全膝关节置换术后的骨溶解：胫骨盘表面的修饰及聚乙烯衬垫灭菌方法对其的影响术 后5至10年的报告

背景：从关节和胫骨假体聚乙烯衬垫后表面转移磨损碎屑，是全膝关节置换术后假体周围骨溶解的主要原因。全膝人工关节假体设计随时问而发生变化，例如对胫骨盘近端表面的粗糙度和聚乙烯衬垫的灭菌方法。我们假设胫骨盘表面抛光和采用空气中γ射线照射之外的其他方法对衬垫灭菌，可降低骨溶解的发生率。方法：从1987年至1998年，我们采用后十字韧带保留型的解剖型组配式全膝人工关节假体系列。对300名患者施行365例全膝关节置换术。术后5至10年，对这些患者的膝关节摄正、侧位X线片。由两位关节置换专家对X线片上的骨溶解状况进行单独评定（骨溶解的界定标准为假体周围存在边缘清晰的非线性松质骨丢失区）。结果：在粗糙表面的胫骨盘的242例膝关节中，使用空气中γ射线照射灭菌的衬垫固定，有34％（82例）骨溶解阳性。用惰性气体中γ射线照射或没有照射的衬垫与抛光表面连接的98例膝关节中，有9％（9例）骨溶解阳性。骨溶解与六项因素相关，这些因素为：一项与患者（男性）相关、一项与胫骨盘（近端表面抛光）相关、三项与聚乙烯衬垫（加工的原材料、灭菌方法及存放时间）相关及一项与手术技术（股骨假体与胫骨假体间的过伸）相关。结论：在这类假体设计中，胫骨盘近端表面采用抛光及衬垫采用更为先进的灭菌方法（不用空气中γ射线照射灭菌）能显著减少骨溶解的发生率，但不能避免骨溶解。     

Matrix Metalloproteinase-2 and Tissue Inhibitor of Metalloproteinase-1 in the Retinal Pigment Epithelium and Interphotoreceptor Matrix: Vectorial Secretion and Regulation

Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) play an essential role in both normal and pathological extracellular matrix degradation, and a TIMP has been associated with at least one type of retinal degeneration. We have studied expression of MMP-2 and TIMP-1 by zymography, immunocytochemistry, and immunoblotting in the retinal pigment epithelium (RPE) from normal, aged and diseased retinas. MMPs and TIMPs were found in the rat RPE, interphotoreceptor matrix (IPM), and in media conditioned by human and rat RPE in culture. In other polarized cells, MMPs and TIMP-2 are secreted vectorially towards the basal lamina. In the RPE, however, MMP-2 and TIMP-1 were secreted preferentially from the apical surface, the surface bordering the IPM. These findings provide new evidence that MMPs and TIMPs could play a role in the turnover of IPM components.Cell homogenates and conditioned media from RPE isolated from mutant Royal College of Surgeons (RCS) rats with inherited retinal dystrophy had similar amounts of MMP-2 and TIMP-1 as those from congenic control rats. The secretion of MMP-2 and TIMP-1 from RPE cell cultures isolated from young and aged human donors varied widely. However, with increasing cell passage number, secretion of MMPs and TIMPs from human RPE increased dramatically. Also, growing human RPE on bovine corneal endothelial cell-generated extracellular matrix instead of plastic reduced the secretion of both MMPs and TIMPs. These data suggest that the integrity of Bruch's membrane may serve to regulate RPE functions in MMP and TIMP secretion and that extracellular matrices contain signals that regulate MMP and TIMP synthesis and/or secretion by the RPE.     

Increased Immune and Inflammatory Responses to Dust Mite Antigen in Rats Exposed to 5 ppm NO2

Immune hypersensitivity to house dust mite antigen (HDM) isa frequent cause of respiratory allergy. The objective of thisstudy was to determine whether exposure to NO₂, a common indoorair pollutant, modulates immune responses to HDM and influencesimmune-mediated lung disease. Brown Norway rats were immunizedip with 100 µg semipurified antigen and Bordetella pertussisadjuvant and challenged 2 weeks later with an intratrachealinjection of 50 µg of a crude antigen preparation. Exposureto 5 ppm NO₂ for 3 hr after both immunization and challengeprocedures resulted in significantly higher levels of antigen-specificserum IgE, local IgA, IgG, and IgE antibody than air controls,and increased numbers of inflammatory cells in the lungs. Lymphocyteresponsiveness to antigen in the spleen and MLN was also significantlyhigher in NO₂-exposed animals. These data show that exposureto a common air pollutant can upregulate specific immune responsesand subsequent immune-mediated pulmonary inflammation.     

Developmental Toxicity of L-Selenomethionine in Macaca fascicularis

Forty pregnant long-tailed macaques were dosed via nasogastricintubation with 0, 25, 150, or 300 µg/kg of L-selenomethionine(Se) daily during organogenesis [Gestational Day (GD) 20–50].Clinical examination of the dams, maternal body weights, sonographicevaluations, clinical chemistry screens, and measures of serumprogesterone and urinary estrone conjugates were used as indicatorsof maternal and fetal status in all animals. The pregnanciesof two to three dams from each dose group were followed untilterm ({small tilde}GD 165); the remainder (N = 7/dose group)were scheduled for hysterotomy on GD 100 ± 2. A standardteratologic evaluation was performed including visceral andskeletal examinations. Fetal liver, kidney, skin, and smooth,cardiac, and skeletal muscles were examined by light microscopy;heart muscle was also evaluated by transmission electron microscopy.Neonates delivered at term remained with the dams and were removedperiodically for morphometric, neurologic, behavorial, and ophthalmologicassessments on Days 1, 8, 15, 22, and 30 of age. Dose-dependentmaternal toxicity as evidenced by anorexia, vomiting, and asignificant reduction in body weight increased with increasingduration of Se exposure. One growth-retarded fetus was recoveredon GD 131 from a compromised dam exposed to 25 /ig/kg-day; oneearly embryonic death (GD 35) and two fetal deaths [GD 68 (followedby maternal death) and GD 123] occurred among animals dosedwith 300 µg/kg-day. Pregnancy loss among treated animalswas not significantly different from concurrent or historicalcontrols. No statistically significant treatment-related effectswere observed at necropsy on GD 100 ± 2. One infant exposedto 150 Mg/kg-day prenatally exhibited a unilateral corticalcataract, which may have been a spontaneous occurrence. Thelimited developmental effects observed and reported teratogenesisin nonmammalian species suggest that comparative pharmacokineticstudies are required before the full public health significanceof elevated Se is understood.     

Separation of the Toxic and Glutathione-Enhancing Effects of the Naturally Occuring Nitrile, Cyanohydroxybutene

Cyanohydroxybutene (CHB) is reported to be hepatotoxic in maleFischer 344 rats at an oral dose of 300 mg/kg and, while nolonger hepatotoxic, pancreatotoxic at 200 mg/kg. In addition,the 200 mg/kg dose causes a persistent elevation in hepaticand pancreatic glutathione (GSH). This study was conducted tode termine if smaller doses of CHB could cause GSH elevationin the absence of toxicity. A single oral dose of 100 mg/kgor multiple lower doses (50 mg/kg daily for 3 days or 30 mg/kgfor 6 days) caused a significant and persistent increase inpancreatic GSH, although hepatic levels were unchanged. Tenmilligrams per kilogram, even daily for 24 days, was withouteffect on hepatic or pancreatic GSH. Neither a single oral doseof 100 mg/kg nor multiple lower doses were associated with toxicity.However, when either 100 or 50 mg/kg were administered intravenously,pancreatic apoptosis was observed. In animals dosed with 100mg/kg iv, mixed histiocytic and suppurative inflammation andfrank pancreatic necrosis also developed and were associatedwith elevated plasma lipase and amylase. The animals receivingCHB intravenously also exhibited elevated GSH levels in bothpancreas and liver. This study shows that oral doses between30 and 100 mg CHB/kg can be used to elevate GSH levels withoutany pancreatotoxicity. However, a single 50 mg CHB/kg dose givenintravenously causes apoptosis, while 100 mg/kg causes severepancreatotoxicity with necrosis.     

What Can Health Communication Science Offer for ACA Implementation? Five Evidence-Informed Strategies for Expanding Medicaid Enrollment

Context: Implementing the Affordable Care Act (ACA) in 2014 will require effective enrollment and outreach efforts to previously uninsured individuals now eligible for coverage.Methods: From 1996 to 2013, the Health Communication Research Laboratory conducted more than 40 original studies with more than 30,000 participants to learn how to improve the reach to and effectiveness of health information for low-income and racial/ethnic minority populations. We synthesized the findings from this body of research and used them to inform current challenges in implementing the ACA.Findings: We found empirical support for 5 recommendations regarding partnerships, outreach, messages and messengers, life priorities of low-income individuals and families, and the information environment. We translated these into 12 action steps.Conclusions: Health communication science can inform the development and execution of strategies to increase the public''s understanding of the ACA and to support the enrollment of eligible individuals into Medicaid or the Health Insurance Marketplace.     

Differential Effect of Adenosine on Anterograde and Retrograde Fast Pathway Conduction in Patients with Atrioventricular Nodal Reentrant Tachycardia

Adenosine and Retrograde Fast Pathway Conduction . Introduction : Several studies have shown that the fast pathway is more responsive to adenosine than the slow pathway in patients with AV nodal reentrant tachycardia. Little information is available regarding the effect of adenosine on anterograde and retrograde fast pathway conduction.
Methods and Results : The effects of adenosine on anterograde and retrograde fast pathway conduction were evaluated in 116 patients (mean age 47 ± 16 years) with typical AV nodal reentrant tachycardia. Each patient received 12 mg of adenosine during ventricular pacing at a cycle length 20 msec longer than the fast pathway VA block cycle length and during sinus rhythm or atrial pacing at 20 msec longer than the fast pathway AV block cycle length. Anterograde block occurred in 98% of patients compared with retrograde fast pathway block in 62% of patients ( P < 0.001). Unresponsiveness of the retrograde fast pathway to adenosine was associated with a shorter AV block cycle length (374 ± 78 vs 333 ± 74 msec, P < 0.01), a shorter VA block cycle length (383 ± 121 vs 307 ± 49 msec, P < 0.001), and a shorter VA interval during tachycardia (53 ± 23 vs 41 ± 17 msec, P < 0.01).
Conclusion : Although anterograde fast pathway conduction is almost always blocked by 12 mg of adenosine, retrograde fast pathway conduction is not blocked by adenosine in 38% of patients with typical AV nodal reentrant tachycardia. This indicates that the anterograde and retrograde fast pathways may be anatomically and/or functionally distinct. Unresponsiveness of VA conduction to adenosine is not a reliable indicator of an accessory pathway.