Treatment of recurrent previously coiled anterior circulation aneurysm with minimally invasive keyhole craniotomy: report of two cases.

The use of minimally invasive techniques has not yet been reported for the treatment of recurrent aneurysms after coil embolization. A 47-year-old man with a long history of headaches had an anterior communicating aneurysm that had previously been coil embolized. Three-year follow-up angiography showed a significant recurrence. A 50-year-old woman with subarachnoid hemorrhage and acute visual loss underwent coil embolization of a large ophthalmic artery aneurysm, which recurred 3 months later. In both cases, a keyhole fronto-orbital one-piece craniotomy was performed. In the first patient, the aneurysm was clip ligated. The coil mass, which had eroded through the dome, was excised. In the second patient, the anterior clinoid was removed and the aneurysm was clip ligated. Postoperative angiography showed no residual aneurysm and no evidence of branch or parent vessel compromise in either patient. Both patients had an uncomplicated postoperative course. Recurrent previously coiled aneurysms are technically challenging to treat. A minimal fronto-orbital craniotomy provides a sufficiently capacious working space for successful treatment of some recurrent aneurysms of the anterior circulation.

Polar production of interleukin-8 by mesothelial cells promotes the transmesothelial migration of neutrophils: role of intercellular adhesion molecule-1.

Migration of polymorphonuclear neutrophils (PMNL) from the vascular compartment into the pleural space occurs rapidly during the development of parapneumonic effusions. This study investigated the polarized secretion of interleukin (IL)-8 in activated pleural mesothelial cells (PMC) and the migration of PMNL across resting, activated PMC monolayers. Results show that PMC produce IL-8 in a polar manner. When PMC were stimulated with Staphylococcus aureus or IL-1beta at the basal or at the apical surface, significantly (P< .05) more IL-8 was released toward the apical surface. This polarized production of IL-8 was confirmed by in situ hybridization. PMNL migration was higher from the basilar to apical than from the apical to basilar surface of PMC. Neutralizing antibodies against IL-8 and intercellular adhesion molecule (ICAM)-1 significantly (P< .001) blocked PMNL migration across activated monolayers. Thus, during pleural inflammation, PMC regulate the influx of PMNL into the pleural space by polar production of IL-8 and expression of ICAM-1.

Interferon enhances the activity of the anticancer ribonuclease, onconase.

Interferons (IFN) are biologic agents involved in the antiviral response and the inhibition of tumor growth. Biochemical pathways of IFN action include the double-stranded RNA-activated oligoadenylate synthetase, RNase L, and double-stranded RNA-dependent protein kinase (PKR). Extracellular ribonucleases, especially onconase, also display antiviral and antitumor properties and involve degradation of RNA. We find that IFN increases the anticancer activity of onconase. These two agents work synergistically, and the effect is seen at the level of translation probably because of the degradation of tRNA.

Skeletal muscle-specific immunotoxin for the treatment of focal muscle spasm.

Intramuscular injection of botulinum toxin type A (BTX) is used to treat many disorders characterized by muscular spasms. The utility of BTX, however, is limited by its short duration of action, the development of resistance after repeated injections, and cross-reactivity with autonomic neurons. To overcome these limitations, we engineered an immunotoxin (ITX) to damage skeletal muscle fibers selectively by chemically linking a monoclonal antibody against the nicotinic acetylcholine receptor to the toxin ricin. In vitro, the ITX was 20,000-fold more toxic to myotubes than myoblasts, consistent with the degree of acetylcholine receptor expression. The gastrocnemius muscles of 30 rats were unilaterally injected with a series of protein toxins at various concentrations and examined histopathologically 7 and 30 days later. ITX produced destructive myopathic changes at a dose 300-fold less than the maximum tolerated dose. Assessment of rat muscle strength after unilateral gastrocnemius injections showed that ITX was more effective and had a longer duration of action than BTX. ITXs may have potential for the treatment of involuntary muscle spasms.

Pleural mesothelial cell expression of C-C (monocyte chemotactic peptide) and C-X-C (interleukin 8) chemokines.

The arrival of inflammatory phagocytic cells, namely neutrophils and mononuclear phagocytes, in the pleural space is a hallmark of pleural inflammation. It is probable that the temporal arrival of cells is mediated via the release of chemotactic cytokines by activated mesothelial cells. We hypothesized that human pleural mesothelial cells activated by bacterial endotoxin lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta), or tumor necrosis factor-alpha (TNF-alpha) release cell-specific chemokines from the C-C and C-X-C family of chemokines, specifically monocyte chemoattractant protein 1 (MCP-1) and IL-8. We evaluated supernatants of stimulated mesothelial cells for biologic chemotactic activity for monocytes and neutrophils and quantitative antigenic protein levels for MCP-1 and IL-8. Expression of the proteins at mRNA level was tested via Northern blot analysis. We found that responses to LPS were significantly higher (P less than 0.05) than control supernatants of unstimulated mesothelial cells. Responses to IL-1 beta and TNF-alpha were significantly greater than those to LPS. Neutralization studies with specific rabbit anti-MCP-1 and IL-1 antibody demonstrated significant decreases in bioactivity for MCP-1 and IL-8, indicating that mesothelial cell-derived MCP-1 and IL-8 play a significant role in the chemotactic activity seen in stimulated mesothelial cell supernatants. On specific enzyme-linked immunosorbent assay testing, stimulated mesothelial cells produced significantly more MCP-1 and IL-8 when stimulated with IL-1 beta or TNF-alpha as compared to LPS. mRNA expression for MCP-1 peaked within 2 to 4 h following stimulation and was noted as early as 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Mesothelial cell modulation of pleural repair: thrombin stimulated mesothelial cells release prostaglandin E2.

Repair of an injured pleura without fibrosis not only requires a re-establishment of the normal pleural mesothelial monolayer but also a downregulation of the inflammatory response, including inhibition of fibroblast proliferation and collagen synthesis. However, the role of the mesothelial cell in regulating these processes in the pleural space remains undefined. We therefore hypothesized that mesothelial cells, stimulated by thrombin, release prostaglandin E2 PGE2, which is capable of inhibiting fibroblast proliferation. In vitro rat visceral mesothelial cells were exposed to thrombin and PGE2 levels in the supernatant were measured using a competitive radioimmunoassay. Our results demonstrated that mesothelial cells produce PGE2 in a dose- and time-dependent manner. In addition, both anti-thrombin 3 and indomethacin completely blocked the PGE2 released. Finally, conditioned media from thrombin-stimulated mesothelial cells inhibited fibroblast [3H]thymidine incorporation. These results demonstrate that the mesothelial cell is capable of contributing to the repair process of pleural injury by the release of a local factor such as PGE2.

Recruitment of inflammatory cells to the pleural space. Chemotactic cytokines, IL-8, and monocyte chemotactic peptide-1 in human pleural fluids.

Pleural effusions secondary to various diseases are associated with the presence of different inflammatory cells. The role of selective chemotactic cytokines in the recruitment of phagocytes to the pleural space is unclear. IL-8 and monocyte chemotactic peptide-1 (MCP-1) are recently described cytokines that are chemotactic for neutrophils and monocytes, respectively. We prospectively studied 63 patients, using strictly defined criteria for their selection. IL-8 concentrations were elevated in both empyema fluid (9.15 +/- 0.89 ng/ml) and parapneumonic effusions (4.7 +/- 0.697 ng/ml) when compared with pleural effusions secondary to other diseases. IL-8 levels were higher in empyema fluid than in parapneumonic effusions (p = 0.01). There was a significant correlation between IL-8 levels and the total numbers of neutrophils in empyema fluids (r = 0.80). Chemotactic activity for neutrophils was elevated in empyema fluid and the addition of IL-8 neutralizing serum decreased bioactivity by 32.22%. Malignant pleural effusions had the highest levels of MCP-1 (12.0 +/- 3.7 ng/ml) when compared with others. Cytology-positive pleural fluids (n = 10) had a higher level of MCP-1 than cytology-negative effusions (p = < 0.05). Malignant pleural fluid MCP-1 levels correlated (r = 0.70) with the absolute number of monocytes in the pleural fluid. Neutralization of monocyte chemotactic activity of malignant pleural fluid by specific neutralizing serum caused a 70.3% inhibition of bioactivity. Immunohistochemical staining of malignant pleural fluid localized antigenic MCP-1 to malignant cells. We conclude that both IL-8 and MCP-1 play major but not exclusive roles in the recruitment of neutrophils and monocytes from the vascular compartment to the pleural space.

Bridging the nursing research-practice gap through research utilization.

This article explores the gap that currently exists between nursing research and nursing practice. The aim is to promote the conversion of new knowledge into practical innovations. Barriers to research utilization in practice settings come from both the academic and clinical arenas. Innovative models and strategies are needed to overcome these barriers. The purposes and value of research utilization and the clinical and academic strategies that facilitate research are discussed. Supporting clinical studies are provided as exemplars.

Alcohol-induced inhibition of alveolar macrophage oxidant release in vivo and in vitro.

Alcohol consumption is known to predispose the host to more frequent and severe bacterial infections, suggesting that alcohol compromises the normal immune function of the lung. The pulmonary alveolar macrophage is the resident host defense cell in the lung and forms the first line of defense against invading microorganisms. One of the mechanisms whereby alveolar macrophages kill bacteria is by releasing toxic oxygen radical species, such as superoxide anion and hydrogen peroxide. We hypothesized that chronic alcohol consumption caused alveolar macrophage dysfunction leading to inhibition of oxidant production when stimulated. Our data demonstrate that alveolar macrophages harvested from alcohol-treated rats release significantly lower quantity (p < 0.05) of both superoxide anion and hydrogen peroxide when stimulated with several different types of stimuli including heat-killed Staphylococcus aureus, soluble immune complexes or phorbol myristate acetate. Pair-fed control rats who received isocaloric quantities of maltose dextrin in their diet to compensate for the alcohol were able to produce oxidants in equal quantities when stimulated, to rats who were fed a normal diet. Similar results were noted in vitro experiments when alveolar macrophages harvested from normal rats were incubated in vitro in alcohol-containing media and then stimulated with the aforementioned stimuli. Alveolar macrophages, which had been incubated in alcohol for 4 hr, showed significant decreases in their ability to produce superoxide anion. This defect was noticeable for a period up to 8 hr following removal of alveolar macrophages from the alcohol-containing media.(ABSTRACT TRUNCATED AT 250 WORDS)

Concentration dependence of transmission losses in UV-laser irradiated bovine alpha-, beta H-, beta L- and gamma-crystallin solutions.

Experiments with calf lens protein fractions in aqueous buffer solutions at room temperature showed that beta H-, beta L- and gamma-crystallin fractions became opaque following ultraviolet exposure at 308 nm, while the alpha-crystallin fraction remained transparent. Transmission loss, due to UV-irradiation, for all of the crystallin samples was studied in the concentration range of 0.1 mg/mL to 1.0 mg/mL, and for alpha- and gamma-crystallin, in the range up to 5 mg/mL. With increased concentrations of beta H-, beta L- and gamma-crystallin, the rate of opacification increased. However, with alpha-crystallin, the loss of transmission was negligible for all of the concentrations and irradiation times studied. Opacification of the crystallins was accompanied by formation of higher molecular weight insoluble proteins as detected by SDS-PAGE.

Mechanism of tetracycline-hydrochloride-induced pleurodesis. Tetracycline-hydrochloride-stimulated mesothelial cells produce a growth-factor-like activity for fibroblasts.

Intrapleural instillation of tetracycline hydrochloride (TCN) is an effective means of achieving pleural fibrosis. However, its mechanism of action remains unknown. To evaluate the hypothesis that TCN stimulates pleural mesothelial cells to release growth-factor-like activity for fibroblasts we performed the following experiments. Rat visceral pleural mesothelial cells were incubated with TCN at doses ranging from 0.01 microgram/ml to 100 mg/ml. The conditioned media (CM) were collected after incubation for 2 to 48 h. CM caused fibroblasts to increase incorporation of thymidine when compared with CM that was unexposed to TCN (p less than 0.05). This growth-factor-like activity continued to be produced by mesothelial cells for 48 h after removal of TCN from the medium. There was a dose-response relationship since increasing doses of TCN to as much as 1 mg/ml caused increasing production of growth-factor-like activity without mesothelial cell injury as measured by trypan blue exclusion. The growth factor activity was a competence-type activity. It coeluted with human PDGF at a molecular weight of 31,000. It was heat-stable (100 degrees C for 10 min) and sensitive to trypsin and papain but not to heat-inactivated trypsin. Addition of cycloheximide or actinomycin D inhibited its production. TCN did not have any direct effect on fibroblasts. Bleomycin CM did not contain growth-factor-like activity for fibroblasts. These data demonstrate that TCN stimulates mesothelial cells to release a growth-factor-like activity for fibroblasts. This phenomenon may play an important role in TCN-induced pleural fibrosis.

What is nursing research: evolving approaches to methods and content.

In addressing what constitutes nursing research in the 1990s, approaches to conducting nursing research and examples of studies are discussed in the context of historical forces. The early studies were characteristically educational in focus and quantitative by design. Nursing research has come a long way in regard to foci of the questions asked, diversity of approaches to knowledge development, and sophistication of research methods. Three approaches are described to illustrate the diversity in nursing research: quantitative, qualitative, and triangulation.

Analysis of photo-oxidized amino acids in tryptic peptides of calf lens gamma-II crystallin.

Insoluble and crosslinked proteins and increased pigmentation in the eye lens are features of aging and cataracts. Determining the amino acids which are involved in insolubilization, crosslinking and visible light scattering will shed light on the mechanisms by which cataracts form. Calf lens gamma-II crystallin was irradiated at 295 nm, digested and separated into tryptic peptides. Additional tryptic peptides were found in the digest of irradiated gamma-II which were not present in the dark control digest. These peptides were identified by amino acid sequencing and shown to correspond to expected tryptic fragments of the protein, indicating more facile digestion in the UV-irradiated protein than in dark controls. Amino acid analysis of the irradiated protein and peptides showed losses of histidine, methionine and cysteine residues as compared to control samples. Tryptophan, which is not detected by amino acid analysis, was also found to be reactive since losses in its fluorescence intensity were observed after irradiation. Some of the photochemically active amino acids had lower than expected responses in amino acid sequencing experiments. This suggested specific sites of photochemical activity in the various peptides. The evidence for peptide crosslinks is also discussed.