Do total shoulder arthroplasty implants corrode?

BACKGROUND: Total shoulder arthroplasty (TSA) has become the gold-standard treatment to relieve joint pain and disability in patients with glenohumeral osteoarthritis who do not respond to conservative treatment. An adverse reaction to metal debris released due to fretting corrosion has been a major concern in total hip arthroplasty. To date, it is unclear how frequently implant corrosion occurs in TSA and whether it is a cause of implant failure. This study aimed to characterize and quantify corrosion and fretting damage in a single anatomic TSA design and to compare the outcomes to the established outcomes of total hip arthroplasty. METHODS: We analyzed 21 surgically retrieved anatomic TSAs of the same design (Tornier Aequalis Pressfit). The retrieved components were microscopically examined for taper corrosion, and taper damage was scored. Head and stem taper damage was quantitatively measured with a non-contact optical coordinate-measuring machine. In selected cases, damage was further characterized at high magnifications using scanning electron microscopy. Energy-dispersive x-ray spectroscopy and metallographic evaluations were performed to determine underlying alloy microstructure and composition. Comparisons between groups with different damage features were performed with independent-samples t tests; Mann-Whitney tests and multivariate linear regression were conducted to correlate damage with patient factors. The level of statistical significance was set at P < .05. RESULTS: The average material loss for head and stem tapers was 0.007 mm3 and 0.001 mm3, respectively. Material loss was not correlated with sex, age, previous implant, or time in situ (P > .05). We observed greater volume loss in head tapers compared with stem tapers (P = .002). Implants with evidence of column damage had larger volumetric material loss than those without such evidence (P = .003). Column damage aligned with segregation bands within the alloy (preferential corrosion sites). The average angular mismatch was 0.03° (standard deviation, 0.0668°), with negative values indicating distal engagement and positive values indicating proximal engagement. Implants with proximal engagement were significantly more likely to have column damage than those with distal engagement (P = .030). DISCUSSION: This study has shown not only that the metal components of TSA implants can corrode but also that the risk of corrosion can be reduced by (1) eliminating preferential corrosion sites and (2) ensuring distal engagement to prevent fluid infiltration into the modular junction.

Effects of nitrite infusion on skeletal muscle vascular control during exercise in rats with chronic heart failure.

Chronic heart failure (CHF) reduces nitric oxide (NO) bioavailability and impairs skeletal muscle vascular control during exercise. Reduction of NO2 (-) to NO may impact exercise-induced hyperemia, particularly in muscles with pathologically reduced O2 delivery. We tested the hypothesis that NO2 (-) infusion would increase exercising skeletal muscle blood flow (BF) and vascular conductance (VC) in CHF rats with a preferential effect in muscles composed primarily of type IIb + IId/x fibers. CHF (coronary artery ligation) was induced in adult male Sprague-Dawley rats. After a >21-day recovery, mean arterial pressure (MAP; carotid artery catheter) and skeletal muscle BF (radiolabeled microspheres) were measured during treadmill exercise (20 m/min, 5% incline) with and without NO2 (-) infusion. The myocardial infarct size (35 ± 3%) indicated moderate CHF. NO2 (-) infusion increased total hindlimb skeletal muscle VC (CHF: 0.85 ± 0.09 ml·min(-1)·100 g(-1)·mmHg(-1) and CHF + NO2 (-): 0.93 ± 0.09 ml·min(-1)·100 g(-1)·mmHg(-1), P < 0.05) without changing MAP (CHF: 123 ± 4 mmHg and CHF + NO2 (-): 120 ± 4 mmHg, P = 0.17). Total hindlimb skeletal muscle BF was not significantly different (CHF: 102 ± 7 and CHF + NO2 (-): 109 ± 7 ml·min(-1)·100 g(-1) ml·min(-1)·100 g(-1), P > 0.05). BF increased in 6 (∼21%) and VC in 8 (∼29%) of the 28 individual muscles and muscle parts. Muscles and muscle portions exhibiting greater BF and VC after NO2 (-) infusion comprised ≥63% type IIb + IId/x muscle fibers. These data demonstrate that NO2 (-) infusion can augment skeletal muscle vascular control during exercise in CHF rats. Given the targeted effects shown herein, a NO2 (-)-based therapy may provide an attractive "needs-based" approach for treatment of the vascular dysfunction in CHF.

Microvascular oxygen pressures in muscles comprised of different fiber types: Impact of dietary nitrate supplementation.

Nitrate (NO3(-)) supplementation via beetroot juice (BR) preferentially improves vascular conductance and O2 delivery to contracting skeletal muscles comprised predominantly of type IIb + d/x (i.e. highly glycolytic) fibers following its reduction to nitrite and nitric oxide (NO). To address the mechanistic basis for NO3(-) to improve metabolic control we tested the hypothesis that BR supplementation would elevate microvascular PO2 (PO2mv) in fast twitch but not slow twitch muscle. Twelve young adult male Sprague-Dawley rats were administered BR ([NO3(-)] 1 mmol/kg/day, n = 6) or water (control, n = 6) for 5 days. PO2mv (phosphorescence quenching) was measured at rest and during 180 s of electrically-induced 1-Hz twitch contractions (6-8 V) of the soleus (9% type IIb +d/x) and mixed portion of the gastrocnemius (MG, 91% type IIb + d/x) muscles. In the MG, but not the soleus, BR elevated contracting steady state PO2mv by ~43% (control: 14 ± 1, BR: 19 ± 2 mmHg (P < 0.05)). This higher PO2mv represents a greater blood-myocyte O2 driving force during muscle contractions thus providing a potential mechanism by which NO3(-) supplementation via BR improves metabolic control in fast twitch muscle. Recruitment of higher order type II muscle fibers is thought to play a role in the development of the VO2 slow component which is inextricably linked to the fatigue process. These data therefore provide a putative mechanism for the BR-induced improvements in high-intensity exercise performance seen in humans.

Novel coexisting mangrove-coral habitats: Extensive coral communities located deep within mangrove canopies of Panama, a global classification system and predicted distributions.

Marine ecosystems are structured by coexisting species occurring in adjacent or nested assemblages. Mangroves and corals are typically observed in adjacent assemblages (i.e., mangrove forests and coral reefs) but are increasingly reported in nested mangrove-coral assemblages with corals living within mangrove habitats. Here we define these nested assemblages as "coexisting mangrove-coral" (CMC) habitats and review the scientific literature to date to formalize a baseline understanding of these ecosystems and create a foundation for future studies. We identify 130 species of corals living within mangrove habitats across 12 locations spanning the Caribbean Sea, Red Sea, Indian Ocean, and South Pacific. We then provide the first description, to our knowledge, of a canopy CMC habitat type located in Bocas del Toro, Panama. This canopy CMC habitat is one of the most coral rich CMC habitats reported in the world, with 34 species of corals growing on and/or among submerged red mangrove aerial roots. Based on our literature review and field data, we identify biotic and abiotic characteristics common to CMC systems to create a classification framework of CMC habitat categories: (1) Lagoon, (2) Inlet, (3) Edge, and (4) Canopy. We then use the compiled data to create a GIS model to suggest where additional CMC habitats may occur globally. In a time where many ecosystems are at risk of disappearing, discovery and description of alternative habitats for species of critical concern are of utmost importance for their conservation and management.

Dietary nitrate supplementation: impact on skeletal muscle vascular control in exercising rats with chronic heart failure.

Chronic heart failure (CHF) results in central and peripheral derangements that ultimately reduce skeletal muscle O2 delivery and impair exercise tolerance. Dietary nitrate (NO3 (-)) supplementation improves skeletal muscle vascular function and tolerance to exercise. We tested the hypothesis that NO3 (-) supplementation would elevate exercising skeletal muscle blood flow (BF) and vascular conductance (VC) in CHF rats. Myocardial infarction (MI) was induced (coronary artery ligation) in young adult male rats. After 21 days of recovery, rats randomly received 5 days of NO3 (-)-rich beetroot juice (CHF + BR, n = 10) or a placebo (CHF, n = 10). Mean arterial pressure (carotid artery catheter) and skeletal muscle BF (radiolabeled microspheres) were measured during treadmill exercise (20 m/min, 5% grade). CHF-induced dysfunction, as determined by myocardial infarction size (29 ± 3% and 33 ± 4% in CHF and CHF + BR, respectively) and left ventricular end-diastolic pressure (18 ± 2 and 18 ± 2 mmHg in CHF and CHF + BR, respectively), and exercising mean arterial pressure (131 ± 3 and 128 ± 4 mmHg in CHF and CHF + BR, respectively) were not different (P > 0.05) between groups. Total exercising hindlimb skeletal muscle BF (95 ± 5 and 116 ± 9 ml·min(-1)·100 g(-1) in CHF and CHF + BR, respectively) and VC (0.75 ± 0.05 and 0.90 ± 0.05 ml·min(-1)·100 g(-1)·mmHg(-1) in CHF and CHF + BR, respectively) were 22% and 20% greater in BR-supplemented rats, respectively (P < 0.05). During exercise, BF in 9 and VC in 10 hindlimb muscles and muscle portions were significantly greater in the CHF + BR group. These results provide strong evidence that dietary NO3 (-) supplementation improves skeletal muscle vascular function during exercise in rats with CHF and, thus, support the use of BR as a novel therapeutic modality for the treatment of CHF.

Skeletal Muscle Vascular Control During Exercise: Impact of Nitrite Infusion During Nitric Oxide Synthase Inhibition in Healthy Rats.

The nitric oxide synthase (NOS)-independent pathway of nitric oxide (NO) production in which nitrite (NO2 (-)) is reduced to NO may have therapeutic applications for those with cardiovascular diseases in which the NOS pathway is downregulated. We tested the hypothesis that NO2 (-) infusion would reduce mean arterial pressure (MAP) and increase skeletal muscle blood flow (BF) and vascular conductance (VC) during exercise in the face of NOS blockade via L-NAME. Following infusion of L-NAME (10 mg kg(-1), L-NAME), male Sprague-Dawley rats (3-6 months, n = 8) exercised without N(G)-nitro-L arginine methyl ester (L-NAME) and after infusion of sodium NO2 (-) (7 mg kg(-1); L-NAME + NO2 (-)). MAP and hindlimb skeletal muscle BF (radiolabeled microsphere infusions) were measured during submaximal treadmill running (20 m min(-1), 5% grade). Across group comparisons were made with a published control data set (n = 11). Relative to L-NAME, NO2 (-) infusion significantly reduced MAP (P < 0.03). The lower MAP in L-NAME+NO2 (-) was not different from healthy control animals (control: 137 ± 3 L-NAME: 157 ± 7, L-NAME + NO2 (-): 136 ± 5 mm Hg). Also, NO2 (-) infusion significantly increased VC when compared to L-NAME (P < 0.03), ultimately negating any significant differences from control animals (control: 0.78 ± 0.05, L-NAME: 0.57 ± 0.03, L-NAME + NO2 (-); 0.69 ± 0.04 mL min(-1) 100 g(-1) mm Hg(-1)) with no apparent fiber-type preferential effect. Overall, hindlimb BF was decreased significantly by L-NAME; however, in L-NAME + NO2 (-), BF improved to a level not significantly different from healthy controls (control: 108 ± 8, L-NAME: 88 ± 3, L-NAME + NO2 (-): 94 ± 6 mL min(-1) 100 g(-1), P = 0.38 L-NAME vs L-NAME + NO2 (-)). Individuals with diseases that impair NOS activity, and thus vascular function, may benefit from a NO2 (-)-based therapy in which NO bioavailability is elevated in an NOS-independent manner.

Efficacy of indinavir-ritonavir-based regimens in HIV-1-infected patients with prior protease inhibitor failures.

OBJECTIVE: To assess responses to indinavir (IDV)-ritonavir (RTV)-based regimens among HIV-1 infected patients with prior failure of protease inhibitors, and to assess the effects of adherence to therapy and pre-existing genotypic and phenotypic resistance on this response. METHODS: Twenty-eight patients initiating salvage regimens with IDV-RTV (800 mg and 200 mg twice daily, respectively) plus one or more reverse transcriptase inhibitor (RTI) were identified retrospectively. Genotypic and phenotypic susceptibilities to multiple antiretroviral agents were determined on viral samples collected at initiation of the salvage regimens, and adherence to therapy was determined through patient self-reporting. Response to therapy (viral RNA

Radiation improves intratumoral gene therapy for induction of cancer vaccine in murine prostate carcinoma.

Our goal was to convert murine RM-9 prostate carcinoma cells in vivo into antigen-presenting cells capable of presenting endogenous tumor antigens and triggering a potent T-helper cell-mediated immune response essential for the generation of a specific antitumor response. We showed that generating the major histocompatibility complex (MHC) class I+/class II+/Ii- phenotype, within an established subcutaneous RM-9 tumor nodule, led to an effective immune response limiting tumor growth. This phenotype was created by intratumoral injection of plasmid cDNAs coding for interferon gamma, MHC class II transactivator, and an antisense reverse gene construct (RGC) for a segment of the gene for Ii protein (-92,97). While this protocol led to significant suppression of tumor growth, there were no disease-free survivors. Nevertheless, irradiation of the tumor nodule on the day preceding initiation of gene therapy yielded 7 of 16 mice that were disease-free in a long-term follow up of 57 days compared to 1 of 7 mice receiving radiotherapy alone. Mice receiving radiotherapy and gene therapy rejected challenge with parental RM-9 cells and demonstrated specific cytotoxic T-cell activity in their splenocytes but not the mouse cured by radiation alone. These data were reproduced in additional experiments and confirmed that tumor irradiation prior to gene therapy resulted in complete tumor regression and specific tumor immunity in more than 50% of the mice. Increasing the number of plasmid injections after tumor irradiation induced tumor regression in 70% of the mice. Administering radiation before this novel gene therapy approach, that creates an in situ tumor vaccine, holds promise for the treatment of human prostate carcinoma.

Turning tumor cells in situ into T-helper cell-stimulating, MHC class II tumor epitope-presenters: immuno-curing and immuno-consolidation.

Immunological control or cure of tumors depends on initiating a robust T helper cell response to MHC class II epitopes of tumor-associated antigens. T helper cells regulate the potency of cytotoxic T lymphocyte and antibody responses. We have developed a novel approach to stimulate T helper cells by converting tumor cells into MHC class II molecule-positive, antigen presenting cells. Furthermore, using antisense methods, we suppress expression of the Ii protein, that normally blocks the antigenic peptide binding site of MHC class II molecules during synthesis in the endoplasmic reticulum. In such gene-engineered tumor cells, the MHC class II molecules pick up antigenic peptides, which have been transported into the endoplasmic reticulum for binding to MHC class I molecules. All nucleated cells create such "surveys of self" to detect viral or malignant transformation. Our method extends that survey of self to MHC class II endogenous tumor-associated antigens. Simultaneous presentation of tumor antigens by both MHC class I and II generates a robust and long-lasting antitumor immune response. Injecting murine tumors with genes, which induce MHC class II molecules and suppress Ii protein, cures a significant number of animals with renal and prostate tumors. We have developed analogous human gene vectors that are suitable for most patients and cancers, because they are monomorphic and active in all HLA-DR alleles. We review our findings, and analyze remaining issues for preclinical study and the design of clinical trials.

Tumor irradiation followed by intratumoral cytokine gene therapy for murine renal adenocarcinoma.

To circumvent the toxicity caused by systemic injection of cytokines, cytokine cDNA genes encoding the human interleukin IL-2 cDNA (Ad-IL-2) and murine interferon IFN-gamma gene (Ad- IFN-gamma) were inserted into adenoviral vectors. These constructs were used for intratumoral gene therapy of murine renal adenocarcinoma Renca tumors. Treatment with three doses of Ad-IL-2 or Ad- IFN-gamma, given a day apart, was more effective than single-dose gene therapy. We found that tumor irradiation enhanced the therapeutic efficacy of Ad-IL-2 and Ad-IFN-gamma intratumoral gene therapy. Tumor irradiation, administered 1 day prior to three doses of Ad-IL-2 treatment, was more effective than radiation or Ad-IL-2 alone, resulting in tumor growth arrest in all mice, increased survival and a consistent increase in complete tumor regression response rate. Complete responders rejected Renca tumor challenge and demonstrated specific cytotoxic T-cell activity, indicative of specific tumor immunity. The effect of radiation combined with three doses of Ad-IFN-gamma was less pronounced and did not lead to tumor immunity. Histological observations showed that irradiation of the tumor prior to gene therapy increased tumor destruction and inflammatory infiltrates in the tumor nodules. These findings demonstrate that tumor irradiation improves the efficacy of Ad-IL-2 gene therapy for induction of antitumor immune response.

Responsiveness of experimental prostate carcinoma bone tumors to neutron or photon radiation combined with cytokine therapy.

PURPOSE: To improve the outcome of radiotherapy for prostate carcinoma bone tumors, we investigated bone tumor irradiation with photons or neutrons followed by interleukin 2 (IL-2) therapy in a tumor model. METHODS AND MATERIALS: Implantation of PC-3 cells in nude mouse femur cavity induced a bone tumor that progressed to the formation of a palpable tumor, at the hip joint, by Day 20. Established bone tumors were irradiated with photons or neutrons, and a day later, mice were treated with IL-2 therapy for 3 weekly cycles. RESULTS: PC-3 bone tumors responded to radiation with photons or neutrons in a dose-dependent manner. Combination of photon or neutron radiation with IL-2 therapy increased tumor growth delay, compared to that with photons or neutrons alone. Radiation alone or combined with IL-2 significantly increased mouse survival compared to that with IL-2 or no treatment. After combined therapy, a complete inhibition of bone tumor growth was observed in 45% to 50% of the mice. Histologically, the combined therapy resulted in greater tumor destruction associated with fibrosis, new bone formation, and inflammatory infiltrates than that observed with each modality alone. CONCLUSIONS: The efficacy of tumor irradiation with neutrons or photons was enhanced by IL-2 therapy for the treatment of prostate carcinoma bone tumors.

Guardianship for your own good: Improving the well-being of respondents and wards in the USA.

Adult guardianship is a coercive exercise of the state's power over an innocent individual, justified only by: 1) the ward's incapacity; and 2) the need to protect the ward's well-being. The raison d'être of guardianship is to improve the well-being of the incapacitated ward. Studies of actual guardianship proceedings have long indicated serious ongoing concerns with the process. Repeated revisions of statutes have attempted to improve guardianship procedures, with some success. However, relatively little attention has been paid to the actual effect of guardianship on the well-being of respondents and wards, when the system functions as intended. The presumption that guardianship, when not abused, is in the best interests of an incapacitated adult is called into serious question by empirical research into the role of internal locus of control and autonomy on human well-being. Indeed, a wide range of data indicates that guardianship itself can have significant negative effects on the physical and mental well-being of respondents and wards. The guardianship system must be reformed to maximize the therapeutic effects of guardianship and to minimize the unnecessarily anti-therapeutic effects. I examine the effects of guardianship from a therapeutic jurisprudence perspective and propose and analyze modifications that could enhance the therapeutic effects of guardianship.

Mixed external cavity mode dynamics in a semiconductor laser.

We observe experimentally and numerically novel mixed-mode dynamic states of a diode laser subject to two delayed optical feedbacks. These states have been proposed and analyzed within the framework of the Lang-Kobayashi single-feedback model. Such states are combinations of two distinct external cavity modes and can be identified through a characteristic sequence of a Hopf bifurcation followed by a secondary quasi-periodic bifurcation. We present experimental and numerical results that demonstrate such sequences.