Search

Prosthetic hip-associated cobalt toxicity (PHACT) is caused by elevated blood cobalt concentrations after hip arthroplasty. The aim of this study is to determine which symptoms are reported most frequently and in what type of bearing. We also try to determine the blood level of cobalt concentrations associated with toxicological symptoms. A systematic review was conducted on the 10th of July according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A methodological quality assessment (risk of bias (RoB)) was performed. Primary outcomes were the reported symptoms of cobalt toxicity and the level of cobalt concentrations in blood. These levels were associated with toxicological symptoms. A total of 7645 references were found of which 67 relevant reports describing 79 patients. The two most used bearings in which PHACT was described were metal-on-metal (MoM) bearings (38 cases) and revised (fractured) ceramic-on-ceramic (CoC) bearings where the former ceramic head was replaced by a metal head (32 cases). Of all reported symptoms, most were seen in the neurological system, of which 24% were in the sensory system and 19.3% were in central/peripheral system, followed by the cardiovascular (22.1%) system. The mean cobalt concentration for MoM-bearings was 123.7 ± 96.8 ppb and 1078.2 ± 1267.5 ppb for the revised fractured CoC-bearings. We recommend not to use a metal-based articulation in the revision of a fractured CoC bearing and suggest close follow-up with yearly blood cobalt concentration controls in patients with a MoM bearing or a revised fractured CoC bearing. Level of Evidence: Level V, systematic review

Prosthetic hip-associated cobalt toxicity (PHACT) is caused by elevated blood cobalt concentrations after hip arthroplasty.The aim of this study is to determine which symptoms are reported most frequently and in what type of bearing. We also try to determine the blood level of cobalt concentrations associated with toxicological symptoms.A systematic review was conducted on the 10th of July according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A methodological quality assessment (risk of bias (RoB)) was performed. Primary outcomes were the reported symptoms of cobalt toxicity and the level of cobalt concentrations in blood. These levels were associated with toxicological symptoms. A total of 7645 references were found of which 67 relevant reports describing 79 patients.The two most used bearings in which PHACT was described were metal-on-metal (MoM) bearings (38 cases) and revised (fractured) ceramic-on-ceramic (CoC) bearings where the former ceramic head was replaced by a metal head (32 cases).Of all reported symptoms, most were seen in the neurological system, of which 24% were in the sensory system and 19.3% were in central/peripheral system, followed by the cardiovascular (22.1%) system.The mean cobalt concentration for MoM-bearings was 123.7 +/- 96.8 ppb and 1078.2 +/- 1267.5 ppb for the revised fractured CoC-bearings.We recommend not to use a metal-based articulation in the revision of a fractured CoC bearing and suggest close follow-up with yearly blood cobalt concentration controls in patients with a MoM bearing or a revised fractured CoC bearing.

Nanoparticle‐based magnetic hyperthermia is a well‐known thermal therapy platform studied to treat solid tumors, but its use for monotherapy is limited due to incomplete tumor eradication at hyperthermia temperature (45 °C). It is often combined with chemotherapy for obtaining a more effective therapeutic outcome. Cubic‐shaped cobalt ferrite nanoparticles (Co–Fe NCs) serve as magnetic hyperthermia agents and as a cytotoxic agent due to the known cobalt ion toxicity, allowing the achievement of both heat and cytotoxic effects from a single platform. In addition to this advantage, Co–Fe NCs have the unique ability to form growing chains under an alternating magnetic field (AMF). This unique chain formation, along with the mild hyperthermia and intrinsic cobalt toxicity, leads to complete tumor regression and improved overall survival in an in vivo murine xenograft model, all under clinically approved AMF conditions. Numerical calculations identify magnetic anisotropy as the main Co–Fe NCs’ feature to generate such chain formations. This novel combination therapy can improve the effects of magnetic hyperthermia, inaugurating investigation of mechanical behaviors of nanoparticles under AMF, as a new avenue for cancer therapy This work was partially funded by the European Research Council (starting grant ICARO, Contract No. 678109) and partially by the AIRC project (Contract No. 14527). The authors also acknowledge Centro de Supercomputación de Galicia (CESGA) for the computational resources. D.S. acknowledges Xunta de Galicia for financial support under the I2C Plan and the Strategic Grouping in Materials (AeMAT; Grant No. ED431E2018/08). This work made use of computational facilities funded by the Small items of research equipment at the University of York ENERGY (Grant No. EP/K031589/1) SI

The purpose of this study was to investigate the sublethal Co toxicity on rainbow trout (Oncorhynchus mykiss). Trout were exposed to Co and selected parameters were evaluated at intervals of 1, 15 and 30 days. Fish exposed to higher levels of Co grew slower than fish exposed to lower levels of Co. Weight gain, specific growth rate (SGR) decreased linearly with the increase of cobalt in the water. The body condition factor (CF) of fish reared in water with low cobalt concentration decreased substantially but this decrease was not significant for fish exposed to higher cobalt concentration. The values of the feed conversion ratio (FCR) increased in fish exposed to higher levels of Co. Co significantly changed the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and decreased at day 30, and in both cases this decrease was more remarkable at day 15 so that the level of AST and ALT reached the control value at day 30. The alkaline phosphatase (ALP) level also showed a remarkable 15-day decline. There was a significant increase in glucose (G) concentration in both Co-exposed groups on day 15. However, serum cholesterol (Chl) was significantly reduced on day 15 and increased on day 30; there were no significant differences in both exposed Co-groups. The triglyceride (TG) level also decreased substantially. There was no regular pattern of total protein (TP) in the serum, so that no significant differences were found in the level of TP between low and high-exposed fish. In summary, this study suggests that exposure of essential trace elements such as cobalt may change growth and biochemical parameters, and that measurement of these parameters may be used in toxicological studies to determine the general health status of fish.

Cobalt (Co) and its compounds are widely distributed in nature and are part of numerous anthropogenic activities. Although cobalt has a biologically necessary role as metal constituent of vitamin B-12, excessive exposure has been shown to induce various adverse health effects. This review provides an extended overview of the possible Co sources and related intake routes, the detection and quantification methods for Co intake and the interpretation thereof, and the reported health effects. The Co sources were allocated to four exposure settings: occupational, environmental, dietary and medical exposure. Oral intake of Co supplements and internal exposure through metal-on-metal (MoM) hip implants deliver the highest systemic Co concentrations. The systemic health effects are characterized by a complex clinical syndrome, mainly including neurological (e.g. hearing and visual impairment), cardiovascular and endocrine deficits. Recently, a biokinetic model has been proposed to characterize the dose-response relationship and effects of chronic exposure. According to the model, health effects are unlikely to occur at blood Co concentrations under 300 [mu g/1(100 mu g/1 respecting a safety factor of 3) in healthy individuals, hematological and endocrine dysfunctions are the primary health endpoints, and chronic exposure to acceptable doses is not expected to pose considerable health hazards. However, toxic reactions at lower doses have been described in several cases of malfunctioning MoM hip implants, which may be explained by certain underlying pathologies that increase the individual susceptibility for Co-induced systemic toxicity. This may be associated with a decrease in Co bound to serum proteins and an increase in free ionic Co2+. As the latter is believed to be the primary toxic form, monitoring of the free fraction of Co2+ might be advisable for future risk assessment. Furthermore, future research should focus on longitudinal studies in the clinical setting of MoM hip implant patients to further elucidate the dose-response discrepancies.

Cobalt toxicity is a well-documented complication of total hip arthroplasty (THA) when cobalt-chrome implants are utilized. A recent area of attention is “cobaltism, ” which results from cobalt exposure from cobalt-containing orthopedic implants, chemistry kits, weather indicators, antiquated anemia therapies, cement, fly ash, dyes, mineral wool, asbestos, molds for ceramic tiles, mining, porcelain paint, orthopedic implants, and dental hardware. Like other transition metals, cobalt is a multiorgan toxin. Organ systems affected by acute cobalt poisoning include endocrine, gastrointestinal, central and peripheral nervous system, hematologic, cardiovascular, and metabolic. Chronic inhalational exposures affect the pulmonary system and dermatologic system.

As adverse events related to metal on metal hip arthroplasty have been better understood, there has been increased interest in toxicity related to the high circulating levels of cobalt ions. However, distinguishing true toxicity from benign elevations in cobalt levels can be challenging. The purpose of this review is to examine the use of cobalt alloys in total hip arthroplasty, to review the methods of measuring circulating cobalt levels, to define a level of cobalt which is considered pathological and to review the pathophysiology, risk factors and treatment of cobalt toxicity. To the best of our knowledge, there are 18 published cases where cobalt metal ion toxicity has been attributed to the use of cobalt-chromium alloys in hip arthroplasty. Of these cases, the great majority reported systemic toxic reactions at serum cobalt levels more than 100 μg/L. This review highlights some of the clinical features of cobalt toxicity, with the goal that early awareness may decrease the risk factors for the development of cobalt toxicity and/or reduce its severity. Take home message: Severe adverse events can arise from the release of cobalt from metal-on-metal arthroplasties, and as such, orthopaedic surgeons should not only be aware of the presenting problems, but also have the knowledge to treat appropriately. Cite this article: Bone Joint J 2016;98-B:14–20.

Recently, the use of metal-on-metal articulations in total hip arthroplasty (THA) has led to an increase in adverse events owing to local soft-tissue reactions from metal ions and wear debris. While the majority of these implants perform well, it has been increasingly recognised that a small proportion of patients may develop complications secondary to systemic cobalt toxicity when these implants fail. However, distinguishing true toxicity from benign elevations in cobalt ion levels can be challenging.The purpose of this two part series is to review the use of cobalt alloys in THA and to highlight the following related topics of interest: mechanisms of cobalt ion release and their measurement, definitions of pathological cobalt ion levels, and the pathophysiology, risk factors and treatment of cobalt toxicity. Historically, these metal-on-metal arthroplasties are composed of a chromium-cobalt articulation.The release of cobalt is due to the mechanical and oxidative stresses placed on the prosthetic joint. It exerts its pathological effects through direct cellular toxicity.This manuscript will highlight the pathophysiology of cobalt toxicity in patients with metal-on-metal hip arthroplasties.Take home message: Patients with new or evolving hip symptoms with a prior history of THA warrant orthopaedic surgical evaluation. Increased awareness of the range of systemic symptoms associated with cobalt toxicity, coupled with prompt orthopaedic intervention, may forestall the development of further complications.Cite this article: Bone Joint J 2016;98-B:6–13.

Symptomatic cobalt toxicity from a failed total hip replacement is a rare, but devastating complication. Potential clinical findings include cardiomyopathy, hypothyroidism, skin rash, visual and hearing impairment, polycythaemia, weakness, fatigue, cognitive impairment, and neuropathy. The case is presented of a 74 year-old man in whom, after a ceramic–ceramic replacement and two episodes of prosthetic dislocation, it was decided to replace it with a polyethylene–metal total hip arthroplasty (THA). At 6 months after the revision he developed symptoms of cobalt toxicity, confirmed by analytical determination (serum cobalt level = 651.2 μg/L). After removal of the prosthesis, the levels of chromium and cobalt in blood and urine returned to normal, with the patient currently being asymptomatic. It is recommended to use a new ceramic on ceramic bearing at revision, in order to minimise the risk of wear-related cobalt toxicity following breakage of ceramic components.

We report two Australian patients with possible cobalt toxicity related to metal-on-metal total hip replacements. Both patients were treated for osteoarthritis with a DePuy ASR (articular surface replacement) XL Acetabular Hip System prosthesis, which contains cobalt and chromium, and which has recently been recalled from the market.

Cobalt (Co) commonly co-exists with copper (Cu) in natural soils, but the information about their combined effects on plants is poorly available. In this study, we hydroponically investigated the combined effects of Co and Cu on two barley genotypes differing in Co toxicity tolerance to reveal the interaction pattern of these two metals. The results showed that single treatment of Co or Cu at the dose of 100 μM led to a significant decrease of growth and photosynthetic rate, and a significant increase of lipid peroxidation, ROS radicals as well as anti-oxidative enzyme (SOD, CAT and GR) activities and glutathione content, with the extent of effect being less in Yan66 than Ea52. The combined treatment of Co and Cu alleviated the toxicity of both metals in comparison with each metal treatment alone, as reflected by improved growth and photosynthesis, and much slight oxidative stress. The alleviation of metal toxicity upon combined treatment is mainly attributed to a drastic reduction of Co uptake and its translocation from roots to shoots. It may be suggested that interaction of Co and Cu on their uptake and movement in plants is antagonistic.

Svrha istraživanja je bila ispitati subletalnu toksičnost kobalta (Co) kod kalifornijske pastrve (Oncorhynchus mykiss). Ribe su bile izložene Co i odabrani pokazatelji su procijenjeni u intervalima od 1, 15 i 30 dana. Pastrve izložene višim razinama Co imale su sporiji rast od riba izloženih nižim razinama Co. Prirast mase (WG) i specifična stopa rasta (SGR) linearno se smanjivala s porastom kobalta u vodi. Kondicijski faktor riba izloženoj nižoj koncentraciji Co bio je značajno smanjen. Vrijednostikonverzije hrane (FCR) su se povećale kod riba izloženoj višim koncentracijama kobalta. Co je značajno promijenio aktivnost enzima AST i ALT te se smanjio tijekom 30 dana. Razina alkalne fosfataze (ALP) također je pokazala značajan pad ali već tijekom 15 dana. Došlo je i do značajnog povećanja koncentracije glukoze (G) u obje skupine izložene Co 15.ti dan. Međutim, kolesterol u serumu (Chl) je bio značajno smanjen 15.og dana, a povećao se tijekom30 dana istraživanja. Razina triglicerida (TG) također se značajno smanjila a značajne razlike u razini ukupnih proteina (TP) nisu utvrđene između riba izložene niskoj i visokoj koncentraciji Co. Istraživanjem se utvrdilo da izlaganje esencijalnim elemenatima u tragovima kao što je kobalt može utjecati na rast i biokemijske parametre pastrve. Mjerenje navedenih pokazatelja u istraživanju semože upotrijebiti u toksikološkim analizama za utvrđivanje općeg zdravstvenog stanja ribe., The purpose of this study was to investigate the sublethal Co toxicity on rainbow trout (Oncorhynchus mykiss). Trout were exposed to Co and selected parameters were evaluated at intervals of 1, 15 and 30 days. Fish exposed to higher levels of Co grew slower than fish exposed to lower levels of Co. Weight gain, specific growth rate (SGR) decreased linearlywith the increase of cobalt in the water. The body condition factor (CF) of fish reared in water with low cobalt concentration decreased substantially but this decrease was not significant for fish exposed to higher cobaltconcentration. The values of the feed conversion ratio (FCR) increased in fish exposed to higher levels of Co. Co significantly changed the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and decreased at day 30, and in both cases this decrease was more remarkable at day 15 so that the level of AST and ALT reached the control value at day 30. The alkaline phosphatase (ALP) level also showed a remarkable 15-day decline. There was a significant increase in glucose (G) concentration in both Co-exposed groups on day 15. However, serum cholesterol (Chl) was significantly reduced on day 15 and increased on day 30; there were no significant differences in both exposed Co-groups. The triglyceride (TG) level also decreased substantially. There was no regular pattern of total protein (TP) in the serum, so that no significant differences were found in the level of TP between low and high-exposed fish. In summary, this study suggests that exposure of essential trace elements such as cobalt may change growth and biochemical parameters, and that measurement of these parameters may be used in toxicological studies to determine the general health status of fish.

Cobalt is a widely used in the industrial production of hard metals. Cobalt ingestion has been reported to cause widespread systemic toxicity, but its effects on vision have been sparsely reported. The authors report the case of a patient who ingested cattle magnets, which remained in his stomach for an unknown duration of time. These magnets largely consist of cobalt that gradually leached into his blood stream, resulting in protean systemic manifestations, which included optic atrophy.

Prosthetic hip-associated cobalt toxicity (PHACT) is gaining recognition due to the use of metal-on-metal total hip replacements. Identifying true toxicity from merely elevated cobalt levels can be extremely difficult due to the lack of available data. An extensive review of the medical literature was undertaken to characterize cobalt toxicity from prosthetic hips. As an objective approach to making the diagnosis of PHACT, we suggest the following criteria: (1) elevated serum or whole blood cobalt levels due to a prosthetic hip, (2) at least two test-confirmed findings consistent with cobalt toxicity, and (3) exclusion of other etiologies. Adhering to objective diagnostic data for PHACT is a realistic and prudent method by which to eliminate the subjectivity of vague or difficult to identify complaints. These diagnostic criteria are not meant to evaluate prosthetic hardware failure, but as a means to identify systemic cobalt toxicity. Finally, assessment of cobalt toxicity from prosthetic hips should be done in conjunction with a medical toxicologist.

This case illustrates the potential for systemic cobalt toxicity in non-metal-on-metal bearings and its potentially devastating consequences. We present a 71-year-old male with grinding sensations in his right hip following ceramic-on-ceramic total hip arthroplasty (THA). After diagnosing a fractured ceramic liner, the hip prosthesis was revised into a metal-on-polyethylene bearing. At one year postoperatively, X-rays and MARS-MRI showed a fixed reversed hybrid THA, with periarticular densities, flattening of the femoral head component, and a pattern of periarticular metal wear debris and pseudotumor formation. Before revision could take place, the patient was admitted with the clinical picture of systemic cobalt toxicity, supported by excessively high serum cobalt and chromium levels, and ultimately died. At autopsy dilated cardiomyopathy as cause of death was hypothesized. A third body wear reaction between ceramic remnants and the metal femoral head very likely led to excessive metal wear, which contributed systemic cobalt toxicity leading to neurotoxicity and heart failure. This case emphasizes that fractured ceramic-on-ceramic bearings should be revised to ceramic-on-ceramic or ceramic-on-polyethylene bearings, but not to metal-on-polyethylene bearings. We aim to increase awareness among orthopedic surgeons for clinical clues for systemic cobalt intoxication, even when there is no metal-on-metal bearing surface.

Symptomatic cobalt toxicity from a failed total hip replacement is a rare, but devastating complication. Potential clinical findings include cardiomyopathy, hypothyroidism, skin rash, visual and hearing impairment, polycythaemia, weakness, fatigue, cognitive impairment, and neuropathy. The case is presented of a 74year-old man in whom, after a ceramic-ceramic replacement and two episodes of prosthetic dislocation, it was decided to replace it with a polyethylene-metal total hip arthroplasty (THA). At 6months after the revision he developed symptoms of cobalt toxicity, confirmed by analytical determination (serum cobalt level=651.2mug/L). After removal of the prosthesis, the levels of chromium and cobalt in blood and urine returned to normal, with the patient currently being asymptomatic. It is recommended to use a new ceramic on ceramic bearing at revision, in order to minimise the risk of wear-related cobalt toxicity following breakage of ceramic components.

Heavy metals pollution of soils become the most serious environmental problem resulted in decreased soil fertility and crop yield losses. Cobalt (Co), as a beneficial element, can be a contaminant in soils due to agricultural additives or metal refineries, it causes irreversible damage to several physiological and metabolic constituents at higher concentrations. In this investigation we study the effects of different Co concentrations (0, 50,150, 250, 350 µM as CoCl2) on growth and physiological processes in wheat (Triticum aestivum) plants and discuss the role of spraying with salicylic acid (0.5 mM) for ameliorating effect of cobalt toxicity in wheat leaves. Cobalt causing a significant reduction in fresh and dry biomass, shoot height, water content and total photosynthetic pigments. This was accompanied with accumulation of H2O2 and MDA contents and induction of some antioxidant enzymes activities. There was an increase in SOD activity with increasing Co concentration then decline, a significant increase in APX and PPO activities while CAT was significantly declined. Spraying wheat seedlings with salicylic acid can be recognized to significantly increase in all tested growth parameters and that was attributed to decrease, to some extent, the accumulation of H2O2 and MDA and improve the activity of antioxidant enzymes.

Cobalt metallosis after revision metal-on-polyethylene total hip arthroplasty for catastrophic failure of ceramic components is uncommon but a potentially devastating complication. Common findings associated with heavy metal toxicity include cardiomyopathy, hypothyroidism, skin rashes, visual disturbances, hearing changes, polycythemia, weakness, fatigue, cognitive deterioration, and neuropathy. We report a case of a 57-year-old woman who presented with complaints of progressively worsening hip pain, fatigue, memory loss, lower extremity sensory loss, persistent tachycardia, and ocular changes 5 years after synovectomy and revision of a failed ceramic-on-ceramic total hip arthroplasty to metal-on-polyethylene components. A cobalt level of 788.1 ppb and chromium level of 140 ppb were found on presentation and subsequently decreased to 468.8 ppb and 105.9 ppb, respectively, 2 weeks after revision to a ceramic-on-polyethylene total hip arthroplasty. Improvement of symptoms accompanied this decrease in cobalt and chromium levels. Revision of failed ceramic arthroplasties with later-generation ceramics to avoid this potential complication is recommended.

Cobalt (Co) contamination in soils is becoming a severe issue in environment safety and crop production. Calcium (Ca), as a macro-nutrient element, shows the antagonism with many divalent heavy metals and the capacity of alleviating oxidative stress in plants. In this study, the protective role of Ca in alleviating Co stress was hydroponically investigated using two barley genotypes differing in Co toxicity tolerance. Barley seedlings exposed to 100µM Co showed the significant reduction in growth and photosynthetic rate, and the dramatic increase in the contents of reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH) and oxidized glutathione (GSSG), and the activities of anti-oxidative enzymes, with Ea52 (Co-sensitive) being much more affected than Yan66 (Co-tolerant). Addition of Ca in growth medium alleviated Co toxicity by reducing Co uptake and enhancing the antioxidant capacity. The effect of Ca in alleviating Co toxicity was much greater in Yan66 than in Ea52. The results indicate that the alleviation of Co toxicity in barley plants by Ca is attributed to the reduced Co uptake and enhanced antioxidant capacity.

A 39-year-old female with elevated serum cobalt levels from her bilateral hip prostheses presented with a 3-week history of blurred vision in her left eye. Optical coherence tomography revealed patchy degeneration of the photoreceptor-retinal pigment epithelium (RPE) complex. The lesions were hypofluorescent on indocyanine green angiography. We postulate that this is a case of implant-related chorio-retinal cobalt toxicity.

The influence of cobalt speciation on the toxicity of cobalt to methylotrophic methanogenesis in anaerobic granular sludge was investigated. The cobalt speciation was studied with three different media that contained varying concentrations of complexing ligands [carbonates, phosphates and ethylenediaminetetraacetic acid (EDTA)]. Three fractions (nominal added, dissolved and free) of cobalt were determined in the liquid media and were correlated with data from batch toxicity experiments. The average concentration of cobalt that was required for 50% inhibition of methanogenic activity (IC50) for free Co2+ in the three sets of measurements was 13 micromol/L with a standard deviation of 22% and a similarity of 72% between the data obtained in the three different media for the range of cobalt concentrations investigated. The standard deviation of the IC50 for the other two fractions was much higher, i.e. 85 and 144% for the added cobalt and dissolved cobalt, respectively, and the similarity was almost 0% for both fractions. Complexation (and precipitation) with EDTA, phosphates and carbonates was shown to decrease the toxicity of cobalt on methylotrophic methanogenesis. The free cobalt concentration is proposed to be the key parameter to correlate with cobalt toxicity. Thus, the toxicity of cobalt to granular sludge can be estimated based on the equilibrium-free cobalt concentration.

The facultative anaerobic enterobacterium Escherichia coli requires the activity of nickel-containing hydrogenase for its anaerobic growth. Deficiency of the specific nickel transport system led to a hydrogenase-minus phenotype and slowed down the fermentative growth in the nik mutant. Addition of 300 pM nickel to the growth medium could restore the hydrogenase activity. This restoration resulted in the recovery of anaerobic growth. A fur- ther increase of nickel concentration inhibited growth. Thus nickel shows an antagonistic effect on the anaerobic growth of E. coli. To study the mech- anism of nickel toxicity, two classes of nickel-resistant mutants were isolated. The nkr mutant was obtained by selecting colonies grown on nickel-containing minimal plate. It acquired simultaneously the resistance to cobalt. A nonspecific magnesium transport mutant corA was isolated on cobalt-containing plate. The corA mutant was also resistant to nickel. When analyzing the influence of nickel and cobalt on the bacterial growth, we obtained two interesting observations. First, anaerobic growth was less sensitive than aerobic growth to cobalt toxicity. In contrast, nickel toxicity did not vary from the growth conditions. Second, cobalt seems to abolish the growth, while nickel appears to slow down the growth rate under the condition used. Environ Health Perspect 1 02(Suppl 3):297-300 (1 994).

There is public concern over the long term systemic health effects of metal released from implanted medical devices that use metal alloys. Systemic toxic side effects have been associated with excessive metal ion release from implants into human biological specimen's circulation, in which cobalt and chromium plays an important role. Cobalt intoxication has become more frequent due to the wide use of metallic medical implants. Despite the technological improvements in replacement metallic medical implants, wear and corrosion products associated with the metal compounds of these implants may result in systemic reactions and toxicities. The current review encompasses a literature of the systemic toxicity studies concerning the effect of metallic wear debris released from wear and corrosion of specific types of implanted medical devices, resulting in a postoperative increase in metal ion levels in bodily fluids and at different organ sites. Release of metallic debris is mainly in the form of particles and ions of different valences, and oxides composed of cobalt and chromium. Toxicological, clinically significant, data regarding "potential hazards" of circulating metals after systemic chronic exposure to the metal ions from metals have been included. This review further highlights some of the clinical features of cobalt toxicity.

A 63-year-old woman was referred to the specialised knee revision clinic with ongoing knee pain after total knee replacement. She incidentally had cobalt and chromium levels measured. These were seen to be elevated. Comprehensive assessment and investigation did not identify any other source of cobalt or chromium. Aseptic loosening of the knee was diagnosed, and the knee was revised. At the time of surgery, the tissue was seen to be darkened consistent with metallosis. Multiple samples excluded infection on extended cultures. Aspirated fluid showed that periprosthetic fluid had elevated cobalt levels. The knee was successfully revised with good symptomatic outcome and significantly, over the course of several months post-revision, the cobalt and chromium levels returned to normal.

Three experiments were conducted to investigate the interaction of cobalt with sulfur-containing amino acids in the chick. Fortified corn-soybean meal diets were fed and tissue concentrations of cobalt were assessed. In Experiment 1, three levels of cobalt (0, 250, and 500 microgram/g) were fed in the presence and absence of .50% supplemental DL-methionine. Dietary additions of cobalt depressed growth rate and caused cobalt accumulation in the liver and kidney. Supplemental methionine in excess of the requirement for maximal chick weight gains partially alleviated the depression in performance and decreased cobalt accumulation in the liver and kidney. Two levels of cobalt (0 and 500 microgram/g) were fed in the presence and absence of .59% supplemental L-cysteine.HCl.H2O (isosulfurous to .50% DL-methionine) in Experiment 2. Again, cobalt depressed performance and accumulated in the liver and kidney. The surfeit of cysteine increased weight gain and decreased cobalt accumulation in the liver but not in the kidney. In Experiment 3, two levels of cobalt (0 and 250 microgram/g) were fed in the presence and absence of two levels of excess DL-methionine (.50 and 1.0%) or two levels of excess cysteine.HCl.H2O (.59 and 1.18%). Multiple linear regression analysis of gain on sulfur consumed from methionine or cysteine indicated that cysteine was almost 6 times more efficacious than methionine in alleviating cobalt toxicity. In fact, cysteine supplemented at a level of 1.18% completely alleviated the growth depression caused by 250 microgram/g cobalt. Both methionine and cysteine reduced cobalt accumulation in the liver and kidney, but the liver was affected to a greater extent than the kidney.