Placebo-controlled study of montelukast and budesonide on short-term growth in prepubertal asthmatic children

BACKGROUND: Inhaled corticosteroids and anti-leukotriene agents are widely used in the treatment of pediatric asthma. Although data on the effect of corticosteroids on growth are available, there are few such data on anti-leukotriene agents. The aim of this study was to assess the influence of montelukast on short-term lower leg growth rate (LLGR) in prepubertal children with asthma. METHODS: Forty-two boys (6- to 12-year old) and 29 girls (6- to 11-year old) with mild asthma were randomized to 1 of 2 crossover arms, with two treatment sequences per arm: montelukast 5 mg once daily/placebo or inhaled dry powder budesonide 200 microg twice daily/placebo. Budesonide was used as a positive control to ensure that the method was sensitive enough to detect a suppression of LLGR. The 3-week double-blind treatment period was followed by a 3-week washout. Primary outcome was LLGR over the 3-week treatment, measured by knemometry. RESULTS: Ninety-four percent of patients completed the study. Mean LLGR was similar between patients receiving montelukast and placebo treatments: mean difference, -0.02 mm/week [95% confidence interval -0.14, 0.11]. Mean LLGR in patients receiving budesonide was significantly less than for those receiving placebo (difference of -0.16 mm/week [-0.25, -0.06], P = 0.002). Mean LLGR was similar for patients taking placebo in the two arms (0.43 and 0.44 mm/week). CONCLUSION: Montelukast 5 mg did not significantly affect short-term LLGR in prepubertal children.     

Reinstatement of conditioned responses in human differential fear conditioning

The present study aimed at investigating reinstatement of conditioned responding in human classical conditioning using a differential fear conditioning paradigm. Reinstatement is defined as the return of extinguished conditioned responses due to the experience of one or more unexpected USs. As expected the reinstatement group showed reinstatement of US-expectancy while a similar return of conditioned responses was not present in the control group. In the fear ratings a similar pattern was observed. In addition, and in line with previous findings, we found that the more negative the CS+ remained after extinction, the more return of conditioned responding was observed. Clinical implications and suggestions for further research are discussed.     

Diffusion of Surgical Techniques in Early Stage Breast Cancer: Variables Related to Adoption and Implementation of Sentinel Lymph Node Biopsy

Background Understanding how physicians acquire and adopt new technologies for cancer diagnosis and treatment is poorly understood, yet is critical to the dissemination of evidence-based practices. Sentinel lymph node biopsy (SLNB) has recently become a standard technique for axillary staging in early breast cancer and is an ideal platform for studying medical technology diffusion. We sought to describe the timing of SLNB adoption and patterns of surgeon interactions with the following educational sources: local university training program, surgical literature, national meetings/courses, national specialty centers, and other local surgeons. Methods A cross-sectional survey that used semistructured interviews was used to assess timing of adoption, practice patterns, and learning sources for SLNB among surgical oncologists and general surgeons in a single metropolitan area. Results A total of 44 eligible surgeons were identified; 38 (86%) participated. All surgical oncologists (11 of 11) and most general surgeons (26 of 27) had implemented SLNB. Surgical oncologists were older (mean 51 vs. 48 years, P = .02) and had used SLNB longer (6.1 vs. 3.3 years, P = .01) than general surgeons. By use of social network diagrams, surgical oncologists and the university training program were shown to be key intermediaries between general surgeons and national specialty centers. Surgeons in group practice tended to use more learning sources than solo practitioners. Conclusions Surgical oncologists and university-based surgeons play key educational roles in disseminating new cancer treatments and therefore have a professional responsibility to educate other community physicians to increase the use of the most current, evidence-based practices.     

Synthesis and in vitro antiplatelet activity of new 4-(1-piperazinyl)coumarin derivatives. Human platelet phosphodiesterase 3 inhibitory properties of the two most effective compounds described and molecular modeling study on their interactions with phosphodiesterase 3A catalytic site

The synthesis and in vitro antiplatelet activity significant data of coumarin derivatives 5i-x and quinolin-2(1H)-one derivatives 22a,b, as well as the corresponding structure-activity relationships are described. The recently reported 8-methyl-4-(1-piperazinyl)-7-(3-pyridylmethoxy)coumarin 5f and its potent 7-(2-morpholinoethoxy)-substituted new analogue 5u were notably more effective inhibitors of pure human platelet PDE3 than milrinone and cilostazol: these data were related, through a molecular modeling study, with the molecular interactions of the four compounds with the human PDE3A catalytic site.     

Antioxidant activity of indigo and its preventive effect against ethanol-induced DNA damage in rat gastric mucosa

Ethanol-induced oxidative damage is commonly associated with the generation of reactive oxygen molecules, leading to oxidative stress. Considering that antioxidant activity is an important mechanism of action involved in cytoprotection, the aim of this work was to evaluate the antioxidant properties of the alkaloid indigo (1) (2 mg/kg, P. O.), obtained from the leaves of Indigofera truxillensis Kunth (Fabaceae), on rat gastric mucosa submitted to ethanol-induced (100%, 1 mL, P. O.) gastric ulcer. Enzymatic assays and DNA fragmentation analysis were performed. When ethanol was administered to the control group, the sulfhydryl content (SH) and the glutathione peroxidase (GPx) activity decreased by 41% and 50%, respectively; in contrast, superoxide dismutase (SOD) and glutathione reductase (GR) activities increased by 56% and 67%, respectively. Additionally, myeloperoxidase (MPO) activity, a marker for free radical generation caused by polymorphonuclear neutrophil (PMN) tissue infiltration, also increased 4.5-fold after ethanol treatment. Rat gastric mucosa exposed to ethanol showed DNA fragmentation. Indigo alkaloid pretreatment protected rats from ethanol-induced gastric lesions. This effect was determined by the ulcerative lesion area (ULA), indicating an inhibition of around 80% at 2 mg/kg. This alkaloid also diminished GPx activity, which was higher than that observed with ethanol alone. However, this effect was counterbalanced by increased GR activity. Indigo was unable to restore alterations in SOD activity promoted by ethanol. After indigo pretreatment, SH levels and MPO activity remained normal and gastric mucosa DNA damage caused by ethanol was also partially prevented by indigo. These results suggest that the gastroprotective mechanisms of indigo include non-enzymatic antioxidant effects and the inhibition of PMN infiltration which, in combination, partially protect the gastric mucosa against ethanol-induced DNA damage.     

Pharmacokinetics and tumor uptake of a derivatized form of paclitaxel associated to a cholesterol-rich nanoemulsion (LDE) in patients with gynecologic cancers

Objective: A cholesterol-rich nanoemulsion termed LDE concentrates in cancer tissues after injection into the bloodstream. The association of a derivatized paclitaxel to LDE showed lower toxicity and increased antitumoral activity as tested in a B16 melanoma murine model. Here, the pharmacokinetics of LDE–paclitaxel oleate and the ability of LDE to concentrate the drug in the tumor were investigated in patients with gynecologic cancers. Methods: Either LDE–paclitaxel oleate doubly labeled with [¹⁴C]-cholesteryl oleate and [³H]-paclitaxel oleate or [³H]-paclitaxel-cremophor was intravenously injected into eight patients. Blood samples were collected over 24 h to determine the plasma decay curves. Fractional clearance rate (FCR) and pharmacokinetic parameters were calculated by compartmental analysis. Also, specimens of tumors and the corresponding normal tissues were excised during the surgery for radioactivity measurement. Results: The LDE and paclitaxel oleate FCR were similar (0.092 ± 0.039 and 0.069 ± 0.027 h⁻¹, respectively, n = 5, P = 0.390). FCR of paclitaxel oleate associated to LDE was smaller than that of paclitaxel-cremophor (0.231 ± 0.128 h⁻¹, P = 0.028). Paclitaxel oleate T _1/2 and AUC were greater than those of paclitaxel-cremophor (T _1/2 = 14.51 ± 3.23 and 6.62 ± 2.05 h and AUC = 2.49 ± 0.35 and 1.26 ± 0.40, respectively, P = 0.009, P = 0.004). The amount of paclitaxel and LDE-radioactive labels in the tumor was 3.5 times greater than in the normal tissues. Conclusion: Paclitaxel oleate associated to LDE is stable in the bloodstream and has greater plasma half-life and AUC than those for paclitaxel-cremophor. LDE concentrates 3.5 times more paclitaxel in malignant tissues than in normal tissues. Therefore, association to LDE is an interesting strategy for using paclitaxel to treat gynecologic cancers.     

Platelet activation by collagen is increased in retinal vein occlusion

Retinal vein occlusion (RVO) is the most common retinal vascular disorder second to diabetic retinopathy. The main risk factors in patients with RVO are hypertension, diabetes, hyperlipidemia, increased blood viscosity and glaucoma. The pathogenesis of RVO has not yet been clarified. In these events platelets could play a very important role. In the present study the platelet response to collagen was deeply investigated. Experiments were carried out on a selected group of RVO patients, which were compared to a group of healthy subjects matched for age, sex, clinical and metabolic characteristics. In resting and activated platelets of both groups of subjects p72syk phosphorylation, phospholipase Cgamma2 phosphorylation, protein kinase C activation, intra-cellular calcium levels and nitric oxide formation were measured. Results show that platelets of patients were more responsive to collagen or ADP than healthy subjects and that the response was significantly different (p < 0.0005) at low concentrations of these agonists. In platelets of patients stimulated with collagen increased phosphorylation of p72syk and phospholipase Cgamma2 was found. Also protein kinase C was more activated in patients. In addition intracellular calcium rise induced by collagen was significantly higher in patients than in healthy subjects. RVO patients showed a lower basal level of nitric oxide both in resting and stimulated platelets compared to healthy subjects. Altogether these results suggest that the platelet hyperaggregability described in patients might be an important factor in the development of RVO contributing to the thrombogenic effects.     

Polylactide/Perfluoropolyether Block Copolymers: Potential Candidates for Protective and Surface Modifiers

Perfluoropolyethers are a well known and widely used family of polymers, suitable as protectives. Their main drawback is the lack of solubility, which is complete only in chlorofluorocarbons. In this work a series of A‐B‐A block copolymers (FluoPLA), with a relative low molecular weight, were prepared by ROP of L ‐ and D ,L ‐lactide (PLA) in the presence of a hydroxy‐terminated perfluoropolyether as macroinitiator. In fact the use of block copolymers leads to different advantages, i.e. a limited segregation phenomena and higher polymer solubility. The resulting polymers were characterized (by NMR, IR, HPLC‐SEC, DSC, LS) and tested as potential protective and surface modifiers for cultural heritage (ESEM‐EDS, solar‐box technique, colorimeter analysis).

     

Comparison between resorbable plates vs. titanium plates for treatment of zygomatic fractures: a systematic review with meta-analysis

Purpose

To compare resorbable plates with titanium plates for the fixation of zygomatic fractures, taking into account postoperative complications.

Methods

This systematic review followed the guidelines of PRISMA and the recommendations of the Cochrane Handbook and was registered in PROSPERO. The electronic search was performed in the Web of Science, PubMed, Virtual Health Library, and Cochrane Library databases and in the gray literature. The study selection and the data extraction were performed by three calibrated and independent researchers. The assessment of the risk of bias in the studies was performed using the Cochrane Risk of Bias Tool for clinical trials. Meta-analyses were performed using Review Manager Software version 5.3, using the Peto’s Odds Ratios (PORs), and when I² > 30, the random effect model was used. The evaluation of the quality of the evidence was carried out through GRADE.

Results

A total of 2651 studies were screened and only nine were included; 7 of which were used for quantitative assessment. The follow-up time for patients ranged from 6 months to 5 years. All studies showed a low risk of bias in the “incomplete outcome data” domain. The need for plate removal (POR: 0.11, 95% CI: 0.02 to 0.81, I² = 0%) and dehiscence (POR 0.12, 95% CI 0.02 to 0.63, I² = not applied) was lower for the group of patients who used resorbable plates than for titanium plates.

Conclusion

There was no difference in the occurrence of infection, diplopia, or paresthesia between the fixation methods. Resorbable plates showed better postoperative clinical performance.

     

Teaching two boys with autism spectrum disorders to request the continuation of toy play using an iPad®-based speech-generating device

We evaluated a set of instructional procedures for teaching two nonverbal boys with autism spectrum disorders (ASD) to request the continuation of toy play using an iPad^®-based speech-generating device (SGD). The effects of the instructional procedures were evaluated in a multiple baseline across participants design. Instruction focused on teaching the boys to select a TOY PLAY symbol from the iPad^® screen when their toy play was briefly interrupted. The instructional procedures included behavior chain interruption, time delay, graduated guidance, and differential reinforcement. Results showed that both boys learned to use the SGD to request and maintained this skill without prompting. SGD-based requesting also generalized to other objects/activities. Acquisition of SGD-based requesting was associated with decreases in reaching and aggressive behavior. Results suggest that systematic instruction with the iPad^®-based SGD effectively replaced reaching and aggression with socially acceptable communication.