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We report here the novel finding that HIV-negative factor (Nef) protein is present in considerable numbers of peripheral blood mononuclear cells (PBMCs) from viremic HIV-infected patients not on antiretroviral therapy (ART) and also in patients receiving virologically suppressive ART, though to a smaller degree. Interestingly, these Nef-positive PBMCs constitute predominantly uninfected bystander cells. These results may explain systemic pathology in HIV patients, even in those receiving ART.

We reduce and analyze, in a uniform way, all of the data obtained by the Solar Disk Sextant (SDS) experiment, concerning high-precision measurements of the solar radius and oblateness, in the bandwidth 590 {–} 670 nm, made onboard stratospheric balloons during a series of flights carried out in 1992, 1994, 1995, and 1996. The measured radius value appears anti-correlated with the level of solar activity, ranging from about 959.5 to 959.7 arcsec. Its variation from year to year is outside the error range, which is mostly due to a systematic diurnal behavior, particularly evident in the 1996 flight. The oblateness shows an analogous temporal behavior, ranging from about (4.3 to 10.3) × 10−6.

Background: Determining T-cell phenotypes of lung cells obtained by bronchoalveolar lavage (BAL) is frequently clinically useful, particularly for evaluating causes of interstitial lung disease. The current standard of determining CD4/CD8 T-cell subsets by immunohistochemical (IHC) staining of cytocentrifuge slides is labor-intensive and subject to interpreter variation. Flow cytometry (FCM) is a precise and rapid method commonly used in research to characterize cells in the lung. However, few studies address the methodology of analysis of BAL lymphocytes by FCM. Methods: Patients underwent bronchoscopy for clinical purposes. A BAL cell differential and T-cell subtype was requested by the treating physician to supplement the evaluation of patients with suspected interstitial lung disease. We used a commercially available T-cell antibody reagent, approved for analysis of blood via FCM, for T-cell subtyping of clinical BAL specimens. Results: The percentages of CD4 and CD8 T-cell populations, as well as the CD4/CD8 ratios showed excellent correlation with IHC staining of cytocentrifuge slides regardless of the acquisition program used, as long as the gating strategy remained consistent (r ≥ 0.9693 for CD4, r ≥ 0.9589 for CD8, and r ≥ 0.9485 for the CD4/CD8 ratio). Conclusion: These findings validate the use of standardized, commercially available antibody cocktails for BAL lymphocyte subtyping, making this technique available to clinicians and researchers with access to a three-color or four-color flow cytometer. © 2006 International Society for Analytical Cytology

Patients infected with HIV frequently have a CD8+ lymphocytic alveolitis consisting of HIV-specific CD8+CD57− cytotoxic T lymphocytes. However, in late stage disease, there is expansion of a CD8+CD57+ population with suppressive properties. We examined role of lymphocyte apoptosis in the expansion of the CD8+CD57+ lymphocytes in late stage HIV in the lung and blood compartment in human subjects. Fas was expressed on virtually all lung lymphocytes from HIV-infected and normal subjects. Fas ligand expression was increased in HIV infection in both CD8+CD57+ and CD8+CD57− lymphocytes, though a significantly greater percentage of CD8+CD57+ cells expressed this marker. CD8+CD57+ lymphocytes in normal and HIV-infected subjects underwent more apoptosis than CD8+CD57− cells. However, in late stage HIV infection, the percentage of CD8+CD57+ cells undergoing apoptosis declined. These data demonstrate that under normal conditions CD8+CD57+ cells appear destined to undergo programmed cell death. Expansion of suppressive CD8+CD57+ cells in the lungs of HIV-infected subjects with advanced disease may be due to the failure of this normal regulatory process.

The American Lung Association of Indiana (ALA-I), in conjunction with participating Indiana hospitals, developed the Lung Center concept as a mechanism to provide standardized delivery of lung health education. The goal of this pilot study was to evaluate initial experience with the Lung Center program "Overcoming Your Asthma," a two-session asthma education program, and identify areas needing improvement. A total of 305 participants responded to a 31-item questionnaire at baseline (immediately prior to program exposure) and again at 1 month (n = 75) and 6 months (n = 30) after participation. Overall, delivery of the ALA-I Lung Center asthma education program improved respondents' experience with asthma. At one month after the educational session, the program improved participant knowledge about asthma. This was associated with modest improvements in treatment behaviors, economic outcomes and asthma symptoms such as reduced breathing difficulties, wheezing and asthma exacerbations, and improvement in sleep. Improvements were not uniformly sustained at 6 months. In summary, the Lung Center asthma education program appears to benefit patients with asthma. The results provide preliminary evidence to support continued delivery of asthma education in Lung Centers. Future efforts should emphasize education to improve treatment attitudes and behaviors.

CD1d is an MHC class I-like surface molecule that presents endogenous glycoplipid antigens. The effect of HIV infection on CD1d surface expression has not yet been reported. FACS analysis revealed significantly lower levels of CD1d on CD14 + monocytes from HIV-infected subjects compared to HIV-infected subjects on HAART and healthy controls. CD1d expression correlated inversely with viral load in infected individuals. CD1d surface expression on human cell lines was downregulated after infection with M-tropic HIV, T-tropic HIV, or after exposure to HIV gp120 in vitro. These data suggest that CD1d-mediated responses are altered during HIV infection and may thus contribute to the global immunodeficiency seen in these patients.

Repeated measurements of erosion rates on seashore platforms on Kaikoura Peninsula, South Island, New Zealand were gathered over a 28-month period using a micro-erosion meter (MEM). The resultant hierarchical dataset was analysed using multilevel regression modeling. Results indicate that there is persistent variation of rates across measurement occasions within individual points and significant variation is also found across sites (or local 'contexts'). There is little evidence for significant variation across individual points. The explanatory variables of platform/rock type, distance along platform and seasonality all have a significant effect on the erosion rates and aid the explanation of some of the variation in erosion rates across sites.

We tested the hypothesis that human immunodeficiency virus (HIV)-infected adults have a specific defect in anti-pneumococcal capsular polysaccharide (Pn-specific) immunoglobulin (Ig) in fluid obtained from the lower respiratory tract. Higher levels of total IgG and IgM were present in bronchoalveolar lavage samples from HIV-infected subjects than in those from HIV-uninfected subjects. Pn-specific IgG and IgM in bronchoalveolar lavage samples were not significantly different between HIV-infected and -uninfected subjects. After pneumococcal infection, HIV-infected patients had higher bronchoalveolar lavage levels of Pn-specific IgG than HIV-infected patients without recent infection (geometric means, 387 vs. 30 ng/mL, P=.001).

The lung is a common site of disease in HIV infection. Virus has been detected in BAL fluid (BALF) and saliva. However, the relationship between viral loads detected at different levels of the respiratory tract is unknown.We measured simultaneous HIV viral loads in parotid saliva (PS), bronchial fluid (BF), BALF, and plasma by reverse transcription polymerase chain reaction in 20 HIV-infected individuals.HIV was detected in 53% of BALF samples, 15% of BF samples, 5% of PS samples, and 88% of plasma samples. Viral loads in plasma and BALF samples were positively correlated. There were significantly higher levels of HIV viral load in both plasma and BALF in subjects with CD4 counts of200 cells/ microL compared to those with higher counts. Antiretroviral therapy (ART) was associated with lower BALF and plasma viral loads, and the effect in BALF was independent of the plasma viral load. Interestingly, smoking also was associated with lower levels of both BAL and BF viral loads, independent of the plasma viral load.These data demonstrate that while HIV can be detected in the respiratory tract, the viral load is influenced by both local factors (ie, level of the respiratory tree and cigarette smoking) and systemic factors (ie, ART and peripheral CD4 count).

Anti-tumor necrosis factor-alpha (TNF-alpha) antibodies are frequently used to treat inflammatory diseases. However, these drugs also have immunosuppressive effects. We report on three patients who developed disseminated histoplasmosis on therapy with TNF-alpha inhibitors. In vitro assays were used to characterize the role of these agents in host defense against Histoplasma capsulatum. Intracellular proliferation of H. capsulatum was measured in alveolar macrophages and peripheral monocytes of normal volunteers in the presence and absence of the TNF-alpha antibody, infliximab. Both infliximab and control antibody enhanced fungal growth in monocytes and alveolar macrophages, suggesting this was a nonspecific antibody response. Despite similar intracellular fungal loads in the presence of both antibodies, lymphocyte proliferation in response to blood monocytes and alveolar macrophages infected with H. capsulatum was inhibited by the addition of physiologic doses of infliximab, whereas control antibody had no effect. The production of H. capsulatum-induced interferon-gamma and TNF-alpha was assessed in 5-day cultures containing lymphocytes and alveolar macrophages or monocytes. Interferon-gamma secretion was significantly reduced in the presence of infliximab. In summary, patients receiving anti-TNF-alpha therapy are at risk for developing disseminated histoplasmosis. This may be due to a defect in the TH1 arm of cellular immunity.

Studies of state-society relations continue to assume that the Soviet Union was the quintessential “strong” state, able to dominate a weak society at every stage of the policy process. Evidence gleaned from the former Soviet defense industry, however, reveals that the Soviet state, at least since the Brezhnev era, had difficulty implementing some of its highest priority objectives. While the Soviet state may have possessed considerable despotic power, its infrastructural power was lacking in many areas. Soviet authorities never managed to construct policy levers that could consistently influence defense industrial managers to behave in the ways they desired.

Cigarette smoking (CS), the main risk factor for COPD (chronic obstructive pulmonary disease) in developed countries, decreases alveolar macrophages (AM) clearance of both apoptotic cells and bacterial pathogens. This global deficit of AM engulfment may explain why active smokers have worse outcomes of COPD exacerbations, episodes characterized by airway infection and inflammation that carry high morbidity and healthcare cost. When administered as intravenous supplementation, the acute phase-reactant alpha-1 antitrypsin (A1AT) reduces the severity of COPD exacerbations in A1AT deficient (AATD) individuals and of bacterial pneumonia in murine models, but the effect of A1AT on AM scavenging functions has not been reported. Apoptotic cell clearance (efferocytosis) was measured in human AM isolated from patients with COPD, in primary rat AM or differentiated monocytes exposed to CS ex vivo, and in AM recovered from mice exposed to CS. A1AT (100 μg/mL, 16 h) significantly ameliorated efferocytosis (by ~50%) in AM of active smokers or AM exposed ex vivo to CS. A1AT significantly improved AM global engulfment, including phagocytosis, even when cells were simultaneously challenged with apoptotic and Fc-coated (bacteria-like) targets. The improved efferocytosis in A1AT-treated macrophages was associated with inhibition of tumor necrosis factor-α converting enzyme (TACE) activity, decreased mannose receptor shedding, and markedly increased abundance of efferocytosis receptors (mannose- and phosphatidyl serine receptors and the scavenger receptor B2) on AM plasma membrane. Directed airway A1AT treatment (via inhalation of a nebulized solution) restored in situ airway AM efferocytosis after CS exposure in mice. The amelioration of CS-exposed AM global engulfment may render A1AT as a potential therapy for COPD exacerbations.

© 2014, American Thoracic Society. All rights reserved. Investigation of the human microbiome has become an important field of research facilitated by advances in sequencing technologies. The lung, which is one of the latest body sites being explored for the characterization of human-associated microbial communities, has a microbiome that is suspected to play a substantial role in health and disease. In this review, we provide an overview of the basics of microbiome studies. Challenges in the study of the lung microbiome are highlighted, and further attention is called to the optimization and standardization of methodologies to explore the role of the lung microbiome in health and disease. We also provide examples of lung microbial communities associated with disease or infection status and discuss the role of fungal species in the lung. Finally, we review studies demonstrating that the environmental microbiome can in fluence lung health and disease, such as the finding that the diversity of microbial exposure correlates inversely with the development of childhood asthma.

Alveolar macrophages (AM) apoptotic cell clearance function (efferocytosis) is dysregulated in COPD due to cigarette smoke (CS) exposure via production of ceramides and sphingosine (SHP). CS also alters the maturation of the autophagosomes (AP) blocking the autophagic flux. We hypothesized that impairment of both AP maturation and efferocytosis share an identical mechanism of cytoskeletal derangement linked to HDAC6 inactivation and sphingosine accumulation. AM obtained via bronchoalveolar lavage from human smoker and non-smoker donors or from Sprague Dawley rats exposed to CS (3 months) were subject to engulfment assays quantified by flow cytometry. HDAC6 was evaluated by real-time PCR or Western blot. Both CS and SPH significantly impaired efferocytosis in rat and human AM (50% and 80% inhibition; p

Rationale: The ability to determine the respiratory microbiome from bronchoalveolar lavage (BAL) is controversial due to oral contamination during bronchoscopy. To determine if processing BAL improved the ability to distinguish lung from oral wash microbiomes, we compared the oral and lung microbiome from whole and acellular BAL in 34 subjects. Methods: Oral wash samples and bronchoscopy with BAL were performed. After removing an aliquot of whole unprocessed BAL, the remaining was centrifuged at 1,500 rpm for 10 minutes and the supernatant harvested as acellular BAL. DNA was isolated from 2 ml of oral wash and 5 ml of acellular and whole BAL using the Qiagen DNeasy kit (Qiagen, Valencia, CA). DNA encoding 16s ribosomal RNA was amplified using NEB Phusion enzyme (NEB, Ipswich, MA) and degenerate of eubacterial primers that amplify the variable regions 1 through 3. DNA sequencing was performed using 454 sequencing. Results: The amount of genomic DNA isolated from whole BAL was 100-fold higher compared with acellular BAL. Despite this, the number of high-quality genera bacterial reads (RDP classifier > 90%) was identical between the two groups (whole BAL, 4,903 ± 3,209; acellular BAL, 4,245 ± 2,632). Bray-Curtis distances between oral wash and acellular BAL were significantly higher than the distance between whole BAL and oral wash (P = 0.000035), indicating acellular BAL was significantly more different from oral wash compared with whole BAL. Visually, the overlap between oral wash and whole BAL can be seen on the dendogram in Figure 1 (BA = acellular BAL; BW = whole BAL; OR = oral wash). Figure 1. Dendogram showing clustering using bray-curtis dissimilarity at the genus level. Blue = acellular bronchoalveolar lavage (BAL); red = whole BAL; green = oral wash. Conclusions: The difference between acellular BAL and oral wash is significantly greater than the difference between whole BAL and oral wash. We suggest this represents greater contamination of whole BAL by upper airway organisms. We speculate acellular BAL provides a better representation of the true lower respiratory tract microbiome.

(2001). Russian Health Care Reform at the Regional Level: Status and Impact. Post-Soviet Geography and Economics: Vol. 42, No. 3, pp. 202-219.

Our goals in this endeavor were two-fold. From a pedagogical perspective, we hoped to increase the level and quality of contact between the students and faculty, provide students with greater opportunities for interacting and cooperating in large and small groups, facilitate active learning, and open alternate paths of learning and achievement for students who do not respond well to more conventional approaches.I In terms of course content, our intent was to allow the students to

The implementation of Russia's 1993 legislation on obligatory medical insurance has been characterized by wide regional variation. Two areas in particular illustrate this phenomenon: for the last five years Moscow has enjoyed a sophisticated, well-developed insurance system, while the Nizhny Novgorod region has only recently taken the most rudimentary steps toward implementation of the law. Despite their radically differing approaches to the market-based insurance reforms, however, Moscow and Nizhny Novgorod continue to enjoy roughly the same quality of available health care services, at similar costs to consumers. They also suffer some of the same continued systemic defects inherited from the Soviet era. A comparison of the two regions demonstrates that, while reform of the Soviet health care system was desperately needed, the Russian version of obligatory medical insurance has not proved to be the panacea its architects intended. In fact, even its original pioneers are now moving forward with new schemes to correct some of its deficiencies.

This article examines recent difficulties in the Russian space program through the analytic lens of the Russian political and economic reform effort. It argues that Russia’s problems go beyond a lack of financing. Instead, lack of investment and ‘brain drain’ have caused deep infrastructural problems which would take years of restored funding and political priority to fix. Russia’s continued activity in space stems almost solely from inertia left over from the Soviet period, and from funding provided by foreign partners anxious to exploit the cheap, sturdy elements of that Soviet legacy.

To revitalise their health services, governments in the former socialist states of Central and Eastern Europe are experimenting with a new wonder drug called market mechanisms. This is rather like the doctor who gives penicillin to a patient who has a known allergy to it but will die without it. It is necessary to understand the associated dangers so that appropriate measures may be taken to prevent the treatment from killing the patient.l

To assess whether the joint review of radiologic studies by the primary care physician and the radiologist affects patient care and health care costs.Prospective study.Student health clinic at a university hospital.University students seen during acute care visits.Joint weekly review of all radiologic studies ordered at the student health clinic between July 1992 and June 1993 by a staff radiologist and internist.The outcome measures were: (1) change of radiologic diagnosis after review process and its effect on patient management; (2) expenses saved or incurred by the review process. Of 323 films ordered, 305 were reviewed, resulting in revisions of 23 (8%) of the initial readings. Sixteen revisions (5%) led to a change in patient management; the remainder were clinically insignificant. In these 16 cases, cancellation or simplification of further workup resulted in savings of $1,967. The cost for extra physician time was $5,499. Thus, the review process incurred a net cost of $3,532. Except for the reduction in diagnostic studies, no therapeutic benefit for the patients could be identified. Film readings in our radiology department were conservative, with a positive predictive value of 85% and a negative predictive value of 99.7%.Routinely reviewing every radiologic study did not affect patient outcome in an outpatient clinic with low prevalence of disease. Given our radiologists' conservative film-reading practice, a review of only abnormal studies may prove more cost-effective in a healthy population. This type of assessment has implications for improving the efficiency of a changing health care system.

Human immunodeficiency virus (HIV)-infected individuals are at risk for pulmonary infections with encapsulated bacterial pathogens. This could reflect impaired production of opsonizing antibodies in the lower respiratory tract. We examined antibody production in the alveolar space by measuring immunoglobulin concentrations in bronchoalveolar lavage (BAL) of HIV-infected patients and normal volunteers and by assessing the ability of alveolar macrophages (AM) to induce immunoglobulin production in normal peripheral blood mononuclear cells (PBMC). BAL from HIV-infected patients contained significantly less IgG than normal BAL. IgA and IgM concentrations were similar in both groups. Normal AM supported IgG and IgA production in PBMC. While HIV AM could induce IgA production in PBMC, in no instance did they induce IgG secretion. HIV AM produced significantly more transforming growth factor-beta (TGF-beta), a factor known to suppress IgG production, than normal AM. Finally, TGF-beta antibodies blocked the inhibitory effect of HIV AM on normal IgG secretion without affecting IgA secretion. These findings demonstrate impaired production of opsonizing IgG in the alveolar space of HIV-infected subjects and implicate excess TGF-beta production by AM as the cause of this impairment.

Human immunodeficiency virus (HIV)-positive patients frequently develop a CD3+/CD8+ cytotoxic T cell lymphocytic alveolitis. This could occur through in situ expansion of lung lymphocytes. We evaluated lung and blood lymphocyte proliferation in asymptomatic HIV-infected individuals by measuring spontaneous and cytokine-induced tritiated thymidine incorporation. Interleukin (IL)-2 and IL-4 secretion was determined with the use of enzyme-linked immunosorbent assay, Western blotting, and immunoprecipitation techniques. Spontaneous proliferation by lung lymphocytes from HIV-positive patients was significantly greater than that of normal volunteers. Proliferation was confined to the CD8+ lymphocyte subset. Over time, spontaneous proliferation declined unless autologous alveolar macrophages (AM) were added, suggesting AM were providing additional stimulatory signals to lung lymphocytes. Lung and blood lymphocytes proliferated in response to IL-2 but not IL-4. Lymphocytes in HIV-infected lung spontaneously produced and secreted more IL-2 than either normal lung lymphocytes or autologous blood lymphocytes. IL-4 production was not detectable in either group. These findings support the hypothesis that lymphocytic alveolitis in asymptomatic HIV-positive patients results from IL-2-dependent in situ proliferation of CD3+/CD8+ cytotoxic T cells.

The incidence of tuberculosis is increasing on a global scale, in part due to its strong association with human immunodeficiency virus (HIV) infection. Attachment of Mycobacterium tuberculosis to its host cell, the alveolar macrophage (AM), is an important early step in the pathogenesis of infection. Bronchoalveolar lavage of HIV-infected individuals demonstrated the presence of a factor which significantly enhances the attachment of tubercle bacilli to AMs 3-fold relative to a normal control population. This factor is surfactant protein A (SP-A). SP-A levels are increased in the lungs of HIV-infected individuals. SP-A levels and attachment of M. tuberculosis to AMs inversely correlate with peripheral blood CD4 lymphocyte counts. Elevated concentrations of SP-A during the progression of HIV infection may represent an important nonimmune risk factor for acquiring tuberculosis, even before significant depletion of CD4 lymphocytes in the peripheral blood occurs.

Previous work has shown that alveolar macrophages (AM) from human immunodeficiency virus (HIV)-infected patients are superior accessory cells (AC) and secrete greater amounts of T cell-stimulatory cytokines than do normal AM. We now examine the role of AM-T cell adherence in AM AC function by examining the ability of beta 2 integrins and intercellular adhesion molecule-1 (ICAM-1) to block adherence and lymphoproliferation. Mitogen-induced (concanavalin A, pokeweed mitogen) adhesion and proliferation were studied in the presence and absence of mAb directed against beta 2 integrins and ICAM-1. AM from normal subjects and HIV-positive patients were used as AC, and normal T cells were used as responders. Normal and HIV AM bound equal numbers of T cells under similar conditions. Adherence was blocked by antibodies to beta 2 integrins and ICAM-1 in both groups. Con A-induced lymphoproliferation was positively correlated with adherence in normal volunteers. In contrast, greater Con A-induced AM-T cell adherence in HIV-positive patients was associated with worse AC function. Antibodies that impaired AM-T cell adherence completely inhibited AC function in both groups when added at the beginning of mitogen assays, indicating that initial contact was required. However, the addition of antibodies after 4 h inhibited lymphoproliferation less in HIV-infected individuals than in normal volunteers, suggesting that prolonged AM-T cell adherence was less important for optimal AC function in these patients. Using these and previous results, we present a model for AM AC function in normal volunteers and HIV-infected individuals.

To determine the effects of smoking on alveolar macrophage (AM) accessory cell (AC) function and the incidence of lymphocytic alveolitis in asymptomatic HIV-infected individuals.AM AC function in smoking and nonsmoking HIV-positive volunteers was measured in concanavalin A and pokeweed mitogen assays. Mitogen-induced AM-T-cell adherence was determined. AM cytokine secretion was analyzed by interleukin (IL)-6 bioassay and IL-1 enzyme-linked immunosorbent assay (ELISA). The incidence of lymphocytic alveolitis in both groups was determined.AM from smokers were significantly poorer AC than AM from nonsmokers. Though AM-T-cell adherence was unaffected by smoking, IL-1 and IL-6 secretion was significantly impaired. Lymphocytic alveolitis was significantly less common in HIV-infected smokers.Smoking reduces AM AC function in HIV-infected individuals, probably by impairing secretion of cytokines important in T-cell proliferation. This may explain the decreased incidence of lymphocytic alveolitis in HIV-infected people who smoke.

This article discusses the future of the Russian military, civil and commercial space programmes in the context of the country's industrial policy. While the uncertain outcome of economic reform, difficulty in adapting to new situations and a struggle for control over the programme between the civilian Russian Space Agency (RSA) and the military old guard may act as initial constraints on Russian space activities, new entrepreneurial tendencies, changed military requirements and foreign investment may all help to invigorate the programme.

The MOHAVE-2009 campaign brought together diverse instrumentation for measuring atmospheric water vapor. We report on the participation of the ALVICE mobile laboratory in the MOHAVE-2009 campaign. In an appendix we also report on the performance of the corrected Vaisala RS92 radiosonde during the campaign. A new radiosonde based calibration algorithm is presented that reduces the influence of atmospheric variability on the derived calibration constant. The MOHAVE-2009 campaign permitted all Raman lidar systems participating to discover and address measurement biases in the upper troposphere and lower stratosphere. The ALVICE lidar system was found to possess a wet bias which was attributed to fluorescence of insect material that was deposited on the telescope early in the mission. A correction technique is derived and applied to the ALVICE lidar water vapor profiles. Other sources of wet biases are discussed and data from other Raman lidar systems are investigated revealing that wet biases in upper tropospheric and lower stratospheric water vapor measurements appear to be quite common in Raman lidar systems. Lower stratospheric climatology of water vapor is investigated both as a means to check for the existence of these wet biases in Raman lidar data and as a source of correction for the data. The correction is offered as a general method to both quality control Raman water vapor lidar data and to correct those data that have signal-dependent bias. The influence of the correction is shown to be small at regions in the upper troposphere where recent work indicates detection of trends in atmospheric water vapor may be most resistant to additional noise sources. The correction shown here holds promise for permitting useful upper tropospheric water vapor profiles to be consistently measured by Raman lidar within NDACC and elsewhere despite the prevalence of instrumental and atmospheric effects that can contaminate the very low signal to noise measurements in the UT.

Purpose The purpose of this study was to evaluate outcomes of a consistent arthroscopic stabilization technique for recurrent posterior instability. Methods Thirty-four consecutive shoulders with symptomatic recurrent posterior instability were treated with arthroscopic repair and evaluated at a mean follow-up of 36 months (range, 12 to 67 months). Two patients were excluded because of prior surgery, leaving 32 for further analysis. The mean age was 21.4 years (range, 15 to 33 years). There were 26 male and 6 female patients, and in 59% the dominant shoulder was affected. A known traumatic injury had occurred in 25 (78%), but only 2 (6%) had a documented dislocation. Arthroscopic repair was performed with the patient in the lateral decubitus position through an anterosuperior 12-o'clock viewing portal. Suture anchor repairs were performed in 30 cases and plication to the intact labrum in 4. A sling and derotation wedge were used for 4 weeks, followed by progressive active range of motion, with weight lifting at 3 months and return to contact sports at 6 months. Of the 34 cases, 22 met the inclusion and exclusion criteria and had complete preoperative and postoperative shoulder outcome scores. Results Significant improvement ( P = .001) from preoperatively to final follow-up was seen for American Shoulder and Elbow Surgeons scores, from 68 to 93; Simple Shoulder Test scores, from 9.3 to 11.6; and visual analog scale scores, from 3.5 to 0.8. All patients returned to their previous level of athletic activity. Two patients reported postoperative instability; none required reoperation. There were no other postoperative complications. Conclusions This study represents a consecutive series of patients with recurrent posterior instability who underwent arthroscopic posterior stabilization. In this population arthroscopic posterior labral repair and capsular plication provided significant clinical improvement and low rates of recurrent instability and revision surgery. Level of Evidence Level IV, therapeutic case series.

A decreased clearance of apoptotic cells (efferocytosis) by alveolar macrophages (AM) may contribute to inflammation in emphysema. The up-regulation of ceramides in response to cigarette smoking (CS) has been linked to AM accumulation and increased detection of apoptotic alveolar epithelial and endothelial cells in lung parenchyma. We hypothesized that ceramides inhibit the AM phagocytosis of apoptotic cells. Release of endogenous ceramides via sphingomyelinase or exogenous ceramide treatments dose-dependently impaired apoptotic Jurkat cell phagocytosis by primary rat or human AM, irrespective of the molecular species of ceramide. Similarly, in vivo augmentation of lung ceramides via intratracheal instillation in rats significantly decreased the engulfment of instilled target apoptotic thymocytes by resident AM. The mechanism of ceramide-induced efferocytosis impairment was dependent on generation of sphingosine via ceramidase. Sphingosine treatment recapitulated the effects of ceramide, dose-dependently inhibiting apoptotic cell clearance. The effect of ceramide on efferocytosis was associated with decreased membrane ruffle formation and attenuated Rac1 plasma membrane recruitment. Constitutively active Rac1 overexpression rescued AM efferocytosis against the effects of ceramide. CS exposure significantly increased AM ceramides and recapitulated the effect of ceramides on Rac1 membrane recruitment in a sphingosine-dependent manner. Importantly, CS profoundly inhibited AM efferocytosis via ceramide-dependent sphingosine production. These results suggest that excessive lung ceramides may amplify lung injury in emphysema by causing both apoptosis of structural cells and inhibition of their clearance by AM.

Hypothesis Revision shoulder arthroplasty represents a complex and difficult problem for the treating surgeon, with multiple potential complications. In the setting of a well-fixed humeral component, removal can lead to fractures and compromise the outcome of the revision. The current study describes and evaluates the results of a novel vertical humeral osteotomy (VHO) for stem extraction. We hypothesized that the VHO will enable successful stem extraction without perioperative or postoperative fractures. Materials and methods Twenty-seven patients were retrospectively identified who had a VHO for revision shoulder arthroplasty, with 23 patients available for final follow-up. Records and radiographs were reviewed for postoperative complications. Final follow-up was completed with the inclusion of shoulder scores. Results There were no perioperative or postoperative fractures on clinical examination and radiographic review at an average follow-up of 41 months. Average American Shoulder and Elbow Surgeons (ASES) score was 64.7 (contralateral ASES, 76.9), average Simple Shoulder Test was 6.3, and the visual analog score pain average was 1.3. There were no instability events. Discussion The glenoid is the more common site for failure in both hemiarthroplasty and total shoulder arthroplasty. This can lead to a difficult revision procedure if the ingrown or cemented humeral stem requires removal. Conclusion In the current study, we found the VHO was an effective tool for the removal of the humeral prosthesis with no perioperative or postoperative fractures.

BACKGROUND: Obstructive sleep apnoea (OSA) is a common disease that leads to daytime sleepiness and cognitive impairment. Attempts to investigate changes in brain morphology that may underlie these impairments have led to conflicting conclusions. This study was undertaken to aim to resolve this confusion, and determine whether OSA is associated with changes in brain morphology in a large group of patients with OSA, using improved voxel-based morphometry analysis, an automated unbiased method of detecting local changes in brain structure. METHODS: 60 patients with OSA (mean apnoea hypopnoea index 55 (95% CI 48 to 62) events/h, 3 women) and 60 non-apnoeic controls (mean apnoea hypopnoea index 4 (95% CI 3 to 5) events/h, 5 women) were studied. Subjects were imaged using T1-weighted 3-D structural MRI (69 subjects at 1.5 T, 51 subjects at 3 T). Differences in grey matter were investigated in the two groups, controlling for age, sex, site and intracranial volume. Dedicated cerebellar analysis was performed on a subset of 108 scans using a spatially unbiased infratentorial template. RESULTS: Patients with OSA had a reduction in grey matter volume in the right middle temporal gyrus compared with non-apnoeic controls (p

Objective The effects of obstructive sleep apnoea (OSA) on the markers of glucose metabolism and other hormones are of interest, particularly since there is growing evidence that OSA may be a risk factor for disorders such as insulin resistance. However, interpreting these studies depends on the target hormone not having a diurnal rhythm and the circadian rhythm not being altered by the sleep fragmentation that occurs in OSA. Therefore, the aim of our study was to test the hypothesis that OSA displaces the circadian rhythm. Methods We carried out a prospective, observational, controlled, parallel study in 22 OSA patients (mean [SD] age: 45.1 [8.8]years; apnoea/hypopnoea index (AHI): 37 [24] events/h) and 22 age matched healthy subjects (age: 47.9 [7.9]years; AHI: 3 [1] events/h). Saliva samples for the measurement of melatonin were collected from participants resting in dim light at 30min intervals between 19:30 and 22:30h. Dim light melatonin onset (DLMO), a marker of the circadian phase, was taken at the end of the 30min interval in which the greatest rise in melatonin occurred. Results The group median (interquartile range) DLMO did not differ in OSA patients compared to healthy subjects (OSA patients: 90 [60–150]min; healthy subjects: 135 [90–150]min, p =0.19). Conclusion The circadian phase is the same in OSA patients and healthy subjects using salivary melatonin concentration as a marker of the circadian phase.

Although cognitive deficits are well documented in patients with sleep apnea, the impact on memory remains unclear.To test the hypotheses that (1) patients with obstructive sleep apnea have memory impairment and (2) memory impairment is commensurate with disease severity.Patients with obstructive sleep apnea and healthy volunteers (apnea-hypopnea index5 events/h) completed a test battery specially designed to differentiate between aspects of memory (semantic, episodic, and working) versus attention. Sleepiness was measured on the basis of the Epworth Sleepiness Scale and Oxford Sleep Resistance test. Memory performance in patients versus control subjects was compared (Mann-Whitney U test; P0.01, Bonferroni corrected for multiple comparisons) and relationships between performance and disease severity were analyzed by linear regression.Sixty patients and healthy control subjects matched for age (mean +/- SD: patients, 51 +/- 9 yr; control subjects, 50 +/- 9 yr) and education (patients, 14 +/- 3 yr; control subjects, 15 +/- 3 yr) participated. Patients demonstrated impaired Logical Memory Test results (immediate recall: patients, median [range], 36 [9-69]; control subjects, 43 [19-64], P = 0.0004; and delayed recall: patients, 22 [6-42]; control subjects, 27 [10-46]; P = 0.0001). There were minimal differences in attention, visual episodic, semantic, or working memory; patients performed better than control subjects on Spatial Span forward and backward. Regression analysis revealed that Logical Memory Test performance was not significantly related to disease severity after controlling for age, education, and sleepiness.Obstructive sleep apnea is associated with impairment in verbal, but not visual, memory. The impairment was present across a range of disease severity and was not explained by reduced attention. Such verbal memory impairment may affect daytime functioning and performance.

Aims: Prior studies have shown that HAART is associated with decreased HIV viral load in the lungs. The correlation between antiretroviral exposure in bronchoalveolar lavage (BAL) fluid and virologic response was evaluated in patients starting HAART and enrolled in The AIDS Clinical Trial Group Protocol 723. Materials & methods: A total of 24 subjects underwent blood and BAL sampling prior to starting HAART, and after 4 and 24 weeks of HAART. Drug concentrations and HIV RNA were measured in paired plasma and BAL samples. Results: Antiretroviral drugs, including efavirenz, were detectable in BAL fluid of HIV-infected subjects beginning HAART. Efavirenz was also associated with a higher likelihood of clearing HIV RNA from the lungs. Conclusion: These results suggest the excellent pulmonary virologic response to antiretroviral therapy may, in part, be due to penetration of antiretroviral drugs into the alveolar compartment.

Mononuclear phagocytes, including alveolar macrophages (AM), can be chronically infected with HIV and thus serve as a reservoir for the virus. Acting as AC during the generation of an immune response, HIV-infected mononuclear phagocytes can facilitate viral T cell infection by several mechanisms, including direct contact of T cells with HIV-infected macrophages as well as cytokine-induced up-regulation of latent T cell infection. Our laboratory has shown that AM from HIV-infected individuals have enhanced AC function compared to normal AM. In this study we explored AM production and secretion of IL-1 beta and IL-6, two cytokines critical for optimal AC function, in normal volunteers and HIV-infected patients. Cultured AM supernatants and lysates were generated in the presence and absence of LPS and standard mitogens. In initial mixing experiments HIV AM supernatants enhanced mitogen-induced T cell proliferation using normal AM as AC significantly more than normal AM supernatants, suggesting that HIV AM secreted more T cell stimulatory factors than normal AM. Neither group could enhance T cell proliferation induced by HIV AM suggesting these cells already secreted optimal levels of these factors. AM from HIV+ individuals produced and secreted more IL-1 beta (measured by ELISA) and IL-6 (measured in a B9 bioassay and by immunoprecipitation) than normal AM both spontaneously and in the presence of low LPS concentrations and mitogens. In some cases depleting HIV AM supernatants of IL-1 beta and IL-6 on immunoaffinity columns abrogated their enhancement properties indicating that these cytokines were important in the observed enhancement. However, in other patients different factors must also be involved as depletion of IL-1 beta and IL-6 in their AM supernatants had no effect on enhancement function. These results show that HIV AM secretory products are important in the enhanced AC function demonstrated by these cells. However, although augmented IL-1 beta and IL-6 secretion likely contribute significantly to this enhancement, other AC secretory factors and/or functions must also be involved.