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Biomedical subjects

K Merritt

Publications and source records attributed to K Merritt.

At least 19 recordsLinked to original sources
PubMed2001

Significance of the type and the size of biomaterial particles on phagocytosis and tissue distribution.

Particulates generated by dissolution or wear of injected or implanted biomaterials may migrate into various tissues and lead to activation of the host's inflammatory and immune responses. The purpose of this study was to evaluate the relevance of size and chemical composition of biomaterial particles on the pattern of particle distribution in host tissues. Adult female B6C3F1 mice were injected intraperitoneally with polymethylmethacrylate (PMMA) particles (size 1.4 and 6.4 micro in diameter) and polystyrene (PS) particles (size 1.2, 5.2, and 12.5 micro in diameter), and euthanized 1, 7, and 28 days later. Peritoneal exudate cells (PECs) were collected and the number of cells and percentage of actively phagocytic cells was determined. Macroscopic examination of the tissues in the peritoneal cavity peritoneum revealed visible accumulations of the colored PS particles in the adipose tissues adjacent to the spleen and pancreas, and caudal to the stomach. Distribution of the PS particles appeared similar regardless of the particle size. The location of PMMA particles, which were not colored, could not be distinguished from host tissue and could not be observed in this manner. Intensive phagocytosis of the small and medium sized particles by peritoneal macrophages was observed on day 1, and was diminishing by day 7 after injection. The largest PS particles (12.5 micro) were not engulfed by the peritoneal macrophages. Histological examination of the spleen, lymph nodes, and the adjacent adipose tissues revealed a marked difference in the deposition patterns of the two polymers used. PS particles, regardless of size, were accumulated primarily in the white adipose tissues adjacent to the spleen and pancreas gland, but very few particles were observed in the splenic tissue. On the other hand, mice injected with PMMA particles of either size had enlarged and activated spleens with marked deposits of particles in the red pulp. These results indicate that these PS and PMMA particles induce different patterns and intensities of the host response. The chemical makeup of the particle is more important in the distribution pattern than is the size of the particle.

Animals↗
PubMed2001

Metal sensitivity in patients with orthopaedic implants.

All metals in contact with biological systems undergo corrosion. This electrochemical process leads to the formation of metal ions, which may activate the immune system by forming complexes with endogenous proteins. Implant degradation products have been shown to be associated with dermatitis, urticaria, and vasculitis. If cutaneous signs of an allergic response appear after implantation of a metal device, metal sensitivity should be considered. Currently, there is no generally accepted test for the clinical determination of metal hypersensitivity to implanted devices. The prevalence of dermal sensitivity in patients with a joint replacement device, particularly those with a failed implant, is substantially higher than that in the general population. Until the roles of delayed hypersensitivity and humoral immune responses to metallic orthopaedic implants are more clearly defined, the risk to patients may be considered minimal. It is currently unclear whether metal sensitivity is a contributing factor to implant failure.

Antibody Formation↗
PubMed2000

Safety and cleaning of medical materials and devices.

A study was undertaken to evaluate different procedures to safely remove microorganisms, protein, and mammalian cells from materials and provide a suitable method for cleaning and assessing effectiveness of cleaning medical devices for reuse or for analysis of failure. Safety considerations for the personnel performing the cleaning or handling the device after cleaning are important issues. Polystyrene plates (96 well) were used to simulate device surfaces not amenable to manual scrubbing. Staphylococcus epidermidis, Candida albicans, Escherichia coli, Pseudomonas aeruginosa, and oral flora were grown in the plates. The plates were stained with crystal violet and the optical densities recorded. The results indicated that E. coli did not adhere well and Pseudomonas formed clumps that were easily detached from the surface of the plates. However, S. epi, C. albicans, and the oral organisms formed adherent biofilms that were difficult to remove from the plates. Detergents with enzymes and sodium hypochlorite (NaOCl) bleach were both effective in removing the biofilm. Other detergents and surfactants were not effective. The aldehyde agents did not remove the organisms and made further cleaning difficult. Allowing the biofilm to dry first made cleaning very difficult. Only the NaOCl bleach could subsequently remove the dried or aldehyde fixed organisms from the wells. The same 96-well polystyrene plate format was used to measure the amount of protein and cell adherence as well as the effectiveness of subsequent cleaning. Bradford reagent was used to detect protein as a measure of the cleaning efficacy. As with the bacteria, NaOCl bleach was effective at removing the protein and cells that had been dried or fixed by formalin or alcohol, whereas detergent with enzymes was not very effective. This study confirmed that used medical devices, contaminated with microorganisms, protein, and/or mammalian cells, should not be allowed to dry before cleaning and that a thorough cleaning procedure should precede sterilization or disinfection (with the exception of NaOCl bleach which also cleans).

Bacteria↗
PubMed1999

Decontaminating particles exposed to bacterial endotoxin (LPS).

Lipopolysaccharide (LPS), which comes from the cell wall of gram-negative bacteria, can stimulate murine macrophage cells to produce nitric oxide (NO), cytokines, such as tumor necrosis factor-alpha, and interleukins, such as IL-6. When examining the biological effects of particles on macrophages, it is important to have no contaminating LPS associated with the particles and none with any cell culture media or supplies since even very low levels of LPS are stimulatory. The presence or absence of LPS was observed in two ways: (1) the amount of NO produced by RAW 264.7 murine macrophage cells, and (2) the Limulus amebocyte lysate (LAL) test. Treating particles with 70% ethanol at room temperature for 48 h, followed by washing the polymethylmethacrylate (PMMA) particles with endotoxin-free phosphate-buffered saline three times, decontaminated LPS and LPS-treated PMMA particles. When given LPS that had been treated with 70% ethanol for 48 h at room temperature or at 37 degrees C, cells did not produce NO above control levels. Negative LAL tests indicated the presence of extremely low levels or the complete absence of LPS in 70% ethanol-treated LPS.

Animals↗
PubMed1999

Tissue colonization from implantable biomaterials with low numbers of bacteria.

This study was undertaken to evaluate the risk of infection (defined as the recovery of the relevant organism from the implant site) in a mouse model when low numbers of bacteria were present on an implanted biomaterial. Segments of different types of suture with adherent bacteria were implanted subcutaneously into mice. The infection risk with Staphylococcus aureus was greater than with Staphylococcus epidermidis RP62A or Candida albicans. The infection risk with the implantation of multifilament sutures was significantly greater than with monofilament sutures. When <10 colony forming units (cfu) of S. aureus were present on monofilament suture material, the infection rate was 3%. When <10 cfu of S. aureus were present on multifilament suture material, the infection rate was 7%. An infection rate of 15% occurred with <10 cfu of S. aureus on multifilament nylon sutures. When >10 but <20 cfu of S. aureus were present, the infection rates were 4 and 51%, respectively. These data confirm that the infection rate with multifilament sutures (or porous materials) is greater than with monofilament sutures (or solid materials) when the organisms are encountered at implantation (acute model) and indicate that a significant risk of infection may occur when only a few organisms are on a device at implantation.

Animals↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗