The Use of General Anesthesia in Revision Joint Arthroplasty.

BACKGROUND: Several studies have suggested that spinal anesthesia gives superior outcomes for primary total joint arthroplasty (TJA). However, there is a lack of available data regarding contemporary general anesthesia (GA) approaches for revision TJA utilized at high-volume joint arthroplasty centers. METHODS: We retrospectively reviewed a series of 850 consecutive revision TJAs (405 revision total hip arthroplasties and 445 revision total knee arthroplasties) performed over 4 years at a single institution that uses a contemporary GA protocol and reported on the lengths of stay, early recovery rates, perioperative complications, and readmissions. RESULTS: Of the revision arthroplasty patients, 74.4% (632 of 850) were discharged on postoperative day 1 and 68.5% (582 of 850) of subjects were able to participate in physical therapy on the day of surgery. Only 6 patients (0.7%) required an intensive care unit stay postoperatively. The 90-day readmission rate over this time was 11.3% (n = 96), while the reoperation rate was 9.4% (n = 80). CONCLUSIONS: While neuraxial anesthesia is commonly preferred when performing revision TJA, we have demonstrated favorable safety and efficiency metrics utilizing GA in conjunction with contemporary enhanced recovery pathways. Our data support the notion that modern GA techniques can be successfully used in revision TJA.

Total Knee Periprosthetic Joint Infection in the Setting of Hematologic Malignancy: Considerations for Management.

Patients with malignancy are often profoundly immunocompromised due to chemotherapy, placing them at potential increased risk for periprosthetic joint infection (PJI). However, there is little information regarding PJI management in these patients. We describe 4 patients with a history of primary total knee arthroplasty followed by diagnosis of multiple myeloma or Waldenström macroglobulinemia who received chemotherapy within 4 months prior to PJI. The Musculoskeletal Infection Society major and minor criteria and either debridement, antibiotics, and implant retention or a 2-stage approach appear to be effective for acute or chronic PJI, respectively. We recommend an anticoagulant be administered concomitantly with antineoplastics that significantly increase deep vein thrombosis risk, and we recommend long-term oral suppressive antibiotics postoperatively, especially if chemotherapy will be resumed. Additional studies are needed to investigate risks and benefits of PJI prophylaxis during chemotherapy and long-term suppressive antibiotics after PJI treatment.

Rapid Recovery After Total Joint Arthroplasty Using General Anesthesia.

BACKGROUND: Multiple papers have purported the superiority of spinal anesthesia used in total joint arthroplasty (TJA). However, there is a paucity of data available for modern general anesthesia (GA) regimens used at high-volume joint replacement centers. METHODS: We retrospectively reviewed a series of 1527 consecutive primary TJAs (644 total hip arthroplasties and 883 total knee arthroplasties) performed over a 3-year span at a single institution that uses a contemporary GA protocol and report on the length of stay, early recovery rates, perioperative complications, and readmissions. RESULTS: From the elective TJAs performed using a modern GA protocol, 96.3% (n = 1471) of patients discharged on postoperative day 1, and 97.2% (n = 1482) of subjects were able to participate with physical therapy on the day of surgery. Only 6 patients (0.4%) required an intensive care unit stay postoperatively. The 90-day readmission rate over this time was 2.4% (n = 36), while the reoperation rate was 1.3% (n = 20). DISCUSSION: Neuraxial anesthesia for TJA is commonly preferred in high-volume institutions utilizing contemporary enhanced recovery pathways. Our data support the notion that the utilization of modern GA techniques that limit narcotics and certain inhalants can be successfully used in short-stay primary total joint arthroplasty. LEVEL OF EVIDENCE: IV- Case series.

miR-675 mediates downregulation of Twist1 and Rb in AFP-secreting hepatocellular carcinoma.

BACKGROUND: Alpha-fetoprotein (AFP)-secreting hepatocellular carcinomas (HCC) represent a genetically distinct subset of tumors often associated with a worse prognosis. However, the molecular mechanisms that underlie these phenotypic differences remain poorly understood. METHODS: HCC tumor samples from 27 patients were profiled using the Affymetrix 133 Plus 2.0 GeneChips. GeneGO Metacore software was used to identify altered biologic pathways. Expression validation was confirmed by RT-PCR. Manipulation of miR-675 by overexpression and antagomir-mediated knockdown was carried out with subsequent evaluation of effects on cell behavior by cell cycle, proliferation, invasion, and growth in soft agar assays. RESULTS: We identified a strong relationship between primary tumor H19 gene expression and elevated serum AFP. H19 has recently been identified to encode microRNA-675 (miR-675), and we confirmed the relationship in an independent sample of patients. Pathway analyses of the effect of miR-675 overexpression in hepatoma cells revealed a predominant upregulation of cell adhesion and cell cycle initiation pathways. We have demonstrated that miR-675 mediates increases in proliferation and an accumulation of cells with tetraploid DNA content associated with a repression of Rb. We also demonstrated that overexpression of miR-675 alters cellular morphology, reduces invasive potential, and increases anchorage-independent growth capacity. These findings are consistent with a mesenchymal-to-epithelial transition, associated with a reduction in the expression of the key EMT mediator, Twist1. CONCLUSIONS: Expression of the miR-675 in hepatocellular carcinoma links a dramatic upregulation of proliferative and growth capacity with inhibition of motility in HCC cells.

Passive coherent beam combining of quantum-cascade lasers with a Dammann grating.

An external cavity using a binary phase grating has been developed to achieve coherent combining of five quantum-cascade lasers emitting at 4.65 µm. The grating phase profile is designed to combine five beams of equal intensities into a single beam with a good efficiency (~75%). The performances of this cavity concerning output power, stability, combining efficiency and beam quality are detailed. We report a CW combining efficiency of 66% corresponding to an output power of ~0.5 W with a good beam quality (M(2)<1.6).

Stakeholder analysis for health research: case studies from low- and middle-income countries.

OBJECTIVES: Future Health Systems: Innovations for Equity (FHS) is working in six partner countries in Asia and Africa, focusing on strengthening the research-policy interface in relation to specific health system research projects. These projects present an opportunity to study the influence of stakeholders on research and policy processes. STUDY DESIGN: Qualitative stakeholder analysis. METHODS: Stakeholder analysis was conducted in each FHS country using a structured approach. A cross-country evaluation was performed concentrating on six key areas: chosen research topic; type of intervention considered; inclusion/exclusion of stakeholder groups; general stakeholder considerations; power level, power type and agreement level of stakeholders; and classification of and approaches to identified stakeholders. RESULTS: All six countries identified a range of stakeholders but each country had a different focus. Four of the six countries identified stakeholders in addition to the guidelines, while some of the stakeholder categories were not identified by countries. The mean power level of identified stakeholders was between 3.4 and 4.5 (1=very low; 5=very high). The percentage of classified stakeholders that were either drivers or supporters ranged from 60% to 91%. CONCLUSION: Three important common areas emerge when examining the execution of the FHS country stakeholder analyses: clarity on the purpose of the analyses; value of internal vs external analysts; and the role of primary vs secondary analyses. This paper adds to the global body of knowledge on the utilization of stakeholder analysis to strengthen the research-policy interface in the developing world.

Menin interacts with IQGAP1 to enhance intercellular adhesion of beta-cells.

Multiple endocrine neoplasia type 1 (MEN1) is a dominantly inherited tumor syndrome that results from the mutation of the MEN1 gene that encodes protein menin. Stable overexpression of MEN1 has been shown to partially suppress the Ras-mediated morphological changes of fibroblast cells. Little is known about the molecular mechanisms by which menin decreases the oncogenic effects on cell morphology and other phenotypes. Here we showed that ectopic expression of menin in pretumor beta-cells increases islet cell adhesion and reduces cell migration. Our further studies revealed that menin interacts with the scaffold protein, IQ motif containing GTPase activating protein 1 (IQGAP1), reduces GTP-Rac1 interaction with IQGAP1 but increases epithelial cadherin (E-cadherin)/beta-catenin interaction with IQGAP1. Consistent with an essential role for menin in regulating beta-cell adhesion in vivo, accumulations of beta-catenin and E-cadherin are reduced at cell junctions in the islets from Men1-excised mice. Together, these results define a novel menin-IQGAP1 pathway that controls cell migration and cell-cell adhesion in endocrine cells.

Equity in health in unequal societies: meeting health needs in contexts of social change.

The paper explores the implications for health policy of the segmentation of society into social groups with very different levels of income and wealth. Discourses on equity in health are presently dominated by a debate between 'European' and 'American' models of health delivery. This has led to a focus on ideal outcomes rather than practical options for organising and financing health services in poor countries undergoing rapid change. The paper argues for a more explicit acknowledgement of the dynamic character of health development and the political nature of the negotiations regarding the use of government powers. Unregulated markets for health care are neither equitable nor efficient. Government must play a role in supporting the organisation of health services used by different social groups. Countries with low levels of inequality may be able to provide universal access to relatively sophisticated health services. Otherwise, governments need to operate within a segmented system. This means the negotiation of strategies to reduce the burden of sickness and premature death, whilst meeting the needs of different social groups. The discussion is organised in terms of the powers of government to require individuals and institutions to transfer resources for social uses, enforce regulations and generate and disseminate information. The paper concludes that governments committed to equity-enhancing health development need to increase their capacity to facilitate coalition building and manage change. It proposes an international public health legal framework that might include a definition of minimum standards for certain health services, to be underwritten by national and international financial commitments.

The UNC-104/KIF1 family of kinesins.

Most UNC-104/KIF1 kinesins are monomeric motors that transport membrane-bounded organelles toward the plus ends of microtubules. Recent evidence implies that KIF1A, a synaptic vesicle motor, moves processively. This surprising behavior for a monomeric motor depends upon a lysine-rich loop in KIF1A that binds to the negatively charged carboxyl terminus of tubulin and, in the context of motor processivity, compensates for the lack of a second motor domain on the KIF1A holoenzyme.

Decentralizing rural health services: a case study in China.

Many low and middle-income countries have decentralized their public health services in an effort to improve their equity, efficiency and effectiveness. This paper presents a case study of a poor rural county in China that devolved finance and management of basic health services to townships, the lowest level of government. It finds little evidence that townships mobilized additional financial resources or that they were able to address major management problems effectively. It cautions against unrealistically rapid decentralization of health services in poor rural areas.

Molecular interactions among protein phosphatase 2A, tau, and microtubules. Implications for the regulation of tau phosphorylation and the development of tauopathies.

Hyperphosphorylated forms of the neuronal microtubule (MT)-associated protein tau are major components of Alzheimer's disease paired helical filaments. Previously, we reported that ABalphaC, the dominant brain isoform of protein phosphatase 2A (PP2A), is localized on MTs, binds directly to tau, and is a major tau phosphatase in cells. We now describe direct interactions among tau, PP2A, and MTs at the submolecular level. Using tau deletion mutants, we found that ABalphaC binds a domain on tau that is indistinguishable from its MT-binding domain. ABalphaC binds directly to MTs through a site that encompasses its catalytic subunit and is distinct from its binding site for tau, and ABalphaC and tau bind to different domains on MTs. Specific PP2A isoforms bind to MTs with distinct affinities in vitro, and these interactions differentially inhibit the ability of PP2A to dephosphorylate various substrates, including tau and tubulin. Finally, tubulin assembly decreases PP2A activity in vitro, suggesting that PP2A activity can be modulated by MT dynamics in vivo. Taken together, these findings indicate how structural interactions among ABalphaC, tau, and MTs might control the phosphorylation state of tau. Disruption of these normal interactions could contribute significantly to development of tauopathies such as Alzheimer's disease.

Rural health prepayment schemes in China: towards a more active role for government.

A large majority of China's rural population were members of health prepayment schemes in the 1970's. Most of these schemes collapsed during the transition to a market economy. Some localities subsequently reestablished schemes. In early 1997 a new government policy identified health prepayment as a major potential source of rural health finance. This paper draws on the experience of existing schemes to explore how government can support implementation of this policy. The decision to support the establishment of health prepayment schemes is part of the government's effort to establish new sources of finance for social services. It believes that individuals are more likely to accept voluntary contributions to a prepayment scheme than tax increases. The voluntary nature of the contributions limits the possibilities for risk-sharing and redistribution between rich and poor. This underlines the need for the government to fund a substantial share of health expenditure out of general revenues, particularly in poor localities. The paper notes that many successful prepayment schemes depend on close supervision by local political leaders. It argues that the national programme will have to translate these measures into a regulatory system which defines the responsibilities of scheme management bodies and local governments. A number of prepayment schemes have collapsed because members did not feel they got value for money. Local health bureaux will have to cooperate with prepayment schemes to ensure that health facilities provide good quality services at a reasonable cost. Users' representatives can also monitor performance. The paper concludes that government needs to clarify the relationship between health prepayment schemes and other actors in rural localities in order to increase the chance that schemes will become a major source rural health finance.

Health expenditure and finance: who gets what?

The methods used in South Africa's first comprehensive review of health finance and expenditure are outlined. Special measures were adopted to make the process acceptable to all concerned during a period of profound political transition. The estimation of indicators of access to public sector resources for districts sorted by per capita income allowed the health care problems of disadvantaged communities to be highlighted.

Towards equity in health in an unequal society.

South Africa is one of the world's most unequal societies and its health sector mirrors these inequalities. Since the first democratic elections in 1994 the government has been under enormous pressure to diminish disparities between population groups in access to health services. This paper documents the structural inequalities in the health sector and discusses the strategic options that are being considered for reducing them. The overall level of health expenditure is high, amounting to 8.5% of GDP. However, less than 40% of expenditure is on public health services and three quarters of that is on acute care hospitals. A more detailed analysis of public health expenditure reveals large differences between census districts. The districts where household incomes are low tend to have fewer public health services. Public health expenditure per capita was lower than the estimated cost of providing basic primary health care in a fifth of districts. The most urgent need is to improve the services likely to reduce excess mortality and morbidity. This will involve additional funding of primary health service services, particularly in underserved localities. Government cannot increase public health rapidly and it will have to re-allocate funding from hospitals. The paper discusses options for achieving this, including the introduction of social health insurance. It argues that restructuring the health sector is complex and there is a risk of failure. Governments should base their strategies on a good understanding of the health sector and of the likely impact of different reform options.

In vitro reconstitution of microtubule plus end-directed, GTPgammaS-sensitive motility of Golgi membranes.

Purified Golgi membranes were mixed with cytosol and microtubules (MTs) and observed by video enhanced light microscopy. Initially, the membranes appeared as vesicles that moved along MTs. As time progressed, vesicles formed aggregates from which membrane tubules emerged, traveled along MTs, and eventually generated extensive reticular networks. Membrane motility required ATP, occurred mainly toward MT plus ends, and was inhibited almost completely by the H1 monoclonal antibody to kinesin heavy chain, 5'-adenylylimidodiphosphate, and 100 microM but not 20 microM vanadate. Motility was also blocked by GTPgammaS or A1F4- but was insensitive to A1C13, NaF, staurosporin, or okadaic acid. The targets for GTPgammaS and A1F4- were evidently of cytosolic origin, did not include kinesin or MTs, and were insensitive to several probes for trimeric G proteins. Transport of Golgi membranes along MTs mediated by a kinesin has thus been reconstituted in vitro. The motility is regulated by one or more cytosolic GTPases but not by protein kinases or phosphatases that are inhibited by staurosporin or okadaic acid, respectively. The pertinent GTPases are likely to be small G proteins or possibly dynamin. The in vitro motility may correspond to Golgi-to-ER or Golgi-to-cell surface transport in vivo.

A role for cyclin-dependent kinase(s) in the modulation of fast anterograde axonal transport: effects defined by olomoucine and the APC tumor suppressor protein.

Proteins that interact with both cytoskeletal and membrane components are candidates to modulate membrane trafficking. The tumor suppressor proteins neurofibromin (NF1) and adenomatous polyposis coli (APC) both bind to microtubules and interact with membrane-associated proteins. The effects of recombinant NF1 and APC fragments on vesicle motility were evaluated by measuring fast axonal transport along microtubules in axoplasm from squid giant axons. APC4 (amino acids 1034-2844) reduced only anterograde movements, whereas APC2 (aa 1034-2130) or APC3 (aa 2130-2844) reduced both anterograde and retrograde transport. NF1 had no effect on organelle movement in either direction. Because APC contains multiple cyclin-dependent kinase (CDK) consensus phosphorylation motifs, the kinase inhibitor olomoucine was examined. At concentrations in which olomoucine is specific for cyclin-dependent kinases (5 microM), it reduced only anterograde transport, whereas anterograde and retrograde movement were both affected at concentrations at which other kinases are inhibited as well (50 microM). Both anterograde and retrograde transport also were inhibited by histone H1 and KSPXK peptides, substrates for proline-directed kinases, including CDKs. Our data suggest that CDK-like axonal kinases modulate fast anterograde transport and that other axonal kinases may be involved in modulating retrograde transport. The specific effect of APC4 on anterograde transport suggests a model in which the binding of APC to microtubules may limit the activity of axonal CDK kinase or kinases in restricted domains, thereby affecting organelle transport.