Unusual presentation in Haiti of a recurrent giant cell tumor of bone affecting the distal radius: A case report.

INTRODUCTION: Giant cell tumor of bone (GCTB) is a benign-aggressive tumor that has a high-rate of recurrence with curettage resection alone. Patients with GCTB in underserved regions of the world can have progression of the tumor with significant disability due to a lack of specialty care. We present a case of an en bloc resection of an aggressive, recurrent GCTB of the radius with excellent function and no evidence of tumor recurrence two years after surgery. PRESENTATION OF CASE: A 22-year-old right-hand dominant female in Haiti developed an aggressive recurrence of a giant cell tumor of bone (GCTB) of the distal radius. Treatment consisted of en bloc resection of the distal radius with the proximal row of the carpus and centralization of the ulna. At two-year follow-up, the patient maintained good functional capacity with no clinical or radiological evidence of recurrence. DISCUSSION: GCTB can cause significant destruction of the bone and articular surface if not treated adequately. Treatment options should be considered carefully in underserved regions of the world based on the resources available. This case exemplifies that complex limb-salvage surgery is possible when coordination of care between international and local surgeons is provided with an emphasis on continuity of care post-operatively. CONCLUSION: En bloc resection with centralization of the ulna remains a viable technique to address aggressive GCTB of the distal radius and can be appropriate in resource-limited settings.

Preparation, characterization and in vitro response of bioactive coatings on polyether ether ketone.

Polyether ether ketone (PEEK) is a highly heat-resistant thermoplastic with excellent strength and elastic modulus similar to human bone, making it an attractive material for orthopedic implants. However, the hydrophobic surface of PEEK implants induces fibrous encapsulation which is unfavorable for stable implant anchorage. In this study, PEEK was coated via ion-beam-assisted deposition (IBAD) using a two-layer design of yttria-stabilized zirconia (YSZ) as a heat-protection layer, and hydroxyapatite (HA) as a top layer to improve osseointegration. Microstructural analysis of the coatings showed a dense, uniform columnar grain structure in the YSZ layer and no delamination from the substrate. The HA layer was found to be amorphous and free of porosities in its as-deposited state. Subsequent heat treatment via microwave energy followed by autoclaving crystallized the HA layer, confirmed by SEM and XRD analysis. An in vitro study using MC3T3 preosteoblast cells showed improved bioactivity in heat-treated sample groups. Cell proliferation, differentiation, and mineralization were analyzed by MTT assay and DNA content, osteocalcin expression, and Alizarin Red S (AR-S) content, respectively. Initial cell growth was increased, and osteogenic maturation and mineralization were accelerated most on coatings that underwent a combined microwave and autoclave heat treatment process as compared to uncoated PEEK and amorphous HA surfaces. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 560-567, 2017.

Deposition, Heat Treatment And Characterization of Two Layer Bioactive Coatings on Cylindrical PEEK.

Polyether ether ketone (PEEK) rods were coated via ion beam asssited deposition (IBAD) at room temperature. The coating consists of a two-layer design of yttria-stabilized zirconia (YSZ) as a heat-protection layer, and hydroxyapatite (HA) as a top layer to increase bioactivity. A rotating substrate holder was designed to deposit an even coating on the cylindrical surface of PEEK rods; the uniformity is verified by cross-sectional measurements using scanning electron microscopy (SEM). Deposition is followed by heat treatment of the coating using microwave annealing and autoclaving. Transmission electron microscopy (TEM) showed a dense, uniform columnar grain structure in the YSZ layer that is well bonded to the PEEK substrate, while the calcium phosphate layer was amorphous and pore-free in its as-deposited state. Subsequent heat treatment via microwave energy introduced HA crystallization in the calcium phosphate layer and additional autoclaving further expanded the crystallization of the HA layer. Chemical composition evaluation of the coating indicated the Ca/P ratios of the HA layer to be near that of stoichiometric HA, with minor variations through the HA layer thickness. The adhesion strength of as-deposited HA/YSZ coatings on smooth, polished PEEK surfaces was mostly unaffected by microwave heat treatment, but decreased with additional autoclave treatment. Increasing surface roughness showed improvement of bond strength.

Hydroxyapatite coating on PEEK implants: Biomechanical and histological study in a rabbit model.

A bioactive two-layer coating consisting of hydroxyapatite (HA) and yttria-stabilized zirconia (YSZ) was investigated on cylindrical polyetheretherketone (PEEK) implants using ion beam assisted deposition (IBAD). Post-deposition heat treatments via variable frequency microwave annealing with and without subsequent autoclaving were used to crystallize the as-deposited amorphous HA layer. Microstructural analysis, performed by TEM and EDS, showed that these methods were capable of crystallizing HA coating on PEEK. The in vivo response to cylindrical PEEK samples with and without coating was studied by implanting uncoated PEEK and coated PEEK implants in the lateral femoral condyle of 18 rabbits. Animals were studied in two groups of 9 for observation at 6 or 18weeks post surgery. Micro-CT analysis, histology, and mechanical pull-out tests were performed to determine the effect of the coating on osseointegration. The heat-treated HA/YSZ coatings showed improved implant fixation as well as higher bone regeneration and bone-implant contact area compared to uncoated PEEK. The study offers a novel method to coat PEEK implants with improved osseointegration.

Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD.

BACKGROUND AND OBJECTIVES: Roxadustat (FG-4592), an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis, regulates iron metabolism, and reduces hepcidin, was evaluated in this phase 2b study for safety, efficacy, optimal dose, and dose frequency in patients with nondialysis CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The 145 patients with nondialysis CKD and hemoglobin ≤10.5 g/dl were randomized into one of six cohorts of approximately 24 patients each with varying roxadustat starting doses (tiered weight and fixed amounts) and frequencies (two and three times weekly) followed by hemoglobin maintenance with roxadustat one to three times weekly. Treatment duration was 16 or 24 weeks. Intravenous iron was prohibited. The primary end point was the proportion of patients achieving hemoglobin increase of ≥1.0 g/dl from baseline and hemoglobin of ≥11.0 g/dl by week 17 (16 weeks of treatment). Secondary analyses included mean hemoglobin change from baseline, iron utilization, and serum lipids. Safety was evaluated by frequency/severity of adverse events. RESULTS: Of the 145 patients enrolled, 143 were evaluable for efficacy. Overall, 92% of patients achieved hemoglobin response. Higher compared with lower starting doses led to earlier achievement of hemoglobin response. Roxadustat-induced hemoglobin increases were independent of baseline C-reactive protein levels and iron repletion status. Overall, over the first 16 treatment weeks, hepcidin levels decreased by 16.9% (P=0.004), reticulocyte hemoglobin content was maintained, and hemoglobin increased by a mean (±SD) of 1.83 (±0.09) g/dl (P<0.001). Overall mean total cholesterol level was reduced by a mean (±SD) of 26 (±30) mg/dl (P<0.001) after 8 weeks of therapy, independent of the use of statins or other lipid-lowering agents. No drug-related serious adverse events were reported. CONCLUSIONS: In patients with nondialysis CKD who were anemic, various starting dose regimens of roxadustat were well tolerated and achieved anemia correction with reduced serum hepcidin levels. After anemia correction, hemoglobin was maintained by roxadustat at various dose frequencies without intravenous iron supplementation.

Fabrication of functional nanowire devices on unconventional substrates using strain-release assembly.

We report three representative nanowire (NW) devices for applications in stretchable electronics, strain sensing, and optical sensing. Fabrication of such devices is based on a recently developed strain-release assembly method. NWs are first aligned transversely on an elastomeric substrate using the strain-release assembly. Constant resistance is achieved in silicon (Si) NW devices stretched up to ~40% of axial strain, highlighting a new concept of transverse buckling. Combining the NW assembly with transfer printing extends suitable device substrates beyond elastomers to other unconventional materials (e.g., flexible and transparent materials). Following this combined process, flexible SiNW strain sensors are fabricated on plastics capable of sensing up to 1.6% bending strain and gauge factors >1000; flexible zinc oxide NW ultraviolet sensors are demonstrated with quick recovery (~2 s) and excellent repeatability on plastics. Our results show promise for the strain-release assembly as a simple and cost-effective process to fabricate NW devices on unconventional substrates.

Strain-release assembly of nanowires on stretchable substrates.

A simple yet effective method for assembly of highly aligned nanowires (NWs) on stretchable substrates is reported. In this method, NWs were first transferred to a strained stretchable substrate. After the strain was released, the NWs aligned in the transverse direction and the area coverage of the NWs on the substrate increased. This method can be applied to any NWs deposited on a stretchable film and can be repeated multiple times to increase the alignment and density of the NWs. For silver (Ag) and silicon (Si) NWs on poly(dimethylsiloxane) (PDMS) substrates, the probability of NW alignment increased from 29% to 90% for Ag NWs, and from 25% to 88% for Si NWs after two assembly steps; the density increased by 60% and 75% for the Ag and Si NWs, respectively. The large-strain elasticity of the substrate and the static friction between the NWs and the substrate play key roles in this assembly method. We find that a model that takes into account the volume incompressibility of PDMS reliably predicts the degree of NW alignment and NW density. The utility of this assembly method was demonstrated by fabricating a strain sensor array composed of aligned Si NWs on a PDMS substrate, with a device yield of 95%.

Down-regulation of neutral sphingomyelinase in androgen-dependent smooth muscle.

BACKGROUND: During puberty, proliferation of guinea pig seminal vesicle smooth muscle (SVM) is mediated by androgen-induced basal release of norepinephrine (NE), signaling through the post-junctional alpha1-adrenoceptor. In the adult, the SVM is terminally differentiated, such that cell number is androgen resistant. Sphingomyelinase activation generates second messenger ceramides, which in vascular smooth muscle have been reported to counter the alpha1-adrenoceptor-mediated contractile response and activate apoptosis. Accordingly, we hypothesized that SVM sphingomyelinase down-regulation by androgen may facilitate NE-induced proliferation and subsequent transition to the terminally differentiated state of the adult. MATERIALS AND METHODS: Pre-pubertal and adult guinea pigs were orchiectomized and treated+/-dihydrotestosterone (DHT). SVM was harvested free of epithelium, frozen, and stored for enzymatic analyses. Using radioactive sphingomyelin substrate, optimized reaction conditions for both neutral and acidic sphingomyelinase were established and used to assay the enzymes. RESULTS: Although acidic sphingomyelinase was stimulated by androgen in both the proliferative and amitotic phases of smooth muscle development, neutral sphingomyelinase was irreversibly reduced 35% at the time of DHT-induced proliferation. CONCLUSIONS: Decreased concentrations of a second messenger ceramide attenuate apoptosis and increase sensitivity to alpha(1)-adrenoceptor-mediated mitogenic signaling. Therefore, DHT-dependent suppression of neutral sphingomyelinase activity may reduce ceramide concentrations and facilitate NE-dependent smooth muscle growth.

N-acetylcysteine in the prevention of radiocontrast-induced nephropathy.

N-acetylcysteine is a remarkably active agent shown to be useful in a variety of clinical settings. The drug has actions relevant to radiocontrast-induced nephropathy (RCIN) that include vasodilatation, enhancement of renal medullary blood flow, and antioxidant properties. The drug's pharmacokinetics are remarkable for almost complete first pass metabolism after oral administration, resulting in no free drug reaching the circulation. After intravenous administration, extensive reaction with tissue and plasma proteins greatly limits the amount of circulating free drug. Given the difficulty achieving free drug in the systemic circulation, it is highly likely that the drug works via its metabolites. The primary mechanism may be through L-cysteine as a cellular source for glutathione production. Clinical studies of N-acetylcysteine in the prevention of RCIN have yielded highly mixed results; five were dramatically positive, and eight others had no demonstrable efficacy at all. The following will review the individual studies, attempt to reconcile the divergent results, and propose future research needs.

Screening for prostate cancer: a survey of New Zealand general practitioners.

AIM: To determine the views of general practitioners (GPs) in relation to screening for prostate cancer. METHODS: A questionnaire was sent to a random, national sample of 575 New Zealand general practitioners, stratified to include equal numbers of rural and urban GPs. RESULTS: The response rate to the questionnaire was 66.3%. A 55-year-old man presenting for an annual checkup or requesting advice about screening for prostate cancer would be given a prostate specific antigen (PSA) test by 74% of GPs. If the same man had a family history of prostate or breast cancer, 93% of GPs would carry out a PSA test. Most GPs overestimated the effectiveness of screening tests for prostate cancer and were uncertain about the importance of associated risk factors. Some form of screening for prostate cancer is performed by 97.5% of GPs, and 50% of GPs support a national population-screening programme. 'Watchful waiting' is considered to be a reasonable treatment option for a man with localised prostate cancer and less than 10 years' life expectancy by 40% of GPs compared with 2% for a man with more than 10 years' life expectancy. CONCLUSIONS: Most GPs undertake screening for prostate cancer, even though there is no evidence that screening improves life expectancy and quality of life.

Treating interdialytic hyperkalemia with fludrocortisone.

Hyperkalemia is a frequent and dangerous problem in dialysis patients. Many factors contribute to potentially life-threatening potassium elevation and most remedies used to treat hyperkalemia are handicapped by the consequences of the separate pools of intra- and extracellular potassium. Besides the kidney, the colon has the ability to excrete potassium, which can help lower total body potassium. Several prior authors have addressed the colon's ability to up-regulate potassium secretion, including the effect of aldosterone on fecal potassium content. Potentially dangerous intradialytic maneuvers to lower potassium levels may be avoidable with the use of the mineralocorticoid agonist fludrocortisone.

A randomized controlled trial of N-acetylcysteine to prevent contrast nephropathy in cardiac angiography.

BACKGROUND: Contrast nephropathy (CN) is a common cause of renal dysfunction after cardiac angiography. Recently, N-acetylcysteine (NAC) has been found to reduce the risk of CN after CT imaging with contrast enhancement. The purpose of the current study was to evaluate the efficacy of NAC for the prevention of CN in the setting of cardiac angiography. METHODS: Eligible patients were those undergoing cardiac angiography with serum creatinine>1.7 mg/dL. Patients were randomized to one of two groups: Group 1, IV hydration and NAC, 1200 mg one hour before angiography, and a second dose 3 hours after; Group 2, IV hydration and placebo. CN was defined as an increase of 0.5 mg/dL in serum creatinine. RESULTS: Seventy-nine patients completed the study. There were no significant differences between the groups in baseline characteristics, duration of angiography, mean volume of dye infused or mean IV hydration. Contrast nephropathy developed in 24.0% of subjects, 26.3% NAC, and 22.0% placebo (P = NS). Among subjects with diabetes mellitus, there was no significant difference in the rate of CN between the groups (42.1% NAC, 27.8% placebo; P = 0.09). The independent predictors of CN risk were diabetes mellitus and preexisting chronic renal insufficiency. CONCLUSIONS: NAC was not effective for the prevention of CN after cardiac angiography.

The Ottawa ankle rules for the use of diagnostic X-ray in after hours medical centres in New Zealand.

AIMS: The aims of this study were to measure baseline use of Ottawa ankle rules (OAR), validate the OAR and, if appropriate, explore the impact of implementing the Rules on X-ray rates in a primary care, after hours medical centre setting. METHODS: General practitioners (GPs) were surveyed to find their awareness of ankle injury guidelines. Data concerning diagnosis and X-ray utilisation were collected prospectively for patients presenting with ankle injuries to two after hours medical centres. The OAR were applied retrospectively, and the sensitivity and specificity of the OAR were compared with GPs clinical judgement in ordering X-rays. The outcome measures were X-ray utilisation and diagnosis of fracture. RESULTS: Awareness of the OAR was low. The sensitivity of the OAR for diagnosis of fractures was 100% (95% CI: 75.3 - 100) and the specificity was 47% (95% CI: 40.5 - 54.5). The sensitivity of GPs clinical judgement was 100% (95% CI: 75.3 - 100) and the specificity was 37% (95% CI: 30.2 - 44.2). Implementing the OAR would reduce X-ray utilisation by 16% (95% CI: approx 10.8 - 21.3). CONCLUSIONS: The OAR are valid in a New Zealand primary care setting. Further implementation of the rules would result in some reduction of X-rays ordered for ankle injuries, but less than the reduction found in previous studies.

Androgen induced norepinephrine release from postganglionic neurons mediates accessory sex organ smooth muscle proliferation.

PURPOSE: Guinea pig seminal vesicle smooth muscle displays an initial androgen dependent, proliferative response during early puberty, followed by progression to an androgen resistant, amitotic state in adults. We determined the role of norepinephrine in androgen dependent pubertal proliferation and in the subsequent terminal differentiation of adult seminal vesicle smooth muscle. MATERIALS AND METHODS: Guinea pig seminal vesicle provided a suitable model since its unique anatomy allowed clean harvest of smooth muscle without epithelium. Norepinephrine release from postganglionic adrenergic nerve terminals in seminal vesicle smooth muscle was measured using several techniques. Prazosin sensitive electrical field stimulation of contractile responses qualitatively assessed norepinephrine release. Norepinephrine release was quantified directly in vitro from incubated seminal vesicle smooth muscle minces and indirectly ex vivo from intact tissue using the endogenous seminal vesicle smooth muscle concentration ratio of 3,4-dihydroxyphenylglycol-to-norepinephrine (Sigma Chemical Co., St. Louis, Missouri). Norepinephrine mediated seminal vesicle smooth muscle proliferation was assessed by the time course relationships of androgen induced norepinephrine release, protein kinase C activation-depletion and increases in total DNA, the impact of in vivo reserpine induced norepinephrine depletion on protein kinase C activation-depletion and the mitogenic response, and the alpha1-adrenoceptor mediated mitogenic response in cultured seminal vesicle smooth muscle cells. RESULTS: In prepubertal smooth muscle androgen induced norepinephrine release from postganglionic neurons. The effect was independent of preganglionic innervation. Increased norepinephrine release was concurrent with the onset of androgen induced protein kinase C activation-depletion and cellular proliferation. In vivo norepinephrine depletion to 1% or less of control values by chronic reserpine treatment selectively antagonized the androgen induced increases in smooth muscle DNA and protein kinase C down-regulation. Norepinephrine depletion by reserpine neither induced apoptosis nor altered cell number. Cell culture experiments demonstrated that alpha1-adrenoceptors mediated the proliferative response to norepinephrine. Together these findings indicate that increased norepinephrine release has an obligatory role in androgen dependent muscle cell proliferation during puberty. Terminally differentiated smooth muscle in adults was characterized by androgen resistance to elevated norepinephrine release and protein kinase C activation. CONCLUSIONS: Androgen induced norepinephrine release from postganglionic neurons in seminal vesicle smooth muscle mediated the proliferative response that occurs in early pubertal development. Normal uncoupling of elevated norepinephrine release and protein kinase C activation-depletion may represent a key event in the normal terminal differentiation of accessory sex organ smooth muscle in adults.