Leif Persen

Cancellous bone as an antibiotic carrier.

We compared the release characteristics of antibiotics from in vivo and in vitro processed morselized cancellous bone. The bone was impregnated with 7 antibiotics and compressed into a wire-mesh cylinder. In vitro, the bone was processed by daily transfer of the cylinder with its contents into test tubes with broth. The amount of antibiotic eluted from the bone was measured after 1, 3 and 7 days. In vivo, the cylinder was implanted intramuscularly in the interscapular region in rats. After 1, 3 and 7 days, the cylinder was removed and the amount of antibiotic eluted in broth was measured. The results showed that morselized cancellous bone can act as a carrier of antibiotics in vitro and in vivo. The elution profiles of netilmicin-, vancomycin-, clindamycin- and rifampicin-impregnated cancellous bone processed in vitro and in vivo were similar.

Adsorption and release of antibiotics from morselized cancellous bone. In vitro studies of 8 antibiotics.

We studied the basic release patterns of antibiotics from cancellous bone in vitro. Antibiotic-impregnated bone was compressed into a wire-mesh cylinder and the release of antibiotic was assessed by two different in vitro methods: agar diffusion and broth elution. The zones of inhibition were measured on seeded agar and the amounts of antibiotics released in elution tubes were assessed by a bioassay. The study continued for 21 days with daily transfer of the cylinders. The results indicated that benzylpenicillin, dicloxacillin, cephalotin, netilmicin, clindamycin, vancomycin, ciprofloxacin and rifampicin were adsorbed to cancellous bone in vitro. Compared to broth elution, agar diffusion showed a prolonged period of release, owing to the small amounts of antibiotic leaking out of the cylinder into the agar. The betalactams had antibacterial activity in broth for a shorter time than the other antibiotics. The release patterns of the betalactams were similar, in spite of their differences in thermal stability. Only rifampicin showed a concentration higher than MIC for longer than 21 days.

Cortical allograft as a vehicle for antibiotic delivery

Background Infection can be a devastating complication after implantation of a cortical bone allograft. The allograft could act as a vehicle for local antibiotic prophylaxis. Material and methods We studied the release of antibiotics in vitro from cortical bone allografts impregnated with antibiotics for different periods of time. We also studied whether cortical allografts impregnated with antibiotics could eradicate Staphylococcus aureus from an experimentally infected graft in vivo. In the in vitro study, pieces of cortical bone were impregnated with netilmicin, vancomycin, ciprofloxacin and rifampicin for 1 h, 10 h and 100 h. The antibiotics were eluted into phosphate-buffered saline (PBS) for 7 days, with daily transfer of the bone into fresh PBS. In the in vivo study, cortical allografts impregnated with antibiotics were placed in rats intramuscularly. 10 μL of an S. aureus suspension (0.6 × 105 CFU) was placed in the intramedullary cavity. After 15 days, the allografts were removed and examined for bacterial growth. Results The amount of antibiotics released in vitro was influenced by the time used for antibiotic impregnation of the bone. Allografts impregnated with netilmicin, vancomycin and rifampicin effectively eradicated perioperative contamination with S. aureus in vivo. Interpretation This study shows that a cortical bone allograft would be an effective vehicle for local antibiotic delivery.

A comprehensive microbiological evaluation of fifty-four patients undergoing revision surgery due to prosthetic joint loosening.

The diagnosis of a chronic prosthetic joint infection (PJI) is challenging, and no consensus exists regarding how best to define the criteria required for microbiological identification. A general view is that culture of periprosthetic biopsies suffers from inadequate sensitivity. Recently, molecular analyses have been employed in some studies but the specificity of molecular analyses has been questioned, mainly due to contamination issues. In a prospective study of 54 patients undergoing revision surgery due to prosthetic joint loosening, we focused on two aspects of microbiological diagnosis of chronic PJI. First, by collecting diagnostic specimens in a highly standardized manner, we aimed at investigating the adequacy of various specimens by performing quantitative bacteriological culture. Second, we designed and performed real-time 16S rRNA gene PCR analysis with particular emphasis on minimizing the risk of false-positive PCR results. The specimens analysed included synovial fluid, periprosthetic biopsies from the joint capsule and the interface membrane, and specimens from the surface of the explanted prosthesis rendered accessible by scraping and sonication. No antibiotics were given prior to specimen collection. Based on five diagnostic criteria recently suggested, we identified 18 PJIs, all of which fulfilled the criterion of ≥2 positive cultures of periprosthetic specimens. The rate of culture-positive biopsies from the interface membrane was higher compared to specimens from the joint capsule and synovial fluid, and the interface membrane contained a higher bacterial load. Interpretational criteria were applied to differentiate a true-positive PCR from potential bacterial DNA contamination derived from the reagents used for DNA extraction and amplification. The strategy to minimize the risk of false-positive PCR results was successful as only two PCR results were false-positive out of 216 negative periprosthetic specimens. Although the PCR assays themselves were very sensitive, three patients with low bacterial numbers in periprosthetic specimens tested negative by real-time PCR. This overall lowered sensitivity is most likely due to the reduced specimen volume used for PCR analysis compared to culture and may also be due to interference from human DNA present in tissue specimens. According to the protocol in the present study, 16S rRNA gene real-time PCR did not identify more cases of septic prosthetic loosening than did culture of adequate periprosthetic biopsies.

Release of netilmicin and vancomycin from cancellous bone

First, we studied the effect of the following variables used for netilmicin- and vancomycin-impregnation of cancellous bone: a) antibiotic concentration of the impregnation fluid, b) time used for impregnation, c) pH of the impregnation fluid, d) the degree of bone morselizing and e) antibiotic combination. An increase in the antibiotic concentration of the impregnation fluid increased the amount of antibiotics released from bone. In addition, the amount of vancomycin eluted was also dependent on the time used for impregnation. The fraction of the total amount of netilmicin and vancomycin released after 24 h was 80% and 30%, respectively. More netilmicin and vancomycin were eluted from bone impregnated with antibiotics at pH 7 than the amount eluted from bone impregnated at pH 3. More netilmicin was eluted from fine morselized bone than from coarse morselized bone. By combining netilmicin and vancomycin in the impregnation fluid, the release of vancomycin was reduced. Secondly, we analyzed if the release of antibiotics from bone was complete: 99.9% of the total amount of netilmicin adsorbed to the bone was released by elution during 6 weeks. Finally, after implantation of netilmicin-impregnated bone in rabbit femur condyle, we measured netilmicin and vancomycin in serum: peak serum values of netilmicin were 4.2 (3.7-4.7) mg/L 2-3 h postoperatively.

High local concentrations without systemic adverse effects after impaction of netilmicin-impregnated bone

Background When cancellous bone is impregnated with antibiotics the subsequent release of antibiotics from the bone shows a high early release. Hence, impaction of large amounts of netilmicin-impregnated bone may cause toxic netilmicin values in serum.Patients and methods We studied kidney and otovestibular function after impacting 50 g of netilmicin-impregnated cancellous bone during revision hip or knee arthroplasty in 20 patients. The bone was impacted in the acetabulum (n = 8), proximal femur (n = 9) and distal femur/proximal tibia (n = 3). Serum creatinine concentration was measured and audiometry was performed before and after the operation. Netilmicin concentrations in serum, joint fluid, and in urine were recorded postoperatively at regular intervals. We analyzed pharmacokinetics in two study groups receiving bone impregnated with netilmicin (50 mL), at either 50 mg netilmicin/mL (group I) or 100 mg netilmicin/mL (group II).Results Neither netilmicin-induced renal toxicity, nor otovestibular toxicity was registered. Peak serum netilmicin values in group I and group II were 0.9 (0.5–1.3) mg/L and 1.8 (0.6–4.0) mg/L, respectively (p = 0.04). Peak netilmicin concentrations in wound drainage fluid in group I and group II were 237 (9–647) mg/L and 561 (196–1132) mg/L, respectively (p = 0.01). In both groups, netilmicin was recovered in urine samples for approximately 4 weeks.Interpretation 50 grams of cancellous bone impregnated with 100 mg/mL netilmicin solution was impacted in the hip or knee joint with no adverse effects. Extremely high local concentrations of netilmicin in joint fluid were recorded postoperatively. The use of antibioitic-impregnated cancellous could be an option when performing revision of hip and knee prostheses.

Improved comfort and function of arm prosthesis after implantation of a Humerus-T-Prosthesis in trans-humeral amputees

The use of arm prosthesis in trans-humeral amputees is limited; due to the cone form of the amputation stump. A Humerus-T-Prosthesis was implanted in three patients to create artificial humerus condyles. Two of the patients were successfully rehabilitated with the application of a new type trans-humeral arm prosthesis. This arm prosthesis had a socket which is suspended and stabilized by the humerus and implant only. Traction and rotational stability were secured by adjustable pressure adaptation around the artificial condyles. The third patient developed a pressure wound over the lateral part of the artificial condyle that later healed. He also was subject to a new trauma with a fracture of the ipsilateral scapula and until now has had limited the use of his new arm prosthesis. It was concluded that this new concept for prosthesis fitting of trans-humeral amputees looks promising, but alternative designs of the implant should be tested.

The round thermal jet : undisturbed and in cross-flow

Abstract This paper investigates the round jet exiting from a cut-off circular pipe into still air. It examines the similarity properties in the same way as the senior author has done for the two-dimensional jet. The same type of relations are found as in the previous case. It can be concluded that the free turbulence exhibits no relation with the jets Reynolds number and that consequently the nozzle geometry exclusively governs the flow. The case of a heated circular jet is incorporated in the investigation and the same conclusions are drawn for the temperature field as for the velocity field. The result throws light on the dispute between Taylor and Prandtl regarding the mixing length in the two fields. The second part of the paper examines the similarity properties of the temperature field of the jet when it exits into a cross-flow of different temperature.

Periprosthetic fracture caused by stress shielding after implantation of a femoral condyle endoprosthesis in a transfemoral amputee—a case report

A femoral condyle endoprosthesis (FCE) was implanted in a 48-year-old transfemorally amputated woman with the intention of making the amputation stump fully endbearing (Figure 1). The implant was a customized endoprosthesis of titanium alloy (Scandinavian Customized Prosthesis AS, Trondheim, Norway), based on experience of the Unique Customized Femoral Stem (Aamodt et al. 1999). Cross-sectional CT images were used to retrieve the inner cortical contours of the femoral diaphysis, and the stem was designed to fit closely within the femoral canal (Aamodt et al. 1999). The stem was fully coated with a dual layer of titanium and hydroxyapatite. During implantation, a small fissure occurred at the anterior aspect of the distal part of the femur, which was secured with 2 cerclage wires. There were no other peroperative or postoperative complications. After 6 weeks of unloading, the patient received a new artificial limb with a prosthetic socket that allowed endbearing. At the 12-month follow-up, the patient was using a knee disarticulation socket that terminated below the groin and the tuber ischiadicum. Radiographs showed improved alignment of the amputated leg (Figure 2) and the patient reported only minor stump pain, even with full endbearing. The skin was normal, probably because of the large bearing surface of the artificial condyle (Jensen 1996). Figure 1. Preoperative computer construction of the femoral condyle endoprosthesis (FCE) inside the residual femur. Figure 2. Femoral alignment before and after insertion of the FCE. The patient experienced a minor trauma 24 months after surgery while using the external prosthesis, and radiographs revealed a periprosthetic fracture of the femur. During removal of the stem, considerable periprosthetic bone loss was found at the distal part of the stem. This bone loss had developed gradually, and could be observed on radiographs as early as 6 months after implantation of the FCE (Figure 3). Culture of tissue samples harvested during the reoperation gave no evidence of infection that could explain the bone loss. Radiographs taken 15 months after removal of the FCE showed bone apposition in the distal part of the femur (Figure 3). Figure 3. Gradual bone loss at 6 and 12 months, fracture at 24 months, and bone regeneration after removal of the implant. A. Postoperatively. B. At the 6-month follow-up. C. At the 12-month follow-up. D. Fracture at 24 months. E. Fracture postoperatively. F. 15 ...

Stratified two-phase flow in circular pipes

Abstract The paper discusses the stratified flow of liquid and gas in a circular pipe under the condition that the two components do not react with each other. If mass flow occurs across the interphase the influence of the entrainment of liquid droplets into the gas or the redeposition of them on the walls or on the interphase is accounted for by a lump parameter expressing the integrated effect of this phenomenon. The inclusion of this feature of the flow is shown to have a dramatic effect on the normal depth of the liquid phase under given conditions. Explicit analytical equations for the pressure drop and conditions determining the shape of the interphase including possible ‘hydraulic jumps’ are given. A special feature of the approach is the way in which the variation of the pressure in the liquid phase due to gravity is accounted for. The results in the paper may be used as a basis for experimental evaluation of the integrated shear stress at the interphase.