Cefamandole bile levels in patients with hepatobiliary disease.

Intraoperative biliary cefamandole concentrations were determined in 16 patients with hepatobiliary pathology. These included seven patients with cholelithiasis, five with acute cholecystitis, two with recurrent ascending cholangitis, and two with liver abscesses. Bile collected 0.5 to 2.5 h after the last antibiotic dose of 1 g administered by intravenous drip showed therapeutically effective concentrations of cefamandole in 84% (11 of 13) of gall bladder samples with a median of 220 micrograms/ml (range, 1.6 to 1,400), and in 100% (13 of 13) of common bile duct samples with a median of 1,100 micrograms/ml (range, 9.0 to greater than 2,000). Only with complete aseptic cystic duct obstruction was cefamandole undetectable in gall bladder bile.     

Concentrations of kanamycin and amikacin in human gallbladder bile and wall.

The concentrations of amikacin and kanamycin were determined in the serum, gallbladder bile, and gallbladder wall of 20 patients undergoing elective cholecystectomy. Of 20 patients, 14 received 500 mg of amikacin intramuscularly and 6 received 500 mg of kanamycin intramuscularly at various times before surgery. In patients receiving kanamycin, detectable levels appeared in bile within 90 min after drug administration, and in five of six patients concentrations ranged from 1.9 to 23 micrograms/ml. Levels of kanamycin in gallbladder wall ranged from 8.0 to 14 micrograms/g. In patients receiving amikacin, detectable levels appeared in bile within 48 min after drug administration and ranged from 1.3 to 7.5 micrograms/ml in 12 of 14 patients. Levels of amikacin in gallbladder wall ranged from 4.7 to 34 micrograms/g. The presence of an obstructed cystic duct did not preclude the entry of either antibiotic into gallbladder bile, and this may reflect passage of antibiotic through the gallbladder wall rather than accumulation via bile secretion.     

Biliary Tract Excretion of Cefazolin, Cephalothin, and Cephaloridine in the Presence of Biliary Tract Disease

The biliary tract excretion of three cephalosporins, cefazolin, cephaloridine, and cephalothin, was compared in patients with biliary tract disease. In the absence of obstruction, mean antibiotic levels in bile from gall bladder and common duct in patients undergoing cholecystectomy were highest for cefazolin (17 and 31 mug/ml, respectively) than either cephaloridine (7 and 9 mug/ml) or cephalothin (1 and 4 mug/ml). Biliary tract levels generally paralleled serum levels. In no patient with cystic duct obstruction were any of the cephalosporins detectable in appreciable amounts in gall bladder bile. In patients with T-tube drainage given each of the three different cephalosporins on separate days, concentrations of cefazolin in bile were many-fold higher than either cephaloridine or cephalothin. Peak levels of cefazolin in T-tube bile averaged 51 mug/ml after intravenous and 26 mug/ml after intramuscular administration, whereas mean peak levels of cephalothin and cephaloridine were only 6 and 16 mug/ml, respectively. Here, too, T-tube levels reflected serum concentrations and obstruction to biliary flow impaired excretion of each of the drugs.     

Biliary excretion of ceftizoxime in humans

Biliary concentrations of a new cephalosporin, ceftizoxime, were measured in bile collected in 8 cholecystectomized patients provided with T-tube drainage and in 14 patients where bile was obtained by puncture of the gall bladder and choledochus during cholecystectomy. In patients with external biliary drainage, a mean biliary peak of 150.3 +/- SEM 49.8 micrograms/ml has been observed 2 h after intravenous injection of 2 g of ceftizoxime; the antibiotic activity amounted still to 17.3 +/- 6.0 micrograms/ml after 6 h. Assays performed during operation showed the following simultaneous concentrations 1 h after 2 g of ceftizoxime given intravenously: serum: 85.3 +/- 8.1 micrograms/ml; main duct bile: 279.8 +/- 40.0 micrograms/ml; gallbladder bile: 119.9 +/- 19.4 micrograms/ml. These findings were compared with the biliary excretion of 8 other cephalosporins studied previously under the same conditions. The results of the present study suggest that administration of ceftizoxime may be effective in the treatment of biliary tract infections.     

Hepatobiliary kinetics and excretion of ciprofloxacin.

The biliary excretion and metabolism of ciprofloxacin was studied in 25 hospitalized patients: 19 undergoing routine cholecystectomy and 6 with indwelling biliary drainage catheters. An intravenous dose of 200 mg of ciprofloxacin given 2.5 to 3.0 h prior to cholecystectomy resulted in concentrations in common duct bile, gallbladder bile, and gallbladder wall of 5.69 +/- 4.8, 5.43 +/- 3.34, and 2.52 +/- 1.30 micrograms/g, respectively, all at least fourfold greater than simultaneous concentrations in serum. Ciprofloxacin concentrations in common duct bile exceeded peak concentrations in serum in all but two patients with common duct obstruction. Multiple preoperative doses of ciprofloxacin prior to cholecystectomy increased concentrations in gallbladder bile by eightfold. Six patients with indwelling biliary drainage catheters also received 200 mg of ciprofloxacin intravenously. Less than 1% of the administered dose was excreted in bile as unchanged ciprofloxacin, and there was extensive metabolism. However, peak ciprofloxacin concentrations of 2.83 +/- 0.76 micrograms/ml in serum produced peak concentrations of 10.69 +/- 5.30 micrograms/ml in bile within 1.5 h after infusion and maintained concentrations of at least 0.5 microgram/ml in common duct bile for over 12 h in all patients. It appears that ciprofloxacin concentrations in bile will exceed the MICs for most susceptible biliary pathogens for a period of at least 12 h after a 200-mg intravenous dose.     

Biliary excretion of imipenem-cilastatin in hospitalized patients.

Imipenem-cilastatin concentrations in bile were measured in 12 cholecystectomy patients (group 1) and 12 patients with common duct drainage (group 2). Six patients in each group received 0.5 g, and six received 1.0 g intravenously over 30 to 60 min. In group 1, bile was collected a mean of 85 min postinfusion. The mean concentrations of imipenem in bile were 1.3 microgram/ml after the 0.5-g dose and 3.5 micrograms/ml after the 1.0-g dose. The mean concentrations of cilastatin in bile were 9.0 micrograms/ml after the 0.5-g dose and 38.0 micrograms/ml after the 1.0-g dose. In patients with common duct drainage, bile was collected predose and 0 to 2, 2 to 3, 3 to 4, and 4 to 6 h postinfusion. Peak imipenem concentrations in bile were 4.4 micrograms/ml after the 0.5-g dose and 8.6 micrograms/ml after the 1.0-g dose. Peak cilastatin concentrations in bile were 4.6 micrograms/ml for the 0.5-g dose and 10.9 micrograms/ml for the 1.0-g dose. Peak imipenem concentrations in bile occurred a mean of 2.3 h after administration of the drug; cilastatin peak concentrations occurred at a mean of 2.4 h. Less than 0.3% of each drug was recovered in the bile. Our results suggest that imipenem enters bile by simple diffusion and in most patients attains concentrations sufficient to inhibit susceptible organisms. In contrast, cilastatin had a bimodal entry into bile. Some patients had very high concentrations in bile, whereas others had very low or undetectable concentrations, suggesting that cilastatin may be actively secreted into the bile.     

Biliary levels of ceforanide.

Ceforanide levels in plasma, gallbladder bile, gallbladder tissue, and common bile duct were studied in 10 patients with normal biliary tracts and in 35 patients with biliary disease at various intervals after intravenous injection of 1 g of the drug. Peak blood levels were obtained within 1 h of administration (mean, 67 +/- 15 micrograms/ml). Patients with a normal bilary tract, as well as patients with chronic cholecystitis and a patent cystic duct, achieved high gallbladder bile levels of ceforanide within 2 h (mean, 76 +/- 25 micrograms/ml) and attained even higher levels by 4 h (mean, 182 +/- 51 micrograms/ml). However, all patients with chronic cholecystitis and an occluded cystic duct had very low drug concentrations in the gallbladder bile (14 +/- 7 micrograms/ml at 2 h). Despite this difference in gallbladder bile levels, ceforanide levels of 21 +/- 3 micrograms/g were achieved at 1 to 3 h in gallbladder tissue in both groups with chronic cholecystitis. The concentration of ceforanide in common bile duct was 149 +/- 59 micrograms/ml at 2 h after administration, with levels over 60 micrograms/ml present from 1 to 4 h after administration. These results indicate that ceforanide reaches high levels in the biliary tract. Its potential value in the prevention and treatment of biliary infections should be assessed.     

Biliary concentrations of piperacillin in patients undergoing cholecystectomy.

Piperacillin is a new semisynthetic, expanded-spectrum penicillin with marked activity against Pseudomonas aeruginosa. The biliary excretion of piperacillin was studied in patients undergoing cholecystectomy. Concentrations of piperacillin in common duct bile at 35 to 90 min postinfusion of 1-g doses ranged from 31 to 920 micrograms/ml, with a mean (+/- standard deviation) of 467 +/- 363 micrograms/ml. Gallbladder piperacillin levels at 30 to 75 min postinfusion ranged from 2.2 to 80 micrograms/ml, with a mean of 27 +/- 31 micrograms/ml. No correlation occurred with peak serum level of antibiotic, creatinine, bilirubin, or alkaline phosphatase. Significant amounts of piperacillin were excreted via the biliary system.     

B超快速胆囊胆道造影剂及其功能检测分析研究

本文利用快速胆囊、胆道造影剂对５０例正常人及１０８例胆系疾病患者进行胆囊收缩功能对比分析，结果显示：该造影剂对正常人胆囊３０分钟收缩率为９８％，胆囊炎６８．５％，胆石症６０％，胆囊息肉８０％。由于造影剂刺激肝细胞分泌胆汁，使胆总管内胆汁流量加大，可使胆总管中下段显像率达８２．５％。该造影剂提供了一种新的影像学检查方法，具有重要临床应用价值。     

B超在腹腔镜胆囊切除术前的应用

本文根据腹腔胆囊切除术前病人胆囊的大小、形态、胆囊壁厚薄，胆周有无粘连，胆囊结石及胆总管情况，胆疲乏有无先天性畸形，将患者分为Ａ、Ｂ、Ｃ、Ｄ四个组，为临床提供了较为全面的选择依据。与手术对照，Ｂ超符合率９７．８％。对于减轻病人痛苦，减少手术风险，降低ＬＣ手术中转率具有重要临床价值。     

Biliary elimination of mezlocillin: an experimental and clinical study

The biliary elimination of mezlocillin, a new semisynthetic penicillin of the acyl-ureido-penicillin group, was investigated in vitro in rabbit liver preparations and in vivo in humans. Experimentally, mezlocillin recovery in the bile during perfusion of isolted rabbit liver (3 h; n = 5) averaged 20.3% of the administrered dose (10 mg). The mean peak concentration in the bile (758 +/- 129.3 micrograms/ml) was reached between 0.5 and 1 h. Biliary clearance was 169 ml/h. In healthy subjects (n = 5), the concentrations of antibiotic measured in the duodenal fluid during a period of 4 h after intravenous administration of 5 g of mezlocillin ranged between 440 and 637 micrograms/ml. In 10 cholecystectomized patients provided with a T-tube, intramuscular injection of 1 g of mezlocillin resulted in a biliary peak concentration of 295.7 +/- 58.1 micrograms/ml. Mean total amount of antibiotic eliminated in the bile over 12 h corresponded to 2.6% of the administered dose. Assays performed during surgery after intravenous administration of 2 g of mezlocillin (n = 10) showed antibiotic activity of 895 +/- 196 micrograms/ml in the common duct bile and 402 +/- 133 micrograms/ml in the gallbladder bile. These data were compared with the values determined for 11 other beta-lactamines studied under identical conditions.     

The concentration of latamoxef achieved in the bile and gallbladder wall of patients with cholecystitis

This study reports the clinical and pharmacokinetic results following an injection of latamoxef (moxalactam disodium) in patients undergoing cholecystectomy for symptomatic cholelithiasis. Two groups were involved in the study. Group A consisted of 22 patients who received 1 g of intramuscular latamoxef at the time of premedication prior to surgery, and group B consisted of 12 patients each of whom received an intravenous dose of 0.5 g of latamoxef at the time of anaesthetic induction. Latamoxef levels were then measured in peripheral blood, gall bladder bile, common bile duct (CBD) bile and gall bladder wall. Despite a significant difference in the sampling times, inhibitory levels were obtained in the majority of samples in both groups, singularly high levels being assayed in CBD bile. We conclude that an intravenous dosage of latamoxef (0.5 g) given with anaesthetic induction is as effective as 1 g intramuscular dosage given with the pre-medication.     

Piperacillin distribution into bile, gallbladder wall, abdominal skeletal muscle, and adipose tissue in surgical patients.

The concentrations of piperacillin in serum, bile, gallbladder wall, abdominal skeletal muscle, and adipose tissue were measured simultaneously at various times after the intravenous administration of a single 5-g dose to each of 14 patients undergoing biliary tract surgery. Piperacillin concentrated in the bile with peak levels exceeding 4,000 micrograms/ml. In a single patient with cystic duct obstruction, trace gallbladder bile piperacillin levels were measured. Gallbladder wall concentrations of piperacillin tended to be higher than corresponding serum concentrations, with a correlation observed between tissue values and the degree of acute gallbladder inflammation and gallbladder bile piperacillin concentrations. Mean peak muscle and adipose tissue piperacillin concentrations of 31 and 27 micrograms/g, respectively, were reached at between 2 and 3 h after the start of infusion. These concentrations exceeded the minimum inhibitory concentration for a majority of susceptible organisms. A single 5-g dose of piperacillin achieved therapeutic levels in gallbladder wall, intraabdominal skeletal muscle, and adipose tissue and concentrated in the bile of patients with patent biliary tracts.     

光亮胆道造影法在腹腔镜胆囊切除术中的应用研究

目的在腹腔镜胆囊切除术(Laparoscopic cholecystectomy，LC)中利用光亮胆道造影法(light cholangiography，LCP)显示胆管走向，预防胆道损伤。方法在LC中分别经十二指肠乳头向胆总管置入光导纤维(light cholangiography through duodenum，LCPD)及经胆囊管置入光导纤维(light cholangiography through cysstic duct，LCPC)，导入冷光源，在腹腔镜电视图像中直接观看从胆管内透出的光亮，从而判断胆管的解剖位置。结果两种途径置入光导纤维行光亮胆道造影法均能在LC中提供直视胆道图像。LCPD操作复杂，但能提供全面的胆道图像。LCPC主要提供胆囊管及胆囊的胆道图像，与LCPD相比操作极为方便。结论光亮胆道造影法能清楚、直接地显示胆管走向。在解剖不清的LC中，能有效地帮助术者进行解剖，提高手术安全性，具有很高的实用价值。     

Cefmenoxime penetration into gallbladder bile and tissue.

Cefmenoxime concentrations in gallbladder bile and tissue were assessed in patients undergoing cholecystectomy. A 0.5-g intravenous dose produced mean concentrations in bile of 54.1 micrograms/ml at 62.9 min and 56.3 micrograms/ml at 194 min after the dose was given. A 1.0-g intravenous dose produced concentrations in bile of 117.9 micrograms/ml at 53 min and 169.7 micrograms/ml of 194 min after the dose was given. Mean concentrations in tissue ranged from 6.1 to 17.9 micrograms/g. Biliary tree penetration was dose and time dependent. Therapeutic concentrations were achieved.     

经腹腔镜逆行胆囊切除术在临床中的应用分析

目的探讨经腹腔镜胆囊切除术中采取逆行胆囊切除在临床中的应用。方法回顾总结我院100例手术，均采取腹腔镜下逆行切除胆囊。结果经采取该术式均无胆瘘、胆管损伤等并发症的发生。结论经采取腹腔镜逆行胆囊切除术对于复杂性胆囊是一种行之有效的方法，降低了胆管损伤及中转开腹率。     

Echographic diagnosis of calculous lesions of the bile ducts

The author presented methods and results of ultrasonic diagnosis of concrements in intrahepatic (4), lobar (5), cystic (24) and common bile (20) ducts. In technically difficult cases the starting point of an acoustic shadow route was the only sign permitting concrement localization in the duct. Indirect signs of occluding choledocholithiasis were dilatated lumen of intrahepatic and proximal (with respect to the site of occlusion) extrahepatic ducts, a concrement filled cavity and the tense gall bladder wall, the absence of echographic signs of tumor involvement of the peritoneal cavity organs. The dilatation of the ducts and gall bladder cavity were more noticeable in patients with a long history of cholestasis. The lamination of the gall bladder content into zones of different echogenicity, the filling of the dilatated ducts with the content of inhomogeneous acoustic transparency indicated the complication of occluding choledocholithiasis by purulent cholangitis.     

PHYSIOLOGICAL CAUSES FOR THE VARIED CHARACTER OF STASIS BILE

The gall bladder and ducts exert opposite influences upon the bile. The ducts fail to concentrate and thicken it with mucus as the bladder does, but dilute it slightly with a thin secretion of their own that is colorless and devoid of cholates even when the organism is heavily jaundiced. The fluid may readily be collected into a rubber bag connected with an isolated duct segment. It continues to be formed against a considerable pressure, and, in the dog, is slightly alkaline to litmus, clear, almost watery, practically devoid of cholesterol, and of low specific gravity to judge from the one specimen tested. In obstructed ducts separated from the gall bladder, or connecting with one so changed pathologically that the concentrating faculty has been lost, such fluid gradually replaces the small amount of bile originally pent up. It is the so called "white bile" of surgeons. When obstructed ducts connect with an approximately normal gall bladder the stasis fluid is entirely different, owing to the bladder activity. At first there accumulates in quantity a true bile much inspissated by loss of fluid through the bladder wall, darkened by a change in the pigment, and progressively thickened with bladder mucus. As time passes duct secretion mingles with the tarry accumulation and very gradually replaces it. The inspissation of the bile, as indicated by the pigment content, is at its greatest after only a day or two of stasis. The differing influences of the ducts and bladder upon the bile must obviously have much to do with the site of origin of calculi and their clinical consequences. The concentrating activity of the bladder cannot but be a potent element in the formation of stones. We have discussed these matters at some length. Intermittent biliary stasis is admittedly the principal predisposing cause of cholelithiasis; and the stasis is to be thought of as effective, in many instances at least, through the excessive biliary inspissation for which it gives opportunity. In this way a normal gall bladder can become, merely through functional activity, a menace to the organism. In patients with the tendency to stones frequent feedings may lessen the danger of their formation.     

Trimethoprim and sulfadiazine penetration into bile and gallbladder in acute cholecystitis

The concentrations of trimethoprim (TMP) and sulfadiazine (SDZ) in serum, bile and gallbladder wall of 9 patients with acute cholecystitis were measured after b.i.d. treatment with 160 mg of TMP + 500 mg of SDZ. The samples were collected 2-4 h after the last dose. Mean TMP concentrations were 1.71 +/- (SE) 0.51 micrograms/ml, 4.53 +/- 5.26 micrograms/ml and 2.31 +/- micrograms/g in serum, bile and gallbladder, respectively. Mean SDZ concentrations were 22.2 +/- 14.9 micrograms/ml in serum, 9.37 +/- 8.99 micrograms/ml in bile and 16.1 +/- 10.1 micrograms/g in gallbladder. The average ratios of bile-serum and gallbladder-serum concentrations were 2.64 and 1.35 for TMP and 0.42 and 0.73 for SDZ. There was a significant correlation between serum and gallbladder concentrations of both TMP and SDZ. No correlation existed between serum and bile levels.     

Concentration of norfloxacin in human gallbladder tissue and bile after single-dose oral administration.

Concomitant concentrations of norfloxacin in serum and in gallbladder tissue and bile were determined in 10 patients after a single oral dose of 400 mg given before cholecystectomy. Concentrations in gallbladder bile ranged from 0.6 to 15.6 micrograms/ml, with a mean bile/serum ratio of 7.0. The mean concentration in gallbladder tissue was 1.8 +/- 0.8 (standard error) micrograms/g.