EU sampling strategies for the detection of veterinary drug residues in aquaculture species: are they working?

Over the past 50 years, the culture of aquatic species in controlled conditions to enhance production has grown in importance and now provides nearly 50% of the world's seafood supply. In part, this expansion has been made possible by the use of antibiotics, antifungals, and other veterinary medicines to control disease and improve welfare. Despite guidelines being available, the sampling programmes for drug residue surveillance of aquaculture products recommended by the CODEX Alimentarius Commission were withdrawn in 2008 and put under review. Directive 96/23/EC sets out legislation to govern how sampling programmes for drug residue surveillance should be conducted within the EU. This directive applies both to produce raised within the EU and also imported products from third countries. This communication examines the existing EU sampling regimen for aquaculture products and comments on its possible application in a global context. We examine UK statutory sampling data that, while indicating the effectiveness of the directive, also suggests that the directive may lead to unnecessary sampling. Regarding imports, examination of the Rapid Alert System for Food and Feed (RASFF) database using process control charts and statistical modelling suggests that the sampling regimen described in the directive is effective but not sufficiently flexible for the range of aquaculture practices that exist. Limitations of the directive, datasets, and practices are further discussed.

The effect of operative fit and hydroxyapatite coating on the mechanical and biological response to porous implants.

UNLABELLED: Femoral intramedullary implants were constructed by threading 4.0-millimeter-thick disks with a titanium-alloy (Ti-6Al-4V) porous bead coating onto a two-millimeter-diameter threaded rod. Each porous-coated disk, which was 6.0, 8.0, 9.0, or 10.0 millimeters in diameter, was separated by a two-millimeter-thick acrylic disk with a diameter of ten millimeters. Implants with and without a hydroxyapatite coating of twenty-five micrometers were inserted into fifteen skeletally mature adult mongrel dogs. The femoral canal was sequentially reamed bilaterally to a ten-millimeter diameter, resulting in uniform initial implant-bone interface gaps of 0.0, 0.5, 1.0, and 2.0 millimeters. Each animal received paired hydroxyapatite-coated and uncoated implants. Three animals each were killed at four, eight, twelve, twenty-four, and fifty-two weeks after the implantation. The harvested femora were sectioned through the acrylic spacers, transverse to the long axis, to produce individual push-out test specimens for mechanical testing. Characteristics of interface attachment were determined with test fixtures that supported the surrounding bone to within 150 micrometers of the interface. Histological sections were prepared, and the amount of bone within the porous structure and the amount of the original gap that was filled with new bone were quantified with a computerized video image-analysis system. Mechanical attachment strength and bone ingrowth were found to increase with the time after implantation and with a decrease in the size of the gap. Placement of the implant in proximal (cancellous) compared with distal (cortical) locations had no significant effect on the strength of attachment, bone ingrowth, or gap-filling. However, implants with a large initial gap (1.0 or 2.0 millimeters) demonstrated greater attachment strength in cancellous bone than in cortical bone. With a few exceptions, hydroxyapatite-coated implants with an initial gap of 1.0 millimeter or less demonstrated significantly increased mechanical attachment strength and bone ingrowth at all time-periods. Interface attachment strengths were positively correlated with bone ingrowth, the time after implantation, the use of a hydroxyapatite coating, and decreasing initial gap size. CLINICAL RELEVANCE: Initial implant-bone apposition is thought to be a prerequisite for good biological fixation. This apposition is often not achieved because of the design of the implant or instruments and the operative technique. Poor initial fit during the operation may decrease the longevity of the implant. The results of the present study indicate that attachment strength and bone ingrowth are significantly affected by gaps in the interface, particularly those of more than 1.0 millimeter.(ABSTRACT TRUNCATED AT 400 WORDS)

A seven-year clinical evaluation of soft-tissue effects of hydroxylapatite-coated vs. uncoated subperiosteal implants.

Subperiosteal implants have been providing a treatment modality for the edentulous and partially edentulous patient for over 35 years. A recent innovation in subperiosteal dental implant materials technology is the use of hydroxylapatite (HA) coating as a surface coating on the implanted metal framework. The purpose of this study was to compare the intermediate-term soft-tissue performance of HA-coated subperiosteal dental implants with that of uncoated subperiosteal dental implants at equivalent time periods. Four choices of each implant variety were followed for approximately six years. At five years, one patient died, so one HA-coated implant was lost to further follow-up. One uncoated subperiosteal needed to be removed at four years, due to unremitting dehiscence around the post area. The remaining implants were followed, and results indicate that the early healing sequelae appear to be hastened and that the intermediate-term status is non-problematic for all implants. Hard-tissue reactions are not necessarily apparent by direct observation. The HA-coated implants were associated with a kinder soft-tissue response, typified by a tighter, healthier soft-tissue seal around the perigingival abutment posts and no post-implantation strut dehiscence complications. HA coating appears to represent an incremental increase in performance of uncoated metallic subperiosteal dental implants, for soft-tissue as well as hard-tissue response.

Calcium phosphate coatings: understanding the chemistry and biology and their effective use.

Unlike titanium dental implants, hydroxyapatite (HA)-coated implants have the ability to form a chemical bond with bone. Clinicians must understand the chemical, physical, and mechanical properties of HA, as well as the differences between superior and inferior HA coatings. In fact, because not all HA coatings are the same, there are guidelines to analyze the coatings according to chemical composition, density, crystallinity, levels of impurities, surface roughness, and tensile and shear strengths. HA coatings have shown definite advantages over uncoated implants, but improvements are still needed in areas such as attachment, porosity, and crystallinity.

Hydroxylapatite coating of porous implants improves bone ingrowth and interface attachment strength.

The effect of a plasma-sprayed hydroxylapatite (HA) coating on the degree of bone ingrowth and interface shear attachment strength was investigated using a canine femoral transcortical implant model. Cylindrical implants were fabricated by sintering spherical Co-Cr-Mo particles 500-710 microns in diameter; the nominal implant dimensions were 5.95 +/- 0.05 mm diameter by 18 mm in length. One half of each implant was coated with hydroxylapatite, 25-30 microns in thickness, by a plasma-spray technique. Using strict aseptic technique, the implants were placed through both femoral cortices into defects approximately 0.05 mm undersized. After 2, 4, 6, 8, 12, 18, 26, and 52 weeks, the implants were harvested and subjected to mechanical pullout testing and undecalcified histologic evaluation. The application of the HA coating to porous implants enhanced both the amount of bone ingrowth and the interface attachment strength at all time periods. These differences were statistically significant for the percent of bone ingrowth at the 4-, 6-, 12-, 18-, 26-, and 52-week time periods, and interface shear strength values were significantly different at the 6-, 8-, 12-, 18-, and 26-week time periods. The rate of development of interface strength and bone ingrowth was also more rapid for the HA-coated implants. No evidence of any disruption, mechanical failure, or biologic resorption of the HA coating was observed. The results of the present study--demonstrating a beneficial effect of the HA coating at all time periods--are believed to be due to the use of paired comparisons, which allow assessment of subtle differences that might otherwise have been obscured by normal biological variability.

Calcium phosphate coatings for dental implants. Current status and future potential.

The initial experience with high-quality HA coatings has been positive. The application of HA coatings to metallic substrate implants represents the first time that the body can be directed as to where, and to some extent how, it should respond to their implantation, representing a truly incremental increase from metals material technology and an interim step towards more tailorable, biologically active systems. It remains clear at this writing that all HA-coatings are not created equal and it remains an environment of "buyer beware." There is cause for optimism as new advances in the three essential criteria will only improve the current success rate. These advances and increases in efficacy will, as always, be pioneered in the dental and oral surgical disciplines.

Finite element analysis of interface geometry effects on the crestal bone surrounding a dental implant.

Using a two-dimensional axisymmetric finite element analysis technique, different geometrical configurations of implants, abutments, and interfaces have been investigated to alter the stress distribution in the crestal bone region. The crestal bone region is of particular interest due to observations of progressive bone resorption (saucerization). The ability of a prosthetic restoration-implant construct to transfer an appropriate stress at this region will, by definition of Wolff's law (bone's response to strain) and principles of bone remodeling, help to maintain the integrity of the surrounding bone via force transfer. The two geometries investigated involved a traditional flat mating surface and a slanted (oblique) mating surface. In both models a vertical load of 400 N (63 N/rad across 2 pi radians) was applied to the abutment apex. In the crestal bone region the oblique mating surface increased the transfer of horizontal stress 67 percent over the traditional flat mating surface design. The magnitude of stress transferred and the area which it was transferred across was increased in this region. Results indicate potentially more favorable mechanical conditions for bone maintenance surrounding an endosseous dental implant may be achieved if force is transferred preferentially via circumferential grooves and an oblique (dished) implant-abutment mating surface. These theoretical results are consistent with basic principles of stress transfer, stress shielding, and remodeling as well as clinical observations of bone maintenance and resorption.

Enhanced bone ingrowth and fixation strength with hydroxyapatite-coated porous implants.

The effect of a hydroxyapatite (HA) coating on the interface attachment strength, rate of development of attachment strength, and degree of bone ingrowth of porous implants was investigated. Implants with ideal surgical fits and those having interface gap spaces were evaluated using femoral transcortical and intramedullary models. The application of a thin HA coating to porous implants significantly enhanced both interface attachment strength and bone ingrowth. The rate of development of interface strength and bone ingrowth was also more rapid with the HA-coated system. There was no evidence of any disruption, loss, or resorption of the HA coating.

Experimental coating defects in hydroxylapatite-coated implants.

Defects in hydroxyapatite (HA)-coated metallic implant systems, including cracks, flakes, or scratches, may occur at the time of surgery or in time because of in vivo loading. Such defects may affect the bone-implant interface response because of increased local metallic corrosion and ion release. Using a canine transcortical push-out model, the interface mechanics and histology of HA-coated titanium and cobalt-chromium-molybdenum alloy implants with and without coating defects were evaluated. The coating defects extended through the HA material to the underlying metallic substrate. Interface mechanical testing and undecalcified histologic techniques were used to evaluate differences in interface response at three, five, six, ten, 12, and 32 weeks postimplantation. There were no statistically significant differences between the HA-coated implants with and without defects for either interface shear strength or stiffness; however, both HA-coated implant types developed significantly greater interface strength and stiffness when compared to uncoated metallic implants. Histologically, in all areas away from the defect, a progression to nearly complete mineralization of osseous tissue directly onto the HA-coated surface was observed with no interpositional fibrous tissue layer. At early time periods (up to six weeks) in the area of the coating defect, bone apposition and mineralization appeared to stop at the edge of the HA coating. At later time periods (greater than ten weeks), the area of the defect was filled with mineralized osseous tissue in approximately one-half of the specimens. A thin fibrous interpositional layer was observed at the interface of the exposed metal substrate.

The tri-spade drill for endosseous dental implant installation.

Many aspects of endosseous dental implant practice have been addressed over the past several decades. While most of this attention has centered on the dental implant body itself and, most recently, on various aspects of prosthetic restoration, the installation armamentarium for site preparation and implant placement has been neglected. Drills, in particular, have received minimal attention, with most drills currently used for implant placement being identical, or nearly identical, to century-old wood or metal cutting instruments. The tri-spade drill design represents an innovation that has evolved from analysis of currently used implant drills, drill mechanics, and the mechanical and physical properties of bone, in consideration of the clinical realities of contemporary endosseous implant placement. The tri-spade drill design, which features three cutting edges, is much more stable in the hands of the practicing clinician. It reduces crestal chatter upon entry into the bone site (a stable drilling situation), resulting in a more perfectly prepared final hole for placement of a cylindrical root-form dental implant. The drill tip angle is designed specifically for use with bone; the reaming action associated with the sharpened cutting edges adjacent to the large side flutes also allows for efficient debris removal. The tri-spade drill design represents an incremental increase in the dental implant armamentarium and efficacy for the installation of endosseous cylindrical dental implants.

Biologic response to hydroxylapatite-coated titanium hips. A preliminary study in dogs.

Hydroxylapatite (HA)-coated and uncoated Ti-6A1-4V alloy femoral endoprostheses were evaluated in adult dogs. The femoral stems had proximal anterior, posterior, and medial pockets of either a commercially pure titanium porous coating or a grooved macrotexture. They also had a medial collar, with an inferior surface pocket of either the porous coating or the grooved macrotexture. HA-coated and uncoated specimens of each type were evaluated. The devices were placed as unilateral hemiarthroplasties in 12 dogs and remained in function for up to 52 weeks. Histologic sections from the uncoated grooved implants showed no direct bone-implant apposition in the proximal regions after up to 10 weeks; the HA-coated grooved implants demonstrated extensive direct bone-coating apposition after 5 weeks. Sections from uncoated porous implants evaluated after 10 weeks demonstrated approximately equivalent in-growth to those sections from the HA-coated devices after 6 weeks. All HA-coated implants demonstrated consistent bone-implant apposition with no fibrous tissue interposition. The HA-coated surfaces were associated with increased bone deposition and proliferation at early implantation periods. In no histologic section examined was there any evidence of deterioration of the HA coating, nor was any separation of the coating from the substrate material observed.

Designing to counteract the effects of initial device instability: materials and engineering.

Implants for hard tissue replacement have evolved over the last few decades, but a critical assessment of their design reveals that most dental implants and most orthopedic appliances for any given indication are basically similar in design to their commercial competitors. Some unique features are contained in the outer 0.7 mm, but shadow pictures of the devices could almost be superimposed upon one another. Near-optimal designs have evolved for the materials systems commonly in use. The fight to minimize initial instability of implants, which leads to failure, has caused certain attachment mechanisms to emerge as acceptable, based upon research that indicates firm fixation in bone has resulted in longer average implant lifetime. The problem of initial stabilization is one of materials and design, both of which are necessary for a successful implant system. The nonmetallic calcium phosphate glass and ceramics technology available today provides materials that may counteract the effects of initial device instability by not relying on mechanical means of retention, alone, but chemical as well.

Hydroxyapatite-coated titanium for orthopedic implant applications.

The interface mechanical characteristics and histology of commercially pure (CP) titanium- and hydroxyapatite- (HA) coated Ti-6Al-4V alloy were investigated. Interface shear strength was determined using a transcortical push-out model in dogs after periods of three, five, six, ten, and 32 weeks. Undecalcified histologic techniques with implants in situ were used to interpret differences in mechanical response. The HA-coated titanium alloy implants developed five to seven times the mean interface strength of the uncoated, beadblasted CP titanium implants. The mean values for interface shear strength increased up to 7.27 megaPascals (MPa) for the HA-coated implants after ten weeks of implantation, and the maximum mean value of interface shear strength for the uncoated CP titanium implants was 1.54 MPa. For both implant types there was a slight decrease in mean shear strength from the maximum value to that obtained after the longest implantation period (32 weeks). Histologic evaluations in all cases revealed mineralization of interface bone directly onto the HA-coated implant surface, with no fibrous tissue layer interposed between the bone and HA visible at the light microscopic level. The uncoated titanium implants had projections of bone to the implant surface with apparent direct bone-implant apposition observed in some locations. Measurements of the HA coating material made from histologic sections showed no evidence of significant HA resorption in vivo after periods of up to 32 weeks.

Hydroxyapatite-coated porous titanium for use as an orthopedic biologic attachment system.

The biologic attachment characteristics of hydroxyapatite (HA)-coated porous titanium and uncoated porous titanium implants were investigated. The implants were placed transcortically in the femora of adult mongrel dogs and evaluated after periods of three, six, and 12 weeks. The HA coating was applied using a modified plasma spray process to samples with pore volume and pore size of the porous coating expanded to equal the pore morphology of uncoated porous specimens. Mechanical push-out testing revealed that the bone-porous material interface shear strength increased with time in situ for both the uncoated and HA-coated implants. The use of the HA coating on porous titanium, however, did not significantly increase attachment strength. Histologic and microradiographic sections yielded similar qualitative results in the amount of bone grown into each system. After three weeks, both systems displayed primarily woven bone occupying approximately 50% of the available porous structure. Six and 12 weeks postimplantation, each system displayed more extensive bone ingrowth, organization, and mineralization, with only limited areas of immature bone. Histologically, differences were noted at the ingrown bone-porous material interface between the two implant types. The HA coating supported mineralization directly onto its surface, and a thin osseous layer was found lining all HA-coated surfaces. An extremely thin fibrous layer was observed separating the uncoated titanium particle surface from ingrown bone. There was no extensive direct apposition or lining of the ingrown bone to the uncoated porous titanium particle surfaces.

The effect of surface macrotexture and hydroxylapatite coating on the mechanical strengths and histologic profiles of titanium implant materials.

A mechanical and histological evaluation of uncoated and hydroxylapatite-coated titanium implant materials was performed. Cylindrical implants of uncoated commercially pure (CP) titanium and hydroxylapatite-coated Ti-6Al-4V alloy were studied using a transcortical model, with implants evaluated after periods of 3, 5, 10, and 32 weeks. All implants had a surface macrotexture consisting of a series of semicircular annular grooves, approximately 750 micron in maximum depth. The attachment characteristics of interface shear stiffness and interface shear strength were determined by mechanical push-out testing. Nondecalcified histologic and microradiographic techniques, with implants in situ, were used to evaluate the response to the implant materials and the presence of the surface macrotexture. Mechanical testing results indicated that the hydroxylapatite-coated implants exhibited significantly greater values of maximum interface shear strength than the uncoated implants after all time periods. Interface shear stiffness was also significantly greater at all time periods for the hydroxylapatite-coated implants as compared to the uncoated implants. Histological evaluation after 3 weeks revealed an osteoid layer covering on all areas coated with the hydroxylapatite material; mineralization of this layer appeared to be complete after 10 weeks. In all cases, longer-term implants demonstrated mineralization of interface bone directly onto the hydroxylapatite coating, and in no case was a fibrous layer observed between the hydroxylapatite coating and the interface bone. Sections from the uncoated CP titanium implants revealed a thin fibrous layer present in nearly all areas. Only isolated regions of direct bone-implant apposition were observed for the uncoated implants. The presence of this fibrous tissue layer, however, apparently did not adversely affect the development of considerable attachment strength. The results from this study indicate that the hydroxylapatite coating can significantly increase the attachment strength of implants which rely upon bone apposition for fixation. In addition, the hydroxylapatite coating provides an osteophilic surface for bone deposition, and allows for a more rapid development of implant-bone attachment.

Hydroxylapatite blocks and particles as bone graft substitutes in orthognathic and reconstructive surgery.

A three-year clinical evaluation of 98 patients in whom dense hydroxylapatite in particle and block form had been placed in facial contour defects and osteotomy sites, and in cystic and reconstructive defects, alone or with autogenous bone, was conducted. The results indicate that the implants were effective in reducing operating time and potential for infection and relapse, as well as in reducing or eliminating the necessity of a donor site. The clinical response was excellent, and complications with both forms were minor, generally related to lack of initial fixation or failure to use autogenous bone in specific situations.