Efficacy and safety of bilastine in Japanese patients with perennial allergic rhinitis: A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III study.

BACKGROUND: Bilastine, a novel non-sedating second-generation H1 antihistamine, has been approved in most European countries since 2010. This study aimed to evaluate the superiority of bilastine over placebo in Japanese patients with perennial allergic rhinitis (PAR). METHODS: This randomized, double-blind, placebo-controlled, parallel-group, phase III study (trial registration number JapicCTI-142600) evaluated the effect of a 2-week treatment period with bilastine (20 mg once daily), fexofenadine (60 mg twice daily), or a matched placebo (double dummy) in patients with PAR. All patients were instructed to record individual nasal and ocular symptoms in diaries daily. The primary endpoint was the mean change in total nasal symptom scores (TNSS) from baseline to Week 2 (Days 10-13). RESULTS: A total of 765 patients were randomly allocated to receive bilastine, fexofenadine, or placebo (256, 254, and 255 patients, respectively). The mean change in TNSS from baseline at Week 2 was significantly decreased by bilastine (-0.98) compared to placebo (-0.63, P = 0.023). Bilastine and fexofenadine showed no significant difference in the primary endpoint. However, the mean change in TNSS from baseline on Day 1 was more significantly decreased by bilastine (-0.99) than by placebo (-0.28, P < 0.001) or fexofenadine (-0.62, P = 0.032). The active drugs also improved instantaneous TNSS 1 h after the first and before the second drug administration on Day 1 (P < 0.05). The study drugs were well tolerated. CONCLUSIONS: After 2-week treatment period, bilastine 20 mg once daily was effective and tolerable in Japanese patients with PAR, and exhibited a rapid onset of action.

[Regression of metastatic hepatic cancer from gastric cancer by polysaccharide K and UFT administration--a case report].

Various treatments for hepatic metastasis of gastric cancer have been attempted, but problems remain with respect to long-term effectiveness and recurrence. Case reports have indicated the tumor regression effect of polysaccharide K(PSK)combined with chemotherapy, and meta-analysis has shown that PSK combined with chemotherapy improves the prognosis compared to chemotherapy alone. However, marked improvement of disease following PSK administration is rarely reported. We report a case of hepatic metastasis of gastric cancer in which low-dose UFT and PSK therapy resulted in regression of metastatic hepatic lesions and improvement of tumor markers. A 78-year-old man had synchronous hepatic metastasis of gastric cancer. Gastrectomy and microwave coagulation therapy using Microtase were conducted, followed by postoperative adjuvant chemotherapy with UFT 300 mg/day. Recurrences of metastatic hepatic lesion and new hepatic lesion were observed 6 months after surgery. Addition of PSK to UFT chemotherapy was selected as the treatment for recurrences, resulting in disappearance of the hepatic lesions and normalization of tumor markers. The patient is alive without recurrence at this writing, 38 months after surgery.

Functional connectivity during monitoring for visuomotor incongruence.

Previous human studies on monitoring for visuomotor incongruence emphasized the contribution of the fronto-parietal network and revealed significant activation of the right dorsolateral prefrontal cortex (DLPFC) and the right rostral inferior parietal lobule. Using functional MRI, this study investigated the brain regions involved in explicit monitoring for incongruence between motor intention and visual and/or proprioceptive information, particularly focusing on the fronto-parietal network. During in-phase bimanual movements, a static image of the participant's own hands was randomly inserted within real-time visual feedback of the movements to produce a mismatch between the actual performance and the visual input. The results of our task were similar to those of previous studies, in that greater activity was observed in the right DLPFC during incongruence conditions than during congruence conditions. However, the anatomical location of the DLPFC cluster was found in a more ventral region, compared with previous studies. Psychophysiological interaction analysis for the entire brain, using the right DLPFC as a seed region, indicated significantly greater functional connectivity with the bilateral dorsal premotor cortex, middle temporal gyri (area V5), and right rostral inferior parietal lobule (area PFt).

Long-term safety and efficacy of bilastine following up to 12 weeks or 52 weeks of treatment in Japanese patients with allergic rhinitis: Results of an open-label trial.

OBJECTIVE: Bilastine is a novel second-generation antihistamine. This open-label, single-arm, phase III study evaluated the safety and efficacy of long-term treatment with bilastine in Japanese patients with seasonal (SAR) or perennial allergic rhinitis (PAR). METHODS: Patients with SAR or PAR who met the registration criteria and did not violate the exclusion criteria received bilastine (20mg, once daily) for 12 weeks (treatment period). Patients with PAR who met the transition criteria could elect to continue the bilastine treatment for an additional 40 weeks (continuous treatment period: a total of 52 weeks). Safety and tolerability were the primary outcomes, and the main secondary endpoint was to evaluate changes in efficacy variables from baseline measurements. RESULTS: Fifty-eight patients with SAR and 64 patients with PAR received bilastine (20mg/day) for 12 weeks. Fifty-five patients with PAR transitioned to the continuous treatment period. Adverse events (AEs) were reported by 17.2% of patients with SAR and by 31.3% of patients with PAR, and adverse drug reactions (ADRs) were reported by 6.3% of patients with PAR but by no patients with SAR during the 12-week treatment period. All of the ADRs were mild in severity. During the 52-week treatment period, AEs and ADRs were reported by 73.4% and 6.3% of patients with PAR, respectively. All of the ADRs occurred during the 12-week treatment period, and none during the continuous treatment period. The AEs were categorized using the System Organ Class of nervous system disorders; 4.7% of patients reported headache, but none reported somnolence. One serious AE was reported, but it was considered to be unrelated to the bilastine treatment. There were no deaths, and no patients withdrew from the study because of AEs. In patients with SAR, bilastine significantly decreased the total nasal symptom score (TNSS), total ocular symptom score (TOSS), and total symptom score (TSS) relative to baseline. Prolonged treatment with bilastine resulted in the maintenance of a significant reduction in TNSS, TOSS, and TSS from the baseline in patients with PAR. Improvement of quality of life was also observed in patients with SAR and PAR. CONCLUSION: Bilastine was safe, well tolerated, and effective for patients with SAR and PAR. The observed improvement was maintained for the duration of the study, with no loss of drug efficacy (registration number JapicCTI-142622).

Overexpression of ErbB4 is an independent marker for lymph node metastasis in Japanese patients with oral squamous cell carcinoma.

OBJECTIVE: Overexpression of the epidermal growth factor receptor (EGFR) family is common in oral squamous cell carcinoma (OSCC). Therefore, we analyzed the expression profiles of the four EGFR family members (ErbB1, ErbB2, ErbB3, and ErbB4) in OSCC of Japanese patients. STUDY DESIGN: Sixty-eight primary tumors and 18 normal oral mucosal tissue specimens were evaluated in this study. We analyzed EGFR family members using quantitative polymerase chain reaction and immunohistochemistry, as well as their relationships with clinical factors. RESULTS: The expression level of ErbB1 messenger RNA (mRNA) was markedly increased in OSCC. By comparing the gene expression levels of EGFR family members in OSCC tissues that had lymph node metastasis with those in the absence of lymph node metastasis, we found that ErbB4 mRNA expression was increased significantly. There was also a significant correlation between the mRNA expression level of ErbB4 and those of ErbB2 and ErbB3 in cases with lymph node metastasis. Moreover, we confirmed protein expression of ErbB4 in the cytoplasm and membrane of tumor cells, which was stronger in cases with lymph node metastasis. CONCLUSIONS: ErbB4 is an independent marker for lymph node metastasis in OSCC.

Development of phase-separated scintillators with light-guiding properties.

Alkali halide systems that function as phase-separated scintillators (PSSs) with light-guiding properties are sucessfully created. Furthermore, it is the matrix phases of the PSSs which display the light-guiding properties. CsI-NaCl:Tl is a practical material pair because of its high pixel light output and good spatial resolution.

Effect of pretreatment with fexofenadine on the safety of immunotherapy in patients with allergic rhinitis.

BACKGROUND: Allergen-specific immunotherapy, although not a cure, remains the only treatment available that can alter the natural course of an allergic disease. However, the risk of allergen specific immunotherapy-related systemic reactions (SRs), reported to occur in approximately 1% to 14% of patients and which can range from mild to fatal in seriousness, represents a barrier to implementing this unique and effective treatment option. OBJECTIVE: To explore the possibility that pretreatment with the H1-antihistamine fexofenadine could prevent the occurrence of severe SRs induced by immunotherapy in Japanese patients with allergic rhinitis. METHODS: In this open-label, multicenter study, 134 patients receiving immunotherapy for allergic rhinitis were randomized 1:1 to a group receiving pretreatment with fexofenadine hydrochloride (60 mg) 2 hours before immunization injection (n = 67) or to a control group receiving no pretreatment (n = 67). Patients were further grouped into those who received cedar pollen immunotherapy and those who received dust mite immunotherapy. RESULTS: Pretreatment with fexofenadine 2 hours before immunotherapy significantly reduced the occurrence of severe SRs (P = .03), significantly increased the proportion of patients receiving cedar pollen immunotherapy who achieved the target maintenance dose (TMD) (P = .03), and significantly reduced the length of time to attain the TMD (P = .047 and P = .003 for patients receiving cedar pollen and dust mite immunotherapy, respectively). CONCLUSIONS: This study suggests a novel role for fexofenadine in enhancing the safety of immunotherapy and increasing the proportion of patients achieving the TMD.

Room-temperature grating-based morphological hole burning in Sm2+-doped glass powders.

We have observed grating-based morphological hole burning in Sm2+-doped glass powders at room temperature. When photobleaching on the 4f(6)-4f(5)5d transition of Sm2+ is combined with multiple light scattering, holes are produced in frequency and wave-vector domains. The hole profile depends on the amount of light absorption of Sm2+; it sharpens as the absorption decreases. The variation of the hole shape is explained theoretically based on a diffusion approximation.