scholarly journals Methotrexate in saliva and risk in the development of chemotherapeutic mucositis in children

2019 ◽  
pp. 99-104
Author(s):  
T. V. Papruzhenka ◽  
S. P. Borys ◽  
O. V. Krasko
Keyword(s):  
Oral Cavity ◽  
Anticancer Therapy ◽  
Mixed Effects ◽  
High Dose ◽  
Time Points ◽  
Methotrexate Concentration ◽  
Significant Difference ◽  
Oral Liquid ◽  
Analysis Of Dynamics ◽  
Method R

The aim of the study was to assess the possible direct effect of anticancer therapy with methotrexate (MTX) in bio liquids on the oral mucosa in the development of oral mucositis (OM). Twenty one children and adolescents participated in this study. Chemotherapy with MTX was administered in the following concentrations of 1; 2; 5 g/m2 of body surface area during 24 hours (including four episodes with OM). Twenty seven episodes of chemotherapy with high dose MTX were assessed in the samples of saliva on the 6th; 12; 24; 42; 48; 54 hour from the start of infusion and in the samples of blood on the 42; 48; 54 hour from the start of infusion. Сoncentration of methotrexate was measured by standard fluorescent polarization immunoassay using MTX reagent pac kit according to the manufacturer's instructions. Analysis of dynamics of methotrexate concentration in samples was performed using a linear model of mixed effects, on the basis of which the average values ​​(M) and confidence intervals for them were calculated (95 % CI). The analysis of the correlation of the levels of methotrexate in the blood and oral liquid was performed at individual time points (42; 48 and 54 hours) using the Spearman method (r). It was determined that excretion of MTX in the oral cavity repeated its clearance in blood. MTX concentration in saliva was less than 1/10 from its concentration in blood. During the first day, MTX concentration had decimicromol level and then until 54 hour it had santimicromol level. MTX concentration in saliva on the 6; 12; 24 hour in children with OM was lower by 2 times than in children without OM (P < 0,001). There was no significant difference in those parameters between two groups (with or without OM) in the following observed hours. This data does not support hypothesis concerning involvement of salivary MTX in OM pathogenesis.

The clinical effect of Chitosan nanoparticles against Helicobacter pylori

2020 ◽  
Vol 10 (7) ◽  
pp. 1116-1121
Author(s):  
Jing Wang ◽  
Xinhong Wang ◽  
Min Li ◽  
Suxiang Fan
Keyword(s):  
Triple Therapy ◽  
Clinical Efficacy ◽  
Adverse Reactions ◽  
Chitosan Nanoparticles ◽  
High Dose ◽  
Significant Difference ◽  
Oral Liquid ◽  
Group A ◽  
The Difference ◽  
Group B

The objective of this study was to observe the clinical effect of Chitosan nanoparticles therapy on Helicobacter pylori (HP) infection. Three treatment groups (A, B, and control group C) were randomly assigned with 60 cases of HP each, making 180 cases. Group C received standard triple therapy (omeprazole + amoxicillin + clarithromycin), group A got a routine dose of Chitosan nanoparticles plus triple therapy, and group B got a high dose of Chitosan nanoparticles plus triple therapy. The course of treatment in each group was 7 days. The eradication rate, clinical efficacy and adverse reactions were observed. Up to 172 patients finished the experiment, with 59 patients in Group A, 57 in Group B and 56 in Group C. In a total analysis set (FAS), the eradication rates of HP in Group A, Group B and Group C were 80.00%, 80.70%, and 71.67%, respectively. There was no significant difference between the two groups (P > 0.05). In accordance with the PPS, the HP eradication rates of group A, B, and C were 81.36%, 80.70% and 76.79%, respectively, and there was no significant difference between the two groups (P > 0.05). The clinical efficacy of group A, B, and C were 91.67%, 91.23%, and 70.00%, respectively. The differences among the three groups were statistically significant (P < 0.05). In accordance with the PPS, the clinical efficacy of group A, B and C was 93.22%, 91.23%, and 75.00%, respectively. With a P-value of less than 0.05, the results indicated that the difference between the two groups was statistically significant. There were 21 adverse reactions in the experiment, including 3 in group A, 6 in group B, and 12 in group C. The difference was statistically significant (P < 0.05) between group A and B compared with group C, the difference was statistically significant (P < 0.05); the difference between group A and group B was statistically significant (P < 0.05). In conclusion the therapeutic effect of Chitosan nanoparticles and oral liquid, combined with triple therapy on HP infection is satisfactory, with less adverse reactions are. However, the findings suggest that it is not desirable to use a high dose Chitosan nanoparticles and oral liquid.

scholarly journals Daily Weight-Based Busulfan with Cyclophosphamide and Etoposide (Bu/Cy/VP) Produces Comparable Outcomes to 4-Times-Daily Busulfan Dosing for Lymphoma Patients Undergoing Autologous Stem Cell Transplantation (ASCT)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1987-1987
Author(s):  
Brian T. Hill ◽  
Lisa A. Rybicki ◽  
Catherine Weber ◽  
Deepa Jagadeesh ◽  
Aaron T. Gerds ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Therapeutic Dose ◽  
High Dose ◽  
Extraction Technology ◽  
Advisory Committees ◽  
Time Points ◽  
Dose Monitoring ◽  
Significant Difference ◽  
Before And After

Abstract INTRODUCTION: High dose busulfan (Bu) is an integral component of many commonly-used preparative regimens for both allogeneic and autologous transplantation. Data on the efficacy and toxicity of q6 vs. q24 hour dosing are of significant clinical interest. In order to facilitate a therapeutic dose-monitoring protocol, we transitioned from q6 to q24 Bu dosing as part of our standard Bu/Cy/VP ASCT preparative regimen for patients with Hodgkin (HL) and Non-Hodgkin Lymphoma (NHL) in July 2012. We present comparative outcomes of q24 Bu dosing vs historical controls receiving q6 Bu. METHODS We retrospectively reviewed 400 consecutive eligible lymphoma patients who underwent ASCT from 2007-2013 with Bu/Cy/VP. All patients received Cy 60 mg/kg IV over 4 hours on days -3 and -2 and VP 60 mg/kg as continuous infusion on days -5 and -4. Bu was given at a dose of either 0.8 mg/kg q6 (N = 307) x 14 doses for patients transplanted between 2007-July, 2012 or 2.8 mg/kg q 24 hours (N = 93) on days -9 through -6 for subsequent patients. Outcomes assessed from date of transplant were: relapse, non-relapse mortality (NRM), relapse-free survival (RFS) and overall survival (OS). Toxicity was assessed using pulmonary and liver function tests (PFTs and LFTs) at specified time-points before and after ASCT. In addition, for a subset of 22 patients receiving q24 Bu, we measured serial Bu serum levels after the first dose of Bu with an in-house liquid chromatography-tandem mass spectrometry assay using turbulent flow online extraction technology (Bunch, et al. J Chromatogr B Analyt Technol Biomed Life Sci, 2010. 878(31): p. 3255-8) and subsequently determined the cumulative Bu area-under the curve (AUC). RESULTS Baseline patient and disease characteristics of patients dosed with q6 and q24 Bu were similar. The median age was 55 (range 20-78) years; 63% were males. 18% had HL and 82% had NHL with a comparable distribution of subtypes in both groups. Patients in both groups had comparable rates of prior chemotherapy regimens and of complete/partial remission at the time of ASCT. Due to a change in institutional guidelines, plerixafor was more commonly incorporated in peripheral blood stem cell mobilization regimen in the q24 group compared to q6 cohort (70% vs. 39%, P <0.001). However, CD34+ doses were same in the two dosing cohorts. In terms of toxicity of the two dosing approaches, there was no significant difference in FEV1 or DLCO before and after transplant in the q6 vs q24 cohorts. LFTs measured at four time points were generally lower with q24 Bu, particularly AST and alkaline phosphatase (P=0.007 each), but these difference were not clinically significant. The median follow-up was longer in the q6 than q24 group (48.2 months vs. 21.3 months, P < 0.001). 18 month outcomes of the two dosing cohorts were comparable (see Table and Figure). We observed significant variation in AUC with weight-based dosing of Bu (AUC range 12,104 - 23,084 µM-min) with a median of 17,568 µM -min, which has served as a baseline for subsequent therapeutic-dose monitoring. CONCLUSIONS Q24 Bu dosing in combination with Cy/VP is more convenient than q6 hours, has equivalent outcomes, and results in no increase in either hepatic or pulmonary toxicity. Consistent with previous reports, there is a significant range of Bu AUC levels, with a standard deviation of 12%. These data provide rationale for our prospective clinical trial of real-time therapeutic dose monitoring with q24 Bu dosing. Table 1. Q6 dosing Q24 dosing P-value OS 78% 80% 0.79 RFS 63% 61% 0.99 NRM 5% 3% 0.95 Relapse 30% 36% 0.46 18 month outcomes of q6 vs q24 Bu dosing Figure 1. RFS and OS for lymphoma patients undergoing ASCT with Bu/Cy/VP treated with q6 vs. q24 hour weight-based Bu dosing. Figure 1. RFS and OS for lymphoma patients undergoing ASCT with Bu/Cy/VP treated with q6 vs. q24 hour weight-based Bu dosing. Figure 2. Figure 2. Disclosures Hill: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Majhail:Gamida Cell Ltd.: Consultancy; Anthem Inc.: Consultancy.

scholarly journals Results from a pilot study on the oral microbiome in children and adolescents with chronic nonbacterial osteomyelitis

2021 ◽  
Author(s):  
Mona Zeus ◽  
Stefan Janssen ◽  
Hans-Jürgen Laws ◽  
Ute Fischer ◽  
Arndt Borkhardt ◽  
...  
Keyword(s):  
Pilot Study ◽  
Oral Cavity ◽  
Disease Activity ◽  
Children And Adolescents ◽  
Oral Microbiome ◽  
Rrna Gene ◽  
Significant Shift ◽  
Time Points ◽  
Significant Difference ◽  
Chronic Nonbacterial Osteomyelitis

Abstract Objective To analyze the composition of the oral microbiome in children and adolescents with chronic nonbacterial osteomyelitis (CNO) with respect to age distribution, gender differences, effects of medication, disease activity and the influence of body site. Methods The oral microbiome of 20 patients (12 male and 8 female; median age 10.3 years) and 36 controls were examined. Two different sites of the oral cavity were swabbed at two time points. Current medication and disease activity were evaluated and registered at these time points. Samples were subjected to amplicon sequencing of the V4 region of the 16S rRNA gene and Qiime2 was used to calculate alpha and beta diversity for multiple alternative metrics. Results On the basis of relative abundances of 975 different suboperational taxonomic units in high throughput next generation sequencing, a significant shift in the composition of the oral microbiome (p < 0.02) was observed among patients being treated with different medications. There was a significant difference in bacterial communities between the group aged 3–8 years old and the group aged 9–14 years old. Significant differences were also seen in bacterial colonization on different sites in the oral cavity, but not with respect to gender or disease activity. Conclusion We present first data of a pilot study of the oral microbiome in children and adolescents with CNO, a rare autoinflammatory bone disease. Differences of the oral microbiome of diseased children to normal adult controls revealed a possible role of the oral microbiome as modulatory target or biomarker in CNO.

Time Course of Simulator Sickness in Asian Military Pilots

2020 ◽  
Vol 91 (11) ◽  
pp. 892-896
Author(s):  
Janine En Qi Loi ◽  
Magdalene Li Ling Lee ◽  
Benjamin Boon Chuan Tan ◽  
Brian See
Keyword(s):  
Air Force ◽  
Time Course ◽  
Simulator Training ◽  
Simulator Sickness ◽  
Time Points ◽  
True Prevalence ◽  
Subjective Scale ◽  
Significant Difference ◽  
Simulator Sickness Questionnaire ◽  
Military Pilots

INTRODUCTION: This study sought to determine the incidence, severity, and time-course of simulator sickness (SS) among Asian military pilots following flight simulator training.METHODS: A survey was conducted on Republic of Singapore Air Force pilots undergoing simulator training. Each subject completed a questionnaire immediately after (0H), and at the 3-h (3H) and 6-h (6H) marks. The questionnaire included the simulator sickness questionnaire (SSQ) and a subjective scale to rate their confidence to fly.RESULTS: In this study, 258 pilots with a median age of 31.50 yr (range, 2155 yr) and mean age of 32.61 6.56 yr participated. The prevalence of SS was 48.1% at 0H, 30.8% at 3H, and 16.4% at 6H. Based on a threshold of an SSQ score >10, the prevalence of operationally significant SS was 33.3% at 0H, 13.2% at 3H, and 8.1% at 6H. The most frequent symptoms were fatigue (38.1%), eye strain (29.0%), and fullness of head (19.9%). There was no significant difference in mean scores between rotary and fixed wing pilots. Older, more experienced pilots had greater scores at 0H, but this association did not persist. A correlation was found between SSQ score and self-reported confidence.DISCUSSION: To our knowledge, this study is the first to report the prevalence of operationally significant SS in Asian military pilots over serial time points. Most pilots with SS are able to subjectively judge their fitness to fly. Sensitivity analysis suggests the true prevalence of SS symptoms at 3H and 6H to be closer to 23.8% and 12.0%, respectively.Loi JEQ, Lee MLL, Tan BBC, See B. Time course of simulator sickness in Asian military pilots. Aerosp Med Hum Perform. 2020; 91(11):892896.

Isolation of an Anti-fatigue Preparation from Cellulase-treated Maca by Hydroalcoholic Extraction

2017 ◽  
Vol 17 (1) ◽  
pp. 93-98
Author(s):  
Zheng Yue ◽  
Zhang Wen-Cheng ◽  
Wu Ze-Yu ◽  
Fu Chuan-Xiang ◽  
Gao Han ◽  
...  
Keyword(s):  
Positive Control ◽  
Glycogen Storage ◽  
Hepatic Glycogen ◽  
Time To Exhaustion ◽  
High Dose ◽  
Hydroalcoholic Extract ◽  
Swimming Time ◽  
Significant Difference ◽  
Pre Treatment ◽  
Better Than

The purpose of this study was to evaluate the anti-fatigue activity of maca hydroalcoholic extract (ME), which mainly contains macamides and polysaccharides. ME was prepared by circumfluence extraction with enzymatic pre-treatment. Anti-fatigue activity of ME was investigated in weight-loaded forced swimming mice, with pure macamides and commercially available maca tablet as positive control. Compared with normal group, pure macamides treatment group could prolong the swimming time to exhaustion, but there was no statistically significant difference (P > 0.05); while ME (middle-dose and high-dose groups) could effectively prolong the swimming durations (P < 0.05). Supplementation with pure macamides significantly decreased blood lactic acid (BLA), whereas ME significantly increased hepatic glycogen (HG), decreased BLA, and blood urea nitrogen (BUN) compared with those in normal control (P < 0.05). The results suggested that the anti-fatigue effect of ME was better than that of pure macamides, which can be explained by the increase of glycogen storage and the reduction of metabolites accumulation.

Antibiotic Distribution in a Bone Cement Spacer Model

2007 ◽  
Vol 17 (4) ◽  
pp. 218-223 ◽  
Author(s):  
K. Shiramizu ◽  
V. Lovric ◽  
A.M.D. Leung ◽  
W.R. Walsh
Keyword(s):  
Liquid Phase ◽  
Bone Cement ◽  
Cross Sections ◽  
High Dose ◽  
Cement Spacer ◽  
Traditional Technique ◽  
Low Viscosity ◽  
Significant Difference ◽  
Group A ◽  
Medium Viscosity

Purpose To mix high dose antibiotic powder to the bone cement more easily, Hanssen et al reported mixing the antibiotics with the cement during its liquid phase but made no comments about the relevance of cement viscosity and antibiotic distribution. The purpose of this study was to investigate the effect of the cement mixing technique and cement viscosity on the antibiotics distribution in a cement spacer model. Methods Thirty cylindrical models from three groups were examined. Group A was made by mixing the antibiotics with medium viscosity cement prior to adding the liquid monomer (traditional technique). Group B was made by mixing the antibiotics with medium viscosity cement during its liquid phase (Hanssen's technique). Group C was made by traditional technique with low viscosity cement. In all groups 2 g of tetracycline was used. Three 0.1 mm thick cross sections from each spacer model were examined under the fluorescent microscope. The fluorescent spots of tetracycline were calculated automatically in pixels. To evaluate the distribution of the antibiotics in the spacer model, we selected the cross section with the highest number of pixels and the one with the lowest number of pixels from each of the three cross sections and calculated the difference between them. The distribution disequilibrium was compared between group A and B, A and C. Results No significant difference was observed in either comparison. Conclusion The Hanssen's mixing technique can be used when using high dose antibiotics, and either medium or low viscosity cement could be used in terms of antibiotic distribution.

scholarly journals Anesthetic Techniques for Fetal Surgery

2013 ◽  
Vol 118 (4) ◽  
pp. 796-808 ◽  
Author(s):  
Pornswan Ngamprasertwong ◽  
Erik C. Michelfelder ◽  
Shahriar Arbabi ◽  
Yun Suk Choi ◽  
Christopher Statile ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiac Function ◽  
Fetal Surgery ◽  
Left Ventricular ◽  
High Dose ◽  
Anesthetic Techniques ◽  
Uterine Blood Flow ◽  
Fetal Cardiac Function ◽  
Significant Difference ◽  
Fetal Acidosis

Abstract Background: Use of high-dose inhalational anesthesia during open fetal surgery may induce maternal–fetal hemodynamic instability and fetal myocardial depression. The authors’ preliminary human retrospective study demonstrated less fetal bradycardia and left ventricular systolic dysfunction with lower dose desflurane supplemented with propofol and remifentanil IV anesthesia (SIVA). In this animal study, the authors compare maternal–fetal effects of high-dose desflurane anesthesia (HD-DES) and SIVA. Methods: Of 26 instrumented midgestational ewes, data from 11 animals exposed to both SIVA and HD-DES in random sequences and six animals exposed to HD-DES while maternal normotension was maintained were analyzed. Maternal electroencephalography was used to guide comparable depths of anesthesia in both techniques. Hemodynamic parameters, blood gas, and fetal cardiac function from echocardiography were recorded. Results: Compared with SIVA, HD-DES resulted in significant maternal hypotension (mean arterial pressure difference, 19.53 mmHg; 95% CI, 17.6–21.4; P &lt; 0.0001), fetal acidosis (pH 7.11 vs. 7.24 at 150 min, P &lt; 0.001), and decreased uterine blood flow. In the HD-DES group with maternal normotension, uterine blood flow still declined and fetal acidosis persisted, with no statistically significant difference from the group exposed to HD-DES that had maternal hypotension. There was no statistically significant difference in fetal cardiac function. Conclusion: In sheep, SIVA affects maternal hemodynamics less and provides better fetal acid/base status than high-dose desflurane. Fetal echocardiography did not reflect myocardial dysfunction in this model.

Relapse After Early-Stage, Favorable Hodgkin Lymphoma: Disease Characteristics and Outcomes With Conventional or High-Dose Chemotherapy

2021 ◽  
Vol 39 (2) ◽  
pp. 107-115
Author(s):  
Paul J. Bröckelmann ◽  
Horst Müller ◽  
Teresa Guhl ◽  
Karolin Behringer ◽  
Michael Fuchs ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Early Stage ◽  
High Dose Chemotherapy ◽  
Sensitivity Analyses ◽  
High Dose ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Significant Difference ◽  
First Diagnosis

PURPOSE We evaluated disease and treatment characteristics of patients with relapse after risk-adapted first-line treatment of early-stage, favorable, classic Hodgkin lymphoma (ES-HL). We compared second-line therapy with high-dose chemotherapy and autologous stem cell transplantation (ASCT) or conventional chemotherapy (CTx). METHODS We analyzed patients with relapse after ES-HL treated within the German Hodgkin Study Group HD10+HD13 trials. We compared, by Cox proportional hazards regression, progression-free survival (PFS) after relapse (second PFS) treated with either ASCT or CTx and performed sensitivity analyses with overall survival (OS) from relapse and Kaplan-Meier statistics. RESULTS A total of 174 patients’ disease relapsed after treatment in the HD10 (n = 53) and HD13 (n = 121) trials. Relapse mostly occurred > 12 months after first diagnosis, predominantly with stage I-II disease. Of 172 patients with known second-line therapy, 85 received CTx (49%); 70, ASCT (41%); 11, radiotherapy only (6%); and 4, palliative single agent therapies (2%). CTx was predominantly bleomycin, etoposide, doxorubicin cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP [68%]), followed by the combination regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (19%), or other regimens (13%). Patients aged > 60 years at relapse had shorter second PFS (hazard ratio [HR], 3.0; P = .0029) and were mostly treated with CTx (n = 33 of 49; 67%) and rarely with ASCT (n = 8; 16%). After adjustment for age and a disadvantage of ASCT after the more historic HD10 trial, we did not observe a significant difference in the efficacy of CTx versus ASCT for second PFS (HR, 0.7; 95% CI, 0.3 to 1.6; P = .39). In patients in the HD13 trial who were aged ≤ 60 years, the 2-year, second PFS rate was 94.0% with CTx (95% CI, 85.7% to 100%) versus 83.3% with ASCT (95% CI, 71.8% to 94.8%). Additional sensitivity analyses including OS confirmed these observations. CONCLUSION After contemporary treatment of ES-HL, relapse mostly occurred > 12 months after first diagnosis. Polychemotherapy regimens such as BEACOPP are frequently administered and may constitute a reasonable treatment option for selected patients with relapse after ES-HL.

scholarly journals Cytotoxicity assessment of different doses of ozonated water on dental pulp cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ferdiye Küçük ◽  
Sibel Yıldırım ◽  
Serap Çetiner
Keyword(s):  
Cell Viability ◽  
Repeated Measures ◽  
Dental Pulp ◽  
Control Group ◽  
Dental Pulp Cells ◽  
Time Points ◽  
Significant Difference ◽  
Pulp Cells ◽  
Time Point ◽  
Ozonated Water

Abstract Background The purpose of this study was to assess the cytotoxicity of various concentrations of ozonated water (OW) on human primary dental pulp cells. Methods Human primary dental pulp cells were isolated from exfoliated primary canine teeth of an 11-year-old patient with good systemic and oral health. Afterwards, cells were divided into 6 experimental groups; four groups of OW in concentrations of 2 mg/L, 4 mg/L, 8 mg/L, and 16 mg/L, untreated control group, and cell culture without cells. Cytotoxicity was evaluated after exposure for 5-min exposure using Mosmann’s Tetrazolium Toxicity (MTT) assay at 0 h and 48 h time points. Data were analyzed using a repeated measures analysis of variance and Post-hoc tests were performed using Bonferroni correction for multiple comparisons. Results All experimental groups showed proliferation at 0 h time point. However, all groups also experienced a decrease in overtime at 48 h time point (p < 0.05). At both time points 2 mg/L OW showed the highest cell viability as well as proliferation. At 0 h time point, the increase in cell viability for all experimental groups was found statistically significant when compared to positive control group (p < 0.05). At 48 h time point, although 8 mg/L and 16 mg/L OW showed statistically significant reduction in compare to 0 h time point, 2 mg/L and 4 mg/L OW groups didn’t experience any statistically significant difference (p < 0.05). Conclusion Considering our findings, due to ozonated water's induced a higher proliferation rate of dental pulp cells, indicating their biocompatibility and a possible adjuvant on irrigating agent in regenerative endodontic procedures.

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