In-vitro activity of polyhexanide alone and in combination with antibiotics against Staphylococcus aureus.

BACKGROUND: The resistance of Staphylococcus aureus is increasing, not only to antibiotics but also to antiseptics. AIM: To investigate the activity of the antiseptic polyhexanide and several antibiotics against clinical isolates of meticillin-susceptible and meticillin-resistant Staphylococcus aureus (MSSA and MRSA, respectively). Polyhexanide was tested alone and in combination with oxacillin, penicillin G, ampicillin, cefazolin, cefuroxime, imipenem, gentamicin, erythromycin, doxycycline, levoflocaxin, linezolid and vancomycin. METHODS: Fifty MSSA and 50 MRSA strains, including one vancomycin-intermediate (VISA) strain, were tested. All strains were typed by pulsed-field gel electrophoresis (PFGE) to exclude testing of clonal isolates. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined using the serial broth microdilution technique according to DIN 58940. Combinations of polyhexanide and different antibiotics were investigated using the checkerboard technique. FINDINGS: Polyhexanide MICs and MBCs in the range of 0.5-2mg/L were found for both MSSA and MRSA, and the VISA strain had MIC and MBC values of 2mg/L. All isolates were regarded as susceptible to polyhexanide, and no antagonism was observed between polyhexanide and the tested antibiotics. Synergism between polyhexanide and some bacteriostatic antibiotics (erythromycin, doxycycline and linezolid) was found for some strains. CONCLUSIONS: Polyhexanide appears to be suitable for the topical treatment of S. aureus alone and in combination with antibiotics.

Activity of the antiseptic polyhexanide against meticillin-susceptible and meticillin-resistant Staphylococcus aureus.

Staphylococcus aureus is one of the most important pathogens, with increasing emergence of meticillin-resistant S. aureus (MRSA) strains. This is associated not only with multiresistance to antibiotics but also with increasing resistance to topical antibiotics and antiseptics. As the antiseptic polyhexanide has only a low risk of emergence of resistant strains, the aim of the study was to obtain data on the sensitivity of S. aureus towards polyhexanide. The effect of polyhexanide was tested against 80 meticillin-susceptible S. aureus (MSSA) and 80 MRSA strains from sporadic cases as well as against 6 MRSA outbreak strains. The clonal diversity of the 166 strains was proven by pulsed-field gel electrophoresis (PFGE). Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined by the serial broth microdilution technique according to DIN 58940. Time-kill studies were performed for reference strains MSSA ATCC 29213 and MRSA ATCC 33591. MICs and MBCs in the range of 0.5-2mg/L were found. According to a created epidemiological cut-off (ECOFF) value of 4mg/L, all strains were regarded as susceptible to polyhexanide, including MRSA epidemic strains and MSSA and MRSA sporadic strains with various antibiotic susceptibility patterns. Addition of up to 4% albumin to the test medium did not change the MICs and MBCs. Time-kill studies showed reduction rates of 4log10CFU/mL for 200mg/L and 5log10CFU/mL for 400mg/L polyhexanide within 5-30min. It is concluded that polyhexanide is suitable for topical eradication of S. aureus.

[Filling of metaphyseal defects with nanocrystalline hydroxyapatite (Ostim) for fractures of the radius]. / Verwendung von nanokristallinem Hydroxyapatit (Ostim) bei der Versorgung von Radiusfrakturen.

AIM OF THE STUDY: In this study, innovative bone replacement material was tested after complicated metaphyseal radius fractures with the affected joints. MATERIAL AND METHODS: In all, 11 C 2, 11 C 3 and 3 A 3 radius fractures were treated by surgery combining an angularly stable palmar plate osteosynthesis with defect filling using nanocrystalline hydroxyapatite. Examinations were conducted preoperatively and postoperatively after 4 weeks, 12 weeks and 9-12 months. RESULTS: After 10.5+/-1.4 months, inclination angles of 8.7+/-1.8 degrees (dorsopalmar) and 18.8+/-2.9 degrees (radioulnar) were measured at the treated fractures, the ulnar drift was 0.6+/-1.8 mm. According to the Gartland/Werley scale, 10 therapeutic results were considered "excellent", 12 "good" and 3 "fair". CONCLUSION: An angularly stable plate osteosynthesis with metaphyseal defect filling using nanocrystalline hydroxyapatite for the treatment of A 3, C 2 and C 3 radius fractures showed satisfactory radiological and clinical results.

[In vitro studies on various PMMA bone cements: a first comparison of new materials for arthroplasty]. / In-vitro-Untersuchung unterschiedlicher PMMA-Knochenzemente--ein erster Vergleich neuer Materialien für die Endoprothetik.

AIM: Two clinically established PMMA bone cements (Refobacin Palacos R and Palacos R + G) and two newer cements not yet in widespread clinical use (Refobacin Bone Cement R and SmartSet GHV) were tested in vitro for practically relevant differences. METHODS: The tests included chemical analyses, handling properties and testing according to the ISO standard for PMMA bone cements. RESULTS: The results obtained indicate clearly that the copolymers used in Refobacin Bone Cement R and SmartSet GHV differ from those used in the Palacos cements. There were also significant differences in viscosity behaviour and waiting time (p < 0.01 for Palacos cements versus Refobacin Bone Cement R) as an expression of different handling properties. The hardening times under ISO 5833 conditions also differed significantly (p < 0.01 and p < 0.05 for Palacos cements compared with Refobacin Bone Cement R and p < 0.01 for Refobacin Bone Cement R compared with SmartSet GHV). CONCLUSION: In view of these differences in material properties, the clinical data from long-term use of the bone cements Refobacin Palacos R and Palacos R + G cannot be extrapolated to the newly developed PMMA cements Refobacin Bone Cement R and Smart GHV. Before broad clinical use of these cements, prospective clinical studies using RSA or DEXA and, as a second step, statistically powerful prospective comparative studies should be performed. Until these data are available, patients in whom Refobacin Bone Cement R and SmartSet GHV are used should be informed that the material employed deviates from the standard procedures for cemented joint replacement in the Scandinavian arthroplasty registers and that the long-term consequences cannot, in the final instance, be foreseen. This is essential in order to avoid later malpractice claims on the grounds of inadequate information.

Open reduction and palmar plate-osteosynthesis in combination with a nanocrystalline hydroxyapatite spacer in the treatment of comminuted fractures of the distal radius.

In a prospective study, we used the nanocrystalline hydroxyapatite paste Ostim (Osartis, Obernburg, Germany) in combination with a palmar plate to treat comminuted radius fractures with a metaphyseal and articular component in order to examine the clinical use of Ostim as a bone substitute. Twenty-one patients with 22 radius fractures of AO types C2 and C3 were included in the study. The measurements, taken 10.2+/-1.3 months after the initial treatment, revealed a dorsopalmar tilt of 8.8+/-3.7 degrees , a radioulnar inclination of 18.8+/-2.8 degrees and an ulnar variance of 0.8+/-1.8mm. According to the Gartland and Werley evaluation, eight of the treated fractures attained an excellent, 11 a good and the remaining three a fair result. The study demonstrates that Ostim, in combination with angularly stable osteosynthesis, can be used as an acceptable bone substitute for the treatment of type C2 and C3 radial fractures.

Low molecular weight heparin-induced skin necrosis-a systematic review.

BACKGROUND: Low molecular weight heparins (LMWHs) are currently used as a standard for anti-thrombotic therapy. Skin necrosis caused by LMWH is a rare and probably under-reported complication. The aim of our systematic review is to analyse the present literature for cases of LMWH-induced skin necrosis, emphasising the pathogenesis, clinical pattern, and management of this rare side effect. METHODS: We performed a Medline literature search (PubMed database) and manual cross-referencing to identify all articles related to LMWH-induced skin necrosis. Data were analysed for type of LMWH used, time until skin necrosis occurred, localisation, size, laboratory findings, switch anticoagulant, complications, and outcome. Additionally, the case of a patient from our hospital is presented. RESULTS: We included a total of 20 articles (21 cases) reporting on LMWH-induced skin necrosis. Skin necrosis occurred locally and distant from the injection site. Heparin-induced antibodies were frequently observed (positive 9/11 articles, negative 2/11). However, severe thrombocytopenia (platelet count <100,000 cells/ml) occurred in only four cases, while platelet count remained normal in 50% of the cases. After patients had been switched to other anti-thrombotic drugs, the clinical course was usually benign; however, reconstructive surgery was necessary in two cases. CONCLUSION: LMWH-induced skin necrosis may occur as part of the heparin-induced thrombocytopenia (HIT) syndrome, but other pathomechanisms, including allergic reactions and local trauma, may also be involved. When HIT is excluded, unfractionated heparin is a safe switch anticoagulant. Otherwise, non-heparin preparations such as hirudin or fondaparinux should be preferred.

Effect of low molecular weight heparin (dalteparin) and fondaparinux (Arixtra) on human osteoblasts in vitro.

BACKGROUND: The prolonged administration of heparin for prevention and treatment of venous thromboembolism has been associated with a risk of heparin-induced osteoporosis. Fondaparinux is a new antithrombotic drug that specifically inhibits factor Xa. Because of the known interactions of other antithrombotic agents with bone remodelling, the effects of fondaparinux on human osteoblasts were analysed in vitro. METHODS: Primary human osteoblast cell cultures were incubated with either the low molecular weight heparin dalteparin at concentrations of 30, 300 and 900 microg/ml or with fondaparinux at concentrations of 25, 50, 100, 150, 200 and 250 microg/ml. Cellular proliferation rate and protein synthesis were measured. Expression of genes encoding osteocalcin, collagen type I and alkaline phosphatase was examined by reverse transcriptase-polymerase chain reaction. RESULTS: Incubation with dalteparin led to a significant, dose-dependent inhibition of osteoblast proliferation, inhibition of protein synthesis, and inhibited expression of phenotype markers (osteocalcin and alkaline phosphatase genes) after 3 and 7 days. No inhibitory effects were observed in the fondaparinux-treated cells. CONCLUSION: Fondaparinux did not inhibit osteoblast proliferation in vitro and may reduce the risk of heparin-induced osteoporosis associated with long-term heparin administration.

[The evaluation of balloonkyphoplasty for osteoporotic vertebral fractures. An interdisciplinary concept]. / Die Wertigkeit der Ballonkyphoplastie bei der osteoporotischen Wirbelkörperfraktur. Ein interdisziplinäres Konzept.

BACKGROUND DATA: Patients with osteoporotic vertebral compression fractures frequently complain of pain and a loss of function and mobility. Such fractures are associated with an increased mortality. The common treatment with bed rest, bracing or osteosynthesis does not lead to satisfying results. With two new surgical techniques, vertebroplasty and kyphoplasty, an internal stabilisation of osteoporotic vertebral fractures is possible. METHODS: All patients were treated by kyphoplasty. With a minimal invasive dorsal approach, an inflatable bone tamp is placed in the fractured vertebral body. This tamp can restore the vertebral body height and create a cavity, which is filled with bone cement under low pressure. The advantage of kyphoplasty compared to vertebroplasty is the restoration of the vertebral height and a decreased cement leakage rate. We performed a prospective, interdisciplinary study with a follow-up of 12 months. We treated 192 vertebral fractures in 102 patients. Augmentation was performed with polymethylmethacrylate in 138 cases and with a new injectable calcium phosphate-cement in 54 vertebral bodies. Outcome data were obtained with two different spine-scores and by the radiomorphometric evaluation of x-rays before and after treatment. RESULTS: We noticed a significant improvement in pain and function in 89% of the patients. All patients showed a regain of vertebral height of on average 17%. In 7% of all treated vertebral bodies, we noticed cement leakage, which was, however, far below the rates published for vertebroplasty (20-70%). There were two complications, bleeding due to an unknown coagulopathy and a violation of the myelon by malpunction. CONCLUSION: Kyphoplasty is a reliable and minimally invasive method for stabilizing fractured osteoporotic vertebral bodies. Improvement of pain and function and a regain in height of the treated vertebral body can be accomplished.

[Balloon kyphoplasty of vertebral compression fractures with a new calcium phosphate cement]. / Augmentation von Wirbelkörperfrakturen mit einem neuen Calciumphosphat-Zement nach Ballon-Kyphoplastie.

QUESTION: Can the same levels of pain reduction and increase in function be achieved in kyphoplasty procedures with Calcibon as with polymethylmethacrylate (PMMA) cement? PATIENTS AND METHODS: In a prospective, interdisciplinary single-center study, 99 patients (173 vertebral fractures) were treated with kyphoplasty. Augmentation was performed with PMMA in 66 cases (127 vertebral bodies) and with Calcibon in 33 patients (46 vertebral bodies). Outcome data were obtained with a VAS spine score and by radiomorphometric evaluation of X-rays before and after treatment. RESULTS: Pain and function improved in 87% of the patients; an average of 16% of the lost vertebral height was regained. A 9% cement leakage rate was observed with PMMA and 10% with Calcibon. There was no significant difference in pain reduction and radiomorphometric evaluation between the two techniques. CONCLUSION: Kyphoplasty is a reliable, minimally invasive method to stabilize fractured vertebral bodies. Augmentation with Calcibon improves pain and function and enables the treated vertebral body to regain of height.

Osteoblast growth inhibition by unfractionated heparin and by low molecular weight heparins: an in-vitro investigation.

Osteoporosis is a rare but potentially severe complication under high-dose, long-term unfractionated heparin therapy. Low-molecular-weight heparins (LMWHs) have gained increased importance in antithrombotic therapy over the past decade. Whether this heterogeneous group of drugs carries a comparable risk of osteoporosis in long-term application is unknown. In a standardized in vitro model, the effects of 4 different low-molecular-weight heparins (nadroparin, enoxaparin, dalteparin, certoparin) on osteoblast growth were studied at the same dose (50 microg/mL). As control, the effect of unfractionated heparin (Liquemin) was tested on human osteoblasts in vitro at an equal dose. Human osteoblast cell cultures were incubated with equal doses of the heparins, and cell concentrations were measured after 48 and 96 hours. In addition, a fluorescence assay was performed to detect potential cytotoxic effect of heparins on bone cells. In comparison to control groups of non-incubated cell cultures, LMWHs caused a significant inhibition of osteoblast growth (p<0.05). Therefore, the risk of osteoporosis under long-term therapy with high doses of LMWHs cannot be excluded and should be further evaluated in clinical trials.

[Influence of unfractionated and low-molecular-weight heparin on bone healing: an animal model]. / Beeinflussung der Knochenheilung durch unfraktionierte und niedermolekulare Heparine: eine tierexperimentelle Studie.

The inhibition of bone metabolism and development of osteoporosis under treatment with unfractionated heparins (UFH) have been discussed, whereas the pathomechanism and the question of whether low-molecular-weight heparins (LMWH) have an influence on bone healing as well remain unclear. In a blinded trial, three groups of ten rabbits received subcutaneous injections of an unfractionated heparin (sodium heparin), a low-molecular-weight heparin (certoparin), or normal saline over a period of 6 weeks after a standardized bone defect had been applied to both femur condyles. Healing of the defects was investigated in a depth of 1 and 2 mm and the remaining volume of the bone defects was measured. After therapy with UFH, the volume of the defects remained significantly larger in a depth of 1 mm (UFH/control: p<0.001; UFH/LMWH: p<0.005) and in the total depth (UFH/control: p<0.005; UFH/LMWH: p<0.025). After therapy with LMWH, there was no inhibition of defect healing (p>0.05). This study shows that the influence of heparins on fracture healing can be reduced significantly by using LMWH instead of UFH.

[Mechanical stimulation of venous blood flow in below-the-knee plaster cast]. / Mechanische Förderung des venösen Rückflusses im Unterschenkelgipsverband.

Physical methods became recently more important as an alternative to anticoagulation for prophylaxis of thromboembolism and were studied for their efficacy. The AV-impulse-system proved efficient in reducing thromboembolic complications in patients undergoing hip surgery by increasing the return of venous blood in the deep veins of the leg. In a preclinical trial we studied the influence of the AV-impulse-system and of active forefoot movement on venous blood return in 12 lower extremities of 6 healthy individuals immobilized in below the knee plaster casts. Our results show a significant increase in venous blood flow caused by the AV-impulse-system (p < 0.05) and by active forefoot movements (p < 0.05). Prevention of thromboembolic complications in trauma and orthopaedic patients immobilized in plaster cast seems possible by using the AV-impulse-system which significantly increases the venous blood flow independent from patient compliance.

A new bioresorbable polymer for screw augmentation in the osteosynthesis of osteoporotic cancellous bone: a biomechanical evaluation.

The aim of the study was to assess the mechanical efficacy of a new resorbable polymer developed on the basis of alkylene bis(dilactoyl)-methacrylate to improve the anchorage of osteosynthesis material in cancellous bone. Cancellous bone screws were inserted in bovine as well as in human vertebrae and human femoral condyles and were augmented with the new polymer or polymethylmethacrylate (PMMA), respectively. Nonaugmented screws were used as controls. A removal torque test, a dynamic fatigue test, and a pullout test were performed. Augmentation with the new polymer increased the removal torque by 84% in human femoral bone. In the dynamic fatigue test of bovine vertebrae, the removal torque after cyclic loading was 115% higher for the new polymer compared to the nonaugmented controls. In the human vertebrae, the reinforcement with the new polymer increased the removal torque after dynamic loading by 114%. The augmentation with the new polymer increased the pullout force by 88% in bovine vertebrae and by 118% in human vertebrae in comparison to nonaugmented screws. It was concluded that augmentation by the new resorbable polymer significantly enhanced the anchorage of bone screws in cancellous bone. The mechanical efficiency of the new polymer was comparable to that of PMMA cement.

[Effectiveness of an improved antiseptic in treatment of contaminated soft tissue wounds]. / Wirksamkeit eines neuartigen Antisepticum in der Behandlung kontaminierter Weichteilwunden.

A novel antiseptic biguanide has been shown to be more bactericidal and tissue compatible in vitro than other antiseptics. In our controlled, prospective and randomized double-blind study on patients with bacteria-contaminated wound types 2-4, one group (n = 45) was treated with humid cotton swab dressings of 0.2% Lavasept solution compared with Ringer solution (n = 35). No deterioration of wound healing was observed in either group. Lavasept treatment resulted in faster and significant reduction of gram-positive germs. The tissue compatibility of Lavasept was evaluated as significantly better than Ringer solution.

Prevention of deep venous thrombosis associated with superficial thrombophlebitis of the leg by early saphenous vein ligation.

BACKGROUND: Thrombophlebitis of the superficial veins of the leg used to be regarded as a mild and uncomplicated disease, particularly in German speaking countries. PATIENTS AND METHODS: In a retrospective clinical study from 6/91 until 12/96 we followed the progress of all patients (n = 398) with thrombophlebitis of the vena saphena magna or parva. Parameters of interest were: the incidence of concomitant deep vein thrombosis and subsequent pulmonary embolism. All patients underwent colour duplex scanning, most of them repeatedly. In cases of proven ascending superficial thrombosis, or involvement of the saphenofemoral junction, proximal saphenous vein ligation was performed (n = 56, 49 vena saphena magna and 7 vena saphena parva). Among these groups, there were 10 patients with malignant disease (18%), ten with a history of thrombosis (18%), another five comprised diabetes, recent major surgery and organ transplantation. RESULTS: In 56 operations we found free-floating thrombi 6x (11%), 19x the sapheno-femoral junction was involved (33%), 24x the saphenous vein close to the junction (43%). Three patients develop deep vein thrombosis, despite surgery (0.75% of all and 5% of the operated cases). 2 patients suffered from (non-lethal) pulmonary embolism (0.5% and 3.5%, respectively). One embolism occurred before vein ligation. Perioperative morbidity amounted to 8.5% (superficial wound infection, hematoma). CONCLUSION: Venous ligation is probably effective in reducing the rate of fatal pulmonary embolism.

Implantable vascular access systems: experience in 1500 patients with totally implanted central venous port systems.

Totally implantable venous access systems are widely used, but large-scale studies evaluating these systems are lacking. In this study 1500 patients (719 male, 781 female) with an average age of 49 years (15-86 years) were fitted with subcutaneously implanted venous access systems, in most cases for long-term chemotherapy. All patients were observed until removal of the system, death, or the end of treatment. A retrospective analysis showed an average catheter life of 284 patient-days. A total of 1308 (87%) of the patients had no implant-related complications. Catheter infections occurred in 3.2% of the patients and catheter thromboses in 2.5%. Rarer complications, such as catheter malfunction, migration of the catheter, skin necrosis, catheter fracture, catheter disconnection, and pneumothorax, occurred in another 4.3% of the patients. The complications led to explantation of 178 access systems (11.9%). There was a significant difference (p < 0.05) between the low rate of infections and other complications in the group of patients with solid tumors (2% and 4%, respectively) and the rate in patients with hematologic diseases (6% and 8%, respectively). This study confirms the safety and convenience of using totally implantable venous access systems in patients on long-term chemotherapy.

[Causation and injury pattern in in-line skating]. / Unfallursachen und Verletzungsmuster beim In-line-Skating.

Accident proceedings and injuries were investigated in a consecutive series of 70 patients (65.2% male, 34.8% female, age: 18 +/- 9 years) presented to the emergency department after in-line skate falls. 52.7% wore no protective equipment. 41.8% used knee pads, 27.3% wrist guards, 12.7% elbow pads, and 5.5% each helmets and gloves. The most common cause of fall were obstacles/irregularities (32.7%) on a dry and plain surface. The upper extremity (67.9%) and the head (12.8%) were the most commonly injured body parts. 47.8% in-line skaters sustained fractures. The distal radius (51.5%) was most commonly injured body parts. 47.8% in-line skaters sustained fractures. The distal radius (51.5%) was most commonly fractured. Injuries to novice skaters were more often severe. Advanced freestyle and jumping in-line skaters sustained even injuries of the trunk. Life-threatening injuries of the abdomen and the head may occur. The use of a complete personal protection equipment is recommended.