Successful medical treatment of EBV smooth muscle tumor in a renal transplant recipient

Belingheri M, Comoli P, Locatelli F, Baldanti F, Martina V, Giani M, Ferraresso M, Cro L, Edefonti A, Ghio L. Successful medical treatment of EBV smooth muscle tumor in a renal transplant recipient.
Pediatr Transplantation 2010: 14:E101–E104. © 2009 John Wiley & Sons A/S. Abstract: EBV is associated with various malignancies in patients with acquired or induced immune impairment. EBV‐SMT is very uncommon in immunocompromised patients, and a kidney localization has been described only anecdotally. We report the case of a 17‐yr‐old kidney transplant recipient diagnosed as having an EBV‐SMT inside the renal graft, which was successfully managed by minimizing isolated immunosuppression.     

PLGA-dendron nanoparticles enhance immunogenicity but not lethal antibody production of a DNA vaccine against anthrax in mice

Dendriplexes, complexes of dendrons and condensed plasmids containing the gene for protective antigen (PA) of Bacillus anthracis, were encapsulated in poly-lactide-co-glycolide (PLGA) particles using the double emulsion method. The two dendrons employed are a dendron with three C(18) chains (C(18) dendron) and one with no attached hydrocarbon chains (the C(0) dendron). Three types of particles were examined, namely PLGA-C(18) dendriplexes, PLGA-C(0) dendriplexes and the control PLGA-naked DNA system. These were characterised by standard biophysical methods such as photon correlation spectroscopy (PCS) and scanning electron microscopy to select the complexes for in vivo testing. Three intramuscular immunizations were carried out using 14 microg of DNA per dose at weekly intervals in BALB/c mice. Antibodies against rPA were measured using ELISA. Results indicate that the PLGA-C(18) dendriplex particles produced superior levels of anti-PA IgG antibodies in comparison to animals immunized with the PLGA-C(0) dendriplex particles. The level of antibody production was dependent on the number of immunizations, higher antibody levels being measured after two booster vaccinations. However toxin neutralizing antibodies were absent in all treatment groups, and it is likely that the mice lack protection against lethal toxin and anthrax infection. Further studies are needed to optimize the formulation of DNA vaccines and increase the level of anti-lethal toxin antibodies and enhance their functionality.     

Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis

The Hedgehog (Hh) pathway has been implicated in pancreatic cancer but its role remains controversial. To delineate the cell populations able to respond to Hh ligand stimulation, we expressed an oncogenic allele of Smoothened (SmoM2) to cell autonomously activate Hh signaling in the mouse pancreas. Surprisingly, we found that expression of SmoM2 in epithelial cells was not able to activate the pathway and had no impact on pancreatic development or neoplasia. In contrast, activation of Smo in the mesenchyme led to Hh pathway activation, indicating that only the tumor stroma is competent to transduce the Hh signal. Using a Ptc-LacZ reporter mouse, we show that Hh signaling is active in stromal cells surrounding Hh-expressing tumor epithelium in various mouse pancreatic cancer models. Activation of the Hh pathway in the tumor stroma of human pancreatic and metastatic cancer specimens was confirmed by quantitative RT-PCR of microdissected tissue samples. These data support a paracrine model of Hh-mediated tumorigenesis, in which tumor cells secrete Hh ligand to induce tumor-promoting Hh target genes in adjacent stroma.     

Biocompatibility of natural latex implanted into dental alveolus of rats

The present study investigated the biocompatibility of a biopolymer based on vegetable latex extracted from the Hevea brasiliensis rubber tree, implanted into the bony alveolar cavity after dental extraction in rats. A granule of latex (area = 0.25 +/- 0.04 mm(2)) was implanted inside the alveolus immediately after extraction of the upper right incisor, and the animals were sacrificed 7, 21 and 42 days after the procedure. The hemi-maxillas were decalcified and processed for embedding in paraffin to obtain semi-serial longitudinal sections 5 mum thick, and then stained with hematoxylin-eosin. The latex granule was observed in the cervical third of the alveolus without any foreign body reaction, or persistence of the initial acute inflammatory reaction. Bone repair in the areas adjacent to the material was quantified, and a decrease was noted in the thickness of the fibrous capsule surrounding the implants from 92.8 +/- 9.3 microm on day 7 to 9.4 +/- 1.8 microm on day 42 (ANOVA, P = 0.01). The quantitative data confirmed acceleration of bone formation (statistically significant at 5%) in parallel with a decrease of connective tissue in the areas around the implants. These results show that the tested material is biologically compatible, and progressively integrated into the alveolar bone, simultaneously accelerating bone formation and playing an important role in the healing process.     

The nature of hope in hospitalized chronically ill patients

BACKGROUND: Hope as a universal human phenomenon has been studied from various perspectives often conceptualized as having a unified set of attributes. In this study however hope is viewed to be experienced by people in various patterns structured by different orientations and emphases depending upon their life circumstances. There is a paucity of studies in the literature examining patterns of hope experienced by people in chronic illness or in special life circumstances. OBJECTIVES: The aim of this study was to discover patterns of hope in hospitalized chronically ill patients and to identify the major threads that structure various patterns of hope experienced by them. DESIGN: Q-methodology, which is an approach designed to discover patterns in various subjective experiences, was used as the method for data collection and theory generation. Q-methodology involves five steps in its approach, the first two as the first phase and the last three as the second phase. The study was carried out at a general acute-care, tertiary hospital in a New England state in the US. The study obtained data from a convenient sample of 12 chronically ill patients and 16 oncology nurses for the first phase, and a different convenient sample of 20 chronically ill patients for the second phase. RESULTS AND CONCLUSIONS: Five patterns of subjective experiences of hope emerged as: (a) externalism orientation, (b) pragmatism orientation, (c) reality orientation, (d) future orientation, and (e) internalism orientation. This means that chronically ill patients experience hope in various ways by focusing on different dimensions of meaning, suggesting the conceptualization of hope as a unitary construct may not reflect people's experiences of hope accurately. The major implication of the study is to rethink ways to assess patients' hope in terms of pattern differences rather than in terms of quantity.     

Evaluation of Temperature-Sensitive,Indocyanine Green-Encapsulating Micelles for Noninvasive Near-Infrared Tumor Imaging

Purpose  

Indocyanine green (ICG), an FDA-approved near infrared (NIR) dye, has potential application as a contrast agent for tumor detection. Because ICG binds strongly to plasma proteins and exhibits aqueous, photo, and thermal instability, its current applications are largely limited to monitoring blood flow. To address these issues, ICG was encapsulated and stabilized within polymeric micelles formed from the thermo-sensitive block copolymer Pluronic F-127, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), to increase the stability and circulation time of ICG.     

Perspective: Imaging-based observational databases for clinical problem solving: the role of informatics

Imaging has become a prevalent tool in the diagnosis and treatment of many diseases, providing a unique in vivo, multi-scale view of anatomic and physiologic processes. With the increased use of imaging and its progressive technical advances, the role of imaging informatics is now evolving—from one of managing images, to one of integrating the full scope of clinical information needed to contextualize and link observations across phenotypic and genotypic scales. Several challenges exist for imaging informatics, including the need for methods to transform clinical imaging studies and associated data into structured information that can be organized and analyzed. We examine some of these challenges in establishing imaging-based observational databases that can support the creation of comprehensive disease models. The development of these databases and ensuing models can aid in medical decision making and knowledge discovery and ultimately, transform the use of imaging to support individually-tailored patient care.     

Conducting multisite research studies in nursing education: brief practice of CPR skills as an exemplar

Few large, multisite studies have been conducted in nursing education, and literature pertaining to conducting those studies is lacking. We recently completed a randomized trial to examine the effects of brief practice on nursing students' retention of CPR psychomotor skills. The purpose of this article is to describe strategies for implementing a multisite study in nursing education, using our research as an exemplar. Strategies are presented for structuring a multisite study; selecting, preparing, and communicating with team members across sites; selecting sites; recruiting and retaining participants; managing the technical aspects of an intervention; and collecting and managing data. Ethical considerations also are explored.     

Cathepsin B-sensitive polymers for compartment-specific degradation and nucleic acid release

Degradable cationic polymers are desirable for in vivo nucleic acid delivery because they offer significantly decreased toxicity over non-degradable counterparts. Peptide linkers provide chemical stability and high specificity for particular endopeptidases but have not been extensively studied for nucleic acid delivery applications. In this work, enzymatically degradable peptide-HPMA copolymers were synthesized by RAFT polymerization of HPMA with methacrylamido-terminated peptide macromonomers, resulting in polymers with low polydispersity and near quantitative incorporation of peptides. Three peptide-HPMA copolymers were evaluated: (i) pHCathK(10), containing peptides composed of the linker phe-lys-phe-leu (FKFL), a substrate of the endosomal/lysosomal endopeptidase cathepsin B, connected to oligo-(L)-lysine for nucleic acid binding, (ii) pHCath(D)K(10), containing the FKFL linker with oligo-(D)-lysine, and (iii) pH(D)Cath(D)K(10), containing all (D) amino acids. Cathepsin B degraded copolymers pHCathK(10) and pHCath(D)K(10) within 1 h while no degradation of pH(D)Cath(D)K(10) was observed. Polyplexes formed with pHCathK(10) copolymers show DNA release by 4 h of treatment with cathepsin B; comparatively, polyplexes formed with pHCath(D)K(10) and pH(D)Cath(D)K(10) show no DNA release within 8 h. Transfection efficiency in HeLa and NIH/3T3 cells were comparable between the copolymers but pHCathK(10) was less toxic. This work demonstrates the successful application of peptide linkers for degradable cationic polymers and DNA release.