Examining self and partners for syphilis among men who have sex with men: five US cities, 2009-2011.

To increase self-examination for syphilis among men who have sex with men (MSM), we developed educational materials to increase knowledge of primary and secondary syphilis manifestations. Materials were piloted in five cities' infectious disease or MSM clinics. Self- and partner-examination behaviour was assessed with an anonymous questionnaire. Of 1459 participants, 914 men had had sex with a man in the previous three months; the 171 MSM who reported having read the materials were significantly more likely to examine themselves (anus, adjusted prevalence ratio [aPR] 1.3, 95% confidence interval [CI] 1.15-1.52), mouth, penis and skin, and their partners' anus (aPR 1.3, 95% CI 1.03-1.73) and mouth (aPR 1.6, 95% CI 1.1-2.26). Further research is needed to determine whether educational materials affect early detection and treatment of primary and secondary syphilis and reduce transmission.

Asbestos upregulates expression of the urokinase-type plasminogen activator receptor on mesothelial cells.

Inhalation of asbestos is associated with pathologic changes in the pleural space, including pleural thickening, pleural plaques, and mesothelioma. These processes are characterized by altered local proteolysis, cellular proliferation, and cell migration, suggesting that the urokinase-type plasminogen activator receptor (uPAR) could be involved in the pathogenesis of asbestos-induced pleural disease. We hypothesized that mesothelial cell uPAR expression is induced by exposure to asbestos. To test this hypothesis, we used complementary techniques in rabbit and human mesothelial cells to determine whether uPAR expression is altered by exposure to asbestos. uPAR expression was induced by chrysotile and crocidolite asbestos, but not by wollastonite, as indicated by binding of radiolabeled urokinase-type plasminogen activator (uPA) to rabbit or human mesothelial cells. uPA was not induced by fiber exposure. Exposure to exogenous uPA increased uPA activity of cells exposed to wollastonite but not asbestos-treated MeT5A cells. uPAR expression increased further when asbestos was preincubated with vitronectin (VN) or serum. Increases in uPAR expression were confirmed by binding of uPA to uPAR in cell membrane preparations and immunofluorescent staining of uPAR at the cell surface, and were associated with increases in steady-state uPAR messenger RNA. Mesothelial cell uPAR expression was also induced by media from monocytes cultured with asbestos incubated with VN and serum. By antibody neutralization, the latter effect appeared to be in part mediated by transforming growth factor-beta. We found that asbestos increases uPAR at the surface of rabbit and human mesothelial cells, suggesting that altered expression of this receptor could be involved in asbestos-induced remodeling of the pleural mesothelium.

Alterations in lung defense and unusual infections in chronic bronchitis.

Cigarette smoking is the primary irritant responsible for the syndrome of chronic bronchitis. In addition to the symptoms of cough and sputum production, smoking leads to structural changes and immunologic alterations that place the patient with chronic bronchitis at increased risk for tracheobronchial infections. This article reviews the modifications in lung defenses that occur as a result of chronic bronchitis. The uncommon infectious agents that are seen in chronic bronchitis are also discussed including clinical presentation, diagnosis, and treatment.

Changing strategies for treatment of chronic bronchitis.

There has been a recent re-examination of the therapeutic approach to chronic bronchitis, with or without airflow obstruction, partly as a result of intense interest in asthma therapy. Although the mainstay of therapy in chronic bronchitis is still smoking cessation, there has been a shift in importance and use of therapeutic interventions based on pathophysiological considerations. The presence of airway inflammation and bronchial hyperreactivity in chronic bronchitis, analogous to asthma, has spurred interest in the use of anti-inflammatory agents such as inhaled steroids, with the hope that these drugs will have the same favorable effects on airflow obstruction as in asthma. Recognition of the relative importance of cholinergic stimulation in airflow obstruction associated with chronic bronchitis has elevated the role of anticholinergic agents to primary therapy. And lastly, evolving understanding of the role of infectious agents in exacerbations of chronic bronchitis is having an impact on the perceived importance of antibiotics in this setting. This article will discuss the rationale, evidence of efficacy, and current role for each of these treatment modalities in chronic bronchitis.

Effects of continuous high dose rhGM-CSF infusion on human monocyte activity.

In this study we describe the time-dependent effects of a high dose (750 micrograms/ml/24 hr) continuous infusion of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on monocyte number, cytokine release, and superoxide anion production. Blood was taken from patients prior to rhGM-CSF infusion (day 0), and on days 1, 7, and 14 of infusion. The mean concentration of monocytes per ml of blood increased progressively from 4.3 x 10(5) on day 0 to 21 x 10(5) on day 14 of infusion. There was no significant change in the basal release of tumor necrosis factor alpha (TNF-alpha) or interleukin 1 beta (IL-1 beta) induced by rhGM-CSF. However, the lipopolysaccharide (LPS)-stimulated release of TNF-alpha by monocytes increased significantly on day 1 of infusion, and by day 14 had increased 8-fold. IL-1 beta release from LPS-stimulated monocytes increased slightly by day 7, and by almost 10-fold by day 14 of infusion. When maximally stimulated with phorbol dibutyrate, the monocytes demonstrated an increased (although not significant) capacity to produce superoxide anion on days 7 and 14 of infusion. No change in basal superoxide anion production was seen at any day of infusion. These GM-CSF-induced changes in stimulated cytokine and superoxide anion release could not be reproduced by treating monocytes with rhGM-CSF in vitro. In summary, a two week, high dose infusion of rhGM-CSF resulted in increases in circulating monocyte concentration, and in the stimulated release of TNF-alpha and IL-1 beta, and superoxide anion production from these monocytes. These primed monocytes could enhance the ability of neutropenic patients to fight infection.

Fibrin glue in otology and neurotology.

The recent development of simple, low-cost methods for producing autologous fibrin glue have given rise to a variety of uses in routine otologic and neurotologic procedures. Some of the current applications used by the authors are discussed, and a brief review of the literature is presented. Included are methods of positioning and securing implants, closure of wound edges, and application as an adjunct to achieving watertight dural closures with intracranial procedures. Representative cases are presented. No adverse reactions or specific problems related to the glue have been noted. A simple production method is included, as well as comparison with other commonly available tissue glue products.

Human alveolar macrophage cytokine release in response to in vitro and in vivo asbestos exposure.

The lung macrophage is proposed to be involved in the development of asbestos-induced pulmonary fibrosis. Knowledge of the effects of long-term asbestos exposure on lung macrophage cytokine release should better define the role of the macrophage in fibrogenesis. This study examines the effects of acute in vitro asbestos exposure and chronic in vivo asbestos exposure on human alveolar macrophage cytokine release. As indicators of asbestos-induced macrophage activation, the cellular release of IL-1 beta, TNF-alpha, IL-6, GM-CSF, and PGE2 was measured during a 24-h in vitro culture. Alveolar macrophages from normal volunteers were cultured in vitro with chrysotile asbestos. Of the factors measured, only TNF-alpha was elevated in response to asbestos exposure. Alveolar macrophages from asbestos-exposed individuals were placed into one of two groups based on their exposure history. These two groups were matched for age, smoking history, and diagnosis; none met the criteria for asbestosis. Cells isolated from subjects that had been exposed to asbestos for more than 10 years secreted enhanced basal amounts of IL-1 beta, TNF-alpha, IL-6, and PGE2, while those who had been exposed for less than 10 years did not. The results indicate that while asbestos had minimal acute effects on cytokine production by the human alveolar macrophage, intense, chronic exposure to asbestos leads to the enhanced basal release of significant amounts of several cytokines that have activity for the fibroblast, even in the absence of overt fibrosis.

Bleomycin stimulation of cytokine secretion by the human alveolar macrophage.

Bleomycin (BLM) is a very effective antineoplastic drug for many gynecologic and urinary tract carcinomas. However, its use, e.g., cumulative dosage, often is limited by the pulmonary fibrosis that it causes. The mechanism by which BLM causes fibrosis is not understood but is proposed to involve the pulmonary macrophage, a central cell in the cytokine network of the lung. To examine the direct effects of this drug on the human alveolar macrophage, we have treated human alveolar macrophages (isolated from normal subjects by bronchoalveolar lavage) with BLM in vitro and examined resultant macrophage secretory products that have importance for inflammatory and fibrotic processes. A 24-h treatment with BLM (0.5-100 mU/ml) was found to result in 1) a concentration-dependent decrease in the ability of the macrophage to produce superoxide anion in response to phorbol 12,13-dibutyrate, 2) an increase in secreted interleukin-1 beta (IL-1 beta), and 3) a decrease in intracellular levels of adenosine 3',5'-cyclic monophosphate. Kinetic studies revealed a time-dependent appearance of BLM-induced cytokines; tumor necrosis factor-alpha could be detected as early as 4 h after stimulation, followed by IL-1 beta at 8 h. The secretion of these cytokines was found to precede the release of prostaglandin E2, which became significant only at 24 h. Taken together, the present results imply that the human alveolar macrophage does not contribute to BLM-induced oxidant injury of the lung but that it may contribute to the development of BLM-induced pulmonary fibrosis.

In vitro bioactivity of asbestos for the human alveolar macrophage and its modification by IgG.

The alveolar macrophage (AM) is likely to play a central role in the initiation and development of the fibrosis associated with asbestos exposure due to its ability to produce factors that modulate cellular functions of the immune system of the lung. In this study, we examine the effects of IgG, albumin, and dipalmitoylphosphatidylcholine (DPPC), the major protein and lipid constituents of alveolar lining fluid, on the interaction between the human AM and chrysotile and crocidolite asbestos, silica, and aluminum beads. We show that both chrysotile and crocidolite asbestos, but not silica and aluminum beads, stimulate the human AM to produce superoxide anion. Preincubating chrysotile and crocidolite asbestos with IgG resulted in an enhancement of their ability to stimulate superoxide anion production. IgG subclasses were studied to determine the subclass specificity of this enhancing effect; on a molar basis, IgG1 was the most potent. After preincubation with IgG, both silica and aluminum also stimulated superoxide anion production to levels similar to the IgG-preincubated asbestos. When albumin and DPPC were included in the preincubation mixture, the IgG-mediated enhancement of superoxide anion production by asbestos was unaffected, while that of silica and aluminum was abolished. In summary, these results indicate that IgG can significantly enhance the bioactivity of particulates for human AM in vitro, and that chrysotile and crocidolite asbestos are unique in their ability to retain this enhancement in the presence of albumin and DPPC. These results are consistent with the suggestion that superoxide anion production by the AM may play an important role in the development of asbestosis.

Equilibrium binding of spin-labeled fatty acids to bovine serum albumin: suitability as surrogate ligands for natural fatty acids.

Electron paramagnetic resonance (EPR) and saturation transfer EPR (ST-EPR) spectroscopies were used to characterize the binding of spin-labeled fatty acid (SLFA) to bovine serum albumin (BSA). Association constants of three stearic acid derivatives labeled with a nitroxyl radical at C-5, C-12, or C-16 were estimated by EPR spectroscopy as the ratio of SLFA to BSA was increased from about 0 to 9. The values were compared to those for unmodified stearate. With all three SLFA, it was apparent that the nitroxyl residue modified the binding pattern. For SLFA:BSA ratios up to 1, which probably involves the site(s) on BSA most specific for long-chain FA, the C-16 derivative bound with an affinity similar to that of the natural FA. At higher ratios, the association constants for this SLFA were lower than those for stearate. The C-12 and C-5 derivatives showed only low-affinity binding relative to stearate. The spectral parameter, W, was constant for SLFA:BSA ratios between 0 and 1 in the case of C-16 compound, indicating physical homogeneity of the high-affinity binding site. At higher ratios, the spectra changed progressively, indicating inhomogeneity of the lower affinity binding sites although parallel changes in association constants were not observed. Changes in W due to Heisenberg spin exchange were ruled out. By examining the mobility profile of the bound SLFA by both EPR and ST-EPR techniques, it was shown that the nitroxyl group was maximally immobilized when attached near the center of the carbon chain of the bound SLFA.

Enhancement of free radical reduction by elevated concentrations of ascorbic acid in avian dystrophic muscle.

It has been postulated that the degenerative process in dystrophic muscle results from increased concentrations of free radicals, peroxides, or lipid hydroperoxides. Therefore, the reduction of the free radical tanol (2,2,6,6-tetramethyl-4-piperidinol-1-oxyl) by extracts of muscles of dystrophic and normal chickens was studied. Pectoral (white) and thigh (red) muscles were used. For initial rate measurements, the various muscle extracts were added to an equal volume of 0.2 mM tanol. Reaction mixtures were introduced into the EPR cavity in a standard aqueous flat cell. Rates were measured by continuously monitoring the decrease in signal amplitude of the center (MI = 0) solution tanol EPR resonance line (in-phase first harmonic absorption signal). With extracts from dystrophic white muscle, the reduction rate was 75% faster than normal, whereas in dystrophic red muscle extracts the rate was normal. This agreed with previous observations that white muscle is more severely affected than red in dystrophic chickens. The primary reductant was identified as reduced ascorbic acid, and the rate of reduction of tanol correlated directly with the concentrations of ascorbic acid in the various muscle extracts as shown by chemical analysis. The results suggest an involvement of the intracellular redox status in the pathogenesis of avian muscular dystrophy.

Laser stepedotomy for otosclerosis.

The argon laser microscope recently developed by the author is used to vaporize the stapes tendon, the posterior crus and a rosette of holes in the stapes footplate in the surgical treatment of otosclerosis. An autogenous vein--stainless steel piston assembly is used to reconstruct the stapes portion of the ossicular chain. The surgical technique and results in a preliminary series of 11 patients are reported. Rationale and advantages over conventional stapedectomy are discussed.

Electron paramagnetic resonance and saturation transfer electron paramagnetic resonance studies on erythrocytes from goats with and without heritable myotonia.

Erythrocytes from myotonic goats, an animal model of heritable myotonia, and normal goats were studied using electron paramagnetic resonance (EPR) and saturation transfer electron paramagnetic resonance (ST-EPR) spin labeling techniques. Three fatty acid spin labels with the nitroxide moiety at progressively greater distances from the carboxyl group were used to monitor different regions within the erythrocyte membrane. Since spin labels have been shown to induce hemolytic and morphologic alterations in erythrocytes, conditions for minimizing these alterations were first defined by hemolysis studies and scanning electron microscopy. Using these defined conditions for our studies we observed no significant differences in any of the EPR or ST-EPR parameters for normal and myotonic goat erythrocytes with any of the fatty acid spin labels used. Our results do not support the theory that myotonia is the result of a generalized membrane defect characterized by increased membrane fluidity as determined by fatty acid spin labels.

Erythrocyte membrane abnormalities in Duchenne muscular dystrophy monitored by saturation transfer electron paramagnetic resonance spectroscopy.

Saturation transfer electron paramagnetic resonance and the spin label 2-(3-carboxypropyl)-4,4-dimethyl-2-tridecyl-3-oxazolidinyloxyl were used to study erythrocytes from patients with Duchenne muscular dystrophy or Becker syndrome and from age-matched normal boys. There were significant differences in the spectral intensities of erythrocytes from Duchenne patients when compared to controls. Spectral intensities increased with time in the former; no such change was observed in the latter. Saturation transfer electron paramagnetic resonance spectra of erythrocytes from patients with Becker syndrome were significantly different from those from Duchenne patients but were not significantly different from normals. These observations suggest the possible usefulness of these techniques in the differential diagnosis of Duchenne muscular dystrophy. Spin label concentration spectral studies suggest that the observed spectral differences between Duchenne patients and controls were due to differential spin exchange phenomena.