Barry Sampson | Imperial College London (original) (raw)

Papers by Barry Sampson

Research paper thumbnail of 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

The Journal of bone and joint surgery. American volume, Jan 2, 2014

We designed a prospective, single-center study to assess whether blood metal ion levels could pre... more 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 patie...

Research paper thumbnail of Zinc, copper, and selenium tissue levels and their relation to subcutaneous abscess, minor surgery, and wound healing in humans

Biological trace element research, 2013

Trace element involvement in wounds left to heal by secondary intention needs clarification. We h... more Trace element involvement in wounds left to heal by secondary intention needs clarification. We have previously reported faster healing of wounds following acute surgery compared with elective excision of pilonidal sinus disease. The effect of topical zinc on the closure of the excisional wounds was mediocre compared with placebo. In contrast, parenteral zinc, copper, and selenium combined appear effective for wound healing in humans. We have investigated zinc, copper, and selenium with respect to (a) impact of acute versus chronic pilonidal sinus and (b) regional concentrations within granulating wounds treated topically with placebo or zinc in 42 (33 males) pilonidal disease patients. Baseline serum and skin concentrations of copper correlated (r S = 0.351, p = 0.033, n = 37), but not of zinc or selenium. Patients with abscesses had elevated serum C-reactive protein (CRP) and copper levels (+29 %; p < 0.001) compared with the elective patients consistent with the strong correla...

Research paper thumbnail of An analysis of metal ion levels in the joint fluid of symptomatic patients with metal-on-metal hip replacements

The Journal of bone and joint surgery. British volume, 2011

We retrospectively analysed concentrations of chromium and cobalt ions in samples of synovial flu... more We retrospectively analysed concentrations of chromium and cobalt ions in samples of synovial fluid and whole blood taken from a group of 92 patients with failed current-generation metal-on-metal hip replacements. We applied acid oxidative digestion to our trace metal analysis protocol, which found significantly higher levels of metal ion concentrations in blood and synovial fluid than a non-digestive method. Patients were subcategorised by mode of failure as either 'unexplained pain' or 'defined causes'. Using this classification, chromium and cobalt ion levels were present over a wider range in synovial fluid and not as strongly correlated with blood ion levels as previously reported. There was no significant difference between metal ion concentrations and manufacturer of the implant, nor femoral head size below or above 50 mm. There was a moderately positive correlation between metal ion levels and acetabular component inclination angle as measured on three-dimens...

Research paper thumbnail of Changes in blood ion levels after removal of metal-on-metal hip replacements

Acta Orthopaedica, 2014

Since little is known about the kinetics of metal ion clearance from the body and the rate of res... more 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.

Research paper thumbnail of A Case of Hyperzincemia with Functional Zinc Depletion: A New Disorder?

Pediatric Research, 1997

We report the case of an 1l-y-old boy with a plasma Zn concentration greater than 200 micromol/L,... more We report the case of an 1l-y-old boy with a plasma Zn concentration greater than 200 micromol/L, but with symptoms consistent with Zn deficiency. He has had hepatosplenomegaly, rashes, stunted growth (&lt;3rd centile), anemia, and impaired immune function since infancy. He also has vasculitis and osteoporosis. A plasma Zn-binding protein has been separated and characterized by a combination of size exclusion and ion exchange chromatography and electrophoretic studies and by immunologic methods. Antibodies to the partially purified protein have been raised in rabbits. Size exclusion chromatography shows that Zn is bound to a protein with a mass 110000-300000 kD. Electrophoretic and mass spectrometry studies suggest that the protein may be composed of several subunits. One component of the isolated protein reacts with antiserum to alpha2-macroglobulin; immunoprecipitation studies confirm that the protein is not alpha2-macroglobulin or a histidine-rich glycoprotein. Kinetic studies of zinc metabolism in the patient and his mother with stable Zn isotopes show the presence of increased exchangeable Zn, with a rapid flux from plasma to a stable pool. Liver and muscle Zn and Cu concentrations are raised, but with no abnormal liver histology. Immunoreactive metallothionein in the liver is increased. We suggest that this boy may suffer from a previously unrecognized inborn error of Zn metabolism causing symptomatic zinc deficiency.

Research paper thumbnail of High precision isotope measurements reveal poor control of copper metabolism in Parkinsonism

Metallomics, 2013

Disordered copper metabolism may be important in the aetiology of Parkinsonism, as caeruloplasmin... more Disordered copper metabolism may be important in the aetiology of Parkinsonism, as caeruloplasmin is a key enzyme in handling oxidative stress and is involved in the synthesis pathway of dopamine. The human Cu metabolism of ten Parkinsonism patients was compared to ten healthy controls with the aid of a stable 65 Cu isotope tracer. The analyses of blood serum 65 Cu/ 63 Cu ratios yielded individual isotopic profiles, which indicate that the Cu metabolism is less controlled in patients with Parkinsonism.

Research paper thumbnail of Microfocus study of metal distribution and speciation in tissue extracted from revised metal on metal hip implants

Journal of Physics: Conference Series, 2009

... Alister J Hart 1, Ann Sandison2, Paul Quinn3, Barry Sampson4, Kirk D Atkinson8, John A Skinne... more ... Alister J Hart 1, Ann Sandison2, Paul Quinn3, Barry Sampson4, Kirk D Atkinson8, John A Skinner5, Angela Goode6, Jonathan J Powell7, J Frederick W ... 3 Science Division, Diamond Light Source,Harwell Science and Innovation Campus, Didcot, Oxon, OX11 0DE, UK ...

Research paper thumbnail of A new separation procedure for Cu prior to stable isotope analysis by MC-ICP-MS

Journal of Analytical Atomic Spectrometry, 2011

A novel ion exchange chromatography was developed for the separation of Cu from biological sample... more A novel ion exchange chromatography was developed for the separation of Cu from biological samples prior to stable isotope analyses. In contrast to previous methods, the new technique makes use of the different distribution coefficients of Cu(I) and Cu(II) to anion exchange resin and this helps to significantly improve the purity of the Cu separates obtained from biological samples, whilst maintaining crucial quantitative yields. Careful method validation confirmed that the procedure yields sufficiently pure Cu fractions after a single pass through the anion exchange columns, with a recovery of 100 AE 2%. Subsequent isotopic analyses of the Cu by multi-collector inductively coupled plasma mass spectrometry, using admixed Ni for mass bias correction, produced accurate Cu stable isotope data with a reproducibility of AE0.04& for pure standard solutions and of AE0.15& for samples of biological origin.

Research paper thumbnail of Insufficient Acetabular Version Increases Blood Metal Ion Levels after Metal-on-metal Hip Resurfacing

Clinical Orthopaedics and Related Research®, 2011

Background Many factors affect the blood metal ion levels after metal-on-metal (MOM) hip arthropl... more Background Many factors affect the blood metal ion levels after metal-on-metal (MOM) hip arthroplasty. The main surgically adjustable variable is the amount of coverage of the head provided by the cup which is a function of the inclination and version angles. However, most studies have used plain radiographs which have questionable precision and accuracy, particularly for version and large diameter metal heads; further, these studies do not simultaneously assess version and inclination. Thus the relationship between version and blood metal ions levels has not been resolved. Questions/purposes We determined whether cup inclination and version influence blood metal ion levels while adjusting for age at assessment, gender, body mass index, horizontal femoral offset, head size, manufacturer hip type, and Oxford hip score. Patients and Methods We prospectively followed 100 individuals (51 females, 49 males) with unilateral MOM hip resurfacing who underwent clinical assessment, CT scanning, and blood metal ion measurement. Multiple regression analysis was used to determine which variables were predictors of blood metal ion levels and to model the effect of these variables. Results Only cup inclination, version angles, and gender influenced blood cobalt or chromium levels. Cobalt and chromium levels positively correlated with inclination angle and negatively correlated with version angle. The effect of changes in version angle was less than for inclination angle. Based on our observations, we developed a formula to predict the effect of these parameters on metal ion levels. Conclusions Our data suggest insufficient cup version can cause high blood metal ions after MOM hip arthroplasty. We were unable to show that excessive version caused high levels.

Research paper thumbnail of Copper deficiency myeloneuropathy in a patient with haemachromatosis: a case report

Cases Journal, 2009

A 64-year-old British Caucasian man presented with red skin wheals and breathlessness and then de... more 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.

Research paper thumbnail of The chemical form of metallic debris in tissues surrounding metal-on-metal hips with unexplained failure

Acta Biomaterialia, 2010

Implant-derived material from metal-on-metal (MOM) hip arthroplasties may be responsible for an u... more Implant-derived material from metal-on-metal (MOM) hip arthroplasties may be responsible for an unexplained tissue inflammatory response. The chemical form of the metal species in the tissues is predominantly chromium (Cr), but the currently used techniques have not been able to determine whether this is Cr(III) phosphate or Cr(III) oxide. The analytical challenge must overcome the fact that the metal in the tissues is at a relatively low concentration and tissue preparation or the microscopy beam used can affect the results. Microfocus X-ray spectroscopy using a synchrotron beam is useful in addressing both these issues. Using this technique we compared tissue from failed MOM hips with: (1) tissue from metalon-polyethylene (MOP) hips; (2) chemical standards; (3) metal discs cut from MOM hips. The most abundant implant-related species in all MOM hip tissues contained Cr. Comparison with standards revealed the chemical form was Cr(III) phosphate, which did not vary with manufacturer type (four types analysed) or level of blood metal ions. Cobalt (Co) and molybdenum (Mo) were occasionally present in areas of high Cr. Co was normally found in a metallic state in the tissue, while Mo was found in an oxidized state. The variety of metallic species may have arisen from corrosion, wear or a combination of both. No evidence of Cr(VI) was seen in the tissues examined.

Research paper thumbnail of Cobalt from metal-on-metal hip replacements may be the clinically relevant active agent responsible for periprosthetic tissue reactions

Acta Biomaterialia, 2012

Some types of metal-on-metal (MOM) hip replacements have unacceptably high rates of failure, such... more Some types of metal-on-metal (MOM) hip replacements have unacceptably high rates of failure, such as the Ultima TPS MOM hip, with 13.8% failure at 5 years. This has been attributed to an inflammatory reaction following the release of cobalt (Co) and chromium (Cr) from the bearing surfaces and modular junctions. There is in vitro evidence that Co is more important than Cr in the inflammatory process, but there are no reported human tissue studies of the analysis of implant-derived metals.

Research paper thumbnail of 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

The Journal of bone and joint surgery. American volume, Jan 2, 2014

We designed a prospective, single-center study to assess whether blood metal ion levels could pre... more 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 patie...

Research paper thumbnail of Zinc, copper, and selenium tissue levels and their relation to subcutaneous abscess, minor surgery, and wound healing in humans

Biological trace element research, 2013

Trace element involvement in wounds left to heal by secondary intention needs clarification. We h... more Trace element involvement in wounds left to heal by secondary intention needs clarification. We have previously reported faster healing of wounds following acute surgery compared with elective excision of pilonidal sinus disease. The effect of topical zinc on the closure of the excisional wounds was mediocre compared with placebo. In contrast, parenteral zinc, copper, and selenium combined appear effective for wound healing in humans. We have investigated zinc, copper, and selenium with respect to (a) impact of acute versus chronic pilonidal sinus and (b) regional concentrations within granulating wounds treated topically with placebo or zinc in 42 (33 males) pilonidal disease patients. Baseline serum and skin concentrations of copper correlated (r S = 0.351, p = 0.033, n = 37), but not of zinc or selenium. Patients with abscesses had elevated serum C-reactive protein (CRP) and copper levels (+29 %; p < 0.001) compared with the elective patients consistent with the strong correla...

Research paper thumbnail of An analysis of metal ion levels in the joint fluid of symptomatic patients with metal-on-metal hip replacements

The Journal of bone and joint surgery. British volume, 2011

We retrospectively analysed concentrations of chromium and cobalt ions in samples of synovial flu... more We retrospectively analysed concentrations of chromium and cobalt ions in samples of synovial fluid and whole blood taken from a group of 92 patients with failed current-generation metal-on-metal hip replacements. We applied acid oxidative digestion to our trace metal analysis protocol, which found significantly higher levels of metal ion concentrations in blood and synovial fluid than a non-digestive method. Patients were subcategorised by mode of failure as either 'unexplained pain' or 'defined causes'. Using this classification, chromium and cobalt ion levels were present over a wider range in synovial fluid and not as strongly correlated with blood ion levels as previously reported. There was no significant difference between metal ion concentrations and manufacturer of the implant, nor femoral head size below or above 50 mm. There was a moderately positive correlation between metal ion levels and acetabular component inclination angle as measured on three-dimens...

Research paper thumbnail of Changes in blood ion levels after removal of metal-on-metal hip replacements

Acta Orthopaedica, 2014

Since little is known about the kinetics of metal ion clearance from the body and the rate of res... more 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.

Research paper thumbnail of A Case of Hyperzincemia with Functional Zinc Depletion: A New Disorder?

Pediatric Research, 1997

We report the case of an 1l-y-old boy with a plasma Zn concentration greater than 200 micromol/L,... more We report the case of an 1l-y-old boy with a plasma Zn concentration greater than 200 micromol/L, but with symptoms consistent with Zn deficiency. He has had hepatosplenomegaly, rashes, stunted growth (&lt;3rd centile), anemia, and impaired immune function since infancy. He also has vasculitis and osteoporosis. A plasma Zn-binding protein has been separated and characterized by a combination of size exclusion and ion exchange chromatography and electrophoretic studies and by immunologic methods. Antibodies to the partially purified protein have been raised in rabbits. Size exclusion chromatography shows that Zn is bound to a protein with a mass 110000-300000 kD. Electrophoretic and mass spectrometry studies suggest that the protein may be composed of several subunits. One component of the isolated protein reacts with antiserum to alpha2-macroglobulin; immunoprecipitation studies confirm that the protein is not alpha2-macroglobulin or a histidine-rich glycoprotein. Kinetic studies of zinc metabolism in the patient and his mother with stable Zn isotopes show the presence of increased exchangeable Zn, with a rapid flux from plasma to a stable pool. Liver and muscle Zn and Cu concentrations are raised, but with no abnormal liver histology. Immunoreactive metallothionein in the liver is increased. We suggest that this boy may suffer from a previously unrecognized inborn error of Zn metabolism causing symptomatic zinc deficiency.

Research paper thumbnail of High precision isotope measurements reveal poor control of copper metabolism in Parkinsonism

Metallomics, 2013

Disordered copper metabolism may be important in the aetiology of Parkinsonism, as caeruloplasmin... more Disordered copper metabolism may be important in the aetiology of Parkinsonism, as caeruloplasmin is a key enzyme in handling oxidative stress and is involved in the synthesis pathway of dopamine. The human Cu metabolism of ten Parkinsonism patients was compared to ten healthy controls with the aid of a stable 65 Cu isotope tracer. The analyses of blood serum 65 Cu/ 63 Cu ratios yielded individual isotopic profiles, which indicate that the Cu metabolism is less controlled in patients with Parkinsonism.

Research paper thumbnail of Microfocus study of metal distribution and speciation in tissue extracted from revised metal on metal hip implants

Journal of Physics: Conference Series, 2009

... Alister J Hart 1, Ann Sandison2, Paul Quinn3, Barry Sampson4, Kirk D Atkinson8, John A Skinne... more ... Alister J Hart 1, Ann Sandison2, Paul Quinn3, Barry Sampson4, Kirk D Atkinson8, John A Skinner5, Angela Goode6, Jonathan J Powell7, J Frederick W ... 3 Science Division, Diamond Light Source,Harwell Science and Innovation Campus, Didcot, Oxon, OX11 0DE, UK ...

Research paper thumbnail of A new separation procedure for Cu prior to stable isotope analysis by MC-ICP-MS

Journal of Analytical Atomic Spectrometry, 2011

A novel ion exchange chromatography was developed for the separation of Cu from biological sample... more A novel ion exchange chromatography was developed for the separation of Cu from biological samples prior to stable isotope analyses. In contrast to previous methods, the new technique makes use of the different distribution coefficients of Cu(I) and Cu(II) to anion exchange resin and this helps to significantly improve the purity of the Cu separates obtained from biological samples, whilst maintaining crucial quantitative yields. Careful method validation confirmed that the procedure yields sufficiently pure Cu fractions after a single pass through the anion exchange columns, with a recovery of 100 AE 2%. Subsequent isotopic analyses of the Cu by multi-collector inductively coupled plasma mass spectrometry, using admixed Ni for mass bias correction, produced accurate Cu stable isotope data with a reproducibility of AE0.04& for pure standard solutions and of AE0.15& for samples of biological origin.

Research paper thumbnail of Insufficient Acetabular Version Increases Blood Metal Ion Levels after Metal-on-metal Hip Resurfacing

Clinical Orthopaedics and Related Research®, 2011

Background Many factors affect the blood metal ion levels after metal-on-metal (MOM) hip arthropl... more Background Many factors affect the blood metal ion levels after metal-on-metal (MOM) hip arthroplasty. The main surgically adjustable variable is the amount of coverage of the head provided by the cup which is a function of the inclination and version angles. However, most studies have used plain radiographs which have questionable precision and accuracy, particularly for version and large diameter metal heads; further, these studies do not simultaneously assess version and inclination. Thus the relationship between version and blood metal ions levels has not been resolved. Questions/purposes We determined whether cup inclination and version influence blood metal ion levels while adjusting for age at assessment, gender, body mass index, horizontal femoral offset, head size, manufacturer hip type, and Oxford hip score. Patients and Methods We prospectively followed 100 individuals (51 females, 49 males) with unilateral MOM hip resurfacing who underwent clinical assessment, CT scanning, and blood metal ion measurement. Multiple regression analysis was used to determine which variables were predictors of blood metal ion levels and to model the effect of these variables. Results Only cup inclination, version angles, and gender influenced blood cobalt or chromium levels. Cobalt and chromium levels positively correlated with inclination angle and negatively correlated with version angle. The effect of changes in version angle was less than for inclination angle. Based on our observations, we developed a formula to predict the effect of these parameters on metal ion levels. Conclusions Our data suggest insufficient cup version can cause high blood metal ions after MOM hip arthroplasty. We were unable to show that excessive version caused high levels.

Research paper thumbnail of Copper deficiency myeloneuropathy in a patient with haemachromatosis: a case report

Cases Journal, 2009

A 64-year-old British Caucasian man presented with red skin wheals and breathlessness and then de... more 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.

Research paper thumbnail of The chemical form of metallic debris in tissues surrounding metal-on-metal hips with unexplained failure

Acta Biomaterialia, 2010

Implant-derived material from metal-on-metal (MOM) hip arthroplasties may be responsible for an u... more Implant-derived material from metal-on-metal (MOM) hip arthroplasties may be responsible for an unexplained tissue inflammatory response. The chemical form of the metal species in the tissues is predominantly chromium (Cr), but the currently used techniques have not been able to determine whether this is Cr(III) phosphate or Cr(III) oxide. The analytical challenge must overcome the fact that the metal in the tissues is at a relatively low concentration and tissue preparation or the microscopy beam used can affect the results. Microfocus X-ray spectroscopy using a synchrotron beam is useful in addressing both these issues. Using this technique we compared tissue from failed MOM hips with: (1) tissue from metalon-polyethylene (MOP) hips; (2) chemical standards; (3) metal discs cut from MOM hips. The most abundant implant-related species in all MOM hip tissues contained Cr. Comparison with standards revealed the chemical form was Cr(III) phosphate, which did not vary with manufacturer type (four types analysed) or level of blood metal ions. Cobalt (Co) and molybdenum (Mo) were occasionally present in areas of high Cr. Co was normally found in a metallic state in the tissue, while Mo was found in an oxidized state. The variety of metallic species may have arisen from corrosion, wear or a combination of both. No evidence of Cr(VI) was seen in the tissues examined.

Research paper thumbnail of Cobalt from metal-on-metal hip replacements may be the clinically relevant active agent responsible for periprosthetic tissue reactions

Acta Biomaterialia, 2012

Some types of metal-on-metal (MOM) hip replacements have unacceptably high rates of failure, such... more Some types of metal-on-metal (MOM) hip replacements have unacceptably high rates of failure, such as the Ultima TPS MOM hip, with 13.8% failure at 5 years. This has been attributed to an inflammatory reaction following the release of cobalt (Co) and chromium (Cr) from the bearing surfaces and modular junctions. There is in vitro evidence that Co is more important than Cr in the inflammatory process, but there are no reported human tissue studies of the analysis of implant-derived metals.