The effect of external fixator on bone metabolism in patients with open fracture of extremities.

This experiment aimed to explore the influence mechanism of external fixator on open fracture. A total of 128 patients with open tibiofibular fractures were included in this study. The patients were randomly divided into external fixator group (n=64) and control group (n=64) according to the order of admission. Double-blind controlled observation was used. The levels of osteocalcin (BGP), ß-CTX, P1 NP, BALP, including haptoglobin (Hp), ceruloplasmin (CER), serum adrenocorticotropic hormone (ACTH), cortisol (COR), C-reactive protein (CRP), white blood cell (WBC) and interleukin-6 (IL-6) were recorded in different groups. The postoperative VAS score and quality of life were recorded. Log-rank was used to analyze the difference in postoperative adverse reaction rates among different groups. External fixation stent treatment increased BGP, PINP, and BALP expression and decreased ß-CTX, Hp, CER, ACTH, COR, CRP, WBC, and IL-6 levels. Patients in the external fixation stent group had significantly lower VAS score quality of life scores and incidence of adverse events than the control group. External fixation stents protect open fracture patients by promoting bone metabolism.

Extracellular Matrix Applications in the Treatment of Open Fractures With Complex Wounds and Large Soft Tissue Defects.

Use of biologic scaffolds such as extracellular matrix (ECM) is a promising trend in the treatment of complex wounds in orthopedic trauma patients. In this clinical series we describe the technique of the successful application of porcine urinary bladder ECM products in the treatment of open fractures of the extremities with complex wounds and large soft tissue defects. The clinical outcomes demonstrated that even in challenging cases where local flap coverage of bone or neurovascular structures is not possible, sequential xenograft implantation allowed us to achieve a stable soft tissue envelope. Different forms of ECM products are easy to apply in the presence of orthopedic hardware. In certain wounds, complete closure can be achieved even without subsequent skin grafting. We recommend relatively earlier application of xenograft.

Effects of hyperbaric oxygen therapy on open tibial fractures in rabbits after transient seawater immersion.

OBJECTIVE: To explore the effect and mechanism of hyperbaric oxygen (HBO2) therapy of open tibial fractures in rabbits after transient seawater immersion. METHODS: Forty-eight (48) New Zealand rabbits were randomly and averagely divided into an HBO2 therapy group (Group A) and a control group (Group B). All rabbits were subjected to unilateral open tibial fractures, while immersed in artificial seawater (20-22 °C) for three hours prior to debridement and external fixation. Group A was treated with HBO2 at 2 atmospheres absolute (ATA) for 50 minutes once daily for two weeks; Group B received postoperative routine treatments only. The fracture zone in each group was compared by radiological, histological and immunohistochemical examinations. RESULTS: In Group A, bony callus and mature osteocytes without infiltration of inflammatory cells were observed in the fracture zone. Vascular endothelial growth factor (VEGF) was expressed mainly in the cytoplasm of osteoblasts, chondrocytes and osteocytes, and exhibited significant changes at different time points. The gray value of bony callus in Group A was 190.58 ± 7.52; that of Group B was 144 ± 8.11. Difference between the groups was statistically significant (P ⟨ 0.01). The content of malondialdehyde (MDA) in Group A was significantly lower than Group B (P ⟨ 0.01), and the activity of superoxide dismutase (SOD) in Group A was higher than Group B (P ⟨ 0.01) at four weeks. There were no significant differences in MDA content and SOD activity between groups at eight and 12 weeks. CONCLUSIONS: HBO2 treatment of open tibial fractures in seawater can reduce the inflammatory reaction and reperfusion injury, and promote osteocytic proliferation and fracture healing.

Bone penetrance of locally administered vancomycin powder in a rat femur fracture model.

INTRODUCTION: Locally delivered, crystalline vancomycin has been suggested as a potential prophylactic measure against the development of deep and superficial surgical site infection. Clinical expectations regarding the duration and peak of drug concentration in local tissues following administration are unknown. Our goal was to develop concentration vs time curves for locally administered vancomycin powder in a high-energy, open femur fracture rat model in local tissues and to compare that data to two well performed similar, systemic administration studies. METHODS: After approval for animal research, 24 adult Sprague-Dawley rats sustained closed, midshaft femoral fracture under anesthesia. Fractures were caused via blunt guillotine with 750g metal rod dropped 50cm. Injured hindlimbs were surgically opened at fracture to simulate open injury and stabilized using 0.054 Kirschner wires. Vancomycin powder was administered using weight-based protocol (goal: 25mg/kg). Rats were sacrificed in groups of 4 at 4, 8, 24, 48, 72, 96h. Samples harvested included rat-tail venous blood prior to sacrifice, and femoral bone and anterior thigh soft-tissue were harvested post-mortem. High Performance Liquid Chromatography (HPLC) was performed on all samples. RESULTS: Concentration vs. time curves demonstrated that the surrounding soft-tissues demonstrated highest maximum concentration (1.5mg vancomycin/g muscle). Bone reached maximum average of 199µg vancomycin/g femur: approximately 13% of maximal soft-tissue absorption. Plasma reached maximum concentration of 1.8µg/mL plasma. All peaks at t=4h. Within 48h, average muscle vancomycin concentration dropped to 3µg/g muscle (0.2% maximum muscle concentration) and the average bone concentration dropped to 1.9µg/g femur (0.9% maximum bone concentration). Vancomycin was undetectable on all samples at 96h. Comparison to classical animal studies suggest local delivery to bone exceeds that of IV dosing for approximately 48h and may peak near concentrations of 102 multiples. CONCLUSIONS: Locally administered vancomycin provides drug delivery in excess of IV dosing for approximately 48h after intervention. Exponential decay demonstrates rapid removal of drug to near undetectable levels in bone, plasma, and local soft tissue thereafter in a rat model. Local delivery may generate concentrations exceeding that achievable by steady state systemic dosing for 48h.

Myogenic progenitors contribute to open but not closed fracture repair.

BACKGROUND: Bone repair is dependent on the presence of osteocompetent progenitors that are able to differentiate and generate new bone. Muscle is found in close association with orthopaedic injury, however its capacity to make a cellular contribution to bone repair remains ambiguous. We hypothesized that myogenic cells of the MyoD-lineage are able to contribute to bone repair. METHODS: We employed a MyoD-Cre+:Z/AP+ conditional reporter mouse in which all cells of the MyoD-lineage are permanently labeled with a human alkaline phosphatase (hAP) reporter. We tracked the contribution of MyoD-lineage cells in mouse models of tibial bone healing. RESULTS: In the absence of musculoskeletal trauma, MyoD-expressing cells are limited to skeletal muscle and the presence of reporter-positive cells in non-muscle tissues is negligible. In a closed tibial fracture model, there was no significant contribution of hAP+ cells to the healing callus. In contrast, open tibial fractures featuring periosteal stripping and muscle fenestration had up to 50% of hAP+ cells detected in the open fracture callus. At early stages of repair, many hAP+ cells exhibited a chondrocyte morphology, with lesser numbers of osteoblast-like hAP+ cells present at the later stages. Serial sections stained for hAP and type II and type I collagen showed that MyoD-lineage cells were surrounded by cartilaginous or bony matrix, suggestive of a functional role in the repair process. To exclude the prospect that osteoprogenitors spontaneously express MyoD during bone repair, we created a metaphyseal drill hole defect in the tibia. No hAP+ staining was observed in this model suggesting that the expression of MyoD is not a normal event for endogenous osteoprogenitors. CONCLUSIONS: These data document for the first time that muscle cells can play a significant secondary role in bone repair and this knowledge may lead to important translational applications in orthopaedic surgery. Please see related article: http://www.biomedcentral.com/1741-7015/9/136.

Local antibiotic delivery using tailorable chitosan sponges: the future of infection control?

OBJECTIVES: Local antibiotic delivery is a viable and attractive option for preventing infection. Unfortunately, the current options are limited and often necessitate surgical removal. This study evaluates the ability of a biodegradable and biocompatible chitosan sponge to minimize infection by delivering local antibiotics within the wound. METHODS: A complex musculoskeletal wound was created on the hindlimb of goats and contaminated with Pseudomonas aeruginosa (lux) or Staphylococcus aureus (lux) bacteria. These bacteria are genetically engineered to emit photons, allowing for quantification with a photon-counting camera system. The wounds were closed and similarly débrided and irrigated with 9 L normal saline using bulb-syringe irrigation 6 hours after inoculation. Goats were assigned to different treatment groups: a control group with no adjunctive treatment and an experimental group using a chitosan sponge loaded with either amikacin (for wounds contaminated with P. aeruginosa) or vancomycin (for wounds contaminated with S. aureus). The wounds were closed after the procedure and evaluated 48 hours after initial contamination. Serum levels of the antibiotics were also measured at 6, 12, 24, 36, and 42 hours after treatment was initiated. RESULTS: The wounds treated with the antibiotic-loaded chitosan sponge had significantly less bacteria than the untreated wounds (P < 0.05). The highest serum levels were 6 hours after treatment but remained less than 15% of target serum levels for systemic treatment. At study end point, all sponges were between 60% and 100% degraded. CONCLUSIONS: The chitosan sponges are effective delivering the antibiotic and reducing the bacteria within the wounds.

Effect of a transpositional muscle flap on VEGF mRNA expression in a canine fracture model.

The effect of sepsis on neovascularization in fractures that follows open fractures is important to the understanding of bone and soft-tissue healing. An animal model was designed that mimics the open fracture and the clinical repair of the human, high-energy open fracture. Vascular endothelial growth factor (VEGF) mRNA levels in canine bone samples were determined in samples from days 0 and 7. Canine right tibiae were fractured with a penetrating, captive-bolt device and then repaired in a standard clinical fashion using an interlocking intramedullary nail. Animals were subject to one of the following experimental protocols: tibial fracture (group I, n = 3); tibial fracture and Staphylococcus aureus inoculation at the fracture site (group II, n = 3); and tibial fracture and S. aureus inoculation with a rotational gastrocnemius muscle flap (group III, n = 3). Bone samples were harvested on days 0 and 7 and prepared for reverse transcriptase polymerase chain reaction assay. Primers for VEGF were commercially prepared and assay products were sequenced. The assay products were associated with Genebank VEGF mRNA sequences. VEGF mRNA levels increased significantly in the fracture-alone group from day 0 to day 7 (n = 3, p < 0.05). In the fracture and S. aureus group (group I), VEGF mRNA expression decreased 79 percent (p < 0.05). In animals with fractures inoculated with S. aureus and a transpositional muscle flap (group III), VEGF mRNA expression was increased 38 percent from day 0 to day 7 (p < 0.05) and was similar to the increase observed in the fracture-alone group. These results demonstrate that S. aureus decreased the normal increase of VEGF mRNA expression during bone wound healing. Use of the transpositional muscle flap in the presence of S. aureus increased VEGF mRNA expression over time to the expression pattern observed in the fracture-alone group. This experimental model demonstrates that specific biological signals and cellular pathways are influenced by bacterial infection and type of surgical closure.

Unravelling the secrets of foetal wound healing: an insight into fracture repair in the mouse foetus and perspectives for clinical application.

This study was designed to investigate the nature of mammalian foetal fracture healing in utero. A compound 'pinch' fracture was created in the foetal mouse ulna at the end of the second trimester, prior to mineralisation, and healing observed in whole mount limbs and in histological section. Cartilaginous ends gained initial contact within a perichondrial sleeve by 24 h. Bony union was achieved within 48 h by cartilage remodelling during the phase of primary endochondral ossification in the limb, a process to which adult fracture healing aspires. The molecular response to wounding was investigated using a whole mount in situ hybridisation technique and antisense mRNA probes to three target genes (BMP-2, BMP-4 and GDF-5). These experiments failed to identify altered expression in wounded limbs compared with controls.

The effect of muscle flap transposition to the fracture site on TNFalpha levels during fracture healing.

The trauma and sepsis that follow open fractures and wounds may lead to the production of various cytokines. Understanding wound healing requires a direct knowledge of the specific cytokines and the respective wound fluid levels that are present at the wound site. An animal model was designed that mimics the open fracture and the clinical repair of the human, high-energy open fracture. Canine right tibiae were fractured with a penetrating, captive-bolt device, then repaired in a standard clinical fashion using an interlocking intramedullary nail. Before primary wound closure, microdialysis probes were placed at the fracture site and in a muscle located at a contralateral site. Canines received one of the following experimental protocols: (1) tibial fracture (n = 5); (2) tibial fracture plus Staphylococcus aureus inoculation at the fracture site (n = 5); and (3) tibial fracture, S. aureus inoculation, and a rotational gastrocnemius muscle flap (n = 5). Microdialysis fluid samples were collected intermittently for 7 days. Tumor necrosis factor alpha (TNFalpha) levels at the fracture site were significantly elevated 3 to 34-fold (p<0.02), as compared with respective serum levels at all time points for all treatment groups. Fracture site TNFalpha levels were elevated (p<0.02) in days 1 through 6, as compared with the baseline and contralateral in all treatment groups. At days 1 through 6, the TNFalpha levels of the muscle flap group fracture site were significantly decreased by approximately 50 percent (p<0.05), as compared with the fractures without muscle flaps and regardless of additional S. aureus inoculation. On day 7, fracture site TNFalpha levels in all animal groups were similar, yet remained well above those of baseline TNFalpha. These results demonstrate that S. aureus does not further elevate TNFalpha levels in the presence of an open fracture and that a muscle flap reduces pro-inflammatory TNFalpha levels during early wound healing. This experimental model allows for the characterization of specific biological signals and cellular pathways that are influenced by bacterial infection and surgical closure. These data provide a scientific framework on which to judge or validate therapeutic regimens for open-fracture wound healing.

[Biochemical parameters of the metabolism of the intercellular substance of connective tissue, correlating with morphometric signs of long bone lesions in an open aseptic fracture]. / Biokhimicheskie pokazateli metabolizma mezhkletochnogo veshchestva soedinitel'noi tkani, korreliruiushchie s morfometricheskimi priznakami porazheniia dlinnoi kosti pri otkrytom asepticheskom perelome.

The aim of the research was experimental study of dynamics and correlative dependences between biochemical connective tissue matrix metabolism indices (blood serum collagenase, cathepsin B, elastase, antielastase activity, hydroxyproline fractions and glycosaminoglycans concentration) and tissue damage morphometric indices after long bone aseptic osteotomy of rat in terms 3 h-60 days. The most strong and significant correlation was found between cathepsin B, elastase activity indices and dimensions of bone marrow ischemic damage focuses and summarised periosteal regenerates volume in bone fragments.

Pharmacokinetics of once-daily dosing of gentamicin in surgical intensive care unit patients with open fractures.

OBJECTIVE: To compare the first-dose pharmacokinetic parameters of gentamicin 6 mg/kg and 2 mg/kg in stable, nonobese surgical intensive care unit patients with open extremity fractures receiving gentamicin prophylactically. METHODS: Serial blood samples were obtained over 8 or 24 hours following the first dose of gentamicin. Serum concentrations of gentamicin were measured using fluorescence polarization immunoassay and analyzed by noncompartmental means. RESULTS: Eleven patients were enrolled, 7 in the 6 mg/kg group and 4 in the 2 mg/kg group. The median (6 vs. 2 mg/kg) age was 29 versus 28 years; serum creatinine 80 versus 88 mumol/L; and APACHE II score 13 versus 10. The mean +/- SD (micrograms/mL) of concentration at the end of the 30-minute infusion (Cmax), concentration 30 minutes after the end of the infusion (Cpk), and concentration at the end of the dosing interval for 6 versus 2 mg/kg were: 35.0 +/- 19.0 versus 10.1 +/- 1.77; 17.0 +/- 2.7 versus 5.4 +/- 0.4, and 0.45 +/- 0.31 versus 0.69 +/- 0.11, respectively. Area under the curve0-infinity (AUC0-infinity), apparent volume of distribution, and half-life were: 89.0 +/- 28.9 versus 26.1 +/- 1.2 mg.h/L, 0.40 +/- 0.10 versus 0.47 +/- 0.14 L/kg, and 4.0 +/- 1.1 versus 4.3 +/- 1.5 h, respectively. CONCLUSIONS: The first-dose pharmacokinetics of gentamicin 6 mg/kg resulted in a proportional rise in Cmax, Cpk, and AUC0-infinity compared with gentamicin 2 mg/kg in patients with open fractures, but with greater variability.

[Adenohypophyseal hormone and corticosteroid content in the blood and urine in light mechanical injury]. / Soderzhanie nekotorykh gormonov adenogipofiza i kortikosteroidov v krovi i mochi bol'nykh pri legkoi mekhanicheskoi travme.

A considerably increased content of adrenocorticotropic, somatotropic and thyreo-stimulating hormones of the hypophysis in the blood serum, as well as corticosteroids in the blood and especially in the day urine was noted in 27 male patients with the first 4--8 days after light mechanical traumas not resulting in pronounced disturbances of homeostasis and having favourable outcomes. It has been shown that a simultaneous assessment of cortisole and corticosterone in the day urine is most informative among the studied forms of adrenal hormones (17-OCS, cortisole, corticosterone) in the evaluation of the functional state of the adrenal cortex and corticosteroid balance in the organism of the patients.

Use of the ventilatory equivalent to separate hypermetabolism from increased dead space ventilation in the injured or septic patient.

Normal subjects and surgical patients were studied with a noninvasive canopy-spirometer system which provides prolonged measurements of gas exchange and pattern of breathing. Values for normal subjects agreed with published values. Twenty-nine patients undergoing uncomplicated elective operation had a mean preoperative minute ventilation of 3.44 +/- 0.84 L/min/m2, a VO2 of 0.132 +/- 0.022 L/min/m2, and VCO2 of 0.105 +/- 0.017 L/min/m2, and the postoperative values on the third to fifth day were not statistically different. The ventilatory equivalent (V.E.CO2) or the liters of air moved per liter of CO2 excreted has been used instead of the dead space/tidal volume (VD/VT) ratio for the indication of levels of minute ventilation, which are excessive for the associated metabolic demands for gas exchange. Thirty-eight runs on 18 acutely ill surgical patients showed mean increases in minute ventilation of 85%; the associated increases in metabolism averaged 17%. Therefore, their V.E.CO2 increased from a normal of 31 +/- 6 to 50.7 +/- 8, indicating a sharp increase in dead space ventilation. The additional clinical information provided by the serial graphic presentation of V.E.CO2 supplements what is learned from successive numbers representing the trend in VD/VT.

[Interrelationship of calcium and magnesium in the case of a varying magnesium content in the diet of jaw fracture patients]. / O vzaimootnoshenii kal'tsiia i magniia pri razlichnom soderzhanii magniia v diete u bol'nykh s perelomami cheliustei.

In 12 patients with jaw-bones fractures an investigation of calcium and magnesium metabolism was carried out with a view of elucidating its possible relation to the course of repair of the bone tissue. A reciprocal dependence in the calcium and magnesium ions exchange in lesions of the jaws and an intensified accumulation of these ions by the time of the initial formation of the secondary callus were revealed. Investigations have confirmed the important role of magnesium in the metabolism of the bone tissue and a study of two diets with different magnesium content justified recommending its daiy allowance of about 550 mg for the given patients' population.