Non-viral delivery of interleukin-2 and soluble Flk-1 inhibits metastatic and primary tumor growth in renal cell carcinoma

Treatments for renal cell carcinoma, while promising, are still limited by toxicity and cost. In the hopes of finding a novel compound or combination, we developed a plasmid containing the genes for interleukin-2 (IL-2) and soluble vascular endothelial growth factor receptor 2 (msFlk1). The plasmid, p2CMVIL2/msFlk1, demonstrated similar in vitro transgene expression of IL-2 or msFlk1 compared to their single-agent counterparts. Subcutaneous tumor growth was significantly inhibited in the p2CMVIL2/msFlk1 group when delivered locally by the non-viral water soluble polymer, WSLP and exhibited a 50% increase in survival over glucose and single-agent controls. In vivo experimentation demonstrated that WSLP/msFlk1 decreased microvessel density in pCMVmsFlk1 and p2CMVIL2/msFlk1 treated groups. Furthermore, tumor-infiltrating lymphocytes expressing CD45RO and CD68 were increased within the tumor microenvironment upon p2CMVIL2/msFlk1 treatment. To determine the effects of p2CMVIL2/msFlk1 in an experimental RENCA lung metastases model, therapeutic DNA was delivered systemically following complexation with the angiogenic endothelial-targeting polymer PEI-g-PEG-RGD. The p2CMVIL2/msFlk1 treatment significantly reduced metastases by 56% over single-agent therapy and increased survival proportions by 50% over all groups. Our work clearly demonstrates that non-viral delivery of p2CMVIL2/msFlk1 can inhibit RENCA growth in a synergistic manner and may represent a new treatment for renal carcinoma.     

The time to onset and overall analgesic efficacy of rofecoxib 50 mg: a meta-analysis of 13 randomized clinical trials

OBJECTIVE: To determine the time to onset of analgesia of rofecoxib based on a patient-level meta-analysis of randomized, placebo-controlled, postoperative oral surgery pain studies. METHODS: A search on MEDLINE and of Merck data on file was conducted to identify studies that met the inclusion criteria. Meta-analysis inclusion criteria required that patients were treated with a single oral dose of rofecoxib 50 mg when they experienced moderate or severe pain after surgical extraction of > or = 2 third molars; study design involved patient randomization, double-blinding, and matching placebo, and onset data from individual patients were available. The meta-analysis of time to onset also required that studies used the two-stopwatch method. Eleven studies fulfilled the onset criteria and included patients who received a single dose of rofecoxib 50 mg (N = 1220) or placebo (N = 483). These studies were analyzed to determine time to onset of analgesia, time to perceptible pain relief, percentage of patients achieving onset of analgesia, and duration of analgesia. Six of the 11 studies included a nonselective nonsteroidal anti-inflammatory drug (N = 303) and were included in the onset meta-analysis for comparison. The meta-analysis of overall efficacy also required that data on total pain relief scores over 8 hours were available. Over-all effectiveness of analgesia was based on analysis of 13 studies involving 1330 rofecoxib patients and 570 placebo patients on the endpoints of total pain relief scores over 8 hours and patient global assessment of response to therapy at 24 hours. Eight of the 13 studies with a nonselective nonsteroidal anti-inflammatory drug comparator (N = 391) were included for the efficacy meta-analysis. RESULTS: Patient demographics and baseline characteristics were similar across treatment groups in each study. Median time to onset of analgesia for rofecoxib was 34 minutes (95% CI, 31-38 minutes), significantly faster than placebo, which did not achieve onset within the 4 hours the assessment was conducted (P < 0.001). Duration of analgesia for rofecoxib 50 mg was > 24 hours. Rofecoxib achieved a greater mean total pain relief score over 8 hours than placebo (17.4 versus 4.4; P < 0.001) and a greater patient response rate on patient global assessment of response to therapy at 24 hours than placebo (73% versus 16%; P < 0.001). Outcomes were similar between the rofecoxib group and the nonselective nonsteroidal anti-inflammatory drug group. CONCLUSION: In this meta-analysis of over 1200 rofecoxib-treated patients, a single dose of rofecoxib 50 mg demonstrated a rapid onset of analgesia in approximately half an hour combined with sustained effectiveness, supporting its use as a treatment of acute pain.     

The Correlation Between Lateral Bowing Angle of the Femur and the Location of Atypical Femur Fractures

This study is the first to report the use of data on incomplete atypical femur fracture (AFF) to evaluate the curvature of femur and explore the relationship between lateral femoral bowing angle (FBA) and AAF location. In this study, we obtained 17 cases of incomplete AFF and calculated the accurate lateral FBA and location ratio of the incomplete fracture. Incomplete fracture location was defined as a percentage (length from lesion to greater trochanter tip/entire femur length %; greater trochanter tip: 0 %; femoral condyles: 100 %). A lateral FBA of 7° was set as the point of demarcation. Eleven femurs had a lateral FBA ≤ 7° (group 1), with a median lateral FBA of 4.75° (IQR 2.5–5.9°) and a median of incomplete AFF location at 25.2 % (IQR 23.4–30.1 %). Another six femurs had a FBA > 7° (group 2) with a median of 1.8° (IQR 10.2–14.3°) and a median location at 47.7 % (IQR 38.6–54.5 %). There was a significant statistical difference in location (p < 0.05) between the two groups. The rate of BP use was 87.5 % in group 1 which was higher than 60 % in group 2. There was some degree of positive correlation between the bowing angle and location in simple linear regression (r ² = 0.549, p < 0.001, ß = 1.789). AAFs located in diaphysis were associated with large lateral FBA. On the other hand, AAFs located in subtrochanteric region were more commonly found in femurs with smaller lateral FBA. In conclusion, the degree of the FBA was associated with AFF location.     

Combination therapy of focused ultrasound and radio-frequency for noninvasive body contouring in Asians with MRI photographic documentation

Previous studies have shown that single or multiple treatments by focused ultrasound are effective and safe. However, most include focused ultrasound only and not radio-frequency treatment. There is paucity of magnetic resonance imaging (MRI) measurements and pictures in the literature. This study aimed to assess the efficacy, safety, and pain and satisfaction levels of the combination therapy of focused ultrasound and radio-frequency for improving body contours. Thirty-two Asian patients received 3 sequential treatments every 2 weeks in the abdominal region. Safety parameters and adverse events were recorded. The subjects’ pain and satisfaction levels were evaluated using a five-point Likert scale. Two patients underwent MRI study randomly. There was a mean reduction in circumference of 3.91?±?1.8 cm (p?≤?0.001). In MRI measurement, the average in fat thickness reduction was 21.4 and 25 % on the upper and lower abdomen, respectively. There were three mild and self-limited localized adverse events. The satisfaction survey showed that 71.9 % was satisfied with the results, while pain level evaluation showed that 90.5 % felt no pain. Combination therapy of focused ultrasound and radio-frequency for noninvasive body contouring is an effective, safe, and painless procedure in Asians. Although the change is minor compared to traditional surgical procedure, it is real, definite, and effective.     

Factors associated with depression and anxiety in patients with end-stage renal disease receiving maintenance hemodialysis

Objectives

To investigate anxiety, depression, and related factors in patients with end-stage renal disease (ESRD) receiving maintenance hemodialysis and provide a reference for the establishment of a healthier life for such patients.

Methods

A total of 81 patients were enrolled in the study. Qualified participants filled out self-rating anxiety scale (SAS) and depression self-assessment scale (SDS) questionnaires as well as assessments of health knowledge and health self-efficacy. Linear regression analysis was performed to relate demographic factors, lifestyle habits, and nutrition parameters to SDS and SAS score indices.

Results

The mean SAS and SDS score indices for the 81 patients were 52.96 and 46.71, respectively; 56 patients (69.1 %) had a depressive disorder (SDS score ≥ 50), and 31 patients (36.9 %) had anxiety symptoms (SAS score ≥ 50). SAS score index correlated with gender (p < .05) and history of alcohol use (p < .01), whereas SDS score index correlated with administration of erythropoietin (EPO) (p < .05) as well as gender and history of alcohol use.

Conclusion

History of alcohol consumption may predict less depressive symptoms and more anxiety among Chinese patients living in a northeastern Chinese city with ESRD. EPO administration may reduce anxiety in patients with ESRD. Female patients were more prone to anxiety, whereas males were more likely to show symptoms of depression. These factors should be evaluated by nephrologists treating patients with ESRD.     

Spontaneous regression of congenital corneal opacity

Graefe's Archive for Clinical and Experimental Ophthalmology - To determine the incidence of spontaneous regression of congenital corneal opacity (CCO) and identify clinical factors associated...