The inhibition of bacterial adhesion to a tobramycin-impregnated polymethylmethacrylate substratum

Tobramycin sulfate powder (1.2 g) was mixed with Palacos polymethylmethacrylate (PMMA) bone cement (40 g) to produce 100 discs containing 5.9 mg tobramycin per disc. These discs were used to evaluate the inhibition of bacterial adhesion to an antibiotic-laden biomaterial. Tobramycin-impregnated PMMA discs and control discs containing no tobramycin were exposed in vitro to Staphylococcus epidermidis. Colonization was quantitated using plate count techniques and electron microscopy. Tobramycin-impregnated surfaces reduced adhesive bacteria colonization by 1 log relative to control discs. These observations suggest that tobramycin-impregnated PMMA may not be significantly effective in preventing colonization of the biomaterial substratum and PMMA may be a poor choice as a drug delivery vehicle in biomaterial and compromised tissue-centered infections.     

Keratotomy model of pseudomonas keratitis: gentamicin chemotherapy.

BACKGROUND: Chemotherapy of bacterial keratitis requires frequent application of antibiotic drops. Collagen shields containing antibiotics could reduce the need for frequent antibiotic application. To determine the effect of gentamicin-containing collagen shields and gentamicin drops on Pseudomonas keratitis, a new keratotomy model of infection was employed. METHODS: Model--contact lenses (58% water content) presoaked in 1% bovine serum albumin and exposed to 10(8) colony forming units per mL of Pseudomonas aeruginosa strain 27853, were found to reproducibly retain 5.9 (log base 10) colony-forming units. Rabbit corneas were scarified centrally with two perpendicular intersecting diamond knife cuts (5 mm x 5 mm x 0.2 mm), and bacteria-impregnated contact lenses were positioned and held in place for 24 hours with partial tarsorrhaphies. Treatment--Fourteen hours after lens removal (38 hours after infection), corneas were treated for 8 hours with collagen shields hydrated in saline (control), or shields impregnated with 800 micrograms gentamicin during manufacture, or one drop every 30 minutes of fortified gentamicin drops (14 mg/mL). The rabbits were killed and corneas collected for bacterial enumeration after 8 hours of treatment (46 hours after infection). RESULTS: Model--Slit-lamp examination and microbiologic confirmation showed uniformity of keratitis in all eyes. Treatment--Corneas treated with saline (controls) contained 6.4 (log base 10) Pseudomonas. Corneas treated with gentamicin-impregnated collagen shields (total drug = 800 micrograms) and fortified gentamicin drops (total drug = 21 mg) showed a reduction in viable bacteria of 2 logs and 6 logs, respectively, relative to the control. CONCLUSIONS: In this new model of Pseudomonas keratitis, the amount of gentamicin introduced into collagen shields during manufacture effectively reduced bacterial growth in infected rabbit corneas. However, larger amounts of drug applied as fortified drops on a frequent dosing schedule were more effective by a factor of three. Treatment of keratitis with antibiotic-impregnated collagen shields may reduce the need for very frequent application of topical drops, but may be more effective with topical drop supplementation to increase the amount of drug available over the course of therapy.     

In vitro bacteriological evaluation of the effectiveness of antimicrobial irrigating solutions.

Nineteen strains of pathogenic aerobic bacteria were exposed for fifteen seconds in vitro to varying concentrations of five antibiotics and of polyvinyl povidone iodine in saline solution. The presence of human plasma in the solution (30 per cent by volume) did not affect bacterial sensitivity to the antibiotics. Most of the bacteria were sensitive to the solutions during that brief exposure. Bacteria which were more sensitive by disc sensitivity tests were more sensitive to the solutions. Polyvinyl povidone iodine sterilized all cultures in concentrations as low as 25 per cent. It is proposed that the use of appropriate antimicrobial solutions as wound irrigants may reduce postoperative infection rates by killing bacteria which contaminate the surface of the wound during operation.     

Efficacy of intraperitoneal antibiotics in the treatment of severe fecal peritonitis

A study was performed with rabbits to examine the efficacy of treatments for fecal peritonitis and, specifically, to determine whether it is beneficial to include antibiotics in the saline used to irrigate the peritoneum. A standardized inoculum of human stool suspension was placed in the peritoneal cavity of the rabbits. Fifty-six rabbits were studied to compare the effect of treatments begun 2 hours after peritoneal soiling. The administration of no treatment resulted in 100% mortality (14 of 14). Parenteral cefotetan 25 mg/kg intramuscularly (IM) twice a day (BID) with no other treatment reduced mortality to 50% (p less than 0.05). Cefotetan 25 mg/kg IM BID plus irrigation of the peritoneum with plain saline further reduced mortality to 21% (3 of 14, p less than 0.05). Cefotetan 25 mg/kg IM BID plus irrigation of the peritoneum with saline containing cefotetan 1.0 mg/mL reduced mortality to 14% (2 of 14, p = not significant). These treatments also produced a progressive decrease in the number of intraperitoneal abscesses from 24.0 +/- 2.1 (mean +/- SEM) in the animals receiving no treatment to 9.7 +/- 1.2 abscesses in the animals receiving peritoneal irrigation with saline containing cefotetan (p less than 0.001). A second experiment then was performed specifically to examine the efficacy of intraperitoneal antibiotics. A lethal fecal inoculum was determined in rabbits receiving conventional therapy, i.e., parenteral antibiotics (cefotetan) and irrigation of the peritoneum with plain saline. With two hours delay before treatment, cefotetan 25 mg/kg IM BID and irrigation with plain saline produced 80% mortality (11 of 14). Cefotetan 25 mg/kg IM BID plus cefotetan 1.0 mg/mL in the saline washout reduced mortality to 21% (3 of 14, p = 0.003) and markedly reduced the number of intraperitoneal abscesses from 13.4 +/- 0.7 in the animals receiving irrigation with plain saline to 8.1 +/- 0.8 in the animals receiving irrigation with saline containing cefotetan (p less than 0.0001). Thus, intraperitoneal irrigation with antibiotics was highly effective. Serum antibiotic levels drawn 30 minutes after irrigation were 112.7 +/- 22.4 micrograms/mL in animals that received irrigation with plain saline, and 101.7 +/- 15.2 micrograms/mL in animals that received irrigation with saline containing cefotetan. These serum levels were not significantly different. With 6 hours delay before treatment, all therapy was less effective. Cefotetan 25 mg/kg IM BID and irrigation with plain saline resulted in 100% mortality (14 of 14). With 6 hours delay, cefotetan 25 mg/kg IM BID and irrigation with saline containing cefotetan reduced mortality to 80% (11 of 14).(ABSTRACT TRUNCATED AT 400 WORDS)     

Elution of gentamicin and vancomycin from polymethylmethacrylate beads and hip spacers in vivo

Background and purpose Late infections after total hip arthroplasty are still a problem. Treatment procedures include resection arthroplasty with implantation of antibiotic-loaded beads or implantation of an antibiotic-impreganted spacer. However, little is known about antibiotic elution from bone cement beyond the first 2–3 postoperative days in humans.Methods 17 hip spacers (80g PMMA, 1g gentamicin, and 4 g vancomycin) and 11 chains (40 g PMMA, 0.5 g gentamicin, and 2 g vancomycin) in 28 patients were studied. The release of both agents was measured in the drainage fluid on a daily basis. The drains were left in situ until less than 50 mL was produced per day. The elution of both antibiotics was determined by fluorescence polarization immunoassay. Systemic antibiotics were given postoperatively according to antibiogram. If possible, no gentamicin or vancomycin was given.Results Peak mean concentrations from beads and spacers were reached for gentamicin (1,160 (12–371) µg/mL and 21 (0.7–39) µg/mL, respectively) and for vancomycin (80 (21–198) µg/mL and 37 (3.3–72) µg/mL) on day 1. The last concentrations to be determined were 3.7 µg/mL gentamicin and 23 µg/mL vancomycin in the beads group after 13 days, and 1.9 µg/mL gentamicin and 6.6 µg/mL vancomycin in the spacer group after 7 days. Between the fifth and seventh day, an intermittent increase in elution of vancomycin from both beads and spacers and of gentamicin from spacers was noticed. No renal or hepatic dysfunction was observed.Interpretation Beads showed higher elution characteristics in vivo than the spacers due to their larger surface area; however, a great amount of inter-subject variability was seen for both beads and spacers. The inferior elution properties of spacers emphasize the importance of additional systemic antibiotics for this treatment procedure during the postoperative period. Future studies should clarify whether the dose of antibiotics or length of antibiotic therapy may be reduced in the case of bead implantation, without jeopardizing the control of infection.     

High concentration and bioactivity of vancomycin and aztreonam eluted from Simplex cement spacers in two-stage revision of infected hip implants: a study of 46 patients at an average follow-up of 107 days.

This study investigated the release of antibiotics in vivo, from an articulating polymethylmethacrylate (PMMA) spacer used in two-stage revision arthroplasty of infected hip implants. Forty-six patients who underwent two-stage revision hip arthroplasty for infections were managed with an interim PMMA spacer loaded with a high dose of vancomycin and aztreonam. Serum and aliquots of drainage collected after the first-stage surgery, and joint fluid obtained at the time of the second-stage surgery were analyzed for antibiotic concentrations by high performance liquid chromatography and bioactivity by tube dilution bioassay. Following implantation, the highest levels of antibiotics were measured in aliquots of drainage on the first day (vancomycin: 1538.0 +/- 243.6 microg/mL; aztreonam: 1003.5 +/- 323.5 microg/mL), decreasing to 571.9 +/- 169.4 microg/mL for vancomycin and 313.6 +/- 88.3 microg/mL for aztreonam after 7 days. Antibiotic concentrations in serum were very low (vancomycin: 0.58 +/- 0.2 microg/mL, range: 0.1-1.6 microg/mL; aztreonam: 0.46 +/- 0.3 microg/mL, range: 0.1-0.9 microg/mL at 24 h) and there was no systemic adverse effect. At a mean 107 days after the first-stage surgery, the concentrations of antibiotics in joint fluid were well above the minimal inhibitory concentration of most common microorganisms. The released antibiotics were bioactive against the test organisms. Based on the observed results, we confirmed the safety and effectiveness of in vivo drug delivery from antibiotic-impregnated PMMA hip spacers.     

Ketamine and the inhibition of albumin extravasation in chemical peritonitis in rat

BACKGROUND AND OBJECTIVE: It was previously reported that topical ketamine inhibits albumin extravasation in a rat chemical peritonitis model. Using the same model, the present study investigated whether intravenous ketamine inhibited this extravasation. METHODS: Twenty-four rats anaesthetized with pentobarbital (75 mg kg(-1)) were randomly assigned to two groups: ketamine and a 0.9% NaCl (saline) group (n = 12 each). Ketamine 1% or saline 0.1 mL kg(-1) min(-1) was given intravenously for 60 min to the respective group. After the abdomen had been opened, peritonitis was elicited by topically applying a filter paper containing 0.02 M HCl 0.07 mL onto the surface of the appendix or caecum for 5 min. Fifteen minutes after removal of the filter paper, Evans' blue dye (50 mg kg(-1)) was injected intravenously. The extravasated dye was colorimetrically quantified by a spectrophotometer at 620 nm. RESULTS: The infusion of ketamine significantly reduced Evans' blue extravasation: 5.26 (range 4.18-6.34) microg per 100 mg tissue compared with the saline group control: 6.81 (5.93-7.69) microg per 100 mg tissue (P < 0.05). CONCLUSIONS: It is suggested that ketamine anaesthesia may reduce albumin extravasation in inflammatory tissues.     

An experimental study on pyogenic osteomyelitis with special reference to the analysis of the therapeutic effects of antibiotics in vivo (author's transl)]

Experimental osteomyelitis was produced in mice by the Ueno's method for the purpose of evaluating therapeutic effects of the antibiotics. The results were as follows: 1) Experimental osteomyelitis produced with penicillin-G sensitive bacteria was completely cured by PC-G 1.8 mg per mouse a day, which provided maintenance of the concentration in serum more than 10 times of MIC for over 12 hours. The dosis of 0.18 mg per mouse per day was insufficient to bring a complete healing. 2) Experimental osteomyelitis produced with penicillin-G resistant bacteria did not heal completely, despite the administration of MPI-PC, a synthetic penicillin designed against penicillin resistant staphylococci, in a dosis of 5 mg twice a day, probably by the following reasons. Since MPI-PC is water-soluble, it is difficult to maintain the concentration in serum more than 10 times of MIC for over 1 hour. In other word, the bacteria was exposed to the effective antibiotic concentration for only one hour twice a day. 3) It was experimentally proved that earlier administration of antibiotics following inoculation provided quicker elimination of bacteria. 4) When bactericidal antibiotics were used, administration twice a day in half dosis gave better results compared with the full dosis once a day. 5) This experimental model of osteomyelitis proved quite useful for quantitative analysis of the effects of antibiotics, which would be applicable as a good method for evaluation of antibiotics to be developed in the future.     

A single dose of endotoxin increases intestinal permeability in healthy humans

To investigate the effects of endotoxin on gut barrier function, we performed paired studies of intestinal permeability in healthy humans (N = 12) receiving intravenous Escherichia coli endotoxin (4 ng/kg) or 0.9% saline solution. Two nonmetabolizable sugars, lactulose and mannitol, which are standard permeability markers, were administered orally, 30 minutes before and 120 minutes after the test injection. The 12-hour urinary excretion of these substances after endotoxin/saline solution administration was used to quantitate intestinal permeability. After endotoxin administration systemic absorption and excretion of lactulose increased almost two-fold (mean +/- SEM, 263 +/- 36 mumol per 12 hours vs 145 +/- 19 mumol per 12 hours during saline studies). Similar but less marked alterations in mannitol absorption and excretion occurred after endotoxin injection (5.7 +/- 0.3 mmol per 12 hours vs 4.9 +/- 0.3 mmol per 12 hours). When individual 12-hour lactulose excretion after endotoxin administration was related to the magnitude of systemic responses, a significant relationship occurred between lactulose excretion and elaboration of norepinephrine and between lactulose excretion and minimum white blood cell count. These data suggest that a brief exposure to circulating endotoxin increases the permeability of the normal gut. These observations are consistent with the hypothesis that during critical illness, prolonged or repeated exposure to systemic endotoxins or associated cytokines may significantly compromise the integrity of the gastrointestinal mucosal barrier.     

The elution of colistimethate sodium from polymethylmethacrylate and calcium phosphate cement beads

Gram-negative bacilli resistance to all antibiotics, except for colistimethate sodium (CMS), is an emerging healthcare concern. Incorporating CMS into orthopedic cement to treat bone and soft-tissue infections due to these bacteria is attractive, but the data regarding the elution of CMS from cement are conflicting. The in vitro analysis of the elution of CMS from polymethylmethacrylate (PMMA) and calcium phosphate (CP) cement beads is reported. PMMA and CP beads containing CMS were incubated in phosphate-buffered saline and the eluate sampled at sequential time points. The inhibition of the growth of a strain of Acinetobacter baumannii complex by the eluate was measured by disk diffusion and microbroth dilution assays, and the presence of CMS in the eluate was measured by mass spectroscopy. Bacterial growth was inhibited by the eluate from both PMMA and CP beads. Mass spectroscopy demonstrated greater elution of CMS from CP beads than PMMA beads. The dose of CMS in PMMA beads was limited by failure of bead integrity. CMS elutes from both CP and PMMA beads in amounts sufficient to inhibit bacterial growth in vitro. The clinical implications of these findings require further study.     

Antibacterial activity of antibiotics in acrylic bone cement.

The release of various penicillins and other antibiotics from two brands of polymerised bone cement has been studied in vitro and in vivo in mice. Bone cement plugs containing antibiotics demonstrated antibacterial activity as a result of diffusion of antibiotic from the plugs into the surrounding medium. With all antibiotics tested, from 2-5 to 10 per cent of the antibiotic in the cement was released in vitro in active form within twenty-four hours. Most of the activity appeared within three hours of the start of the test, but in some cases low levels of activity were detected after four days. Antibiotic cement plugs implanted in mice and rats produced low concentrations of antibiotic in the blood up to two hours after implantation, but activity was seldom detected subsequently. In general, penicillins and non-penicillin antibiotics showed similar diffusion characteristics, and the pattern of release in vitro and in vivo was consistent with the leaching of antibiotic from, or near, the surface of the bone cement.     

Elution of vancomycin, daptomycin, and amikacin from acrylic bone cement.

Increasing antibiotic resistance of bacteria that infect prosthetic joints has stimulated interest in the incorporation of more effective antimicrobial agents into polymethylmethacrylate (PMMA). Vancomycin and daptomycin are effective against nearly all staphylococci and streptococci, and amikacin has a broader spectrum against gram-negative bacilli than do other aminoglycosides such as gentamicin. These three antibiotics maintained bioactivity after incorporation into several commonly used preparations of PMMA and eluted readily into the surrounding medium. Preparing PMMA under negative atmospheric pressure, which decreases porosity, caused a 50% reduction in antibiotic release; the addition of 25% dextran, which increases porosity, greatly facilitated elution of these antibiotics. Based on their broad antibacterial effect against gram-positive and gram-negative bacteria, inclusion of vancomycin and amikacin in PMMA merits clinical study. The addition of these antibiotics to PMMA, together with dextran, may be applicable when structural integrity is unimportant but a substantial local antimicrobial effect is desired, such as in the use of antibiotic-containing beads to treat osteomyelitis.     

Serial changes in the rate of proteoglycan synthesis after chemonucleolysis of rabbit intervertebral discs.

STUDY DESIGN: Serial changes in the rate of proteoglycan synthesis in rabbit discs after chemonucleolytic treatment with chymopapain and chondroitinase ABC were measured using an in vitro method. OBJECTIVES: To determine the retained ability of the intervertebral disc to synthesize proteoglycans after chemonucleolytic treatment. SUMMARY OF BACKGROUND DATA: Most previous studies describe radiologic and histologic changes that occur after chemonucleolytic treatment. However, in humans it is not clear whether reconstitution of the disc space with normal nucleus proteoglycans can occur with time. METHODS: Twenty-five rabbits were treated with chymopapain (10 units/0.1 mL/disc) and chondroitinase ABC (5 units/0.1 mL/disc) by intradisc injection. Five rabbits were killed at each interval, 1, 2, 4, 8 and 12 weeks after injection. Radiologic changes in the disc height were noted, and the rate of proteoglycan synthesis was determined biochemically. RESULTS: After injection, no significant recovery of disc height was seen in either enzyme group after the initial disc narrowing. The average rate of proteoglycan synthesis in control rabbit intervertebral discs, those which had not been surgically treated, was 27.1 (x 10(-6) mmols sulphate/hour/dry weight). Twelve weeks after injection, the values were 21.6 in the saline group, 8.9 in the chondroitinase ABC group, and 8.2 in the chymopapain group. CONCLUSIONS: Doses within the therapeutic range can damage disc cells, at least in the rabbit, so that proteoglycan synthesis declined to 30% of control rates, and no significant recovery of disc height was observed.     

Early antibiotics and debridement independently reduce infection in an open fracture model

Most animal studies indicate that early irrigation and debridement reduce infection after an open fracture. Unfortunately, these studies often do not involve antibiotics. Clinical studies indicate that the timing of initial debridement does not affect the rate of infection but these studies are observational and fraught with confounding variables. The purpose of this study was to control these variables using an animal model incorporating systemic antibiotics and surgical treatment. We used a rat femur model with a defect which was contaminated with Staphylococcus aureus and treated with a three-day course of systemic cefazolin (5 mg/kg 12-hourly) and debridement and irrigation, both of which were initiated independently at two, six and 24?hour time points. After 14 days the bone and hardware were harvested for separate microbiological analysis. No animal that received antibiotics and surgery two hours after injury had detectable bacteria. When antibiotics were started at two hours, a delay in surgical treatment from two to six hours significantly increased the development of infection (p = 0.047). However, delaying surgery to 24 hours increase the rate of infection, but not significantly (p = 0.054). The timing of antibiotics had a more significant effect on the proportion of positive samples than earlier surgery. Delaying antibiotics to six or 24 hours had a profoundly detrimental effect on the infection rate regardless of the timing of surgery. These findings are consistent with the concept that bacteria progress from a vulnerable planktonic form to a treatment-resistant biofilm.     

Rapid release of gentamicin from collagen sponge. In vitro comparison with plastic beads

The gentamicin-containing collagen sponge is a new product intended for local application in bone and soft-tissue infections. The release of gentamicin from the collagen sponges was compared in vitro to that from polymethyl-methacrylate (PMMA) beads. A static and kinetic experimental design was used. In the static model, pieces of collagen sponge or PMMA beads were added to 20 mL of distilled water, and during the following hours the gentamicin concentrations in the water were repeatedly measured. This simple model was extended to the kinetic model as the released gentamicin was removed from the water exponentially by means of an infusion-withdrawal pump. The gentamicin was released from the carrier substances with increasing half lives. During the first 4 hours, the half life increased from 0.2 to 1.5 hours for the collagen sponge and from 3 to 78 hours for the PMMA beads. After 1.5 hours, 95 percent of the gentamicin was released from the sponges, whereas only 8 percent was released from the beads.     

In vitro elution of ciprofloxacin from polymethylmethacrylate cement beads

The use of antibiotic-impregnated polymethylmethacrylate (PMMA) cement beads for the local delivery of antibiotics in the treatment of chronic osteomyelitis has become a standard orthopaedic practice. The increasing resistance to antibiotics of organisms associated with orthopaedic infections has led to interest in the incorporation of more effective antibiotics into PMMA cement. Ciprofloxacin, a synthetic fluoroquinolone, is potent against a broad spectrum of bacteria associated with osteomyelitis. In this study, strands of ciprofloxacin-impregnated PMMA cement beads were prepared with 0.2, 0.5, or 1.0 g of ciprofloxacin per 40 g of PMMA. The elution concentration of ciprofloxacin was at least 1–2 mcg/ml for 7 days (0.2 g), 30 days (0.5 g), and 42 days (1.0 g). This concentration is equivalent to the minimum inhibitory concentration for the common pathogens associated with osteomyelitis. Concurrent systemic and local ciprofloxacin therapy appears to be a method for the treatment of chronic osteomyelitis.     

Contamination of polyethylene cups with polymethyl methacrylate particles: an experimental study

The articulating surfaces of 6 ultra-high molecular weight polyethylene cups were exposed to curing polymethyl methacrylate (PMMA) bone-cement and examined with scanning electron microscopy and laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS). Three of the cups were exposed to blood and bone-cement, and the rest were exposed to bone-cement only. After removal of the bone-cement bulk, PMMA particles were found and identified in all 6 cups. The particles were verified by identifying zirconium with energy-dispersive x-ray fluorescence spectroscopy in 5 cups and with LA-ICPMS in 1 cup. The degree of surface contamination was estimated with LA-ICPMS. The number of zirconium-containing particles detected was on average 10 to 20/mm2. PMMA bone-cement left in polyethylene cups during polymerization can contaminate the articulating surface with adherent PMMA particles.     

Effective bactericidal activity of tobramycin and vancomycin eluted from acrylic bone cement

We studied the bioactivity of vancomycin and tobramycin eluted from methylmethacrylate bone cement. Aliquots of the drainage were obtained at 1, 6, 12 and 24 hours following total hip prosthetic implantation with vancomycin-tobramycin-loaded cement in 3 patients. The samples were analyzed with fluorescence polarization immunoassay and bioassay, using group B streptococcus for vancomycin and Escherichia coli for tobramycin. These bacteria were selected due to the effectiveness of vancomycin and poor effectiveness of tobramycin against group B streptococcus and conversely with E. coli. The immunodetection of vancomycin averaged 14 (1 hour), 9 (6 hours), 10 (12 hours) and 11 microg/mL (24 hours). The bioassay averaged 47, 36, 79 and 41 microg/mL (p = 0.03). The immunodetection of tobramycin averaged 43, 21, 18 and 14 microg/mL; and bioassay 30, 15, 15 and 12 microg/mL (p = 0.1). Both antibiotics eluted with a highly effective bactericidal activity. Our findings indicate that the presence of tobramycin has a synergistic-like effect on the bactericidal activity of vancomycin, which has not been previously reported. We recommend a combination of vancomycin and tobramycin with cement for the treatment of orthopedic infections caused by gram-positive organisms.     

内毒素预处理对内毒素血症大鼠肺的作用及机制探讨

目的 观察内毒素预处理对内毒素血症大鼠肺的作用及其机制。方法 将雄性Wistar大鼠84只随机分为7组：生理盐水(NS)组,内毒素脂多糖(LPS)2h、4h、6h组和LPS预处理2h、4h、6h组,每组12只。LPS预处理各组大鼠经腹腔注射LPS0．25mg／kg,24h后再注射LPS0．5mg/kg,NS组和LPS各组在上述时间均给予等容量NS;第2次腹腔注射72h后,LPS各组和LPS预处理各组大鼠经静脉注入(静注)LPS 10mg／kg,NS组注射等量NS。NS组在静注NS后6h,LPS2h、4h、6h组和LPS预处理2h、4h、6h组在静注LPS后2、4、6h时各取6只大鼠取血,行血气分析;取左侧肺组织检测细胞间黏附分子-1(ICAM-1)mRNA及抑制性κB-α(IκB-α)蛋白表达;计数右肺支气管肺泡灌洗液(BALF)中白细胞数,测蛋白含量。上述7组另取6只大鼠,在上述相同时点取全肺,计算肺体指数,测定髓过氧化酶(MPO)。结果 LPS各组大鼠较NS组大鼠肺体指数、BALF中白细胞数和蛋白及肺组织MPO含量均增加,氧分压和HCO3^-下降;而LPS预处理各组大鼠上述各指标变化明显减轻。肺组织ICAM-1 mRNA在LPS2h、4h和6h组表达递增,而在LPS预处理各组表达显著减少;LPS2h组肺组织IκB-α蛋白表达较NS组减少,而LPS预处理2h组较LPS2h组表达增加。结论 内毒素预处理可防止内毒素血症时的肺损伤,可能与内毒素预处理使肺组织IκB-α蛋白生成增加和(或)消耗减少有关。     

The compressive properties of bone cements containing large doses of antibiotics

The addition of large amounts of antibiotics to bone cement provides a convenient local delivery, but may influence the compressive properties of the cement. Flucloxacillin and vancomycin were added to Simplex P (Stryker, Limerick, Ireland) and VersaBond (Smith & Nephew) cements. Tripling the antibiotic dose from 2 to 6 g had little effect on the static compressive properties 24 hours after curing. After 4 weeks in phosphate-buffered saline, there was marked decrease in properties with the addition of antibiotics. Compressive strength of cements with 6 g of antibiotic was reduced to near or below the ASTM and ISO minimum of 70 MPa after 4 weeks in phosphate-buffered saline. Microcomputer tomography revealed increased porosity and clumping of the radiopacifier with the addition of antibiotics.