Is the synovial fluid cobalt-to-chromium ratio related to the serum partitioning of metal debris following metal-on-metal hip arthroplasty?

OBJECTIVES: We investigated the reliability of the cobalt-chromium (CoCr) synovial joint fluid ratio (JFR) in identifying the presence of a severe aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) response and/or suboptimal taper performance (SOTP) following metal-on-metal (MoM) hip arthroplasty. We then examined the possibility that the CoCr JFR may influence the serum partitioning of Co and Cr. METHODS: For part A, we included all revision surgeries carried out at our unit with the relevant data, including volumetric wear analysis, joint fluid (JF) Co and Cr concentrations, and ALVAL grade (n = 315). Receiver operating characteristic curves were constructed to assess the reliability of the CoCr JFR in identifying severe ALVAL and/or SOTP. For part B, we included only patients with unilateral prostheses who had given matched serum and whole blood samples for Co and Cr analysis (n = 155). Multiple regression was used to examine the influence of JF concentrations on the serum partitioning of Co and Cr in the blood. RESULTS: A CoCr JFR > 1 showed a specificity of 83% (77% to 88%) and sensitivity of 63% (55% to 70%) for the detection of severe ALVAL and/or SOTP. In patients with CoCr JFRs > 1, the median blood Cr to serum Cr ratio was 0.99, compared with 0.71 in patients with CoCr JFRs < 1 (p < 0.001). Regression analysis demonstrated that the blood Cr to serum Cr value was positively associated with the JF Co concentration (p = 0.011) and inversely related to the JF Cr concentration (p < 0.001). CONCLUSION: Elevations in CoCr JFRs are associated with adverse biological (severe ALVAL) or tribocorrosive processes (SOTP). Comparison of serum Cr with blood Cr concentrations may be a useful additional clinical tool to help to identify these conditions.Cite this article: D. J. Langton, S. Natu, C. F. Harrington, J. G. Bowsher, A. V. F. Nargol. Is the synovial fluid cobalt-to-chromium ratio related to the serum partitioning of metal debris following metal-on-metal hip arthroplasty? Bone Joint Res 2019;8:146-155. DOI: 10.1302/2046-3758.83.BJR-2018-0049.R1.

Analysis of soluble or titanium dioxide derived titanium levels in human whole blood: consensus from an inter-laboratory comparison.

Exposure to titanium (Ti), via the ingestion of pigment grade Ti dioxide (TiO2), is commonplace for westernised populations. It may also occur as a consequence of metal ion leaching in subjects bearing Ti-containing implants. Accurate exposure analysis requires fit-for-purpose analytical methodology, especially for true measures of baseline levels. Inductively coupled plasma (ICP) techniques are, mainly, now used for bio-analysis of Ti. Since whole blood reference materials, certified for natural low levels of Ti, are not currently available, we undertook an inter-laboratory comparison of pooled human blood from fasted volunteers ±low level (+∼2.5 µg L-1) or high level (+10-20 µg L-1) spikes of soluble Ti or TiO2 particles. Seven established laboratories were enrolled to analyse the samples using ICP based techniques, which included at least one of ICP optical emission spectrometry (ICP-OES), high resolution ICP mass spectrometry (HR-ICP-MS), triple quadrupole ICP-MS (ICP-MS/MS) or single quadrupole ICP-MS (SQ-ICP-MS). Five laboratories diluted the blood for analysis whilst two performed acid digestion. Overall, we showed that the laboratories could, mostly, quantitatively detect modest levels of spiked Ti in blood. Markedly varying levels of Ti, however, were reported for the same baseline pooled sample (0.4-24.6 µg L-1) and, in this study, specificity was poor for SQ-ICP-MS. Digestion of samples caused sample contamination compromising limits of detection and accuracy, whilst simple dilution had no such problem, and remained linear in response for spikes with ionic and TiO2 particles. We conclude that measuring baseline levels of Ti in whole blood is challenging but should be readily achievable down to 0.5-1.5 µg L-1, if sample preparation avoids contamination and instrument techniques are used that negate polyatomic or isobaric interferences from the sample matrix. We also remind those relying upon Ti bio-analytical data for their experimental outcomes that (a) spiking and recovery experiments provide information only on linearity of detection but not at all on accuracy as this will not detect constant positive errors and that (b) biological standard materials for Ti generally contain high levels of the analyte and tend to mask baseline analytical errors. Caution may be required in interpreting the findings of some published Ti/TiO2 bio-exposure studies.

Cells deficient in the base excision repair protein, DNA polymerase beta, are hypersensitive to oxaliplatin chemotherapy.

A significant proportion of human cancers overexpress DNA polymerase beta (Pol beta), the major DNA polymerase involved in base excision repair. The underlying mechanism and biological consequences of overexpression of this protein are unknown. We examined whether Pol beta, expressed at levels found in tumor cells, is involved in the repair of DNA damage induced by oxaliplatin treatment and whether the expression status of this protein alters the sensitivity of cells to oxaliplatin. DNA damage induced by oxaliplatin treatment of HCT116 and HT29 colon cancer cells was observed to be associated with the stabilization of Pol beta protein on chromatin. In comparison with HCT116 colon cancer cells, isogenic oxaliplatin-resistant (HCT-OR) cells were found to have higher constitutive levels of Pol beta protein, faster in vitro repair of a DNA substrate containing a single nucleotide gap and faster repair of 1,2-GG oxaliplatin adduct levels in cells. In HCT-OR cells, small interfering RNA knockdown of Pol beta delayed the repair of oxaliplatin-induced DNA damage. In a different model system, Pol beta-deficient fibroblasts were less able to repair 1,2-GG oxaliplatin adducts and were hypersensitive to oxaliplatin treatment compared with isogenic Pol beta-expressing cells. Consistent with previous studies, Pol beta-deficient mouse fibroblasts were not hypersensitive to cisplatin treatment. These data provide the first link between oxaliplatin sensitivity and DNA repair involving Pol beta. They demonstrate that Pol beta modulates the sensitivity of cells to oxaliplatin treatment.

A survey of arsenic in foodstuffs on sale in the United Kingdom and imported from Bangladesh.

Arsenic is a highly toxic element and its presence in food composites is a matter of concern to the well being of both humans and animals. Arsenic-contaminated groundwater is often used in Bangladesh and West Bengal (India) to irrigate crops used for food and animal consumption, which could potentially lead to arsenic entering the human food chain. In this study, we used graphite furnace atomic absorption spectroscopy to determine the total arsenic concentrations in a range of foodstuffs, including vegetables, rice and fish, imported into the United Kingdom from Bangladesh. The mean and range of the total arsenic concentration in all the vegetables imported from Bangladesh were 54.5 and 5-540 microg/kg, respectively. The highest arsenic values found were for the skin of Arum tuber, 540 microg/kg, followed by Arum Stem, 168 microg/kg, and Amaranthus, 160 microg/kg. Among the other samples, freshwater fish contained total arsenic levels between 97 and 1318 microg/kg. The arsenic content of the vegetables from the UK was approximately 2- to 3-fold lower than those observed for the vegetables imported from Bangladesh. The levels of arsenic found in vegetables imported from Bangladesh in this study, in some cases, are similar to those previously recorded for vegetables grown in arsenic-affected areas of West Bengal, India, although lower than the levels reported in studies from Bangladesh. While the total arsenic content detected in our study in vegetables, imported from Bangladesh, is far less than the recommended maximum permitted level of arsenic, it does provide an additional source of arsenic in the diet. This raises the possibility that the level of arsenic intake by certain sectors of the UK population may be significantly higher then the general population and requires further investigations.

A method for the quantitative analysis of iron speciation in meat by using a combination of spectrophotometric methods and high-performance liquid chromatography coupled to sector field inductively coupled plasma mass spectrometry.

The determination of the heme and non-heme iron fractions in raw and cooked beef steak by using spectrophotometric methods and high-performance liquid chromatography coupled to a double-focusing sector field inductively coupled plasma mass spectrometer (HPLC-SF-ICPMS) is reported. Size exclusion chromatography coupled to SF-ICPMS was used to measure the iron-containing biomolecules in the samples. This approach allowed for the direct on-line detection of the most abundant iron isotope 56Fe without interference from 40Ar16O. The HPLC-ICPMS results for the iron speciation analysis of a raw beef steak, used as an analytical quality control (AQC) sample, showed that the main iron biomolecule present was the heme iron-containing protein myoglobin. For the AQC sample, the agreement among the HPLC-ICPMS method, the non-heme iron spectrophotometric method, and the total iron concentration showed 100% recovery of iron. The sum of the different iron-containing compounds determined using the developed HPLC-ICPMS method accounted for all the iron-containing compounds extracted. The analysis of myoglobin in steak by HPLC-ICPMS showed that on cooking the concentration was reduced by 85%. However, a spectrophotometric method specific for heme iron showed that it was still intact, even after heating to 80 degrees C. The measurement of the total iron in the cooked steak and the HPLC extracts by inductively coupled plasma optical emission spectroscopy (ICP-OES) indicated that the extraction method for the HPLC analysis was no longer applicable and that loss of the heme group from the protein rendered it incompatible with the size exclusion separation. The detection limit (concentration equivalent to 3 times the baseline for a blank injection) of the HPLC-ICPMS method was 2.4 ng as iron. The results demonstrate that a combination of analytical methods can be used to provide valuable information about dietary levels of nutritionally important metal-containing compounds as well as the efficiency of established extraction methods for raw and cooked meat samples.

Simplex optimisation of conditions for the determination of antimony in environmental samples by using electrothermal atomic absorption spectrometry.

Analysis of the total antimony in plant material was unsuccessful using the electrothermal atomic absorption spectrometry (ETAAS) conditions recommended by the instrument manufacturer. For this reason, an optimisation procedure utilising the Plackett-Burman method, simplex optimisation and visualisation of the generated response surface via principal components analysis, was carried out. The Plackett-Burman method was used to eliminate four of the initial variables chosen. Four variables (atomisation temperature, atomisation time, ash temperature and modifier concentration) were subsequently optimised using the composite modified simplex method and the results were visualised as a contour diagram, after reduction to two principal components. The optimised conditions were used for the analysis of both an acid digested pine needle standard reference material (NIST 1575) and a pond weed sample, collected from a contaminated site at Yellowknife Bay, Yellowknife, NWT, Canada. The total concentration of antimony present in the pine needles was statistically indistinguishable from the non-certified value, as was the value for the pond weed sample, compared with a value determined by neutron activation analysis (NAA). The results for the analysis of the pond weed sample by ETAAS agreed with those obtained from a subsequent analysis by inductively coupled plasma-mass spectrometry.

Simplex optimisation of conditions for the determination of antimony in environmental samples by using electrothermal atomic absorption spectrometry.

Analysis of the total antimony in plant material was unsuccessful using the electrothermal atomic absorption spectrometry (ETAAS) conditions recommended by the instrument manufacturer. For this reason, an optimisation procedure utilising the Plackett-Burman method, simplex optimisation and visualisation of the generated response surface via principal components analysis, was carried out. The Plackett-Burman method was used to eliminate four of the initial variables chosen. Four variables (atomisation temperature, atomisation time, ash temperature and modifier concentration) were subsequently optimised using the composite modified simplex method and the results were visualised as a contour diagram, after reduction to two principal components. The optimised conditions were used for the analysis of both an acid digested pine needle standard reference material (NIST 1575) and a pond weed sample, collected from a contaminated site at Yellowknife Bay, Yellowknife, NWT, Canada. The total concentration of antimony present in the pine needles was statistically indistinguishable from the non-certified value, as was the value for the pond weed sample, compared with a value determined by neutron activation analysis (NAA). The results for the analysis of the pond weed sample by ETAAS agreed with those obtained from a subsequent analysis by inductively coupled plasma-mass spectrometry.