The ocular tolerability of a new ophthalmic drug delivery system (NODS)

In an open label, two period cross-over study we compared the ocular tolerability of NODS vs. Isopto-Naturale^R eye drops. Thirty healthy volunteers were asked to rate the application system they were using for ocular discomfort, utilizing a visual analog scale in which 100=no ocular discomfort and 0=severe ocular discomfort. In addition each subject had to answer a questionaire and underwent a full ophthalmic control before, at day 7, at day 14 and at day 21 of the study. Each application form had to be applied to one eye only once a day for 7 days, followed by a washout period of 1 week. The type of application form was then changed and again had to be applied to one eye only for 7 consecutive days, followed by a final ophthalmic examination. The mean irritation score was recorded at day 7 and at day 21 of the study. Volunteers had no history of eye disease, no acute pathology of the eye, no contact lenses, no conditional foreign body of the cornea within the last four weeks prior to the study or within the study, no local therapy, no systemic therapy, no diabetes, no pregnancy. Informed consent was obtained. At day 1 one of the two application forms was given to each volunteer in a randomized order. 29 volunteers finished the protocol (16 male, 13 female); mean age: 26 years (range 20–32 years). The mean irritation score of NODS: 35 (2-81); the mean irritation score of Isopto-Naturale^R: 80.4 (45.5–99). The difference of mean irritation score (NODS vs. Isopto-Naturale^R): 46.7 (3.3–82.1) (p<0.01). The results of the study indicate that in healthy volunteers NODS are not as well tolerated as conventional eye drops when compared for ocular discomfort. However, the chance of applying drugs without preservatives and the possibility of increasing the rate of bioavailability from the new route (NODS) as well as the proportionally reduced risk to the patient of systemic side effects after NODS application of any type of drugs should be taken into consideration.     

生长抑素类似物对肝癌细胞凋亡及c-myc蛋白表达的影响

目的　探讨生长抑素类似物 8肽 (SS 8)对人原发性肝癌细胞凋亡和c myc蛋白表达的影响。 方法　体外培养肝癌细胞SMMC 772 1 ,用 1 0 μg/mlSS 8处理后 ,流式细胞仪检测肝癌细胞凋亡率和c myc蛋白的表达。 结果　与对照组相比 ,SS 8使实验组S期和G2 /M期细胞数减少、G0 /G1 期细胞数增加 ,两组细胞的凋亡率分别为 6 .1 %和1 4 .2 % ,差异有显著性意义 (P<0 .0 5)。经SS 8作用 2 4h后 ,实验组c myc蛋白表达水平为 0 .833± 0 .0 35 ,与对照组相比差异无显著性意义 (P>0 .1 0 ) ,而在SS 8作用 48、72、96、1 2 0和 1 4 4h后 ,实验组c myc蛋白表达水平分别为 0 .81 8±0 .0 4、0 .72 1± 0 .0 2 9、0 .669± 0 .0 2 6、0 .648± 0 .0 4 5和 0 .642± 0 .0 2 8,较对照组显著降低 (P<0 .0 5)。结论　SS 8有诱导肝癌细胞SMMC 772 1凋亡和降低c myc蛋白表达的作用     

Effect of tamsulosin on the number and intensity of ureteral colic in patients with lower ureteral calculus

BACKGROUND: We aimed to objectively determine whether tamsulosin as an alpha(1)-blocker was effective in patients who had ureterolithiasis located in the lower part of the ureter. METHODS: Sixty patients with lower ureteral calculi (juxtavesical or intramural portion) were included in the present study. Conservative treatment, such as hydration and tenoxicam as a non-steroidal anti-inflammatory drug, was given to group 1 (30 patients). Group 2 (30 patients) was given tamsulosin (0.4 mg daily) in addition to the conservative treatment. All patients were followed up and questioned about the numbers and intensity of ureteral colic, and the rates of spontaneous passage after the procedure. RESULTS: Spontaneous passage was observed in 22 of the 30 patients in group 1 (73.3%) and 26 of the 30 patients in group 2 (86.6%). The difference within groups 1 and 2 was not significant (P=0.196). The difference between both groups was not statistically significant either, with the stone diameter being 6 mm (P=0.635) or >6 mm (P=0.407). As group 1 patients were passing their stones, they had more ureteral colic episodes than group 2 patients. This difference was statistically significant and correlated well with the administration of tamsulosin (P=0.038). Group 1 patients reported higher scores according to a visual analog scale than group 2 patients. Also, this difference was statistically significant (P=0.000). CONCLUSIONS: We think that the treatment of alpha(1)-blockers decreased the number of ureteral colic episodes and the intensity of pain during spontaneous passage at the lower ureteral calculi. Also, it will be beneficial to patients' quality of life.     

Visual analog scales can assess the severity of rhinitis graded according to ARIA guidelines

BACKGROUND: The allergic rhinitis and its impact on asthma (ARIA) guidelines provide a new classification of allergic rhinitis, but a quantitative analysis for severity assessment is lacking. OBJECTIVE: To study whether a visual analog scale (VAS) for global rhinitis symptoms could be used to assess the disease severity according to ARIA. METHODS: Three thousand fifty-two allergic rhinitis patients seen in primary care were tested. Fifty three per cent had an objective diagnosis of allergy and 58% of the patients were treated. Patients were categorized according to ARIA guidelines. The severity of nasal symptoms was assessed using a VAS. Quality of life was measured using the rhinoconjunctivitis quality of life questionnaire (RQLQ). RESULTS: Severity had more impact on VAS levels than duration: mild intermittent rhinitis (3.5, 2.4-5.0 cm), mild persistent rhinitis (4.5, 3.2-5.6 cm), moderate/severe intermittent rhinitis (6.7, 5.3-7.7 cm) and moderate/severe persistent rhinitis (7.2, 6.1-8.2 cm). The receiver operating characteristic curve results showed that patients with a VAS of under 5 cm could be classified as 'mild' rhinitis (negative predictive value: 93.5%) and those with a VAS of over 6 cm as 'moderate/severe' rhinitis (positive predictive value: 73.6%). Receiver operating characteristic curves and a logistic regression showed that current treatment and allergy diagnosis have no effect on the assessment of rhinitis severity using VAS. Visual analog scale and the RQLQ global score were significantly correlated (rho = 0.46; P < 0.0001). CONCLUSION: A simple and quantitative method (VAS) can be used for the quantitative evaluation of severity of allergic rhinitis.     

Curcumin analog B14 has high bioavailability and enhances the effect of anti‐breast cancer cells in vitro and in vivo

Curcumin has a variety of anticancer properties, but low bioavailability prevents its use in chemotherapeutic applications. To address this problem, we tested the efficacy of the synthetic curcumin analog B14 in breast cancer cells and explored the mechanism by which B14 inhibits proliferation and metastasis of breast cancer cells. We used the breast cancer cell line MCF‐7, MDA‐MB‐231 to study the anticancer effects of B14 and assessed cell viability, cell migration and invasion, cell cycle, and apoptosis, in addition, the antitumor effect of B14 in vivo was examined in mice bearing MDA‐MB‐231 cells. We found that, as the concentration of B14 increased, cell viability decreased in a dose‐dependent manner. Compound B14 exerted the best antitumor activity and selectivity for MCF‐7 and MDA‐M‐231 cells (IC₅₀ = 8.84 μmol/L and 8.33 μmol/L, respectively), while its IC₅₀ value for MCF‐10A breast epithelial cells was 34.96 μmol/L. B14 has been shown to be a multi‐targeted drug that alters the expression of cyclin D1, cyclin E1, and cyclin‐dependent kinase 2 (CDK2), and ultimately induces G1 phase cell cycle arrest. At the same time, B14 activates the mitochondrial apoptosis pathway in breast cancer cells. Furthermore, B14 was more effective than curcumin in inhibiting cell migration, invasion, and colony formation. In tumor‐bearing mice, analog B14 significantly reduced tumor growth and inhibited cell proliferation and angiogenesis. The pharmacokinetic test found that B14 was more stable than curcumin in vivo. Our data reveal the therapeutic potential of the curcumin analog B14 and the underlying mechanisms to fight breast cancer cells.     

视觉模拟量表和语言评价量表用于术后疼痛评估的比较

目的探讨是否可以使用简单的语言评价量表代替视觉模拟量表进行手术后疼痛的评估。方法将美国麻醉医师协会(ASA)Ⅰ -Ⅲ级的120例患者依其受教育程度的高低分2组 :初中及初中以下文化程度组(Ⅰ组 ,n=45) ,高中及高中以上文化程度组 (Ⅱ组 ,n=75)。患者于术后进行视觉模拟量表(VAS)和语言评价量表(VRS)的填写。麻醉医生对如何进行量表的填写向患者进行解释 ,并记录以下数据 :每位患者VAS和VRS的数值 ,填写VAS和VRS量表前向患者解释的次数 (Nvas和Nvrs)。结果Ⅰ组和Ⅱ组的VAS和VRS评分均有显著相关性 (P<0.01) ,其相关系数分别为0.936和0.901。在Ⅰ组中Nvas较Nvrs高 (P<0.05) ,同时Nvas在Ⅰ组中较Ⅱ组中高 (P<0.05) ,但在Ⅱ组中Nvas和Nvrs无显著差异(P>0.05)。结论在对患者进行术后疼痛评定时VRS和VAS具有良好的相关性 ,而VRS更适用于文化程度低及抽象概念理解有困难的患者 ,如老人     

Clinically Important Change in the Visual Analog Scale after Adequate Pain Control

OBJECTIVES: To define the minimum clinically important difference (MCID) for the visual analog scale (VAS) of pain severity by measuring the change in VAS associated with adequate pain control. METHODS: The authors conducted a prospective, observational study. Adult emergency department (ED) patients with acute pain (<72 hours) were eligible. Patients rated their pain severity on a 100-mm VAS on presentation and at discharge. Patients were asked if they would accept any analgesic, then if they would accept a parenteral analgesic before treatment. At discharge, they were asked whether they had received adequate pain control. RESULTS: The authors enrolled 143 patients (mean age, 36 years; 54% female). The mean decrease in VAS was -30.0 mm (95% confidence interval [CI] = -36.4 to -23.6) for the 116 of 143 (81%) patients with adequate pain control at discharge vs. -5.7 (95% CI = -11.2 to -0.3) for the 27 with inadequate pain control (p < 0.001). At discharge, the mean VAS was 31.3 mm for those with adequate pain control vs. 55.1 for those without. Mean VAS for the 114 of 143 patients who would accept any analgesics initially was 64.7 vs. 47.1 for the 29 reporting no analgesic need. Initially, 77 patients would accept parenteral analgesics (mean VAS = 72.5 mm). CONCLUSIONS: A mean reduction in VAS of 30.0 mm represents a clinically important difference in pain severity that corresponds to patients' perception of adequate pain control. Defining MCID based on adequate analgesic control rather than minimal detectable change may be more appropriate for future analgesic trials, when effective treatments for acute pain exist.     

Proximal vs Distal Approach of Ultrasound-guided Suprascapular Nerve Block for Patients With Adhesive Capsulitis of the Shoulder: Prospective Randomized Controlled Trial

ObjectivesTo evaluate the early clinical outcomes of ultrasound (US)-guided suprascapular nerve block (SSNB) using a proximal approach compared with a distal approach for outpatient treatment of adhesive capsulitis.DesignRandomized controlled trial.SettingOutpatient clinicParticipantsParticipants (N=47) with symptomatic adhesive capsulitis.InterventionsParticipants were randomly assigned to either US-guided SSNB using a proximal approach (n=23, proximal group) or a distal approach (n=24, distal group).Main Outcome MeasuresThe primary outcome measure was the visual analog scale (VAS) for pain at week 12. Secondary outcomes included the American Shoulder Elbow Surgeon’s (ASES) score, University California Los Angeles score, Short Form-36 mental and physical component summaries, and range of motion. All patients completed clinical follow-up at 2, 6, and 12 weeks after treatment. On US images, depth and insertion angle of needle during injection were measured.ResultsThe VAS significantly improved in both groups at week 12. After treatment, no significant differences were found in early clinical outcomes (weeks 2, 6, and 12) between groups (all P>.05), except that ASES at 2 weeks showed a significantly higher score in the distal group than in the proximal group (87.1±4.8 and 83.0±6.3, respectively; P=.014). The mean depth and insertion angle of needle was significantly lower (depth: 13.4±3.9 and 30.6±4.3 mm, respectively; P<.001; insertion angle: 19.6°±6.4° and 38.7°±5.8°; P<.001) in the proximal group than in the distal group.ConclusionsThis study demonstrated that proximal approach of US-guided SSNB provided favorable short-term outcomes of pain and functional improvement and that outcomes were comparable to those of the distal approach in adhesive capsulitis. The suprascapular nerve was located more superficially and easily identified in the proximal approach, suggesting that this method might improve the accuracy of injection.     

A Comparative Study of Treatment Interventions for Patellar Tendinopathy: A Randomized Controlled Trial

ObjectivesTo determine the additional effect of dry needling (DN) or percutaneous needle electrolysis (PNE) combined with eccentric exercise (EE) and determine which is the most effective for patients with patellar tendinopathy (PT).DesignBlinded, randomized controlled trial, with follow-up at 10 and 22 weeks.SettingsRecruitment was performed in sport clubs. Diagnosis and intervention were conducted at San Jorge University.ParticipantsPatients (N=48) with PT with pain for at least 3 months between the ages of 18 and 45 years.InterventionsThree interventions were carried out: DN and EE, PNE and EE, and EE with sham needle as the control group.Main Outcome MeasuresDisability was measured using the Victorian Institute of Sports Assessment Questionnaire, patellar tendon. Visual analog scale was used to measure pain over time, the Short Form-36 was used to measure quality of life, and ultrasound was used to measure structural abnormalities.ResultsA total of 48 participants (42 men, 6 women; average age, 32.46y; SD, 7.14y) were enrolled. The improvement in disability and pain in each group between baseline and post-treatment and baseline and follow-up was significant (P≤.05), without differences among groups.ConclusionDN or PNE combined with an EE program has not shown to be more effective than a program of only EE to improve disability and pain in patients with PT in the short (10wk) and medium (22wk) terms. Clinical improvements were not associated with structural changes in the tendon.