Effect of central sensitization on dizziness-related symptoms of persistent postural-perceptual dizziness.

BACKGROUND: Persistent postural-perceptual dizziness (PPPD) is a chronic functional dizziness symptom triggered by psychological stress, but its pathophysiology is unknown. Central sensitization is considered the cause of functional diseases, such as medically unexplained symptoms, and is a psychosocially affected condition. However, the association between dizziness symptoms in PPPD and central sensitization remains unclear. Thus, we conducted a cross-sectional study on the relation between dizziness symptoms and central sensitization in PPPD. METHODS: We recruited 61 outpatients with dizziness who met the PPPD diagnostic criteria. In addition to the evaluation of dizziness symptoms using the Dizziness Handicap Inventory, the participants were evaluated using the Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index, and Central Sensitization Inventory (CSI). A CSI score of 40 or higher was defined as central sensitization syndrome (CSS), and the severity of each condition in CSS and non-CSS participants was compared. We also evaluated the association between dizziness symptoms and central sensitization and coexisting symptoms using linear multiple regression analysis. RESULTS: We analyzed the data of 50 valid responses (valid response rate of 82.0 percent). Compared with the non-CSS group, the CSS group had a higher degree of disability owing to dizziness and a higher rate of complications of anxiety and depression. The regression analysis results showed that the severity of central sensitization was a related factor that could enhance the dizziness symptoms of PPPD. CONCLUSIONS: Central sensitization may affect the dizziness symptoms of PPPD as an exacerbating factor.

Preparation of Nanoparticles Including Antisolvent Drugs by the Combination of Roll Milling and High-pressure Homogenization.

DESCRIPTION: Design methods of nanoparticle formulations are divided into break-down methods and build-up methods. The former is further divided into dry and wet processes. For drug nanoparticle preparations, the wet process is generally employed, and organic solvents are used in most formulations. METHOD: In this study, we investigate the preparation of nifedipine (IB) and griseofulvin (GF) nanoparticles without using organic solvent. Both IB and GF nanoparticles, with a mean particle size of approximately 50 nm, were prepared without organic solvent by employing a combination of roll milling and high-pressure homogenization. RESULT: The X-ray diffraction peak of the IB and GF samples prepared by roll milling was present at a position (2θ) identical to that of IB and GF crystals, indicating that no peak shift was induced by interaction with phospholipids. CONCLUSION: These findings demonstrate that most IB and GF nanoparticles exist as crystals in phospholipids.

RUNX transcription factors potentially control E-selectin expression in the bone marrow vascular niche in mice.

Although the function of Runt-related (RUNX) transcription factors has been well characterized in leukemogenesis and regarded as an ideal target in antileukemia strategies, the effect of RUNX-inhibition therapy on bone marrow niche cells andr its impact on the engraftment of acute myeloid leukemia (AML) cells have largely been unknown. Here, we provide evidence suggesting the possible involvement of RUNX transcription factors in the transactivation of E-selectin, a member of selectin family of cell adhesion molecules, on the vascular endothelial cells of the mice bone marrow niche. In our experiments, gene switch-mediated silencing of RUNX downregulated E-selectin expression in the vascular niche and negatively controlled the engraftment of AML cells in the bone marrow, extending the overall survival of leukemic mice. Our work identified the novel role of RUNX family genes in the vascular niche and showed that the vascular niche, a home for AML cells, could be strategically targeted with RUNX-silencing antileukemia therapies. Considering the excellent efficacy of RUNX-inhibition therapy on AML cells themselves as we have previously reported, this strategy potentially targets AML cells both directly and indirectly, thus providing a better chance of cure for poor-prognostic AML patients.

Comparison of the Control of Nausea and Vomiting among Several Moderately Emetic-Risk Chemotherapy Regimens.

BACKGROUND: Different antiemetic medications with or without aprepitant are recommended for moderately emetic-risk chemotherapy (MEC) depending on the emetic potential of chemotherapy agents, although the criterion for the use of aprepitant is still unclear. The present study was designed to compare the control of chemotherapy-induced nausea and vomiting (CINV) among several MEC regimens used in the outpatient chemotherapy setting. MATERIALS AND METHODS: A single center prospective observational study was carried out in 326 patients who received 2,061 chemotherapy cycles from January 2013 to December 2014. Antiemetic medication consisting of two-drug combination of granisetron (day 1) and dexamethasone (days 1-3) was carried out in 87.6% of patients receiving the first chemotherapy cycle. The checklist for CINV was provided to all patients, and the control of CINV was evaluated on the next visit based on the checklist. Complete inhibition of nausea and vomiting during acute and delayed periods were compared among MEC regimens. RESULTS: Two hundred and one patients received the first cycle of chemotherapy, in which the rates of complete inhibition of nausea and vomiting were 87.6% and 95.5%, respectively, during acute period, and 68.2% and 92.0%, respectively, during delayed period. There were no significant differences in the control of CINV among oxaliplatin, carboplatin and irinotecan, except for the cyclophosphamide-base regimen. CONCLUSIONS: Two-drug antiemetic medication of 5-HT3 receptor antagonist and dexamethasone was sufficiently effective for prevention of CINV in most MEC regimens.

Simultaneous and rapid determination of gefitinib, erlotinib and afatinib plasma levels using liquid chromatography/tandem mass spectrometry in patients with non-small-cell lung cancer.

A simultaneous, selective, sensitive and rapid liquid chromatography/tandem mass spectrometry method was developed and validated for the quantification of gefitinib, erlotinib and afatinib in 250 µL samples of human blood plasma. Diluted plasma samples were extracted using a liquid-phase extraction procedure with tert-butyl methyl ether. The three drugs were separated by high-performance liquid chromatography using a C18 column and an isocratic mobile phase running at a flow rate of 0.2 mL/min for 5 min. The drugs were detected using a tandem mass spectrometer with electrospray ionization using imatinib as an internal standard. Calibration curves were generated over the linear concentration range of 0.05-100 nm in plasma with a lower limit of quantification of 0.01 or 0.05 nm for all compounds. Finally, the validated method was applied to a clinical pharmacokinetic study in patients with nonsmall-cell lung cancer (NSCLC) following the oral administration of afatinib. These results indicate that this method is suitable for assessing the risks and benefits of chemotherapy in patients with NSCLC and is useful for therapeutic drug monitoring for NSCLC treatment. As far as we know, this is the first report on LC-MS/MS method for the simultaneous quantification of NSCLC tyrosine kinase inhibitor plasma concentrations including afatinib. Copyright © 2015 John Wiley & Sons, Ltd.

Control of chemotherapy-induced nausea in patients receiving outpatient cancer chemotherapy.

BACKGROUND: Control of chemotherapy-induced nausea is still incomplete, regardless of adherence to the antiemetic guideline. The present study was designed to assess the control rates of nausea and vomiting in the outpatient chemotherapy clinic and to determine risk factors for nausea. METHODS: A single-center prospective observational study was carried out in 779 patients who received 5511 chemotherapy cycles from January 2013 to December 2014 in the outpatient chemotherapy clinic. A checklist for adverse events was provided to all patients, and nausea and vomiting were monitored on the next visit. Complete protection from nausea and vomiting during acute (within 24 h) and delayed (during 2-7 days) periods was assessed. RESULTS: Under the condition of 76-99 % rates of adherence to the Japanese Society of Clinical Oncology guideline for antiemesis, the rates of complete protection from acute and delayed nausea in the first cycle of chemotherapy were 60 % and 45 %, respectively, for high emetic risk chemotherapy (HEC), and 85 % and 70 % for moderate emetic risk chemotherapy (MEC). The rates were improved in the overall cycles. On the other hand, vomiting was well controlled, in which complete protection ranged from 83 % (HEC) to 99 % (minimum). A multivariate analysis indicated that being female, age less than 60 years, high or moderate risk chemotherapy, and anthracycline/cyclophosphamide (A/C) were significant risks for overall nausea. Indeed, the control of delayed nausea was extremely poor in the first cycle of A/C, although there was no difference in the control of nausea among MEC. CONCLUSION: Antiemetic medication in consideration of the risk factors is required to improve the control of nausea.

Prevention of radiation esophagitis by polaprezinc (zinc L-carnosine) in patients with non-small cell lung cancer who received chemoradiotherapy.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) plays an important role in multimodality therapy for non-small cell lung cancer. However, esophagitis often develops as a complication of CCRT, causing treatment delays and reducing the patient's quality of life. We examined the efficacy of polaprezinc (PZ), zinc L-carnosine used for the therapy of gastric ulcer, against the onset of esophagitis caused by CCRT for lung cancer. PATIENTS AND METHODS: Patients who concurrently underwent chemotherapy with carboplatin and paclitaxel and thoracic radiotherapy at Gifu University Hospital during a period of January 2011 and May 2015 were the subjects of the present study. Patients received a mixture of sodium alginate solution and aluminum-magnesium hydroxide gel with (PZ group) or without (control group) PZ for prevention of radiation esophagitis. RESULTS: PZ significantly inhibited the development of grade ≥2 radiation esophagitis (HR 0.397, 95% confidence interval, 0.160-0.990; P=0.047). In addition, PZ lowered the incidence of grade ≥2 esophagitis at the time point of 40 Gy irradiation (26.3% versus 63.2%, P=0.05). However, there were no significant differences in the incident rates of other adverse events associated with chemoradiotherapy between the PZ group and control group. Moreover, PZ had no significant influence on the tumor response rate. CONCLUSION: PZ significantly retarded the development as well as the incidence of grade ≥2 esophagitis without affecting the tumor response.

Prophylactic Effect of Oral Minocycline in Combination with Topical Steroid and Skin Care Against Panitumumab-induced Acneiform Rash in Metastatic Colorectal Cancer Patients.

BACKGROUND: Although the anti-EGFR monoclonal antibody panitumumab is effective in treating colorectal cancer, the occurrence of severe skin disorders often discontinues therapy. Herein, we investigated by a retrospective chart review the effect of prophylactic oral minocycline in combination with skin treatment using moisturizer on the incidence of skin disorders and tumor response in metastatic colorectal cancer patients who received panitumumab. PATIENTS AND METHODS: In a total of 55 patients, 38 patients were eligible, consisting the pre-emptive group (N=25) and reactive group (N=13). Acneiform rash and other adverse events were graded according to the CTCAE v4.0. RESULTS: The occurrence of acneiform rash (grade ≥2) was significantly lower in pre-emptive group than in reactive group (44.0% vs. 84.6%, p=0.04). No significant differences in the occurrence of other adverse events were observed between the two groups. Tumor response was not significantly different between the two groups (36.0% vs. 7.7%, OR, 6.75; 95% confidence interval (CI)=0.75-60.76, p=0.12). Mean time to treatment failure was 149.7 days and 110.2 days in the pre-emptive group and reactive treatment group, respectively (HR=0.58; 95% CI= 0.26-1.28, p=0.18). CONCLUSION: Prophylactic oral minocycline combined with skin care reduced panitumumab-induced acneiform rash without a significant influence on tumor response.

[Evaluation of the efforts of pharmaceutical care services before medical examination at an outpatient cancer chemotherapy clinic].

In the outpatient cancer chemotherapy clinic of Gifu University Hospital, pharmacists contributed to the provision of safe and efficacious cancer chemotherapy as full-time staff, together with doctors, nurses and other medical staff. Since April 2010, three pharmacists have been in charge of the provision of pharmaceutical care services(PCS)to all patients. Furthermore, pharmaceutical intervention before medical examination(pre-PCS)was initiated in May 2011. As a consequence, the time spent for patient education and monitoring significantly(p<0. 001)increased from 39. 7±3. 2min/patient in 2010 to 48. 0±2. 6min/patient in 2011. The number of proposals on prescriptions also significantly increased, 2. 5 times, compared to 2010. The percentage of the acceptance of proposals was 94% in fiscal year 2011. Importantly, pre-PCS improved the control of chemotherapy-induced nausea and vomiting, peripheral neuropathy and skin rash. These results suggest that pre-PCS by pharmacists would be beneficial to progress the quality of outpatient cancer chemotherapy.

A randomized controlled non-inferiority study comparing the antiemetic effect between intravenous granisetron and oral azasetron based on estimated 5-HT3 receptor occupancy.

BACKGROUND: The acute antiemetic effect was compared between oral azasetron and intravenous granisetron based on the 5-hydroxytryptamine(3) (5-HT(3)) receptor occupancy theory. PATIENTS AND METHODS: Receptor occupancy was estimated from reported data on plasma concentrations and affinity constants to 5-HT(3) receptor. A randomized non-inferiority study comparing acute antiemetic effects between oral azasetron and intravenous granisetron was performed in 105 patients receiving the first course of carboplatin-based chemotherapy for lung cancer. RESULTS: Azasetron exhibited the highest 5-HT(3) receptor occupancy among various first-generation 5-HT(3) antagonists. The complete response to oral azasetron was shown to be non-inferior to that of intravenous granisetron, in which the risk difference was 0.0004 (95% confidence interval: -0.0519-0.0527). The lower limit of the confidence intervals did not exceed the negative non-inferiority margin (-0.1). The complete response during the overall period was not different (68% versus 67%). CONCLUSION: Oral azasetron was found to be non-inferior to intravenous granisetron in the acute antiemetic effect against moderately emetogenic chemotherapy.