The PALM Technique: histological findings of masked phototherapeutic keratectomy on rabbit corneas

BACKGROUND: To compare the corneal healing response between conventional and phototherapeutic keratectomy through a masking agent, in rabbit corneas. METHODS: 24 adult rabbits underwent phototherapeutic keratectomy. Animals were divided in two groups: 12 received photoablation through a masking agent (PALM gel) and the remaining 12 received conventional phototherapeutic keratectomy of equal depth and served as control. Light and transmission electron microscopy was performed in specimens of both groups obtained: immediately after, four hours, one week, one, three and six months after treatment. RESULTS: Reepitheliazation was complete within five days in all eyes. Light and transmission electron microscopy did not reveal any differences of the healing process in the experimental eyes compared to the controls. CONCLUSION: Photoablation through the PALM technique did not result any evident alterations of the reepithelisation and stromal healing process

Prolastin, a pharmaceutical preparation of purified human α1-antitrypsin, blocks endotoxin-mediated cytokine release

BACKGROUND: α1-antitrypsin (AAT) serves primarily as an inhibitor of the elastin degrading proteases, neutrophil elastase and proteinase 3. There is ample clinical evidence that inherited severe AAT deficiency predisposes to chronic obstructive pulmonary disease. Augmentation therapy for AAT deficiency has been available for many years, but to date no sufficient data exist to demonstrate its efficacy. There is increasing evidence that AAT is able to exert effects other than protease inhibition. We investigated whether Prolastin, a preparation of purified pooled human AAT used for augmentation therapy, exhibits anti-bacterial effects. METHODS: Human monocytes and neutrophils were isolated from buffy coats or whole peripheral blood by the Ficoll-Hypaque procedure. Cells were stimulated with lipopolysaccharide (LPS) or zymosan, either alone or in combination with Prolastin, native AAT or polymerised AAT for 18 h, and analysed to determine the release of TNFα, IL-1β and IL-8. At 2-week intervals, seven subjects were submitted to a nasal challenge with sterile saline, LPS (25 μg) and LPS-Prolastin combination. The concentration of IL-8 was analysed in nasal lavages performed before, and 2, 6 and 24 h after the challenge. RESULTS: In vitro, Prolastin showed a concentration-dependent (0.5 to 16 mg/ml) inhibition of endotoxin-stimulated TNFα and IL-1β release from monocytes and IL-8 release from neutrophils. At 8 and 16 mg/ml the inhibitory effects of Prolastin appeared to be maximal for neutrophil IL-8 release (5.3-fold, p < 0.001 compared to zymosan treated cells) and monocyte TNFα and IL-1β release (10.7- and 7.3-fold, p < 0.001, respectively, compared to LPS treated cells). Furthermore, Prolastin (2.5 mg per nostril) significantly inhibited nasal IL-8 release in response to pure LPS challenge. CONCLUSION: Our data demonstrate for the first time that Prolastin inhibits bacterial endotoxin-induced pro-inflammatory responses in vitro and in vivo, and provide scientific bases to explore new Prolastin-based therapies for individuals with inherited AAT deficiency, but also for other clinical conditions

Laboratory demonstration of a prozone-like effect in HRP2-detecting malaria rapid diagnostic tests: implications for clinical management

Background: Malaria rapid diagnostic tests (RDTs) are now widely used for prompt on-site diagnosis in remote endemic areas where reliable microscopy is absent. Aberrant results, whereby negative test results occur at high parasite densities, have been variously reported for over a decade and have led to questions regarding the reliability of the tests in clinical use. Methods. In the first trial, serial dilutions of recombinant HRP2 antigen were tested on an HRP2-detectiing RDT. In a second trial, serial dilutions of culture-derived Plasmodium falciparum parasites were tested against three HRP2-detecting RDTs. Results: A prozone-like effect occurred in RDTs at a high concentration of the target antigen, histidine-rich protein-2 (above 15,000 ng/ml), a level that corresponds to more than 312000 parasites per L. Similar results were noted on three RDT products using dilutions of cultured parasites up to a parasite density of 25%. While reduced line intensity was observed, no false negative results occurred. Conclusions: These results suggest that false-negative malaria RDT results will rarely occur due to a prozone-like effect in high-density infections, and other causes are more likely. However, RDT line intensity is poorly indicative of parasite density in high-density infections and RDTs should, therefore, not be considered quantitative. Immediate management of suspected severe malaria should rely on clinical assessment or microscopy. Evaluation against high concentrations of antigen should be considered in malaria RDT product development and lot-release testing, to ensure that very weak or false negative results will not occur at antigen concentrations that might be seen clinically

Communities’ Development in CVEs and Sustaining Functions of On-line Tutorship

Abstract. The impact of Collaborative Virtual Environments (CVEs) on communities ’ development is a topic still rather unexplored. All the interaction processes mediated by these technological environments are characterised, from both psychosocial and discursive points of view, by absolutely new practices and by the absence of some communication features, typical of face-to face. The “Community of Practice ” model, allows us to analyse the growth of virtual communities along the construction of a shared repertoire, the involvement in a common enterprise and the sharing of a mutual engagement. Communities of practice use technology in social and material contexts, sharing meanings about the technology uses and peculiarities through a continuous negotiating process. The analysis is aimed at describing how a community of practice is established in a virtual world where both textual and graphical interactions are allowed. Conversational and quantitative results show: a) how the community of practice evolves over the time, b) the specificity of the interactions mediated by the virtual environment; c) the role of different participants in the management of discourse in interaction, with a detailed analysis of the on-line tutorship impact on the development of the community

Giuseppe Riva Carlo Galimberti (Eds.)

The impact of Collaborative Virtual Environments (CVEs) on communities&apos; development is a topic still rather unexplored. All the interaction processes mediated by these technological environments are characterised, from both psychosocial and discursive points of view, by absolutely new practices and by the absence of some communication features, typical of face-to face. The &quot;Community of Practice&quot; model, allows us to analyse the growth of virtual communities along the construction of a shared repertoire, the involvement in a common enterprise and the sharing of a mutual engagement. Communities of practice use technology in social and material contexts, sharing meanings about the technology uses and peculiarities through a continuous negotiating process

Clinical features and outcomes of plasma cell leukemia: a single-institution experience in the era of novel agents

Plasma cell leukemia (PCL) is a rare hematologic malignancy with aggressive clinical and biologic features. Data regarding its prognosis with the use of the novel agents, <em>i.e</em>., the immunomodulatory drugs thalidomide and lenalidomide, and the proteasome inhibitor bortezomib, are limited. We retrospectively reviewed clinical outcomes, response to therapy, and survival of 17 patients seen at the Penn State Hershey Cancer Institute since the availability of novel agents (2006-2011). Twelve patients had primary PCL (pPCL), and 5 second- ary PCL (sPCL). PCL was associated with aggressive clinicobiological features, such as high-risk cytogenetics, elevated serum beta-2-microglobulin and lactate dehydrogenase, International Staging System stage III, and rapid relapse after therapy. With the use of thalidomide, lenalidomide, and bortezomib in 53%, 53%, and 88% patients, respectively, median overall survival (OS) was 18 months in the whole group (95% confidence interval, 11-21 months), and 21 and 4 months in pPCL and sPCL, respectively (P=0.015). OS was inferior to that of 313 consecutive patients with multiple myeloma (MM) treated in the same period, even when compared with a subset of 47 MM with high-risk cytogenetics. Although our data are limited by the small sample size, we conclude that novel agents may modestly improve survival in patients with PCL, when compared to historical controls. Novel therapies do not seem to overcome the negative prognosis of PCL as compared with MM