Symptomatic improvement of diffuse esophageal spasm after botulinum toxin injection

Diffuse esophageal spasm, an uncommon esophageal motility disorder, has recently been defined using high-resolution manometry. Patients with distal esophageal spasm usually complain of chest pain or dysphagia. The etiology and pathophysiology of this disorder are poorly known, and treatment options are limited. However, some options to improve symptoms are available, including endoscopic injection of botulinum toxin. Nevertheless, few reports have described the effects of endoscopic injection of botulinum toxin in patients with symptomatic diffuse esophageal spasm with clear endoscopic and high-resolution manometry images. Here, we report a case of diffuse esophageal spasm diagnosed with high-resolution manometry and treated by endoscopic injection of botulinum toxin with good results at the 7-month follow-up.     

Effects of chlorinated Pd precursors and preparation methods on properties and activity of Pd/TiO2 catalysts

We investigated the effects of Pd precursors and preparation methods on the physicochemical properties and performance of Pd/TiO₂ catalysts in the photocatalytic degradation of methyl violet. To confirm the influence of the precursors, Pd/TiO₂ catalysts were prepared via chemical reduction (CR) using four different Pd precursors. Additionally, to determine the effects of preparation methods, Pd/TiO₂ catalysts were fabricated using K₂PdCl₄ precursor via three different methods: CR, deposition–precipitation (DP), and impregnation. The CO chemisorption results showed that the catalyst prepared via DP using the K₂PdCl₄ precursor, i.e., Pd/TiO₂_K_DP, displayed the highest Pd dispersion of 12.42% owing to the stable formation of Pd(OH)₂, which strongly interacted with the –OH groups on the TiO₂ support. Although the catalyst prepared via CR using the Pd(NH₃)₄Cl₂·H₂O (PA) precursor, i.e., Pd/TiO₂_PA_CR, had the lowest Pd dispersion of 0.7%, it exhibited the highest absorption of 26% after 30 min in the dark. It was found that high Pd²⁺/Pd⁰ ratio in dark conditions adversely affected the absorption of MV owing to electrostatic repulsion between the cationic dyes and metal nanoparticles. However, the Pd dispersion and the specific surface area played a key role in the photocatalytic activity under UV irradiation. Pd/TiO₂_K_CR with higher Pd dispersion showed the highest photocatalytic activity and reaction rate of 0.0212 min⁻¹.

We investigated the effects of Pd precursors and preparation methods on the physicochemical properties and performance of Pd/TiO₂ catalysts in the photocatalytic degradation of methyl violet.     

An enhanced treatment effect can be expected from a higher serum thyroglobulin level after radioactive iodine therapy

Annals of Nuclear Medicine - The aim of this study was to investigate if increased serum thyroglobulin (Tg) levels after radioactive iodine (RAI) showed more therapeutic effects in patients with...     

Use of a Target‐Mediated Drug Disposition Model to Predict the Human Pharmacokinetics and Target Occupancy of GC1118, an Anti‐epidermal Growth Factor Receptor Antibody

GC1118 is an anti‐epidermal growth factor receptor (EGFR) monoclonal antibody that is currently under clinical development. In this study, the pharmacokinetics (PK) of GC1118 were modelled in monkeys to predict human PK and receptor occupancy (RO) profiles. The serum concentrations of GC1118 and its comparator (cetuximab) were assessed in monkeys with a non‐compartmental analysis and a target‐mediated drug disposition (TMDD) model after intravenous infusion (3–25 mg/kg) of these drugs. The scaling exponent of the EGFR synthesis rate was determined using a sensitivity analysis. The human cetuximab exposures were simulated by applying different exponents (0.7–1.0) for the EGFR synthesis rate in the allometric monkey PK model. Simulated C_max and area under the curve values therein were compared with those previously reported in the literature to find the best exponent for the EGFR synthesis rate in human beings. The TMDD model appropriately described the monkey PK profile, which showed a decrease in clearance (CL; 1.2–0.4 ml/hr/kg) as the dose increased. The exponents for CL (0.75) and volume of distribution (Vd; 1.0) were used for the allometric scaling to predict human PK. The allometric coefficient for the EGFR synthesis rate chosen by the sensitivity analysis was 0.85, and the RO profiles that could not be measured experimentally were estimated based on the predicted concentrations of the total target and the drug–target complex. Our monkey TMDD model successfully predicts human PK and RO profiles of GC1118 and can be used to determine the appropriate dose for a first‐in‐human study investigating this drug.     

High preoperative neutrophil–lymphocyte ratio predicts biochemical recurrence in patients with localized prostate cancer after radical prostatectomy

Purpose

To investigate the association between preoperative neutrophil–lymphocyte ratio (NLR) and oncological outcomes in patients with localized prostate cancer (PCa) after radical prostatectomy (RP).

Methods

We retrospectively reviewed the records of 1367 patients who underwent RP between November 2003 and April 2012. Patients who underwent a concurrent biopsy/procedure in other organs, had evidence of acute infection, or had systemic inflammatory disease were excluded. We divided the patients by NLR level and analyzed their perioperative outcomes. To determine NLR significance, we performed a multivariate logistic regression analysis of the pathological adverse outcomes and a Cox proportional hazard analysis of the biochemical recurrence (BCR), which was defined as a prostate-specific antigen level ≥0.2 ng/mL on two consecutive tests.

Results

Among the 1367 patients, 158 (11.6 %) in the high-NLR (≥2.5) group had a higher biopsy Gleason score (p < 0.001), pathological Gleason score (p < 0.001), and pathological stage (p < 0.001) than patients in the low-NLR (<2.5) group (n = 1209, 88.4 %). Multivariate analysis revealed that high NLR was significantly correlated with adverse pathological outcomes of higher pathological stage (HR 1.688; 95 % CI 1.142–2.497; p = 0.009) and extracapsular extension (HR 1.698; 95 % CI 1.146–2.516; p = 0.008). Kaplan–Meier analysis showed significantly worse BCR-free survival (p < 0.001) in patients with a high NLR. A high NLR was a significant predictor of BCR after RP (HR 1.358; 95 % CI 1.008–1.829; p = 0.044).

Conclusions

High NLR was significantly related to unfavorable clinicopathological outcomes and worse BCR-free survival. Further studies are needed to clarify the correlation between NLR and PCa.