Efficacy and duration of analgesia from a sustained-release lidocaine sheet in humans

BACKGROUNDWe have synthesized a sustained-releaselidocaine sheet (SRLS) and injectable sustained-release lidocaine particles(SRLP) using biodegradable polymers. In the present study, we performed anexploratory first clinical trial of the SRLS in healthy volunteers as a preludeto patient administration. This trial is meant as an initial intervention inultimately developing and refining the SRLP. METHODSWe evaluated the intensity and duration ofanalgesia of the SRLS compared with 8% lidocaine spray. In Protocol 1, weapplied the SRLS piece to the mucous membrane of the nasal vestibule. Weexamined the local pain threshold over 72 h after administration, and removedthe SRLS after 72 h. Individuals that finished Protocol 1 underwent Protocol 2,in which we applied 8% lidocaine spray. RESULTSTwelve volunteers were enrolled and seven ofthese volunteers finished Protocol 1. All seven individuals who completedProtocol 1 also completed Protocol 2. The mean pain thresholds were 32 g, 78 g,90 g, 90 g, 87 g, and 87 g at pre-administration and 4 h, 10 h, 24 h, 48 h, and72 h after administration, respectively, in Protocol 1, and 36 g, 85 g, 49 g,and 33 g at pre-administration and 15 min, 2 h, and 4 h, respectively, inProtocol 2. CONCLUSIONA sustained-release lidocaine usingbiodegradable polymers was applied as a sheet in humans for the first time inthe world. It maintained significant analgesia for 72 h without majortoxicities. Furthermore, degree of analgesia provided by the SRLS throughoutthe entire study was similar to that provided by the 8% lidocaine spray. It may suitable for management ofpostoperative pain especially in outpatients

Whole Blood Interferon-Gamma Assay for Baseline Tuberculosis Screening among Japanese Healthcare Students

BACKGROUND: The whole blood interferon-gamma assay (QuantiFERON-TB-2G; QFT) has not been fully evaluated as a baseline tuberculosis screening test in Japanese healthcare students commencing clinical contact. The aim of this study was to compare the results from the QFT with those from the tuberculin skin test (TST) in a population deemed to be at a low risk for infection with Mycobacterium tuberculosis. METHODOLOGY/PRINCIPAL FINDINGS: Healthcare students recruited at Okayama University received both the TST and the QFT to assess the level of agreement between these two tests. The interleukin-10 levels before and after exposure to M tuberculosis-specific antigens (early-secreted antigenic target 6-kDa protein [ESAT-6] and culture filtrate protein 10 [CFP-10]) were also measured. Of the 536 healthcare students, most of whom had been vaccinated with bacillus-Calmette-Guérin (BCG), 207 (56%) were enrolled in this study. The agreement between the QFT and the TST results was poor, with positive result rates of 1.4% vs. 27.5%, respectively. A multivariate analysis also revealed that the induration diameter of the TST was not affected by the interferon-gamma concentration after exposure to either of the antigens but was influenced by the number of BCG needle scars (p = 0.046). The whole blood interleukin-10 assay revealed that after antigen exposure, the median increases in interleukin-10 concentration was higher in the subgroup with the small increase in interferon-gamma concentration than in the subgroup with the large increase in interferon-gamma concentration (0.3 vs. 0 pg/mL; p = 0.004). CONCLUSIONS/SIGNIFICANCE: As a baseline screening test for low-risk Japanese healthcare students at their course entry, QFT yielded quite discordant results, compared with the TST, probably because of the low specificity of the TST results in the BCG-vaccinated population. We also found, for the first time, that the change in the interleukin-10 level after exposure to specific antigens was inversely associated with that in the interferon-gamma level in a low-risk population

Prediction of anastomotic leakage

Background : Anastomotic leakage after esophagectomy is significantly associated with more severe complications, such as sepsis and mortality. Early prediction for anastomotic leakage is usually difficult and needs to be treated rapidly. In the current study, we investigated the correlation between hemodynamic and several complications after esophagectomy in patients with esophageal cancer, using the FloTrac system. Materials and Methods : Between April 2013 and December 2014, 39 patients with a mean age of 66.6 ± 8.9 years underwent postoperative supervision using the FloTrac sensor / Vigileo monitoring system after curative surgery for esophageal cancer. We retrospectively evaluated the association between the number of aberrant cardiac index (CI) along with stroke volume variability (SVV) values and clinicopathological parameters of postoperative complications in this report. Results : There were significant positive correlations between the number of aberrant values of CI along with SVV and depth of invasion during pathological stage. Concerning major postoperative complications, there was a significant positive correlation between the number of aberrant values of CI and anastomotic leakage. Discussion: The hemodynamic change by employing the FloTrac system could predicts the complication of anastomotic leakage after esophagectomy. Adequate management of hemodynamic stability by utilizing it will reduce the complications of anastomotic leakage

Trapping a pentagonal molecule in a self-assembled molecular network: an alkoxylated isosceles triangular molecule does the job

We herein report a unique example of on-surface adaptive self-assembly. A pentagon-shaped macrocycle, cyclic [5]meta-phenyleneacetylene [5]CMPA, is trapped by the adaptive supramolecular network formed by an isosceles triangular molecule, alkoxy substituted dehydrobenzo[14]annulene [14]ISODBA at the liquid/graphite interface, leading to a highly ordered and large-area bicomponent self-assembled molecular network (SAMN), as revealed by scanning tunneling microscopy (STM).status: publishe

Education program for prevention of outdoor accidents in middle-high aged trekkers: Monitoring of change in blood pressure and heart rate during exercise

This is an observational study to evaluate cardiovascular parameters during an educational trekking program. The number of alpine accidents involving elderly trekkers has been increasing in developed countries in recent years. Many middle-high aged trekkers have potential cardiovascular risks of which they are unaware. More than 77% of trekkers involved in alpine accidents in Japan were aged >40 years. The most common cardiovascular conditions were stroke or heart attack while trekking at altitude. An alpine club conducted an 8-month education program with participants aged >40 years in the setting of a mountain-side town. Blood pressure and heart rate during outdoor exercise were monitored, and any other adverse effects were recorded. As a result, the cardiovascular parameters evaluated during the first and final trek presented a physiological and similar behavior, however, lower heart rate values were registered at the highest point of the route in the final trek (p < 0.05). The trend of these parameters was similar in males and females, and there was little correlation between the cardiovascular parameters and age. In conclusion, the lower heart rate values may indicate the higher risk awareness of trekkers while self-pacing the physical activity outdoors, which may indicate the positive effect of the education program in increasing the safety of such unsupervised activities

Sustained-release lidocaine sheet for pain following tooth extraction: A randomized, single-blind, dose-response, controlled, clinical study of efficacy and safety

Background: We have synthesized a sustained-release lidocaine sheet (SRLS) using biodegradable polymers and previously demonstrated its safety and long-term analgesic effect in the normal mucous membrane of healthy human volunteers.Objectives: The aim of this clinical study was to evaluate the efficacy, safety, and appropriate dose of the SRLS for pain following tooth extraction.Design: Randomized, single-blind, dose-response, controlled, clinical study (Phase 1/2).Methods: The patients in this trial were enrolled between January 2014 and December 2016. A total of 99 patients were randomly divided into 5 groups as follows: the Non-administration group received the conventional extraction; the Poly Lactic-co-Glycolic Acid (PLGA) 100 mg control group received the PLGA matrix without lidocaine; the SRLS 100 mg group received a single sheet of SRLS 100 mg; the SRLS 200 mg group received double sheets of SRLS 100 mg; and the SRLS 400 mg administration group received four sheets of SRLS 100 mg. A study drug was inserted into the defect socket after the extraction, and postoperative pain intensity, satisfaction with postoperative pain relief, adverse events, and postoperative supplemental analgesic rescue use (time, dose) were investigated by patient self-report.Results: In total, 94 (94.9%) patients completed the study. There were no significant differences in postoperative pain intensity, satisfaction with postoperative pain relief, and postoperative supplemental analgesic rescue use among the 5 groups. There were no serious side effects, including a plasma concentration increase of lidocaine, attributable to the SRLS.Conclusions: Administration of the SRLS at 100 mg may have clinical therapeutic potential for pain relief following tooth extraction. The safety of the SRLS for patients undergoing tooth extraction was demonstrated

Electrostatically Driven Guest Binding in a Self-Assembled Porous Network at the Liquid/Solid Interface

We present here the construction of a self-assembled two-dimensional (2D) porous monolayer bearing a highly polar 2D space to study guest co-adsorption through electrostatic interactions at the liquid/solid interface. For this purpose, a dehydrobenzo[12]annulene (DBA) derivative, DBA-TeEG, having tetraethylene glycol (TeEG) groups at the end of the three alternating alkoxy chains connected by p-phenylene linkers was synthesized. As a reference host molecule, DBA-C10, having nonpolar C10 alkyl chains at three alternating terminals, was employed. As guest molecules, hexagonal phenylene-ethynylene macrocycles (PEMs) attached by triethylene glycol (TEG) ester and hexyl ester groups, PEM-TEG and PEM-C6, respectively, at each vertex of the macrocyclic periphery were used. Scanning tunneling microscopy observations at the 1,2,4-trichlorobenzene/highly oriented pyrolytic graphite interface revealed that PEM-TEG was immobilized in the pores formed by DBA-TeEG at higher probability because of electrostatic interactions such as dipole-dipole and hydrogen bonding interactions between oligoether units of the host and guest, in comparison to PEM-C6 with nonpolar groups. These observations are discussed based on molecular mechanics simulations to investigate the role of the polar functional groups. When a nonpolar host matrix formed by DBA-C10 was used, however, only phase separation and preferential adsorption were observed; virtually no host-guest complexation was discernible. This is ascribed to the strong affinity between the guest molecules which form by themselves densely packed van der Waals networks on the surface.status: publishe