Magnetic alginate microspheres: system for the position controlled delivery of nerve growth factor

The use of polymeric carriers containing dispersed magnetic nanocrystalline particles for targeted delivery of drugs in clinical practice has attracted the interest of the scientific community. In this paper a system comprised of alginate microparticles with a core of magnetite and carrying nerve growth factor (NGF) is described. The magnetic properties of these microspheres, typical of superparamagnetic materials, allow precise and controlled delivery to the intended tissue environment. Experiments carried out on PC12 cells with magnetic alginate microspheres loaded with NGF have confirmed the induction of cell differentiation which is strongly dependent on the distance from the microsphere cluster. In addition, finite element modelling (FEM) of the release profile from the microspheres in culture, indicated the possibility of creating defined and predictable NGF gradients from the loaded microspheres. These observations on the carriage and release of growth factors by the proposed microparticles open new therapeutic options for both neuronal regeneration and of the development of effective neuronal interfaces.     

18F-FDG-PET/CT to Select Patients with Peritoneal Carcinomatosis for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Background

Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with significantly longer survival in patients with peritoneal carcinomatosis (PC). So far, no morphological imaging method has proven to accurately assess the intra-abdominal tumor spread. This study was designed to predict tumor load in patients with PC using dual-modality ¹⁸FDG-PET/CT and to compare the results with those of PET and CT alone by correlating imaging findings with intraoperative staging.

Methods

Twenty-two patients with PC from gastrointestinal (n = 13), ovarian cancer (n = 8), and mesothelioma (n = 1) underwent contrast-enhanced ¹⁸FDG-PET/CT before surgery and HIPEC. In a retrospective analysis PET, CT, and fused PET/CT were separately and blindly reviewed for the extent of peritoneal involvement using the Peritoneal Cancer Index (PCI). Imaging results were correlated with the intraoperative PCI using Pearson’s correlation coefficient and linear regression analysis.

Results

There was a strong correlation between the PCI obtained with PET/CT and the surgical PCI with respect to the total score (r = 0.951) as well as in the regional analysis (small bowel, r = 0.838; other, r = 0.703). The correlation was slightly lower for CT alone (total score, r = 0.919; small bowel, r = 0.754; other, r = 0.666) and significantly lower (p = 0.002) for PET alone (total score, r = 0.793; small bowel, r = 0.553, other, 0.507).

Conclusions

Contrast-enhanced CT is superior compared with PET alone to predict the extent of PC. In our patient group, the combination of both modalities (contrast enhanced PET/CT) yielded the best results and proved to be a useful tool for selecting candidates for peritonectomy and HIPEC.     

A single institution experience with biochemical recurrence after radical prostatectomy for tumors that on pathology are of small volume or "insignificant"

ObjectiveSmall volume prostate cancers (<0.5 cc, svPC), and insignificant prostate cancers (<0.5 cc and Gleason scores <7, InsigPC) are considered clinically insignificant by some investigators. The aim of this study is to determine the biochemical recurrence rate (BCR) of svPC and InsigPC in prostatectomy specimens.MethodsIn total, 502 patients with prostate cancer, treated with radical prostatectomy (RP) between 1992 and 2005 and with detailed pathological classification, were included in the present study. Patients were postoperatively followed for a median period of 39.5 months (0.6–150). A total of 82 specimens (16.3%) with svPC including 64 (12.8%) with InsigPC were identified. BCR was defined as 2 consecutive PSA levels >0.10 ng/ml.ResultsIn the total group, the median age at the time of surgery was 62.7 years (42.4–73.4) and the median preoperative PSA level was 8.0 ng/ml. Patients with InsigPC had Gleason scores of 4 in 7%, 5 in 37%, and 6 in 56%. Positive surgical margins were identified in 13 (15.9%) svPC and in 8 (12.7%) InsigPC specimens. The 5-year risk of BCR for the svPC group and the insigPC group was 10% (95% CI 2–18%, 7 and 5 patients, respectively) vs. 35% (95% CI 29–41%) in the rest of the cohort (log rank P = 0.001).ConclusionPatients with svPC and patients with InsigPC have a significantly lower risk of BCR. However, even in this seemingly very favorable patient group, 1 in 10 patients will develop a BCR after RP. Therefore, new studies are needed to examine what the prognostic relevance is of small-volume tumors.     

Factors affecting nightmares in children: parents’ vs. children’s ratings

Objective  The present study investigated the relationship between daytime symptomatology and nightmare frequency in school-aged children by eliciting daytime symptoms and nightmare frequency from children directly in addition to questionnaires completed by their parents. Methods  A sample of 4,834 parents and 4,531 of their children (age range: 8–11 years) completed each a sleep questionnaire and the strengths and difficulties questionnaire (SDQ). Results  The results of the study clearly indicate that there is an underestimation of nightmare frequency in the parents’ ratings compared to the children’s data (effect size: d = 0.30) and the closeness between influencing factors and nightmare frequency is considerably higher for the data based on the children’s responses; the proportion of explained variance was twice as high. Conclusions  Therefore, it seems important for research and clinical practice to not to rely on parents’ information but to ask the children about the occurrence of nightmares.     

Improved spatial learning in aged rats by genetic activation of protein kinase C in small groups of hippocampal neurons

Age-related decline in human cognition is well known, and there are correlative changes in the function of neocortical and hippocampal neurons. Similarly, age-related decline in learning has been observed in rodents, including deficits in a hippocampal-dependent learning paradigm, the Morris water maze. Furthermore, there are correlative deficits in specific signaling pathways, including protein kinase C (PKC) pathways, in cerebellar, hippocampal, or neocortical neurons. PKC pathways are strong candidates for mediating the molecular changes that underlie spatial learning, as they play critical roles in neurotransmitter release and synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), and deletion of specific PKC genes results in deficits in learning. Conversely, genetic activation of PKC pathways in small groups of hippocampal or cortical neurons enhances learning in specific paradigms. In this study, the authors delivered a constitutively active PKC into small groups of hippocampal dentate granule neurons in aged rats (using a herpes simplex virus-1 vector). Aged 2-year-old rats that received the constitutively active PKC displayed improved performance in the Morris water maze relative to controls in three different measures. These results indicate that PKC pathways play an important role in mediating spatial learning in aged rats. Additionally, these results represent a system for studying the neural mechanisms underlying aging-related learning deficits, and potentially developing gene therapies for cognitive and age-related deficits.     

Effect of lung volume reduction surgery on resting pulmonary hemodynamics in severe emphysema

RATIONALE: To determine the effect of medical treatment versus lung volume reduction surgery (LVRS) on pulmonary hemodynamics. METHODS: Three clinical centers of the National Emphysema Treatment Trial (NETT) screened patients for additional inclusion into a cardiovascular (CV) substudy. Demographics were determined, and lung function testing, six-minute-walk distance, and maximum cardiopulmonary exercise testing were done at baseline and 6 months after medical therapy or LVRS. CV substudy patients underwent right heart catheterization at rest prerandomization (baseline) and 6 months after treatment. MEASUREMENTS AND MAIN RESULTS: A total of 110 of the 163 patients evaluated for the CV substudy were randomized in NETT (53 were ineligible), 54 to medical treatment and 56 to LVRS. Fifty-five of these patients had both baseline and repeat right heart catheterization 6 months postrandomization. Baseline demographics and lung function data revealed CV substudy patients to be similar to the remaining 1,163 randomized NETT patients in terms of age, sex, FEV(1), residual volume, diffusion capacity of carbon monoxide, Pa(O(2)), Pa(CO(2)), and six-minute-walk distance. CV substudy patients had moderate pulmonary hypertension at rest (Ppa, 24.8 +/- 4.9 mm Hg); baseline hemodynamic measurements were similar across groups. Changes from baseline pressures to 6 months post-treatment were similar across treatment groups, except for a smaller change in pulmonary capillary wedge pressure at end-expiration post-LVRS compared with medical treatment (-1.8 vs. 3.5 mm Hg, p = 0.04). CONCLUSIONS: In comparison to medical therapy, LVRS was not associated with an increase in pulmonary artery pressures.