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Sample records for 4-week treatment phase

  1. Auricular point acupressure for chronic pain: a feasibility study of a 4-week treatment protocol.

    PubMed

    Yeh, Chao Hsing; Chien, Lung-Chang; Huang, Li Chun; Suen, Lorna Kwai-Ping

    2014-01-01

    This 1-group, 4-week observational study aimed to (1) assess the feasibility of recruiting, retention, and completion of a 4-week auricular point acupressure (APA) treatment protocol for chronic pain in adult patients and (2) assess the effects of APA in pain reduction (pain severity and pain interference) among these patients. The participants received a 4-week APA treatment protocol in weekly cycles. Each weekly cycle included 5 days with APA seeds taped onto the ear and 2 days without. Each participant was called every day to monitor adherence to the treatment protocol (the actual times the participant pressed the seeds each day and the duration of applied pressure), to answer analgesic use, and to answer the pain intensity questionnaire. Thirty participants were initially enrolled in this study, but 5 did not continue. The retention rate was 83% (n = 25). Approximately 60% of the participants (n = 15) adhered to the 4-week APA and completed all data assessments. At baseline assessment, only 40% of all participants (n = 12 of 30) were confident that APA would reduce and eliminate pain; nonetheless, all participants reported fewer episodes of pain occurrences and pain intensity with the APA treatment. For the participants who completed the 4-week APA protocol (n = 15), 96% (n = 14) decreased analgesic medication intake and 88% (n = 13) felt "much better" after the APA treatment. Participants reported an average reduction of 63% in the worst pain intensity at day 7. By the end of the 4-week APA protocol, an even greater reduction in pain intensity was reported (66%, n = 10, at day 28). The participants who did not complete the treatment protocol reported an average pain reduction of 29%, which fluctuated to 22% before they dropped out. Auricular point acupressure is feasible for patients with chronic pain. The preliminary findings of this feasibility study show a reduction in pain intensity and improvement in physical function, which demonstrate the potential for

  2. Glutamate Levels in the Associative Striatum Before and After 4 Weeks of Antipsychotic Treatment in First-Episode Psychosis

    PubMed Central

    de la Fuente-Sandoval, Camilo; León-Ortiz, Pablo; Azcárraga, Mariana; Stephano, Sylvana; Favila, Rafael; Díaz-Galvis, Leonardo; Alvarado-Alanis, Patricia; Ramírez-Bermúdez, Jesús; Graff-Guerrero, Ariel

    2013-01-01

    IMPORTANCE Increased glutamate levels in the right associative striatum have been described in patients during a first episode of psychosis. Whether this increase would persist after effective antipsychotic treatment is unknown. OBJECTIVES To compare the glutamate levels in antipsychotic-naive patients with first-episode psychosis in the right associative striatum and right cerebellar cortex using proton magnetic resonance spectroscopy before and 4 weeks after antipsychotic treatment and to compare these results with normative data from sex-matched healthy control subjects. DESIGN, SETTING, AND PARTICIPANTS Before-after trial in an inpatient psychiatric research unit among 24 antipsychotic-naive patients with first-episode psychosis and 18 healthy controls matched for age, sex, handedness, and cigarette smoking. INTERVENTIONS Participants underwent 2 proton magnetic resonance spectroscopy studies: patients were imaged at baseline and after 4 weeks of antipsychotic treatment, while controls were imaged at baseline and at 4 weeks after the baseline measurement. Patients were treated with oral risperidone (open label) for 4 weeks with dosages that were titrated on the basis of clinical judgment. MAIN OUTCOMES AND MEASURES Glutamate levels were estimated using LCModel (version 6.2-1T) and were corrected for the cerebrospinal fluid proportion within the voxel. RESULTS Patients with first-episode psychosis had higher levels of glutamate in the associative striatum and the cerebellum during the antipsychotic-naive condition compared with controls. After clinically effective antipsychotic treatment, glutamate levels significantly decreased in the associative striatum, with no significant change in the cerebellum. No differences in glutamate levels were observed between groups at 4 weeks. CONCLUSIONS AND RELEVANCE Increased glutamate levels observed at baseline in patients with first-episode psychosis normalized after 4 weeks of clinically effective antipsychotic treatment

  3. Exploratory, Phase II Controlled Trial of Shiunko Ointment Local Application Twice a Day for 4 Weeks in Ethiopian Patients with Localized Cutaneous Leishmaniasis

    PubMed Central

    Na-Bangchang, Kesara; Ahmed, Oumer; Hussein, Jemal; Hirayama, Kenji; Kongjam, Panida; Aseffa, Abraham; Karbwang, Juntra

    2016-01-01

    The clinical efficacy and safety of Shiunko ointment (phase II clinical trial) was investigated in 40 Ethiopian patients with cutaneous leishmaniasis. Patients were randomized to receive treatment with Shiunko ointment or placebo (n = 20, each), applied on the lesion twice a day for 4 weeks. Clinicoparasitological assessments were performed before treatment, weekly for 4 weeks, and then 4, 8, and 12 weeks after the end of treatment. A marked reduction in lesion size was observed on week 16 of treatment in the Shiunko compared with placebo group (69% and 22% reduction, resp.). The overall rate of lesion reduction during the four weeks of treatment was significantly faster in the Shiunko group. Shiunko provided significant effect on wound closure in patients with ulcerated lesion. The clinical efficacy and tolerability of Shiunko were comparable to placebo with regard to its clinicoparasitological response (cure rate and parasitological clearance). Results of this preliminary study may suggest that Shiunko could be useful as adjuvant or as complementary treatment, not as alternatives to current treatment. Its attractive action includes fast lesion healing with a significantly smaller lesion at week 16 of treatment compared with placebo. In addition, its action was promoted in ulcerative lesions. PMID:27195014

  4. Very low calorie diet without aspartame in obese subjects: improved metabolic control after 4 weeks treatment

    PubMed Central

    2014-01-01

    Background Very low calorie diet (VLCD) is routinely used in programs for treatment of obesity and before bariatric surgery in order to reduce risk of postoperative complications. Aspartame, an artificial sweetener, is commonly used in VLCD and is well approved as a food additive without any adverse effects. The development of a new fructose containing VLCD formula without aspartame raises questions as to effects on glucose and lipid control. Methods As part of an ongoing study of a novel bariatric surgery procedure, twenty-five obese subjects with mean body mass index (BMI) 39.8 kg/m2 and mean age of 48.8 years enrolled in a single center observational study. Seven subjects presented with type 2 diabetes mellitus. The subjects underwent four weeks dietary treatment with VLCD Slanka (Slanka®). Blood samples including fasting plasma glucose, HbA1c, cholesterol and triglycerides were performed at start and after four weeks of diet. Blood pressure and weight were noted. Results All subjects completed the diet without any adverse events. Mean weight reduction was 8.2 kg with 95% confidence interval 7.1–9.2 kg (p = 0.001). Excess weight (i.e. proportion of weight exceeding BMI 25) loss decreased by median 19.5% (inter quartile range (IQR) 16,8-24,2). Median fasting plasma glucose was at inclusion 5,6 mmol/l (IQR 5,3-6,8) and after diet 4.8 mmol/l (IQR 4,6-5,2) (p = 0.001). Median HbA1c changed from 39 mmol/mol (IQR 37–44) to 37 mmol/mol (IQR 35–43) (p = 0.001). There was also significant reduction in cholesterol and triglyceride levels as well as in systolic blood pressure. Changes in other monitored blood chemistry values were without clinical importance. Conclusion Four weeks treatment with fructose containing VLCD of obese subjects preparing for bariatric surgery gave a substantial weight reduction without any significant negative metabolic effects. PMID:25069603

  5. Treatment with α-Lipoic Acid over 16 Weeks in Type 2 Diabetic Patients with Symptomatic Polyneuropathy Who Responded to Initial 4-Week High-Dose Loading

    PubMed Central

    Garcia-Alcala, Hector; Santos Vichido, Celia Isabel; Islas Macedo, Silverio; Genestier-Tamborero, Christelle Nathalie; Minutti-Palacios, Marissa; Hirales Tamez, Omara; García, Carlos; Ziegler, Dan

    2015-01-01

    Effective treatment of diabetic sensorimotor polyneuropathy remains a challenge. To assess the efficacy and safety of α-lipoic acid (ALA) over 20 weeks, we conducted a multicenter randomized withdrawal open-label study, in which 45 patients with type 2 diabetes and symptomatic polyneuropathy were initially treated with ALA (600 mg tid) for 4 weeks (phase 1). Subsequently, responders were randomized to receive ALA (600 mg qd; n = 16) or to ALA withdrawal (n = 17) for 16 weeks (phase 2). During phase 1, the Total Symptom Score (TSS) decreased from 8.9 ± 1.8 points to 3.46 ± 2.0 points. During phase 2, TSS improved from 3.7 ± 1.9 points to 2.5 ± 2.5 points in the ALA treated group (p < 0.05) and remained unchanged in the ALA withdrawal group. The use of analgesic rescue medication was higher in the ALA withdrawal group than ALA treated group (p < 0.05). In conclusion, in type 2 diabetic patients with symptomatic polyneuropathy who responded to initial 4-week high-dose (600 mg tid) administration of ALA, subsequent treatment with ALA (600 mg qd) over 16 weeks improved neuropathic symptoms, whereas ALA withdrawal was associated with a higher use of rescue analgesic drugs. This trial is registered with ClinicalTrials.gov Identifier: NCT02439879. PMID:26345602

  6. Treatment with α-Lipoic Acid over 16 Weeks in Type 2 Diabetic Patients with Symptomatic Polyneuropathy Who Responded to Initial 4-Week High-Dose Loading.

    PubMed

    Garcia-Alcala, Hector; Santos Vichido, Celia Isabel; Islas Macedo, Silverio; Genestier-Tamborero, Christelle Nathalie; Minutti-Palacios, Marissa; Hirales Tamez, Omara; García, Carlos; Ziegler, Dan

    2015-01-01

    Effective treatment of diabetic sensorimotor polyneuropathy remains a challenge. To assess the efficacy and safety of α-lipoic acid (ALA) over 20 weeks, we conducted a multicenter randomized withdrawal open-label study, in which 45 patients with type 2 diabetes and symptomatic polyneuropathy were initially treated with ALA (600 mg tid) for 4 weeks (phase 1). Subsequently, responders were randomized to receive ALA (600 mg qd; n = 16) or to ALA withdrawal (n = 17) for 16 weeks (phase 2). During phase 1, the Total Symptom Score (TSS) decreased from 8.9 ± 1.8 points to 3.46 ± 2.0 points. During phase 2, TSS improved from 3.7 ± 1.9 points to 2.5 ± 2.5 points in the ALA treated group (p < 0.05) and remained unchanged in the ALA withdrawal group. The use of analgesic rescue medication was higher in the ALA withdrawal group than ALA treated group (p < 0.05). In conclusion, in type 2 diabetic patients with symptomatic polyneuropathy who responded to initial 4-week high-dose (600 mg tid) administration of ALA, subsequent treatment with ALA (600 mg qd) over 16 weeks improved neuropathic symptoms, whereas ALA withdrawal was associated with a higher use of rescue analgesic drugs. This trial is registered with ClinicalTrials.gov Identifier: NCT02439879. PMID:26345602

  7. Ovarian Features after 2 Weeks, 3 Weeks and 4 Weeks Transdermal Testosterone Gel Treatment and Their Associated Effect on IVF Outcomes in Poor Responders

    PubMed Central

    Kim, Chung-Hoon; Ahn, Jun-Woo; Moon, Jei-Won; Kim, Sung-Hoon; Chae, Hee-Dong; Kang, Byung-Moon

    2014-01-01

    This study was performed to investigate the effect of of transdermal testosterone gel (TTG) on controlled ovarian stimulation (COS) and IVF outcomes and ovarian morphology according to pretreatment duration in poor responders. A total of 120 women were recruited for this pilot study. They were randomized into control, 2 weeks, 3 weeks or 4 weeks TTG treatment groups. For three TTG treatment groups, 12.5 mg TTG was applied daily for 2 weeks, 3 weeks or 4 weeks in preceding period of study stimulation cycle. After 3 weeks of TTG pretreatment, significant increase of antral follicle count (AFC) and significant decreases of mean follicular diameter (MFD) and resistance index (RI) value of ovarian stromal artery were observed (p=0.026, p<0.001, p<0.01, respectively). The total dose of rhFSH administered for COS significantly decreased after 3 and 4 weeks TTG treatment both compared with control group (p<0.001, p<0.001). The numbers of oocytes retrieved and mature oocytes were significanty higher in 3 and 4 weeks TTG treatment groups than control group (p<0.001, p<0.001 in the number of oocytes retrieved; p<0.001, p<0.001 in the number of mature oocytes). The clinical pregnancy rate and live birth rate were increased only in 4 weeks TTG treatment group compared with control group (p=0.030 and p=0.042, respectively). These data demonstrated that TTG pretreatment for 3 to 4 weeks increases AFC and ovarian stromal blood flow, thereby potentially improving the ovarian response to COS and IVF outcome in poor responders undergoing IVF/ICSI. PMID:25949183

  8. Ovarian Features after 2 Weeks, 3 Weeks and 4 Weeks Transdermal Testosterone Gel Treatment and Their Associated Effect on IVF Outcomes in Poor Responders.

    PubMed

    Kim, Chung-Hoon; Ahn, Jun-Woo; Moon, Jei-Won; Kim, Sung-Hoon; Chae, Hee-Dong; Kang, Byung-Moon

    2014-09-01

    This study was performed to investigate the effect of of transdermal testosterone gel (TTG) on controlled ovarian stimulation (COS) and IVF outcomes and ovarian morphology according to pretreatment duration in poor responders. A total of 120 women were recruited for this pilot study. They were randomized into control, 2 weeks, 3 weeks or 4 weeks TTG treatment groups. For three TTG treatment groups, 12.5 mg TTG was applied daily for 2 weeks, 3 weeks or 4 weeks in preceding period of study stimulation cycle. After 3 weeks of TTG pretreatment, significant increase of antral follicle count (AFC) and significant decreases of mean follicular diameter (MFD) and resistance index (RI) value of ovarian stromal artery were observed (p=0.026, p<0.001, p<0.01, respectively). The total dose of rhFSH administered for COS significantly decreased after 3 and 4 weeks TTG treatment both compared with control group (p<0.001, p<0.001). The numbers of oocytes retrieved and mature oocytes were significanty higher in 3 and 4 weeks TTG treatment groups than control group (p<0.001, p<0.001 in the number of oocytes retrieved; p<0.001, p<0.001 in the number of mature oocytes). The clinical pregnancy rate and live birth rate were increased only in 4 weeks TTG treatment group compared with control group (p=0.030 and p=0.042, respectively). These data demonstrated that TTG pretreatment for 3 to 4 weeks increases AFC and ovarian stromal blood flow, thereby potentially improving the ovarian response to COS and IVF outcome in poor responders undergoing IVF/ICSI. PMID:25949183

  9. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Portal Vein Thrombosis: Impact of Early Response to 4 Weeks of Treatment

    PubMed Central

    Lin, Chen-Chun; Hung, Chien-Fu; Chen, Wei-Ting; Lin, Shi-Ming

    2015-01-01

    Aim The aim of the study was to investigate the impact of early response (ER) to hepatic arterial infusion chemotherapy (HAIC) on outcomes of patients with advanced hepatocellular carcinoma (HCC) complicated with major portal vein tumor thrombosis (PVTT). Methods Thirty-nine patients receiving HAIC with low-dose cisplatin, 5-fluorouracil (5FU), and leucovorin were enrolled. One course of HAIC consisted of 5 days of treatment and 2 days rest per week for 4 consecutive weeks. ER was categorized as complete response, partial response, or minor response and was determined by World Health Organization criteria with dynamic computed tomography findings performed within 1 week after the first course of HAIC. Results Thirteen (33%) patients achieved an ER. Twelve (92.3%) of these 13 ER patients achieved a higher overall response than all but one (3.8%) of the 26 non-early responders (NERs) (p<0.001). ER was the exclusive independent favorable factor for survival (p=0.003). Downstaging of tumors was noted in 76.9% of ERs, and these patients could proceed to locoregional therapies. ER patients subsequently had a higher 1-year survival (76.9% vs. 3.8%, p<0.001) and 6-month progression-free survival (PFS) (84.6% vs. 15.4%, p<0.001) than those for NERs. Only 8% of patients experienced grade 3 or higher toxicity during the first 4-week course of HAIC. Conclusions HAIC can yield a satisfactory ER for advanced HCC with PVTT. Moreover, achievement of ER after HAIC in advanced HCC with PVTT is strongly associated with better overall survival and PFS. PMID:26734578

  10. Multicenter Study of Decitabine Administered Daily for 5 Days Every 4 Weeks to Adults With Myelodysplastic Syndromes: The Alternative Dosing for Outpatient Treatment (ADOPT) Trial

    PubMed Central

    Steensma, David P.; Baer, Maria R.; Slack, James L.; Buckstein, Rena; Godley, Lucy A.; Garcia-Manero, Guillermo; Albitar, Maher; Larsen, Julie S.; Arora, Sujata; Cullen, Michael T.; Kantarjian, Hagop

    2009-01-01

    Purpose Decitabine, a DNA-targeted hypomethylating agent, is approved by the United States Food and Drug Administration for treatment of patients with myelodysplastic syndromes (MDS) on a schedule of 15 mg/m2 administered via intravenous (IV) infusion every 8 hours for 3 days. This study assessed the efficacy and safety of an alternative dosing regimen administered on an outpatient basis in academic and community-based practices. Patients and Methods Patients were treated with decitabine 20 mg/m2 by IV infusion daily for 5 consecutive days every 4 weeks. Eligible patients were ≥ 18 years of age and had MDS (de novo or secondary) of any French-American-British (FAB) subtype and an International Prognostic Scoring System (IPSS) score ≥ 0.5. The primary end point was the overall response rate (ORR) by International Working Group (IWG 2006) criteria; secondary end points included cytogenetic responses, hematologic improvement (HI), response duration, survival, and safety. Results Ninety-nine patients were enrolled; the ORR was 32% (17 complete responses [CR] plus 15 marrow CRs [mCRs]), and the overall improvement rate was 51%, which included 18% HI. Similar response rates were observed in all FAB subtypes and IPSS risk categories. Among patients who improved, 82% demonstrated responses by the end of cycle 2. Among 33 patients assessable for a cytogenetic response, 17 (52%) experienced cytogenetic CR (n = 11) or partial response (n = 6). Conclusion Decitabine given on a 5-day schedule provided meaningful clinical benefit for patients with MDS, with more than half demonstrating improvement. This suggests that decitabine can be administered in an outpatient setting with comparable efficacy and safety to the United States Food and Drug Administration–approved inpatient regimen. PMID:19528372

  11. Relief of Night-time Symptoms Associated With Gastroesophageal Reflux Disease Following 4 Weeks of Treatment With Pantoprazole Magnesium: The Mexican Gastroesophageal Reflux Disease Working Group

    PubMed Central

    Orr, William; Vargas-Romero, José Antonio; Remes-Troche, José María; Morales-Arámbula, Miguel; Soto-Pérez, Julio César; Mateos-Pérez, Gualberto; Sobrino-Cossío, Sergio; Teramoto-Matsubara, Oscar; López-Colombo, Aurelio; Orozco-Gamiz, Antonio; Saez-Ríos, Adolfo; Arellano-Plancarte, Araceli; Chiu-Ugalde, Jazmin; Tholen, Anne; Horbach, Silke; Lundberg, Lars; Fass, Ronnie

    2014-01-01

    Background/Aims To evaluate the effectiveness of pantoprazole magnesium (pantoprazole-Mg) 40 mg in the relief of esophageal and extra-esophageal symptoms of gastroesophageal reflux disease (GERD), particularly night-time symptoms. Methods Patients (aged 18-50 years) with 3-month history of heartburn and/or acid regurgitation plus at least one other symptom in the last week were enrolled in a nationwide, prospective and observational study in Mexico. Patients received pantoprazole-Mg 40 mg once daily during 4 weeks. Symptoms were assessed through a physician-administered structured interview and the patient-completed ReQuest in Practice™ questionnaire. Night-time GERD was defined as arousal from sleep during the night due to GERD-associated symptoms. Results Out of 4,343 patients included at basal visit, 3,665 were considered for the effectiveness per protocol analysis. At baseline, patients had a median of 8 GERD related symptoms. Patients with night-time GERD symptoms (42.7%) were more likely to have extra-esophageal symptoms (P < 0.001) than other GERD patients. Pantoprazole-Mg 40 mg once daily for 4 weeks improved a broad range of GERD-associated symptoms from baseline (80% reduction on physicians assessments; 68-77% reduction on ReQuest in Practice™ dimensions), including both day- and night-time GERD symptoms; improvements were the greatest for extra-esophageal symptoms in patients with night-time symptoms. Pantoprazole-Mg was well tolerated. Conclusions Pantoprazole-Mg 40 mg significantly improved a broad range of esophageal and extra-esophageal GERD related symptoms including sleep disturbances, as well as well-being, in patients with daytime or night-time GERD, making it a good option for patients with GERD, especially when extra-esophageal and night-time symptoms are present. PMID:24466446

  12. 1 CFR 12.4 - Weekly Compilation of Presidential Documents.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ....4 Section 12.4 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER AVAILABILITY OF OFFICE OF THE FEDERAL REGISTER PUBLICATIONS OFFICIAL DISTRIBUTION WITHIN FEDERAL GOVERNMENT § 12.4 Weekly... based on a written request to the Director of the Federal Register. (2) Congressional committees....

  13. 1 CFR 12.4 - Weekly Compilation of Presidential Documents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Weekly Compilation of Presidential Documents. 12.4 Section 12.4 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER AVAILABILITY OF OFFICE OF THE FEDERAL REGISTER PUBLICATIONS OFFICIAL DISTRIBUTION WITHIN FEDERAL GOVERNMENT § 12.4 Weekly Compilation of Presidential Documents....

  14. 1 CFR 12.4 - Weekly Compilation of Presidential Documents.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ....4 Section 12.4 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER AVAILABILITY OF OFFICE OF THE FEDERAL REGISTER PUBLICATIONS OFFICIAL DISTRIBUTION WITHIN FEDERAL GOVERNMENT § 12.4 Weekly... based on a written request to the Director of the Federal Register. (2) Congressional committees....

  15. 1 CFR 12.4 - Weekly Compilation of Presidential Documents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 1 General Provisions 1 2011-01-01 2011-01-01 false Weekly Compilation of Presidential Documents. 12.4 Section 12.4 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER AVAILABILITY OF OFFICE OF THE FEDERAL REGISTER PUBLICATIONS OFFICIAL DISTRIBUTION WITHIN FEDERAL GOVERNMENT § 12.4 Weekly Compilation of Presidential Documents....

  16. 1 CFR 12.4 - Weekly Compilation of Presidential Documents.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    .... 12.4 Section 12.4 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER AVAILABILITY OF OFFICE OF THE FEDERAL REGISTER PUBLICATIONS OFFICIAL DISTRIBUTION WITHIN FEDERAL GOVERNMENT § 12.4 Weekly... based on a written request to the Director of the Federal Register. (2) Congressional committees....

  17. A 4-week toxicity study of methionine in male rats.

    PubMed

    Chin, Keigi; Toue, Sakino; Kawamata, Yasuko; Watanabe, Akiko; Miwa, Tadashi; Smriga, Miro; Sakai, Ryosei

    2015-01-01

    To examine 4-week toxicity of l-methionine (methionine), 5-week-old Fisher strain male rats were fed on diets containing 0, 0.1, 0.3, 0.9, 2.7 (w/w) of added methionine. Although no deaths were recorded, the highest dose of methionine (2.7% [w/w] of diet) reduced food intake and significantly suppressed growth rate. Growth suppression was characterized by an increase in hemolysis, splenic, and hepatic accumulation of hemosiderin, hemolytic anemia, and promotion of hematopoiesis. Other changes observed in the highest methionine intake group were a decrease in white blood cell count, thymus atrophy, and histological abnormalities in the adrenal gland and testis. Small, but significant, growth suppression, accompanied by some minor changes in plasma biochemical parameters, was also seen in rats fed on a test diet containing 0.9% (w/w) of additional methionine. Thus, no-observed-adverse-effect-level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) of diet-added methionine were determined at 0.3% and 0.9% (w/w), corresponding to 236 and 705 mg/kg/d body weight, respectively. Since the basal diet contained protein-bound methionine at 0.5% (w/w), NOAEL and LOAEL of total dietary methionine were estimated at 0.8% and 1.4% (w/w) of diet. PMID:25939350

  18. A papulopustular, vesicular, crusted rash in a 4-week-old neonate.

    PubMed

    Subramaniam, Sathyaseelan; Rutman, Maia S; Wenger, Jodi K

    2013-11-01

    Scabies is commonly seen worldwide, in its usual classic form when afflicting older children and adults. However, neonatal scabies is described as its own entity in the literature. We present a case of a 4-week-old infant with a generalized papulopustular, vesicular, and crusted rash who was diagnosed with scabies. We contrast the differing clinical features of neonatal and classic scabies, describe possible mimickers of this diagnostic dilemma, and review current treatment options available for scabies in this very young age group. PMID:24196092

  19. Parental Perspectives of a 4-Week Family-Based Lifestyle Intervention for Children with Obesity

    PubMed Central

    Pearson, Erin S.; Irwin, Jennifer D.; Burke, Shauna M.; Shapiro, Sheree

    2013-01-01

    Objectives: The childhood obesity epidemic is now recognized as one of the most serious public health challenges of the 21st century. Community-based behaviour modification treatment programs involving both children and their families are warranted. The purpose of this study was to explore the experiences of parents whose children participated in the Children's Health and Activity Modification Program (C.H.A.M.P.): a 4-week lifestyle program delivered as a day-camp for obese children at risk for type II diabetes and their families. Parents were required to attend four half-day education sessions during the intervention period. Methods: Seven focus groups were conducted immediately following the 4-week interventions offered in August 2008 and 2009. The perspectives of 38 parents representing 32 children aged 8-14 with obesity (i.e., body mass index > the 95th percentile) were shared. Results: Overall, parents were pleased with the impact of the program and proud of their children's accomplishments (e.g., increased physical activity levels, enhanced self-esteem, weight loss). Several facilitators to success (e.g., social support; a positive environment) and barriers to its maintenance (e.g., time management; unsupportive family members) were identified, and recommendations were made for future programs. Although parents found the half-day sessions valuable, post-programmatic bi-monthly booster session adherence declined over the one-year follow-up period. Conclusion: Delivered as a 4-week day-camp, C.H.A.M.P. represents a unique approach to the treatment of childhood obesity. Future family-based interventions should consider avenues for intensifying the parental program component whilst employing strategies to promote parental adherence in service of enhancing long-term sustainability of health behaviour changes. PMID:23445699

  20. Safety and efficacy of polycalcium for improving biomarkers of bone metabolism: a 4-week open-label clinical study.

    PubMed

    Choi, Jae-Suk; Park, Mi-Yeon; Kim, Jong-Dae; Cho, Hyung Rae; Choi, In Soon; Kim, Joo-Wan

    2013-03-01

    Polycalcium is a mixture of Polycan and calcium lactate-gluconate 1:9 (w/w) with demonstrated antiosteoporosis activity in vitro and in vivo studies. These studies were a 4-week open-label, single-center trial to evaluate the efficacy of oral Polycalcium on bone metabolism and safety. In total, 30 healthy women (range 40-60 years) were administered 400 mg of Polycalcium for 4 weeks. The primary efficacy parameter was urinary deoxypyridinoline (DPYR) levels, and serum osteocalcin (OSC), bone-specific alkaline phosphatase (BALP), urinary cross-linked C-telopeptide of type-1 collagen (CTx), urinary cross-linked N-telopeptide of type-1 collagen (NTx), calcium (Ca), and phosphorus (P) levels, which were evaluated for comparison before and after administration of Polycalcium. After 4 weeks of Polycalcium administration, 27 subjects completed the test plan. Three subjects withdrew their consent to participate. The values of blood OSC, BALP, serum Ca, and serum P from baseline to 4 weeks of treatment were changed by -28.44%, 14.37%, 6.11%, and 1.42%, respectively. Biomarkers of bone resorption: urinary DPYR, serum CTx, serum NTx, urinary Ca, and urinary P, at baseline after 4 weeks of treatment were changed by -13.40%, 6.67%, -5.13%, -22.43%, and -3.04%, respectively. Additionally, when considering the subjects' adverse effects and the results of the blood and urine tests over the 4-week trial period, the dose of 400  mg Polycalcium showed efficacy for improving bone metabolism and was well tolerated and safe. Polycalcium was apparently safe and efficacious. PMID:23477624

  1. Safety and Efficacy of Polycalcium for Improving Biomarkers of Bone Metabolism: A 4-Week Open-Label Clinical Study

    PubMed Central

    Choi, Jae-Suk; Park, Mi-Yeon; Kim, Jong-Dae; Cho, Hyung Rae

    2013-01-01

    Abstract Polycalcium is a mixture of Polycan and calcium lactate–gluconate 1:9 (w/w) with demonstrated antiosteoporosis activity in vitro and in vivo studies. These studies were a 4-week open-label, single-center trial to evaluate the efficacy of oral Polycalcium on bone metabolism and safety. In total, 30 healthy women (range 40–60 years) were administered 400 mg of Polycalcium for 4 weeks. The primary efficacy parameter was urinary deoxypyridinoline (DPYR) levels, and serum osteocalcin (OSC), bone-specific alkaline phosphatase (BALP), urinary cross-linked C-telopeptide of type-1 collagen (CTx), urinary cross-linked N-telopeptide of type-1 collagen (NTx), calcium (Ca), and phosphorus (P) levels, which were evaluated for comparison before and after administration of Polycalcium. After 4 weeks of Polycalcium administration, 27 subjects completed the test plan. Three subjects withdrew their consent to participate. The values of blood OSC, BALP, serum Ca, and serum P from baseline to 4 weeks of treatment were changed by −28.44%, 14.37%, 6.11%, and 1.42%, respectively. Biomarkers of bone resorption: urinary DPYR, serum CTx, serum NTx, urinary Ca, and urinary P, at baseline after 4 weeks of treatment were changed by −13.40%, 6.67%, −5.13%, −22.43%, and −3.04%, respectively. Additionally, when considering the subjects' adverse effects and the results of the blood and urine tests over the 4-week trial period, the dose of 400 mg Polycalcium showed efficacy for improving bone metabolism and was well tolerated and safe. Polycalcium was apparently safe and efficacious. PMID:23477624

  2. Effect of Curriculum Change on Exam Performance in a 4-Week Psychiatry Clerkship

    ERIC Educational Resources Information Center

    Niedermier, Julie; Way, David; Kasick, David; Kuperschmidt, Rada

    2010-01-01

    Objective: The authors investigated whether curriculum change could produce improved performance, despite a reduction in clerkship length from 8 to 4 weeks. Methods: The exam performance of medical students completing a 4-week clerkship in psychiatry was compared to national data from the National Board of Medical Examiners' Psychiatry Subject…

  3. Tipepidine in children with attention deficit/hyperactivity disorder: a 4-week, open-label, preliminary study

    PubMed Central

    Sasaki, Tsuyoshi; Hashimoto, Kenji; Tachibana, Masumi; Kurata, Tsutomu; Okawada, Keiko; Ishikawa, Maki; Kimura, Hiroshi; Komatsu, Hideki; Ishikawa, Masatomo; Hasegawa, Tadashi; Shiina, Akihiro; Hashimoto, Tasuku; Kanahara, Nobuhisa; Shiraishi, Tetsuya; Iyo, Masaomi

    2014-01-01

    Background Tipepidine (3-[di-2-thienylmethylene]-1-methylpiperidine) has been used solely as a nonnarcotic antitussive in Japan since 1959. The safety of tipepidine in children and adults has already been established. It is reported that tipepidine inhibits G-protein-coupled inwardly rectifying potassium (GIRK)-channel currents. The inhibition of GIRK channels by tipepidine is expected to modulate the level of monoamines in the brain. We put forward the hypothesis that tipepidine can improve attention deficit/hyperactivity disorder (ADHD) symptoms by modulating monoaminergic neurotransmission through the inhibition of GIRK channels. The purpose of this open-label trial was to confirm whether treatment with tipepidine can improve symptoms in pediatric patients with ADHD. Subjects and methods This was a 4-week, open-label, proof-of-efficacy pilot study for pediatric subjects with ADHD. Ten pediatric ADHD subjects (70% male; mean age, 9.9 years; combined [inattentive and hyperactive/impulsive] subtype, n=7; inattentive subtype, n=3; hyperimpulsive subtype, n=0) received tipepidine hibenzate taken orally at 30 mg/day for 4 weeks. All subjects were assessed using the ADHD Rating Scale IV (ADHD-RS), Japanese version, and the Das–Naglieri Cognitive Assessment System (DN-CAS), Japanese version. Results A comparison of baseline scores and 4-week end-point scores showed that all the ADHD-RS scores (total scores, hyperimpulsive subscores, and inattentive subscores) improved significantly (P<0.001). Furthermore, a comparison of baseline DN-CAS total scores and 4-week end-point scores showed a mild trend of improvement (P=0.093). Tipepidine was well tolerated, with no patients discontinuing medication because of side effects. Conclusion Our pilot study suggests that tipepidine therapy may prove to be an effective alternative treatment for pediatric patients with ADHD. Nonetheless, more detailed randomized, double-blind trials are needed to confirm tipepidine’s efficacy

  4. 6-weekly bevacizumab versus 4-weekly ranibizumab for neovascular age-related macular degeneration: a 2-year outcome

    PubMed Central

    Chiam, Patrick J; Ho, Vivian W; Hickley, Nicholas M; Kotamarthi, Venkat

    2016-01-01

    AIM To compare visual acuity and central macular thickness (CMT) changes in neovascular age related macular degeneration patients treated with either 6 weekly bevacizumab regimen or 4 weekly ranibizumab on an as required basis. METHODS Patients made an informed choice between bevacizumab 1.25 mg or ranibizumab 0.5 mg. The selected treatment was administered in the first 3 visits. Bevacizumab patients were followed-up 6 weekly and ranibizumab 4 weekly. Retreatment criteria was based on the reduction of >5 letters in the best-corrected visual acuity (BCVA), the presence of retinal fluid on optical coherence tomography (OCT) or new retinal haemorrhage. RESULTS Visual acuity at 2y bevacizumab patients gained 7.0 letters and ranibizumab 9.2 (P=0.31, 95% CI -6.4 to 2.0). At 2y 86% of bevacizumab and 94% ranibizumab patients had not lost 15 letters or more (P=0.13). Mean CMT decreased at 2y bevacizumab by 146 µm, ranibizumab 160 µm (P=0.72). Mean number of injections was at 2y bevacizumzb 11.9, ranibizumab 10.3 (P=0.023). CONCLUSION Bevacizumab 6 weekly on an as required basis was not demonstrably non-inferior to ranibizumab 4 weekly pro re nata (prn) in terms of BCVA and change in CMT. In the bevacizumab group, one more injection was required in the second year compared to the ranibizumab group. PMID:27162727

  5. Effects of a 4-week youth baseball conditioning program on throwing velocity.

    PubMed

    Escamilla, Rafael F; Fleisig, Glenn S; Yamashiro, Kyle; Mikla, Tony; Dunning, Russell; Paulos, Lonnie; Andrews, James R

    2010-12-01

    Effects of a 4-week youth baseball conditioning program on throwing velocity. This study examined the effects of a 4-week youth baseball conditioning program on maximum throwing velocity. Thirty-four youth baseball players (11-15 years of age) were randomly and equally divided into control and training groups. The training group performed 3 sessions (each 75 minutes) weekly for 4 weeks, which comprised a sport specific warm-up, resistance training with elastic tubing, a throwing program, and stretching. Throwing velocity was assessed initially and at the end of the 4-week conditioning program for both control and training groups. The level of significance used was p < 0.05. After the 4-week conditioning program, throwing velocity increased significantly (from 25.1 ± 2.8 to 26.1 ± 2.8 m·s) in the training group but did not significantly increase in the control group (from 24.2 ± 3.6 to 24.0 ± 3.9 m·s). These results demonstrate that the short-term 4-week baseball conditioning program was effective in increasing throwing velocity in youth baseball players. Increased throwing velocity may be helpful for pitchers (less time for hitters to swing) and position players (decreased time for a runner to advance to the next base). PMID:21068687

  6. PERSISTENT EFFECTS OF REPEATED INHALATION OF TOLUENE: 4 WEEKS VS. 13 WEEKS.

    EPA Science Inventory

    Understanding and predicting the extent of neurotoxic damage from repeated exposure to volatile organic compounds (VOCs) is a problem for many EPA programs. Eighty adult, male Long-Evans rats inhaled toluene (0, 10, 100, or 1000 ppm) 6 hr/day, 5 days/week for 4 weeks in a systema...

  7. Eco-Challenge: A 4-Week Approach to Eco-Action.

    ERIC Educational Resources Information Center

    Raines, J. Thayer

    1991-01-01

    Describes Challenge Wilderness Camp (Bradford, Vermont), a 4-week residential program designed to teach boys, ages 9-16, environmental ethics through first-hand experiences. The camp incorporates land and waste management policies and procedures; programs in outdoor skills instruction; and wilderness trips including backpacking, off-trail hiking,…

  8. 32 CFR Appendix E to Part 110 - Application of 4-Week Summer Field Training Formula (Sample)

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Formula (Sample) E Appendix E to Part 110 National Defense Department of Defense OFFICE OF THE SECRETARY... COMMUTATION INSTEAD OF UNIFORMS FOR MEMBERS OF THE SENIOR RESERVE OFFICERS' TRAINING CORPS Pt. 110, App. E Appendix E to Part 110—Application of 4-Week Summer Field Training Formula (Sample) Zone I Zone II...

  9. Effects of a 4-Week Multimodal Rehabilitation Program on Quality of Life, Cardiopulmonary Function, and Fatigue in Breast Cancer Patients

    PubMed Central

    Do, Junghwa; Cho, Youngki

    2015-01-01

    Purpose This study examines the effects of a rehabilitation program on quality of life (QoL), cardiopulmonary function, and fatigue in breast cancer patients. The program included aerobic exercises as well as stretching and strengthening exercises. Methods Breast cancer patients (n=62) who had completed chemotherapy were randomly assigned to an early exercise group (EEG; n=32) or a delayed exercise group (DEG; n=30). The EEG underwent 4 weeks of a multimodal rehabilitation program for 80 min/day, 5 times/wk for 4 weeks. The DEG completed the same program during the next 4 weeks. The European Organization for Research and Treatment of Cancer-Core Quality of Life Questionnaire (EORTC QLQ-C30), EORTC Breast Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23), predicted maximal volume of oxygen consumption (VO2max), and fatigue severity scale (FSS) were used for assessment at baseline, and at 2, 4, 6, and 8 weeks. Results After 8 weeks, statistically significant differences were apparent in global health, physical, role, and emotional functions, and cancer-related symptoms such as fatigue and pain, nausea, and dyspnea on the EORTC QLQ-C30; cancer-related symptoms involving the arm and breast on the EORTC QLQ-BR23; the predicted VO2max; muscular strength; and FSS (p<0.050), according to time, between the two groups. Conclusion The results of our study suggest that a supervised multimodal rehabilitation program may improve the physical symptoms, QoL, and fatigue in patients with breast cancer. PMID:25834616

  10. 40 CFR 35.2108 - Phased or segmented treatment works.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Phased or segmented treatment works. 35... ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2108 Phased or segmented treatment works. Grant funding may be awarded for a phase or segment of a treatment works,...

  11. 40 CFR 35.2108 - Phased or segmented treatment works.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... segmented treatment works. Grant funding may be awarded for a phase or segment of a treatment works, subject to the limitations of § 35.2123, although that phase or segment does not result in compliance with... make the treatment works of which the phase or segment is a part operational and comply with...

  12. 40 CFR 35.2108 - Phased or segmented treatment works.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... segmented treatment works. Grant funding may be awarded for a phase or segment of a treatment works, subject to the limitations of § 35.2123, although that phase or segment does not result in compliance with... make the treatment works of which the phase or segment is a part operational and comply with...

  13. A 4-week instructed minimalist running transition and gait-retraining changes plantar pressure and force.

    PubMed

    Warne, J P; Kilduff, S M; Gregan, B C; Nevill, A M; Moran, K A; Warrington, G D

    2014-12-01

    The purpose of this study is to compare changes in plantar pressure and force using conventional running shoes (CRS) and minimalist footwear (MFW) pre and post a 4-week MFW familiarization period. Ten female runners (age: 21 ± 2 years; stature: 165.8 ± 4.5 cm; mass: 55.9 ± 3.2 kg) completed two 11 km/h treadmill runs, 24 hours apart, in both CRS and MFW (pretest). Plantar data were measured using sensory insoles for foot strike patterns, stride frequency, mean maximum force ( M ⁢ F ¯ ), mean maximum pressure ( M ⁢ P ¯ ) and eight mean maximum regional pressures. Subjects then completed a 4-week familiarization period consisting of running in MFW and simple gait-retraining, before repeating the tests (posttest). During the pretests, 30% of subjects adopted a forefoot strike in MFW, following familiarization this increased to 80%; no change occurred in CRS. A significant decrease in M ⁢ F ¯ in both MFW and CRS (P = 0.024) was observed from pre-post, and a significant decrease in heel pressures in MFW. M ⁢ P ¯ was higher in MFW throughout testing (P < 0.001).A 4-week familiarization to MFW resulted in a significant reduction in M ⁢ F ¯ in both the CRS and MFW conditions, as well as a reduction in heel pressures. Higher M ⁢ P ¯ was observed throughout testing in the MFW condition. PMID:24004458

  14. Effects of 4 weeks preoperative exercise on knee extensor strength after anterior cruciate ligament reconstruction

    PubMed Central

    Kim, Do Kyung; Hwang, Ji Hye; Park, Won Hah

    2015-01-01

    [Purpose] After an anterior cruciate ligament injury and subsequent reconstruction, quadriceps muscle weakness and disruption of proprioceptive function are common. The purpose of this study was to examine the effects of a 4 weeks preoperative exercise intervention on knee strength power and function post-surgery. [Subjects and Methods] Eighty male patients (27.8±5.7 age), scheduled for reconstruction surgery, were randomly assigned to two groups, the preoperative exercise group (n=40) and a no preoperative exercise group (n=40). The preoperative exercise group participated in a 4-week preoperative and 12-week post-operative programs, while the no preoperative exercise group participated only in the 12-week postoperative exercise program. Isokinetic measured of quadriceps strength were obtained at 4 weeks before and 3 months after surgery. [Results] The knee extensor strength deficits measured at 60°/s and 180°/s was significantly lower in the preoperative exercise group compared with the no preoperative exercise group. At 3 months after surgery, the extensor strength deficit was 28.5±9.0% at 60°/sec and 23.3±9.0% at 180°/sec in the preoperative exercise group, whereas the no preoperative exercise group showed extensor strength deficits of 36.5±10.7% and 27.9±12.6% at 60°/sec and 180°/sec, respectively. The preoperative exercise group demonstrated significant improvement the single-leg hop distance. [Conclusion] Four week preoperative exercise may produce many positive effects post reconstruction surgery, including faster recovery of knee extensor strength and function, as measured by single-leg hop ability. PMID:26504270

  15. Nicotine Intake From Electronic Cigarettes on Initial Use and After 4 Weeks of Regular Use

    PubMed Central

    Hajek, Peter; Phillips, Anna; Myers Smith, Katie; West, Oliver; McRobbie, Hayden

    2015-01-01

    Introduction: Electronic cigarettes (EC) have the potential to generate a substantial public health benefit if there is a switch from smoking to EC use on a population scale. The nicotine delivery from EC is likely to play a major role in their attractiveness to smokers. We assessed nicotine delivery from a first-generation EC and the effect of experience with its use on nicotine intake. Methods: Six smokers provided pharmacokinetic (PK) data after their first use of EC and again following 4 weeks of use. Results: The peak nicotine levels were achieved within 5min of starting the EC use, which suggests that EC may provide nicotine via pulmonary absorption. There were large individual differences in nicotine intake. Compared with the PK profile when using EC for the first time, 4 weeks of practice generated a 24% increase in the peak plasma concentrations (from 4.6 to 5.7ng/ml; nonsignificant) and a 79% increase in overall nicotine intake (AUC0→inf increased from 115 to 206 ng*min/ml; p < .05). Conclusions: First-generation EC provide faster nicotine absorption than nicotine replacement products, but to compete successfully with conventional cigarettes, EC may need to provide higher doses of nicotine. Nicotine intake from EC can increase with practice, but further studies are needed to confirm this effect. PMID:25122503

  16. Enterococcus faecium Mediastinitis Complicated by Disseminated Candida parapsilosis Infection after Congenital Heart Surgery in a 4-Week-Old Baby.

    PubMed

    Renk, Hanna; Neunhoeffer, Felix; Hölzl, Florian; Hofbeck, Michael; Kumpf, Matthias

    2015-01-01

    Background. Cardiac surgery offers multiple treatment options for children with congenital heart defects. However, infectious complications still remain a major cause of morbidity and mortality in these patients. Mediastinitis is a detrimental complication in children undergoing cardiac surgery. The risk of mediastinitis after delayed sternal closure is up to 10%. Case Presentation. We report a case of Enterococcus faecium mediastinitis in a 4-week-old female baby on extracorporeal membrane oxygenation after Norwood procedure. Although repeated antibiotic irrigation, debridement, and aggressive antibiotic treatment were started early, the pulmonary situation deteriorated. Candida parapsilosis was isolated from bronchoalveolar lavage after pulmonary hemorrhage. Disseminated C. parapsilosis infection with pulmonary involvement was treated with liposomal amphotericin B. Subsequently, inflammatory markers increased again and eventually C. parapsilosis was isolated from the central venous catheter. Conclusion. Children undergoing delayed sternal closure have a higher risk of mediastinitis. Therefore, antibiotic prophylaxis, for example, for soft tissue infection seems justified. However, long-term antibiotic treatment is a risk factor for fungal superinfection. Antifungal treatment of disseminated C. parapsilosis infection may fail in PICU patients with nonbiological material in place due to capacity of this species to form biofilms on medical devices. Immediate removal of central venous catheters and other nonbiological material is life-saving in these patients. PMID:26605096

  17. Enterococcus faecium Mediastinitis Complicated by Disseminated Candida parapsilosis Infection after Congenital Heart Surgery in a 4-Week-Old Baby

    PubMed Central

    Renk, Hanna; Neunhoeffer, Felix; Hölzl, Florian; Hofbeck, Michael; Kumpf, Matthias

    2015-01-01

    Background. Cardiac surgery offers multiple treatment options for children with congenital heart defects. However, infectious complications still remain a major cause of morbidity and mortality in these patients. Mediastinitis is a detrimental complication in children undergoing cardiac surgery. The risk of mediastinitis after delayed sternal closure is up to 10%. Case Presentation. We report a case of Enterococcus faecium mediastinitis in a 4-week-old female baby on extracorporeal membrane oxygenation after Norwood procedure. Although repeated antibiotic irrigation, debridement, and aggressive antibiotic treatment were started early, the pulmonary situation deteriorated. Candida parapsilosis was isolated from bronchoalveolar lavage after pulmonary hemorrhage. Disseminated C. parapsilosis infection with pulmonary involvement was treated with liposomal amphotericin B. Subsequently, inflammatory markers increased again and eventually C. parapsilosis was isolated from the central venous catheter. Conclusion. Children undergoing delayed sternal closure have a higher risk of mediastinitis. Therefore, antibiotic prophylaxis, for example, for soft tissue infection seems justified. However, long-term antibiotic treatment is a risk factor for fungal superinfection. Antifungal treatment of disseminated C. parapsilosis infection may fail in PICU patients with nonbiological material in place due to capacity of this species to form biofilms on medical devices. Immediate removal of central venous catheters and other nonbiological material is life-saving in these patients. PMID:26605096

  18. Strategies for Early Non-response to Antipsychotic Drugs in the Treatment of Acute-phase Schizophrenia

    PubMed Central

    Ito, Hiroto

    2014-01-01

    As a strategy for antipsychotic treatment of schizophrenia, monotherapy is clearly optimal when both effective and tolerated. When a patient fails to respond to an adequate dose of an antipsychotic, alternatives include switching, administering a higher dose (above the licensed dose), polypharmacy or clozapine. Clozapine is the only option with established efficacy, but is less manageable than other antipsychotics. We therefore reviewed other options, focusing on the treatment of acute-phase schizophrenia. According to recent evidence, an antipsychotic may be viewed as ineffective within 1-4 weeks in acute-phase practice, although some differences may exist among antipsychotics. Whether a switching strategy is effective might depend on the initial antipsychotic and which antipsychotic is switched to. As weak evidence points toward augmentation being superior to continuation of the initial antipsychotic, inclusion of augmentation arms in larger studies comparing strategies for early non-responders in the acute-phase is justified. With respect to high-doses, little evidence is available regarding acute-phase treatment, and the issue remains controversial. Although evidence for antipsychotic switching, augmentation, and high-doses has gradually been accumulating, more studies performed in real clinical practice with minimal bias are required to establish strategies for early non-response to an antipsychotic drug in the treatment of acute-phase schizophrenia. PMID:24851115

  19. Comparison of efficacy of three different desensitizing agents for in-office relief of dentin hypersensitivity: A 4 weeks clinical study

    PubMed Central

    Jena, Amit; Shashirekha, Govind

    2015-01-01

    Aim: To evaluate the effectiveness of three different pastes containing 5% NovaMin, 8% arginine, and 15% hydroxyapatite nanoparticles (n-HA) respectively in the treatment of dentin hypersensitivity (DH). Materials and Methods: A 4 weeks study was conducted on 45 adult patients with cervical abrasions leading to hypersensitivity of two or more teeth anterior to molars. Patients were divided into three toothpaste groups. Group I: 5% NovaMin, Group II: 8% arginine, Group III: 15% n-HA. Sensitivity was assessed at baseline, immediately after application and after 1-week and 4 weeks. Tactile stimuli response using a visual analog scale and standard cold air blast using Schiff cold air sensitivity scale were used to compare the efficacies of toothpastes after a single application. Statistical Analysis: Two-way analysis of variance and post-hoc Tukey test were used and P ≤ 0.05 was considered statistically significant. Results: Visual analog scale analysis: Group III and Group II showed statistically significant reduction in DH at all-time intervals when compared with Group I. In SCA analysis there is no statistically significant difference between Group II and Group III immediately after application. Conclusion: Toothpaste containing 15% n-HA was found to be most effective in reduction of DH after a single application up to a period of 4 weeks followed by 8% arginine and 5% NovaMin toothpastes. PMID:26430303

  20. Integrated thermal treatment system sudy: Phase 2, Results

    SciTech Connect

    Feizollahi, F.; Quapp, W.J.

    1995-08-01

    This report presents the second phase of a study on thermal treatment technologies. The study consists of a systematic assessment of nineteen thermal treatment alternatives for the contact-handled mixed low-level waste (MLLW) currently stored in the US Department of Energy complex. The treatment alternatives consist of widely varying technologies for safely destroying the hazardous organic components, reducing the volume, and preparing for final disposal of the MLLW. The alternatives considered in Phase 2 were innovative thermal treatments with nine types of primary processing units. Other variations in the study examined the effect of combustion gas, air pollution control system design, and stabilization technology for the treatment residues. The Phase 1 study, the results of which have been published as an interim report, examined ten initial thermal treatment alternatives. The Phase 2 systems were evaluated in essentially the same manner as the Phase 2 systems. The assumptions and methods were the same as for the Phase 1 study. The quantities, and physical and chemical compositions, of the input waste used in he Phase 2 systems differ from those in the Phase 1 systems, which were based on a preliminary waste input database developed at the onset of the Integrated Thermal Treatment System study. The inventory database used in the Phase 2 study incorporates the latest US Department of Energy information. All systems, both primary treatment systems and subsystem inputs, have now been evaluated using the same waste input (2,927 lb/hr).

  1. Pathogenicity evaluation of different Newcastle disease virus chimeras in 4-week-old chickens.

    PubMed

    Susta, Leonardo; Miller, Patti J; Afonso, Claudio L; Estevez, Carlos; Yu, Qingzhong; Zhang, Jian; Brown, Corrie C

    2010-12-01

    The aim of this study was to evaluate the disease-inducing ability of four chimeric Newcastle disease viruses (NDV) by clinicopathological assessment. The infectious clones were previously generated by insertion of hemagglutinin-neuraminidase (HN) and/or fusion (F) genes from virulent strains (Turkey North Dakota and California 02) into a mesogenic strain (Anhinga) backbone. Groups of 4-week-old chickens were inoculated via eye drop instillation, clinical signs were monitored daily, and necropsies with collection of tissues were performed at 2, 5, 10, and 14 days post infection. Tissue sections were evaluated for histopathology and immunohistochemistry for NDV nucleoprotein. All viruses replicated successfully in the natural host, although viral recovery, seroconversion, and extent of immunohistochemical staining were greatest from birds infected with those viruses containing both F and HN genes from the same virulent virus. There was minimal to no increase in clinicopathologic disease due to infection with the chimeras compared to the recombinant backbone. However, all birds developed histological evidence of encephalitis. The results suggest that the inherent virulence of Turkey North Dakota and California 2002 strains is due to more than the simple presence of their F and HN genes. PMID:20614237

  2. A 2-year-old with 4 weeks of daily fever.

    PubMed

    Darby, John B; Liddell, Lucette; DeGuzman, Marietta; McClain, Kenneth L; Rubenstein, Jared; Chase, Lindsay; Marquez, Lucila

    2015-05-01

    A 2-year-old female presents for evaluation of 4 weeks of daily fevers. When the fevers began, she had mild upper respiratory tract symptoms, which quickly resolved. The fevers persisted, however, with a maximum of 40°C. The child's review of symptoms was significant for a 1-kg weight loss over the past month. Ten months before presentation, she had moved from Saudi Arabia with her family. One week before the onset of symptoms, she had visited a petting zoo. During episodes of fever, the patient was ill-appearing and had an elevated heart rate and respiratory rate. On examination, she was found to be thin, febrile, tachycardic, and with scattered lymphadenopathy. Results of laboratory tests were remarkable for an elevated white blood cell count of 16,100 cells per uL with a neutrophilic predominance. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated at 99 mm/h and 27 mg/dL, respectively. A chest radiograph indicated a small amount of fluid in the interlobar fissures. Our expert panel examines her case, offers a definition of fever of unknown origin, and makes diagnostic considerations. PMID:25917994

  3. A 4-week Repeated Dose Toxicity Study of Glycine in Rats by Gavage Administration

    PubMed Central

    Shibui, Yusuke; Miwa, Tadashi; Yamashita, Mayumi; Chin, Keigi; Kodama, Terutaka

    2013-01-01

    In order to examine the toxicity profile of glycine, an authorized food additive, a solution of glycine in water for injection was administered orally (via gavage) to male SD rats (Crl:CD(SD)) once daily for 4 weeks at doses of 500, 1000 and 2000 mg/kg/day in a volume of 10 mL/kg. Control animals received vehicle only. No animals died, and no glycine-related changes were observed in body weight, food consumption, water consumption, hematology, organ weight, gross pathological examination or histopathological examination. In urinalysis, daily urinary volume and urinary Cl excretion were significantly higher in the 2000 mg/kg/day dose group, and urine pH and urinary protein showed lower trends in the glycine-treated groups. However, these changes were considered to be of little toxicological significance, because there were no histopathological changes in the kidneys or urinary bladder and no changes in other urinary parameters. As regards blood chemistry, phospholipids were significantly higher in the 2000 mg/kg/day dose group. However, the increase was small and was not considered to be toxicologically significant. In conclusion, none of the animals in any of the glycine-treated groups showed changes that were considered toxicologically significant. Therefore, the no-observed-adverse-effect level of glycine was estimated to be at least 2000 mg/kg/day under the conditions of this study. PMID:24526813

  4. A 4-week Repeated Dose Toxicity Study of Glycine in Rats by Gavage Administration.

    PubMed

    Shibui, Yusuke; Miwa, Tadashi; Yamashita, Mayumi; Chin, Keigi; Kodama, Terutaka

    2013-12-01

    In order to examine the toxicity profile of glycine, an authorized food additive, a solution of glycine in water for injection was administered orally (via gavage) to male SD rats (Crl:CD(SD)) once daily for 4 weeks at doses of 500, 1000 and 2000 mg/kg/day in a volume of 10 mL/kg. Control animals received vehicle only. No animals died, and no glycine-related changes were observed in body weight, food consumption, water consumption, hematology, organ weight, gross pathological examination or histopathological examination. In urinalysis, daily urinary volume and urinary Cl excretion were significantly higher in the 2000 mg/kg/day dose group, and urine pH and urinary protein showed lower trends in the glycine-treated groups. However, these changes were considered to be of little toxicological significance, because there were no histopathological changes in the kidneys or urinary bladder and no changes in other urinary parameters. As regards blood chemistry, phospholipids were significantly higher in the 2000 mg/kg/day dose group. However, the increase was small and was not considered to be toxicologically significant. In conclusion, none of the animals in any of the glycine-treated groups showed changes that were considered toxicologically significant. Therefore, the no-observed-adverse-effect level of glycine was estimated to be at least 2000 mg/kg/day under the conditions of this study. PMID:24526813

  5. Adaptation to a long term (4 weeks) arginine- and precursor (glutamate, proline and aspartate)-free diet☆

    PubMed Central

    Tharakan, John F.; Yu, Yong M.; Zurakowski, David; Roth, Rachel M.; Young, Vernon R.; Castillo, Leticia

    2008-01-01

    Summary Background & aims It is not known whether arginine homeostasis is negatively affected by a “long term” dietary restriction of arginine and its major precursors in healthy adults. To assess the effects of a 4-week arginine- and precursor-free dietary intake on the regulatory mechanisms of arginine homeostasis in healthy subjects. Methods Ten healthy adults received a complete amino acid diet for 1 week (control diet) and following a break period, six subjects received a 4-week arginine, proline, glutamate and aspartate-free diet (APF diet). The other four subjects continued for 4 weeks with the complete diet. On days 4 and 7 of the first week and days 25 and 28 of the 4-week period, the subjects received 24-h infusions of arginine, citrulline, leucine and urea tracers. Results During the 4-week APF, plasma arginine fluxes for the fed state, were significantly reduced. There were no significant differences for citrulline, leucine or urea fluxes. Arginine de novo synthesis was not affected by the APF intake. However, arginine oxidation was significantly decreased. Conclusions In healthy adults, homeostasis of arginine under a long term arginine- and precursor-free intake is achieved by decreasing catabolic rates, while de novo arginine synthesis is maintained. PMID:18590940

  6. Acoustic Treatment Design Scaling Methods. Phase 2

    NASA Technical Reports Server (NTRS)

    Clark, L. (Technical Monitor); Parrott, T. (Technical Monitor); Jones, M. (Technical Monitor); Kraft, R. E.; Yu, J.; Kwan, H. W.; Beer, B.; Seybert, A. F.; Tathavadekar, P.

    2003-01-01

    The ability to design, build and test miniaturized acoustic treatment panels on scale model fan rigs representative of full scale engines provides not only cost-savings, but also an opportunity to optimize the treatment by allowing multiple tests. To use scale model treatment as a design tool, the impedance of the sub-scale liner must be known with confidence. This study was aimed at developing impedance measurement methods for high frequencies. A normal incidence impedance tube method that extends the upper frequency range to 25,000 Hz. without grazing flow effects was evaluated. The free field method was investigated as a potential high frequency technique. The potential of the two-microphone in-situ impedance measurement method was evaluated in the presence of grazing flow. Difficulties in achieving the high frequency goals were encountered in all methods. Results of developing a time-domain finite difference resonator impedance model indicated that a re-interpretation of the empirical fluid mechanical models used in the frequency domain model for nonlinear resistance and mass reactance may be required. A scale model treatment design that could be tested on the Universal Propulsion Simulator vehicle was proposed.

  7. Integrated thermal treatment system study -- Phase 2 results. Revision 1

    SciTech Connect

    Feizollahi, F.; Quapp, W.J.

    1996-02-01

    This report presents the second phase of a study on thermal treatment technologies. The study consists of a systematic assessment of nineteen thermal treatment alternatives for the contact-handled mixed low-level waste (MLLW) currently stored in the US Department of Energy complex. The treatment alternatives consist of widely varying technologies for safely destroying the hazardous organic components, reducing the volume, and preparing for final disposal of the MLLW. The alternatives considered in Phase 2 were innovative thermal treatments with nine types of primary processing units. Other variations in the study examined the effect of combustion gas, air pollution control system design, and stabilization technology for the treatment residues. The Phase 1 study examined ten initial thermal treatment alternatives. The Phase 2 systems were evaluated in essentially the same manner as the Phase 1 systems. The alternatives evaluated were: rotary kiln, slagging kiln, plasma furnace, plasma gasification, molten salt oxidation, molten metal waste destruction, steam gasification, Joule-heated vitrification, thermal desorption and mediated electrochemical oxidation, and thermal desorption and supercritical water oxidation. The quantities, and physical and chemical compositions, of the input waste used in the Phase 2 systems differ from those in the Phase 1 systems, which were based on a preliminary waste input database developed at the onset of the Integrated Thermal Treatment System study. The inventory database used in the Phase 2 study incorporates the latest US Department of Energy information. All systems, both primary treatment systems and subsystem inputs, have now been evaluated using the same waste input (2,927 lb/hr). 28 refs., 88 figs., 41 tabs.

  8. Adaptation to a long term (4 weeks) arginine- and precursor (glutamate, proline and aspartate)-free diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is not known whether arginine homeostasis is negatively affected by a "long-term" dietary restriction of arginine and its major precursors in healthy adults. To assess the effects of a 4-week arginine- and precursor-free dietary intake on the regulatory mechanisms of arginine homeostasis in healt...

  9. A 4-week Repeated dose Oral Toxicity Study of Mecasin in Sprague-Dawley Rats to Determine the Appropriate Doses for a 13-week, Repeated Toxicity Test

    PubMed Central

    Cha, Eunhye; Lee, Jongchul; Lee, Seongjin; Park, Manyong; Song, Inja; Son, Ilhong; Song, Bong-Keun; Kim, Dongwoung; Lee, Jongdeok

    2015-01-01

    Objectives: In this study, we investigated the 4-week repeated-dose oral toxicity of gami-jakyak gamcho buja decoction (Mecasin) to develop safe treatments. Methods: In order to investigate the 4-week oral toxicity of Mecasin, we administered Mecasin orally to rats. Sprague-Dawley (SD) rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of Mecasin of 500, 1,000, and 2,000 mg/kg of body weight were administered to the experimental groups, and a dose of normal saline solution of 10 mL/kg was administered to the control group. We examined the survival rate, weight, clinical signs, and gross findings for four weeks. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: No deaths occurred in any of the four groups. No significant changes in weights or food consumption between the control group and the experimental groups were observed. Serum biochemistry revealed that some groups showed significant decrease in inorganic phosphorus (IP) (P < 0.05). During necropsy on the rats, one abnormal macroscopic feature, a slight loss of fur, was observed in the mid dosage (1,000 mg/ kg) male group. No abnormalities were observed in any other rats. In histopathological findings, the tubular basophilia and cast of the kidney and extramedullary hematopoiesis of the spleen were found. However, those changes were minimal and had occurred naturally or sporadically. No other organ abnormalities were observed. Conclusion: During this 4-week, repeated, oral toxicity test of Mecasin in SD rats, no toxicity changes due to Mecasin were observed in any of the male or the female rats in the high dosage group. Thus, we suggest that the doses in a 13-week, repeated test should be 0, 500, 1,000, and 2,000 mg/kg respectively. PMID:26998389

  10. Oral Hygiene Behaviour Change During the Nonsurgical Periodontal Treatment Phase

    PubMed Central

    Shamani, Saeed; Jansson, Leif

    2012-01-01

    The purpose of the present study was to investigate the frequency of smoking cessation and the use of proximal tooth cleaning routines after a nonsurgical periodontal treatment phase in a Specialist clinic of Periodontology and to evaluate if these behaviour changes had any influence on the periodontal healing results. The investigation was conducted as a retrospective longitudinal study on a randomly selected population of 100 patients referred for periodontal treatment. The variables were registered from the dental records and the radiographs. Forty-six individuals declared that they were smokers at baseline and one individual of those quitted smoking during the nonsurgical treatment period. The percentage of individuals who performed proximal tooth cleaning daily was significantly increased from 56% to 72% during the treatment period. The patients practising proximal tooth cleaning daily had significantly lower Plaque index before as well as after the nonsurgical periodontal treatment phase compared to those without the routine. The subjects who did not perform tooth cleaning daily before the treatment and who did not introduce this routine had significantly deeper periodontal pockets compared to those who performed inter-dental cleaning daily before treatment or who had adopted the routine during the treatment phase. However, there were no significant differences according to number of deepened periodontal pockets after nonsurgical treatment irrespective of proximal cleaning routines. In the future, motivational interviewing may be a more effective method to achieve a behaviour change if an extended education of dental hygienists within this area will be implemented. PMID:23284591

  11. Effects of a Baking Soda Gum on extrinsic dental stain: results of a longitudinal 4-week assessment.

    PubMed

    Soparkar, P; Newman, M B

    2001-07-01

    An evaluation of the effects of ARM & HAMMER DENTAL CARE The Baking Soda Gum (AHDC) on extrinsic dental stain was made in 48 subjects presenting with measurable extrinsic stain. The subjects were randomized to use either the baking soda gum or a non-baking soda placebo gum for 20 minutes twice daily after lunch and dinner while brushing once daily. The procedure of limited brushing was chosen to simulate the level of hygiene normally practiced by participants entering a clinical study. After 4 weeks, the reduction in measurable extrinsic stain in the baking soda gum group was statistically significant (P = .0044) relative to baseline. Statistical analysis of the placebo gum group revealed no significant change in extrinsic stain from baseline. The magnitude of the unadjusted longitudinal reduction in extrinsic stain in the baking soda gum group was 29.7% at 4 weeks. PMID:11913306

  12. [Pharmacokinetic studies following 2 and 4-week Felbinac gel administration to the knee joint].

    PubMed

    Bolten, W; Waldorf-Bolten, E; Sarfert, D; Lehmann, W; Miehlke, W

    1990-01-01

    Twelve patients with osteoarthrosis were locally treated with Felbinac Gel (biphenyl acetic acid (BPAA) 3%) three times daily for 14 days (five patients), 28 days (six patients) or 42 days (one patient) before elective knee joint surgery. BPAA plasma concentrations as of the seventh day of treatment were steady at between 423 and 1040 ng/ml. In surgery, synovial and tissue samples were taken to determine BPAA concentrations. Moderate and sometimes higher synovial BPAA levels in the treated knee joint compared to the contralateral knee seem to indicate a combined direct and systemic absorption. The highest BPAA concentrations (1497-13939 ng/g) were measured in the skin. Drug levels in the synovial membrane (36-994 ng/g), the synovia (104-768 ng/ml), tendon (less than 10-197 ng/g), cartilage (less than 10-109 ng/g), muscle (12-101 ng/g), and subcutis (16-97 ng/g) were lower. BPAA neither accumulates in the skin, nor in any other peri-articular tissue. A steady state was reached as of the 14th day of treatment at the latest. None of the patients reported any local or systemic side effects. PMID:2085060

  13. One Phase versus Two Phase Treatment in Mixed Dentition: A Critical Review.

    PubMed

    Suresh, M; Ratnaditya, Akurathi; Kattimani, Vivekanand S; Karpe, Shameem

    2015-08-01

    The mixed dentition is the developmental period after the permanent first molars and incisors have erupted, and before the remaining deciduous teeth are lost. Phase I treatment is usually done early in this period. Mixed dentition treatment goals often focus on skeletal rather than dental correction. To design a treatment plan, the clinician must understand the growth and development patterns, and the known effects of the chosen treatment modality. Jaw growth affects orthodontic treatment, usually favorably, but sometimes unfavorably. When and how much growth will occur is completely unpredictable. However, we know some useful facts about jaw growth in the mixed dentition. The two areas that remain controversial in the orthodontic literature are the treatment of crowding and of Class II malocclusions in the mixed dentition. Is there a benefit to early treatment for these problems? This question has yet to be fully answered by researchers. Hence, we planned for review of all available literature to come to a consensus about preventive or interceptive orthodontics or in other words Phase 1 and Phase 2 treatment. The clinician can diagnose and intercept certain developing problems with early treatment. Many other cases should be supervised, but not treated until the permanent teeth are in place. We must base our decision to treat on experience, knowledge of growth and dental development, and research. PMID:26464559

  14. Window Treatment Phase I and Other Energy II Conservation Measures.

    ERIC Educational Resources Information Center

    Donohue, Philip E.

    Six different energy-saving treatments for large window areas were tested by Tompkins-Cortland Community College (TCCC) to coordinate energy saving with building design. The TCCC building has an open space design with 33,000 square feet of external glass and other features causing heating problems and high energy costs. Phase I of the…

  15. Treatment of Incest Perpetrators: A Five-Phase Model.

    ERIC Educational Resources Information Center

    Frenken, Jos

    1994-01-01

    A five-phase treatment program for fathers who committed incest includes crisis intervention and assessment; analysis of the sequence of events, thoughts, moods, and behaviors preceding sexual contact; client takes responsibility for the abuse; origin of the abuse is put into the context of client's problems and intrafamilial problems; and…

  16. Treatment of incest perpetrators: a five-phase model.

    PubMed

    Frenken, J

    1994-04-01

    The author's experiences with treating fathers who committed incest and were sentenced to undergo therapy are discussed in this paper. The treatment consists of five phases. Following crisis intervention and assessment, an analysis is made of the sequence of events, thoughts, moods, and behaviors that precede sexual contact. In the third phase, the client's sense of guilt is brought out and he actively takes responsibility for the sexual abuse of his daughter. In the fourth phase, the origin of the sexual abuse is clarified as it is put into the context of his own problems and the problems within the family. In the fifth phase, strategies for relapse prevention are practiced. In addition there are partner-relationship sessions with the couple as well as family counseling sessions. Up to now none of the clients have recidivized. PMID:8187021

  17. A 4-Week, Repeated, Intravenous Dose, Toxicity Test of Mountain Ginseng Pharmacopuncture in Sprague-Dawley Rats

    PubMed Central

    Lee, Kwangho; Yu, Junsang; Sun, Seungho; Kwon, Kirok; Lim, Chungsan

    2014-01-01

    Objectives: Mountain ginseng pharmacopuncture (MGP) is a pharmacopuncture made by distilling extract from mountain cultivated ginseng or mountain wild ginseng. This pharmacopuncture is injected intravenously, which is a quick, lossless way of strongly tonifying Qi function. The present study was undertaken to evaluate a 4-week, repeated, intravenous injection, toxicity test of MGP in Sprague-Dawley (SD) rats. Methods: Twenty male and female 6-week-old SD rats were used as subjects. We divided the SD rats into 4 groups: the high-dosage (10 mL/kg), medium-dosage (5 mL/kg), low-dosage (2.5 mL/kg) and control (normal saline) groups. MGP or normal saline was injected intravenously into the caudal vein of the rats once daily for 4 weeks. Clinical signs, body weights, and food consumption were monitored during the observation period, and hematology, serum biochemistry, organ weight, necropsy, and histological examinations were conducted once the observations had been completed. Results: No mortality was observed in any of the groups during the observation period. No changes due to MGP were observed in the experimental groups regarding clinical signs, body weights, food consumption, hematology, serum biochemistry, organ weight and necropsy. No histological changes due to MGP were observed in any of the male or female rats in the high-dosage group. Conclusion: During this 4-week, repeated, intravenous injection, toxicity test of MGP in SD rats, no toxic changes due to MGP were observed in any of the male or female rats in the high-dosage group. Thus, we suggest that the high and the low doses in a 13-week, repeated test should be 10 mL/kg and 2.5 mL/kg, respectively. PMID:25780717

  18. Neuromuscular Adaptations After 2 and 4 Weeks of 80% Versus 30% 1 Repetition Maximum Resistance Training to Failure.

    PubMed

    Jenkins, Nathaniel D M; Housh, Terry J; Buckner, Samuel L; Bergstrom, Haley C; Cochrane, Kristen C; Hill, Ethan C; Smith, Cory M; Schmidt, Richard J; Johnson, Glen O; Cramer, Joel T

    2016-08-01

    Jenkins, NDM, Housh, TJ, Buckner, SL, Bergstrom, HC, Cochrane, KC, Hill, EC, Smith, CM, Schmidt, RJ, Johnson, GO, and Cramer, JT. Neuromuscular adaptations after 2 and 4 weeks of 80% versus 30% 1 repetition maximum resistance training to failure. J Strength Cond Res 30(8): 2174-2185, 2016-The purpose of this study was to investigate the hypertrophic, strength, and neuromuscular adaptations to 2 and 4 weeks of resistance training at 80 vs. 30% 1 repetition maximum (1RM) in untrained men. Fifteen untrained men (mean ± SD; age = 21.7 ± 2.4 years; weight = 84.7 ± 23.5 kg) were randomly assigned to either a high-load (n = 7) or low-load (n = 8) resistance training group and completed forearm flexion resistance training to failure 3 times per week for 4 weeks. Forearm flexor muscle thickness (MT) and echo intensity, maximal voluntary isometric (MVIC) and 1RM strength, and the electromyographic, mechanomyographic (MMG), and percent voluntary activation (%VA) responses at 10-100% of MVIC were determined at baseline, 2, and 4 weeks of training. The MT increased from baseline (2.9 ± 0.1 cm) to week 2 (3.0 ± 0.1 cm) and to week 4 (3.1 ± 0.1 cm) for the 80 and 30% 1RM groups. MVIC increased from week 2 (121.5 ± 19.1 Nm) to week 4 (138.6 ± 22.1 Nm) and 1RM increased from baseline (16.7 ± 1.6 kg) to weeks 2 and 4 (19.2 ± 1.9 and 20.5 ± 1.8 kg) in the 80% 1RM group only. The MMG amplitude at 80 and 90% MVIC decreased from baseline to week 4, and %VA increased at 20 and 30% MVIC for both groups. Resistance training to failure at 80 vs. 30% 1RM elicited similar muscle hypertrophy, but only 80% 1RM increased muscle strength. However, these disparate strength adaptations were difficult to explain with neuromuscular adaptations because they were subtle and similar for the 80 and 30% 1RM groups. PMID:26848545

  19. Effect of 4 weeks of basic military training on peripheral blood leucocytes and urinary excretion of catecholamines and cortisol.

    PubMed

    Makras, Polyzois; Koukoulis, George N; Bourikas, George; Papatheodorou, George; Bedevis, Konstantinos; Menounos, Panagiotis; Pappas, Dimitrios; Kartalis, George

    2005-08-01

    In this study, we assessed the effects of a 4 week basic military physical training programme for male recruits of the Hellenic Air Force on the number and distribution of circulating immune cells and adrenergic and adrenocortical hormonal responses. One group of recruits (exercised, n = 48) participated in moderate intermittent physical exercise, whereas a second group (non-exercised controls, n = 9) performed only light work in the barracks. Both groups participated in the same non-physical, classroom-type training and testing. Military training by the exercised group resulted in significant increases in CD4+ T-lymphocytes, renal cortisol excretion and the urinary noradrenaline/adrenaline ratio, together with reductions in neutrophils and the neutrophil/lymphocyte ratio. In the exercised group, the urinary noradrenaline/adrenaline ratio correlated positively with the training-induced changes in CD4+ T-lymphocytes and negatively with changes in the neutrophil/lymphocyte ratio. No significant relationship was found between training-induced increases in cortisol excretion and any of the peripheral blood cell alterations. Our results indicate that 4 weeks of military training consisting of intermittent moderate exercise resulted in a significant increase in CD4+ T-lymphocytes and reduction in neutrophils. These changes were probably driven by alterations in hormonal status, including the significant impact of sympathetic nervous system activation. PMID:16195034

  20. Complex PTSD and phased treatment in refugees: a debate piece

    PubMed Central

    ter Heide, F. Jackie June; Mooren, Trudy M.; Kleber, Rolf J.

    2016-01-01

    Background Asylum seekers and refugees have been claimed to be at increased risk of developing complex posttraumatic stress disorder (complex PTSD). Consequently, it has been recommended that refugees be treated with present-centred or phased treatment rather than stand-alone trauma-focused treatment. This recommendation has contributed to a clinical practice of delaying or waiving trauma-focused treatment in refugees with PTSD. Objective The aim of this debate piece is to defend two theses: (1) that complex trauma leads to complex PTSD in a minority of refugees only and (2) that trauma-focused treatment should be offered to all refugees who seek treatment for PTSD. Methods The first thesis is defended by comparing data on the prevalence of complex PTSD in refugees to those in other trauma-exposed populations, using studies derived from a systematic review. The second thesis is defended using conclusions of systematic reviews and a meta-analysis of the efficacy of psychotherapeutic treatment in refugees. Results Research shows that refugees are more likely to meet a regular PTSD diagnosis or no diagnosis than a complex PTSD diagnosis and that prevalence of complex PTSD in refugees is relatively low compared to that in survivors of childhood trauma. Effect sizes for trauma-focused treatment in refugees, especially narrative exposure therapy (NET) and culturally adapted cognitive-behaviour therapy (CA-CBT), have consistently been found to be high. Conclusions Complex PTSD in refugees should not be assumed to be present on the basis of complex traumatic experiences but should be carefully diagnosed using a validated interview. In line with treatment guidelines for PTSD, a course of trauma-focused treatment should be offered to all refugees seeking treatment for PTSD, including asylum seekers. PMID:26886486

  1. Urine naloxone concentration at different phases of buprenorphine maintenance treatment.

    PubMed

    Heikman, Pertti; Häkkinen, Margareeta; Gergov, Merja; Ojanperä, Ilkka

    2014-03-01

    In spite of the benefits of buprenorphine-naloxone co-formulation (BNX) in opioid maintenance treatment, the naloxone component has not prevented parenteral use of BNX. Current laboratory methods are not sufficient to differentiate between therapeutic and illicit use of buprenorphine, and little is known about urine naloxone concentrations. Measurement of urine naloxone, together with buprenorphine and norbuprenorphine, might help to determine the naloxone source and administration route. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for this purpose. Naloxone, buprenorphine, and norbuprenorphine total concentrations were measured in urine samples from opioid-dependent patients before and during stable and unstable phases of maintenance treatment with BNX. The limit of quantification in urine was 1.0 µg/L for naloxone, buprenorphine and norbuprenorphine. Before treatment, all samples contained buprenorphine but the median naloxone concentration was 0 µg/L. During the maintenance treatment with BNX all urine samples were positive for naloxone, buprenorphine and norbuprenorphine. The naloxone concentration at a stable phase of treatment (median 60 µg/L, range 5-200 µg/L) was not different from the naloxone concentration at an unstable phase (70 µg/L, 10-1700 µg/L). Applying an upper limit of 200 µg/L to the sample, the median naloxone/buprenorphine ratio was higher in the high than in the low naloxone concentration group (0.9 vs 0.3, respectively). This study suggests that naloxone in urine can act as an indicator of compliance with BNX. Parenteral use of BNX was associated with a high naloxone/buprenorphine ratio. Negative naloxone with positive buprenorphine suggests the use/abuse of buprenorphine alone. PMID:23512803

  2. Analysis of Convective Heat Transfer Enhancement by Nanofluids: Single-Phase and Two-Phase Treatments

    NASA Astrophysics Data System (ADS)

    Kakaç, S.; Pramuanjaroenkij, A.

    2016-06-01

    Nanofluids have been investigated regarding their advantages and potentialities for the purpose of increasing convective heat transfer rates inside thermal systems where they are used as working fluids. Researchers in thermophysics have investigated these fluids experimentally and numerically. This review provides extensive theoretical information concerning nanofluids in the single-phase and two-phase treatments. Important published works on nanofluid properties and correlations are summarized and reviewed in detail. Heat transfer enhancement by nanofluids is a challenging problem due to the difficulties inherent in the model of the physical mechanism of interaction between the paricles. Here the interaction between the phases is modeled by several two-phase models, and the results are given in graphical and tabular forms. Despite the advantages of the mixture model, such as imlementation of physical properties and less computational power requirements, some studies showed that the results of the single-phase and two-phase models are very similar. The main difference consists in the effect of the drift velocities of the phases relative to each other.

  3. Analysis of Convective Heat Transfer Enhancement by Nanofluids: Single-Phase and Two-Phase Treatments

    NASA Astrophysics Data System (ADS)

    Kakaç, S.; Pramuanjaroenkij, A.

    2016-05-01

    Nanofluids have been investigated regarding their advantages and potentialities for the purpose of increasing convective heat transfer rates inside thermal systems where they are used as working fluids. Researchers in thermophysics have investigated these fluids experimentally and numerically. This review provides extensive theoretical information concerning nanofluids in the single-phase and two-phase treatments. Important published works on nanofluid properties and correlations are summarized and reviewed in detail. Heat transfer enhancement by nanofluids is a challenging problem due to the difficulties inherent in the model of the physical mechanism of interaction between the paricles. Here the interaction between the phases is modeled by several two-phase models, and the results are given in graphical and tabular forms. Despite the advantages of the mixture model, such as imlementation of physical properties and less computational power requirements, some studies showed that the results of the single-phase and two-phase models are very similar. The main difference consists in the effect of the drift velocities of the phases relative to each other.

  4. A Two Phase Treatment of an Infected Hip Endoprosthesis.

    PubMed

    Ciriviri, Jasmin; Talevski, Darko; Nestorovski, Zoran; Vraniskoski, Tode; Mishevska-Perchinkova, Snežana

    2015-01-01

    The revision of the two phase treatment represents a golden standard in the treatment of infected endoprosthesis. Throughout this study, the results of 21 patients with an infected hip endoprosthesis treated in two phases have been processed, with the use of an antibiotic spacer, within the period of 2009 and 2012. Thereby, a unique protocol for diagnosis and treatment of infections has been applied to all the patients, which entails a preoperational x-ray image, laboratory findings (Se, CRP), as well as a puncture aspiration with a microbiological and biochemical examination of the aspirated fragments. The operational treatment consists of: taking a sample for microbiological and histopathological diagnosis, removal of the implanted endoprosthesis, excision of the avascular and necrotic tissue and installing an antibiotic spacer. Postoperatively, the patients are treated with a parenteral application of an antibiotics based on an antibiogram, throughout a period of two weeks, and later on an oral treatment, a combination of two antibiotics, depending on the antibiogram, within the following four to six weeks. After the appeasement of the local findings and the laboratory results, a revision with a removal of the antibiotic spacer and reimplantation of an endoprosthesis - revisional or primary has been conducted on the patients, depending on the bone deficit. The functionality of the joint is graded based on the Haris Hip Score. The patients are being observed postoperatively for a period of 12 to 36 months. A definite reimplantation has been applied to 20 patients, while one patient has been treated with a resection method. The Haris Hip Score was 45 preoperatively, and 80 postoperatively. The applied protocol of the treatment of infected endoprosthesis is effective in the eradication of the infection and the final reimplantation. PMID:27442385

  5. CAM Provider Use and Expenditures by Cancer Treatment Phase

    PubMed Central

    Lafferty, William E.; Tyree, Patrick T.; Devlin, Sean M.; Andersen, M. Robyn; Diehr, Paula K.

    2008-01-01

    Objective To assess cancer patients’ utilization of complementary and alternative medical providers and the associated expenditures by specific treatment phases. Study Design Cross-sectional analysis of medical services utilization and expenditures during three therapeutic intervals: an initial treatment phase, continuing care, and end-of-life. Methods Analysis of an insurance claims database that had been matched to the Washington State SEER cancer registry. Results Of 2,900 registry-matched cancer patients 63.2% were female, the median age was 54 years, and 92.7% were white. Breast cancer was the most frequent diagnosis (52.7%), followed by prostate cancer (24.7%), lung cancer (10.1%), colon cancer (7.0%), and hematologic malignancies (5.6%). CAM provider using patients were 26.5% of the overall cohort (18.5% used chiropractors, 7.7% naturopathic physicians, 5.3% massage therapists, and 4.2% saw acupuncturists). The proportion of CAM using patients was similar during each treatment phase. All patients used some conventional care. Female gender, a breast cancer diagnosis, age, and white race were significant predictors of CAM use. Diagnosis of a musculoskeletal problem occurred at sometime during the study for 72.1% of cancer patients. CAM provider visits were 7.2% of total outpatient medical visits and 85.1% of CAM visits resulted in a musculoskeletal diagnosis. Expenditures for CAM providers were 0.3%, 1.0%, and 0.1% of all expenditures during the initial, continuing, and end-of-life phases respectively. Conclusion For cancer patients, musculoskeletal issues were the most commonly listed diagnosis made by a CAM provider. Although expenditures associated with CAM are a small proportion of the total, additional studies are necessary to determine the importance patients place on access to these services. PMID:18471036

  6. Influence of 4 weeks of bovine colostrum supplementation on neutrophil and mucosal immune responses to prolonged cycling.

    PubMed

    Jones, A W; Thatcher, R; March, D S; Davison, G

    2015-12-01

    Bovine colostrum (COL) has been advocated as a nutritional countermeasure to exercise-induced immune dysfunction. The aims of this study were to identify the effects of 4 weeks of COL supplementation on neutrophil responses and mucosal immunity following prolonged exercise. In a randomized double-blind, parallel group design, participants [age 28 ± 8 years; body mass 79 ± 7 kg; height 182 ± 6 cm; maximal oxygen uptake (V̇O2max) 55 ± 9 mL/kg/min] were assigned to 20 g per day of COL (n = 10) or an isoenergetic/isomacronutrient placebo (PLA; n = 10) for 4 weeks. Venous blood and unstimulated saliva samples were obtained before and after 2.5 h of cycling at 15% Δ (∼55-60% V̇O2max). A significantly greater formyl-methionyl-leucyl phenylalanine-stimulated oxidative burst was observed in the COL group compared with PLA group (P < 0.05) and a trend toward a time × group interaction (P = 0.06). However, there was no effect of COL on leukocyte trafficking, phorbol-12-myristate-13-acetate-stimulated oxidative burst, bacterial-stimulated neutrophil degranulation, salivary secretory IgA, lactoferrin or lysozyme (P > 0.05). These findings provide further evidence of the beneficial effects of COL on receptor-mediated stimulation of neutrophil oxidative burst in a model of exercise-induced immune dysfunction. PMID:25727914

  7. Managing Noncommunicable Diseases in an African Community: Effects, Compliance, and Barriers to Participation in a 4-Week Exercise Intervention.

    PubMed

    Onagbiye, Sunday O; Moss, Sarah J; Cameron, Melainie

    2016-04-01

    To determine the compliance, barriers, and effects of participation in a 4-week exercise intervention aimed at reducing risk factors for noncommunicable diseases among community-dwelling adults from a low-resourced area of South Africa. An exercise program and associated pre-posttest were performed by 76 participants (men, n = 26 and women, n = 50) aged 35 to 65 years. Baseline and end tests included height, weight, hip and waist circumference, heart rate, blood pressure, glucose, cholesterol, quality of life, and cardiorespiratory fitness measurements. The intervention consisted of 3 days/week combined aerobic and resistance exercise at an intensity of 70% heart rate reserved as determined at baseline. Compliance and barriers to participation were determined post-intervention by means of attendance registers and interviews. ANCOVA with adjustment for pretest was performed for all repeated variables. The Cronbach's alpha coefficients for exercise benefits were 0.81 and for barriers 0.84. Of the 26 men (40.8 ± 5.45 years) and 50 women (43.6 ± 7.8 years) recruited, 54 completed the intervention (71% compliance). The 4-week aerobic exercise intervention significantly reduced body mass, rate of perceived exertion, and mental components summary in men, and body mass, body mass index, VO2max, rate of perceived exertion, glucose, physical components summary, and mental components summary in women. Participants reported that the exercise milieu as a major barrier to exercise compliance while the interviews reported lack of time. A 1-month exercise intervention elucidated positive changes in risk factors for noncommunicable diseases in a low-resource community. A drop-out rate of 29% in this study is consistent with other exercise intervention trials. Exploration of the reported barriers may be useful for planning to increase compliance with future programs. PMID:27154904

  8. Anxiety and Anger Symptoms in Hwabyung Patients Improved More following 4 Weeks of the Emotional Freedom Technique Program Compared to the Progressive Muscle Relaxation Program: A Randomized Controlled Trial

    PubMed Central

    Suh, Jin Woo; Chung, Sun Yong; Kim, Sang Young; Lee, Jung Hwan; Kim, Jong Woo

    2015-01-01

    Background. The Emotional Freedom Technique (EFT) is a meridian-based psychological therapy. The present clinical trial investigates the effectiveness of EFT as a new treatment option for Hwabyung (HB) patients experiencing anger and compares the efficacy to the Progressive Muscle Relaxation (PMR), the conventional meditation technique. Methods. The EFT and progressive muscle relaxation (PMR) methods were performed on 27 HB patients, and their capacities to alleviate anxiety, anger, and emotional status were compared. After a 4-week program, a survey was conducted; patients then completed a self-training program for 4 weeks, followed by a second survey. Results. During the initial 4 weeks, the EFT group experienced a significant decrease in the HB symptom scale, anger state, and paranoia ideation (p < 0.05). Over the entire 9-week interval, there were significant decreases in the HB symptom scale, anxiety state, anger state, anger trait, somatization, anxiety, hostility, and so on in EFT group (p < 0.05). Conclusion. The EFT group showed improved psychological symptoms and physical symptoms greater than those observed in the PMR group. EFT more effectively alleviated HB symptoms compared to PMR. EFT group showed better maintenance during self-training, suggesting good model of self-control treatment in HB patients. PMID:26539218

  9. Treatment of glycerol phase formed by biodiesel production.

    PubMed

    Hájek, Martin; Skopal, Frantisek

    2010-05-01

    Glycerol is a by-product of biodiesel produced by transesterification and is contained in the glycerol phase together with many other materials such as soaps, remaining catalyst, water, and esters formed during the process. The content of glycerol is approximately 30-60 wt.%. In this paper, treatments of the glycerol phase to obtain glycerol with a purity of 86 wt.% (without distillation) and a mixture of fatty acids with esters (1:1) or only a mixture of fatty acids with a purity of 99 wt.% are presented. The treatment was carried out by removing of alkaline substances and esters. Fatty acids were produced by saponification of the remaining esters and subsequent neutralization of alkaline substances by phosphoric, sulfuric, hydrochloric, or acetic acids. Salts are by-products and, in the case of phosphoric acid can be used as potash-phosphate fertilizer. The process of treatment is easy and environmentally friendly, because no special chemicals or equipment are required and all products are utilizable. PMID:20074939

  10. Antidepressant Efficacy of Adjunctive Aerobic Activity and Associated Biomarkers in Major Depression: A 4-Week, Randomized, Single-Blind, Controlled Clinical Trial

    PubMed Central

    Siqueira, Cristiana Carvalho; Valiengo, Leandro L.; Carvalho, André F.; Santos-Silva, Paulo Roberto; Missio, Giovani; de Sousa, Rafael T.; Di Natale, Georgia; Gattaz, Wagner F.; Moreno, Ricardo Alberto; Machado-Vieira, Rodrigo

    2016-01-01

    Background Major depressive disorder (MDD) is a highly prevalent, heterogeneous and systemic medical condition. Treatment options are limited, and recent studies have suggested that physical exercise can play an important role in the therapeutics of MDD. The aim of this study was to evaluate the antidepressant efficacy of adjunctive aerobic activity in association with pharmacotherapy (selective serotonin reuptake inhibitor) in symptomatic MDD as well as its association with physiological biomarkers. Methods In this randomized, single-blind, add-on, controlled clinical trial, 57 patients (18–55 years of age) were followed-up for 28 days. All patients were drug-free, had been diagnosed with symptomatic MDD and received flexible dose of sertraline during the trial. Patients were randomized to either a 4-week program (4x/week) of add-on aerobic exercise (exercise group, N = 29) or no activity (control group, N = 28). Depression severity was assessed using the Hamilton Rating Scale for Depression (HAM-D) as the primary outcome. At baseline and endpoint, all patients underwent a comprehensive metabolic/cardiopulmonary exercise testing—including determination of maximal oxygen uptake (VO2max), VO2 at the second ventilatory threshold (VO2-VT2), and oxygen pulse (O2 pulse). Results Depression scores significantly decreased in both groups after intervention. Importantly, patients in the aerobic exercise group required lower sertraline dose compared to the control group (sertraline monotherapy). The VO2max and O2 pulse parameters increased over time only in the exercise group and remained unchanged in the control group. Conclusions The present findings suggest that a 4-week training of aerobic exercise significantly improves functional capacity in patients with MDD and may be associated with antidepressant efficacy. This approach may also decrease the need for higher doses of antidepressants to achieve response. Further studies in unmedicated and treatment-resistant MDD

  11. Two-phase surgical treatment of anteromedial knee injuries.

    PubMed

    Felli, Lamberto; Franzi, Paolo; Oliva, Fabio; Pizzella, Luca

    2008-05-01

    The treatment of severe anteromedial knee injuries over the years has undergone various types of approach, changing from proposals, such as combined surgical repair of the anterior cruciate ligament and medial compartment, to the more current protocol which involves conservative treatment of the peripheral injury and later reconstruction of the anterior cruciate ligament. However, in serious ruptures of the medial ligament compartment, conservative treatment does not make it possible to recover peripheral stability, thus transferring abnormal forces onto the anterior cruciate pro-ligament graft which can gradually deteriorate the transplant itself. Thus in severe anteromedial injuries a treatment with two distinct surgical phases is proposed, using direct immediate suture of the peripheral compartment and, after a period of rehabilitation, later replacement of the anterior cruciate ligament by arthroscope graft. Given the obtained results and the few complications observed in 25 cases, it is probable that this therapeutic scheme can be proposed in selected cases of severe ligament laxity of the medial compartment associated with rupture of the anterior cruciate ligament. PMID:18317869

  12. Spatial-Temporal Co-Circulation of Dengue Virus 1, 2, 3, and 4 Associated with Coinfection Cases in a Hyperendemic Area of Brazil: A 4-Week Survey.

    PubMed

    Andrade, Elisa H P; Figueiredo, Leandra B; Vilela, Ana P P; Rosa, Júlio C C; Oliveira, Jaquelline G; Zibaoui, Hassan M; Araújo, Valdelaine E M; Miranda, Daniela P J; Ferreira, Paulo C P; Abrahão, Jonatas S; Kroon, Erna G

    2016-05-01

    Dengue is currently regarded as a major public health problem worldwide. In a hyperendemic region during an outbreak, we detected the co-circulation of all Dengue virus (DENV) serotypes including two different genotypes of DENV-3 and DENV-4, and concurrent infections with up to three serotypes were identified in symptomatic patients. A total of 49 acute phase plasma samples from patients clinically suspected of dengue were collected during the 4 weeks of May 2013. DENV-1-4 was detected by reverse transcriptase semi-nested polymerase chain reaction in 33 samples (67.3%), of which 26 DNA fragments were sequenced. Twenty samples (76.9%) were identified with a single DENV serotype and six (23.1%) with more than one serotype. DENV-3 was the predominant serotype of the outbreak. On the basis of phylogenetic analyses, DENV-1 isolates belong to genotype V, DENV-2 to American-Asian genotype, DENV-3 to genotypes I and III, and DENV-4 to genotypes I and II. PMID:26976882

  13. Thermophilic slurry-phase treatment of petroleum hydrocarbon waste sludges

    SciTech Connect

    Castaldi, F.J.; Bombaugh, K.J.; McFarland, B.

    1995-12-31

    Chemoheterotrophic thermophilic bacteria were used to achieve enhanced hydrocarbon degradation during slurry-phase treatment of oily waste sludges from petroleum refinery operations. Aerobic and anaerobic bacterial cultures were examined under thermophilic conditions to assess the effects of mode of metabolism on the potential for petroleum hydrocarbon degradation. The study determined that both aerobic and anaerobic thermophilic bacteria are capable of growth on petroleum hydrocarbons. Thermophilic methanogenesis is feasible during the degradation of hydrocarbons when a strict anaerobic condition is achieved in a slurry bioreactor. Aerobic thermophilic bacteria achieved the largest apparent reduction in chemical oxygen demand, freon extractable oil, total and volatile solid,s and polycyclic aromatic hydrocarbons (PAHs) when treating oily waste sludges. The observed shift with time in the molecular weight distribution of hydrocarbon material was more pronounced under aerobic metabolic conditions than under strict anaerobic conditions. The changes in the hydrocarbon molecular weight distribution, infrared spectra, and PAH concentrations during slurry-phase treatment indicate that the aerobic thermophilic bioslurry achieved a higher degree of hydrocarbon degradation than the anaerobic thermophilic bioslurry during the same time period.

  14. A 4-Week Home-Based Aerobic and Resistance Exercise Program During Radiation Therapy: A Pilot Randomized Clinical Trial

    PubMed Central

    Mustian, Karen M.; Peppone, Luke; Darling, Tom V.; Palesh, Oxana; Heckler, Charles E.; Morrow, Gary R.

    2011-01-01

    During radiation therapy, cancer patients may report cancer-related fatigue (CRF), which impairs aerobic capacity, strength, muscle mass, and, ultimately, quality of life (QOL). The purpose of this pilot clinical trial was to examine the feasibility and initial efficacy of a home-based aerobic and progressive resistance exercise intervention for aerobic capacity, strength, muscle mass, CRF, and QOL. Daily steps walked (DSW), daily minutes of resistance exercise (MRE), and number of resistance exercise days (RED) were assessed to evaluate intervention adherence. Breast and prostate cancer patients (n = 38) beginning radiation therapy were randomized to undergo 4 weeks of exercise or no exercise. Participants in the exercise group demonstrated good adherence to the exercise intervention, with significantly more DSW, MRE, and RED at post intervention and 3 month follow-up than controls. Participants in the exercise intervention exhibited significantly higher QOL and significantly lower CRF post intervention and at 3-month follow-up than controls. Results of this pilot study provide positive preliminary evidence that exercise during radiation may be beneficial for cancer patients. PMID:19831159

  15. Time-dependency of mice lung recovery after a 4-week exposure to traffic or biomass air pollutants.

    PubMed

    Mazzoli-Rocha, Flavia; Oliveira, Vinícius Rosa; Barcellos, Bárbara Chaves; Moreira, Dayse Kelly Molina; Saldiva, Paulo Hilário Nascimento; Faffe, Débora Souza; Zin, Walter Araújo

    2016-08-01

    The time-dependency of lung recovery after 3 intranasal instillations per week during four weeks of distilled water (C groups) or particles (15μg) from traffic (U groups) or biomass burning (B groups) was observed in BALB/c mice. Lung mechanics [static elastance (Est), viscoelastic component of elastance (ΔE), lung resistive (ΔP1) and viscoelastic/inhomogeneous (ΔP2) pressures] and histology were analyzed 1 (C1, U1, B1), 2 (C2, U2, B2), 7 (C7, U7, B7) or 14 days (C14, U14, B14) after the last instillation. Est, ΔE, ΔP1 and ΔP2 were higher in U1 and B1 than in C1, returning to control values at day 2, except for ΔP1 that normalized after 7 days. Alveolar collapse, bronchoconstriction index and alveolar lesion were larger in U1 and B1 than in C1, however collapse returned to baseline at 7 days, while the others normalized in 2 days. A 4-week exposure to U and B induced lung impairment that resolved 7 days after the last exposure. PMID:27179431

  16. Population Pharmacokinetic Analysis of Raltegravir Pediatric Formulations in HIV-infected Children 4 weeks to 18 years of age†

    PubMed Central

    Rizk, Matthew L.; Du, Lihong; Bennetto-Hood, Chantelle; Wenning, Larissa; Teppler, Hedy; Homony, Brenda; Graham, Bobbie; Fry, Carrie; Nachman, Sharon; Wiznia, Andrew; Worrell, Carol; Smith, Betsy; Acosta, Edward P.

    2015-01-01

    P1066 is an open-label study of raltegravir in HIV+ youth, ages 4 weeks-18 years. Here we summarize P1066 pharmacokinetic (PK) data and a population PK model for the pediatric chewable tablet and oral granules. Raltegravir PK parameters were calculated using non-compartmental analysis. A two-compartment model was developed using data from P1066 and an adult study of the pediatric formulations. Inter-individual variability was described by an exponential error model, and residual variability was captured by an additive/proportional error model. Twelve-hour concentrations (C12hr) were calculated from the model-derived elimination rate constant and 8-hour observed concentration. Simulated steady-state concentrations were analyzed by non-compartmental analysis. Target area-under-the-curve (AUC0-12hr) and C12hr were achieved in each cohort. For the pediatric formulations, geometric mean AUC0-12hr values were 18.0–22.6 μM*hr across cohorts, and C12hr values were 71–130 nM, with lower coefficients of variation vs the film-coated tablet. A two-compartment model with first-order absorption adequately described raltegravir plasma PK in pediatric and adult patients. Weight was a covariate on clearance and central volume, and incorporated using allometric scaling. Raltegravir chewable tablets and oral granules exhibited PK parameters consistent with those from prior adult studies and older children in P1066, as well as lower variability than the film-coated tablet. PMID:25753401

  17. The effects of 4 weeks of jump training on landing knee valgus and crossover hop performance in female basketball players.

    PubMed

    Herrington, Lee

    2010-12-01

    Female basketball players would appear particularly prone to knee injuries. These injuries have been associated with the nature of the sport, but more specifically with the particular movement strategies adopted. A valgus or abducted position of the knee on landing has been reported to be associated with a number of different knee injuries. Jump-training programs have been reported to improve both landing knee valgus and functional performance. The majority of the jump-training programs have been of 6 weeks' duration, 3 sessions per week often lasting up to 1 hour. For most sports coaches, team conditioners, and athletes, this duration and program length is not acceptable. The aim of this study was to assess if an abridged jump-training program could have similar effects to those previously reported. Fifteen female basketball players had their knee valgus angles assessed during 2 landing tasks, drop jump landing, and when undertaking a jump shot and along with crossover hop distance before and after a progressive jump-training program. The jump-training program lasted 4 weeks, 3 times per week, each session lasting 15 minutes. After training, crossover hop distance showed an average percentage improvement on distance jumped of 73.6% (p = 0.001); the drop jump knee valgus angle in the left leg on average was reduced by 9.8° (p = 0.002), right leg reduced by 12.3° (p = 0.0001); during the jump shot, the knee valgus angle in the left leg showed a mean reduction of 4.5° (p = 0.035), and the right leg was reduced by 4.3° (p = 0.01). The study undertaken achieved comparable results to those previously reported with an abridged program over considerably shortened session duration and training period. PMID:20664369

  18. Aluminium surface treatment with ceramic phases using diode laser

    NASA Astrophysics Data System (ADS)

    Labisz, K.; Tański, T.; Brytan, Z.; Pakieła, W.; Wiśniowski, M.

    2016-07-01

    Ceramic particles powder feeding into surface layer of engineering metal alloy is a well-known and widely used technique. New approach into the topic is to obtain finely distributed nano-sized particles involved in the aluminium matrix using the traditional laser technology. In this paper are presented results of microstructure investigation of cast aluminium-silicon-copper alloys surface layer after heat treatment and alloying with ceramic carbides of WC and ZrO2 using high-power diode laser. The surface layer was specially prepared for the reason of reducing the reflectivity, which is the main problem in the up-to-date metal matrix composites production. With scanning electron microscopy, it was possible to determine the deformation process and distribution of WC and ZrO2 ceramic powder phase. Structure of the surface after laser treatment changes, revealing three zones—remelting zone, heat-affected zone and transition zone placed over the Al substrate. The structural changes of ceramic powder, its distribution and morphology as well as microstructure of the matrix material influence on functional properties, especially wear resistance and hardness of the achieved layer, were investigated.

  19. Variations in urine excretion of steroid hormones after an acute session and after a 4-week programme of strength training.

    PubMed

    Timón Andrada, Rafael; Maynar Mariño, M; Muñoz Marín, D; Olcina Camacho, G J; Caballero, M J; Maynar Mariño, J I

    2007-01-01

    Performing strength exercise, whether acutely or in a training programme, leads to alterations at the hypothalamic-pituitary-testicular and hypothalamic-pituitary-adrenal axes. One way to evaluate these changes is by analysis of the excretion of steroid hormones in the urine. The present study determined the variations in the urine profile of glucuroconjugated steroids after a single session of strength exercise and after a 4-week programme of strength training. The subjects were a group (n = 20) of non-sportsman male university students who worked out 3 days a week [Monday (M), Wednesday (W) and Friday (F)], performing the exercises at 70-75% of one repetition maximum strength (1-RM). Four urine samples were collected per subject: (A) before and (B) after a standard session prior to initiating the training programme, and (C) before and (D) after the same standard session at the end of the study, and they were assayed by gas chromatography coupled to mass spectrometry. The concentrations of the different hormones were determined relatively to the urine creatinine level (ng steroid/mg creatinine) to correct for diuresis. After the exercise sessions, both before and after the training programme, there was a fall in the urine excretion of androgens and estrogens, but no statistically significant changes in the excretion of tetrahydrocortisol (THF) and tetrahydrocortisone (THE). The anabolic/catabolic hormones ratio also decreased after the acute session, although only androstenodione + dehydroepiandrosterone (DHEA)/THE + THF ratio had a significant decrease (P < 0.05). After the training programme, there was a significant (P < 0.01) improvement in the strength of the muscle groups studied, and an increased urinary excretion of all the androgens with respect to the initial state of repose, with the difference being significant in the case of epitestosterone (Epit) (P < 0.05). The androsterone (A) + etiocholanolone (E)/THE + THF ratio increased significantly (P < 0

  20. Healing defective CVD-graphene through vapor phase treatment

    NASA Astrophysics Data System (ADS)

    van Lam, Do; Kim, Sang-Min; Cho, Youngji; Kim, Jae-Hyun; Lee, Hak-Joo; Yang, Jun-Mo; Lee, Seung-Mo

    2014-05-01

    Structural defects present on chemical vapor deposition (CVD)-graphene have usually originated from the growth stage and transfer process. They limit the electronic transport properties of graphene and degrade performance of related devices. Here we report that these inherent atomic defects could be selectively healed by a simple vapor phase treatment performed in equipment conventionally used for atomic layer deposition (ALD). The unique chemistry of Al2O3 ALD facilitated selective depositions of AlxOy compounds on the defects, which could be readily probed and visualized using AFM imaging. The healing agent, AlxOy, was observed to bind tightly to the defects and lead to doping of the CVD-graphene, which was reflected in the noticeable improvement in electrical sheet resistance. In contrast with the chemically doped graphene, the ALD-treated graphenes revealed notable long-term stability under environmental conditions. Our approach promises selective healing of defects present in most materials and possibly ensures considerable improvement in electrical and mechanical properties. ALD with a broad spectrum of material selection could be a versatile tool for upgrading properties of materials.Structural defects present on chemical vapor deposition (CVD)-graphene have usually originated from the growth stage and transfer process. They limit the electronic transport properties of graphene and degrade performance of related devices. Here we report that these inherent atomic defects could be selectively healed by a simple vapor phase treatment performed in equipment conventionally used for atomic layer deposition (ALD). The unique chemistry of Al2O3 ALD facilitated selective depositions of AlxOy compounds on the defects, which could be readily probed and visualized using AFM imaging. The healing agent, AlxOy, was observed to bind tightly to the defects and lead to doping of the CVD-graphene, which was reflected in the noticeable improvement in electrical sheet resistance

  1. Functioning of family system in pediatric oncology during treatment phase.

    PubMed

    Perricone, Giovanna; Polizzi, Concetta; Morales, Maria Regina; Marino, Santo; Scacco, Cinzia Favara

    2012-10-01

    The study focuses on parents' psychological implications caused by the treatment of their children suffering from tumor. It investigates some specific mothers' resource factors such as their strategies of coping and the perception of their own family functioning in terms of cohesion and adaptability. The study was performed with 34 mothers of children suffering from acute lymphoblastic leukemia (ALL), during the treatment phase. The used tools were the Coping Orientation to Problem Experienced--New Italian Version, to investigate coping strategies, and the Family Adaptability and Cohesion Evaluation Scale-III, to analyze both real and ideal perception of family functioning. The data related to coping, show how the involved mothers tend to mainly use the strategies of positive aptitude, orientation toward problem and social support (F = 99.88, df = 4, P < .01). The family functioning, in terms of adaptability, is described as chaotic relating to both the real (χ(2) = 13.29, df = 3, P = .004) and ideal (χ(2) = 11.52, df = 2, P = .003) family, whereas in terms of cohesion, it is perceived as chiefly disengaged in the real family (χ(2) = 12.3, df = 3, P = .006) and as enmeshed in the ideal one (χ(2) = 12.58, df = 3, P = .006). Statistically positive correlations were only detected between adaptability and avoidance (r = 0.49, P < .01); adaptability and orientation toward problem (r = 0.36, P < .05); and adaptability and transcendent orientation (r = -0.04, P < .05). Despite the critical situation, the mothers have shown optimistic view, care for problem management and capability to ask for help. These coping strategies allow the therapeutic alliance between families and health care workers, so useful for the quality of childcare. PMID:22732085

  2. Caffeine treatment prevents rapid eye movement sleep deprivation-induced impairment of late-phase long-term potentiation in the dentate gyrus.

    PubMed

    Alhaider, Ibrahim A; Alkadhi, Karim A

    2015-11-01

    The CA1 and dentate gyrus (DG) are physically and functionally closely related areas of the hippocampus, but they differ in various respects, including their reactions to different insults. The purpose of this study was to determine the protective effects of chronic caffeine treatment on late-phase long-term potentiation (L-LTP) and its signalling cascade in the DG area of the hippocampus of rapid eye movement sleep-deprived rats. Rats were chronically treated with caffeine (300 mg/L drinking water) for 4 weeks, after which they were sleep-deprived for 24 h. L-LTP was induced in in anaesthetized rats, and extracellular field potentials from the DG area were recorded in vivo. The levels of L-LTP-related signalling proteins were assessed by western blot analysis. Sleep deprivation markedly reduced L-LTP magnitude, and basal levels of total cAMP response element-binding protein (CREB), phosphorylated CREB (P-CREB), and calcium/calmodulin kinase IV (CaMKIV). Chronic caffeine treatment prevented the reductions in the basal levels of P-CREB, total CREB and CaMKIV in sleep-deprived rats. Furthermore, caffeine prevented post-L-LTP sleep deprivation-induced downregulation of P-CREB and brain-derived neurotrophic factor in the DG. The current findings show that caffeine treatment prevents acute sleep deprivation-induced deficits in brain function. PMID:26449851

  3. An Online Documentary Film to Motivate Quit Attempts Among Smokers in the General Population (4Weeks2Freedom): A Randomized Controlled Trial

    PubMed Central

    Michie, Susan; Walmsley, Matthew; West, Robert

    2016-01-01

    Introduction: Online motivational films to promote quit attempts could encourage large numbers of smokers to stop at low unit cost. We evaluated an online film documenting the experiences of smokers who recorded the first month of their successful attempts to quit (4Weeks2Freedom). The film was designed to boost motivation and self-efficacy and provide role-models to promote ex-smoker identities. Methods: This was a randomized trial with individual assignment to a no-intervention control (n = 1016), an informational film (n = 1004), or 4Weeks2Freedom (n = 999). The development of 4Weeks2Freedom was informed by PRIME theory and focus-group testing with smokers. The 90-minute film was available online to view in one sitting or as chapters over 4 weeks to coincide with the progress of an attempt. The primary outcome was a quit attempt in the 4 weeks between assignment and study endpoint by intent-to-treat. Results: Participants smoked a mean of 13 cigarettes per day and 31% reported not wanting to stop. At follow-up, 55% reported viewing the informational control film and 56% viewing 4Weeks2Freedom. There was no detectable effect compared with the no-intervention control (OR = 0.99, 95% CI = 0.81 to 1.21, 24.3% vs. 24.5%) or informational control film (OR = 0.99, 95% CI = 0.80 to 1.21, 24.3% vs. 24.6%). Calculation of Bayes factors ruled out insensitive data and indicated the intervention was no more effective than either the no-intervention control (Bayes factor = 0.20) or informational control film (Bayes factor = 0.27). The pattern of results was unchanged in sensitivity analyses that examined the effect among only those who viewed the films. Conclusion: The online documentary film (4Weeks2Freedom) designed to boost motivation and self-efficacy and to promote ex-smoker identity does not appear to prompt quit attempts among smokers. Implications: This trial found that an online documentary film (4Weeks2Freedom) designed to boost motivation and self-efficacy and to

  4. Healing defective CVD-graphene through vapor phase treatment.

    PubMed

    Van Lam, Do; Kim, Sang-Min; Cho, Youngji; Kim, Jae-Hyun; Lee, Hak-Joo; Yang, Jun-Mo; Lee, Seung-Mo

    2014-06-01

    Structural defects present on chemical vapor deposition (CVD)-graphene have usually originated from the growth stage and transfer process. They limit the electronic transport properties of graphene and degrade performance of related devices. Here we report that these inherent atomic defects could be selectively healed by a simple vapor phase treatment performed in equipment conventionally used for atomic layer deposition (ALD). The unique chemistry of Al2O3 ALD facilitated selective depositions of AlxOy compounds on the defects, which could be readily probed and visualized using AFM imaging. The healing agent, AlxOy, was observed to bind tightly to the defects and lead to doping of the CVD-graphene, which was reflected in the noticeable improvement in electrical sheet resistance. In contrast with the chemically doped graphene, the ALD-treated graphenes revealed notable long-term stability under environmental conditions. Our approach promises selective healing of defects present in most materials and possibly ensures considerable improvement in electrical and mechanical properties. ALD with a broad spectrum of material selection could be a versatile tool for upgrading properties of materials. PMID:24756318

  5. Phase I Design for Completely or Partially Ordered Treatment Schedules

    PubMed Central

    Wages, Nolan A.; O’Quigley, John; Conaway, Mark R.

    2013-01-01

    The majority of methods for the design of Phase I trials in oncology are based upon a single course of therapy, yet in actual practice it may be the case that there is more than one treatment schedule for any given dose. Therefore, the probability of observing a dose-limiting toxicity (DLT) may depend upon both the total amount of the dose given, as well as the frequency with which it is administered. The objective of the study then becomes to find an acceptable combination of both dose and schedule. Past literature on designing these trials has entailed the assumption that toxicity increases monotonically with both dose and schedule. In this article, we relax this assumption for schedules and present a dose-schedule finding design that can be generalized to situations in which we know the ordering between all schedules and those in which we do not. We present simulation results that compare our method to other suggested dose-schedule finding methodology. PMID:24114957

  6. AUTOMATED MONITORING OF WASTEWATER TREATMENT EFFICIENCY - PHASE I

    EPA Science Inventory

    Wastewater treatments minimize the transmission of pathogens and are required by EPA with established treatment and monitoring requirements. The efficiency of treatment processes is determined by measuring the inactivation of indicator organisms (e.g., fecal coliform...

  7. A phase I multicenter study of antroquinonol in patients with metastatic non-small-cell lung cancer who have received at least two prior systemic treatment regimens, including one platinum-based chemotherapy regimen

    PubMed Central

    LEE, YU-CHIN; HO, CHING-LIANG; KAO, WOEI-YAU; CHEN, YUH-MIN

    2015-01-01

    Antroquinonol is isolated from Antrodia camphorata, a camphor tree mushroom, and is a valuable traditional Chinese herbal medicine that exhibits pharmacological activities against several diseases, including cancer. This first-in-human phase I study of antroquinonol included patients with metastatic non-small-cell lung cancer who had received at least two prior systemic treatment regimens. An open-label, dose escalation, pharmacokinetic (PK) study was conducted to determine the maximum tolerable dose (MTD), dose-limiting toxicities (DLTs), and safety/tolerability and preliminary efficacy profiles of antroquinonol. The patients received escalating doses of once-daily antroquinonol in 4-week cycles (up to 3 cycles). The escalated doses were 50–600 mg. PKs were evaluated on day 1 and 28 of cycle 1. Between January, 2011 and October, 2012, 13 patients with metastatic adenocarcinoma were enrolled. No DLTs occurred in any patient at any dose level. Tmax was observed between 1.00 and 3.70 h under single-dose conditions, and at 1.92–4.05 h under multiple-dose conditions. The mean elimination half-life ranged between 1.30 and 4.33 h, independent of the treatment dose. Antroquinonol at all dose levels had a mild toxicity profile, with no reported treatment-related mortality. The most common treatment-related adverse events were diarrhea, vomiting and nausea. The best tumor response was stable disease in 3 patients. In conclusion, antroquinonol at all dose levels, administered daily for 4 weeks, was generally safe and well tolerated, without DLTs. The recommended dose level for a phase II study is ≥600 mg daily. PMID:26807250

  8. Initial Outcomes From a 4-Week Follow-Up Study of the Text4baby Program in the Military Women’s Population: Randomized Controlled Trial

    PubMed Central

    Wallace Bihm, Jasmine; Szekely, Daniel; Nielsen, Peter; Murray, Elizabeth; Abroms, Lorien; Snider, Jeremy

    2014-01-01

    Background The use of mobile phone technologies for health promotion and disease prevention has advanced rapidly in recent years. Text4baby is a theory-based mobile health (mHealth) program in which text messages are delivered to pregnant women and new mothers to improve their health care beliefs and behaviors and improve health status and clinical outcomes. Recent evaluations of Text4baby have found that it improves targeted health attitudes and beliefs, but effects on behavior have not yet been determined. Objective In this study, investigators aimed to evaluate Text4baby in the military women’s population. Methods Investigators conducted a randomized controlled trial at Madigan Army Medical Center in Tacoma, Washington, from December 2011 through September 2013. All participants were pregnant women first presenting for care at Madigan. Investigators conducted a baseline assessment using a 24-item, self-administered online survey of attitudes and behaviors related to Text4baby message content. Participants were randomized to Text4baby plus usual care (intervention) or usual care alone (control). Investigators analyzed treatment effects of Text4baby on short-term targeted outcomes 4 weeks post enrollment. Results For this study, 943 patients were randomized and completed a baseline assessment. The average patient age was 28 years and nearly 70% self-identified as Caucasian. 48.7% of enrollees (459/943) completed the first follow-up assessment. Higher rates of single and working/in-school patients dropped out of the intervention arm of the study, and we adjusted for this finding in subsequent models. However, while investigators were unable to re-survey these participants, only 1.9% of Text4baby enrollees (18/943) dropped the service during the study period. Adjusted and unadjusted logistic generalized estimating equation models were developed to assess intervention effects on measured outcomes. In the model adjusting for age, marital status, having had a

  9. Effect of a 4-week Nordic walking training on the physical fitness and self-assessment of the quality of health of women of the perimenopausal age

    PubMed Central

    Saulicz, Mariola; Saulicz, Edward; Myśliwiec, Andrzej; Wolny, Tomasz; Knapik, Andrzej; Rottermund, Jerzy

    2015-01-01

    Aim of the study To determine the effect of a 4-week Nordic walking training on the physical fitness of women of the perimenopausal age and self-assessment of the quality of their health. Material and methods Eighty-four women between 48 and 58 years of age were included in the study. Half of the group (42) was assigned to the control group and the other half was assigned to the experimental group. In both groups studied, physical fitness was evaluated using a modified Fullerton's test and a quality of life self-assessment SF-36 (Short Form of Health Status Questionnaire). Similar tests were repeated 4 weeks later. In the experimental group, a Nordic walking training was conducted between the two tests. During 4 weeks, 10 training sessions were performed, each session was 60 minutes long, and there was an interval of 2 days between the sessions. Results A 4-week Nordic walking training resulted in a significant improvement (p < 0.001) of physical fitness as demonstrated by an increased strength and flexibility of the upper and lower part of the body and the ability to walk a longer distance during a 6-minute walking test. Women participating in the training also showed a significant improvement in health in terms of both physical health (p < 0.001) and mental health (p < 0.001). Conclusions A 4-week Nordic walking training has a positive effect on the physical fitness of the women in the perimenopausal age. Participation in training contributes also to a clearly higher self-assessment of the quality of health. PMID:26327897

  10. A double-blind, randomized, and active-controlled phase III study of Herbiron drink in the treatment of iron-deficiency anemia in premenopausal females in Taiwan

    PubMed Central

    Lee, Ching-Tzu; Jeng, Cherng-Jye; Yeh, Lian-Shung; Yen, Ming-Shyen; Chen, Shih-Ming; Lee, Chyi-Long; Lin, Willie; Hsu, Chun-Sen

    2016-01-01

    Background About 468 million non-pregnant women are estimated to suffer from iron-deficiency anemia (IDA) worldwide. The highest prevalence of IDA occurs in the Taiwanese population. Objective To evaluate the effectiveness of Herbiron to increase iron absorption in women with IDA. Design Phase III double-blind, randomized, active-controlled, and parallel comparative study enrolled 124 patients with IDA and consisted of a 2-week run-in period, randomization, 12 weeks of supplementation, and 4 weeks of follow-up. The treatment group received Herbiron drink 50 mL p.o., b.i.d., before meals (daily iron intake: 21 mg/day) plus placebo tablets. The control group received a ferrous sulfate tablet, t.i.d., plus placebo 50-mL drink before meals (daily iron intake: 195 mg/day). Results Both treatments significantly improved hemoglobin and all secondary efficacy endpoints. Most IDA patients treated with Herbiron or ferrous sulfate finished the study in the normal range. Ferrous sulfate treatment induced a rapid rate of hemoglobin synthesis, which plateaued by week 8, whereas Herbiron treatment increased the rate of hemoglobin synthesis more slowly, likely due to its nine-fold lower iron content. Gastrointestinal adverse events (diarrhea, abdominal pain, dyspepsia, and nausea) but not infectious adverse events were significantly more common in the ferrous sulfate group (n=11, 18.3%) than those in the Herbiron group (n=1, 1.6%) (p=0.004). Conclusion Twelve weeks of Herbiron treatment delivering 21mg of iron or ferrous sulfate treatment delivering 195 mg of iron induced normal hemoglobin levels in 62 or 91% of non-pregnant women with IDA in Taiwan, respectively, suggesting dose-dependent and bioavailability effects. PMID:27343206

  11. Comparative assessment of the effectiveness and tolerability of lornoxicam 8 mg BID and diclofenac 50 mg TID in adult indian patients with osteoarthritis of the hip or knee: A 4-week, double-blind, randomized, comparative, multicenter study

    PubMed Central

    Goregaonkar, Arvind; Mathiazhagan, K.J.; Shah, Ravindra R.; Kapoor, Paramjeet Singh; Taneja, Praveen; Sharma, Akhilesh; Bolmall, Chandrashekhar; Baliga, Vidyagauri P.

    2009-01-01

    Background: Reports of cardiovascular adverse events (AEs) associated with the use of cyclooxygenase-2 inhibitors for the treatment of osteoarthritis (OA) have prompted the quest for a better-tolerated NSAID. Objective: The aim of this study was to compare the effectiveness and tolerability of lornoxicam 8 mg BID and diclofenac 50 mg TID in adult Indian patients with OA of the hip or knee. Methods: This 4-week, double-blind, randomized, comparative, multicenter study was undertaken to compare oral lornoxicam and diclofenac in patients with OA. Patients who met the selection criteria were enrolled consecutively from the outpatient clinics of each of the participating hospitals in India. Participants completed the Western Ontario and McMasters Individual Osteoarthritis Index (WOMAC-OA), WOMAC Composite Index (WOMAC-CI) (for pain, stiffness, and physical function), and a 10-cm visual analog scale (VAS) (0–10 where 0 = no pain and 10 = worst possible pain or severe or excruciating pain) at each study visit (weeks 0 [baseline], 2, and 4 [or at early termination]). Patients' and physicians' global assessments of arthritis control were measured at each study visit when laboratory and clinical AEs were also monitored. The primary end points were the WOMAC-OA, the WOMAC-CI, and VAS scores for pain among the patients who completed the study. Results: Of the 273 patients (159 men, 114 women; mean [SD] age, 44.73 [10.72] years; range, 28–68 years) enrolled in the study, 13 (7 in the lornoxicam group and 6 in the diclofenac group) were lost to follow-up and their effectiveness and tolerability results were not included in the study analysis. Over the 4-week study period, both drugs provided significant (P < 0.05) sustained relief of OA symptoms compared with baseline. Compared with baseline, the mean pain score (WOMAC-CI) decreased 90.6% (13.88 [4.47] vs 1.30 [1.49]; P < 0.05) in the lornoxicam group and 88.9% (14.15 [4.56] vs 1.57 [1.49]; P < 0.05) in the diclofenac group

  12. Decontamination and inspection plan for phase 2 closure of the 300-Area waste acid treatment system

    SciTech Connect

    Hays, C.B.

    1998-02-06

    This decontamination and inspection plan (DIP) describes decontamination and verification activities in support of Phase 2 closure of the 300 Area Waste Acid Treatment System (WATS). Phase 2, the second phase of three proposed phases of closure for WATS, provides for closure of all WATS portions of the 334-A Building and some, but not all, WATS portions of the 333 and 303-F Buildings. Closure of the entire unit will not occur until all three closure phases have been completed. The DIP also describes the designation and management-process for waste and debris generated during Phase 2 closure activities. Information regarding the decontamination and verification methods for Phase 1 closure can be found in Decontamination and Inspection Plan, for Phase 1 closure of the 300 Area Waste Acid Treatment System, 21 WHC-SD-ENV-AP-001. Information regarding Phase 3 closure will be provided in later documents.

  13. A randomized phase 2a efficacy and safety trial of the topical Janus kinase inhibitor tofacitinib in the treatment of chronic plaque psoriasis

    PubMed Central

    Ports, WC; Khan, S; Lan, S; Lamba, M; Bolduc, C; Bissonnette, R; Papp, K

    2013-01-01

    Background Tofacitinib (CP-690,550) is a novel Janus kinase inhibitor in development as an oral formulation for the treatment of several inflammatory diseases including psoriasis. Objectives This phase 2a study aimed to assess the efficacy, systemic safety, local tolerability and systemic pharmacokinetics of topical tofacitinib in mild-to-moderate plaque psoriasis. Methods Two tofacitinib ointment formulations were evaluated in this multicentre, double-blind, vehicle-controlled trial (NCT01246583). Seventy-one patients were randomized 2 : 1 : 2 : 1 to 2% tofacitinib ointment 1, vehicle 1, 2% tofacitinib ointment 2 and vehicle 2, each administered twice daily for 4 weeks to a single fixed 300 cm2 treatment area containing a target plaque with or without one or more nontarget plaques and normal skin. Results The primary endpoint of percentage change from baseline in the Target Plaque Severity Score at week 4 demonstrated statistically significant improvement for ointment 1 [least squares mean (LSM) –54·4%] vs. vehicle 1 (LSM –41·5%), but not ointment 2 (LSM –24·2%) vs. vehicle 2 (LSM –17·2%). Secondary endpoints (target plaque area and Itch Severity Item) improved similarly for tofacitinib ointment vs. corresponding vehicle. Adverse event (AE) occurrence was similar across treatment groups. All AEs were mild or moderate and none were serious or led to subject discontinuation. One application-site AE (erythema) was reported. Tofacitinib mean systemic exposure was minimal and was greater for ointment 1 than for ointment 2. Conclusions Tofacitinib ointment 1 was well tolerated and efficacious compared with vehicle for the treatment of plaque psoriasis. Further study of topical tofacitinib for psoriasis treatment is warranted. PMID:23387374

  14. Cocoa extract intake for 4 weeks reduces postprandial systolic blood pressure response of obese subjects, even after following an energy-restricted diet

    PubMed Central

    Ibero-Baraibar, Idoia; Suárez, Manuel; Arola-Arnal, Anna; Zulet, M. Angeles; Martinez, J. Alfredo

    2016-01-01

    Background Cardiometabolic profile is usually altered in obesity. Interestingly, the consumption of flavanol-rich foods might be protective against those metabolic alterations. Objective To evaluate the postprandial cardiometabolic effects after the acute consumption of cocoa extract before and after 4 weeks of its daily intake. Furthermore, the bioavailability of cocoa extract was investigated. Design Twenty-four overweight/obese middle-aged subjects participated in a 4-week intervention study. Half of the volunteers consumed a test meal enriched with 1.4 g of cocoa extract (415 mg flavanols), while the rest of the volunteers consumed the same meal without the cocoa extract (control group). Glucose and lipid profile, as well as blood pressure and cocoa metabolites in plasma, were assessed before and at 60, 120, and 180 min post-consumption, at the beginning of the study (Postprandial 1) and after following a 4-week 15% energy-restricted diet including meals containing or not containing the cocoa extract (Postprandial 2). Results In the Postprandial 1 test, the area under the curve (AUC) of systolic blood pressure (SBP) was significantly higher in the cocoa group compared with the control group (p=0.007), showing significant differences after 120 min of intake. However, no differences between groups were observed at Postprandial 2. Interestingly, the reduction of postprandial AUC of SBP (AUC_Postprandial 2-AUC_Postprandial 1) was higher in the cocoa group (p=0.016). Furthermore, cocoa-derived metabolites were detected in plasma of the cocoa group, while the absence or significantly lower amounts of metabolites were found in the control group. Conclusions The daily consumption of cocoa extract within an energy-restricted diet for 4 weeks resulted in a greater reduction of postprandial AUC of SBP compared with the effect of energy-restricted diet alone and independently of body weight loss. These results suggest the role of cocoa flavanols on postprandial blood

  15. Functional Improvement After 4-Week Rehabilitation Therapy and Effects of Attention Deficit in Brain Tumor Patients: Comparison With Subacute Stroke Patients

    PubMed Central

    Han, Eun Young; Kim, Bo Ryun; Kim, Ha Jeong

    2015-01-01

    Objective To confirm functional improvement in brain tumor patients after 4-week conventional rehabilitation therapy, to compare the cognitive impairment of brain tumor patients with subacute stroke patients using computerized neuropsychological testing, and to determine the effects on functional outcomes of daily activity. Methods From April 2008 to December 2012, 55 patients (29 brain tumor patients and 26 subacute stroke patients) were enrolled. All patients were assessed with a computerized neuropsychological test at baseline. Motricity Index, Korean version of Mini Mental Status Examination, and Korean version of Modified Barthel Index scores were assessed at the beginning and end of 4-week rehabilitation. Conventional rehabilitation therapy was applied to both groups for 4 weeks. Results Functional outcomes of all patients in both groups significantly improved after 4-week rehabilitation therapy. In brain tumor patients, the initial Motricity Index, cognitive dysfunction, and visual continuous performance test correction numbers were strong predictors of initial daily activity function (R2=0.778, p<0.01). The final Motricity Index and word-black test were strong predictors of final daily activity function (R2=0.630, p<0.01). In patients with subacute stroke, the initial Motricity index was an independent predictor of initial daily activity function (R2=0.245, p=0.007). The initial daily activity function and color of color word test were strong predictors of final daily activity function (R2=0.745, p<0.01). Conclusion Conventional rehabilitation therapy induced functional improvement in brain tumor patients. Objective evaluation of cognitive function and comprehensive rehabilitation including focused cognitive training should be performed in brain tumor patients for improving their daily activity function. PMID:26361592

  16. Effects of 4 Weeks of Explosive-type Strength Training for the Plantar Flexors on the Rate of Torque Development and Postural Stability in Elderly Individuals.

    PubMed

    Kobayashi, Y; Ueyasu, Y; Yamashita, Y; Akagi, R

    2016-06-01

    This study aimed to investigate the effect of a 4-week explosive-type strength training program for the plantar flexors on the rate of torque development and postural stability. The participants were 56 elderly men and women divided into training (17 men and 15 women) and control (14 men and 10 women) groups. The participants in the training group underwent explosive-type strength training of the plantar flexors 2 days per week for 4 weeks. Training consisted of 3 sets of 10 repetitions of explosive plantar flexion lasting less than 1 s. The following parameters were determined: muscle volume of the plantar flexors estimated by the muscle thickness and lower leg length, maximal voluntary contraction torque and rate of torque development of plantar flexion, and one-leg standing ability. The training increased the maximal voluntary contraction torque and rate of torque development, but corresponding increases in muscle volume and one-leg standing ability were not found. These results suggest that, for elderly individuals, the 4-week explosive-type strength training of the plantar flexors is effective for increasing the maximal voluntary contraction torque and rate of torque development of plantar flexion but is not effective for improving postural stability. PMID:26990722

  17. No Evidence of Pritelivir Resistance Among Herpes Simplex Virus Type 2 Isolates After 4 Weeks of Daily Therapy

    PubMed Central

    Edlefsen, Paul T.; Birkmann, Alexander; Huang, Meei-Li; Magaret, Craig A.; Kee, Jia Jin; Diem, Kurt; Goldner, Thomas; Timmler, Burkhard; Stoelben, Susanne; Ruebsamen-Schaeff, Helga; Zimmermann, Holger; Warren, Terri; Wald, Anna; Corey, Lawrence

    2016-01-01

    Background. Pritelivir is a novel helicase-primase inhibitor in clinical development for treatment of herpes simplex virus type 2 (HSV-2) infections. In preclinical work, resistance-mediating mutations were identified in the HSV-2 genome at 3 loci in the UL5 gene and 1 locus in UL52. Methods. To evaluate whether daily pritelivir treatment results in emergence of resistance-mediating mutations, we analyzed HSV-2 strains detected in genital swab specimens from trial participants who were randomly assigned to receive different dosages of pritelivir. We sequenced resistance regions from 87 participants' samples, the UL5 gene in 73 samples from 44 participants, and the UL52 gene in 71 samples from 43 participants. Results. We found no evidence that pritelivir induced known resistance-mediating mutations or for amino acid variation at other loci. In one participant's HSV-2 isolate, we found a previously unidentified mutation close to the putative resistance-mediating region in UL5 and subsequently determined in vitro susceptibility to pritelivir. We characterized mutations from 32 cultivated HSV-2 isolates previously found to be susceptible to pritelivir in vitro and identified several novel mutations that most likely reflect preexisting variation in circulating HSV-2. Conclusions. This study demonstrates evidence of retained susceptibility of HSV-2 to pritelivir in immunocompetent persons following daily therapy for up to 28 days. PMID:27056950

  18. One-, two- and three-phase viscosity treatments for basaltic lava flows.

    PubMed

    Harris, Andrew J L; Allen, John S

    2008-01-01

    Lava flows comprise three-phase mixtures of melt, crystals, and bubbles. While existing one-phase treatments allow melt phase viscosity to be assessed on the basis of composition, water content, and/or temperature, two-phase treatments constrain the effects of crystallinity or vesicularity on mixture viscosity. However, three-phase treatments, allowing for the effects of coexisting crystallinity and vesicularity, are not well understood. We investigate existing one- and two-phase treatments using lava flow case studies from Mauna Loa (Hawaii) and Mount Etna (Italy) and compare these with a three-phase treatment that has not been applied previously to basaltic mixtures. At Etna, melt viscosities of 425 ± 30 Pa s are expected for well-degassed (0.1 w. % H(2)O), and 135 ± 10 Pa s for less well-degassed (0.4 wt % H(2)O), melt at 1080°C. Application of a three-phase model yields mixture viscosities (45% crystals, 25-35% vesicles) in the range 5600-12,500 Pa s. This compares with a measured value for Etnean lava of 9400 ± 1500 Pa s. At Mauna Loa, the three-phase treatment provides a fit with the full range of field measured viscosities, giving three-phase mixture viscosities, upon eruption, of 110-140 Pa s (5% crystals, no bubble effect due to sheared vesicles) to 850-1400 Pa s (25-30% crystals, 40-60% spherical vesicles). The ability of the three-phase treatment to characterize the full range of melt-crystal-bubble mixture viscosities in both settings indicates the potential of this method in characterizing basaltic lava mixture viscosity. PMID:21691456

  19. Collaborative study on fifteen compounds in the rat-liver Comet assay integrated into 2- and 4-week repeat-dose studies.

    PubMed

    Rothfuss, Andreas; O'Donovan, Mike; De Boeck, Marlies; Brault, Dominique; Czich, Andreas; Custer, Laura; Hamada, Shuichi; Plappert-Helbig, Ulla; Hayashi, Makoto; Howe, Jonathan; Kraynak, Andrew R; van der Leede, Bas-jan; Nakajima, Madoka; Priestley, Catherine; Thybaud, Veronique; Saigo, Kazuhiko; Sawant, Satin; Shi, Jing; Storer, Richard; Struwe, Melanie; Vock, Esther; Galloway, Sheila

    2010-09-30

    A collaborative trial was conducted to evaluate the possibility of integrating the rat-liver Comet assay into repeat-dose toxicity studies. Fourteen laboratories from Europe, Japan and the USA tested fifteen chemicals. Two chemicals had been previously shown to induce micronuclei in an acute protocol, but were found negative in a 4-week Micronucleus (MN) Assay (benzo[a]pyrene and 1,2-dimethylhydrazine; Hamada et al., 2001); four genotoxic rat-liver carcinogens that were negative in the MN assay in bone marrow or blood (2,6-dinitrotoluene, dimethylnitrosamine, 1,2-dibromomethane, and 2-amino-3-methylimidazo[4,5-f]quinoline); three compounds used in the ongoing JaCVAM (Japanese Center for the Validation of Alternative Methods) validation study of the acute liver Comet assay (2,4-diaminotoluene, 2,6-diaminotoluene and acrylamide); three pharmaceutical-like compounds (chlordiazepoxide, pyrimethamine and gemifloxacin), and three non-genotoxic rodent liver carcinogens (methapyrilene, clofibrate and phenobarbital). Male rats received oral administrations of the test compounds, daily for two or four weeks. The top dose was meant to be the highest dose producing clinical signs or histopathological effects without causing mortality, i.e. the 28-day maximum tolerated dose. The liver Comet assay was performed according to published recommendations and following the protocol for the ongoing JaCVAM validation trial. Laboratories provided liver Comet assay data obtained at the end of the long-term (2- or 4-week) studies together with an evaluation of liver histology. Most of the test compounds were also investigated in the liver Comet assay after short-term (1-3 daily) administration to compare the sensitivity of the two study designs. MN analyses were conducted in bone marrow or peripheral blood for most of the compounds to determine whether the liver Comet assay could complement the MN assay for the detection of genotoxins after long-term treatment. Most of the liver genotoxins

  20. 40 CFR 35.2108 - Phased or segmented treatment works.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the enforceable requirements of the Act, provided: (a) The grant agreement requires the recipient to... enforceable requirements of the Act according to a schedule specified in the grant agreement regardless of... secondary treatment requirement waiver under section 301(h) of the Act....

  1. NOVEL NANOPARTICULATE CATALYSTS FOR IMPROVED VOC TREATMENT DEVICES - PHASE I

    EPA Science Inventory

    Catalytic oxidation of VOCs is increasingly used for treatment of large-volume emissions at relatively dilute VOC levels. The best performing catalytic oxidation devices for attainment of very high VOC destruction levels employ precious metal catalysts, the costs of which a...

  2. Integrated thermal treatment system study: Phase 1 results. Volume 1

    SciTech Connect

    Feizollahi, F.; Quapp, W.J.; Hempill, H.G.; Groffie, F.J.

    1994-07-01

    An integrated systems engineering approach is used for uniform comparison of widely varying thermal treatment technologies proposed for management of contact-handled mixed low-level waste (MLLW) currently stored in the US Department of Energy complex. Ten different systems encompassing several incineration design options are studied. All subsystems, including facilities, equipment, and methods needed for integration of each of the ten systems are identified. Typical subsystems needed for complete treatment of MLLW are incoming waste receiving and preparation (characterization, sorting, sizing, and separation), thermal treatment, air pollution control, primary and secondary stabilization, metal decontamination, metal melting, mercury recovery, lead recovery, and special waste and aqueous waste treatment. The evaluation is performed by developing a preconceptual design package and planning life-cycle cost (PLCC) estimates for each system. As part of the preconceptual design process, functional and operational requirements, flow sheets and mass balances, and conceptual equipment layouts are developed for each system. The PLCC components estimated are technology development, production facility construction, pre-operation, operation and maintenance, and decontamination and decommissioning. Preconceptual design data and other technology information gathered during the study are examined and areas requiring further development, testing, and evaluation are identified and recommended. Using a qualitative method, each of the ten systems are ranked.

  3. Effect of consuming a purple-fleshed sweet potato beverage on health-related biomarkers and safety parameters in Caucasian subjects with elevated levels of blood pressure and liver function biomarkers: a 4-week, open-label, non-comparative trial.

    PubMed

    Oki, Tomoyuki; Kano, Mitsuyoshi; Watanabe, Osamu; Goto, Kazuhisa; Boelsma, Esther; Ishikawa, Fumiyasu; Suda, Ikuo

    2016-01-01

    An open-label study with one treatment arm was conducted to investigate changes in health-related biomarkers (blood pressure and liver enzyme activity) and the safety of 4 weeks of consuming a purple-fleshed sweet potato beverage in Caucasian subjects. Twenty healthy adults, 18-70 years of age, with a body mass index >25 kg/m(2), elevated blood pressure and elevated levels of liver function biomarkers consumed two cartons of purple-fleshed sweet potato beverage (125 ml, including 117 mg anthocyanin per carton) daily for 4 weeks. Hematology, serum clinical profile, dipstick urinalysis and blood pressure were determined before consumption, at 2 and 4 weeks of consumption and after a 2-week washout period. A trend was found toward lowering systolic blood pressure during the treatment period (p=0.0590). No significant changes were found in diastolic blood pressure throughout the study period. Systolic blood pressure was significantly lower after 4 weeks of consumption compared with before consumption (p=0.0125) and was significantly higher after the 2-week washout period compared with after consumption (p=0.0496). The serum alanine aminotransferase level significantly increased over time, but aspartate aminotransferase and γ-glutamyltransferase levels stayed within the normal range of reference values. Safety parameters of the blood and urine showed no clinically relevant changes. The consumption of a purple-fleshed sweet potato beverage for 4 weeks resulted in no clinically relevant changes in safety parameters of the blood and urine and showed a trend toward lowering systolic blood pressure. PMID:27508114

  4. Effect of consuming a purple-fleshed sweet potato beverage on health-related biomarkers and safety parameters in Caucasian subjects with elevated levels of blood pressure and liver function biomarkers: a 4-week, open-label, non-comparative trial

    PubMed Central

    OKI, Tomoyuki; KANO, Mitsuyoshi; WATANABE, Osamu; GOTO, Kazuhisa; BOELSMA, Esther; ISHIKAWA, Fumiyasu; SUDA, Ikuo

    2016-01-01

    An open-label study with one treatment arm was conducted to investigate changes in health-related biomarkers (blood pressure and liver enzyme activity) and the safety of 4 weeks of consuming a purple-fleshed sweet potato beverage in Caucasian subjects. Twenty healthy adults, 18–70 years of age, with a body mass index >25 kg/m2, elevated blood pressure and elevated levels of liver function biomarkers consumed two cartons of purple-fleshed sweet potato beverage (125 ml, including 117 mg anthocyanin per carton) daily for 4 weeks. Hematology, serum clinical profile, dipstick urinalysis and blood pressure were determined before consumption, at 2 and 4 weeks of consumption and after a 2-week washout period. A trend was found toward lowering systolic blood pressure during the treatment period (p=0.0590). No significant changes were found in diastolic blood pressure throughout the study period. Systolic blood pressure was significantly lower after 4 weeks of consumption compared with before consumption (p=0.0125) and was significantly higher after the 2-week washout period compared with after consumption (p=0.0496). The serum alanine aminotransferase level significantly increased over time, but aspartate aminotransferase and γ-glutamyltransferase levels stayed within the normal range of reference values. Safety parameters of the blood and urine showed no clinically relevant changes. The consumption of a purple-fleshed sweet potato beverage for 4 weeks resulted in no clinically relevant changes in safety parameters of the blood and urine and showed a trend toward lowering systolic blood pressure. PMID:27508114

  5. Intravenous immunoglobulins for the treatment of mild to moderate Alzheimer’s disease: a phase II, randomised, double-blind, placebo-controlled dose-finding trial

    PubMed Central

    Dodel, Richard; Rominger, Axel; Bartenstein, Peter; Barkhof, Frederik; Blennow, Kai; Förster, Stefan; Winter, Yaroslav; Bach, Jan-Philipp; Popp, Julius; Alferink, Judith; Wiltfang, Jens; Buerger, Katharina; Otto, Markus; Antuono, Piero; Jacoby, Michael; Richter, Ralph; Stevens, James; Melamed, Isaac; Goldstein, Jerome; Haag, Stefan; Wietek, Stefan; Farlow, Martin; Jessen, Frank

    2016-01-01

    Background Three small trials have suggested effects of intravenous immunoglobulins (IVIG) on biomarkers and symptoms of mild-to-moderate Alzheimer’s disease (AD). We explored the safety, the effective dose, and the infusion interval for Octagam®10% in this patients’ group. Methods The study was a 24-week multicentre, double-blind, placebo-controlled phase II trial with 8 treatment arms at 7 sites in the USA and 5 sites in Germany. Participants aged 50–85 years were randomised (using a computer-generated randomisation sequence) to either 4 weekly infusions (n=22) (0.2 g/0.5 g/0.8 g/kg body weight), 2 weekly infusions (0.1g/0.25 g/0.4 g/kg) (n=21) or to placebo (n=7, 4-weekly, n=8, 2 weekly). The primary endpoint was the mean area under the curve (AUC) of plasma Aβ1–40 after the last infusion for one infusion interval. We considered the AUC of plasma Aβ1–40 being more representative of the potential effect of IVIG than a single time point measurement. Secondary outcomes included changes in (a) the concentrations of Aβ1–40, Aβ1–42, anti-Aβ autoantibodies in CSF/plasma and tau/ptau181 in CSF, (b) cognitive and functional scales, and (c) brain imaging (MRI/FDG-PET). Patients’ safety was assessed by recording of adverse events, clinical examinations, MRI investigations, electrocardiography and laboratory tests. The infusions were performed by site personnel who were otherwise not involved in any other assessments; therefore, the patients, caregivers, and investigators were blinded to the treatment allocations. The study medication was blinded by using intransparent overpouches and infusion lines. The trial is registered at ClinicalTrials.gov (NCT00812565) and controlled-trials.com (ISRCTN64846759). Findings Fifty-six patients were randomized. AUC of plasma Aβ1–40, was not significantly different from the placebo for five of the six IVIG arms (median with range: −18.00 [−1347.0; 1068.5] for 0.2 g/kg; 364.25 [−5834.5; 1953.5] for 0.5 g

  6. Accelerated Radiotherapy, Carbogen, and Nicotinamide (ARCON) in the Treatment of Advanced Bladder Cancer: Mature Results of a Phase II Nonrandomized Study

    SciTech Connect

    Hoskin, Peter; Rojas, Ana Ph.D. Saunders, Michele

    2009-04-01

    Purpose: We previously showed that accelerated radiotherapy combined with carbogen and nicotinamide (ARCON) was an effective approach to use in the radical treatment of patients with advanced bladder carcinoma. Interim analysis from this Phase II study showed that it achieved a high level of locoregional control and overall survival (OS) and an acceptable level of adverse events. Methods and Materials: From 1994 to 2000, a total of 105 consecutive patients with high-grade superficial or muscle-invasive bladder carcinoma were given accelerated radiotherapy (50-55 Gy in 4 weeks) with carbogen alone or ARCON. End points of the study were OS, disease-specific, and local regional relapse-free survival, and for late adverse events, urinary (altered urination frequency, incontinence, hematuria, and urgency) and bowel dysfunction (stool frequency and blood loss). Results: At 5 and 10 years, local regional relapse-free survival rates were 44% after ARCON excluding the effect of salvage treatment and 62% after ARCON including the effect of salvage treatment (p = 0.04). Five- and 10-year rates were 35% and 27% for OS and 47% and 46% for disease-specific survival. The highest actuarial rate for Grade 3 or worse late urinary or bowel dysfunction was observed for altered urinary frequency (44% of patients had urinary events every 1 hour or less) and stool frequency of four or more events (26% at 5 years). Conclusions: Historic comparisons with other studies indicate no evidence of an increase in severe or worse adverse events and good permanent control of bladder disease after ARCON radiotherapy.

  7. Changes in the Capillarity of the Rat Extensor Digitorum Longus Muscle 4 Weeks after Nerve Injury Studied by 2D Measurement Methods.

    PubMed

    Čebašek, Vita; Ribarič, Samo

    2016-01-01

    We have previously shown by 3D study that 2 weeks after nerve injury there was no change in the length of capillaries per muscle fibre length in rat extensor digitorum longus muscle (EDL). The primary goal of the present 2D study was to determine the capillarity of rat EDL 4 weeks after various modes of nerve injury. Additionally, we wished to calculate the same capillary/fibre parameters that were used in our 3D stereological study. EDL muscles derived from denervated (4 weeks after nerve injury), re-innervated (4 weeks after two successive nerve crushes) and age-matched controls from the beginning (CON-1) and the end (CON-2) of the experiment were analysed in two ways. Global indices of capillarity, such as capillary density (CD) and capillary/fibre (C/F) ratio, were determined by automatic analysis, local indices as the number (CAF) and the length of capillaries around individual muscle fibres (Lcap) in relation to muscle fibre size were estimated manually by tracing the muscle fibre outlines and the transversally and longitudinally cut segments of capillaries seen in 5-µm-thin muscle cross sections. Four weeks after both types of nerve injury, CD increased in comparison to the CON-2 group (p < 0.001) due to atrophied muscle fibres in denervated muscles and probably proliferation of capillaries in re-innervated ones. Higher C/F, CAF (both p < 0.001) and Lcap (p < 0.01) in re-innervated than denervated EDL confirmed this assumption. Calculated capillary/fibre parameters were comparable to our previous 3D study, which strengthens the practical value to the adapted 2D method used in this study. PMID:27023720

  8. The association between maternal-reported responses to infant crying at 4 weeks and 6 months and offspring depression at 18: a longitudinal study.

    PubMed

    Williams, Catherine J; Kessler, David; Fernyhough, Charles; Lewis, Glyn; Pearson, Rebecca M

    2016-04-01

    The purpose of the present study is to examine the association between maternal response to infant crying and the psychological health of the child in later life. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort, consisting of 15,247 pregnancies, 10,278 with exposure variables and 3201 complete cases were identified as having exposure, covariate and outcome data. Using a postal questionnaire, mothers were asked regarding their infant at 4 weeks and 6 months, 'If they cry what do you do?': (a) pick them up immediately; (b) if they cry, leave them for a while, and if they do not stop, pick them up; or (c) never pick them up until you are ready. Outcome was an International Statistical Classification-10th revision criteria (ICD-10) diagnosis of depression at 18 years for the infant. Offspring of mothers who at 4 weeks reported that they never picked their infants up until they were ready were more likely to have depression at 18 years (OR = 2.06, CI 0.95-4.47, adjusted for sociodemographic confounding variables). There was no evidence for an association at 6 months. Including adjustment variables reduced the strength of our association; an observed objective measure of maternal response rather than a self-report may have more accurately determined the mother's actual responses. There is some evidence for an association between maternal reporting of responses to infant crying at 4 weeks and risk of developing depression at 18 years. If this association is found to be causal, interventions encouraging mothers to represent and respond to their infants' emotional states may help prevent offspring depression. PMID:26837614

  9. Phase II clinical trials on Investigational drugs for the Treatment of Pancreatic Cancers

    PubMed Central

    Kim, Edward J.; Semrad, Thomas J.; Bold, Richard J.

    2015-01-01

    Introduction Despite some recent advances in treatment options, pancreatic cancer remains a devastating disease with poor outcomes. In a trend contrary to most malignancies, both incidence and mortality continue to rise due to pancreatic cancer. The majority of patients present with advanced disease and there are no treatment options for this stage that have demonstrated a median survival greater than 1 year. As the penultimate step prior to phase III studies involving hundreds of patients, phase II clinical trials provide an early opportunity to evaluate the efficacy of new treatments that are desperately needed for this disease. Areas Covered This review covers the results of published phase II clinical trials in advanced pancreatic adenocarcinoma published within the past 5 years. The treatment results are framed in the context of the current standards of care and the historic challenge of predicting phase III success from phase II trial results. Expert opinion Promising therapies remain elusive in pancreatic cancer based on recent phase II clinical trial results. Optimization and standardization of clinical trial design in the phase II setting, with consistent incorporation of biomarkers, is needed to more accurately identify promising therapies that warrant phase III evaluation. PMID:25809274

  10. Silo 3 Waste Treatment Phase I Physical Testing Final Report

    SciTech Connect

    Langton, C.A.

    2001-03-13

    A characterization study of the Fernald Silo 3 waste was performed at the request of Rocky Mountain Remedial Services, LLC (RMRS) to support treatment of the waste with the Envirobond reagents and Envirobrick process. The Savannah River Technology Center (SRTC) performed the characterization under a Work for Others Agreement WOF-00-007. Physical property testing was subcontracted to the Clemson Environmental Technologies Laboratory (CETL). This report is intended to transmit the results of the physical property testing conducted at the CETL. Results of the physical property testing are summarized in a final report from Steve Hoeffner, CETL.

  11. Gasifier waste water treatment: Phase I cooling tower assessment

    SciTech Connect

    Mann, M.D.; Willson, W.G.; Hendrikson, J.G.; Winton, S.L.

    1985-02-01

    Details of an advanced study of the treatability of waste waters from the fixed-bed gasification of lignite describe the test equipment and results at a pilot plant in North Dakota using stripped-gas liquor (SGL) as cooling tower makeup. Ammonia, alkalinity, phenol, and other non-hydantoin organics were removed from the cooling water by stripping and/or biological degradation, with the phenol concentration in the exhaust air exceeding the odor threshold. It will be necessary to control foaming of the circulating water, but both glycol and silicon based agents performed well during the test. It will also be necessary to reduce the high level of biofouling on heat transfer surfaces, although stainless steel fouling was not a major problem. The conclusion is that SGL is limited by potentially serious operating problems without additional treatment. 5 references, 4 figures, 7 tables.

  12. Effects of 4-Week Intensive Active-Resistive Training with an EMG-Based Exoskeleton Robot on Muscle Strength in Older People: A Pilot Study.

    PubMed

    Son, Jongsang; Ryu, Jeseong; Ahn, Soonjae; Kim, Eun Joo; Lee, Jung Ah; Kim, Youngho

    2016-01-01

    This study aims to investigate the idea that an active-resistive training with an EMG-based exoskeleton robot could be beneficial to muscle strength and antagonist muscle cocontraction control after 4-week intensive elbow flexion/extension training. Three older people over 65 years participated the training for an hour per session and completed total 20 sessions during four weeks. Outcome measures were chosen as the maximum joint torque and cocontraction ratio between the biceps/triceps brachii muscles at pre-/post-training. The Wilcoxon signed-ranks test was performed to evaluate paired difference for the outcome measures. As a result, there was no significant difference in the maximum flexion or extension torque at pre- and post-training. However, the cocontraction ratio of the triceps brachii muscle as the antagonist was significantly decreased by 9.8% after the 4-week intensive training. The active-resistive training with the exoskeleton robot in the older people yielded a promising result, showing significant changes in the antagonist muscle cocontraction. PMID:27006942

  13. Effects of a 4-week static stretch training program on passive stiffness of human gastrocnemius muscle-tendon unit in vivo.

    PubMed

    Nakamura, Masatoshi; Ikezoe, Tome; Takeno, Yohei; Ichihashi, Noriaki

    2012-07-01

    Static stretch is commonly used to prevent contracture and to improve joint mobility. However, it is unclear whether the components of the muscle-tendon unit are affected by a static stretch training program. This study investigated the effect of a four-week static stretch training program on the viscoelastic properties of the muscle-tendon unit and muscle. The subjects comprised 18 male participants (mean age 21.4 ± 1.7 years). The range of motion (ROM), passive torque, myotendinous junction (MTJ) displacement and, muscle fascicle length of the gastrocnemius muscle were assessed using both ultrasonography and a dynamometer while the ankle was passively dorsiflexed. After the initial test, the participants were assigned either to a group that stretched for 4 weeks (N = 9) or to a control group (N = 9). The tests were repeated after the static stretch training program. The ROM and MTJ displacement significantly increased, and the passive torque at 30° significantly decreased, in the stretching group after the study period. However, there was no significant increase in muscle fascicle length. These results suggest that a 4-week static stretch training program changes the flexibility of the overall MTU without causing concomitant changes in muscle fascicle length. PMID:22124523

  14. Effects of 4-Week Intensive Active-Resistive Training with an EMG-Based Exoskeleton Robot on Muscle Strength in Older People: A Pilot Study

    PubMed Central

    Son, Jongsang; Ryu, Jeseong; Ahn, Soonjae; Kim, Eun Joo; Lee, Jung Ah; Kim, Youngho

    2016-01-01

    This study aims to investigate the idea that an active-resistive training with an EMG-based exoskeleton robot could be beneficial to muscle strength and antagonist muscle cocontraction control after 4-week intensive elbow flexion/extension training. Three older people over 65 years participated the training for an hour per session and completed total 20 sessions during four weeks. Outcome measures were chosen as the maximum joint torque and cocontraction ratio between the biceps/triceps brachii muscles at pre-/post-training. The Wilcoxon signed-ranks test was performed to evaluate paired difference for the outcome measures. As a result, there was no significant difference in the maximum flexion or extension torque at pre- and post-training. However, the cocontraction ratio of the triceps brachii muscle as the antagonist was significantly decreased by 9.8% after the 4-week intensive training. The active-resistive training with the exoskeleton robot in the older people yielded a promising result, showing significant changes in the antagonist muscle cocontraction. PMID:27006942

  15. 5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus sunitinib or bevacizumab as first-line treatment for metastatic colorectal cancer: a randomized Phase IIb study

    PubMed Central

    Hecht, J Randolph; Mitchell, Edith P; Yoshino, Takayuki; Welslau, Manfred; Lin, Xun; Chow Maneval, Edna; Paolini, Jolanda; Lechuga, Maria Jose; Kretzschmar, Albrecht

    2015-01-01

    Background Sunitinib is an oral inhibitor of tyrosine kinase receptors implicated in tumor proliferation, angiogenesis, and metastasis. In this randomized, multicenter, open-label Phase IIb study, sunitinib plus mFOLFOX6 (oxaliplatin plus leucovorin plus 5-fluorouracil) was compared with bevacizumab plus mFOLFOX6 as first-line therapy in patients with metastatic colorectal cancer. Methods Patients were stratified by performance status, baseline lactate dehydrogenase level, and prior adjuvant treatment, and randomized 1:1 to receive sunitinib 37.5 mg/day for 4 weeks on and 2 weeks off plus mFOLFOX6 every 2 weeks or bevacizumab 5 mg/kg every 2 weeks plus mFOLFOX6 every 2 weeks. The primary endpoint was progression-free survival. Secondary endpoints included objective response rate, overall survival, safety, and quality of life. Results Enrollment was closed early following accrual of 191 patients, based on an interim analysis showing an inferior trend in the primary progression-free survival efficacy endpoint for sunitinib. Ninety-six patients were randomized to sunitinib plus mFOLFOX6 and 95 to bevacizumab plus mFOLFOX6. Median progression-free survival was 9.3 months and 15.4 months, respectively, but the objective response rate was similar between the study arms. Median overall survival was 23.7 months and 34.1 months, respectively. Dose reductions and interruptions were more common with sunitinib. Hematologic toxicity was more common in the sunitinib arm. Conclusion While the results of the sunitinib arm are comparable with those of previously reported FOLFOX combinations, the sunitinib-based combination was associated with more toxicity than that observed with bevacizumab and mFOLFOX6. The bevacizumab arm had an unexpectedly good outcome, and was much better than that seen in the Phase III trials. Combination therapy with sunitinib plus mFOLFOX6 is not recommended for patients with metastatic colorectal cancer. PMID:26109878

  16. Comparative ability of various PCBs, PCDFs, and TCDD to induce cytochrome P450 1A1 and 1A2 activity following 4 weeks of treatment (short communication)

    SciTech Connect

    De Vito, M.J.; Maier, W.E.; Diliberto, J.J.; Birnbaum, L.S.

    1993-01-01

    The toxic equivalency factors (TEF) have been proposed for dibenzo-p-dioxins, dibenzofurans and polychlorinated biphenyls (PCBs). The proposed TEFs, which are presently being evaluated in the authors' laboratory are currently used to estimate the potential health risk associated with exposure to complex mixtures containing these chemicals. Hepatic cytochrome P-450 1A1 and 1A2 activities were determined for all chemicals tested and compared to those from TCDD treated mice. These initial studies indicate that the interim TEFs for the dibenzofurans adequately predict the relative induction potency for these compounds. However, the TEFs proposed for the dioxin-like PCBs overestimate the potency of these compounds by factors of 10-10,000. The present study indicates that more experimental data is required before TEFs for PCBs are used in regulatory decision making.

  17. A novel, implicit treatment for language comprehension processes in right hemisphere brain damage: Phase I data

    PubMed Central

    Tompkins, Connie A.; Blake, Margaret T.; Wambaugh, Julie; Meigh, Kimberly

    2012-01-01

    Background This manuscript reports the initial phase of testing for a novel, “Contextual constraint” treatment, designed to stimulate inefficient language comprehension processes in adults with right hemisphere brain damage (RHD). Two versions of treatment were developed to target two normal comprehension processes that have broad relevance for discourse comprehension and that are often disrupted by RHD: coarse semantic coding and suppression. The development of the treatment was informed by two well-documented strengths of the RHD population. The first is consistently better performance on assessments that are implicit, or nearly so, than on explicit, metalinguistic measures of language and cognitive processing. The second is improved performance when given linguistic context that moderately-to-strongly biases an intended meaning. Treatment consisted of providing brief context sentences to prestimulate, or constrain, intended interpretations. Participants made no explicit associations or judgments about the constraint sentences; rather, these contexts served only as implicit primes. Aims This Phase I treatment study aimed to determine the effects of a novel, implicit, Contextual Constraint treatment in adults with RHD whose coarse coding or suppression processes were inefficient. Treatment was hypothesized to speed coarse coding or suppression function in these individuals. Methods & Procedures Three adults with RHD participated in this study, one (P1) with a coarse coding deficit and two (P2, P3) with suppression deficits. Probe tasks were adapted from prior studies of coarse coding and suppression in RHD. The dependent measure was the percentage of responses that met predetermined response time criteria. When pre-treatment baseline performance was stable, treatment was initiated. There were two levels of contextual constraint, Strong and Moderate, and treatment for each item began with the provision of the Strong constraint context. Outcomes & Results

  18. Contribution of siloxanes to COD loading at wastewater treatment plants: phase transfer, removal, and fate at different treatment units.

    PubMed

    Surita, Sharon C; Tansel, Berrin

    2015-03-01

    Cyclic volatile methylsiloxanes (cVMSs) are entering to waste stream in increasing quantities due to their increasing use in personal care products (i.e., shampoos, creams). The cVMSs have high vapor pressures and low solubilities and are mostly transferred into the gaseous phase via volatilization; however, some are sorbed onto biosolids. The purpose of this study was to track and estimate the phase transfer (water, solids, gas), fate, and contribution to COD loading of selected siloxanes (D4, D5 and D6) which are the most commonly found cVMSs in the wastewater systems. Removal efficiencies of the wastewater treatment units were evaluated based on the partitioning characteristics of the cVMSs in gas, liquid, and biosolids phases. The contributions of the siloxanes present in the influent and effluent were estimated in terms of COD levels based on the theoretical oxygen demand (ThOD) of the siloxanes. Siloxanes constitute approximately 39 and 0.001mgL(-1) of the COD in the influents and effluent. Oxidation systems showed higher removal efficiencies based COD loading in comparison to the removal efficiencies achieved aeration tanks and filtration systems. Treatment systems effectively remove the siloxanes from the aqueous phase with over 94% efficiency. About 50% of the siloxanes entering to the wastewater treatment plant accumulate in biosolids. PMID:25528947

  19. Results of treatment with an intensive combination induction regimen containing idarubicin in children with acute myeloblastic leukemia: preliminary report of the Argentine Group for Treatment of Acute Leukemia.

    PubMed

    Sackmann-Muriel, F; Fernández-Barbieri, M A; Santarelli, M T; Matus-Ridley, M; Rosso, A; Negri-Aranguren, P; Cerutti, I; Gomel, M; Kvicala, R

    1993-12-01

    In April 1990, the Argentine Group for Treatment of Acute Leukemia began a multicenter trial for the treatment of previously untreated acute myeloblastic leukemia patients who were under 21 years of age. Initial treatment consisted of an 8-day induction phase with cytarabine together with idarubicin on days 3 to 5 and etoposide on days 6 to 8. A multidrug consolidation phase was subsequently administered and, after a treatment-free interval of 2 to 4 weeks, two 5-day intensification courses with high-dose cytarabine and etoposide were delivered with a 4-week interval between each course. Continuation therapy was started 2 to 4 weeks after the second course, with 6-thioguanine daily and cytarabine daily for 4 days every 4 weeks. Treatment was stopped after 18 months in children in continuous complete remission. A preliminary evaluation of this ongoing study included 36 patients with a mean age of 7.5 years (age range, 5 months to 16 years). The majority of patients had a French-American-British classification of M2 (n = 13) or M4 (n = 8). Complete remission was achieved by 91.7% of patients, while one died from sepsis in bone marrow hypoplasia and two were regarded as treatment failures. At a median follow-up of 12 months (range, 2 to 23 months) there were 12 adverse events: six bone marrow relapses, one bone marrow/skin relapse, and five deaths in complete remission (all deaths occurred during the consolidation phase). During the induction phase most of the patients experienced prolonged myelosuppression, and grade 3 to 4 toxicity (according to the Children's Cancer Group criteria) was frequently seen. Alopecia was universal. However, toxicity was manageable. We conclude that idarubicin in combination with cytarabine and etoposide is a highly effective regimen for induction in children with acute myeloblastic leukemia. PMID:8290970

  20. Ultrasound Microbubble Treatment Enhances Clathrin-Mediated Endocytosis and Fluid-Phase Uptake through Distinct Mechanisms

    PubMed Central

    Fekri, Farnaz; Delos Santos, Ralph Christian; Karshafian, Raffi

    2016-01-01

    Drug delivery to tumors is limited by several factors, including drug permeability of the target cell plasma membrane. Ultrasound in combination with microbubbles (USMB) is a promising strategy to overcome these limitations. USMB treatment elicits enhanced cellular uptake of materials such as drugs, in part as a result of sheer stress and formation of transient membrane pores. Pores formed upon USMB treatment are rapidly resealed, suggesting that other processes such as enhanced endocytosis may contribute to the enhanced material uptake by cells upon USMB treatment. How USMB regulates endocytic processes remains incompletely understood. Cells constitutively utilize several distinct mechanisms of endocytosis, including clathrin-mediated endocytosis (CME) for the internalization of receptor-bound macromolecules such as Transferrin Receptor (TfR), and distinct mechanism(s) that mediate the majority of fluid-phase endocytosis. Tracking the abundance of TfR on the cell surface and the internalization of its ligand transferrin revealed that USMB acutely enhances the rate of CME. Total internal reflection fluorescence microscopy experiments revealed that USMB treatment altered the assembly of clathrin-coated pits, the basic structural units of CME. In addition, the rate of fluid-phase endocytosis was enhanced, but with delayed onset upon USMB treatment relative to the enhancement of CME, suggesting that the two processes are distinctly regulated by USMB. Indeed, vacuolin-1 or desipramine treatment prevented the enhancement of CME but not of fluid phase endocytosis upon USMB, suggesting that lysosome exocytosis and acid sphingomyelinase, respectively, are required for the regulation of CME but not fluid phase endocytosis upon USMB treatment. These results indicate that USMB enhances both CME and fluid phase endocytosis through distinct signaling mechanisms, and suggest that strategies for potentiating the enhancement of endocytosis upon USMB treatment may improve targeted

  1. Ultrasound Microbubble Treatment Enhances Clathrin-Mediated Endocytosis and Fluid-Phase Uptake through Distinct Mechanisms.

    PubMed

    Fekri, Farnaz; Delos Santos, Ralph Christian; Karshafian, Raffi; Antonescu, Costin N

    2016-01-01

    Drug delivery to tumors is limited by several factors, including drug permeability of the target cell plasma membrane. Ultrasound in combination with microbubbles (USMB) is a promising strategy to overcome these limitations. USMB treatment elicits enhanced cellular uptake of materials such as drugs, in part as a result of sheer stress and formation of transient membrane pores. Pores formed upon USMB treatment are rapidly resealed, suggesting that other processes such as enhanced endocytosis may contribute to the enhanced material uptake by cells upon USMB treatment. How USMB regulates endocytic processes remains incompletely understood. Cells constitutively utilize several distinct mechanisms of endocytosis, including clathrin-mediated endocytosis (CME) for the internalization of receptor-bound macromolecules such as Transferrin Receptor (TfR), and distinct mechanism(s) that mediate the majority of fluid-phase endocytosis. Tracking the abundance of TfR on the cell surface and the internalization of its ligand transferrin revealed that USMB acutely enhances the rate of CME. Total internal reflection fluorescence microscopy experiments revealed that USMB treatment altered the assembly of clathrin-coated pits, the basic structural units of CME. In addition, the rate of fluid-phase endocytosis was enhanced, but with delayed onset upon USMB treatment relative to the enhancement of CME, suggesting that the two processes are distinctly regulated by USMB. Indeed, vacuolin-1 or desipramine treatment prevented the enhancement of CME but not of fluid phase endocytosis upon USMB, suggesting that lysosome exocytosis and acid sphingomyelinase, respectively, are required for the regulation of CME but not fluid phase endocytosis upon USMB treatment. These results indicate that USMB enhances both CME and fluid phase endocytosis through distinct signaling mechanisms, and suggest that strategies for potentiating the enhancement of endocytosis upon USMB treatment may improve targeted

  2. Phase II Evaluation of Gefitinib in Patients With Newly Diagnosed Grade 4 Astrocytoma: Mayo/North Central Cancer Treatment Group Study N0074

    SciTech Connect

    Uhm, Joon H.; Ballman, Karla V.; Wu Wenting; Giannini, Caterina; Krauss, J.C.; Buckner, Jan C.; James, C.D.; Scheithauer, Bernd W.; Behrens, Robert J.; Flynn, Patrick J.; Schaefer, Paul L.; Dakhill, Shaker R.; Jaeckle, Kurt A.

    2011-06-01

    Purpose: Amplification of the epidermal growth factor receptor (EGFR) gene represents one of the most frequent gene alterations in glioblastoma (GBM). In the current study, we evaluated gefitinib, a potent EGFR inhibitor, in the treatment of adults with newly diagnosed GBM. Methods and Materials: Ninety-eight patients (96 evaluable) were accrued between May 18, 2001, and August 2, 2002. All were newly diagnosed GBM patients who were clinically and radiographically stable/improved after radiation treatment (enrollment within 5 weeks of radiation completion). No prior chemotherapy was permitted. EGFR amplification/mutation, as assessed by fluorescence in situ hybridization and immunohistochemistry, was not required for treatment with gefitinib but was studied when tissues were available. Gefitinib was administered at 500 mg each day; for patients receiving dexamethasone or enzyme-inducing (CYP3A4) agents, dose was escalated to a maximum of 1,000 mg QD. Treatment cycles were repeated at 4-week intervals with brain magnetic resonance imaging at 8-week intervals. Results: Overall survival (OS; calculated from time of initial surgery) at 1 year (primary end point) with gefitinib was 54.2%, which was not statistically different compared with that of historical control population (48.9%, data from three previous Phase III North Central Cancer Treatment Group studies of newly diagnosed GBM patients). Progression-free survival (PFS) at 1 year post-RT (16.7%) was also not significantly different to that of historical controls (30.3%). Clinical outcome was not affected by EGFR status (amplification or vIII mutation). Fatigue (41%), rash (62%), and loose stools (58%) constituted the most frequent adverse events, the majority of these being limited to Grade 1/2. Of note, the occurrence of drug-related adverse effects, such as loose stools was associated with improved OS. Conclusions: In our evaluation of nearly 100 patients with newly diagnosed GBM, treatment with adjuvant

  3. Effects of heat treatment and formulation on the phase composition and chemical durability of the EBR-ll ceramic waste form.

    SciTech Connect

    Ebert, W. E.; Dietz, N. L.; Janney, D. E.

    2006-01-31

    High-level radioactive waste salts generated during the electrometallurgical treatment of spent sodium-bonded nuclear fuel from the Experimental Breeder Reactor-II will be immobilized in a ceramic waste form (CWF). Tests are being conducted to evaluate the suitability of the CWF for disposal in the planned federal high-level radioactive waste repository at Yucca Mountain. In this report, the results of laboratory tests and analyses conducted to address product consistency and thermal stability issues called out in waste acceptance requirements are presented. The tests measure the impacts of (1) variations in the amounts of salt and binder glass used to make the CWF and (2) heat treatments on the phase composition and chemical durability of the waste form. A series of CWF materials was made to span the ranges of salt and glass contents that could be used during processing: between 5.0 and 15 mass% salt loaded into the zeolite (the nominal salt loading is 10.7%, and the process control range is 10.6 to 11.2 mass%), and between 20 and 30 mass% binder glass mixed with the salt-loaded zeolite (the nominal glass content is 25% and the process control range is 20 to 30 mass%). In another series of tests, samples of two CWF products made with the nominal salt and glass contents were reheated to measure the impact on the phase composition and durability: long-term heat treatments were conducted at 400 and 500 C for durations of 1 week, 4 weeks, 3 months, 6 months, and 1 year; short-term heat treatments were conducted at 600, 700, 800, and 850 C for durations of 4, 28, 52, and 100 hours. All of the CWF products that were made with different amounts of salt, zeolite, and glass and all of the heat-treated CWF samples were analyzed with powder X-ray diffraction to measure changes in phase compositions and subjected to 7-day product consistency tests to measure changes in the chemical durability. The salt loading had the greatest impact on phase composition and durability. A

  4. Decontamination and inspection plan for Phase 3 closure of the 300 area waste acid treatment system

    SciTech Connect

    LUKE, S.N.

    1999-02-01

    This decontamination and inspection plan (DIP) describes decontamination and verification activities in support of Phase 3 closure of the 300 Area Waste Acid Treatment System (WATS). Phase 3 is the third phase of three WATS closure phases. Phase 3 attains clean closure conditions for WATS portions of the 334 and 311 Tank Farms (TF) and the 333 and 303-F Buildings. This DIP also describes designation and management of waste and debris generated during Phase 3 closure activities. Information regarding Phase 1 and Phase 2 for decontamination and verification activities closure can be found in WHC-SD-ENV-AP-001 and HNF-1784, respectively. This DIP is provided as a supplement to the closure plan (DOE/RL-90-11). This DIP provides the documentation for Ecology concurrence with Phase 3 closure methods and activities. This DIP is intended to provide greater detail than is contained in the closure plan to satisfy Ecology Dangerous Waste Regulations, Washington Administrative Code (WAC) 173-303-610 requirement that closure documents describe the methods for removing, transporting, storing, and disposing of all dangerous waste at the unit. The decontamination and verification activities described in this DIP are based on the closure plan and on agreements reached between Ecology and the U.S. Department of Energy, Richland Operations Office (DOE-RL) during Phase 3 closure activity workshops and/or project manager meetings (PMMs).

  5. Knee Extension Range of Motion at 4 Weeks Is Related to Knee Extension Loss at 12 Weeks After Anterior Cruciate Ligament Reconstruction

    PubMed Central

    Noll, Sarah; Garrison, J. Craig; Bothwell, James; Conway, John E.

    2015-01-01

    Background: The anterior cruciate ligament (ACL) is commonly torn, and surgical reconstruction is often required to allow a patient to return to their prior level of activity. Avoiding range of motion (ROM) loss is a common goal, but little research has been done to identify when ROM loss becomes detrimental to a patient’s future function. Purpose: To determine whether there is a relationship between early knee side-to-side extension difference after ACL reconstruction and knee side-to-side extension difference at 12 weeks. The hypothesis was that early (within the first 8 weeks) knee side-to-side extension difference will be predictive of knee side-to-side extension difference seen at 12 weeks. Study Design: Cohort study; Level of evidence, 3. Methods: Knee side-to-side extension difference measures were taken on 74 patients undergoing ACL reconstruction rehabilitation at the initial visit and 4, 8, and 12 weeks postoperatively. Visual analog scores (VAS) and International Knee Documentation Committee (IKDC) scores were also recorded at these time frames. Results: There was a strong relationship between knee extension ROM at 4 and 12 weeks (r = 0.639, P < .001) and 8 and 12 weeks (r = 0.742, P < .001). When the variables of knee extension ROM at initial visit and 4 and 8 weeks were entered into a regression analysis, the predictor variable explained 61% (R2 = 0.611) of variance for knee extension ROM at 12 weeks, with 4 weeks (R2 = 0.259) explaining the majority of this variance. Conclusion: This study found that a patient’s knee extension at 4 weeks was strongly correlated with knee extension at 12 weeks. Clinical Relevance: This information may be useful for clinicians treating athletic patients who are anxious for return to sport by providing them an initial goal to work toward in hopes of ensuring successful rehabilitation of their knee. PMID:26675061

  6. Deep-cryogenic-treatment-induced phase transformation in the Al-Zn-Mg-Cu alloy

    NASA Astrophysics Data System (ADS)

    Li, Chun-mei; Cheng, Nan-pu; Chen, Zhi-qian; Guo, Ning; Zeng, Su-min

    2015-01-01

    An aluminum alloy (Al-Zn-Mg-Cu) subjected to deep cryogenic treatment (DCT) was systematically investigated. The results show that a DCT-induced phase transformation varies the microstructures and affects the mechanical properties of the Al alloy. Both Guinier-Preston (GP) zones and a metastable η' phase were observed by high-resolution transmission electron microscopy. The phenomenon of the second precipitation of the GP zones in samples subjected to DCT after being aged was observed. The viability of this phase transformation was also demonstrated by first-principles calculations.

  7. [Primary results and long-term outcome of an ambulatory, cardiac rehabilitation model (phase II) after myocardial infarct, dilatation treatment and heart operation].

    PubMed

    Gysan, D B; Heinzler, R; Schmidt, K

    1997-09-01

    From October 1994 to July 1996, 128 patients (30 women, 98 men) participated in an outpatient cardiac rehabilitation program (phase II). Our objectives were to demonstrate risk-factor modification and increased work-load capacity resulting directly from the rehabilitation in terms of primary results and long-term effects, 6 months (n = 59) and 12 months (n = 30) after termination of the program. We observed how many of the patients were able to be occupationally re-integrated after completion of phase II rehabilitation. During the 4-week program, the work-load capacity increased significantly from 1.2 W/kg to 1.5 W/kg (p < or = 0.05). After 6 months (1.4 W/kg) and 1 year (1.5 W/kg), consistently high workload capacities were noted. Total cholesterol decreased significantly from 247 mg/dl to 201 mg/dl (p < or = 0.05) during the 4-week program. After 6 months (219 mg/dl) and 1 year (210 mg/dl) significant reductions persisted (p < or = 0.05). Similar results with LDL-cholesterol were seen: 185 mg/dl before entering the program, 146 mg/dl after 4 weeks, 158 mg/dl after 6 months and 151 mg/dl after 1 year. Triglyceride levels showed a significant reduction (p < or = 0.05), 189 mg/dl before entering in the program, 148 mg/dl after 4 weeks, 143 mg/dl after 6 months, and 135 mg/dl after 1 year. The HDL-levels increased slightly as a long-term effect, i.e., from 51 mg/dl to 49 mg/dl during the 4 week program, and 57 mg/dl after 6 and 12 months. Of the patients questioned (n = 73), 73% found the program very good, 27% said it was good, and no patient was dissatisfied. Of the 63 patients who were actively employed before becoming ill and later entered our program, 51 (81%) were able to be immediately re-integrated into their previous occupation. In several cases this re-integration took 7 weeks. Seven (11%) patients applied for pension, and 5 (8%) patients remained unemployed on sick-leave. PMID:9441530

  8. The Mechanism of η Phase Precipitation in A286 Superalloy During Heat Treatment

    NASA Astrophysics Data System (ADS)

    Seifollahi, M.; Razavi, S. H.; Kheirandish, Sh.; Abbasi, S. M.

    2013-10-01

    In this research, the mechanism of eta (η-Ni3Ti) phase precipitation in iron-nickel-based A286 superalloy was assessed during aging heat treatment in the temperature range between 650 and 900 °C for the times of 1-30 h. Optical microscopy, scanning electron microscopy, differential thermal analysis, and x-ray diffractometry were used to describe the η phase transformation. The results showed that the major precipitates at temperatures below 840 °C were γ' and η. The η phase started to precipitate at the expense of the γ' phase after prolonged aging. The η phase existed in the samples aged at temperature higher than 760 °C with cellular morphology. The η volume fraction increased with increasing heat treatment time. In addition, when the aging temperature was increased from 760 to 820 °C, the η volume fraction increased and then decreased after 840 °C. The η phase morphology also changed from cellular to Widmanstätten-type during aging. The time-temperature-precipitation diagrams of these morphologies are presented. The results indicated the differences in precipitation mechanisms of η phase at 840 and 860 °C.

  9. Phase separation of cesium from lead borosilicate glass by heat treatment under a reducing atmosphere.

    PubMed

    Xu, Zhanglian; Okada, Takashi; Nishimura, Fumihiro; Yonezawa, Susumu

    2016-11-01

    A phase-separation technique for removing sodium from glass using a heat-treatment method under a reducing atmosphere was previously developed for sodium recovery from waste glass. In this study, this technique was applied to cesium-containing lead borosilicate glass to concentrate the cesium in phase-separated sodium-rich materials for efficient cesium extraction. The theoretical phase-separation temperature of the sodium-rich phase was simulated by thermodynamic equilibrium calculations and was predicted to occur below 700°C for lead borosilicate glass. Experimentally, a simulated lead borosilicate glass was melted at 1000°C and subsequently annealed below 700°C under a CO-containing reducing atmosphere. The phase separation of cesium was found to occur with sodium enrichment on the glass surface that was in contact with the gas phase, promoting cesium extraction from the treated glass using water. The cesium extraction efficiency was affected by the surface area of the treated glass that was in contact with water, and under the examined conditions, the cesium extraction efficiency was up to 66%. Phase separation using reductive heat treatment, combined with a water leaching technique, is suggested to be effective for extracting cesium incorporated in borosilicate glass waste. PMID:27368086

  10. Diagnosis, Cause, and Treatment Approaches for Delayed Sleep-Wake Phase Disorder.

    PubMed

    Magee, Michelle; Marbas, Emily M; Wright, Kenneth P; Rajaratnam, Shantha M W; Broussard, Josiane L

    2016-09-01

    Delayed sleep-wake phase disorder (DSWPD) is commonly defined as an inability to fall asleep and wake at societal times resulting in excessive daytime sleepiness. Although the cause is multifaceted, delays in sleep time are largely driven by misalignment between the circadian pacemaker and the desired sleep-wake timing schedule. Current treatment approaches focus on correcting the circadian delay; however, there is a lack of data investigating combined therapies for treatment of DSWPD. PMID:27542884

  11. Factors Associated with Fatality during the Intensive Phase of Anti-Tuberculosis Treatment

    PubMed Central

    Casals, M.; Caminero, J. A.; García-García, J. M.; Jiménez-Fuentes, M. A.; Medina, J. F.; Millet, J. P.; Ruiz-Manzano, J.; Caylá, J.

    2016-01-01

    Objective To determine the case-fatality rate (CFR) at the end of the intensive phase of tuberculosis (TB) treatment, and factors associated with fatality. Methods TB patients diagnosed between 2006 and 2013 were followed-up during treatment. We computed the CFR at the end of the intensive phase of TB treatment, and the incidence of death per 100 person-days (pd) of follow-up. We performed survival analysis using the Kaplan-Meier method and Cox regression, and calculate hazard ratios (HR) and 95% confidence intervals (CI). Results A total of 5,182 patients were included, of whom 180 (3.5%) died; 87 of these deaths (48.3%) occurred during the intensive phase of treatment, with a CFR of 1.7%. The incidence of death was 0.028/100 pd. The following factors were associated with death during the intensive phase: being >50 years (HR = 36.9;CI:4.8–283.4); being retired (HR = 2.4;CI:1.1–5.1); having visited the emergency department (HR = 3.1;CI:1.2–7.7); HIV infection (HR = 3.4;CI:1.6–7.2); initial standard treatment with 3 drugs (HR = 2.0;CI:1.2–3.3) or non-standard treatments (HR = 2.68;CI:1.36–5.25); comprehension difficulties (HR = 2.8;CI:1.3–6.1); and smear-positive sputum (HR = 2.3-CI:1.0–4.8). Conclusion There is a non-negligible CFR during the intensive phase of TB, whose reduction should be prioritised. The CFR could be a useful indicator for evaluating TB programs. PMID:27487189

  12. Estrogenic and AhR activities in dissolved phase and suspended solids from wastewater treatment plants.

    PubMed

    Dagnino, Sonia; Gomez, Elena; Picot, Bernadette; Cavaillès, Vincent; Casellas, Claude; Balaguer, Patrick; Fenet, Hélène

    2010-05-15

    The distribution of estrogen receptor (ERalpha) and Aryl Hydrocarbon Receptor (AhR) activities between the dissolved phase and suspended solids were investigated during wastewater treatment. Three wastewater treatment plants with different treatment technologies (waste stabilization ponds (WSPs), trickling filters (TFs) and activated sludge supplemented with a biofilter system (ASB)) were sampled. Estrogenic and AhR activities were detected in both phases in influents and effluents. Estrogenic and AhR activities in wastewater influents ranged from 41.8 to 79 ng/L E(2) Eq. and from 37.9 to 115.5 ng/L TCDD Eq. in the dissolved phase and from 5.5 to 88.6 ng/g E(2) Eq. and from 15 to 700 ng/g TCDD Eq. in the suspended solids. For both activities, WSP showed greater or similar removal efficiency than ASB and both were much more efficient than TF which had the lowest removal efficiency. Moreover, our data indicate that the efficiency of removal of ER and AhR activities from the suspended solid phase was mainly due to removal of suspended solids. Indeed, ER and AhR activities were detected in the effluent suspended solid phase indicating that suspended solids, which are usually not considered in these types of studies, contribute to environmental contamination by endocrine disrupting compounds and should therefore be routinely assessed for a better estimation of the ER and AhR activities released in the environment. PMID:20303573

  13. A Comparison of Phase and Speckle Tracking Registration Methods for Motion Correction during HIFU Treatment

    NASA Astrophysics Data System (ADS)

    Yates, Tara; Smith, Penny Probert; Noble, Alison; Leslie, Tom; Kennedy, James

    2007-05-01

    The accuracy of treatment monitoring and planning is instrumental to the acceptance of HIFU surgery. The ability to locate, analyze and track a feature of interest during treatment will be affected by patient motion. Additionally, statistical analysis and temperature monitoring algorithms would benefit from the registration of successive frames. In this work two registration algorithms, which have had extensive trials in other imaging applications, are investigated. Their ability to reduce patient respiratory and cardiac motion is within ultrasound sequences, taken during HIFU treatments, is compared. The first algorithm is based on an intensity block matching approach with a similarity measure that incorporates speckle statistics explicitly. The second method registers phase representations of the image with a more general similarity measure. These methods would be expected to succeed on different aspects of the image: phase measurements give weight to features and are rotation and contrast invariant, whereas methods to track speckle are successful in images that lack strong features. In general phase based methods of registration are more robust and have the potential to be extended to multimodality registration (such as MRI to Ultrasound), however in this case tracking speckle may produce better results due to the low signal to noise ratio in ultrasound images taken during HIFU treatments. Numerous examples from HIFU surgery are presented to highlight the performance of each method under a various motion constraints. It is shown that the phase based algorithm is generally superior, except in the close proximity to the skin.

  14. Sunitinib Plus Paclitaxel Versus Bevacizumab Plus Paclitaxel for First-Line Treatment of Patients With Advanced Breast Cancer: A Phase III, Randomized, Open-Label Trial

    PubMed Central

    Robert, Nicholas J.; Saleh, Mansoor N.; Paul, Devchand; Generali, Daniele; Gressot, Laurent; Copur, Mehmet S.; Brufsky, Adam M.; Minton, Susan E.; Giguere, Jeffrey K.; Smith, John W.; Richards, Paul D.; Gernhardt, Diana; Huang, Xin; Liau, Katherine F.; Kern, Kenneth A.; Davis, John

    2015-01-01

    Introduction A multicenter, open-label phase III study was conducted to test whether sunitinib plus paclitaxel prolongs progression-free survival (PFS) compared with bevacizumab plus paclitaxel as first-line treatment for patients with HER2− advanced breast cancer. Patients and Methods Patients with HER2− advanced breast cancer who were disease free for ≥ 12 months after adjuvant taxane treatment were randomized (1:1; planned enrollment 740 patients) to receive intravenous (I.V.) paclitaxel 90 mg/m2 every week for 3 weeks in 4-week cycles plus either sunitinib 25 to 37.5 mg every day or bevacizumab 10 mg/kg I.V. every 2 weeks. Results The trial was terminated early because of futility in reaching the primary endpoint as determined by the independent data monitoring committee during an interim futility analysis. At data cutoff, 242 patients had been randomized to sunitinib-paclitaxel and 243 patients to bevacizumab-paclitaxel. Median PFS was shorter with sunitinib-paclitaxel (7.4 vs. 9.2 months; hazard ratio [HR] 1.63 [95% confidence interval (CI), 1.18–2.25]; 1-sided P = .999). At a median follow-up of 8.1 months, with 79% of sunitinib-paclitaxel and 87% of bevacizumab-paclitaxel patients alive, overall survival analysis favored bevacizumab-paclitaxel (HR 1.82 [95% CI, 1.16–2.86]; 1-sided P = .996). The objective response rate was 32% in both arms, but median duration of response was shorter with sunitinib-paclitaxel (6.3 vs. 14.8 months). Bevacizumab-paclitaxel was better tolerated than sunitinib-paclitaxel. This was primarily due to a high frequency of grade 3/4, treatment-related neutropenia with sunitinib-paclitaxel (52%) precluding delivery of the prescribed doses of both drugs. Conclusion The sunitinib-paclitaxel regimen evaluated in this study was clinically inferior to the bevacizumab-paclitaxel regimen and is not a recommended treatment option for patients with advanced breast cancer. PMID:21569994

  15. A study on verifying the effectiveness of 4-week composite weight-loss dietary supplement ingestion on body composition and blood lipid changes in middle-aged women

    PubMed Central

    Chun, Yoonseok; Lee, Namju; Park, Sok; Sung, Suhyun; Jung, Matthew; Kim, Jongkyu

    2015-01-01

    Purpose The purpose of this study was to investigate the effectiveness of a composite weight-loss dietary supplement on body composition and blood lipid changes in middle-aged women. Methods Thirty seven middle-aged women living in the Kyunggi area participated in this study and they were randomly divided into 2 groups (Dietary supplement ingestion group; DG, n = 20 and Placebo group; PG, n = 17). Blood draw and dual energy x-ray (DEXA) measurements were conducted to examine changes in body composition and blood lipids. Results There were no significant changes in weight and BMI in both groups. There was an interaction between the composite weight-loss dietary supplement intake and lean body mass in DG and there was a significant decrease in percent body fat in DG. Blood lipid changes in the study results showed that there was no significant difference in TC, TG, and LDL in both groups; however, there was a significant interaction between the composite weight-loss dietary supplement intake and HDL-C as well as an increase in the HDL-C of DG. Conclusion In conclusion, it seems that 4-week ingestion of the composite weight-loss dietary supplement decreased body fat, increased lean body mass, and increased HDL-C. Therefore, the composite weight-loss dietary supplement is expected to prevent obesity and induce health improvements in middle-aged women. PMID:26527460

  16. Compliance, Palatability and Feasibility of PALEOLITHIC and Australian Guide to Healthy Eating Diets in Healthy Women: A 4-Week Dietary Intervention.

    PubMed

    Genoni, Angela; Lo, Johnny; Lyons-Wall, Philippa; Devine, Amanda

    2016-01-01

    (1) BACKGROUND/OBJECTIVES: The Paleolithic diet has been receiving media coverage in Australia and claims to improve overall health. The diet removes grains and dairy, whilst encouraging consumption of fruits, vegetables, meat, eggs and nuts. Our aim was to compare the diet to the Australian Guide to Healthy Eating (AGHE) in terms of compliance, palatability and feasibility; (2) SUBJECTS/METHODS: 39 healthy women (age 47 ± 13 years, BMI 27 ± 4 kg/m²) were randomised to an ad-libitum Paleolithic (n = 22) or AGHE diet (n = 17) for 4-weeks. A food checklist was completed daily, with mean discretionary consumption (serves/day) calculated to assess compliance. A 12-item questionnaire was administered post intervention to assess palatability and feasibility; (3) RESULTS: The AGHE group reported greater daily consumption of discretionary items (1.0 + 0.6 vs. 0.57 + 0.6 serves/day, p = 0.03). Compared to the AGHE group, the Paleolithic group reported a significantly greater number of events of diarrhoea (23%, 0%, p = 0.046), costs associated with grocery shopping (69%, 6% p < 0.01) and belief that the diet was not healthy (43%, 0% p < 0.01); (4) CONCLUSIONS: Compliance to both diets was high but the potential side effects and increased cost suggest that the Paleolithic diet may not be practical in clinical/public health settings. Further studies are required to assess longer term feasibility. PMID:27509519

  17. Compliance, Palatability and Feasibility of PALEOLITHIC and Australian Guide to Healthy Eating Diets in Healthy Women: A 4-Week Dietary Intervention

    PubMed Central

    Genoni, Angela; Lo, Johnny; Lyons-Wall, Philippa; Devine, Amanda

    2016-01-01

    (1) Background/Objectives: The Paleolithic diet has been receiving media coverage in Australia and claims to improve overall health. The diet removes grains and dairy, whilst encouraging consumption of fruits, vegetables, meat, eggs and nuts. Our aim was to compare the diet to the Australian Guide to Healthy Eating (AGHE) in terms of compliance, palatability and feasibility; (2) Subjects/Methods: 39 healthy women (age 47 ± 13 years, BMI 27 ± 4 kg/m2) were randomised to an ad-libitum Paleolithic (n = 22) or AGHE diet (n = 17) for 4-weeks. A food checklist was completed daily, with mean discretionary consumption (serves/day) calculated to assess compliance. A 12-item questionnaire was administered post intervention to assess palatability and feasibility; (3) Results: The AGHE group reported greater daily consumption of discretionary items (1.0 + 0.6 vs. 0.57 + 0.6 serves/day, p = 0.03). Compared to the AGHE group, the Paleolithic group reported a significantly greater number of events of diarrhoea (23%, 0%, p = 0.046), costs associated with grocery shopping (69%, 6% p < 0.01) and belief that the diet was not healthy (43%, 0% p < 0.01); (4) Conclusions: Compliance to both diets was high but the potential side effects and increased cost suggest that the Paleolithic diet may not be practical in clinical/public health settings. Further studies are required to assess longer term feasibility. PMID:27509519

  18. Phase transition ordering-separation: A new approach to heat treatment of alloys

    NASA Astrophysics Data System (ADS)

    Ustinovshchikov, Yu. I.

    2015-09-01

    The problems of the consequence of heat treatment of alloys performed using the concept of an ordering-separation phase transition are considered. Fe50Cr50 and Ni88Al12 alloys and U13 steel are used as examples to show that this transition occurs at a temperature specific for each system, and a change in the sign of the chemical interaction between alloy component atoms changes the direction of diffusion fluxes in alloys into the opposite direction, which changes the type of microstructure. The detection of this phase transition radically changes the generally accepted concepts of heat treatment of alloys. This finding calls for transmission electron microscopy investigations to modify the phase diagrams where this phase transition was detected. It is concluded that quenching of alloys from a so-called solid-solution field, which is usually performed before tempering (aging), is an unnecessary and useless operation, since the final structure of an alloy forms upon tempering (aging) irrespective of the structure existing before this heat treatment.

  19. Phase transformations on the surface of YAG composite ceramics under the action of directed laser treatment

    NASA Astrophysics Data System (ADS)

    Vlasova, M.; Márquez Aguilar, P. A.; Escobar Martinez, A.; Kakazey, M.; Guardian Tapia, R.; Trujillo Estrada, A.

    2016-07-01

    The laser treatment of composite ceramics based on Y3Al5O12 with Y2Ti2O7, Al2Y4O9, and Al2O3 additives is accompanied by the melting of the surface layer and formation of tracks. In the volume of tracks, the partial dissociation of Y3Al5O12, Y2Ti2O7, and Al2Y4O9, and the formation of new phases such as YAlO3 of orthorhombic and hexagonal modifications along with the appearance of additional content of Y3Al5O12 and Al2O3 are observed. The content of all these phases depends on the irradiation mode and the phase composition of the ceramics. With increase in the corundum content in ceramic specimens, in the tracks, the Al2O3 content increases, and the Y3Al5O12 content decreases. In the volume of tracks, Y3Al5O12 crystallites are textured. The size of YAG crystallites and their crystallographic texturing depend on the irradiation mode and Y3Al5O12/Al2O3 phase ratio. On the surface of tracks, a layer enriched in YAlO3 forms. Thus, as a result of laser treatment, on the surface of the ceramics, a two-layer coating with a radically new phase composition and specific texture of Y3Al5O12 crystallites forms.

  20. Transitioning from multi-phase to single-phase microfluidics for long-term culture and treatment of multicellular spheroids.

    PubMed

    McMillan, Kay S; Boyd, Marie; Zagnoni, Michele

    2016-09-21

    When compared to methodologies based on low adhesion or hanging drop plates, droplet microfluidics offers several advantages for the formation and culture of multicellular spheroids, such as the potential for higher throughput screening and the use of reduced cell numbers, whilst providing increased stability for plate handling. However, a drawback of the technology is its characteristic compartmentalisation which limits the nutrients available to cells within an emulsion and poses challenges to the exchange of the encapsulated solution, often resulting in short-term cell culture and/or viability issues. The aim of this study was to develop a multi-purpose microfluidic platform that combines the high-throughput characteristics of multi-phase flows with that of ease of perfusion typical of single-phase microfluidics. We developed a versatile system to upscale the formation and long-term culture of multicellular spheroids for testing anticancer treatments, creating an array of fluidically addressable, compact spheroids that could be cultured in either medium or within a gel scaffold. The work provides proof-of-concept results for using this system to test both chemo- and radio-therapeutic protocols using in vitro 3D cancer models. PMID:27477673

  1. Phase Transformation Behavior at Low Temperature in Hydrothermal Treatment of Stable and Unstable Titania Sol

    PubMed

    So; Park; Kim; Moon

    1997-07-15

    Nanosize titania sol was prepared from titanium tetraisopropoxide (TTIP) and conditions for the formation of stable sol were identified. As the H+/TTIP mole ratio decreased and H2O/TTIP mole ratio increased, stable sol was likely to be formed. The size and crystallinity remained unchanged after hydrothermal treatment of the stable sol at between 160 and 240°C. However, hydrothermal treatment of unstable sol produced rod-like particles and crystallinity of particles was changed from anatase to rutile. This difference in phase transformation at low hydrothermal treatment temperature was likely to be caused by the fact that stable sol remained to be stable even after hydrothermal treatment, while unstable sol had a tendency to be aggregated. PMID:9268523

  2. Efficacy of budesonide therapy in the early phase of treatment of adult coeliac disease patients with malabsorption: an in vivo/in vitro pilot study.

    PubMed

    Ciacci, C; Maiuri, L; Russo, I; Tortora, R; Bucci, C; Cappello, C; Santonicola, A; Luciani, A; Passananti, V; Iovino, P

    2009-12-01

    1. Budesonide is a glucocorticosteroid with a local anti-inflammatory effect. Coeliac disease is an immune-mediated disease caused by gluten ingestion in intolerant patients. The aim of the present study was to investigate the efficacy of budesonide in malabsorptive coeliac patients and its effect in an in vitro gliadin challenge. 2. Twenty coeliac patients with malabsorption were enrolled in the present study and were randomly assigned to one of two 4 week treatments: (i) a gluten-free diet alone; or (ii) a gluten-free diet plus 6 mg budesonide daily. At the end of 4 weeks treatment, all patients underwent clinical evaluation, laboratory tests and self-evaluation of well-being using a visual analogue scale. Intestinal biopsies from five coeliac patients (selected randomly) and four non-coeliac disease controls who underwent upper endoscopy for intestinal bleeding were challenged with gliadin (0.5 mg/mL) and budesonide (10-30 microg/mL) for 3 and 24 h. Biopsies were tested by immunohistochemistry and immunofluorescence for known markers of inflammation. 3. Treatment of patients with 6 mg budesonide daily for 4 weeks resulted in increased bodyweight, a decreased number of evacuations and decreased stool weight compared with patients on a gluten-free diet alone for 4 weeks. Well-being scores were higher in patients treated with both a gluten-free diet and budesonide compared with those receiving a gluten-free diet alone. 4. In vitro studies showed that budesonide reduced epithelial tyrosine phosphorylation and expression of histocompatibility leucocyte antigen complex DR (HLA-DR) elicited by gliadin-derived peptides. In addition, the expression of cyclo-oxygenase (COX)-2 and intercellular adhesion molecule (ICAM)-1 in the lamina propria was reduced in patients treated with both gliadin and budesonide compared with patients treated with gliadin alone. Budesonide alone decreased HLA-DR in crypt enterocytes, as well as ICAM-1 and COX-2 expression in the lamina propria

  3. Pulmonary and cardiovascular effects of traffic-related particulate matter: 4-week exposure of rats to roadside and diesel engine exhaust particles.

    PubMed

    Gerlofs-Nijland, Miriam E; Totlandsdal, Annike I; Kilinç, Evren; Boere, A John F; Fokkens, Paul H B; Leseman, Daan L A C; Sioutas, Constantinos; Schwarze, Per E; Spronk, Henri M; Hadoke, Patrick W F; Miller, Mark R; Cassee, Flemming R

    2010-12-01

    Traffic-related particulate matter (PM) may play an important role in the development of adverse health effects, as documented extensively in acute toxicity studies. However, rather little is known about the impacts of prolonged exposure to PM. We hypothesized that long-term exposure to PM from traffic adversely affects the pulmonary and cardiovascular system through exacerbation of an inflammatory response. To examine this hypothesis, Fisher F344 rats, with a mild pulmonary inflammation at the onset of exposure, were exposed for 4 weeks, 5 days/week for 6 h a day to: (a) diluted diesel engine exhaust (PM(DEE)), or: (b) near roadside PM (PM(2.5)). Ultrafine particulates, which are largely present in diesel soot, may enter the systemic circulation and directly or indirectly trigger cardiovascular effects. Hence, we assessed the effects of traffic-related PM on pulmonary inflammation and activity of procoagulants, vascular function in arteries, and cytokine levels in the heart 24 h after termination of the exposures. No major adverse health effects of prolonged exposure to traffic-related PM were detected. However, some systemic effects due to PM(DEE) exposure occurred including decreased numbers of white blood cells and reduced von Willebrand factor protein in the circulation. In addition, lung tissue factor activity is reduced in conjunction with reduced lung tissue thrombin generation. To what extent these alterations contribute to thrombotic effects and vascular diseases remains to be established. In conclusion, prolonged exposure to traffic-related PM in healthy animals may not be detrimental due to various biological adaptive response mechanisms. PMID:21126152

  4. Two-phase treatment of patients with crossbite and tendency toward skeletal Class III malocclusion*

    PubMed Central

    Bayerl, Maria de Lourdes Machado

    2014-01-01

    Angle Class III malocclusion is characterized by an inadequate anteroposterior dental relationship which may or may not be accompanied by skeletal changes. In general, patients are distressed by a significantly compromised facial aspect which, when associated with a deficient middle third, encourages patients to seek treatment. This article reports a two-phase treatment carried out in a female patient aged six years and six months with a tendency towards a Class III skeletal pattern. This case was presented to the Brazilian Board of Orthodontics and Facial Orthopedics (BBO). It is representative of the Discrepancy Index (DI) category, and fulfills part of the requirements for obtaining BBO Diploma. PMID:25279531

  5. Functional design criteria for Project W-252, Phase II Liquid Effluent Treatment and Disposal: Revision 1

    SciTech Connect

    Hatch, C.E.

    1994-11-10

    This document provides the functional design criteria required for the Phase 2 Liquid Effluent Treatment and Disposal Project, Project W-252. Project W-252 shall provide new facilities and existing facility modifications required to implement Best Available Technology/All Known, Available, and Reasonable Methods of Prevention, Control, and Treatment (BAT/AKART) for the 200 East Phase II Liquid Effluent Streams. The project will also provide a 200 East Area Phase II Effluent Collection System (PTECS) for connection to a disposal system for relevant effluent streams to which BAT/AKART has been applied. Liquid wastestreams generated in the 200 East Area are currently discharged to the soil column. Included in these wastestreams are cooling water, steam condensate, raw water, and sanitary wastewaters. It is the policy of the DOE that the use of soil columns to treat and retain radionuclides and nonradioactive contaminants be discontinued at the earliest practical time in favor of wastewater treatment and waste minimization. In 1989, the DOE entered into an interagency agreement with Ecology and EPA. This agreement is referred to as the Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement). Project W-252 is one of the projects required to achieve the milestones set forth in the Tri-Party Agreement. One of the milestones requires BAT/AKART implementation for Phase II streams by October 1997. This Functional Design Criteria (FDC) document provides the technical baseline required to initiate Project W-252 to meet the Tri-Party Agreement milestone for the application of BAT/AKART to the Phase II effluents.

  6. Halide based shock-wave treatment of fluid-rich natural phases

    NASA Astrophysics Data System (ADS)

    Schlothauer, T.; Schimpf, C.; Brendler, E.; Keller, K.; Kroke, E.; Heide, G.

    2015-11-01

    For the synthesis of high pressure phases from natural minerals and the shock wave treatment of fluid bearing phases a halide based method was developed. The experiments were performed in the pressure range between 25 and 162 GPa with a success rate for the new method of 100% for the new method. Based on the Impedance Corrected Sample Recovery Capsule under avoiding the adiabatic decompression a direct comparison between different loading paths and sample holder geometries is possible. The recovered samples show neither indications of melting in the case of kaolinite and very limited degassing in the case of carbonates. The recovery of amorphous water bearing Al-Si-phases with Aluminum in four-, five- and six-fold coordination was possible. The samples were analyzed with scanning electron microscopy, x-ray diffraction, nuclear-magnetic-resonance- and infra-red-spectroscopy and the results were directly compared.

  7. Early responses of human cancer cells upon photodynamic treatment monitored by laser phase microscopy

    NASA Astrophysics Data System (ADS)

    Roelofs, Theo A.; Graschew, Georgi; Perevedentseva, Elena V.; Rakowsky, Stefan; Dressler, Cathrin; Beuthan, Juergen; Schlag, Peter M.

    2001-04-01

    Photodynamic treatment of cancer cells is known to eventually cause cell death in most cases. The precise pathways and the time course seem to vary among different cell types and modes of photodynamic treatment. In this contribution, the focus was put on the responses of human colon carcinoma cells HCT-116 within the first 15 minutes after laser irradiation in the presence of Photofrin« II (PII). To monitor the cell response in this early time period laser phase microscopic imaging was used, a method sensitive to changes in overall cell shape and intracellular structures, mediated by changes in the local refractive index. Laser irradiation of cells loaded with PII induced a significant reduction of the phase shifts, which probably reflects the induced damage to the different cellular membrane structures. The data suggest that even within the first 30 s after the onset of laser illumination, a significant reduction of the phase shifts can be detected. These results underline that laser phase microscopy is a suitable diagnostic tool for cellular research, also in the early time domain.

  8. Phase II Pilot Study of Bevacizumab in Combination with Temozolomide and Regional Radiation Therapy for Up-Front Treatment of Patients With Newly Diagnosed Glioblastoma Multiforme: Interim Analysis of Safety and Tolerability

    SciTech Connect

    Lai, Albert Filka, Emese; McGibbon, Bruce; Nghiemphu, Phioanh Leia; Graham, Carrie; Yong, William H.; Mischel, Paul; Liau, Linda M.; Bergsneider, Marvin; Pope, Whitney; Selch, Michael; Cloughesy, Tim

    2008-08-01

    Purpose: To assess interim safety and tolerability of a 10-patient, Phase II pilot study using bevacizumab (BV) in combination with temozolomide (TMZ) and regional radiation therapy (RT) in the up-front treatment of patients with newly diagnosed glioblastoma. Methods and Materials: All patients received standard external beam regional RT of 60.0 Gy in 30 fractions started within 3 to 5 weeks after surgery. Concurrently TMZ was given daily at 75 mg/m{sup 2} for 42 days during RT, and BV was given every 2 weeks at 10 mg/kg starting with the first day of RT/TMZ. After a 2-week interval upon completion of RT, the post-RT phase commenced with resumption of TMZ at 150 to 200 mg/m{sup 2} for 5 days every 4 weeks and continuation of BV every 2 weeks. Results: For these 10 patients, toxicities were compiled until study discontinuation or up to {approx}40 weeks from initial study treatment for those remaining on-study. In terms of serious immediate or delayed neurotoxicity, 1 patient developed presumed radiation-induced optic neuropathy. Among the toxicities that could be potentially treatment related, relatively high incidences of fatigue, myelotoxicity, wound breakdown, and deep venous thrombosis/pulmonary embolism were observed. Conclusion: The observed toxicities were acceptable to continue enrollment toward the overall target group of 70 patients. Preliminary efficacy analysis shows encouraging mean progression-free survival. At this time data are not sufficient to encourage routine off-label use of BV combined with TMZ/RT in the setting of newly diagnosed glioblastoma without longer follow-up, enrollment of additional patients, and thorough efficacy assessment.

  9. Acupuncture as a primary and independent treatment in the acute phases of sudden sensorineural hearing loss

    PubMed Central

    Jin, Yuanyuan; Lu, Ming

    2016-01-01

    Abstract Sudden sensorineural hearing loss (SSHL) is an otological emergency defined as a rapid hearing loss, seriously affects patient's social life. To data, no study has reported the treatment by acupuncture alone in the acute phase. In this report, Acupuncture and Moxibustion therapy of excitation-focus transfer is outlined. The patient was a 26-year-old young woman who had an SSHL coupled with ear fullness. The patient had no past medical history, but she had undergone variable emotions and had a history of excessive noise exposure. The patient refused to receive any medicine especially steroids and hyperbaric oxygen therapy. She just only received acupuncture treatment. Her symptoms and outcome measurements were improved every week and completely recovered after the last week. Even though the article presents a single case and is based on self-reports, there are very clear trends on how patients with SSHL responded to acupuncture treatments. PMID:27368045

  10. "Poker" association of weekly alternating 5-fluorouracil, irinotecan, bevacizumab and oxaliplatin (FIr-B/FOx) in first line treatment of metastatic colorectal cancer: a phase II study

    PubMed Central

    2010-01-01

    Background This phase II study investigated efficacy and safety of weekly alternating Bevacizumab (BEV)/Irinotecan (CPT-11) or Oxaliplatin (OHP) associated to weekly 5-Fluorouracil (5-FU) in first line treatment of metastatic colorectal carcinoma (MCRC). Methods Simon two-step design: delta 20% (p0 50%, p1 70%), power 80%, α 5%, β 20%. Projected objective responses (ORR): I step, 8/15 patients (pts); II step 26/43 pts. Schedule: weekly 12 h-timed-flat-infusion/5-FU 900 mg/m2, days 1-2, 8-9, 15-16, 22-23; CPT-11 160 mg/m2 plus BEV 5 mg/kg, days 1,15; OHP at three dose-levels, 60-70-80 mg/m2, days 8, 22; every 4 weeks. Results Fifty consecutive, unselected pts < 75 years were enrolled: median age 63; young-elderly (yE) 24 (48%); liver metastases (LM) 33 pts, 66% Achieved OHP recommended dose, 80 mg/m2. ORR 82% intent-to-treat and 84% as-treated analysis. Median progression-free survival 12 months. Equivalent efficacy was obtained in yE pts. Liver metastasectomies were performed in 26% of all pts and in 39% of pts with LM. After a median follow-up of 21 months, median overall survival was 28 months. Cumulative G3-4 toxicities per patient: diarrhea 28%, mucositis 6%, neutropenia 10%, hypertension 2%. They were equivalent in yE pts. Limiting toxicity syndromes (LTS), consisting of the dose-limiting toxicity, associated or not to G2 or limiting toxicities: 44% overall, 46% in yE. Multiple versus single site LTS, respectively: overall, 24% versus 20%; yE pts, 37.5% versus 8%. Conclusion Poker combination shows high activity and efficacy in first line treatment of MCRC. It increases liver metastasectomies rate and can be safely administered. Trial registration Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali (OsSC) Agenzia Italiana del Farmaco (AIFA) Numero EudraCT 2007-004946-34 PMID:20958992

  11. Chelation efficacy and erythroid response during deferasirox treatment in patients with myeloproliferative neoplasms in fibrotic phase.

    PubMed

    Latagliata, Roberto; Montagna, Chiara; Porrini, Raffaele; Di Veroli, Ambra; Leonetti, Sabrina Crescenzi; Niscola, Pasquale; Ciccone, Fabrizio; Spadea, Antonio; Breccia, Massimo; Maurillo, Luca; Rago, Angela; Spirito, Francesca; Cedrone, Michele; De Muro, Marianna; Montanaro, Marco; Andriani, Alessandro; Bagnato, Antonino; Montefusco, Enrico; Alimena, Giuliana

    2016-06-01

    At present, very few data are available on deferasirox (DFX) in the treatment of patients with Philadelphia-negative myeloproliferative neoplasms in fibrotic phase (FP-MPN) and transfusion dependence. To address this issue, a retrospective analysis of 28 patients (22 male and 6 female) with FP-MPN and iron overload secondary to transfusion dependence was performed, based on patients enrolled in the database of our regional cooperative group who received treatment with DFX. DFX was started after a median interval from diagnosis of 12.8 months (IR 7.1-43.1) with median ferritin values of 1415 ng/mL (IR 1168-1768). Extra-hematological toxicity was reported in 16 of 28 patients (57.1%), but only two patients discontinued treatment due to toxicity. Among 26 patients evaluable for response (≥6 months of treatment), after a median treatment period of 15.4 months (IR 8.1-22.3), 11 patients (42.3%) achieved a stable and consistent reduction in ferritin levels <1000 ng/mL. As for hematological improvement, 6 of 26 patients (23%) showed a persistent (>3 months) rise of Hb levels >1.5 g/dL, with disappearance of transfusion dependence in four cases. Treatment with DFX is feasible and effective in FP-MPN with iron overload. Moreover, in this setting, an erythroid response can occur in a significant proportion of patients. PMID:26277477

  12. Coarsening Kinetics and Morphological Evolution in a Two-Phase Titanium Alloy During Heat Treatment

    NASA Astrophysics Data System (ADS)

    Xu, Jianwei; Zeng, Weidong; Jia, Zhiqiang; Sun, Xin; Zhao, Yawei

    2016-03-01

    The effects of alpha/beta heat treatment on microstructure evolution of Ti-17 alloy with a lamellar colony structure are established. Heat treatment experiments are conducted at 1103 or 1063 K for times ranging from 10 min to 8 h. The main features of microstructure evolution during heat treatment comprise static globularization and coarsening of primary alpha phase. Such behaviors can be accelerated by higher heat treatment temperature. Furthermore, globularization and coarsening behaviors show a faster rate at higher prestrain. In order to better understand the microstructure evolution of Ti-17 alloy during alpha/beta heat treatment, static globularization and coarsening behaviors are modeled in the theoretical frame of the Johnson-Mehl-Avarmi-Kolmogorov (JMAK) and Lifshitz-Slyozov-Wagner (LSW) theories, respectively. The JMAK and LSW kinetics parameters are derived under different experimental conditions. Agreements between measurements and predictions are found, indicating that the JMAK and LSW theories can be used to predict and trace static globularization and coarsening processes of Ti-17 alloy during alpha/beta heat treatment.

  13. Effects of 4-Week Training Intervention with Unknown Loads on Power Output Performance and Throwing Velocity in Junior Team Handball Players

    PubMed Central

    Sabido, Rafael; Hernández-Davó, Jose Luis; Botella, Javier; Moya, Manuel

    2016-01-01

    Purpose To compare the effect of 4-week unknown vs known loads strength training intervention on power output performance and throwing velocity in junior team handball players. Methods Twenty-eight junior team-handball players (17.2 ± 0.6 years, 1.79 ± 0.07 m, 75.6 ± 9.4 kg)were divided into two groups (unknown loads: UL; known loads: KL). Both groups performed two sessions weekly consisting of four sets of six repetitions of the bench press throw exercise, using the 30%, 50% and 70% of subjects’ individual 1 repetition maximum (1RM). In each set, two repetitions with each load were performed, but the order of the loads was randomised. In the KL group, researchers told the subjects the load to mobilise prior each repetition, while in the UL group, researchers did not provide any information. Maximal dynamic strength (1RM bench press), power output (with 30, 50 and 70% of 1RM) and throwing velocity (7 m standing throw and 9 m jumping throw) were assessed pre- and post-training intervention. Results Both UL and KL group improved similarly their 1RM bench press as well as mean and peak power with all loads. There were significant improvements in power developed in all the early time intervals measured (150 ms) with the three loads (30, 50, 70% 1RM) in the UL group, while KL only improved with 30% 1RM (all the time intervals) and with 70% 1RM (at certain time intervals). Only the UL group improved throwing velocity in both standing (4.7%) and jumping (5.3%) throw (p > 0.05). Conclusions The use of unknown loads has led to greater gains in power output in the early time intervals as well as to increases in throwing velocity compared with known loads. Therefore unknown loads are of significant practical use to increase both strength and in-field performance in a short period of training. PMID:27310598

  14. Effects of 4 Weeks of High-Intensity Interval Training and β-Hydroxy-β-Methylbutyric Free Acid Supplementation on the Onset of Neuromuscular Fatigue.

    PubMed

    Miramonti, Amelia A; Stout, Jeffrey R; Fukuda, David H; Robinson, Edward H; Wang, Ran; La Monica, Michael B; Hoffman, Jay R

    2016-03-01

    This study investigated the effects of high-intensity interval training (HIIT) and β-hydroxy-β-methylbutyric free acid (HMB) supplementation on physical working capacity at the onset of neuromuscular fatigue threshold (PWC(FT)). Thirty-seven participants (22 men, 15 women; 22.8 ± 3.4 years) completed an incremental cycle ergometer test (graded exercise test [GXT]); electromyographic amplitude from the right vastus lateralis was recorded. Assessments occurred preceding (PRE) and after 4 weeks of supplementation (POST). Participants were randomly assigned to control (C, n = 9), placebo (P, n = 14), or supplementation (S, n = 14) groups. Both P and S completed 12 HIIT sessions, whereas C maintained normal diet and activity patterns. The PWC(FT) (W) was determined using the maximal perpendicular distance (D(MAX)) method. Electromyographic amplitude (μVrms) over time was used to generate a cubic regression. Onset of fatigue (TF) was the x-value of the point on the regression that was at D(MAX) from a line between the first and last data points. The PWC(FT) was estimated using TF and GXT power-output increments. The 2-way analysis of variance (ANOVA) (group × time) resulted in a significant interaction for PWC(FT) (F = 6.69, p = 0.004). Post hoc analysis with 1-way ANOVA resulted in no difference in PWC(FT) among groups at PRE (F = 0.87, p = 0.43); however, a difference in PWC(FT) was shown for POST (F = 5.46, p = 0.009). Post hoc analysis among POST values revealed significant differences between S and both P (p = 0.034) and C (p = 0.003). No differences (p = 0.226) were noted between P and C. Paired samples t-tests detected significant changes after HIIT for S (p < 0.001) and P (p = 0.016), but no change in C (p = 0.473). High-intensity interval training increased PWC(FT), but HMB with HIIT was more effective than HIIT alone. Furthermore, it seems that adding HMB supplementation with HIIT in untrained men and women may further improve endurance performance

  15. Rapid phase-correlated rescanning irradiation improves treatment time in carbon-ion scanning beam treatment under irregular breathing

    NASA Astrophysics Data System (ADS)

    Mori, Shinichiro; Furukawa, Takuji

    2016-05-01

    To shorten treatment time in pencil beam scanning irradiation, we developed rapid phase-controlled rescanning (rPCR), which irradiates two or more isoenergy layers in a single gating window. Here, we evaluated carbon-ion beam dose distribution with rapid and conventional PCR (cPCR). 4 dimensional computed tomography (4DCT) imaging was performed on 12 subjects with lung or liver tumors. To compensate for intrafractional range variation, the field-specific target volume (FTV) was calculated using 4DCT within the gating window (T20–T80). We applied an amplitude-based gating strategy, in which the beam is on when the tumor is within the gating window defined by treatment planning. Dose distributions were calculated for layered phase-controlled rescanning under an irregular respiratory pattern, although a single 4DCT data set was used. The number of rescannings was eight times. The prescribed doses were 48 Gy(RBE)/1 fr (where RBE is relative biological effectiveness) delivered via four beam ports to the FTV for the lung cases and 45 Gy(RBE)/2 fr delivered via two beam ports to the FTV for the liver cases. In the liver cases, the accumulated dose distributions showed an increased magnitude of hot/cold spots with rPCR compared with cPCR. The results of the dose assessment metrics for the cPCR and rPCR were very similar. The D 95, D max, and D min values (cPCR/rPCR) averaged over all the patients were 96.3  ±  0.9%/96.0  ±  1.2%, 107.3  ±  3.6%/107.1  ±  2.9%, and 88.8  ±  3.2%/88.1  ±  3.1%, respectively. The treatment times in cPCR and rPCR were 110.7 s and 53.5 s, respectively. rPCR preserved dose conformation under irregular respiratory motion and reduced the total treatment time compared with cPCR.

  16. Rapid phase-correlated rescanning irradiation improves treatment time in carbon-ion scanning beam treatment under irregular breathing.

    PubMed

    Mori, Shinichiro; Furukawa, Takuji

    2016-05-21

    To shorten treatment time in pencil beam scanning irradiation, we developed rapid phase-controlled rescanning (rPCR), which irradiates two or more isoenergy layers in a single gating window. Here, we evaluated carbon-ion beam dose distribution with rapid and conventional PCR (cPCR). 4 dimensional computed tomography (4DCT) imaging was performed on 12 subjects with lung or liver tumors. To compensate for intrafractional range variation, the field-specific target volume (FTV) was calculated using 4DCT within the gating window (T20-T80). We applied an amplitude-based gating strategy, in which the beam is on when the tumor is within the gating window defined by treatment planning. Dose distributions were calculated for layered phase-controlled rescanning under an irregular respiratory pattern, although a single 4DCT data set was used. The number of rescannings was eight times. The prescribed doses were 48 Gy(RBE)/1 fr (where RBE is relative biological effectiveness) delivered via four beam ports to the FTV for the lung cases and 45 Gy(RBE)/2 fr delivered via two beam ports to the FTV for the liver cases. In the liver cases, the accumulated dose distributions showed an increased magnitude of hot/cold spots with rPCR compared with cPCR. The results of the dose assessment metrics for the cPCR and rPCR were very similar. The D 95, D max, and D min values (cPCR/rPCR) averaged over all the patients were 96.3  ±  0.9%/96.0  ±  1.2%, 107.3  ±  3.6%/107.1  ±  2.9%, and 88.8  ±  3.2%/88.1  ±  3.1%, respectively. The treatment times in cPCR and rPCR were 110.7 s and 53.5 s, respectively. rPCR preserved dose conformation under irregular respiratory motion and reduced the total treatment time compared with cPCR. PMID:27100312

  17. Investigation of stripping of volatile organic contaminants in municipal wastewater treatment systems, Phase II

    SciTech Connect

    Thompson, D.

    1990-01-01

    Volatile organic contaminants (VOCs) are the largest group of compounds on the effluent monitoring priority pollutant list and are among the most frequently detected in raw wastewater. Their removal by treatment facilities is a major concern in Ontario's Municipal Industrial Strategy for Abatement (MISA) program. In 1987 an investigation of VOC stripping at water pollution control plants was begun. Phase I concluded that many VOCs are stripped from wastewater treatment plants. Phase II was conducted from January 1988 to April 1989 and consisted of a validation of the accuracy of sampling and analytical protocols used in Phase I; a determination of the relative importance of stripping, biological removal and sorption on to secondary sludge from activated sludge aeration basins; and an examination of the impact of the diffuser type (fine or coarse bubble diffusers), airflow rate and solids retention time on VOC stripping. An experimental design was developed using tap water dosed with 10 candidate VOCs as the aeration basin influent; Burlington Skyway wastewater; and Toronto Highland Creek wastewater.

  18. Aptamer-based Proteomic Signature of Intensive Phase Treatment Response in Pulmonary Tuberculosis

    PubMed Central

    Nahid, Payam; Bliven-Sizemore, Erin; Jarlsberg, Leah G.; Mary, A; Groote, De; Johnson, John L.; Muzanyi, Grace; Engle, Melissa; Weiner, Marc; Janjic, Nebojsa; Sterling, David G.; Ochsner, Urs A.

    2014-01-01

    Background New drug regimens of greater efficacy and shorter duration are needed for tuberculosis (TB) treatment. The identification of accurate, quantitative, non-culture based markers of treatment response would improve the efficiency of Phase 2 TB drug testing. Methods In an unbiased biomarker discovery approach, we applied a highly multiplexed, aptamer-based, proteomic technology to analyze serum samples collected at baseline and after 8 weeks of treatment from 39 patients with pulmonary TB from Kampala, Uganda enrolled in a Centers for Disease Control and Prevention (CDC) TB Trials Consortium Phase 2B treatment trial. Results We identified protein expression differences associated with 8-week culture status, including Coagulation Factor V, SAA, XPNPEP1, PSME1, IL-11 Rα, HSP70, Galectin-8, α2-Antiplasmin, ECM1, YES, IGFBP-1, CATZ, BGN, LYNB, and IL-7. Markers noted to have differential changes between responders and slow-responders included nectin-like protein 2, EphA1 (Ephrin type-A receptor 1), gp130, CNDP1, TGF-b RIII, MRC2, ADAM9, and CDON. A logistic regression model combining markers associated with 8-week culture status revealed an ROC curve with AUC=0.96, sensitivity=0.95 and specificity=0.90. Additional markers showed differential changes between responders and slow-responders (nectin-like protein), or correlated with time-to-culture-conversion (KLRK1). Conclusions Serum proteins involved in the coagulation cascade, neutrophil activity, immunity, inflammation, and tissue remodeling were found to be associated with TB treatment response. A quantitative, non-culture based, five-marker signature predictive of 8-week culture status was identified in this pilot study. PMID:24629635

  19. Phase 2 THOR Steam Reforming Tests for Sodium Bearing Waste Treatment

    SciTech Connect

    Nicholas R. Soelberg

    2004-01-01

    About one million gallons of acidic, hazardous, and radioactive sodium-bearing waste is stored in stainless steel tanks at the Idaho Nuclear Technology and Engineering Center (INTEC), which is a major operating facility of the Idaho National Engineering and Environmental Laboratory. Steam reforming is a candidate technology being investigated for converting the waste into a road ready waste form that can be shipped to the Waste Isolation Pilot Plant in New Mexico for interment. A steam reforming technology patented by Studsvik, Inc., and licensed to THOR Treatment Technologies has been tested in two phases using a Department of Energy-owned fluidized bed test system located at the Science Applications International Corporation (SAIC) Science and Technology Applications Research Center located in Idaho Falls, Idaho. The Phase 1 tests were reported earlier in 2003. The Phase 2 tests are reported here. For Phase 2, the process feed rate, stoichiometry, and chemistry were varied to identify and demonstrate process operation and product characteristics under different operating conditions. Two test series were performed. During the first series, the process chemistry was designed to produce a sodium carbonate product. The second series was designed to produce a more leach-resistant, mineralized sodium aluminosilicate product. The tests also demonstrated the performance of a MACT-compliant off-gas system.

  20. Profile of acotiamide in the treatment of functional dyspepsia

    PubMed Central

    Ueda, Masahiro; Iwasaki, Eisuke; Suzuki, Hidekazu

    2016-01-01

    Efficacy of acotiamide for improving symptoms in patients with functional dyspepsia was shown by several clinical trials. In a randomized, double-blind, placebo-controlled, parallel-group comparative Phase III trial conducted in Japan, 100 mg of acotiamide three times a day for 4 weeks was more effective than a placebo for improving symptoms, and quality of life. Acotiamide was well-tolerated treatment, with no significant adverse events. The aim of this review was to summarize the current evidence of the efficacy of acotiamide in the treatment of patients with functional dyspepsia. PMID:27103837

  1. Safety and Clinical Activity of a Combination Therapy Comprising Two Antibody-Based Targeting Agents for the Treatment of Non-Hodgkin Lymphoma: Results of a Phase I/II Study Evaluating the Immunoconjugate Inotuzumab Ozogamicin With Rituximab

    PubMed Central

    Fayad, Luis; Offner, Fritz; Smith, Mitchell R.; Verhoef, Gregor; Johnson, Peter; Kaufman, Jonathan L.; Rohatiner, Ama; Advani, Anjali; Foran, James; Hess, Georg; Coiffier, Bertrand; Czuczman, Myron; Giné, Eva; Durrant, Simon; Kneissl, Michelle; Luu, Kenneth T.; Hua, Steven Y.; Boni, Joseph; Vandendries, Erik; Dang, Nam H.

    2013-01-01

    Purpose Inotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. We performed a phase I/II study to determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics of INO plus rituximab (R-INO) for treatment of relapsed/refractory CD20+/CD22+ B-cell non-Hodgkin lymphoma (NHL). Patients and Methods A dose-escalation phase to determine the MTD of R-INO was followed by an expanded cohort to further evaluate the efficacy and safety at the MTD. Patients with relapsed follicular lymphoma (FL), relapsed diffuse large B-cell lymphoma (DLBCL), or refractory aggressive NHL received R-INO every 4 weeks for up to eight cycles. Results In all, 118 patients received one or more cycles of R-INO (median, four cycles). Most common grade 3 to 4 adverse events were thrombocytopenia (31%) and neutropenia (22%). Common low-grade toxicities included hyperbilirubinemia (25%) and increased AST (36%). The MTD of INO in combination with rituximab (375 mg/m2) was confirmed to be the same as that for single-agent INO (1.8 mg/m2). Treatment at the MTD yielded objective response rates of 87%, 74%, and 20% for relapsed FL (n = 39), relapsed DLBCL (n = 42), and refractory aggressive NHL (n = 30), respectively. The 2-year progression-free survival (PFS) rate was 68% (median, not reached) for FL and 42% (median, 17.1 months) for relapsed DLBCL. Conclusion R-INO demonstrated high response rates and long PFS in patients with relapsed FL or DLBCL. This and the manageable toxicity profile suggest that R-INO may be a promising option for CD20+/CD22+ B-cell NHL. PMID:23295790

  2. Improving the treatment of non-aqueous phase TCE in low permeability zones with permanganate.

    PubMed

    Chokejaroenrat, Chanat; Comfort, Steve; Sakulthaew, Chainarong; Dvorak, Bruce

    2014-03-15

    Treating dense non-aqueous phase liquids (DNAPLs) embedded in low permeability zones (LPZs) is a particularly challenging issue for injection-based remedial treatments. Our objective was to improve the sweeping efficiency of permanganate (MnO4(-)) into LPZs to treat high concentrations of TCE. This was accomplished by conducting transport experiments that quantified the penetration of various permanganate flooding solutions into a LPZ that was spiked with non-aqueous phase (14)C-TCE. The treatments we evaluated included permanganate paired with: (i) a shear-thinning polymer (xanthan); (ii) stabilization aids that minimized MnO2 rind formation and (iii) a phase-transfer catalyst. In addition, we quantified the ability of these flooding solutions to improve TCE destruction under batch conditions by developing miniature LPZ cylinders that were spiked with (14)C-TCE. Transport experiments showed that MnO4(-) alone was inefficient in penetrating the LPZ and reacting with non-aqueous phase TCE, due to a distinct and large MnO2 rind that inhibited the TCE from further oxidant contact. By including xanthan with MnO4(-), the sweeping efficiency increased (90%) but rind formation was still evident. By including the stabilization aid, sodium hexametaphosphate (SHMP) with xanthan, permanganate penetrated 100% of the LPZ, no rind was observed, and the percentage of TCE oxidized increased. Batch experiments using LPZ cylinders allowed longer contact times between the flooding solutions and the DNAPL and results showed that SHMP+MnO4(-) improved TCE destruction by ∼16% over MnO4(-) alone (56.5% vs. 40.1%). These results support combining permanganate with SHMP or SHMP and xanthan as a means of treating high concentrations of TCE in low permeable zones. PMID:24491441

  3. Treatment with Benznidazole during the Chronic Phase of Experimental Chagas' Disease Decreases Cardiac Alterations

    PubMed Central

    Garcia, Simone; Ramos, Carolina O.; Senra, Juliana F. V.; Vilas-Boas, Fabio; Rodrigues, Maurício M.; Campos-de-Carvalho, Antonio C.; Ribeiro-dos-Santos, Ricardo; Soares, Milena B. P.

    2005-01-01

    Chagas' disease, caused by Trypanosoma cruzi infection, is one of the main causes of death due to heart failure in Latin American countries. Benznidazole, the chemotherapeutic agent most often used for the treatment of chagasic patients, is highly toxic and has limited efficacy, especially in the chronic phase of the disease. In the present study we used a mouse model of chronic Chagas' disease to investigate the effects of benznidazole treatment during the chronic phase on disease progression. The hearts of benznidazole-treated mice had decreased parasitism and myocarditis compared to the hearts of untreated chagasic mice. Both groups of Trypanosoma cruzi-infected mice had significant alterations in their electrocardiograms compared to those of the healthy mice. However, untreated mice had significantly higher cardiac conduction disturbances than benznidazole-treated mice, including intraventricular conduction disturbances, atrioventricular blocks, and extrasystoles. The levels of antibodies against T. cruzi antigens (epimastigote extract, P2β, and trans-sialidase) as well as antibodies against peptides of the second extracellular loops of β1-adrenergic and M2-muscarinic cardiac receptors were also lower in the sera from benznidazole-treated mice than in the sera from untreated mice. These results demonstrate that treatment with benznidazole in the chronic phase of infection prevents the development of severe chronic cardiomyopathy, despite the lack of complete parasite eradication. In addition, our data highlight the role of parasite persistence in the development of chronic Chagas' disease and reinforce the importance of T. cruzi elimination in order to decrease or prevent the development of severe chagasic cardiomyopathy. PMID:15793134

  4. Treatment of reactive interfaces in pore-scale reactive transport with the phase-field method

    NASA Astrophysics Data System (ADS)

    Huber, C.; Di Palma, P. R.

    2014-12-01

    The two major challenges for continuum reactive transport models are the treatment of interfaces between different phases (multi-fluids like DNAPL-water, or solid-fluid) and the ability to model transient chemical gradients at the pore-scale. Pore-scale models allow us to deal naturally with chemical gradients at the discrete scale and they generally consider interfaces as boundary conditions that satisfy a local, but modified, mass balance equation. In other word grains do not take part in the mass balance of chemical species besides providing a boundary condition for the fluid. For instance, heterogeneous reactions at solid-fluid boundaries are framed as a balance between incoming chemical flux and reactions. Due to complex topology of interfaces in natural porous media, the treatment of heterogeneous reactions depends on the orientation of the interface and therefore requires a special care. It can become complicated and tedious especially when interfaces are allowed to evolve with time. Approaches such as the enthalpy method, which was developed for solving moving interfaces during melting processes, offer the advantage of a treatment that is independent of the shape of the moving interface. Similar methods have been used for modeling multiphase flows with diffuse interface successfully. Here, we expand on these approaches and introduce a phase-field approach to introduce heterogeneous reactions in single and multiphase reactive flows at the pore-scale. Mass conservation is solved in each phase and we introduce interface conditions as a source/sink term in the conservation equation rather than a boundary condition. The advantages are that the method becomes independent of the (time-dependent) topology of the interface and automatically enforces local mass conservation between the different constituents of the domain. We show validations of the model and applications to multispecies reactive transport, isotope fractionation during calcite growth and finally

  5. Feasibility of oral administration of S-1 as adjuvant chemotherapy in gastric cancer: 4-week S-1 administration followed by 2-week rest vs. 2-week administration followed by 1-week rest

    PubMed Central

    YAMATSUJI, TOMOKI; FUJIWARA, YASUHIRO; MATSUMOTO, HIDEO; HATO, SHINJI; NAMIKAWA, TSUTOMU; HANAZAKI, KAZUHIRO; TAKAOKA, MUNENORI; HAYASHI, JIRO; SHIGEMITSU, KAORI; YOSHIDA, KAZUHIRO; URAKAMI, ATSUSHI; UNO, FUTOSHI; NISHIZAKI, MASAHIKO; KAGAWA, SHUNSUKE; NINOMIYA, MOTOKI; FUJIWARA, TOSHIYOSHI; HIRAI, TOSHIHIRO; NAKAMURA, MASAFUMI; HAISA, MINORU; NAOMOTO, YOSHIO

    2015-01-01

    In 2006, the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) demonstrated that S-1 is an effective adjuvant therapy for gastric cancer. Following that study, S-1 has been used as the standard adjuvant therapy for gastric cancer in Japan. However, the 1-year completion rate was only 65.8% in the ACTS-GC study and feasibility remains a critical issue. We conducted a study to evaluate the feasibility of 2 weekly administration regimens of S-1 as adjuvant chemotherapy in gastric cancer. The criteria for eligibility included histologically proven stage II (excluding T1), IIIA or IIIB gastric cancer with D2 lymph-node dissection. The patients were randomly assigned to either arm A (S-1 administration for 4 weeks followed by 2 weeks of rest) or arm B (S-1 administration for 2 weeks followed by 1 week of rest). In each arm, treatment was continued for 12 months unless recurrence or severe adverse events were observed. The primary endpoint was feasibility (protocol treatment completion rate). The secondary endpoints were safety, relapse-free survival and overall survival. A total of 47 patients were assigned to arms A or B between May, 2008 and February, 2010. During the first interim analysis, the protocol treatment completion rates in arms A and B were 83 and 100%, respectively at 6 months and 49 and 89%, respectively, at 12 months (P=0.0046). Therefore, S-1 administration for 2 weeks followed by 1 week rest was more feasible as adjuvant chemotherapy in gastric cancer. Grade 3 adverse events in arm A included fatigue (8.0%), anorexia (8.0%), nausea (4.0%), vomiting (4.0%) and hand-foot syndrome (4.0%), whereas none were observed in arm B. There were no reported grade 4 adverse events in either arm. In conclusion, the 2-week S-1 administration followed by 1-week rest regimen appears to be a more feasible oral administration regimen for S-1 as adjuvant chemotherapy in gastric cancer. PMID:26137261

  6. Change of Mandibular Position during Two-Phase Orthodontic Treatment of Skeletal Class II in the Chinese Population

    PubMed Central

    Hägg, Urban; Wong, Ricky Wing Kit; Liao, Chongshan; Yang, Yanqi

    2015-01-01

    The aim of this study was to evaluate the change in mandibular position during a two-phase orthodontic treatment of skeletal Class II malocclusion. Thirty consecutively treated Chinese male adolescents who had undergone two-phase treatment with Herbst appliance and fixed appliance and fulfilled the specific selection criteria were sampled. Cephalograms taken at T0 (before treatment), T1 (at the end of functional appliance treatment), and T2 (at the end of fixed appliance treatment) were analyzed. The change in sagittal positioning of the mandible was 6.8±3.44 mm in phase I (T0-T1), 0.4±2.79 mm in phase II (T1-T2), and 7.2±4.61 mm in total. The mandible came forward in 100% of the patients at T1. In phase II, it came forward in one-third (positive group) remained unchanged in one-third (stable group) and went backward in one-third (negative group) of the patients. At T2, it came forward twice as much in the positive group compared to the negative group. Mandibular length was significantly increased in 100% of the patients in both phases. In conclusion, during the treatment with functional appliance, the mandibular prognathism increases in all patients, whereas during the treatment with fixed appliance there is no significant change in mandibular prognathism. PMID:25695103

  7. The Stability of CI02 as a Product of Gas Phase Decontamination Treatments

    SciTech Connect

    D. W. Simmons

    1994-09-01

    The gas phase decontamination project is investigating the use of chlorine trifluoride (ClF{sub 3}) to fluorinate nonvolatile uranium deposits to produce uranium hexafluoride (UF{sub 6}) gas. The potential existence of chlorine dioxide (ClO{sub 2}) during gas phase decontamination with ClF{sub 3} has been the subject of recent safety discussions. Some of the laboratory data collected during feasibility studies of the gas phase process has been evaluated for the presence of ClO{sub 2} in the product gas stream. The preliminary evidence to date can be summarized as follows: (1) ClO{sub 2} was not detected in the flow loop in the absence of ClF{sub 3}; (2) ClO{sub 2} was not detected in the static reactors in the absence of both ClF{sub 3} and ClF; and (3) ClO{sub 2} was detected in a static reactor in the absence of all fluorinating gases. The experimental evidence suggests that ClO{sub 2} will not exist in the presence of ClF{sub 3}, ClF, or UF{sub 6}. The data analyzed to date is insufficient to determine the stability of ClO{sub 2} in the presence of ClO{sub 2}F. Thermodynamic calculations of the ClF{sub 3} + H{sub 2}O system support the experimental evidence, and suggest that ClO{sub 2} will not exist in the presence of ClO{sub 2}F. Additional experimental efforts are needed to provide a better understanding of the gas phase ClF{sub 3} treatments and the product gases. However, preliminary evidence to date suggests that ClO{sub 2} should not be present as a product during the normal operations of the gas phase decontamination project.

  8. SLUDGE TREATMENT PROJECT PHASE 1 SLUDGE STORAGE OPTIONS ASSESSMENT OF T PLANT VERSUS ALTERNATE STORAGE FACILITY

    SciTech Connect

    RUTHERFORD WW; GEUTHER WJ; STRANKMAN MR; CONRAD EA; RHOADARMER DD; BLACK DM; POTTMEYER JA

    2009-04-29

    The CH2M HILL Plateau Remediation Company (CHPRC) has recommended to the U.S. Department of Energy (DOE) a two phase approach for removal and storage (Phase 1) and treatment and packaging for offsite shipment (Phase 2) of the sludge currently stored within the 105-K West Basin. This two phased strategy enables early removal of sludge from the 105-K West Basin by 2015, allowing remediation of historical unplanned releases of waste and closure of the 100-K Area. In Phase 1, the sludge currently stored in the Engineered Containers and Settler Tanks within the 105-K West Basin will be transferred into sludge transport and storage containers (STSCs). The STSCs will be transported to an interim storage facility. In Phase 2, sludge will be processed (treated) to meet shipping and disposal requirements and the sludge will be packaged for final disposal at a geologic repository. The purpose of this study is to evaluate two alternatives for interim Phase 1 storage of K Basin sludge. The cost, schedule, and risks for sludge storage at a newly-constructed Alternate Storage Facility (ASF) are compared to those at T Plant, which has been used previously for sludge storage. Based on the results of the assessment, T Plant is recommended for Phase 1 interim storage of sludge. Key elements that support this recommendation are the following: (1) T Plant has a proven process for storing sludge; (2) T Plant storage can be implemented at a lower incremental cost than the ASF; and (3) T Plant storage has a more favorable schedule profile, which provides more float, than the ASF. Underpinning the recommendation of T Plant for sludge storage is the assumption that T Plant has a durable, extended mission independent of the K Basin sludge interim storage mission. If this assumption cannot be validated and the operating costs of T Plant are borne by the Sludge Treatment Project, the conclusions and recommendations of this study would change. The following decision-making strategy, which is

  9. Rituximab for treatment of inhibitors in haemophilia A. A Phase II study.

    PubMed

    Leissinger, C; Josephson, C D; Granger, S; Konkle, B A; Kruse-Jarres, R; Ragni, M V; Journeycake, J M; Valentino, L; Key, N S; Gill, J C; McCrae, K R; Neufeld, E J; Manno, C; Raffini, L; Saxena, K; Torres, M; Marder, V; Bennett, C M; Assmann, S F

    2014-09-01

    The development of antibodies against infused factor VIII (FVIII) in patients with haemophilia A is a serious complication leading to poorly controlled bleeding and increased morbidity. No treatment has been proven to reduce high titre antibodies in patients who fail immune tolerance induction or are not candidates for it. The Rituximab for the Treatment of Inhibitors in Congenital Hemophilia A (RICH) study was a phase II trial to assess whether rituximab can reduce anamnestic FVIII antibody (inhibitor) titres. Male subjects with severe congenital haemophilia A and an inhibitor titre ≥5 Bethesda Units/ml (BU) following a FVIII challenge infusion received rituximab 375 mg/m² weekly for weeks 1 through 4. Post-rituximab inhibitor titres were measured monthly from week 6 through week 22 to assess treatment response. Of 16 subjects who received at least one dose of rituximab, three (18.8%) met the criteria for a major response, defined as a fall in inhibitor titre to <5 BU, persisting after FVIII re-challenge. One subject had a minor response, defined as a fall in inhibitor titre to <5 BU, increasing to 5-10 BU after FVIII re-challenge, but <50% of the original peak inhibitor titre. Rituximab is useful in lowering inhibitor levels in patients, but its effect as a solo treatment strategy is modest. Future studies are indicated to determine the role of rituximab as an adjunctive therapy in immune tolerisation strategies. PMID:24919980

  10. Laboratory investigation of aluminum solubility and solid-phase properties following alum treatment of lake waters.

    PubMed

    Berkowitz, Jacob; Anderson, Michael A; Graham, Robert C

    2005-10-01

    Water samples from two southern California lakes adversely affected by internal nutrient loading were treated with a 20 mg/L dose of Al3+ in laboratory studies to examine Al solubility and solid-phase speciation over time. Alum [Al2(SO4)3 . 18 H2O] applications to water samples from Big Bear Lake and Lake Elsinore resulted in a rapid initial decrease in pH and alkalinity followed by a gradual recovery in pH over several weeks. Dissolved Al concentrations increased following treatment, reaching a maximum of 2.54 mg/L after 17 days in Lake Elsinore water and 0.91 mg/L after 48 days in Big Bear Lake water; concentrations in both waters then decreased to <0.25 mg/L after 150 days. The solid phase was periodically collected and analyzed using X-ray diffraction (XRD), differential scanning calorimetry-thermogravimetric analysis (DSC-TGA), scanning electron microscopy (SEM), and surface area analyses to investigate the nature of the reaction products and crystallinity development over time. Poorly ordered, X-ray amorphous solid phases transformed over time to relatively well-ordered gibbsite, with strong diffraction peaks at 4.8 and 4.3 A. XRD also indicated the formation of a second (possibly aluminosilicate) crystalline phase after 150 days in Lake Elsinore water. Surface areas also decreased over time as crystals reordered to form gibbsite/microcrystalline gibbsite species. DSC-TGA results suggested that the initially formed amorphous Al(OH)3 underwent transformation to >45% gibbsite. These results were supported by geochemical modeling using Visual MINTEQ, with Al solubility putatively controlled by amorphous Al(OH)3 shortly after treatment and approaching that of microcrystalline gibbsite after about 150 days. These findings indicate that Al(OH)3 formed after alum treatment undergoes significant chemical and mineralogical changes that may alter its effectiveness as a reactive barrier to phosphorus release from lake sediments. PMID:16139325

  11. Multicenter, Randomized, Open-Label, Phase III Trial of Decitabine Versus Patient Choice, With Physician Advice, of Either Supportive Care or Low-Dose Cytarabine for the Treatment of Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    PubMed Central

    Kantarjian, Hagop M.; Thomas, Xavier G.; Dmoszynska, Anna; Wierzbowska, Agnieszka; Mazur, Grzegorz; Mayer, Jiri; Gau, Jyh-Pyng; Chou, Wen-Chien; Buckstein, Rena; Cermak, Jaroslav; Kuo, Ching-Yuan; Oriol, Albert; Ravandi, Farhad; Faderl, Stefan; Delaunay, Jacques; Lysák, Daniel; Minden, Mark; Arthur, Christopher

    2012-01-01

    Purpose This multicenter, randomized, open-label, phase III trial compared the efficacy and safety of decitabine with treatment choice (TC) in older patients with newly diagnosed acute myeloid leukemia (AML) and poor- or intermediate-risk cytogenetics. Patients and Methods Patients (N = 485) age ≥ 65 years were randomly assigned 1:1 to receive decitabine 20 mg/m2 per day as a 1-hour intravenous infusion for five consecutive days every 4 weeks or TC (supportive care or cytarabine 20 mg/m2 per day as a subcutaneous injection for 10 consecutive days every 4 weeks). The primary end point was overall survival (OS); the secondary end point was the complete remission (CR) rate plus the CR rate without platelet recovery (CRp). Adverse events (AEs) were recorded. Results The primary analysis with 396 deaths (81.6%) showed a nonsignificant increase in median OS with decitabine (7.7 months; 95% CI, 6.2 to 9.2) versus TC (5.0 months; 95% CI, 4.3 to 6.3; P = .108; hazard ratio [HR], 0.85; 95% CI, 0.69 to 1.04). An unplanned analysis with 446 deaths (92%) indicated the same median OS (HR, 0.82; 95% CI, 0.68 to 0.99; nominal P = .037). The CR rate plus CRp was 17.8% with decitabine versus 7.8% with TC (odds ratio, 2.5; 95% CI, 1.4 to 4.8; P = .001). AEs were similar for decitabine and cytarabine, although patients received a median of four cycles of decitabine versus two cycles of TC. The most common drug-related AEs with decitabine were thrombocytopenia (27%) and neutropenia (24%). Conclusion In older patients with AML, decitabine improved response rates compared with standard therapies without major differences in safety. An unplanned survival analysis showed a benefit for decitabine, which was not observed at the time of the primary analysis. PMID:22689805

  12. A single-institution phase II trial of radiation, temozolomide, erlotinib, and bevacizumab for initial treatment of glioblastoma

    PubMed Central

    Clarke, Jennifer L.; Molinaro, Annette M.; Phillips, Joanna J.; Butowski, Nicholas A.; Chang, Susan M.; Perry, Arie; Costello, Joseph F.; DeSilva, Ashley A.; Rabbitt, Jane E.; Prados, Michael D.

    2014-01-01

    Background Both the epidermal growth factor receptor and vascular endothelial growth factor pathways are frequently overexpressed in glioblastoma multiforme. This study combined bevacizumab, a vascular endothelial growth factor inhibitor, and erlotinib, an epidermal growth factor receptor inhibitor, with standard radiation and temozolomide (TMZ), with the goal of improving overall survival (OS). Methods Treatment consisted of fractionated radiotherapy to 60 Gy, with daily TMZ at 75 mg/m2/d and erlotinib 150–200 mg/d (or 500–600 mg/d for patients on enzyme-inducing antiepileptic drugs). Bevacizumab was given at 10 mg/kg every 2 weeks, starting ≥4 weeks after surgery. After radiotherapy, adjuvant TMZ was given at 200 mg/m2/d × 5d per 28-day cycle, with unchanged erlotinib and bevacizumab doses. Treatment continued until progression or for 12 months. Efficacy was compared against an institutional historical control. A sample of 55 patients was calculated to provide 85% power to detect a hazard ratio of 0.67 for OS. Results Fifty-nine patients were enrolled for efficacy analysis after a 15-patient safety lead-in. For the efficacy group, median age was 54 years; median KPS was 90. Gross total and subtotal resections were achieved in 33% and 53%, respectively. The most frequent related grade 3/4 adverse effects were lymphopenia, thrombocytopenia, neutropenia, diarrhea, weight loss, and fatigue. One patient died of disseminated aspergillosis. Median OS was 19.8 months (vs 18 mo for HC, P = .33) and median progression-free survival was 13.5 months (vs 8.6 mo for HC, P = .03). Conclusions The combination of bevacizumab, erlotinib, TMZ, and radiotherapy appears to be well tolerated and improved progression-free survival but did not reach the primary endpoint of improved OS. PMID:24637230

  13. Rotation of nilotinib and imatinib for first-line treatment of chronic phase chronic myeloid leukemia.

    PubMed

    Gugliotta, Gabriele; Castagnetti, Fausto; Breccia, Massimo; Gozzini, Antonella; Usala, Emilio; Carella, Angelo M; Rege-Cambrin, Giovanna; Martino, Bruno; Abruzzese, Elisabetta; Albano, Francesco; Stagno, Fabio; Luciano, Luigia; D'Adda, Mariella; Bocchia, Monica; Cavazzini, Francesco; Tiribelli, Mario; Lunghi, Monia; Pia Falcone, Antonietta; Musolino, Caterina; Levato, Luciano; Venturi, Claudia; Soverini, Simona; Cavo, Michele; Alimena, Giuliana; Pane, Fabrizio; Martinelli, Giovanni; Saglio, Giuseppe; Rosti, Gianantonio; Baccarani, Michele

    2016-06-01

    The introduction of second-generation tyrosine-kinase inhibitors (TKIs) has generated a lively debate on the choice of first-line TKI in chronic phase, chronic myeloid leukemia (CML). Despite the TKIs have different efficacy and toxicity profiles, the planned use of two TKIs has never been investigated. We report on a phase 2 study that was designed to evaluate efficacy and safety of a treatment alternating nilotinib and imatinib, in newly diagnosed BCR-ABL1 positive, chronic phase, CML patients. One hundred twenty-three patients were enrolled. Median age was 56 years. The probabilities of achieving a complete cytogenetic response, a major molecular response, and a deep molecular response (MR 4.0) by 2 years were 93%, 87%, and 61%, respectively. The 5-year overall survival and progression-free survival were 89%. Response rates and survival are in the range of those reported with nilotinib alone. Moreover, we observed a relatively low rate of cardiovascular adverse events (5%). These data show that the different efficacy and toxicity profiles of TKIs could be favorably exploited by alternating their use. Am. J. Hematol. 91:617-622, 2016. © 2016 Wiley Periodicals, Inc. PMID:26971721

  14. Novel agents and new combination treatments on phase I studies on solid tumors and pancreatic cancer.

    PubMed

    Strimpakos, Alexios S; Syrigos, Kostas N; Saif, Muhammad W

    2012-07-01

    Pancreatic cancer is a relatively rare malignancy with a very aggressive natural course, not restrained by the existing current treatments. At the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting, the results of few phase I clinical studies on solid tumors and pancreatic cancer were presented. In particular, in the field of immunotherapy, a pilot phase I study tested for first time a carcinoembryonic antigen (CEA)-based vaccine (Abstract #2561) on patients with pancreatic adenocarcinoma and another one the optimal dose and efficacy of trabedersen, an inhibitor of tissue growth factor-beta 2 (TGF-β2) aiming to enhance antitumor immune responses (Abstract #4034). Other phase I studies explored the pharmacokinetic and pharmacodynamic properties of an oral gemcitabine pro-drug (LY2334737; Abstract #2554), or of the combination of gemcitabine with sirolimus (Abstract #3096) or the combination of gemcitabine with an inhibitor of mitogen-activated protein kinase (MAPK), extracellular signal-regulated protein kinase (ERK) (MEK 1/2; Abstract #4034). PMID:22797386

  15. Hydrodynamical description of first-order phase transitions: Analytical treatment and numerical modeling

    NASA Astrophysics Data System (ADS)

    Skokov, V. V.; Voskresensky, D. N.

    2009-09-01

    Solutions of hydrodynamical equations are presented for an equation of state allowing for a first-order phase transition. The numerical analysis is supplemented by analytical treatment provided the system is close to the critical point. The processes of growth and dissolution of seeds of various sizes and shapes in meta-stable phases (like super-cooled vapor and super-heated liquid) are studied, as well as the dynamics of unstable modes in the spinodal region. We show that initially nonspherical seeds acquire spherical shape with passage of time. Applications to the description of the first-order phase transitions in nuclear systems, such as the nuclear gas-liquid transition occurring in low energy heavy-ion collisions and the hadron-quark transition in the high energy heavy-ion collisions are discussed. In both cases we point out the important role played by effects of viscosity and surface tension. It is shown that fluctuations dissolve and grow as if the fluid were effectively very viscous. Even in the spinodal region seeds may grow slowly due to viscosity and critical slowing down. This prevents the enhancement of fluctuations in the near-critical region, which is frequently considered as a signal of the critical point in heavy-ion collisions.

  16. Unbiased estimation in seamless phase II/III trials with unequal treatment effect variances and hypothesis-driven selection rules.

    PubMed

    Robertson, David S; Prevost, A Toby; Bowden, Jack

    2016-09-30

    Seamless phase II/III clinical trials offer an efficient way to select an experimental treatment and perform confirmatory analysis within a single trial. However, combining the data from both stages in the final analysis can induce bias into the estimates of treatment effects. Methods for bias adjustment developed thus far have made restrictive assumptions about the design and selection rules followed. In order to address these shortcomings, we apply recent methodological advances to derive the uniformly minimum variance conditionally unbiased estimator for two-stage seamless phase II/III trials. Our framework allows for the precision of the treatment arm estimates to take arbitrary values, can be utilised for all treatments that are taken forward to phase III and is applicable when the decision to select or drop treatment arms is driven by a multiplicity-adjusted hypothesis testing procedure. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. PMID:27103068

  17. In Situ Mercury Stabilization (ISMS) Treatment: Technology Maturation Project Phase I Status Report

    SciTech Connect

    Kalb,P.D.; Milian, L.

    2008-03-01

    further developed it has the potential for large-scale in-situ treatment of contaminated soils that could substantially reduce the prohibitive cost of thermal desorption and/or excavation and disposal. Licensing and spin-off technology development opportunities would then be viable. Depending on performance and regulatory acceptance, the treated mercury could either be excavated for disposal elsewhere or left in place as a stable alternative. Excavated spent treatment rods could be processed by the SPSS process to reduce the potential for dispersion and lower leachability even further. The Phase I objectives of the In Situ Mercury Stabilization Treatment Process Technology Maturation Project were to: (1) replicate the original bench-scale results that formed the basis for BNL's patent application, i.e., mercury contamination in soil will migrate to and react with 'rods' containing sulfur and/or sulfur compounds, (2) provide enough information to evaluate a decision to conduct further development, and (3) establish some of the critical parameters that require further technology maturation during Phase II. The information contained in this report summarizes the work conducted in Phase I to meet these objectives.

  18. Relationship between Acute Phase of Chronic Periodontitis and Meteorological Factors in the Maintenance Phase of Periodontal Treatment: A Pilot Study

    PubMed Central

    Takeuchi, Noriko; Ekuni, Daisuke; Tomofuji, Takaaki; Morita, Manabu

    2015-01-01

    The acute phase of chronic periodontitis may occur even in patients during supportive periodontal therapy. However, the details are not fully understood. Since the natural environment, including meteorology affects human health, we hypothesized that weather conditions may affect occurrence of acute phase of chronic periodontitis. The aim of this study was to investigate the relationship between weather conditions and acute phase of chronic periodontitis in patients under supportive periodontal therapy. Patients who were diagnosed with acute phase of chronic periodontitis under supportive periodontal therapy during 2011–2013 were selected for this study. We performed oral examinations and collected questionnaires and meteorological data. Of 369 patients who experienced acute phase of chronic periodontitis, 153 had acute phase of chronic periodontitis without direct-triggered episodes. When using the autoregressive integrated moving average model of time-series analysis, the independent covariant of maximum hourly range of barometric pressure, maximum hourly range of temperature, and maximum daily wind speed were significantly associated with occurrence of acute phase of chronic periodontitis (p < 0.05), and 3.1% of the variations in these occurrence over the study period were explained by these factors. Meteorological variables may predict occurrence of acute phase of chronic periodontitis. PMID:26251916

  19. Relationship between Acute Phase of Chronic Periodontitis and Meteorological Factors in the Maintenance Phase of Periodontal Treatment: A Pilot Study.

    PubMed

    Takeuchi, Noriko; Ekuni, Daisuke; Tomofuji, Takaaki; Morita, Manabu

    2015-08-01

    The acute phase of chronic periodontitis may occur even in patients during supportive periodontal therapy. However, the details are not fully understood. Since the natural environment, including meteorology affects human health, we hypothesized that weather conditions may affect occurrence of acute phase of chronic periodontitis. The aim of this study was to investigate the relationship between weather conditions and acute phase of chronic periodontitis in patients under supportive periodontal therapy. Patients who were diagnosed with acute phase of chronic periodontitis under supportive periodontal therapy during 2011-2013 were selected for this study. We performed oral examinations and collected questionnaires and meteorological data. Of 369 patients who experienced acute phase of chronic periodontitis, 153 had acute phase of chronic periodontitis without direct-triggered episodes. When using the autoregressive integrated moving average model of time-series analysis, the independent covariant of maximum hourly range of barometric pressure, maximum hourly range of temperature, and maximum daily wind speed were significantly associated with occurrence of acute phase of chronic periodontitis (p < 0.05), and 3.1% of the variations in these occurrence over the study period were explained by these factors. Meteorological variables may predict occurrence of acute phase of chronic periodontitis. PMID:26251916

  20. Therapeutic Immunization In HIV Infected Ugandans Receiving Stable Antiretroviral Treatment: A Phase I Safety Study4

    PubMed Central

    Kityo, Cissy; Bousheri, Stephanie; Akao, Juliette; Ssali, Francis; Byaruhanga, Rose; Ssewanyana, Isaac; Muloma, Prossy; Myalo, Sula; Magala, Rose; Lu, Yichen; Mugyenyi, Peter; Cao, Huyen

    2011-01-01

    Therapeutic immunizations in HIV infection may boost immunity during antiretroviral treatment. We report on the first therapeutic vaccine trial in Uganda, Africa. This open label Phase I trial was designed to assess the safety, tolerability and immunogenicity of a therapeutic HIV-1 vaccine candidate. Thirty HIV positive volunteers receiving a stable regimen of antiretroviral therapy with CD4 counts > 400 were recruited for the safety evaluation of LFn-p24C, a detoxified anthrax-derived polypeptide fused to the subtype C HIV gag protein p24. The vaccine was well tolerated and HIV RNA levels remained undetectable following three immunizations. CD4 counts in vaccine recipients were significantly higher compared to the control individuals after 12 months. HIV-specific responses were associated with higher gain in CD4 counts following LFn-p24C immunizations. Volunteers were subsequently asked to undergo a 30-day period of observed treatment interruption. 8/24 (30%) individuals showed no evidence of viral rebound during treatment interruption. All demonstrated prompt suppression of viral load following resumption of ART. Our data demonstrates the safety of LFn-p24C and suggests that adjunct therapeutic immunization may benefit select individuals in further boosting an immune response. PMID:21211581

  1. Follow-up of 6-10-Year-Old Stuttering Children after Lidcombe Program Treatment: A Phase I Trial

    ERIC Educational Resources Information Center

    Koushik, Sarita; Shenker, Rosalee; Onslow, Mark

    2009-01-01

    Purpose: This Phase I trial sought to establish (1) whether the Lidcombe Program is viable for school-age children, (2) whether there is any indication that it requires modification for school-age children, (3) whether treatment effects are durable, (4) how many treatment sessions appear to be required to significantly reduce stuttering frequency…

  2. Comparison of different numerical treatments for x-ray phase tomography of soft tissue from differential phase projections

    NASA Astrophysics Data System (ADS)

    Pelliccia, Daniele; Vaz, Raquel; Svalbe, Imants; Morgan, Kaye S.; Marathe, Shashidhara; Xiao, Xianghui; Assoufid, Lahsen; Anderson, Rebecca A.; Topczewski, Jacek; Bryson-Richardson, Robert J.

    2015-04-01

    X-ray imaging of soft tissue is made difficult by their low absorbance. The use of x-ray phase imaging and tomography can significantly enhance the detection of these tissues and several approaches have been proposed to this end. Methods such as analyzer-based imaging or grating interferometry produce differential phase projections that can be used to reconstruct the 3D distribution of the sample refractive index. We report on the quantitative comparison of three different methods to obtain x-ray phase tomography with filtered back-projection from differential phase projections in the presence of noise. The three procedures represent different numerical approaches to solve the same mathematical problem, namely phase retrieval and filtered back-projection. It is found that obtaining individual phase projections and subsequently applying a conventional filtered back-projection algorithm produces the best results for noisy experimental data, when compared with other procedures based on the Hilbert transform. The algorithms are tested on simulated phantom data with added noise and the predictions are confirmed by experimental data acquired using a grating interferometer. The experiment is performed on unstained adult zebrafish, an important model organism for biomedical studies. The method optimization described here allows resolution of weak soft tissue features, such as muscle fibers.

  3. Comparison of different numerical treatments for x-ray phase tomography of soft tissue from differential phase projections.

    PubMed

    Pelliccia, Daniele; Vaz, Raquel; Svalbe, Imants; Morgan, Kaye S; Marathe, Shashidhara; Xiao, Xianghui; Assoufid, Lahsen; Anderson, Rebecca A; Topczewski, Jacek; Bryson-Richardson, Robert J

    2015-04-21

    X-ray imaging of soft tissue is made difficult by their low absorbance. The use of x-ray phase imaging and tomography can significantly enhance the detection of these tissues and several approaches have been proposed to this end. Methods such as analyzer-based imaging or grating interferometry produce differential phase projections that can be used to reconstruct the 3D distribution of the sample refractive index. We report on the quantitative comparison of three different methods to obtain x-ray phase tomography with filtered back-projection from differential phase projections in the presence of noise. The three procedures represent different numerical approaches to solve the same mathematical problem, namely phase retrieval and filtered back-projection. It is found that obtaining individual phase projections and subsequently applying a conventional filtered back-projection algorithm produces the best results for noisy experimental data, when compared with other procedures based on the Hilbert transform. The algorithms are tested on simulated phantom data with added noise and the predictions are confirmed by experimental data acquired using a grating interferometer. The experiment is performed on unstained adult zebrafish, an important model organism for biomedical studies. The method optimization described here allows resolution of weak soft tissue features, such as muscle fibers. PMID:25802946

  4. Modeling stress-relaxation behavior of the periodontal ligament during the initial phase of orthodontic treatment.

    PubMed

    Romanyk, Dan L; Melenka, Garrett W; Carey, Jason P

    2013-09-01

    The periodontal ligament is the tissue that provides early tooth motion as a result of applied forces during orthodontic treatment: a force-displacement behavior characterized by an instantaneous displacement followed by a creep phase and a stress relaxation phase. Stress relaxation behavior is that which provides the long-term loading to and causes remodelling of the alveolar bone, which is responsible for the long-term permanent displacement of the tooth. In this study, the objective was to assess six viscoelastic models to predict stress relaxation behavior of rabbit periodontal ligament (PDL). Using rabbit stress relaxation data found in the literature, it was found that the modified superposition theory (MST) model best predicts the rabbit PDL behavior as compared to nonstrain-dependent and strain-dependent versions of the Burgers four-parameter and the five-parameter viscoelastic models, as well as predictions by Schapery's viscoelastic model. Furthermore, it is established that using a quadratic form for MST strain dependency provides more stable solutions than the cubic form seen in previous studies. PMID:23722595

  5. Influence of plasma treatment time on plasma induced vapor phase grafting modification of PBO fiber surface

    NASA Astrophysics Data System (ADS)

    Song, B.; Meng, L. H.; Huang, Y. D.

    2012-05-01

    The surface of poly-p-phenylene benzobisthiazole (PBO) fibers was treated through oxygen plasma induced vapor phase grafting (PIVPG) method under various oxygen plasma pre-treatment time conditions. The surface chemical composition, surface morphologies and surface free energy of pristine and treated PBO fibers were studied using X-ray photoelectron spectroscopy, atomic force microscopy, scanning electron microscopy, and Cahn DCAA system. The mechanics property of these fibers was evaluated by tensile strength and interfacial shear strength (IFSS). It was found that the surface characteristics of treated PBO fibers occurred significant change compare with the pristine PBO fibers. After treatment, the polar functional groups were introduced on the fiber surface. Carbon concentration decreased; oxygen concentration and elemental ratio of oxygen to carbon increased. Acrylic acid can react with the activated PBO fibers surface, which led to the fiber surface roughness increased. The surface free energy increased from 41.4 mN/m to 62.8 mN/m when PBO fibers were plasma pre-treated for 10 min, while the IFSS of PBO fibers with epoxy resin increased from 36.6 MPa to 55.8 MPa. Therefore, PIVPG can be used to enhance the interfacial bond between PBO fibers and epoxy resin.

  6. Electrocoagulation: Simply a Phase Separation Technology? The Case of Bronopol Compared to Its Treatment by EAOPs.

    PubMed

    Bocos, Elvira; Brillas, Enric; Sanromán, M Ángeles; Sirés, Ignasi

    2016-07-19

    Electrocoagulation (EC) has long been considered a phase separation process, well suited for industrial wastewater treatment since it causes a quick, drastic decay of organic matter content. This research demonstrates that EC also behaves, at least for some molecules like the industrial preservative bronopol, as an effective transformation technology able to yield several breakdown products. This finding has relevant environmental implications, pointing to EC as a greener process than described in literature. A thorough optimization of EC was performed with solutions of bronopol in a simulated water matrix, yielding the complete disappearance of the parent molecule within 20 min at 200 mA (∼20 mA/cm(2)), using Fe as the anode and cathode. A 25% of total organic carbon (TOC) abatement was attained as maximum, with bronopol being converted into bromonitromethane, bromochloromethane, formaldehyde and formic acid. N atoms were accumulated as NO3(-), whereas Br(-) was stable once released. This suggests that mediated oxidation by active chlorine, as well as by hydroxyl radicals resulting from its reaction with iron ions, is the main transformation mechanism. Aiming to enhance the mineralization, a sequential combination of EC with electro-Fenton (EF) as post-treatment process was proposed. EF with boron-doped diamond (BDD) anode ensured the gradual TOC removal under the action of (•)OH and BDD((•)OH), also transforming Br(-) into BrO3(-). PMID:27328254

  7. Phase impact factor: a novel parameter for determining optimal CT phase in 4D radiation therapy treatment planning for mobile lung cancer

    NASA Astrophysics Data System (ADS)

    Song, Yulin; Huang, Xiaolei; Mueller, Boris; Mychalczak, Borys

    2008-03-01

    Due to respiratory motion, lung tumor can move up to several centimeters. If respiratory motion is not carefully considered during the radiation treatment planning, the highly conformal dose distribution with steep gradients could miss the target. To address this issue, the common strategy is to add a population-derived safety margin to the gross tumor volume (GTV). However, during a free breathing CT simulation, the images could be acquired at any phase of a breathing cycle. With such a generalized uniform margin, the planning target volume (PTV) may either include more normal lung tissue than required or miss the GTV at certain phases of a breathing cycle. Recently, respiration correlated CT (4DCT) has been developed and implemented. With 4DCT, it is now possible to trace the tumor 3D trajectories during a breathing cycle and to define the tumor volume as the union of these 3D trajectories. The tumor volume defined in this way is called the internal target volume (ITV). In this study, we introduced a novel parameter, the phase impact factor (PIF), to determine the optimal CT phase for intensity modulated radiation therapy (IMRT) treatment planning for lung cancer. A minimum PIF yields a minimum probability for the GTV to move out of the ITV during the course of an IMRT treatment, providing a minimum probability of a geometric miss. Once the CT images with the optimal phase were determined, an IMRT plan with three to five co-planner beams was computed and optimized using the inverse treatment planning technique.

  8. A Feasibility Study of a Web Based Performance Improvement System for Substance Abuse Treatment Providers

    PubMed Central

    Forman, Robert; Crits-Christoph, Paul; Kaynak, Övgü; Worley, Matt; Hantula, Donald A.; Kulaga, Agatha; Rotrosen, John; Chu, Melissa; Gallop, Robert; Potter, Jennifer; Muchowski, Patrice; Brower, Kirk; Strobbe, Stephen; Magruder, Kathy; Chellis, A’Delle H.; Clodfelter, Tad; Cawley, Margaret

    2007-01-01

    We report here on the feasibility of implementing a semi-automated performance improvement system - Patient Feedback (PF) - that enables real-time monitoring of patient ratings of therapeutic alliance, treatment satisfaction, and drug/alcohol use in outpatient substance abuse treatment clinics. The study was conducted in 6 clinics within the National Institute on Drug Abuse Clinical Trials Network. It involved a total of thirty-nine clinicians and 6 clinic supervisors. Throughout the course of the study (4 week training period, 4 week baseline, 12 week intervention, 4 week post-intervention assessment, 1 year sustainability phase) there was an overall collection rate of 75.5% of the clinic patient census. In general, the clinicians in these clinics had very positive treatment satisfaction and alliance ratings throughout the study. However, one clinic had worse drug use scores at baseline than other participating clinics, and showed a decrease in self-reported drug use at post-intervention. Although the implementation of the PF system proved to be feasible in actual clinical settings, further modifications of the PF system are needed to enhance any potential clinical usefulness. PMID:17499954

  9. Adaptive and innovative Radiation Treatment FOR improving Cancer treatment outcomE (ARTFORCE); a randomized controlled phase II trial for individualized treatment of head and neck cancer

    PubMed Central

    2013-01-01

    Background Failure of locoregional control is the main cause of recurrence in advanced head and neck cancer. This multi-center trial aims to improve outcome in two ways. Firstly, by redistribution of the radiation dose to the metabolically most FDG-PET avid part of the tumour. Hereby, a biologically more effective dose distribution might be achieved while simultaneously sparing normal tissues. Secondly, by improving patient selection. Both cisplatin and Epidermal Growth Factor Receptor (EGFR) antibodies like Cetuximab in combination with Radiotherapy (RT) are effective in enhancing tumour response. However, it is unknown which patients will benefit from either agent in combination with irradiation. We will analyze the predictive value of biological markers and 89Zr-Cetuximab uptake for treatment outcome of chemoradiation with Cetuximab or cisplatin to improve patient selection. Methods ARTFORCE is a randomized phase II trial for 268 patients with a factorial 2 by 2 design: cisplatin versus Cetuximab and standard RT versus redistributed RT. Cisplatin is dosed weekly 40 mg/m2 for 6 weeks. Cetuximab is dosed 250mg/m2 weekly (loading dose 400 mg/m2) for 6 weeks. The standard RT regimen consists of elective RT up to 54.25 Gy with a simultaneous integrated boost (SIB) to 70 Gy in 35 fractions in 6 weeks. Redistributed adaptive RT consists of elective RT up to 54.25 Gy with a SIB between 64-80 Gy in 35 fractions in 6 weeks with redistributed dose to the gross tumour volume (GTV) and clinical target volume (CTV), and adaptation of treatment for anatomical changes in the third week of treatment. Patients with locally advanced, biopsy confirmed squamous cell carcinoma of the oropharynx, oral cavity or hypopharynx are eligible. Primary endpoints are: locoregional recurrence free survival at 2 years, correlation of the median 89Zr-cetuximab uptake and biological markers with treatment specific outcome, and toxicity. Secondary endpoints are quality of life, swallowing function

  10. Second phase HCV RNA decline during telaprevir based therapy increases with drug effectiveness: implications for treatment duration

    PubMed Central

    Guedj, Jeremie; Perelson, Alan S.

    2011-01-01

    Hepatitis C virus (HCV) RNA decay during antiviral therapy is characterized by a rapid first phase followed by a slower second phase. The current understanding of viral kinetics attributes the magnitude of the first phase decay to the treatment effectiveness, whereas the second phase decay is attributed to the progressive loss of infected cells. Here we analyzed data from 44 patients treated with telaprevir, a potent HCV protease inhibitor. Using a viral kinetic model that accounts for the pharmacokinetics of telaprevir, we found that the second phase slope of viral decline to be strongly correlated with the treatment effectiveness and to be roughly four-fold more rapid than has been reported with interferon-based therapies. Since telaprevir is not known to increase the death rate of infected cells, our results suggest the second phase slope of viral decline is driven not only by the death of infected cells but may also involve other mechanisms, such as a treatment effectiveness-dependent degradation of intracellular viral RNA. As a consequence of the enhanced viral decay caused by the high antiviral effectiveness of telaprevir, we predict that if drug resistance could be avoided by using an appropriate combination of antiviral agents, treatment duration needed to clear HCV might be dramatically shortened. Indeed, we predict that in 95% of fully compliant patients, the last virus particle should be eliminated by week 7 of therapy. If the remaining infected hepatocytes act as a potential reservoir for the renewal of infection, no more than 10 weeks of treatment should be sufficient to clear the infection in 95% of fully compliant patients. However, if patients miss doses, treatment duration would need to be extended. PMID:21384401

  11. Impact of Antipsychotic Treatment on Nonfasting Triglycerides in the CATIE Schizophrenia Trial Phase 1

    PubMed Central

    Meyer, Jonathan M.; Davis, Vicki G.; McEvoy, Joseph P.; Goff, Donald C.; Nasrallah, Henry A.; Davis, Sonia M.; Daumit, Gail L.; Hsiao, John; Swartz, Marvin S.; Stroup, T. Scott; Lieberman, Jeffrey A.

    2008-01-01

    Background Recent literature documents a stronger association between nonfasting triglycerides (TG) and cardiovascular risk compared to fasting TG. Given concerns over antipsychotic effects on serum TG, this analysis explored changes in nonfasting TG in phase 1 of the CATIE Schizophrenia Trial. Methods Change in nonfasting TG, adjusted for baseline value, was compared between antipsychotic treatment groups using subjects with nonfasting laboratory assessments at baseline and 3 months. Results Among the 246 subjects there were significant treatment differences in 3-month change from baseline (p=0.009). The greatest increases in median and adjusted mean nonfasting TG levels were seen among those randomized to quetiapine (mean +54.7 mg/dl, median +26 mg/dl) and olanzapine (mean +23.4 mg/dl, median +26.5 mg/dl), while ziprasidone was neutral (mean +0.0 mg/dl, median + 8 mg/dl), and decreases were seen with risperidone (mean −18.4 mg/dl, median −6.5 mg/dl) and perphenazine (mean −1.3 mg/dl, median −22 mg/dl). Pairwise comparisons indicated a significant between-group difference for perphenazine vs. olanzapine (p=0.002) and a trend for perphenazine vs. quetiapine (p=0.006). Conclusions This analysis provides further evidence for differential antipsychotic metabolic liabilities, and confirms signals for the effects of olanzapine and quetiapine on serum TG seen in earlier CATIE analyses. Future consensus recommendations will clarify the role of nonfasting TG monitoring in routine clinical practice. PMID:18534821

  12. Phase II evaluation of S-adenosyl-L-methionine (SAMe) for the treatment of hot flashes

    PubMed Central

    Kadakia, Kunal C.; Loprinzi, Charles L.; Atherton, Pamela J.; Fee-Schroeder, Kelliann C.; Sood, Amit; Barton, Debra L.

    2016-01-01

    Purpose Hot flashes are a significant source of symptom burden that negatively impacts quality of life (QOL). For women who have contraindications to, or are unwilling to consider, estrogens or antidepressants for bothersome hot flashes, there are limited effective pharmacologic or complementary and alternative medicines. Methods This single-arm phase II trial studied the efficacy of S-adenosyl-L-methionine (SAMe) for the treatment of hot flashes. Eligible women were required to have reported ≥14 hot flashes per week for ≥1 month. The patients were treated with SAMe at a dose of 400 mg twice daily to evaluate whether a reduction in hot flash score appeared to be better than the historical placebo response of approximately 25 %. The women kept a daily hot flash diary during a baseline week and then daily during weeks 2–7. The primary endpoint was the change from baseline to week 7 in hot flash score and hot flash frequency. Secondary endpoints included toxicity analyses and the effect of SAMe on QOL. Results From October 28, 2010 to January 30, 2012, 43 women were treated with SAMe. The decrease in mean percent of baseline hot flash score and frequency was 35.4 and 32.6 %, respectively. When compared to the historical placebo response of 25 %, the effect of SAMe on hot flash score was not statistically significant (p=0.09). Treatment was well tolerated with expected grade 1/2 gastrointestinal toxicity and no negative effect on QOL. Conclusions The use of SAMe does not appear to significantly reduce hot flashes more than would be expected with a placebo. PMID:26248653

  13. The transferability from rat subacute 4-week oral toxicity study to translational research exemplified by two pharmaceutical immunosuppressants and two environmental pollutants with immunomodulating properties.

    PubMed

    Kemmerling, Jessica; Fehlert, Ellen; Kuper, C Frieke; Rühl-Fehlert, Christine; Stropp, Gisela; Vogels, Jack; Krul, Cyrille; Vohr, Hans-Werner

    2015-07-15

    Exposure to chemicals may have an influence on the immune system. Often, this is an unwanted effect but in some pharmaceuticals, it is the intended mechanism of action. Immune function tests and in depth histopathological investigations of immune organs were integrated in rodent toxicity studies performed according to an extended OECD test guideline 407 protocol. Exemplified by two immunosuppressive drugs, azathioprine and cyclosporine A, and two environmental chemicals, hexachlorobenzene and benzo[a]pyrene, results of subacute rat studies were compared to knowledge in other species particular in humans. Although immune function has a high concordance in mammalian species, regarding the transferability from rodents to humans various factors have to be taken into account. In rats, sensitivity seems to depend on factors such as strain, sex, stress levels as well as metabolism. The two immunosuppressive drugs showed a high similarity of effects in animals and humans as the immune system was the most sensitive target in both. Hexachlorobenzene gave an inconsistent pattern of effects when considering the immune system of different species. In some species pronounced inflammation was observed, whereas in primates liver toxicity seemed more obvious. Generally, the immune system was not the most sensitive target in hexachlorobenzene-treatment. Immune function tests in rats gave evidence of a reaction to systemic inflammation rather than a direct impact on immune cells. Data from humans are likewise equivocal. In the case of benzo[a]pyrene, the immune system was the most sensitive target in rats. In the in vitro plaque forming cell assay (Mishell-Dutton culture) a direct comparison of cells from different species including rat and human was possible and showed similar reactions. The doses in the rat study had, however, no realistic relation to human exposure, which occurs exclusively in mixtures and in a much lower range. In summary, a case by case approach is necessary

  14. Aging assessment of nuclear air-treatment system HEPA filters and adsorbers. Volume 1, Phase 1

    SciTech Connect

    Winegardner, W.K.

    1993-08-01

    A Phase I aging assessment of high-efficiency particulate air (HEPA) filters and activated carbon gas adsorption units (adsorbers) was performed by the Pacific Northwest Laboratory (PNL) as part of the US Nuclear Regulatory Commission`s (NRC) Nuclear Plant Aging Research (NPAR) Program. Information concerning design features; failure experience; aging mechanisms, effects, and stressors; and surveillance and monitoring methods for these key air-treatment system components was compiled. Over 1100 failures, or 12 percent of the filter installations, were reported as part of a Department of Energy (DOE) survey. Investigators from other national laboratories have suggested that aging effects could have contributed to over 80 percent of these failures. Tensile strength tests on aged filter media specimens indicated a decrease in strength. Filter aging mechanisms range from those associated with particle loading to reactions that alter properties of sealants and gaskets. Low radioiodine decontamination factors associated with the Three Mile Island (TMI) accident were attributed to the premature aging of the carbon in the adsorbers. Mechanisms that can lead to impaired adsorber performance include oxidation as well as the loss of potentially available active sites as a result of the adsorption of pollutants. Stressors include heat, moisture, radiation, and airborne particles and contaminants.

  15. Effect of the sulfide phase on the properties of steel after heat treatment

    SciTech Connect

    Sadovskii, V.D.; Kut'in, A.B.; Gerbikh, N.M.

    1988-05-01

    The results of investigations concerned with the effect of the cooling regimes in the austenitic range on the nature of the segregation of sulfides in steels are presented. Experiments were carried out mainly with steel 18Kh2N4MA conventionally melted with low (0.008%) and high (0.04%) sulfur content and after electroslag remelting (ESR) (0.005% S). Results from an investigation of the change of morphology in dependence on the temperature and time of isothermal holding are presented in a diagram illustrating segregation for the predominating kinds of sulfides. The change of morphology and the nature of the distribution of sulfides affected both the fracture and impact toughness of the steel. The effect of the cooling rate from the overheating temperature on the impact toughness of ESR steels and of conventionally melted steels was examined. For ESR steels, characterized by low sulfur content, it was found that the mechanical properties can be changed by controlling the shape and distribution of inclusions of the nonmetallic phase, viz., manganese sulfides, during heat treatment.

  16. TREATMENT OF PRODUCED WATERS USING A SURFACTANT MODIFIED ZEOLITE/VAPOR PHASE BIOREATOR SYSTEM

    SciTech Connect

    LYNN E. KATZ; KERRY A. KINNEY; R.S. BOWMAN; E.J. SULLIVAN

    2003-10-01

    Co-produced water from the oil and gas industry is by some estimates the largest single waste stream in the country, aside from nonhazardous industrial wastes. Characteristics of produced water include high total dissolved solids content, dissolved organic constituents such as benzene and toluene, an oil and grease component, and chemicals added during the oil-production process. While most of the produced water is disposed via reinjection, some of them must be treated to remove organic constituents before the water is discharged. An efficient, cost-effective treatment technology is needed to remove these constituents. Surfactant-modified zeolite (SMZ) has been used successfully to treat contaminated ground water for organic and inorganic constituents. In addition, the low cost of natural zeolites makes their use attractive in water-treatment applications. Our previous DOE research work (DE-AC26-99BC15221) demonstrated that SMZ could successfully remove BTEX compounds from the produced water. In addition, SMZ could be regenerated through a simple air sparging process. The primary goal of this project is to develop a robust SMZ/VPB treatment system to efficiently remove the organic constituents from produced water in a cost-effective manner. This report summarizes work of this project from March 2003 through September 2003. We have continued our investigation of SMZ regeneration from our previous DOE project. Ten saturation/stripping cycles have been completed for SMZ columns saturated with BTEX compounds. The results suggest that BTEX sorption capacity is not lost after ten saturation/regeneration cycles. The composition of produced water from a site operated by Crystal Solutions Ltd. in Wyoming has been characterized and was used to identify key semi-volatile components. Isotherms with selected semi-volatile components have been initiated and preliminary results have been obtained. The experimental vapor phase bioreactors for this project have been designed and

  17. The acute phase of inflammatory response involved in the wound-healing process after excimer laser treatment

    PubMed Central

    Resan, Mirko; Vukosavljevic, Miroslav; Vojvodic, Danilo; Pajic-Eggspuehler, Brigitte; Pajic, Bojan

    2016-01-01

    Purpose To evaluate the participation of proinflammatory cytokines in the acute phase of corneal wound-healing response after excimer laser treatment. Methods The study included 68 myopic eyes up to −3.0 diopters divided into two groups: 1) eyes treated with laser in situ keratomileusis (LASIK) (n=31) and 2) eyes treated with photorefractive keratectomy (PRK) (n=37). Each group was then divided into three subgroups based on tear sampling times: before (0 hours), 1 hour after, and 24 hours after treatment. The tear fluid was sampled from lower lateral tear meniscus using a cellulose microsurgical sponge. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 in tear fluid were determined by flow cytometry method. Results Statistical significance was observed in the concentrations of TNF-α (P=0.0421) and IL-1β (P=0.0225) between samples collected 1 and 24 hours after PRK treatment in favor of samples collected 1 hour after treatment. IL-6 concentration changes showed a significant increase in the PRK group in both time intervals following treatment compared to pretreatment (0 hour/1 hour, P=0.0031; 0 hour/24 hours, P=0.0059). For IL-8 concentrations, significant differences were observed between control and experimental groups in samples collected 1 hour after LASIK and 1 hour after PRK treatment (P<0.001 for both groups), and IL-8 concentrations between control and experimental groups in samples collected 24 hours after LASIK and 24 hours after PRK treatment were greater after PRK treatment (P=0.0005). Comparison of average concentration values of proinflammatory cytokines in all the tested samples between LASIK and PRK groups showed significantly higher levels of IL-1β in the LASIK group 24 hours after treatment (P=0.0134), and of IL-6 in the PRK group 24 hours after treatment (P=0.0031). Conclusion The acute phase of corneal wound healing after excimer laser treatment is defined by an intensive inflammatory response. After PRK

  18. A COMPARISON OF LIQUID AND GAS-PHASE PHOTOOXIDATION TREATMENT OF METHYL TERTIARY BUTYL ETHER: SYNTHETIC AND FIELD SAMPLES

    EPA Science Inventory

    The feasibility of photo-oxidation treatment of metyl tert-butyl either (MTBE) in water was investigated using two systems, 1) a slurry falling film photo-reactor, and 2) an integrated air-stripping with gas phase photooxidation system. MTBE-contaminated synthetic water and field...

  19. Short-Course Accelerated Radiotherapy in Palliative Treatment of Advanced Pelvic Malignancies: A Phase I Study

    SciTech Connect

    Caravatta, Luciana; Padula, Gilbert D.A.; Macchia, Gabriella; Ferrandina, Gabriella; Bonomo, Pierluigi; Deodato, Francesco; Massaccesi, Mariangela; Mignogna, Samantha; Tambaro, Rosa; Rossi, Marco; Flocco, Mariano; Scapati, Andrea; and others

    2012-08-01

    Purpose: To define the maximum tolerated dose of a conformal short-course accelerated radiotherapy in patients with symptomatic advanced pelvic cancer. Methods and Materials: A phase I trial in 3 dose-escalation steps was designed: 14 Gy (3.5-Gy fractions), 16 Gy (4-Gy fractions), and 18 Gy (4.5-Gy fractions). The eligibility criteria included locally advanced and/or metastatic pelvic cancer and Eastern Cooperative Oncology Group performance status of {<=}3. Treatment was delivered in 2 days with twice-daily fractionation and at least an 8-hour interval. Patients were treated in cohorts of 6-12 to define the maximum tolerated dose. The dose-limiting toxicity was defined as any acute toxicity of grade 3 or greater, using the Radiation Therapy Oncology Group scale. Pain was recorded using a visual analog scale. The effect on quality of life was evaluated according to Cancer Linear Analog Scale (CLAS). Results: Of the 27 enrolled patients, 11 were male and 16 were female, with a median age of 72 years (range 47-86). The primary tumor sites were gynecologic (48%), colorectal (33.5%), and genitourinary (18.5%). The most frequent baseline symptoms were bleeding (48%) and pain (33%). Only grade 1-2 acute toxicities were recorded. No patients experienced dose-limiting toxicity. With a median follow-up time of 6 months (range 3-28), no late toxicities were observed. The overall (complete plus partial) symptom remission was 88.9% (95% confidence interval 66.0%-97.8%). Five patients (41.7%) had complete pain relief, and six (50%) showed >30% visual analog scale reduction. The overall response rate for pain was 91.67% (95% confidence interval 52.4%-99.9%). Conclusions: Conformal short course radiotherapy in twice-daily fractions for 2 consecutive days was well tolerated up to a total dose of 18 Gy. A phase II study is ongoing to confirm the efficacy on symptom control and quality of life indexes.

  20. Developing Treatment for Adolescents Who Stutter: A Phase I Trial of the Camperdown Program

    ERIC Educational Resources Information Center

    Hearne, Anna; Packman, Ann; Onslow, Mark; O'Brian, Sue

    2008-01-01

    Purpose: To investigate in detail how adolescents who stutter perform during treatment, with the aim of informing treatment development for this age group. Method: The Camperdown Program was conducted with 3 adolescents who stutter. Their performance during treatment was recorded in detail, and outcome measures were collected before treatment and…

  1. Effects of Two-Phase Treatment with the Herbst and Preadjusted Edgewise Appliances on the Upper Airway Dimensions

    PubMed Central

    Koay, Woei Li; Tse, Christine Shuk Kwan; Gu, Min

    2016-01-01

    Aims. To assess the effects of two-phase treatment with the Herbst and the preadjusted edgewise appliances on upper airway dimensions and to investigate the correlation between changes in the upper airway dimensions and skeletal morphologies. Methods. A total of 27 Chinese male adolescents aged 12.8 ± 1.3 years were selected. Lateral cephalograms were collected to assess the skeletal morphology and upper airway dimensions. Results. Following Herbst appliance treatment, the upper airway space was significantly enlarged, with the retropalatal (U-MPW) increasing by 1.1 ± 1.6 mm (P < 0.001), the retroglossal (PASmin) increasing by 1.3 ± 2.9 mm (P < 0.05), and the hypopharynx (V-LPW) enlarging by 1.6 ± 3.0 mm (P < 0.01). PASmin was found to show a negative correlation to the mandibular plane angle (MnPl-SN) by r = −0.413 (P < 0.05). There was no significant change (P > 0.05) in upper airway dimensions during the second-phase treatment. Conclusions. Herbst appliance treatment increased the oropharyngeal and hypopharyngeal airway dimensions among adolescents with Class II malocclusion, and the effects were maintained throughout the second treatment phase with a preadjusted edgewise appliance. There was a negative correlation between the change in the depth of the retroglossal pharynx and the mandibular plane angle. PMID:27073805

  2. Treatment of Produced Water Using a Surfactant Modified Zeolite/Vapor Phase Bioreactor System

    SciTech Connect

    Lynn E. Katz; Kerry A. Kinney; Robert S. Bowman; Enid J. Sullivan; Soondong Kwon; Elaine B. Darby; Li-Jung Chen; Craig R. Altare

    2006-01-31

    Co-produced water from the oil and gas industry accounts for a significant waste stream in the United States. Produced waters typically contain a high total dissolved solids content, dissolved organic constituents such as benzene and toluene, an oil and grease component as well as chemicals added during the oil-production process. It has been estimated that a total of 14 billion barrels of produced water were generated in 2002 from onshore operations (Veil, 2004). Although much of this produced water is disposed via reinjection, environmental and cost considerations can make surface discharge of this water a more practical means of disposal. In addition, reinjection is not always a feasible option because of geographic, economic, or regulatory considerations. In these situations, it may be desirable, and often necessary from a regulatory viewpoint, to treat produced water before discharge. It may also be feasible to treat waters that slightly exceed regulatory limits for re-use in arid or drought-prone areas, rather than losing them to reinjection. A previous project conducted under DOE Contract DE-AC26-99BC15221 demonstrated that surfactant modified zeolite (SMZ) represents a potential treatment technology for produced water containing BTEX. Laboratory and field experiments suggest that: (1) sorption of benzene, toluene, ethylbenzene and xylenes (BTEX) to SMZ follows linear isotherms in which sorption increases with increasing solute hydrophobicity; (2) the presence of high salt concentrations substantially increases the capacity of the SMZ for BTEX; (3) competitive sorption among the BTEX compounds is negligible; and, (4) complete recovery of the SMZ sorption capacity for BTEX can be achieved by air sparging the SMZ. This report summarizes research for a follow on project to optimize the regeneration process for multiple sorption/regeneration cycles, and to develop and incorporate a vapor phase bioreactor (VPB) system for treatment of the off-gas generated during

  3. Evaluating the Stability of Open Bite Treatments and Its Predictive Factors in the Retention Phase during Permanent Dentition

    PubMed Central

    Salehi, Parisa; Pakshir, Hamid Reza; Hoseini, Seyed Ali Reza

    2015-01-01

    Statement of the Problem Orthodontists often find challenges in treating the anterior open bite and maintaining the results. Purpose This retrospective study was aimed to evaluate the stability of corrected open bite in the retention phase during permanent dentition. Materials and Method A total number of 37 patients, including 20 males and 17 females, with the mean age of 18±2.1 years at the beginning of the treatment were studied after correction of the anterior open bite. Overbites of the patients were measured from their lateral cephalograms before (T1), at the end (T2) and at least 3 years after the end of the treatment in the presence of their fixed retainers (T3).The mean overbite changes and the number of patients with open bite, due to treatment relapse, at T3 were calculated. The relationship between the pre-treatment factors and the treatment relapse was assessed at T1 and T2. Also the effects of treatment methods, extraction and adjunctive use of removable appliances on the post-treatment relapse were evaluated. Results The mean overbite change during the post-treatment period was -0.46±0.7 mm and six patients (16.2%) had relapse in the follow-up recall. Cephalometric Jaraback index showed statistically significant, but weak correlation with overbite changes after the treatment (p= 0.035; r= -0.353). No significant difference was found between the extraction and non-extraction groups (p= 0.117) the use and the type of the removable appliances (p= 0.801). Conclusion Fixed retainers alone are insufficient for stabilizing the results of corrected open bite. The change of overbite in the retention phase could not be predicted from cephalometric measurements. Extraction and use of adjunctive removable appliance did not have any effect on the treatment relapse. PMID:25759854

  4. What is still missing in acute-phase treatment of stroke: a prospective observational study.

    PubMed

    Mazzucco, Sara; Turri, Giulia; Mirandola, Rina; Bovi, Paolo; Bisoffi, Giulia

    2013-04-01

    Early recognition of stroke symptoms and activation of emergency medical service (EMS) positively affects prognosis after a stroke. To assess stroke awareness among stroke patients and medical personnel in the catchment area of Verona Hospital and how it affects stroke care, we prospectively studied timing of acute stroke care in relation to patients' characteristics. Patients admitted to Medical Departments of Verona University Hospital between January 1st and December 31st 2009 with a diagnosis of TIA or stroke were enrolled. Outcome measures were: time between (i) symptoms onset and hospital arrival, (ii) hospital arrival and brain CT scan, blood examination, ECG and neurological evaluation. The following patient/event characteristics were also collected: means of hospital arrival, sex, age, degree of disability, type of event (first or recurrent) and acute-phase treatment. Of 578 patients providing complete information, 60 % arrived to the emergency department with the EMS (EMS+ group), while 40 % arrived on their own (EMS-). EMS+ group was older than EMS- (mean age 76.2, SD 13.2, vs. 72.3, SD 13, respectively), displayed more severe symptoms (mRS 4 vs. 2) and shorter time interval between symptoms onset and hospital arrival, hospital arrival and CT scan, ECG, laboratory tests and neurological evaluation (p < 0.0001); 22 % of the EMS+ patients were stroke recurrences versus 29 % of the EMS- (p = 0.058); 85 % of thrombolised patients were EMS+. We conclude that there is a lack of awareness of stroke symptoms and risks of recurrence even among patients who already had a stroke and among medical personnel. PMID:22466805

  5. Treatment of Produced Waters Using a Surfactant Modified Zeolite/Vapor Phase Bioreactor System

    SciTech Connect

    Soondong Kwon; Elaine B. Darby; Li-Jung Chen; Lynn E. Katz; Kerry A. Kinney; R. S. Bowman; E. J. Sullivan

    2005-03-11

    This report summarizes work performed on this project from October 2004 through March 2005. In previous work, a surfactant modified zeolite (SMZ) was shown to be an effective system for removing BTEX contaminants from produced water. Additional work on this project demonstrated that a compost-based biofilter could biodegrade the BTEX contaminants found in the SMZ regeneration waste gas stream. However, it was also determined that the BTEX concentrations in the waste gas stream varied significantly during the regeneration period and the initial BTEX concentrations were too high for the biofilter to handle effectively. A series of experiments were conducted to determine the feasibility of using a passive adsorption column placed upstream of the biofilter to attenuate the peak gas-phase VOC concentrations delivered to the biofilter during the SMZ regeneration process. In preparation for the field test of the SMZ/VPB treatment system in New Mexico, a pilot-scale SMZ system was also designed and constructed during this reporting period. Finally, a cost and feasibility analysis was also completed. To investigate the merits of the passive buffering system during SMZ regeneration, two adsorbents, SMZ and granular activated carbon (GAC) were investigated in flow-through laboratory-scale columns to determine their capacity to handle steady and unsteady VOC feed conditions. When subjected to a toluene-contaminated air stream, the column containing SMZ reduced the peak inlet 1000 ppmv toluene concentration to 630 ppmv at a 10 second contact time. This level of buffering was insufficient to ensure complete removal in the downstream biofilter and the contact time was longer than desired. For this reason, using SMZ as a passive buffering system for the gas phase contaminants was not pursued further. In contrast to the SMZ results, GAC was found to be an effective adsorbent to handle the peak contaminant concentrations that occur early during the SMZ regeneration process. At a one

  6. Double-blind, placebo-controlled, randomized, right-left study comparing calcipotriol monotherapy with a combined treatment of calcipotriol and diflucortolone valerate in chronic plaque psoriasis.

    PubMed

    Salmhofer, W; Maier, H; Soyer, H P; Hönigsmann, H; Hödl, S

    2000-01-01

    A double-blind, randomized clinical study was conducted to compare the efficacy and tolerability of twice-daily topical calcipotriol treatment with a combination treatment of calcipotriol once a day in the morning and diflucortolone valerate in the evening. Sixty-three patients with a clinical diagnosis of chronic plaque psoriasis and comparable psoriatic lesions on both sides of the body were included. After a washout phase of 1 week, psoriatic lesions were treated for 4 weeks with calcipotriol ointment twice daily on one side of the body and a combination of calcipotriol and diflucortolone valerate ointment on the other side. The treatment period was followed by a period of 4 weeks without any treatment. The psoriasis area and severity index (PASI) was used to compare the 2 groups. Furthermore, the overall therapeutic results were assessed independently by the investigators and by the patients. Both treatment regimens showed a significant, nearly identical, reduction in PASI. The mean PASI for calcipotriol alone was 5.7 at baseline, 1.9 after 4 weeks of treatment and 3.8 at the end of the follow-up period. For combination therapy, these values were 5.7, 1.8 and 3.8, respectively. There was a statistically significant advantage in favor of combined calcipotriol and diflucortolone valerate treatment at weeks 1 and 2 (p < 0.05); however, at the end of the treatment phase the difference between the 2 therapies was not significant. Subjective evaluation of efficacy by both the investigators and the patients revealed no difference between the 2 treatments. The frequency of side effects (e.g. irritation) was low in both groups. In conclusion, both therapies were effective for the treatment of chronic plaque-type psoriatic lesions. The combination of calcipotriol and a topical steroid appeared to produce a more rapid clinical response and was shown to be as effective as calcipotriol therapy alone. PMID:11234559

  7. Once-daily USL255 as adjunctive treatment of partial-onset seizures: Randomized phase III study

    PubMed Central

    Chung, Steve S; Fakhoury, Toufic A; Hogan, R Edward; Nagaraddi, Venkatesh N; Blatt, Ilan; Lawson, Balduin; Arnold, Stephan; Anders, Bob; Clark, Annie M; Laine, Dawn; Meadows, R Shawn; Halvorsen, Mark B

    2014-01-01

    Objective To evaluate the efficacy and safety of USL255, Qudexy™ XR (topiramate) extended-release capsules, as an adjunctive treatment for refractory partial-onset seizures (POS) in adults taking one to three concomitant antiepileptic drugs. Methods In this global phase III study (PREVAIL; NCT01142193), 249 adults with POS were randomized 1:1 to once-daily USL255 (200 mg/day) or placebo. The primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and responder rate (proportion of patients with ≥50% reduction in seizure frequency). Seizure freedom was also assessed. Safety (adverse events, clinical and laboratory findings), as well as treatment effects on quality of life (QOLIE-31-P) and clinical global impression of change (CGI-C), were evaluated. Results Across the entire 11-week treatment phase, USL255 significantly reduced the median percent seizure frequency and significantly improved responder rate compared with placebo. Efficacy over placebo was observed early in treatment, in patients with highly refractory POS, and in those with the most debilitating seizure types (i.e., complex partial, partial secondarily generalized). USL255 was safe and generally well tolerated with a low incidence of neurocognitive adverse events. USL255 was associated with significant clinical improvement without adversely affecting quality of life. Significance The PREVAIL phase III clinical study demonstrated that once-daily USL255 (200 mg/day) significantly improved seizure control and was safe and generally well tolerated with few neurocognitive side effects. PMID:24902983

  8. Significant Treatment Effect of Bupropion in Patients With Bipolar Disorder but Similar Phase-Shifting Rate as Other Antidepressants

    PubMed Central

    Li, Dian-Jeng; Tseng, Ping-Tao; Chen, Yen-Wen; Wu, Ching-Kuan; Lin, Pao-Yen

    2016-01-01

    Abstract Bupropion is widely used for treating bipolar disorder (BD), and especially those with depressive mood, based on its good treatment effect, safety profile, and lower risk of phase shifting. However, increasing evidence indicates that the safety of bupropion in BD patients may not be as good as previously thought. The aim of this study was to summarize data on the treatment effect and safety profile of bupropion in the treatment of BD via a meta-analysis. Electronic search through PubMed and ClinicalTrials.gov was performed. The inclusion criteria were: (i) studies comparing changes in disease severity before and after bupropion treatment or articles comparing the treatment effect of bupropion in BD patients with those receiving other standard treatments; (ii) articles on clinical trials in humans. The exclusion criteria were (i) case reports/series, and (ii) nonclinical trials. All effect sizes from 10 clinical trials were pooled using a random effects model. We examined the possible confounding variables using meta-regression and subgroup analysis. Bupropion significantly improved the severity of disease in BD patients (P < 0.001), and the treatment effect was similar to other antidepressants/standard treatments (P = 0.220). There were no significant differences in the dropout rate (P = 0.285) and rate of phase shifting (P = 0.952) between BD patients who received bupropion and those who received other antidepressants. We could not perform a detailed meta-analysis of every category of antidepressant, nor could we rule out the possible confounding effect of concurrent psychotropics or include all drug side effects. Furthermore, the number of studies recruited in the meta-analysis was relatively small. Our findings reconfirm the benefits of bupropion for the treatment of bipolar depression, which are similar to those of other antidepressants. However, the rate of phase shifting with bupropion usage was not as low compared to other

  9. Phased surgical treatment of barium enema-induced rectal injury and retention of barium in the pelvic floor space

    PubMed Central

    Yang, Xuefei; Xia, Ligang; Huang, Jun; Wang, Jianping

    2014-01-01

    Iatrogenic injuries caused by barium enema are rarely reported. Following a phased surgical protocol for up to one year, we have successfully treated a patient with rectal injury and severe infection of the pelvic floor space complicated with retention of large amounts of barium and vaginal fistula. In this article, the phased surgery planning for the treatment of rectal injury complicated with vaginal fistula is discussed in terms of the pros and cons, and the observed effect and evolution of barium retained in the pelvic floor space are described. PMID:25405155

  10. Volatile composition and aroma activity of guava puree before and after thermal and dense phase carbon dioxide treatments.

    PubMed

    Plaza, Maria Lourdes; Marshall, Maurice R; Rouseff, Russell Lee

    2015-02-01

    Volatiles from initially frozen, dense phase carbon dioxide (DPCD)- and thermally treated guava purees were isolated by solid phase microextraction (SPME), chromatographically separated and identified using a combination of gas chromatography-mass spectrometry (GC-MS), GC-olfactometry (GC-O), and GC-pulsed flame photometric detector (GC-PFPD, sulfur mode). Fifty-eight volatiles were identified using GC-MS consisting of: 6 aldehydes, 2 acids, 15 alcohols, 6 ketones, 21 esters, and 8 terpenes. Eleven volatiles were newly identified in guava puree. Hexanal was the most abundant volatile in all 3 types of guava puree. Ten sulfur compounds were identified using GC-PFPD of which 3 possessed aroma activity and 3 were not previously reported in guava puree. Both treatments profoundly reduced total sulfur peak areas and produced different peak patterns compared to control. Thermal treatment reduced total sulfur peak area 47.9% compared to a loss of 34.7% with DPCD treatment. Twenty-six volatiles possessed aroma activity. (Z)-3-Hexenyl hexanoate was the major contributor to the aroma of the freshly thawed and DPCD-treated guava puree. DPCD treatment reduced total MS ion chromatogram (MS TIC) peak area 35% but produced a GC-O aroma profile very similar to control. Whereas thermal treatment reduced total TIC peak area only 8.7% compared to control but produced a 35% loss in total GC-O peak intensities. PMID:25588413

  11. The international Study to Predict Optimized Treatment in Depression (iSPOT-D): outcomes from the acute phase of antidepressant treatment.

    PubMed

    Saveanu, Radu; Etkin, Amit; Duchemin, Anne-Marie; Goldstein-Piekarski, Andrea; Gyurak, Anett; Debattista, Charles; Schatzberg, Alan F; Sood, Satish; Day, Claire V A; Palmer, Donna M; Rekshan, William R; Gordon, Evian; Rush, A John; Williams, Leanne M

    2015-02-01

    We aimed to characterize a large international cohort of outpatients with MDD within a practical trial design, in order to identify clinically useful predictors of outcomes with three common antidepressant medications in acute-phase treatment of major depressive disorder (MDD). The international Study to Predict Optimized Treatment in Depression has presently enrolled 1008 treatment-seeking outpatients (18-65 years old) at 17 sites (five countries). At pre-treatment, we characterized participants by symptoms, clinical history, functional status and comorbidity. Participants were randomized to receive escitalopram, sertraline or venlafaxine-extended release and managed by their physician following usual treatment practices. Symptoms, function, quality of life, and side-effect outcomes were assessed 8 weeks later. The relationship of anxiety to response and remission was assessed by comorbid Axis I diagnosis, presence/absence of anxiety symptoms, and dimensionally by anxiety symptom severity. The sample had moderate-to-severe symptoms, but substantial comorbidity and functional impairment. Of completers at week 8, 62.2% responded and 45.4% reached remission on the 17-item Hamilton Rating Scale for Depression; 53.3% and 37.6%, respectively on the 16-item Quick Inventory of Depressive Symptoms. Functional improvements were seen across all domains. Most participants had side effects that occurred with a frequency of 25% or less and were reported as being in the "none" to minimal/mild range for intensity and burden. Outcomes did not differ across medication groups. More severe anxiety symptoms at pre-treatment were associated with lower remission rates across all medications, independent of depressive severity, diagnostic comorbidity or side effects. Across medications, we found consistent and similar improvements in symptoms and function, and a dimensional prognostic effect of comorbid anxiety symptoms. These equivalent outcomes across treatments lay the foundation for

  12. Structure-phase states evolution in Al-Si alloy under electron-beam treatment and high-cycle fatigue

    SciTech Connect

    Konovalov, Sergey Alsaraeva, Krestina Gromov, Victor Semina, Olga; Ivanov, Yurii

    2015-10-27

    By methods of scanning and transmission electron diffraction microscopy the analysis of structure-phase states and defect substructure of silumin subjected to high-intensity electron beam irradiation in various regimes and subsequent fatigue loading up to failure was carried out. It is revealed that the sources of fatigue microcracks are silicon plates of micron and submicron size are not soluble in electron beam processing. The possible reasons of the silumin fatigue life increase under electron-beam treatment are discussed.

  13. Household costs of illness during different phases of tuberculosis treatment in Central Asia: a patient survey in Tajikistan

    PubMed Central

    2010-01-01

    Background Illness-related costs incurred by patients constitute a severe economic burden for households especially in low-income countries. High household costs of illness lead to impoverishment; they impair affordability and equitable access to health care and consequently hamper tuberculosis (TB) control. So far, no study has investigated patient costs of TB in the former Soviet Union. Methods All adult new pulmonary TB cases enrolled into the DOTS program in 12 study districts during the study period were enrolled. Medical and non-medical expenditure as well as loss of income were quantified in two interviews covering separate time periods. Costs of different items were summed up to calculate total costs. For missing values, multiple imputation was applied. Results A cohort of 204 patients under DOTS, 114 men and 90 women, participated in the questionnaire survey. Total illness costs of a TB episode averaged $1053 (c. $4900 purchasing power parity, PPP), of which $292, $338 and $422 were encountered before the start of treatment, during intensive phase and in continuation phase, respectively. Costs per month were highest before the start of treatment ($145) and during intensive phase ($153) and lower during continuation phase ($95). These differences were highly significant (paired t-test, p < 0.0005 for both comparisons). Conclusions The illness-related costs of an episode of TB exceed the per capita GDP of $1600 PPP about two-and-a-half times. Hence, these costs are catastrophic for concerned households and suggest a high risk for impoverishment. Costs are not equally spread over time, but peak in early stages of treatment, exacerbating the problem of affordability. Mitigation strategies are needed in order to control TB in Tajikistan and may include social support to the patients as well as changes in the management of TB cases. These mitigation strategies should be timed early in treatment when the cost burden is highest. PMID:20078897

  14. Studies of porosity, connectivity, and parasitic phases in textured Bi-2212/Ag after non-melt heat treatments

    NASA Astrophysics Data System (ADS)

    Lu, F.; Damborsky, K.; McIntyre, P.; McInturff, A.; Pogue, N.; Smit, Klaus; Sooby, E.

    2012-06-01

    Specimens of cold-pressed, highly textured Bi-2212 powders were subjected to sintering heat treatments to evaluate the impact of sintering upon texture, density, connectivity, microstructure, and growth of parasitic phases. A regime of non-melt sintering parameters were identified that produce near-solid density, strong texture, extensive growth of the Bi-2212 phase in the textured a-b planes, and no significant growth of parasitic phases. This favorable regime is stable over a sintering temperature range from 865°C - 875°C. The results establish one element of our strategy for fabrication of highperformance Bi-2212/Ag wire using textured powder in a 'jelly-roll' configuration.

  15. Phenolic wastewater treatment through extractive recovery coupled with biodegradation in a two-phase partitioning membrane bioreactor.

    PubMed

    Praveen, Prashant; Loh, Kai-Chee

    2015-12-01

    A two-phase partitioning membrane bioreactor (TPPMB) was designed and operated for treatment of high strength phenolic wastewater through extraction/stripping and concomitant biodegradation. Tributyl phosphate dissolved in kerosene was used as the organic phase, sodium hydroxide as the stripping phase and Pseudomonas putida for biodegradation. In a semi-dispersive approach, organic phase dispersed in the stripping solution was contacted with wastewater through semi-permeable membranes for removal of phenol from wastewater, while the microorganisms were inoculated directly into the wastewater for biodegradation. The TPPMB exhibited high phenol removal rates, and phenol concentrations of 1000-3000mg/L were reduced to undetected amounts within 2-4h. Up to 80% phenol was recovered through extraction, while the remaining was metabolized by the microorganisms. Phenol recovery in the TPPMB was enhanced by increasing the mass transfer rate of phenol through the membranes, and it was also estimated that phenol diffusion through the aqueous boundary layer on the tube side was the rate limiting step. The flexibility in adjusting inoculation time in the TPPMB prevented microorganisms from adverse effects of substrate inhibition, which facilitated complete removal of phenol from the wastewater. TPPMB retained the advantages of both solvent extraction and biodegradation, and it can be highly promising for the treatment of toxic industrial wastewater. PMID:26210322

  16. Functional design criteria for project W-252, phase II liquid effluent treatment and disposal. Revision 2

    SciTech Connect

    Hatch, C.E.

    1995-05-01

    This document is the Functional Design Criteria for Project W-252. Project W-252 provides the scope to provide BAT/AKART (best available technology...) to 200 Liquid Effluent Phase II streams (B-Plant). This revision (Rev. 2) incorporates a major descoping of the project. The descoping was done to reflect a combination of budget cutting measures allowed by a less stringent regulatory posture toward the Phase II streams

  17. Intravitreal Sirolimus for the Treatment of Geographic Atrophy: Results of a Phase I/II Clinical Trial

    PubMed Central

    Petrou, Philip A.; Cunningham, Denise; Shimel, Katherine; Harrington, Molly; Hammel, Keri; Cukras, Catherine A.; Ferris, Frederick L.; Chew, Emily Y.; Wong, Wai T.

    2015-01-01

    Purpose. To investigate the safety and effects of intravitreal sirolimus for the potential treatment of geographic atrophy (GA). Methods. The study was a single-center, open-label, phase I/II trial enrolling six participants with bilateral GA treated with intravitreal sirolimus in only one randomly assigned eye, with the fellow eye as control. The primary efficacy outcome measure was the change in total GA area from baseline on color fundus photography (CFP); secondary outcomes included changes in GA area on fundus autofluorescence (FAF), visual acuity, central retinal thickness (CRT), and macular sensitivity from baseline. Results. Although no systemic adverse events were attributed to treatment, two of six participants had ocular adverse events that were possibly associated. The treated eye of one participant developed abnormal paralesional changes on FAF that were associated with accelerated retinal thinning. This accelerated retinal thinning was also seen in the treated eye of a second participant. Because of concern that these events were associated with treatment, treatment was suspended. Comparisons of treated and fellow eyes for change in visual acuity, change in GA area, and change in CRT showed no evidence of treatment benefit and generally favored the untreated fellow eye. Conclusions. While paralesional FAF changes and rapid retinal thinning observed are potentially part of the natural course of GA, they may possibly be related to treatment. No general evidence of anatomical or functional benefit was detected in treated eyes. Further data on intravitreal sirolimus for GA treatment will be available from a larger phase II trial. (ClinicalTrials.gov number, NCT01445548.) PMID:25525171

  18. Effectiveness of manipulative physiotherapy for the treatment of a neurogenic cervicobrachial pain syndrome: a single case study -- experimental design.

    PubMed

    Cowell, I M; Phillips, D R

    2002-02-01

    A single case study ABC design was used to evaluate the effectiveness of manipulative physiotherapy in a 44-year-old woman with an 8-month history of neurogenic cervicobrachial pain. Clinical examination demonstrated significant signs of upper quadrant neural tissue mechanosensitivity indicating that neural tissue was the dominant tissue of origin for the subject's complaint of pain. Magnetic resonance imaging revealed correlating discal pathology at the C5/6 intersegmental level. The study involved a 4-week pre-assessment phase, a 4-week treatment phase and a 2-week home exercise phase. Functional disability was measured using the Northwick Park Neck Pain Questionnaire and pain was assessed using the McGill Short Form Pain Questionnaire. Cervical motion was measured by a cervical range of motion device (CROM) and the range of shoulder abduction with a mediclino inclinometer. Manipulative physiotherapy treatment involved a cervical lateral glide mobilization technique. Following treatment, visual analysis revealed beneficial effects on pain, functional disability as well as cervical and shoulder mobility. These improvements were maintained over the home exercise phase and at 1-month follow-up. The single case limits generalization of the findings, but the results support previous studies in this area and gives further impetus to controlled clinical trials. PMID:11884154

  19. Acute phase response induced following tumor treatment by photodynamic therapy: relevance for the therapy outcome

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Merchant, Soroush; Stott, Brandon; Cecic, Ivana; Payne, Peter; Sun, Jinghai

    2006-02-01

    Acute phase response is an effector process orchestrated by the innate immune system for the optimal mobilization of the resources of the organism distant from the local insult site needed in the execution of a host-protecting reaction. Our research has shown that mice bearing tumors treated by photodynamic therapy (PDT) exhibit the three major hallmarks of acute phase response: release of acute phase reactants, neutrophilia, and pituitary/adrenal axis activation. Of particular interest in this study were acute phase proteins that have a pivotal role in the clearance of dead cells, since the occurrence of this process in PDT-treated tumors emerges as a critical event in the course of PDT-associated host response. It is shown that this type of acute phase reactants, including complement proteins (C3, C5, C9, mannose-binding lectin, and ficolin A) and related pentraxins (serum amyloid P component and PTX3), are upregulated following tumor PDT and accumulate in the targeted lesions. Based on the recently accumulated experimental evidence it is definitely established that the acute phase response is manifested in the hosts bearing PDT-treated tumors and it is becoming clear that this effector process is an important element of PDT-associated host response bearing in impact on the eventual outcome of this therapy.

  20. Syllable-Timed Speech Treatment for School-Age Children Who Stutter: A Phase I Trial

    ERIC Educational Resources Information Center

    Andrews, Cheryl; O'Brian, Sue; Harrison, Elisabeth; Onslow, Mark; Packman, Ann; Menzies, Ross

    2012-01-01

    Purpose: This clinical trial determined the outcomes of a simple syllable-timed speech (STS) treatment for school-age children who stutter. Method: Participants were 10 children, ages 6-11 years, who stutter. Treatment involved training the children and their parents to use STS at near normal speech rates. The technique was practiced in the clinic…

  1. FOULING-RESISTANT CERAMIC MEMBRANES FOR TREATMENT OF METASTABLE OIL/WATER EMULSIONS - PHASE I

    EPA Science Inventory

    Billions of gallons of oily wastewaters are generated daily by a variety of industrial sources. One class of oily wastewaters, metastable oil/water emulsions, encompasses waste streams for which a need exists for more cost-effective and reliable treatment. Current treatment...

  2. Changes in hormone and lipid levels in male patients with focal seizures when switched from carbamazepine to lacosamide as adjunctive treatment to levetiracetam: A small phase IIIb, prospective, multicenter, open-label trial.

    PubMed

    Elger, Christian E; Rademacher, Michael; Brandt, Christian; Elmoufti, Sami; Dedeken, Peter; Eckhardt, Klaus; Tennigkeit, Frank; De Backer, Marc

    2016-09-01

    Treatment with enzyme-inducing antiepileptic drugs (AEDs) such as carbamazepine (CBZ) can lead to changes in reproductive, endocrine, and lipid parameters, resulting in clinical symptoms for some patients. Previous studies indicate that these changes can be reversed by switching to a nonenzyme-inducing AED. Lacosamide is a newer-generation AED, not known to induce or strongly inhibit cytochrome P450 (CYP450) enzymes. In this phase IIIb, prospective, multicenter, open-label, single-arm trial (NCT01375374), the serum concentrations of CYP-related reproductive hormones, thyroid hormones, and lipids were assessed in otherwise healthy male patients with focal seizures (N=11), before and after a switch from CBZ (600-1200mg/day at baseline) to lacosamide (target dose: 400mg/day by the end of titration) as adjunctive treatment to the nonenzyme-inducing AED levetiracetam (LEV, stable dosage of >1000mg/day throughout). Cross titration took place over 4weeks, followed by an 8-week maintenance period. Serum measurements were conducted at baseline and at the end of maintenance. The median serum sex-hormone-binding globulin (SHBG) concentration was towards the higher end of the normal range at baseline and decreased following the switch (61.7 to 47.5nmol/L, N=10, p=0.027 by Wilcoxon signed-rank test). Free androgen index (100×testosterone/SHBG) and free thyroxine serum concentration increased (25.4 to 36.4 and 13.0 to 14.9pmol/L, respectively, both N=10 and p=0.002). At baseline, the median progesterone serum concentration was below the normal range (0.7nmol/L), whereas median cholesterol and low-density lipoprotein concentrations were above the normal range (5.5 and 3.6mmol/L, respectively). By the end of maintenance, all measured parameters were within the normal range. The safety and tolerability profile of lacosamide was consistent with that observed in previous studies. Furthermore, antiseizure efficacy appeared to be maintained, suggesting that deinduction of CYP enzymes

  3. Fractionated administration of irinotecan and cisplatin for treatment of non-small-cell lung cancer: a phase II study of Okayama Lung Cancer Study Group

    PubMed Central

    Ueoka, H; Tanimoto, M; Kiura, K; Tabata, M; Takigawa, N; Segawa, Y; Takata, I; Eguchi, K; Okimoto, N; Harita, S; Kamei, H; Shibayama, T; Watanabe, Y; Hiraki, S; Harada, M

    2001-01-01

    A phase II study of fractionated administration of irinotecan (CPT-11) and cisplatin (CDDP) in patients with non-small-cell lung cancer (NSCLC) was conducted. Between January 1996 and January 1998, 44 previously untreated patients with stage IIIB or IV NSCLC were enrolled. CDDP at a dose of 60 mg m–2was given first and followed by CPT-11 at a dose of 50 mg m–2. Both drugs were given by 1-hour infusion on days 1 and 8, and repeated every 4 weeks up to 4 cycles. 42 patients were evaluated for response and 44 for survival and toxicity. 20 patients (48%: 95% confidence interval 32–63%) achieved an objective response. The median duration of responses was 8 months, and the median survival time and the 1-year survival rate were 12.5 months and 56.8%, respectively. Major toxicities were neutropenia and diarrhoea. Grade 3 or 4 neutropenia occurred in 70.5% of the patients and one patient died of sepsis. Grade 3 or 4 diarrhoea was experienced in 25.0%, but manageable by conventional therapy. In conclusion, fractionated administration of CPT-11 and CDDP was highly effective for advanced NSCLC with manageable toxicities. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11437395

  4. Structural and phase changes in carbides of the high-speed steel upon heat treatment

    NASA Astrophysics Data System (ADS)

    Chaus, A. S.

    2016-07-01

    The effect of austenitizing temperature on structural and phase changes in carbides of the tungsten-molybdenum high-speed steel has been studied. The results of metallographic analysis and energy dispersive microanalysis have been discussed. It has been shown that an increase in austenitizing temperature from 1180 to 1260°C causes structural transformations in carbide particles of eutectic origin crushed upon hot plastic deformation, which are related to their dissolution and coalescence, and changes in the phase composition of the carbides themselves.

  5. Phase 2 TWR Steam Reforming Test for Sodium-Bearing Waste Treatment

    SciTech Connect

    Nicholas R. Soelberg; Doug Marshall; Dean Taylor; Steven Bates

    2004-01-01

    About one million gallons of acidic, hazardous, and radioactive sodium-bearing waste (SBW) is stored in stainless steel tanks a the Idaho Nuclear Technology and Engineering Center (INTEC), which is a major operating facility of the Idaho National Engineering and Environmental Laboratory (INEEL). Steam reforming is a candidate technology being investigated for converting the SBW into a road ready waste form that can be shipped to the Waste Isolation Pilot Plant in New Mexico for interment. Fluidized bed steam reforming technology, licensed to ThermoChem Waste Remediation, LLC (TWR) by Manufacturing Technology Conversion International, was tested in two phases using an INEEL (Department of Energy) fluidized bed test system located at the Science Applications International Corporation (SAIC) Science and Technology Applications Research Center in Idaho Falls, Idaho. The Phase 1 tests were reported earlier. The Phase 2 tests are reported here. For Phase 2, the process feed rate, reductant stoichiometry, and process temperature were varied to identify and demonstrate how the process might be optimized to improve operation and product characteristics. The first week of testing was devoted primarily to process chemistry and the second week was devoted more toward bed stability and particle size control.

  6. Nanoalloying and phase transformations during thermal treatment of physical mixtures of Pd and Cu nanoparticles

    NASA Astrophysics Data System (ADS)

    Mukundan, Vineetha; Yin, Jun; Joseph, Pharrah; Luo, Jin; Shan, Shiyao; Zakharov, Dmitri N.; Zhong, Chuan-Jian; Malis, Oana

    2014-04-01

    Nanoscale alloying and phase transformations in physical mixtures of Pd and Cu ultrafine nanoparticles are investigated in real time with in situ synchrotron-based x-ray diffraction complemented by ex situ high-resolution transmission electron microscopy. The combination of metal-support interaction and reactive/non-reactive environment was found to determine the thermal evolution and ultimate structure of this binary system. At 300 °C, the nanoparticles supported on silica and carbon black intermix to form a chemically ordered CsCl-type (B2) alloy phase. The B2 phase transforms into a disordered fcc alloy at higher temperature (> 450 °C). The alloy nanoparticles supported on silica and carbon black are homogeneous in volume, but evidence was found of Pd surface enrichment. In sharp contrast, when supported on alumina, the two metals segregated at 300 °C to produce almost pure fcc Cu and Pd phases. Upon further annealing of the mixture on alumina above 600 °C, the two metals interdiffused, forming two distinct disordered alloys of compositions 30% and 90% Pd. The annealing atmosphere also plays a major role in the structural evolution of these bimetallic nanoparticles. The nanoparticles annealed in forming gas are larger than the nanoparticles annealing in helium due to reduction of the surface oxides that promotes coalescence and sintering.

  7. THE DISTRIBUTION AND SOLID-PHASE SPECIATION OF AS IN IRON-BASED TREATMENT MEDIA

    EPA Science Inventory

    Arsenic concentrations (Total Recoverable As by EPA Method 3051) and solid-phase speciation (by X-ray Absorption Near-Edge Spectroscopy-XANES) were assessed as a function of depth through Fe-media beds for two commercially available products from pilot-scale field tests. These r...

  8. Waste activated sludge treatment based on temperature staged and biologically phased anaerobic digestion system.

    PubMed

    Yu, Jingwen; Zheng, Mingxia; Tao, Tao; Zuo, Jiane; Wang, Kaijun

    2013-10-01

    The concept of temperature staged and biological phased (TSBP) was proposed to enhance the performance of waste-activated sludge anaerobic digestion. Semi-continuous experiments were used to investigate the effect of temperature (35 to 70 degrees C) as well as the hydraulic retention time (HRT) (2, 4 and 6 days) on the acidogenic phase. The results showed that the solubilization degree of waste-activated sludge increased from 14.7% to 30.1% with temperature increasing from 35 to 70 degrees C, while the acidification degree was highest at 45 degrees C (17.6%), and this was quite different from the temperature impact on hydrolysis. Compared with HRT of 2 and 6 days, 4 days was chosen as the appropriate HRT because of its relatively high solubilization degree (24.6%) and acidification degree (20.1%) at 45 degrees C. The TSBP system combined the acidogenic reactor (45 degrees C, 4 days) with the methanogenic reactor (35 degrees C, 16 days) and the results showed 84.8% and 11.4% higher methane yield and volatile solid reduction, respectively, compared with that of the single-stage anaerobic digestion system with HRT of 20 days at 35 degrees C. Moreover, different microbial morphologies were observed in the acidogenic- and methanogenic-phase reactors, which resulted from the temperature control and HRT adjustment. All the above results indicated that 45 degrees C was the optimum temperature to inhibit the activity of methanogenic bacteria in the acidogenic phase, and temperature staging and phase separation was thus accomplished. The advantages of the TSBP process were also confirmed by a full-scale waste-activated sludge anaerobic digestion project which was an energy self-sufficient system. PMID:24494492

  9. Effects of gelatin sponge combined with moist wound-healing nursing intervention in the treatment of phase III bedsore

    PubMed Central

    LI, YANLING; YAO, MEIYING; WANG, XIA; ZHAO, YANQING

    2016-01-01

    Pressure sore pertains to tissue damage or necrosis that occurs due to lack of adequate nutrition following long-term exposure to pressure and decreased blood circulation. The aim of the study was to examine the effects of gelatin sponge combined with moist wound-healing nursing intervention in the treatment of phase III bedsore. In total, 50 patients with phase III bedsore were included in the present study. The patients were randomly divided into the control (n=25) and observation (n=25) groups. Patients in the control group received conventional nursing, while those in the observation group received gelatin sponge combined with moist wound healing nursing. The effects of the two nursing methods were compared and analyzed. The results showed that the improvement rate of the observation group was significantly higher than that of the control group (P<0.05). The Branden score and area of pressure sore of the observation group were significantly lower than those of the control group (P<0.05). The frequency and time of dressing change and the average cost of hospitalization of the observation group were significantly lower than those of the control group (P<0.001). In conclusion, gelatin sponge combined with moist wound-healing nursing intervention may significantly improve the treatment of phase III bedsore. PMID:27313666

  10. Effective treatment of olive mill effluents from two-phase and three-phase extraction processes by batch membranes in series operation upon threshold conditions.

    PubMed

    Ochando-Pulido, J M; Hodaifa, G; Victor-Ortega, M D; Rodriguez-Vives, S; Martinez-Ferez, A

    2013-12-15

    Production of olive oil results in the generation of high amounts of heavy polluted effluents characterized by extremely variable contaminants degree, leading to sensible complexity in treatment. In this work, batch membrane processes in series comprising ultrafiltration (UF), nanofiltration (NF) and reverse osmosis (RO) are used to purify the effluents exiting both the two-phase and tree-phase extraction processes to a grade compatible to the discharge in municipal sewer systems in Spain and Italy. However, one main problem in applying this technology to wastewater management issues is given by membrane fouling. In the last years, the threshold flux theory was introduced as a key tool to understand fouling problems, and threshold flux measurement can give valuable information regarding optimal membrane process design and operation. In the present manuscript, mathematical approach of threshold flux conditions for membranes operation is addressed, also implementing proper pretreatment processes such as pH-T flocculation and UV/TiO2 photocatalysis with ferromagnetic-core nanoparticles in order to reduce membranes fouling. Both influence the organic matter content as well as the particle size distribution of the solutes surviving in the wastewater stream, leading, when properly applied, to reduced fouling, higher rejection and recovery values, thus enhancing the economic feasibility of the process. PMID:23602253

  11. Clinical studies in dermatology require a post-treatment observation phase to define the impact of the intervention on the natural history of the complaint.

    PubMed

    Sinclair, Rodney; Turner, Graham A; Jones, D Andrew R; Luo, Shengjun

    2016-08-01

    The use of a post-treatment period of observation or "regression phase" is common in pharmaceutical and cosmetic clinical dermatology studies. Regression phases can be incorporated into a variety of study designs, ranging from simple post-treatment observation for a defined period, as has been used for moisturizers, antidandruff formulations, and treatments for acne, to more complex randomized intermittent-treatment designs, as used in studies of psoriasis pharmacotherapies. Extensive information can be derived from a regression phase. Notably, it can provide useful data on the persistence of effect and time to relapse after treatment cessation, which are particularly relevant to skin conditions in which consumer or patient adherence to treatment is suboptimal. By incorporating a regression phase, a clinical study can more closely reflect "real-world" behavior, e.g., the switching by consumers from antidandruff to beauty shampoos. The regression phase can also help to differentiate between products that show similar effectiveness during the treatment phase, and monitoring post-treatment physiological end points can provide valuable evidence on the safety and mechanism of action of the therapy. PMID:27025208

  12. Sequential combined treatment with allopurinol and benznidazole in the chronic phase of Trypanosoma cruzi infection: a pilot study

    PubMed Central

    Perez-Mazliah, D. E.; Alvarez, M. G.; Cooley, G.; Lococo, B. E.; Bertocchi, G.; Petti, M.; Albareda, M. C.; Armenti, A. H.; Tarleton, R. L.; Laucella, S. A.; Viotti, R.

    2013-01-01

    Objectives Even though the use of combined drugs has been proved to be effective in other chronic infections, assessment of combined treatment of antiparasitic drugs in human Chagas' disease has not been performed. Herein, a pilot study was conducted to evaluate the tolerance and side effects of a sequential combined treatment of two antiparasitic drugs, allopurinol and benznidazole, in the chronic phase of Trypanosoma cruzi infection. Patients and methods Changes in total and T. cruzi-specific T and B cells were monitored during a median follow-up of 36 months. Allopurinol was administered for 3 months (600 mg/day) followed by 30 days of benznidazole (5 mg/kg/day) in 11 T. cruzi-infected subjects. Results The combined sequential treatment of allopurinol and benznidazole was well tolerated. The levels of T. cruzi-specific antibodies significantly decreased after sequential combined treatment, as determined by conventional serology and by a multiplex assay using recombinant proteins. The frequency of T. cruzi-specific interferon-γ-producing T cells significantly increased after allopurinol treatment and decreased to background levels following benznidazole administration in a substantial proportion of subjects evaluated. The levels of total naive (CD45RA + CCR7 + CD62L+) CD4 + and CD8 + T cells were restored after allopurinol administration and maintained after completion of the combined drug protocol, along with a decrease in T cell activation in total peripheral CD4 + and CD8 + T cells. Conclusions This pilot study shows that the combination of allopurinol and benznidazole induces significant modifications in T and B cell responses indicative of a reduction in parasite burden, and sustains the feasibility of administration of two antiparasitic drugs in the chronic phase of Chagas' disease. PMID:23104493

  13. Treatment of Produced Waters Using a Surfactant Modified Zeolite/Vapor Phase Bioreactor System

    SciTech Connect

    Lynn E. Katz; Kerry A. Kinney; R. S. Bowman; E. J. Sullivan

    2004-09-11

    This report summarizes work performed on this project from April 2004 through September 2004. Our previous work demonstrated that a polyurethane foam biofilter could successfully biodegrade the BTEX contaminants found in the SMZ regeneration waste gas stream. However, establishing the biomass on the polyurethane foam packing was relatively time consuming and daily recirculation of a concentrated nutrient solution was required for efficient operation of the foam biofilter. To simplify the start up and operating requirements of the biofilter system, a simple, compost-based biofilter was investigated for its ability to treat the BTEX contaminants generated during the SMZ regeneration process. The investigation of the compost biofilter was divided into three experimental phases that spanned 180 days of biofilter operation. During Phase 1, the biofilter was continuously supplied a BTEX-contaminated waste gas stream. During Phase 2, a series of periodic shutdown tests were conducted to assess how the biofilter responded when the BTEX feed was discontinued for periods ranging from 1 day to 2.8 days. The Phase 3 experiments focused on determining how the biofilter would handle periodic spikes in inlet BTEX concentration as would be expected when it is coupled with an SMZ column. Results from the continuous feed (Phase 1) experiments demonstrated that the compost biofilter could maintain BTEX removals of greater than 98% within two weeks of startup. Results of the shutdown experiments indicated that benzene removal was the most sensitive to interruptions in the BTEX feed. Nevertheless, the BTEX removal efficiency exceeded 95% within 6 hours of reestablishing the BTEX feed to the biofilter. When the biofilter was subjected to periodic spikes in BTEX concentration (Phase 3), it was found that the total BTEX removal efficiency stabilized at approximately 75% despite the fact that the biofilter was only fed BTEX contaminants 8 hours per day. Finally, the effects of nutrient

  14. Hermitian-phase-operator treatment of the superfluid states in a quantum two-well problem

    SciTech Connect

    Kostrun, Marijan

    2004-07-01

    We apply the Hermitian phase operator method (HPOM), as discussed by Pegg and Barnett [D. T. Pegg and S. M. Barnett, Phys. Rev. A 39, 1665 (1989)] to a two-well Bose-Hubbard model. Application of the HPOM formalism yields an approximate quantum phase model, or a Schroedinger-like differential equation for the phase variable {theta}, which is a conjugate variable to the half of the number difference between the wells, m=(N{sub 1}-N{sub 2})/2. In the construction of the model we take care so that the Hermiticity of the original Bose-Hubbard model in number representation is inherited. We demonstrate that the quantum phase model supersedes two theoretical models suggested for the group of so-called 'normal' states, for which <{theta}>==0: a non-Hermitian 'exact quantum phase model' by Anglin, Drummond, and Smerzi [J. R. Anglin, P. Drummond, and A. Smerzi, Phys. Rev. A 64, 063605 (2001) ], and the 'phonon model' by Javanainen and Ivanov [J. Javanainen and M. Yu. Ivanov, Phys. Rev. A 60, 2351 (1999)]. We apply the HPOM to the so called 'superfluid' states, for which =0 and <{theta}>={pi}, and find their superfluid phonon model. We find that the superfluid phonon model has a threshold point M={delta}/(4gN)=1, at which the model diverges. Here, {delta} is the tunneling rate between the wells and g is the self-interaction, while N is the total number of particles. The above threshold phonon model is quite accurate in the description of the number and phase statistics of the superfluid states. We show that at the threshold point HPOM itself can be exactly solved. However, the agreement between the exact solution and the HPOM solution is poor: close to the threshold assumes values {approx}N{sup 2}, thus voiding the second order expansion the HPOM is based on, N{sup 2}.

  15. Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies

    PubMed Central

    Burri, Christian; Yeramian, Patrick D.; Merolle, Ada; Serge, Kazadi Kyanza; Mpanya, Alain; Lutumba, Pascal; Mesu, Victor Kande Betu Ku; Lubaki, Jean-Pierre Fina; Mpoto, Alfred Mpoo; Thompson, Mark; Munungu, Blaise Fungula; Josenando, Théophilo; Bernhard, Sonja C.; Olson, Carol A.; Blum, Johannes; Tidwell, Richard R.; Pohlig, Gabriele

    2016-01-01

    Background Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT. Methods The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent. Findings/Conclusion Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3. PMID:26881924

  16. Prophylactic nimodipine treatment for cochlear and facial nerve preservation after vestibular schwannoma surgery: a randomized multicenter Phase III trial.

    PubMed

    Scheller, Christian; Wienke, Andreas; Tatagiba, Marcos; Gharabaghi, Alireza; Ramina, Kristofer F; Ganslandt, Oliver; Bischoff, Barbara; Zenk, Johannes; Engelhorn, Tobias; Matthies, Cordula; Westermaier, Thomas; Antoniadis, Gregor; Pedro, Maria Teresa; Rohde, Veit; von Eckardstein, Kajetan; Kretschmer, Thomas; Kornhuber, Malte; Steighardt, Jörg; Richter, Michael; Barker, Fred G; Strauss, Christian

    2016-03-01

    OBJECT A pilot study of prophylactic nimodipine and hydroxyethyl starch treatment showed a beneficial effect on facial and cochlear nerve preservation following vestibular schwannoma (VS) surgery. A prospective Phase III trial was undertaken to confirm these results. METHODS An open-label, 2-arm, randomized parallel group and multicenter Phase III trial with blinded expert review was performed and included 112 patients who underwent VS surgery between January 2010 and February 2013 at 7 departments of neurosurgery to investigate the efficacy and safety of the prophylaxis. The surgery was performed after the patients were randomly assigned to one of 2 groups using online randomization. The treatment group (n = 56) received parenteral nimodipine (1-2 mg/hr) and hydroxyethyl starch (hematocrit 30%-35%) from the day before surgery until the 7th postoperative day. The control group (n = 56) was not treated prophylactically. RESULTS Intent-to-treat analysis showed no statistically significant effects of the treatment on either preservation of facial nerve function (35 [67.3%] of 52 [treatment group] compared with 34 [72.3%] of 47 [control group]) (p = 0.745) or hearing preservation (11 [23.4%] of 47 [treatment group] compared with 15 [31.2%] of 48 [control group]) (p = 0.530) 12 months after surgery. Since tumor sizes were significantly larger in the treatment group than in the control group, logistic regression analysis was required. The risk for deterioration of facial nerve function was adjusted nearly the same in both groups (OR 1.07 [95% CI 0.34-3.43], p = 0.91). In contrast, the risk for postoperative hearing loss was adjusted 2 times lower in the treatment group compared with the control group (OR 0.49 [95% CI 0.18-1.30], p = 0.15). Apart from dose-dependent hypotension (p < 0.001), no clinically relevant adverse reactions were observed. CONCLUSIONS There were no statistically significant effects of the treatment. Despite the width of the confidence intervals, the

  17. A new general methodology for incorporating physico-chemical transformations into multi-phase wastewater treatment process models.

    PubMed

    Lizarralde, I; Fernández-Arévalo, T; Brouckaert, C; Vanrolleghem, P; Ikumi, D S; Ekama, G A; Ayesa, E; Grau, P

    2015-05-01

    This paper introduces a new general methodology for incorporating physico-chemical and chemical transformations into multi-phase wastewater treatment process models in a systematic and rigorous way under a Plant-Wide modelling (PWM) framework. The methodology presented in this paper requires the selection of the relevant biochemical, chemical and physico-chemical transformations taking place and the definition of the mass transport for the co-existing phases. As an example a mathematical model has been constructed to describe a system for biological COD, nitrogen and phosphorus removal, liquid-gas transfer, precipitation processes, and chemical reactions. The capability of the model has been tested by comparing simulated and experimental results for a nutrient removal system with sludge digestion. Finally, a scenario analysis has been undertaken to show the potential of the obtained mathematical model to study phosphorus recovery. PMID:25746499

  18. Advanced conceptual design report. Phase II. Liquid effluent treatment and disposal Project W-252

    SciTech Connect

    1995-01-31

    This Advanced Conceptual Design Report (ACDR) provides a documented review and analysis of the Conceptual Design Report (CDR), WHC-SD-W252-CDR-001, June 30, 1993. The ACDR provides further design evaluation of the major design approaches and uncertainties identified in the original CDR. The ACDR will provide a firmer basis for the both the design approach and the associated planning for the performance of the Definitive Design phase of the project.

  19. Phase I/II Trial Evaluating Carbon Ion Radiotherapy for Salvaging Treatment of Locally Recurrent Nasopharyngeal Carcinoma

    PubMed Central

    Kong, Lin; Hu, Jiyi; Guan, Xiyin; Gao, Jing; Lu, Rong; Lu, Jiade J.

    2016-01-01

    , carbon ion radiation therapy offers an ideal alternate to conventional X-ray irradiation. Methods and Design: The recommended dose of re-irradiation using CIRT for locally recurrent NPC will be determined in the dose-escalating phase (Phase I) of the study. Efficacy in terms of local progression-free survival (LPFS) and overall survival (OS) will be studied in the second phase of the study. Increasing doses of CIRT using raster scanning technology from 55GyE (22×2.5 GyE) to 65 GyE (26× 2.5 GyE) will be delivered in the Phase I part of the study. The primary endpoint of the Phase I part of the study is acute and sub-acute toxicities; the primary endpoint in the Phase II part is local progression-free survival and overall survival. Using the historical 2-year OS rate of 50% in locally recurrent NPC patients treated with photon or proton, we hypothesize that CIRT can improve the 2-year OS rate to 70%. Discussion: The utilization of conventional radiation techniques including IMXT, brachytherapy, or stereotactic radiation therapy provides moderate efficacy in the treatment of locally recurrent NPC due to the limitations in dose distribution and biological effectiveness. Improved outcome in terms of treatment-induced toxicity, LC, LPFS, and OS are expected using CIRT due to the physical and biological characteristics of carbon ion beam. However, the recommended dose of CIRT used in re-irradiation for the local NPC focus remain to be determined. The recommended dose as well as the efficacy of CIRT in the treatment of locally recurrent NPC will be evaluated in the present trial. PMID:27162535

  20. Effect of Intercritical Heat Treatment on the Abrasive Wear Behaviour of Plain Carbon Dual Phase Steel

    NASA Astrophysics Data System (ADS)

    Manoj, M. K.; Pancholi, V.; Nath, S. K.

    Dual phase (DP) steels have been prepared from low carbon steel (0.14% C) at intercritical temperature 740°C and time is varied from 1 minute to 30 minutes followed by water quenching. These steels have been characterized by optical microscopy, FE-SEM, hardness measurements, tensile properties and electron backscattered diffraction (EBSD) studies. Tensile properties of a typical dual phase steel are found to be 805 MPa ultimate tensile strength with 18% total elongation. Martensite volume fraction of D P steel (determined by EBSD technique) prepared at 740°C for 6 minutes is found to be 10.2% and the grain size of ferrite and martensite found to be 14.39 micron and 1.05 microns respectively. Abrasive wear resistance of dual phase steels has been determined by pin on drum wear testing machine. DP steels have been found to be 25% more wear resistant than that of normalized steel. Short intercritical heating time followed by water quenching gives higher wear resistance by virtue of smaller and well dispersed martensite island in the matrix of ferrite.

  1. Translational and Early Phase Strategies for Treatment Development: Report of ISCTM Autumn 2013 Symposium

    PubMed Central

    Young, Jared W.; Potter, William Z.; Riley, Steve; Groeneveld, Geert J.; Kinon, Bruce J.; Egan, Mike F.; Feltner, Douglas E.

    2015-01-01

    For decades, there has been a distinct disconnect translating a compound’s effects from basic neuroscience into clinical efficacy. This disconnect has not only been in terms of generating approved compounds, but also in rejecting targets. During the drug discovery process there are key points to be adhered to that would strengthen the likelihood of a compound being translated to the clinic. These points include 1) the importance of translational pharmacology whereby preclinical pharmacological data should predict clinical efficacy; 2) rigorous early phase drug evaluation to enhance early go/no-go decisionmaking; 3) using exposure response modeling to predict drug efficacy during proof-of-concept trials; 4) designing and conducting the appropriate proof-of-concept study; and 5) optimizing Phase II studies to set the stage for success in Phase III trials. These topics were covered in The International Society for CNS Clinical Trials and Methodology (ISCTM) Autumn 2013 meeting on the topic of translational and early development strategies and tools led by Drs. Potter and Feltner. This report comprises a review of those proceedings with a concluding summary to advance future clinical trials. PMID:25977839

  2. Reduction phases of thin iron-oxide nanowires upon thermal treatment and Li exposure

    SciTech Connect

    Angelucci, Marco Frau, Eleonora; Grazia Betti, Maria; Hassoun, Jusef; Hong, Inchul; Panero, Stefania; Scrosati, Bruno; Mariani, Carlo

    2014-04-28

    Iron oxide nanostructures, a promising alternative to carbon-based anode in lithium-ion batteries, can be produced using a hard template route. This procedure guarantees the formation of Fe{sub 2}O{sub 3} nanowires with comparable diameter and size (average diameter 8 nm) with a dominant cubic γ-phase at the surface. Lithium exposure of the iron oxide nanowires in ultra-high-vacuum (UHV) conditions induces reduction of the Fe ion, leading to a Fe{sub 3}O{sub 4} and then to a Fe{sup 2+} phase, as determined by means of core-level photoemission spectroscopy. Mild annealing of Fe{sub 2}O{sub 3} in UHV determines an oxygen content reduction for the nanowires at lower temperature with respect to the bulk phase. The morphology and the evolution of the electronic properties upon reduction have been compared to those of micro-sized bulk-like grains, to unravel the role of the reduced size and surface-volume ratio.

  3. SOLID-PHASE TREATMENT OF A PENTACHLOROPHENOL- CONTAMINATED SOIL USING LIGNIN-DEGRADING FUNGI

    EPA Science Inventory

    The abilities of three lignin-degrading fungi, Phanerochaete chrysosporium, Phanerochaete sordida, and Trametes hirsuta, to deplete pentachlorophenol (PCP) from soil contaminated with PCP and creosote were evaluated. A total of seven fungal and three control treatments ...

  4. HANDLING AND DISPOSAL OF SLUDGES FROM COMBINED SEWER OVERFLOW TREATMENT. PHASE II - IMPACT ASSESSMENT

    EPA Science Inventory

    This report documents the results of an assessment of the effort that the United States will have to exert in the area of sludge handling and disposal if, in fact, full-scale treatment of combined sewer overflows is to become a reality. The results indicate that nationwide an ave...

  5. EVALUATION OF OPERATION AND MAINTENANCE FACTORS LIMITING MUNICIPAL WASTEWATER TREATMENT PLANT PERFORMANCE. PHASE II

    EPA Science Inventory

    Many of the country's wastewater treatment plants do not meet design expectations and NPDES permit standards. A research project was initiated to identify, quantify and rank the causes of this poor performance by comprehensive evaluations of 50 plants in nine western states. The ...

  6. ELECTRICITY GENERATION FROM ANAEROBIC WASTEWATER TREATMENT IN MICROBIAL FUEL CELLS (MFCS) - PHASE I

    EPA Science Inventory

    Municipal wastewater treatment plants represent a huge energy ‘sink’ in the United States. Estimates are that these plants consume up to 3 percent of the total amount of power consumed annually. Ironically, the wastewater is concentrated with materials (carbohydrates) which ...

  7. FOULING-RESISTANT CERAMIC MEMBRANES FOR TREATMENT OF METASTABLE OIL/WATER EMULSIONS - PHASE II

    EPA Science Inventory

    Billions of gallons of oily wastewaters are generated daily by a variety of industrial sources. A large fraction of these are oil/water emulsions for which current treatment technologies are often costly and ineffective. Although such emulsions can be separated using crossf...

  8. Internal friction measurements of phase transformations during the process of deep cryogenic treatment of a tool steel

    NASA Astrophysics Data System (ADS)

    Li, Shaohong; Min, Na; Li, Junwan; Wu, Xiaochun

    2013-10-01

    This paper reports internal friction measurements in die steel with the aim of clarifying phase transformation mechanisms during deep cryogenic treatment (DCT). Internal friction peaks appeared in the quenched sample and the DCT treated material during the process of cooling down to -160 °C from room temperature (20 °C) and then heating up to room temperature for multiple cycles in high vacuum. However, internal friction peaks do not appear in annealed material. It is concluded that the internal friction peaks are attributed to stress-induced martensite formation based on thermal hysteresis phenomena. That is, retained austenite is mostly transformed into martensite during the DCT.

  9. Electronic Monitoring of Medication Adherence in Early Maintenance Phase Treatment for Pediatric Leukemia and Lymphoma: Identifying Patterns of Nonadherence

    PubMed Central

    Drotar, Dennis; Alderfer, Melissa; Donewar, Crista Wetherington; Ewing, Linda; Katz, Ernest R.; Muriel, Anna

    2015-01-01

    Objective To describe patterns of treatment adherence to early maintenance phase therapy for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). Methods Using an objective observational method (electronic monitoring), adherence was examined for 139 patients aged 7–19 years diagnosed with ALL or LBL across 6 centers. Results The mean adherence percentage was 86.2%. Adherence rates declined over the 1-month of follow-up to 83%. 3 linear trajectories of 6-mercaptopurine adherence were identified: (1) exemplary adherence (n = 99): Averaging nearly 100%; (2) deteriorating (n = 23): Adherence decreased from 100 to 60%; and (3) chronically poor adherence (n = 9): Averaging 40%. Conclusions Adherence promotion interventions might be tailored to subgroups of patients who demonstrated problematic patterns of treatment adherence that could place them at risk for relapse. This research demonstrates the importance of using objective real-time measures of medication adherence for measuring and documenting adherence patterns. PMID:24365698

  10. Evaluating a novel treatment for coronary artery inflammation in acute Kawasaki disease: A Phase I/IIa trial of atorvastatin

    PubMed Central

    Tremoulet, Adriana H; Jain, Sonia; Burns, Jane C

    2016-01-01

    Introduction Since the 1980s, the primary treatment of acute Kawasaki disease (KD) has been intravenous immunoglobulin and aspirin. However, 5-10% of children with acute KD will develop coronary artery abnormalities despite treatment within the first ten days after fever onset. There is no approved adjunctive therapy to prevent progression of coronary artery damage in these patients Areas covered The rationale and study design of a Phase I/IIa trial of atorvastatin in children with acute KD and coronary artery inflammation is presented. The studies of host genetics and KD pathogenesis leading up to this trial are reviewed. Expert opinion The repurposing of well-studied drugs used in the adult population is a cost-effective and efficient strategy to identify new therapies for pediatric diseases. Exploiting the anti-inflammatory, non-lipid-lowering effects of statins may open up new applications for this class of drugs for the pediatric age group.

  11. Dasatinib in the Treatment of Chronic Myeloid Leukemia in Accelerated Phase After Imatinib Failure: The START A Trial

    PubMed Central

    Apperley, Jane F.; Cortes, Jorge E.; Kim, Dong-Wook; Roy, Lydia; Roboz, Gail J.; Rosti, Gianantonio; Bullorsky, Eduardo O.; Abruzzese, Elisabetta; Hochhaus, Andreas; Heim, Dominik; de Souza, Carmino A.; Larson, Richard A.; Lipton, Jeffrey H.; Khoury, H. Jean; Kim, Hyeoung-Joon; Sillaber, Christian; Hughes, Timothy P.; Erben, Philipp; Van Tornout, Jan; Stone, Richard M.

    2009-01-01

    Purpose Patients with chronic myelogenous leukemia in accelerated phase (CML-AP) that is resistant or intolerant to imatinib have limited therapeutic options. Dasatinib, a potent inhibitor of BCR-ABL and SRC-family kinases, has efficacy in patients with CML-AP who have experienced treatment failure with imatinib. We now report follow-up data from the full patient cohort of 174 patients enrolled onto a phase II trial to provide a more complete assessment of the efficacy and safety of dasatinib in this population. Patients and Methods Patients with imatinib-resistant (n = 161) or -intolerant (n = 13) CML-AP received dasatinib 70 mg orally twice daily. Results At a median follow-up of 14.1 months (treatment duration, 0.1 to 21.7 months), major and complete hematologic responses were attained by 64% and 45% of patients, respectively, and major and complete cytogenetic responses were achieved in 39% and 32% of patients, respectively. Responses were achieved irrespective of imatinib status (resistant or intolerant), prior stem-cell transplantation, or the presence of prior BCR-ABL mutation. The 12-month progression-free survival and overall survival rates were 66% and 82%, respectively. Dasatinib was generally well tolerated; the most frequent nonhematologic severe treatment-related adverse event was diarrhea (52%; grade 3 to 4, 8%). Cytopenias were common, including grade 3 to 4 neutropenia (76%) and thrombocytopenia (82%). Pleural effusion occurred in 27% of patients (grade 3 to 4, 5%). Conclusion Dasatinib is effective in patients with CML-AP after imatinib treatment failure. PMID:19487385

  12. Improvement and further development in CESM/CAM5: gas-phase chemistry and inorganic aerosol treatments

    NASA Astrophysics Data System (ADS)

    He, J.; Zhang, Y.

    2014-09-01

    Gas-phase chemistry and subsequent gas-to-particle conversion processes such as new particle formation, condensation, and thermodynamic partitioning have large impacts on air quality, climate, and public health through influencing the amounts and distributions of gaseous precursors and secondary aerosols. Their roles in global air quality and climate are examined in this work using the Community Earth System Model version 1.0.5 (CESM1.0.5) with the Community Atmosphere Model version 5.1 (CAM5.1) (referred to as CESM1.0.5/CAM5.1). CAM5.1 includes a simple chemistry that is coupled with a 7-mode prognostic Modal Aerosol Model (MAM7). MAM7 includes classical homogenous nucleation (binary and ternary) and activation nucleation (empirical first-order power law) parameterizations, and a highly simplified inorganic aerosol thermodynamics treatment that only simulates particulate-phase sulfate and ammonium. In this work, a new gas-phase chemistry mechanism based on the 2005 Carbon Bond Mechanism for Global Extension (CB05_GE) and several advanced inorganic aerosol treatments for condensation of volatile species, ion-mediated nucleation (IMN), and explicit inorganic aerosol thermodynamics for sulfate, ammonium, nitrate, sodium, and chloride have been incorporated into CESM/CAM5.1-MAM7. Compared to the simple gas-phase chemistry, CB05_GE can predict many more gaseous species, and thus could improve model performance for PM2.5, PM10, PM components, and some PM gaseous precursors such as SO2 and NH3 in several regions as well as aerosol optical depth (AOD) and cloud properties (e.g., cloud fraction (CF), cloud droplet number concentration (CDNC), and shortwave cloud forcing, SWCF) on the global scale. The modified condensation and aqueous-phase chemistry could further improve the prediction of additional variables such as HNO3, NO2, and O3 in some regions, and new particle formation rate (J) and AOD on the global scale. IMN can improve the prediction of secondary PM2

  13. Research on soybean protein wastewater treatment by the integrated two-phase anaerobic reactor

    PubMed Central

    Yu, Yaqin

    2015-01-01

    The start-up tests of treating soybean protein wastewater by the integrated two-phase anaerobic reactor were studied. The results showed that the soybean protein wastewater could be successfully processed around 30 days when running under the situation of dosing seed sludge with the influent of approximately 2000 mg/L and an HRT of 40 h. When the start-up was finished, the removal rate of COD by the reactor was about 80%. In the zone I, biogas mainly revealed carbon dioxide (CO2) and hydrogen (H2). Methane was the main component in the zone 2 which ranged from 53% to 59% with an average of 55%. The methane content in biogas increased from the zone I to II. It indicated that the methane-producing capacity of the anaerobic sludge increased. It was found that the uniquely designed two-phase integrated anaerobic reactor played a key role in treating soybean protein wastewater. The acidogenic fermentation bacteria dominated in the zone I, while methanogen became dominant in the zone II. It realized the relatively effective separation of hydrolysis acidification and methanogenesis process in the reactor, which was benefit to promote a more reasonable space distribution of the microbial communities in the reactor. There were some differences between the activities of the sludge in the two reaction zones of the integrated two-phase anaerobic reactor. The activity of protease was higher in the reaction zone I. And the coenzyme F420 in the reaction zone II was twice than that in the reaction zone I, which indicated that the activity of the methanogens was stronger in the reaction zone II. PMID:26288554

  14. Phase and structural transformations in U and U-Nb alloy upon severe deformation and heat treatments

    NASA Astrophysics Data System (ADS)

    Zuev, Yu. N.; Sagaradze, V. V.; Pecherkina, N. L.; Kabanova, I. I.; Svyatov, I. L.; Bondarchuk, S. V.; Belyaev, D. V.

    2013-12-01

    Transmission electron microscopy was used to analyze the twin and dislocation structure of samples of commercial uranium in the initial (undeformed) state and after severe deformation using explosive loading by plane and spherical waves of various intensity. It has been shown that an increase in the intensity of explosive loading by a plane wave leads, first, to an increase in the density of randomly distributed dislocations and twins and, then, to the development of polygonization processes with the formation of a subgrain structure of the α phase. Crystallographic analysis of the initial and deformation-induced twins in uranium has shown the presence of predominantly {130} twins of mixed type and, in singular cases, {172} and {176} twins of the second kind. It has been established that the retained spherical shells have a distinctly pronounced zonal structure, which contains information on the forward and reverse martensitic phase transformations of uranium (α ↔ β(γ) ↔ L, etc.) that occur under shock-wave loading by spherical waves. Conditions are determined for the manifestation of structural heredity in the U-6 wt % Nb alloy with recovery of the size and shape of grains of the initial high-temperature γ phase during the forward γ → α″ martensitic transformation upon cooling and during reverse α″ → γ transformation upon heating. Elimination of the structural heredity with significant grain refinement of the high-temperature γ phase occurs in the process of repeated quenching from 700°C after one type of preliminary treatments (cold deformation of α″ martensite, recrystallization of the deformed α″ phase, high-temperature aging of the initial α″ martensite, and eutectoid decomposition).

  15. Firstline treatment for chronic phase chronic myeloid leukemia patients should be based on a holistic approach.

    PubMed

    Breccia, Massimo; Alimena, Giuliana

    2015-02-01

    New selective and more potent drugs for the cure of chronic phase chronic myeloid leukemia patients are now available: physicians in some countries must decide the best option, selecting one of the drugs available. What the main prognostic factors are in order to make this selection remains a matter of discussion. Introducing a 'holistic approach' for the first time in chronic myeloid leukemia, as practiced in other diseases, and looking at the patient in a complete picture, considering several variables, such as comorbidities, age, concomitant drugs, lifestyle and patient expectations, may be of help to understand, patient by patient, the best therapeutic strategy. PMID:25431965

  16. Phase Transformations and Microstructural Observations During Subcritical Heat Treatments of a High-Chromium Cast Iron

    NASA Astrophysics Data System (ADS)

    Karantzalis, A. E.; Lekatou, A.; Kapoglou, A.; Mavros, H.; Dracopoulos, V.

    2012-06-01

    In this study, Cr white iron of 18.23 wt.% was subjected to a series of subcritical heat treatments. At both temperatures of 350 and 450 °C, no precipitation of secondary carbides was observed, and the overall microstructure resembles to that of the as-cast condition. At 550 °C, hardness values increased slightly compared to the as-cast values. No evidence of secondary carbide formation was observed. At 650 and 750 °C, extensive-to-complete transformation to pearlite-ferrite structures has occurred. Some evidence of secondary carbide precipitation especially for prolonged treatment periods was not adequate to obstruct the hardness decrease due to the dominating effect of pearlitic-ferritic formation. At 850 °C, secondary carbide precipitation and martensite formation lead to high hardness values.

  17. Acute phase treatment of venous thromboembolism: advanced therapy. Systemic fibrinolysis and pharmacomechanical therapy.

    PubMed

    Konstantinides, Stavros V; Wärntges, Simone

    2015-06-01

    Venous thromboembolism, which encompasses deep-vein thrombosis and acute pulmonary embolism (PE), represents a major contributor to global disease burden worldwide. For patients who present with cardiogenic shock or persistent hypotension (acute high-risk PE), there is consensus that immediate reperfusion treatment applying systemic fibrinolysis or, in the case of a high bleeding risk, surgical or catheter-directed techniques, is indicated. On the other hand, for the large, heterogeneous group of patients presenting without overt haemodynamic instability, the indications for advanced therapy are less clear. The recently updated guidelines of the European Society of Cardiology emphasise the importance of clinical prediction rules in combination with imaging procedures (assessment of right ventricular function) and laboratory biomarkers (indicative of myocardial stress or injury) for distinguishing between an intermediate and a low risk for an adverse early outcome. In intermediate-high-risk PE defined by the presence of both right ventricular dysfunction on echocardiography (or computed tomography) and a positive troponin (or natriuretic peptide) test, the bleeding risks of full-dose fibrinolytic treatment have been shown to outweigh its potential clinical benefits unless clinical signs of haemodynamic decompensation appear (rescue fibrinolysis). Recently published trials suggest that catheter-directed, ultrasound-assisted, low-dose local fibrinolysis may provide an effective and particularly safe treatment option for some of these patients. PMID:25789580

  18. Biological vapor-phase treatment using biofilter and biotrickling filter reactors: Practical operating regimes

    SciTech Connect

    Togna, A.P.; Singh, M. )

    1994-05-01

    The biological treatment of volatile organic compounds (VOCs) and air toxics has received increased attention in recent years. Biotreatment of airborne contaminants offers an inexpensive alternative to conventional air treatment technologies such as carbon adsorption and incineration. Most biological air treatment technologies commercially available are fixed-film systems that rely on growth of a biofilm layer on an inert organic support such as compost or peat (biofilters), or an inorganic support such as ceramic or plastic (biotrickling filters). If designed properly, these systems combine the advantages of high biomass concentration with high specific surface area for mass transfer. At economically viable vapor residence times (1 to 1.5 minutes), biofilters can be used for treating vapor streams containing up to approximately 1500 [mu]g/L of readily biodegradable compounds. Biotrickling filters may offer greater performance than biofilters at high contaminant loadings, possibly due to higher internal biomass concentrations. Both systems are best suited for treating vapor streams containing one or two major compounds. If designed properly, biofilters are especially well suited for treating streams that vary in concentration from minute to minute. 11 refs., 8 figs.

  19. Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase

    PubMed Central

    2012-01-01

    Objective Sulfur mustard (SM) is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980–1988). It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries. Method This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment. Results Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments. PMID:23351279

  20. The Rural Physician and Myocardial Infarction: Part 2: The Hospital Phase of Treatment

    PubMed Central

    Black, Douglas P.

    1984-01-01

    A critical review of the literature reveals several facts which are important in helping the rural physician decide where and how patients with myocardial infarction should be treated. The effectiveness of coronary care units has not been well established, even for patients admitted during the early phase of the disease; they do not benefit the majority of patients admitted five or more hours after the onset of symptoms. Transporting patients over relatively long distances during the early phase results in increased mortality. The survival rates for patients treated in small hospitals is quite comparable to that of patients treated in coronary care units. The majority of rural patients with myocardial infarction are therefore more appropriately treated in a small local hospital than by being transferred to a coronary care unit. Those coronary care units which have been established in small hospitals do not appear to have reduced mortality. Patients with myocardial infarction who are being treated in small hospitals should be observed carefully, but electronic monitoring should be used only when there is a specific indication. PMID:21279063

  1. A new method of two-phase anaerobic digestion for fruit and vegetable waste treatment.

    PubMed

    Wu, Yuanyuan; Wang, Cuiping; Liu, Xiaoji; Ma, Hailing; Wu, Jing; Zuo, Jiane; Wang, Kaijun

    2016-07-01

    A novel method of two-phase anaerobic digestion where the acid reactor is operated at low pH 4.0 was proposed and investigated. A completely stirred tank acid reactor and an up-flow anaerobic sludge bed methane reactor were operated to examine the possibility of efficient degradation of lactate and to identify their optimal operating conditions. Lactate with an average concentration of 14.8g/L was the dominant fermentative product and Lactobacillus was the predominant microorganism in the acid reactor. The effluent from the acid reactor was efficiently degraded in the methane reactor and the average methane yield was 261.4ml/gCOD removed. Organisms of Methanosaeta were the predominant methanogen in granular sludge of methane reactor, however, after acclimation hydrogenotrophic methanogens enriched, which benefited for the conversion of lactate to acetate. The two-phase AD system exhibited a low hydraulic retention time of 3.56days and high methane yield of 348.5ml/g VS removed. PMID:26995617

  2. Tyrosine kinase inhibitors as a first-line treatment in patients with newly diagnosed chronic myeloid leukemia in chronic phase: A mixed-treatment comparison.

    PubMed

    Firwana, Belal; Sonbol, Mohamad Bassam; Diab, Maria; Raza, Shahzad; Hasan, Rim; Yousef, Ibrahim; Zarzour, Ahmad; Garipalli, Archana; Doll, Donald; Murad, M Hassan; Al-Kali, Aref

    2016-03-15

    Tyrosine kinase inhibitors (TKI) are the initial treatment for majority of newly diagnosed patients with chronic myelogenous leukemia (CML) in chronic phase (CP) and are associated with marked improvement in hematological, cytogenetic, molecular response and survival rates compared with other therapies. In this review, we summarize the evidence of TKI efficacy for patients with newly diagnosed CP-CML. Six trials at low risk of bias evaluating TKIs as an initial treatment in adults with newly diagnosed CP-CML and enrolling 2,456 patients were included. Follow-up times ranged from a median of 3 months to 5 years. Direct comparison showed statistically higher rates of major molecular response (MMR ≤ 0.1%(IS)) achievement with second-generation TKIs at 12 months which was sustained throughout treatment period. Bayesian mixed-treatment comparison (MTC) analysis demonstrated superiority of both nilotinib and dasatinib over imatinib in terms of efficacy. Nilotinib was associated with higher deeper molecular responses (MR(4.5) ≤ 0.0032%(IS)) at 60 months than dasatinib but no difference in MMR. The differences between nilotinib and dasatinib are likely clinically trivial. Among TKIs, nilotinib was found to have the best survival profile. Both nilotinib and dasatinib are associated with significantly better MMR compared to imatinib that is sustained over 60 months. This analysis shows that new-generation TKIs are not only showing faster response but also maintaining a more potent one through longer follow-up period. It is important to note out that MTC is not a substitute for well-conducted RCTs investigating direct comparisons. PMID:26455714

  3. A group-based approach to stabilisation and symptom management in a phased treatment model for refugees and asylum seekers

    PubMed Central

    Robertson, Mary E. A.; Blumberg, Jocelyn M.; Gratton, Jacqui L.; Walsh, Eileen G.; Kayal, Hamodi

    2013-01-01

    Background Traumatised asylum seekers and refugees may present with significant and complex mental health problems as a result of prolonged, extreme, and multiple traumatic events. This is further complicated by ongoing complex social circumstances. Concepts In our work at the Traumatic Stress Clinic (TSC), the understanding afforded by the concept of complex posttraumatic stress disorder (PTSD) together with the related notion of a phased treatment model, provides a useful framework for organising our work with this population. Clinical Applications An explication of complex PTSD as it applies to our client group is presented, followed by a description of our phased treatment model and an outline of the core principles, which guide our clinical approach. Our symptom management and stabilisation groups have been developed and refined over time and draw on techniques from a variety of cognitive behavioural therapies. These are described in some detail with illustrative clinical case vignettes. Conclusion This paper concludes with some reflections on the challenges inherent to working with this complex client group. PMID:24371509

  4. A multicentre phase II study of carboplatin and prolonged oral etoposide in the treatment of cancer of unknown primary site (CUPS).

    PubMed Central

    Warner, E.; Goel, R.; Chang, J.; Chow, W.; Verma, S.; Dancey, J.; Franssen, E.; Dulude, H.; Girouard, M.; Correia, J.; Gallant, G.

    1998-01-01

    Cisplatin-based combination chemotherapy is frequently used to treat patients with carcinoma of unknown primary site (CUPS). Response rates in the literature range from 12% to 26% and median survival from 5 to 7 months. The goal of this study was to evaluate the combination of carboplatin and prolonged oral etoposide in patients with CUPS, with the hope of minimizing toxicity but improving efficacy and convenience. Treatment consisted of carboplatin, 300 mg m(-2) on day 1, and oral etoposide 50 mg on days 1-20, every 4 weeks for up to nine cycles. A total of 33 patients were treated and all were evaluable for toxicity. Non-haematological toxicity was mild to moderate, with the exception of one case of grade 4 stomatitis. Grade 4 leucopenia was observed in eight (24%) patients and sepsis in four (12%), with two and possibly three treatment-related deaths. For the 26 patients evaluable for response, the response rate was 23% with responses lasting a median of 11 months (range 7-13 months), with one patient still responding at 12 months. An additional nine patients (35%) had stable disease. Median survival for all patients was 5.6 months (range 2 weeks to 33 months). The combination of carboplatin with prolonged oral etoposide has moderate activity similar to that of other platinum-based regimens and is a well tolerated, convenient, outpatient regimen. Dosing according to estimated creatinine clearance to achieve a carboplatin AUC of 6.0 mg ml(-1) min might have decreased the incidence of severe myelotoxicity without compromising the regimen's efficacy. PMID:9649162

  5. Effects of Melt Thermal-Rate Treatment on Fe-Containing Phases in Hypereutectic Al-Si Alloy

    NASA Astrophysics Data System (ADS)

    Wang, Qinglei; Geng, Haoran; Zhang, Shuo; Jiang, Huawei; Zuo, Min

    2013-11-01

    In this paper, effects of melt thermal-rate treatment (MTRT) on Fe-containing phases in hypereutectic Al-Si alloy were investigated. Results show that MTRT can refine microstructures and improve castability, mechanical properties, wear characteristics, and corrosion resistance of Fe-containing Al-Si alloy. When Al-15Si-2.7Fe alloy is treated with MTRT by 1203 K (930 °C) melt: coarse primary Si and plate-like Fe-containing phase both can be refined to small blocky morphology, and the long needle-like Fe-containing phase disappears almost entirely; ultimate tensile strength and elongation are 195 MPa and 1.8 pct, and increase by 12.7 and 50 pct, respectively; and the wear loss and coefficient of friction decrease 7 to 17 and 24 to 30 pct, respectively, compared with that obtained with conventional casting technique. Corrosion resistance of the alloy treated with MTRT by 1203 K (930 °C) melt is the best, that is it has the lowest i corr value and the highest E corr value. Besides, effects of MTRT on Al-15Si-xFe (x = 0.2, 0.7, 1.7, 3.7, 4.7) alloys were also studied, MTRT can only refine microstructure and improve mechanical properties of Al-15Si alloy with 0.7 to 3.7 pct Fe content greatly in the present work.

  6. Kinetics of phase growth in Nb3Sn formation for heat treatment optimization

    SciTech Connect

    Emanuela Barzi; Sara Mattafirri

    2002-10-25

    The kinetics of growth and superconducting properties of Nb{sub 3}Sn are investigated as a function of the heat treatment (HT) duration and temperature for Internal Tin and Powder-in-Tube strands at 650, 700 and 750 C. For all times and temperatures, the Nb{sub 3}Sn layer thickness is measured, the critical current at 4.2 K is tested as a function of magnetic field, and the upper critical field is evaluated. Results of the layer critical current density are also shown as a function of HT duration and temperature.

  7. High-resolution algorithms of sharp interface treatment for compressible two-phase flows

    NASA Astrophysics Data System (ADS)

    Zhang, Xueying; Yang, Haiting

    2015-03-01

    In this paper, a kind of arbitrary high order derivatives (ADER) scheme based on the generalised Riemann problem is proposed to simulate multi-material flows by a coupling ghost fluid method. The states at cell interfaces are reconstructed by interpolating polynomials which are piece-wise smooth functions. The states are treated as the equivalent of the left and right states of the Riemann problem. The contact solvers are extrapolated in the vicinity of contact points to facilitate ghost fluids. The numerical method is applied to compressible flows with sharp discontinuities, such as the collision of two fluids of different physical states and gas-liquid two-phase flows. The numerical results demonstrate that unexpected physical oscillations through the contact discontinuities can be prevented effectively and the sharp interface can be captured efficiently.

  8. Treatment of gas-phase trichloroethene by UV/O{sub 3} process

    SciTech Connect

    Young Ku; Yung-Shuen Shen

    1996-12-31

    The reaction behaviors of the photolysis of gas-phase trichloroethene (TCE) in presence of ozone was studied. The distributions and temporal behaviors of TCE and chlorinated intermediates were studied and described in terms of a two-step consecutive dechlorination kinetic model. The decomposition of TCE (324 ppmv) was found to be completed (99%) within 22 seconds and the rate was increased with increasing light intensity. Supplementary ozone would have more contribution to the dechlorination of chlorinated intermediates than that of TCE by the UV/O{sub 3} process. The enhancement of UV light intensity would promote the dechlorination of TCE more effectively than the supplement of ozone. 8 refs., 6 figs.

  9. Treatment of Produced Waters Using a Surfactant Modified Zeolite/Vapor Phase Bioreactor System

    SciTech Connect

    Lynn E. Katz; Kerry A. Kinney; R. S. Bowman; E. J. Sullivan

    2004-03-11

    This report summarizes work of this project from October 2003 through March 2004. The major focus of the research was to further investigate BTEX removal from produced water, to quantify metal ion removal from produced water, and to evaluate a lab-scale vapor phase bioreactor (VPB) for BTEX destruction in off-gases produced during SMZ regeneration. Batch equilibrium sorption studies were conducted to evaluate the effect of semi-volatile organic compounds commonly found in produced water on the sorption of benzene, toluene, ethylbenzene, and xylene (BTEX) onto surfactant-modified zeolite (SMZ) and to examine selected metal ion sorption onto SMZ. The sorption of polar semi-volatile organic compounds and metals commonly found in produced water onto SMZ was also investigated. Batch experiments were performed in a synthetic saline solution that mimicked water from a produced water collection facility in Wyoming. Results indicated that increasing concentrations of semi-volatile organic compounds increased BTEX sorption. The sorption of phenol compounds could be described by linear isotherms, but the linear partitioning coefficients decreased with increasing pH, especially above the pKa's of the compounds. Linear correlations relating partitioning coefficients of phenol compounds with their respective solubilities and octanol-water partitioning coefficients were developed for data collected at pH 7.2. The sorption of chromate, selenate, and barium in synthetic produced water were also described by Langmuir isotherms. Experiments conducted with a lab-scale vapor phase bioreactor (VPB) packed with foam indicated that this system could achieve high BTEX removal efficiencies once the nutrient delivery system was optimized. The xylene isomers and benzene were found to require the greatest biofilter bed depth for removal. This result suggested that these VOCs would ultimately control the size of the biofilter required for the produced water application. The biofilter recovered

  10. Treatment of primary glioblastoma multiforme with cetuximab, radiotherapy and temozolomide (GERT) – phase I/II trial: study protocol

    PubMed Central

    Combs, Stephanie E; Heeger, Steffen; Haselmann, Renate; Edler, Lutz; Debus, Jürgen; Schulz-Ertner, Daniela

    2006-01-01

    Background The implementation of combined radiochemotherapy (RCHT) with temozolomide (TMZ) has lead to a significant increase in overall survival times in patients with Glioblastoma multiforme (GBM), however, outcome still remains unsatisfactory. The majority of GBMs show an overexpression and/or amplification of the epidermal growth factor receptor (EGFR). Therefore, addition of EGFR-inhibition with cetuximab to the current standard treatment approach with radiotherapy and TMZ seems promising. Methods/design GERT is a one-armed single-center phase I/II trial. In a first step, dose-escalation of TMZ from 50 mg/m2 to 75 mg/m2 together with radiotherapy and cetuximab will be performed. Should safety be proven, the phase II trial will be initiated with the standard dose of 75 mg/m2 of TMZ. Cetuximab will be applied in the standard application dose of 400 mg/m2 in week 1, thereafter at a dose of 250 mg/m2 weekly. A total of 46 patients will be included into this phase I/II trial. Primary endpoints are feasibility and toxicity, secondary endpoints are overall and progression-free survival. An interim analysis will be performed after inclusion of 15 patients into the main study. Patients' enrolment will be performed over a period of 2 years. The observation time will end 2 years after inclusion of the last patient. Discussion The goal of this study is to evaluate the safety and efficacy of combined RCHT-immunotherapy with TMZ and cetuximab as first-line treatment for patients with primary GBM. PMID:16709245

  11. Drivers of microbial community composition in mesophilic and thermophilic temperature-phased anaerobic digestion pre-treatment reactors.

    PubMed

    Pervin, Hasina M; Dennis, Paul G; Lim, Hui J; Tyson, Gene W; Batstone, Damien J; Bond, Philip L

    2013-12-01

    Temperature-phased anaerobic digestion (TPAD) is an emerging technology that facilitates improved performance and pathogen destruction in anaerobic sewage sludge digestion by optimising conditions for 1) hydrolytic and acidogenic organisms in a first-stage/pre-treatment reactor and then 2) methogenic populations in a second stage reactor. Pre-treatment reactors are typically operated at 55-65 °C and as such select for thermophilic bacterial communities. However, details of key microbial populations in hydrolytic communities and links to functionality are very limited. In this study, experimental thermophilic pre-treatment (TP) and control mesophilic pre-treatment (MP) reactors were operated as first-stages of TPAD systems treating activated sludge for 340 days. The TP system was operated sequentially at 50, 60 and 65 °C, while the MP rector was held at 35 °C for the entire period. The composition of microbial communities associated with the MP and TP pre-treatment reactors was characterised weekly using terminal-restriction fragment length polymorphism (T-RFLP) supported by clone library sequencing of 16S rRNA gene amplicons. The outcomes of this approach were confirmed using 454 pyrosequencing of gene amplicons and fluorescence in-situ hybridisation (FISH). TP associated bacterial communities were dominated by populations affiliated to the Firmicutes, Thermotogae, Proteobacteria and Chloroflexi. In particular there was a progression from Thermotogae to Lutispora and Coprothermobacter and diversity decreased as temperature and hydrolysis performance increased. While change in the composition of TP associated bacterial communities was attributable to temperature, that of MP associated bacterial communities was related to the composition of the incoming feed. This study determined processes driving the dynamics of key microbial populations that are correlated with an enhanced hydrolytic functionality of the TPAD system. PMID:24216229

  12. A Phase 2 Randomized Trial of a Rifapentine plus Moxifloxacin-Based Regimen for Treatment of Pulmonary Tuberculosis

    PubMed Central

    Conde, Marcus B.; Mello, Fernanda C. Q.; Duarte, Rafael Silva; Cavalcante, Solange C.; Rolla, Valeria; Dalcolmo, Margareth; Loredo, Carla; Durovni, Betina; Armstrong, Derek T.; Efron, Anne; Barnes, Grace L.; Marzinke, Mark A.; Savic, Radojka M.; Dooley, Kelly E.; Cohn, Silvia; Moulton, Lawrence H.; Chaisson, Richard E.; Dorman, Susan E.

    2016-01-01

    Background The combination of rifapentine and moxifloxacin administered daily with other anti-tuberculosis drugs is highly active in mouse models of tuberculosis chemotherapy. The objective of this phase 2 clinical trial was to determine the bactericidal activity, safety, and tolerability of a regimen comprised of rifapentine, moxifloxacin, isoniazid, and pyrazinamide administered daily during the first 8 weeks of pulmonary tuberculosis treatment. Methods Adults with sputum smear-positive pulmonary tuberculosis were randomized to receive either rifapentine (approximately 7.5 mg/kg) plus moxifloxacin (investigational arm), or rifampin (approximately 10 mg/kg) plus ethambutol (control) daily for 8 weeks, along with isoniazid and pyrazinamide. The primary endpoint was sputum culture status at completion of 8 weeks of treatment. Results 121 participants (56% of accrual target) were enrolled. At completion of 8 weeks of treatment, negative cultures using Löwenstein-Jensen (LJ) medium occurred in 47/60 (78%) participants in the investigational arm vs. 43/51 (84%, p = 0.47) in the control arm; negative cultures using liquid medium occurred in 37/47 (79%) in the investigational arm vs. 27/41 (66%, p = 0.23) in the control arm. Time to stable culture conversion was shorter for the investigational arm vs. the control arm using liquid culture medium (p = 0.03), but there was no difference using LJ medium. Median rifapentine area under the concentration-time curve (AUC0-24) was 313 mcg*h/mL, similar to recent studies of rifapentine dosed at 450–600 mg daily. Median moxifloxacin AUC0-24 was 28.0 mcg*h/mL, much lower than in trials where rifapentine was given only intermittently with moxifloxacin. The proportion of participants discontinuing assigned treatment for reasons other than microbiological ineligibility was higher in the investigational arm vs. the control arm (11/62 [18%] vs. 3/59 [5%], p = 0.04) although the proportions of grade 3 or higher adverse events were

  13. Gas-Phase Treatment of Technetium in the Vadose Zone at the Hanford Site Central Plateau

    SciTech Connect

    Truex, Michael J.; Szecsody, James E.; Zhong, Lirong; Qafoku, Nikolla

    2014-09-01

    Technetium-99 (Tc-99) is present in the vadose zone of the Hanford Central Plateau and is a concern with respect to the protection of groundwater. The persistence, limited natural attenuation mechanisms, and geochemical behavior of Tc-99 in oxic vadose zone environments must be considered in developing effective alternatives for remediation. This report describes a new in situ geochemical manipulation technique for decreasing Tc-99 mobility using a combination of geochemical Tc-99 reduction with hydrogen sulfide gas and induced sediment mineral dissolution with ammonia vapor, which create conditions for deposition of stable precipitates that decrease the mobility of Tc-99. Laboratory experiments were conducted to examine changes in Tc-99 mobility in vadose zone sediment samples to evaluate the effectiveness of the treatment under a variety of operational and sediment conditions.

  14. Efficacy of thalidomide for the treatment of amyotrophic lateral sclerosis: a phase II open label clinical trial.

    PubMed

    Stommel, Elijah W; Cohen, Jeffrey A; Fadul, Camilo E; Cogbill, Christopher H; Graber, David J; Kingman, Linda; Mackenzie, Todd; Channon Smith, Jacqueline Y; Harris, Brent T

    2009-01-01

    Neuroinflammation through the cytokine, tumor necrosis factor-alpha (TNF-alpha) is thought to play an important role in the pathogenesis of amyotrophic lateral sclerosis (ALS). We conducted a preliminary phase II trial of thalidomide, which reduces levels of TNF-alpha pre-transcriptionally and post-transcriptionally in vivo and has been shown to prolong disease duration and extend the lifespan of transgenic animal models of ALS. Patients who met diagnostic criteria for ALS received thalidomide at escalating doses to a target dose of 400 mg/day. The primary endpoints in the trial were the ALS Functional Rating Scale (ALSFRS) and pulmonary function testing (PFT) curves after nine months of thalidomide treatment that were compared to historical controls. Secondary endpoints were: survival stratified for newly diagnosed and progressive disease, toxicity, quality of life, and serum cytokine measurements. Twenty-three patients were enrolled, but only 18 were evaluable for the primary outcome. There was no improvement in the ALSFRS or PFT compared to historical controls. Thalidomide had several side-effects in our ALS patients. There was no significant shift in cytokine profile after treatment compared to baseline. In conclusion, treatment of ALS with the TNF-alpha inhibitor, thalidomide, does not appear to effectively modulate disease progression and can cause adverse effects. PMID:19922130

  15. Changes in Ba phases in BaO/Al₂O₃ upon thermal aging and H₂O treatment

    SciTech Connect

    Kim, Do Heui; Chin, Ya-Huei; Kwak, Ja Hun; Szanyi, Janos; Peden, Charles HF

    2005-12-01

    The effects of thermal aging and H₂O treatment on the physicochemical properties of a BaO/Al₂O₃ model catalyst were investigated by means of XRD, BET, TEM/EDX and NO₂ TPD. Thermal aging at 1000 °C for 10 hrs resulted in conversion of dispersed BaCO₃ into low surface area crystalline BaAl₂O₄. It was found that H₂O treatment on a BaO/Al₂O₃ sample at room temperature transformed not only the BaAl₂O₄, but also the dispersed BaCO₃ into highly crystalline BaCO₃ segregated from the Al₂O₃ support, as evidenced in TEM/EDX and XRD analysis. The sample containing dispersed BaCO3 in the initial phase segregated more severely than the BaAl₂O₄ containing one, with the Ba in the BaAl₂O₄ matrix exhibiting higher resistance towards segregation. Contacting the BaO/Al₂O₃ sample with liquid water over a prolong period of time leads to an increase in crystallinity of the segregated BaCO₃. These phenomena imply that special care must be taken during catalyst synthesis and during realistic operation of Pt/BaO/Al₂O₃ NOx trap catalysts since both processes involve potential exposure of the material with liquid H₂O. Based on the results, a model to explain the behavior of Ba containing species upon thermal aging and H₂O treatment is proposed.

  16. Efficacy and Safety of Artemether in the Treatment of Chronic Fascioliasis in Egypt: Exploratory Phase-2 Trials

    PubMed Central

    Keiser, Jennifer; Sayed, Hanan; El-Ghanam, Maged; Sabry, Hoda; Anani, Saad; El-Wakeel, Aly; Hatz, Christoph; Utzinger, Jürg; el-Din, Sayed Seif; El-Maadawy, Walaa; Botros, Sanaa

    2011-01-01

    Background Fascioliasis is an emerging zoonotic disease of considerable veterinary and public health importance. Triclabendazole is the only available drug for treatment. Laboratory studies have documented promising fasciocidal properties of the artemisinins (e.g., artemether). Methodology We carried out two exploratory phase-2 trials to assess the efficacy and safety of oral artemether administered at (i) 6×80 mg over 3 consecutive days, and (ii) 3×200 mg within 24 h in 36 Fasciola-infected individuals in Egypt. Efficacy was determined by cure rate (CR) and egg reduction rate (ERR) based on multiple Kato-Katz thick smears before and after drug administration. Patients who remained Fasciola-positive following artemether dosing were treated with single 10 mg/kg oral triclabendazole. In case of treatment failure, triclabendazole was re-administered at 20 mg/kg in two divided doses. Principal Findings CRs achieved with 6×80 mg and 3×200 mg artemether were 35% and 6%, respectively. The corresponding ERRs were 63% and nil, respectively. Artemether was well tolerated. A high efficacy was observed with triclabendazole administered at 10 mg/kg (16 patients; CR: 67%, ERR: 94%) and 20 mg/kg (4 patients; CR: 75%, ERR: 96%). Conclusions/Significance Artemether, administered at malaria treatment regimens, shows no or only little effect against fascioliasis, and hence does not represent an alternative to triclabendazole. The role of artemether and other artemisinin derivatives as partner drug in combination chemotherapy remains to be elucidated. PMID:21909440

  17. Effect of Destabilizing Heat Treatment on Solid-State Phase Transformation in High-Chromium Cast Irons

    NASA Astrophysics Data System (ADS)

    Efremenko, Vasily; Shimizu, Kazumichi; Chabak, Yuliia

    2013-12-01

    This work describes the influence of secondary carbide precipitation at destabilizing heat treatment on kinetics of austenite phase transformation at a subcritical range of temperatures in high-Cr cast irons, alloyed with 4 to 6 wt pct of Mn or by complex Mn-Ni-Mo (Mn-Cu-Mo). The samples were soaked at 1073 K to 1373 K (800 °C to 1100 °C) (destabilization) or at 573 K to 973 K (300 °C to 700 °C) (subcritical treatment); the combination of destabilization and subcritical treatment was also used. The investigation was carried out with application of optical and electron microscopy and bulk hardness measurement. Time-temperature-transformation (TTT) curves of secondary carbide precipitation and pearlite transformation for as-cast austenite and destabilized austenite were built in this work. It was determined that the secondary carbide precipitation significantly inhibited the pearlite transformation rate at 823 K to 973 K (550 °C to 700 °C). The inhibition effect is more evident in cast irons alloyed with complex Mn-Ni-Mo or Mn-Cu-Mo. The possible reasons for transformation decelerating could be austenite chemical composition change (enriching by Ni, Si, and Cu, and depleting by Cr) and stresses induced by secondary carbide precipitation.

  18. Allogeneic clonal mesenchymal stem cell therapy for refractory graft-versus-host disease to standard treatment: a phase I study.

    PubMed

    Yi, Hyeon Gyu; Yahng, Seung-Ah; Kim, Inho; Lee, Je-Hwan; Min, Chang-Ki; Kim, Jun Hyung; Kim, Chul Soo; Song, Sun U

    2016-01-01

    Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical-grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose (1×10(6) cells/kg), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial. PMID:26807024

  19. Improvement and further development in CESM/CAM5: gas-phase chemistry and inorganic aerosol treatments

    NASA Astrophysics Data System (ADS)

    He, J.; Zhang, Y.

    2013-10-01

    Gas-phase chemistry and subsequent gas-to-particle conversion processes such as new particle formation, condensation, and thermodynamic partitioning have large impacts on air quality, climate, and public health through influencing the amounts and distributions of gaseous precursors and secondary aerosols. Their roles in global air quality and climate are examined in this work using the Community Earth System Model version 1.0.5 (CESM1.0.5) with the Community Atmosphere Model version 5.1 (CAM5.1) (referred to as CESM1.0.5/CAM5.1). CAM5.1 includes a simple chemistry that is coupled with a 7-mode prognostic Modal Aerosol Model (MAM7). MAM7 includes classical homogenous nucleation (binary and ternary) and activation nucleation (empirical first-order power law) parameterizations, and a highly-simplified inorganic aerosol thermodynamics treatment that only simulates sulfate (SO42-) and ammonium (NH4+). In this work, a new gas-phase chemistry mechanism based on the 2005 Carbon Bond Mechanism for Global Extension (CB05_GE) and several advanced inorganic aerosol treatments for condensation of volatile species, ion-mediated nucleation (IMN), and explicit inorganic aerosol thermodynamics have been incorporated into CESM/CAM5.1-MAM7. Comparing to the simple gas-phase chemistry, CB05_GE can predict many more gaseous species, and improve model performance for PM2.5, PM10, PM2.5 components, and some PM gaseous precursors such as SO2 and NH3 in several regions, as well as aerosol optical depth (AOD) and cloud properties (e.g., cloud fraction (CF), cloud droplet number concentration (CDNC), and shortwave cloud forcing (SWCF)) on globe. The modified condensation and aqueous-phase chemistry further improves the predictions of additional variables such as HNO3, NO2, and O3 in some regions, and new particle formation rate (J) and AOD over globe. IMN can improve the predictions of secondary PM2.5 components, PM2.5, and PM10 over Europe, as well as AOD and CDNC over globe. The explicit

  20. Quasiparticle-random-phase approximation treatment of the transverse wobbling mode reconsidered

    NASA Astrophysics Data System (ADS)

    Frauendorf, S.; Dönau, F.

    2015-12-01

    The quasiparticle-random-phase approximation is used to study the properties of the wobbling bands in 163Lu. Assuming that the wobbling mode represents pure isoscalar orientation oscillations results in too low wobbling frequencies and transition probabilities between the one- and zero-phonon wobbling bands that are strongly collective but yet too weak for B (E2 ) out and too strong for B (M1 ) out . The inclusion of an LL interaction, which couples the wobbling mode to the scissors mode, generates the right upshift of the wobbling frequencies and the right suppression of the B (M1 ) out values toward the experimental values, but does not change the B (E2 ) out values. In analogy to the quenching of low-energy E 1 transition by coupling to the isovector giant dipole resonance, a general reduction of the M 1 transitions between quasiparticle configurations caused by coupling to the scissors mode is suggested. The small B (E2 ) out values are related to small triaxiality of the density distribution, which is found by all mean field calculations for the triaxial strongly deformed nuclei in the mass 160 region.

  1. Dense Nonaqueous-Phase Liquid Architecture in Fractured Bedrock: Implications for Treatment and Plume Longevity.

    PubMed

    Schaefer, Charles E; White, Erin B; Lavorgna, Graig M; Annable, Michael D

    2016-01-01

    Partitioning tracer testing was performed in discrete intervals within a fractured bedrock tetrachloroethene (PCE) dense nonaqueous-phase liquid (DNAPL) source area to assess the fracture flow field and DNAPL architecture. Results confirmed that the partitioning tracer testing was able to identify and quantify low levels of residual DNAPL along flow paths in hydraulically conductive fractures. DNAPL fracture saturations (Sn) ranged from undetectable to 0.007 (DNAPL volume/fracture volume). A comparison of the fracture flow field to the DNAPL distribution indicated that the highest value of Sn was observed in the least transmissive fracture (or fracture zone). Application of a simple ambient dissolution model showed that the DNAPL present in this low transmissivity zone would persist longer than the DNAPL present in more transmissive fractures and would persist for 200 years (in the absence of any degradation reactions). Assessment of PCE mass distribution between the rock matrix and fractures showed that, due to the presence of DNAPL, the rock matrix accounted for less than 10% of the total PCE mass. The evaluation of PCE concentration profiles in the rock matrix and the estimated diffusional flux from the rock matrix suggest that the elevated PCE groundwater concentrations observed in the fractures likely are due to the presence of the residual DNAPL sources and that removal of the residual DNAPL sources within the fractures would result in a significant decrease in dissolved PCE concentrations in the source area. PMID:26619000

  2. Determination of neonicotinoid insecticides in environmental samples by micellar electrokinetic chromatography using solid-phase treatments.

    PubMed

    Ettiene, Gretty; Bauza, Roberto; Plata, María R; Contento, Ana M; Ríos, Angel

    2012-10-01

    A sensitive and reliable method based on MEKC has been developed and validated for trace determination of neonicotinoid insecticides (thiamethoxam, acetamiprid, and imidacloprid) and the metabolite 6-chloronicotinic acid in water and soil matrices. Optimum separation of the neonicotinoid insecticides was obtained on a 58 cm long capillary (75 μm id) using as the running electrolyte 40 mM SDS, 5 mM borate (pH 10.4), and 5% (v/v) methanol at a temperature of 25°C, a voltage of 25 kV and with hydrodynamic injection (10 s). The analysis time was less than 7 min. Prior to MEKC determination, the samples were purified and enriched by carrying out extraction-preconcentration steps. For aqueous samples, off-line SPE with a sorptive material such as Strata-X (polymeric hydrophobic sorbent) and octadecylsilane (C₁₈) was carried out to clean up and preconcentrate the insecticides. However, for soil samples, matrix solid-phase dispersion (MSPD) was applied with C₁₈ used as the dispersant. Good linearity, accuracy, and precision were obtained and the detection limits were in the range between 0.01 and 0.07 μg mL⁻¹ for river water and 0.17 and 0.37 μg g⁻¹ for soil samples. Recovery levels reached greater than 92% for all of the assayed neonicotinoids in river water samples with Strata-X. In soil matrices, the best recoveries (63-99%) were obtained with MSPD. PMID:22997021

  3. Effect of 4-week feeding of deoxynivalenol- or T-2-toxin-contaminated diet on lipid peroxidation and glutathione redox system in the hepatopancreas of common carp (Cyprinus carpio L.).

    PubMed

    Pelyhe, Csilla; Kövesi, Benjámin; Zándoki, Erika; Kovács, Balázs; Szabó-Fodor, Judit; Mézes, Miklós; Balogh, Krisztián

    2016-05-01

    The purpose of study was to investigate the effects of T-2 toxin (4.11 mg T-2 toxin and 0.45 mg HT-2 toxin kg(-1) feed) and deoxynivalenol (5.96 and 0.33 mg 15-acetyl deoxynivalenol (DON) kg(-1) feed) in 1-year-old common carp juveniles in a 4-week feeding trial. The exposure of mycotoxins resulted in increased mortality in both groups consuming mycotoxin-contaminated diet. Parameters of lipid peroxidation were not affected during the trial, and antioxidant defence also did not show response to oxidative stress; however, glutatione peroxidase activity slightly, but significantly, decreased in the T-2 toxin group. Glutathione S-transferase activity showed moderate decrease as effect of T-2 toxin, which suggests its effect on xenobiotic transformation. Reduced glutathione concentration showed moderate changes as effect of DON exposure, but T-2 toxin has no effect. Expression of phospholipid hydroperoxide glutathione peroxidase (GPx4) genes showed different response to mycotoxin exposure. T-2 toxin caused dual response in the expression of gpx4a (early and late downregulation and mid-term upregulation), but continuous upregulation was found as effect of deoxynivalenol. Expression of the other gene, gpx4b, was upregulated by both trichothecenes during the whole period. The results suggested that trichothecenes have some effect on free radical formation and antioxidant defence, but the changes depend on the duration of exposure and the dose applied, and in case of glutathione peroxidase, there was no correlation between expression of genes and enzyme activity. PMID:26920403

  4. Differences in the detection of highly pathogenic avian influenza H5N1 virus in feather samples from 4-week-old and 24-week-old infected Pekin ducks (Anas platyrhynchos var. domestica).

    PubMed

    Aiello, Roberta; Beato, Maria Serena; Mancin, Marzia; Rigoni, Michela; Tejeda, Aurora Romero; Maniero, Silvia; Capua, Ilaria; Terregino, Calogero

    2013-08-30

    Previous studies have reported the detection of H5N1 HPAI virus in feathers from ducks naturally and experimentally infected and suggested that feather calami (FC) could be used as diagnostic samples for the early detection of H5N1 HPAI infections. Ducks are readily infected with H5N1 HPAI viruses although the development of clinical signs and deaths were reported as age-related with younger birds being more susceptible. The correlation between age and virus localisation in FC of infected ducks has not been studied to date. In the present study juvenile (4-week-old) and adult (24-week-old) Pekin ducks (Anas platyrhynchos var. domestica) were infected experimentally with a clade 2.2 H5N1 HPAI virus (A/duck/Nigeria/1071-23/2007). Tracheal (Tr) and cloacal (Cl) swabs and FC were collected at 3, 5, 7 and 10 days post infection and tested by RRT-PCR and a double antibody sandwich-ELISA (DAS-ELISA) developed in house. Virus was detected in swabs and FC of challenged ducks with a higher rate of detection in juvenile ducks. In this age group virus was detected over a longer period of time in FC compared to swabs. Our study showed that FC samples collected from young ducks are a valid diagnostic specimen for H5N1 HPAI virus detection. The DAS-ELISA on FC proved to be a suitable alternative diagnostic test when molecular and/or virus isolation techniques are not available therefore it could be useful in the diagnosis of H5N1 HPAI infections in under-resourced countries. PMID:23608476

  5. Five-year Local Control in a Phase II Study of Hypofractionated Intensity Modulated Radiation Therapy With an Incorporated Boost for Early Stage Breast Cancer

    SciTech Connect

    Freedman, Gary M.; Anderson, Penny R.; Bleicher, Richard J.; Litwin, Samuel; Li Tianyu; Swaby, Ramona F.; Ma, Chang-Ming Charlie; Li Jinsheng; Sigurdson, Elin R.; Watkins-Bruner, Deborah; Morrow, Monica; Goldstein, Lori J.

    2012-11-15

    Purpose: Conventional radiation fractionation of 1.8-2 Gy per day for early stage breast cancer requires daily treatment for 6-7 weeks. We report the 5-year results of a phase II study of intensity modulated radiation therapy (IMRT), hypofractionation, and incorporated boost that shortened treatment time to 4 weeks. Methods and Materials: The study design was phase II with a planned accrual of 75 patients. Eligibility included patients aged {>=}18 years, Tis-T2, stage 0-II, and breast conservation. Photon IMRT and an incorporated boost was used, and the whole breast received 2.25 Gy per fraction for a total of 45 Gy, and the tumor bed received 2.8 Gy per fraction for a total of 56 Gy in 20 treatments over 4 weeks. Patients were followed every 6 months for 5 years. Results: Seventy-five patients were treated from December 2003 to November 2005. The median follow-up was 69 months. Median age was 52 years (range, 31-81). Median tumor size was 1.4 cm (range, 0.1-3.5). Eighty percent of tumors were node negative; 93% of patients had negative margins, and 7% of patients had close (>0 and <2 mm) margins; 76% of cancers were invasive ductal type: 15% were ductal carcinoma in situ, 5% were lobular, and 4% were other histology types. Twenty-nine percent of patients 29% had grade 3 carcinoma, and 20% of patients had extensive in situ carcinoma; 11% of patients received chemotherapy, 36% received endocrine therapy, 33% received both, and 20% received neither. There were 3 instances of local recurrence for a 5-year actuarial rate of 2.7%. Conclusions: This 4-week course of hypofractionated radiation with incorporated boost was associated with excellent local control, comparable to historical results of 6-7 weeks of conventional whole-breast fractionation with sequential boost.

  6. A Phase I study of concurrent radiotherapy and capecitabine as adjuvant treatment for operable rectal cancer

    SciTech Connect

    Jin Jing

    2006-03-01

    Purpose: To determine the maximum tolerated dose and the dose-limiting toxicity of capecitabine with standard radiotherapy (RT) as adjuvant treatment in patients with rectal cancer. Methods and Materials: Patients with Stage II/III rectal cancer after surgery were eligible. Total RT dose was delivered as DT 50 Gy in fractions of 2.0 Gy/day for 5 weeks to the pelvic area. Capecitabine was administered concurrently with RT in escalating doses, twice daily with a 12-h interval, for two cycles of 14 days separated by a 7-day rest. Dose-limiting toxicity included Grade 3 or Grade 4 hematologic and nonhematologic toxicity. Results: Twenty-four patients were enrolled at the following dose levels: 1,000 (3 patients), 1,200 (3 patients), 1,400 (3 patients), 1,500 (3 patients), 1,600 (6 patients), and 1,700 mg/m{sup 2}/day (6 patients). Dose-limiting toxicity was observed in 1 patient at 1,600 mg/m{sup 2}/day (Grade 3 diarrhea) and in 2 patients at 1,700 mg/m{sup 2}/day (1 patient had Grade 3 and 1 Grade 4 diarrhea). Conclusion: The maximum tolerated dose (MTD) of capecitabine given concurrently with RT was 1,600 mg/m{sup 2}, daily from the 1st to the 14th day, with a 7-day rest, for two cycles.

  7. Masked Repetition Priming in Treatment of Anomia: A Phase 2 Study

    PubMed Central

    2015-01-01

    Purpose Previous research has demonstrated that exposure to masked primes may improve naming accuracy for individuals with anomia. This study investigates the effect of repeated exposures to masked identity primes paired with pictures over multiple trials, sessions, and days on the ability of people with anomia to name those pictures. Method Four participants with anomia completed this single-subject, multiple-baseline design study. Twelve treatment sessions were conducted for each of 2 semantic categories. Comparisons of performance on naming probes were made between items that were primed, unprimed but seen the same number of times, and unprimed and seen only during naming probes. Results All participants showed some gains in naming trained items although to varying degrees, and trained (primed) items generally showed greater improvement than untrained items seen the same number of times. Cross-category generalization was observed for some participants, but little to no within-category generalization occurred. Minimal changes occurred on measures of general language ability. Conclusions These data provide continued evidence that masked repetition priming can have a positive effect on naming for people with anomia. Factors that may influence participant response and additional questions that must be settled for this line of research to continue are discussed. PMID:26381369

  8. Randomized Phase 2 Trial of the Oncolytic Virus Pelareorep (Reolysin) in Upfront Treatment of Metastatic Pancreatic Adenocarcinoma.

    PubMed

    Noonan, Anne M; Farren, Matthew R; Geyer, Susan M; Huang, Ying; Tahiri, Sanaa; Ahn, Daniel; Mikhail, Sameh; Ciombor, Kristen K; Pant, Shubham; Aparo, Santiago; Sexton, Jennifer; Marshall, John L; Mace, Thomas A; Wu, Christina S; El-Rayes, Bassel; Timmers, Cynthia D; Zwiebel, James; Lesinski, Gregory B; Villalona-Calero, Miguel A; Bekaii-Saab, Tanios S

    2016-06-01

    Pelareorep causes oncolysis in tumor cells with activated Ras. We hypothesized that pelareorep would have efficacy and immunomodulatory activity in metastatic pancreatic adenocarcinoma (MPA) when combined with carboplatin and paclitaxel. A randomized phase 2 study (NCT01280058) was conducted in treatment-naive patients with MPA randomized to two treatment arms: paclitaxel/carboplatin + pelareorep (Arm A, n = 36 evaluable patients) versus paclitaxel/carboplatin (Arm B, n = 37 evaluable patients). There was no difference in progression-free survival (PFS) between the arms (Arm A PFS = 4.9 months, Arm B PFS = 5.2 months, P = 0.6), and Kirsten rat sarcoma viral oncogene (KRAS) status did not impact outcome. Quality-adjusted Time without Symptoms or Toxicity analysis revealed that the majority of PFS time was without toxicity or progression (4.3 months). Patient immunophenotype appeared important, as soluble immune biomarkers were associated with treatment outcome (fractalkine, interleukin (IL)-6, IL-8, regulated on activation, normal T cell expressed and secreted (RANTES), and vascular endothelial growth factor (VEGF)). Increased circulating T and natural killer (NK)-cell subsets were also significantly associated with treatment outcome. Addition of pelareorep was associated with higher levels of 14 proinflammatory plasma cytokines/chemokines and cells with an immunosuppressive phenotype (Tregs, cytotoxic T lymphocyte associated protein 4 (CTLA4)(+) T cells). Overall, pelareorep was safe but does not improve PFS when administered with carboplatin/paclitaxel, regardless of KRAS mutational status. Immunologic studies suggest that chemotherapy backbone improves immune reconstitution and that targeting remaining immunosuppressive mediators may improve oncolytic virotherapy. PMID:27039845

  9. PGE(1) treatment of severe intermittent claudication (short-term versus long-term, associated with exercise)--efficacy and costs in a 20-week, randomized trial.

    PubMed

    Belcaro, G; Nicolaides, A N; Agus, G; Cesarone, M R; Geroulakos, G; Pellegrini, L; De Sanctis, M T; Incandela, L; Ricci, A; Mondani, P; De Angelis, R; Ippolito, E; Barsotti, A; Vasdekis, S; Ledda, A; Christopoulos, D; Errichi, B M; Helmis, H; Cornelli, U; Ramaswami, G; Dugall, M; Bucci, M; Martines, G; Ferrari, P G; Corsi, M; Di Francescantonio, D

    2000-08-01

    The efficacy, safety, and cost of prostaglandin E1 (PGE1) in the treatment of severe intermittent claudication was studied comparing a long-term treatment protocol (LTP) with a short-term treatment protocol (STP) in a randomized 20-week study. The study included 980 patients (883 completed the study) with an average total walking distance of 85.5 +/-10 m (range 22-119). Phase 1 was a 2-week run-in phase (no treatment) for both protocols. In LTP, phase 2 was the main treatment phase. In the LTP, treatment was performed with 2-hour infusions (60 microg PGE1, 5 days each week for 4 weeks. In phase 3 (4-week interval period) PGE1 was administered twice a week (same dosage). In phase 4 (monitoring lasting 3 months, from week 9 to 20) no drugs were used. In STP phase 2 treatment was performed in 2 days by a 2-hour infusion (first day: morning 20 microg, afternoon 40 microg; second day morning and afternoon 60 microg). The reduced dosage was used only at the first cycle (week 0) to evaluate tolerability or side effects. Full dosage (60 microg bid) was used for all other cycles. The same cycle was repeated at the beginning of weeks 4, 8, and 12. The observation period was between weeks 12 and 20. A treadmill test was performed at inclusion, at the beginning of each phase, and at the end of 20th week. A similar progressive physical training plan (based on walking) and a reduction in risk factors levels plan was used in both groups. Intention-to-treat analysis indicated an increase in walking distance, which improved at 4 weeks and at 20 weeks in the STP more than in the LTP group. At 4 weeks the variation (increase) in pain-free walking (PFWD) was 167.8% (of the initial value) in the LTP group and 185% in the STP group (p<0.05). At 4 weeks the variation (increase) in total walking distance (TWD) was 227.6% of the initial value in the LTP group and 289% in the STP group (p<0.05). At 20 weeks the increase in PFWD was 496% of the initial value in the LTP group vs 643% in the

  10. Phase, compositional, and morphological changes of human dentin after Nd:YAG laser treatment.

    PubMed

    Lin, C P; Lee, B S; Lin, F H; Kok, S H; Lan, W H

    2001-06-01

    Although techniques for repairing root fracture have been proposed, the prognosis is generally poor. If the fusion of a root fracture by laser is possible, it will offer an alternative to extraction. Our group has attempted to use lasers to fuse a low melting-point bioactive glass to fractured dentin. This report is focused on the phase, compositional, and morphological changes observed by means of X-ray diffractometer, Fourier transforming infrared spectroscopy, and scanning electron microscopy-energy dispersive X-ray spectroscopy in human dentin after exposure to Nd:YAG laser. The irradiation energies were from 150 mJ/ pulse-10 pps-4 s to 150 mJ/pulse-30 pps-4 s. After exposure to Nd:YAG laser, dentin showed four peaks on the X-ray diffractometer that corresponding to a-tricalcium phosphate (TCP) and beta-TCP at 20 = 30.78 degrees/34.21 degrees and 32.47 degrees/33.05 degrees, respectively. The peaks of a-TCP and beta-TCP gradually increased in intensity with the elevation of irradiation energy. In Fourier transforming infrared analysis, two absorption bands at 2200 cm(-1) and 2015 cm(-1) could be traced on dentin treated by Nd:YAG laser with the irradiation energies beyond 150 mJ/pulse-10 pps-4 s. The energy dispersive X-ray results showed that the calcium/phosphorus ratios of the irradiated area proportionally increased with the elevation of irradiation energy. The laser energies of 150 mJ/ pulse-30 pps-4 s and 150 mJ/pulse-20 pps-4 s could result in the a-TCP formation and collagen breakdown. However, the formation of glass-like melted substances without a-TCP at the irradiated site was induced by the energy output of 150 mJ/ pulse-10 pps-4 s. Scanning electron micrographs also revealed that the laser energy of 150 mJ/ pulse-10 pps-4 s was sufficient to prompt melting and recrystallization of dentin crystals without cracking. Therefore, we suggest that the irradiation energy of Nd:YAG laser used to fuse a low melting-point bioactive glass to dentin is 150 m

  11. Superior efficacy of calcipotriene and betamethasone dipropionate aerosol foam versus ointment in patients with psoriasis vulgaris – A randomized phase II study

    PubMed Central

    Koo, John; Tyring, Stephen; Werschler, William P.; Bruce, Suzanne; Olesen, Martin; Villumsen, John; Bagel, Jerry

    2016-01-01

    Abstract Background: An aerosol foam formulation of fixed combination calcipotriene 0.005% (as hydrate; Cal) plus betamethasone dipropionate 0.064% (BD) was developed to improve psoriasis treatment. Objectives: To compare the efficacy and safety of Cal/BD aerosol foam with Cal/BD ointment after 4 weeks. Methods: In this Phase II, multicenter, investigator-blind, 4-week trial, adult patients with psoriasis vulgaris were randomized to Cal/BD aerosol foam, Cal/BD ointment, aerosol foam vehicle or ointment vehicle (3:3:1:1). The primary efficacy endpoint was the proportion of patients at week 4 who achieved treatment success (clear or almost clear with at least a two-step improvement) according to the physician’s global assessment of disease severity. Results: In total, 376 patients were randomized. At week 4, significantly more patients using Cal/BD aerosol foam achieved treatment success (54.6% versus 43.0% [ointment]; p = 0.025); mean modified (excluding the head, which was not treated) psoriasis area and severity index score was significantly different between Cal/BD aerosol foam and Cal/BD ointment (mean difference –0.6; p = 0.005). Rapid, continuous itch relief occurred with both active treatments. One adverse drug reaction was reported with Cal/BD aerosol foam (application site itch). Conclusions: Cal/BD aerosol foam demonstrates significantly greater efficacy and similar tolerability compared with Cal/BD ointment for psoriasis treatment. PMID:26444907

  12. Effects of treatment with an Hsp90 inhibitor in tumors based on 15 phase II clinical trials

    PubMed Central

    Wang, He; Lu, Mingjie; Yao, Mengqian; Zhu, Wei

    2016-01-01

    Heat shock protein (Hsp)90 serves as a chaperone protein that promotes the proper folding of proteins involved in a variety of signal transduction processes involved in cell growth. Hsp90 inhibitors, which inhibit the activity of critical client proteins, have emerged as the accessory therapeutic agents for multiple human cancer types. To better understand the effects of Hsp90 inhibitors in cancer treatment, the present study reviewed 15 published phase II clinical trials to investigate whether Hsp90 inhibitors will benefit patients with cancer. Information of complete response, partial response, stable disease, objective response and objective response rate was collected to evaluate clinical outcomes. Overall, Hsp90 inhibitors are effective against a variety of oncogene-addicted cancers, including those that have developed resistance to specific receptors.

  13. A 63 element 1.75 dimensional ultrasound phased array for the treatment of benign prostatic hyperplasia

    PubMed Central

    Saleh, Khaldon Y; Smith, Nadine Barrie

    2005-01-01

    Background Prostate cancer and benign prostatic hyperplasia are very common diseases in older American men, thus having a reliable treatment modality for both diseases is of great importance. The currently used treating options, mainly surgical ones, have numerous complications, which include the many side effects that accompany such procedures, besides the invasive nature of such techniques. Focused ultrasound is a relatively new treating modality that is showing promising results in treating prostate cancer and benign prostatic hyperplasia. Thus this technique is gaining more attention in the past decade as a non-invasive method to treat both diseases. Methods In this paper, the design, construction and evaluation of a 1.75 dimensional ultrasound phased array to be used for treating prostate cancer and benign prostatic hyperplasia is presented. With this array, the position of the focus can be controlled by changing the electrical power and phase to the individual elements for electronically focusing and steering in a three dimensional volume. The array was designed with a maximum steering angle of ± 13.5° in the transverse direction and a maximum depth of penetration of 11 cm, which allows the treatment of large prostates. The transducer piezoelectric ceramic, matching layers and cable impedance have been designed for maximum power transfer to tissue. Results To verify the capability of the transducer for focusing and steering, exposimetry was performed and the results correlated well with the calculated field. Ex vivo experiments using bovine tissue were performed with various lesion sizes and indicated the capability of the transducer to ablate tissue using short sonications. Conclusion A 1.75 dimensional array, that overcame the drawbacks associated with one-dimensional arrays, has been designed, built and successfully tested. Design issues, such as cable and ceramic capacitances, were taken into account when designing this array. The final prototype

  14. Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations

    PubMed Central

    Müller, Martin C.; Cortes, Jorge E.; Kim, Dong-Wook; Druker, Brian J.; Erben, Philipp; Pasquini, Ricardo; Branford, Susan; Hughes, Timothy P.; Radich, Jerald P.; Ploughman, Lynn; Mukhopadhyay, Jaydip

    2009-01-01

    Dasatinib is a BCR-ABL inhibitor with 325-fold higher potency than imatinib against unmutated BCR-ABL in vitro. Imatinib failure is commonly caused by BCR-ABL mutations. Here, dasatinib efficacy was analyzed in patients recruited to phase 2/3 trials with chronic-phase chronic myeloid leukemia with or without BCR-ABL mutations after prior imatinib. Among 1043 patients, 39% had a preexisting BCR-ABL mutation, including 48% of 805 patients with imatinib resistance or suboptimal response. Sixty-threedifferent BCR-ABL mutations affecting 49 amino acids were detected at baseline, with G250, M351, M244, and F359 most frequently affected. After 2 years of follow-up, dasatinib treatment of imatinib-resistant patients with or without a mutation resulted in notable response rates (complete cytogenetic response: 43% vs 47%) and durable progression-free survival (70% vs 80%). High response rates were achieved with different mutations except T315I, including highly imatinib-resistant mutations in the P-loop region. Impaired responses were observed with some mutations with a dasatinib median inhibitory concentration (IC50) greater than 3nM; among patients with mutations with lower or unknown IC50, efficacy was comparable with those with no mutation. Overall, dasatinib has durable efficacy in patients with or without BCR-ABL mutations. All trials were registered at http://www.clinicaltrials.gov as NCT00123474, NCT00101660, and NCT00103844. PMID:19779040

  15. Chronic myelogenous leukemia in chronic phase transforming into acute leukemia under treatment with dasatinib 4 months after diagnosis.

    PubMed

    Nakamura, Yukitsugu; Tokita, Katsuya; Nagasawa, Fusako; Takahashi, Wataru; Nakamura, Yuko; Sasaki, Ko; Ichikawa, Motoshi; Mitani, Kinuko

    2016-03-01

    We report a 64-year-old woman morphologically diagnosed with chronic myelogenous leukemia in the chronic phase. Despite having achieved a complete hematological response following treatment with dasatinib, she developed lymphoblastic crisis 4 months later. Blastic cells were in a CD45-negative and SSC-low fraction, and positive for CD10, CD19, CD34, and HLA-DR expression and rearrangement in the immunoglobulin heavy chain gene. Chemotherapy using the HyperCVAD/MA regimen led to a complete cytogenetic response, and after cord blood transplantation, she obtained a complete molecular remission. However, the crisis recurred 6 months later. Another salvage therapy using L-AdVP regimen followed by nilotinib led to a complete molecular remission. Retrospective analyses using flow cytometry and polymerase chain reaction revealed a minimal blastic crisis clone present in the initial marrow in chronic phase. This case is informative as it suggests that sudden blastic crisis may occur from an undetectable blastic clone present at initial diagnosis and that leukemic stem cells may survive cytotoxic chemotherapy that eliminates most of the blastic cells. PMID:26662559

  16. Effect of heat treatment on phase composition and crystal structure of thin WSi2 films on silicon substrates

    NASA Astrophysics Data System (ADS)

    Biryukov, Y. P.; Dostanko, A. P.; Maltsev, A. A.; Shakhlevich, G. M.

    1984-10-01

    An experimental study of WSi2 films on silicon substrates with either 111 or 100 orientation was made, for the purpose of determining the effect of annealing by heat treatment on their phase composition and crystal structure. Films of 0.2 micron thickness were deposited at a rate of 0.5 nm/s on a silicon surface which was predecontaminated of SiO2 layers and adsorbate atoms by ion sputtering in one vacuum cycle. Deposition was by condensation, with the substrate held at various temperatures from 390 to 500 C, and then annealed in an argon atmosphere at various temperatures from 700 to 1000 C for 30 min. Subsequent phase analysis at room temperature was performed with a DRON-2 X-ray diffractometer, using a CuK (sub alpha)-radiation source and covering the 20 = 10 to 130 deg range of angles by the Debye-Sherer method, while the surface morphology was examined under an electron microscope.

  17. Vapor-Phase Stoichiometry and Heat Treatment of CdTe Starting Material for Physical Vapor Transport

    NASA Technical Reports Server (NTRS)

    Su, Ching-Hua; Sha, Yi-Gao; Lehoczky, S. L.; Liu, Hao-Chieh; Fang, Rei; Brebrick, R. F.

    1998-01-01

    Six batches of CdTe, having total amounts of material from 99 to 203 g and gross mole fraction of Te, X(sub Te), 0.499954-0.500138, were synthesized from pure Cd and Te elements. The vapor-phase stoichiometry of the assynthesized CdTe batches was determined from the partial pressure of Te2, P(sub Te2) using an optical absorption technique. The measured vapor compositions at 870 C were Te-rich for all of the batches with partial pressure ratios of Cd to Te2, P(sub Cd)/P(sub Te2), ranging from 0.00742 to 1.92. After the heat treatment of baking under dynamic vacuum at 870 C for 8 min, the vapor-phase compositions moved toward that of the congruent sublimation, i.e. P(sub Cd)/P(sub Te2) = 2.0, with the measured P(sub Cd)/P(sub Te2) varying from 1.84 to 3.47. The partial pressure measurements on one of the heat-treated samples also showed that the sample remained close to the congruent sublimation condition over the temperature range 800-880 C.

  18. Assessment of Differences in Phase 1 and Phase 2 Test Observations for Waste Treatment Plant Pulse Jet Mixer Tests with Non-Cohesive Solids

    SciTech Connect

    Meyer, Perry A.; Baer, Ellen BK; Bamberger, Judith A.; Fort, James A.; Minette, Michael J.

    2010-10-27

    The purpose of this work was to assess the apparent discrepancy in critical suspension velocity (UCS) between M3 Phase 1 (Meyer et al. 2009) and Phase 2 testing conducted by Energy Solutions (ES) at Mid-Columbia Engineering (MCE) and to address the applicability of Phase 1 scale-up laws to Phase 2 test results. Three Phase 2 test sequences were analyzed in detail. Several sources of discrepancy were identified including differences in nominal versus actual velocity, definition of model input parameters, and definition of UCS. A remaining discrepancy was shown to not be solely an artifact of Phase 1 data correlations, but was fundamental to the tests. The non-prototypic aspects of Phase 1 testing were reviewed and assessed. The effects of non-prototypic refill associated with the closed loop operation of the jets, previously known to affect cloud height, can be described in terms of a modified settling velocity. When the modified settling velocity is incorporated into the Phase 1 “new” physical model the adjusted new physical model does a better job of predicting the Phase 2 test results. The adjusted new physical model was bench marked with data taken during three prototypic drive tests. Scale-up behavior of the Phase 1 tests was reviewed. The applicability of the Phase 1 scale-up behavior to Phase 2 prototypic testing was analyzed. The effects of non-prototypic refill caused measured values of UCS to be somewhat reduced at larger scales. Hence the scale-up exponents are believed to be smaller than they would have been had there been prototypic refill. Estimated scale-up exponents for the Phase 2 testing are 0.40 for 8-tube tests and 0.36 for 12-tube tests.

  19. Treatment of unresectable stage IV metastatic melanoma with aviscumine after anti-neoplastic treatment failure: a phase II, multi-centre study

    PubMed Central

    2014-01-01

    Background Aviscumine, a recombinant plant protein, is an immune modulator that induces ribotoxic stress at the 28S ribosomal RNA subunit. In this way cytokine release and T-cell responses are enhanced. This phase II trial was conducted to test the efficacy and safety of aviscumine in patients with systemically pre-treated metastatic melanoma stage IV. Methods A total of 32 patients with progressive stage IV melanoma after failure of standard therapy were enrolled onto a single-arm, multi-centre, open-label, phase II trial. All patients had an ECOG performance status of 0 or 1. Patients received 350 ng aviscumine twice weekly by subcutaneous injection until progression. The primary end points were progression-free survival (PFS) and overall survival (OS). Safety was assessed as adverse events (AEs). Tumor response was assessed every eight weeks and survival of patients was followed up to one year after the end of therapy. Thirty one patients (intent-to-treat population (ITT)) were assessed for efficacy; safety was assessed in the whole population. Results One patient achieved a partial response (PR) and 10 patients showed stable disease/no change (SD). The median progression-free survival (mPFS) was 63 days (95% CI 57–85) and median overall survival (mOS) was 335 days (95% CI 210–604). In total 210 treatment-emergent adverse events were recorded. Grade 1 or 2 AEs occurred in 72% of patients and were mostly application-site effects such as pruritus Grade 3–4 treatment-emergent drug-related adverse events occurred in 9% of patients. Conclusion These results suggest that aviscumine may have a clinical impact in patients with previously treated metastatic melanoma and provide rationale for further clinical evaluation of this agent. In the light of effective new immune checkpoint blockers it might be a candidate for combinations with these agents. Trial registration ClinicalTrials.gov: NCT00658437 PMID:25324973

  20. Treatment

    MedlinePlus

    ... Prevention Treatment 2003 U.S. Outbreak African Rodent Importation Ban For Clinicians Clinical Recognition Specimen Collection Treatment Smallpox ... Examining Animals with Suspected Monkeypox African Rodent Importation Ban Resources Related Links Poxvirus Molluscum Contagiosum Orf Virus ( ...

  1. Effect of Carbon Ion Radiotherapy for Sacral Chordoma: Results of Phase I-II and Phase II Clinical Trials

    SciTech Connect

    Imai, Reiko; Kamada, Tadashi; Tsuji, Hiroshi; Sugawara, Shinji; Serizawa, Itsuko; Tsujii, Hirohiko; Tatezaki, Shin-ichiro

    2010-08-01

    Purpose: To summarize the results of treatment for sacral chordoma in Phase I-II and Phase II carbon ion radiotherapy trials for bone and soft-tissue sarcomas. Patients and Methods: We performed a retrospective analysis of 38 patients with medically unresectable sacral chordomas treated with the Heavy Ion Medical Accelerator in Chiba, Japan between 1996 and 2003. Of the 38 patients, 30 had not received previous treatment and 8 had locally recurrent tumor after previous resection. The applied carbon ion dose was 52.8-73.6 Gray equivalents (median, 70.4) in a total of 16 fixed fractions within 4 weeks. Results: The median patient age was 66 years. The cranial tumor extension was S2 or greater in 31 patients. The median clinical target volume was 523 cm{sup 3}. The median follow-up period was 80 months. The 5-year overall survival rate was 86%, and the 5-year local control rate was 89%. After treatment, 27 of 30 patients with primary tumor remained ambulatory with or without supportive devices. Two patients experienced severe skin or soft-tissue complications requiring skin grafts. Conclusion: Carbon ion radiotherapy appears effective and safe in the treatment of patients with sacral chordoma and offers a promising alternative to surgery.

  2. Change in Metabolic Syndrome Parameters With Antipsychotic Treatment in the CATIE Schizophrenia Trial: Prospective Data From Phase 1

    PubMed Central

    Meyer, Jonathan M.; Davis, Vicki G.; Goff, Donald C.; McEvoy, Joseph P.; Nasrallah, Henry A.; Davis, Sonia M.; Rosenheck, Robert A.; Daumit, Gail L.; Hsiao, John; Swartz, Marvin S.; Stroup, T. Scott; Lieberman, Jeffrey A.

    2008-01-01

    Background The metabolic syndrome (MS) is associated with increased risk for diabetes mellitus and coronary heart disease, and is highly prevalent among schizophrenia patients. Given concerns over antipsychotic metabolic effects, this analysis explored MS status and outcomes in phase 1 of the CATIE Schizophrenia Trial. Methods The change in proportion of subjects with MS and individual criteria was compared between antipsychotic treatment groups, along with mean changes for individual criteria. Primary analyses examined subjects with fasting laboratory assessments at baseline and 3 months. Other analyses examined 3-month changes in MS status, waist circumference (WC), HDL cholesterol and blood pressure in all subjects, metabolic changes at the end of phase 1 participation (EOP), and repeated measures changes in HDL, blood pressure (BP) and WC over phase 1. Results At 3 months, there were no significant between-drug differences for the change in proportion of subjects meeting MS status or individual MS criteria in the smaller fasting cohort (n=281) or for those meeting criteria for parameters not dependent on fasting status (BP, HDL, WC) among all subjects (n=660). Among all subjects whose MS status could be determined at 3 months (n=660), MS prevalence increased for olanzapine (from 34.8% to 43.9%), but decreased for ziprasidone (from 37.7% to 29.9%) (p=.001). Although effect sizes varied across subgroups, at 3 months olanzapine and quetiapine had the largest mean increase in waist circumference (0.7 in for both) followed by risperidone (0.4 in), compared to no change for ziprasidone (0.0 in) and a decrease in waist circumference for perphenazine (−0.4 in). Olanzapine also demonstrated significantly different changes in fasting triglycerides at 3 months (+21.5 mg/dl) compared to ziprasidone (−32.1 mg/dl). EOP exposure data was obtained, on average, nine months from baseline for all metabolic variables. Results from EOP and repeated measures analyses were

  3. Phase 1 Clinical Trial of Intratumoral Reovirus Infusion for the Treatment of Recurrent Malignant Gliomas in Adults

    PubMed Central

    Kicielinski, Kimberly P; Chiocca, E Antonio; Yu, John S; Gill, George M; Coffey, Matt; Markert, James M

    2014-01-01

    Reovirus, an oncolytic RNA virus exhibiting antiglioma activity, was shown in a previous single institution phase 1 study found that the inoculation of the virus to be well tolerated in patients with recurrent malignant glioma (MG). The goals of multicenter study reported herein were to determine the dose-limiting toxicity, maximum tolerated dose, and target lesion response rate when reovirus was administered in a novel fashion via intratumoral infusion for 72 hours in patients with recurrent malignant glioma. Fifteen adult patients were treated in a dose escalation study ranging from 1 × 108 to 1 × 1010 tissue culture infectious dose 50, tentimes the dose achieved in the previous trial. Neurological, functional examinations, and imaging studies were completed pre- and postinfusion. There was one grade 3 adverse event (convulsions) felt to be possibly related to treatment, but no grade 4 adverse events considered probably or definitely related to treatment. Dose-limiting toxicity were not identified and a maximum tolerated dose was not reached. Evidence of antiglioma activity was seen in some patients. This first report of intratumoral infusion of reovirus in patients with recurrent malignant glioma demonstrated the approach to be safe and well tolerated, warranting further studies. PMID:24553100

  4. High Quality of Liquid Phase-Deposited SiON on GaAs MOS Capacitor with Multiple Treatments

    NASA Astrophysics Data System (ADS)

    Lee, Ming-Kwei; Yen, Chih-Feng; Yeh, Min-Yen

    2016-08-01

    Silicon oxynitride (SiON) film on a p-type (100) GaAs substrate by liquid phase deposition has been characterized. Aqueous solutions of hydrofluosilicic acid, ammonia and boric acid were used as growth precursors. The electrical characteristics of SiON film are much improved on GaAs with (NH4)2S treatment. With post-metallization annealing (PMA), hydrogen ions further passivate traps in the SiON/GaAs film and interface. Both PMA and (NH4)2S treatments on a SiON/GaAs MOS capacitor produce better interface quality and lower interface state density (Dit) compared with ones without hydrogen and sulfur passivations. The leakage current densities are improved to 7.1 × 10-8 A/cm2 and 1.8 × 10-7 A/cm2 at ±2 V. The dielectric constant of 5.6 and the effective oxide charges of -5.3 × 1010 C/cm2 are obtained. The hysteresis offset of the hysteresis loop is only 0.09 V. The lowest Dit is 2.7 × 1011 cm-2/eV at an energy of about 0.66 eV from the edge of the valence band.

  5. High Quality of Liquid Phase-Deposited SiON on GaAs MOS Capacitor with Multiple Treatments

    NASA Astrophysics Data System (ADS)

    Lee, Ming-Kwei; Yen, Chih-Feng; Yeh, Min-Yen

    2016-05-01

    Silicon oxynitride (SiON) film on a p-type (100) GaAs substrate by liquid phase deposition has been characterized. Aqueous solutions of hydrofluosilicic acid, ammonia and boric acid were used as growth precursors. The electrical characteristics of SiON film are much improved on GaAs with (NH4)2S treatment. With post-metallization annealing (PMA), hydrogen ions further passivate traps in the SiON/GaAs film and interface. Both PMA and (NH4)2S treatments on a SiON/GaAs MOS capacitor produce better interface quality and lower interface state density (Dit) compared with ones without hydrogen and sulfur passivations. The leakage current densities are improved to 7.1 × 10-8 A/cm2 and 1.8 × 10-7 A/cm2 at ±2 V. The dielectric constant of 5.6 and the effective oxide charges of -5.3 × 1010 C/cm2 are obtained. The hysteresis offset of the hysteresis loop is only 0.09 V. The lowest Dit is 2.7 × 1011 cm-2/eV at an energy of about 0.66 eV from the edge of the valence band.

  6. Assessment of Labrasol/Labrafil/Transcutol (4/4/2, v/v/v) as a non-clinical vehicle for poorly water-soluble compounds after 4-week oral toxicity study in Wistar rats.

    PubMed

    Delongeas, J-L; de Conchard, G Vermeil; Beamonte, A; Bertheux, H; Spire, C; Maisonneuve, C; Becourt-Lhote, N; Goldfain-Blanc, F; Claude, N

    2010-01-01

    Drug safety research is frequently faced with the challenge of the selection of appropriate vehicles for use in in vivo non-clinical safety assessment studies. Reported here are the results of blend Labrasol, Labrafil and Transcutol, [L/L/T, (4/4/2, v/v/v)], excipients used as bioavailability enhancer and solubilizer for poorly water-soluble compounds and tested daily for 4 weeks by oral route in Wistar rats (10/sex/group) at dose volumes of 5, 10 or 20 mL/kg/day and compared to controls given 20 mL/kg/day of 1% (w/v) hydroxyethylcellulose in purified water. L/L/T was broadly well tolerated at 5 mL/kg/day and lethal at 20 mL/kg/day in 1 of 20 rats treated at this level. Changes in appearance and behaviour were observed from 10 mL/kg/day with volume-related incidence, severity and duration. Reduced feed intake observed from 5 (females) or 10 mL/kg/day (males) resulted in low bodyweights for high volume males only (-11% of controls). There was a volume-related induction of hepatic CYP 1A1/2, 2B1/2 and/or 2E1 subfamilies from 5 mL/kg/day, with high liver weight, centrilobular hepatocellular hypertrophy and high ALT, triglyceride and cholesterol serum values at 20 mL/kg/day. Renal tubular dilation in medulla, cortical cell degeneration/necrosis with granular material in adjacent glomerular spaces, crystal deposits in the inner medulla, papilla and/or renal pelvis, and tubular mineralization, associated with proteinuria and calcium oxalate crystalluria, were observed at 20 mL/kg/day as well as vacuolation in the adrenal cortex, with a sex-dependant localization. According to these results, 5 mL/kg/day was considered as an acceptable volume for further use of L/L/T (4/4/2, v/v/v) blend as a vehicle for poorly water soluble drugs in Wistar rat toxicity studies. PMID:20347907

  7. WE-G-BRD-01: Diffusion Weighted MRI for Response Assessment of Inoperable Lung Tumors for Patients Undergoing SBRT Treatment

    SciTech Connect

    Tyagi, N; Wengler, K; Yorke, E; Hunt, M; Deasy, J; Rimner, A

    2014-06-15

    Purpose: To investigate early changes in tumor Apparent Diffusion Coefficients derived from diffusion weighted (DW)-MRI of lung cancer patients undergoing SBRT, as a possible early predictor of treatment response. Methods: DW-MRI scans were performed in this prospective phase I IRB-approved study of inoperable lung tumors at various time-points during the course of SBRT treatments. Axial DW scan using multi b-values ranging from 0–1000 s/mm{sup 2} were acquired in treatment position on a 3T Philips MR scanner during simulation, one hour after the first fraction (8 Gy), after a total of 5 fractions (40 Gy) and 4 weeks after SBRT delivery. A monoexponential model based on a least square fit from all b values was performed on a pixel-by-pixel basis and ADC was calculated. GTVs drawn on 4DCT for planning were mapped on the T2w MRI (acquired at exhale) after deformable registration. These volumes were then mapped on DWI scan for ADC calculation after rigid registration between the anatomical scan and diffusion scan. T2w scan on followup time points were deformably registered to the pretreatment T2 scan. Results: The first two patients in this study were analyzed. Median ADC values were 1.48, 1.48, 1.62 and 1.83 (10{sup −3}×) mm{sup 2}/s at pretreatment, after 8 Gy, after 40 Gy and 4 weeks posttreatment for the first patient and 1.57, 1.53, 1.66 and 1.72 (10{sup −3}×) mm{sup 2}/s for the second patient. ADC increased more significantly after 4 weeks of treatment rather than immediately post treatment, implying that late ADC value may be a better predictor of tumor response for SBRT treatment. The fraction of tumor pixels at high ADC values increased at 4 weeks post treatment. Conclusion: The observed increase in ADC values before the end of radiotherapy may be a surrogate for tumor response, but further patient accrual will be necessary to determine its value.

  8. Dynamically slow solid-to-solid phase transition induced by thermal treatment of DimimFeCl4 magnetic ionic liquid.

    PubMed

    de Pedro, Imanol; Fabelo, Oscar; García-Saiz, Abel; Vallcorba, Oriol; Junquera, Javier; Blanco, Jesús Angel; Waerenborgh, João Carlos; Andreica, D; Wildes, Andrew; Fernández-Díaz, María Teresa; Fernández, Jesús Rodríguez

    2016-08-01

    The results reported here represent the first direct experimental observations supporting the existence of a solid-to-solid phase transition induced by thermal treatment in magnetic ionic liquids (MILs). The phase transitions of the solid phases of 1,3-dimethylimidazolium tetrachloroferrate, DimimFeCl4, are closely related to its thermal history. Two series of solid-to-solid phase transitions can be described in this MIL: (i) from room temperature (RT) phase II [space group (s.g.) = P21] to phase I-a [s.g. = P212121] via thermal quenching or via fast cooling at T > 2 K min(-1); (ii) from phase I-a to phase I-b [s.g. = P21/c] when the temperature was kept above 180 K for several minutes. The latter involves a slow translational and reorientational dynamical process of both the imidazolium cation and the tetrachloroferrate anion and has been characterized using synchrotron and neutron powder diffraction and DFT (density functional theory) studies. The transition is also related to the modification of the super-exchange pathways of low-temperature phases which show a overall antiferromagnetic behavior. A combination of several experimental methods such as magnetometry, Mössbauer and muon spectroscopy together with polarized and non-polarized neutron powder diffraction has been used in order to characterize the different features observed in these phases. PMID:27439896

  9. SU-E-T-510: Mathematical Analysis of Approximate Biological Effective Dose (BED) Calculation for Multi-Phase Radiotherapy Treatment Plans

    SciTech Connect

    Kauweloa, K; Gutierrez, A; Bergamo, A; Stathakis, S; Papanikolaou, N; Mavroidis, P

    2014-06-01

    Purpose: There is growing interest about biological effective dose (BED) and its application in treatment plan evaluation due to its stronger correlation with treatment outcome. An approximate biological effective dose (BEDA) equation was introduced to simplify BED calculations by treatment planning systems in multi-phase treatments. The purpose of this work is to reveal its mathematical properties relative to the true, multi-phase BED (BEDT) equation. Methods: The BEDT equation was derived and used to reveal the mathematical properties of BEDA. MATLAB (MathWorks, Natick, MA) was used to simulate and analyze common and extreme clinical multi-phase cases. In those cases, percent error (Perror) and Bland-Altman analysis were used to study the significance of the inaccuracies of BEDA for different combinations of total doses, numbers of fractions, doses per fractions and α over β values. All the calculations were performed on a voxel-basis in order to study how dose distributions would affect the accuracy of BEDA. Results: When the voxel dose-per-fractions (DPF) delivered by both phases are equal, BEDA and BEDT are equal. In heterogeneous dose distributions, which significantly vary between the phases, there are fewer occurrences of equal DPFs and hence the imprecision of BEDA is greater. It was shown that as the α over β ratio increased the accuracy of BEDA would improve. Examining twenty-four cases, it was shown that the range of DPF ratios for a 3 Perror varied from 0.32 to 7.50Gy, whereas for Perror of 1 the range varied from 0.50 to 2.96Gy. Conclusion: The DPF between the different phases should be equal in order to render BEDA accurate. OARs typically receive heterogeneous dose distributions hence the probability of equal DPFs is low. Consequently, the BEDA equation should only be used for targets or OARs that receive uniform or very similar dose distributions by the different treatment phases.

  10. Hyperbaric oxygen treatment produces an antinociceptive response phase and inhibits astrocyte activation and inflammatory response in a rat model of neuropathic pain.

    PubMed

    Zhao, Bai-Song; Meng, Ling-Xin; Ding, Yuan-Yuan; Cao, Yan-Yan

    2014-06-01

    Hyperbaric oxygen (HBO) treatment has been proven to be a promising candidate for protection of the nervous system after acute injury in animal models of neuropathic pain. The purposes of this study were to examine the antinociceptive response phase induced by HBO treatment in a model of neuropathic pain and to determine the dependence of the treatment's mechanism of alleviating neuropathic pain on the inhibition of spinal astrocyte activation. Neuropathic pain was induced in rats by chronic constriction injury of the sciatic nerve. Mechanical threshold and thermal latency were tested preoperatively and for 1 week postoperatively, four times daily at fixed time points. Methane dicarboxylic aldehyde (MDA) and superoxide dismutase (SOD) parameters were used as indices of oxidative stress response and tested before and after the treatment. The inflammatory cytokines interleukin (IL)-1β and IL-10 were assayed in the sciatic nerve were with enzyme-linked immunoassay. Glial fibrillary acidic protein activation in the spinal cord was evaluated immunohistochemically. The rats exhibited temporary allodynia immediately after HBO treatment completion. This transient allodynia was closely associated with changes in MDA and SOD levels. A single HBO treatment caused a short-acting antinociceptive response phase. Repetitive HBO treatment led to a long-acting antinociceptive response phase and inhibited astrocyte activation. These results indicated that HBO treatment played a dual role in the aggravation and alleviation of neuropathic pain, though the aggravated pain effect (transient allodynia) was far less pronounced than the antinociceptive phase. Astrocyte inhibition and anti-inflammation may contribute to the antinociceptive effect of HBO treatment after nerve injury. PMID:24390961

  11. Preliminary results of a phase I/II study of sodium pentosanpolysulfate in the treatment of chronic radiation-induced proctitis

    SciTech Connect

    Grigsby, P.W.; Pilepich, M.V.; Parsons, C.L. )

    1990-02-01

    This is a report of a phase I/II study of 13 patients treated with sodium pentosanpolysulfate (PPS) for chronic radiation-induced proctitis. A complete response was obtained in 82%, a partial response occurred in 9%, and 9% failed to respond to therapy. No significant toxicity was observed. It is concluded that PPS is an effective treatment for chronic radiation-induced proctitis and a phase III randomized, double-blind study of PPS versus placebo is planned.

  12. Second-phase hepatitis C virus RNA decline during telaprevir-based therapy increases with drug effectiveness: implications for treatment duration.

    PubMed

    Guedj, Jeremie; Perelson, Alan S

    2011-06-01

    Hepatitis C virus (HCV) RNA decay during antiviral therapy is characterized by a rapid first phase, followed by a slower second phase. The current understanding of viral kinetics attributes the magnitude of the first phase of decay to treatment effectiveness, whereas the second phase of decay is attributed to the progressive loss of infected cells. Here, we analyzed data from 44 patients treated with telaprevir, a potent HCV protease inhibitor. Using a viral kinetic model that accounts for the pharmacokinetics of telaprevir, we found the second-phase slope of viral decline to be strongly correlated with treatment effectiveness and to be roughly four-fold more rapid than has been reported with interferon-based therapies. Because telaprevir is not known to increase the death rate of infected cells, our results suggest that the second-phase slope of viral decline is driven not only by the death of infected cells, but may also involve other mechanisms, such as a treatment-effectiveness-dependent degradation of intracellular viral RNA. As a result of the enhanced viral decay caused by the high antiviral effectiveness of telaprevir, we predict that if drug resistance could be avoided by using an appropriate combination of antiviral agents, treatment duration needed to clear HCV might be dramatically shortened. Indeed, we predict that in 95% of fully compliant patients, the last virus particle should be eliminated by week 7 of therapy. If the remaining infected hepatocytes act as a potential reservoir for the renewal of infection, no more than 10 weeks of treatment should be sufficient to clear the infection in 95% of fully compliant patients. However, if patients miss doses, treatment duration would need to be extended. PMID:21384401

  13. Phase II Study of Vorinostat for Treatment of Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma

    PubMed Central

    Kirschbaum, Mark; Frankel, Paul; Popplewell, Leslie; Zain, Jasmine; Delioukina, Maria; Pullarkat, Vinod; Matsuoka, Deron; Pulone, Bernadette; Rotter, Arnold J.; Espinoza-Delgado, Igor; Nademanee, Auayporn; Forman, Stephen J.; Gandara, David; Newman, Edward

    2011-01-01

    Purpose We performed a phase II study of oral vorinostat, a histone and protein deacetylase inhibitor, to examine its efficacy and tolerability in patients with relapsed/refractory indolent lymphoma. Patients and Methods In this open label phase II study (NCT00253630), patients with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL), with ≤ 4 prior therapies were eligible. Oral vorinostat was administered at a dose of 200 mg twice daily on days 1 through 14 of a 21-day cycle until progression or unacceptable toxicity. The primary end point was objective response rate (ORR), with secondary end points of progression-free survival (PFS), time to progression, duration of response, safety, and tolerability. Results All 35 eligible patients were evaluable for response. The median number of vorinostat cycles received was nine. ORR was 29% (five complete responses [CR] and five partial responses [PR]). For 17 patients with FL, ORR was 47% (four CR, four PR). There were two of nine responders with MZL (one CR, one PR), and no formal responders among the nine patients with MCL, although one patient maintained stable disease for 26 months. Median PFS was 15.6 months for patients with FL, 5.9 months for MCL, and 18.8 months for MZL. The drug was well-tolerated over long periods of treatment, with the most common grade 3 adverse events being thrombocytopenia, anemia, leucopenia, and fatigue. Conclusion Oral vorinostat is a promising agent in FL and MZL, with an acceptable safety profile. Further studies in combination with other active agents in this setting are warranted. PMID:21300924

  14. Effect of pre-welding heat-treatments on welding a two-phase Ni{sub 3}Al alloy

    SciTech Connect

    Li, Huaxin; Jones, R.H.

    1994-05-01

    Autogenous gas-tungsten arc welding was performed on a two-phase Ni{sub 3}Al alloy. Plates 3 mm thick were subjected to three pre-welding heat treatments (PWHT): as-cast, annealed at 1100C for 23 h (HT1) and HT1 plus 1120C/30 min/air cool (HT2). As-cast alloy was characterized by dendrites with many eutectic cells located at dendrite boundaries (DBs). The eutectic cells were destroyed by HT1. However, HT2 make no further changes on microstructure. Energy dispersive X-ray spectroscopy (EDX) revealed that the DBs of as-cast alloy were enriched with Zr. The Zr enrichment at DBs was increased further by HT1 and HT2. No solidification crack visible to the unaided eye was found in either fusion zone (FZ) or heat-affected zone (HAZ) due to welding. The FZ consisted of columnar grains with a eutectic structure along the boundaries. The eutectic structure was enriched with, Zr and contained many microcracks and some Zr-rich phases. Micro-solidification cracks were occasionally found along boundaries in FZ. The alloy was sensitive to liquation cracks that occurred along DBs in the HAZ. While PWHT had no effect on the characteristics of the FZ, PWHT had a notable effect on the severity of liquation cracking. The average crack numbers per 5 cm weldment were 12 for as-cast, 14 for HT1, and 17 for HT2. The role of Zr-inducing solidification cracks in FZ and liquation cracks in HAZ is discussed.

  15. Phase I Clinical Trial Assessing Temozolomide and Tamoxifen With Concomitant Radiotherapy for Treatment of High-Grade Glioma

    SciTech Connect

    Patel, Shilpen; DiBiase, Steven; Meisenberg, Barry; Flannery, Todd; Patel, Ashish; Dhople, Anil; Cheston, Sally; Amin, Pradip

    2012-02-01

    Purpose: The new standard treatment of glioblastoma multiforme is concurrent radiotherapy (RT) and temozolomide. The proliferation of high-grade gliomas might be partly dependent on protein kinase C-mediated pathways. Tamoxifen has been shown in vitro to inhibit protein kinase C through estrogen receptor-independent antineoplastic effects. This Phase I trial was designed to determine the maximal tolerated dose (MTD) of tamoxifen when given with temozolomide and concurrent RT to patients with high-grade gliomas. Methods and Materials: A total of 17 consecutive patients in four cohorts with World Health Organization Grade 3 (n = 2) and 4 (n = 15) gliomas were given tamoxifen twice daily during 6 weeks of concurrent RT and temozolomide. Eligibility included histologic diagnosis, age >18 years old, Karnofsky performance status {>=}60, and no previous brain RT or chemotherapy. The starting dose was 50 mg/m{sup 2} divided twice daily. If no dose-limiting toxicities (DLTs) occurred in 3 patients, the dose was escalated in 25-mg/m{sup 2} increments until the MTD was reached. When {>=}2 patients within a cohort experienced a DLT, the MTD had been exceeded. Temozolomide was given with RT at 75 mg/m{sup 2}. A dose of 60 Gy in 2 Gy/d fractions to a partial brain field was delivered. Results: A total of 6 patients in Cohort 4 had received tamoxifen at 125 mg/m{sup 2}. One patient was excluded, and the fourth patient developed Grade 4 thrombocytopenia (DLT). Thus, 3 more patients needed to be enrolled. A deep venous thrombosis (DLT) occurred in the sixth patient. Thus, the MTD was 100 mg/m{sup 2}. Conclusions: The MTD of tamoxifen was 100 mg/m{sup 2} when given concurrently with temozolomide 75 mg/m{sup 2} and RT. Tamoxifen might have a role in the initial treatment of high-grade gliomas and should be studied in future Phase II trials building on the newly established platform of concurrent chemoradiotherapy.

  16. Solution phase and membrane immobilized iron-based free radical reactions: Fundamentals and applications for water treatment

    NASA Astrophysics Data System (ADS)

    Lewis, Scott Romak

    Membrane-based separation processes have been used extensively for drinking water purification, wastewater treatment, and numerous other applications. Reactive membranes synthesized through functionalization of the membrane pores offer enhanced reactivity due to increased surface area at the polymer-solution interface and low diffusion limitations. Oxidative techniques utilizing free radicals have proven effective for both the destruction of toxic organics and non-environmental applications. Most previous work focuses on reactions in the homogeneous phase; however, the immobilization of reactants in membrane pores offers several advantages. The use of polyanions immobilized in a membrane or chelates in solution prevents ferric hydroxide precipitation at near-neutral pH, a common limitation of iron(Fe(II/III))-catalyzed hydrogen peroxide (H 2O2) decomposition. The objectives of this research are to develop a membrane-based platform for the generation of free radicals, degrade toxic organic compounds using this and similar solution-based reactions, degrade toxic organic compounds in droplet form, quantify hydroxyl radical production in these reactions, and develop kinetic models for both processes. In this study, a functionalized membrane containing poly(acrylic acid) (PAA) was used to immobilize iron ions and conduct free radical reactions by permeating H2O2 through the membrane. The membrane's responsive behavior to pH and divalent cations was investigated and modeled. The conversion of Fe(II) to Fe(III) in the membrane and its effect on the decomposition of hydrogen peroxide were monitored and used to develop kinetic models for predicting H2O2 decomposition in these systems. The rate of hydroxyl radical production, and hence contaminant degradation can be varied by changing the residence time, H2O2 concentration, and/or iron loading. Using these membrane-immobilized systems, successful removal of toxic organic compounds, such as pentachlorophenol (PCP), from water

  17. Research on change of phase transformation temperatures and electrical resistance triggered by heat treatment of alloy from Cu-Mn system

    NASA Astrophysics Data System (ADS)

    Karakaya, N.; Aldirmaz, E.

    2016-05-01

    This paper is aimed at studying influence of various heat treatments on transformation temperatures and electrical resistance properties of alloys from binary Cu-Mn system. It was noticed that with an increase in sample's grain size, transformation temperatures also increased. The activation energies of samples were calculated according to Kissinger and Augis-Bennett. Thermogravimetric and differential thermal analysis measurements were used to investigate phase transformations and kinetic parameters. The electrical values of resistance of alloy were investigated at different temperatures. The resistance as a function of quenching temperature showed a decrease. Depending on quenching techniques, Cu-Mn alloy can display different product phases such as parent phase and precipitation.

  18. A Phase II Evaluation of Gefitinib in the Treatment of Persistent or Recurrent Endometrial Cancer: A Gynecologic Oncology Group Study

    PubMed Central

    Leslie, Kimberly K.; Sill, Michael W.; Fischer, Edgar; Darcy, Kathleen M.; Mannel, Robert S.; Tewari, Krishnansu S.; Hanjani, Parviz; Wilken, Jason A.; Baron, Andre T.; Godwin, Andrew K.; Schilder, Russell J.; Singh, Meenakshi; Maihle, Nita J.

    2013-01-01

    Background A phase II trial was performed to evaluate the efficacy and safety of gefitinib in patients with persistent/recurrent endometrial cancer. Methods Women with histologically confirmed persistent/recurrent endometrial cancer were treated with 500 mg oral gefitinib daily until progression or severe toxicity, with progression-free survival (PFS) at six months as the primary endpoint. Tumor expression of total epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor A (PRA) and B (PRB), Ki67, pEGFR and activated extracellular signal-regulated kinase (pERK) were examined pre- and post-treatment. EGFR was sequenced, and serum concentrations of soluble EGFR (sEGFR) at baseline also were examined. Results Of 29 patients enrolled, 26 were evaluable for efficacy and toxicity. Four patients experienced PFS ≥6 months, and one had a complete response which was not associated with an EGFR mutation. The concentration of sEGFR in pretreatment serum was positively correlated with overall survival (OS), but not with responsiveness to gefitinib in this small patient cohort. Expression of tumor biomarkers was not associated with PFS or OS. Co-expression of ER with PRA in primary and recurrent tumors, and pEGFR with pERK in primary tumors was observed. Conclusions This treatment regimen was tolerable but lacked sufficient efficacy to warrant further evaluation in this setting. The possible association between serum sEGFR concentrations and OS, and temporal changes in expression of pEGFR and pERK and the documented CR of one patient are interesting and warrant additional investigation. PMID:23438670

  19. Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage.

    PubMed

    Hurd, Yasmin L; Yoon, Michelle; Manini, Alex F; Hernandez, Stephanie; Olmedo, Ruben; Ostman, Maria; Jutras-Aswad, Didier

    2015-10-01

    Multiple cannabinoids derived from the marijuana plant have potential therapeutic benefits but most have not been well investigated, despite the widespread legalization of medical marijuana in the USA and other countries. Therapeutic indications will depend on determinations as to which of the multiple cannabinoids, and other biologically active chemicals that are present in the marijuana plant, can be developed to treat specific symptoms and/or diseases. Such insights are particularly critical for addiction disorders, where different phytocannabinoids appear to induce opposing actions that can confound the development of treatment interventions. Whereas Δ(9)-tetracannabinol has been well documented to be rewarding and to enhance sensitivity to other drugs, cannabidiol (CBD), in contrast, appears to have low reinforcing properties with limited abuse potential and to inhibit drug-seeking behavior. Other considerations such as CBD's anxiolytic properties and minimal adverse side effects also support its potential viability as a treatment option for a variety of symptoms associated with drug addiction. However, significant research is still needed as CBD investigations published to date primarily relate to its effects on opioid drugs, and CBD's efficacy at different phases of the abuse cycle for different classes of addictive substances remain largely understudied. Our paper provides an overview of preclinical animal and human clinical investigations, and presents preliminary clinical data that collectively sets a strong foundation in support of the further exploration of CBD as a therapeutic intervention against opioid relapse. As the legal landscape for medical marijuana unfolds, it is important to distinguish it from "medical CBD" and other specific cannabinoids, that can more appropriately be used to maximize the medicinal potential of the marijuana plant. PMID:26269227

  20. Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial

    PubMed Central

    Rojek, Amanda; Gannon, Fiona; Carson, Gail; Idriss, Baimba; Massaquoi, Thomas; Gandi, Regina; Joseph, Sebatu; Osman, Hassan K.; Brooks, Timothy J. G.; Simpson, Andrew J. H.; Goodfellow, Ian; Thorne, Lucy; Arias, Armando; Merson, Laura; Castle, Lyndsey; Howell-Jones, Rebecca; Pardinaz-Solis, Raul; Hope-Gill, Benjamin; Ferri, Mauricio; Grove, Jennifer; Kowalski, Mark; Stepniewska, Kasia; Lang, Trudie; Whitehead, John; Olliaro, Piero; Samai, Mohammed; Horby, Peter W.

    2016-01-01

    Background TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. Methods and Findings In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. Conclusions Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. Trial registration Pan African Clinical Trials Registry PACTR201501000997429 PMID:27093560

  1. Rituximab in the Treatment of Refractory Adult and Juvenile Dermatomyositis and Adult Polymyositis: A Randomized, Placebo-phase Trial

    PubMed Central

    Oddis, Chester V.; Reed, Ann M.; Aggarwal, Rohit; Rider, Lisa G.; Ascherman, Dana P.; Levesque, Marc C.; Barohn, Richard J.; Feldman, Brian M.; Harris-Love, Michael O.; Koontz, Diane C.; Fertig, Noreen; Kelley, Stephanie S.; Pryber, Sherrie L.; Miller, Frederick W.; Rockette, Howard E.

    2012-01-01

    Objective To assess the safety and efficacy of rituximab in a randomized, double-blind, placebo-phase, trial of adult and pediatric myositis. Methods Adults with refractory polymyositis and adults and children with refractory dermatomyositis were enrolled. Entry criteria included muscle weakness and ≥2 additional abnormal core set measures (CSM) for adults. JDM patients required ≥ 3 abnormal CSM with or without muscle weakness. Patients were randomized to either ‘rituximab early’ or ‘rituximab late’ and glucocorticoid and immunosuppressive therapy were allowed at entry. The primary endpoint compared the time to achieve the preliminary International Myositis Assessment and Clinical Studies Group definition of improvement (DOI) between the 2 groups. The secondary endpoints were time to achieve ≥20% improvement in muscle strength, and the proportion of early and late rituximab patients achieving DOI at week 8. Results Among 200 randomized patients (76 PM/76 DM/48 JDM), 195 showed no difference in the time to DOI between the rituximab late (n=102) and rituximab early (n=93) groups (p=0.74, log rank) with a median time to DOI of 20.2 weeks and 20.0 weeks respectively. The secondary endpoints also did not significantly differ between the two treatment groups. However, 161 (83%) of randomized patients met the DOI and individual CSM improved in both groups throughout the 44-week trial. Conclusion Although there were no significant differences in the two treatment arms for the primary and secondary endpoints, 83% of refractory adult and juvenile myositis patients met the DOI. The role of B cell depleting therapies in myositis warrants further study with consideration for a different trial design. PMID:23124935

  2. Effect of sequential application of topical adapalene and clindamycin phosphate in the treatment of Japanese patients with acne vulgaris.

    PubMed

    Kubota, Yasuo; Munehiro, Asuka; Shirahige, Yoshie; Nakai, Kozo; Katsuura, Junko; Moriue, Tetsuya; Murakami, Yumi; Matsunaka, Hiroshi; Yoneda, Kozo

    2012-02-01

    The efficacy of combined therapy with a retinoid and antibiotic for Japanese patients with acne vulgaris remains to be established. Further, maintenance strategies limiting the use of topical retinoids must be identified. The objectives of this study are to determine the efficacy of sequential application of topical adapalene and clindamycin phosphate and to assess the impact of this regimen on patients' quality of life. Sixty-six patients were recruited. The regimen comprised two phases. For the 4-week initial treatment, 1% clindamycin phosphate gel was applied twice daily and 0.1% adapalene gel, once. In the 4-week maintenance phase, patients were randomly assigned to the OD group (adapalene applied once daily) or the TW group (adapalene applied once daily on 2 days per week). The acne severity score, lesion counts, microcomedone count, and sebum amount were measured. Quality of life (QOL) was assessed using Skindex-16. All parameters improved significantly by week 4 of initial treatment. No statistically significant differences were found in the improvement of clinical findings between the groups. All QOL scores improved significantly and did not significantly differ between the groups. Our regimen may enable clinical control of acne in Japanese patients and improve their QOL. For limiting retinoid use, weekly application of adapalene during maintenance is suitable. PMID:21254867

  3. Cardiac Atrial Circadian Rhythms in PERIOD2::LUCIFERASE and per1:luc Mice: Amplitude and Phase Responses to Glucocorticoid Signaling and Medium Treatment

    PubMed Central

    Xi, Yang; Li, Lei; Duffield, Giles E.

    2012-01-01

    Circadian rhythms in cardiac function are apparent in e.g., blood pressure, heart rate, and acute adverse cardiac events. A circadian clock in heart tissue has been identified, but entrainment pathways of this clock are still unclear. We cultured tissues of mice carrying bioluminescence reporters of the core clock genes, period 1 or 2 (per1luc or PER2LUC) and compared in vitro responses of atrium to treatment with medium and a synthetic glucocorticoid (dexamethasone [DEX]) to that of the suprachiasmatic nucleus (SCN) and liver. We observed that PER2LUC, but not per1luc is rhythmic in atrial tissue, while both per1luc and PER2LUC exhibit rhythmicity in other cultured tissues. In contrast to the SCN and liver, both per1luc and PER2LUC bioluminescence amplitudes were increased in response to DEX treatment, and the PER2LUC amplitude response was dependent on the time of treatment. Large phase-shift responses to both medium and DEX treatments were observed in the atrium, and phase responses to medium treatment were not attributed to serum content but the treatment procedure itself. The phase-response curves of atrium to both DEX and medium treatments were found to be different to the liver. Moreover, the time of day of the culturing procedure itself influenced the phase of the circadian clock in each of the cultured tissues, but the magnitude of this response was uniquely large in atrial tissue. The current data describe novel entrainment signals for the atrial circadian clock and specifically highlight entrainment by mechanical treatment, an intriguing observation considering the mechanical nature of cardiac tissue. PMID:23110090

  4. Effect of Pre-intercritical Annealing Treatments on the Microstructure and Mechanical Properties of 0.33% Carbon Dual-Phase Steel

    NASA Astrophysics Data System (ADS)

    Shukla, Neha; Das, Suvajeet; Maji, Sumanta; Chowdhury, Subhro Roy; Show, Bijay Kumar

    2015-12-01

    The present study is aimed at understanding the effect of different prior heat treatments on the microstructure and mechanical properties of 0.33% carbon dual-phase (DP) steel. For this purpose, different dual-phase steels were produced by subjecting the as-received steel to `hardening' (DP-H), `hardening + tempering' (DP-HT), and `austempering' (DP-AT) treatments prior to the intercritical annealing treatment. The study reveals that the prior hardening treatment in DP-H steel results in significant refinement of ferrite grains and formation of fine elongated martensite plates having an aspect ratio = 6.1 ± 3. These fine elongated martensites are responsible for poor ductility in DP-H steel. Although DP steel without any prior treatment (DP-AR) and DP-AT steel exhibit high strength and hardness, their ductility is limited by the presence of very hard martensite islands which act as the failure initiation sites in these steels. On the other hand, prior `hardening + tempering' treatment in DP-HT steel results in the formation of nearly spherical-shaped martensite (aspect ratio = 1.24 ± 0.13) along with coarse martensite laths. In addition, the presence of fine carbides is also found along the lath boundaries. These fine spherical martensites and fine carbides provide higher strain hardening to DP-HT steel. Accordingly, DP-HT steel exhibits adequate ductility as well as strength. Therefore, prior `hardening + tempering' treatment was found to the best prior treatment in the present study.

  5. Effects of prior treatment with simvastatin on skeletal muscle structure and mitochondrial enzyme activities during early phases of sepsis

    PubMed Central

    Ozkok, Elif; Yorulmaz, Hatice; Ates, Gulten; Serdaroglu-Oflazer, Piraye; Tamer, Ayse Sule

    2014-01-01

    We investigated the effects of the early phase of sepsis and prior treatment of Simvastatin on muscle structure and mitochondrial enzymes treated with lipopolysaccharide (LPS) in rats. We divided rats into control, LPS, simvastatin, simvastatin + LPS groups. Mitochondrial citrate synthase, complex I, II, I + III, II + III, cytochrome c oxidase (COX) activities were measured. Muscle tissue was stained using modified Gomori trichrome (MGT), succinic dehydrogenase (SDH) and cytochrome oxidase (COX). In all treated groups, complex I and citrate synthase activities were higher than in the controls. In the control and LPS groups, COX activity was increased when compared with simvastatins’. Complex II, II-III activities were higher in the LPS group than in the control group. Complex I-III activities were higher in the Simvastatin and Simvastatin + LPS groups than in the control and LPS groups (P < 0.05). Myopathic changes with LPS group were observed in MGT stained sections. Our findings showed improvements in the alterations of enzyme activities and muscle myofibrils after treating rats with LPS that had received a prior dose of simvastatin. PMID:25674200

  6. Phase II study of gemcitabine and bexarotene (GEMBEX) in the treatment of cutaneous T-cell lymphoma

    PubMed Central

    Illidge, T; Chan, C; Counsell, N; Morris, S; Scarisbrick, J; Gilson, D; Popova, B; Patrick, P; Smith, P; Whittaker, S; Cowan, R

    2013-01-01

    Background: Both gemcitabine and bexarotene are established single agents for the treatment of cutaneous T-cell lymphoma (CTCL). We investigated the feasibility and efficacy of combining these drugs in a single-arm phase II study. Methods: Cutaneous T-cell lymphoma patients who had failed standard skin-directed therapy and at least one prior systemic therapy were given four cycles of gemcitabine and concurrent bexarotene for 12 weeks. Responders were continued on bexarotene maintenance until disease progression or unacceptable toxicity. Results: The median age was 65 years, stage IB (n=5), stage IIA (n=2), stage IIB (n=8), stage III (n=8) and stage IVA (n=12), 17 patients were erythrodermic, 17 patients were B1, and 10 patients were both erythrodermic and B1. Thirty (86%) patients completed four cycles of gemcitabine. In all, 80.0% of patients demonstrated a reduction in modified Severity-Weighted Assessment Tool (mSWAT) score although the objective disease response rate at 12 weeks was 31% (partial response (PR) 31%) and at 24 weeks 14% (PR 14%, stable disease (SD) 23%, progressive disease (PD) 54%, not evaluable 9%). Median progression-free survival was 5.3 months and median overall survival was 21.2 months. Conclusion: The overall response rate of the combination did not reach the specified target to proceed further and is lower than that previously reported for gemcitabine as a single agent. PMID:24136145

  7. Formation of the ZnFe2O4 phase in an electric arc furnace off-gas treatment system.

    PubMed

    Suetens, T; Guo, M; Van Acker, K; Blanpain, B

    2015-04-28

    To better understand the phenomena of ZnFe2O4 spinel formation in electric arc furnace dust, the dust was characterized with particle size analysis, X-ray fluorescence (XRF), electron backscatter diffraction (EBSD), and electron probe micro-analysis (EPMA). Different ZnFe2O4 formation reaction extents were observed for iron oxide particles with different particle sizes. ZnO particles were present as both individual particles and aggregated on the surface of larger particles. Also, the slag particles found in the off-gas were shown not to react with the zinc vapor. After confirming the presence of a ZnFe2O4 formation reaction, the thermodynamic feasibility of in-process separation - a new electric arc furnace dust treatment technology - was reevaluated. The large air intake and the presence of iron oxide particles in the off-gas were included into the thermodynamic calculations. The formation of the stable ZnFe2O4 spinel phase was shown to be thermodynamically favorable in current electric arc furnace off-gas ducts conditions even before reaching the post combustion chamber. PMID:25646901

  8. Gemcitabine and Doxetaxel for Hepatocellular Carcinoma: A Phase II North Central Cancer Treatment Group (NCCTG) Clinical Trial1

    PubMed Central

    Alberts, Steven R.; Reid, Joel M.; Morlan, Bruce W.; Farr, Gist H.; Camoriano, John K.; Johnson, David B.; Egner, James R.; Seay, Thomas E.; Kim, George P.

    2011-01-01

    Objectives Few effective options are available for the treatment of unresectable hepatocellular carcinoma (HCC). Several phase I trials suggest promising activity of a combination of gemcitabine and docetaxel. Methods Patients with unresectable or metastatic HCC were treated with docetaxel 40 mg/m2 (later reduced to 30 mg/m2) and gemcitabine 800 mg/m2 on days 1, 8 every 3 weeks. Twenty-five patients were enrolled in 26 months. Median age was 64 (range 27-78), 17 were male, 14 had liver-only disease and, 11 had extrahepatic disease. Results Of 25 patients evaluable for the primary endpoint (response), 2 (8%) have a confirmed partial response. The median TTP is 2.76 months (95% CI 1.84-6.64 months). Median survival was 12.8 months (95% CI: 5.26-28.00). Two patients died on-study due to adverse events (1 hepatic and 1 renal failure), neither of which were attributed to the study medications. Twenty patients (81%) have experienced grade 3+ adverse events, including 11 with grade 4+ adverse events, primarily neutropenia, thrombocytopenia, diarrhea, and fatigue. Conclusions While this combination appears to have potential benefit, as measured by overall survival, its toxicity and the recent introduction of sorafenib has further limited the use of chemotherapy. Approaches other than chemotherapy are likely to be of the greatest potential benefit. PMID:21555932

  9. Everolimus as second- or third-line treatment of advanced endometrial cancer: ENDORAD, a phase II trial of GINECO

    PubMed Central

    Ray-Coquard, I; Favier, L; Weber, B; Roemer-Becuwe, C; Bougnoux, P; Fabbro, M; Floquet, A; Joly, F; Plantade, A; Paraiso, D; Pujade-Lauraine, E

    2013-01-01

    Background: Patients with recurrent/metastatic endometrial cancer that progresses after chemotherapy have limited treatment options and poor outcomes. Preclinical data suggest the oral mammalian target of rapamycin inhibitor everolimus may provide clinical benefit in these patients. Methods: In this multicenter, open-label, phase 2 study, patients with advanced or metastatic endometrial cancer refractory to one or two previous chemotherapy regimens received everolimus 10 mg per day until progression or unacceptable toxicity. Primary end point was the non-progressive disease rate at 3 months. Secondary end points included duration of response, progression-free, and overall survival (OS), and safety. Results: Forty-four patients were enrolled (median age, 65 years); 66% received one previous chemotherapy regimen. The 3-month non-progressive disease rate was 36% (95% confidence interval 22–52%), including two patients (5%) with partial response (PR). At 6 months, two additional patients experienced PR. Median duration of response was 3.1 months. Median progression-free and OS were 2.8 months and 8.1 months, respectively. The most common adverse events were anaemia (100%), fatigue (93%), hypercholesterolaemia (81%), and lymphopenia (81%). Conclusion: Everolimus demonstrated efficacy and acceptable tolerability in patients with chemotherapy-refractory advanced or metastatic endometrial cancer. These results support the further development of phosphatidylinositol 3-kinase-targeted therapies in endometrial cancer. PMID:23612453

  10. Treatment of Dry Eye Syndrome with Orally Administered CF101: Data from a Phase 2 Clinical Trial

    PubMed Central

    Avni, Isaac; Garzozi, Hanna J.; Barequet, Irina S.; Segev, Fanni; Varssano, David; Sartani, Gil; Chetrit, Noa; Bakshi, Erez; Zadok, David; Tomkins, Oren; Litvin, Gilad; Jacobson, Kenneth A.; Fishman, Sari; Harpaz, Zivit; Farbstein, Motti; Bar Yehuda, Sara; Silverman, Michael H.; Kerns, William D.; Bristol, David R.; Cohn, Ilan; Fishman, Pnina

    2013-01-01

    Objective To explore the safety and efficacy of CF101, an A3 adenosine receptor agonist, in patients with moderate-to-severe dry eye syndrome Design Phase 2, multicenter, randomized, double-masked, placebo-controlled, parallel-group study. Participants 68 patients completed the study, 35 patients in the placebo group and 33 patients in the CF101 group. Intervention Patients were orally treated with either 1 mg CF101 pills or matching vehicle-filled placebo pills, given twice daily for 12 weeks, followed by a 2-week post-treatment observation. Main Outcome Measures Efficacy an improvement of >25% over baseline at week 12 in one of the following parameters: (a) tear break-up time (BUT); (b) superficial punctate keratitis assessed by fluorescein staining (FS); (c) Schirmer tear test 1 (ST1). Safety clinical laboratory safety tests, ophthalmic examinations, intraocular pressure (IOP) measurements, electrocardiographic evaluations, vital sign measurements and monitoring of adverse events. Results A statistically significant increase in the proportion of patients who achieved more than 25% improvement in the corneal staining and in the clearance of corneal staining was noted between the CF101-treated group and the placebo group. Treatment with CF101 resulted in a statistically significant improvement in the mean change from baseline at week 12 of the corneal staining, BUT, and tear meniscus (TM) height in the CF101-treated group CF101 was well tolerated and exhibited an excellent safety profile with no serious adverse events. A statistically significant decrease from baseline was observed in the IOP of the CF101-treated group in comparison with the placebo group. Conclusions CF101, given orally, induced a statistically significant improvement in the corneal staining and an improvement in the BUT and TM in patients with moderate-to-severe dry eye syndrome. The drug was very well tolerated. These data and the anti-inflammatory characteristic of CF101 support further study

  11. Combined phase I/II study of imexon (AOP99.0001) for treatment of relapsed or refractory multiple myeloma.

    PubMed

    Moehler, Thomas M; Feneberg, Reinhard; Ho, Anthony Dick; Golenkov, Anatoly K; Ludwig, Heinz; Kropff, Martin; Khuageva, Nuriet K; Hajda, Jacek; von Broen, Ingo; Goldschmidt, Hartmut

    2010-08-01

    Imexon [AOP99.0001 (4-imino-1,3-diazobicyclo[3. 1. 0]-hexan-2-one)] belongs to a novel class of promising anticancer agents that induce tumor apoptosis through oxidative stress. Clinical experience since the late 1960s has provided initial evidence for a clinical antitumor activity. Our open-label, multicenter phase I clinical trial was designed to further investigate the adverse event (AEs) profile and pharmacokinetics of AOP99.0001 in pretreated myeloma patients and collect initial data on the potential clinical efficacy in this indication. Thirty-six patients with relapsed or refractory myeloma, who had been pretreated with at least two lines of therapy earlier, were included. Imexon was applied intravenously on 5 consecutive days for 2 weeks (d1-5 and d8-12) for a 3-week cycle. The plasma half-life of AOP99.0001 and its active metabolite AOP99.0002 was found to be approximately 1.2 and 2.6 h, respectively. The mean duration of treatment with Imexon was 6.8 weeks in a dose range between 50 and 1000 mg/m without reaching dose-limiting toxicity. Drug-related AEs occurring with a frequency of greater than 10% were fatigue, nausea, constipation, headache, asthenia, anemia, thrombocytopenia, leukopenia and creatinine increase. A total of nine severe adverse events occurred in three patients. No mortality was encountered when patients were on treatment with Imexon. Preliminary antimyeloma efficacy of AOP99.0001 was observed with 1 minimal response, 12 (36%) stable disease responses, and all other evaluable patients had progressive disease. Remarkably, the patient with minimal response also experienced a complete clinical resolution of myeloma-associated polyneuropathy. Overall, Imexon was safe and well tolerated in the dose range investigated. Imexon showed minor clinical activity as a single agent in heavily pretreated myeloma patients. On account of its unique mechanism of action, favorable toxicity profile, initial clinical evidence for antimyeloma activity, and

  12. Integration of Antiretroviral Therapy with Tuberculosis Treatment

    PubMed Central

    Abdool Karim, Salim S.; Naidoo, Kogieleum; Grobler, Anneke; Padayatchi, Nesri; Baxter, Cheryl; Gray, Andrew L.; Gengiah, Tanuja; Gengiah, Santhanalakshmi; Naidoo, Anushka; Jithoo, Niraksha; Nair, Gonasagrie; El-Sadr, Wafaa M.; Friedland, Gerald; Abdool Karim, Quarraisha

    2011-01-01

    Background We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, optimal time to initiate ART during tuberculosis treatment remains contentious. Methods To address this, we conducted a 3-arm, open-label randomized controlled trial in South Africa in acid-fast bacilli smear positive patients (n=642) with HIV and CD4+ counts <500 cells/mm3. Findings on the early therapy group (ART initiated within 4 weeks of tuberculosis treatment initiation, n=214) and late therapy group (ART initiated within the first 4 weeks of the continuation phase of tuberculosis treatment, n=215) are presented here. Results Median CD4+ count and viral load at baseline was 150 cells/mm3 and 161000 copies/ml, being similar in both groups. Incidence rate of AIDS or death was 6.9 (18/259.4) and 7.8 (19/244.2) per 100 person-years in the early and late therapy groups respectively (Incidence Rate Ratio (IRR)=0.89; 95%Confidence Interval (95%CI): 0.44,1.79; P=0.73). However, in patients with CD4+ counts <50 cells/mm3, the incidence rates of AIDS or death were 8.5 (early) and 26.3 (late) per 100 person-years (IRR=0.32; 95%CI: 0.07,1.13; P=0.06). Immune reconstitution inflammatory syndrome (IRIS) incidence rates were 20.2 (early) and 7.7 (late) per 100 person-years (IRR=2.62; 95%CI: 1.48,4.82; P<0.001). Adverse events requiring antiretroviral drug switches occurred in 10 (early) and 1 (late) patients (P=0.006). Conclusions The benefits of AIDS-free survival balanced against the risks of IRIS and ART-related adverse events, support early ART initiation in patients with CD4+ counts <50 cells/mm3 and deferred ART initiation to the continuation phase of tuberculosis treatment when CD4+ counts are higher. PMID:22010915

  13. EVALUATION OF DEMONSTRATED AND EMERGING TECHNOLOGIES FOR THE TREATMENT OF CONTAMINATED LAND AND GROUNDWATER (PHASE III) - 1999 SPECIAL SESSION ON MONITORED NATURAL ATTENUATION

    EPA Science Inventory

    This report includes the papers presented at the NATO/CCMS Pilot Study Meeting in Angers, France, May 9-14, 1999, for the special session on Monitored Natural Attenuation (MNA). This is the Phase III of the Evaluation of Demonstrated and Emerging Technologies for the Treatment a...

  14. Phase I: the pipeline-gas demonstration plant. Demonstration plant engineering and design. Volume 18. Plant Section 2700 - Waste Water Treatment

    SciTech Connect

    1981-05-01

    Contract No. EF-77-C-01-2542 between Conoco Inc. and the US Department of Energy provides for the design, construction, and operation of a demonstration plant capable of processing bituminous caking coals into clean pipeline quality gas. The project is currently in the design phase (Phase I). This phase is scheduled to be completed in June 1981. One of the major efforts of Phase I is the process and project engineering design of the Demonstration Plant. The design has been completed and is being reported in 24 volumes. This is Volume 18 which reports the design of Plant Section 2700 - Waste Water Treatment. The objective of the Waste Water Treatment system is to collect and treat all plant liquid effluent streams. The system is designed to permit recycle and reuse of the treated waste water. Plant Section 2700 is composed of primary, secondary, and tertiary waste water treatment methods plus an evaporation system which eliminates liquid discharge from the plant. The Waste Water Treatment Section is designed to produce 130 pounds per hour of sludge that is buried in a landfill on the plant site. The evaporated water is condensed and provides a portion of the make-up water to Plant Section 2400 - Cooling Water.

  15. Heat treatment induced intermetallic phase transition of arc-sprayed coating prepared by the wires combination of aluminum-cathode and steel-anode

    NASA Astrophysics Data System (ADS)

    Chen, Yongxiong; Liang, Xiubing; Wei, Shicheng; Liu, Yan; Xu, Binshi

    2009-07-01

    A method to prepare intermetallic composite coatings employing the cost-efficient electric arc spraying twin wires assistant with suitable heat treatment was developed. In this study, a Fe-Al composite coating was produced by spraying twin wires, i.e. a carbon steel wire as the anode and an aluminum wire as the cathode. The inter-deposited Fe-Al coating was transformed in-situ to Fe-Al intermetallic composite coating after a post annealing treatment. The effect of annealing treatment conditions on phase composition, microstructure and mechanical properties of the coating was investigated by using XRD, SEM, EDS and OM as well as microhardness tester. The results show that the desirable intermetallic phases such as Fe 2Al 5, FeAl and Fe 3Al are obtained under the annealing condition. The main oxide in the coating is FeO which can partially transform to Fe 3O 4 up to the annealing condition.

  16. Immunoresistance in cervical dystonia patients after treatment with abobotulinumtoxinA.

    PubMed

    Coleman, Chandra; Hubble, Jean; Schwab, Joseph; Beffy, Jean-Luc; Picaut, Philippe; Morte, Carles

    2012-07-01

    Formation of antibodies against botulinum toxin type A has been observed following treatment of Cervical Dystonia (CD). We present the immunological findings from two 12-week Phase III prospective, randomized, double-blind, single-dose, placebo-controlled studies (Study 1, n = 116; Study 2, n = 136). Patients in both studies were administered abobotulinumtoxinA 500U or placebo intramuscularly at baseline. Patients could receive up to three or four additional treatments (250-1000U) in an open-label follow-up period. Blood samples were collected at baseline and during treatment to test for antibodies to abobotulinumtoxinA using a radioimmunoprecipitation assay (Study 2 only) and a mouse protection assay. Loss of response was predefined using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score at 4 weeks following injection. No subjects in Study 1 and one individual in Study 2 developed neutralizing antibodies (nABs) during the double-blind treatment phase; the individual who developed immunoresistance had received botulinum toxin type A treatment prior to the study and did not respond to treatment. Two subjects demonstrated a change in nAB status during open-label treatment and overall responsiveness was maintained in these patients. In conclusion, the development of immunoresistance was rare and, in the presence of circulating nABs, patients may still gain benefit from intramuscular abobotulinumtoxinA treatment. PMID:22356470

  17. A Phase II Multicenter Trial With Rivaroxaban in the Treatment of Livedoid Vasculopathy Assessing Pain on a Visual Analog Scale

    PubMed Central

    Drabik, Attyla; Hillgruber, Carina

    2014-01-01

    Background Livedoid vasculopathy is an orphan skin disease characterized by recurrent thrombosis of the cutaneous microcirculation. It manifests itself almost exclusively in the ankles, the back of the feet, and the distal part of the lower legs. Because of the vascular occlusion, patients suffer from intense local ischemic pain. Incidence of livedoid vasculopathy is estimated to be around 1:100,000. There are currently no approved treatments for livedoid vasculopathy, making off-label therapy the only option. In Europe, thromboprophylactic treatment with low-molecular-weight heparins has become widely accepted. Objective The aim of this trial is the statistical verification of the therapeutic effects of the anticoagulant rivaroxaban in patients suffering from livedoid vasculopathy. Methods We performed a therapeutic phase IIa trial designed as a prospective, one-armed, multicenter, interventional series of cases with a calculated sample size of 20 patients. The primary outcome is the assessment of local pain on the visual analog scale (VAS) as an intraindividual difference of 2 values between baseline and 12 weeks. Results Enrollment started in December 2012 and was still open at the date of submission. The study is expected to finish in November 2014. Conclusions Livedoid vasculopathy is associated with increased thrombophilia in the cutaneous microcirculation and the continuous use of anticoagulants helps improve the symptoms. The causes of cutaneous infarctions are heterogenous, but ultimately follow the known mechanisms of the coagulation cascade. Rivaroxaban affects the coagulation cascade and inhibits the factor Xa–dependent conversion of prothrombin to thrombin, thereby considerably reducing the risk of thrombosis. Trial Registration Trial Registration EudraCT Number: 2012-000108-13-DE; https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000108-13 (Archived by WebCite at http://www.webcitation.org/6UCktWVCA); German Clinical

  18. Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis.

    PubMed

    Gordon, Kenneth B; Blauvelt, Andrew; Papp, Kim A; Langley, Richard G; Luger, Thomas; Ohtsuki, Mamitaro; Reich, Kristian; Amato, David; Ball, Susan G; Braun, Daniel K; Cameron, Gregory S; Erickson, Janelle; Konrad, Robert J; Muram, Talia M; Nickoloff, Brian J; Osuntokun, Olawale O; Secrest, Roberta J; Zhao, Fangyi; Mallbris, Lotus; Leonardi, Craig L

    2016-07-28

    Background Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. Methods We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. Results In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and

  19. Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor

    PubMed Central

    Kavanaugh, Arthur; Mease, Philip J; Gomez-Reino, Juan J; Adebajo, Adewale O; Wollenhaupt, Jürgen; Gladman, Dafna D; Lespessailles, Eric; Hall, Stephen; Hochfeld, Marla; Hu, ChiaChi; Hough, Douglas; Stevens, Randall M; Schett, Georg

    2014-01-01

    Objectives Apremilast, an oral phosphodiesterase 4 inhibitor, regulates inflammatory mediators. Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy. Methods In the 24-week, placebo-controlled phase of PALACE 1, patients (N=504) were randomised (1:1:1) to placebo, apremilast 20 mg twice a day (BID) or apremilast 30 mg BID. At week 16, patients without ≥20% reduction in swollen and tender joint counts were required to be re-randomised equally to either apremilast dose if initially randomised to placebo or remained on their initial apremilast dose. Patients on background concurrent DMARDs continued stable doses (methotrexate, leflunomide and/or sulfasalazine). Primary outcome was the proportion of patients achieving 20% improvement in modified American College of Rheumatology response criteria (ACR20) at week 16. Results At week 16, significantly more apremilast 20 mg BID (31%) and 30 mg BID (40%) patients achieved ACR20 versus placebo (19%) (p<0.001). Significant improvements in key secondary measures (physical function, psoriasis) were evident with both apremilast doses versus placebo. Across outcome measures, the 30-mg group generally had higher and more consistent response rates, although statistical comparison was not conducted. The most common adverse events were gastrointestinal and generally occurred early, were self-limiting and infrequently led to discontinuation. No imbalance in major adverse cardiac events, serious or opportunistic infections, malignancies or laboratory abnormalities was observed. Conclusions Apremilast was effective in the treatment of psoriatic arthritis, improving signs and symptoms and physical function. Apremilast demonstrated an acceptable safety profile and was generally well tolerated. Clinical trial registration number NCT

  20. A phase I/pilot study of radiofrequency ablation for the treatment of recurrent pediatric solid tumors

    PubMed Central

    Hoffer, Fredric A.; Daw, Najat C.; Xiong, Xiaoping; Anghelescu, Doralina; Krasin, Matthew; Yan, Xiaowei; Davidoff, Andrew M.; Furman, Wayne L.; Rodriguez-Galindo, Carlos; Spunt, Sheri L.

    2010-01-01

    Background This prospective study was designed to be the first to evaluate the toxicity of radiofrequency ablation (RFA) in patients with recurrent pediatric solid tumors. Methods From 2003 through 2008, we conducted a phase I/pilot study of RFA for recurrent pediatric solid tumors. A multidisciplinary cancer management team selected appropriate candidates for the study. Imaging-guided RFA was performed percutaneously. Repeat RFA was performed for recurrences when appropriate. Toxicity and imaging response was assessed at 1 and 3 months prospectively. Accrual stopped in 2006 and data collection stopped in 2008. Results Sixteen patients (age 4 – 33 years, median 15 years) and 56 tumor sites were treated in 37 RFA sessions including 38 pulmonary, 11 musculoskeletal, and 7 hepatic lesions (82 lesion-treatments). Post-procedural pain was moderate (median 5 on a scale from 1 to 10) and lasted a median of 9 days. Prolonged hospitalization (beyond 1 day) occurred 17 times (range 2–25 days, median 3 days). Hypoxia supported by supplemental oxygen occurred in 8 of 16 patients and resolved within one month after each RFA. No patient had tumor lysis syndrome but myoglobinuria/hemoglobinuria occurred in 6 of 16 patients all without renal damage. Serious complications from pulmonary RFA included two diaphragmatic hernias. Twenty-four of 82 (29%) lesions imaged remained ablated at the end of the study. Conclusion The toxicity from RFA of recurrent pediatric solid tumors is real but limited and RFA may offer a local tumor control alternative in carefully selected cases. PMID:19180637

  1. CF102 for the Treatment of Hepatocellular Carcinoma: A Phase I/II, Open-Label, Dose-Escalation Study

    PubMed Central

    Stemmer, Salomon M.; Benjaminov, Ofer; Medalia, Gal; Ciuraru, Noab B.; Silverman, Michael H.; Bar-Yehuda, Sara; Fishman, Sari; Harpaz, Zivit; Farbstein, Motti; Cohen, Shira; Patoka, Renana; Singer, Barak; Kerns, William D.

    2013-01-01

    Background. The A3 adenosine receptor (A3AR) is overexpressed in the tumor and in the peripheral blood mononuclear cells of patients with hepatocellular carcinoma (HCC). The orally active drug candidate CF102, an A3AR agonist, induces apoptosis of HCC cells via deregulation of the Wnt signaling pathway. In this open label phase I/II trial, the safety and clinical effects of CF102 were assessed in patients with advanced unresectable HCC. Methods. The primary objectives of this trial were to examine the safety and pharmacokinetic (PK) behavior of CF102 given orally (1, 5, and 25 mg BID) in 28-day cycles. Evaluation of anti-tumor effects and the utilization of A3AR as a biological predictive marker of response to CF102 were the secondary objectives. Results. Eighteen patients received CF102—six at each dose level. No serious drug-related adverse events or dose-limiting toxicities were observed. CF102 demonstrated good oral bioavailability and linear PK behavior. Median overall survival in the study population, 67% of whom had received prior sorafenib, was 7.8 months, and for Child Pugh B patients (28%) it was 8.1 months. Stable disease by RECIST was observed in four patients for at least 4 months. CF102 maintained liver function over a 6-month period. A correlation between receptor overexpression levels at baseline and patients' overall survival was found. One of the patients who presented with skin nodules that were biopsy-proven to be HCC metastases prior to the trial showed complete metastasis regression during three months of treatment with CF102. Conclusions. CF102 is safe and well-tolerated, showing favorable PK characteristics in Child Pugh A and B HCC patients, justifying further clinical development. PMID:23299770

  2. Treatment of Advanced Pancreatic Carcinoma with 90Y-Clivatuzumab Tetraxetan: A Phase I Single-Dose Escalation Trial

    PubMed Central

    Gulec, Seza A.; Cohen, Steven J.; Pennington, Kenneth L.; Zuckier, Lionel S.; Hauke, Ralph J.; Horne, Heather; Wegener, William A.; Teoh, Nick; Gold, David V.; Sharkey, Robert M.; Goldenberg, David M.

    2014-01-01

    Purpose Humanized antibody hPAM4 specifically binds a mucin glycoprotein expressed in pancreatic adenocarcinomas. This phase I study evaluated a single dose of 90Y-clivatuzumab tetraxetan (90Y-labeled hPAM4) in patients with advanced pancreatic cancer. Experimental Design Twenty-one patients (4 stage III; 17 stage IV) received 111In-hPAM4 for imaging and serum sampling before 90Y-hPAM4. Study procedures evaluated adverse events, safety laboratories, computed tomography (CT) scans, biomarkers, pharmacokinetics, radiation dosimetry, and immunogenicity (HAHA). Results 111In-hPAM4 showed normal biodistribution with radiation dose estimates to red marrow and solid organs acceptable for radioimmunotherapy and with tumor targeting in 12 patients. One patient withdrew before 90Y-hPAM4; otherwise, 20 patients received 90Y doses of 15 (n = 7), 20 (n = 9), and 25 mCi/m2 (n = 4). Treatment was well tolerated; the only significant drug-related toxicities were (NCI CTC v.3) grade 3 to 4 neutropenia and thrombocytopenia increasing with 90Y dose. There were no bleeding events or serious infections, and most cytopenias recovered to grade 1 within 12 weeks. Three patients at 25 mCi/m2 encountered dose-limiting toxicity with grade 4 cytopenias more than 7 days, establishing 20 mCi/m2 as the maximal tolerated 90Y dose. Two patients developed HAHA of uncertain clinical significance. Most patients progressed rapidly and with CA19-9 levels increasing within 1 month of therapy, but 7 remained progression-free by CT for 1.5 to 5.6 months, including 3 achieving transient partial responses (32%–52% tumor diameter shrinkage). Conclusion 90Y-Clivatuzumab tetraxetan was well tolerated with manageable hematologic toxicity at the maximal tolerated 90Y dose, and is a potential new therapeutic for advanced pancreatic cancer. PMID:21527562

  3. Application of a Persistent Dissolved-phase Reactive Treatment Zone for Mitigation of Mass Discharge from Sources Located in Lower-Permeability Sediments

    PubMed Central

    Marble, J.C.; Brusseau, M.L.; Carroll, K.C.; Plaschke, M.; Fuhrig, L.; Brinker, F.

    2015-01-01

    The purpose of this study is to examine the development and effectiveness of a persistent dissolved-phase treatment zone, created by injecting potassium permanganate solution, for mitigating discharge of contaminant from a source zone located in a relatively deep, low-permeability formation. A localized 1,1-dichloroethene (DCE) source zone comprising dissolved- and sorbed-phase mass is present in lower permeability strata adjacent to a sand/gravel unit in a section of the Tucson International Airport Area (TIAA) Superfund Site. The results of bench-scale studies conducted using core material collected from boreholes drilled at the site indicated that natural oxidant demand was low, which would promote permanganate persistence. The reactive zone was created by injecting a permanganate solution into multiple wells screened across the interface between the lower-permeability and higher-permeability units. The site has been monitored for nine years to characterize the spatial distribution of DCE and permanganate. Permanganate continues to persist at the site, and a substantial and sustained decrease in DCE concentrations in groundwater has occurred after the permanganate injection.. These results demonstrate successful creation of a long-term, dissolved-phase reactive-treatment zone that reduced mass discharge from the source. This project illustrates the application of in-situ chemical oxidation as a persistent dissolved-phase reactive-treatment system for lower-permeability source zones, which appears to effectively mitigate persistent mass discharge into groundwater. PMID:26300570

  4. Cannabidiol Post-Treatment Alleviates Rat Epileptic-Related Behaviors and Activates Hippocampal Cell Autophagy Pathway Along with Antioxidant Defense in Chronic Phase of Pilocarpine-Induced Seizure.

    PubMed

    Hosseinzadeh, Mahshid; Nikseresht, Sara; Khodagholi, Fariba; Naderi, Nima; Maghsoudi, Nader

    2016-04-01

    Abnormal and sometimes severe behavioral and molecular symptoms are usually observed in epileptic humans and animals. To address this issue, we examined the behavioral and molecular aspects of seizure evoked by pilocarpine. Autophagy can promote both cell survival and death, but there are controversial reports about the neuroprotective or neurodegenerative effects of autophagy in seizure. Cannabidiol has anticonvulsant properties in some animal models when used as a pretreatment. In this study, we investigated alteration of seizure scores, autophagy pathway proteins, and antioxidant status in hippocampal cells during the chronic phase of pilocarpine-induced epilepsy after treatment with cannabidiol. Cannabidiol (100 ng, intracerebroventricular injection) delayed the chronic phase of epilepsy. Single administration of cannabidiol during the chronic phase of seizure significantly diminished seizure scores such as mouth clonus, head nodding, monolateral and bilateral forelimb clonus and increased the activity of catalase enzyme and reduced glutathione content. Such a protective effect in the behavioral scores of epileptic rats was also observed after repeated administrations of cannabidiol at the onset of the silent phase. Moreover, the amount of Atg7, conjugation of Atg5/12, Atg12, and LC3II/LC3I ratio increased significantly in epileptic rats treated with repeated injections of cannabidiol. In short, our results suggest that post-treatment of Cannabidiol could enhance the induction of autophagy pathway and antioxidant defense in the chronic phase of epilepsy, which could be considered as the protective mechanisms of cannabidiol in a temporal lobe epilepsy model. PMID:26738731

  5. SUPERFUND TREATABILITY CLEARINGHOUSE: FINAL REPORT: DEVELOPMENT OF OPTIMUM TREATMENT SYSTEM FOR WASTEWATER LAGOONS PHASE II - SOLVENT EXTRACTION LABORATORY TESTING

    EPA Science Inventory

    The U.S. Army surveyed innovative treatment techniques for restoration of hazardous waste lagoons and selected solvent extraction as cost-effective restoration for further study. This treatability study focuses on treatment of organic (explosive) contaminated lagoon sediments w...

  6. Significant Treatment Effect of Bupropion in Patients With Bipolar Disorder but Similar Phase-Shifting Rate as Other Antidepressants: A Meta-Analysis Following the PRISMA Guidelines.

    PubMed

    Li, Dian-Jeng; Tseng, Ping-Tao; Chen, Yen-Wen; Wu, Ching-Kuan; Lin, Pao-Yen

    2016-03-01

    Bupropion is widely used for treating bipolar disorder (BD), and especially those with depressive mood, based on its good treatment effect, safety profile, and lower risk of phase shifting. However, increasing evidence indicates that the safety of bupropion in BD patients may not be as good as previously thought. The aim of this study was to summarize data on the treatment effect and safety profile of bupropion in the treatment of BD via a meta-analysis. Electronic search through PubMed and ClinicalTrials.gov was performed. The inclusion criteria were: (i) studies comparing changes in disease severity before and after bupropion treatment or articles comparing the treatment effect of bupropion in BD patients with those receiving other standard treatments; (ii) articles on clinical trials in humans. The exclusion criteria were (i) case reports/series, and (ii) nonclinical trials. All effect sizes from 10 clinical trials were pooled using a random effects model. We examined the possible confounding variables using meta-regression and subgroup analysis. Bupropion significantly improved the severity of disease in BD patients (P < 0.001), and the treatment effect was similar to other antidepressants/standard treatments (P = 0.220). There were no significant differences in the dropout rate (P = 0.285) and rate of phase shifting (P = 0.952) between BD patients who received bupropion and those who received other antidepressants. We could not perform a detailed meta-analysis of every category of antidepressant, nor could we rule out the possible confounding effect of concurrent psychotropics or include all drug side effects. Furthermore, the number of studies recruited in the meta-analysis was relatively small. Our findings reconfirm the benefits of bupropion for the treatment of bipolar depression, which are similar to those of other antidepressants. However, the rate of phase shifting with bupropion usage was not as low compared to other antidepressants as

  7. Epidermal permeability barrier in the treatment of keratosis pilaris.

    PubMed

    Kootiratrakarn, Tanawatt; Kampirapap, Kowit; Chunhasewee, Chakkrapong

    2015-01-01

    Objectives. To evaluate and compare the efficacy, safety, hydrating properties, and tolerability of 10% lactic acid (LA) and 5% salicylic acid (SA) in the therapy of keratosis pilaris (KP). Material and Method. Patients with KP were randomized for treatment with either 10% LA or 5% SA creams being applied twice daily for 3 months. The patients were clinically assessed at baseline and after 4, 8, and 12 weeks of treatment and 4 weeks after treatment. The functional properties of the stratum corneum (SC) were determined before treatment, 12 weeks, and follow-up phase by high-frequency conductance and transepidermal water loss (TEWL). Results. At the end of the trial, the mean reduction of the lesions from baseline was statistically significant for 10% LA (66%) and 5% SA (52%). During the treatment, higher conductance values were found on both group and this improvement was maintained until the follow up period. No significant differences in transepidermal water loss were observed after treatment. The adverse effects were limited to mild irritation localized on the skin without systemic side effect. Conclusion. The study demonstrated that 10% LA and 5% SA are beneficial to treat KP with the significantly clearance and marked improvement as by instrumental evaluation. PMID:25802513

  8. Epidermal Permeability Barrier in the Treatment of Keratosis Pilaris

    PubMed Central

    Kootiratrakarn, Tanawatt; Kampirapap, Kowit; Chunhasewee, Chakkrapong

    2015-01-01

    Objectives. To evaluate and compare the efficacy, safety, hydrating properties, and tolerability of 10% lactic acid (LA) and 5% salicylic acid (SA) in the therapy of keratosis pilaris (KP). Material and Method. Patients with KP were randomized for treatment with either 10% LA or 5% SA creams being applied twice daily for 3 months. The patients were clinically assessed at baseline and after 4, 8, and 12 weeks of treatment and 4 weeks after treatment. The functional properties of the stratum corneum (SC) were determined before treatment, 12 weeks, and follow-up phase by high-frequency conductance and transepidermal water loss (TEWL). Results. At the end of the trial, the mean reduction of the lesions from baseline was statistically significant for 10% LA (66%) and 5% SA (52%). During the treatment, higher conductance values were found on both group and this improvement was maintained until the follow up period. No significant differences in transepidermal water loss were observed after treatment. The adverse effects were limited to mild irritation localized on the skin without systemic side effect. Conclusion. The study demonstrated that 10% LA and 5% SA are beneficial to treat KP with the significantly clearance and marked improvement as by instrumental evaluation. PMID:25802513

  9. Personality and symptom change in treatment-refractory inpatients: evaluation of the phase model of change using Rorschach,TAT, and DSM-IV Axis V.

    PubMed

    Fowler, J Christopher; Ackerman, Steven J; Speanburg, Stefanie; Bailey, Adrian; Blagys, Matthew; Conklin, Adam C

    2004-12-01

    In this study, we examined global treatment outcomes during 16 months of intensive, psychodynamic treatment for 77 inpatients suffering from treatment-refractory disorders. Hypotheses based on the phase model of treatment change (Howard, Lueger, Maling, & Martinovich, 1993; Howard, Moras, Brill, Martinovich, & Lutz, 1996) were supported in the study results. Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) Axis V scales assessing behavioral functioning demonstrated large and medium effect size change, whereas stable, enduring personality functioning assessed by psychoanalytic Rorschach scales and the Social Cognition and Object Relations Scale (Westen, 1995) for the Thematic Apperception Test (Murray, 1943) demonstrated small and medium effect size change. We also report assessment of reliable change index and clinical significance. The ecological validity of Rorschach measures is supported by significant validity coefficients (in the hypothesized directions) between implicit measures of personality functioning and behavioral ratings. PMID:15548467

  10. Simple Heat Treatment for Production of Hot-Dip Galvanized Dual Phase Steel Using Si-Al Steels

    NASA Astrophysics Data System (ADS)

    Equihua-Guillén, F.; García-Lara, A. M.; Muñíz-Valdes, C. R.; Ortíz-Cuellar, J. C.; Camporredondo-Saucedo, J. E.

    2014-01-01

    This work presents relevant metallurgical considerations to produce galvanized dual phase steels from low cost aluminum-silicon steels which are produced by continuous strip processing. Two steels with different contents of Si and Al were austenized in the two-phase field ferrite + austenite (α + γ) in a fast manner to obtain dual phase steels, suitable for hot-dip galvanizing process, under typical parameters of continuous annealing processing line. Tensile dual phase properties were obtained from specimens cooled from temperature below Ar3, held during 3 min, intermediate cooling at temperature above Ar1 and quenching in Zn bath at 465 °C. The results have shown typical microstructure and tensile properties of galvanized dual phase steels. Finally, the synergistic effect of aluminum, silicon, and residual chromium on martensite start temperature ( M s), critical cooling rate ( C R), volume fraction of martensite, and tensile properties has been studied.

  11. Holmium-166 radioembolization for the treatment of patients with liver metastases: design of the phase I HEPAR trial

    PubMed Central

    2010-01-01

    Background Intra-arterial radioembolization with yttrium-90 microspheres ( 90Y-RE) is an increasingly used therapy for patients with unresectable liver malignancies. Over the last decade, radioactive holmium-166 poly(L-lactic acid) microspheres ( 166Ho-PLLA-MS) have been developed as a possible alternative to 90Y-RE. Next to high-energy beta-radiation, 166Ho also emits gamma-radiation, which allows for imaging by gamma scintigraphy. In addition, Ho is a highly paramagnetic element and can therefore be visualized by MRI. These imaging modalities are useful for assessment of the biodistribution, and allow dosimetry through quantitative analysis of the scintigraphic and MR images. Previous studies have demonstrated the safety of 166Ho-PLLA-MS radioembolization ( 166Ho-RE) in animals. The aim of this phase I trial is to assess the safety and toxicity profile of 166Ho-RE in patients with liver metastases. Methods The HEPAR study (Holmium Embolization Particles for Arterial Radiotherapy) is a non-randomized, open label, safety study. We aim to include 15 to 24 patients with liver metastases of any origin, who have chemotherapy-refractory disease and who are not amenable to surgical resection. Prior to treatment, in addition to the standard technetium-99m labelled macroaggregated albumin ( 99mTc-MAA) dose, a low radioactive safety dose of 60-mg 166Ho-PLLA-MS will be administered. Patients are treated in 4 cohorts of 3-6 patients, according to a standard dose escalation protocol (20 Gy, 40 Gy, 60 Gy, and 80 Gy, respectively). The primary objective will be to establish the maximum tolerated radiation dose of 166Ho-PLLA-MS. Secondary objectives are to assess tumour response, biodistribution, performance status, quality of life, and to compare the 166Ho-PLLA-MS safety dose and the 99mTc-MAA dose distributions with respect to the ability to accurately predict microsphere distribution. Discussion This will be the first clinical study on 166Ho-RE. Based on preclinical studies

  12. Ivermectin vs. lindane in the treatment of scabies.

    PubMed

    Goldust, Mohamad; Rezaee, Elham; Raghifar, Ramin; Naghavi-Behzad, Mohammad

    2013-01-01

    Scabies is commonly treated with acaricides but the treatment of choice is still controversial. This study aimed at comparing the efficacy of oral ivermectin vs. lindane lotion 1% for the treatment of scabies. Four hundred fourty patients with scabies were enrolled, and randomized into two groups: the first group received a single dose of oral ivermectin 200 microg/kg body weight, and the second group were treated with two applications of topical lindane lotion 1%, with a 1-week interval. Treatment was evaluated at intervals of 2 and 4 weeks, and if there was treatment failure at the 2-week follow-up, treatment was repeated. Single dose of oral ivermectin provided a cure rate of 63.6% at the 2-week follow-up, which increased to 81.8% at the 4-week follow-up after repeating the treatment. Treatment with two applications of lindane lotion 1%, with a 1-week interval between them, was effective in 45.4% of patients at the 2-week follow-up, which increased to 63.6% at the 4-week follow-up after this treatment was repeated. Single dose ivermectin was as effective as two applications of lindane lotion 1% at the 2-week follow-up. After repeating the treatment, ivermectin was superior to lindane lotion 1% at the 4-week follow up. PMID:23829057

  13. Treatment of scabies, permethrin 5% cream vs. crotamiton 10% cream.

    PubMed

    Pourhasan, Abolfazl; Goldust, Mohamad; Rezaee, Elham

    2013-01-01

    Scabies is one of the three most common skin disorders in children, along with tinea and pyoderma. The treatment of choice is still controversial. The aim of this study is to compare the efficacy of permethrin 5% cream vs. crotamiton 10% cream in the treatment of scabies. In total, 350 patients with scabies were enrolled, and randomized into two groups. The first group received permethrin 5% cream on two occasions with a one-week interval, while the second group received topical crotamiton 10% cream and were told to apply this twice daily for five consecutive days. The treatment was evaluated at intervals of 2 and 4 weeks, and the treatment was repeated if treatment failure was found at the 2-week follow-up. Two applications of permethrin 5 % cream provided a cure rate of 70% at the 2-week follow-up, which increased to 85% at the 4-week follow-up after repeating the treatment. Treatment with single applications of crotamiton 10% cream was effective in 45% of patients at the 2-week follow-up, which increased to 65% at the 4-week follow-up after this treatment was repeated. Two applications of permethrin 5% cream was as effective as single applications of crotamiton 10% cream at the 2-week follow-up. After repeating the treatment, permethrin 5 % cream was superior to crotamiton 10% cream at the 4-week follow up. PMID:24881286

  14. Phase composition in NiTi near-surface layers after electron beam treatment and its variation depending on beam energy density

    SciTech Connect

    Ostapenko, Marina G.; Meisner, Ludmila L.; Lotkov, Aleksandr I. E-mail: egu@ispms.tsc.ru; Gudimova, Ekaterina Y. E-mail: egu@ispms.tsc.ru

    2014-11-14

    In the work, we study the mechanisms of structural phase state formation in NiTi surface layers after low-energy pulsed electron beam irradiation depending on the electron beam energy density. It is revealed that after electron beam treatment of the NiTi specimens at energy densities E{sub 1} = 15 J/cm{sup 2}, E{sub 2} = 20 J/cm{sup 2}, and E{sub 3} = 30 J/cm{sup 2}, a series of effects is observed: the absence of the Ti2Ni phase and the presence of new peaks correspond to the B19′ martensite phase with monoclinic structure. Estimation of the relative volume content of the B2 and B19′ phases from the total intensity of their peaks shows that the percentage of the martensite phase increases from ∼5 vol.% in the NiTi specimen irradiated at E{sub 1} = 15 J/cm{sup 2} to ∼80 vol.% in the NiTi specimen irradiated at E{sub 3} = 30 J/cm{sup 2}. It is found that in the NiTi specimens irradiated at E ≤ 20 J/cm{sup 2}, the layer that contains a martensite phase resides not on the surface but at some depth from it.

  15. Small-angle polarized neutron scattering study of the mesostructure of phase precipitates in the steel P91 after heat treatment

    NASA Astrophysics Data System (ADS)

    Runov, V. V.; Skorobogatykh, V. N.; Runova, M. K.; Sumin, V. V.

    2014-01-01

    This paper reports on the results of the analysis of the mesostructure of phase precipitates formed in the steel P91 during heat treatment in the temperature range of 600-820°C after quenching at 1050°C for 30 min. Measurements have been performed by the small-angle polarized neutron scattering (SAPNS) method with the separation of nuclear-magnetic interference scattering. The characteristic sizes of the phases precipitated during heat treatment have been determined to be in the range of 150-450 Å. It has been demonstrated that the method is highly effective for solving problems of this class, which is based on the possibility to separate and investigate nuclear-magnetic contrast scattering against the background of the total nuclear and magnetic small-angle scattering.

  16. [EFFICACY AND SECURITY OF A CONVENTIONAL PROCEDURE OF PLASMAPHERESIS IN COMPLEX OF TREATMENT OF NONBILIARY ACUTE PANCREATITIS IN EARLY PHASE OF THE DISEASE].

    PubMed

    Mishalov, V G; Markulan, L Yu; Matveyev, R M

    2016-02-01

    Abstract Efficacy and security of a plasmapheresis procedure in complex of treatment of nonbiliary acute pancreatitis in early phase of the disease were established, basing on the treatment results analysis in 48 patients. The plasmapheresis results were estimated in accordance to changes revealed in the intoxication leukocytic index (ILI), a general protein (GP) content, general calcium (GC) in the blood plasm and of the activated partial thrombin time (APTHT). Application of plasmapheresis in patients, suffering purulent pancreatitis in the enzymal phase, have guaranteed a staged reduction of ILI by (34.86 ± 1.27)%, the APTHT enhancement from (35.15 ± 0.37) to (52.01 ± 0.62) sec, a trustworthy lowering of the GP by (4.35 ± 0.02) g/L at average and of GC in a blood plasmby (10.45 ± 0.38)%. PMID:27244915

  17. Phase 1 and pharmacologic study of MS-275, a histone deacetylase inhibitor, in adults with refractory and relapsed acute leukemias

    PubMed Central

    Jiemjit, Anchalee; Trepel, Jane B.; Sparreboom, Alex; Figg, William D.; Rollins, Sandra; Tidwell, Michael L.; Greer, Jacqueline; Chung, Eun Joo; Lee, Min-Jung; Gore, Steven D.; Sausville, Edward A.; Zwiebel, James; Karp, Judith E.

    2007-01-01

    MS-275 is a benzamide derivative with potent histone deacetylase (HDAC) inhibitory and antitumor activity in preclinical models. We conducted a phase 1 trial of orally administered MS-275 in 38 adults with advanced acute leukemias. Cohorts of patients were treated with MS-275 initially once weekly × 2, repeated every 4 weeks from 4 to 8 mg/m2, and after 13 patients were treated, once weekly × 4, repeated every 6 weeks from 8 to 10 mg/m2. The maximum-tolerated dose was 8 mg/m2 weekly for 4 weeks every 6 weeks. Dose-limiting toxicities (DLTs) included infections and neurologic toxicity manifesting as unsteady gait and somnolence. Other frequent non-DLTs were fatigue, anorexia, nausea, vomiting, hypoalbuminemia, and hypocalcemia. Treatment with MS-275 induced increase in protein and histone H3/H4 acetylation, p21 expression, and caspase-3 activation in bone marrow mononuclear cells. No responses by classical criteria were seen. Our results show that MS-275 effectively inhibits HDAC in vivo in patients with advanced myeloid leukemias and should be further tested, preferably in patients with less-advanced disease. PMID:17179232

  18. Optimization of the Homogenization Heat Treatment of Nickel-Based Superalloys Based on Phase-Field Simulations: Numerical Methods and Experimental Validation

    NASA Astrophysics Data System (ADS)

    Rettig, Ralf; Ritter, Nils C.; Müller, Frank; Franke, Martin M.; Singer, Robert F.

    2015-12-01

    A method for predicting the fastest possible homogenization treatment of the as-cast microstructure of nickel-based superalloys is presented and compared with experimental results for the single-crystal superalloy ERBO/1. The computational prediction method is based on phase-field simulations. Experimentally determined compositional fields of the as-cast microstructure from microprobe measurements are being used as input data. The software program MICRESS is employed to account for multicomponent diffusion, dissolution of the eutectic phases, nucleation, and growth of liquid phase (incipient melting). The optimization itself is performed using an iterative algorithm that increases the temperature in such a way that the microstructural state is always very close to the incipient melting limit. Maps are derived allowing describing the dissolution of primary γ/ γ'-islands and the elimination of residual segregation with respect to temperature and time.

  19. The evolution of phase transformation in Ni/Ni3Al laminated composite under high temperature treatments

    NASA Astrophysics Data System (ADS)

    Shmorgun, V.; Gurevich, L.; Bogdanov, A.; Trunov, M.

    2016-02-01

    In this study the impact of isothermal annealing on the phase transformation rate in laminated Ni/Ni2Al3 composite was investigated. The method of nickel-aluminide coatings of the required chemical composition fabrication was proposed.

  20. Effects of a difference in respiratory cycle between treatment planning and irradiation for phase-controlled rescanning and carbon pencil beam scanning

    PubMed Central

    Inaniwa, T; Furukawa, T; Zenklusen, S; Shirai, T; Noda, K

    2013-01-01

    Objective: To evaluate the impact of variation in respiratory cycle between treatment planning and irradiation for pencil beam scanning and phase-controlled rescanning (PCR) on the resulting dose distribution, we conducted a simulation study based on four-dimensional CT (4DCT) data for lung cancer patients. Methods: 4DCT data were acquired for seven patients with lung tumours. Treatment planning was designed to ensure the delivery of 95% of the prescribed dose to the clinical target volume in respective phases of the 4DCT by taking account of intrafractional beam range variations. Carbon ion pencil beam scanning dose distributions were calculated for various respiratory cycles that differed from the reference respiration (=4.4 s) but which stayed regular during irradiation. The number of rescannings was changed to 1, 4 or 8 times. PCR was correlated with the gating window in treatment planning to calculate the beam weighting map. Results: 8×PCR improved dose conformation to the target for all irradiation respiratory cycles. Minimum dose (Dmin) and lowest dose encompassing 95% of the target (D95) values with 4×PCR were decreased from 94.1% and 98.1% to 88.4% and 93.5% with an altered irradiation respiratory cycle of 2.4 s. However, these values were improved with 8×PCR to over 94.9% for Dmin and 98.6% for D95 for respective irradiation respiratory cycles. Conclusion: Pencil beam scanning treatment with eight or more PCRs consistently improved dose conformation for moving lung targets even when different respiratory cycles were used for treatment planning and irradiation. Advances in knowledge: Scanning treatment with eight or more rescannings consistently improved dose homogeneity to a moving target even though respiratory cycles varied during treatment. PMID:23833034

  1. Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors

    PubMed Central

    Cives, M; Kunz, P L; Morse, B; Coppola, D; Schell, M J; Campos, T; Nguyen, P T; Nandoskar, P; Khandelwal, V; Strosberg, J R

    2015-01-01

    Pasireotide long-acting repeatable (LAR) is a novel somatostatin analog (SSA) with avid binding affinity to somatostatin receptor subtypes 1, 2, 3 (SSTR1,2,3) and 5 (SSTR5). Results from preclinical studies indicate that pasireotide can inhibit neuroendocrine tumor (NET) growth more robustly than octreotide in vitro. This open-label, phase II study assessed the clinical activity of pasireotide in treatment-naïve patients with metastatic grade 1 or 2 NETs. Patients with metastatic pancreatic and extra-pancreatic NETs were treated with pasireotide LAR (60 mg every 4 weeks). Previous systemic therapy, including octreotide and lanreotide, was not permitted. Tumor assessments were performed every 3 months using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), overall radiographic response rate (ORR), and safety. Twenty-nine patients were treated with pasireotide LAR (60 mg every 4 weeks) and 28 were evaluable for response. The median PFS was 11 months. The most favorable effect was observed in patients with low hepatic tumor burden, normal baseline chromogranin A, and high tumoral SSTR5 expression. Median OS has not been reached; the 30-month OS rate was 70%. The best radiographic response was partial response in one patient (4%), stable disease in 17 patients (60%), and progressive disease in ten patients (36%). Although grade 3/4 toxicities were rare, pasireotide LAR treatment was associated with a 79% rate of hyperglycemia including 14% grade 3 hyperglycemia. Although pasireotide appears to be an effective antiproliferative agent in the treatment of advanced NETs, the high incidence of hyperglycemia raises concerns regarding its suitability as a first-line systemic agent in unselected patients. SSTR5 expression is a potentially predictive biomarker for response. PMID:25376618

  2. HANDLING AND DISPOSAL OF SLUDGES FROM COMBINED SEWER OVERFLOW TREATMENT: PHASE I CHARACTERIZATION (EPA/600/2-77/053A)

    EPA Science Inventory

    This report summarizes the results of a characterization and treatment test program undertaken to develop optimum means of handling and disposal of residual sludges from combined sewer overflow (CSO) treatment systems. Desk top engineering reviews were also conducted to gather, a...

  3. Adjusting for confounding effects of treatment switching in a randomized phase II study of dabrafenib plus trametinib in BRAF V600+ metastatic melanoma.

    PubMed

    Latimer, Nicholas R; Amonkar, Mayur M; Stapelkamp, Ceilidh; Sun, Peng

    2015-12-01

    Patients with BRAF V600E mutation-positive melanoma who were assigned to 150 mg dabrafenib twice daily combined with 2 mg trametinib once daily in a phase I/II study showed a median overall survival (OS) of 23.8 months, compared with 20.2 months for patients assigned to dabrafenib alone [hazard ratio (HR)=0.73, 95% confidence interval (CI) 0.43-1.24; data cutoff March 2013], on the basis of an intention-to-treat analysis. Because patients assigned to dabrafenib monotherapy were allowed to switch to combination therapy upon disease progression, we attempted to adjust for confounding effects on OS. Randomization-based adjustment methods, Rank Preserving Structural Failure Time Models and the Iterative Parameter Estimation algorithm, were used. Two analyses, 'treatment group' (assumes that treatment effect continues beyond treatment discontinuation) and 'on treatment' (assumes that the treatment effect disappears upon treatment discontinuation), were used to test assumptions on the durability of the treatment effect. A total of 45/54 (83%) patients assigned to dabrafenib monotherapy switched to the trametinib/dabrafenib combination. Adjusted OS HRs ranged from 0.47 to 0.50, depending on the analysis, compared with the unadjusted OS HR of 0.73. CIs continued to cross 1.00; thus, adjusted estimates did not provide statistically significant evidence of a treatment benefit on survival. Reduction of HRs after adjusting for the effect of treatment switching suggests that the intention-to-treat analysis underestimates the effect of dabrafenib plus trametinib on OS, although several factors, such as small trial size and methodological assumptions, affect the certainty of the conclusions. PMID:26340744

  4. Opportunities for Open Automated Demand Response in Wastewater Treatment Facilities in California - Phase II Report. San Luis Rey Wastewater Treatment Plant Case Study

    SciTech Connect

    Thompson, Lisa; Lekov, Alex; McKane, Aimee; Piette, Mary Ann

    2010-08-20

    This case study enhances the understanding of open automated demand response opportunities in municipal wastewater treatment facilities. The report summarizes the findings of a 100 day submetering project at the San Luis Rey Wastewater Treatment Plant, a municipal wastewater treatment facility in Oceanside, California. The report reveals that key energy-intensive equipment such as pumps and centrifuges can be targeted for large load reductions. Demand response tests on the effluent pumps resulted a 300 kW load reduction and tests on centrifuges resulted in a 40 kW load reduction. Although tests on the facility?s blowers resulted in peak period load reductions of 78 kW sharp, short-lived increases in the turbidity of the wastewater effluent were experienced within 24 hours of the test. The results of these tests, which were conducted on blowers without variable speed drive capability, would not be acceptable and warrant further study. This study finds that wastewater treatment facilities have significant open automated demand response potential. However, limiting factors to implementing demand response are the reaction of effluent turbidity to reduced aeration load, along with the cogeneration capabilities of municipal facilities, including existing power purchase agreements and utility receptiveness to purchasing electricity from cogeneration facilities.

  5. Long-term outcome of a phase 2 trial with nilotinib 400 mg twice daily in first-line treatment of chronic myeloid leukemia

    PubMed Central

    Gugliotta, Gabriele; Castagnetti, Fausto; Breccia, Massimo; Levato, Luciano; D’Adda, Mariella; Stagno, Fabio; Tiribelli, Mario; Salvucci, Marzia; Fava, Carmen; Martino, Bruno; Cedrone, Michele; Bocchia, Monica; Trabacchi, Elena; Cavazzini, Francesco; Usala, Emilio; Rossi, Antonella Russo; Bochicchio, Maria Teresa; Soverini, Simona; Alimena, Giuliana; Cavo, Michele; Pane, Fabrizio; Martinelli, Giovanni; Saglio, Giuseppe; Baccarani, Michele; Rosti, Gianantonio

    2015-01-01

    Nilotinib is a second-generation tyrosine kinase inhibitor that has been approved for the first-line treatment of chronic-phase chronic myeloid leukemia, based on the results of a prospective randomized study of nilotinib versus imatinib (ENESTnd). Apart from this registration study, very few data are currently available on first-line nilotinib treatment. We report here the long-term, 6-year results of the first investigator-sponsored, GIMEMA multicenter phase 2, single-arm trial with nilotinib 400 mg twice daily as first-line treatment in 73 patients with chronic-phase chronic myeloid leukemia. Six-year overall survival and progression-free survival rates were 96%, with one death after progression to blast phase. At 6 years, 75% of the patients were still on nilotinib. The cumulative incidence of major molecular response was 98%; only one patient had a confirmed loss of major molecular response. The cumulative incidence of deep molecular response (MR 4.0) was 76%. Deep molecular response was stable (≥2 years) in 34% of these patients. Cardiovascular adverse events, mainly due to arterial thrombosis, occurred in 11/73 patients (15%), after 24 to 76 months of therapy. They were more frequent in elderly patients, and in those with baseline cardiovascular risk factors. None was fatal, although there was a relevant morbidity. This is the study with the longest follow-up of a high dose of nilotinib (400 mg twice daily): it highlights the high efficacy and the cardiovascular toxicity of the drug (CTG.NCT.00481052). PMID:26113419

  6. Long-term outcome of a phase 2 trial with nilotinib 400 mg twice daily in first-line treatment of chronic myeloid leukemia.

    PubMed

    Gugliotta, Gabriele; Castagnetti, Fausto; Breccia, Massimo; Levato, Luciano; D'Adda, Mariella; Stagno, Fabio; Tiribelli, Mario; Salvucci, Marzia; Fava, Carmen; Martino, Bruno; Cedrone, Michele; Bocchia, Monica; Trabacchi, Elena; Cavazzini, Francesco; Usala, Emilio; Russo Rossi, Antonella; Bochicchio, Maria Teresa; Soverini, Simona; Alimena, Giuliana; Cavo, Michele; Pane, Fabrizio; Martinelli, Giovanni; Saglio, Giuseppe; Baccarani, Michele; Rosti, Gianantonio

    2015-09-01

    Nilotinib is a second-generation tyrosine kinase inhibitor that has been approved for the first-line treatment of chronic-phase chronic myeloid leukemia, based on the results of a prospective randomized study of nilotinib versus imatinib (ENESTnd). Apart from this registration study, very few data are currently available on first-line nilotinib treatment. We report here the long-term, 6-year results of the first investigator-sponsored, GIMEMA multicenter phase 2, single-arm trial with nilotinib 400 mg twice daily as first-line treatment in 73 patients with chronic-phase chronic myeloid leukemia. Six-year overall survival and progression-free survival rates were 96%, with one death after progression to blast phase. At 6 years, 75% of the patients were still on nilotinib. The cumulative incidence of major molecular response was 98%; only one patient had a confirmed loss of major molecular response. The cumulative incidence of deep molecular response (MR 4.0) was 76%. Deep molecular response was stable (≥ 2 years) in 34% of these patients. Cardiovascular adverse events, mainly due to arterial thrombosis, occurred in 11/73 patients (15%), after 24 to 76 months of therapy. They were more frequent in elderly patients, and in those with baseline cardiovascular risk factors. None was fatal, although there was a relevant morbidity. This is the study with the longest follow-up of a high dose of nilotinib (400 mg twice daily): it highlights the high efficacy and the cardiovascular toxicity of the drug (CTG.NCT.00481052). PMID:26113419

  7. Feasibility of adjuvant chemotherapy with S-1 consisting of a 4-week administration and a two-week rest period in patients with completely resected non-small cell lung cancer

    PubMed Central

    OKUMURA, SHUNSUKE; SASAKI, TAKAAKI; SATOH, KAZUHIRO; KITADA, MASAHIRO; NAGASE, ATSUSHI; YATSUYANAGI, EIJI; OHSAKI, YOSHINOBU

    2013-01-01

    The efficacy of adjuvant chemotherapy with S-1 in patients with completely resected non-small cell lung cancer (NSCLC) has yet to be clarified, and the appropriate schedule for the adjuvant chemotherapy with S-1 remains unknown. A phase II study was conducted to evaluate the feasibility and efficacy of adjuvant chemotherapy with S-1. Patients enrolled in this study were 20–75 years old, had pathological stage IB-IIIA NSCLC, and had received complete resection of NSCLC. S-1 (80 mg/m2) was administered orally to the patients for four weeks followed by a two-week rest period (conventional schedule), for a maximum of eight cycles. The primary endpoint was relative dose intensity (RDI), while the secondary endpoints were safety and 1 year of disease-free survival (1y-DFS). Between May 2007 and October 2009, 28 patients were enrolled. The RDI was 63.1% (95% CI, 48.6–77.7). No grade 3 or worse hematological toxicity was observed. Grade 3 non-hematological toxicities were observed in four patients. No grade 4 or worse hematological toxicity was detected. The probability of 1y-DFS was 85.7% (95% CI, 72.8–98.6). In the subgroup analysis, the median RDI of patients over 65 years old was lower compared to the other patients (44.8 vs. 100%; P=0.013; Mann-Whitney U test). Creatinine clearance (CCr) was lower in the older group, with more grade 2 or 3 non-hematological toxicities in the elderly patients. These results suggest that the conventional schedule of adjuvant chemotherapy with S-1 is not likely to be feasible in older patients with completely resected NSCLC. PMID:24649134

  8. Reduced frequency treatment with bortezomib plus dexamethasone for elderly patients with relapsed and/or refractory multiple myeloma: a phase 2 study of the Japanese Myeloma Study Group (JMSG-0902).

    PubMed

    Ozaki, Shuji; Hata, Hiroyuki; Abe, Masahiro; Saitoh, Takayuki; Hanamura, Ichiro; Yano, Hiroki; Sunami, Kazutaka; Kosugi, Hiroshi; Sawamura, Morio; Nakazato, Tomonori; Masunari, Taro; Mori, Mayumi; Takagi, Toshiyuki; Murakami, Hirokazu; Shimizu, Kazuyuki

    2016-05-01

    Bortezomib is one of the most widely used novel drugs for the treatment of multiple myeloma (MM). However, twice-weekly intravenous administration is associated with innegligible adverse events and treatment discontinuation. We therefore evaluated the long-term efficacy and feasibility of reduced frequency treatment with intravenous bortezomib in elderly patients with relapsed and/or refractory MM. A total of 47 bortezomib-naïve patients (median age 75 years) received bortezomib (1.3 mg/m(2), intravenously) and dexamethasone (20 mg) on days 1, 8, and 15 of every 4-week cycle. Twenty-six patients completed the planned 8 cycles. Best responses were stringent complete response (sCR) in 5 patients, very good partial response (VGPR) in 3, PR in 15, stable disease (SD) in 18, and disease progression (PD) in 6, respectively. Median progression-free and overall survivals were 9.6 and 35.1 months, respectively. After progression, 11 patients were retreated with bortezomib-based regimens and another 24 patients with immunomodulatory drugs. Multivariate analysis revealed that ISS 3, t(4;14), and <4 therapy cycles were significantly poor prognostic factors and that subsequent therapy with bortezomib-based regimens was a favorable factor for extended OS. The common adverse events were diarrhea, constipation, and peripheral neuropathy with no grade 4 toxicity. In conclusion, reduced frequency treatment with intravenous bortezomib + dexamethasone is an effective option for elderly patients with MM. PMID:27044390

  9. Balanced control of both hyper and hypo-inflammatory phases as a new treatment paradigm in sepsis

    PubMed Central

    Chondropoulos, Spiros; Gkirkas, Konstantinos; Meletiadis, Josef; Dimopoulou, Ioanna

    2016-01-01

    The immune response of the host against invading pathogens is clinically manifested as sepsis. Sepsis is a complicated process characterized by distinct phases that usually occur in a sequential manner. The initial hyper-inflammation helps in elimination of the pathogen, but potentially may lead to excessive tissue injury. Hypo-inflammation helps in restoring immune homeostasis, but may lead to significant immune suppression and death from secondary infections if not appropriately controlled. Immune-modulating intervention in sepsis should be based on a balanced control of both the hyper and the hypo-inflammatory phase. PMID:27162689

  10. Work productivity among treatment-naïve patients with genotype 1 chronic hepatitis C infection receiving telaprevir combination treatment.

    PubMed

    Aggarwal, J; Vera-Llonch, M; Donepudi, M; Suthoff, E; Younossi, Z; Goss, T F

    2015-01-01

    Work productivity is impacted in hepatitis C virus (HCV)-infected patients and has been linked to treatment. In two Phase 3 trials, ADVANCE and ILLUMINATE, treatment-naïve genotype 1 chronic HCV-infected patients received 12-week telaprevir (T) with 24 (T12PR24)- or 48 (T12PR48)-week peginterferon alfa-2a/ribavirin. The objective of this analysis was to examine the impact of chronic HCV infection and its treatment with combination therapy on work productivity. The 5-item, self-reported work productivity questionnaire (WPQ) was administered in Phase 3 trials to assess unemployment status, days unable to work due to HCV/treatment, reduced hours worked and impact on productivity in prior 4 weeks. Descriptive statistics and multivariate regression analyses were employed in analyses of pooled trial data. About 1147 patients were included; 22% (n = 255) were unemployed at baseline, with 8% being unemployed due to health reasons. At week 12, there were no differences by treatment regimen in the number of days unable to work. At week 48, improvements were observed earlier among patients receiving the shorter duration of T combination treatment. Mean (95% CI) change from baseline in days unable to work was -0.48 (-0.85, -0.11) days for T12PR24, 1.43 (0.63, 2.24) days for T12PR48 and 1.24 (0.18, 2.30) days for PR48 with placebo. Predictors of days unable to work were identified and include demographic characteristics, pretreatment and on-treatment levels of fatigue, as well regional variation. In post hoc analyses of the ADVANCE and ILLUMINATE trials, work productivity decreased during the initial 12 weeks regardless of treatment group. PMID:24528927

  11. Scale-Up Information for Gas-Phase Ammonia Treatment of Uranium in the Vadose Zone at the Hanford Site Central Plateau

    SciTech Connect

    Truex, Michael J.; Szecsody, James E.; Zhong, Lirong; Thomle, Jonathan N.; Johnson, Timothy C.

    2014-09-01

    Uranium is present in the vadose zone at the Hanford Central Plateau and is of concern for protection of groundwater. The Deep Vadose Zone Treatability Test Plan for the Hanford Central Plateau identified gas-phase treatment and geochemical manipulation as potentially effective treatment approaches for uranium and technetium in the Hanford Central Plateau vadose zone. Based on laboratory evaluation, use of ammonia vapor was selected as the most promising uranium treatment candidate for further development and field testing. While laboratory tests have shown that ammonia treatment effectively reduces the mobility of uranium, additional information is needed to enable deployment of this technology for remediation. Of importance for field applications are aspects of the technology associated with effective distribution of ammonia to a targeted treatment zone, understanding the fate of injected ammonia and its impact on subsurface conditions, and identifying effective monitoring approaches. In addition, information is needed to select equipment and operational parameters for a field design. As part of development efforts for the ammonia technology for remediation of vadose zone uranium contamination, field scale-up issues were identified and have been addressed through a series of laboratory and modeling efforts. This report presents a conceptual description for field application of the ammonia treatment process, engineering calculations to support treatment design, ammonia transport information, field application monitoring approaches, and a discussion of processes affecting the fate of ammonia in the subsurface. The report compiles this information from previous publications and from recent research and development activities. The intent of this report is to provide technical information about these scale-up elements to support the design and operation of a field test for the ammonia treatment technology.

  12. Amplitude-based gated phase-controlled rescanning in carbon-ion scanning beam treatment planning under irregular breathing conditions using lung and liver 4DCTs

    PubMed Central

    Mori, Shinichiro; Inaniwa, Taku; Furukawa, Takuji; Takahashi, Wataru; Nakajima, Mio; Shirai, Toshiyuki; Noda, Koji; Yasuda, Shigeo; Yamamoto, Naoyoshi

    2014-01-01

    Amplitude-based gating aids treatment planning in scanned particle therapy because it gives better control of uncertainty with the gate window. We have installed an X-ray fluoroscopic imaging system in our treatment room for clinical use with an amplitude-based gating strategy. We evaluated the effects of this gating under realistic organ motion conditions using 4DCT data of lung and liver tumors. 4DCT imaging was done for 24 lung and liver patients using the area-detector CT. We calculated the field-specific target volume (FTV) for the gating window, which was defined for a single respiratory cycle. Prescribed doses of 48 Gy relative biological effectiveness (RBE)/fraction/four fields and 45 Gy RBE/two fractions/two fields were delivered to the FTVs for lung and liver treatments, respectively. Dose distributions were calculated for the repeated first respiratory cycle (= planning dose) and the whole respiratory data (= treatment dose). We applied eight phase-controlled rescannings with the amplitude-based gating. For the lung cases, D95 of the treatment dose (= 96.0 ± 1.0%) was almost the same as that of the planning dose (= 96.6 ± 0.9%). Dmax/Dmin of the treatment dose (= 104.5 ± 2.2%/89.4 ± 2.6%) was slightly increased over that of the planning dose (= 102.1 ± 1.0%/89.8 ± 2.5%) due to hot spots. For the liver cases, D95 of the treatment dose (= 97.6 ± 0.5%) was decreased by ∼ 1% when compared with the planning dose (= 98.5 ± 0.4%). Dmax/Dmin of the treatment dose was degraded by 3.0%/0.4% compared with the planning dose. Average treatment times were extended by 46.5 s and 65.9 s from those of the planning dose for lung and liver cases, respectively. As with regular respiratory patterns, amplitude-based gated multiple phase-controlled rescanning preserves target coverage to a moving target under irregular respiratory patterns. PMID:24835238

  13. Amplitude-based gated phase-controlled rescanning in carbon-ion scanning beam treatment planning under irregular breathing conditions using lung and liver 4DCTs.

    PubMed

    Mori, Shinichiro; Inaniwa, Taku; Furukawa, Takuji; Takahashi, Wataru; Nakajima, Mio; Shirai, Toshiyuki; Noda, Koji; Yasuda, Shigeo; Yamamoto, Naoyoshi

    2014-09-01

    Amplitude-based gating aids treatment planning in scanned particle therapy because it gives better control of uncertainty with the gate window. We have installed an X-ray fluoroscopic imaging system in our treatment room for clinical use with an amplitude-based gating strategy. We evaluated the effects of this gating under realistic organ motion conditions using 4 DCT data of lung and liver tumors. 4 DCT imaging was done for 24 lung and liver patients using the area-detector CT. We calculated the field-specific target volume (FTV) for the gating window, which was defined for a single respiratory cycle. Prescribed doses of 48 Gy relative biological effectiveness (RBE)/fraction/four fields and 45 Gy RBE/two fractions/two fields were delivered to the FTVs for lung and liver treatments, respectively. Dose distributions were calculated for the repeated first respiratory cycle (= planning dose) and the whole respiratory data (= treatment dose). We applied eight phase-controlled rescannings with the amplitude-based gating. For the lung cases, D95 of the treatment dose (= 96.0 ± 1.0%) was almost the same as that of the planning dose (= 96.6 ± 0.9%). D(max)/D(min) of the treatment dose (= 104.5 ± 2.2%/89.4 ± 2.6%) was slightly increased over that of the planning dose (= 102.1 ± 1.0%/89.8 ± 2.5%) due to hot spots. For the liver cases, D95 of the treatment dose (= 97.6 ± 0.5%) was decreased by ∼ 1% when compared with the planning dose (= 98.5 ± 0.4%). D(max)/D(min) of the treatment dose was degraded by 3.0%/0.4% compared with the planning dose. Average treatment times were extended by 46.5 s and 65.9 s from those of the planning dose for lung and liver cases, respectively. As with regular respiratory patterns, amplitude-based gated multiple phase-controlled rescanning preserves target coverage to a moving target under irregular respiratory patterns. PMID:24835238

  14. THE DISTRIBUTION, SOLID-PHASE SPECIATION, AND DESORPTION/DISSOLUTION OF AS IN IRON-BASED TREATMENT MEDIA

    EPA Science Inventory

    Arsenic concentrations (Total Recoverable As by EPA Method 3051) and solid-phase speciation (by X-ray Absorption Near-Edge Spectroscopy-XANES) were assessed as a function of depth through Fe-media beds for two commercially available products from pilot-scale field tests. These re...

  15. Opportunities for Energy Efficiency and Open Automated Demand Response in Wastewater Treatment Facilities in California -- Phase I Report

    SciTech Connect

    Lekov, Alex; Thompson, Lisa; McKane, Aimee; Song, Katherine; Piette, Mary Ann

    2009-04-01

    This report summarizes the Lawrence Berkeley National Laboratory?s research to date in characterizing energy efficiency and automated demand response opportunities for wastewater treatment facilities in California. The report describes the characteristics of wastewater treatment facilities, the nature of the wastewater stream, energy use and demand, as well as details of the wastewater treatment process. It also discusses control systems and energy efficiency and automated demand response opportunities. In addition, several energy efficiency and load management case studies are provided for wastewater treatment facilities.This study shows that wastewater treatment facilities can be excellent candidates for open automated demand response and that facilities which have implemented energy efficiency measures and have centralized control systems are well-suited to shift or shed electrical loads in response to financial incentives, utility bill savings, and/or opportunities to enhance reliability of service. Control technologies installed for energy efficiency and load management purposes can often be adapted for automated demand response at little additional cost. These improved controls may prepare facilities to be more receptive to open automated demand response due to both increased confidence in the opportunities for controlling energy cost/use and access to the real-time data.

  16. Transition alumina phases induced by heat treatment of boehmite: An X-ray diffraction and infrared spectroscopy study

    SciTech Connect

    Boumaza, A.; Favaro, L.; Ledion, J.; Sattonnay, G.; Brubach, J.B.; Berthet, P.; Huntz, A.M.; Roy, P.; Tetot, R.

    2009-05-15

    During high temperature oxidation of alumina-forming alloys, various transition aluminas are formed before reaching the most stable alpha-Al{sub 2}O{sub 3} phase. In particular, the gamma, delta and theta transition aluminas are concerned. Precise studies on the development, the microstructure and the properties of the oxide layers are not straightforward owing to the difficulty to unambiguously distinguish the various polymorphs by X-ray diffraction (XRD) alone. To remove this difficulty, we propose a procedure which combines XRD and infrared (IR) spectroscopy. gamma, delta, theta and alpha-Al{sub 2}O{sub 3} phases, prepared by dehydration of aluminium oxihydroxide AlOOH (boehmite), were measured by XRD and IR spectroscopy on all samples. Thus, reference IR spectra were obtained for all alumina phases, as well as an assignment of the main band in agreement with previous studies, and coherent with the structural evolution of various polymorphs. This precise characterization may constitute a basis for further investigations on thin layers of alumina formed under various experimental conditions (temperature, atmosphere, etc.). - Graphical abstract: Infrared spectra of alumina sequence gamma->delta->theta->alpha-Al{sub 2}O{sub 3} obtained from 24h calcinations of boehmite at 873 K (a), 1123K (b), 1223 K (c), 1273 K (d), 1293 K (e), 1383 K (f), 1573 K (g).

  17. Sustained-Release Methylphenidate in a Randomized Trial of Treatment of Methamphetamine Use Disorder

    PubMed Central

    Ling, Walter; Chang, Linda; Hillhouse, Maureen; Ang, Alfonso; Striebel, Joan; Jenkins, Jessica; Hernandez, Jasmin; Olaer, Mary; Mooney, Larissa; Reed, Susan; Fukaya, Erin; Kogachi, Shannon; Alicata, Daniel; Holmes, Nataliya; Esagoff, Asher

    2014-01-01

    Background and aims No effective pharmacotherapy for methamphetamine (MA) use disorder has yet been found. This study evaluated sustained-release methylphenidate (MPH-SR) compared with placebo (PLA) for treatment of MA use disorder in people also undergoing behavioural support and motivational incentives. Design This was a randomized, double-blind, placebo-controlled design with MPH-SR or PLA provided for 10 weeks (active phase) followed by 4 weeks of single-blind PLA. Twice-weekly clinic visits, weekly group counseling (CBT), and motivational incentives (MI) for MA-negative urine drug screens (UDS) were included. Setting Treatment sites were in Los Angeles, California (LA) and Honolulu, Hawaii (HH), USA. Participants 110 MA-dependent (via DSM-IV) participants (LA = 90; HH = 20). Measurements The primary outcome measure is self-reported days of MA use during the last 30 days of the active phase. Included in the current analyses are drug use (UDS and self-report), retention, craving, compliance (dosing, CBT, MI), adverse events, and treatment satisfaction. Findings No difference was found between treatment groups in self-reported days of MA use during the last 30 days of the active phase (p=0.22). In planned secondary outcomes analyses, however, the MPH group had fewer self-reported MA use days from baseline through the active phase compared with the PLA group (p=0.05). The MPH group also had lower craving scores and fewer marijuana-positive UDS than the PLA group in the last 30 days of the active phase. The two groups had similar retention, other drug use, adverse events, and treatment satisfaction. Conclusions Methylphenidate may lead to a reduction in concurrent methamphetamine use when provided as treatment for patients undergoing behavioural support for moderate to severe methamphetamine use disorder but this requires confirmation. PMID:24825486

  18. A phase 2 study of idelalisib plus rituximab in treatment-naïve older patients with chronic lymphocytic leukemia.

    PubMed

    O'Brien, Susan M; Lamanna, Nicole; Kipps, Thomas J; Flinn, Ian; Zelenetz, Andrew D; Burger, Jan A; Keating, Michael; Mitra, Siddhartha; Holes, Leanne; Yu, Albert S; Johnson, David M; Miller, Langdon L; Kim, Yeonhee; Dansey, Roger D; Dubowy, Ronald L; Coutre, Steven E

    2015-12-17

    Idelalisib is a first-in-class oral inhibitor of PI3Kδ that has shown substantial activity in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). To evaluate idelalisib as initial therapy, 64 treatment-naïve older patients with CLL or small lymphocytic leukemia (median age, 71 years; range, 65-90) were treated with rituximab 375 mg/m(2) weekly ×8 and idelalisib 150 mg twice daily continuously for 48 weeks. Patients completing 48 weeks without progression could continue to receive idelalisib on an extension study. The median time on treatment was 22.4 months (range, 0.8-45.8+). The overall response rate (ORR) was 97%, including 19% complete responses. The ORR was 100% in patients with del(17p)/TP53 mutations and 97% in those with unmutated IGHV. Progression-free survival was 83% at 36 months. The most frequent (>30%) adverse events (any grade) were diarrhea (including colitis) (64%), rash (58%), pyrexia (42%), nausea (38%), chills (36%), cough (33%), and fatigue (31%). Elevated alanine transaminase/aspartate transaminase was seen in 67% of patients (23% grade ≥3). The combination of idelalisib and rituximab was highly active, resulting in durable disease control in treatment-naïve older patients with CLL. These results support the further development of idelalisib as initial treatment of CLL. This study is registered at ClinicalTrials.gov as #NCT01203930. PMID:26472751

  19. Dental plaque associated with self-ligating brackets during the initial phase of orthodontic treatment: A 3-month preliminary study

    PubMed Central

    Al-Anezi, Saud A

    2014-01-01

    Background: To compare changes in the amount and distribution of dental plaque associated with placement of elastomeric modules over a self-ligating bracket during orthodontic treatment and to relate these changes to the periodontal inflammation. Materials and Methods: A cross-arch randomization trial was carried out at Bristol Dental School, United Kingdom. Clinical measurements of periodontal inflammation and plaque accumulation and microbiological test were done on 24 patients aged 11-14 years [Mean (SD) age = 12.6 (1.01) years] wearing fixed appliances (Damon 2 brackets, Ormco, Orange, CA, USA) at the start and 3 months into fixed orthodontic treatment. Results: In the first 3 months of treatment there was no statistically significant difference in bleeding on probing between incisors with and without elastomeric modules (P = 0.125 and 0.508, respectively). The difference in plaque accumulation was not statistically significant (P = 0.78). The difference in probing depths between the incisors was not statistically significant (P = 0.84). The microbiological analysis showed no difference. Conclusions: Based on this preliminary 3 months study, elastomeric modules were not significantly associated with any increased risk during treatment when compared to self-ligating brackets. The longer term studies are needed to further confirm the findings of the present study. PMID:24987657

  20. A phase 2 study of idelalisib plus rituximab in treatment-naïve older patients with chronic lymphocytic leukemia

    PubMed Central

    Lamanna, Nicole; Kipps, Thomas J.; Flinn, Ian; Zelenetz, Andrew D.; Burger, Jan A.; Keating, Michael; Mitra, Siddhartha; Holes, Leanne; Yu, Albert S.; Johnson, David M.; Miller, Langdon L.; Kim, Yeonhee; Dansey, Roger D.; Dubowy, Ronald L.; Coutre, Steven E.

    2015-01-01

    Idelalisib is a first-in-class oral inhibitor of PI3Kδ that has shown substantial activity in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). To evaluate idelalisib as initial therapy, 64 treatment-naïve older patients with CLL or small lymphocytic leukemia (median age, 71 years; range, 65-90) were treated with rituximab 375 mg/m2 weekly ×8 and idelalisib 150 mg twice daily continuously for 48 weeks. Patients completing 48 weeks without progression could continue to receive idelalisib on an extension study. The median time on treatment was 22.4 months (range, 0.8-45.8+). The overall response rate (ORR) was 97%, including 19% complete responses. The ORR was 100% in patients with del(17p)/TP53 mutations and 97% in those with unmutated IGHV. Progression-free survival was 83% at 36 months. The most frequent (>30%) adverse events (any grade) were diarrhea (including colitis) (64%), rash (58%), pyrexia (42%), nausea (38%), chills (36%), cough (33%), and fatigue (31%). Elevated alanine transaminase/aspartate transaminase was seen in 67% of patients (23% grade ≥3). The combination of idelalisib and rituximab was highly active, resulting in durable disease control in treatment-naïve older patients with CLL. These results support the further development of idelalisib as initial treatment of CLL. This study is registered at ClinicalTrials.gov as #NCT01203930. PMID:26472751

  1. Structure-phase state and mechanical properties of surface layers in titanium nikelide single crystals after shock mechanical treatment

    NASA Astrophysics Data System (ADS)

    Surikova, N.; Panin, V.; Vlasov, I.; Narkevich, N.; Surikov, N.; Tolmachev, A.

    2015-10-01

    The influence of ultrasonic shock surface treatment (USST) on refine structure and mechanical characteristics of surface layers and deformation behaviour of volume samples of TiNi(Fe, Mo) shape memory effect alloy single crystals is studied using optical and transmission electron microscope, X-ray diffraction, nanoindentation, mechanical attrition testing and experiments on uniaxial tension.

  2. Structure-phase state and mechanical properties of surface layers in titanium nikelide single crystals after shock mechanical treatment

    SciTech Connect

    Surikova, N. Panin, V. Vlasov, I.; Narkevich, N. Tolmachev, A.; Surikov, N.

    2015-10-27

    The influence of ultrasonic shock surface treatment (USST) on refine structure and mechanical characteristics of surface layers and deformation behaviour of volume samples of TiNi(Fe, Mo) shape memory effect alloy single crystals is studied using optical and transmission electron microscope, X-ray diffraction, nanoindentation, mechanical attrition testing and experiments on uniaxial tension.

  3. Effects of laser immunotherapy on late-stage, metastatic breast cancer patients in a Phase II clinical trial

    NASA Astrophysics Data System (ADS)

    Ferrel, Gabriela L.; Zhou, Feifan; Li, Xiaosong; Hode, Tomas; Nordquist, Robert E.; Alleruzzo, Luciano; Chen, Wei R.

    2014-03-01

    Laser immunotherapy (LIT), a novel technique with a local intervention to induce systemic antitumor effects, was developed to treat metastatic cancers. The pre-clinical studies of LIT have shown its unique characteristics in generating a specific antitumor immunity in treating metastatic tumors in rats and mice. For late-stage, metastatic breast cancer patients, who were considered to be out of other available treatment options, we conducted a small Phase II clinical trial using LIT starting in 2009 in Lima, Peru. This Phase II study was closed in December of 2012, as acknowldged by the Ministry of Health (MOH) of Peur letter 438-2014-OGITT/INS dated March 5th, 2014. Ten patients were enrolled and received LIT in one or multiple 4-week treatment cycles. At the study closing date, four patients were alive and two of them remained cancer free. Here, following the successful conclusion of our Phase II study, we report the clinical effects of LIT on metastatic breast cancer patients. Specifically, we present the overall status of all the patients three years after the treatment and also the outcomes of two long-term surviving patients.

  4. Phase I/II trial of 2-weekly docetaxel combined with cisplatin plus fluorouracil in metastatic esophageal cancer (JCOG0807).

    PubMed

    Hironaka, Shuichi; Tsubosa, Yasuhiro; Mizusawa, Junki; Kii, Takayuki; Kato, Ken; Tsushima, Takahiro; Chin, Keisho; Tomori, Akihisa; Okuno, Tatsuya; Taniki, Toshikatsu; Ura, Takashi; Matsushita, Hisayuki; Kojima, Takashi; Doki, Yuichiro; Kusaba, Hitoshi; Fujitani, Kazumasa; Taira, Koichi; Seki, Shiko; Nakamura, Tsutomu; Kitagawa, Yuko

    2014-09-01

    We carried out a phase I/II trial of adding 2-weekly docetaxel to cisplatin plus fluorouracil (CF) therapy (2-weekly DCF regimen) in esophageal cancer patients to investigate its safety and antimetastatic activity. Patients received 2-weekly docetaxel (30 mg/m(2) [dose level (DL)1] or 40 mg/m(2) [DL2] with a 3 + 3 design in phase I, on days 1 and 15) in combination with fixed-dose CF (80 mg/m(2) cisplatin, day 1; 800 mg/m(2) fluorouracil, days 1-5) repeated every 4 weeks. The primary endpoint was dose-limiting toxicity (DLT) in phase I and central peer review-based response rate in phase II. At least 22 responders among 50 patients were required to satisfy the primary endpoint with a threshold of 35%. Sixty-two patients were enrolled in phase I and II. In phase I, 10 patients were enrolled with DLT of 0/3 at DL1 and 2/7 in DL2. Considering DLT and treatment compliance, the recommended phase II dose was determined as DL1. In phase II, the response rate was 62% (P < 0.0001; 95% confidence interval, 48-75%); median overall survival and progression-free survival were 11.1 and 5.8 months, respectively. Common grade 3/4 adverse events were neutropenia (25%), anemia (36%), hyponatremia (29%), anorexia (24%), and nausea (11%). No febrile neutropenia was observed. Pneumonitis caused treatment-related death in one patient. The 2-weekly DCF regimen showed promising antimetastatic activity and tolerability. A phase III study comparing this regimen with CF therapy is planned by the Japan Clinical Oncology Group. This study was registered at the UMIN Clinical Trials Registry as UMIN 000001737. PMID:25041052

  5. Toward Online Adaptive Hyperthermia Treatment Planning: Correlation Between Measured and Simulated Specific Absorption Rate Changes Caused by Phase Steering in Patients

    SciTech Connect

    Kok, H. Petra; Ciampa, Silvia; Kroon-Oldenhof, Rianne de; Steggerda-Carvalho, Eva J.; Stam, Gerard van; Zum Vörde Sive Vörding, Paul J.; Stalpers, Lukas J.A.; Geijsen, Elisabeth D.; Bardati, Fernando; Bel, Arjan; Crezee, Johannes

    2014-10-01

    Purpose: Hyperthermia is the clinical application of heat, in which tumor temperatures are raised to 40°C to 45°C. This proven radiation and chemosensitizer significantly improves clinical outcome for several tumor sites. Earlier studies of the use of pre-treatment planning for hyperthermia showed good qualitative but disappointing quantitative reliability. The purpose of this study was to investigate whether hyperthermia treatment planning (HTP) can be used more reliably for online adaptive treatment planning during locoregional hyperthermia treatments. Methods and Materials: This study included 78 treatment sessions for 15 patients with non-muscle-invasive bladder cancer. At the start of treatments, temperature rise measurements were performed with 3 different antenna settings optimized for each patient, from which the absorbed power (specific absorption rate [SAR]) was derived. HTP was performed based on a computed tomography (CT) scan in treatment position with the bladder catheter in situ. The SAR along the thermocouple tracks was extracted from the simulated SAR distributions. Correlations between measured and simulated (average) SAR values were determined. To evaluate phase steering, correlations between the changes in simulated and measured SAR values averaged over the thermocouple probe were determined for all 3 combinations of antenna settings. Results: For 42% of the individual treatment sessions, the correlation coefficient between measured and simulated SAR profiles was higher than 0.5, whereas 58% showed a weak correlation (R of <0.5). The overall correlation coefficient between measured and simulated average SAR was weak (R=0.31; P<.001). The measured and simulated changes in average SAR after adapting antenna settings correlated much better (R=0.70; P<.001). The ratio between the measured and simulated quotients of maximum and average SARs was 1.03 ± 0.26 (mean ± SD), indicating that HTP can also correctly predict the relative amplitude of

  6. Local Heat Application for the Treatment of Buruli Ulcer: Results of a Phase II Open Label Single Center Non Comparative Clinical Trial

    PubMed Central

    Vogel, Moritz; Bayi, Pierre F.; Ruf, Marie-Thérèse; Bratschi, Martin W.; Bolz, Miriam; Um Boock, Alphonse; Zwahlen, Marcel; Pluschke, Gerd; Junghanss, Thomas

    2016-01-01

    Background. Buruli ulcer (BU) is a necrotizing skin disease most prevalent among West African children. The causative organism, Mycobacterium ulcerans, is sensitive to temperatures above 37°C. We investigated the safety and efficacy of a local heat application device based on phase change material. Methods. In a phase II open label single center noncomparative clinical trial (ISRCTN 72102977) under GCP standards in Cameroon, laboratory confirmed BU patients received up to 8 weeks of heat treatment. We assessed efficacy based on the endpoints ‘absence of clinical BU specific features’ or ‘wound closure’ within 6 months (“primary cure”), and ‘absence of clinical recurrence within 24 month’ (“definite cure”). Results. Of 53 patients 51 (96%) had ulcerative disease. 62% were classified as World Health Organization category II, 19% each as category I and III. The average lesion size was 45 cm2. Within 6 months after completion of heat treatment 92.4% (49 of 53, 95% confidence interval [CI], 81.8% to 98.0%) achieved cure of their primary lesion. At 24 months follow-up 83.7% (41 of 49, 95% CI, 70.3% to 92.7%) of patients with primary cure remained free of recurrence. Heat treatment was well tolerated; adverse effects were occasional mild local skin reactions. Conclusions. Local thermotherapy is a highly effective, simple, cheap and safe treatment for M. ulcerans disease. It has in particular potential as home-based remedy for BU suspicious lesions at community level where laboratory confirmation is not available. Clinical Trials Registration. ISRCT 72102977. PMID:26486698

  7. Association of cisplatin and intra-arterial injection of {sup 131}I-lipiodol in treatment of hepatocellular carcinoma: Results of phase II trial

    SciTech Connect

    Raoul, Jean-Luc . E-mail: raoul@rennes.fnclcc.fr; Boucher, Eveline; Olivie, Damien; Guillygomarc'h, Anne; Boudjema, Karim; Garin, Etienne

    2006-03-01

    Purpose: Intra-arterial injections of {sup 131}I-lipiodol ({sup 131}I-Lip) provide an effective treatment for hepatocellular carcinoma. In hepatocellular carcinoma cell cultures, concurrent administration of cisplatin increases the cytotoxicity of {sup 131}I. The efficacy and tolerance of intra-arterial injections of {sup 131}I-Lip combined with systemic cisplatin was tested in a phase II trial. Methods and Materials: The inclusion criteria were proven unresectable nonmetastatic hepatocellular carcinoma, compensated liver disease, and adequate laboratory test findings. Treatment comprised the combination of intra-arterial injection of {sup 131}I-Lip (2.2 GBq) with intravenous infusion of low-dose cisplatin. The combined treatment could be repeated. Results: A total of 41 patients were included; 37 had cirrhosis and 38 had measurable tumors. One to four treatments (median, two) were given. The cisplatin dose was 75 mg for the first course and 72 mg for the second. Grade 3-4 (n/n) adverse effects were observed in 14 patients, polymorphonuclear leukocytes (3/0), platelets (5/1), asthenia (1/0), pain (1/0), and vomiting (1/0). Four patients developed pulmonary toxicity; 2 cases were likely related to {sup 131}I-Lip administration and 1 was fatal. The response rate was 47% (18 of 38), and the 1- and 2-year survival rate was 73% {+-} 7% and 48% {+-} 9%, respectively. Conclusion: This combination had a tolerable toxicity profile and provided an objective response rate, warranting a phase III trial.

  8. Phase I-II Trial of Cetuximab, Capecitabine, Oxaliplatin, and Radiotherapy as Preoperative Treatment in Rectal Cancer

    SciTech Connect

    Roedel, Claus Arnold, Dirk; Hipp, Matthias; Liersch, Torsten; Dellas, Kathrin; Iesalnieks, Igors; Hermann, Robert Michael; Lordick, Florian; Hohenberger, Werner; Sauer, Rolf

    2008-03-15

    Purpose: To evaluate the safety and activity of preoperative radiotherapy (RT) with concurrent cetuximab, capecitabine, and oxaliplatin in rectal cancer patients. Patients and Methods: A total of 60 patients with rectal cancer (T3-T4 or N+, M1 allowed) entered the trial at five investigator sites; the data from 58 patients were assessable. Cetuximab was given as an initial dose of 400 mg/m{sup 2} 7 days before the start of RT, and then at 250 mg/m{sup 2} once weekly during RT (50.4 Gy in 28 fractions). Capecitabine and oxaliplatin were administered according to an established schedule of oxaliplatin (50 mg/m{sup 2} on Days 1, 8, 22, and 29) and capecitabine (Days 1-14 and 22-35) at three dose levels: 1,000, 1,300, and 1,650 mg/m{sup 2}/d during the Phase I part of the study. The main endpoint of the Phase II was the pathologic complete response rate. Results: Thirteen patients were included in the Phase I part of the study, and the maximal tolerated dose was not reached. Overall, 48 patients were treated at the recommended dose of capecitabine (1,650 mg/m{sup 2}) and 45 patients (94%) underwent surgery. A pathologic complete response was observed in 4 patients (9%), and moderate (n = 12), minimal (n = 10), and no tumor regression (n = 2) was noted in 24 (53%) of 45 patients. The mean radiation dose intensity, cetuximab, capecitabine, oxaliplatin was 98%, 95%, 94%, and 94%, respectively. The incidence of Grade 3-4 diarrhea was restricted to 19%. Postoperative complications of any grade occurred in 33% of patients. Conclusions: The results of our study have shown that cetuximab can be combined safely with capecitabine and oxaliplatin plus RT. The low pathologic complete response rate achieved should stimulate additional preclinical investigations to establish the best sequence of triple combinations.

  9. Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure

    PubMed Central

    Riches, Marcie L.; Kernan, Nancy A.; Brochstein, Joel A.; Mineishi, Shin; Termuhlen, Amanda M.; Arai, Sally; Grupp, Stephan A.; Guinan, Eva C.; Martin, Paul L.; Steinbach, Gideon; Krishnan, Amrita; Nemecek, Eneida R.; Giralt, Sergio; Rodriguez, Tulio; Duerst, Reggie; Doyle, John; Antin, Joseph H.; Smith, Angela; Lehmann, Leslie; Champlin, Richard; Gillio, Alfred; Bajwa, Rajinder; D’Agostino, Ralph B.; Massaro, Joseph; Warren, Diane; Miloslavsky, Maja; Hume, Robin L.; Iacobelli, Massimo; Nejadnik, Bijan; Hannah, Alison L.; Soiffer, Robert J.

    2016-01-01

    Hepatic veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT). Untreated hepatic VOD/SOS with multi-organ failure (MOF) is associated with >80% mortality. Defibrotide has shown promising efficacy treating hepatic VOD/SOS with MOF in phase 2 studies. This phase 3 study investigated safety and efficacy of defibrotide in patients with established hepatic VOD/SOS and advanced MOF. Patients (n = 102) given defibrotide 25 mg/kg per day were compared with 32 historical controls identified out of 6867 medical charts of HSCT patients by blinded independent reviewers. Baseline characteristics between groups were well balanced. The primary endpoint was survival at day +100 post-HSCT; observed rates equaled 38.2% in the defibrotide group and 25% in the controls (23% estimated difference; 95.1% confidence interval [CI], 5.2-40.8; P = .0109, using a propensity-adjusted analysis). Observed day +100 complete response (CR) rates equaled 25.5% for defibrotide and 12.5% for controls (19% difference using similar methodology; 95.1% CI, 3.5-34.6; P = .0160). Defibrotide was generally well tolerated with manageable toxicity. Related adverse events (AEs) included hemorrhage or hypotension; incidence of common hemorrhagic AEs (including pulmonary alveolar [11.8% and 15.6%] and gastrointestinal bleeding [7.8% and 9.4%]) was similar between the defibrotide and control groups, respectively. Defibrotide was associated with significant improvement in day +100 survival and CR rate. The historical-control methodology offers a novel, meaningful approach for phase 3 evaluation of orphan diseases associated with high mortality. This trial was registered at www.clinicaltrials.gov as #NCT00358501. PMID:26825712

  10. Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure.

    PubMed

    Richardson, Paul G; Riches, Marcie L; Kernan, Nancy A; Brochstein, Joel A; Mineishi, Shin; Termuhlen, Amanda M; Arai, Sally; Grupp, Stephan A; Guinan, Eva C; Martin, Paul L; Steinbach, Gideon; Krishnan, Amrita; Nemecek, Eneida R; Giralt, Sergio; Rodriguez, Tulio; Duerst, Reggie; Doyle, John; Antin, Joseph H; Smith, Angela; Lehmann, Leslie; Champlin, Richard; Gillio, Alfred; Bajwa, Rajinder; D'Agostino, Ralph B; Massaro, Joseph; Warren, Diane; Miloslavsky, Maja; Hume, Robin L; Iacobelli, Massimo; Nejadnik, Bijan; Hannah, Alison L; Soiffer, Robert J

    2016-03-31

    Hepatic veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT). Untreated hepatic VOD/SOS with multi-organ failure (MOF) is associated with >80% mortality. Defibrotide has shown promising efficacy treating hepatic VOD/SOS with MOF in phase 2 studies. This phase 3 study investigated safety and efficacy of defibrotide in patients with established hepatic VOD/SOS and advanced MOF. Patients (n = 102) given defibrotide 25 mg/kg per day were compared with 32 historical controls identified out of 6867 medical charts of HSCT patients by blinded independent reviewers. Baseline characteristics between groups were well balanced. The primary endpoint was survival at day +100 post-HSCT; observed rates equaled 38.2% in the defibrotide group and 25% in the controls (23% estimated difference; 95.1% confidence interval [CI], 5.2-40.8;P= .0109, using a propensity-adjusted analysis). Observed day +100 complete response (CR) rates equaled 25.5% for defibrotide and 12.5% for controls (19% difference using similar methodology; 95.1% CI, 3.5-34.6;P= .0160). Defibrotide was generally well tolerated with manageable toxicity. Related adverse events (AEs) included hemorrhage or hypotension; incidence of common hemorrhagic AEs (including pulmonary alveolar [11.8% and 15.6%] and gastrointestinal bleeding [7.8% and 9.4%]) was similar between the defibrotide and control groups, respectively. Defibrotide was associated with significant improvement in day +100 survival and CR rate. The historical-control methodology offers a novel, meaningful approach for phase 3 evaluation of orphan diseases associated with high mortality. This trial was registered at www.clinicaltrials.gov as #. PMID:26825712

  11. Daily Pomegranate Intake Has No Impact on PSA Levels in Patients with Advanced Prostate Cancer - Results of a Phase IIb Randomized Controlled Trial

    PubMed Central

    Stenner-Liewen, Frank; Liewen, Heike; Cathomas, Richard; Renner, Christoph; Petrausch, Ulf; Sulser, Tullio; Spanaus, Katharina; Seifert, Hans Helge; Strebel, Räto Thomas; Knuth, Alexander; Samaras, Panagiotis; Müntener, Michael

    2013-01-01

    Pomegranate has been shown to prolong PSA doubling time in early prostate cancer, but no data from a placebo controlled trial has been published yet. The objective of this study was to prospectively evaluate the impact of pomegranate juice in patients with prostate cancer. We conducted a phase IIb, double blinded, randomized placebo controlled trial in patients with histologically confirmed prostate cancer. Only patients with a PSA value ≥ 5ng/ml were included. The subjects consumed 500 ml of pomegranate juice or 500 ml of placebo beverage every day for a 4 week period. Thereafter, all patients received 250 ml of the pomegranate juice daily for another 4 weeks. PSA values were taken at baseline, day 14, 28 and on day 56. The primary endpoint was the detection of a significant difference in PSA serum levels between the groups after one month of treatment. Pain scores and adherence to intervention were recorded using patient diaries. 102 patients were enrolled. The majority of patients had castration resistant prostate cancer (68%). 98 received either pomegranate juice or placebo between October 2008 and May 2011. Adherence to protocol was good, with 94 patients (96%) completing the first period and 87 patients (89%) completing both periods. No grade 3 or higher toxicities occurred within the study. No differences were detected between the two groups with regard to PSA kinetics and pain scores. Consumption of pomegranate juice as an adjunct intervention in men with advanced prostate cancer does not result in significant PSA declines compared to placebo. PMID:24069070

  12. A phase 2 randomized dose-ranging study of the JAK2-selective inhibitor fedratinib (SAR302503) in patients with myelofibrosis

    PubMed Central

    Pardanani, A; Tefferi, A; Jamieson, C; Gabrail, N Y; Lebedinsky, C; Gao, G; Liu, F; Xu, C; Cao, H; Talpaz, M

    2015-01-01

    In this phase 2 open-label randomized study, 31 patients with intermediate-2 or high-risk myelofibrosis received fedratinib 300, 400 or 500 mg once daily in consecutive 4-week cycles. Mean spleen volume reductions at 12 weeks (primary end point) were 30.3% (300 mg), 33.1% (400 mg) and 43.3% (500 mg). Spleen response rates (patients achieving ⩾35% spleen reduction) at 12/24 weeks were 30%/30% (300 mg), 50%/60% (400 mg) and 64%/55% (500 mg), respectively. By 4 weeks, improvements in myelofibrosis (MF)-associated symptoms were observed. At 48 weeks, 68% of patients remained on fedratinib and 16% had discontinued because of adverse events (AEs). Common grade 3/4 AEs were anemia (58%), fatigue (13%), diarrhea (13%), vomiting (10%) and nausea (6%). Serious AEs included one case of reversible hepatic failure and one case of Wernicke's encephalopathy (after analysis cutoff). Fedratinib treatment led to reduced STAT3 phosphorylation but no meaningful change in JAK2V617F allele burden. Significant modulation (P<0.05, adjusted for multiple comparisons) of 28 cytokines was observed, many of which correlated with spleen reduction. These data confirm the clinical activity of fedratinib in MF. After the analysis cutoff date, additional reports of Wernicke's encephalopathy in other fedratinib trials led to discontinuation of the sponsored clinical development program. PMID:26252788

  13. Adipokines and treatment with niacin.

    PubMed

    Westphal, Sabine; Borucki, Katrin; Taneva, Elena; Makarova, Ruma; Luley, Claus

    2006-10-01

    Adipokines may serve as an important etiologic link between atherosclerosis and obesity. Because adipose tissue is one site of action of the lipid-lowering drug niacin, we investigated whether niacin treatment would affect not only lipids but also adipokines. Twenty-four patients were treated with extended-release niacin. During the first 4 weeks the daily dose was increased at weekly intervals from 375 to 1000 mg, which was maintained for 4 weeks. Thereafter, the dose was 1500 mg for another 6 weeks. Adiponectin increased by 54% and 94%, respectively, resistin was lowered only moderately, and leptin not at all. Because adiponectin has repeatedly been shown to be negatively associated with atherosclerotic risk, its pronounced increase may bring about additional atheroprotection by niacin beyond its improvement in lipids. PMID:16979396

  14. The two-phase leaching of Pb, Zn and Cd contaminated soil using EDTA and electrochemical treatment of the washing solution.

    PubMed

    Finzgar, Neza; Lestan, Domen

    2008-11-01

    The feasibility of a novel two-phase method for remediation of Pb (1374 mg kg(-1)), Zn (1007 mg kg(-1)), and Cd (9.1 mg kg(-1)) contaminated soil was evaluated. In the first phase we used EDTA for leaching heavy metals from the soil. In the second phase we used an electrochemical advanced oxidation process (EAOP) for the treatment and reuse of washing solution for soil rinsing (removal of the soil-retained, chelant-mobilized metallic species). In EAOP, a boron-doped diamond anode was used for the generation of hydroxyl radicals and oxidative decomposition of EDTA-metal complexes at a constant current density (15 mA cm(-2)). The released metals were removed from the solution by filtration as insoluble participate and by electro-deposition on the cathode. Four consecutive additions of 5.0 mm ol kg(-1) EDTA (total 20 mmol kg(-1)) removed 44% Pb, 14% Zn and 35% Cd from the soil. The mobility of the Pb, Zn and Cd (Toxicity Characteristic Leaching Procedure) left in the soil after remediation was reduced by 1.6, 3.4 and 1.5 times, respectively. The Pb oral availability (Physiologically Based Extraction Test) in the simulated stomach phase was reduced by 2.4 and in the intestinal phase by 1.7 times. The discharge solution was clear, almost colorless, with pH 7.73 and 0.47 mg L(-1) Pb, 1.03 mg L(-1) Zn, bellow the limits of quantification of Cd and 0.023 mM EDTA. The novel method enables soil leaching with small water requirements and no wastewater generation or other emissions into the environment. PMID:18762318

  15. Neutrophil to lymphocyte ratio in the pre-treatment phase of final-line chemotherapy predicts the outcome of patients with recurrent ovarian cancer

    PubMed Central

    NAKAMURA, KEIICHIRO; NAGASAKA, TAKESHI; NISHIDA, TAKESHI; HARUMA, TOMOKO; OGAWA, CHIKAKO; KUSUMOTO, TOMOYUKI; SEKI, NORIKO; HIRAMATSU, YUJI

    2016-01-01

    Inflammation and tumor immunology are associated with prognosis in a variety of cancers. The aim of the present retrospective study was to identify associations between the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), cancer antigen 125 (CA125) concentrations, tumor response, performance status (PS) and survival of patients that developed recurrent ovarian cancer subsequent to receiving chemotherapy. The NLR and PLR measured prior to fourth-line chemotherapy were significantly increased compared with those measured prior to second-line chemotherapy (P=0.029 and 0.049, respectively). By using receiver operating characteristic curves, the cut-off values were determined for the NLR, PLR and CA125 levels that were measured during the pre-treatment phase, which predicted the outcomes. According to univariate analyses, pre-treatment NLR >3.91, PLR >299.0 and PS 2 were each significantly associated with poor outcomes (P=0.001, 0.005 and 0.021, respectively). According to multivariate analyses, only pre-treatment NLR was associated with poor outcome (P=0.035). The present findings indicate that pre-treatment NLR is an important predictor of prognosis in patients with ovarian cancer that experience recurrence following chemotherapy. PMID:27313726

  16. Treatment of advanced pancreatic cancer with 5-fluorouracil, folinic acid and interferon alpha-2A: results of a phase II trial.

    PubMed Central

    Bernhard, H.; Jäger-Arand, E.; Bernhard, G.; Heike, M.; Klein, O.; Riemann, J. F.; Meyer zum Büschenfelde, K. H.; Dippold, W.; Knuth, A.

    1995-01-01

    Interferon alpha-2a (IFN-alpha) and folinic acid (FA) have been shown to modulate the cytotoxic effects of 5-fluorouracil (5-FU) in the treatment of cancer. A phase II study was initiated to evaluate the effect of a combination of 5-FU/FA/IFN-alpha in patients with advanced pancreatic cancer. Sixty previously untreated patients with advanced adenocarcinoma of the pancreas were treated with 500 mg m-2 FU via an intravenous bolus 1 h after the initiation of a 2 h infusion of 500 mg m-2 FA. Before starting the FA infusion, 6 million units (MU) of IFN-alpha was administered subcutaneously. The treatment was repeated once a week. Of 57 evaluable patients, eight (14%) had a partial response (PR), eight (14%) a minor response (MR) and 28 (49%) no change of disease (NC). Thirteen patients (23%) had progressive disease (PD). The median survival time was 10 months for all patients, 22 months for patients with partial remission and 5 months for patients with progressive disease. Many patients with tumour-related pain whose tumours were affected in terms of PR, MR, NC were free of pain during treatment with this regimen (22/36 patients). The common toxicities observed were fever (56%), nausea (37%) and diarrhoea (33%). These data suggest that biochemical modulation of 5-FU with FA and IFN-alpha has some positive effects in the treatment of pancreatic cancer of moderate toxicity. PMID:7819023

  17. Highly Reliable Liquid-Phase-Deposited SiO2 with Nitrous Oxide Plasma Post-Treatment for Low-Temperature-Processed Polysilicon Thin Film Transistors

    NASA Astrophysics Data System (ADS)

    Yeh, Ching-Fa; Chen, Darren Chi-Hsiang; Lu, Cheng-Yu; Liu, Chung; Lee, Su-Tseng; Liu, Cheng-Hong; Chen, Tai-Ju

    2002-10-01

    Low-temperature (˜300°C) N2O-plasma post-treatment for liquid-phase-deposited (LPD) gate oxide has been proposed for the first time. This treatment successfully takes the place of conventional furnace annealing in O2 ambient. Results of physicochemical and electrical characteristics show that N2O-plasma post-treated LPD-SiO2 has a high electrical breakdown field and low interface state density. In addition, N2O-plasma treatment also improves the Si-rich phenomenon of LPD-SiO2. From the comparison with pure N2O-plasma oxidation film, LPD-SiO2 with its short re-oxidation time in N2O plasma plays an important role in relieving interfacial stress. Finally, the novel technology is applied to the gate oxide of low-temperature-processed (LTP) polysilicon thin film transistors (poly-Si TFTs). The device performance reveals excellent electrical characteristics, and the reliability shows a satisfactory result, as well as the gate oxide reliability. It is believed that the N2O-plasma post-treatment not only improves the oxide quality, but also effectively passivates the trap states of poly-Si TFTs.

  18. Semicontinuous Low-Dose-Rate Teletherapy for the Treatment of Recurrent Glial Brain Tumors: Final Report of a Phase I/II Study

    SciTech Connect

    Siker, Malika L.; Firat, Selim Y.; Mueller, Wade; Krouwer, Hendrikus; Schultz, Christopher J.

    2012-02-01

    Purpose: Semicontinuous low-dose-rate teletherapy (SLDR) is a novel irradiation strategy that exploits the increased radiosensitivity of glial cells in a narrow range of reduced dose rate. We present the final report of a prospective Phase I/II study testing the feasibility of SLDR for the treatment of recurrent gliomas. Methods and Materials: Patients with previously irradiated recurrent gliomas were enrolled from November 1993 to March 1998. Patients received SLDR, delivered 6 to 8 hours/day at a dose rate of 40 to 50 cGy/hour for a total dose of 30 to 35 Gy given over 12 days using a modified cobalt-60 treatment unit. Acute central nervous system toxicity after SLDR treatment was the primary endpoint. Overall survival was a secondary endpoint. Results: Twenty patients were enrolled (14 World Health Organization Grade 4 glioma, 5 Grade 2 glioma, 1 ependymoma). No patients developed {>=}Grade 3 central nervous system toxicity at 3 months without radiographic evidence of tumor progression. Overall survival after SLDR was 56% at 6 months, 28% at 12 months, and 17% at 24 months. One patient survived >48 months, and 1 patient survived >60 months after SLDR treatment. Re-resection before SLDR treatment significantly improved 1-year overall survival for all patients and patients with Grade 4 glioma. Conclusion: The delivery of SLDR is feasible in patients with recurrent gliomas and resulted in improved outcomes for patients who underwent re-resection. There were 2 long-term survivors (>48 months). This pilot study supports the notion that reduced dose rate influences the efficacy and tolerance of reirradiation in the treatment of recurrent gliomas.

  19. Sexual dysfunction during treatment of major depressive disorder with vilazodone, citalopram, or placebo: results from a phase IV clinical trial

    PubMed Central

    Gommoll, Carl; Chen, Dalei; Nunez, Rene; Mathews, Maju

    2015-01-01

    Sexual dysfunction commonly occurs with major depressive disorder (MDD). Vilazodone, a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist antidepressant approved for the treatment of MDD in adults, was evaluated to determine its effects on sexual function. The primary study was a double-blind, randomized, controlled trial comparing vilazodone 20 and 40 mg/day with placebo; citalopram 40 mg/day was an active control (NCT01473381; http://www.clinicaltrials.gov). Post-hoc analyses evaluated change from baseline to week 10 on the Changes in Sexual Functioning Questionnaire (CSFQ); no inferential statistics were performed. CSFQ scores increased for women [1.2 (citalopram) to 3.0 (vilazodone 40 mg)] and men [1.2 (vilazodone 40 mg) to 3.5 (placebo)] in all treatment groups. Greater changes in CSFQ scores were seen in responders [women: 2.33 (citalopram) to 5.06 (vilazodone 40 mg); men: 2.26 (vilazodone 40 mg) to 4.35 (placebo)] versus nonresponders. CSFQ change from baseline was small for patients with normal baseline sexual function; in patients with baseline sexual dysfunction, CSFQ scores improved across groups [women: 2.35 (citalopram) to 4.52 (vilazodone 40 mg); men 2.83 (vilazodone 40 mg) to 6.43 (placebo)]. Across treatment groups, baseline sexual function improved in women and men, MDD responders, and patients with baseline sexual dysfunction. PMID:26039688

  20. Assessment of Periodontopathogens in Subgingival Biofilm of Banded and Bonded Molars in Early Phase of Fixed Orthodontic Treatment.

    PubMed

    Mártha, Krisztina; Lőrinczi, Lilla; Bică, Cristina; Gyergyay, Réka; Petcu, Blanka; Lazăr, Luminița

    2016-03-01

    To assess the prevalence and occurrence of eleven periodontopathogens in subgingival biofilm of banded and bonded molars during the first period of fixed orthodontic treatment. Subjects were selected from patients referred to orthodontic treatment and were divided in two groups: group A comprised fifteen patients (14.4±2.45 years of age) who received orthodontic bands on first permanent molars and group B of ten patients (15.7±1.87 years of age) with directly bonded tubes on the labial surface of the same teeth. Subgingival sample collection was performed before bands and tubes application and 4-7 weeks after attachment placement. DNA-strip tehnique was used to assess the presence of eleven putative periodontopathogens at each time point. Fusobacterium nucleatum, Eikenella corrodens and Capnocytophaga spp. were found in a large number of samples, other periodontopathogens were present in a smaller rate. The 4-7 weeks after attachment placement a slight increase of putative species was observed in both groups. The presence of orthodontic tubes and bands influence the accumulation and composition of subgingival microbiota. Higher level of oral hygiene should be achieved before and during orthodontic treatment in order to prevent any side effects on periodontal tissues. PMID:27020873

  1. Sexual dysfunction during treatment of major depressive disorder with vilazodone, citalopram, or placebo: results from a phase IV clinical trial.

    PubMed

    Clayton, Anita H; Gommoll, Carl; Chen, Dalei; Nunez, Rene; Mathews, Maju

    2015-07-01

    Sexual dysfunction commonly occurs with major depressive disorder (MDD). Vilazodone, a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist antidepressant approved for the treatment of MDD in adults, was evaluated to determine its effects on sexual function. The primary study was a double-blind, randomized, controlled trial comparing vilazodone 20 and 40 mg/day with placebo; citalopram 40 mg/day was an active control (NCT01473381; http://www.clinicaltrials.gov). Post-hoc analyses evaluated change from baseline to week 10 on the Changes in Sexual Functioning Questionnaire (CSFQ); no inferential statistics were performed. CSFQ scores increased for women [1.2 (citalopram) to 3.0 (vilazodone 40 mg)] and men [1.2 (vilazodone 40 mg) to 3.5 (placebo)] in all treatment groups. Greater changes in CSFQ scores were seen in responders [women: 2.33 (citalopram) to 5.06 (vilazodone 40 mg); men: 2.26 (vilazodone 40 mg) to 4.35 (placebo)] versus nonresponders. CSFQ change from baseline was small for patients with normal baseline sexual function; in patients with baseline sexual dysfunction, CSFQ scores improved across groups [women: 2.35 (citalopram) to 4.52 (vilazodone 40 mg); men 2.83 (vilazodone 40 mg) to 6.43 (placebo)]. Across treatment groups, baseline sexual function improved in women and men, MDD responders, and patients with baseline sexual dysfunction. PMID:26039688

  2. Biological treatment of two-phase olive mill wastewater (TPOMW, alpeorujo): polyhydroxyalkanoates (PHAs) production by Azotobacter strains.

    PubMed

    Cerrone, Federico; Sánchez-Peinado, Maria del Mar; Juárez-Jimenez, Belén; González-López, Jesús; Pozo, Clementina

    2010-03-01

    Azotobacter chroococcum H23 (CECT 4435), Azotobacter vinelandii UWD, and Azotobacter vinelandii (ATCC 12837), members of the family Pseudomonadaceae, were used to evaluate their capacity to grow and accumulate polyhydroxyalkanoates (PHAs) using two-phase olive mill wastewater (TPOMW, alpeorujo) diluted at different concentrations as the sole carbon source. The PHAs amounts (g/l) increased clearly when the TPOMW samples were previously digested under anaerobic conditions. The MNR analysis demonstrated that the bacterial strains formed only homopolymers containing beta-hydroxybutyrate, either when grown in diluted TPOMW medium or diluted anaerobically digested TPOMW medium. COD values of the diluted anaerobically digested waste were measured before and after the aerobic PHA-storing phase, and a clear reduction (72%) was recorded after 72 h of incubation. The results obtained in this study suggest the perspectives for using these bacterial strains to produce PHAs from TPOMW, and in parallel, contribute efficiently to the bioremediation of this waste. This fact seems essential if bioplastics are to become competitive products. PMID:20372033

  3. Novel multi-source phase-controlled radiofrequency technology for non-ablative and micro-ablative treatment of wrinkles, lax skin and acne scars.

    PubMed

    Elman, Monica; Harth, Yoram

    2011-01-01

    The basic properties of lasers and pulsed light sources limit their ability to deliver high energy to the dermis and subcutaneous tissues without excessive damage to the epidermis. Radiofrequency was shown to penetrate deeper than optical light sources independent of skin color. The early RF-based devices used single source bipolar RF, which is safe but limited in use due to the superficial flow of energy between the two bipolar electrodes. Another type of single source RF employs a single electrode (monopolar) in which the RF energy flows from one electrode on the surface of the skin through the entire body to a plate under the body. Although more effective than bipolar, this devices require intense active cooling of the skin and may be associated with considerable pain and other systemic and local safety concerns. Latest generation of RF technology developed by EndyMed Medical Ltd. (Caesarea, Israel) utilizes simultaneously six or more phase controlled RF generators (3DEEP technology). The multiple electrical fields created by the multiple sources "repel" or "attract" each other, leading to the precise 3 dimensional delivery of RF energy to the dermal and sub-dermal targets minimizing the energy flow through the epidermis without the need for active cooling. Confocal microscopy of the skin has shown that 6 treatment sessions of Multisource RF technology improve skin structure features. The skin after treatment had longer and narrower dermal papilla and denser and finer collagen fiber typical to younger skin as compared to pre treatment skin. Ultrasound of the skin showed after 6 treatment sessions reduction of 10 percent in the thickness of the subcutaneous fat layer. Non ablative facial clinical studies showed a significant reduction of wrinkles after treatment further reduced at 3 months follow-up. Body treatment studies showed a circumference reduction of 2.9 cm immediately after 6 treatments, and 2 cm at 12 months after the end of treatment, proving long term

  4. A Phase I Trial of Tipifarnib With Radiation Therapy, With and Without Temozolomide, for Patients With Newly Diagnosed Glioblastoma

    SciTech Connect

    Nghiemphu, Phioanh Leia; Wen, Patrick Y.; Drappatz, Jan; Fink, Karen; Malkin, Mark G.; Lieberman, Frank S.; DeAngelis, Lisa M.; Torres-Trejo, Alejandro; Chang, Susan M.; Abrey, Lauren; Fine, Howard A.; Demopoulos, Alexis; Lassman, Andrew B.; Kesari, Santosh; Prados, Michael D.; Cloughesy, Timothy F.

    2011-12-01

    Purpose: To determine the maximum tolerated dose (MTD) of tipifarnib in combination with conventional radiotherapy for patients with newly diagnosed glioblastoma. The MTD was evaluated in three patient cohorts, stratified based on concurrent use of enzyme-inducing antiepileptic drugs (EIAED) or concurrent treatment with temozolomide (TMZ): Group A: patients not receiving EIAED and not receiving TMZ; Group A-TMZ: patients not receiving EIAED and receiving treatment with TMZ; Group B: any patients receiving EIAED but not TMZ. Patients and Methods: After diagnostic surgery or biopsy, treatment with tipifarnib started 5 to 9 days before initiating radiotherapy, twice daily, in 4-week cycles using discontinuous dosing (21 out of 28 days), until toxicity or progression. For Group A-TMZ, patients also received TMZ daily during radiotherapy and then standard 5/28 days dosing after radiotherapy. Dose-limiting toxicity (DLT) was determined over the first 10 weeks of therapy for all cohorts. Results: Fifty-one patients were enrolled for MTD determination: 10 patients in Group A, 21 patients in Group A-TMZ, and 20 patients in Group B. In the Group A and Group A-TMZ cohorts, patients achieved the intended MTD of 300 mg twice daily (bid) with DLTs including rash and fatigue. For Group B, the MTD was determined as 300 mg bid, half the expected dose. The DLTs included rash and one intracranial hemorrhage. Thirteen of the 20 patients evaluated in Group A-TMZ were alive at 1 year. Conclusion: Tipifarnib is well tolerated at 300 mg bid given discontinuously (21/28 days) in 4-week cycles, concurrently with standard chemo/radiotherapy. A Phase II study should evaluate the efficacy of tipifarnib with radiation and TMZ in patients with newly diagnosed glioblastoma and not receiving EIAED.

  5. Solid-State Transformation of Iron-Rich Intermetallic Phases in Al-Cu 206 Cast Alloys During Solution Heat Treatment

    NASA Astrophysics Data System (ADS)

    Liu, K.; Cao, X.; Chen, X.-G.

    2013-08-01

    The solid-state transformation of the iron-rich intermetallic phases in Al-Cu 206 cast alloys during the solution heat treatment was studied by using Scanning Electron Microscope (SEM), Electron Back Scattered Diffraction (EBSD), Differential Scanning Calorimeter (DSC), and Transmission Electron Microscope (TEM). At a normal solution treatment temperature of 793 K (520 °C), no visible variation is observed for the β-Fe phase solidified from the Al alloy melt. With increasing soaking time, however, the Chinese script α-Fe becomes unstable and progressively transforms into platelet β-Fe, termed as solid-state-transformed (STed) β-Fe to distinguish it from the β-Fe directly solidified from the Al alloy melt. The STed β-Fe preferentially nucleates on the α-Fe and then grows from the α-Fe/Al interface into α-Fe and/or Al matrix with a much higher growth rate in the α-Fe. The incomplete solid-state transformation from α-Fe into STed β-Fe leads to the fragmentation of the α-Fe. The formation of the STed β-Fe with increasing size and volume fraction after longer soaking time can deteriorate the tensile properties.

  6. Riluzole for the treatment of acute traumatic spinal cord injury: rationale for and design of the NACTN Phase I clinical trial.

    PubMed

    Fehlings, Michael G; Wilson, Jefferson R; Frankowski, Ralph F; Toups, Elizabeth G; Aarabi, Bizhan; Harrop, James S; Shaffrey, Christopher I; Harkema, Susan J; Guest, James D; Tator, Charles H; Burau, Keith D; Johnson, Michele W; Grossman, Robert G

    2012-09-01

    In the immediate period after traumatic spinal cord injury (SCI) a variety of secondary injury mechanisms combine to gradually expand the initial lesion size, potentially leading to diminished neurological outcomes at long-term follow-up. Riluzole, a benzothiazole drug, which has neuroprotective properties based on sodium channel blockade and mitigation of glutamatergic toxicity, is currently an approved drug that attenuates the extent of neuronal degeneration in patients with amyotrophic lateral sclerosis. Moreover, several preclinical SCI studies have associated riluzole administration with improved functional outcomes and increased neural tissue preservation. Based on these findings, riluzole has attracted considerable interest as a potential neuroprotective drug for the treatment of SCI. Currently, a Phase I trial evaluating the safety and pharmacokinetic profile of riluzole in human SCI patients is being conducted by the North American Clinical Trials Network (NACTN) for Treatment of Spinal Cord Injury. The current review summarizes the existing preclinical and clinical literature on riluzole, provides a detailed description of the Phase I trial, and suggests potential opportunities for future investigation. Clinical trial registration no.: NCT00876889. PMID:22985381

  7. Treatment-Related Death in Patients with Small-Cell Lung Cancer in Phase III Trials over the Last Two Decades

    PubMed Central

    Ochi, Nobuaki; Hotta, Katsuyuki; Takigawa, Nagio; Oze, Isao; Fujiwara, Yoshiro; Ichihara, Eiki; Hisamoto, Akiko; Tabata, Masahiro; Tanimoto, Mitsune; Kiura, Katsuyuki

    2012-01-01

    Introduction Treatment-related death (TRD) remains a serious problem in small-cell lung cancer (SCLC), despite recent improvements in supportive care. However, few studies have formally assessed time trends in the proportion of TRD over the past two decades. The aim of this study was to determine the frequency and pattern of TRD over time. Methods We examined phase 3 trials conducted between 1990 and 2010 to address the role of systemic treatment for SCLC. The time trend was assessed using linear regression analysis. Results In total, 97 trials including nearly 25,000 enrolled patients were analyzed. The overall TRD proportion was 2.95%. Regarding the time trend, while it was not statistically significant, it tended to decrease, with a 0.138% decrease per year and 2.76% decrease per two decades. The most common cause of death was febrile neutropenia without any significant time trend in its incidence over the years examined (p = 0.139). However, deaths due to febrile neutropenia as well as all causes in patients treated with non-platinum chemotherapy increased significantly (p = 0.033). Conclusions The overall TRD rate has been low, but not negligible, in phase III trials for SCLC over the past two decades. PMID:22880112

  8. Masitinib in the treatment of active rheumatoid arthritis: results of a multicentre, open-label, dose-ranging, phase 2a study

    PubMed Central

    Tebib, Jacques; Mariette, Xavier; Bourgeois, Pierre; Flipo, René-Marc; Gaudin, Philippe; Le Loët, Xavier; Gineste, Paul; Guy, Laurent; Mansfield, Colin D; Moussy, Alain; Dubreuil, Patrice; Hermine, Olivier; Sibilia, Jean

    2009-01-01

    Introduction Since current treatment options for patients suffering from active rheumatoid arthritis (RA) remain inadequate, especially for those unresponsive to disease-modifying antirheumatic drugs (DMARDs), new and improved medication is needed. This study evaluates the safety and efficacy of masitinib (AB1010), a potent and selective protein tyrosine kinase inhibitor of c-KIT, in the monotherapy treatment of DMARD-refractory RA. Methods This was a multicentre, uncontrolled, open-label, randomised, dose-ranging, phase 2a trial. Masitinib was administered orally to 43 patients who had inadequate response to DMARDs, at initial randomised dosing levels of 3 and 6 mg/kg per day over a 12-week period. Dose adjustment was permitted based upon tolerability and response criteria. Efficacy was assessed via American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70) responses, disease activity score using 28 joint counts (DAS28), index of improvement in RA (ACRn) and C-reactive protein (CRP) improvement, relative to baseline at week 12. Results Improvement was observed in all efficacy endpoints, including ACR20/50/70 scores of 54%, 26% and 8%, respectively, and a reduction in CRP level by greater than 50% for approximately half the population. This improvement was sustainable throughout an extension phase (> 84 weeks) and was also independent of initial DMARD resistance (anti-tumour necrosis factor-alpha and/or methotrexate). A relatively high patient withdrawal rate (37%) required the use of last observation carried forward (LOCF) data imputation. Incidence of adverse events was high (95%), although the majority were of mild or moderate severity with a considerable decline in frequency observed after 12 weeks of treatment. Two nonfatal serious adverse events were reported. Dose-response analyses tentatively indicate that an initial dosing level of 6.0 mg/kg per day administered orally in two daily intakes is the most appropriate, based upon potency

  9. Cook Like a Chef 1- and 4-Week Camp Models

    ERIC Educational Resources Information Center

    Condrasky, Margaret D.; Johnson, Glenda; Corr, Anne; Sharp, Julia L.

    2015-01-01

    Children participating in cooking classes gain confidence in their abilities to prepare food. If children are to make informed, healthy, food ingredient and cooking method choices, they need to be equipped with these necessary skills, as well as with nutrition competence. Extension programs that incorporate nutrition and hands-on cooking can…

  10. A Phase I/II adaptive design to determine the optimal treatment regimen from a set of combination immunotherapies in high-risk melanoma.

    PubMed

    Wages, Nolan A; Slingluff, Craig L; Petroni, Gina R

    2015-03-01

    In oncology, vaccine-based immunotherapy often investigates regimens that demonstrate minimal toxicity overall and higher doses may not correlate with greater immune response. Rather than determining the maximum tolerated dose, the goal of the study becomes locating the optimal biological dose, which is defined as a safe dose demonstrating the greatest immunogenicity, based on some predefined measure of immune response. Incorporation of adjuvants, new or optimized peptide vaccines, and combining vaccines with immune modulators may enhance immune response, with the aim of improving clinical response. Innovative dose escalation strategies are needed to establish the safety and immunogenicity of new immunologic combinations. We describe the implementation of an adaptive design for identifying the optimal treatment strategy in a multi-site, FDA-approved, phase I/II trial of a novel vaccination approach using long-peptides plus TLR agonists for resected stage IIB-IV melanoma. Operating characteristics of the design are demonstrated under various possible true scenarios via simulation studies. Overall performance indicates that the design is a practical Phase I/II adaptive method for use with combined immunotherapy agents. The simulation results demonstrate the method's ability to effectively recommend optimal regimens in a high percentage of trials with manageable sample sizes. The numerical results presented in this work include the type of simulation information that aid review boards in understanding design performance, such as average sample size and frequency of early trial termination, which we hope will augment early-phase trial design in cancer immunotherapy. PMID:25638752

  11. Bevacizumab and temozolomide versus temozolomide alone as neoadjuvant treatment in unresected glioblastoma: the GENOM 009 randomized phase II trial.

    PubMed

    Balana, Carmen; De Las Penas, Ramon; Sepúlveda, Juan Manuel; Gil-Gil, Miguel J; Luque, Raquel; Gallego, Oscar; Carrato, Cristina; Sanz, Carolina; Reynes, Gaspar; Herrero, Ana; Ramirez, Jose Luis; Pérez-Segura, Pedro; Berrocal, Alfonso; Vieitez, Jose Maria; Garcia, Almudena; Vazquez-Estevez, Sergio; Peralta, Sergi; Fernandez, Isaura; Henriquez, Ivan; Martinez-Garcia, Maria; De la Cruz, Juan Jose; Capellades, Jaume; Giner, Pilar; Villà, Salvador

    2016-05-01

    We sought to determine the impact of bevacizumab on reduction of tumor size prior to chemoradiotherapy in unresected glioblastoma patients. Patients were randomized 1:1 to receive temozolomide (TMZ arm) or temozolomide plus bevacizumab (TMZ + BEV arm). In both arms, neoadjuvant treatment was temozolomide (85 mg/m(2), days 1-21, two 28-day cycles), concurrent radiation plus temozolomide, and six cycles of adjuvant temozolomide. In the TMZ + BEV arm, bevacizumab (10 mg/kg) was added on days 1 and 15 of each neoadjuvant cycle and on days 1, 15 and 30 of concurrent treatment. The primary endpoint was investigator-assessed response to neoadjuvant treatment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and the impact on outcome of MGMT methylation in tumor and serum. One hundred and two patients were included; 43 in the TMZ arm and 44 in the TMZ + BEV arm were evaluable for response. Results favored the TMZ + BEV arm in terms of objective response (3 [6.7 %] vs. 11 [22.9 %]; odds ratio 4.2; P = 0.04). PFS and OS were longer in the TMZ + BEV arm, though the difference did not reach statistical significance. MGMT methylation in tumor, but not in serum, was associated with outcome. More patients experienced toxicities in the TMZ + BEV than in the TMZ arm (P = 0.06). The combination of bevacizumab plus temozolomide is more active than temozolomide alone and may well confer benefit in terms of tumor shrinkage in unresected patients albeit at the expense of greater toxicity. PMID:26847813

  12. Surgical treatment for locally advanced lower third rectal cancer after neoadjuvent chemoradiation with capecitabine: prospective phase II trial

    PubMed Central

    Elwanis, Mostafa Abd; Maximous, Doaa W; Elsayed, Mohamed Ibrahim; Mikhail, Nabiel NH

    2009-01-01

    Introduction Treatment of rectal cancer requires a multidisciplinary approach with standardized surgical, pathological and radiotherapeutic procedures. Sphincter preserving surgery for cancer of the lower rectum needs a long-course of neoadjuvant treatments to reduce tumor volume, to induce down-staging that increases circumferential resection margin, and to facilitate surgery. Aim To evaluate the rate of anal sphincter preservation in low lying, resectable, locally advanced rectal cancer and the resectability rate in unresectable cases after neoadjuvent chemoradiation by oral Capecitabine. Patients and methods This trial included 43 patients with low lying (4–7 cm from anal verge) locally advanced rectal cancer, of which 33 were resectable. All patients received preoperative concurrent chemoradiation (45 Gy/25 fractions over 5 weeks with oral capecitabine 825 mg/m2 twice daily on radiotherapy days), followed after 4–6 weeks by total mesorectal excision technique. Results Preoperative chemoradiation resulted in a complete pathologic response in 4 patients (9.3%; 95% CI 3–23.1) and an overall downstaging in 32 patients (74.4%; 95% CI 58.5–85). Sphincter sparing surgical procedures were done in 20 out of 43 patients (46.5%; 95% CI 31.5–62.2). The majority (75%) were of clinical T3 disease. Toxicity was moderate and required no treatment interruption. Grade II anemia occurred in 4 patients (9.3%, 95% CI 3–23.1), leucopenia in 2 patients (4.7%, 95% CI 0.8–17) and radiation dermatitis in 4 patients (9.3%, 95% CI 3–23.1) respectively. Conclusion In patients with low lying, locally advanced rectal cancer, preoperative chemoradiation using oral capecitabine 825 mg/m2, twice a day on radiotherapy days, was tolerable and effective in downstaging and resulted in 46.5% anal sphincter preservation rate. PMID:19508705

  13. Different surface charge of colistin-susceptible and -resistant Acinetobacter baumannii cells measured with zeta potential as a function of growth phase and colistin treatment

    PubMed Central

    Soon, Rachel L.; Nation, Roger L.; Cockram, Stewart; Moffatt, Jennifer H.; Harper, Marina; Adler, Ben; Boyce, John D.; Larson, Ian; Li, Jian

    2011-01-01

    Objectives Electrostatic forces mediate the initial interaction between cationic colistin and Gram-negative bacterial cells. Lipopolysaccharide (LPS) loss mediates colistin resistance in some A. baumannii strains. Our aim was to determine the surface charge of colistin-susceptible and –resistant A. baumannii as a function of growth phase and in response to polymyxin treatment. Methods The zeta potential of A. baumannii ATCC 19606 and 10 clinical multidrug-resistant strains (MICs 0.5–2 mg/L) was assessed. Colistin-resistant derivatives (MIC >128 mg/L) of wild-type strains were selected in the presence of 10 mg/L colistin, including the LPS-deficient lpxA mutant, ATCC 19606R. To determine the contribution of LPS to surface charge, two complemented ATCC 19606R derivatives were examined, namely ATCC 19606R + lpxA (containing an intact lpxA gene) and ATCC 19606R + V (containing empty vector). Investigations were conducted as a function of growth phase and polymyxin treatment (1, 4 and 8 mg/L). Results Wild-type cells exhibited a greater negative charge (−60.5 ± 2.36 to −26.2 ± 2.56 mV) thancolistin-resistant cells (−49.2 ± 3.09 to −19.1 ± 2.80 mV) at mid-log phase (ANOVA, P < 0.05). Opposing growth-phase trends were observed for both phenotypes: wild-type cells displayed reduced negative charge and colistin-resistant cells displayed increased negative charge at stationary compared with mid-logarithmic phase. Polymyxin exposure resulted in a concentration-dependent increase in zeta potential. Examination of ATCC 19606R and complemented strains supported the importance of LPS in determining surface charge, suggesting a potential mechanism of colistin resistance. Conclusions Zeta potential differences between A. baumannii phenotypes probably reflect compositional outer-membrane variations that impact the electrostatic component of colistin activity. PMID:21081544

  14. Precursor system of liquid crystalline phase containing propolis microparticles for the treatment of periodontal disease: development and characterization.

    PubMed

    Bruschi, Marcos Luciano; de Freitas, Osvaldo; Lara, Elza Helena Guimarã Es; Panzeri, Heitor; Gremião, Maria Palmira Daflon; Jones, David Simon

    2008-03-01

    Precursor systems of liquid crystalline phase were prepared using the surfactant PPG-5-Ceteth-20, isopropyl myristate, and water; gelatin microparticles containing propolis were then added into these systems. Homogeneity of dispersion, the in-system microparticle morphology, and sedimentation behavior of each formulation were evaluated. The rheological and mechanical properties (hardness, compressibility, and adhesiveness), the work of syringing, and the propolis release profile were also evaluated. All the formulations exhibited pseudoplastic flow and thixotropy, and they displayed storage modulus, loss modulus, dynamic viscosity, and loss tangent that depended on temperature, frequency, and composition. Mechanical properties varied significantly among the formulations being affected by changes in the composition and temperature. Raising the concentration of surfactant and adding propolis microparticles significantly decreased the work of syringing. The drug release was non-Fickian (anomalous) and there was no significant difference between the tested systems in the times required for 10%, 30%, and 50% release of the initial drug loading. PMID:18363142

  15. Neonatal monosodium glutamate treatment counteracts circadian arrhythmicity induced by phase shifts of the light-dark cycle in female and male Siberian hamsters.

    PubMed

    Prendergast, Brian J; Onishi, Kenneth G; Zucker, Irving

    2013-07-12

    Studies of rats and voles suggest that distinct pathways emanating from the anterior hypothalamic-retrochiasmatic area and the mediobasal hypothalamic arcuate nucleus independently generate ultradian rhythms (URs) in hormone secretion and behavior. We evaluated the hypothesis that destruction of arcuate nucleus (ARC) neurons, in concert with dampening of suprachiasmatic nucleus (SCN) circadian rhythmicity, would compromize the generation of ultradian rhythms (URs) of locomotor activity. Siberian hamsters retain-->of both sexes treated neonatally with monosodium glutamate (MSG) that destroys ARC neurons were subjected in adulthood to a circadian disrupting phase-shift protocol (DPS) that produces SCN arrhythmia. MSG treatments induced hypogonadism and obesity, retain-->and markedly reduced the size of the optic chiasm and optic nerves. MSG-treated hamsters exhibited normal entrainment to the light-dark cycle, but MSG treatretain-->ment counteracted the circadian arrhythmicity induced by the DPS protocol: only 6% of retain-->MSG-treated hamsters exhibited circadian arrhythmia, whereas 50% of control hamsters were circadian disrupted. In MSG-treated hamsters that retained circadian rhythmicity after DPS treatment, quantitative parameters of URs appeared normal, but in the two MSG-treated hamsters that became circadian arrhythmic after DPS, both dark-phase and light-phase URs were abolished. Although preliminary, these data are consistent with reports in voles suggesting that the combined disruption of SCN and ARC function impairs the expression of behavioral URs. The data also suggest that light thresholds for entrainment of circadian rhythms may be lower than those required to disrupt circadian organization. PMID:23701725

  16. The efficacy of topical ivermectin versus malation 0.5% lotion for the treatment of scabies.

    PubMed

    Goldust, Mohamad; Rezaee, Elham

    2013-05-01

    Objective: There are different medications for the treatment of scabies but the treatment of choice is still controversial. This study aimed at comparing the efficacy of topical ivermectin versus malation 0.5% lotion for the treatment of scabies. Methods: In total, 340 patients with scabies were enrolled, and randomized into two groups: the first group received 1% ivermectin applied topically to the affected skin and the second group received topical malation 0.5% lotion and were told to apply this twice with 1 week interval. Treatment was evaluated at intervals of 2 and 4 weeks, and if there was treatment failure at the 2-week follow-up, treatment was repeated. Results: Two application of topical ivermectin provided a cure rate of 67.6% at the 2-week follow-up, which increased to 85.2% at the 4-week follow-up after repeating the treatment. Treatment with two applications of malation 0.5% lotion was effective in 44.1% of patients at the 2-week follow-up, which increased to 67.6% at the 4-week follow-up after this treatment was repeated. Conclusion:Two application of ivermectin was as effective as single applications of malation 0.5% lotion at the 2-week follow-up. After repeating the treatment, ivermectin was superior to malation 0.5% lotion at the 4-week follow up. PMID:23472617

  17. A comparative study of the therapeutic effect of dithranol cream 0.1% and 0.25% with that of dithranol stylus 0.1% and 0.2% in the treatment of psoriasis.

    PubMed

    Gisslèn, H; Nordin, P

    1983-01-01

    In Dithranol cream the oily phase is emulsified with an aqueous phase to make the preparation more convenient to apply. The cream also contains ascorbic acid as an antioxidant, which protects dithranol against atmospheric oxidation, thus increasing its stability. A stylus containing dithranol, ol. cacao, paraffin and vaselinum has been used as a comparative drug. The stylus is routinely used in this clinic. Sixty patients with stable psoriasis were pre-assigned into two treatment groups, receiving at random Dithranol cream 0.1%, 0.25% and Dithranol stylus 0.1%, 0.2%, respectively. Both groups started their treatment with the 0.1% preparation once a day for 2 weeks followed by the 0.2% or 0.25% preparations once a day for another 2 weeks. The following laboratory tests: Hb, WBC, Diff, S-ALAT, S-ASAT and S-creatinine were recorded before and after treatment. Staining of clothes was none to slight in 70% (21/30) of the patients using Dithranol stylus 0.2%, and 80% (24/30) in the patients using Dithranol cream 0.25%. The sensation of burning was none to slight in 83% (25/30) of the patients and skin discolouration was none to slight in approximately 80% (24/30) of the patients using the Dithranol stylus 0.2% and Dithranol cream 0.25% preparations. Both groups showed significant improvement in all effect-variables after 2 and 4 weeks' treatment compared to initial. The results are over all better after 4 weeks' treatment than after 2. No abnormal values due to dithranol treatment could be found in the laboratory tests. PMID:6832465

  18. Treatment of Bacterial Vaginosis: A Multicenter, Double-Blind, Double-Dummy, Randomised Phase III Study Comparing Secnidazole and Metronidazole

    PubMed Central

    Bohbot, Jean-Marc; Vicaut, Eric; Fagnen, Didier; Brauman, Michel

    2010-01-01

    Objective. Multiple-dose metronidazole oral therapy is currently the reference treatment for bacterial vaginosis (BV). This double-blind, double-dummy, noninferiority study compared the efficacy of secnidazole, another nitroimidazole with pharmacokinetics allowing a single dose regimen, to this standard treatment. Methods. A total of 577 patients were randomized to receive metronidazole (500 mg, b.i.d for seven days) or secnidazole (2 g, once). Therapeutic cure at D28 was defined as the resolution of vaginal discharge, positive KOH whiff test, vaginal pH >4.5 and Nugent score >7 on Gram-stained vaginal fluid. Results. According to this primary endpoint, the single-dose secnidazole regimen was shown to be at least as effective as the multiple-dose metronidazole regimen (60.1 % cured women vs 59.5% , 95% confidence interval with a noninferiority margin of 10%: [−0.082; 0.0094]). Safety profiles were comparable in both groups. Conclusion. The secnidazole regimen studied represents an effective, convenient therapeutic alternative that clinicians should consider in routine practice. PMID:20885970

  19. New sorbent in the dispersive solid phase extraction step of quick, easy, cheap, effective, rugged, and safe for the extraction of organic contaminants in drinking water treatment sludge.

    PubMed

    Cerqueira, Maristela B R; Caldas, Sergiane S; Primel, Ednei G

    2014-04-01

    Recent studies have shown a decrease in the concentration of pesticides, pharmaceuticals and personal care products (PCPs) in water after treatment. A possible explanation for this phenomenon is that these compounds may adhere to the sludge; however, investigation of these compounds in drinking water treatment sludge has been scarce. The sludge generated by drinking water treatment plants during flocculation and decantation steps should get some special attention not only because it has been classified as non-inert waste but also because it is a very complex matrix, consisting essentially of inorganic (sand, argil and silt) and organic (humic substances) compounds. In the first step of this study, three QuEChERS methods were used, and then compared, for the extraction of pesticides (atrazine, simazine, clomazone and tebuconazole), pharmaceuticals (amitriptyline, caffeine, diclofenac and ibuprofen) and PCPs (methylparaben, propylparaben, triclocarban and bisphenol A) from drinking water treatment sludge. Afterwards, the study of different sorbents in the dispersive solid phase extraction (d-SPE) step was evaluated. Finally, a new QuEChERS method employing chitin, obtained from shrimp shell waste, was performed in the d-SPE step. After having been optimized, the method showed limits of quantification (LOQ) between 1 and 50 μg kg(-1) and the analytical curves showed r values higher than 0.98, when liquid chromatography tandem mass spectrometry was employed. Recoveries ranged between 50 and 120% with RSD≤15%. The matrix effect was evaluated and compensated with matrix-matched calibration. The method was applied to drinking water treatment sludge samples and methylparaben and tebuconazole were found in concentration

  20. Phase I dose-finding study of sorafenib with FOLFOX4 as first-line treatment in patients with unresectable locally advanced or metastatic gastric cancer

    PubMed Central

    Chi, Yihebali; Yang, Jianliang; Yang, Sheng; Sun, Yongkun; Jia, Bo

    2015-01-01

    Objective To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and efficacy of sorafenib in combination with FOLFOX4 (oxaliplatin/leucovorin (LV)/5-fluorouracil) as first-line treatment for advanced gastric cancer, we performed a phase I dose-finding study in nine evaluable patients with unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. Methods According to modified Fibonacci method, the design of this study was to guide elevation of the sorafenib dosage to the next level (from 200 mg twice daily to 400 mg twice daily and then, if tolerated, 600 mg twice daily). If the patient achieved complete response (CR), partial response (PR) or stable disease (SD) after eight cycles of treatment, combination chemotherapy was scheduled to be discontinued and sorafenib monotherapy continued at the original dose until either disease progression or unacceptable toxicity. Results In sorafenib 200 mg twice daily group, DLT was observed in 1 of 6 patients, and in 400 mg twice daily group, it was observed in 2 of 3 patients. Seven of 9 (77.8%) evaluable patients achieved PR, with a median overall survival (OS) of 11.8 [95% confidence interval (CI): 8.9-14.7] months. Common adverse effects include hand-foot syndrome, leukopenia, neutropenia, anorexia, and nausea. Conclusions Twice-daily dosing of sorafenib 200 mg in combination with FOLFOX4 was proven effective and safe for the treatment of advanced gastric cancer, and could be an appropriate dosage for subsequent phase II clinical studies. PMID:26157320

  1. Hypericum treatment of mild depressions with somatic symptoms.

    PubMed

    Hübner, W D; Lande, S; Podzuweit, H

    1994-10-01

    In a randomized, placebo-controlled, double-blind study, 39 patients with depression with somatic symptoms were treated with hypericum extract LI 160. The therapy lasted for 4 weeks; the dosage was 300 mg three times daily. At the onset of the study as well as after 2 and 4 weeks, the following criteria were analyzed: HAMD, B-L, CGI, and vegetative symptoms. The results show a significant improvement in the active treatment group at the 5% level as compared to placebo. Seventy percent of the patients treated with LI 160 were free of symptoms after 4 weeks. Typical symptoms of the depression such as lack of activity, tiredness, fatigue, and disturbed sleep, were especially responsive. In no case were any undesirable side effects observed. PMID:7857500

  2. Effects of randomized supplementation of methionine or alanine on cysteine and glutathione production during the early phase of treatment of children with edematous malnutrition123

    PubMed Central

    Green, Curtis O; Hsu, Jean W; Taylor-Bryan, Carolyn; Reid, Marvin; Forrester, Terrence; Jahoor, Farook

    2014-01-01

    Background: We have shown that a low glutathione concentration and synthesis rate in erythrocytes are associated with a shortage of protein-derived cysteine in children with edematous severe acute malnutrition (SAM). Objective: We tested the hypothesis that methionine supplementation may increase protein-derived cysteine and upregulate cysteine synthesis, thereby improving glutathione synthesis during the early treatment of edematous SAM. Design: The cysteine flux, its de novo synthesis and release from protein breakdown, and erythrocyte glutathione synthesis rate were measured in 12 children with edematous SAM in the fed state by using stable isotope tracers at 3 clinical phases as follows: 3 ± 1 d (±SE) [clinical phase 1 (CP1)], 8 ± 1 d [clinical phase 2 (CP2)], and 14 ± 2 d (clinical phase 3) after admission. Subjects were randomly assigned to receive equimolar supplements (0.5 mmol ⋅ kg−1 ⋅ d−1) of methionine or alanine (control) immediately after CP1. Results: In the methionine compared with the alanine group, cysteine flux derived from protein breakdown was faster at CP2 than CP1 (P < 0.05), and the change in plasma cysteine concentration from CP1 to CP2 was greater (P < 0.05). However, there was no evidence of a difference in cysteine de novo synthesis and its total flux or erythrocyte glutathione synthesis rate and concentration between groups. Conclusions: Methionine supplementation increased cysteine flux from body protein but had no significant effect on glutathione synthesis rates. Although cysteine is made from methionine, increased dietary cysteine may be necessary to partially fulfill its demand in edematous SAM because glutathione synthesis rates and concentrations were less than previous values shown at full recovery. This study was registered at clinicaltrials.gov as NCT00473031. PMID:24598154

  3. A randomized, placebo-controlled phase III trial of masitinib plus gemcitabine in the treatment of advanced pancreatic cancer

    PubMed Central

    Deplanque, G.; Demarchi, M.; Hebbar, M.; Flynn, P.; Melichar, B.; Atkins, J.; Nowara, E.; Moyé, L.; Piquemal, D.; Ritter, D.; Dubreuil, P.; Mansfield, C. D.; Acin, Y.; Moussy, A.; Hermine, O.; Hammel, P.

    2015-01-01

    Background Masitinib is a selective oral tyrosine–kinase inhibitor. The efficacy and safety of masitinib combined with gemcitabine was compared against single-agent gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDAC). Patients and methods Patients with inoperable, chemotherapy-naïve, PDAC were randomized (1 : 1) to receive gemcitabine (1000 mg/m2) in combination with either masitinib (9 mg/kg/day) or a placebo. The primary endpoint was overall survival (OS) in the modified intent-to-treat population. Secondary OS analyses aimed to characterize subgroups with poor survival while receiving single-agent gemcitabine with subsequent evaluation of masitinib therapeutic benefit. These prospectively declared subgroups were based on pharmacogenomic data or a baseline characteristic. Results Three hundred and fifty-three patients were randomly assigned to receive either masitinib plus gemcitabine (N = 175) or placebo plus gemcitabine (N = 178). Median OS was similar between treatment-arms for the overall population, at respectively, 7.7 and 7.1 months, with a hazard ratio (HR) of 0.89 (95% CI [0.70; 1.13]. Secondary analyses identified two subgroups having a significantly poor survival rate when receiving single-agent gemcitabine; one defined by an overexpression of acyl–CoA oxidase-1 (ACOX1) in blood, and another via a baseline pain intensity threshold (VAS > 20 mm). These subgroups represent a critical unmet medical need as evidenced from median OS of 5.5 months in patients receiving single-agent gemcitabine, and comprise an estimated 63% of patients. A significant treatment effect was observed in these subgroups for masitinib with median OS of 11.7 months in the ‘ACOX1’ subgroup [HR = 0.23 (0.10; 0.51), P = 0.001], and 8.0 months in the ‘pain’ subgroup [HR = 0.62 (0.43; 0.89), P = 0.012]. Despite an increased toxicity of the combination as compared with single-agent gemcitabine, side-effects remained manageable. Conclusions The

  4. High-temperature forced-air treatment alters the quantity of flavor-related, volatile constituents present in navel and Valencia oranges.

    PubMed

    Obenland, D M; Arpaia, M L; Austin, R K; MacKey, B E

    1999-12-01

    A number of volatile compounds that contribute to orange flavor were quantified following high-temperature forced-air (HTFA) treatment of the fruit to determine if a relationship exists between the flavor loss that is observed following HTFA treatment and the volatile composition of the juice. Following different durations of HTFA treatment, fruit were stored for a period of 4 weeks and juiced and the juice subjected to headspace analysis using either a Tenax/Carbotrap column or a solid-phase microextraction device for trapping of the volatiles. alpha-Pinene, beta-myrcene, and limonene were reduced in amount by 60%, 58%, and 34%, respectively, over the course of the 5-h HTFA treatment. The influence of heat on the amount of decanal was less clear, although in one of the two fruit lots there was little change. The amount of ethanol was reduced by 70% after the initial hour of HTFA treatment and then steadily increased to exceed the initial amount during the remaining 4 h of the treatment. Taste evaluations of the fruit showed a reduction of flavor quality following 4 h or more of treatment. Percent acidity and soluble solids, two other very important determinants of flavor, were nearly unchanged by treatment. Alterations in the volatile constituents of oranges by HTFA treatment may be an important reason behind the negative impact of this treatment on flavor quality. PMID:10606592

  5. Magnetoliposomes prepared by reverse-phase followed by sequential extrusion: characterization and possibilities in the treatment of inflammation.

    PubMed

    García-Jimeno, Sonia; Escribano, Elvira; Queralt, Josep; Estelrich, Joan

    2011-02-28

    Anionic ferrofluid was encapsulated in 200nm-diameter liposomes. The process involved phase-reverse evaporation followed by sequential extrusion. Magnetoliposomes were characterized by transmission electron microscopy, Doppler laser electrophoresis, SQUID magnetometry, dynamic light scattering and iron content by atomic absorption spectrophotometry. The absence of hysteresis of the magnetic power of particles at room temperature is characteristic of a material with superparamagnetic properties. The encapsulation efficiency was determined for several iron/phospholipid ratios, and this parameter ranged from 0.016 to 0.024mg iron per mmole of phospholipids, depending on the initial magnetite concentration. In comparison with magnetoliposomes that were obtained solely by extrusion, this method afforded significantly better encapsulation (P=0.0002). Magnetic particles were intravenously administered to healthy or inflammation-induced mice. After 1h, the content of iron was determined in exudates, liver, spleen and plasma. Magnetoliposomes accumulated in the exudates collected from the inflammation site, which suggests that these particles could be loaded with the drugs needed to treat some inflammatory processes. PMID:21129463

  6. Quantification of synthetic organic chemicals in biological treatment process effluent using solid-phase microextraction and gas chromatography

    SciTech Connect

    Magbanua, B.S. Jr.; Mitchell, D.R.; Fehniger, S.M.; Bowyer, R.L.; Grady, C.P.L. Jr.

    2000-02-01

    Solid-phase microextraction (SPME), a technique that uses a polymer-coated, fused-silica fiber to selectively extract organic analyses from a sample matrix, followed by gas chromatography (GC), was used to quantify selected synthetic organic chemicals (SOCs) in biological reactor effluent. By selecting an appropriate combination of SPME fiber, GC column, and GC detector, assays to quantify either a suite of SOCs or single selected SOCs were developed. Phenol, 4-chlorophenol, 2-nitrophenol, 4-nitrophenol, 2,4,-dinitrophenol, isophorone, m-toluate, m-sylene, and di-n-butylphthalate were quantified simultaneously using an 85-{micro}m polyacrylate SPME fiber, a 5% diphenyl-95% dimethyl polysiloxane capillary column, and a flame ionization detector. m-Xylene was quantified using a 100-{micro}m polydimethylsiloxane SPME fiber, a 5% diphenyl-95% dimethyl polysiloxane capillary column, and a mass spectrometric detector. Dichloromethane was quantified using an 85-{micro}m polyacrylate SPME fiber, a Carbopack B/1% SP-1000 packed column, and an electron capture detector. All three assays enabled detection of the target analyses to low concentrations ({micro}g/L) with minimal sample volume and processing requirements.

  7. Effect of thermal treatment on the nano-structure and phase transformation of metakaolin-based geopolymers.

    PubMed

    Kim, Yongsung; Kang, Seunggu

    2014-11-01

    Enhancement of the mechanical strength of metakaolin-based geopolymers activated with NaOH was attempted by calcining metakaolin at a higher temperature than that commonly reported. Increasing the calcination temperature from 750 degrees C to 1150 degrees C promoted the recrystallization of mullite. Two type of zeolite of sodium aluminum silicate hydrates were found in the geopolymers made of metakaolin calcined at 750 degrees C-1050 degrees C. The h-zeolite [Na6(AlSiO4)6 x H2O] was not found in the geopolymer made of metakaolin calcined above 900 degrees C, while Z-zeolite [Na2O x Al2O3 x SiO2 x H2O] remained in specimens calcined at up to 1050 degrees C, All zeolite disappeared above 1150 degrees C. The pozzolanic reaction generates very small particles of 10-30 nm on the surface of metakaolin grains of 0.2-0.6 μm, rendering the matrix denser by binding the grains. The maximum compressive strength was revealed with the geopolymer made of metakaolin calcined at 1050 degrees C. The reason for the increased strength of the geopolymer obtained using higher calcination temperature is thought to be the combined effects of matrix hardening by geopolymeric reaction and reinforcement by mullite crystal phases. PMID:25958625

  8. Delay in commencing treatment for MDR TB at a specialised TB treatment centre in KwaZulu-Natal.

    PubMed

    Narasimooloo, R; Ross, A

    2012-06-01

    Background. According to the National Department of Health (NDoH) guidelines, patients diagnosed with MDR TB must be referred to a specialised treatment centre for initiation of effective therapy. MDR TB is difficult to diagnose and the centralised referral model is beset with challenges that contribute to treatment delays, increased patient morbidity and mortality, and MDR TB nosocomial transmission. Culture and DST takes 8 weeks or longer to obtain results while line probe assays (LPAs) can give a result in hours. LPAs and the GeneXpert MTB/Rif (GX) are ground-breaking discoveries for TB diagnosis. However, they are not easily accessible or available to those needing it, so culture and sensitivity testing remains the gold standard for diagnosis. Aim. This study aimed to assess the delay in the initiation of MDR TB treatment and profiled the patients being referred to a specialised drug-resistant treatment centre in KwaZulu-Natal. Results. Of all the patients, 75% referred showed a mean delay of 12.4 weeks from the date of sputum collection for culture and drug sensitivity testing to the start of treatment. Most of the patients were symptomatic for TB and HIV-positive. Discussion. Our findings suggest that current policy on the initiation of effective treatment needs urgent revision. Staff should be appropriately trained in LPA and GX technology to reduce delays in initiating treatment for MDR TB. The NDoH's plans for rapid diagnosis and reducing the treatment burden on centralised MDR TB management facilities are in the early phases of implementation and will take years to achieve favourable and significant outcomes. Conclusion. There is a significant delay in initiating definitive management for MDR TB. PMID:22668906

  9. Comparison of permethrin 2.5 % cream vs. Tenutex emulsion for the treatment of scabies.

    PubMed

    Goldust, Mohamad; Rezaee, Elham; Raghifar, Ramin; Naghavi-Behzad, Mohammad

    2013-01-01

    Scabies is a common parasitic infestation that is an important public-health problem in many resource-poor regions. It is commonly treated with the insecticides but the treatment of choice is still controversial. This study aimed at comparing the efficacy of permethrin 2.5% cream vs. Tenutex emulsion for the treatment of scabies. In total, 440 patients with scabies were enrolled, and randomized into two groups The first group received permethrin 2.5% cream twice with one week interval and the second group received Tenutex emulsion and were told to apply this once whole-body application. Treatment was evaluated at intervals of 2 and 4 weeks, and if there was treatment failure at the 2-week follow-up, treatment was repeated.Two application of permethrin 2.5% cream provided a cure rate of 63.6% at the 2-week follow-up, which increased to 86.3% at the 4-week follow-up after repeating the treatment. Treatment with single applications of Tenutex emulsion was effective in 45.4% of patients at the 2-week follow-up, which increased to 59.1% at the 4-week follow-up after this treatment was repeated.Two application of permethrin 2.5% cream was as effective as single applications of Tenutex emulsion at the 2-week follow-up. After repeating the treatment, permethrin 2.5% cream was superior to Tenutex emulsion at the 4-week follow up. PMID:23829056

  10. A two-phased screening paradigm for evaluating candidate medications for cocaine cessation or relapse prevention: Modafinil, levodopa-carbidopa, naltrexone

    PubMed Central

    Schmitz, Joy M.; Green, Charles E.; Stotts, Angela L.; Lindsay, Jan A.; Rathnayaka, Nuvan S.; Grabowski, John; Moeller, F. G.

    2014-01-01

    Background Cocaine pharmacotherapy trials are often confounded by considerable variability in baseline cocaine-use levels, obscuring possible medication efficacy. Testing the feasibility of using a prerandomization, abstinence-induction protocol, we screened three candidate medications to explore treatment response in patients who did, or did not, achieve abstinence during an extended baseline phase. Method Eligible treatment-seeking, cocaine-dependent subjects entered a 4-week baseline period (Phase I) with high-value abstinence contingent vouchers and two motivational interviewing sessions, followed by a 12-week medication trial (Phase II) with random assignment stratified on Phase I abstinence status to (1) modafinil (400mg/d), (2) levodopa/carbidopa (800/200mg/d), (3) naltrexone (50mg/d), or (4) placebo. Treatment consisted of thrice-weekly clinic visits for urine benzoylecgonine testing and weekly cognitive behavioral therapy with contingency management targeting medication compliance. Results Of the 118 subjects enrolled, 81 (80%) completed Phase I, with 33 (41%) achieving abstinence, defined a priori as 6 consecutive cocaine-negative urines. Tests of the interaction of each medication (active vs. placebo) by baseline status (abstinent vs. nonabstinent) permitted moderator effect analysis. Overall, baseline abstinence predicted better outcome. Cocaine-use outcomes for levodopa and naltrexone treatment differed as a function of Phase I abstinence status, with both medications producing benefit in nonabstinent but not baseline-abstinent subjects. There was no evidence of a moderator effect for modafinil. Conclusions The two-phase screening trial demonstrated that subgrouping of patients with respect to baseline abstinence status is feasible and clinically useful for exploring cocaine cessation and relapse-prevention effects of candidate medications. PMID:24424425

  11. Sustained release of isoniazid from polylactide microspheres prepared using solid/oil drug loading method for tuberculosis treatment.

    PubMed

    Zhang, Limei; Li, Ying; Zhang, Yun; Zhu, Chunyan

    2016-07-01

    Polylactide (PLA) microspheres were prepared using the solid-in-oil (S/O) spray-drying method to achieve the sustained release of a hydrophilic drug for the treatment of tuberculosis, via intratracheal instillation. Isoniazid (IN), a low-molecular-weight hydrophilic drug, was used as a model drug. The effects of various sizes of micronized IN powder, different drug/polymer ratios, spray-drying process parameters, and drug-release characteristics were studied to optimize the manufacturing parameters. A high entrapment efficiency (87.3%) was obtained using this method; furthermore, the microspheres were spherical and smooth. They were individually and homogenously distributed, with a mean diameter of 5.6 μm; furthermore, they showed a satisfactory extended sustained-release phase. After administration of the microspheres to rats, pulmonary drug concentrations were maintained at a relatively stable level for up to 4 weeks. PMID:27278371

  12. Potential application of sludge produced from coal mine drainage treatment for removing Zn(II) in an aqueous phase.

    PubMed

    Cui, Mingcan; Jang, Min; Cho, Sang-Hyun; Khim, Jeehyeong

    2011-01-01

    Various analyses of physico-chemical characteristics and batch tests were conducted with the sludge obtained from a full-scale electrolysis facility for treating coal mine drainage in order to find the applicability of sludge as a material for removing Zn(II) in an aqueous phase. The physico-chemical analysis results indicated that coal mine drainage sludge (CMDS) had a high specific surface area and also satisfied the standard of toxicity characteristic leaching procedure (TCLP) because the extracted concentrations of certain toxic elements such as Pb, Cu, As, Hg, Zn, and Ni were much less than their regulatory limits. The results of X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) showed that the CMDS mainly consists of goethite (70%) and calcite (30%) as a weight basis. However, the zeta potential analysis represented that the CMDS had a lower isoelectric point of pH (pH(IEP)) than that of goethite or calcite. This might have been caused by the complexation of negatively charged anions, especially sulfate, which usually exists with a high concentration in coal mine drainage. The results of Fourier transform infrared (FT-IR) spectrometry analysis revealed that Zn(II) was dominantly removed as a form of precipitation by calcite, such as smithsonite [ZnCO₃] or hydrozincite [Zn₅(CO₃)₂(OH)₆]. Recycling sludge, originally a waste material, for the removal process of Zn(II), as well as other heavy metals, could be beneficial due to its high and speedy removal capability and low economic costs. PMID:21063752

  13. Phase II study of accelerated fractionation radiation therapy with carboplatin followed by vincristine chemotherapy for the treatment of glioblastoma multiforme

    SciTech Connect

    Levin, V.A.; Yung, W.K.A.; Kyritsis, A.P.

    1995-09-30

    The purpose of this investigation was to conduct a Phase II one-arm study to evaluate the long-term efficacy and safety of accelerated fractionated radiotherapy combined with intravenous carboplatin for patients with previously untreated glioblastoma multiforme tumors. Between 1988 and 1992, 83 patients received 1.9-2.0 Gy radiation three times a day with 2-h infusions of 33 mg/m{sup 2} carboplatin for two 5-day cycles separated by 2 weeks. Seventy-four of the 83 patients (89%) received one or more courses of PCV; their median survival was 55 weeks. Total resection was performed in 20% (15 of 74), subtotal resection in 69% (51 or 74), and biospy in 11% (8 of 74); reoperation (total or subtotal resection) was performed in 28 patients (37%). Survival was worst for those {ge} 61 year old (median 35 weeks). Fits of the Cox proportional hazards regression model showed covariated individually predictive of improved survival were younger age (p <0.01), smaller log of radiation volume (p = 0.008), total or subtotal resection vs. biopsy (p = 0.056), and higher Karnofsky performance status (p = 0.055). A multivariate analysis showed that age (p = 0.013) and extent of initial surgery (p = 0.003) together were predictive of a better survival with no other variables providing additional significance. Only 8.4% (7 of 83) of patients had clinically documented therapy-associated neurotoxicity ({open_quotes}radiation necrosis{close_quotes}). When comparable selection criteria were applied, the survival in this study is similar to the results currently attainable with other chemoradiation approaches. The relative safety of accelerated fractionated radiotherapy, as used in this study with carboplatin, enables concomitant full-dose administration of chemotherapy or radiosensitizing agents in glioblastoma multiforme patients. 42 refs., 3 figs., 5 tabs.

  14. Extended phase-correlated rescanning irradiation to improve dose homogeneity in carbon-ion beam liver treatment

    NASA Astrophysics Data System (ADS)

    Ogata, Risa; Mori, Shinichiro; Yasuda, Shigeo

    2014-09-01

    We previously reported that an adequate number of simple layered phase-correlated rescanning (PCR) irradiations improve dose conformation to a moving target. However, if PCR is not completed within a single gating window due to the particular irradiation specifications selected in advance and/or layer size, the iso-energy layer is completed using next gating window, and the effect of rescanning is effectively nullified. To solve this problem, we developed extended PCR irradiation. Extended PCR is conceptually based on simple PCR. It differs in that the dose rate is adjusted to irradiate the number of rescans within multiple gating windows when simple PCR is not finished within a single gating window. This process is repeated until the total prescribed dose is given. Here, 4DCT imaging was performed under free-breathing conditions in 10 patients with hepatocellular carcinoma. 4D dose distributions for a single field approach were performed with simple PCR and extended PCR using 4DCT. A total dose of 11.25 Gy(RBE) was administered to the field-specific target volume. The number of rescans was changed from 1 to 10. Respiratory gating of a 30% duty cycle around exhalation was applied. Dose assessment metrics (CTV-D95, CTV-Dmin, CTV-Dmax) with PCR improved with an increasing number of rescans, and largely plateaued at five or more rescans. Minimum D95 and Dmin values, and maximum Dmax and HI values fluctuated at odd and even numbers of rescans. Extended PCR improved all dose assessment metrics whereas PCR did not. Values with extended PCR were mostly constant with three or more rescans, or in other words independent of the number of rescans. Extended PCR improved dose conformation to a moving target with greater efficacy than simple PCR when more than two gating windows were necessary. Extended PCR can be applied to irradiation machines having a low maximum dose rate.

  15. Treatment of nasopharyngeal carcinoma using simultaneous modulated accelerated radiation therapy via helical tomotherapy: a phase II study

    PubMed Central

    Du, Lei; Zhang, Xin Xin; Feng, Lin Chun; Chen, Jing; Yang, Jun; Liu, Hai Xia; Xu, Shou Ping; Xie, Chuan Bin

    2016-01-01

    Abstract Background The aim of the study was to evaluate short-term safety and efficacy of simultaneous modulated accelerated radiation therapy (SMART) delivered via helical tomotherapy in patients with nasopharyngeal carcinoma (NPC). Methods Between August 2011 and September 2013, 132 newly diagnosed NPC patients were enrolled for a prospective phase II study. The prescription doses delivered to the gross tumor volume (pGTVnx) and positive lymph nodes (pGTVnd), the high risk planning target volume (PTV1), and the low risk planning target volume (PTV2), were 67.5 Gy (2.25 Gy/F), 60 Gy (2.0 Gy/F), and 54 Gy (1.8 Gy/F), in 30 fractions, respectively. Acute toxicities were evaluated according to the established RTOG/EORTC criteria. This group of patients was compared with the 190 patients in the retrospective P70 study, who were treated between September 2004 and August 2009 with helical tomotherapy, with a dose of 70-74 Gy/33F/6.5W delivered to pGTVnx and pGTVnd. Results The median follow-up was 23.7 (12–38) months. Acute radiation related side-effects were mainly problems graded as 1 or 2. Only a small number of patients suffered from grade 4 leucopenia (4.5%) or thrombocytopenia (2.3%). The local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), local-nodal relapse-free survival (LNRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.7%, 95.5%, 92.2%, 92.7% and 93.2%, at 2 years, respectively, with no significant difference compared with the P70 study. Conclusions Smart delivered via the helical tomotherapy technique appears to be associated with an acceptable acute toxicity profile and favorable short-term outcomes for patients with NPC. Long-term toxicities and patient outcomes are under investigation. PMID:27247555

  16. Long Term Field Development of a Surfactant Modified Zeolite/Vapor Phase Bioreactor System for Treatment of Produced Waters for Power Generation

    SciTech Connect

    Lynn Katz; Kerry Kinney; Robert Bowman; Enid Sullivan; Soondong Kwon; Elaine Darby; Li-Jung Chen; Craig Altare

    2007-12-31

    The main goal of this research was to investigate the feasibility of using a combined physicochemical/biological treatment system to remove the organic constituents present in saline produced water. In order to meet this objective, a physical/chemical adsorption process was developed and two separate biological treatment techniques were investigated. Two previous research projects focused on the development of the surfactant modified zeolite adsorption process (DE-AC26-99BC15221) and development of a vapor phase biofilter (VPB) to treat the regeneration off-gas from the surfactant modified zeolite (SMZ) adsorption system (DE-FC26-02NT15461). In this research, the SMZ/VPB was modified to more effectively attenuate peak loads and to maintain stable biodegradation of the BTEX constituents from the produced water. Specifically, a load equalization system was incorporated into the regeneration flow stream. In addition, a membrane bioreactor (MBR) system was tested for its ability to simultaneously remove the aromatic hydrocarbon and carboxylate components from produced water. The specific objectives related to these efforts included the following: (1) Optimize the performance VPBs treating the transient loading expected during SMZ regeneration: (a) Evaluate the impact of biofilter operating parameters on process performance under stable operating conditions. (b) Investigate how transient loads affect biofilter performance, and identify an appropriate technology to improve biological treatment performance during the transient regeneration period of an SMZ adsorption system. (c) Examine the merits of a load equalization technology to attenuate peak VOC loads prior to a VPB system. (d) Evaluate the capability of an SMZ/VPB to remove BTEX from produced water in a field trial. (2) Investigate the feasibility of MBR treatment of produced water: (a) Evaluate the biodegradation of carboxylates and BTEX constituents from synthetic produced water in a laboratory-scale MBR. (b

  17. Treatment of olive-mill wastewater from a two-phase process by chemical oxidation on an industrial scale.

    PubMed

    Nieto, L M; Hodaifa, G; Vives, S R; Casares, J A G; Driss, S B; Grueso, R

    2009-01-01

    This study offers a solution for reducing the environmental effect of wastewaters generated by the olive-oil industry. Olive-oil companies produce variable quantities of wastewaters, which require treatment for disposal or reuse. Today, regulations are becoming increasingly strict regarding the parameters measured in these effluents. In Spain, the resolution by the president of the Hydrographical Confederation of the Guadalquivir on water use 2004 set parameter limits as follows: pH = 6.0-9.0, total suspended solid = 500 mg/L; and COD and BOD(5) (20)=1,500 mg O(2)/L. For the year 2006, maximum values for COD and BOD(5) (20) were fixed at 1,000 mg O(2)/L. To solve this problem, a study has been made to derive irrigation water from the above-mentioned effluents through chemical oxidation based on the Fenton's process. This would be first step towards using a closed-circuit system in olive-oil mills to treat and reuse effluents. PMID:19474497

  18. Cost-effectiveness of Tyrosine Kinase Inhibitor Treatment Strategies for Chronic Myeloid Leukemia in Chronic Phase After Generic Entry of Imatinib in the United States

    PubMed Central

    Padula, William V.; Larson, Richard A.; Dusetzina, Stacie B.; Apperley, Jane F.; Hehlmann, Rudiger; Baccarani, Michele; Eigendorff, Ekkehard; Guilhot, Joelle; Guilhot, Francois; Hehlmann, Rudiger; Mahon, Francois-Xavier; Martinelli, Giovanni; Mayer, Jiri; Müller, Martin C.; Niederwieser, Dietger; Saussele, Susanne; Schiffer, Charles A.; Silver, Richard T.; Simonsson, Bengt

    2016-01-01

    Background: We analyzed the cost-effectiveness of treating incident chronic myeloid leukemia in chronic phase (CML-CP) with generic imatinib when it becomes available in United States in 2016. In the year following generic entry, imatinib’s price is expected to drop 70% to 90%. We hypothesized that initiating treatment with generic imatinib in these patients and then switching to the other tyrosine-kinase inhibitors (TKIs), dasatinib or nilotinib, because of intolerance or lack of effectiveness (“imatinib-first”) would be cost-effective compared with the current standard of care: “physicians’ choice” of initiating treatment with any one of the three TKIs. Methods: We constructed Markov models to compare the five-year cost-effectiveness of imatinib-first vs physician’s choice from a US commercial payer perspective, assuming 3% annual discounting ($US 2013). The models’ clinical endpoint was five-year overall survival taken from a systematic review of clinical trial results. Per-person spending on incident CML-CP treatment overall care components was estimated using Truven’s MarketScan claims data. The main outcome of the models was cost per quality-adjusted life-year (QALY). We interpreted outcomes based on a willingness-to-pay threshold of $100 000/QALY. A panel of European LeukemiaNet experts oversaw the study’s conduct. Results: Both strategies met the threshold. Imatinib-first ($277 401, 3.87 QALYs) offered patients a 0.10 decrement in QALYs at a savings of $88 343 over five years to payers compared with physician’s choice ($365 744, 3.97 QALYs). The imatinib-first incremental cost-effectiveness ratio was approximately $883 730/QALY. The results were robust to multiple sensitivity analyses. Conclusion: When imatinib loses patent protection and its price declines, its use will be the cost-effective initial treatment strategy for CML-CP. PMID:26944912

  19. Cost-effectiveness of Tyrosine Kinase Inhibitor Treatment Strategies for Chronic Myeloid Leukemia in Chronic Phase After Generic Entry of Imatinib in the United States

    PubMed Central

    Padula, William V.; Larson, Richard A.; Dusetzina, Stacie B.; Apperley, Jane F.; Hehlmann, Rudiger; Baccarani, Michele; Eigendorff, Ekkehard; Guilhot, Joelle; Guilhot, Francois; Hehlmann, Rudiger; Mahon, Francois-Xavier; Martinelli, Giovanni; Mayer, Jiri; Müller, Martin C.; Niederwieser, Dietger; Saussele, Susanne; Schiffer, Charles A.; Silver, Richard T.; Simonsson, Bengt

    2016-01-01

    Background: We analyzed the cost-effectiveness of treating incident chronic myeloid leukemia in chronic phase (CML-CP) with generic imatinib when it becomes available in United States in 2016. In the year following generic entry, imatinib’s price is expected to drop 70% to 90%. We hypothesized that initiating treatment with generic imatinib in these patients and then switching to the other tyrosine-kinase inhibitors (TKIs), dasatinib or nilotinib, because of intolerance or lack of effectiveness (“imatinib-first”) would be cost-effective compared with the current standard of care: “physicians’ choice” of initiating treatment with any one of the three TKIs. Methods: We constructed Markov models to compare the five-year cost-effectiveness of imatinib-first vs physician’s choice from a US commercial payer perspective, assuming 3% annual discounting ($US 2013). The models’ clinical endpoint was five-year overall survival taken from a systematic review of clinical trial results. Per-person spending on incident CML-CP treatment overall care components was estimated using Truven’s MarketScan claims data. The main outcome of the models was cost per quality-adjusted life-year (QALY). We interpreted outcomes based on a willingness-to-pay threshold of $100 000/QALY. A panel of European LeukemiaNet experts oversaw the study’s conduct. Results: Both strategies met the threshold. Imatinib-first ($277 401, 3.87 QALYs) offered patients a 0.10 decrement in QALYs at a savings of $88 343 over five years to payers compared with physician’s choice ($365 744, 3.97 QALYs). The imatinib-first incremental cost-effectiveness ratio was approximately $883 730/QALY. The results were robust to multiple sensitivity analyses. Conclusion: When imatinib loses patent protection and its price declines, its use will be the cost-effective initial treatment strategy for CML-CP.

  20. A Phase II Study of High-Dose-Rate Afterloading Brachytherapy as Monotherapy for the Treatment of Localized Prostate Cancer

    SciTech Connect

    Corner, Carie Rojas, Ana Maria; Bryant, Linda; Ostler, Peter; Hoskin, Peter

    2008-10-01

    Purpose: A Phase II dose escalation study has been undertaken to evaluate high-dose-rate brachytherapy (HDRBT) monotherapy for prostate cancer. Methods and Materials: A total of 110 patients have been entered, all with locally advanced cancer. Three dose levels have been used; 34 Gy in four fractions, 36 Gy in four fractions, and 31.5 Gy in three fractions. These equate to 226Gy{sub 1.5}, 252Gy{sub 1.5}, and 252Gy{sub 1.5}, respectively. Thirty patients have received 34 Gy, 25 received 36 Gy, and 55 patients received 31.5 Gy. Acute and late toxicity was analyzed using the International Prostate Symptom Score, and urologic and rectal events were scored using the Radiation Therapy Oncology Group/Common Terminology Criteria scoring systems. Results: Seven patients required urethral catheterization at 2 weeks; 3 receiving 34 Gy, 1 receiving 36 Gy, and 3 receiving 31.5 Gy. Only 3 patients remained catheterized at 12 weeks. Radiation Therapy Oncology Group 1 and 2 gastrointestinal toxicity at 2 weeks was seen in 61%, 68%, and 77%, respectively. Grade 3 bladder toxicity was seen in 2 patients at 6 months, 1 each from the 36 Gy and 31.5 Gy arms. One patient from the 31.5-Gy cohort reported Grade 2 bowel toxicity at 6 months. Prostate-specific antigen (PSA), stratified for androgen deprivation therapy (ADT) and no-ADT patients ranged from 16.1-22.9 {mu}g/L and 11.1-12.5 {mu}g/L, respectively. This fell at 12 months to 0.2-0.6 {mu}g/L and 0.5-1.4 {mu}g/L, respectively. No PSA relapses have yet been seen with a median follow-up of 30 months (34 Gy), 18 months (36 Gy), and 11.8 months (31.5 Gy). Conclusions: Early results suggest an excellent biochemical response with no differences seen in acute and late toxicity between doses of 34 Gy/four fractions, 36 Gy/four fractions, or 31.5 Gy/three fractions.

  1. Alcohol consumption and colon cancer prognosis among participants in north central cancer treatment group phase III trial N0147.

    PubMed

    Phipps, Amanda I; Shi, Qian; Limburg, Paul J; Nelson, Garth D; Sargent, Daniel J; Sinicrope, Frank A; Chan, Emily; Gill, Sharlene; Goldberg, Richard M; Kahlenberg, Morton; Nair, Suresh; Shields, Anthony F; Newcomb, Polly A; Alberts, Steven R

    2016-09-01

    Alcohol consumption is associated with a modest increased risk of colon cancer, but its relationship with colon cancer survival has not been elucidated. Using data from a phase III randomized adjuvant trial, we assessed the association of alcohol consumption with colon cancer outcomes. Patients completed a risk factor questionnaire before randomization to FOLFOX or FOLFOX + cetuximab (N = 1984). Information was collected on lifestyle factors, including smoking, physical activity and consumption of different types of alcohol. Cox models assessed the association between alcohol consumption and outcomes of disease-free survival (DFS), time-to-recurrence (TTR) and overall survival (OS), adjusting for age, sex, study arm, body mass, smoking, physical activity and performance status. No statistically significant difference in outcomes between ever and never drinkers were noted [hazard ratio (HR)DFS  = 0.86, HRTTR  = 0.87, HROS  = 0.86, p-values = 0.11-0.17]. However, when considering alcohol type, ever consumers of red wine (n = 628) had significantly better outcomes than never consumers (HRDFS  = 0.80, HRTTR  = 0.81, HROS  = 0.78, p-values = 0.01-0.02). Favorable outcomes were confirmed in patients who consumed 1-30 glasses/month of red wine (n = 601, HR = 0.80-0.83, p-values = 0.03-0.049); there was a suggestion of more favorable outcomes in patients who consumed >30 glasses/month of red wine (n = 27, HR = 0.33-0.38, p-values = 0.05-0.06). Beer and liquor consumption were not associated with outcomes. Although alcohol consumption was not associated with colon cancer outcomes overall, mild to moderate red wine consumption was suggestively associated with longer OS, DFS and TTR in stage III colon cancer patients. PMID:27060850

  2. Phase I Trial of Vertebral Intracavitary Cement and Samarium (VICS): Novel Technique for Treatment of Painful Vertebral Metastasis

    SciTech Connect

    Ashamalla, Hani; Cardoso, Erico; Macedon, Mark; Guirguis, Adel; Weng Lijun; Ali, Shamsah; Mokhtar, Bahaa; Ashamalla, Michael; Panigrahi, Nokul

    2009-11-01

    Purpose: Kyphoplasty is an effective procedure to alleviate pain in vertebral metastases. However, it has no proven anticancer activity. Samarium-153-ethylene diamine tetramethylene phosphonate ({sup 153}Sm-EDTMP) is used for palliative treatment of bone metastases. A standard dose of 1 mCi/kg is administrated intravenously. The present study was conducted to determine the feasibility of intravertebral administration of {sup 153}Sm with kyphoplasty. Methods and Materials: A total of 33 procedures were performed in 26 patients. Of these 26 patients, 7 underwent procedures performed at two vertebral levels. The mean age of the cohort was 64 years (range, 33-86). The kyphoplasty procedure was performed using a known protocol; 1-4 mCi of {sup 153}Sm was admixed with the bone cement and administered under tight radiation safety measures. Serial nuclear body scans were obtained. Pain assessment was evaluated using a visual analog pain score. Results: All patients tolerated the procedure well. No procedure-related morbidities were noted. No significant change had occurred in the blood counts at 1 month after the procedure. One case was not technically satisfactory. Nuclear scans revealed clear radiotracer uptake in the other 32 vertebrae injected. Except for the first patient, no radiation leakage was encountered. The mean pain score using the visual analog scale improved from 8.6 before to 2.8 after the procedure (p < .0001). Follow-up bone scans demonstrated a 43% decrease in the tracer uptake. Conclusion: The results of our study have shown that the combination of intravertebral administration of {sup 153}Sm and kyphoplasty is well tolerated with adequate pain control. No hematologic adverse effects were found. A reduction of the bone scan tracer uptake was observed in the injected vertebrae. Longer follow-up is needed to study the antineoplastic effect of the procedure.

  3. Microbial Community Dynamics of an Urban Drinking Water Distribution System Subjected to Phases of Chloramination and Chlorination Treatments

    PubMed Central

    Hwang, Chiachi; Ling, Fangqiong; Andersen, Gary L.; LeChevallier, Mark W.

    2012-01-01

    Water utilities in parts of the U.S. control microbial regrowth in drinking water distribution systems (DWDS) by alternating postdisinfection methods between chlorination and chloramination. To examine how this strategy influences drinking water microbial communities, an urban DWDS (population ≅ 40,000) with groundwater as the source water was studied for approximately 2 years. Water samples were collected at five locations in the network at different seasons and analyzed for their chemical and physical characteristics and for their microbial community composition and structure by examining the 16S rRNA gene via terminal restriction fragment length polymorphism and DNA pyrosequencing technology. Nonmetric multidimension scaling and canonical correspondence analysis of microbial community profiles could explain >57% of the variation. Clustering of samples based on disinfection types (free chlorine versus combined chlorine) and sampling time was observed to correlate to the shifts in microbial communities. Sampling location and water age (<21.2 h) had no apparent effects on the microbial compositions of samples from most time points. Microbial community analysis revealed that among major core populations, Cyanobacteria, Methylobacteriaceae, Sphingomonadaceae, and Xanthomonadaceae were more abundant in chlorinated water, and Methylophilaceae, Methylococcaceae, and Pseudomonadaceae were more abundant in chloraminated water. No correlation was observed with minor populations that were detected frequently (<0.1% of total pyrosequences), which were likely present in source water and survived through the treatment process. Transient microbial populations including Flavobacteriaceae and Clostridiaceae were also observed. Overall, reversible shifts in microbial communities were especially pronounced with chloramination, suggesting stronger selection of microbial populations from chloramines than chlorine. PMID:22941076

  4. A phase II study of AZD2171 (cediranib) in the treatment of patients with acute myeloid leukemia or high-risk myelodysplastic syndrome

    PubMed Central

    Mattison, Ryan; Jumonville, Alcee; Flynn, Patrick James; Moreno-Aspitia, Alvaro; Erlichman, Charles; Laplant, Betsy; Juckett, Mark B.

    2015-01-01

    Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) not fit for intensive treatment need novel therapy options. Vascular endothelial growth factor (VEGF) receptor inhibition is one potential mechanism by which AML and MDS could be treated. The receptor tyrosine kinase inhibitor AZD2171 (cediranib) has activity against VEGF receptors KDR and FLT-1. This multicenter phase II study was designed to test cediranib's activity in patients with AML or high-risk MDS. The primary endpoint was confirmed disease response defined