Adenovirus vector expressing keratinocyte growth factor using CAG promoter impairs pulmonary function of mice with elastase-induced emphysema.

Pulmonary emphysema impairs quality of life and increases mortality. It has previously been shown that administration of adenovirus vector expressing murine keratinocyte growth factor (KGF) before elastase instillation prevents pulmonary emphysema in mice. We therefore hypothesized that therapeutic administration of KGF would restore damage to lungs caused by elastase instillation and thus improve pulmonary function in an animal model. KGF expressing adenovirus vector, which prevented bleomycin-induced pulmonary fibrosis in a previous study, was constructed. Adenovirus vector (1.0 × 109 plaque-forming units) was administered intratracheally one week after administration of elastase into mouse lungs. One week after administration of KGF-vector, exercise tolerance testing and blood gas analysis were performed, after which the lungs were removed under deep anesthesia. KGF-positive pneumocytes were more numerous, surfactant protein secretion in the airspace greater and mean linear intercept of lungs shorter in animals that had received KGF than in control animals. Unexpectedly, however, arterial blood oxygenation was worse in the KGF group and maximum running speed, an indicator of exercise capacity, had not improved after KGF in mice with elastase-induced emphysema, indicating that KGF-expressing adenovirus vector impaired pulmonary function in these mice. Notably, vector lacking KGF-expression unit did not induce such impairment, implying that the KGF expression unit itself may cause the damage to alveolar cells. Possible involvement of the CAG promoter used for KGF expression in impairing pulmonary function is discussed.

Management of a centenarian who underwent emergency laparoscopic cholecystectomy under general anesthesia with subcostal transversus abdominis plane block.

The anesthetic management of centenarians is challenging, since they have loss of functional reserve in all organs. The mortality rate of 25 % is reported in patients over 100 years old who underwent emergency surgery. The transversus abdominis plane block has been shown to provide effective analgesia in laparoscopic cholecystectomy. A 101-year-old woman was diagnosed with grade I (mild) acute cholecystitis with gallstones. An emergency laparoscopic cholecystectomy was scheduled. The patient had a history of hypertension. The patient's laboratory data showed that she had mild coagulopathy, anemia, thrombocytopenia, and decreased renal function. After induction of general anesthesia, an ultrasound-guided, bilateral subcostal transversus abdominis plane block was performed. Her postoperative course was uneventful. Using the preoperative subcostal transversus abdominis plane block, we were able to avoid hemodynamic instability and to reduce opioid dosage in a centenarian who underwent emergency laparoscopic cholecystectomy under general anesthesia.

Incidence of dizziness and vertigo in Japanese primary care clinic patients with lifestyle-related diseases: an observational study.

OBJECTIVE: Dizziness and vertigo are highly prevalent symptoms among patients presenting at primary care clinics, and peripheral vestibular disorder (PVD) is their most frequent cause. However, the incidence of PVD has not been well documented. This study aimed to investigate the incidence of dizziness, vertigo, and PVD among patients presenting at a primary care clinic. DESIGN: This was an observational study. SETTING AND PARTICIPANTS: Between November 2011 and March 2013, we observed 393 patients, all at least 20 years old, who had been treated for chronic diseases such as hypertension, dyslipidemia, and diabetes mellitus for at least 6 months at a primary clinic (Oki Clinic) in Japan. OUTCOME: The main outcome of interest was new incidence of dizziness, vertigo, and PVD events. During the 1-year follow-up period, the otorhinolaryngologist diagnosed and reported new PVD events. RESULTS: The mean age of the 393 participants at entry was 65.5 years. Of the study participants, 12.7%, 82.4%, and 92.6% had diabetes mellitus, hypertension, and dyslipidemia, respectively. We followed up all the participants (100%). During the 662.5 person-years of follow-up, 121 cases of dizziness or vertigo (dizziness/vertigo) and 76 cases of PVD were observed. The incidence of dizziness/vertigo and PVD was 194.7 (95% confidence interval: 161.6-232.6) per 1,000 person-years and 115.7 (95% confidence interval: 92.2-142.6) per 1,000 person-years, respectively. There were 61 cases of acute peripheral vestibulopathy, 12 of benign paroxysmal positional vertigo, and three of Meniere's disease among the 76 PVD patients. CONCLUSION: We reported the incidence of dizziness/vertigo among Japanese primary care clinic patients, which was higher than that usually observed in the general population. Furthermore, we described the incidence of PVD and found that it was a major cause of dizziness/vertigo.

Highly enantioselective asymmetric 1,3-dipolar cycloaddition of azomethine ylide catalyzed by a copper(I)/ClickFerrophos complex.

A copper(I)/ClickFerrophos complex catalyzed the asymmetric 1,3-dipolar cycloaddition reaction of methyl N-benzylideneglycinate (the source of azomethine ylides) with vinyl sulfone to give the exo-2,4,5-trisubstituted pyrrolidine in good yield with high enantioselectivity (99% ee). The complex also effectively catalyzed reactions of other dipolarophiles such as acrylates, maleate, and maleimides to give the exo-2,4,5-, and 2,3,4,5-substituted pyrrolidine derivatives with high diastereo- and enantioselectivities.

ClickFerrophos: new chiral ferrocenyl phosphine ligands synthesized by click chemistry and the use of their metal complexes as catalysts for asymmetric hydrogenation and allylic substitution.

The new ferrocenyl P,P- and P,N-ligands 5 and 6 (collectively, "ClickFerrophos") were readily prepared in four steps using Click Chemistry methodology, starting from the commercially available aminoferrocene 1. Rhodium and ruthenium complexes of ClickFerrophos 5 were effective catalysts for the hydrogenation of alkenes and ketones, respectively, producing products with up to 99.7% ee. The analogous palladium complex with 6 worked well for asymmetric allylic alkylation.