72 results found
Channavajjhala SK, Bramley R, Peltz T, et al., 2019, Urinary extracellular vesicle protein profiling and endogenous lithium clearance support excessive renal sodium wasting and water reabsorption in thiazide-induced hyponatremia, Kidney International Reports, Vol: 4, Pages: 139-147, ISSN: 2468-0249
Introduction: Thiazide diuretics are among the most widely used antihypertensive medications worldwide. Thiazide-induced hyponatremia (TIH) is 1 of their most clinically significant adverse effects. A priori TIH must result from excessive saliuresis and/or water reabsorption. We hypothesized that pathways regulating the thiazide-sensitive sodium-chloride cotransporter NCC and the water channel aquaporin-2 (AQP2) may be involved. Our aim was to assess whether patients with TIH would show evidence of altered NCC and AQP2 expression in urinary extracellular vesicles (UEVs), and also whether abnormalities of renal sodium reabsorption would be evident using endogenous lithium clearance (ELC). Methods: Blood and urine samples were donated by patients admitted to hospital with acute symptomatic TIH, after recovery to normonatremia, and also from normonatremic controls on and off thiazides. Urinary extracellular vesicles were isolated and target proteins evaluated by western blotting and by nanoparticle tracking analysis. Endogenous lithium clearance was assessed by inductively coupled plasma mass spectrometry. Results: Analysis of UEVs by western blotting showed that patients with acute TIH displayed reduced total NCC and increased phospho-NCC and AQP2 relative to appropriate control groups; smaller differences in NCC and AQP2 expression persisted after recovery from TIH. These findings were confirmed by nanoparticle tracking analysis. Renal ELC was lower in acute TIH compared to that in controls and convalescent case patients. Conclusion: Reduced NCC expression and increased AQP2 expression would be expected to result in saliuresis and water reabsorption in TIH patients. This study raises the possibility that UEV analysis may be of diagnostic utility in less clear-cut cases of thiazide-associated hyponatremia, and may help to identify patients at risk for TIH before thiazide initiation.
Swiatkowska I, Mosselmans JFW, Geraki T, et al., 2017, Synchrotron analysis of human organ tissue exposed to implant material., Journal of Trace Elements in Medicine and Biology, Vol: 46, Pages: 128-137, ISSN: 0946-672X
BACKGROUND: Orthopaedic implants made of cobalt-chromium alloy undergo wear and corrosion that can lead to deposition of cobalt and chromium in vital organs. Elevated cardiac tissue cobalt levels are associated with myocardial injury while chromium is a well-established genotoxin. Though metal composition of tissues surrounding hip implants has been established, few investigators attempted to characterize the metal deposits in systemic tissues of total joint arthroplasty patients. METHODS: We report the first use of micro-X-ray fluorescence coupled with micro-X-ray absorption spectroscopy to probe distribution and chemical form of cobalt, chromium and titanium in postmortem samples of splenic, hepatic and cardiac tissue of patients with metal-on-polyethylene hip implants (n = 5). RESULTS: Majority of the cobalt was in the 2+ oxidation state, while titanium was present exclusively as titanium dioxide, in either rutile or anatase crystal structure. Chromium was found in a range of forms including a highly oxidised, carcinogenic species (CrV/VI), which has never been identified in human tissue before. CONCLUSIONS: Carcinogenic forms of chromium might arise in vital organs of total joint arthroplasty patients. Further studies are warranted with patients with metal-on-metal implants, which tend to have an increased release of cobalt and chromium compared to metal-on-polyethylene hips.
Baldwin EJ, Harrington DJ, Sampson B, et al., 2016, Safety of long-term restrictive diets for peroxisomal disorders: vitamin and trace element status of patients treated for Adult Refsum Disease, INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Vol: 70, Pages: 229-235, ISSN: 1368-5031
Jones AJ, Gokhale PJ, Allison TF, et al., 2015, Evidence for bystander signalling between human trophoblast cells and human embryonic stem cells, Scientific Reports, Vol: 5, ISSN: 2045-2322
Maternal exposure during pregnancy to toxins can occasionally lead to miscarriage and malformation. It is currently thought that toxins pass through the placental barrier, albeit bi-layered in the first trimester, and damage the fetus directly, albeit at low concentration. Here we examined the responses of human embryonic stem (hES) cells in tissue culture to two metals at low concentration. We compared direct exposures with indirect exposures across a bi-layered model of the placenta cell barrier. Direct exposure caused increased DNA damage without apoptosis or a loss of cell number but with some evidence of altered differentiation. Indirect exposure caused increased DNA damage and apoptosis but without loss of pluripotency. This was not caused by metal ions passing through the barrier. Instead the hES cells responded to signalling molecules (including TNF-α) secreted by the barrier cells. This mechanism was dependent on connexin 43 mediated intercellular ‘bystander signalling’ both within and between the trophoblast barrier and the hES colonies. These results highlight key differences between direct and indirect exposure of hES cells across a trophoblast barrier to metal toxins. It offers a theoretical possibility that an indirectly mediated toxicity of hES cells might have biological relevance to fetal development.
Papamargaritis D, Aasheim ET, Sampson B, et al., 2015, Copper, selenium and zinc levels after bariatric surgery in patients recommended to take multivitamin-mineral supplementation, JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY, Vol: 31, Pages: 167-172, ISSN: 0946-672X
Hart AJ, Sabah SA, Sampson B, et al., 2014, Surveillance of Patients with Metal-on-Metal Hip Resurfacing and Total Hip Prostheses: A Prospective Cohort Study to Investigate the Relationship Between Blood Metal Ion Levels and Implant Failure., J Bone Joint Surg Am, Vol: 96, Pages: 1091-1099
BACKGROUND: We designed a prospective, single-center study to assess whether blood metal ion levels could predict implant failure in patients managed with unilateral metal-on-metal hip resurfacing or total hip arthroplasty. METHODS: Five hundred and ninety-seven patients who had received unilateral Articular Surface Replacement prostheses at least twelve months earlier were recruited. Blood metal ion levels were compared between the group of patients with failed implants and the group with non-failed implants. Implant failure was defined as prostheses associated with revision, an intention to revise, or poor patient-reported hip function (Oxford Hip Score, <31 of 48). Specificity, sensitivity, area under the curve, positive and negative predictive values, and odds ratios were calculated. Logistic regression analysis was used to identify other risk factors for implant failure. RESULTS: Patients with failed arthroplasty had significantly higher blood cobalt and chromium ion levels than did patients with non-failed arthroplasty (p < 0.01). Blood cobalt ion levels were disproportionately raised in patients with failed total hip arthroplasty (8.2 μg/L) compared with patients with failed hip resurfacing (2.5 μg/L) (p = 0.018). Blood chromium ion levels were not significantly different in patients with failed total hip arthroplasty and failed hip resurfacing (p = 0.058). The maximum value of either metal ion had good discriminant ability to predict implant failure (area under the curve, 0.76). A 7-μg/L cutoff had a positive predictive value of 0.75 (95% confidence interval, 0.66 to 0.82) and a negative predictive value of 0.82 (95% confidence interval, 0.78 to 0.86). In patients managed with total hip arthroplasty, for each increase of 1 μg/L there was a 23% (p < 0.001) increase in the odds of them being in the failed group. For patients managed with hip resurfacing, the increase in odds was 5% (p < 0.001). CONCLUSIONS: Raised levels of blood metal
Durrani SK, Noble PC, Sampson B, et al., 2014, Changes in blood ion levels after removal of metal-on-metal hip replacements: 16 patients followed for 0-12 months, Acta Orthopaedica, Vol: 85, Pages: 259-265, ISSN: 1745-3674
Background and purpose — In patients with metal-on-metal (MoM) hip prostheses, pain and joint effusions may be associated with elevated blood levels of cobalt and chromium ions. Since little is known about the kinetics of metal ion clearance from the body and the rate of resolution of elevated blood ion levels, we examined the time course of cobalt and chromium ion levels after revision of MoM hip replacements.Patients and methods — We included 16 patients (13 female) who underwent revision of a painful MoM hip (large diameter, modern bearing) without fracture or infection, and who had a minimum of 4 blood metal ion measurements over an average period of 6.1 (0–12) months after revision.Results — Average blood ion concentrations at the time of revision were 22 ppb for chromium and 43 ppb for cobalt. The change in ion levels after revision surgery varied extensively between patients. In many cases, over the second and third months after revision surgery ion levels decreased to 50% of the values measured at revision. Decay of chromium levels occurred more slowly than decay of cobalt levels, with a 9% lag in return to normal levels. The rate of decay of both metals followed second-order (exponential) kinetics more closely than first-order (linear) kinetics.Interpretation — The elimination of cobalt and chromium from the blood of patients who have undergone revision of painful MoM hip arthroplasties follows an exponential decay curve with a half-life of approximately 50 days. Elevated blood levels of cobalt and chromium ions can persist for at least 1 year after revision, especially in patients with high levels of exposure.
Mirastschijski U, Martin A, Jorgensen LN, et al., 2013, Zinc, Copper, and Selenium Tissue Levels and Their Relation to Subcutaneous Abscess, Minor Surgery, and Wound Healing in Humans, BIOLOGICAL TRACE ELEMENT RESEARCH, Vol: 153, Pages: 76-83, ISSN: 0163-4984
Hart AJ, Quinn PD, Lali F, et al., 2012, Cobalt from metal-on-metal hip replacements may be the clinically relevant active agent responsible for periprosthetic tissue reactions, ACTA BIOMATERIALIA, Vol: 8, Pages: 3865-3873, ISSN: 1742-7061
Beckerson J, Sampson B, Kanfer E, et al., 2012, Plasma zinc, copper and selenium in subjects planned for haematopoietic stem cell transplant and their change during treatment, 38th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation (EBMT), Publisher: NATURE PUBLISHING GROUP, Pages: S192-S192, ISSN: 0268-3369
Sampson, Hart, 2012, Clinical usefulness of blood metal measurements to assess the failure of metal-on-metal orthopaedic implants., Annals of Clinical Biochemistry, Vol: 49, Pages: 118-131, ISSN: 0004-5632
In April 2010, a Medicines and Healthcare Products Regulatory Agency safety alert concerning all metal-on-metal (MOM) hipreplacements recommended measuring chromium and cobalt concentrations when managing patients with painfulprostheses. The need for this review is illustrated by the recent surge in requests for these blood tests from orthopaedicsurgeons following this alert. The aim is to provide guidance to laboratories in assessing these requests and advisingclinicians on interpretation. First, we summarize the basic terminology regarding the types of hip replacements, with emphasison the MOM type. Second, we describe the clinical concerns over implant-derived wear debris in the local tissues and distantsites. Analytical aspects of the measurement of the relevant metal ions and what factors affect the levels measured arediscussed. The application of inductively coupled plasma mass spectrometry techniques to the measurement of these metalsis considered in detail. The biological effects of metal wear products are summarized with local toxicity and systemicbiological effects considered, including carcinogenicity, genotoxicity and systemic toxicity. Clinical cases are used to illustratepertinent points.
Larner F, Sampson B, Rehkamper M, et al., 2012, High precision isotope measurements show poorer control of copper metabolism in Parkinsonism., Movement Disorders
Bain PG, Sampson B, 2012, A study of copper indices in Parkinson’s disease and essential tremor., XVIth Congress of the European Federation of Neurological Societies
Objective: To examine the relationships between copper indices and age, age of symptom onset and disease duration in PD & ET.Methods: Ninety-nine consecutive outpatients with PD and 56 with ET had blood drawn for measurement of serum copper (Cu) and caeruloplasmin (Cp). Serum percentage free copper was calculated: % Free Cu = [total Cu – Cu bound to Cp]/Total Cu.Results: In ET mean serum Cu: 18.0 µmol/L, Cp: 0.34 g/L & % Free Cu: 11.4%. Females had higher Cu than males. There were significant positive correlations between age and Cu & Cp levels, and age of onset with Cp & % Free Cu. Partial correlations, adjusting for age & gender, showed positive correlations between age of onset with Cu & Cp (p=0.001 & p= 0.011 respectively) and negative correlations between tremor duration and Cu & Cp (p=0.001 & p= 0.011 respectively).In PD mean serum Cu: 16.6 µmol/L, Cp: 0.32 g/L & % Free Cu: 9.85%. In PD there were no significant correlations between age, age of onset or disease duration and any of the copper indices, even after adjusting for age and gender. Cu (but not Cp or % Free Cu) was significantly lower in PD than ET (p=0.026). Conclusion: We demonstrate significant relationships in ET between serum Cu & Cp levels and age of onset and tremor duration. This relationship was not found in PD. An explanation for these findings is that Cu & Cp provide some temporal protection from manifesting ET.
Hart AJ, Sabah SA, Bandi AS, et al., 2011, Sensitivity and specificity of blood cobalt and chromium metal ions for predicting failure of metal-on-metal hip replacement, JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME, Vol: 93B, Pages: 1308-1313, ISSN: 0301-620X
Hart AJ, Skinner JA, Henckel J, et al., 2011, Insufficient Acetabular Version Increases Blood Metal Ion Levels after Metal-on-metal Hip Resurfacing, CLINICAL ORTHOPAEDICS AND RELATED RESEARCH, Vol: 469, Pages: 2590-2597, ISSN: 0009-921X
Davda K, Lali FV, Sampson B, et al., 2011, An analysis of metal ion levels in the joint fluid of symptomatic patients with metal-onmetal hip replacements, JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME, Vol: 93B, Pages: 738-745, ISSN: 0301-620X
Larner F, Rehkaemper M, Coles BJ, et al., 2011, A new separation procedure for Cu prior to stable isotope analysis by MC-ICP-MS, JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY, Vol: 26, Pages: 1627-1632, ISSN: 0267-9477
Hart AJ, Quinn PD, Sampson B, et al., 2010, The chemical form of metallic debris in tissues surrounding metal-on-metal hips with unexplained failure, ACTA BIOMATERIALIA, Vol: 6, Pages: 4439-4446, ISSN: 1742-7061
Scurr C, Sampson B, Ball J, et al., 2009, Copper deficiency myeloneuropathy in a patient with haemachromatosis: a case report., Cases J, Vol: 2
A 64-year-old British Caucasian man presented with red skin wheals and breathlessness and then developed a progressive neurological syndrome. Investigation revealed hereditary haemachromatosis, porphyria, and a myelodysplastic syndrome. No unifying diagnosis was made, and his neurological symptoms remained unexplained, until further studies revealed an underlying copper deficiency.
Hart AJ, Sandison A, Quinn P, et al., 2009, Microfocus study of metal distribution and speciation in tissue extracted from revised metal on metal hip implants, J. Phys.: Conf. Ser., Vol: 190
Kirk P, Firmin DN, Sampson B, et al., 2005, Validation of T2*technique in ex-vivo myocardial tissue., 47th Annual Meeting of the American-Society-of-Hematology, Publisher: AMER SOC HEMATOLOGY, Pages: 7B-7B, ISSN: 0006-4971
Fessatou S, Fagerhol MK, Roth J, et al., 2005, Severe anemia and neutropenia associated with hyperzincemia and hypercalprotectinemia, JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY, Vol: 27, Pages: 477-480, ISSN: 1077-4114
Sandra Mutuma, Barry Sampson, Paul Amuna, et al., 2005, An observational study of a cohort of primiparous women of high socio-economic status and their pregnancy outcomes, 12th Interanlal Symposium on Trace Element Metabolism in Man and Animals
Barry Sampson, Therese Panetta, Jan Petrik, et al., 2005, Toxic and essential trace elements in blood and urine from Slovak populations from areas exposed to increased levels of PCBs, 12th International Symposium on Trace Element Metabolism in Man and Animals
Barry Sampson, Therese Panetta, Jab Petrik, et al., 2004, Concentrations of toxic and essential trace elements determined by DRC ICPMS in Slovak populations from areas exposed to increased levels of PCBs, 12th Biennial National Atmoc Spectrocopy Symposium
Therese Panetta, Barry Sampson, 2004, Application of ICPMS in the routine clinical laboratory. Determination of essential and toxic trace elements in serum and whole blood., 12th Biennoial National Atomic Spectroscopy Sym posium
Barbato A, Cappuccio FP, Folkerd EJ, et al., 2004, Metabolic syndrome and renal sodium handling in three ethnic groups living in England, DIABETOLOGIA, Vol: 47, Pages: 40-46, ISSN: 0012-186X
Sampson B, Fagerhol MK, Sunderkotter C, et al., 2002, Hyperzincaemia and hypercalprotectinaemia: a new disorder of zinc metabolism, LANCET, Vol: 360, Pages: 1742-1745, ISSN: 0140-6736
Lansdown ABG, Sampson B, Rowe A, 2001, Experimental observations in the rat on the influence of cadmium on skin wound repair, INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Vol: 82, Pages: 35-41, ISSN: 0959-9673
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