[Efficacy and Safety of A0001 (Brilliant Blue G250) for Internal Limiting Membrane Staining and Peeling: Phase III Investigator-initiated Multicenter Clinical Trial].

PURPOSE: To investigate the efficacy and safety of A0001 (brilliant blue G250) for visualization of the internal limiting membrane (ILM) during and after vitrectomy. METHODS: Patients (n = 31) requiring ILM peeling during vitrectomy were enrolled in this clinical trial. After injection of A0001 (range: 0.0625 to 0. 125 mg), the staining grade and the peeling ease of the ILM were evaluated in five steps (levels 0 to 4). The safety of A0001 was investigated for 7 days after surgery. RESULTS: From the evaluation of a primary endpoint by the Independent Data Monitoring Committee (IDMC) and a secondary endpoint by each surgeon, A0001 was effective in all cases at three or more levels ( ≥ level 2 was defined as effective) for evaluation of the grade of visualization and operating ease. Adverse events occurring in two or more cases included elevated intraocular pressure, eye pain, eye discharges, and retinal bleeding. One serious adverse event was a case of unclosed macular hole after vitrectomy, but the patient recovered after reoperation. CONCLUSIONS: A0001 was effective and safe for visualization of the ILM during vitrectomy, and there was an improvement in ease of operation.

DVC1-0101 to treat peripheral arterial disease: a Phase I/IIa open-label dose-escalation clinical trial.

We here report the results of a Phase I/IIa open-label four dose-escalation clinical study assessing the safety, tolerability, and possible therapeutic efficacy of a single intramuscular administration of DVC1-0101, a new gene transfer vector based on a nontransmissible recombinant Sendai virus (rSeV) expressing the human fibroblast growth factor-2 (FGF-2) gene (rSeV/dF-hFGF2), in patients with peripheral arterial disease (PAD). Gene transfer was done in 12 limbs of 12 patients with rest pain, and three of them had ischemic ulcer(s). No cardiovascular or other serious adverse events (SAEs) caused by gene transfer were detected in the patients over a 6-month follow-up. No infectious viral particles, as assessed by hemagglutination activity, were detected in any patient during the study. No representative elevation of proinflammatory cytokines or plasma FGF-2 was seen. Significant and continuous improvements in Rutherford category, absolute claudication distance (ACD), and rest pain were observed (P < 0.05 to 0.01). To the best of our knowledge, this is the first clinical trial of the use of a gene transfer vector based on rSeV. The single intramuscular administration of DVC1-0101 to PAD patients was safe and well tolerated, and resulted in significant improvements of limb function. Larger pivotal studies are warranted as a next step.

Root canal system of the maxillary canine.

To better assess the efficacy of mechanical preparation of root canals, transparent specimens of 250 extracted maxillary canines were investigated for canal configuration, thickness and curvature of the root canal, condition of any accessory canals, and location of the apical foramen. Fewer than 40% of the specimens showed accessory canals that were mechanically impossible to clean. The majority of the lateral branches were small, greater than a #15 file, and none of the branches were larger than a #20 file. Although apical foramina located away from the apex were observed in 30% of the maxillary teeth, 96% of all apical foramina were within 0.5 mm of the apex. Data on the thickness of the root and main canal in the apical portion and curvature of the root canal suggest that, for adequate apical preparation, a #60 file must be able to reach the apical constriction.

An Open-label Phase I/IIa Clinical Trial of 11ß-HSD1 Inhibitor for Cushing's Syndrome and Autonomous Cortisol Secretion.

CONTEXT: 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitors demonstrate antimetabolic and antisarcopenic effects in Cushing's syndrome (CS) and autonomous cortisol secretion (ACS) patients. OBJECTIVE: To confirm the efficacy and safety of S-707106 (11ß-HSD1 inhibitor) administered to CS and ACS patients. DESIGN: A 24-week single-center, open-label, single-arm, dose-escalation, investigator-initiated clinical trial on a database. SETTING: Kyushu University Hospital, Kurume University Hospital, and related facilities. PATIENTS: Sixteen patients with inoperable or recurrent CS and ACS, with mildly impaired glucose tolerance. INTERVENTION: Oral administration of 200 mg S-707106 after dinner, daily, for 24 weeks. In patients with insufficient improvement in oral glucose tolerance test results at 12 weeks, an escalated dose of S-707106 (200 mg twice daily) was administered for the residual 12 weeks. MAIN OUTCOME MEASURES: The rate of participants responding to glucose tolerance impairment, defined as those showing a 25% reduction in the area under the curve (AUC) of plasma glucose during the 75-g oral glucose tolerance test at 24 weeks. RESULTS: S-707106 administration could not achieve the primary endpoint of this clinical trial (>20% of responsive participants). AUC glucose decreased by -7.1% [SD, 14.8 (90% CI -14.8 to -1.0), P = 0.033] and -2.7% [14.5 (-10.2 to 3.4), P = 0.18] at 12 and 24 weeks, respectively. S-707106 administration decreased AUC glucose significantly in participants with a high body mass index. Body fat percentage decreased by -2.5% [1.7 (-3.3 to -1.8), P < 0.001] and body muscle percentage increased by 2.4% [1.6 (1.7 to 3.1), P < 0.001]. CONCLUSIONS: S-707106 is an effective insulin sensitizer and antisarcopenic and antiobesity medication for these patients.

Safety and efficacy of brilliant blue g250 (BBG) for lens capsular staining: a phase III physician-initiated multicenter clinical trial.

PURPOSE: To evaluate the safety and efficacy of BBG (Brilliant Blue G250) for lens capsular staining during cataract surgery with continuous curvilinear capsulorhexis. STUDY DESIGN: Prospective clinical study. METHODS: This clinical trial enrolled 30 eyes of 30 patients who underwent cataract surgery with BBG (0.25 mg/mL Brilliant Blue G250) for capsular staining. Visualization of the lens capsule and the ease of capsulorhexis with BBG staining were evaluated in five grades (grade 0 to 4) by the Independent Data Monitoring Committee and the surgeons. The safety of BBG was also evaluated in terms of ocular and systemic tolerance for 7 days after surgery. RESULTS: The use of BBG improved visualization of the lens capsule and complete capsulorhexis was performed in all patients. The major endpoint (Independent Data Monitoring Committee evaluation) showed that use of BBG improved visualization of the lens capsule and the ease of capsulorhexis (grades 2 to 4); the committee's grading results were similar to those of the surgeons. Frequent complications observed in more than two eyes were conjunctival injection, corneal edema and intraocular pressure elevation. No severe complications were observed in ocular and systemic evaluations. CONCLUSION: BBG staining contributed to improved visualization of the lens capsule and aided in the completion of capsulorhexis during cataract surgery. The use of BBG for capsular staining also exhibited favorable safety results.

The development of the nursing action master file.

The nursing action master was developed through collecting terms used by the nurses. The nursing action terms were classified in 2 of the basics and specialty. The nursing action master consists of four hierarchical structures. Serial numbers and ID are set in every hierarchy. It started from 2006 to supply the master and it is revised every year. The number of the publication records is 1,053 basic nursing practice standard terms.

The development of method for continuous improvement of master file of the nursing practice terminology.

Nursing Action Master and Nursing Observation Master were released from 2002 to 2008. Two kinds of format, an Excel format and a CSV format file are prepared for maintaining them. Followings were decided as a basic rule of the maintenance: newly addition, revision, deletion, the numbering of the management and a rule of the coding. The master was developed based on it. We do quality assurance for the masters using these rules.

Structural visualization of expert nursing: Cancer pain management.

Nurses' knowledge and making decisions in Cancer Pain Management contribute much to the improvement of cancer patients' QOL. Based on the practice of a expert nurse involved in Cancer Pain Management, we have developed the algorithm, which clarified that nurses implement much of observations or complicated decision-makings in Cancer Pain Manage Hereafter it is a significant challenge to examine its consistency and validity to develop its system.

A hospital survey on the utilization of the master file of the standardized nursing practice terminology in Japan.

A common language in nursing facilitates better communication among nurses and other healthcare providers, assuring better nursing care, hence better patient outcomes. As we developed and disseminated the standardized terminology of nursing which provided nurses with a set of terms to describe nursing observations and nursing actions, we run a survey to see how much it was recognized and utilized in actual clinical settings. The result showed that approximately 60% of the respondents were cognizant of our terminology, and again 60% of them were either actually using the terminology or interested in using it in the future. For them, the main purposes of utilizing the terminology were nursing documentation and care planning. Sometimes it was used as an educational tool. This suggests that we should further develop a tool to assist nurses with their documentation and care planning alongside the revision of the terminology itself.

Developing the nursing care plans using the "master file of standardized nursing practice terminology" in Japan.

A common language in nursing facilitates better communication among nurses and healthcare team, assuring better nursing care, hence better patient outcomes. As we developed and disseminated the standardized terminology of nursing which provided nurses with a set of terms to describe nursing observations and nursing actions, we developed a certain number of nursing care plans using the terms in it. The nursing care plans included those for the patients requiring medical (pharmaceutical)/surgical procedures or the patients showing some signs and symptoms. Generally, nurses found that the nursing care plans were useful and flexible enough to allow for the modification according to the needs of each individual patient. In conclusion, the nursing care plans based on the standardized terminology showed its relevance to the clinical settings.

Evidence for the binding of phosphate ion to the C-terminus region in Abeta1-40 using heteronuclear NMR analyses.

Amyloid fibril formation of amyloid beta peptide 1-40 (Abeta 1-40) was reported to be retarded in the presence of 150mM phosphate buffer at pH 7 [Monji, Ustumi, Ueda, Imoto, Yoshida, Hashioka, Tashiro and Tashiro, J. Neurochemistry, 77, 1425-1432 (2007)]. In order to elucidate the reason why phosphate ion retards the amyloid fibril formation, we examined the preferential binding sites of phosphate ion to Abeta 1-40 using chemical shift perturbation analysis of heteronuclear NMR. In titration analysis of (15)N-labeled Abeta1-40 in the presence of 150 mM phosphate ion or 150 mM chloride ion, we identified the residues affected by these ions in Abeta 1-40. As a result, we found the tendency that phosphate ion preferentially bound to some residues located on the C-terminus region where the region was reported to be the potential beta-strand region in Abeta1-40. Therefore, we suggested that phosphate ions interacted with the potential beta-strand region in Abeta1-40 to be hard to form beta-sheet in Abeta 1-40, resulting in retardation of the amyloid fibril formation.