Drug use investigation on the safety and efficacy of tigecycline in Japan (all-case post-marketing surveillance).

INTRODUCTION: We conducted a drug use investigation to investigate the safety and efficacy of tigecycline, which has been approved for clinical use for the treatment of multidrug-resistant gram-negative infections in Japan. METHODS: This was an open-label, observational, multicenter cohort study that included all patients who received tigecycline. RESULTS: A total of 116 patients were registered between December 2012 and April 2016 and all of them were evaluated for safety and efficacy. Among them, 64 patients aged ≥65 years (55.2%) and five children aged <15 years (4.3%) were included. Of these patients, 47 (40.5%) met the approved indications of tigecycline. Adverse drug reactions (ADRs) were observed in 41 patients (35.3%) with a total of 74 events. Serious ADRs were observed in 15 patients (12.93%) with a total of 33 events. There were 42 deaths, and 6 of these were considered to be caused by ADRs. Among the 116 patients, 65 achieved clinical response at the end of the observation period, and the efficacy rate was 73.9%. Furthermore, 46 patients were assessed as "cure" at the test of cure visit, and the cure rate was 59.0%. The eradication rate was 47.5% at the end of the observation period. Classified by pathogenic bacteria, the eradication rate of patients infected with the approved pathogens was 54.5%. CONCLUSIONS: Tigecycline was well-tolerated, and no additional safety concerns were noted. It was effective considering that most patients had poor physical conditions. The overall benefit-risk balance of tigecycline was favorable.

Fractal photonic bandgap fibers.

Photonic bandgap fibers have a critical constraint determined by wavelength. The principle of scale invariance requires that features remain unchanged even as the scale of an object changes. This paper introduces a new concept for fractal photonic crystal fibers integrating these two. Our simulation confirmed single-mode transmission is possible for a fiber whose core diameter exceeds 35 times the wavelength.

Multi-Touch Tabletop System Using Infrared Image Recognition for User Position Identification.

A tabletop system can facilitate multi-user collaboration in a variety of settings, including small meetings, group work, and education and training exercises. The ability to identify the users touching the table and their positions can promote collaborative work among participants, so methods have been studied that involve attaching sensors to the table, chairs, or to the users themselves. An effective method of recognizing user actions without placing a burden on the user would be some type of visual process, so the development of a method that processes multi-touch gestures by visual means is desired. This paper describes the development of a multi-touch tabletop system using infrared image recognition for user position identification and presents the results of touch-gesture recognition experiments and a system-usability evaluation. Using an inexpensive FTIR touch panel and infrared light, this system picks up the touch areas and the shadow area of the user's hand by an infrared camera to establish an association between the hand and table touch points and estimate the position of the user touching the table. The multi-touch gestures prepared for this system include an operation to change the direction of an object to face the user and a copy operation in which two users generate duplicates of an object. The system-usability evaluation revealed that prior learning was easy and that system operations could be easily performed.

Preferential adsorption of amino-terminated silane in a binary mixed self-assembled monolayer.

The composition and structure of a binary mixed self-assembled monolayer (SAM) of 3-aminopropyltriethoxysilane (APS, NH(2)(CH(2))(3)Si(OCH(2)CH(3))(3)) and octadecyltrimethoxysilane (ODS, CH(3)(CH(2))(17)Si(OCH(3))(3)) on a silicon oxide surface have been characterized by water contact-angle measurements, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and sum frequency generation (SFG) vibrational spectroscopy. XPS demonstrated that APS in the mixed SAM is significantly enriched in comparison to that in solution, indicating the preferential adsorption of APS during the SAM formation. AFM observations showed that the mixed SAM becomes rougher. SFG revealed that the coadsorption of APS induced a conformation disordering in the ODS molecules present in the mixed SAM. The surface enrichment of APS has been explained in terms of differences in the surface adsorption rates of the two components as well as in the self-congregation states of APS molecules in the bulk solution. Furthermore, the structure of the water molecules on the mixed SAM surface in contact with the aqueous solutions at different pH's has also been studied. The results indicate that the mixed-SAM modified surface is positively charged at pH < 5 and negatively charged at pH > 7.

Milling in Seconds Accelerates Acetylation of Cellulose in Hours.

A new sustainable synthetic method for cellulose acetate was developed by a combination of I2-catalyzed solid-liquid acetylation of cellulose and a milling process reducing the crystallinity of cellulose within a few seconds. Milled low-crystalline cellulose was acetylated faster than the original cellulose with higher crystallinity. The plausible factors of acceleration were the conversion of the hydroxy group in hydrogen bonds into reactive ones and the efficient formation of the catalytic species I+ by the enhanced formation of I3 - assisted by the amorphous domain of the milled cellulose, while the morphological and structural changes were ignorable.

A plasmonic photocatalyst consisting of silver nanoparticles embedded in titanium dioxide.

Titanium dioxide (TiO2) displays photocatalytic behavior under near-ultraviolet (UV) illumination. In another scientific field, it is well understood that the excitation of localized plasmon polaritons on the surface of silver (Ag) nanoparticles (NPs) causes a tremendous increase of the near-field amplitude at well-defined wavelengths in the near UV. The exact resonance wavelength depends on the shape and the dielectric environment of the NPs. We expected that the photocatalytic behavior of TiO2 would be greatly boosted if it gets assisted by the enhanced near-field amplitudes of localized surface plasmon (LSP). Here we show that this is true indeed. We named this new phenomenon "plasmonic photocatalysis". The key to enable plasmonic photocatalysis is to deposit TiO2 on a NP comprising an Ag core covered with a silica (SiO2) shell to prevent oxidation of Ag by direct contact with TiO2. The most appropriate diameter for Ag NPs and thickness for the SiO2 shell giving rise to LSP in the near UV were estimated from Mie scattering theory. Upon implementing a device that took these design considerations into account, the measured photocatalytic activity under near UV illumination of such a plasmonic photocatalyst, monitored by decomposition of methylene blue, was enhanced by a factor of 7. The enhancement of the photocatalytic activity increases with a decreased thickness of the SiO2 shell. The plasmonic photocatalysis will be of use as a high performance photocatalyst in nearly all current applications but will be of particular importance for applications in locations of minimal light exposure.

Wettability control of a solid surface by utilizing photocatalysis.

This paper describes a strategic approach utilizing a photocatalyst to obtain a solid surface with a high level of sustainable wettability (hydrophilicity or hydrophobicity). We clarified that the substances adsorbed on the surface could be successfully removed by photocatalytic oxidation resulting in sustainable high hydrophilic and high hydrophobic states. In addition to the conventional redox reaction, photoinduced wettability conversion plays an inevitable role in obtaining a superhydrophilic state. Both of the aforementioned photoinduced properties can be applied to sustain a high level of hydrophilicity. A superhydrophobic surface can be designed based on the Cassie theory. However, a combination with the usual TiO2 photocatalyst leads to a decrease in hydrophobicity because the photocatalyst becomes hydrophilic itself as a result of the photoinduced hydrophilic reaction. Utilizing the newly developed hydroxyapatite doped with Ti(IV) ions (TiHAP) photocatalyst, which has a considerably reduced hydrophilic effect, a superhydrophobic surface can be sustained after exposing it to outdoor conditions for a long period. As for sustaining the hydrophobic state, the introduction of a material design based on dynamic wettability leads to the possibility of novel functional materials with a high dynamic hydrophobicity. Our study shows that a high level of wettability (hydrophilic or hydrophobic) of a solid surface as that sustained by biologic action is possible by utilizing photocatalysis.

[A case report of primary adenocarcinoma of small intestine successfully treated with FOLFOX].

This is an account of a case of primary adenocarcinoma of the small intestine successfully treated with chemotherapy. A 46-year-old man was admitted with a complaint of severe abdominal distension. Abdominal computerized tomography revealed bowel obstruction, and this was found at surgery to be due to a tumor at the jejunum 100 cm distal from the Treitz ligament. Pathological diagnosis of the resected specimen was adenocarcinoma. Although adjuvant chemotherapy with doxifluridine 800 mg/day was given, a recurrent lesion at the abdominal wall was detected 19 months after surgery. Colonoscopy simultaneously revealed stenosis at the descending colon. The patient was subsequently treated with resection of the mass at the abdominal wall, and colostomy was made at the transverse colon to circumvent the stenosis due to peritoneal carcinomatosis. It was not long before another recurrence developed at the abdominal wall with a subsequent rise in tumor markers. mFOLFOX6 (oxaliplatin 85 mg/m2, levofolinate calcium 200 mg/m2, 5-FU 400/2,400 mg/m2) was given, and the patient responded. Primary small intestinal adenocarcinoma is a rare disease with a dismal prognosis. Due to rarity of the disease, clinical trials have not been performed, and little is known about the effect of chemotherapy. The current patient survived for 4 years and 5 months after the diagnosis, owing at least partially to the mFOLFOX6 which was found to be the only active regimen.

The angiotensin II receptor blocker candesartan cilexetil reduces neointima proliferation after coronary stent implantation: a prospective randomized study under intravascular ultrasound guidance.

OBJECTIVES: The purpose of this study was to evaluate whether an angiotensin II receptor blocker, candesartan cilexetil, reduced neointima formation after coronary stent implantation by way of serial intravascular ultrasound analysis. BACKGROUND: Previous experimental studies have suggested that angiotensin II receptor blocker reduced neointima formation after vascular injury. However, it is unclear whether candesartan cilexetil has a similar effect on human coronary artery. METHODS: We recruited 50 consecutive patients with stable angina pectoris and 60 stenotic lesions. Patients were prospectively randomized into 2 groups: (1) 25 patients with 31 lesions received candesartan cilexetil (4-12 mg/d), and (2) 25 patients with 29 lesions did not receive the drug. Follow-up intravascular ultrasound was performed 6 m after the stent implantation. Cross-sectional images were obtained at 1-mm intervals within the stent, and the stent volume (SV), lumen volume (LV), and neointima volume (NV = SV - LV) were calculated using Simpson's rule. The percentage neointima volume obstruction (%NV) was calculated as NV/SV x 100. RESULTS: Clinical and angiographic backgrounds were comparable between the 2 groups. At follow-up, the candesartan group had smaller SV and larger LV (SV, 156.3 +/- 53.7 vs 165.4 +/- 61.8 mm3 , ns; LV, 122.2 +/- 49.0 vs 113.1 +/- 45.5 mm3 , ns), and significantly smaller NV and significantly smaller %NV than the control group (NV, 34.2 +/- 16.6 vs 52.3 +/- 32.6 mm3 , P < .01; %NV, 22.7 +/- 10.9% vs 31.3 +/- 13.4%, P < .01). CONCLUSIONS: Candesartan treatment decreases neointima formation and hence may reduce in-stent restenosis.

Palladium-catalyzed allylation of imines with allyl alcohols.

A catalytic system, Pd(OAc)2 (10 mol %)-P(n-Bu)3 (20 mol %)-Et3B (360 mol %), promotes allylic alcohols to undergo the allylation of anisidine-imines of aromatic and aliphatic aldehydes and furnishes homoallylamines in good to moderate yields. The reaction shows unique stereoselectivity, giving anti-isomers selectively. [reaction: see text]

Obesity and smoking: relationship with waist circumference and obesity-related disorders in men undergoing a health screening.

This study investigated whether smoking habits had a differential influence on waist circumference and obesity-related disorders in nonobese and obese men. We investigated 359 men with smoking habits confirmed by their spouses, including 172 nonobese men (BMI<25) and 187 obese men (BMI>or=25). There were 113 nonobese smokers and 129 obese smokers. Obesity-related disorders were defined as hypertension, dyslipidemia, hyperglycemia, hyperuricemia, or treatment for one or more of these disorders. Nonobese subjects showed no differences of age, BMI, and waist circumference between smokers and nonsmokers, but smokers had a higher incidence of obesity-related disorders. Obese smokers were younger than obese nonsmokers and had a larger waist circumference, but a similar prevalence of obesity-related disorders. The prevalence of obesity-related disorders was similar between obese nonsmokers and smokers, but the smokers were younger. In nonobese subjects, smoking may increase obesity-related disorders by a mechanism other than visceral fat accumulation. In obese subjects, however, smoking may promote visceral fat accumulation. Further investigations will be necessary to better elucidate the relationship between the promotion of visceral fat accumulation in obese subjects by smoking and obesity-related disorders.

Histological grading of adrenal and extra-adrenal pheochromocytomas and relationship to prognosis: a clinicopathological analysis of 116 adrenal pheochromocytomas and 30 extra-adrenal sympathetic paragangliomas including 38 malignant tumors.

Pheochromocytomas and extra-adrenal sympathetic paragangliomas show varied histological patterns, and it is difficult to diagnose malignancy or predict the clinical course using current histological criteria. In the present study, we reviewed 146 sympathetic paragangliomas including 116 adrenal (102 unilateral, 14 bilateral) and 30 extra-adrenal tumors including 38 metastatic tumors. We developed a scoring scale according to the following six factors: histological pattern, cellularity, coagulation necrosis, vascular/capsular invasion, Ki-67 immunoreactivity, and types of catecholamine produced. The tumors were classified as well (WD), moderately (MD), and poorly differentiated (PD) types according to their scores. The frequency of these tumor types were 113 WD (77%), 27 MD (19%), and 6 PD (4%). Metastasis was observed in 15 of 113 WD (13%), 17 of 27 MD (63%), and all 6 PD (100%). Five-year survivals of patients with metastases were 92% with WD, 69% with MD, 0% with PD. Respective 10-yr survivals were 83%, 38%, and 0%. Differences between groups were statistically significant. The data show that using this grading scoring system for sympathetic paragangliomas correlates with both metastatic potential and patient survival.

A trial to assess the amount of insulin antibodies in diabetic patients by surface plasmon resonance.

OBJECTIVE: To measure the amount and affinity of insulin antibodies, we performed a trial to establish a new method for quantitative and qualitative analysis of these antibodies by using surface plasmon resonance (BIAcore system). METHODS: Real-time detection of insulin antibody interaction and kinetic analysis were performed using the BIAcore system. PATIENTS OR MATERIALS: Eight diabetic patients with insulin antibodies and whose fasting total immunoreactive insulin levels were more than 100 microU/ml were selected. The patients with and without recurrent hypoglycemia were classified into hypoglycemic episode-positive or hypoglycemic episode-negative groups, respectively. Seven diabetic patients without insulin antibodies were selected as controls. RESULTS: In the 8 patients, the concentration of insulin antibodies ranged from 2.91 to 16.3 microg/ml and insulin antibodies were not detected in the control group. The apparent KD (dissociation constant) and kd (the dissociation rate constant) values of the patients were much larger than those seen for the anti-human insulin monoclonal antibody. The KD values were significantly higher in the hypoglycemic episode-positive group than in the hypoglycemic episode-negative group (p<0.05). No significant differences in the concentration, the ka (the association rate constant) and the kd values were noted between the groups. CONCLUSION: The data suggests that insulin antibodies of the patients have an apparently lower affinity status in sera as compared with that for the anti-human insulin monoclonal antibody, and dissociate easily from the immune-complex in the sera, especially in cases where there is recurrent hypoglycemia in the patients. Therefore insulin antibody characteristics are one of the causative factors in hypoglycemic episodes.

Long-term stabilization of respiratory conditions in patients with spinal muscular atrophy type 2 by continuous positive airway pressure: a report of two cases.

Spinal muscular atrophy (SMA) type 2 is a motor neuron disease that leads to severe congenital muscle atrophy. The majority of adult patients are at risk of death due to respiratory failure. Here, we report on two patients with SMA type 2 who repeatedly developed bronchitis and pneumonia. The patient in Case 1 was a 48-year-old female lacking exon 7 of the survival motor neuron gene (SMN) 1. The patient in Case 2 was a 37-year-old female lacking exons 7 and 8 in SMN 1 and exon 5 in the neuronal apoptosis inhibitory protein (NAIP) gene. We applied continuous positive airway pressure (CPAP) in both cases because their data on polysomnography showed obstructive sleep apnea (OSA). CPAP treated their respiratory symptoms as well as those due to OSA. Moreover, CPAP stabilized the respiratory condition of Case 1 for seven years and seven months and that of Case 2 for five years and four months. These findings suggest that CPAP alone can achieve long-term improvement in the respiratory condition in patients with SMA type 2.

Sliding behavior of water droplets on flat polymer surface.

Flat films of methyl methacrylate-fluoroalkyl methacrylate copolymers were prepared, and their hydrophobicity was investigated. It was revealed that the F concentration directly affects the static hydrophobicity on the flat polymer surface in a systematic manner. Furthermore, the sliding behavior of a water droplet on these surfaces depends on the static hydrophobicity; the sliding motion changes from constant velocity to constant acceleration with an increase in the water contact angle.

Sulphonylurea receptors differently modulate ICC pacemaker Ca2+ activity and smooth muscle contractility.

Appropriate gastrointestinal motility is essential to properly control the body energy level. Intracellular Ca2+ ([Ca2+]i) oscillations in interstitial cells of Cajal (ICCs; identified with c-Kit immunoreactivity) are considered to be the primary mechanism for the pacemaker activity in gastrointestinal motility. In the present study, RT-PCR examinations revealed predominant expression of the type 1 isoform of sulphonylurea receptors (SUR1) in ICCs of the mouse ileum, but expression of SUR2 was predominant in smooth muscle. In cell clusters prepared from the same tissue, smooth muscle contractility and pacemaker [Ca2+]i activity in ICCs were found to be differentially modulated by K(ATP) channel openers and sulphonylurea compounds, in accordance with the expression of SUR isoforms. 1 microM cromakalim nearly fully suppressed the mechanical activity in smooth muscle, whereas ICC pacemaker [Ca2+]i oscillations persisted. Greater concentrations (approximately 10 microM) of cromakalim attenuated pacemaker [Ca2+]i oscillations. This effect was not reversed by changing the reversal potential of K+, but was prevented by glibenclamide. Diazoxide at 30 muM terminated ICC pacemaker [Ca2+]i oscillations, but again treatment with high extracellular K+ did not restore them. These results suggest that SUR can modulate pacemaker [Ca2+]i oscillations via voltage-independent mechanism(s), and also that intestinal pacemaking and glucose control are closely associated with SUR.

Bactericidal activity of copper-deposited TiO2 thin film under weak UV light illumination.

The bactericidal activity of copper-deposited titanium dioxide thin film (Cu/TiO2) was investigated under very weak ultraviolet (UV) light illumination. To elucidate the roles of the film photocatalyst and the deposited copper in the bactericidal activity, cells from a copper-resistant Escherichia coli (E. coli) strain were utilized. A decrease in survival rate was not observed with the copper-resistant cells under dark conditions, but when illuminated with a very weak UV intensity of 1 microW/cm2, the survival rate decreased, suggesting photocatalytic bactericidal activity. The decay curve of survival on the Cu/TiO2 film under very weak UV light illumination consisted of two steps, similar to the survival change of normal E. coli on TiO2 films under rather strong UV illumination. The first step is due to the partial decomposition of the outer membrane in the cell envelope by a photocatalytic process, followed by permeation of the copper ions into the cytoplasmic membrane. The second step is due to a disorder of the cytoplasmic membrane caused by the copper ions, which results in a loss of the cell's integrity. These processes explain why the Cu/TiO2 film system shows an effective bactericidal activity even under very weak UV light illumination.

Design of a photocatalyst for bromate decomposition: surface modification of TiO2 by pseudo-boehmite.

The rate of BrO3- reduction by a commercial TiO2 photocatalyst under UV illumination in an aqueous solution was increased by lowering the pH from 7 to 5. The effect is attributable to an enhancement of the electrical interaction between BrO3- and the positively charged surfaces of the TiO2 photocatalyst. The surface charge can be controlled by a surface modification of the TiO2 photocatalyst without controlling the pH of the water. In fact, the isoelectric point of surface-modified TiO2 was higher than that of the unloaded TiO2 photocatalyst, resulting in an increase in the rate of the photocatalytic reduction of BrO3- at a neutral pH. This increase is explained by an increase in the amount of adsorbed BrO3- on the photocatalyst surface.

Neurofibromin and NF1 gene analysis in composite pheochromocytoma and tumors associated with von Recklinghausen's disease.

Composite tumor of pheochromocytoma and neuroblastoma, or ganglioneuroma, or ganglioneuroblastoma (composite pheochromocytoma), also known as mixed neuroendocrine and neural tumor, are sometimes combined with neurofibromatosis type 1 (NF1). To better understand the relationship between NF1 and composite pheochromocytoma, an immunohistochemical study using anti-neuro-fibromin that is an NF1 gene product and DNA sequence of NF1 Exon 31 were carried out in five cases of composite pheochromocytoma and in various tumors from five patients with NF1. Neurofibromin was not expressed in Schwann cells and sustentacular cells of composite pheochromocytomas and was very weakly or negatively expressed in neurofibroma of NF1 patients. However, it was strongly expressed in ganglionic cells and pheochromocytoma cells of the composite pheochromocytomas and also in mucosal ganglioneuromas, a gangliocytic paraganglioma, and in pheochromocytomas from the patients with NF1. Although there was no mutation in NF1 Exon 31, it could not be ruled out that there were mutations in other sites of the NF1 gene. Neurofibromin insufficiency may induce abnormal proliferation of Schwann cells in composite pheochromocytomas as well as in neurofibromatosis.