Pharmacokinetics of ceftiofur sodium in neonatal foals after intramuscular injection.
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Animals↗
Biomedical subjects
K Merritt
Publications and source records attributed to K Merritt.
The effect of stainless steel, cobalt-chromium, titanium alloy, and titanium on the respiratory burst activity of human polymorphonuclear leukocytes.
Although infection is a serious complication associated with the use of orthopedic prosthetic implants, the impact of the metal used in these devices on host defense is poorly understood. The authors investigated the effect of stainless steel, titanium, titanium alloy, and cobalt-chromium alloy on the respiratory burst of polymorphonuclear leukocytes (PMN), a vital component of bactericidal activity. In the presence of stainless steel powder or supernatants obtained from the incubation of stainless steel in buffer, superoxide production by PMN was significantly impaired. Titanium, titanium alloy, and cobalt-chrome alloy had no significant effect on superoxide production. Nickel and chromium, the only metal ions detectable in the stainless steel supernatant, did not impair superoxide production when tested at concentrations similar to those found in the supernatant. Inhibition of PMN superoxide production may play a role in the establishment and persistence of stainless steel device-related infections.
Cell Survival↗
Serum and skin concentrations after multiple-dose oral administration of trimethoprim-sulfadiazine in dogs.
Six healthy adult mixed breed dogs were each given 5 oral doses of trimethoprim (TMP)/sulfadiazine (SDZ) at 2 dosage regimens: 5 mg of TMP/kg of body weight and 25 mg of SDZ/kg every 24 hours (experiment 1) and every 12 hours (experiment 2). Serum and skin concentrations of each drug were measured serially throughout each experiment and mean serum concentrations of TMP and SDZ were determined for each drug for 24 hours (experiment 1) and 12 hours (experiment 2) after the last dose was given. In experiment 1, mean serum TMP concentration was 0.67 +/- 0.02 micrograms/ml, and mean skin TMP concentration was 1.54 +/- 0.40 micrograms/g. Mean serum SDZ concentration was 51.1 +/- 12.2 micrograms/ml and mean skin SDZ concentration was 59.3 +/- 9.8 micrograms/g. In experiment 2, mean serum TMP concentration was 1.24 +/- 0.35 micrograms/ml and mean skin TMP concentration was 3.03 +/- 0.54 micrograms/g. Mean serum SDZ concentration was 51.6 +/- 9.3 micrograms/ml and mean skin SDZ concentration was 71.1 +/- 8.2 micrograms/g. After the 5th oral dose in both experiments, mean concentration of TMP and SDZ in serum and skin exceeded reported minimal inhibitory concentrations of TMP/SDZ (less than or equal to 0.25/4.75 micrograms/ml) for coagulase-positive Staphylococcus sp. It was concluded that therapeutically effective concentrations in serum and skin were achieved and maintained when using the manufacturer's recommended dosage of 30 mg of TMP/SDZ/kg (5 mg of TMP/kg and 25 mg of SDZ/kg) every 24 hours.
Administration, Oral↗
Effect of probenecid on the pharmacokinetics of flunixin meglumine and phenylbutazone in healthy mares.
Pharmacokinetic values for flunixin meglumine (1 mg/kg of body weight) and phenylbutazone (4 mg/kg) dosages were determined after a single IV injection with and without concurrent intragastric administration of probenecid (50 mg/kg) in 6 healthy mares. Significant difference was not apparent in the pharmacokinetic values of flunixin meglumine with and without concurrent probenecid administration. Significant (P less than or equal to 0.05) increase was evident in the 12-hour mean concentration of phenylbutazone (11.45 +/- 1.66 micrograms/ml without probenecid; 14.56 +/- 1.20 micrograms/ml with probenecid) along with significant (P less than or equal to 0.05) reduction in its volume of distribution at steady state associated with concurrent probenecid administration (218.6 +/- 11.52 ml/kg without probenecid; 169.4 +/- 9.25 ml/kg with probenecid).
Animals↗
Effect of Staphylococcus epidermidis on adherence of Pseudomonas aeruginosa and Proteus mirabilis to polymethyl methacrylate (PMMA) and gentamicin-containing PMMA.
The goals of this study were to determine 1) effect of Staphylococcus epidermidis adherence and biofilm production on adherence of the opportunistic pathogens Proteus mirabilis and Pseudomonas aeruginosa to polymethyl methacrylate (PMMA); 2) if the biofilm killed by autoclaving altered adherence of other organisms; 3) if adherence of S. epidermidis to gentamicin-containing PMMA altered adherence of the opportunistic pathogens P. mirabilis and P. aeruginosa to gentamicin-containing PMMA. Results show that biofilms formed by S. epidermidis, whether alive or dead, significantly increased adherence of Pseudomonas. Adherence of Proteus was significantly increased on dead biofilms and increased, but not significantly (p = less than 0.1), on live ones. Greatest adherence seen in the study was to autoclaved biofilms. Significant adherence of Proteus and Pseudomonas was found on gentamicin-containing PMMA specimens, which were preincubated with S. epidermidis for formation on the biofilm. These results indicate that a biofilm is formed on PMMA-gentamicin specimens and this may impair the ability of gentamicin to kill other organisms.
Bacterial Adhesion↗
Cell association of fretting corrosion products generated in a cell culture.
The nature and distribution of corrosion products released into the body from orthopaedic implants remains an important issue. Various approaches to study this problem have been taken, such as the injection of metal salts, the injection of corrosion products, analysis of retrieved implants and adjacent tissue, and stimulated corrosion in vivo, with collection of body fluids and tissues for analysis. Tissue culture techniques have also been used to study the cellular response to metal salts or to corrosion or wear products that were generated in a separate environment. In this study, fretting corrosion of stainless steel plates and screws and of cobalt-chromium alloy plates with stainless steel screws was undertaken within a cell culture. The results showed that the cell cultures remained viable despite considerable metal ion release. Nickel was released in all cultures with fretting corrosion and was found mainly in the tissue culture medium (supernatant of the harvested cultures). Cobalt was detected only in those cultures with fretting corrosion of the cobalt-chromium alloy, and it was present mainly in the tissue culture medium. Chromium was released in all cultures with fretting corrosion, and it was found to be associated mainly with the cells with little in the culture medium. This compartmentalization of cell-associated chromium and fluid-associated cobalt and nickel supports in vivo studies showing chromium accumulation in red blood cells or tissue sites and comparatively low levels of nickel and cobalt.
Animals↗
Factors influencing bacterial adherence to biomaterials.
The adherence of bacteria to implanted medical devices is believed to be important in the development of implant associated infections. Measures which reduce bacterial adherence should reduce the incidence of these infections. However, in order to assess the importance of adherence, the effectiveness of methods to reduce adherence, and compare data from different laboratories, the conditions of the in vitro studies on adherence need to be specified. There are currently no correct and incorrect methods, however, methods used need to be carefully described. The studies reported here indicate that the definition of adherence needs to be established, with the use of polystyrene as the reference material recommended. Since the adherent organisms lose adherence traits with culture, cultures must be selected for adherence regularly. It is important to control the number of organisms/ml but the volume used is not important. The medium used to grow the organisms and the use of stationary, rocking or flow conditions will alter adherence and need to be specified and be consistent within a set of experiments. Culture conditions, methods of rinsing the material, methods of elution and counting, or direct counting of organisms on the material need to be specified. Finally, as much information as possible on the bulk and surface properties of the material should be provided. The handling of the material for the experiments should be careful and defined. Fingerprints, contact with protein, wet surfaces vs dry surfaces, etc., will all affect the subsequent adherence. The materials should not be re-used since the removal of the adherent proteins or the biofilm is very difficult. Progress can be made in this important area if the details of procedures are specified.
Animals↗
The effects of heat treatments and bead size on the corrosion of porous F75 in saline and serum.
An accelerated anodic corrosion method was used to study the effects of heat treatment and bead size on corrosion and metal ion release of porous coated F75 cylinders in saline and serum. Three heat treatments were used: a standard process for F75 implants (HTA), the standard plus an additional hour in air to produce a thin oxide film (HTA'), and a sintering in high vacuum to produce a chromium-depleted surface (HTB). Three bead sizes of similar composition were used, with approximate sizes of 215, 300, and 560 microns. The results demonstrated that HTA' had the lowest corrosion rate and that of HTB was significantly greater than either HTA or HTA'. The corrosion rates of HTA and HTA' were significantly greater in serum as compared with saline, whereas that of HTB was not affected by the presence of serum, suggesting an interaction between chromium and serum proteins. Bead size had a minimal effect on the corrosion rate of HTA'. For HTA, the small beads had the highest corrosion rate; the lowest was with the medium-sized beads. Bead size had the most significant effect with HTB, with that of the smaller beads having the higher corrosion rates. The effects of bead size were less consistent in serum, suggesting that protein adsorption may mask some of the surface area effects. It is concluded that the oxide film does reduce corrosion, that proteins do have an influence on the corrosion of F75, and that this method can be a useful tool for studying the effects of improved heat treatment methods on the corrosion rate of F75 implants.
Blood↗
In vitro biocompatibility of polyetheretherketone and polysulfone composites.
Short carbon fiber reinforced composites could potentially replace some of the metal alloys used in orthopedic implants. In particular, polysulfone and, more recently, polyetheretherketone have been considered as the matrix material for carbon fiber reinforced composite implant materials. ASTM standards F813 and F619 for direct contact cell culture evaluation and extraction were employed to determine the in vitro biocompatibility of a carbon fiber composite of polyetheretherketone, PEEK, in comparison to a carbon fiber reinforced polysulfone composite. The cell cultures were assessed qualitatively by microscopy and quantitatively using an enzyme assay to determine cytotoxicity. Overall, the cellular response to the PEEK and polysulfone composites were negligible indicating that further in vivo studies with these materials are appropriate.
Animals↗
Modulation of cell adhesion by modification of titanium surfaces with covalently attached self-assembled monolayers.
The surface of titanium has been modified by covalent attachment of an organic monolayer anchored by a siloxane network. This coating completely covers the metal and allows controlled modification of surface properties by the exposed chemical endgroups of the monolayer forming surfactant. The attachment of such a film allows different bulk materials (e.g., glass and titanium) to have identical surface properties and this can be used in regulating cell adhesion responses. This control over surface functionality can modulate the functions of fibronectin in regulating attachment and neurite formation by neuronal cells. The effect on bacterial adherence that is achieved by using such monolayers to vary surface hydrophilicity is also assessed.
Bacterial Adhesion↗
Elimination of nickel, cobalt, and chromium following repeated injections of high dose metal salts.
A study was conducted to determine the ability of hamsters to eliminate in the urine, or store in the organs, large quantities of metal salts given over a period of several months. In addition, the effect of prior immunization on metal ion clearance was determined. The results indicated that nickel was rapidly eliminated in the urine and that the level in the organs was similar to that of control animals. Cobalt was eliminated more slowly than was nickel. The organ levels of cobalt were similar to those of control animals with a slight elevation in the liver of the injected animals. Chromium was eliminated in the urine very slowly, was red cell associated, and the levels were elevated in all the organs (liver, lung, spleen, kidney) compared to control. Prior immunization with metal salts increased the storage of chromium.
Animals↗
AES analysis of stainless steel corroded in saline, in serum and in vivo.
Auger electron spectroscopic (AES) studies were conducted to examine the surface film of stainless steel specimens which had been subjected to passive and anodic corrosion in vitro and in vivo. Anodic corrosion was accelerated by the application of a +500 mV (SCE) potential for 30 minutes. Experiments performed in 0.9% saline indicated little alteration in the nature of the surface film compared to a freshly prepared control specimen. Auger analysis of specimens in 10% serum or in vivo revealed that passive film thickness was dependent on the corrosive environment. The films of specimens immersed under freely corroding conditions in 10% serum or in vivo were similar to the control film. Accelerated corrosion performed in 10% calf serum resulted in significant film thickening. The thickest films were from accelerated corrosion in vivo. The mechanism for the altered surface films produced by corrosion in vivo or in serum as compared to saline needs to be investigated further.
Animals↗
Use of an enzyme linked immunosorbent assay (ELISA) for quantification of proteins on the surface of materials.
This study demonstrates the usefulness of an enzyme linked immunosorbent assay (ELISA) for detection and quantification of protein on the surface of materials. Bovine serum albumin (BSA) and bovine gamma globulin (BGG) were the proteins used. Titanium and stainless steel were the materials tested. The proteins were detected with the use of rabbit antiserum specific for BSA and for BGG. This reaction was quantitated by the use of horseradish peroxidase conjugated goat anti-rabbit gamma globulin. The technique is described in detail. The technique was demonstrated to be suitable for quantitation of protein from 0.01 mg/mL to 0.1 mg/mL on the surface of 3 mm X 10 mm materials. The technique was also demonstrated to be suitable for determining the surface area of solid materials. It is a simple technique and suitable for most biomaterials laboratories.
Adsorption↗
Effect of proteins and pH on fretting corrosion and metal ion release.
The objectives of this study were to determine the effect of proteins and protein charge on the corrosion of stainless steel. As Zwitter ions, proteins have a positive charge in solutions acidic to their isoelectric point (pI) and a negative charge in solutions basic to the pI. Fretting corrosion rates of stainless-steel plates and screws as determined by weight loss and metal ion release were studied in saline and protein solutions with the pH adjusted to 3, 5, and 8. Alterations in pH did not affect the corrosion rate in saline solutions. However, alterations of the pH in albumin solutions did affect the corrosion rate. In protein solutions acidic to the isoelectric point the presence of the positively charged albumin did not alter the corrosion rates as compared to that in saline. However, the presence of negatively charged proteins in solutions basic to their isoelectric points decreased the amount of corrosion. Thus, the effect of proteins on fretting corrosion is dependent on the charge on the protein. When the release of nickel was compared to the release of chromium, it was shown that the release was in proportion to the composition of the alloy when fretting corrosion took place in saline. The nickel/chromium ratio in the albumin and gamma globulin solutions was increased relative to that predicted indicating preferential release of nickel in protein solutions.
Animals↗
In vitro and in vivo metal ion release.
A series of experiments was conducted to study in vitro and in vivo metal ion release and the urine excretion of metal ions. Metal salts were injected and urine analyzed. Anodic potentials were applied to stainless steel and cobalt-chromium-molybdenum (CCM) specimens to cause an acceleration of corrosion rates. Corrosion experiments were done in saline, 10% serum and in a subcutaneous space in hamsters. Corrosion rates were determined by measurements of weight loss and calculations of net charge transfer. Metal ion concentrations were determined with graphite furnace atomic absorption spectroscopy, and were calculated from total charge using Faraday's law. The results with stainless steel showed that the weight loss and metal ion release from stainless steel in vitro and in vivo can be calculated using Faraday's Law, assuming release in proportion to alloy composition. The results with CCM indicated that release rates in vitro can be used to determine the proportionality of release in vivo. All the nickel and most of the cobalt was rapidly excreted, while less than 50% of the chromium was excreted. The excretion of metals following salt injection or in vivo corrosion were very similar.
Animals↗
In vitro studies of fretting corrosion of orthopaedic materials.
Two models were used to study fretting corrosion of surgical alloys. In the first, the amount of load and motion between plates and screws was controlled, and corrosion rates of stainless steel and MP35N were determined by measurements of component weight loss and metal ion concentration in the test solutions. Stainless steel had the higher rate of fretting corrosion. The addition of 10% serum to saline resulted in a significant reduction of the corrosion rate of stainless steel and MP35N. The use of stainless steel screws in a mixed-metal combination with MP35N and titanium plates showed minimal effects on the performance of the stainless steel screws but an increase in fretting corrosion of the MP35N plates. In the second model, plates were applied to glass fiber-reinforced plastic tubes as bone analogues and subjected to cyclic axial loads. These results demonstrated a reduction in fretting corrosion rates associated with an increase in screw torque and a decrease in axial load. Corrosion rates were minimal with intact tubes simulating healed fractures and greatest with an oblique-cut fracture simulation. These models have proven useful for the evaluation of fretting corrosion rates of different alloys and for evaluation of variables such as fracture stability.
Alloys↗
Electrochemical studies on the influence of proteins on the corrosion of implant alloys.
The effect of proteins on corrosion rates of 316L stainless steel, commercially pure titanium and titanium 6-aluminium 4-vanadium was studied in the static and fretting modes. The static mode was studied using cylindrical specimens as per ASTM F-746, and static fracture fixation plates. The fretting mode was studied using a two-hole plate fretting machine which caused a cyclic rocking motion between the plate and the screws, as per ASTM F-897. Electrochemical techniques of polarization resistance and Tafel slope measurements were used to study effects of proteins on the anodic and cathodic corrosion reactions. It was found that proteins increased the corrosion rate of the stainless steel and C.P. titanium cylindrical specimens, but did not have an effect on the Ti-6AI-4V cylinders. In the fretting mode proteins decreased the corrosion rate of the stainless steel plates, but did not have an appreciable effect on either of the titanium alloys. The presence of proteins appeared to cause an increase in the anodic Tafel constant and a decrease in the cathodic Tafel constant of stainless steel specimens. Significant differences in the shapes of the cathodic Tafel slopes were also seen with cylinders with different surface conditions, and static versus fretting plates.
Alloys↗
Factors increasing the risk of infection in patients with open fractures.
A study was undertaken to determine what factors are important in determining whether or not a patient with an open fracture will develop an infection. Debrided tissue was cultured to determine quantitative bacterial counts. The patients' subsequent records were evaluated and the infection rate correlated with culture data and other factors that might be associated with development of infection. Of the 70 patients evaluated, 13 (19%) became infected. When the infection rate was correlated with the use of fixation devices, it was found that 1/19 (5%) of the patients with no implants, 3/16 (19%) of the patients with external fixation devices, and 9/35 (26%) of the patients with internal fixation became infected. Most of the infections were caused by Gram-negative bacteria. There was little correlation between the bacterial counts in the first piece of tissue taken at debridement and the development of infection. There was significant correlation between the bacterial count in the last piece of tissue taken at debridement and the development of infection. Thus the infection was correlated with what was in the tissue when the patient left the operating room and not with what was in the tissue when the patient entered the operating room.
Adult↗