml/kg）制成大鼠急性坏死性胰腺炎模型,以工具药L-硝基精氧酸（L-NNA）和内源性NO的阻断Evans Blue的漏出代表微血管的通透性,观察内源性NO对胰腺组织损伤程度、胰腺内Evans Blue漏出等的影响。结果 牛磺胆酸钠胆管注射造成大鼠胰腺组织明显坏死和炎性细胞浸润,以及血清淀粉酶浓度升高、胰腺湿/干重比率产加和明显的胰腺组织内Evans Blue积聚。以L-NNA（12.5mg/kg）阻断内源性NO后,胰腺组织坏死和炎性细胞浸润进一步加重,并使血清淀粉酶浓度升高,胰腺湿/干重比率增加,Evans Blue的漏出率也较之单纯胰腺炎组大鼠明显增加。结论 内源性NO具有胰腺保护作用,其保护机制可能与维持胰腺微血管的完整性有关。