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Aim: The aim of this project was to develop and demonstrate the feasibility of a comprehensive cognitive training intervention to build self-efficacy for implementation of cognitive strategies in people with diabetes., Background: People with diabetes are at greater risk than the general population for developing cognitive dysfunction. Some attention has been paid to the effect of cognitive impairments on diabetes self-management, but even when cognitive problems have been identified, few interventions have been tailored for those with diabetes., Methods: The intervention combines in-person classes and home-based online computer training. Development, in 2017, included (a) adaptation of prior established, tested interventions; (b) interviews with stakeholders; and (c) integration of course content., Results: Information provided by the stakeholders was used to modify an existing intervention to meet the needs of people with diabetes so that feasibility testing could occur. Despite initial difficulty with recruitment, the intervention was found to be feasible, and nineteen participants found it to be acceptable., Conclusion: This comprehensive cognitive training intervention targeting type 2 diabetes and cognitive dysfunction demonstrates that existing interventions can be adapted for use with people with diabetes., (© 2020 John Wiley & Sons Australia, Ltd.)

Objectives: To assess the role of the cerebro-placental ratio (CPR) in predicting adverse fetal outcomes among women with sickle cell disease (SCD)., Methods: A prospective cohort study at Korle-Bu Teaching Hospital, Accra, Ghana, between January and June 2016. Pregnant women with SCD at 34 gestational weeks or more underwent weekly fetal umbilical and middle cerebral artery Doppler assessment until delivery. Participants were categorized into two study arms based on CPR (<1.1 or ≥1.1). The primary outcome, a composite of adverse perinatal outcomes including intrauterine growth restriction, stillbirth, low birthweight, and neonatal intensive care unit admission, was compared between groups., Results: Overall, 48 pregnant women with SCD were enrolled, and 5 had a fetus with CPR less than 1.1. Low CPR (<1.1) had a sensitivity and specificity of 29.4% and 100%, respectively, for predicting composite adverse perinatal outcomes. Sensitivity and specificity were, respectively, 100% and 93.5% for predicting stillbirth, and 40.2% and 97.4% for predicting low birthweight. Perinatal outcomes did not differ between the two major sickle cell genotypes (hemoglobin SS and hemoglobin SC)., Conclusions: Among women with SCD, CPR less than 1.1 was associated with adverse perinatal outcomes, particularly low birthweight and stillbirth., (© 2020 International Federation of Gynecology and Obstetrics.)

Background: In this study, we investigate the moderated association of school connectedness and alcohol expectancies with adolescent drinking., Methods: Two large community samples were obtained with 2 repeated attempted censuses of all students attending a large suburban school district. Participants completed a self-administered questionnaire that assessed substance use, alcohol expectancies, and school connectedness. We used logistic regression analyses on the training sample and confirmed with Bayesian test intervals with the test sample., Results: Party related alcohol expectancies and school connectedness interacted in their explanatory association with recent drinking and binging, such that school connectedness had a protective association only for youth with lower positive expectancies. These findings were the result of pre-planned exploratory analysis, which were confirmed with out-of-sample test data., Conclusions: The potential benefits for student health behaviors resulting from improved school connectedness may be dependent on at least one dimension of alcohol expectancies, at the individual level., (© 2019, American School Health Association.)

Musculoskeletal infections (MSKI) remain the bane of orthopedic surgery, and result in grievous illness and inordinate costs that threaten healthcare systems. As prevention, diagnosis, and treatment has remained largely unchanged over the last 50 years, a 2nd International Consensus Meeting on Musculoskeletal Infection (ICM 2018, https://icmphilly.com) was completed. Questions pertaining to all areas of MSKI were extensively researched to prepare recommendations, which were discussed and voted on by the delegates using the Delphi methodology. The questions, including the General Assembly (GA) results, have been published (GA questions). However, as critical outcomes include: (i) incidence and cost data that substantiate the problems, and (ii) establishment of research priorities; an ICM 2018 research workgroup (RW) was assembled to accomplish these tasks. Here, we present the result of the RW consensus on the current and projected incidence of infection, and the costs per patient, for all orthopedic subspecialties, which range from 0.1% to 30%, and $17,000 to $150,000. The RW also identified the most important research questions. The Delphi methodology was utilized to initially derive four objective criteria to define a subset of the 164 GA questions that are high priority for future research. Thirty-eight questions (23% of all GA questions) achieved the requisite > 70% agreement vote, and are highlighted in this Consensus article within six thematic categories: acute versus chronic infection, host immunity, antibiotics, diagnosis, research caveats, and modifiable factors. Finally, the RW emphasizes that without appropriate funding to address these high priority research questions, a 3rd ICM on MSKI to address similar issues at greater cost is inevitable., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Objective: To examine the cytotoxicity of epigenetic drugs independently and in combination with chemotherapy on ovarian cancer cells Caov-3, and to investigate their ability to acquire chemoresistance in omental microenvironments and whether epigenetic drugs can counteract this chemoresistance., Methods: A pilot study was conducted in Cooper University Hospital, NJ, USA from August 1 to October 31, 2017, among women undergoing surgeries for uterine and ovarian cancer. Cytotoxicity assays using IC 50 values of epigenetic drugs and paclitaxel and cisplatin were performed on Caov-3. Omental adipose-derived stem cells (OASCs) were isolated from omentum with/without metastases. Caov-3 was cultured with OASCs' conditioned medium and subjected to different drugs. Cell viability and secretome was measured using MTT and Elisa, respectively., Results: Three women met the eligibility criteria and were included in the study. Epigenetic drugs alone or in combination with chemotherapy showed 85%-94% increased cytotoxicity against Caov-3 (P≤0.005). Metastatic OASCs conditioned medium showed up to 27-fold increase in tumorigenic factors and promoted chemoresistance (28%-35%; P < 0.050) against chemotherapy. Epigenetic therapy resulted in up to a 40-fold reversal in this chemoresistance., Conclusion: Epigenetic therapies could have an important role in treating a subgroup of ovarian cancer patients that demonstrate resistance to first-line chemotherapy., (© 2019 International Federation of Gynecology and Obstetrics.)

Current influenza A virus (IAV) vaccines stimulate antibody responses that are directed against variable regions of the virus, and are therefore ineffective against divergent strains. As CD8 + T cells target the highly conserved, internal IAV proteins, they have the potential to increase heterosubtypic immunity. Early T-cell priming events influence lasting memory, which is required for long-term protection. However, the early responding, IAV-specific cells are difficult to monitor because of their low frequencies. Here, we tracked the dissemination of endogenous IAV-specific CD8 + T cells during the initial phases of the immune response following IAV infection. We exposed a significant population of recently activated, CD25 + CD43 + IAV-specific T cells that were not detected by tetramer staining. By tracking this population, we found that initial T-cell priming occurred in the mediastinal lymph nodes, which gave rise to the most expansive IAV-specific CD8 + T-cell population. Subsequently, IAV-specific CD8 + T cells dispersed to the bronchoalveolar lavage and blood, followed by spleen and liver, and finally to the lung. These data provide important insight into the priming and tissue dispersion of an endogenous CD8 + T-cell response. Importantly, the CD25 + CD43 + phenotype identifies an inclusive population of early responding CD8 + T cells, which may provide insight into TCR repertoire selection and expansion. A better understanding of this response is critical for designing improved vaccines that target CD8 + T cells., (© 2018 The Authors Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australasian Society for Immunology Inc.)

Background: Despite the paucity of data available, orally administered angiotensin-converting enzyme (ACE) inhibitors are empirically used in horses with valvular regurgitation., Objective: Evaluate the echocardiographic and hormonal changes in response to oral benazepril in horses with left-sided valvular regurgitation., Study Design: Prospective, randomised double-blind, placebo-controlled trial., Methods: Horses with mitral valve (MR) and/or aortic valve regurgitation (AR) received oral benazepril (n = 6) at a dosage of 1 mg/kg q 12 h or a placebo (n = 5) for 28 days. Echocardiography was performed before drug administration and after 28 days of treatment. Plasma renin activity, serum ACE activity, angiotensin II concentration, aldosterone concentration and biochemical variables were measured before drug administration and after 7 and 28 days of treatment., Results: Relative to baseline, horses treated with benazepril had statistically significant reduction in left ventricular internal diameter in systole (mean difference between groups = -0.97 cm; 95% CI = -1.5 to -0.43 cm), aortic sinus diameter (-0.31 cm; -0.54 to -0.07 cm), and percentage of the aortic annulus diameter occupied by the base of the AR jet (-17.05%; -31.17 to -2.93%) compared with horses receiving a placebo. In addition, horses treated with benazepril had a significantly greater increase in cardiac output (11.95 L/min; 1.17-22.73 L/min) and fractional shortening (7.59%; 3.3-11.88%) compared with horses receiving a placebo. Despite profound serum ACE inhibition, renin activity and concentrations of angiotensin II and aldosterone were not significantly different between treatment groups or among time points., Main Limitations: Very small sample size and short treatment period., Conclusions: Treatment with oral benazepril resulted in statistically significant echocardiographic changes that might indicate reduced cardiac afterload in horses with left-sided valvular regurgitation. Additional studies with a larger sample size will be necessary to determine if administration of benazepril is beneficial in horses with valvular regurgitation. The Summary is available in Spanish - see Supporting Information., (© 2017 EVJ Ltd.)

Little is known about individuals' motivation, perception, and treatment beliefs towards the use of genetic information in risk estimates for coronary heart disease (CHD). In this study, participants at intermediate 10-year risk of CHD were randomized to receive either their estimated conventional risk score (CRS) alone, or a CRS and a genetic risk score (GRS), by a genetic counselor. Surveys on motivation to participate in and perception of genetic testing for CHD were administered at 3 months and treatment beliefs at 6 months following risk disclosure. Survey responses used Likert scales. Linear and logistic regression were used for analysis. Overall, motivation to participate in genomic clinical trials was favorable and did not differ between the CRS and GRS groups (16.95 ± 0.82 vs. 17.58 ± 0.83, p = 0.091), but participants who initially received their GRS indicated a greater desire to find ways to improve health as a reason for participation (OR: 0.53 (95%CI: 0.29, 0.94), p = 0.028). Perception of genetic testing was also favorable in both groups (15.29 ± 0.39 vs. 15.12 ± 0.40, p = 0.835). Participants who initially received their GRS were more inclined to recommend genetic testing to family and friends (9.95 ± 1.88 vs. 10.52 ± 2.17, p = 0.023). In the MI-GENES study, motivation to participate in and perception of genetic testing among study participants were overall favorable. Genetic risk disclosure was associated with increased motivation to recommend genetic testing to family and friends.

Background: Benazepril has been shown to inhibit circulating angiotensin-converting enzyme (ACE) activity in horses but the optimal dosage is unknown., Objectives: To determine the lowest tested dose of benazepril that results in ≥75% attenuation in the response of arterial blood pressure (BP) to exogenous angiotensin I (ANG-I) administration., Study Design: Prospective experimental study., Methods: A total of 5 healthy horses were instrumented for the direct measurement of BP. Each horse received 4 intragastric doses of benazepril (0.5, 1, 2 and 4 mg/kg bwt) with a washout period of 7 days between doses. Prior to and 2, 12 and 24 h after benazepril administration, each horse received intravenous (i.v.) boluses of ANG-I at 20, 60 and 200 ng/kg. Attenuation of the systolic arterial pressure (SBP) response to ANG-I and serum ACE activity were quantified and expressed as percentage of inhibition., Results: There was a significant effect of benazepril dose (P = 0.004) and time (P = 0.004) on the percentage of inhibition of the systolic pressor response to ANG-I. Regardless of benazepril dose, the percentage of inhibition was significantly greater 2 h after administration of benazepril compared with 12 and 24 h. At an ANG-I dose of 20 ng/kg, the percentage of inhibition after administration of benazepril at 1 mg/kg bwt (46.6 ± 18.9%) was significantly greater than that achieved after 0.5 mg/kg bwt (19 ± 14%) but not significantly different from that achieved at higher doses of benazepril. Benazepril doses ≥1 mg/kg bwt resulted in serum ACE inhibition of at least 90%., Main Limitations: Small sample size and resulting low statistical power., Conclusions: Attenuation of the rise in SBP in response to ANG-I after administration of benazepril is modest in horses despite adequate serum ACE inhibition. A dose of 1 mg/kg bwt would be recommended for future investigations of benazepril for the management of cardiovascular diseases in horses., (© 2016 EVJ Ltd.)

Once universally considered a rapidly fatal condition, cancer has increasingly become a chronic medical condition and comorbidities and adverse effects of cancer therapies have become increasingly significant. One of the leading advancements that has gained traction for the treatment of a variety of malignancies is the class of small molecule tyrosine kinase inhibitors (TKIs). Although, in many aspects revolutionary, TKIs have their own profile of side effects, including cardiovascular side effects, the most common being hypertension (HTN), congestive heart failure, corrected QT (QTc) prolongation, and instances of premature coronary heart disease. Herein, we describe the mechanisms of small TKI-induced cardiovascular toxicity and related intracellular signaling. In particular, systems-based approaches to the understanding of small TKI-induced cardiovascular toxicity are addressed. The pathophysiology of synergic cardiovascular toxicity from TKIs, anthracyclines, and monoclonal antibodies (e.g., trastuzumab, bevacizumab) is illustrated. Finally, recommendations are made for implementing systems medicine in clinical practice, for individualized cardiovascular wellness after cancer therapy., (© 2016 American Society for Clinical Pharmacology and Therapeutics.)

It has now been demonstrated that the μ, δ1 , δ2 , and κ1 opioid receptor (OR) agonists represent the most promising group of opioids for the creation of drugs enhancing cardiac tolerance to the detrimental effects of ischemia/reperfusion (I/R). Opioids are able to prevent necrosis and apoptosis of cardiomyocytes during I/R and improve cardiac contractility in the reperfusion period. The OR agonists exert an infarct-reducing effect with prophylactic administration and prevent reperfusion-induced cardiomyocyte death when ischemic injury of heart has already occurred; that is, opioids can mimic preconditioning and postconditioning phenomena. Furthermore, opioids are also effective in preventing ischemia-induced arrhythmias., (© 2016 Wiley Periodicals, Inc.)

Objectives: The objective of this study was to investigate the role of peripheral μ, δ1, δ2, and nociceptin opioid receptors agonists in the regulation of cardiac tolerance to the arrhythmogenic effect of ischemia/reperfusion in rats., Methods: Anesthetized open-chest male Wistar rats were subjected to either 45 minutes of left coronary artery occlusion (phase 1a 10 minutes and phase 2b 35 minutes) and 2 hours of reperfusion in Experiment 1 or 10 minutes of ischemia and 10 minutes of reperfusion in Experiment 2. In Experiment 1, saline or vehicle controls and the mu-specific opioids dermorphin-H (Derm-H) and ([d-Ala2, N-Me-Phe4, Gly-ol5] enkephalin (DAMAGO); the delta-1-specific opioid d-Pen2,5enkephalin (DPDPE); nociceptin; and the delta-2-specific opioids deltorphin-II (Delt-II), Delt-Dvariant (Delt-Dvar), and deltorphin-E (Delt-E) were infused 15 minutes prior to ischemia. In Experiment 2, DPDPE, Delt-D, Delt-Dvar, and Delt-E were infused at 15 minutes prior to ischemia. The universal opioid receptor antagonist naltrexone, the peripherally acting antagonist naloxone methiodide, the selective δ1 antagonist 7-benzylidene naltrexone maleate, and the specific δ2 antagonist naltriben mesylate were infused 25 minutes prior to ischemia., Results: In Experiment 1, pretreatment with the μ opioids Derm-H and DAMGO, DPDPE, and nociceptin at all doses tested did not reduce the incidence of ischemia-induced arrhythmias compared to controls during 45 minutes of ischemia. The δ2 opioids Delt-II (0.12 mg/kg), Delt-Dvar (0.3 mg/kg), and Delt-E (0.18 mg/kg) all demonstrated significant antiarrhythmic effects at the 150 nmol/kg dose compared to saline or vehicle controls. Nine of 19 animals treated with Delt-II were tolerant without ventricular arrhythmias to the arrhythmogenic effect of ischemia during the first 10 minutes of ischemia (phase 1a) and 11 of 19 were without ventricular arrhythmias during the following 35 minutes of ischemia (phase 1b). Delt-II also decreased the incidence of premature ventricular contractions and ventricular tachycardia by almost half during phase 1a. Delt-II did not affect the incidence of ventricular fibrillation (VF). Pretreatment with Delt-Dvar and Delt-E completely blocked the incidence of VF in phase 1b. Delt-E also decreased premature ventricular contractions by 50%, and the incidence of ventricular tachycardia decreased over twofold in phase 1b of ischemia. There was no enhanced tolerance by any of the delta-2 opioids to the arrhythmogenic effect of reperfusion after long-term ischemia. In Experiment 2, after 10 minutes of ischemia and 10 minutes of reperfusion, Delt-II (0.12 mg/kg) reduced the incidence of premature ventricular contractions and ventricular tachycardia compared to controls, and completely blocked the incidence of VF following 10 minutes of reperfusion. Delt-Dvar and Delt-E were without effect, as was DPDPE following 10 minutes of reperfusion. The antiarrhythmic effect of Delt-II during 10 minutes of ischemia and 10 minutes of reperfusion was completely blocked by the peripherally acting opioid receptor inhibitor naloxone methiodide and the selective delta-2 opioid receptor inhibitor naltriben mesylate, but not by the selective delta-1 inhibitor 7-benzylidene naltrexone maleate. The antagonists alone had no effect on arrhythmogenesis., Conclusions: Peripheral delta-2 opioid receptor activation by Delt-II, Delt-Dvar, and Delt-E enhanced cardiac tolerance to the arrhythmogenic effects of ischemia., (© 2013 by the Society for Academic Emergency Medicine.)

Objectives: This study was conducted to test the hypothesis that opioid receptor (OR)-mediated cardioprotection is agonist specific when administered prior to coronary artery occlusion and reperfusion in a rat model., Methods: Anesthetized open-chest male Wistar rats were subjected to 45 minutes of left coronary artery occlusion and 2 hours of reperfusion. Opioid agonists were infused 15 minutes prior to coronary artery occlusion. Two control groups and 15 opioid-treated groups were studied. Controls were infused with either saline alone (n = 16) or dimethyl sulfoxide plus hydroxypropyl-β-cyclodextrin in saline (n = 19). The μ-selective agonist DAMGO was infused at either 150 nmol/kg (n = 15) or 1500 nmol/kg (n = 14), and dermorphin-H was infused at 150 nmol/kg (n = 14). The δ₁ -selective agonist d-Pen²(,)⁵ enkephalin (DPDPE) was infused at 150 nmol/kg (n = 16) or 1500 nmol/kg (n = 14). The δ₂ -selective agonists deltorphin II (n = 16), deltorphin-D(variant) (n = 15), and deltorphin-E (n = 14) were infused at 150 nmol/kg. The selective κ₁ opioid agonist U-50488 was infused at 240 nmol/kg (n = 14), 1500 nmol/kg (n = 14), and 2,400 nmol/kg (n = 14). The selective κ₂ opioid agonist GR-89696 was infused at 150 nmol/kg (n = 14) and 1500 nmol/kg (n = 15). Orphinan FQ (nociceptin), also referred to as OR-like 1 (ORL1), was infused at 220 nmol/kg (n = 15) and 1500 nmol/kg (n = 15). The infarct size/area at risk (IS/AAR) ratio was determined after reperfusion by negative staining with patent blue violet dye. Hemodynamic parameters including heart rate, mean arterial blood pressure (MAP), and rate pressure product (RPP) were determined., Results: Pretreatment with the δ₂ OR agonist deltorphin II (150 nmol/kg) significantly reduced the IS/AAR ratio, while deltorphin-D(variant) and deltorphin-E did not exhibit an infarct-sparing effect at that treatment dose. Activation of δ₁ OR by DPDPE, κ₁ OR by U-50488, κ₂ OR by GR-89696, μ OR by DAMGO, dermorphin-H, and nociceptin had no effect on the IS/AAR ratio. U-50488 at 2,400 nmol/L induced a bradycardic effect. All other opioids had no effect on hemodynamic parameters at the doses tested., Conclusions: Peripheral δ₂ OR activation by deltorphin II induces infarct size reduction in this animal model. Agonists of μ, δ₁, κ₁, κ₂, and nociceptin receptors at the doses tested did not induce cardiac tolerance to ischemia/reperfusion injury in vivo., (© 2010 by the Society for Academic Emergency Medicine.)

Objectives: The authors present evidence that the delta opioid receptor agonist Deltorphin-D(variant) (Delt-D(var)) and hibernating woodchuck plasma (HWP), but not summer-active woodchuck plasma (SAWP), can provide significant neuroprotection from focal ischemia in mice by a mechanism that relies in part on reducing nitric oxide (NO) release in ischemic tissue., Methods: Cerebral ischemia was produced in wild-type and NO synthase-deficient (NOS(-/-)) mice by transient, 1-hour middle cerebral artery occlusion (MCAO). Behavioral deficits were determined at 22 hours and infarct volume was assessed at 24 hours after MCAO. Mice were treated with saline or Delt-D(var) at 2.0 and 4.0 mg/kg, or 200 microL of HWP or SAWP. NOS(-/-) mice were treated with either saline or Delt-D(var) at 4.0 mg/kg. NO release was determined using an N9 microglial cell line pretreated with delta- or mu-specific opioids and HWP or SAWP prior to activation with lipopolysaccharide and interferon-gamma. Nitrate in the medium was measured as an indicator of NO production., Results: Infusion of Delt-D(var) or HWP (but not SAWP) decreased infarct volume and improved behavioral deficits following 1 hour of MCAO and 24 hours of reperfusion. In NOS(-/-) mice, endothelial NOS(+/+) is required to provide Delt-D(var)-induced neuroprotection. Delt-D(var) and HWP dose-dependently decreased NO release in cell culture, while SAWP and other delta- and mu-specific opioids did not., Conclusions: Delt-D(var) and HWP, but not SAWP, are effective neuroprotectant agents in a mouse model of transient MCAO. In cell culture, the mechanism of this ischemic neuroprotection may rely in part on their ability to block NO release.

Only limited information on nonsuicidal deliberate self-harm behavior among nonclinical populations is available, and it is unclear whether coping and emotional difficulties remain among those with a past history of self-harm behavior. The purpose of this study is to examine emotions and coping strategies among three nonclinical groups with a recent, past, and no history of nonsuicidal deliberate self-harm behavior. College students completed self-report measures of self-harm behavior, suicidal thoughts, emotional dispositions, and coping strategies. Contrary to expectations, there were few differences in coping strategies among the three groups ( p > .0033). Those with a recent history (n = 23; in the last 12 months) and past history (n = 32; more than 12 months ago) of self-harm behavior reported greater levels of negative emotion (e.g., hostility, guilt, sadness) than those who have never self-harmed (n = 161; p < .0045). This indicates that although self-harm behavior had discontinued (>12 months ago), negative emotion differences were present, and both recent and past self-harmers merit concern in managing their negative emotions to lower their risk for future difficulties., ((c) 2007 Wiley Periodicals, Inc.)

Exposure to familial alcoholism has been associated with many behavioral and emotional difficulties among offspring. However, few studies have examined environmental risks that often coexist with familial alcoholism, and which may influence the development of offspring psychosocial problems. This study examined potential additive and interactive effects of childhood exposure to family violence and childhood exposure to familial alcoholism on adolescent functioning. Three domains of adolescent functioning were examined in a high-risk community sample of 109 families: lifetime levels of substance use, conduct disorder behaviors, and self-esteem. Results indicated that both childhood exposure to familial alcoholism and childhood exposure to family violence were associated with psychosocial functioning of offspring during adolescence, although the relations differ according to domain of functioning and gender.

Mexican Americans bear a disproportionate burden of type 2 diabetes, and although clinicians and researchers are beginning to develop culturally competent interventions, few instruments are available for measuring variables relevant to health outcomes. The purpose of this study was to determine the psychometric properties of a diabetes-related health belief instrument translated for use with Spanish-speaking Mexican Americans. Three hundred and twenty-six Spanish-speaking Mexican Americans from Starr County, a Texas-Mexico border community, diagnosed with type 2 diabetes participated in the study. Factor analysis was used to examine the factor structure of the instrument, and reliability testing was conducted to determine the internal consistency of the resulting factors. The final instrument had 25 items with four subscales-Barriers, Social Support for Diet, Impact of Job on Therapy, and Benefits of Therapy-and one item to measure, Control. Internal consistency coefficients for these subscales were .56, .62, .86, and .90, respectively. The translated instrument needs to be tested over time with other Hispanic populations., (Copyright 2002 Wiley Periodicals, Inc.)

Introduction: Pyruvate dehydrogenase deficiency is an inherited inborn error of metabolism associated with early neonatal death and long-term neurologic sequelae in survivors. Prenatal diagnosis currently relies on isolation of fetal cells for subsequent genetic and/or biochemical studies. Magnetic resonance imaging and magnetic resonance spectroscopy have been used on occasion for both postnatal diagnosis and management of pyruvate dehydrogenase deficiency. We illustrate a case in which these non-invasive modalities also prove useful for prenatal diagnosis of this condition., Case: A 31-year-old multipara with a history of two prior infants affected with pyruvate dehydrogenase deficiency presented with a spontaneous dichorionic, diamniotic twin pregnancy. Magnetic resonance imaging and magnetic resonance spectroscopy were performed on both fetuses. Magnetic resonance imaging of the presenting (male) fetus demonstrated mild ventriculomegaly, increased extracerebrospinal fluid, and decreased cortical sulcation and gyration. The non-presenting (female) fetus was structurally normal. Magnetic resonance spectroscopy spectra were obtained for both fetuses, and were normal. The diagnosis of pyruvate dehydrogenase deficiency was made in the presenting fetus after delivery on the basis of subsequent mortality from severe lactic acidosis., Conclusion: Prenatal MR imaging of the fetal brain can be used for prenatal diagnosis in fetuses at risk for pyruvate dehydrogenase deficiency. Prenatal MR spectroscopy, although technically feasible, does not appear to have a role in the prenatal diagnosis of this condition., (Copyright 2001 John Wiley & Sons, Ltd.)

A study was undertaken to evaluate different procedures to safely remove microorganisms, protein, and mammalian cells from materials and provide a suitable method for cleaning and assessing effectiveness of cleaning medical devices for reuse or for analysis of failure. Safety considerations for the personnel performing the cleaning or handling the device after cleaning are important issues. Polystyrene plates (96 well) were used to simulate device surfaces not amenable to manual scrubbing. Staphylococcus epidermidis, Candida albicans, Escherichia coli, Pseudomonas aeruginosa, and oral flora were grown in the plates. The plates were stained with crystal violet and the optical densities recorded. The results indicated that E. coli did not adhere well and Pseudomonas formed clumps that were easily detached from the surface of the plates. However, S. epi, C. albicans, and the oral organisms formed adherent biofilms that were difficult to remove from the plates. Detergents with enzymes and sodium hypochlorite (NaOCl) bleach were both effective in removing the biofilm. Other detergents and surfactants were not effective. The aldehyde agents did not remove the organisms and made further cleaning difficult. Allowing the biofilm to dry first made cleaning very difficult. Only the NaOCl bleach could subsequently remove the dried or aldehyde fixed organisms from the wells. The same 96-well polystyrene plate format was used to measure the amount of protein and cell adherence as well as the effectiveness of subsequent cleaning. Bradford reagent was used to detect protein as a measure of the cleaning efficacy. As with the bacteria, NaOCl bleach was effective at removing the protein and cells that had been dried or fixed by formalin or alcohol, whereas detergent with enzymes was not very effective. This study confirmed that used medical devices, contaminated with microorganisms, protein, and/or mammalian cells, should not be allowed to dry before cleaning and that a thorough cleaning procedure should precede sterilization or disinfection (with the exception of NaOCl bleach which also cleans)., (Copyright 2000 John Wiley & Sons, Inc.)

Cobalt-chromium alloy porous coatings have become increasingly popular as a means of achieving a stable, longer lasting fixation on orthopedic implants. However, sintering heat treatments cause changes in the microstructure that result in changes in the corrosion behavior of the porous coatings. Experiments were conducted to examine the effects of microstructure on the corrosion of CoCr porous coatings. Four distinct microstructures were characterized. Light microscopy revealed microstructures A and B had relatively fewer carbides and a large-grain structure, microstructures C and D displayed a finer grain size with significant carbide formation, predominantly within grains and fusion zones. Accelerated anodic corrosion experiments were conducted to study the localized attack of each microstructure. Experiments were conducted using metallographically polished porous-coated disks for durations of 1, 4, 16, 24, and 72 h. The disks were examined with SEM and EDS to observe preferential attack and element depletion. Results showed a progressive dissolution of the matrix, with preferential attack of the grain boundaries and regions adjacent to the carbides due to sensitization. A precipitation layer was found to be Cr-rich and possibly composed of chromium hydroxide or a chromium orthophosphate. In addition, the solution became yellow in color with longer exposure times, possibly due to the presence of chromate ions, as indicated by an increased chromium level detected by AAS.

Contact dermatitis following skin contact with ionic metals occurs in about 15% of the human population, but systemic responses are not as common. It is generally believed that skin contact with metal ions leads to different biological processing compared with systemic contact. The purpose of the experiments presented here was to examine elimination of nickel and cobalt salts following skin application and following injection into the deep tissue of hamsters. In addition uptake of the metal by fibroblasts and by keratinocytes was examined in vitro. The data indicate that elimination of nickel and cobalt in the urine following systemic injection was rapid, as expected, but that elimination following skin application was delayed. Much of the metal was retained in the skin. Uptake of the metal by keratinocytes at low doses was greater than the uptake by the fibroblasts. At high doses the differences were not as great. Thus the conclusion is drawn that metal salts are retained in the skin for an extended period of time and could lead to prolonged antigen processing and consequent immune responses in the dermal tissue. Skin application leads to some systemic distribution but the systemic application did not lead to skin accumulation.

Titanium and its alloy of 6% aluminium and 4% vanadium are used extensively in orthopedic and dental surgery. However, in conditions of motion leading to wear, there is significant generation of wear products with deposition of black debris in the tissue. The questions remain as to how much of this debris is generated and to where it is transported. Previous studies have been hampered by low levels of detected elements giving values just above the background levels found in normal tissue and body fluids. The purpose of these experiments was to increase the body burden of titanium and vanadium by injecting larger doses of titanium and vanadium salts over an extended period of time. Each animal (Syrian hamster) received 100 micrograms of each element once a week for six weeks. The hamster was sacrificed on the seventh week and body fluids and tissue harvested. The results indicate that in the experimental animals there was transport of vanadium with levels above control in urine, plasma, liver, spleen, and the mineralized portion and organic portion of bone. Titanium had less transport but still showed levels in the experimental animals in plasma, kidney, liver, spleen, and both phases of bone above those in the control animals. Neither element was found above control levels in lung or red blood cells. The levels of titanium and vanadium in control bone were high, possibly indicating bone as a site for storage and accumulation of these elements when encountered in the activities of daily living.

Corrosion has been reported at the modular interfaces of total joint replacement implants, but with conflicting theories as to the cause of such damage. The modular design itself leaves the interface susceptible to galvanic, crevice, or fretting corrosion, or a combination of the three. The purpose of this study was to quantify the effect of material combination on fretting corrosion of orthopedic alloys. Each test specimen consisted of a two-hole plate with spherical countersinks and two cortical bone screws. The plates and screws were made of either Ti6Al4V or wrought cobalt-chromium-molybdenum (CCM), and were tested in all mixed-metal and similar-alloy combinations. Fretting corrosion experiments were conducted for 14 days in 10% calf serum, according to ASTM F897. Corrosion damage was evaluated by weight-loss measurements, atomic absorption spectrophotometry and scanning electron microscopy analyses. The results indicated that Ti6Al4V suffered relatively severe damage when fretted against itself, as a result of adhesive galling. The extent of titanium damage was reduced considerably, however, when Ti6Al4V was fretted against wrought CCM. In contrast, there was essentially no difference in wrought CCM damage when the alloys was fretted against itself compared to fretting against Ti6Al4V. Finally, in similar-alloy combinations, Ti6Al4V suffered more severe damage than wrought CCM.

Experiments were undertaken to determine whether hexavalent chromium was released during corrosion of orthopedic implants. Uptake of chromium (Cr) by cells and separation using amberlite resin were the methods used to determine that hexavalent Cr was present. We used salts of chromium as trivalent chromium (chromic chloride) and hexavalent chromium (potassium dichromate) to verify that the amberlite separation technique separates hexavalent Cr into the upper phase and trivalent Cr into the lower phase. The use of the salts also verified that only the hexavalent Cr became red blood cell-associated and that most of this was intracellular rather than membrane bound. The use of the amberlite separation technique demonstrated that the hexavalent Cr in the red blood cells was rapidly reduced to trivalent Cr. Cellular uptake of chromium was documented in red blood cells following corrosion of stainless-steel and cobalt-chromium implants in vivo, in the red blood cells of patients undergoing total joint revisions, and in fibroblasts subjected to products of fretting corrosion of stainless-steel and cobalt-chromium implants. Thus, corrosion of implants can lead to the release of the biologically active hexavalent chromium into the body. This chromium is rapidly reduced to trivalent chromium in cells.

Histological evaluation of retrieved devices allows for assessment of the biological response to the implants. Interaction between the biomaterial and the fluids used in the processing may alter the appearance or composition of the device. This may result in artifacts due to processing which are misinterpreted as being caused by the biological response. Alteration by the fluids used in fixation may be particularly important with materials that have a propensity to interact with aqueous environments, as in the case of calcium phosphate ceramics. Therefore, we examined the effects of various standard histological fixation techniques on hydroxylapatite coated metal implants. Of the techniques examined, fixation with ethanol appeared to affect the surface morphology the least, whereas fixation in unbuffered formalin appeared to affect the bulk composition of these samples the least. Fixation in buffered formalin resulted in marked changes in both surface morphology and bulk composition.

The use of titanium and titanium-6% aluminum-4% vanadium alloy for dental and orthopedic implants has increased in the last decade. The implants are presumed to be compatible because osseointegration, bony apposition, and cell attachment are known. However, the cellular association of titanium and vanadium have remained unknown. This study examined the uptake of salts or fretting corrosion products. Titanium was not observed to be toxic to the cells. Vanadium was toxic at levels greater than 10 micrograms/mL. The percentage of cellular association of titanium was shown to be about 10 times that of vanadium. The percentage of cellular association of either element was greater from fretting corrosion than from the addition of salts. The presence of vanadium did not affect the cellular uptake of titanium. The presence of titanium decreased the cell association of vanadium.

Titanium and titanium-6% aluminum-4% vanadium (Ti-6Al-4V) are known to be biocompatible and corrosion resistant. However, there have been numerous reports of elevated tissue levels of titanium due to passive dissolution, wear, or fretting corrosion of implants. Studies were undertaken to determine whether the fretting corrosion of Ti-6Al-4V could be reduced by surface treatment of one or both surfaces in a fretting situation. Three different surface treatments were studied: ion implantation, physical vapor deposition nitriding, and plasma ion nitriding. The specimens used were screws fretting against the countersinks of a two-hole plate. Fretting corrosion was assessed by weight loss, by chemical analysis of test solutions, and by scanning electron microscopy. Surface treatment of one component, the screws, resulted in reduction in the release of titanium to only 18-32% of that seen with the untreated controls. Weight loss of the untreated plates fretted against physical vapor deposition nitrided screws and plasma ion nitrided screws was reduced to 31 and 38% of the control, respectively. The weight loss of plasma nitrided screws was only 30% that of the control. Nitriding of both plates and screws resulted in a further decrease in plate weight loss and metal release. Plasma ion nitriding of both components had the most significant effect, with the weight loss and titanium release being only 11 and 2% of the control values, respectively.

Corrosion of porous coated cobalt chromium specimens surgically implanted subcutaneously in hamsters was accelerated by application of a fixed anodic potential. Corrosion current measurements were utilized for prediction of metal ion release based on Faraday's law. Daily urine samples were collected pre- and post-stimulation, and, at animal sacrifice, organs and blood samples were taken for chemical analysis. By using in vitro release data from previous studies, and efficiency correction factors, the amount of metal ion release was calculated. The results demonstrated rapid and complete excretion of nickel and molybdenum. Most of the cobalt was excreted, with elevation of cobalt levels in liver, kidney, and lung. Chromium excretion was much lower due to significant red cell binding and in vivo storage, especially in the kidney and spleen.

Data from a previously reported meta-analysis of diabetes patient education literature were reanalyzed to determine the influence of study/subject characteristics, such as study quality and age of subjects, on patient outcomes. Patient knowledge and self-management skills, weight loss, glycosylated hemoglobin levels, and psychological outcomes were analyzed as outcome variables. Seventy-three relevant published and unpublished studies were located. Patient education appeared to be more effective in younger patients, particularly for the knowledge outcome. For all patients, glycosylated hemoglobin levels improved between 1 and 6 months postintervention, but decreased to 1-month levels after 6 months. Length of the educational intervention did not appear to influence outcomes. More rigorous, experimental research designs tended to produce more conservative effect size estimates. Implications for diabetes patient education are discussed.

Hamsters were injected with titanium, aluminum, and vanadium salts either intraperitoneally or intramuscularly to study the transport, storage, and elimination of these metals. Blood samples were taken at 4 h or 24 h, and urine samples were taken at 24, 48, and 72 h. The hamsters were then injected weekly for 5 weeks after the initial injection. Blood and portions of the kidneys, liver, lung, and spleen were taken at sacrifice. All samples were analyzed for titanium, aluminum, and vanadium concentrations using graphite furnace atomic absorption spectroscopy (GFAAS). Titanium was found not to be excreted in the urine, was found in low levels in the blood, and was elevated over control in the kidney, liver, and spleen. Aluminum detection via GFAAS showed wide standard deviations and high levels in controls; however, aluminum was found to be excreted in the urine, and to be transported by the blood in the experimental animals. A small amount accumulated in the liver and spleen. Vanadium was excreted in high levels in the urine. A small amount was found in the blood, and the level in the organs was below the reliable detection limits. The rapid excretion of vanadium might be related to its solubility in physiological conditions, while the limited excretion of titanium may be related to its being insoluble in the physiologic environment.

Polymer composites are being recognized as important implant materials for fracture fixation plates. The use of a composite material is dependent upon the mechanical properties of the material and its biocompatibility. The primary objective of this project was to evaluate 30% chopped-carbon-fiber-reinforced poly(etheretherketone) (CFRPEEK) as a potential material for use as a fracture fixation plate. A two-phase study was conducted. The first phase analyzed the short-term biocompatibility of CFRPEEK through rabbit muscle implant testing. CFRPEEK exhibited a nonspecific foreign body tissue reaction similar to the response observed with ultra-high-molecular-weight polyethylene (UHMWPE). In the second phase, four-hole CFRPEEK plates were implanted as internal fixation devices for transverse midshaft femoral osteotomies in beagles. The plates were effective in promoting fracture healing. A nonspecific foreign body reaction was observed to the plates and to particulate debris.

The nature and distribution of corrosion products released into the body from orthopaedic implants remains an important issue. Various approaches to study this problem have been taken, such as the injection of metal salts, the injection of corrosion products, analysis of retrieved implants and adjacent tissue, and stimulated corrosion in vivo, with collection of body fluids and tissues for analysis. Tissue culture techniques have also been used to study the cellular response to metal salts or to corrosion or wear products that were generated in a separate environment. In this study, fretting corrosion of stainless steel plates and screws and of cobalt-chromium alloy plates with stainless steel screws was undertaken within a cell culture. The results showed that the cell cultures remained viable despite considerable metal ion release. Nickel was released in all cultures with fretting corrosion and was found mainly in the tissue culture medium (supernatant of the harvested cultures). Cobalt was detected only in those cultures with fretting corrosion of the cobalt-chromium alloy, and it was present mainly in the tissue culture medium. Chromium was released in all cultures with fretting corrosion, and it was found to be associated mainly with the cells with little in the culture medium. This compartmentalization of cell-associated chromium and fluid-associated cobalt and nickel supports in vivo studies showing chromium accumulation in red blood cells or tissue sites and comparatively low levels of nickel and cobalt.

Short carbon fiber reinforced composites could potentially replace some of the metal alloys used in orthopedic implants. In particular, polysulfone and, more recently, polyetheretherketone have been considered as the matrix material for carbon fiber reinforced composite implant materials. ASTM standards F813 and F619 for direct contact cell culture evaluation and extraction were employed to determine the in vitro biocompatibility of a carbon fiber composite of polyetheretherketone, PEEK, in comparison to a carbon fiber reinforced polysulfone composite. The cell cultures were assessed qualitatively by microscopy and quantitatively using an enzyme assay to determine cytotoxicity. Overall, the cellular response to the PEEK and polysulfone composites were negligible indicating that further in vivo studies with these materials are appropriate.

The quality of reported research representing a number of disciplines involved in diabetes patient education was investigated in this study. A rigorous literature search identified 47 studies reported between 1954 and 1986 that met inclusion criteria; 29 were published studies, 18 were unpublished. Quality of the research was measured by Duffy's Research Appraisal Checklist (RAC) and also by coding each study as to the number of threats to internal and external validity present. Overall quality as measured by the RAC ranged from 34 to 95 on a 100-point scale. A statistically significant relationship was found between publication date of the research report and quality, indicating improvement in quality during recent years. Quality of published versus unpublished research reports was not found to differ significantly. Recommendations for improving methodological rigor of future studies include: (a) the use of more rigorous designs, particularly those involving control groups such as randomized clinical trials; (b) reporting of more complete data in research reports; and (c) monitoring of the quality of future studies.

An accelerated anodic corrosion method was used to study the effects of heat treatment and bead size on corrosion and metal ion release of porous coated F75 cylinders in saline and serum. Three heat treatments were used: a standard process for F75 implants (HTA), the standard plus an additional hour in air to produce a thin oxide film (HTA'), and a sintering in high vacuum to produce a chromium-depleted surface (HTB). Three bead sizes of similar composition were used, with approximate sizes of 215, 300, and 560 microns. The results demonstrated that HTA' had the lowest corrosion rate and that of HTB was significantly greater than either HTA or HTA'. The corrosion rates of HTA and HTA' were significantly greater in serum as compared with saline, whereas that of HTB was not affected by the presence of serum, suggesting an interaction between chromium and serum proteins. Bead size had a minimal effect on the corrosion rate of HTA'. For HTA, the small beads had the highest corrosion rate; the lowest was with the medium-sized beads. Bead size had the most significant effect with HTB, with that of the smaller beads having the higher corrosion rates. The effects of bead size were less consistent in serum, suggesting that protein adsorption may mask some of the surface area effects. It is concluded that the oxide film does reduce corrosion, that proteins do have an influence on the corrosion of F75, and that this method can be a useful tool for studying the effects of improved heat treatment methods on the corrosion rate of F75 implants.

The effects of adding 1.0 cc of aqueous methylene blue dye as a visual contrast agent to a standard 40 g pack of acrylic bone cement are determined. These cements are evaluated: Simplex P (Radiopaque), Zimmer Bone Cement, and Zimmer LVC Bone Cement. Seven tests were performed. Leach out is less than 2.0% and was undetectable after day 8. Biocompatibility using a rabbit model shows contrast and white cement to be equivalent. Tension, compression, and 3- and 4-point bending strengths are not significantly altered except for a slight increase in 4-point bending strength for contrast Zimmer (regular) bone cement. Dough, set, and working times are decreased by 30-150 s. The ASTM F451 intrusion standards are met for all three contrast cements. Viscosity increases more rapidly for contrast cement, but remains sufficiently low (less than 100 N-s/m2) early after mixing to allow good penetration into bone. Ease of removal and visualization of contrast cement are shown by revision of cemented femoral total hip components in synthetic and cadaver femurs and by debriding cement particles from a soft tissue background coated with blood. The use of contrast bone cement appears to be both safe and efficacious for use in initial and revision total joint replacements. Because of the decreased working times, its use is recommended only by experienced surgeons.

Two models were used to study fretting corrosion of surgical alloys. In the first, the amount of load and motion between plates and screws was controlled, and corrosion rates of stainless steel and MP35N were determined by measurements of component weight loss and metal ion concentration in the test solutions. Stainless steel had the higher rate of fretting corrosion. The addition of 10% serum to saline resulted in a significant reduction of the corrosion rate of stainless steel and MP35N. The use of stainless steel screws in a mixed-metal combination with MP35N and titanium plates showed minimal effects on the performance of the stainless steel screws but an increase in fretting corrosion of the MP35N plates. In the second model, plates were applied to glass fiber-reinforced plastic tubes as bone analogues and subjected to cyclic axial loads. These results demonstrated a reduction in fretting corrosion rates associated with an increase in screw torque and a decrease in axial load. Corrosion rates were minimal with intact tubes simulating healed fractures and greatest with an oblique-cut fracture simulation. These models have proven useful for the evaluation of fretting corrosion rates of different alloys and for evaluation of variables such as fracture stability.

Auger electron spectroscopic (AES) studies were conducted to examine the surface film of stainless steel specimens which had been subjected to passive and anodic corrosion in vitro and in vivo. Anodic corrosion was accelerated by the application of a +500 mV (SCE) potential for 30 minutes. Experiments performed in 0.9% saline indicated little alteration in the nature of the surface film compared to a freshly prepared control specimen. Auger analysis of specimens in 10% serum or in vivo revealed that passive film thickness was dependent on the corrosive environment. The films of specimens immersed under freely corroding conditions in 10% serum or in vivo were similar to the control film. Accelerated corrosion performed in 10% calf serum resulted in significant film thickening. The thickest films were from accelerated corrosion in vivo. The mechanism for the altered surface films produced by corrosion in vivo or in serum as compared to saline needs to be investigated further.

Flexural strength and molecular weight of polymethylmethacrylate bone cement were determined for cement polymerized in vivo in a canine total hip replacement and cement from the same batch polymerized in vitro. Both in vivo and in vitro samples showed a slight increase in flexural strength and modulus at 2 weeks, followed by a nearly equivalent decline at 8 weeks. In vitro and in vivo samples exhibit a comparable stress to failure, but the in vivo samples show a significantly increased strain and decreased modulus. Cement from the proximal region of the prosthesis has significantly decreased flexural strength, lower modulus, and lower molecular weight than cement from the distal region and plug, suggesting that failures in the proximal region of a prosthesis may be due to inferior physical and mechanical properties of the bone cement in that region.

A study was conducted to determine the ability of hamsters to eliminate in the urine, or store in the organs, large quantities of metal salts given over a period of several months. In addition, the effect of prior immunization on metal ion clearance was determined. The results indicated that nickel was rapidly eliminated in the urine and that the level in the organs was similar to that of control animals. Cobalt was eliminated more slowly than was nickel. The organ levels of cobalt were similar to those of control animals with a slight elevation in the liver of the injected animals. Chromium was eliminated in the urine very slowly, was red cell associated, and the levels were elevated in all the organs (liver, lung, spleen, kidney) compared to control. Prior immunization with metal salts increased the storage of chromium.

In vivo experiments were undertaken to study the transport of metal ions away from the intramuscular (IM) injection site and to study the binding of the metals to blood cells. Hamsters were injected intramuscularly with metal salts or with corrosion products generated by fretting corrosion of 316 LVM stainless steel or MP-35N plates and screws. The animals were bled at 0 time, and 2, 4, 6, 24, 48, and 96 h after injection. The concentration of nickel, cobalt, and chromium in the serum, attached to red cells, and attached to white cells was determined. This study showed that metals are rapidly transported from the intramuscular site with high levels in the blood by 2 h. The level of metal in the blood varied considerably with nickel being transported in high concentration to the blood, chromium with a valence of 6+ being transported to the blood, and cobalt and chromium with a valence of 3+ being transported less to the blood. The highest amount of cell binding was observed with chromium 6+. Cobalt showed negligible binding to blood cells. When all the metal salts injected together were compared with the individual salts injected alone, there was no difference. This indicated that the each metal behaves independently of the presence of the others.

A five-year-old boy had multiple agminate Spitz nevi arising in an area of hyperpigmentation that developed concurrently with the nevi. Multiple Spitz nevi occurring in a single group are rare, and their presence on a hyperpigmented background is extremely uncommon. Very few such cases have been described, and all of those lesions arose on a congenital hyperpigmented patch. In contrast, the nevi in our patient appeared to arise on an acquired hyperpigmented patch that was not present at birth, and histologically did not demonstrate features of a congenital nevus. Accurate diagnosis is necessary to avoid unnecessary radical therapy.

The binding of metal ions from salts and from corrosion products of 316 LVM stainless steel and MP-35 to blood cells and serum proteins was studied in vitro. In the first series of experiments, metal salts were added to whole blood and then the blood separated into red cells, white cells, and serum. Nickel from nickel chloride or corrosion products of stainless steel bound in very small quantities to blood cells. Cobalt from cobalt chloride bound to both red cells and white cells. Chromium from chromic chloride (Cr3+) bound to cells in very small quantities whereas chromium from potassium dichromate (Cr6+) and corrosion products showed very high to binding to red cells and some binding to white cells. In a second series of experiments the blood was separated into its components and then the metal salts were added and the binding pattern was identical. In a third series of experiments serum which had interacted with the metal salts or corrosion products was separated into its components by isoelectric focusing on polyacrylamide gels. Almost all of the metal, whatever the source, was detected in the albumin region of the gels indicating strong binding to albumin. These studies on the cell and protein binding of the metals help to explain the dissemination of corrosion products from the site of the implant and subsequent systemic responses by some individuals.

Fretting corrosion of stainless-steel round hole plates and spherical head screws was studied using a simulator that produced a rocking motion of the heads in the plate holes. Experiments were run for 7 days, with the simulator producing 1 oscillation/s for 16 h/day. Fretting corrosion was studied in 0.9% NaCl and in a 10% solution of fetal calf serum in saline. The results showed a tenfold decrease in fretting corrosion when the serum was added to the saline. Measurements of the weight of the two screws and two-hole plate showed those in saline lost 2.9 mg as compared to 0.3 for those in 10% serum. The concentration of nickel in the saline solutions was 12.4 micrograms/mL compared with 0.85 in serum. Visual examination of the solutions and implants revealed that those in saline had a significant amount of corrosion products while those tested in 10% serum were bright and shiny. Recordings of electrical potentials demonstrated that the addition of serum to saline significantly reduced the change in potential from rest to fretting condition.