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Biomedical subjects

K Merritt

Publications and source records attributed to K Merritt.

At least 19 recordsLinked to original sources

Detection of bacterial adherence on biomedical polymers.

The ability to adhere to materials and promote formation of a biofilm is an important feature of the pathogenicity of some organisms, most notably the coagulase negative staphylococci. Various methods to detect bacterial adherence are available, but detection of adherence to nontransparent materials can be difficult. It was the purpose of this study to establish the suitability of a dye elution technique to detect adherence. The technique involves fixing the bacterial film with formalin, staining with crystal violet, eluting the dye with ethanol, and determining the optical density of the solution using 96-well plates and an enzyme immunosorbent assay reader with a 540-nm filter. This technique distinguished a known adherent from a known nonadherent organism and demonstrated that the presence of protein can inhibit adherence, and that adherence of different organisms to different biomedically important polymers can be measured. The dye elution technique was used to evaluate the adherence of known slime-producing polysaccharide antigen-positive (PSA+) and known nonslime-producing polysaccharide antigen-negative (PSA-) Staphylococcus epidermidis organisms to implant grade materials (polyethylene, expanded polytetrafluoroethylene, Dacron, silicone, and collagen) as well as to polystyrene.

Bacterial Adhesion

Improving patient care by reporting problems with medical devices.

Healthcare practitioners are the primary users of medical devices for direct patient care. As such, they are in the best position to recognize problems that result from the use of medical devices. The outcome of a device-related adverse event or product problem, as with any other medical product, can be serious and result in illness injury, or even death. The sooner that FDA learns about a problem, the sooner the agency can take action to protect patient and user safety. Healthcare practitioners are major contributors to the knowledge base related to device use and safety through astute monitoring, rapid identification of device-related problems, and reporting these problems. An understanding of the voluntary and mandatory mechanism of reporting will ensure that device problems are reported appropriately and in a timely manner. As the primary users of medical equipment for direct patient care, health care professionals have the training and expertise to improve patient care by reporting actual and suspected problems with medical devices.

Adverse Drug Reaction Reporting Systems

Tissue response to chronically stimulated implanted epimysial and intramuscular electrodes.

Twenty-four epimysial and 16 intramuscular electrodes were implanted in five adult dogs for periods ranging from 11 to 50 months. Chronic stimulation was applied to half of the electrodes for eight weeks near the end of the implantation period. The tissue response was rated by the amount and appearance of the fibrous tissue and inflammatory cells seen in the capsule lining the region of the electrode. The encapsulation tissues were composed primarily of collagen and fibroblasts and some macrophages and few other inflammatory cells. The epimysial electrodes exhibited more variation between and within electrodes, but had more of the better scores than the intramuscular electrodes. No difference in the distribution of scores was measured between the control and stimulated groups for the epimysial electrodes. While the scores for the intra-muscular electrodes varied very little, variance was sufficient to indicate a trend for poorer ratings with the application of chronic stimulation. Fibrous capsules were generally thinner under the epimysial electrodes than around the intramuscular electrodes. For both electrode types, the thickness was not correlated with the application or level of chronic stimulation. Thickness was shown to be positively correlated to the degree of loss of the sutures used to anchor the epimysial electrodes.

Animals

Production of monoclonal antibodies to study corrosion products of CO-CR biomaterials.

Sensitivity to nickel, cobalt, and chromium is common among the general population. The identification of these sensitivities is generally by the detection of cell-mediated immunity. We have reported previously the use of an indirect enzyme-linked immunosorbent assay method to quantitate metal-specific antibodies in patients with total joint replacements. To study the haptenic potential of these metal ions, rabbit albumin-glutathione-metal complexes with chromium, cobalt, or nickel were injected into mice. The splenocytes from one mouse in each group which developed a strong antibody against GSH-metal complexes were isolated and fused with myeloma cells to produce monoclonal antibodies. Chromium, cobalt, and nickel antibodies had similar affinity and bound with the specific GSH-metal complex. There was very little cross-reactivity between these antibodies. An inhibition assay using these monoclonal antibodies was demonstrated to be a simple technique, suitable for quantitation of free metal in solution.

Animals

Distribution of nickel and cobalt following dermal and systemic administration with in vitro and in vivo studies.

Contact dermatitis following skin contact with ionic metals occurs in about 15% of the human population, but systemic responses are not as common. It is generally believed that skin contact with metal ions leads to different biological processing compared with systemic contact. The purpose of the experiments presented here was to examine elimination of nickel and cobalt salts following skin application and following injection into the deep tissue of hamsters. In addition uptake of the metal by fibroblasts and by keratinocytes was examined in vitro. The data indicate that elimination of nickel and cobalt in the urine following systemic injection was rapid, as expected, but that elimination following skin application was delayed. Much of the metal was retained in the skin. Uptake of the metal by keratinocytes at low doses was greater than the uptake by the fibroblasts. At high doses the differences were not as great. Thus the conclusion is drawn that metal salts are retained in the skin for an extended period of time and could lead to prolonged antigen processing and consequent immune responses in the dermal tissue. Skin application leads to some systemic distribution but the systemic application did not lead to skin accumulation.

3T3 Cells

Effects of Ca and H2O2 added to RPMI on the fretting corrosion of Ti6Al4V.

Titanium and its alloys have demonstrated considerable success in various surgical procedures including orthopedic, dental, and cardiovascular surgery. However, particulate debris from corrosion and wear is present in a considerable quantity in tissue local to the implant. This study evaluated the effect of Ca, since it is present in both serum and bone, and H2O2, since it is produced through local inflammation, on the amount of titanium release. Four sets of Ti6Al4V plates and Ti6Al4V screws were used. Each set was designated to one of four solutions: RPMI (cell culture growth media), RPMI with CaCl2, RPMI with CaCO3, and RPMI with H2O2. A fretter was used to cause corrosion by creating micromotion between two screws and a two-hole plate of Ti6Al4V. After fretting for 72 h, weight loss of the plate and screws and the amount of Ti and vanadium (V) in solution was used to assess the amount of fretting corrosion which had occurred. Results of weight loss and Ti in solution indicated that the presence of H2O2 increased the amount of particulate debris produced in RPMI as compared with RPMI alone. The addition of CaCl2 to RPMI also increased both weight loss and Ti in solution compared with RPMI alone. The addition of CaCO2, however, did not give values significantly different from RPMI alone. Comparison of weight loss and Ti in solution indicated that the increase in fretting corrosion was not different between RPMI with CaCl2 and RPMI with H2O2. The particulate wear debris from the four solutions was black in color and the size of the particulate produced was compared using a Coulter Multisizer. The results indicated that particles produced in the four solutions were not different, with mean values between 1.324 and 1.100 microns, and they were similar in size to the particulate found in tissues surrounding failed total hip replacements. In order to better understand the role of Ca in the fretting corrosion of Ti6Al4V, energy dispersive x-ray analysis (EDXA) using SEM was used to determine elemental composition of one countersink surface of a plate which had been run four times in RPMI with CaCl2. The presence of Ca in the bulk was not significant (% composition < 0.5%). However, Ca was present in two surface particles which were examined at a magnification of 55,000, with a Ca% composition of 63.2% and 19.2%. While results from this study indicate that both soluble Ca(CaCl2) and H2O2 increase the fretting corrosion of Ti6Al4V, the insoluble form of Ca, which would be found in bone and hydroxyapatite, has no effect. These data indicate that it is important to specify the media used in corrosion, dissolution, and elution experiments.

Alloys

The output of the hippocampus is inhibited during social behavior in the male rat.

During sexual behavior in the male rat, peptidergic cells in the medial amygdaloid nucleus become active and release a vasopressin-like peptide. The present experiments were designed to examine hippocampal changes as a result of this peptide's action during sexual behaviors. Chronic field-potential recordings from the hippocampus of male rats were acquired in a wide variety of social and nonsocial circumstances. Hippocampal responses that resemble the known action of the vasopressin-like peptide were seen only with social stimuli such as sexual stimuli and stimuli that led to aggressive behavior between males. The results show that the occasions of peptide action in the hippocampus correlate with the occasions of peptide release as determined by recording from the peptidergic cell bodies. The results are interpreted to indicate that the amygdala projection to the hippocampus has a special role to play in social behavior.

Animals

Distribution of cobalt chromium wear and corrosion products and biologic reactions.

Replacement hip arthroplasty with the use of ultrahigh molecular weight polyethylene for the cup articulating with a metal head has provided a low friction arthroplasty with years of success. However, the search for improved materials and designs for articulating surfaces continues. The use of metallic heads articulating with metallic cups is now being reconsidered for total hip replacements. Success will be enhanced if wear and corrosion of the articulating surfaces can be kept below that of the metal on ultrahigh molecular weight polyethylene couple. Concern has been raised about the release, and biologic fate, of metal species from corrosion and wear. Titanium alloys have been shown to have limitations as an articulating surface showing significant wear, and the alloy per se should not be considered for wear couples in total hip replacements. The cobalt chromium alloys are known to have reasonable wear and corrosion properties and continue to be evaluated. The issue of cobalt chromium wear and corrosion products and how this relates to the biologic performance of total hip replacement devices is reviewed. Under the condition of wear as currently experienced at the articulating surfaces of cobalt chromium alloys and ultrahigh molecular weight polyethylene, the amount of metallic products transferred to the tissues is sufficiently low to be well tolerated by the biologic system. Nickel and cobalt ions arc, rapidly transported from the implant site and eliminated in the urine. Chromium is stored in the tissue and eliminated more slowly. The issue of host hypersensitivity to these elements remains of concern. All 3 elements, in ionic form, are known to cause contact dermatitis. Untoward biologic reactions, including hypersensitivity, should be minimized if wear and corrosion phenomena are minimized.

Alloys

Metal on metal total hip replacement workshop consensus document.

The objective of this workshop was to provide a forum to discuss the reintroduction of metal on metal bearings for clinical use in total hip arthroplasty. Approximately 100 researchers clinicians, and industry representatives presented the state of the art interpretation of the metal on metal total hip replacement's past performance, and the clinical, tribologic, and biologic considerations of all metal bearings. Based on the scientific presentations at the symposium, the extant literature, the clinical experience of the panelists, and the current regulatory, legal, and economic environment, consensus statements were developed.

Alloys

Immune response to synthetic materials. Sensitization of patients receiving orthopaedic implants.

Metallic orthopaedic devices are composed of elements that are known to be skin sensitizers in the general population. There is concern about the possibility of sensitivity reactions in patients bearing these implants. Blood samples were drawn from 22 patients having primary total joint replacement and who had no known prior metal allergies or exposure. Repeat blood samples were drawn 3 months to 1 year later. All preoperative blood samples showed no immune reactions against titanium, cobalt, chromium, or nickel ion solutions in a leukocyte migration inhibition test. Thirty two percent (7 of 22) of the patients developed sensitivity to at least 1 of the antigens, but only 5 percent (1 of 22) developed a severe reaction. Review of the literature and these studies has indicated that such reactions can occur. However, the incidence seems to be very low.

Foreign-Body Reaction

Fretting corrosion accelerates crevice corrosion of modular hip tapers.

The use of multiple-component systems in orthopedic surgery gives the surgeon increased flexibility in choosing the optimal implant, but introduces the possibility of interfacial corrosion. Such corrosion could limit the longevity of prostheses due either to tissue reactions to corrosion products, or to device failure. The incidence and nature of corrosion of modular total hips was evaluated in a consecutive series of 79 retrieved implants from University Hospitals of Cleveland. Surfaces were examined with stereo- and scanning electron microscopy. Several laboratory studies were undertaken to examine mechanisms that might contribute to the initiation of corrosion. The first set of experiments investigated the effect of head neck extension; the second study looked at the effect of material combinations on fretting corrosion and crevice corrosion. Analysis of retrieved implants demonstrated that fretting corrosion played a major role in the initiation of interface corrosion, and that a correlation existed between corrosion and length of neck extensions. Laboratory studies showed that longer head neck extensions may be more susceptible to fretting corrosion because of an instability at the interface. Short-term mixed-metal corrosion studies demonstrated that the coupling of cobalt and titanium alloys did not render the interface more susceptible to corrosion. It is hypothesized that fretting corrosion contributes to the initiation of modular interface corrosion, and that the problem can be reduced by design changes that increase the stability of the interface.

Alloys

Blood-biomaterial interactions in a flow system in the presence of bacteria: effect of protein adsorption.

An in vitro continuous flow system with whole human blood was used to study blood-biomaterial interactions on a base polyurethane and three modified surfaces in the presence and absence of circulating Staphylococcus epidermidis. We hypothesized that the composition of the protein layer adsorbed on the surface of the biomaterial would influence the response of blood components and bacteria. We examined the test surfaces for adsorption of nine plasma proteins and adsorption profiles differed on the four surfaces. The positively charged surface, UC, adsorbed significantly higher amounts of fibronectin (P < .01), von Willebrand factor (P < .01), and fibrinogen (P < .05) than the other materials. As a consequence of increased adsorption of these adhesive proteins, the adhesion of platelets and bacteria was greater on UC than on any other surface. On the base polyurethane, BC, and the negatively charged surface, UA, protein adsorption was low, and these materials were largely free of adherent blood cells and bacteria. The heparinized surface, UH, adsorbed higher quantities (P < .01) of Hageman factor and high molecular weight kininogen relative to the other surfaces. Platelet adhesion, and surface coagulation were prominent on UC, and may have contributed to increased bacterial adhesion on this surface. In the presence of circulating bacteria, adsorption was generally lower than in the absence of bacteria. The pattern of protein adsorption was largely unaffected by the strain of circulating bacteria, but platelet responses (adhesion and activation) were greater in the presence of slime-producing S. epidermidis as compared to the non-slime-producing strain, suggesting that slime may have a direct activating effect on platelets.

Adsorption

Bacteria/blood/material interactions. I. Injected and preseeded slime-forming Staphylococcus epidermidis in flowing blood with biomaterials.

Blood-material interactions were studied using in vitro recirculation with human blood, slime-forming Staphylococcus epidermidis, and cardiovascular materials. Staphylococcus epidermidis, under preseeded or injected conditions, adhered to nonsmooth materials and elevated plasma levels of fibrinopeptide A (FpA) and C3a in the presence of all materials. Increased white blood cell (WBC) and platelet adhesion and thrombospondin and platelet factor 4 (PF4) release were noted for respective materials in the presence of injected bacteria. Materials that adhered significant quantities of injected S. epidermidis exhibited low levels of adsorbed proteins. Materials with high levels of preseeded S. epidermidis showed high levels of adsorbed proteins. Adhesion of preseeded bacteria and blood plasma elevations of C3a and FpA were lowest on semicrystalline polymer substrates, intermediate on halogenated substrates, and highest on amorphous substrates. In the presence of injected bacteria, WBCs and platelets adhered at earlier recirculation times to amorphous substrates than to semicrystalline substrates.

Bacterial Adhesion

Release of hexavalent chromium from corrosion of stainless steel and cobalt-chromium alloys.

Experiments were undertaken to determine whether hexavalent chromium was released during corrosion of orthopedic implants. Uptake of chromium (Cr) by cells and separation using amberlite resin were the methods used to determine that hexavalent Cr was present. We used salts of chromium as trivalent chromium (chromic chloride) and hexavalent chromium (potassium dichromate) to verify that the amberlite separation technique separates hexavalent Cr into the upper phase and trivalent Cr into the lower phase. The use of the salts also verified that only the hexavalent Cr became red blood cell-associated and that most of this was intracellular rather than membrane bound. The use of the amberlite separation technique demonstrated that the hexavalent Cr in the red blood cells was rapidly reduced to trivalent Cr. Cellular uptake of chromium was documented in red blood cells following corrosion of stainless-steel and cobalt-chromium implants in vivo, in the red blood cells of patients undergoing total joint revisions, and in fibroblasts subjected to products of fretting corrosion of stainless-steel and cobalt-chromium implants. Thus, corrosion of implants can lead to the release of the biologically active hexavalent chromium into the body. This chromium is rapidly reduced to trivalent chromium in cells.

Animals

Mixed-metal fretting corrosion of Ti6Al4V and wrought cobalt alloy.

Corrosion has been reported at the modular interfaces of total joint replacement implants, but with conflicting theories as to the cause of such damage. The modular design itself leaves the interface susceptible to galvanic, crevice, or fretting corrosion, or a combination of the three. The purpose of this study was to quantify the effect of material combination on fretting corrosion of orthopedic alloys. Each test specimen consisted of a two-hole plate with spherical countersinks and two cortical bone screws. The plates and screws were made of either Ti6Al4V or wrought cobalt-chromium-molybdenum (CCM), and were tested in all mixed-metal and similar-alloy combinations. Fretting corrosion experiments were conducted for 14 days in 10% calf serum, according to ASTM F897. Corrosion damage was evaluated by weight-loss measurements, atomic absorption spectrophotometry and scanning electron microscopy analyses. The results indicated that Ti6Al4V suffered relatively severe damage when fretted against itself, as a result of adhesive galling. The extent of titanium damage was reduced considerably, however, when Ti6Al4V was fretted against wrought CCM. In contrast, there was essentially no difference in wrought CCM damage when the alloys was fretted against itself compared to fretting against Ti6Al4V. Finally, in similar-alloy combinations, Ti6Al4V suffered more severe damage than wrought CCM.

Alloys

Distribution of titanium and vanadium following repeated injection of high-dose salts.

Titanium and its alloy of 6% aluminium and 4% vanadium are used extensively in orthopedic and dental surgery. However, in conditions of motion leading to wear, there is significant generation of wear products with deposition of black debris in the tissue. The questions remain as to how much of this debris is generated and to where it is transported. Previous studies have been hampered by low levels of detected elements giving values just above the background levels found in normal tissue and body fluids. The purpose of these experiments was to increase the body burden of titanium and vanadium by injecting larger doses of titanium and vanadium salts over an extended period of time. Each animal (Syrian hamster) received 100 micrograms of each element once a week for six weeks. The hamster was sacrificed on the seventh week and body fluids and tissue harvested. The results indicate that in the experimental animals there was transport of vanadium with levels above control in urine, plasma, liver, spleen, and the mineralized portion and organic portion of bone. Titanium had less transport but still showed levels in the experimental animals in plasma, kidney, liver, spleen, and both phases of bone above those in the control animals. Neither element was found above control levels in lung or red blood cells. The levels of titanium and vanadium in control bone were high, possibly indicating bone as a site for storage and accumulation of these elements when encountered in the activities of daily living.

Animals

Use of fibrinolytic agents to coat wire implants to decrease infection. An animal model.

RATIONALE AND OBJECTIVES: Infection is a serious complication of metallic prosthesis implantation and may necessitate removal of the prosthesis. This study uses an animal model to evaluate the effects of coating stainless steel wire implants with fibrinolytic agents to prevent infection after bacterial contamination. METHODS: Three types of steel wire implants were used: plain stainless steel, heparin-coated steel, and urokinase-heparin-coated steel. Wire implants were incubated in a known concentration of Staphylococcus epidermidis and placed into the subcutaneous tissues of three groups of anesthetized hamsters. The implants and surrounding tissues were excised after 1 week and submitted for quantitative cultures. RESULTS: Using 100 organisms as the upper allowable limit to categorize abscesses as noninfected, the following rates of noninfectivity were observed: group 1 (control), 0% noninfected; group 2 (heparin-coated wire), 40% noninfected; and group 3 (urokinase-heparin-coated wire), 50% noninfected. The noninfectivity rates of groups 2 and 3 were significantly higher than the rate of group 1 (P < 0.001). There was no significant difference between groups 2 and 3 (P = 0.19). CONCLUSIONS: Both the heparin-coated and urokinase-heparin-coated wire exhibited significantly decreased infection rates compared with uncoated wire; the heparin coating may inhibit bacterial adherence. The urokinase coating of the heparin-coated wire appears to further decrease the infection rate, but not to a statistically significant degree.

Abscess