Serum and urine metal levels in patients with metal-on-metal surface arthroplasty

The resurgence of metal-on-metal articulating surfaces for hip arthroplasty has also heightened concerns about the degree and magnitude of metal particle generation and the accompanying increase in circulating metal ion concentrations. In this study, we measured the concentration of chromium in serum and urine and the concentration of cobalt in serum in twenty-five patients with modern metal-on-metal surface arthroplasty of the hip in a prospective manner. The results showed that the mean post-operative chromium in serum levels were 22-fold, 23-fold and 21-fold higher at 3, 6 and 12 months post-operative, respectively, than pre-operative levels. The mean post-operative cobalt in serum levels were 8-fold, 7-fold and 6-fold higher at 3, 6 and 12 months post-operative, respectively, than pre-operative levels. The mean post-operative chromium in urine levels were 9-fold, 10-fold and 14-fold higher at 3, 6 and 12 months post-operative, respectively, than pre-operative levels. The values seen in this study with the current generation of surface arthroplasties are: (a) lower than those seen in an earlier generation of surface arthroplasties; (b) in the same range as those observed in association with metal-on-metal conventional total hip replacements, which typically have smaller head sizes; (c) higher than values observed in patients with conventional metal-on-polyethylene articulating couples.     

Mechanical cycling fatigue of PBGA package interconnects

Increased packaging density in micro-electronic products has advantaged attach of BGA, micro-BGA, CSP, and DCA packages. These area array packages are assembled to circuit boards that are reduced in size and thickness, by necessity. These assemblies would include flexible thin laminate circuit boards with area array components attached by solder balls. In normal use, these assemblies would be subjected to numerous ultra-low frequency mechanical deflections; consider a keypad when the user enters telephone numbers. Most of the reliability studies of area array packages have dealt with temperature cycling induced fatigue. However, less attention has been paid to mechanical bending fatigue of these packages.A test method has been developed to elucidate the mechanical bending fatigue issues of BGA, micro-BGA, CSP, and DCA packages attached to printed circuit boards. Appropriate bending fatigue reliability models and their theoretical basis are being developed. The test method and preliminary mechanical cyclic fatigue data on a PBGA package will be presented as a function of printed circuit board thickness. Consideration will be given to fatigue fracture morphology and its relation to solder joint location and rate of crack growth.     

Metal release and excretion from cementless titanium alloy total knee replacements

Concentrations of titanium, aluminum, and vanadium were measured in the serum and urine of patients with titanium alloy cementless primary total knee arthroplasty components. Patients were categorized in one of five groups. In Group 1, the patellar and tibial articulating surfaces were made of carbon fiber reinforced ultrahigh molecular weight polyethylene. In Group 2, the patellar and tibial surfaces were made of ultrahigh molecular weight polyethylene. In Group 3, the femoral titanium alloy articulating surface was nitrogen ion implanted with ultrahigh molecular weight polyethylene patellar and tibial articulating surfaces. Patients in Group 4 had failed patellar components, and Group 5 was comprised of age and gender matched control subjects without implants. Serum concentrations of titanium were approximately 50 times greater in patients with failed patellar components (Group 4) and approximately 10 times greater in patients with carbon fiber reinforced polyethylene bearing surfaces (Group 1) when compared with Groups 2 and 3 and the control subjects (Group 5). For aluminum and vanadium, no detectable differences were observed among any of the groups. In addition, analysis of 24-hour urine samples showed no significant differences in titanium, aluminum, or vanadium concentrations among any of the groups. Elevated serum titanium levels may serve as a marker of patellar component failure or accelerated femoral component wear in total knee replacements with titanium alloy bearings. The toxicologic ramifications of these findings are unknown.     

Metal release in patients who have had a primary total hip arthroplasty. A prospective, controlled, longitudinal study

There is an increasing recognition that, in the long term, total joint replacement may be associated with adverse local and remote tissue responses that are mediated by the degradation products of prosthetic materials. Particular interest has centered on the metal-degradation products of total joint replacements because of the known toxicities of the metal elements that make up the alloys used in the implants. We measured the concentrations of titanium, aluminum, cobalt, and chromium in the serum and the concentration of chromium in the urine of seventy-five patients during a three-year prospective, longitudinal study. Twenty patients had had a so-called hybrid total hip replacement (insertion of a modular cobalt-alloy femoral stem and head with cement and a titanium acetabular cup without cement), fifteen had had insertion of an extensively porous-coated cobalt-alloy stem with a cobalt-alloy head and a titanium-alloy socket without cement, and twenty had had insertion of a proximally porous-coated titanium-alloy stem with a cobalt-alloy head and a titanium socket without cement. The remaining twenty patients did not have an implant and served as controls. The results of our study showed that, thirty-six months postoperatively, patients who have a well functioning prosthesis with components containing titanium have as much as a threefold increase in the concentration of titanium in the serum and those who have a well functioning prosthesis with cobalt-alloy components have as much as a fivefold and an eightfold increase in the concentrations of chromium in the serum and urine, respectively. The predominant source of the disseminated chromium-degradation products is probably the modular head-neck junction and may be a function of the geometry of the coupling. Passive dissolution of extensively porous-coated cobalt-alloy stems was not found to be a dominant mode of metal release. CLINICAL RELEVANCE: Increased concentrations of circulating metal-degradation products derived from orthopaedic implants may have deleterious biological effects over the long term that warrant investigation. This is a particularly timely concern because of recent clinical trends, including the reintroduction of metal-on-metal bearing surfaces and the increasing popularity of extensively porous-coated devices with large surface areas of exposed metal. Accurate monitoring of the concentrations of metal in the serum and urine after total hip replacement also can provide insights into the mechanisms of metal release. Our findings suggest that fretting corrosion at the head-neck coupling is an important source of metal release that can lead to increased concentrations of chromium in the serum. Determinations of the concentrations of metal in the serum and urine may be useful in the diagnosis of patients who are symptomatic after a total joint replacement as increased levels are indicative of at least one mode of mechanical dysfunction (for example, fretting corrosion) of the device.     

Mechanical characterization of plastic ball grid array package flexure using moire interferometry

Most previous studies of PBGA packaging reliability focused on the effect of thermal cycling. However, as portable electronic products such as cellular phones and laptop computers are reduced in size and become more readily available, isothermal flexural fatigue also becomes an important reliability issue. Solder interconnects subjected to mechanically induced deformation may result in failure. In the current work, moire interferometry is used to investigate the influence of PCB flexure on interconnect strains. A versatile testing apparatus is developed to load PBGA packages in four point bending. Moire fringe patterns are recorded and analyzed at various bending loads to examine the variation in displacement and strain between the components. Solder balls across the entire array experience large shear strains, often resulting in plastic deformation, which reduces service life of the package.     

Acute Effect of Caffeine on the Synthesis of Pro-Inflammatory Cytokines in the Hypothalamus and Choroid Plexus during Endotoxin-Induced Inflammation in a Female Sheep Model

This study was designed to determine the effect of acute caffeine (CAF) administration, which exerts a broad spectrum of anti-inflammatory activity, on the synthesis of pro-inflammatory cytokines and their receptors in the hypothalamus and choroid plexus (ChP) during acute inflammation caused by the injection of bacterial endotoxin—lipopolysaccharide (LPS). The experiment was performed on 24 female sheep randomly divided into four groups: control; LPS treated (iv.; 400 ng/kg of body mass (bm.)); CAF treated (iv.; 30 mg/kg of bm.); and LPS and CAF treated. The animals were euthanized 3 h after the treatment. It was found that acute administration of CAF suppressed the synthesis of interleukin (IL-1β) and tumor necrosis factor (TNF)α, but did not influence IL-6, in the hypothalamus during LPS-induced inflammation. The injection of CAF reduced the LPS-induced expression of TNF mRNA in the ChP. CAF lowered the gene expression of IL-6 cytokine family signal transducer (IL6ST) and TNF receptor superfamily member 1A (TNFRSF1) in the hypothalamus and IL-1 type II receptor (IL1R2) in the ChP. Our study on the sheep model suggests that CAF may attenuate the inflammatory response at the hypothalamic level and partly influence the inflammatory signal generated by the ChP cells. This suggests the potential of CAF to suppress neuroinflammatory processes induced by peripheral immune/inflammatory challenges.     

Involvement of adrenoceptors in the ovarian vascular pedicle in the regulation of counter current transfer of steroid hormones to the arterial blood supplying the oviduct and uterus of pigs

The staurosporine analogues CGP 41251, UCN-01 and Ro 31-8220 are specific inhibitors of protein kinase C (PKC). CGP 41251 and UCN-01 exert anti-neoplastic activity against human tumours grown in rodents, and CGP 41251 reverses multidrug resistance. The hypothesis was tested that these agents can induce drug resistance and alter cellular levels of target kinases. Human-derived A549 lung carcinoma cells were exposed for 6 months to CGP 41251, UCN-01 or Ro 31-8220 at gradually increasing concentrations. Cells acquired resistance against these agents, 4.3-fold against CGP 41251 (A549/CGP cells), 4.0-fold against UCN-01 (A549/UCN cells) and 14-fold against Ro 31-8220 (A549/Ro cells). Cells were neither collaterally cross-resistant towards the PKC inhibitors nor resistant against the growth-inhibitory properties of 12-O-tetradecanoylphorbol-13-acetate. However, cross-resistance was observed in A549/CGP cells against staurosporine (13-fold) and in A549/Ro cells against doxorubicin (26-fold). All 3 cell types expressed multidrug resistance-associated protein, and A549/Ro cells expressed P-glycoprotein, as adjudged by Western blot analysis. Phorbol ester-stimulated PKC activity in these cells was decreased by between 57% and 96% compared to wild-type A549 cells. Levels of the PKC isoenzymes alpha and theta in all 3 resistant cell types and of PKC-epsilon in A549/UCN cells were concomitantly reduced. Cells regained drug sensitivity after culture in the absence of drug for 6 (A549/Ro cells), 5 (A549/CGP cells) and 1 (A549/UCN cells) months. Our results suggest the following features of this type of anti-signalling drug: (i) they can induce drug resistance, (ii) they may be potentially useful in combination because of the lack of cross-resistance between them and (iii) they can down-regulate PKC, which may have pharmacological or toxicological consequences.     

Effect of Lipopolysaccharide-Induced Inflammatory Challenge on β-Glucuronidase Activity and the Concentration of Quercetin and Its Metabolites in the Choroid Plexus,Blood Plasma and Cerebrospinal Fluid

Quercetin-3-glucuronide (Q3GA), the main phase II metabolite of quercetin (Q) in human plasma, is considered to be a more stable form of Q for transport with the bloodstream to tissues, where it can be potentially deconjugated by β-glucuronidase (β-Gluc) to Q aglycone, which easily enters the brain. This study evaluates the effect of lipopolysaccharide (LPS)-induced acute inflammation on β-Gluc gene expression in the choroid plexus (ChP) and its activity in blood plasma, ChP and cerebrospinal fluid (CSF), and the concentration of Q and its phase II metabolites in blood plasma and CSF. Studies were performed on saline- and LPS-treated adult ewes (n = 40) receiving Q3GA intravenously (n = 16) and on primary rat ChP epithelial cells and human ChP epithelial papilloma cells. We observed that acute inflammation stimulated β-Gluc activity in the ChP and blood plasma, but not in ChP epithelial cells and CSF, and did not affect Q and its phase II metabolite concentrations in plasma and CSF, except Q3GA, for which the plasma concentration was higher 30 min after administration (p < 0.05) in LPS- compared to saline-treated ewes. The lack of Q3GA deconjugation in the ChP observed under physiological and acute inflammatory conditions, however, does not exclude its possible role in the course of neurodegenerative diseases.