WorldWideScience

Sample records for methotrexate cumulative dose

  1. Methotrexate osteopathy in long-term, low-dose methotrexate treatment for psoriasis and rheumatoid arthritis

    NARCIS (Netherlands)

    Zonneveld, I. M.; Bakker, W. K.; Dijkstra, P. F.; Bos, J. D.; van Soesbergen, R. M.; Dinant, H. J.

    1996-01-01

    In dermatology and rheumatology, methotrexate is frequently prescribed in low dosages per week; in oncology, high dosages per week are prescribed. Methotrexate osteopathy was first reported in children with leukemia treated with high doses of methotrexate. In animal studies, low doses of

  2. Failure Rate of Single Dose Methotrexate in Managment of Ectopic Pregnancy

    Directory of Open Access Journals (Sweden)

    Feras Sendy

    2015-01-01

    Full Text Available Background. One of the treatment modalities for ectopic pregnancy is methotrexate. The purpose of this study is to identify the failure rate of methotrexate in treating patients with ectopic pregnancy as well as the risk factors leading to treatment failure. Methods. A retrospective chart review of 225 patients who received methotrexate as a primary management option for ectopic pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG level less than or equal to 14% in the seventh day after administration of methotrexate. Results. 225 patients had methotrexate. Most of the patients (151 (67% received methotrexate based on the following formula: f 50 mg X body surface area. Single dose of methotrexate was successful in 72% (162/225 of the patients. 28% (63/225 were labeled as failure of single dose of methotrexate because of suboptimal drop in BhCG. 63% (40/63 of failure received a second dose of methotrexate, and 37% (23/63 underwent surgical treatment. Among patient who received initial dose of methotrexate, 71% had moderate or severe pain, and 58% had ectopic mass size of more than 4 cm on ultrasound. Conclusion. Liberal use of medical treatment of ectopic pregnancy results in 71% success rate.

  3. Failure rate of single dose methotrexate in managment of ectopic pregnancy.

    Science.gov (United States)

    Sendy, Feras; AlShehri, Eman; AlAjmi, Amani; Bamanie, Elham; Appani, Surekha; Shams, Taghreed

    2015-01-01

    Background. One of the treatment modalities for ectopic pregnancy is methotrexate. The purpose of this study is to identify the failure rate of methotrexate in treating patients with ectopic pregnancy as well as the risk factors leading to treatment failure. Methods. A retrospective chart review of 225 patients who received methotrexate as a primary management option for ectopic pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG level less than or equal to 14% in the seventh day after administration of methotrexate. Results. 225 patients had methotrexate. Most of the patients (151 (67%)) received methotrexate based on the following formula: f 50 mg X body surface area. Single dose of methotrexate was successful in 72% (162/225) of the patients. 28% (63/225) were labeled as failure of single dose of methotrexate because of suboptimal drop in BhCG. 63% (40/63) of failure received a second dose of methotrexate, and 37% (23/63) underwent surgical treatment. Among patient who received initial dose of methotrexate, 71% had moderate or severe pain, and 58% had ectopic mass size of more than 4 cm on ultrasound. Conclusion. Liberal use of medical treatment of ectopic pregnancy results in 71% success rate.

  4. Methotrexate

    Science.gov (United States)

    ... lymphoma, and leukemia (cancer that begins in the white blood cells). Methotrexate is in a class of ... In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has ...

  5. Uncommon toxicity of low-dose methotrexate: case report

    Directory of Open Access Journals (Sweden)

    Zohreh Yousefi

    2015-10-01

    Full Text Available Background: Standard treatment of Gestational Trophoblastic Disease (GTD is chemotherapy. Single-agent chemotherapy regime including Methotrexate (MTX or Actinomycin. Single-agent is widely used in treatment of persistent trophoblastic disease. We reported an uncommon toxicity of low-dose single-agent methotrexate in a patient. Case Presentation: A 20-year-old woman, primary gravid after two months missed period and spotting with diagnosis of incomplete abortion with uterine size equivalent of ten weeks pregnancy (8-10 cm underwent evacuation curettage. In serial follow-up, based on rise of beta-hCG titer and absence of metastatic disease, it was categorized as low-risk persistent trophoblastic disease. She was referred to gynecology oncology center of Ghaem Hospital, Mashhad University of Medical Sciences in May 2014. Because of rise of beta-hCG titer, after complete metastatic work-up and lack of disease in other sites, persistent disease was diagnosed and candidate for chemotherapy (single agent low-dose. The patient received first course of therapy with MTX (50 mg/m², intra muscular. Unfortunately, after two days of treatment she developed uncommon severe toxicity, fever, severe nausea and vomiting, tachycardia, and generalized weakness. Also, we found hematologic abnormality (WBC: -14000-15000 µI, platelet- 540 µI and sever neutropenia, and abnormal rising in liver function test (SGOT, SGPT (three to four times and renal function test (BUN and Creatinine (two times. In addition, she had disseminated erosive lesion in all of body especially in face. Due to the fatal side effects of chemotherapy, she was admitted to intensive care unit (ICU. Fortunately, after two to three weeks, she was improved by conservative management. After few weeks beta-hCG titer was in normal limit. However she had normal serial beta-hCG in one year of follow-up. Conclusion: It is important to emphasis unpredictable side effects of chemotherapy with low-dose

  6. Intraocular levels of methotrexate after oral low-dose treatment in chronic uveitis.

    Science.gov (United States)

    Puchta, Joachim; Hattenbach, Lars-Olof; Baatz, Holger

    2005-01-01

    To determine the intraocular levels of methotrexate in low-dose treatment of noninfectious uveitis. One day after oral administration, the methotrexate level was measured in the aqueous humor and serum of a patient with noninfectious uveitis, who underwent cataract surgery. A fluorescence polarization immunoassay was used for determination. After oral administration, methotrexate was only measurable in aqueous humor but not in serum. In uveitis, orally administered low-dose methotrexate reaches detectable levels in aqueous humor, even in the absence of detectable levels in serum. Copyright (c) 2005 S. Karger AG, Basel.

  7. Serum Creatinine Versus Plasma Methotrexate Levels to Predict Toxicities in Children Receiving High-dose Methotrexate.

    Science.gov (United States)

    Tiwari, Priya; Thomas, M K; Pathania, Subha; Dhawan, Deepa; Gupta, Y K; Vishnubhatla, Sreenivas; Bakhshi, Sameer

    2015-01-01

    Facilities for measuring methotrexate (MTX) levels are not available everywhere, potentially limiting administration of high-dose methotrexate (HDMTX). We hypothesized that serum creatinine alteration after HDMTX administration predicts MTX clearance. Overall, 122 cycles in 50 patients of non-Hodgkin lymphoma or acute lymphoblastic leukemia aged ≤18 years receiving HDMTX were enrolled prospectively. Plasma MTX levels were measured at 12, 24, 36, 48, 60, and 72 hours; serum creatinine was measured at baseline, 24, 48, and 72 hours. Correlation of plasma MTX levels with creatinine levels and changes in creatinine from baseline (Δ creatinine) were evaluated. Plasma MTX levels at 72 hours showed positive correlation with serum creatinine at 48 hours (P = .011) and 72 hours (P = .013) as also Δ creatinine at 48 hours (P = .042) and 72 hours (P = .045). However, cut-off value of either creatinine or Δ creatinine could not be established to reliably predict delayed MTX clearance. Greater than 50% Δ creatinine at 48 and 72 hours significantly predicted grade 3/4 leucopenia (P = .036 and P = .001, respectively) and thrombocytopenia (P = .012 and P = .009, respectively) but not mucositis (P = .827 and P = .910, respectively). Delayed MTX elimination did not predict any grade 3/4 toxicity. In spite of demonstration of significant correlation between serum creatinine and Δ creatinine with plasma MTX levels at 72 hours, cut-off value of either variable to predict MTX delay could not be established. Thus, either of these cannot be used as a surrogate for plasma MTX estimation. Interestingly, Δ creatinine effectively predicted hematological toxicities, which were not predicted by delayed MTX clearance.

  8. adverse effects of low dose methotrexate in rheumatoid arthritis patients

    International Nuclear Information System (INIS)

    Gilani, S.T.; Khan, D.A.; Khan, F.A.; Ahmed, M.

    2012-01-01

    To determine the frequency of adverse effects attributed to Methotrexate (MTX) toxicity and serum minimum toxic concentration with low dose MTX in Rheumatoid Arthritis (RA) patients. Study Design: Cross-sectional observational study. Place and Duration of Study: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from March 2010 to March 2011. Methodology: One hundred and forty adult patients of RA receiving low dose MTX (10 mg/week) for at least 3 months, ere included by consecutive sampling. Blood samples were collected 2 hours after the oral dose of MTX. Serum alanine transaminase and creatinine were analyzed on Hitachi and blood counts on Sysmex analyzer. Serum MTX concentration was measured on TDX analyzer. Results: Out of one hundred and forty patients; 68 males (49%) and 72 females (51%), 38 developed MTX toxicity (27%), comprising of hepatotoxicity in 12 (8.6%), nephrotoxicity in 3 (2.1%), anaemia in 8 (5.7%), leucopenia in 2 (1.4%), thrombocytopenia in 3 (2.1%), pancytopenia in 2 (1.4%), gastrointestinal adverse effects in 5 (3.6%) and mucocutaneous problems in 3 (2.1%). Receiver operating characteristic curve revealed serum minimum toxic concentration of MTX at cutoff value of 0.71 mu mol/l with a sensitivity of 71% and specificity of 76%. Conclusion: Adverse effects of low dose MTX were found in 27% of RA patients, mainly comprising of hepatotoxicity and haematological problems. MTX toxicity can be detected by therapeutic drug monitoring of serum concentration of 0.71 mu mol/l with sensitivity of 71% and specificity of 76% in the patients on low dose MTX maintenance therapy. (author)

  9. Cumulative radiation dose of multiple trauma patients during their hospitalization

    International Nuclear Information System (INIS)

    Wang Zhikang; Sun Jianzhong; Zhao Zudan

    2012-01-01

    Objective: To study the cumulative radiation dose of multiple trauma patients during their hospitalization and to analyze the dose influence factors. Methods: The DLP for CT and DR were retrospectively collected from the patients during June, 2009 and April, 2011 at a university affiliated hospital. The cumulative radiation doses were calculated by summing typical effective doses of the anatomic regions scanned. Results: The cumulative radiation doses of 113 patients were collected. The maximum,minimum and the mean values of cumulative effective doses were 153.3, 16.48 mSv and (52.3 ± 26.6) mSv. Conclusions: Multiple trauma patients have high cumulative radiation exposure. Therefore, the management of cumulative radiation doses should be enhanced. To establish the individualized radiation exposure archives will be helpful for the clinicians and technicians to make decision whether to image again and how to select the imaging parameters. (authors)

  10. Pancytopenia after low dose methotrexate therapy in a hemodialysis patient: case report and review of literature.

    Science.gov (United States)

    Yang, Ching-Ping; Kuo, Mei-Chuan; Guh, Jinn-Yuh; Chen, Hung-Chun

    2006-01-01

    Methotrexate (MTX) is widely used in the treatment of rheumatoid arthritis (RA) with a side effect of pancytopenia. However, only a few cases of severe pancytopenia caused by low-dose MTX therapy have been reported, and the condition is rarely reported in uremic patients on dialysis therapy. We thereby report a hemodialysis patient who developed severe pancytopenia after oral treatment with low-dose MTX for RA. A 55-year-old woman who had been on regular hemodialysis treatment for 7 yr suffered from RA for 10 yr. She was regularly treated with celecoxib, prednisolone, and sulfasalazine in the past year. Because of the increasing arthralgia, 7.5 mg per week MTX was prescribed 3 months before admission. Stomatitis, fever, general fatigue, multiple skin carbuncles, and easy bruising developed after a cumulative dose of 90 mg. Pancytopenia was found at admission and the nadir of white blood cell count was 250/microL with 28% neutrophils, hematocrit was 22%, and platelet count was 6000/microL. Eosinophil counts increased from 11.5% initially to 26.1% on the sixth admission day. Transfusion with red blood cells and platelets, and appropriate antibiotics and folic acid were prescribed. She continued receiving regular hemodialysis and eventually recovered within 3 weeks.

  11. EFFICACY OF LOW-DOSE METHOTREXATE TREATMENT IN BIRDSHOT CHORIORETINOPATHY

    NARCIS (Netherlands)

    Rothova, Aniki; Ossewaarde-van Norel, Annette; Los, Leonoor I.; Berendschot, Tos T. J. M.

    Purpose: To ascertain the effect of treatment with methotrexate (MTX) on the visual prognosis of birdshot chorioretinopathy (BSCR). Methods: Retrospective case series of 76 consecutive patients with HLA-A29-positive BSCR, of whom 46 were followed for at least 5 years and 18 for longer than 10 years.

  12. Bioavailability of higher dose methotrexate comparing oral and subcutaneous administration in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Hoekstra, Monique; Haagsma, C.; Neef, C; Proost, Johannes H; Knuif, A.; van der Laar, M.

    Objective. To determine the bioavailability of higher oral doses of methotrexate (MTX) in adult patients with rheumatoid arthritis (RA). Methods. A pharmacokinetic analysis was performed in 15 patients with RA taking a stable dose of MTX (greater than or equal to25 mg weekly). Separated by 2 weeks,

  13. Fractional model for pharmacokinetics of high dose methotrexate in children with acute lymphoblastic leukaemia

    Science.gov (United States)

    Popović, Jovan K.; Spasić, Dragan T.; Tošić, Jela; Kolarović, Jovanka L.; Malti, Rachid; Mitić, Igor M.; Pilipović, Stevan; Atanacković, Teodor M.

    2015-05-01

    The aim of this study is to promote a model based on the fractional differential calculus related to the pharmacokinetic individualization of high dose methotrexate treatment in children with acute lymphoblastic leukaemia, especially in high risk patients. We applied two-compartment fractional model on 8 selected cases with the largest number (4-19) of measured concentrations, among 43 pediatric patients received 24-h methotrexate 2-5 g/m2 infusions. The plasma concentrations were determined by fluorescence polarization immunoassay. Our mathematical procedure, designed by combining Post's and Newton's method, was coded in Mathematica 8.0 and performed on Fujicu Celsius M470-2 PC. Experimental data show that most of the measured values of methotrexate were in decreasing order. However, in certain treatments local maximums were detected. On the other hand, integer order compartmental models do not give values which fit well with the observed data. By the use of our model, we obtained better results, since it gives more accurate behavior of the transmission, as well as the local maximums which were recognized in methotrexate monitoring. It follows from our method that an additional test with a small methotrexate dose can be suggested for the fractional system parameter identification and the prediction of a possible pattern with a full dose in the case of high risk patients. A special feature of the fractional model is that it can also recognize and better fit an observed non-monotonic behavior. A new parameter determination procedure can be successfully used.

  14. [Effect of IV hydration with sodium bicarbonate on high-dose methotrexate disposition kinetics].

    Science.gov (United States)

    Tsuda, N; Goto, M; Konishi, H; Yamashina, H

    1984-04-01

    Following two-compartment kinetic analysis, the effect of loading of transfusion with sodium bicarbonate on methotrexate disposition was investigated in 13 cases with malignant tumor, being treated with high-dose methotrexate. The mean values of total body clearance, when administered at doses 50 mg and 100 mg per kg body weight, were 0.369 and 0.402 (l/h) per kg, respectively. No significant relationship was observed between alpha value and total amount of transfusion, of urine or dosage of sodium bicarbonate. The other kinetic parameters on elimination, beta value, K10 and total body clearance, did not also correlate with those values described above. These results suggest that the elimination profile of methotrexate show linear kinetics, and that massive administration of transfusion with sodium bicarbonate be not necessary if pH value of urine exceeds 7.0.

  15. CAN INITIAL βHCG VALUES PREDICT THE NEED FOR SECOND DOSE OF METHOTREXATE IN MEDICAL MANAGEMENT OF ECTOPIC PREGNANCY?

    Directory of Open Access Journals (Sweden)

    Priya Narayanan

    2016-09-01

    Full Text Available INTRODUCTION Prediction of requirement of second dose of methotrexate in patients treated with single dose would help in guiding treatment and counseling. The aim of this study is to determine whether pretreatment beta HCG values can predict the need for second dose of methotrexate in medically managed ectopic pregnancy. MATERIALS AND METHODS 46 women with ectopic pregnancies who were managed medically were included. The median of beta HCG titres on day 1, day 4 and day 7 was assessed in patients who responded to single dose methotrexate and those who required a second dose. RESULTS Out of the 46 patients studied, 41 responded to medical treatment (success 91%. 14 out of 41 required second dose of methotrexate (34%. Two patients required third dose of methotrexate. Five patients required surgery. DISCUSSION The median of day 1 and day 4 beta HCG values were not statistically different between those who responded to single dose methotrexate and those who required a second dose. Only day 7 values were found to be different. CONCLUSION The beta-hCG titre on day 1 and day 4 is not a predictor of requirement of second dose of methotrexate.

  16. Methotrexate Associated Renal Impairment Is Related to Delayed Elimination of High-Dose Methotrexate

    Directory of Open Access Journals (Sweden)

    Shi-Long Yang

    2015-01-01

    Full Text Available Although Methotrexate (MTX is an effective drug for the treatment of acute lymphoblastic leukemia (ALL, the toxicity remains a significant problem. In this prospective study, fifty-four patients with ALL were enrolled. 3 g or 5 g MTX/m2 was administered over 24 hours. Serum MTX concentrations were determined in 24, 48, and 96 hours after MTX infusion. Serum creatinine concentrations and creatinine clearance rate (CCR were determined before and 24 and 48 hours after MTX infusion. A total of 173 courses of MTX infusion were administered. The serum creatinine concentrations did not change much after MTX infusion while the CCR was gradually decreased. MTX clearance status was independently related to CCR decrease, with the risk of 8.07 to develop renal impairment in patients with delayed MTX elimination. Serum creatinine concentration, serum creatinine ratio, CCR, and CCR ratio at 24 hours were all related to MTX elimination delay. Patients with serum creatinine level >35.0 μmol/L, creatinine ratio >1.129, or CCR <100.0 mL/min were more likely to undergo MTX elimination delay. In conclusion, MTX could induce transient renal impairment and compromised renal function will delay MTX clearance. The serum creatinine concentration and the ratio and CCR are useful tools for evaluating MTX elimination status.

  17. Extended duration of prehydration does not prevent nephrotoxicity or delayed drug elimination in high-dose methotrexate infusions

    DEFF Research Database (Denmark)

    Mikkelsen, Torben Stamm; Mamoudou, Aissata Diop; Tuckuviene, Ruta

    2014-01-01

    Alkalized hydration is used as supportive care to prevent renal toxicity during infusions with high-dose methotrexate (HDMTX). In children with acute lymphoblastic leukemia (ALL), the hydration is commonly initiated 4 hours before start of the methotrexate (MTX) infusion. To test if longer durati...

  18. Consensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance

    DEFF Research Database (Denmark)

    Ramsey, Laura B; Balis, Frank M; O'Brien, Maureen M

    2018-01-01

    Acute kidney injury due to high-dose methotrexate (HDMTX) is a serious, life-threatening toxicity that can occur in pediatric and adult patients. Glucarpidase is a treatment approved by the Food and Drug Administration for high methotrexate concentrations in the context of kidney dysfunction...... is above 30 µM, 42-hour concentration is above 10 µM, or 48-hour concentration is above 5 µM and the serum creatinine is significantly elevated relative to the baseline measurement (indicative of HDMTX-induced acute kidney injury), glucarpidase may be indicated. After a 36- to 42-hour HDMTX infusion......: Glucarpidase is a rarely used medication that is less effective when given after more than 60 hours of exposure to high-dose methotrexate, so predicting early which patients will need it is imperative. There are no currently available consensus guidelines for the use of this medication. The indication...

  19. High-dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma.

    Science.gov (United States)

    Akiyama, Hiroki; Takase, Hiroshi; Kubo, Fumito; Miki, Tohru; Yamamoto, Masahide; Tomita, Makoto; Mochizuki, Manabu; Miura, Osamu; Arai, Ayako

    2016-10-01

    In order to prevent central nervous system (CNS) involvement and improve the prognosis of primary intraocular lymphoma (PIOL), we prospectively evaluated the efficacy of combined therapy using intravitreal methotrexate (MTX) and systemic high-dose MTX on treatment-naïve PIOL. Patients with newly diagnosed PIOL whose lymphoma was limited to the eyes were enrolled. The patients were treated with weekly intravitreal MTX until the ocular lesions were resolved, followed by five cycles of systemic high-dose MTX (3.5 g/m 2 ) every other week. Ten patients were enrolled in this study and completed the treatment. All patients achieved complete response for their ocular lesions with rapid decrease of intravitreal interleukin-10 concentration. Adverse events of intravitreal and systemic high-dose MTX were mild and tolerable. With a median follow-up of 29.5 months, four patients (40%) experienced the CNS disease development and the mean CNS lymphoma-free survival (CLFS) time was 51.1 months. Two-year CLFS, which was the primary end-point of the study, was 58.3% (95% confidence interval, 23.0-82.1%). In contrast, eight patients were treated with intravitreal MTX alone in our institute, and their 2-year CLFS was 37.5% (95% confidence interval, 8.7-67.4%). In conclusion, systemic high-dose MTX following intravitreal MTX is feasible and might be effective in preventing CNS involvement of PIOL. Further arrangements are worth considering in order to improve the effects. This study was registered with UMIN Clinical Trials Registry (UMIN000003921). © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  20. Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study

    International Nuclear Information System (INIS)

    Phillips, P.C.; Dhawan, V.; Strother, S.C.; Sidtis, J.J.; Evans, A.C.; Allen, J.C.; Rottenberg, D.A.

    1987-01-01

    Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for 82 Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity

  1. Influence of pre-hydration and pharmacogenetics on plasma methotrexate concentration and renal dysfunction following high-dose methotrexate therapy.

    Science.gov (United States)

    Yanagimachi, Masakatsu; Goto, Hiroaki; Kaneko, Tetsuji; Naruto, Takuya; Sasaki, Koji; Takeuchi, Masanobu; Tanoshima, Reo; Kato, Hiromi; Yokosuka, Tomoko; Kajiwara, Ryosuke; Fujii, Hisaki; Tanaka, Fumiko; Goto, Shoko; Takahashi, Hiroyuki; Mori, Masaaki; Kai, Sumio; Yokota, Shumpei

    2013-12-01

    High-dose methotrexate therapy (HD-MTX) has been well established for the treatment of childhood acute lymphoblastic leukemia (ALL). The aims of this study were to investigate whether clinical and pharmacogenetic factors influence plasma MTX concentration and renal dysfunction in patients treated with HD-MTX. In a total of 127 courses of HD-MTX in 51 patients with childhood ALL, influence of clinical and pharmacogenetic factors on plasma MTX concentration and HD-MTX-related renal dysfunction was evaluated. Clinical factors included age, gender, duration of HD-MTX continuous-infusion and duration of pre-hydration before HD-MTX. Pharmacogenetic factors included 5 gene polymorphisms within the MTX pathway genes, namely, SLC19A1, MTHFR, ABCC2 and ABCG2. Short duration of pre-hydration before HD-MTX is the most important risk factor for prolonged high MTX concentration (p < 0.001, OR 6.40, 95 % CI 2.39-17.16) and renal dysfunction (p = 0.013, OR 3.15, 95 % CI 1.27-7.80). The T allele at MTHFR C677T was the risk factor for prolonged high MTX concentration (p = 0.009, OR 5.54, 95 % CI 1.54-19.85), but not for renal dysfunction. We found the influence of MTHFR C677T polymorphism on prolonged high MTX concentration. We reconfirmed the importance of adequate pre-hydration before HD-MTX to prevent prolonged high MTX concentration and MTX-related renal dysfunction.

  2. Technical Note: SCUDA: A software platform for cumulative dose assessment

    Energy Technology Data Exchange (ETDEWEB)

    Park, Seyoun; McNutt, Todd; Quon, Harry; Wong, John; Lee, Junghoon, E-mail: rshekhar@childrensnational.org, E-mail: junghoon@jhu.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland 21231 (United States); Plishker, William [IGI Technologies, Inc., College Park, Maryland 20742 (United States); Shekhar, Raj, E-mail: rshekhar@childrensnational.org, E-mail: junghoon@jhu.edu [IGI Technologies, Inc., College Park, Maryland 20742 and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Health System, Washington, DC 20010 (United States)

    2016-10-15

    Purpose: Accurate tracking of anatomical changes and computation of actually delivered dose to the patient are critical for successful adaptive radiation therapy (ART). Additionally, efficient data management and fast processing are practically important for the adoption in clinic as ART involves a large amount of image and treatment data. The purpose of this study was to develop an accurate and efficient Software platform for CUmulative Dose Assessment (SCUDA) that can be seamlessly integrated into the clinical workflow. Methods: SCUDA consists of deformable image registration (DIR), segmentation, dose computation modules, and a graphical user interface. It is connected to our image PACS and radiotherapy informatics databases from which it automatically queries/retrieves patient images, radiotherapy plan, beam data, and daily treatment information, thus providing an efficient and unified workflow. For accurate registration of the planning CT and daily CBCTs, the authors iteratively correct CBCT intensities by matching local intensity histograms during the DIR process. Contours of the target tumor and critical structures are then propagated from the planning CT to daily CBCTs using the computed deformations. The actual delivered daily dose is computed using the registered CT and patient setup information by a superposition/convolution algorithm, and accumulated using the computed deformation fields. Both DIR and dose computation modules are accelerated by a graphics processing unit. Results: The cumulative dose computation process has been validated on 30 head and neck (HN) cancer cases, showing 3.5 ± 5.0 Gy (mean±STD) absolute mean dose differences between the planned and the actually delivered doses in the parotid glands. On average, DIR, dose computation, and segmentation take 20 s/fraction and 17 min for a 35-fraction treatment including additional computation for dose accumulation. Conclusions: The authors developed a unified software platform that provides

  3. Mercaptopurine metabolite levels are predictors of bone marrow toxicity following high-dose methotrexate therapy of childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Vang, Sophia Ingeborg; Schmiegelow, Kjeld; Frandsen, Thomas

    2015-01-01

    High-dose methotrexate (HD-MTX) courses with concurrent oral low-dose MTX/6-mercaptopurine (6MP) for childhood acute lymphoblastic leukaemia (ALL) are often followed by neutro- and thrombocytopenia necessitating treatment interruptions. Plasma MTX during HD-MTX therapy guides folinic acid rescue ...

  4. Bioavailibility of higher dose methotrexate comparing oral and subcutaneous route of administration in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Hoekstra, Monique; Hoekstra, M.; Haagsma, Cees; Neef, Cees; Proost, Johannes; van de Laar, Mart A F J; Knuif, Antonius

    2004-01-01

    OBJECTIVE: To determine the bioavailability of higher oral doses of methotrexate (MTX) in adult patients with rheumatoid arthritis (RA). METHODS: A pharmacokinetic analysis was performed in 15 patients with RA taking a stable dose of MTX (> or = 25 mg weekly). Separated by 2 weeks, a pharmacokinetic

  5. Population PK/PD model of homocysteine concentrations after high-dose methotrexate treatment in patients with acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Hauke Rühs

    Full Text Available Elevated homocysteine concentrations have been associated with methotrexate-induced neurotoxicity. Based on methotrexate and homocysteine plasma concentrations of 494 children with acute lymphoblastic leukemia treated with high-dose methotrexate in the TOTAL XV study, a pharmacokinetic/pharmacodynamic (PK/PD model was built with NONMEM. Several compartment and indirect response models were investigated. The pharmacokinetic disposition of methotrexate was best described by a two-compartment model. Homocysteine concentrations were included by an indirect response model where methotrexate inhibition of the homocysteine elimination rate was described by an E(max model. The homocysteine baseline level was found to be age-dependent. Simulations revealed that folinate rescue therapy does not affect peak concentrations of homocysteine but leads to a modestly reduced homocysteine exposure. In conclusion, our PK/PD model describes the increase of methotrexate-induced HCY concentrations with satisfactory precision and can be applied to assess the effect of folinate regimens on the HCY concentration-time course.

  6. Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by background methotrexate dose group.

    Science.gov (United States)

    Fleischmann, R; Mease, P J; Schwartzman, S; Hwang, L-J; Soma, K; Connell, C A; Takiya, L; Bananis, E

    2017-01-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This post hoc analysis investigated the effect of methotrexate (MTX) dose on the efficacy of tofacitinib in patients with RA. ORAL Scan (NCT00847613) was a 2-year, randomized, Phase 3 trial evaluating tofacitinib in MTX-inadequate responder (IR) patients with RA. Patients received tofacitinib 5 or 10 mg twice daily (BID), or placebo, with low (≤12.5 mg/week), moderate (>12.5 to tofacitinib 5 mg BID (N = 321), tofacitinib 10 mg BID (N = 316), or placebo (N = 160); 242, 333, and 222 patients received low, moderate, and high MTX doses, respectively. At months 3 and 6, ACR20/50/70 response rates were greater for both tofacitinib doses vs placebo across all MTX doses. At month 3, mean changes from baseline in CDAI and HAQ-DI were significantly greater for both tofacitinib doses vs placebo, irrespective of MTX category; improvements were maintained at month 6. Both tofacitinib doses demonstrated improvements in DAS28-4(ESR), and less structural progression vs placebo, across MTX doses at month 6. Tofacitinib plus MTX showed greater clinical and radiographic efficacy than placebo in MTX-IR patients with RA, regardless of MTX dose.

  7. Prophylactic CNS therapy in childhood leukemia. Randomized controlled study of high-dose intravenous methotrexate and cranial irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, Takashi; Hiyoshi, Yasuhiko [Kurume Univ., Fukuoka (Japan). School of Medicine; Fujimoto, Takeo

    1982-12-01

    This study was designed to evaluate the efficacy of CNS-prophylaxis with high-dose methotrexate (MTX). Seventy children with previously untreated acute lymphoblastic leukemia (ALL) entered to this study between July 1978 and December 1980. According to initial white blood count (WBC), they were stratified to induce remission with; vincristine and prednine in low initial WBC ( lt 25,000/mm/sup 3/) group and these two agents plus adriamycin in high initial WBC ( gt 25,000/mm/sup 3/) group. After inducing remission, 62 children who achieved CR, received different CNS-prophlaxis; using a regimen of three doses of weekly high-dose MTX (1,000 mg/m/sup 2/) 6-hour infusion, which was repeated every 12 weeks-Group A (n = 14); high-dose MTX followed by 2400 rad cranial irradiation plus three doses of i.t. MT X-Group B (n = 15), 2400 rad cranial irradiation plus three doses of i.t. MTX-Group C (n = 16), and in 17 patients with high initial WBC, same as in Group A-Group D (n = 17). During an intravenous 6-h infusion of MTX at a dose of 1,000 mg/m/sup 2/, the CSF concentration of MTX rose to 2.3 +- 2.4 x 10/sup -6/M after initiation of infusion and remained in 10/sup -7/ M level for 48 hours. CNS-leukemia terminated complete remission in one of 14 children in Group A, two of 15 in Group B, two of 16 in Group C and two of 17 in Group D. The cumulative incidence of CNS-leukemia at 20 months calculated by the technique of Kaplan and Meier was 0% in Group A, 18.1% in Group B, 7.1% in Group C and 50.8% in Group D. There was no statistical difference among Groups A, B and C. These data suggested that CNS-prophylaxis with high-dose intravenous MTX was effective as well as 2400 rad cranial irradiation plus three doses of i.t. MTX in childhood ALL with low initial WBC.

  8. Lead in teeth from lead-dosed goats: Microdistribution and relationship to the cumulative lead dose

    International Nuclear Information System (INIS)

    Bellis, David J.; Hetter, Katherine M.; Jones, Joseph; Amarasiriwardena, Dula; Parsons, Patrick J.

    2008-01-01

    Teeth are commonly used as a biomarker of long-term lead exposure. There appear to be few data, however, on the content or distribution of lead in teeth where data on specific lead intake (dose) are also available. This study describes the analysis of a convenience sample of teeth from animals that were dosed with lead for other purposes, i.e., a proficiency testing program for blood lead. Lead concentration of whole teeth obtained from 23 animals, as determined by atomic absorption spectrometry, varied from 0.6 to 80 μg g -1 . Linear regression of whole tooth lead (μg g -1 ) on the cumulative lead dose received by the animal (g) yielded a slope of 1.2, with r 2 =0.647 (p -1 , were found in circumpulpal dentine. Linear regression of circumpulpal lead (μg g -1 ) on cumulative lead dose (g) yielded a slope of 23 with r 2 =0.961 (p=0.0001). The data indicated that whole tooth lead, and especially circumpulpal lead, of dosed goats increased linearly with cumulative lead exposure. These data suggest that circumpulpal dentine is a better biomarker of cumulative lead exposure than is whole tooth lead, at least for lead-dosed goats

  9. Factors Associated with Myelosuppression Related to Low-Dose Methotrexate Therapy for Inflammatory Rheumatic Diseases

    Science.gov (United States)

    Mori, Shunsuke; Hidaka, Michihiro; Kawakita, Toshiro; Hidaka, Toshihiko; Tsuda, Hiroyuki; Yoshitama, Tamami; Migita, Kiyoshi; Ueki, Yukitaka

    2016-01-01

    Objective Severe myelosuppression is a serious concern in the management of rheumatic disease patients receiving methotrexate (MTX) therapy. This study was intended to explore factors associated with the development of MTX-related myelosuppression and its disease severity. Methods We retrospectively examined a total of 40 cases of MTX-related myelosuppression that had been filed in the registries of participating rheumatology and hematology divisions. Data before onset were compared with those of 120 controls matched for age and sex. Cytopenia was graded according to the National Cancer Institute criteria for adverse events. Data before and at onset were compared between the severe and non-severe groups. Results Non-use of folic acid supplements, concurrent medications, and low renal function were significantly associated with the development of myelosuppression (p disease severity was not dependent on MTX doses. Serum albumin levels and folic acid supplementation are the important factors affecting the severity of MTX-related pancytopenia and neutropenia. PMID:27128679

  10. Dosing algorithm to target a predefined AUC in patients with primary central nervous system lymphoma receiving high dose methotrexate.

    Science.gov (United States)

    Joerger, Markus; Ferreri, Andrés J M; Krähenbühl, Stephan; Schellens, Jan H M; Cerny, Thomas; Zucca, Emanuele; Huitema, Alwin D R

    2012-02-01

    There is no consensus regarding optimal dosing of high dose methotrexate (HDMTX) in patients with primary CNS lymphoma. Our aim was to develop a convenient dosing algorithm to target AUC(MTX) in the range between 1000 and 1100 µmol l(-1) h. A population covariate model from a pooled dataset of 131 patients receiving HDMTX was used to simulate concentration-time curves of 10,000 patients and test the efficacy of a dosing algorithm based on 24 h MTX plasma concentrations to target the prespecified AUC(MTX) . These data simulations included interindividual, interoccasion and residual unidentified variability. Patients received a total of four simulated cycles of HDMTX and adjusted MTX dosages were given for cycles two to four. The dosing algorithm proposes MTX dose adaptations ranging from +75% in patients with MTX C(24) 12 µmol l(-1). The proposed dosing algorithm resulted in a marked improvement of the proportion of patients within the AUC(MTX) target between 1000 and 1100 µmol l(-1) h (11% with standard MTX dose, 35% with the adjusted dose) and a marked reduction of the interindividual variability of MTX exposure. A simple and practical dosing algorithm for HDMTX has been developed based on MTX 24 h plasma concentrations, and its potential efficacy in improving the proportion of patients within a prespecified target AUC(MTX) and reducing the interindividual variability of MTX exposure has been shown by data simulations. The clinical benefit of this dosing algorithm should be assessed in patients with primary central nervous system lymphoma (PCNSL). © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

  11. Pancytopenia associated with low-dose methotrexate therapy – case reports

    Directory of Open Access Journals (Sweden)

    Marija Čeh

    2012-12-01

    Conclusions: With the increasing long-term use of methotrexate, it is important that patients should be monitored during treatment for haematological side-effects, as pancytopenia can be a late manifestation. Furthermore, more attention should be paid to risk factors predisposing hematological toxicity of methotrexate before commencing this drug

  12. Cumulative effective dose associated with radiography and CT of adolescents with spinal injuries.

    Science.gov (United States)

    Lemburg, Stefan P; Peters, Soeren A; Roggenland, Daniela; Nicolas, Volkmar; Heyer, Christoph M

    2010-12-01

    The purpose of this study was to analyze the quantity and distribution of cumulative effective doses in diagnostic imaging of adolescents with spinal injuries. At a level 1 trauma center from July 2003 through June 2009, imaging procedures during initial evaluation and hospitalization and after discharge of all patients 10-20 years old with spinal fractures were retrospectively analyzed. The cumulative effective doses for all imaging studies were calculated, and the doses to patients with spinal injuries who had multiple traumatic injuries were compared with the doses to patients with spinal injuries but without multiple injuries. The significance level was set at 5%. Imaging studies of 72 patients (32 with multiple injuries; average age, 17.5 years) entailed a median cumulative effective dose of 18.89 mSv. Patients with multiple injuries had a significantly higher total cumulative effective dose (29.70 versus 10.86 mSv, p cumulative effective dose to multiple injury patients during the initial evaluation (18.39 versus 2.83 mSv, p cumulative effective dose. Adolescents with spinal injuries receive a cumulative effective dose equal to that of adult trauma patients and nearly three times that of pediatric trauma patients. Areas of focus in lowering cumulative effective dose should be appropriate initial estimation of trauma severity and careful selection of CT scan parameters.

  13. Biochemical criteria of toxicity of therapy with high doses of methotrexate in children with osteosarcoma

    Directory of Open Access Journals (Sweden)

    A. M. Strizhevskaya

    2015-01-01

    Full Text Available Methotrexate (Mtx is a cytotoxic drug from the group of antimetabolites, folic acid antagonists. High-dose (HD Mtx in pediatric oncology are used for the treatment of osteosarcoma (OS, and other types of tumors. This therapy has allowed to achieve a five-year relapse-free survival rates up to 80 % in patients with OS. However, the high toxicity of Mtx is a serious constraint in achieving the maximum therapeutic effect, which in most cases poses the occurrence of side effects in patients on various organs and systems. Treatment should be under strict laboratory monitoring, primarily therapeutic drug monitoring the concentration of Mtx in serum.246 children (boys – 125, girls – 121 aged 5 to 16 years with osteosarcoma (mean age 12.2 years who were treated in N.N. Blokhin Russian Cancer Research Center from 2006 to 2013. Patients were conducted from 1 to 8 courses HD Mtx at a dose of 8 or 12 g/m2 , administered within 4 h of infusion on the background of alkaline prehydrate. Leucovorin was administered intravenously, every 6 hours, starting 24 h from the start of the Mtx infusion. 1137 courses of HD Mtx were conducted with FPIA method (analyzer TDx/Flx, Abbott, USA. The technique of monitoring of homocysteine (Hcy in the blood serum by analyzer Vitros 5/1FS (Johnson & Johnson, USA during the entire course of high-dose Mtx was tested. In groups calculated pharmacokinetic parameters Mtx were tested: area under the pharmacokinetic curve (MtxAUC, clearance of methotrexate (ClMtx, the elimination half-life (T1/2 and the total time of excretion (Ttotal. Normal excretion of Mtx was revealed at 1050 courses Mtx, corresponding to the following values: 4 h – 1109 ± 283 μmol/l; 24 h – 4,67 ± 0,95 μmol/l; 42 h – 0,38 ± 0.16 µmol/l; 48 h – less than 0,23 ± 0.04 µmol/l; 72 h of 0.07 ± 0,03 µmol/l; 96 h of 0.03 ± 0.01 µmol/l. At 87 courses identified delayed Mtx excretion, accounting for 7.6 % of all courses. In all measured parameters

  14. Association between SLC19A1 gene polymorphism and high dose methotrexate toxicity in childhood acute lymphoblastic leukaemia and non Hodgkin malignant lymphoma: introducing a haplotype based approach

    Directory of Open Access Journals (Sweden)

    Kotnik Barbara Faganel

    2017-09-01

    Full Text Available We investigated the clinical relevance of SLC 19A1 genetic variability for high dose methotrexate (HD-MTX related toxicities in children and adolescents with acute lymphoblastic leukaemia (ALL and non Hodgkin malignant lymphoma (NHML.

  15. Palonosetron for the prevention of nausea and vomiting in children with acute lymphoblastic leukemia treated with high dose methotrexate

    DEFF Research Database (Denmark)

    Nadaraja, Sambavy; Mamoudou, Aissata Diop; Thomassen, Harald

    2012-01-01

    High dose methotrexate (HD-MTX), used in the treatment of children with acute lymphoblastic leukemia (ALL), is moderately emetogenic. First generation 5-HT(3) receptor antagonists are effective prophylactic agents but require multiple administrations. Palonosetron has a half life of 36-42 hours...... of palonosetron (5 µg/kg) for the prevention of chemotherapy-induced nausea and vomiting in children 18 years of age with ALL treated with HD-MTX, 5 g/m(2)....

  16. Systemic high-dose methotrexate plus ifosfamide is highly effective for central nervous system (CNS) involvement of lymphoma

    OpenAIRE

    2008-01-01

    Abstract Patients with malignant central nervous system (CNS) involvement of lymphoma have a poor prognosis with intrathecal chemotherapy and radiation. In this paper, we report the results we obtained in such patients by intravenous chemotherapy with high-dose methotrexate and ifosfamide (HDMTX/IFO). The study involved a review of all patients who received HDMTX/IFO for CNS involvement of malignant lymphoma at our hospital. Therapy consisted of 4 g/m2 of MTX (4 h infu...

  17. The use of low dose methotrexate in children with chronic anterior and intermediate uveitis.

    Science.gov (United States)

    Malik, A R; Pavesio, C

    2005-07-01

    To assess the efficacy of low dose methotrexate (MTX) therapy for children with chronic anterior and intermediate uveitis. A retrospective case review of 10 children who received MTX for chronic uveitis at a tertiary referral centre was performed. The following data were recorded for each patient: age, sex, race, duration of uveitis, primary diagnosis, anatomical localisation of uveitis, corticosteroid therapy, dose range of MTX, duration of MTX therapy, and side effects of MTX therapy. Several clinical parameters were evaluated to study the effect of MTX. These included visual acuity, anterior chamber inflammation, and topical and oral corticosteroid requirement. After MTX VA of 6/6 or better was present in 100% right eyes and 80% left eyes (p = 0.055 and p = 0.016, respectively). Anterior chamber inflammation decreased in 60% of children after MTX (p = 0.0168). The requirement of topical steroid decreased from a mean of 5.6 times a day before MTX to 1.5 times a day after MTX (p = 0.005). The dose of oral steroid decreased from a mean of 18 mg per day to 2.85 mg per day (p = 0.012). The most common adverse effect was nausea (20%). No patient required discontinuation of MTX because of side effects. MTX is effective and safe for chronic anterior and intermediate uveitis in children. An increase awareness of its efficacy is required among paediatricians and ophthalmologists to prevent sight threatening complication of chronic uveitis and its treatment with long term use of steroids.

  18. Reduced time for urinary alkalinization before high-dose methotrexate with preadmission oral bicarbonate.

    Science.gov (United States)

    Kintzel, Polly E; Campbell, Alan D; Yost, Kathleen J; Brinker, Brett T; Arradaza, Nicole V; Frobish, Daniel; Wehr, Alison M; O'Rourke, Timothy J

    2012-06-01

    Hydration and urinary alkalinization are essential for reducing renal dysfunction with high dose methotrexate (HDMTX). This report presents an analysis of institutional methods used to achieve adequate urinary alkalinization and output for patients receiving single agent HDMTX. Renal and metabolic parameters of tolerance were examined. Medical records of adult patients receiving HDMTX during the calendar years of 2008-2009 were retrospectively reviewed to determine the time to achieve urine pH > 7. Number of hospital days, bicarbonate dose, ordered hydration rate, urine output, and urine pH were assessed. A survival analysis model was run for time to urine pH > 7 using preadmission oral bicarbonate as a predictor variable and including a frailty term. Observational statistics were performed for other parameters. The analysis included 79 encounters for ten patients. Urine pH > 7 was achieved more rapidly in patients receiving preadmission oral bicarbonate (P = 0.012). The number of patients receiving HDMTX on the same day as admission was greater for those receiving preadmission oral bicarbonate (47%) in comparison to those who did not (2%), and they spent less time in the hospital. A standard regimen for hydration and urinary alkalinization based on this project is reported. The nature and frequency of adverse events were as expected for this treatment. At our institution, the time to achieve urinary alkalinization was reduced for patients receiving preadmission oral bicarbonate which facilitated chemotherapy infusion on the same day as admission and decreased the number of calendar days that patients stayed in the hospital.

  19. Recommendations for the use of methotrexate in rheumatoid arthritis: up and down scaling of the dose and administration routes.

    Science.gov (United States)

    Tornero Molina, Jesús; Ballina García, Francisco Javier; Calvo Alén, Jaime; Caracuel Ruiz, Miguel Ángel; Carbonell Abelló, Jordi; López Meseguer, Antonio; Moreno Muelas, José Vicente; Pérez Sandoval, Trinidad; Quijada Carrera, Jesús; Trenor Larraz, Pilar; Zea Mendoza, Antonio

    2015-01-01

    To describe the optimal therapeutic strategy for use of methotrexate in RA patients over the initial dose, route of administration, dose increase and decrease, patient monitoring, and use of folic/folinic acid. Eleven clinical experts proposed some questions to be solved. A systematic literature search was conducted. The contents were selected in a work session and subsequently validated via email to establish the level of agreement. The initial dose of methotrexate should not be 20mg/week), patient preference, very active disease or to avoid administration errors. Changing to a parenteral administration is proposed when the oral route is not effective enough, gastrointestinal toxicity appears, there is non-compliance or due to cost-effectiveness reasons before using more expensive drugs. On the contrary, due to patient preferences, intolerance to injections, dose reduction <7.5mg/week, non effectiveness of the route, poor compliance or gastrointestinal side effects. There should be a rapid dose escalation if inadequate responses occurr up to 15-20 or even 25mg/week in about 8 weeks, with increments of 2.5-5mg. The reduction will be carried out according to the dose the patient had, with decreases of 2.5-5mg every 3-6 months. Patient monitoring should be performed every 1-1.5 months until stability and then every 1-3 months. This document pretends to solve some common clinical questions and facilitate decision-making in RA patients treated with methotrexate. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  20. Comparison of intermediate-dose methotrexate with cranial irradiation for the post-induction treatment of acute lymphocytic leukemia in children

    International Nuclear Information System (INIS)

    Freeman, A.I.; Weinberg, V.; Brecher, M.L.

    1983-01-01

    The authors compared two regimens with respect to their ability to prolong disease-free survival in 506 children and adolescents with acute lymphocytic leukemia. All responders to induction therapy were randomized to treatment with 2400 rad of cranial irradiation plus intrathecal methotrexate or to treatment with intermediate-dose methotrexate plus intrathecal methotrexate, as prophylaxis for involvement of the central nervous system and other sanctuary areas. Complete responders were stratified into either standard-risk or increased-risk groups on the basis of age and white-cell count at presentation. Among patients with standard risk, hematologic relapses occurred in 9 of 117 given methotrexate and 24 of 120 given irradiation. The rate of central-nervous-system relapse was higher in the methotrexate group (23 of 117) than in the irradiation group. Among patients with increased risk, radiation offered greater protection to the central nervous system than methotrexate; there was no difference in the rate of hematologic relapse. Methotrexate offered better protection against systemic relapse in standard-risk patients and better protection against testicular relapse overall, but it offered less protection against relapses in the central nervous system than cranial irradiation

  1. Radiologic imaging in cystic fibrosis: cumulative effective dose and changing trends over 2 decades.

    LENUS (Irish Health Repository)

    O'Connell, Oisin J

    2012-06-01

    With the increasing life expectancy for patients with cystic fibrosis (CF), and a known predisposition to certain cancers, cumulative radiation exposure from radiologic imaging is of increasing significance. This study explores the estimated cumulative effective radiation dose over a 17-year period from radiologic procedures and changing trends of imaging modalities over this period.

  2. Cumulative cisplatin dose in concurrent chemoradiotherapy for head and neck cancer : A systematic review

    NARCIS (Netherlands)

    Strojan, Primoz; Vermorken, Jan B.; Beitler, Jonathan J.; Saba, Nabil F.; Haigentz, Missak; Bossi, Paolo; Worden, Francis P.; Langendijk, Johannes A.; Eisbruch, Avraham; Mendenhall, William M.; Lee, Anne W. M.; Harrison, Louis B.; Bradford, Carol R.; Smee, Robert; Silver, Carl E.; Rinaldo, Alessandra; Ferlito, Alfio

    Background. The optimal cumulative dose and timing of cisplatin administration in various concurrent chemoradiotherapy protocols for nonmetastatic head and neck squamous cell carcinoma (HNSCC) has not been determined. Methods. The absolute survival benefit at 5 years of concurrent chemoradiotherapy

  3. Fatal pulmonary fibrosis complicating low dose methotrexate therapy for rheumatoid arthritis

    NARCIS (Netherlands)

    van der Veen, M. J.; Dekker, J. J.; Dinant, H. J.; van Soesbergen, R. M.; Bijlsma, J. W.

    1995-01-01

    We report the fatal disease course of 2 aged patients with rheumatoid arthritis (RA). Both had respiratory complaints after 10-15 weeks of treatment with methotrexate (MTX). After withdrawal of MTX, and despite the use of corticosteroids and ventilatory support, both died of respiratory failure.

  4. Evaluation of a post-analysis method for cumulative dose distribution in stereotactic body radiotherapy

    International Nuclear Information System (INIS)

    Imae, Toshikazu; Takenaka, Shigeharu; Saotome, Naoya

    2016-01-01

    The purpose of this study was to evaluate a post-analysis method for cumulative dose distribution in stereotactic body radiotherapy (SBRT) using volumetric modulated arc therapy (VMAT). VMAT is capable of acquiring respiratory signals derived from projection images and machine parameters based on machine logs during VMAT delivery. Dose distributions were reconstructed from the respiratory signals and machine parameters in the condition where respiratory signals were without division, divided into 4 and 10 phases. The dose distribution of each respiratory phase was calculated on the planned four-dimensional CT (4DCT). Summation of the dose distributions was carried out using deformable image registration (DIR), and cumulative dose distributions were compared with those of the corresponding plans. Without division, dose differences between cumulative distribution and plan were not significant. In the condition Where respiratory signals were divided, dose differences were observed over dose in cranial region and under dose in caudal region of planning target volume (PTV). Differences between 4 and 10 phases were not significant. The present method Was feasible for evaluating cumulative dose distribution in VMAT-SBRT using 4DCT and DIR. (author)

  5. [Weekly low-dose methotrexate in rheumatoid arthritis. Review of the literature].

    Science.gov (United States)

    Manganelli, P; Troise Rioda, W

    1993-10-01

    Methotrexate (MTX) is an antifolic drug that in recent years has been largely employed in the treatment of Rheumatoid Arthritis (RA). Both short and long term clinical trials have demonstrated its efficacy and good tolerability. It induces a significant improvement of all clinical variables and a decrease in the erythrocyte sedimentation rate and other acute phase reactants with a steroid sparing effect. The probability of continuing MTX therapy for up to 5 years is 46-55% whereas that of continuing gold, hydroxychloroquine, sulfasalazine or D-penicillamine therapy is less than 20%. MTX is a rapidly acting drug with a clinical response within 4 weeks and a plateau phase after 6 months of therapy. Discontinuation of long-term MTX therapy induces a flare-up of the disease so that patients receiving long-term MTX must continue the drug to maintain clinical benefits. In spite of its clinical efficacy, MTX does not seem to have a significant effect on disease progression as determined radiographically. In this respect, MTX appears to have some superiority when compared to azathioprine, but not when compared to gold salts. MTX has been employed in patients with RA unresponsive to other Disease-Modifying Antirheumatic Drugs (DMARDs), but according to some recent views on the therapeutic strategy of RA, it could be used in early RA as a first choice drug. Toxic effects are the main reason in limiting long-term MTX treatment. Hepatic toxicity is one of the more common side-effects of MTX, but the recognition of its "risk factors" such as alcohol abuse, may reduce it. Acute pneumonitis is one of the more severe complications of MTX therapy and may be life-threatening. In RA patients treated with MTX are also reported complications of immunosuppression, such as Pneumocystis carinii pneumonia whose clinical-radiological picture may be similar to that of acute pneumonitis. The mechanism of action of low-dose weekly MTX in RA is still unclear, but it might be more

  6. Serum creatinine and creatinine clearance for predicting plasma methotrexate concentrations after high-dose methotrexate chemotherapy for the treatment for childhood lymphoblastic malignancies.

    Science.gov (United States)

    Xu, Wei-qun; Zhang, Ling-yan; Chen, Xue-ying; Pan, Bin-hua; Mao, Jun-qing; Song, Hua; Li, Jing-yuang; Tang, Yong-min

    2014-01-01

    Monitoring of plasma methotrexate (MTX) concentrations allows for therapeutic adjustments in treating childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) with high-dose MTX (HDMTX). We tested the hypothesis that assessment of creatinine clearance (CrCl) and/or serum Cr may be a suitable means of monitoring plasma MTX concentrations. All children in the study had ALL or NHL, were in complete remission, and received HDMTX (3 or 5 g/m(2))+leucovorin. Plasma MTX concentrations were measured at 24, 48, and 96 h. CrCl was determined at 24 and 48 h. Correlations between 24- and 48-h plasma MTX concentrations and CrCl and serum Cr concentrations were determined. CrCl and serum Cr concentrations were compared over time between children who had delayed and non-delayed MTX elimination. A total of 105 children were included. There were significant negative correlations between CrCl at 24 and 48 h and plasma MTX concentrations at 24 (both p < 0.001) and 48 h (both p < 0.001). There were significant positive correlations between serum Cr concentrations at both 24 and 48 h and plasma MTX concentrations at 24 (both p < 0.001) and 48 h (both p < 0.001). There were 88 (30.2 %) instances of elimination delay. Children with elimination delay had significantly lower CrCl and higher Cr concentrations at 24 and 48 h compared with children without elimination delay (all p < 0.05). Our findings suggest that, with further refinement, assessment of renal function may be a useful means of monitoring plasma MTX concentrations during HDMTX for ALL and NHL.

  7. Switching From Age-Based Stimulus Dosing to Dose Titration Protocols in Electroconvulsive Therapy: Empirical Evidence for Better Patient Outcomes With Lower Peak and Cumulative Energy Doses.

    Science.gov (United States)

    O'Neill-Kerr, Alex; Yassin, Anhar; Rogers, Stephen; Cornish, Janie

    2017-09-01

    The aim of this study was to test the proposition that adoption of a dose titration protocol may be associated with better patient outcomes, at lower treatment dose, and with comparable cumulative dose to that in patients treated using an age-based stimulus dosing protocol. This was an analysis of data assembled from archived records and based on cohorts of patients treated respectively on an age-based stimulus dosing protocol and on a dose titration protocol in the National Health Service in England. We demonstrated a significantly better response in the patient cohort treated with dose titration than with age-based stimulus dosing. Peak doses were less and the total cumulative dose was less in the dose titration group than in the age-based stimulus dosing group. Our findings are consistent with superior outcomes in patients treated using a dose titration protocol when compared with age-based stimulus dosing in a similar cohort of patients.

  8. Comparison of pharmacokinetics and toxicity after high-dose methotrexate treatments in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Csordas, Katalin; Hegyi, Marta; Eipel, Oliver T; Muller, Judit; Erdelyi, Daniel J; Kovacs, Gabor T

    2013-02-01

    We carried out a detailed comparative study of the pharmacokinetics and toxicity of methotrexate (MTX) and 7-hydroxy-methotrexate (7-OH-MTX) after high-dose intravenous methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL). Overall, 65 children were treated with 5 g/m2/24 h MTX and 88 children were treated with 2 g/m2/24 h MTX according to ALL-BFM 95 and ALL IC-BFM 2002 protocols (mean age: 6.4 years, range 1.0-17.9 years). A total of 583 HD-MTX courses were analyzed. Serum MTX and 7-OH-MTX levels were measured at 24, 36, and 48 h, and cerebrospinal fluid (CSF) MTX levels were determined 24 h after the initiation of the infusion. The area under the concentration-time curve was calculated. Hepatotoxicity, nephrotoxicity, and bone marrow toxicity were estimated by routine laboratory tests. We investigated pharmacokinetics and toxicity in distinct age groups ( 14 years). 5 g/m2/24 h treatments resulted in higher serum and CSF MTX and 7-OH-MTX levels (P treatments did not alter MTX or 7-OH-MTX levels. 7-OH-MTX levels were correlated with nephrotoxicity (r = 0.36, P children aged older than 14 years (P treatments. To predict the development of toxicity, monitoring of the level of the 7-OH-MTX is useful. Monitoring of pharmacokinetics is essential to prevent the development of severe adverse events in adolescents.

  9. Leukoencephalopathy in childhood hematopoietic neoplasm caused by moderate-dose methotrexate and prophylactic cranial radiotherapy -- an MR analysis

    International Nuclear Information System (INIS)

    Matsumoto, Ko; Takahashi, Shoki; Sato, Atsushi; Imaizumi, Masue; Higano, Shuichi; Sakamoto, Kiyohiko; Asakawa, Hiroshi; Tada, Keiya

    1995-01-01

    Purpose: The main purpose of this study was to determine influential factors related to minor leukoencephalopathy (LEP) caused by moderate-dose methotrexate (MTX) and prophylactic cranial radiotherapy (CRT) in childhood hematopoietic malignancies. We also compared the incidence of LEP following this treatment to that reported in the literature following treatment with high-dose MTX alone. Methods and Materials: Thirty-eight pediatric patients of hematopoietic malignancies (37 acute lymphoblastic leukemias, 1 non-Hodgkin lymphoma) who were given CRT (18-24 Gy) as well as prophylactic intrathecal and per os MTX were studied for leukoencephalopathy by magnetic resonance (MR) imaging. All the patients were free from grave neuropsychiatric disturbances. The data were examined to elucidate the influential ones of five factors (patients' age, doses of intrathecal and per os MTX, dose of CRT, interval between treatment, and MR study) to develop LEP using multiple regression analysis. To compare the effect of moderate-dose MTX and prophylactic CRT on LEP to that of high-dose MTX alone, we conducted literature review. Results: Seven out of 38 patients (18%) developed LEP. From multiple regression analysis and partial correlation coefficients, the age and CRT dose seemed influential in the subsequent development of LEP. The incidence of LEP following treatment with moderate-dose MTX and prophylactic CRT appears to be less than that reported in the literature following treatment with intravenous high-dose MTX. However, even moderate-dose MTX in combination with CRT can result in a significant incidence of MR-detectable LEP, particularly in children 6 years of age or younger receiving 24 Gy. Conclusion: Leukoencephalopathy was caused by moderate-dose MTX and prophylactic CRT in pediatric patients, probably less frequently than by high-dose MTX treatment alone. The influential factors were patient's age and CRT dose

  10. Cumulative doses analysis in young trauma patients: a single-centre experience.

    Science.gov (United States)

    Salerno, Sergio; Marrale, Maurizio; Geraci, Claudia; Caruso, Giuseppe; Lo Re, Giuseppe; Lo Casto, Antonio; Midiri, Massimo

    2016-02-01

    Multidetector computed tomography (MDCT) represents the main source of radiation exposure in trauma patients. The radiation exposure of young patients is a matter of considerable medical concern due to possible long-term effects. Multiple MDCT studies have been observed in the young trauma population with an increase in radiation exposure. We have identified 249 young adult patients (178 men and 71 women; age range 14-40 years) who had received more than one MDCT study between June 2010 and June 2014. According to the International Commission on Radiological Protection publication, we have calculated the cumulative organ dose tissue-weighting factors by using CT-EXPO software(®). We have observed a mean cumulative dose of about 27 mSv (range from 3 to 297 mSv). The distribution analysis is characterised by low effective dose, below 20 mSv, in the majority of the patients. However, in 29 patients, the effective dose was found to be higher than 20 mSv. Dose distribution for the various organs analysed (breasts, ovaries, testicles, heart and eye lenses) shows an intense peak for lower doses, but in some cases high doses were recorded. Even though cumulative doses may have long-term effects, which are still under debate, high doses are observed in this specific group of young patients.

  11. Application of the ELDO approach to assess cumulative eye lens doses for interventional cardiologists

    International Nuclear Information System (INIS)

    Farah, J.; Jacob, S.; Clairand, I.; Struelens, L.; Vanhavere, F.; Auvinen, A.; Koukorava, C.; Schnelzer, M.

    2015-01-01

    In preparation of a large European epidemiological study on the relation between eye lens dose and the occurrence of lens opacities, the European ELDO project focused on the development of practical methods to estimate retrospectively cumulative eye lens dose for interventional medical professionals exposed to radiation. The present paper applies one of the ELDO approaches, correlating eye lens dose to whole-body doses, to assess cumulative eye lens dose for 14 different Finnish interventional cardiologists for whom annual whole-body dose records were available for their entire working period. The estimated cumulative left and right eye lens dose ranged from 8 to 264 mSv and 6 to 225 mSv, respectively. In addition, calculations showed annual eye lens doses sometimes exceeding the new ICRP annual limit of 20 mSv. The work also highlights the large uncertainties associated with the application of such an approach proving the need for dedicated dosimetry systems in the routine monitoring of the eye lens dose. (authors)

  12. Individualized toxicity-titrated 6-mercaptopurine increments during high-dose methotrexate consolidation treatment of lower risk childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Frandsen, Thomas Leth; Abrahamsson, Jonas; Lausen, Birgitte Frederiksen

    2011-01-01

    This study explored the feasibility and toxicity of individualized toxicity-titrated 6-mercaptopurine (6MP) dose increments during post-remission treatment with High-dose methotrexate (HDM) (5000 mg/m2, ×3) in 38 patients with Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m2 per...... the remaining patients (P = 0·03). This study shows individualized toxicity-titrated 6MP dosing during consolidation is feasible without increased risk of toxicity....

  13. Methotrexate in the treatment of penile carcinoma.

    Science.gov (United States)

    Sklaroff, R B; Yagoda, A

    1980-01-15

    Eight patients with epidermoid carcinoma of the penis received methotrexate, five with high-dose methotrexate, 250--1500 mg/m2 with citrovorum rescue Q 2--4 weeks, and three with low-dose methotrexate, 0.5--3.0 mg/kg weekly. Three (38%) patients achieved a complete or partial remission which persisted for 11, 3 and 2 months, respectively. Methotrexate appears to be an active agent in the treatment of advanced penile cancer.

  14. Folate, homocysteine, and cobalamin status in patients with rheumatoid arthritis treated with methotrexate, and the effect of low dose folic acid supplement

    DEFF Research Database (Denmark)

    Hornung, Nete; Ellingsen, Torkell; Stengaard-Pedersen, Kristian

    2004-01-01

    OBJECTIVE: To investigate the effect of methotrexate (MTX) treatment of rheumatoid arthritis (RA) on folate metabolism, and to determine the effect of low dose folic acid on toxicity, efficacy, and folate status. METHODS: A 52-week prospective study of 81 patients with RA treated with MTX and self...

  15. The association between cumulative adversity and mental health: considering dose and primary focus of adversity.

    Science.gov (United States)

    Keinan, Giora; Shrira, Amit; Shmotkin, Dov

    2012-09-01

    The study addressed the dose-response model in the association of cumulative adversity with mental health. Data of 1,725 participants aged 50+ were drawn from the Israeli component of the Survey of Health, Ageing, and Retirement in Europe. Measures included an inventory of potentially traumatic events, distress (lifetime depression, depressive symptoms), and well-being (quality of life, optimism/hope). The maximal effect of cumulative trauma emerged in the contrast between 0-2 and 3+ events, where the higher number of events related to higher distress but also to higher well-being. While self-oriented adversity revealed no, or negative, association with well-being, other-oriented adversity revealed a positive association. The study suggests an experiential dose of cumulative adversity leading to a co-activation of distress and well-being. The source of this co-activation seems to be other-oriented adversity.

  16. TH-AB-207A-04: Assessment of Patients’ Cumulative Effective Dose From CT Examinations

    Energy Technology Data Exchange (ETDEWEB)

    Bostani, M; Cagnon, C; Sepahdari, A; Beckett, K; Oshiro, T; McNitt-Gray, M [UCLA School of Medicine, Los Angeles, CA (United States)

    2016-06-15

    Purpose: The Joint Commission requires institutions to consider patient’s age and recent imaging exams when deciding on the most appropriate type of imaging exam. Additionally, knowing patient’s imaging history can help prevent duplicate scans. Radiation dose management software affords new opportunities to identify and utilize patients with high cumulative doses as one proxy for subsequent review of imaging history and opportunities in avoiding redundant exams. Methods: Using dose management software (Radimetrics, Bayer Healthcare) a total of 72073 CT examinations performed from Jan 2015 to Jan 2016 were examined to categorize patients with a cumulative effective dose of 100 mSv and above. This threshold was selected based on epidemiological studies on populations exposed to radiation, which demonstrate a statistical increase of cancer risk at doses above 100 mSv. Histories of patients with highest cumulative dose and highest number of exams were further investigated by a Radiologist for appropriateness of recurrent studies and potential opportunities for reduction. Results: Out of 34762 patients, 927 (2.7%) were identified with a cumulative dose of 100 mSv and above. The highest cumulative dose (842 mSv) belonged to an oncology patient who underwent 2 diagnostic exams and 9 interventional ablative CT guided procedures. The patient with highest number of exams (56 counts) and cumulative dose of 170 mSv was a 17 year old trauma patient. An imaging history review of these two patients did not suggest any superfluous scans. Conclusion: Our limited pilot study suggests that recurrent CT exams for patients with oncologic or severe trauma history may be warranted and appropriate. As a result, for future studies we will be focusing on high dose patient cohorts not associated with oncology or severe trauma. Additionally, the review process itself has suggested areas for potential improvement in patient care, including improved documentation and Radiologist involvement

  17. TH-AB-207A-04: Assessment of Patients’ Cumulative Effective Dose From CT Examinations

    International Nuclear Information System (INIS)

    Bostani, M; Cagnon, C; Sepahdari, A; Beckett, K; Oshiro, T; McNitt-Gray, M

    2016-01-01

    Purpose: The Joint Commission requires institutions to consider patient’s age and recent imaging exams when deciding on the most appropriate type of imaging exam. Additionally, knowing patient’s imaging history can help prevent duplicate scans. Radiation dose management software affords new opportunities to identify and utilize patients with high cumulative doses as one proxy for subsequent review of imaging history and opportunities in avoiding redundant exams. Methods: Using dose management software (Radimetrics, Bayer Healthcare) a total of 72073 CT examinations performed from Jan 2015 to Jan 2016 were examined to categorize patients with a cumulative effective dose of 100 mSv and above. This threshold was selected based on epidemiological studies on populations exposed to radiation, which demonstrate a statistical increase of cancer risk at doses above 100 mSv. Histories of patients with highest cumulative dose and highest number of exams were further investigated by a Radiologist for appropriateness of recurrent studies and potential opportunities for reduction. Results: Out of 34762 patients, 927 (2.7%) were identified with a cumulative dose of 100 mSv and above. The highest cumulative dose (842 mSv) belonged to an oncology patient who underwent 2 diagnostic exams and 9 interventional ablative CT guided procedures. The patient with highest number of exams (56 counts) and cumulative dose of 170 mSv was a 17 year old trauma patient. An imaging history review of these two patients did not suggest any superfluous scans. Conclusion: Our limited pilot study suggests that recurrent CT exams for patients with oncologic or severe trauma history may be warranted and appropriate. As a result, for future studies we will be focusing on high dose patient cohorts not associated with oncology or severe trauma. Additionally, the review process itself has suggested areas for potential improvement in patient care, including improved documentation and Radiologist involvement

  18. Patterns of prednisone use during pregnancy in women with rheumatoid arthritis: Daily and cumulative dose.

    Science.gov (United States)

    Palmsten, Kristin; Rolland, Matthieu; Hebert, Mary F; Clowse, Megan E B; Schatz, Michael; Xu, Ronghui; Chambers, Christina D

    2018-04-01

    To characterize prednisone use in pregnant women with rheumatoid arthritis using individual-level heat-maps and clustering individual trajectories of prednisone dose, and to evaluate the association between prednisone dose trajectory groups and gestational length. This study included pregnant women with rheumatoid arthritis who enrolled in the MotherToBaby Autoimmune Diseases in Pregnancy Study (2003-2014) before gestational week 20 and reported prednisone use without another oral glucocorticoid during pregnancy (n = 254). Information on medication use and pregnancy outcomes was collected by telephone interview plus by medical record review. Prednisone daily dose and cumulative dose were plotted by gestational day using a heat map for each individual. K-means clustering was used to cluster individual trajectories of prednisone dose into groups. The associations between trajectory group and demographics, disease severity measured by the Health Assessment Questionnaire at enrollment, and gestational length were evaluated. Women used prednisone 3 to 292 days during pregnancy, with daily doses ranging from <1 to 60 mg. Total cumulative dose ranged from 8 to 6225 mg. Disease severity, non-biologic disease modifying anti-rheumatic drug use, and gestational length varied significantly by trajectory group. After adjusting for disease severity, non-biologic disease modifying anti-rheumatic drug use, and other covariates, the highest vs lowest daily dose trajectory group was associated with reduced gestational age at delivery (β: -2.3 weeks (95%: -3.4, -1.3)), as was the highest vs lowest cumulative dose trajectory group (β: -2.6 weeks (95%: -3.6, -1.5)). In pregnant women with rheumatoid arthritis, patterns of higher prednisone dose were associated with shorter gestational length compared with lower dose. Copyright © 2018 John Wiley & Sons, Ltd.

  19. Myelotoxicity after high-dose methotrexate in childhood acute leukemia is influenced by 6-mercaptopurine dosing but not by intermediate thiopurine methyltransferase activity

    DEFF Research Database (Denmark)

    Levinsen, Mette; Rosthøj, Susanne; Nygaard, Ulrikka

    2015-01-01

    Purpose: Through enhancement of 6-mercaptopurine (6MP) bioavailability and inhibition of purine de novo synthesis, high-dose methotrexate (HD-MTX) may increase incorporation into DNA of 6-thioguanine nucleotides, the cytotoxic metabolites of 6MP. Patients with intermediate activity of thiopurine...... methyltransferase (TPMTIA) have higher cytosol 6-thioguanine nucleotide levels. We investigated toxicity following HD-MTX during MTX/6MP maintenance therapy in relation to 6MP and TPMT. Methods: Using linear mixed models, we explored myelo- and hepatotoxicity in relation to 6MP dosage and TPMT phenotype following 1......,749 HD-MTX courses to 411 children with acute lymphoblastic leukemia on maintenance therapy. Results: The degree of myelosuppression following HD-MTX was similar for patients with TPMTIA and patients with high TPMT activity (TPMTHA), when HD-MTX started with same blood counts and 6MP doses. However...

  20. Cumulative effective and individual organ dose levels in paediatric patients undergoing multiple catheterizations for congenital heart disease

    International Nuclear Information System (INIS)

    Jones, T.P.; Brennan, P.C.; Ryan, E.

    2017-01-01

    This study examines the cumulative radiation dose levels received by a group of children who underwent multiple cardiac catheterisation procedures during the investigation and management of congenital heart disease (CHD). The purpose is to calculate cumulative doses, identify higher dose individuals, outline the inconsistencies with risk assessment and encourage the establishment of dose databases in order to facilitate the longitudinal research necessary to better understand health risks. A retrospective review of patient records for 117 paediatric patients who have undergone two or more cardiac catheterizations for the investigation of CHD was undertaken. This cohort consisted of patients who were catheterised over a period from September 2002 to August 2014. The age distribution was from newborn to 17 y. Archived kerma-area product (P KA ) and fluoroscopy time (T) readings were retrieved and analysed. Cumulative effective and individual organ doses were determined. The cumulative P KA levels ranged from 1.8 to 651.2 Gycm 2 , whilst cumulative effective dose levels varied from 2 to 259 mSv. The cumulative fluoroscopy time was shown to vary from 8.1 to 193.5 min. Median cumulative organ doses ranged from 3 to 94 mGy. Cumulative effective dose levels are highly variable but may exceed 250 mSv. Individual organ and effective dose measurements remain useful for comparison purposes between institutions although current methodologies used for determining lifetime risks are inadequate. (authors)

  1. A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers

    Directory of Open Access Journals (Sweden)

    Oyoo George O

    2011-03-01

    Full Text Available Abstract Background Previous investigations indicate that methotrexate, an old anticancer drug, could be used at low doses to treat malaria. A phase I evaluation was conducted to assess the safety and pharmacokinetic profile of this drug in healthy adult male Kenyan volunteers. Methods Twenty five healthy adult volunteers were recruited and admitted to receive a 5 mg dose of methotrexate/day/5 days. Pharmacokinetics blood sampling was carried out at 2, 4, 6, 12 and 24 hours following each dose. Nausea, vomiting, oral ulcers and other adverse events were solicited during follow up of 42 days. Results The mean age of participants was 23.9 ± 3.3 years. Adherence to protocol was 100%. No grade 3 solicited adverse events were observed. However, one case of transiently elevated liver enzymes, and one serious adverse event (not related to the product were reported. The maximum concentration (Cmax was 160-200 nM and after 6 hours, the effective concentration (Ceff was Conclusion Low-dose methotraxate had an acceptable safety profile. However, methotrexate blood levels did not reach the desirable Ceff of 250-400-nM required to clear malaria infection in vivo. Further dose finding and safety studies are necessary to confirm suitability of this drug as an anti-malarial agent.

  2. Accurate convolution/superposition for multi-resolution dose calculation using cumulative tabulated kernels

    International Nuclear Information System (INIS)

    Lu Weiguo; Olivera, Gustavo H; Chen Mingli; Reckwerdt, Paul J; Mackie, Thomas R

    2005-01-01

    Convolution/superposition (C/S) is regarded as the standard dose calculation method in most modern radiotherapy treatment planning systems. Different implementations of C/S could result in significantly different dose distributions. This paper addresses two major implementation issues associated with collapsed cone C/S: one is how to utilize the tabulated kernels instead of analytical parametrizations and the other is how to deal with voxel size effects. Three methods that utilize the tabulated kernels are presented in this paper. These methods differ in the effective kernels used: the differential kernel (DK), the cumulative kernel (CK) or the cumulative-cumulative kernel (CCK). They result in slightly different computation times but significantly different voxel size effects. Both simulated and real multi-resolution dose calculations are presented. For simulation tests, we use arbitrary kernels and various voxel sizes with a homogeneous phantom, and assume forward energy transportation only. Simulations with voxel size up to 1 cm show that the CCK algorithm has errors within 0.1% of the maximum gold standard dose. Real dose calculations use a heterogeneous slab phantom, both the 'broad' (5 x 5 cm 2 ) and the 'narrow' (1.2 x 1.2 cm 2 ) tomotherapy beams. Various voxel sizes (0.5 mm, 1 mm, 2 mm, 4 mm and 8 mm) are used for dose calculations. The results show that all three algorithms have negligible difference (0.1%) for the dose calculation in the fine resolution (0.5 mm voxels). But differences become significant when the voxel size increases. As for the DK or CK algorithm in the broad (narrow) beam dose calculation, the dose differences between the 0.5 mm voxels and the voxels up to 8 mm (4 mm) are around 10% (7%) of the maximum dose. As for the broad (narrow) beam dose calculation using the CCK algorithm, the dose differences between the 0.5 mm voxels and the voxels up to 8 mm (4 mm) are around 1% of the maximum dose. Among all three methods, the CCK algorithm

  3. Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6-11 years-old than cumulative high doses of inhaled terbutaline.

    Science.gov (United States)

    Kaae, Rikke; Agertoft, Lone; Pedersen, Sören; Nordvall, S Lennart; Pedroletti, Christophe; Bengtsson, Thomas; Johannes-Hellberg, Ingegerd; Rosenborg, Johan

    2004-10-01

    To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. Twenty boys and girls (6-11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis) 4.5 microg (F4.5) or terbutaline (Bricanyl) 500 microg (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double-blind (active treatments only), crossover trial. Blood pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency. Formoterol and terbutaline had significant beta2-adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration and PR interval, the systemic effects were significantly more pronounced with terbutaline than with formoterol. Thus, mean minimum plasma potassium, was suppressed from 3.56 (95% confidence interval, CI: 3.48-3.65) mmol l(-1) on the day of no treatment to 2.98 (CI: 2.90-3.08) after 10 x F4.5 and 2.70 (CI: 2.61-2.78) mmol l(-1) after 10 x T500, and maximum Q-Tc (heart rate corrected Q-T interval [Bazett's formula]) was prolonged from 429 (CI: 422-435) ms on the day of no treatment, to 455 (CI: 448-462) ms after 10 x F4.5 and 470 (CI: 463-476) ms after 10 x T500. Estimates of relative dose potency indicated that F4.5 microg had the same systemic activity as the clinically less effective dose of 250 microg terbutaline. The duration of systemic effects differed marginally between treatments. Spontaneously reported adverse events (most frequently tremor) were fewer with formoterol (78% of the children) than with terbutaline (95%). A serious adverse event occurred after inhalation of 45 microg formoterol over the 1 h dosing time, that prompted the extension of dosing time to 2.5 h. Multiple inhalations over 2.5 h of

  4. Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6–11 years-old than cumulative high doses of inhaled terbutaline

    Science.gov (United States)

    Kaae, Rikke; Agertoft, Lone; Pedersen, Sören; Nordvall, S Lennart; Pedroletti, Christophe; Bengtsson, Thomas; Johannes-Hellberg, Ingegerd; Rosenborg, Johan

    2004-01-01

    Objectives To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. Methods Twenty boys and girls (6–11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis®) 4.5 µg (F4.5) or terbutaline (Bricanyl®) 500 µg (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler®) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double-blind (active treatments only), crossover trial. Blood pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency. Results Formoterol and terbutaline had significant β2-adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration and PR interval, the systemic effects were significantly more pronounced with terbutaline than with formoterol. Thus, mean minimum plasma potassium, was suppressed from 3.56 (95% confidence interval, CI: 3.48–3.65) mmol l−1 on the day of no treatment to 2.98 (CI: 2.90–3.08) after 10 × F4.5 and 2.70 (CI: 2.61–2.78) mmol l−1 after 10 × T500, and maximum Q-Tc (heart rate corrected Q-T interval [Bazett's formula]) was prolonged from 429 (CI: 422–435) ms on the day of no treatment, to 455 (CI: 448–462) ms after 10 × F4.5 and 470 (CI: 463–476) ms after 10 × T500. Estimates of relative dose potency indicated that F4.5 µg had the same systemic activity as the clinically less effective dose of 250 µg terbutaline. The duration of systemic effects differed marginally between treatments. Spontaneously reported adverse events (most frequently tremor) were fewer with formoterol (78% of the children) than with terbutaline (95%). A serious adverse event occurred after inhalation of 45 µg formoterol over the 1 h dosing time, that prompted the extension of dosing time to 2.5 h

  5. Low Birth Weight, Cumulative Obesity Dose, and the Risk of Incident Type 2 Diabetes

    OpenAIRE

    Feng, Cindy; Osgood, Nathaniel D.; Dyck, Roland F.

    2018-01-01

    Background. Obesity history may provide a better understanding of the contribution of obesity to T2DM risk. Methods. 17,634 participants from the 1958 National Child Development Study were followed from birth to 50 years. Cumulative obesity dose, a measure of obesity history, was calculated by subtracting the upper cut-off of the normal BMI from the actual BMI at each follow-up and summing the areas under the obesity dose curve. Hazard ratios (HRs) for diabetes were calculated using Cox regre...

  6. The influence of detoxification agents on the intensity of side effects caused by medium-high doses of methotrexate in children with acute lymphoblastic leukemia: Case series

    Directory of Open Access Journals (Sweden)

    Šumar Jovana S.

    2014-01-01

    Full Text Available Objective The treatment of childhood acute lymphoblastic leukemia (ALL in Serbia is conducted according to protocol ALL IC BMF-2009. The therapy includes the application of cytostatic drugs methotrexate and 6-mercaptopurine, and drug detoxifying Calcium Folinate. At the moment, 80% of affected children could be cured with current treatment, but resistance to the therapy and its toxic effects remain serious clinical problems. The aim of the study was to investigate the influence of detoxification agents (Calcium Folinate, silymarin and ursodeoxycholic acid on the side effects of methotrexate, applied in this protocol. Methods A modified acute toxicity form (GPOH was used for side effects monitoring. The research included children with either standard or intermediate risk ALL in the consolidation therapy phase, who were hospitalised at the Institute for Child and Youth Health Care of Vojvodina in Novi Sad during the period from July 2010 to February 2011. Results The most frequent side effect after 40 applications of methotrexate in ten children was bone marrow depression. Methotrexate caused: leukopenia in 10 patients, thrombocytopenia in 5 patients; after the use of folic acid, platelet count grew in 8 patients, leukocyte in 2 patients. Less frequent side effects: an increase serum transaminase activity, the state of fever, bronchopneumonia, diarrhoea with mild cramps and hypercalcaemia. Conclusion The application of Calcium Folinate, silymarin and ursodeoxycholic acid prevented the occurrence of severe adverse effects caused by medium-high doses of methotrexate. Observed adverse effects were of mild to moderate intensity, reversible and did not significantly disturb the quality of life in treated patients.

  7. Methotrexate and Pregnancy

    Science.gov (United States)

    ... increased risk for infertility, not birth defects. Low sperm count has been seen in some men using methotrexate. Most of these men were using high doses of the medication, as well as other medications used to treat cancer. Sperm levels returned to normal after the men stopped ...

  8. Cumulative Training Dose's Effects on Interrelationships Between Common Training-Load Models During Basketball Activity.

    Science.gov (United States)

    Scanlan, Aaron T; Fox, Jordan L; Borges, Nattai R; Dascombe, Ben J; Dalbo, Vincent J

    2017-02-01

    The influence of various factors on training-load (TL) responses in basketball has received limited attention. This study aimed to examine the temporal changes and influence of cumulative training dose on TL responses and interrelationships during basketball activity. Ten state-level Australian male junior basketball players completed 4 × 10-min standardized bouts of simulated basketball activity using a circuit-based protocol. Internal TL was quantified using the session rating of perceived exertion (sRPE), summated heart-rate zones (SHRZ), Banister training impulse (TRIMP), and Lucia TRIMP models. External TL was assessed via measurement of mean sprint and circuit speeds. Temporal TL comparisons were performed between 10-min bouts, while Pearson correlation analyses were conducted across cumulative training doses (0-10, 0-20, 0-30, and 0-40 min). sRPE TL increased (P basketball activity. sRPE TL was only significantly related to Lucia TRIMP (r = .66-.69; P basketball training doses lasting beyond 20 min. Thus, the interchangeability of commonly used internal and external TL approaches appears dose-dependent during basketball activity, with various psychophysiological mediators likely underpinning temporal changes.

  9. Double modulation of 5-fluorouracil by methotrexate and high-dose L-leucovorin in advanced colorectal cancer.

    Science.gov (United States)

    Romero, A O; Perez, J E; Cuevas, M A; Lacava, J A; Sabatini, C L; Dominguez, M E; Rodriguez, R; Barbieri, M R; Ortiz, E H; Salvadori, M A; Acuña, L A; Acuña, J M; Langhi, M J; Amato, S; Machiavelli, M R; Leone, B A; Vallejo, C T; Lorusso, V; DeLena, M

    1998-02-01

    A phase II trial was performed to evaluate the efficacy and toxicity of a double modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and L-leucovorin (L-LV) in patients with advanced recurrent (inoperable) or metastatic colorectal carcinoma (ACC). Between July 1993 and October 1995, 41 patients with ACC received a regimen that consisted of MTX 150 mg/m2 i.v., infused over a 20-minute period at hour 0, followed 19 hours later by L-LV 250 mg/m2 in a 2-hour i.v. infusion. 5-FU, 900 mg/m2, was administered by i.v. push injection at hour 20. Beginning 24 hours after MTX administration, all patients received four doses of L-LV, 15 mg/m2 i.m., every 6 hours. Cycles were repeated every 15 days. Two patients were not assessable for response. Objective regression was observed in 11 of 39 (28%) patients, [95% confidence interval (CI), 14-42%]. One (2%) patient achieved complete response (CR) and 10 (26%) partial response (PR). No change was recorded in 15 (39%) patients and progressive disease was noted in 13 (33%) patients. The median time to treatment failure was 6 months and the median survival time was 10 months. Toxicity was within acceptable limits, but one therapy-related death due to severe leukopenia was observed. The dose-limiting toxicity was mucositis. Eight episodes of grade 3 or 4 stomatitis were observed, and were responsible for dosage modifications of MTX and 5-FU. In conclusion, further in experimental and clinical studies are clearly necessary in order to design the best modulatory strategy of 5-FU.

  10. Association of cumulative dose of haloperidol with next-day delirium in older medical ICU patients.

    Science.gov (United States)

    Pisani, Margaret A; Araujo, Katy L B; Murphy, Terrence E

    2015-05-01

    To evaluate the association between cumulative dose of haloperidol and next-day diagnosis of delirium in a cohort of older medical ICU patients, with adjustment for its time-dependent confounding with fentanyl and intubation. Prospective, observational study. Medical ICU at an urban, academic medical center. Age 60 years and older admitted to the medical ICU who received at least one dose of haloperidol (n = 93). Of these, 72 patients were intubated at some point in their medical ICU stay, whereas 21 were never intubated. None. Detailed data were collected concerning time, dosage, route of administration of all medications, as well as for important clinical covariates, and daily status of intubation and delirium using the confusion assessment method for the ICU and a chart-based algorithm. Among nonintubated patients, and after adjustment for time-dependent confounding and important covariates, each additional cumulative milligram of haloperidol was associated with 5% higher odds of next-day delirium with odds ratio of 1.05 (credible interval [CI], 1.02-1.09). After adjustment for time-dependent confounding and covariates, intubation was associated with a five-fold increase in odds of next-day delirium with odds ratio of 5.66 (CI, 2.70-12.02). Cumulative dose of haloperidol among intubated patients did not change their already high likelihood of next-day delirium. After adjustment for time-dependent confounding, the positive associations between indicators of intubation and of cognitive impairment and next-day delirium became stronger. These results emphasize the need for more studies regarding the efficacy of haloperidol for treatment of delirium among older medical ICU patients and demonstrate the value of assessing nonintubated patients.

  11. Method for calculating individual equivalent doses and cumulative dose of population in the vicinity of nuclear power plant site

    International Nuclear Information System (INIS)

    Namestek, L.; Khorvat, D; Shvets, J.; Kunz, Eh.

    1976-01-01

    A method of calculating the doses of external and internal person irradiation in the nuclear power plant vicinity under conditions of normal operation and accident situations has been described. The main difference between the above method and methods used up to now is the use of a new antropomorphous representation of a human body model together with all the organs. The antropomorphous model of human body and its organs is determined as a set of simple solids, coordinates of disposistion of the solids, sizes, masses, densities and composition corresponding the genuine organs. The use of the Monte-Carlo method is the second difference. The results of the calculations according to the model suggested can be used for determination: a critical group of inhabitans under conditions of normal plant operation; groups of inhabitants most subjected to irradiation in the case of possible accident; a critical sector with a maximum collective dose in the case of an accident; a critical radioisotope favouring the greatest contribution to an individual equivalent dose; critical irradiation ways promoting a maximum contribution to individual equivalent doses; cumulative collective doses for the whole region or for a chosen part of the region permitting to estimate a population dose. The consequent method evoluation suggests the development of separate units of the calculationg program, critical application and the selection of input data of physical, plysiological and ecological character and improvement of the calculated program for the separate concrete events [ru

  12. Dose dense cyclophosphamide, methotrexate, fluorouracil is feasible at 14-day intervals: a pilot study of every-14-day dosing as adjuvant therapy for breast cancer.

    Science.gov (United States)

    Drullinsky, Pamela; Sugarman, Steven M; Fornier, Monica N; D'Andrea, Gabriella; Gilewski, Teresa; Lake, Diana; Traina, Tiffany; Wasserheit-Lieblich, Carolyn; Sklarin, Nancy; Atieh-Graham, Deena; Mills, Nancy; Troso-Sandoval, Tiffany; Seidman, Andrew D; Yuan, Jeffrey; Patel, Hamangi; Patil, Sujata; Norton, Larry; Hudis, Clifford

    2010-12-01

    Cyclophosphamide/methotrexate/fluorouracil (CMF) is a proven adjuvant option for patients with early-stage breast cancer. Randomized trials with other regimens demonstrate that dose-dense (DD) scheduling can offer greater efficacy. We investigated the feasibility of administering CMF using a DD schedule. Thirty-eight patients with early-stage breast cancer were accrued from March 2008 through June 2008. They were treated every 14 days with C 600, M 40, F 600 (all mg/m2) with PEG-filgrastim (Neulasta®) support on day 2 of each cycle. The primary endpoint was tolerability using a Simon's 2-stage optimal design. The design would effectively discriminate between true tolerability (as protocol-defined) rates of ≤ 60% and ≥ 80%. The median age was 52-years-old (range, 38-78 years of age). Twenty-nine of the 38 patients completed 8 cycles of CMF at 14-day intervals. Dose-dense adjuvant CMF is tolerable and feasible at 14-day intervals with PEG-filgrastim support.

  13. Pharmacoepidemiology of opiate use in the neonatal ICU: Increasing cumulative doses and iatrogenic opiate withdrawal.

    Science.gov (United States)

    Lewis, Tamorah; Erfe, Betty Luan; Ezell, Tarrah; Gauda, Estelle

    2015-01-01

    Neonatal intensive care unit (ICU) care involves use of opiates to treat postoperative, ventilated, or chronically ill infants. Opiates provide necessary analgesia and sedation, but the morbidities include prolonged neonatal abstinence syndrome (NAS) and extended length of stay for dose tapering. Our objective was to quantify trends in opiate exposure in a tertiary care NICU. The authors hypothesize that medical opiate exposure and resultant ICU-acquired NAS would increase over time. Retrospective cross-sectional cohort study. Tertiary care NICU. High-risk inborn infants admitted in fiscal years 2003-2004, 2007-2008, and 2010-2011. Average cumulative morphine exposure (all opiate doses converted to morphine equivalents) per time epoch was compared in cohorts of clinically similar infants. Linear regression was used to assess the primary outcome, assessing changes in opiate exposure over time. Sixty-three infants were included in the final analysis. The primary analysis assessing cumulative opiate exposure per infant showed an increase of 134 mg per time epoch (95% CI-12, 279 mg, p-value 0.071). There was a statistically significant increase in the percent of infants with a diagnosis of iatrogenic NAS, increasing from 9 to 35 to 50 percent (p-value 0.012).

  14. Cumulative radiation dose caused by radiologic studies in critically ill trauma patients.

    Science.gov (United States)

    Kim, Patrick K; Gracias, Vicente H; Maidment, Andrew D A; O'Shea, Michael; Reilly, Patrick M; Schwab, C William

    2004-09-01

    Critically ill trauma patients undergo many radiologic studies, but the cumulative radiation dose is unknown. The purpose of this study was to estimate the cumulative effective dose (CED) of radiation resulting from radiologic studies in critically ill trauma patients. The study group was composed of trauma patients at an urban Level I trauma center with surgical intensive care unit length of stay (LOS) greater than 30 days. The radiology records were reviewed. A typical effective dose per study for each type of plain film radiograph, computed tomographic scan, fluoroscopic study, and nuclear medicine study was used to calculate CED. Forty-six patients met criteria. The mean surgical intensive care unit and hospital LOS were 42.7 +/- 14.0 and 59.5 +/- 28.5 days, respectively. The mean Injury Severity Score was 32.2 +/- 15.0. The mean number of studies per patient was 70.1 +/- 29.0 plain film radiographs, 7.8 +/- 4.1 computed tomographic scans, 2.5 +/- 2.6 fluoroscopic studies, and 0.065 +/- 0.33 nuclear medicine study. The mean CED was 106 +/- 59 mSv per patient (range, 11-289 mSv; median, 104 mSv). Among age, mechanism, Injury Severity Score, and LOS, there was no statistically significant predictor of high CED. The mean CED in the study group was 30 times higher than the average yearly radiation dose from all sources for individuals in the United States. The theoretical additional morbidity attributable to radiologic studies was 0.78%. From a radiobiologic perspective, risk-to-benefit ratios of radiologic studies are favorable, given the importance of medical information obtained. Current practice patterns regarding use of radiologic studies appear to be acceptable.

  15. Age- and gender-specific estimates of cumulative CT dose over 5 years using real radiation dose tracking data in children

    International Nuclear Information System (INIS)

    Lee, Eunsol; Goo, Hyun Woo; Lee, Jae-Yeong

    2015-01-01

    It is necessary to develop a mechanism to estimate and analyze cumulative radiation risks from multiple CT exams in various clinical scenarios in children. To identify major contributors to high cumulative CT dose estimates using actual dose-length product values collected for 5 years in children. Between August 2006 and July 2011 we reviewed 26,937 CT exams in 13,803 children. Among them, we included 931 children (median age 3.5 years, age range 0 days-15 years; M:F = 533:398) who had 5,339 CT exams. Each child underwent at least three CT scans and had accessible radiation dose reports. Dose-length product values were automatically extracted from DICOM files and we used recently updated conversion factors for age, gender, anatomical region and tube voltage to estimate CT radiation dose. We tracked the calculated CT dose estimates to obtain a 5-year cumulative value for each child. The study population was divided into three groups according to the cumulative CT dose estimates: high, ≥30 mSv; moderate, 10-30 mSv; and low, <10 mSv. We reviewed clinical data and CT protocols to identify major contributors to high and moderate cumulative CT dose estimates. Median cumulative CT dose estimate was 5.4 mSv (range 0.5-71.1 mSv), and median number of CT scans was 4 (range 3-36). High cumulative CT dose estimates were most common in children with malignant tumors (57.9%, 11/19). High frequency of CT scans was attributed to high cumulative CT dose estimates in children with ventriculoperitoneal shunt (35 in 1 child) and malignant tumors (range 18-49). Moreover, high-dose CT protocols, such as multiphase abdomen CT (median 4.7 mSv) contributed to high cumulative CT dose estimates even in children with a low number of CT scans. Disease group, number of CT scans, and high-dose CT protocols are major contributors to higher cumulative CT dose estimates in children. (orig.)

  16. Analysis of Cumulative Dose to Implanted Pacemaker According to Various IMRT Delivery Methods: Optimal Dose Delivery Versus Dose Reduction Strategy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Woo; Hong, Se Mie [Dept. of Radiation Oncology, Konkuk University Medical Center, Seoul (Korea, Republic of)

    2011-11-15

    Cancer patients with implanted cardiac pacemaker occasionally require radiotherapy. Pacemaker may be damaged or malfunction during radiotherapy due to ionizing radiation or electromagnetic interference. Although radiotherapy should be planned to keep the dose to pacemaker as low as possible not to malfunction ideally, current radiation treatment planning (RTP) system does not accurately calculate deposited dose to adjacent field border or area beyond irradiated fields. In terms of beam delivery techniques using multiple intensity modulated fields, dosimetric effect of scattered radiation in high energy photon beams is required to be detailed analyzed based on measurement data. The aim of this study is to evaluate dose discrepancies of pacemaker in a RTP system as compared to measured doses. We also designed dose reduction strategy limited value of 2 Gy for radiation treatment patients with cardiac implanted pacemaker. Total accumulated dose of 145 cGy based on in-vivo dosimetry was satisfied with the recommendation criteria to prevent malfunction of pacemaker in SS technique. However, the 2 mm lead shielder enabled the scattered doses to reduce up to 60% and 40% in the patient and the phantom, respectively. The SS technique with the lead shielding could reduce the accumulated scattered doses less than 100 cGy. Calculated and measured doses were not greatly affected by the beam delivery techniques. In-vivo and measured doses on pacemaker position showed critical dose discrepancies reaching up to 4 times as compared to planned doses in RTP. The current SS technique could deliver lower scattered doses than recommendation criteria, but use of 2 mm lead shielder contributed to reduce scattered doses by 60%. The tertiary lead shielder can be useful to prevent malfunction or electrical damage of implanted pacemakers during radiotherapy. It is required to estimate more accurate scattered doses of the patient or medical device in RTP to design proper dose reduction strategy.

  17. Analysis of Cumulative Dose to Implanted Pacemaker According to Various IMRT Delivery Methods: Optimal Dose Delivery Versus Dose Reduction Strategy

    International Nuclear Information System (INIS)

    Lee, Jeong Woo; Hong, Se Mie

    2011-01-01

    Cancer patients with implanted cardiac pacemaker occasionally require radiotherapy. Pacemaker may be damaged or malfunction during radiotherapy due to ionizing radiation or electromagnetic interference. Although radiotherapy should be planned to keep the dose to pacemaker as low as possible not to malfunction ideally, current radiation treatment planning (RTP) system does not accurately calculate deposited dose to adjacent field border or area beyond irradiated fields. In terms of beam delivery techniques using multiple intensity modulated fields, dosimetric effect of scattered radiation in high energy photon beams is required to be detailed analyzed based on measurement data. The aim of this study is to evaluate dose discrepancies of pacemaker in a RTP system as compared to measured doses. We also designed dose reduction strategy limited value of 2 Gy for radiation treatment patients with cardiac implanted pacemaker. Total accumulated dose of 145 cGy based on in-vivo dosimetry was satisfied with the recommendation criteria to prevent malfunction of pacemaker in SS technique. However, the 2 mm lead shielder enabled the scattered doses to reduce up to 60% and 40% in the patient and the phantom, respectively. The SS technique with the lead shielding could reduce the accumulated scattered doses less than 100 cGy. Calculated and measured doses were not greatly affected by the beam delivery techniques. In-vivo and measured doses on pacemaker position showed critical dose discrepancies reaching up to 4 times as compared to planned doses in RTP. The current SS technique could deliver lower scattered doses than recommendation criteria, but use of 2 mm lead shielder contributed to reduce scattered doses by 60%. The tertiary lead shielder can be useful to prevent malfunction or electrical damage of implanted pacemakers during radiotherapy. It is required to estimate more accurate scattered doses of the patient or medical device in RTP to design proper dose reduction strategy.

  18. Cumulative total effective whole-body radiation dose in critically ill patients.

    Science.gov (United States)

    Rohner, Deborah J; Bennett, Suzanne; Samaratunga, Chandrasiri; Jewell, Elizabeth S; Smith, Jeffrey P; Gaskill-Shipley, Mary; Lisco, Steven J

    2013-11-01

    Uncertainty exists about a safe dose limit to minimize radiation-induced cancer. Maximum occupational exposure is 20 mSv/y averaged over 5 years with no more than 50 mSv in any single year. Radiation exposure to the general population is less, but the average dose in the United States has doubled in the past 30 years, largely from medical radiation exposure. We hypothesized that patients in a mixed-use surgical ICU (SICU) approach or exceed this limit and that trauma patients were more likely to exceed 50 mSv because of frequent diagnostic imaging. Patients admitted into 15 predesignated SICU beds in a level I trauma center during a 30-day consecutive period were prospectively observed. Effective dose was determined using Huda's method for all radiography, CT imaging, and fluoroscopic examinations. Univariate and multivariable linear regressions were used to analyze the relationships between observed values and outcomes. Five of 74 patients (6.8%) exceeded exposures of 50 mSv. Univariate analysis showed trauma designation, length of stay, number of CT scans, fluoroscopy minutes, and number of general radiographs were all associated with increased doses, leading to exceeding occupational exposure limits. In a multivariable analysis, only the number of CT scans and fluoroscopy minutes remained significantly associated with increased whole-body radiation dose. Radiation levels frequently exceeded occupational exposure standards. CT imaging contributed the most exposure. Health-care providers must practice efficient stewardship of radiologic imaging in all critically ill and injured patients. Diagnostic benefit must always be weighed against the risk of cumulative radiation dose.

  19. Cumulative Lung Dose for Several Motion Management Strategies as a Function of Pretreatment Patient Parameters

    International Nuclear Information System (INIS)

    Hugo, Geoffrey D.; Campbell, Jonathon; Zhang Tiezhi; Yan Di

    2009-01-01

    Purpose: To evaluate patient parameters that may predict for relative differences in cumulative four-dimensional (4D) lung dose among several motion management strategies. Methods and Materials: Deformable image registration and dose accumulation were used to generate 4D treatment plans for 18 patients with 4D computed tomography scans. Three plans were generated to simulate breath hold at normal inspiration, target tracking with the beam aperture, and mid-ventilation aperture (control of the target at the mean daily position and application of an iteratively computed margin to compensate for respiration). The relative reduction in mean lung dose (MLD) between breath hold and mid-ventilation aperture (ΔMLD BH ) and between target tracking and mid-ventilation aperture (ΔMLD TT ) was calculated. Associations between these two variables and parameters of the lesion (excursion, size, location, and deformation) and dose distribution (local dose gradient near the target) were also calculated. Results: The largest absolute and percentage differences in MLD were 1.0 Gy and 21.5% between breath hold and mid-ventilation aperture. ΔMLD BH was significantly associated (p TT was significantly associated with excursion, deformation, and local dose gradient. A linear model was constructed to represent ΔMLD vs. excursion. For each 5 mm of excursion, target tracking reduced the MLD by 4% compared with the results of a mid-ventilation aperture plan. For breath hold, the reduction was 5% per 5 mm of excursion. Conclusions: The relative difference in MLD among different motion management strategies varied with patient and tumor characteristics for a given dosimetric target coverage. Tumor excursion is useful to aid in stratifying patients according to appropriate motion management strategies.

  20. Methotrexate osteopathy

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, A.M.; Leonidas, J.C.

    1984-01-01

    Methotrexate osteopathy is an uncommon complication of long-term oral maintenance therapy for childhood neoplasms, most commonly acute lymphocytic leukemia. It is characterized by severe lower extremity pain and by osteoporosis particularly involving the lower extremities and thick dense provisional zones of calcification and growth arrest lines resembling scurvy. Fractures may occur. The appearance must be distinguished from recurrent or metastatic disease.

  1. Methotrexate osteopathy

    International Nuclear Information System (INIS)

    Schwartz, A.M.; Leonidas, J.C.; Tufts Univ., Boston, MA

    1984-01-01

    Methotrexate osteopathy is an uncommon complication of long-term oral maintenance therapy for childhood neoplasms, most commonly acute lymphocytic leukemia. It is characterized by severe lower extremity pain and by osteoporosis particularly involving the lower extremities and thick dense provisional zones of calcification and growth arrest lines resembling scurvy. Fractures may occur. The appearance must be distinguished from recurrent or metastatic disease. (orig.)

  2. Negative impact of high cumulative glucocorticoid dose on bone metabolism of patients with myasthenia gravis.

    Science.gov (United States)

    Braz, Nayara Felicidade Tomaz; Rocha, Natalia Pessoa; Vieira, Érica Leandro Marciano; Gomez, Rodrigo Santiago; Barbosa, Izabela Guimarães; Malheiro, Olívio Brito; Kakehasi, Adriana Maria; Teixeira, Antonio Lucio

    2017-08-01

    This current study aimed to evaluate the frequency of low bone mass, osteopenia, and osteoporosis in patients with myasthenia gravis (MG) and to investigate the possible association between bone mineral density (BMD) and plasma levels of bone metabolism markers. Eighty patients with MG and 62 controls BMD were measured in the right femoral neck and lumbar spine by dual-energy X-ray absorptiometry. Plasma concentrations of osteocalcin, osteopontin, osteoprotegerin, tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-6, dickkopf (DKK-1), sclerostin, insulin, leptin, adrenocorticotropic hormone, parathyroid hormone, and fibroblast growth factor (FGF-23) were analyzed by Luminex®. The mean age of patients was 41.9 years, with 13.5 years of length of illness, and a mean cumulative dose of glucocorticoids 38,123 mg. Patients had significant reduction in BMD of the lumbar, the femoral neck, and in the whole body when compared with controls. Fourteen percent MG patients had osteoporosis at the lumbar spine and 2.5% at the femoral neck. In comparison with controls, patients with MG presented lower levels of osteocalcin, adrenocorticotropic hormone, parathyroid hormone, sclerostin, TNF-α, and DKK-1 and higher levels of FGF-23, leptin, and IL-6. There was a significant negative correlation between cumulative glucocorticoid dose and serum calcium, lumbar spine T-score, femoral neck BMD, T-score, and Z-score. After multivariate analysis, higher TNF-α levels increased the likelihood of presenting low bone mass by 2.62. MG patients under corticotherapy presented low BMD and altered levels of bone markers.

  3. PROGNOSTIC FACTORS FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMAS TREATED WITH HIGH-DOSE METHOTREXATE-BASED CHEMO-RADIOTHERAPY

    Science.gov (United States)

    Nagane, Motoo; Lee, Jeunghun; Shishido-Hara, Yukiko; Suzuki, Kaori; Shimizu, Saki; Umino, Michiru; Kobayashi, Keiichi; Shiokawa, Yoshiaki

    2014-01-01

    BACKGROUND: Chemotherapy with high-dose methotrexate (HD-MTX) followed by whole brain radiotherapy (WBRT) is a conventional approach to treat primary central nervous system lymphomas (PCNSL), but some tumors relapse early leading to unfavorable outcome. Several biomarkers have been identified as prognostic factors in PCNSL, however, the correlation of both clinical factors including those related to MTX metabolism and B-cell differentiation and oncogenic biomarkers with response to and outcome by therapy is yet unclear. METHODS: We investigated 32 immunocompetent patients (19 males, 13 females) with PCNSL (all diffuse large B-cell type) treated with HD-MTX based therapy with or without WBRT since 2000 in our institution. Paraffin-embedded formalin-fixed tumor tissue sections were stained immunohistochemically with antibodies against following factors: B-cell differentiation markers (CD10, Bcl-6, Mum-1, CD138); MTX metabolism-related (MRP family, LRP, DHFR); cell cycle-related (p27KIP1, MIB-1); drug resistance-related (MGMT, MLH1, MSH2, MSH6, PMS2); and oncogenes (Myc, Bcl-2). Correlation between positivity of these factors and clinical outcomes were evaluated using logrank test and cox regression analysis. RESULTS: Among these factors, complete response to HD-MTX was significantly associated with longer progression-free survival (PFS)(P = 0.0012), while Bcl-6 expression as well as histological subtype (non-germinal center B-cell, non-GCB) was closely correlated with shorter PFS. Age (>60) (P = 0.006) and MSH2 expression (P = 0.017) were found to be better predictor for overall survival (OS), but in multivariate analysis, they were no longer significant. Other factors involved in MTX metabolism, DNA repair enzymes, and oncogenes did not affect outcome. CONCLUSIONS: Non-GCB subtype and Bcl-6 expression may be associated with worse outcome in patients with PCNSL treated with HD-MTX, while MTX-metabolism related factors did not influence prognosis. Further

  4. Prediction of the cumulated dose for external beam irradiation of prostate cancer patients with 3D-CRT technique

    Directory of Open Access Journals (Sweden)

    Giżyńska Marta

    2016-03-01

    Full Text Available Nowadays in radiotherapy, much effort is taken to minimize the irradiated volume and consequently minimize doses to healthy tissues. In our work, we tested the hypothesis that the mean dose distribution calculated from a few first fractions can serve as prediction of the cumulated dose distribution, representing the whole treatment. We made our tests for 25 prostate cancer patients treated with three orthogonal fields technique. We did a comparison of dose distribution calculated as a sum of dose distribution from each fraction with a dose distribution calculated with isocenter shifted for a mean setup error from a few first fractions. The cumulative dose distribution and predicted dose distributions are similar in terms of gamma (3 mm 3% analysis, under condition that we know setup error from seven first fractions. We showed that the dose distribution calculated for the original plan with the isocenter shifted to the point, defined as the original isocenter corrected of the mean setup error estimated from the first seven fractions supports our hypothesis, i.e. can serve as a prediction for cumulative dose distribution.

  5. Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6-11 years-old than cumulative high doses of inhaled terbutaline

    DEFF Research Database (Denmark)

    Kaae, Rikke; Agertoft, Lone; Pedersen, Sören

    2004-01-01

    OBJECTIVES: To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. METHODS: Twenty boys and girls (6-11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxi...

  6. A personal radio-frequency dosimeter with cumulative-dose recording capabilities

    International Nuclear Information System (INIS)

    Rochelle, R.W.; Moore, M.R.; Thomas, R.S.; Ewing, P.D.; Hess, R.A.; Hoffheins, B.S.

    1990-01-01

    The radio-frequency (rf) dosimeter developed by the Oak Ridge National Laboratory is a portable, pocket-sized cumulative-dose recording device designed to detect and record the strengths and durations of electric fields present in the work areas of naval vessels. The device measures an integrated dose and records the electric fields that exceed the permissible levels set by the American National Standards Institute. Features of the rf dosimeter include a frequency range of 30 MHz to 10 GHz and a three-dimensional sensor. Data obtained with the rf dosimeter will be used to determine the ambient field-strength profile for shipboard personnel over an extended time. Readings are acquired and averaged over a 6-min period corresponding to the rise time of the core body temperature. These values are stored for up to 6 months, after which the data are transferred to a computer via the dosimeter's serial port. The rf dosimeter should increase knowledge of the levels of electric fields to which individuals are exposed. 13 refs., 16 figs., 2 tabs

  7. Hyper-alkalinization without hyper-hydration for the prevention of high-dose methotrexate acute nephrotoxicity in patients with osteosarcoma.

    Science.gov (United States)

    Mir, Olivier; Ropert, Stanislas; Babinet, Antoine; Alexandre, Jérôme; Larousserie, Frédérique; Durand, Jean-Philippe; Enkaoua, Eric; Anract, Philippe; Goldwasser, François

    2010-11-01

    To evaluate the reliability and renal safety of an original schedule of high-dose methotrexate (HDMTX) administration with hyper-alkalinization, and without hyper-hydration. Patients with osteosarcoma received HDMTX (8-12 g/m(2)) as a 4-h infusion. Hypertonic 8.4% sodium bicarbonate was infused prior to HDMTX, then once daily for 3 days. Methotrexate serum concentrations were measured at hour 4 (Cmax), hour 24, hour 48, and hour 72. Urinary pH was measured on each miction. Serum creatinine was assessed on days 1, 3, and 8. Twenty-six patients (median age: 18 years, range: 15-25) received a total of 344 cycles of HDMTX, including 16 patients treated in an outpatient basis. Urinary pH remained constantly higher than 7.5 in all patients. Grade 1 creatininemia toxicity was observed in 31 cycles (9%), and grade 2 creatinine toxicity was observed in one patient. No episode of acute severe nephrotoxicity was observed. No significant worsening was observed in serum creatinine and calculated creatinine clearance from baseline to the end of therapy (P = 0.74). The main extra-renal toxicity was alkalinization-related hypokalemia from H48. No re-hospitalization was required. Hyper-alkalinization appears an efficient and reliable method to prevent the acute renal toxicity of HDMTX and allows its safe administration in the outpatient setting.

  8. [Late sequelae of central nervous system prophylaxis in children with acute lymphoblastic leukemia: high doses of intravenous methotrexate versus radiotherapy of the central nervous system--review of literature].

    Science.gov (United States)

    Zając-Spychała, Olga; Wachowiak, Jacek

    2012-01-01

    Acute lymphoblastic leukemia is the most common malignancy in children. All current therapy regimens used in the treatment of childhood acute lymphoblastic leukemia include prophylaxis of the central nervous system. Initially it was thought that the best way of central nervous system prophylaxis is radiotherapy. But despite its effectiveness this method, may cause late sequelae and complications. In the programme currently used in Poland to treat acute lymphoblastic leukemia, prophylactic radiotherapy has been reduced by 50% (12 Gy) and is used only in patients stratified into the high risk group and in patients diagnosed as T-cell ALL (T-ALL). Complementary to radiotherapy, intrathecal methotrexate is given alone or in combination with cytarabine and hydrocortisone is given, as well as systemic chemotherapy with intravenous methotrexate is administered in high or medium doses (depending on risk groups and leukemia immunophenotype). Recent studies have shown that high dose irradiation of the central nervous system impairs cognitive development causing memory loss, visuomotor coordination impairment, attention disorders and reduction in the intelligence quotient. It has been proved that the degree of cognitive impairment depends on the radiation dose directed to the medial temporal lobe structures, particularly in the hippocampus and the surrounding cortex. Also, methotrexate used intravenously in high doses, interferes with the metabolism of folic acid which is necessary for normal development and the optimal functioning of neurons in the central nervous system. It has been proved that patients who have been treated with high doses of methotrexate are characterized by reduced memory skills and a lower intelligence quotient. The literature data concerning long term neuroanatomical abnormalities and neuropsychological deficits are ambiguous, and there is still no data concerning current methods of central nervous system prophylaxis with low doses of irradiation in

  9. Cumulative effective dose associated with computed tomography examinations in adolescent trauma patients.

    Science.gov (United States)

    Choi, Seung Joon; Kim, Eun Young; Kim, Hyung Sik; Choi, Hye-Young; Cho, Jinseong; Yang, Hyuk Jun; Chung, Yong Eun

    2014-07-01

    The aims of this study were to analyze cumulative effective dose (cED) and to assess lifetime attributable risk (LAR) of cancer due to radiation exposure during computed tomography (CT) examinations in adolescent trauma patients. Between January 2010 and May 2011, the adolescent patients with trauma were enrolled in this study. Numbers of CT examinations and body regions examined were collated, and cEDs were calculated using dose-length product values and conversion factors. Lifetime attributable risk for cancer incidence and cancer-associated mortality were quantified based on the studies of survivors of the atomic bombs on Japan. Data were stratified according to severity of trauma: minor trauma, injury severity score of less than 16; and major trauma, injury severity score of 16 or greater. A total of 698 CT scans were obtained on the following regions of 484 adolescent patients: head CT, n = 647; rest of the body, n = 41; and thorax, n = 10. Mean cED per patient was 3.4 mSv, and mean LARs for cancer incidence and mortality were 0.05% and 0.02%, respectively. The majority of patients (98.4%) experienced minor trauma, and their mean cED and LARs for cancer incidence and mortality (3.0 mSv and 0.04% and 0.02%, respectively) were significantly lower than those of patients with major trauma (24.3 mSv and 0.31% and 0.15%, respectively, all P values trauma was found to be relatively low in adolescent patients. However, adolescent patients with major trauma were exposed to a substantial amount of radiation during multiple CT examinations.

  10. Re-irradiation: Outcome, cumulative dose and toxicity in patients retreated with stereotactic radiotherapy in the abdominal or pelvic region

    NARCIS (Netherlands)

    H. Abusaris (Huda); M.S. Hoogeman (Mischa); J.J.M.E. Nuyttens (Joost)

    2012-01-01

    textabstractThe purpose of the present study was to explore the outcome, cumulative dose in tumor and organs at risk and toxicity after extra-cranial stereotactic re-irradiation. Twenty-seven patients were evaluated who had been re-irradiated with stereotactic body radiotherapy (SBRT) after

  11. Individualized toxicity-titrated 6-mercaptopurine increments during high-dose methotrexate consolidation treatment of lower risk childhood acute lymphoblastic leukaemia. A Nordic Society of Paediatric Haematology and Oncology (NOPHO) pilot study

    DEFF Research Database (Denmark)

    Frandsen, Thomas L; Abrahamsson, Jonas; Lausen, Birgitte

    2011-01-01

    This study explored the feasibility and toxicity of individualized toxicity-titrated 6-mercaptopurine (6MP) dose increments during post-remission treatment with High-dose methotrexate (HDM) (5000 mg/m(2), ×3) in 38 patients with Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m(2...... the remaining patients (P = 0·03). This study shows individualized toxicity-titrated 6MP dosing during consolidation is feasible without increased risk of toxicity....

  12. Estimated cumulative radiation dose received by diagnostic imaging during staging and treatment of operable Ewing sarcoma 2005-2012

    Energy Technology Data Exchange (ETDEWEB)

    Johnsen, Boel [Haukeland University Hospital, Centre for Nuclear Medicine and PET, Department of Radiology, P.O. Box 1400, Bergen (Norway); Fasmer, Kristine Eldevik [Haukeland University Hospital, Department of Oncology, Medical Physics Section, Bergen (Norway); Boye, Kjetil [Norwegian Radium Hospital, Oslo University Hospital, Department of Oncology, Oslo (Norway); Rosendahl, Karen; Aukland, Stein Magnus [Haukeland University Hospital, Department of Radiology, Paediatric Section, Bergen (Norway); University of Bergen, Department of Clinical Medicine, Bergen (Norway); Trovik, Clement [University of Bergen, Department of Clinical Medicine, Bergen (Norway); Haukeland University Hospital, Department of Surgery, Orthopaedic Section, Bergen (Norway); Biermann, Martin [Haukeland University Hospital, Centre for Nuclear Medicine and PET, Department of Radiology, P.O. Box 1400, Bergen (Norway); University of Bergen, Department of Clinical Medicine, Bergen (Norway)

    2017-01-15

    Patients with Ewing sarcoma are subject to various diagnostic procedures that incur exposure to ionising radiation. To estimate the radiation doses received from all radiologic and nuclear imaging episodes during diagnosis and treatment, and to determine whether {sup 18}F-fluorodeoxyglucose positron emission tomography - computed tomography ({sup 18}F-FDG PET-CT) is a major contributor of radiation. Twenty Ewing sarcoma patients diagnosed in Norway in 2005-2012 met the inclusion criteria (age <30 years, operable disease, uncomplicated chemotherapy and surgery, no metastasis or residual disease within a year of diagnosis). Radiation doses from all imaging during the first year were calculated for each patient. The mean estimated cumulative radiation dose for all patients was 34 mSv (range: 6-70), radiography accounting for 3 mSv (range: 0.2-12), CT for 13 mSv (range: 2-28) and nuclear medicine for 18 mSv (range: 2-47). For the patients examined with PET-CT, the mean estimated cumulative effective dose was 38 mSv, of which PET-CT accounted for 14 mSv (37%). There was large variation in number and type of examinations performed and also in estimated cumulative radiation dose. The mean radiation dose for patients examined with PET-CT was 23% higher than for patients not examined with PET-CT. (orig.)

  13. Estimated cumulative radiation dose received by diagnostic imaging during staging and treatment of operable Ewing sarcoma 2005-2012

    International Nuclear Information System (INIS)

    Johnsen, Boel; Fasmer, Kristine Eldevik; Boye, Kjetil; Rosendahl, Karen; Aukland, Stein Magnus; Trovik, Clement; Biermann, Martin

    2017-01-01

    Patients with Ewing sarcoma are subject to various diagnostic procedures that incur exposure to ionising radiation. To estimate the radiation doses received from all radiologic and nuclear imaging episodes during diagnosis and treatment, and to determine whether 18 F-fluorodeoxyglucose positron emission tomography - computed tomography ( 18 F-FDG PET-CT) is a major contributor of radiation. Twenty Ewing sarcoma patients diagnosed in Norway in 2005-2012 met the inclusion criteria (age <30 years, operable disease, uncomplicated chemotherapy and surgery, no metastasis or residual disease within a year of diagnosis). Radiation doses from all imaging during the first year were calculated for each patient. The mean estimated cumulative radiation dose for all patients was 34 mSv (range: 6-70), radiography accounting for 3 mSv (range: 0.2-12), CT for 13 mSv (range: 2-28) and nuclear medicine for 18 mSv (range: 2-47). For the patients examined with PET-CT, the mean estimated cumulative effective dose was 38 mSv, of which PET-CT accounted for 14 mSv (37%). There was large variation in number and type of examinations performed and also in estimated cumulative radiation dose. The mean radiation dose for patients examined with PET-CT was 23% higher than for patients not examined with PET-CT. (orig.)

  14. Relationship between mutation frequency of GPA locus and cumulative dose among medical diagnostic X-ray workers

    International Nuclear Information System (INIS)

    Wang Jixian; Yu Wenru; Li Benxiao; Fan Tiqiang; Li Zhen; Gao Zhiwei; Chen Zhenjun; Zhao Yongcheng

    2000-01-01

    Objective: To explore the feasibility of using GPA locus mutation assay as a bio-dosimeter for occupational exposure to ionizing radiation. Methods: An improved technique of GPA locus mutation assay was used in th study. The frequencies of mutant RBC in peripheral blood of 55 medical X-ray workers and 50 controls employed in different calendar-year periods were detected. The relationship between mutation frequencies (MFs) and period of entry, working years and cumulative doses were analyzed. Results: The MFs were significantly elevated among X-ray workers employed before 1970. This finding is similar to the result of cancer epidemiological study among medical X-ray workers , in which the cancer risk was significantly increased only X-ray workers employed before 1970. The MFs of GPA increased with increasing cumulative dose. The dose-effect relationship of Nφ MF with cumulative dose was closer than that of NN MF. Conclusion: There are many problems to be solved for using GPA MF assay as a bio-dosimeter such as individual variation, specificity and calibration curve of dose-effect relationship

  15. The influence of folate pathway polymorphisms on high-dose methotrexate-related toxicity and survival in children with non-Hodgkin malignant lymphoma

    Science.gov (United States)

    Erculj, Nina; Kotnik, Barbara Faganel; Debeljak, Marusa; Jazbec, Janez; Dolzan, Vita

    2014-01-01

    Background We evaluated the influence of folate pathway polymorphisms on high-dose methotrexate (HD-MTX) related toxicity in paediatric patients with T-cell non-Hodgkin lymphoma (NHL). Patients and methods In total, 30 NHL patients were genotyped for selected folate pathway polymorphisms. Results Carriers of at least one MTHFR 677T allele had significantly higher MTX area under the time-concentration curve levels at third MTX cycle (P = 0.003). These patients were also at higher odds of leucopoenia (P = 0.006) or thrombocytopenia (P = 0.041) and had higher number of different HD-MTX-related toxicity (P = 0.035) compared to patients with wild-type genotype. Conclusions Our results suggest an important role of MTHFR 677C>T polymorphism in the development of HD-MTX-related toxicity in children with NHL. PMID:25177243

  16. The influence of folate pathway polymorphisms on high-dose methotrexate-related toxicity and survival in children with non-Hodgkin malignant lymphoma

    International Nuclear Information System (INIS)

    Erculj, Nina; Kotnik, Barbara Faganel; Debeljak, Marusa; Jazbec, Janez; Dolzan, Vita

    2014-01-01

    We evaluated the influence of folate pathway polymorphisms on high-dose methotrexate (HD-MTX) related toxicity in paediatric patients with T-cell non-Hodgkin lymphoma (NHL). In total, 30 NHL patients were genotyped for selected folate pathway polymorphisms. Carriers of at least one MTHFR 677T allele had significantly higher MTX area under the time-concentration curve levels at third MTX cycle (P = 0.003). These patients were also at higher odds of leucopoenia (P = 0.006) or thrombocytopenia (P = 0.041) and had higher number of different HD-MTX-related toxicity (P = 0.035) compared to patients with wild-type genotype. Our results suggest an important role of MTHFR 677C>T polymorphism in the development of HD-MTX-related toxicity in children with NHL

  17. Applicability of the tissue stem cell turnover concept on the validity of cumulative dose based radiation risk evaluation

    International Nuclear Information System (INIS)

    Otsuka, Kensuke; Hamada, Nobuyuki; Iwasaki, Toshiyasu; Yoshida, Kazuo

    2011-01-01

    The radiation protection system adopts the linear no-threshold model to achieve proper radiation protection for considering cancer risks resulting from radiation exposure. This model uses cumulative dose to a tissue for risk evaluation in which cumulative dose is related to the amount of DNA damage and consequential induction of gene mutation. In this concept, gene mutation accumulates in tissue stem cells, the putative target of carcinogenesis, with total dose given to the tissue. Unlike high-dose-rate exposure, epidemiological studies in high radiation background areas, such as Kerala in India, revealed that cancer risks is not elevated by the dose to the inhabitants, suggesting that there exists some mechanisms to eliminate the damage/mutation in the exposed tissue under extremely low-dose-rate exposure situations. In this report, the dynamics of tissue stem cell turnover is evaluated as a possible mechanism under extremely low-dose-rate exposure situations. To this end, we reviewed recent literatures studying tissue stem cell turnover, and found that great advances in stem cell research have made it possible to trace a fate of stem cells in tissues. Furthermore, turnover of tissue stem cells is found to occur after irradiation, due to competition of stem cells within tissues. This raises a possibility that radiation effects may not accumulate in a tissue depending on the dose-rate and duration of exposure period. (author)

  18. Methotrexate for ocular inflammatory diseases.

    Science.gov (United States)

    Gangaputra, Sapna; Newcomb, Craig W; Liesegang, Teresa L; Kaçmaz, R Oktay; Jabs, Douglas A; Levy-Clarke, Grace A; Nussenblatt, Robert B; Rosenbaum, James T; Suhler, Eric B; Thorne, Jennifer E; Foster, C Stephen; Kempen, John H

    2009-11-01

    To evaluate the outcome of treatment with methotrexate for noninfectious ocular inflammation. Retrospective cohort study. Patients with noninfectious ocular inflammation managed at 4 tertiary ocular inflammation clinics in the United States observed to add methotrexate as a single, noncorticosteroid immunosuppressive agent to their treatment regimen, between 1979 and 2007, inclusive. Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics, including dosage, route of administration of methotrexate, and main outcome measures, were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers. Control of inflammation, corticosteroid-sparing effects, and incidence of and reason for discontinuation of therapy. Among 384 patients (639 eyes) observed from the point of addition of methotrexate to an anti-inflammatory regimen, 32.8%, 9.9%, 21.4%, 14.6%, 15.1%, and 6.3%, respectively, had anterior uveitis, intermediate uveitis, posterior or panuveitis, scleritis, ocular mucous membrane pemphigoid, and other forms of ocular inflammation. In these groups, complete suppression of inflammation sustained for >or=28 days was achieved within 6 months in 55.6%, 47.4%, 38.6%, 56.4%, 39.5%, and 76.7%, respectively. Corticosteroid-sparing success (sustained suppression of inflammation with prednisone Methotrexate was discontinued within 1 year by 42% of patients. It was discontinued owing to ineffectiveness in 50 patients (13%); 60 patients (16%) discontinued because of side effects, which typically were reversible with dose reduction or discontinuation. Remission was seen in 43 patients, with 7.7% remitting within 1 year of treatment. Our data suggest that adding methotrexate to an anti-inflammatory regimen not involving other noncorticosteroid immunosuppressive drugs is moderately effective for management of inflammatory activity and for achieving

  19. The dose-response relationship between cumulative lifting load and lumbar disk degeneration based on magnetic resonance imaging findings.

    Science.gov (United States)

    Hung, Yu-Ju; Shih, Tiffany T-F; Chen, Bang-Bin; Hwang, Yaw-Huei; Ma, Li-Ping; Huang, Wen-Chuan; Liou, Saou-Hsing; Ho, Ing-Kang; Guo, Yue L

    2014-11-01

    Lumbar disk degeneration (LDD) has been related to heavy physical loading. However, the quantification of the exposure has been controversial, and the dose-response relationship with the LDD has not been established. The purpose of this study was to investigate the dose-response relationship between lifetime cumulative lifting load and LDD. This was a cross-sectional study. Every participant received assessments with a questionnaire, magnetic resonance imaging (MRI) of the lumbar spine, and estimation of lumbar disk compression load. The MRI assessments included assessment of disk dehydration, annulus tear, disk height narrowing, bulging, protrusion, extrusion, sequestration, degenerative and spondylolytic spondylolisthesis, foramina narrowing, and nerve root compression on each lumbar disk level. The compression load was predicted using a biomechanical software system. A total of 553 participants were recruited in this study and categorized into tertiles by cumulative lifting load (ie, lifting load. The best dose-response relationships were found at the L5-S1 disk level, in which high cumulative lifting load was associated with elevated odds ratios of 2.5 (95% confidence interval [95% CI]=1.5, 4.1) for dehydration and 4.1 (95% CI=1.9, 10.1) for disk height narrowing compared with low lifting load. Participants exposed to intermediate lifting load had an increased odds ratio of 2.1 (95% CI=1.3, 3.3) for bulging compared with low lifting load. The tests for trend were significant. There is no "gold standard" assessment tool for measuring the lumbar compression load. The results suggest a dose-response relationship between cumulative lifting load and LDD. © 2014 American Physical Therapy Association.

  20. Relationship of cumulative low-level dose of ionizing radiation on human eye lens and occurrence of cataract

    International Nuclear Information System (INIS)

    Deolalikar, Raghavendra

    2015-01-01

    International Commission on Radiological Protection (ICRP), issued a statement on Tissue Reaction, lowering the equivalent dose limit for eye lens for occupational exposure to 20 mSv per year. With a view to determine presence of any relationship between the cumulative low-level occupational radiation dose to the eye lens and occurrence of cataract, departmental records of the annual medical examination of employees of Narora Atomic Power Plant were examined along with the NAPS eye camps and surgical records of the employees. Analysis of the data showed no demonstrable definite relationship between the two. The analysis of the data and the observations are discussed in this paper. (author)

  1. Quantitative assessment of cumulative damage from repetitive exposures to suberythemogenic doses of UVA in human skin

    International Nuclear Information System (INIS)

    Lavker, R.M.; Kaidbey, K.H.

    1995-01-01

    Daily exposures to relatively small suberythemogenic fluences of UVA (50-200 kJ/m 2 ) for 8 days resulted in cumulative morphological skin alterations indicative of early tissue injury. Histologically, irradiated skin revealed epidermal hyperplasia, inflammation and deposition of lysozyme along the dermal elastic fiber network. Sunburn cells were also present within the epidermis. These changes were quantified by image analysis and were found to be related to the cumulative UVA fluence. A long UVA waveband (UVAI, 340-400 nm) was as effective as a broad UVA band (320-400 nm), suggesting that these changes are induced by longer UVA wavelengths. (author)

  2. A study of the relationship between peak skin dose and cumulative air kerma in interventional neuroradiology and cardiology

    International Nuclear Information System (INIS)

    Neil, S; Padgham, C; Martin, C J

    2010-01-01

    A study of peak skin doses (PSDs) during neuroradiology and cardiology interventional procedures has been carried out using Gafchromic XR-RV2 film. Use of mosaics made from squares held in cling film has allowed doses to the head to be mapped successfully. The displayed cumulative air kerma (CAK) has been calibrated in terms of cumulative entrance surface dose (CESD) and results indicate that this can provide a reliable indicator of the PSD in neuroradiology. Results linking PSD to CESD for interventional cardiology were variable, but CAK is still considered to provide the best option for use as an indicator of potential radiation-induced effects. A CESD exceeding 3 Gy is considered a suitable action level for triggering follow-up of patients in neuroradiology and cardiology for possible skin effects. Application of dose action levels defined in this way would affect 8% of neurological embolisation procedures and 5% of cardiology ablation and multiple stent procedures at the hospitals where the investigations were carried out. A close relationship was observed between CESD and dose-area product (DAP) for particular types of procedure, and DAPs of 200-300 Gy cm 2 could be used as trigger levels where CAK readings were not available. The DAP value would depend on the mean field size and would need to be determined for each application.

  3. Clinical relevance of consolidation radiotherapy and other main therapeutic issues in primary central nervous system lymphomas treated with upfront high-dose methotrexate

    International Nuclear Information System (INIS)

    Reni, Michele; Ferreri, Andres J.M.; Guha-Thakurta, Nandita; Blay, Jean-Yves; Dell'Oro, Stefania; Biron, Pierre; Hochberg, Fred H.

    2001-01-01

    Purpose: To evaluate the optimal dose of methotrexate (MTX) and the efficacy of other drugs, intrathecal chemotherapy (CHT), and radiotherapy (RT) in primary brain lymphomas. Methods and Materials: Two hundred eighty-eight immunocompetent patients with histologically documented, previously untreated primary brain lymphomas, receiving CHT containing high-dose MTX (≥1 g/m 2 ) with or without RT were selected from 19 prospective series. The impact on survival of the MTX dose ( 2 vs.≥3 g/m 2 ), the main drugs, intrathecal CHT, and combination CHT (mono-CHT vs. poly-CHT) was assessed, according to the intention-to-treat principle. The role of post-CHT irradiation (immediate vs. delayed RT) was evaluated in 119 patients with a complete response to CHT. The whole brain and tumor bed dose ( 2 (p=0.04), thiotepa (p=0.03), and intrathecal CHT (p=0.03) improved the OS, and nitrosoureas (p 0.01) correlated with a worse survival. In multivariate analysis, limited to patients receiving MTX ≥3 g/m 2 , only the addition of cytarabine improved the OS; nitrosoureas reduced MTX efficacy. Of the 119 complete responders, 70 received immediate RT. A RT dose of ≥40 Gy to the whole brain or tumor bed did not improve OS. The 3-year OS was similar between the immediate and delayed RT groups. In multivariate analysis, RT delay had no negative impact on survival. Conclusions: MTX ≥3 g/m 2 seems to improve survival in primary brain lymphoma patients. The efficacy of additional drugs, except for cytarabine, remains unproved. Randomized trials are needed to confirm that RT withdrawal yields no detrimental effect in complete responders

  4. Cumulative effective dose and cancer risk for pediatric population in repetitive full spine follow-up imaging: How micro dose is the EOS microdose protocol?

    Science.gov (United States)

    Law, Martin; Ma, Wang-Kei; Lau, Damian; Cheung, Kenneth; Ip, Janice; Yip, Lawrance; Lam, Wendy

    2018-04-01

    To evaluate and to obtain analytic formulation for the calculation of the effective dose and associated cancer risk using the EOS microdose protocol for scoliotic pediatric patients undergoing full spine imaging at different age of exposure; to demonstrate the microdose protocol capable of delivering lesser radiation dose and hence of further reducing cancer risk induction when compared with the EOS low dose protocol; to obtain cumulative effective dose and cancer risk for both genders scoliotic pediatrics of US and Hong Kong population using the microdose protocol. Organ absorbed doses of full spine exposed scoliotic pediatric patients have been simulated with the use of EOS microdose protocol imaging parameters input to the Monte Carlo software PCXMC. Gender and age specific effective dose has been calculated with the simulated organ absorbed dose using the ICRP-103 approach. The associated radiation induced cancer risk, expressed as lifetime attributable risk (LAR), has been estimated according to the method introduced in the Biological Effects of Ionizing Radiation VII report. Values of LAR have been estimated for scoliotic patients exposed repetitively during their follow up period at different age for US and Hong Kong population. The effective doses of full spine imaging with simultaneous posteroanterior and lateral projection for patients exposed at the age between 5 and 18 years using the EOS microdose protocol have been calculated within the range of 2.54-14.75 μSv. The corresponding LAR for US and Hong Kong population was ranged between 0.04 × 10 -6 and 0.84 × 10 -6 . Cumulative effective dose and cancer risk during follow-up period can be estimated using the results and are of information to patients and their parents. With the use of computer simulation and analytic formulation, we obtained the cumulative effective dose and cancer risk at any age of exposure for pediatric patients of US and Hong Kong population undergoing repetitive

  5. Effect of infliximab on renal injury due to methotrexate in rat.

    Science.gov (United States)

    Kirbas, Aynur; Cure, Medine Cumhur; Kalkan, Yildiray; Cure, Erkan; Tumkaya, Levent; Sahin, Osman Zikrullah; Yuce, Suleyman; Kizilkaya, Bayram; Pergel, Ahmet

    2015-05-01

    Methotrexate, an antagonist of folic acid used in the treatment of many cancers and inflammatory diseases, is associated with side effects that limit its usage. Infliximab has been reported to have a protective effect against nephrotoxicity induced by some drugs and ischemic reperfusion. We aimed to investigate whether infliximab has a protective effect against methotrexate-induced nephrotoxicity. We administered methotrexate at a dose of 20 mg/kg as a single intraperitoneal injection in 10 rats (methotrexate group). Another group of 10 rats received a single dose of infliximab, 7 mg/kg, intraperitoneally (infliximab group). The methotrexate and infliximab group received a similar single injection of infliximab 72 hours prior to methotrexate injection. After 72 hours a single dose of methotrexate, 20 mg/kg, was administered intraperitoneally. Five days after methotrexate injection, blood samples were collected and the kidney tissues were removed for biochemical and histological examination. The methotrexate group had significantly higher tissue levels of tumor necrosis factor-α (P = .008), interleukin-1β (P = .04), nitric oxide (P < .001), and adenosine deaminase (P < .001) than the methotrexate and infliximab group after the 5-day study. The methotrexate group also had significantly higher total histological scores (P < .001) and carbonic anhydrase-II activity (P < .001) when compared to the methotrexate and infliximab group. Infliximab has a strong protective effect against methotrexate-induced nephrotoxicity by suppressing cytokines release. It may decrease methotrexate-induced nephrotoxicity by regulating carbonic anhydrase-II enzyme activities and slowing down purine metabolism.

  6. Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Kwon, H H; Bang, S Y; Won, S; Park, Y; Yi, J H; Joo, Y B; Lee, H S; Bae, S C

    2018-01-01

    Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p = 0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, p AVN. Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors ( p AVN in our Korean lupus cohort. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE

  7. Is high dose methotrexate without irradiation of the brain sufficiently effective in prevention of CNS disease in children with acute lymphoblastic leukemia?

    International Nuclear Information System (INIS)

    Cap, J.; Foltinova, A.; Kaiserova, E.; Mojzesova, A.; Sejnova, D.; Jamarik, M.

    1998-01-01

    We present 5-year results of treatment in 93 children suffering from acute lymphoblastic leukemia using two therapeutic protocols containing multidrug chemotherapy including high dose methotrexate. We could ascertain different results in standard and high risk patients. In a group of 62 children with standard risk we observed improvement in complete remission rate being 98.9% after induction phase of therapy, only one patient died on septicemia. Relapse rate in this group was 21.2% and that 14. 7% in the bone marrow and 6.5% in CNS and no testicular relapse at all. In the group of 31 children with high risk leukemia all patients achieved complete remission. Only one of them died on acute pancreatitis due to toxicity. Overall relapse rate in this group was 28.9% with 12.8% of medullary relapse and 16.1 % of CNS relapse. The last one was significantly higher than in the previous study when brain irradiation was a part of therapeutic procedure. It seems that this treatment is effective mainly in the standard risk leukemia, however, in the high risk leukemias this procedure appears to be less effective in preventing CNS leukemia. In this group of patients irradiation of the brain need to be enclosed in the therapy. (authors)

  8. Association between SLC19A1 Gene Polymorphism and High Dose Methotrexate Toxicity in Childhood Acute Lymphoblastic Leukaemia and Non Hodgkin Malignant Lymphoma: Introducing a Haplotype based Approach

    Science.gov (United States)

    Kotnik, Barbara Faganel; Jazbec, Janez; Grabar, Petra Bohanec; Rodriguez-Antona, Cristina

    2017-01-01

    Abstract Background We investigated the clinical relevance of SLC 19A1 genetic variability for high dose methotrexate (HD-MTX) related toxicities in children and adolescents with acute lymphoblastic leukaemia (ALL) and non Hodgkin malignant lymphoma (NHML). Patients and methods Eighty-eight children and adolescents with ALL/NHML were investigated for the influence of SLC 19A1 single nucleotide polymorphisms (SNPs) and haplotypes on HD-MTX induced toxicities. Results Patients with rs2838958 TT genotype had higher probability for mucositis development as compared to carriers of at least one rs2838958 C allele (OR 0.226 (0.071–0.725), p < 0.009). Haplotype TGTTCCG (H4) statistically significantly reduced the risk for the occurrence of adverse events during treatment with HD-MTX (OR 0.143 (0.023–0.852), p = 0.030). Conclusions SLC 19A1 SNP and haplotype analysis could provide additional information in a personalized HD-MTX therapy for children with ALL/NHML in order to achieve better treatment outcome. However further studies are needed to validate the results. PMID:29333125

  9. Estimated cumulative radiation dose from PET/CT in children with malignancies: a 5-year retrospective review

    International Nuclear Information System (INIS)

    Chawla, Soni C.; Federman, Noah; Zhang, Di; Nagata, Kristen; Nuthakki, Soujanya; McNitt-Gray, Michael; Boechat, M.I.

    2010-01-01

    The increasing use of serial PET/CT scans in the management of pediatric malignancies raises the important consideration of radiation exposure in children. To estimate the cumulative radiation dose from PET/CT studies to children with malignancy and to compare with the data in literature. Two hundred forty-eight clinical PET/CT studies performed on 78 patients (50 boys/28 girls, 1.3 to 18 years old from December 2002 to October 2007) were retrospectively reviewed under IRB approval. The whole-body effective dose (ED) estimates for each child were obtained by estimating the effective dose from each PET/CT exam performed using the ImPACT Patient Dosimetry Calculator for CT and OLINDA for PET. The average number of PET/CT studies was 3.2 per child (range: 1 to 14 studies). The average ED of an individual CT study was 20.3 mSv (range: 2.7 to 54.2), of PET study was 4.6 mSv (range: 0.4 to 7.7) and of PET/CT study was 24.8 mSv (range: 6.2 to 60.7). The average cumulative radiation dose per patient from CT studies was 64.4 mSv (range: 2.7 to 326), from PET studies was 14.5 mSv (range: 2.8 to 73) and from PET/CT studies was 78.9 mSv (range: 6.2 to 399). The radiation exposure from serial PET/CT studies performed in pediatric malignancies was considerable; however, lower doses can be used for both PET and CT studies. The ALARA principle must be applied without sacrificing diagnostic information. (orig.)

  10. Cumulative dose 60Co gamma irradiation effects on AlGaN/GaN Schottky diodes and its area dependence

    Science.gov (United States)

    Sharma, Chandan; Laishram, Robert; Rawal, Dipendra Singh; Vinayak, Seema; Singh, Rajendra

    2018-04-01

    Cumulative dose gamma radiation effects on current-voltage characteristics of GaN Schottky diodes have been investigated. The different area diodes have been fabricated on AlGaN/GaN high electron mobility transistor (HEMT) epi-layer structure grown over SiC substrate and irradiated with a dose up to the order of 104 Gray (Gy). Post irradiation characterization shows a shift in the turn-on voltage and improvement in reverse leakage current. Other calculated parameters include Schottky barrier height, ideality factor and reverse saturation current. Schottky barrier height has been decreased whereas reverse saturation current shows an increase in the value post irradiation with improvement in the ideality factor. Transfer length measurement (TLM) characterization shows an improvement in the contact resistance. Finally, diodes with larger area have more variation in the calculated parameters due to the induced local heating effect.

  11. Similar Improvements in Patient-Reported Outcomes Among Rheumatoid Arthritis Patients Treated with Two Different Doses of Methotrexate in Combination with Adalimumab: Results From the MUSICA Trial.

    Science.gov (United States)

    Kaeley, Gurjit S; MacCarter, Daryl K; Goyal, Janak R; Liu, Shufang; Chen, Kun; Griffith, Jennifer; Kupper, Hartmut; Garg, Vishvas; Kalabic, Jasmina

    2018-06-01

    In patients with rheumatoid arthritis (RA), combination treatment with methotrexate (MTX) and adalimumab is more effective than MTX monotherapy. From the patients' perspective, the impact of reduced MTX doses upon initiating adalimumab is not known. The objective was to evaluate the effects of low and high MTX doses in combination with adalimumab initiation on patient-reported outcomes (PROs), in MTX-inadequate responders (MTX-IR) with moderate-to-severe RA. MUSICA was a randomized, double-blind, controlled trial evaluating the efficacy of 7.5 or 20 mg/week MTX, in combination with adalimumab for 24 weeks in MTX-IR RA patients receiving prior MTX ≥ 15 mg/week for ≥ 12 weeks. PROs were recorded at each visit, including physical function, health-related quality-of-life, work productivity, quality-of-sleep, satisfaction with treatment medication, sexual impairment due to RA, patient global assessment of disease activity (PGA), and patient pain. Last observation carried forward was used to account for missing values. At baseline, patients in both MTX dosage groups had similar demographics, disease characteristics, and PRO scores. Overall, initiation of adalimumab led to significant improvements from baseline in the PROs assessed for both MTX dosage groups. Improvements in presenteeism from baseline were strongly correlated with corresponding improvements in SF-36 (vitality), pain, and physical function. Physical and mental well-being had a good correlation with improvement in sleep. Overall, improvements in disease activity from baseline were correlated with improvements in several PROs. The addition of adalimumab to MTX in MTX-IR patients with moderate-to-severe RA led to improvements in physical function, quality-of-life, work productivity, quality of sleep, satisfaction with treatment medication, and sexual impairment due to RA, regardless of the concomitant MTX dosage. AbbVie. Clinicaltrials.gov identifier, NCT01185288.

  12. Risk of therapy-related leukaemia and preleukaemia after Hodgkin's disease. Relation to age, cumulative dose of alkylating agents, and time from chemotherapy

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, J.; Specht, L.; Larsen, S.O.

    1987-01-01

    391 patients treated intensively for Hodgkin's disease were followed for up to 15 years to evaluate the risk of therapy-related acute non-lymphocytic leukaemia (t-ANLL) and preleukaemia. Only two independent factors, patient age and cumulative dose of alkylating agents, were related to the risk...... of t-ANLL. The hazard rate of t-ANLL was roughly proportional to the square of patient age and to the total cumulative dose of alkylating agents. In 320 patients treated with alkylating agents the cumulative risk of t-ANLL increased steadily from 1 year after the start of treatment and reached 13.......0% (SE 3.0) at 10 years after which time there were no further cases. Calculated from cessation of therapy with alkylating agents, however, the cumulative risk curve increased steeply during the first 1-2 years then gradually levelled out and no new cases were observed beyond 7 years. With a 15-year...

  13. Clinical significance of cumulative biological effective dose and overall treatment time in the treatment of carcinoma cervix

    Directory of Open Access Journals (Sweden)

    Mandal Abhijit

    2007-01-01

    Full Text Available The purpose of this retrospective study is to report the radiotherapy treatment response of, and complications in, patients with cervical cancer on the basis of cumulative biologic effective dose (BED and overall treatment time (OTT. Sixty-four (stage II - 35/64; stage III - 29/64 patients of cervical cancer were treated with combination of external beam radiotherapy (EBRT and low dose rate intracavitary brachytherapy (ICBT. The cumulative BED was calculated at Point A (BED 10 ; and bladder, rectal reference points (BED 2.5 using the linear-quadratic BED equations. The local control (LC rate and 5-year disease-free survival (DFS rate in patients of stage II were comparable for BED 10 < 84.5 and BED 10 > 84.5 but were much higher for BED 10 > 84.5 than BED 10 < 84.5 ( P < 0.01 in stage III patients. In the stage II patients, The LC rate and 5-year DFS rate were comparable for OTT < 50 days and for OTT> 50 days but were much higher in stage III patients with OTT < 50 than OTT> 50 days ( P < 0.001. It was also observed that patients who received BED 2.5 < 105 had lesser rectal ( P < 0.001 and bladder complications than BED 2.5 > 105. Higher rectal complication-free survival (CFS R rate, bladder complication-free survival (CFS B rate and all-type late complication-free survival rate were observed in patients who received BED 2.5 < 105 than BED 2.5 > 105. A balanced, optimal and justified radiotherapy treatment schedule to deliver higher BED 10 (>84.5 and lower BED 2.5 (< 105 in lesser OTT (< 50 days is essential in carcinoma cervix to expect a better treatment outcome in all respects.

  14. Índice orientador do tratamento sistêmico da gravidez ectópica íntegra com dose única de metotrexato Index for the systemic treatment of unruptured ectopic pregnancy with a single dose of methotrexate

    Directory of Open Access Journals (Sweden)

    Julio Elito Junior

    1998-04-01

    iguais a cinco estiveram todas relacionadas com o fracasso do tratamento. O índice orientador ajuda-nos a indicar os melhores casos para o tratamento medicamentoso. Não o aconselhamos, portanto, quando a nota for inferior ou igual a cinco; por outro lado, podemos predizer boa evolução do tratamento, quando a nota for superior a cinco.A prospective study was performed with 42 patients with unruptured ectopic pregnancy, which intended to elaborate an index to orient the systemic treatment with the administration of a single intramuscular dose of methotrexate (50 mg/m². Patients were monitored with beta-hCG titers on days 1, 4 and 7 after the methotrexate. When the titers of beta-hCG declined more than 15%, between days 4 and 7 after methotrexate, the patients were discharged and had an outpatient follow-up monitored with beta-hCG titers weekly until the titers were less than 5 mIU/ml, which represents success of the treatment. We prepared an index for the systemic treatment with methotrexate, with five parameters: (1 initial titers of beta-hCG; (2 aspects of the image at ultrasound (hematosalpinx, gestational sac, live embryo; (3 size of the mass; (4 free fluid in cul-de-sac; (5 collor doppler. Each parameter received a grade from 0 to 2. Grade 0 represented bad prognosis, favorable parameters received grade 2 and borderline parameters received grade one. The success rate with a single dose of methotrexate was 69.0% (29/42. The color doppler was performed in 20 of the 42 patients; in this group of 20 patients the success rate was 75.0% (15/20. In the 22 patients who were not submitted to the color doppler, the average grade of the score in the successful cases was 6.6, and in the unsuccessful it was 3.1. In the group who underwent the doppler (20 patients the average was 7.9 in the successful cases and 4.2 in the cases that failed. In the present study the cut-off grade was 5, for most of the patients with grades above 5 had a successful treatment (15/16 - 93

  15. Measurement of soil contamination by radionuclides due to the Fukushima Dai-ichi Nuclear Power Plant accident and associated estimated cumulative external dose estimation

    International Nuclear Information System (INIS)

    Endo, S.; Kimura, S.; Takatsuji, T.; Nanasawa, K.; Imanaka, T.; Shizuma, K.

    2012-01-01

    Soil sampling was carried out at an early stage of the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident. Samples were taken from areas around FDNPP, at four locations northwest of FDNPP, at four schools and in four cities, including Fukushima City. Radioactive contaminants in soil samples were identified and measured by using a Ge detector and included 129m Te, 129 Te, 131 I, 132 Te, 132 I, 134 Cs, 136 Cs, 137 Cs, 140 Ba and 140 La. The highest soil depositions were measured to the northwest of FDNPP. From this soil deposition data, variations in dose rates over time and the cumulative external doses at the locations for 3 months and 1 y after deposition were estimated. At locations northwest of FDNPP, the external dose rate at 3 months after deposition was 4.8–98 μSv/h and the cumulative dose for 1 y was 51 to 1.0 × 10 3 mSv; the highest values were at Futaba Yamada. At the four schools, which were used as evacuation shelters, and in the four urban cities, the external dose rate at 3 months after deposition ranged from 0.03 to 3.8 μSv/h and the cumulative doses for 1 y ranged from 3 to 40 mSv. The cumulative dose at Fukushima Niihama Park was estimated as the highest in the four cities. The estimated external dose rates and cumulative doses show that careful countermeasures and remediation will be needed as a result of the accident, and detailed measurements of radionuclide deposition densities in soil will be important input data to conduct these activities.

  16. Fitness costs of increased cataract frequency and cumulative radiation dose in natural mammalian populations from Chernobyl.

    Science.gov (United States)

    Lehmann, Philipp; Boratyński, Zbyszek; Mappes, Tapio; Mousseau, Timothy A; Møller, Anders P

    2016-01-27

    A cataract is a clouding of the lens that reduces light transmission to the retina, and it decreases the visual acuity of the bearer. The prevalence of cataracts in natural populations of mammals, and their potential ecological significance, is poorly known. Cataracts have been reported to arise from high levels of oxidative stress and a major cause of oxidative stress is ionizing radiation. We investigated whether elevated frequencies of cataracts are found in eyes of bank voles Myodes glareolus collected from natural populations in areas with varying levels of background radiation in Chernobyl. We found high frequencies of cataracts in voles collected from different areas in Chernobyl. The frequency of cataracts was positively correlated with age, and in females also with the accumulated radiation dose. Furthermore, the number of offspring in female voles was negatively correlated with cataract severity. The results suggest that cataracts primarily develop as a function of ionizing background radiation, most likely as a plastic response to high levels of oxidative stress. It is therefore possible that the elevated levels of background radiation in Chernobyl affect the ecology and fitness of local mammals both directly through, for instance, reduced fertility and indirectly, through increased cataractogenesis.

  17. Cumulative inhibitory effect of low-dose aspirin on vascular prostacyclin and platelet thromboxane production in patients with atherosclerosis.

    Science.gov (United States)

    Weksler, B B; Tack-Goldman, K; Subramanian, V A; Gay, W A

    1985-02-01

    The relationship between the antithrombotic and antiplatelet effects of aspirin is complex, since aspirin influences other systems that protect against thrombosis as well as inhibiting platelet function. We investigated possible cumulative effects of low-dose aspirin on vascular production of prostacyclin in patients with documented atherosclerotic cardiovascular disease. Candidates for coronary artery vein graft bypass ingested 20 mg of aspirin daily during the week before surgery, and platelet aggregation, platelet formation of thromboxane A2 (TXA2), aortic and saphenous vein production of prostacyclin (PGI2), and hemostatic status were measured at the time of the bypass surgery. Low-dose aspirin markedly inhibited platelet aggregation responses and reduced TXA2 generation by greater than 90%, effects similar to those observed with much higher doses of aspirin. Both aortic and saphenous vein production of PGI2 were inhibited by 50% compared with PGI2 produced by vascular tissues of control subjects who received no aspirin preoperatively (51 +/- 10 pg 6-keto-PGF1 alpha/mg aortic wet weight [mean +/- SEM] in aspirin-treated subjects vs 130 +/- 16 pg/mg in control subjects, and 71 +/- 8 pg/mg saphenous vein wet weight vs 131 +/- 17 pg/mg). Blood loss at surgery was not significantly increased by preoperative low-dose aspirin as measured by chest tube drainage (754 +/- 229 ml in aspirin-treated subjects vs 645 +/- 271 ml in control subjects), hematocrit nadir (31.2 +/- 1.9% vs 31.8 +/- 1.7%), or transfusions (2.2 +/- 1.3 units of red blood cells vs 2.2 +/- 1.7 units).(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Selectivity of Very High Dose Methotrexate in Mcf-7 and Normal Cells Using a Priming and Non-Toxic 5-Fluorouracil Dose

    National Research Council Canada - National Science Library

    Brown, Donnell

    1997-01-01

    ...) in MCF-7 breast cancer cells versus normal tissues and (b) provide one clear basis for intracellular rescue of only host cells from MTX toxicity when high dose MTX is used in combination with 5-fluorouracil (5-FU...

  19. Involvement of Multiple Transporters-mediated Transports in Mizoribine and Methotrexate Pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Teruo Murakami

    2012-08-01

    Full Text Available Mizoribine is administered orally and excreted into urine without being metabolized. Many research groups have reported a linear relationship between the dose and peak serum concentration, between the dose and AUC, and between AUC and cumulative urinary excretion of mizoribine. In contrast, a significant interindividual variability, with a small intraindividual variability, in oral bioavailability of mizoribine is also reported. The interindividual variability is mostly considered to be due to the polymophisms of transporter genes. Methotrexate (MTX is administered orally and/or by parenteral routes, depending on the dose. Metabolic enzymes and multiple transporters are involved in the pharmacokinetics of MTX. The oral bioavailability of MTX exhibits a marked interindividual variability and saturation with increase in the dose of MTX, with a small intraindividual variability, where the contribution of gene polymophisms of transporters and enzymes is suggested. Therapeutic drug monitoring of both mizoribine and MTX is expected to improve their clinical efficacy in the treatment of rheumatoid arthritis.

  20. Physiological and immunological changes following exposure to low versus high-dose ionizing irradiation; comparative analysis with dose rate and cumulative dose

    International Nuclear Information System (INIS)

    Heesun, Kim; Heewon, Jang; Soungyeon, Song; Shinhye, Oh; Cukcheul, Shin; Meeseon, Jeong; Chasoon, Kim; Kwnaghee, Yang; Seonyoung, Nam; Jiyoung, Kim; Youngwoo, Jin; Changyoung, Cha

    2008-01-01

    Full text: While high-dose of ionizing radiation is generally harmful and causes damage to living organisms some reports suggest low-dose of radiation may not be as damaging as previously thought. Despite increasing evidence regarding the protective effect of low-dose radiation, no studies have directly compared the exact dose-response pattern by high- and low-dose of radiation exposed at high-and low-dose rate. This study aims to explore the cellular and molecular changes in mice exposed to low- and high-dose of radiation exposed at low- and high-dose rate. When C57BL/6 mice (Female, 6 weeks) were exposed at high-dose rate, 0.8 Gy/min, no significant change on the level of WBC, RBC, or platelets was observed up to total dose of 0.5 Gy. However, 2 Gy of radiation caused dramatic reduction in the level of white blood cells (WBC) and platelets. This reduction was accompanied by increased DNA damage in hematopoietic environments. The reduction of WBC was mainly due to the reduction in the number of CD4+ T cells and CD19+ B cells. CD8+ T cells and NK cells appeared to be relatively resistant to high-dose of radiation. This change was also accompanied by the reduction of T- and B- progenitor cells in the bone marrow. In contrast, no significant changes of the number of CD4+ T, CD8+ T, NK, and B cells were observed in the spleen of mice exposed at low-dose-rate (0.7 m Gy/h or 3.95 mGy/h) for up to 2 Gy, suggesting that low-dose radiation does not alter cellular distribution in the spleen. Nevertheless, mice exposed to low-dose radiation exhibited elevation of VEGF, MCP-1, IL-4, Leptin, IL-3, and Tpo in the peripheral blood and slight increases in MIP-2, RANTES, and IL-2 in the spleen. This suggests that chronic γ-radiation can stimulate immune function without causing damage to the immune components of the body. Taken together, these data indicate hormesis of low-dose radiation, which could be attributed to the stimulation of immune function. Dose rate rather than total

  1. Dose-Response Relationship between Cumulative Occupational Lead Exposure and the Associated Health Damages: A 20-Year Cohort Study of a Smelter in China.

    Science.gov (United States)

    Wu, Yue; Gu, Jun-Ming; Huang, Yun; Duan, Yan-Ying; Huang, Rui-Xue; Hu, Jian-An

    2016-03-16

    Long-term airborne lead exposure, even below official occupational limits, has been found to cause lead poisoning at higher frequencies than expected, which suggests that China's existing occupational exposure limits should be reexamined. A retrospective cohort study was conducted on 1832 smelting workers from 1988 to 2008 in China. These were individuals who entered the plant and came into continuous contact with lead at work for longer than 3 months. The dose-response relationship between occupational cumulative lead exposure and lead poisoning, abnormal blood lead, urinary lead and erythrocyte zinc protoporphyrin (ZPP) were analyzed and the benchmark dose lower bound confidence limits (BMDLs) were calculated. Statistically significant positive correlations were found between cumulative lead dust and lead fumes exposures and workplace seniority, blood lead, urinary lead and ZPP values. A dose-response relationship was observed between cumulative lead dust or lead fumes exposure and lead poisoning (p lead dust and fumes doses were 0.68 mg-year/m³ and 0.30 mg-year/m³ for lead poisoning, respectively. The BMDLs of workplace airborne lead concentrations associated with lead poisoning were 0.02 mg/m³ and 0.01 mg/m³ for occupational exposure lead dust and lead fume, respectively. In conclusion, BMDLs for airborne lead were lower than occupational exposure limits, suggesting that the occupational lead exposure limits need re-examination and adjustment. Occupational cumulative exposure limits (OCELs) should be established to better prevent occupational lead poisoning.

  2. Single-dose systemic methotrexate vs expectant management for treatment of tubal ectopic pregnancy: a placebo-controlled randomized trial.

    Science.gov (United States)

    Jurkovic, D; Memtsa, M; Sawyer, E; Donaldson, A N A; Jamil, A; Schramm, K; Sana, Y; Otify, M; Farahani, L; Nunes, N; Ambler, G; Ross, J A

    2017-02-01

    Methotrexate is used routinely worldwide for the medical treatment of clinically stable women with a tubal ectopic pregnancy. This is despite the lack of robust evidence to show its superior effectiveness over expectant management. The aim of our multicenter randomized controlled trial was to compare success rates of methotrexate against placebo for the conservative treatment of tubal ectopic pregnancy. This study took place in two early-pregnancy units in the UK between August 2005 and June 2014. Inclusion criteria were clinically stable women with a conclusive ultrasound diagnosis of a tubal ectopic pregnancy, presenting with a low serum beta human chorionic gonadotropin (β-hCG) level of Women were assigned randomly to a single systemic injection of either 50 mg/m 2 methotrexate or placebo. The primary outcome was a binary indicator for success of conservative management, defined as resolution of clinical symptoms and decline of serum β-hCG to women, 42 of whom were assigned to methotrexate and 38 to placebo. The arms of the study were matched in terms of age, ethnicity, obstetric history, pregnancy characteristics and serum levels of β-hCG and progesterone. The rates of success were similar for the two study arms: 83% with methotrexate and 76% with placebo. On univariate analysis, this difference was not statistically significant (χ 2 (1 degree of freedom) = 0.53; P = 0.47). On multivariate logistic regression, the serum level of β-hCG was the only covariate found to be significantly associated with outcome. The odds of failure increased by 0.15% for each unit increase in β-hCG (odds ratio, 1.0015 (95% CI, 1.0002-1.003); P = 0.02). In 14 women presenting with serum β-hCG of 1000-1500 IU/L, the success rate was 33% in those managed expectantly compared with 62% in those receiving methotrexate. This difference was not statistically significant and a larger sample size would be needed to give sufficient power to detect a difference in the

  3. Cumulative or delayed nephrotoxicity after cisplatin (DDP) treatment.

    Science.gov (United States)

    Pinnarò, P; Ruggeri, E M; Carlini, P; Giovannelli, M; Cognetti, F

    1986-04-30

    The present retrospective study reports data regarding renal toxicity in 115 patients (63 males, 52 females; median age, 56 years) who received cumulative doses of cisplatin (DDP) greater than or equal to 200 mg/m2. DDP was administered alone or in combination at a dose of 50-70 mg/m2 in 91 patients, and at a dose of 100 mg/m2 in 22 patients. Two patients after progression of ovarian carcinoma treated with conventional doses of DDP received 4 and 2 courses, respectively, of high-dose DDP (40 mg/m2 for 5 days) in hypertonic saline. The median number of DDP courses was 6 (range 2-14), and the median cumulative dose was 350 mg/m2 (range, 200-1200). Serum creatinine and urea nitrogen were determined before initiating the treatment and again 13-16 days after each administration. The incidence of azotemia (creatinina levels that exceeded 1.5 mg/dl) was similar before (7.8%) and after (6.1%) DDP doses of 200 mg/m2. Azotemia appears to be related to the association of DDP with other potentially nephrotoxic antineoplastic drugs (methotrexate) more than to the dose per course of DDP. Of 59 patients followed for 2 months or more after discontinuing the DDP treatment, 3 (5.1%) presented creatinine values higher than 1.5 mg/dl. The data deny that the incidence of nephrotoxicity is higher in patients receiving higher cumulative doses of DDP and confirm that increases in serum creatinine levels may occur some time after discontinuation of the drug.

  4. Estimation of organ cumulated activities and absorbed doses on intakes of several 11C labelled radiopharmaceuticals from external measurement with thermoluminescent dosimeters.

    Science.gov (United States)

    Nakamura, T; Hayashi, Y; Watabe, H; Matsumoto, M; Horikawa, T; Fujiwara, T; Ito, M; Yanai, K

    1998-02-01

    We have developed a method for obtaining the cumulated activities in organs from radionuclides, which are injected into the patient in nuclear medicine procedures, by external exposure measurement with thermoluminescent dosimeters (TLDs) which are attached to the patient's body surface close to source organs to obtain information on body-surface doses. As the surface dose is connected to the cumulated activities in source organs through radiation transmission in the human body which can be estimated with the aid of a mathematical phantom, the organ cumulated activities can be obtained by the inverse transform method. The accuracy of this method was investigated by using a water phantom in which several gamma-ray volume sources of known activity were placed to simulate source organs. We then estimated by external measurements the organ cumulated activities and absorbed doses in subjects to whom the radiopharmaceuticals 11C-labelled Doxepin, 11C-labelled YM09151-2 and 11C-labelled Benzotropin were administered in clinical nuclear medicine procedures. The cumulated activities in the brain obtained with TLDs for Doxepin and YM09151-2 are 63.6 +/- 6.2 and 32.1 +/- 12.0 kBq h MBq-1 respectively, which are compared with the respective values of 33.3 +/- 9.9 and 23.9 +/- 6.2 kBq h MBq-1 with direct PET (positron emission tomography) measurements. The agreement between the two methods is within a factor of two. The effective doses of Doxepin, YM09151-2 and Benzotropin are determined as 6.92 x 10(-3), 7.08 x 10(-3) and 7.65 x 10(-3) mSv MBq-1 respectively with the TLD method. This method has great advantages, in that cumulated activities in several organs can be obtained easily with a single procedure, and the measurements of body surface doses are performed simultaneously with the nuclear medicine procedure, as TLDs are too small to interfere with other medical measurements.

  5. Estimation of organ cumulated activities and absorbed doses on intakes of several {sup 11}C labelled radiopharmaceuticals from external measurement with thermoluminescent dosimeters

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Takashi; Hayashi, Yoshiharu; Watabe, Hiroshi; Matsumoto, Masaki; Horikawa, Tohru; Fujiwara, Takehiko; Ito, Masatoshi; Yanai, Kazuhiko [Cyclotron and Radioisotope Center, Tohoku University, Aoba, Aramaki, Sendai 980-77 (Japan)

    1998-02-01

    We have developed a method for obtaining the cumulated activities in organs from radionuclides, which are injected into the patient in nuclear medicine procedures, by external exposure measurement with thermoluminescent dosimeters (TLDs) which are attached to the patient's body surface close to source organs to obtain information on body-surface doses. As the surface dose is connected to the cumulated activities in source organs through radiation transmission in the human body which can be estimated with the aid of a mathematical phantom, the organ cumulated activities can be obtained by the inverse transform method. The accuracy of this method was investigated by using a water phantom in which several gamma-ray volume sources of known activity were placed to simulate source organs. We then estimated by external measurements the organ cumulated activities and absorbed doses in subjects to whom the radiopharmaceuticals {sup 11}C-labelled Doxepin, {sup 11}C-labelled YM09151-2 and {sup 11}C-labelled Benzotropin were administered in clinical nuclear medicine procedures. The cumulated activities in the brain obtained with TLDs for Doxepin and YM09151-2 are 63.6{+-}6.2 and 32.1{+-}12.0 kBq h MBq{sup -1} respectively, which are compared with the respective values of 33.3{+-}9.9 and 23.9{+-}6.2 kBq h MBq{sup -1} with direct PET (positron emission tomography) measurements. The agreement between the two methods is within a factor of two. The effective doses of Doxepin, YM09151-2 and Benzotropin are determined as 6.92x10{sup -3}, 7.08x10{sup -3} and 7.65x10{sup -3} mSv MBq{sup -1} respectively with the TLD method. This method has great advantages, in that cumulated activities in several organs can be obtained easily with a single procedure, and the measurements of body surface doses are performed simultaneously with the nuclear medicine procedure, as TLDs are too small to interfere with other medical measurements. (author)

  6. SU-E-J-106: The Use of Deformable Image Registration with Cone-Beam CT for a Better Evaluation of Cumulative Dose to Organs

    Energy Technology Data Exchange (ETDEWEB)

    Fillion, O; Gingras, L; Archambault, L [Universite Laval, Quebec, Quebec (Canada); Centre de recherche du CHU de Quebec, Quebec, Quebec (Canada); Centre de recherche sur le cancer, Quebec, Quebec (Canada)

    2015-06-15

    Purpose: The knowledge of dose accumulation in the patient tissues in radiotherapy helps in determining the treatment outcomes. This project aims at providing a workflow to map cumulative doses that takes into account interfraction organ motion without the need for manual re-contouring. Methods: Five prostate cancer patients were studied. Each patient had a planning CT (pCT) and 5 to 13 CBCT scans. On each series, a physician contoured the prostate, rectum, bladder, seminal vesicles and the intestine. First, a deformable image registration (DIR) of the pCTs onto the daily CBCTs yielded registered CTs (rCT) . This rCT combined the accurate CT numbers of the pCT with the daily anatomy of the CBCT. Second, the original plans (220 cGy per fraction for 25 fractions) were copied on the rCT for dose re-calculation. Third, the DIR software Elastix was used to find the inverse transform from the rCT to the pCT. This transformation was then applied to the rCT dose grid to map the dose voxels back to their pCT location. Finally, the sum of these deformed dose grids for each patient was applied on the pCT to calculate the actual dose delivered to organs. Results: The discrepancy between the planned D98 and D2 and these indices re-calculated on the rCT, are, on average, of −1 ± 1 cGy and 1 ± 2 cGy per fraction, respectively. For fractions with large anatomical motion, the D98 discrepancy on the re-calculated dose grid mapped onto the pCT can raise to −17 ± 4 cGy. The obtained cumulative dose distributions illustrate the same behavior. Conclusion: This approach allowed the evaluation of cumulative doses to organs with the help of uncontoured daily CBCT scans. With this workflow, the easy evaluation of doses delivered for EBRT treatments could ultimately lead to a better follow-up of prostate cancer patients.

  7. SU-E-J-106: The Use of Deformable Image Registration with Cone-Beam CT for a Better Evaluation of Cumulative Dose to Organs

    International Nuclear Information System (INIS)

    Fillion, O; Gingras, L; Archambault, L

    2015-01-01

    Purpose: The knowledge of dose accumulation in the patient tissues in radiotherapy helps in determining the treatment outcomes. This project aims at providing a workflow to map cumulative doses that takes into account interfraction organ motion without the need for manual re-contouring. Methods: Five prostate cancer patients were studied. Each patient had a planning CT (pCT) and 5 to 13 CBCT scans. On each series, a physician contoured the prostate, rectum, bladder, seminal vesicles and the intestine. First, a deformable image registration (DIR) of the pCTs onto the daily CBCTs yielded registered CTs (rCT) . This rCT combined the accurate CT numbers of the pCT with the daily anatomy of the CBCT. Second, the original plans (220 cGy per fraction for 25 fractions) were copied on the rCT for dose re-calculation. Third, the DIR software Elastix was used to find the inverse transform from the rCT to the pCT. This transformation was then applied to the rCT dose grid to map the dose voxels back to their pCT location. Finally, the sum of these deformed dose grids for each patient was applied on the pCT to calculate the actual dose delivered to organs. Results: The discrepancy between the planned D98 and D2 and these indices re-calculated on the rCT, are, on average, of −1 ± 1 cGy and 1 ± 2 cGy per fraction, respectively. For fractions with large anatomical motion, the D98 discrepancy on the re-calculated dose grid mapped onto the pCT can raise to −17 ± 4 cGy. The obtained cumulative dose distributions illustrate the same behavior. Conclusion: This approach allowed the evaluation of cumulative doses to organs with the help of uncontoured daily CBCT scans. With this workflow, the easy evaluation of doses delivered for EBRT treatments could ultimately lead to a better follow-up of prostate cancer patients

  8. Current and historical individual data about exposure of workers in the rayon industry to carbon disulfide and their validity in calculating the cumulative dose.

    Science.gov (United States)

    Göen, Thomas; Schramm, Axel; Baumeister, Thomas; Uter, Wolfgang; Drexler, Hans

    2014-08-01

    The objective of the study was to investigate how exposure to carbon disulfide (CS2) in a rayon-manufacturing plant has changed within two decades and whether it is possible to calculate valid data for the individual cumulative exposure. The data for CS2 concentration in air and biological exposure monitoring (2-thio-1,3-thiaxolidine-4-carboxylic acid (TTCA) in urine) from two cross-sectional studies, performed in 1992 (n = 362) and 2009 (n = 212) in a German rayon-manufacturing plant, were compared to data obtained from company-internal measurements between the studies. Using the data from the cross-sectional studies and company-internal data, cumulative external exposure and the cumulative internal exposure were calculated for each worker. External and internal CS2 exposure of the employees decreased from 1992 (medians 4.0 ppm and 1.63 mgTTCA/g creatinine) to 2009 (medians 2.5 ppm and 0.86 mg/g). However, company-internal CS2 data do not show a straight trend for this period. The annual medians of the company-internal measurement of external exposure to CS2 have varied between 2.7 and 8.4 ppm, in which median values exceeded 5 ppm generally since 2000. The annual medians for the company-internal biomonitoring assessment ranged between 1.2 and 2.8 mg/g creatinine. The cumulative CS2 exposure ranged from 8.5 to 869.5 ppm years for external exposure and between 1.30 and 176.2 mg/g creatinine years for the internal exposure. Significant correlations were found between the current air pollution and the internal exposure in 2009 but also between the cumulative external and internal CS2 exposure. Current exposure data, usually collected in cross-sectional studies, rarely allow a reliable statement on the cumulative dose, because of higher exposure in the past and of fluctuating courses of exposure. On the other hand, company-internal exposure data may be affected by non-representative measurement strategies. Some verification of the reliability of

  9. An assessment of cumulative external doses from Chernobyl fallout for a forested area in Russia using the optically stimulated luminescence from quartz inclusions in bricks

    DEFF Research Database (Denmark)

    Ramzaev, V.; Bøtter-Jensen, Lars; Thomsen, Kristina Jørkov

    2008-01-01

    . The area was significantly contaminated by Chernobyl fallout with initial (CS)-C-137 ground deposition level of similar to 1.1 MBq m(-2). The accumulated OSL doses in sections of the bricks varied from 141 to 207 mGy, of which between 76 and 146 mGy are attributable to Chernobyl fallout. Using the OSL...... depth-dose profiles obtained from the exposed bricks and the results from a gamma-ray-survey of the area, the Chernobyl-related cumulative gamma-ray dose for a point detector located in free air at a height of 1 m above the ground in the study area was estimated to be ca. 240 mGy for the time period...... starting on 27 April 1986 and ending on 31 July 2004. This result is in good agreement with the result of deterministic modelling of the cumulative gamma-ray dose in free air above undisturbed ground from the Chernobyl source in the Bryansk Region. Over the same time period, the external Chernobyl...

  10. Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats

    Directory of Open Access Journals (Sweden)

    Pedro M. G. Soares

    2011-03-01

    Full Text Available CONTEXT: Methotrexate and other anticancer agents can induce intestinal mucositis, which is one of the most common limiting factor that prevent further dose escalation of the methotrexate. OBJECTIVES: To evaluate the gastric emptying and gastrointestinal transit of liquids in methotrexate-induced intestinal mucositis. METHODS: Wistar rats received methotrexate (2.5 mg/kg/day for 3 days, subcutaneously or saline. After 1, 3 and 7 days, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage and myeloperoxidase activity (biochemical marker of granulocyte infiltration. Others rats were pre-treated with methotrexate or saline, gavage-fed after 3 or 7 days with a standard test liquid meal, and sacrificed 10, 20 or 30-min later. Gastric and small intestine dye recoveries were measured by spectrophotometry. RESULTS: After 3 days of methotrexate, there was an epithelial intestinal damage in all segments, with myeloperoxidase activity increase in both in duodenum and ileum. Seven days after methotrexate, we observed a complete reversion of this intestinal damage. There was an increase in gastric dye recoveries after 10, 20, and 30-min post-prandial intervals after 3 days, but not after 7 days, of methotrexate. Intestine dye recoveries were decreased in the first and second segments at 10 min, in the third at 20 min, and in the second and third at 30 min, only after 3 days of methotrexate treatment. CONCLUSION: Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats.

  11. Double dose: the cumulative effect of TV viewing at home and in preschool on children's activity patterns and weight status.

    Science.gov (United States)

    Taverno Ross, Sharon; Dowda, Marsha; Saunders, Ruth; Pate, Russell

    2013-05-01

    Little is known about how screen-based sedentary behavior at home and in preschool influences children's health and activity patterns. The current study examined the individual and cumulative influence of TV viewing at home and in preschool on children's physical activity (PA) and weight status. Children (n = 339) attending 16 preschools in South Carolina were grouped into high and low TV groups based on parent report of children's TV viewing at home and director report of TV use/rules in preschool. T-tests and mixed model ANOVAs examined differences in weight status and PA (min/hr) by high and low TV groups. Results revealed that children who were classified as High TV both at home and in pre- school had significantly lower levels of moderate-to-vigorous PA compared with their Low TV counterparts (8.3 (0.3) min/hr vs. 7.6 (0.2) min/hr, p TV groups at home or in preschool when examined individually. These findings demonstrate the importance of total environmental TV exposure on preschooler's PA. Longitudinal and observational research to assess preschoolers' cumulative screen-based sedentary behavior and its relationship with PA and weight status is needed.

  12. Methotrexate for primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Giljaca, Vanja; Poropat, Goran; Stimac, Davor

    2010-01-01

    Methotrexate has been used to treat patients with primary biliary cirrhosis as it possesses immunosuppressive properties. The previously prepared version of this review from 2005 showed that methotrexate seemed to significantly increase mortality in patients with primary biliary cirrhosis. Since...... that last review version, follow-up data of the included trials have been published....

  13. Toxic corneal epitheliopathy after intravitreal methotrexate and its treatment with oral folic acid.

    Science.gov (United States)

    Gorovoy, Ian; Prechanond, Tidarat; Abia, Maravillas; Afshar, Armin R; Stewart, Jay M

    2013-08-01

    To determine whether oral folic acid can ameliorate an iatrogenic, visually significant corneal epitheliopathy, which commonly occurs with intravitreal injections of methotrexate for the treatment of intraocular lymphoma. We report 2 cases of visually significant corneal epitheliopathy occurring after intravitreal injections of methotrexate for intraocular lymphoma. The first patient did not receive any treatment for the corneal disease, and the second patient with bilateral intraocular lymphoma received 1 mg of oral folic acid daily, a commonly used dosage for patients on systemic methotrexate. In the first patient without treatment, there was a complete regression of the corneal epithelial disease only when the frequency of intravitreal methotrexate was reduced from weekly to monthly as per a commonly used dosage regimen for methotrexate. In the second patient, the corneal disease improved 80% within 1 week of initiating oral folic acid for her eye already experiencing severe epitheliopathy during her weekly dosing regimen of methotrexate and also had significantly decreased epithelial disease in her second eye that started weekly intravitreal methotrexate several weeks after beginning oral folic acid. Currently, oral folic acid supplements are recommended for patients using systemic methotrexate to minimize drug toxicity. We suggest a similar use in patients undergoing intravitreal methotrexate injections to decrease toxic effects on the corneal epithelium.

  14. Frequency of methotrexate intolerance in rheumatoid arthritis patients using methotrexate intolerance severity score (MISS questionnaire).

    Science.gov (United States)

    Fatimah, Nibah; Salim, Babur; Nasim, Amjad; Hussain, Kamran; Gul, Harris; Niazi, Sarah

    2016-05-01

    The objective of the study was to determine the frequency of methotrexate intolerance in rheumatoid arthritis (RA) patients by applying the methotrexate intolerance severity score (MISS) questionnaire and to see the effect of dose and concomitant use of other disease-modifying antirheumatic drugs (DMARDS) on methotrexate (MTX) intolerance. For the descriptive study, non-probability sampling was carried out in the Female Rheumatology Department of Fauji Foundation Hospital (FFH), Rawalpindi, Pakistan. One hundred and fifty diagnosed cases of RA using oral MTX were selected. The MISS questionnaire embodies five elements: abdominal pain, nausea, vomiting, fatigue and behavioural symptoms. The amplitude of each element was ranked from 0 to 3 being no complaint (0 points), mild (1 point), moderate (2 points) and severe (3 points). A cut-off score of 6 and above ascertained intolerance by the physicians. A total of 33.3 % of the subjects exhibited MTX intolerance according to the MISS questionnaire. Out of which, the most recurring symptom of all was behavioural with a value of 44 % whereas vomiting was least noticeable with a figure of 11 %. About 6.6 % of the women with intolerance were consuming DMARDs in conjunction with MTX. Those using the highest weekly dose of MTX (20 mg) had supreme intolerance with prevalence in 46.2 % of the patients. The frequency of intolerance decreased with a decrease in weekly dose to a minimum of 20 % with 7.5 mg of MTX. MTX intolerance has moderate prevalence in RA patients and if left undetected, the compliance to use of MTX as a first-line therapy will decrease. Methotrexate intolerance is directly proportional to the dose of MTX taken. Also, there is no upstroke seen in intolerance with the use of other disease-modifying agents.

  15. Association between cumulative radiation dose, adverse skin reactions, and changes in surface hemoglobin among women undergoing breast conserving therapy

    Directory of Open Access Journals (Sweden)

    Michael S. Chin

    2017-06-01

    Conclusion: HSI demonstrates promise in the assessment of skin dose as well as an objective measure of skin reaction. The ability to easily identify adverse skin reactions and to modify the treatment plan may circumvent the need for detrimental treatment breaks.

  16. Preliminary mortality survey from 1973 to 1977 of Japanese radiological technologists and analyses of the association of mortality with cumulative doses

    International Nuclear Information System (INIS)

    Aoyama, Takashi; Ishizaka, Masatsuna; Yamamoto, Yoichi; Kano, Eiichi; Nikaido, Osamu.

    1981-01-01

    The Japan Association of Radiologic Technologists reported that, from 1941 to 1978, 395 deaths occurred among Japanese radiological technologists who belong to the association. Using these data, Sakka, Kitabatake and colleagues, and the present authors studied mortality and cause of death among these technologists for 11 years from 1955 to 1965, for 7 years from 1966 to 1972, and for 5 years from 1973 to 1977, respectively. In general, the number of cancer deaths in the three studies was less than expected. However, Kitabatake et al. and the present authors found that deaths from skin cancer were significantly more frequent than expected. The present authors recently estimated the cumulative doses of radiation exposure for the majority of deaths (268 out of 395). The mean dose of radiation related to cancer deaths was then compared with that for non-cancer deaths. Also the proportional mortality ratios for cancers were observed in relation to the estimated dose level. In the present study, however, statistical tests to assess for the relationship between mortality and dose of radiation exposure showed no correlation, for the majority of deaths from cancer. (author)

  17. Dose monitoring using the DICOM structured report: assessment of the relationship between cumulative radiation exposure and BMI in abdominal CT

    International Nuclear Information System (INIS)

    Boos, J.; Lanzman, R.S.; Meineke, A.; Heusch, P.; Sawicki, L.M.; Antoch, G.; Kröpil, P.

    2015-01-01

    Aim: To perform a systematic, large-scale analysis using the Digital Imaging and Communication in Medicine structured report (DICOM-SR) to assess the relationship between body mass index (BMI) and radiation exposure in abdominal CT. Materials and methods: A retrospective analysis of DICOM-SR of 3121 abdominal CT examinations between April 2013 and March 2014 was performed. All examinations were conducted using a 128 row CT system. Patients (mean age 61 ± 15 years) were divided into five groups according to their BMI: group A <20 kg/m 2 (underweight), group B 20–25 kg/m 2 (normal weight), group C 25–30 kg/m 2 (overweight), group D 30–35 kg/m 2 (obese), and group E > 35 kg/m 2 (extremely obese). CT dose index (CTDI vol ) and dose–length product (DLP) were compared between all groups and matched to national diagnostic reference values. Results: The mean CTDI vol and DLP were 5.4 ± 2.9 mGy and 243 ± 153 mGy·cm in group A, 6 ± 3.6 mGy and 264 ± 179 mGy• cm in group B, 7 ± 3.6 mGy and 320 ± 180 mGy• cm in group C, 8.1 ± 5.2 mGy and 375 ± 306 mGy• cm in group D, and 10 ± 8 mGy and 476 ± 403 mGy• cm in group E, respectively. Except for group A versus group B, CTDI vol and DLP differed significantly between all groups (p<0.05). Significantly more CTDI vol values exceeded national diagnostic reference values in groups D and E (2.1% and 6.3%) compared to group B (0.5%, p<0.05). Conclusion: DICOM-SR is a comprehensive, fast, and reproducible way to analyse dose-related data at CT. It allows for automated evaluation of radiation dose in a large study population. Dose exposition is related to the patient's BMI and is increased by up to 96% for extremely obese patients undergoing abdominal CT. - Highlights: • DICOM-SR was used to implement automatic CT-dose monitoring. • DICOM-SR allowed for a fast and comprehensive analysis of CT dose data. • Radiation exposure for abdominal CT was increased by up to 96% for

  18. Methotrexate-induced acute toxic leukoencephalopathy

    Directory of Open Access Journals (Sweden)

    Parag R Salkade

    2012-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is one of the most common malignancies of childhood, which is treated with high doses of methotrexate (MTX, as it crosses the blood-brain barrier and can be administered intravenously and via intrathecal route to eradicate leukemic cells from central nervous system (CNS. Additionally, high doses of MTX not only prevent CNS recurrence but also hematologic relapses. Although, standard treatment protocol for ALL includes multimodality therapy, MTX is usually associated with neurotoxicity and affects periventricular deep white matter region. Methotrexate-induced ′acute toxic leukoencephalopathy′ has varying clinical manifestations ranging from acute neurological deficit to seizures or encephalopathy. Diffusion weighted magnetic resonance imaging (DW-MRI is widely available and routinely used in clinical practice to identify acute stroke and also to distinguish acute stroke from non-stroke like conditions. We report a local teenage Chinese girl who developed 2 discrete episodes of left upper and lower limb weakness with left facial nerve paresis after receiving the 2 nd and 3 rd cycle of high dose of intravenous and intrathecal methotrexate, without having cranial irradiation. After each episode of her neurological deficit, the DW-MRI scan showed focal restricted diffusion in right centrum semiovale. Her left sided focal neurological deficit and facial nerve paresis almost completely subsided on both these occasions within 3 days of symptom onset. Follow-up DW-MRI, after her neurological recovery, revealed almost complete resolution of previously noted restricted diffusion in right centrum semiovale, while the lesion was not evident on concurrent T2W (T2-weighted and FLAIR (Fluid-Attenuated Inversion recovery sequences, nor showed any post contrast enhancement on post gadolinium enhanced T1W (T1-weighted sequences. No residual neurological deficit or intellectual impairment was identified on clinical follow up

  19. Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial.

    Science.gov (United States)

    Fleischmann, Roy; Mysler, Eduardo; Hall, Stephen; Kivitz, Alan J; Moots, Robert J; Luo, Zhen; DeMasi, Ryan; Soma, Koshika; Zhang, Richard; Takiya, Liza; Tatulych, Svitlana; Mojcik, Christopher; Krishnaswami, Sriram; Menon, Sujatha; Smolen, Josef S

    2017-07-29

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. The Oral Rheumatoid Arthritis triaL (ORAL) Strategy aimed to assess the comparative efficacy of tofacitinib monotherapy, tofacitinib plus methotrexate, and adalimumab plus methotrexate for the treatment of rheumatoid arthritis in patients with a previous inadequate response to methotrexate. ORAL Strategy was a 1 year, double-blind, phase 3b/4, head-to-head, non-inferiority, randomised controlled trial in patients aged 18 years or older with active rheumatoid arthritis despite methotrexate therapy. Patients were randomly assigned (1:1:1) to receive oral tofacitinib (5 mg twice daily) monotherapy, oral tofacitinib (5 mg twice daily) plus methotrexate, or subcutaneous adalimumab (40 mg every other week) plus methotrexate at 194 centres in 25 countries. Eligible patients received live zoster vaccine at investigators' discretion. The primary endpoint was the proportion of patients who attained an American College of Rheumatology response of at least 50% (ACR50) at month 6 in the full analysis set (patients who were randomly assigned to a group and received at least one dose of the study treatment). Non-inferiority between groups was shown if the lower bound of the 98·34% CI of the difference between comparators was larger than -13·0%. This trial is registered with ClinicalTrials.gov, number NCT02187055. 1146 patients received treatment (384 had tofacitinib monotherapy; 376 had tofacitinib and methotrexate; and 386 had adalimumab and methotrexate). At 6 months, ACR50 response was attained in 147 (38%) of 384 patients with tofacitinib monotherapy, 173 (46%) of 376 patients with tofacitinib and methotrexate, and 169 (44%) of 386 patients with adalimumab and methotrexate. Non-inferiority was declared for tofacitinib and methotrexate versus adalimumab and methotrexate (difference 2% [98·34% CI -6 to 11]) but not for tofacitinib monotherapy versus either adalimumab and methotrexate (-6

  20. Methotrexate for rheumatoid arthritis patients who are on hemodialysis.

    Science.gov (United States)

    Al-Hasani, Hasanein; Roussou, Euthalia

    2011-12-01

    Methotrexate (MTX) can be toxic to patients suffering from end stage renal disease (ESRD) on hemodialysis even at low doses. This increase in toxicity is more notable in terms of bone marrow suppression in the form of pancytopenia. Many methods of elimination including dialysis itself have been proven ineffective, and alternate treatments with anti-TNF alpha blockers can be considered.

  1. Effect of methotrexate combined with ginger, silymarin or propolis on ...

    African Journals Online (AJOL)

    The present study was performed to evaluate the effect of three natural antioxidants on the adverse effect of methotrexate (MTX) in normal liver cells. TaqMan RT-PCR technology was used to estimate the mRNA expression levels for three genes after rats injection with a single dose of 20 mg/kg b.w MTX or the same MTX ...

  2. Investigation of practical approaches to evaluating cumulative dose for cone beam computed tomography (CBCT) from standard CT dosimetry measurements: a Monte Carlo study.

    Science.gov (United States)

    Abuhaimed, Abdullah; Martin, Colin J; Sankaralingam, Marimuthu; Gentle, David J

    2015-07-21

    A function called Gx(L) was introduced by the International Commission on Radiation Units and Measurements (ICRU) Report-87 to facilitate measurement of cumulative dose for CT scans within long phantoms as recommended by the American Association of Physicists in Medicine (AAPM) TG-111. The Gx(L) function is equal to the ratio of the cumulative dose at the middle of a CT scan to the volume weighted CTDI (CTDIvol), and was investigated for conventional multi-slice CT scanners operating with a moving table. As the stationary table mode, which is the basis for cone beam CT (CBCT) scans, differs from that used for conventional CT scans, the aim of this study was to investigate the extension of the Gx(L) function to CBCT scans. An On-Board Imager (OBI) system integrated with a TrueBeam linac was simulated with Monte Carlo EGSnrc/BEAMnrc, and the absorbed dose was calculated within PMMA, polyethylene (PE), and water head and body phantoms using EGSnrc/DOSXYZnrc, where the body PE body phantom emulated the ICRU/AAPM phantom. Beams of width 40-500 mm and beam qualities at tube potentials of 80-140 kV were studied. Application of a modified function of beam width (W) termed Gx(W), for which the cumulative dose for CBCT scans f (0) is normalized to the weighted CTDI (CTDIw) for a reference beam of width 40 mm, was investigated as a possible option. However, differences were found in Gx(W) with tube potential, especially for body phantoms, and these were considered to be due to differences in geometry between wide beams used for CBCT scans and those for conventional CT. Therefore, a modified function Gx(W)100 has been proposed, taking the form of values of f (0) at each position in a long phantom, normalized with respect to dose indices f 100(150)x measured with a 100 mm pencil ionization chamber within standard 150 mm PMMA phantoms, using the same scanning parameters, beam widths and positions within the phantom. f 100(150)x averages the dose resulting from

  3. Measurement of radiocesium concentration in trees using cumulative gamma radiation dose rate detection systems - A simple presumption for radiocesium concentration in living woods using glass-badge based gamma radiation dose rate detection system

    Energy Technology Data Exchange (ETDEWEB)

    Yoshihara, T.; Hashida, S.N. [Plant Molecular Biology, Laboratory of Environmental Science, Central Research Institute of Electric Power Industry (CRIEPI), 1646 Abiko, Chiba 270-1194 (Japan); Kawachi, N.; Suzui, N.; Yin, Y.G.; Fujimaki, S. [Radiotracer Imaging Gr., Quantum Beam Science Center, Japan Atomic Energy Agency (JAEA), 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan); Nagao, Y.; Yamaguchi, M. [Takasaki Advanced Radiation Research Institute, Japan Atomic Energy Agency (JAEA), 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan)

    2014-07-01

    Radiocesium from the severe accident at the Fukushima Dai-ichi Nuclear Power Plant on 11 March 2011 contaminates large areas. After this, a doubt for forest products, especially of mushroom, is indelible at the areas. Pruned woody parts and litters are containing a considerable amount of radiocesium, and generates a problem at incineration and composting. These mean that more attentive survey for each subject is expected; however, the present survey system is highly laborious/expensive and/or non-effective for this purpose. On the other hand, we can see a glass-badge based gamma radiation dose rate detection system. This system always utilized to detect a personal cumulative radiation dose, and thus, it is not suitable to separate a radiation from a specific object. However, if we can separate a radiation from a specific object and relate it with the own radiocesium concentration, it would enable us to presume the specific concentration with just an easy monitoring but without a destruction of the target nature and a complicated process including sampling, pre-treatment, and detection. Here, we present the concept of the measurement and results of the trials. First, we set glass-badges (type FS, Chiyoda Technol Corp., Japan) on a part of bough (approximately 10 cm in diameter) of Japanese flowering cherry trees (Prunus x yedoensis cv. Somei-Yoshino) with four different settings: A, a direct setting without any shield; B, a setting with an aluminum shield between bough and the glass-badge; C, a setting with a lead shield between bough and the glass-badge; D, a setting with a lead shield covering the glass-badge to shut the radiation from the surrounding but from bough. The deduction between the amount of each setting should separate a specific radiation of the bough from unlimited radiation from the surrounding. Even if the hourly dose rate is not enough to count the difference, a moderate cumulative dose would clear the difference. In fact, results demonstrated a

  4. Cumulative effective radiation dose received by blunt trauma patients arriving to a military level I trauma center from point of injury and interhospital transfers.

    Science.gov (United States)

    Van Arnem, Kerri A; Supinski, David P; Tucker, Jonathan E; Varney, Shawn

    2016-12-01

    Trauma patients sustaining blunt injuries are exposed to multiple radiologic studies. Evidence indicates that the risk of cancer from exposure to ionizing radiation rises in direct proportion to the cumulative effective dose (CED) received. The purpose of this study is to quantify the amount of ionizing radiation accumulated when arriving directly from point of injury to San Antonio Military Medical Center (SAMMC), a level I trauma center, compared with those transferred from other facilities. A retrospective record review was conducted from 1st January 2010 through 31st December 2012. The SAMMC trauma registry, electronic medical records, and the digital radiology imaging system were searched for possible candidates. The medical records were then analyzed for sex, age, mechanism of injury, received directly from point of injury (direct group), transfer from another medical facility (transfer group), computed tomographic scans received, dose-length product, CED of radiation, and injury severity score. A diagnostic imaging physicist then calculated the estimated CED each subject received based on the dose-length product of each computed tomographic scan. A total of 300 patients were analyzed, with 150 patients in the direct group and 150 patients in the transfer group. Both groups were similar in age and sex. Patients in the transfer group received a significantly greater CED of radiation compared with the direct group (mean, 37.6 mSv vs 28 mSv; P=.001). The radiation received in the direct group correlates with a lifetime attributable risk (LAR) of 1 in 357 compared with the transfer group with an increase in LAR to 1 in 266. Patients transferred to our facility received a 34% increase in ionizing radiation compared with patients brought directly from the injury scene. This increased dose of ionizing radiation contributes to the LAR of cancer and needs to be considered before repeating imaging studies. III. Published by Elsevier Inc.

  5. Nodulose por Metotrexato Methotrexate Induced Nodulosis

    Directory of Open Access Journals (Sweden)

    Fernanda Guidolin

    2005-08-01

    Full Text Available A nodulose por metotrexato (MTX é um dos efeitos colaterais pouco conhecidos do uso desse medicamento em doses baixas. Embora classicamente descrita em casos de artrite reumatóide, tem aparecido, também, em outras doenças reumáticas. Descreve-se aqui um caso de nodulose por MTX em uma paciente com artrite reumatóide soropositiva, que utilizava esse medicamento há um ano, com bom controle do processo articular. Segue-se uma breve revisão sobre o assunto.Methotrexate-induced nodulosis is a rare side effect of this drug when it is used in low doses. Although classically described in rheumatoid arthritis patients, it may also appear in other rheumatic disorders. We describe a seropositive rheumatoid arthritis patient who developed methotrexate-induced nodulosis after using this drug for a year, with good control of articular symptoms. This case presentation is followed by a brief revision on the subject.

  6. Pneumocystis jiroveci pneumonia prophylaxis during maintenance therapy influences methotrexate/6-mercaptopurine dosing but not event-free survival for childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Shabaneh, Diana; Bohnstedt, Cathrine

    2012-01-01

    of maintenance therapy. The TMP/SMX2–7 group received lower oral 6MP doses than TMP/SMXnever patients (50.6 vs. 63.9 mg/m2/d; P ANC) (median 1.7 vs. 2.0 × 109/L; P ANC levels (P = 0.04) and male gender (P = 0.......06) were related to reduced EFS. ANC had no effect on EFS among TMP/SMX2–7 patients (P = 0.40) but did for TMP/SMXnever patients (P = 0.02). The difference in the effect on EFS between TMP/SMX2–7 and TMP/SMXnever patients was not significant (P = 0.46). EFS did not differ between TMP/SMX2–7 and TMP...

  7. Delayed elimination of high-dose methotrexate and use of carboxypeptidase G2 in pediatric patients during treatment for acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Svahn, Thommy; Mellgren, Karin; Harila-Saari, Arja

    2017-01-01

    concentration decreased by 75% when measured with immune-based methods, and by 100% when measured with high-performance liquid chromatography. The median time from the start of Mtx infusion to plasma levels ≤ 0.2 μM was 228 hr (range: 48-438). The maximum increase in plasma creatinine was 375% (range: 100...... negative acute lymphoblastic leukemia (ALL) were treated according to the Nordic Organization for Pediatric Hematology and Oncology (NOPHO) ALL 2008 protocol, including administration of six to eight high-dose (5 g/m2 /24 hr) Mtx (HDMtx) courses. The protocol includes recommendations for CPDG2......-1,310). Creatinine peaked after a median of 48 hr (range: 36-86). Mtx elimination time was shorter in patients with body surface area creatinine increase (209 vs. 258 hr; P = 0.034). All patients normalized their renal function...

  8. The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation

    Science.gov (United States)

    Van Dongen, Hans P A.; Maislin, Greg; Mullington, Janet M.; Dinges, David F.

    2003-01-01

    OBJECTIVES: To inform the debate over whether human sleep can be chronically reduced without consequences, we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiological functions were monitored and compared to those for total sleep deprivation. DESIGN: The chronic sleep restriction experiment involved randomization to one of three sleep doses (4 h, 6 h, or 8 h time in bed per night), which were maintained for 14 consecutive days. The total sleep deprivation experiment involved 3 nights without sleep (0 h time in bed). Each study also involved 3 baseline (pre-deprivation) days and 3 recovery days. SETTING: Both experiments were conducted under standardized laboratory conditions with continuous behavioral, physiological and medical monitoring. PARTICIPANTS: A total of n = 48 healthy adults (ages 21-38) participated in the experiments. INTERVENTIONS: Noctumal sleep periods were restricted to 8 h, 6 h or 4 h per day for 14 days, or to 0 h for 3 days. All other sleep was prohibited. RESULTS: Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days resulted in significant cumulative, dose-dependent deficits in cognitive performance on all tasks. Subjective sleepiness ratings showed an acute response to sleep restriction but only small further increases on subsequent days, and did not significantly differentiate the 6 h and 4 h conditions. Polysomnographic variables and delta power in the non-REM sleep EEG-a putative marker of sleep homeostasis--displayed an acute response to sleep restriction with negligible further changes across the 14 restricted nights. Comparison of chronic sleep restriction to total sleep deprivation showed that the latter resulted in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost. A statistical model revealed that, regardless of the mode of sleep deprivation, lapses in behavioral alertness

  9. CT and MRI appearances of methotrexate leucoencephalopathy

    International Nuclear Information System (INIS)

    Wilks, M.J.; Tie, M.L.K.; Pozza, C.H.

    2002-01-01

    Methotrexate is a well recognised cause of diffuse symmetrical leucoencephalopathy. The widespread use of the drug in chemotherapeutic regimes necessitates awareness of this complication. A case report and a brief literature review is presented. A 20-year-old single woman presented to the Emergency Department with a 6-week history of general malaise, lower back pain and a petechial rash. From investigations including blood picture and bone marrow trephine, the diagnosis of acute lymphoblastic leukaemia (ALL) was made. Three cycles of induction chemotherapy were administered consisting of intravenous cytarabine and hydrocortisone and intrathecal methotrexate. Shortly after the third cycle of induction chemotherapy (6 weeks following diagnosis, 2 days following the last dose of intrathecal methotrexate) she presented with an acute neurological episode consisting of muteness and somnolence. Physical examination showed generalised flaccidity to all muscle groups and generalised loss of reflexes. There were no consistent cranial neuropathies and the patient was not neutropenic. Computed tomography of the brain showed extensive symmetric white matter hypodensity extending throughout the corona radiata and deep white matter tracts especially the external capsules. There was no abnormal enhancement with non-ionic contrast administration or evidence of grey matter involvement. Magnetic resonance imaging was subsequently performed, the fluid attenuated inversion recovery images (FLAIR) and T2-weighted image (T2WI) demonstrated marked white matter hyperintensity; the involvement was more extensive than demonstrated on the CT with additional involvement of the subcortical and cerebellar white matter, the basal ganglia and cortex of the mesial temporal and inferior frontal lobes. Gadolinium was not administered. A follow up study after 4 weeks of steroid and folinic acid therapy showed complete resolution of the white matter hyperintensity on the T2WI and FLAIR sequences

  10. The Effect of Total Cumulative Dose, Number of Treatment Cycles, Interval between Injections, and Length of Treatment on the Frequency of Occurrence of Antibodies to Botulinum Toxin Type A in the Treatment of Muscle Spasticity

    Science.gov (United States)

    Bakheit, Abdel Magid O.; Liptrot, Anthea; Newton, Rachel; Pickett, Andrew M.

    2012-01-01

    A large cumulative dose of botulinum toxin type A (BoNT-A), frequent injections, a short interval between treatment cycles, and a long duration of treatment have all been suggested, but not confirmed, to be associated with a high incidence of neutralizing antibodies to the neurotoxin. The aim of this study was to investigate whether these…

  11. Synergistic activity of curcumin with methotrexate in ameliorating Freund's Complete Adjuvant induced arthritis with reduced hepatotoxicity in experimental animals.

    Science.gov (United States)

    Banji, David; Pinnapureddy, Jyothi; Banji, Otilia J F; Saidulu, A; Hayath, Md Sikinder

    2011-10-01

    Methotrexate is employed in low doses for the treatment of rheumatoid arthritis. One of the major drawbacks with methotrexate is hepatotoxicity resulting in poor compliance of therapy. Curcumin is an extensively used spice possessing both anti-arthritic and hepatoprotective potential. The present study was aimed at investigating the effect of curcumin (30 and 100 mg/kg) in combination with subtherapeutic dose of methotrexate (1 mg/kg) is salvaging hepatotoxicity, oxidative stress and producing synergistic anti-arthritic action with methotrexate. Wistar albino rats were induced with arthritis by subplantar injection of Freund's Complete Adjuvant and pronounced arthritis was seen after 9 days of injection. Groups of animals were treated with subtherapeutic dose of methotrexate followed half an hour later with 30 and 100mg/kg of curcumin from day 9 up to days 45 by intraperitoneal route. Methotrexate treatment in Freund's Complete Adjuvant induced arthritic animals produced elevation in the levels of aminotransferases, alkaline phosphatase, total and direct bilirubin. Enhanced oxidative stress in terms of measured lipid peroxides was observed in the methotrexate treated group. Curcumin significantly circumvented hepatotoxicity induced by methotrexate as evidenced by a change in biochemical markers possibly due to its strong anti-oxidant action. Hepatoprotective potential of curcumin was also confirmed from histological evaluation. Sub-therapeutic dose of methotrexate elicited substantial anti-arthritic action when used in combination with curcumin implying that the latter potentiated its action. Concomitant administration of curcumin with methotrexate was also found to minimize liver damage. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. PUVA and methotrexate therapy of psoriasis: how closely do dermatology departments follow treatment guidelines? Psoriasis Audit Workgroup of the British Association of Dermatologists.

    Science.gov (United States)

    Bilsland, D J; Rhodes, L E; Zaki, I; Wilkinson, S M; McKenna, K E; Handfield-Jones, S E; Williams, R E

    1994-08-01

    Following publication of treatment guidelines for patients with psoriasis, a six-centre audit was undertaken to assess current therapeutic practice for two second-line treatments, PUVA and methotrexate. The audit consisted of random sampling of casenotes by external auditors from a paired dermatology department, and assessment by questionnaire. One hundred and eight PUVA and 118 methotrexate casenotes were audited. The commonest indications for treatment were: (a) failure of tropical therapy--PUVA (mean 81% of casenotes), methotrexate (84%); (b) repeated hospital admissions--PUVA (16%), methotrexate (25%). For both PUVA and methotrexate, some aspects of treatment were well documented: PUVA--psoralen dosage (91%), response to PUVA (89%), cumulative lifetime UVA dosage (81%); methotrexate--pretreatment assessment of full blood count (91%), urea and electrolytes (85%), liver function tests (84%). For other aspects documentation was less complete: PUVA--no documentation of presence/absence of skin cancer history (66%), note of photoactive drugs (32%); methotrexate--concurrent medication (69%), history of presence/absence of liver disease (36%). Another aspect which was poorly documented in both PUVA and methotrexate notes was whether advice on contraception/fertility had been given. There was no indication in 29 of 32 casenotes of females of child-bearing age receiving PUVA, and 52 of 63 case notes of relevant patients on methotrexate. This project has demonstrated that formal, multicentre audit based on published guidelines is a practical proposition.

  13. Methotrexate encephalopathy: Two cases in adult cancer patients, who recovered with pathophysiologically based therapy

    Directory of Open Access Journals (Sweden)

    Shodeinde A Coker

    2017-05-01

    Full Text Available Background/Objectives: Neurotoxicity is a serious and sometimes fatal adverse effect that can occur following methotrexate treatment. We describe two adult patients with hematological malignancies with methotrexate encephalopathy who recovered with dextromethorphan therapy. Results: Case 1: A 24-year-old male with acute lymphoblastic leukemia developed the acute onset of bilateral facial weakness and slurred speech after his first treatment with high-dose intravenous methotrexate. The clinical scenario and a head magnetic resonance imaging supported a diagnosis of methotrexate encephalopathy. Treatment with dextromethorphan was coincident with recovery. Case 2: A 65-year-old female with recurrent diffuse large B-cell lymphoma was treated with high-dose intravenous methotrexate. Two weeks after a cycle, she developed hypoactive delirium, marked lethargy, ocular ataxia, and a right-sided facial weakness. Within 2 days of starting dextromethorphan, there was improvement with clinical recovery. Conclusions: These two cases suggest that N-methyl d-aspartate receptor activation by homocysteine may play an important role in the pathogenesis of methotrexate neurotoxicity.

  14. Long-term brain structural magnetic resonance imaging and cognitive functioning in children treated for acute lymphoblastic leukemia with high-dose methotrexate chemotherapy alone or combined with CNS radiotherapy at reduced total dose to 12 Gy

    Energy Technology Data Exchange (ETDEWEB)

    Zajac-Spychala, Olga; Pilarczyk, Jakub; Derwich, Katarzyna; Wachowiak, Jacek [Poznan University of Medical Sciences, Department of Pediatric Oncology, Hematology and Transplantology, Poznan (Poland); Pawlak, Mikolaj A. [Poznan University of Medical Sciences, Department of Neurology and Cerebrovascular Disorders, Poznan (Poland); Karmelita-Katulska, Katarzyna [Poznan University of Medical Sciences, Department of Neuroradiology, Poznan (Poland)

    2017-02-15

    The aim of this study was to assess the long-term side effects of central nervous system prophylaxis (high-dose chemotherapy alone vs chemotherapy and CNS radiotherapy) according to the ALL IC-BFM 2002. Thirty-tree children aged 6.7-19.9 years have been studied. The control group consisted of 12 children newly diagnosed with acute lymphoblastic leukemia. We assessed subcortical gray matter volume using automatic MRI segmentation and cognitive performance to identify differences between two therapeutic schemes and patients prior to treatment. Patients treated with chemotherapy and CNS radiotherapy had smaller hippocampi than two other subgroups and lower IQ score than patients treated with chemotherapy alone. Both treated groups, whether with chemotherapy only or in combination with CNS radiotherapy, had significantly lower volumes of caudate nucleus and performed significantly worse on measures of verbal fluency in comparison with patients prior to treatment. There were no differences in the mean volumes of total white matter, total gray matter, thalamus, putamen, and amygdala between the studied groups. In all children treated according to the ALL IC-BFM 2002 with high-dose chemotherapy, both decreased volume of selected subcortical structures and cognitive impairment was observed, especially in children who received chemotherapy in combination with reduced dose CNS radiotherapy. In all children treated according to the ALL IC-BFM 2002 with high-dose chemotherapy, both decreased volume of selected subcortical structures and cognitive impairment were observed, especially in children who received chemotherapy in combination with CNS radiotherapy. (orig.)

  15. Long-term brain structural magnetic resonance imaging and cognitive functioning in children treated for acute lymphoblastic leukemia with high-dose methotrexate chemotherapy alone or combined with CNS radiotherapy at reduced total dose to 12 Gy

    International Nuclear Information System (INIS)

    Zajac-Spychala, Olga; Pilarczyk, Jakub; Derwich, Katarzyna; Wachowiak, Jacek; Pawlak, Mikolaj A.; Karmelita-Katulska, Katarzyna

    2017-01-01

    The aim of this study was to assess the long-term side effects of central nervous system prophylaxis (high-dose chemotherapy alone vs chemotherapy and CNS radiotherapy) according to the ALL IC-BFM 2002. Thirty-tree children aged 6.7-19.9 years have been studied. The control group consisted of 12 children newly diagnosed with acute lymphoblastic leukemia. We assessed subcortical gray matter volume using automatic MRI segmentation and cognitive performance to identify differences between two therapeutic schemes and patients prior to treatment. Patients treated with chemotherapy and CNS radiotherapy had smaller hippocampi than two other subgroups and lower IQ score than patients treated with chemotherapy alone. Both treated groups, whether with chemotherapy only or in combination with CNS radiotherapy, had significantly lower volumes of caudate nucleus and performed significantly worse on measures of verbal fluency in comparison with patients prior to treatment. There were no differences in the mean volumes of total white matter, total gray matter, thalamus, putamen, and amygdala between the studied groups. In all children treated according to the ALL IC-BFM 2002 with high-dose chemotherapy, both decreased volume of selected subcortical structures and cognitive impairment was observed, especially in children who received chemotherapy in combination with reduced dose CNS radiotherapy. In all children treated according to the ALL IC-BFM 2002 with high-dose chemotherapy, both decreased volume of selected subcortical structures and cognitive impairment were observed, especially in children who received chemotherapy in combination with CNS radiotherapy. (orig.)

  16. Methotrexate for refractory prurigo nodularis

    Directory of Open Access Journals (Sweden)

    Mariam Al Zaabi

    2017-01-01

    Full Text Available Prurigo nodularis (PN is chronic unbearable inflammatory skin disease. Although it was described before a century, not many studies have been conducted regarding the systemic treatment of prurigo nodularis. A 64-year-old male patient has moderate to severe atopic dermatitis superimposed by disseminated pruritic nodules over the trunk and extremities. In spite of topical treatment and Phototherapy, patient condition was deteriorating. Therefore, the patient was treated with multimodalities including high potency topical steroid, intravenous antihistamine, cyclosporine and omalizumab without improvement. Thus the patient has been treated with methotrexate which led to remarkable improvement. Management of prurigo nodularis is often challenging as the etiology of PN in the majority of the cases is unknown. Conservative treatments are often inefficient. This case proves the efficacy of methotrexate in the management of prurigo nodularis.

  17. In vivo anti-psoriatic activity, biodistribution, sub-acute and sub-chronic toxicity studies of orally administered methotrexate loaded chitin nanogel in comparison with methotrexate tablet.

    Science.gov (United States)

    Panonnummal, Rajitha; Jayakumar, R; Anjaneyan, Gopikrishnan; Sabitha, M

    2018-04-15

    The anti-psoriatic efficacy of orally administered methotrexate loaded chitin nanogel (MCNG) was evaluated (two doses- 2.715 mg/kg and 5.143 mg/kg) and compared against orally administered methotrexate tablet MTX (5.143 mg/kg). MCNG at both dose levels of 2.715 mg/kg and 5.143 mg/kg exhibited significant anti-psoriatic activity which is very much comparable with MTX, caused normalization of histological features and inflammatory score associated with induced psoriasis. Biodistribution studies revealed the presence of drug in serum and in vital organs at all the three cases with highest amount in MCNG at 5.143 mg/kg dose, followed by MTX tablet and are lowest in MCNG at 2.715 mg/kg dose. MCNG at the highest dose of 5.143 mg/kg caused liver, lung and kidney toxicities on sub acute toxicity studies and MTX tablet was found to be toxic on liver and lung on sub chronic toxicity studies. MCNG 2.715 mg/kg was found to be safe on both sub acute and sub chronic administrations, suggesting that it can provide sufficient serum and tissue level of methotrexate necessary to clear psoriatic lesions, without inducing systemic toxicity and expected to be a better alternative for orally administered conventional methotrexate tablet for patients who need systemic medications for psoriasis. Copyright © 2018. Published by Elsevier B.V.

  18. Nonmetastatic osteosarcoma of the extremity. Neoadjuvant chemotherapy with methotrexate, cisplatin, doxorubicin and ifosfamide. An Italian Sarcoma Group study (ISG/OS-Oss).

    Science.gov (United States)

    Ferrari, Stefano; Meazza, Cristina; Palmerini, Emanuela; Tamburini, Angela; Fagioli, Franca; Cozza, Raffaele; Ferraresi, Virginia; Bisogno, Gianni; Mascarin, Maurizio; Cefalo, Graziella; Manfrini, Marco; Capanna, Rodolfo; Biagini, Roberto; Donati, Davide; Picci, Piero

    2014-01-01

    Based on the results of the ISG/OS-1 study, the MAP regimen (methotrexate [MTX], doxorubicin [ADM] and cisplatin [CDP] with the addition of ifosfamide [IFO] in poor-responder patients) was investigated in patients with nonmetastatic osteosarcoma of the extremity (ISG/OS-Oss study). Compared with the ISG/OS-1 study (cumulative doses: ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), IFO 30 g/m(2)), the ISG/OS-Oss study reduced the number of MTX cycles from 10 to 5 (cumulative MTX dose: 60 g/m(2)) in order to diminish treatment duration and toxicity. From January 2007 to June 2011, 171 patients (median age 16 years, 60% males) were registered. The limb salvage rate was 94% and the good pathologic response rate 51% (these figures were 92% and 48%, respectively, in the ISG/OS-1 study). At a median follow-up of 39 months (range, 4-80), the 5-year overall survival rate was 80% (95% CI, 73%-87%) and the event-free survival was 50% (95% CI, 39%-59%). For comparison, the 5-year overall and event-free survival rates in ISG/OS-1 were 73% (95% CI, 65%-81%) and 64% (95% CI, 56%-73%), respectively. This study confirms that in nonmetastatic osteosarcoma of the extremity, conservative surgery in more than 90% and a good pathologic response rate of 50% can be expected with primary chemotherapy based on the MAP regimen. The response and resection rates in the ISG/OS-Oss study are in the same range as those of the previous study, whereas the event-free survival is lower than that previously achieved. Since the only difference between the two studies was the cumulative dose of postoperatively given MTX, our data support the importance of the cumulative dose of MTX in the MAP regimen.

  19. The combined application of biological therapy and methotrexate in case of escape phenomenon progressing

    Directory of Open Access Journals (Sweden)

    Ponich E.S.

    2015-09-01

    Full Text Available Aim: the study of the efficacy of methotrexate in patients with the "escape effect" during the ustekinumab therapy. Materials and Methods. The results of methotrexate at a dose of 15-20mg/week in treatment of 4 patients receiving biologic and developed "escape effect". Ustekinumab is used as a hypodermic injection at a dose of 45 mg for a body weight of a patient no more than 100 kg, and 90 mg of body weight over 100 kg, at the zero week, the 4th week and then every 12 weeks. Patients control meets the standard management of patients in biological therapy. Results. The study shows that in the case of the resistance progressing when applying preparations of biological therapy, methotrexate is useful at a dose of 15-20mg/week for up to 6 months. The combined use of biologic therapy and methotrexate in the treatment of patients with psoriasis vulgaris, "escape effect" contributes to the marked regression of clinical symptoms and allows to control the process long enough, which is confirmed by the dynamics of the index PASI, BRS and DLQI. The combined method is highly safe, as evidenced by the lack of inhibition of hematopoiesis, the normal level of hepatic transaminases and serum creatinine, which greatly improves patient compliance in this type of therapy. Conclusion. The article presents the data of the combined application of biological medication therapy (ustekinumab and methotrexate for the treatment of patients with the common form of psoriasis vulgaris. In the case of the development of resistance of biological therapy recommended the appointment of methotrexate. The combined use of methotrexate and biologic therapy in the treatment of patients with psoriasis vulgaris contributes to marked regression of clinical symptoms and allows to control the process for a long time.

  20. Use of methotrexate in patients with uveitis.

    Science.gov (United States)

    Ali, A; Rosenbaum, J T

    2010-01-01

    Methotrexate has been frequently employed to treat ocular inflammatory diseases including uveitis, scleritis, and orbital inflammatory disease. It is effective for intraocular lymphoma when given directly into the eye. No study has assessed its efficacy for eye disease in a randomised, placebo controlled design. This report reviews the literature relevant to methotrexate's utility in the treatment of ocular inflammatory disease.

  1. Clinical and radiographic outcome of a treat-to-target strategy using methotrexate and intra-articular glucocorticoids with or without adalimumab induction

    DEFF Research Database (Denmark)

    Hørslev-Petersen, K; Hetland, M L; Ørnbjerg, L M

    2015-01-01

    OBJECTIVES: To study clinical and radiographic outcomes after withdrawing 1 year's adalimumab induction therapy for early rheumatoid arthritis (eRA) added to a methotrexate and intra-articular triamcinolone hexacetonide treat-to-target strategy (NCT00660647). METHODS: Disease-modifying antirheuma......OBJECTIVES: To study clinical and radiographic outcomes after withdrawing 1 year's adalimumab induction therapy for early rheumatoid arthritis (eRA) added to a methotrexate and intra-articular triamcinolone hexacetonide treat-to-target strategy (NCT00660647). METHODS: Disease.......12). Erosive progression (Δerosion score (ES)/year) was year 1:0.57/0.06 (p=0.02); year 2:0.38/0.05 (p=0.005). Proportion of patients without erosive progression (ΔES≤0) was year 1: 59%/76% (p=0.03); year 2:64%/79% (p=0.04). CONCLUSIONS: An aggressive triamcinolone and synthetic DMARD treat-to-target strategy...... was (re)initiated in 12/12 patients and cumulative triamcinolone dose was 160/120 mg (p=0.15). The treatment target (disease activity score, 4 variables, C-reactive protein (DAS28CRP) ≤3.2 or DAS28>3.2 without swollen joints) was achieved at all visits in ≥85% of patients in year 2; remission rates were...

  2. Methotrexate for the Treatment of Thyroid Eye Disease

    Directory of Open Access Journals (Sweden)

    Diego Strianese

    2014-01-01

    Full Text Available Background/Aim. To evaluate the efficacy of methotrexate for the treatment of thyroid eye disease (TED. Methods. 36 consecutive patients with active TED, previously treated with corticosteroids but stopped due to the occurrence of side effects, were commenced on methotrexate therapy. Two different weekly doses were administered depending on the weight of the patient (7.5 mg or 10 mg. Clinical activity score (7-CAS, visual acuity (VA, ocular motility, exophthalmos, and eyelid position were retrospectively evaluated at 3, 6, and 12 months and compared with baseline data. Results. There was a statistically significant improvement in 7-CAS at 3, 6, and 12 months after treatment (P<0.0001. There was no significant change in visual acuity. Ocular motility disturbances improved at 6 and 12 months (P<0.001. There was no significant change in exophthalmos (mean 24 mm, SD 3 mm or eyelid position (marginal reflex distance mean 6 mm, SD 1.5 mm during the follow-up period. No side effects were registered. Conclusions. Methotrexate therapy is effective in reducing CAS and ocular motility disturbances. No significant improvement in proptosis or eyelid retraction should be expected from this treatment. Eventually, it might be considered a suitable alternative treatment in TED for patients who cannot tolerate steroids.

  3. Relation between treatment efficacy and cumulative dose of alpha interferon in chronic hepatitis B. European Concerted Action on Viral Hepatitis (Eurohep)

    DEFF Research Database (Denmark)

    Krogsgaard, K; Christensen, E; Bindslev, N

    1996-01-01

    Alpha interferon (IFN) is an established treatment of chronic hepatitis B. The effect has been shown to be dose related, recommended dose regimens being associated with a doubling of the spontaneous, baseline HBeAg to anti-HBe seroconversion rate. However, the efficacy of IFN treatment in relation...

  4. SU-C-207A-07: Cumulative 18F-FDG Uptake Histogram Relative to Radiation Dose Volume Histogram of Lung After IMRT Or PSPT and Their Association with Radiation Pneumonitis

    International Nuclear Information System (INIS)

    Shusharina, N; Choi, N; Bortfeld, T; Liao, Z; Mohan, R

    2016-01-01

    Purpose: To determine whether the difference in cumulative 18F-FDG uptake histogram of lung treated with either IMRT or PSPT is associated with radiation pneumonitis (RP) in patients with inoperable stage II and III NSCLC. Methods: We analyzed 24 patients from a prospective randomized trial to compare IMRT (n=12) with vs. PSPT (n=12) for inoperable NSCLC. All patients underwent PET-CT imaging between 35 and 88 days post-therapy. Post-treatment PET-CT was aligned with planning 4D CT to establish a voxel-to-voxel correspondence between post-treatment PET and planning dose images. 18F-FDG uptake as a function of radiation dose to normal lung was obtained for each patient. Distribution of the standard uptake value (SUV) was analyzed using a volume histogram method. The image quantitative characteristics and DVH measures were correlated with clinical symptoms of pneumonitis. Results: Patients with RP were present in both groups: 5 in the IMRT and 6 in the PSPT. The analysis of cumulative SUV histograms showed significantly higher relative volumes of the normal lung having higher SUV uptake in the PSPT patients for both symptomatic and asymptomatic cases (VSUV=2: 10% for IMRT vs 16% for proton RT and VSUV=1: 10% for IMRT vs 23% for proton RT). In addition, the SUV histograms for symptomatic cases in PSPT patients exhibited a significantly longer tail at the highest SUV. The absolute volume of the lung receiving the dose >70 Gy was larger in the PSPT patients. Conclusion: 18F-FDG uptake – radiation dose response correlates with RP in both groups of patients by means of the linear regression slope. SUV is higher for the PSPT patients for both symptomatic and asymptomatic cases. Higher uptake after PSPT patients is explained by larger volumes of the lung receiving high radiation dose.

  5. Double Dose: The cumulative effect of TV viewing at home and in preschool on children’s activity patterns and weight status

    Science.gov (United States)

    Ross, Sharon Taverno; Dowda, Marsha; Saunders, Ruth P.; Pate, Russell R.

    2015-01-01

    Little is known about how screen-based sedentary behavior at home and in preschool influences children’s health and activity patterns. The current study examined the individual and cumulative influence of TV viewing at home and in preschool on children’s physical activity (PA) and weight status. Children (n=339) attending 16 preschools in South Carolina were grouped into high and low TV groups based on parent report of children’s TV viewing at home and director report of TV use/rules in preschool. T-tests and mixed model ANOVAs examined differences in weight status and PA (min/hr) by high and low TV groups. Results revealed that children who were classified as High TV both at home and in preschool had significantly lower levels of moderate-to-vigorous PA compared with their Low TV counterparts. These findings demonstrate the importance of total environmental TV exposure on preschooler’s PA. Longitudinal and observational research to assess preschoolers’ cumulative screen-based sedentary behavior and its relationship with PA and weight status is needed. PMID:23502043

  6. Glucarpidase treatment for methotrexate intoxication: a case report and review of the literature

    NARCIS (Netherlands)

    Boelens, A. D.; Mathôt, R. A. A.; Vlaar, A. P. J.; Bouman, C. S. C.

    2018-01-01

    High-dose methotrexate (MTX) induced acute kidney injury can lead to sustained high systemic MTX levels and severe toxicity. A 39-year-old man with lymphoblastic T-cell lymphoma was admitted to our intensive care unit with elevated serum creatinine and prolonged high serum MTX levels. Standard

  7. EEG with extreme delta brush in young female with methotrexate neurotoxicity supports NMDA receptor involvement

    DEFF Research Database (Denmark)

    Schmidt, Lisbeth Samsø; Kjær, Troels W; Schmiegelow, Kjeld

    2017-01-01

    Sub-acute neurotoxicity is a well-known complication to high-dose and intrathecal methotrexate (MTX) treatment of children with leukemia. Symptoms can be treated safely by dextromethorphan, a non-competitive antagonist to N-methyl-D-aspartic acid receptor (NMDAR). In a female with subacute MTX...

  8. A retrospective review of methotrexate-induced hepatotoxicity among patients with psoriasis in a tertiary dermatology center in Malaysia.

    Science.gov (United States)

    Ng, Lim Chui; Lee, Yin Yin; Lee, Chew Kek; Wong, Su-Ming

    2013-01-01

    Methotrexate (MTX) is a common and efficacious systemic agent used for the treatment of moderate to severe psoriasis. Nevertheless, its use is associated with the risk of hepatotoxicity. This study was performed to study the association of MTX dose with regards to hepatotoxicity as evidenced by deranged transaminases. This was a retrospective review of patients with psoriasis on MTX from 2000 to 2009 at the outpatient dermatology clinic, University Malaya Medical Centre (UMMC). We analyzed patients' demography, serial laboratory investigations, liver ultrasounds, and liver biopsies of patients on MTX. Sixty-six of 710 (9.30%) patients with psoriasis were prescribed MTX throughout the 10-year period. Among them 57.6% developed deranged transaminases, with six requiring MTX withdrawal due to hepatotoxicity. The mean cumulative dose of MTX at the detection of liver enzyme derangement was 552.3 ± 596.1 mg. A high proportion of patients on MTX had deranged transaminases. However, the number of serious events was low. We concluded from this study that the use of MTX is relatively safe in patients with moderate to severe psoriasis. © 2013 The International Society of Dermatology.

  9. Encapsulation of methotrexate loaded magnetic microcapsules for magnetic drug targeting and controlled drug release

    Energy Technology Data Exchange (ETDEWEB)

    Chakkarapani, Prabu [Department of Pharmaceutical Technology & Centre for Excellence in Nanobio Translational Research, Anna University, Bharathidasan Institute of Technology Campus, Tiruchirappalli 620024, Tamil Nadu (India); Subbiah, Latha, E-mail: lathasuba2010@gmail.com [Department of Pharmaceutical Technology & Centre for Excellence in Nanobio Translational Research, Anna University, Bharathidasan Institute of Technology Campus, Tiruchirappalli 620024, Tamil Nadu (India); Palanisamy, Selvamani; Bibiana, Arputha [Department of Pharmaceutical Technology & Centre for Excellence in Nanobio Translational Research, Anna University, Bharathidasan Institute of Technology Campus, Tiruchirappalli 620024, Tamil Nadu (India); Ahrentorp, Fredrik; Jonasson, Christian; Johansson, Christer [Acreo Swedish ICT AB, Arvid Hedvalls backe 4, SE-411 33 Göteborg (Sweden)

    2015-04-15

    We report on the development and evaluation of methotrexate magnetic microcapsules (MMC) for targeted rheumatoid arthritis therapy. Methotrexate was loaded into CaCO{sub 3}-PSS (poly (sodium 4-styrenesulfonate)) doped microparticles that were coated successively with poly (allylamine hydrochloride) and poly (sodium 4-styrenesulfonate) by layer-by-layer technique. Ferrofluid was incorporated between the polyelectrolyte layers. CaCO{sub 3}-PSS core was etched by incubation with EDTA yielding spherical MMC. The MMC were evaluated for various physicochemical, pharmaceutical parameters and magnetic properties. Surface morphology, crystallinity, particle size, zeta potential, encapsulation efficiency, loading capacity, drug release pattern, release kinetics and AC susceptibility studies revealed spherical particles of ~3 µm size were obtained with a net zeta potential of +24.5 mV, 56% encapsulation and 18.6% drug loading capacity, 96% of cumulative drug release obeyed Hixson-Crowell model release kinetics. Drug excipient interaction, surface area, thermal and storage stability studies for the prepared MMC was also evaluated. The developed MMC offer a promising mode of targeted and sustained release drug delivery for rheumatoid arthritis therapy. - Highlights: • Development of methotrexate magnetic microcapsules (MMC) by layer-by-layer method. • Characterization of physicochemical, pharmaceutical and magnetic properties of MMC. • Multiple layers of alternative polyelectrolytes prolongs methotrexate release time. • MMC is capable for targeted and sustained release rheumatoid arthritis therapy.

  10. Methotrexate-loaded biodegradable nanoparticles: preparation ...

    Indian Academy of Sciences (India)

    Administrator

    In the present work, formulation and development of a novel methotrexate ... etc and also evaluated for its in vitro cytotoxic potential against U-343 MGa human neuronal glioblastoma ... 2.3a Particle size, polydispersity index and zeta poten-.

  11. Correlation of RAD51 and radiosensitization of methotrexate

    International Nuclear Information System (INIS)

    Du Liqing; Bai Jianqiang; Liu Qiang; Wang Yan; Zhao Peng; Chen Fenghua; Wang Hong; Fan Feiyue

    2012-01-01

    Objective: To evaluate the correlation between homologous recombination repair protein RAD51 and methotrexate-enhanced radiosensitivity. Methods: Western blot and RT-PCR assays were used to detect RAD51 expression in HOS osteosarcoma cells exposed to γ-ray irradiation alone and in combination with methotrexate. Colony formation assay was used to test the survival fraction of HOS cells exposed to γ-rays and methotrexate. Results: Methotrexate inhibited both protein and RNA expressions of RAD51, and the combination of radiation and methotrexate enhanced the inhibition of RAD51 expression. Moreover, transfection of cells with RAD51 gene decreased cellular sensitivity to methotrexate and γ-rays. The sensitizer enhancement ratios after irradiation in combination with methotrexate were 1.51 and 0.99, respectively. Methotrexate was a preferred radiosensitizer to HOS cell. Conclusions: RAD51 might be involved in the methotrexate-enhanced radiosensitivity. (authors)

  12. Efficacy of etanercept in preventing relapse of uveitis controlled by methotrexate.

    Science.gov (United States)

    Foster, C Stephen; Tufail, Fehma; Waheed, Nadia Khalida; Chu, David; Miserocchi, Elisabetta; Baltatzis, Stefanos; Vredeveld, Cindy M

    2003-04-01

    To evaluate the efficacy of etanercept vs placebo in preventing relapses of uveitis in patients taking methotrexate with control of uveitis and whose methotrexate dosage was being tapered. Patients with chronic or recurrent noninfectious uveitis with inflammation controlled by low-dose methotrexate were randomized to either the drug or placebo group in a double-masked manner, given a methotrexate taper schedule, and followed for 24 weeks. The main outcome measures were control of inflammation, visual acuity, and adverse reactions. Data were analyzed both as an attempt-to-treat analysis and an analysis only of those patients who completed the study. A total of 20 patients were randomized to the drug and placebo groups. Relapse of uveitis occurred in 3 of 10 patients in the treatment group and 5 of 10 patients in the control group. Two patients in the treatment group withdrew prematurely from the study due to adverse effects. There was no significant difference between the treatment and placebo groups with regard to the rate of relapse and the final visual acuity. No patient suffered from any irreversible, long-term morbidity or mortality. Etanercept has no significant efficacy over placebo in preventing relapses of uveitis in patients being tapered from methotrexate.

  13. Methotrexate treatment in progressive tubal ectopic pregnancies and hCG-related clinicosurgical implications

    Directory of Open Access Journals (Sweden)

    Askin Dogan

    2016-06-01

    Full Text Available Our aim was to evaluate the relationship between the success of methotrexate treatment and β-hCG levels in progressive tubal ectopic pregnancies. We defined a retrospective cohort of 394 progressive tubal ectopic pregnancy patients treated with methotrexate. A single-dose methotrexate protocol using 50 mg/m2 was administered to patients with progressive tubal ectopic pregnancy. Surgery was performed in patients who exhibited signs of acute abdomen due to tubal rupture. Of 394 patients that received methotrexate treatment, 335 (84.6% responded to medical treatment, while the remaining 59 (15.36% underwent surgery due to treatment failure. β-hCG levels in the failure group were significantly higher as compared with the success group at Day 1, Day 4, and Day 7 (2116±3157 vs. 4178±3422, 2062±3551 vs. 4935±4103, and 1532±3007 vs. 3900±4783, respectively. The receiver operating characteristics curve for β-hCG levels at Day 1 was 0.738, with a cutoff value of 1418 mIU/mL, while sensitivity and specificity values reached the optimum for treatment success (83.1% and 59.4%, respectively. Medical treatment with methotrexate achieved an 85.02% success rate for the treatment of progressive tubal ectopic pregnancy, while success rates for medical treatment decreased significantly when initial β-hCG levels were >1418 mIU/mL.

  14. Early medical abortion with methotrexate and misoprostol.

    Science.gov (United States)

    Borgatta, L; Burnhill, M S; Tyson, J; Leonhardt, K K; Hausknecht, R U; Haskell, S

    2001-01-01

    To evaluate the introduction of an early medical abortion program with methotrexate and misoprostol, using a standardized protocol. A total of 1973 women at 34 Planned Parenthood sites participated in a case series of early medical abortion. Ultrasound was used to confirm gestational age of less than 49 days from the first day of the last menstrual period. Women were given intramuscular methotrexate 50 mg/m(2) of body surface area on day 1, and then they inserted misoprostol 800 microg vaginally at home on day 5, 6, or 7. Women were advised to have a suction curettage if the pregnancy appeared viable 2 weeks after methotrexate or if any gestational sac persisted 4 weeks after methotrexate. Outcomes were complete medical abortion and suction curettage. Sixteen hundred fifty-nine women (84.1%) had a complete medical abortion, and 257 (13.0%) had suction curettage. The most common reason for curettage was patient option (8.9%). At 2 weeks after methotrexate use, 1.4% of women had curettage because of a viable pregnancy; at 4 weeks, 1.6% of women had curettage because of a persistent but nonviable pregnancy. One percent of women had curettage because of physician recommendation, most commonly for bleeding. Suction curettage rates decreased with site experience (P <.006) and were lower at early gestational ages (P <.004) and in nulliparous women (P <.004). Medical abortion with methotrexate and misoprostol is safe and effective and can be offered in a community setting.

  15. Dose-Response Relationship between Cumulative Occupational Lead Exposure and the Associated Health Damages: A 20-Year Cohort Study of a Smelter in China

    OpenAIRE

    Yue Wu; Jun-Ming Gu; Yun Huang; Yan-Ying Duan; Rui-Xue Huang; Jian-An Hu

    2016-01-01

    Long-term airborne lead exposure, even below official occupational limits, has been found to cause lead poisoning at higher frequencies than expected, which suggests that China’s existing occupational exposure limits should be reexamined. A retrospective cohort study was conducted on 1832 smelting workers from 1988 to 2008 in China. These were individuals who entered the plant and came into continuous contact with lead at work for longer than 3 months. The dose-response relationship between o...

  16. Infliximab plus methotrexate is superior to methotrexate alone in the treatment of psoriatic arthritis in methotrexate-naive patients: the RESPOND study.

    Science.gov (United States)

    Baranauskaite, Asta; Raffayová, Helena; Kungurov, N V; Kubanova, Anna; Venalis, Algirdas; Helmle, Laszlo; Srinivasan, Shankar; Nasonov, Evgeny; Vastesaeger, Nathan

    2012-04-01

    To compare the efficacy and safety of treatment with infliximab plus methotrexate with methotrexate alone in methotrexate-naive patients with active psoriatic arthritis (PsA). In this open-label study, patients 18 years and older with active PsA who were naive to methotrexate and not receiving disease-modifying therapy (N=115) were randomly assigned (1:1) to receive either infliximab (5 mg/kg) at weeks 0, 2, 6 and 14 plus methotrexate (15 mg/week); or methotrexate (15 mg/week) alone. The primary assessment was American College of Rheumatology (ACR) 20 response at week 16. Secondary outcome measures included psoriasis area and severity index (PASI), disease activity score in 28 joints (DAS28) and dactylitis and enthesitis assessments. At week 16, 86.3% of patients receiving infliximab plus methotrexate and 66.7% of those receiving methotrexate alone achieved an ACR20 response (palone experienced a 75% or greater improvement in PASI (palone group. Treatment with infliximab plus methotrexate in methotrexate-naive patients with active PsA demonstrated significantly greater ACR20 response rates and PASI75 improvement compared with methotrexate alone and was generally well tolerated. This trial is registered in the US National Institutes of Health clinicaltrials.gov database, identifier NCT00367237.

  17. Methotrexate information booklet study 2008.

    LENUS (Irish Health Repository)

    Mohammad, A

    2012-02-01

    INTRODUCTION: I n order to assess the value of using the methotrexate information booklet, we conducted a single blind prospective controlled trial of the patients attending two rheumatology services. METHODS: The active-arm (n=40) used the MTX information booklet for the patients\\' education and the control-arm (n=38) did not. Patients\\' interviews were conducted over a 6-month period using an MTX-questionnaire. RESULTS: The entire active-arm patients (100%) were taking folic-acid and 32 (80%) knew the reason why they were taking folic-acid vs. [30 (79%) and 10 (26%) in the control-arm]. In the active-arm 35 (88%) knew the reason for their monthly blood tests vs. 18 (47%) in the control-arm. The entire active-arm was aware of the need for contraception use and MTX-side effects vs. 23 (60%) and 15 (40%) in the control-arm respectively. CONCLUSIONS: The use of the MTX information booklet in our cohort improved their understanding of the treatment.

  18. Cumulative Poisson Distribution Program

    Science.gov (United States)

    Bowerman, Paul N.; Scheuer, Ernest M.; Nolty, Robert

    1990-01-01

    Overflow and underflow in sums prevented. Cumulative Poisson Distribution Program, CUMPOIS, one of two computer programs that make calculations involving cumulative Poisson distributions. Both programs, CUMPOIS (NPO-17714) and NEWTPOIS (NPO-17715), used independently of one another. CUMPOIS determines cumulative Poisson distribution, used to evaluate cumulative distribution function (cdf) for gamma distributions with integer shape parameters and cdf for X (sup2) distributions with even degrees of freedom. Used by statisticians and others concerned with probabilities of independent events occurring over specific units of time, area, or volume. Written in C.

  19. Efficacy of Methotrexate in patients with plaque type psoriasis

    Science.gov (United States)

    Haider, Sabiqa; Wahid, Zarnaz; Najam-us-Saher; Riaz, Farzana

    2014-01-01

    Objective: To assess the efficacy of Methotrexate in patients with plaque type psoriasis. Methods: This descriptive study was conducted in the department of Dermatology, Civil Hospital Karachi from September 2009 to March 2010. Seventy three patients between 18 to 50 years of age suffering from plaque type psoriasis with PASI score of >10 were included in the study after taking the informed consent. Oral methotrexate in a dose of 7.5 mg/week was given for 8 weeks. The data collected included demographic profile (age and gender), duration of disease, site of involvement, size of plaque, severity of plaque measured by Psoriasis Area and Severity Index (PASI) score before starting the treatment and at the end of treatment. Efficacy was labeled with a PASI score of ≤5 at the end of 8 weeks. Results: Out of 73 patients there were 45 (61.6%) males and 28 (38.4%) females. The mean ±SD age was 40.0±12.6 years. The mean baseline PASI score showed clear and comparable improvement from a mean ± SD PASI score of 14.8±4.2 to 4.9±4.3.Twenty nine (40%) patients had an almost complete remission during the 8 weeks of treatment. Partial remission was achieved in 44 (60%) patients. The clearance time for psoriasis ranged from 5-7 weeks (mean 6±0.89 weeks). Conclusion: Treatment with methotrexate for chronic plaque psoriasis brings satisfactory disease control and improved quality of life. PMID:25225524

  20. Herpes simplex type 2 encephalitis and methotrexate medication: a fortuitous or causative association in a patient with spondyloarthritis?

    Science.gov (United States)

    Lupo, Julien; Dos Santos, Ophélie; Germi, Raphaele; Baccard-Longère, Monique; Stahl, Jean-Paul; Epaulard, Olivier; Morand, Patrice

    2017-01-01

    It is unclear whether immunosuppression is a risk factor for herpes encephalitis. Herein, we describe a rare case of herpes simplex virus type 2 encephalitis in a patient treated with low-dose methotrexate for HLA-B27-associated spondyloarthritis. The patient was successfully treated with acyclovir but presented sequelae of encephalitis. Here we discuss the possible role of low-dose methotrexate therapy as a risk factor of neurological herpes reactivation and severe disease. The host-related and viral risk factors are also addressed.

  1. Targeting TNF-α and NF-κB activation by bee venom: role in suppressing adjuvant induced arthritis and methotrexate hepatotoxicity in rats.

    Science.gov (United States)

    Darwish, Samar F; El-Bakly, Wesam M; Arafa, Hossam M; El-Demerdash, Ebtehal

    2013-01-01

    Low dose methotrexate is the cornerstone for the treatment of rheumatoid arthritis. One of its major drawbacks is hepatotoxicity, resulting in poor compliance of therapy. Dissatisfied arthritis patients are likely to seek the option of complementary and alternative medicine such as bee venom. The combination of natural products with modern medicine poses the possibility of potential interaction between the two groups and needs investigation. The present study was aimed to investigate the modulatory effect of bee venom acupuncture on efficacy, toxicity, and pharmacokinetics and tissue disposition of methotrexate. Complete Freund's adjuvant induced arthritic rats were treated for 3 weeks with methotrexate and/or bee venom. Arthritic score, ankle diameter, paw volume and tissue expression of NF-κB and TNF-α were determined to assess anti-arthritic effects, while anti-nociceptive effects were assessed by gait score and thermal hyperalgesia. Methotrexate toxicity was assessed by measuring serum TNF-α, liver enzymes and expression of NF-κB in liver. Combination therapy of bee venom with methotrexate significantly improved arthritic parameters and analgesic effect as compared to methotrexate alone. Bee venom ameliorated serum TNF-α and liver enzymes elevations as well as over expression of NF-κB in liver induced by methotrexate. Histological examination supported the results. And for the first time bee venom acupuncture was approved to increase methotrexate bioavailability with a significant decrease in its elimination. bee venom potentiates the anti-arthritic effects of methotrexate, possibly by increasing its bioavailability. Also, it provides a potent anti-nociceptive effect. Furthermore, bee venom protects against methotrexate induced hepatotoxicity mostly due to its inhibitory effect on TNF-α and NF-κB.

  2. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE)).

    Science.gov (United States)

    Emery, P; Deodhar, A; Rigby, W F; Isaacs, J D; Combe, B; Racewicz, A J; Latinis, K; Abud-Mendoza, C; Szczepanski, L J; Roschmann, R A; Chen, A; Armstrong, G K; Douglass, W; Tyrrell, H

    2010-09-01

    This phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment. Patients with active disease on stable MTX (10-25 mg/week) were randomised to rituximab 2 x 500 mg (n=168), rituximab 2 x 1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) > or =2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2 x 500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48. At week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2 x 500 mg) + MTX, rituximab (2 x 1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48. Rituximab (at 2 x 500 mg and 2 x 1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses.

  3. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naïve with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE))

    Science.gov (United States)

    Emery, P; Deodhar, A; Rigby, W F; Isaacs, J D; Combe, B; Racewicz, A J; Latinis, K; Abud-Mendoza, C; Szczepański, L J; Roschmann, R A; Chen, A; Armstrong, G K; Douglass, W; Tyrrell, H

    2010-01-01

    Objectives This phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment. Methods Patients with active disease on stable MTX (10–25 mg/week) were randomised to rituximab 2×500 mg (n=168), rituximab 2×1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) ≥2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2×500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48. Results At week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2×500 mg) + MTX, rituximab (2×1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48. Conclusions Rituximab (at 2×500 mg and 2×1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses. PMID:20488885

  4. Cumulative dose of hydroxychloroquine is associated with a decrease of resting heart rate in patients with systemic lupus erythematosus: a pilot study.

    Science.gov (United States)

    Cairoli, E; Danese, N; Teliz, M; Bruzzone, M J; Ferreira, J; Rebella, M; Cayota, A

    2015-10-01

    The use of hydroxychloroquine (HCQ) in patients with systemic lupus erythematosus (SLE) offers a wide range of benefits. However, there are evidence in favour of cardiotoxicity, including heart conduction disturbances and congestive heart failure. To determine the effects of HCQ in the resting heart rate (RHR) of SLE patients. Included were patients with non active SLE, with a sedentary lifestyle and treated with HCQ. Excluded were patients on beta blocker treatment, trained patients, pacemaker's users and patients with clinical or analytical evidence of anemia, renal disease, obstructive pulmonary disease, obesity, uncontrolled thyroid disease, fever or current infection. Standard 12-lead electrocardiogram was performed in the resting condition (supine decubitus and orthostatic position). Comparison between groups was performed using Mann-Whitney U test. A multiple linear regression was performed. A p value 365 g). Non significant differences were found in age, sex, prednisone dose or SLEDAI. The mean RHR was 73 ± 6 beats/min in the low-HCQ and 65 ± 7 beats/min in the high-HCQ, with a significant decrease of 11% (p = 0.003). In multiple linear regressions, there were non significant association between the decrease of RHR and prednisone dose, age, SLEDAI or TSH, but there was significant association between RHR and CD-HCQ (p = 0.024) and RHR and time of exposure to HCQ (p = 0.029). CD-HCQ higher than 365 g was associated with a significant decrease (11%) in RHR in non-active SLE patients, although a larger prospective study is required to allow more definitive conclusions. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  5. Histology and Gadolinium Distribution in the Rodent Brain After the Administration of Cumulative High Doses of Linear and Macrocyclic Gadolinium-Based Contrast Agents

    Science.gov (United States)

    Lohrke, Jessica; Frisk, Anna-Lena; Frenzel, Thomas; Schöckel, Laura; Rosenbruch, Martin; Jost, Gregor; Lenhard, Diana Constanze; Sieber, Martin A.; Nischwitz, Volker; Küppers, Astrid; Pietsch, Hubertus

    2017-01-01

    Objectives Retrospective studies in patients with primary brain tumors or other central nervous system pathologies as well as postmortem studies have suggested that gadolinium (Gd) deposition occurs in the dentate nucleus (DN) and globus pallidus (GP) after multiple administrations of primarily linear Gd-based contrast agents (GBCAs). However, this deposition has not been associated with any adverse effects or histopathological alterations. The aim of this preclinical study was to systematically examine differences between linear and macrocyclic GBCAs in their potential to induce changes in brain and skin histology including Gd distribution in high spatial resolution. Materials and Methods Fifty male Wistar-Han rats were randomly allocated into control (saline, n = 10 rats) and 4 GBCA groups (linear GBCAs: gadodiamide and gadopentetate dimeglumine, macrocyclic GBCAs: gadobutrol and gadoteridol; n = 10 rats per group). The animals received 20 daily intravenous injections at a dose of 2.5 mmol Gd/kg body weight. Eight weeks after the last GBCA administration, the animals were killed, and the brain and skin samples were histopathologically assessed (hematoxylin and eosin; cresyl violet [Nissl]) and by immunohistochemistry. The Gd concentration in the skin, bone, brain, and skeletal muscle samples were analyzed using inductively coupled plasma mass spectroscopy (ICP-MS, n = 4). The spatial Gd distribution in the brain and skin samples was analyzed in cryosections using laser ablation coupled with ICP-MS (LA-ICP-MS, n = 3). For the ultra-high resolution of Gd distribution, brain sections of rats injected with gadodiamide or saline (n = 1) were assessed by scanning electron microscopy coupled to energy dispersive x-ray spectroscopy and transmission electron microscopy, respectively. Results No histological changes were observed in the brain. In contrast, 4 of 10 animals in the gadodiamide group but none of the animals in other groups showed macroscopic and histological

  6. Histology and Gadolinium Distribution in the Rodent Brain After the Administration of Cumulative High Doses of Linear and Macrocyclic Gadolinium-Based Contrast Agents.

    Science.gov (United States)

    Lohrke, Jessica; Frisk, Anna-Lena; Frenzel, Thomas; Schöckel, Laura; Rosenbruch, Martin; Jost, Gregor; Lenhard, Diana Constanze; Sieber, Martin A; Nischwitz, Volker; Küppers, Astrid; Pietsch, Hubertus

    2017-06-01

    Retrospective studies in patients with primary brain tumors or other central nervous system pathologies as well as postmortem studies have suggested that gadolinium (Gd) deposition occurs in the dentate nucleus (DN) and globus pallidus (GP) after multiple administrations of primarily linear Gd-based contrast agents (GBCAs). However, this deposition has not been associated with any adverse effects or histopathological alterations. The aim of this preclinical study was to systematically examine differences between linear and macrocyclic GBCAs in their potential to induce changes in brain and skin histology including Gd distribution in high spatial resolution. Fifty male Wistar-Han rats were randomly allocated into control (saline, n = 10 rats) and 4 GBCA groups (linear GBCAs: gadodiamide and gadopentetate dimeglumine, macrocyclic GBCAs: gadobutrol and gadoteridol; n = 10 rats per group). The animals received 20 daily intravenous injections at a dose of 2.5 mmol Gd/kg body weight. Eight weeks after the last GBCA administration, the animals were killed, and the brain and skin samples were histopathologically assessed (hematoxylin and eosin; cresyl violet [Nissl]) and by immunohistochemistry. The Gd concentration in the skin, bone, brain, and skeletal muscle samples were analyzed using inductively coupled plasma mass spectroscopy (ICP-MS, n = 4). The spatial Gd distribution in the brain and skin samples was analyzed in cryosections using laser ablation coupled with ICP-MS (LA-ICP-MS, n = 3). For the ultra-high resolution of Gd distribution, brain sections of rats injected with gadodiamide or saline (n = 1) were assessed by scanning electron microscopy coupled to energy dispersive x-ray spectroscopy and transmission electron microscopy, respectively. No histological changes were observed in the brain. In contrast, 4 of 10 animals in the gadodiamide group but none of the animals in other groups showed macroscopic and histological nephrogenic systemic fibrosis-like skin

  7. [Hemiparesis and facial palsy caused by methotrexate].

    Science.gov (United States)

    Rueda Arenas, E; García Corzo, J; Franco Ospina, L

    2013-12-01

    Methotrexate used in the treatment of acute lymphocytic leukemia, can cause neurotoxicity, including a rare presentation with hemiparesis. We describe two teenagers, who during the implementation of the M phase of the protocol, suffered hemiparesis, facial paresis and dysarthria which quickly reversed. Leukemia involvement of the central nervous system and stroke, were ruled out. We briefly review the pathophysiology of methotrexate neurotoxicity, the characteristics of the focal paresis presentation and magnetic resonance image findings. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  8. Experience of Parenteral Administration of Methotrexate in a Female Patient Suffering from Early Juvenile Idiopathic Arthritis and Uveitis

    Directory of Open Access Journals (Sweden)

    Т. V. Sleptsova

    2015-01-01

    Full Text Available Represented here is a case of early juvenile idiopathic arthritis associated with uveitis diagnosed in a three-year-old female patient subject to treatment with the standard methotrexate dosage. At the initial stage of treatment, the child demonstrated severe articular syndrome, inflammatory reactions affecting eyeball surfaces, increased laboratory indicators of the illness and functional insufficiency. Successful overcoming of methotrexate resistance through dosage increased up to 20 mg/m2 of body surface per week was described. Over three months of subcutaneous methotrexate treatment with a 15 mg/m2-per-week dose, the child showed milder joint exudation an, arthralgia, less lengthy morning stiffness, although there was no 50% improvement based on ACRpedi criteria, and uveitis was first recognized in the subactive phase. The dose was increased up to 20 mg/m2 per week. By the eighth week of methotrexate treatment, uveal inflammation reversed. Non-active phase and remission were detected in 6 and 12 months respectively. The remission has persisted for 6 years. No side effects have been observed throughout methotrexate treatment. 

  9. Sequence-dependent toxicity profile in modified FAMTX (fluorouracil-adriamycin-methotrexate) chemotherapy with lenograstim support for advanced gastric cancer: a feasibility study

    NARCIS (Netherlands)

    Westermann, A. M.; Taal, B. G.; Swart, M.; Boot, H.; Craanen, M.; Gerritsen, W. R.

    2000-01-01

    For advanced irresectible gastric cancer, sequential high-dose methotrexate and 5-fluorouracil (both on day 1) combined with adriamycin on day 15 (FAMTX regimen), cycled every 28 days, is a fairly effective but toxic treatment, with a high incidence of neutropenic fever, dose reductions and dose

  10. Cumulative radiation effect

    International Nuclear Information System (INIS)

    Kirk, J.; Cain, O.; Gray, W.M.

    1977-01-01

    Cumulative Radiation Effect (CRE) represents a scale of accumulative sub-tolerance radiation damage, with a unique value of the CRE describing a specific level of radiation effect. Computer calculations have been used to simplify the evaluation of problems associated with the applications of the CRE-system in radiotherapy. In a general appraisal of the applications of computers to the CRE-system, the various problems encountered in clinical radiotherapy have been categorised into those involving the evaluation of a CRE at a point in tissue and those involving the calculation of CRE distributions. As a general guide, the computer techniques adopted at the Glasgow Institute of Radiotherapeutics for the solution of CRE problems are presented, and consist basically of a package of three interactive programs for point CRE calculations and a Fortran program which calculates CRE distributions for iso-effect treatment planning. Many examples are given to demonstrate the applications of these programs, and special emphasis has been laid on the problem of treating a point in tissue with different doses per fraction on alternate treatment days. The wide range of possible clinical applications of the CRE-system has been outlined and described under the categories of routine clinical applications, retrospective and prospective surveys of patient treatment, and experimental and theoretical research. Some of these applications such as the results of surveys and studies of time optimisation of treatment schedules could have far-reaching consequences and lead to significant improvements in treatment and cure rates with the minimum damage to normal tissue. (author)

  11. Mycophenolate mofetil after methotrexate failure or intolerance in the treatment of scleritis and uveitis.

    Science.gov (United States)

    Sobrin, Lucia; Christen, William; Foster, C Stephen

    2008-08-01

    To evaluate the outcomes of treatment with mycophenolate mofetil in patients with scleritis and uveitis refractory to or intolerant of methotrexate. Retrospective noncomparative case series. Eighty-five patients with scleritis and/or uveitis who failed with or did not tolerate methotrexate and were subsequently treated with mycophenolate mofetil between 1998 and 2006. We reviewed medical records of patients who were treated with mycophenolate mofetil after methotrexate intolerance or failure at one tertiary uveitis referral practice. We recorded dose and duration of methotrexate and mycophenolate mofetil therapy, inflammation grade, Snellen visual acuity (VA), use of other immunomodulatory therapy, and adverse events. Multivariate logistic regression was used to identify factors associated with inflammation control. Control of inflammation, steroid-sparing effect, VA, and adverse effects were assessed. Inflammation was controlled with mycophenolate mofetil in 47 patients (55%), with 5 achieving durable remission off all medication. In multivariate logistic regression analysis that adjusted for gender and age, the odds of inflammation control were lower for patients with scleritis (odds ratio [OR], 0.19; 95% confidence interval [CI], 0.04-0.93; P = 0.04) than for patients without scleritis. Among patients without scleritis, the odds of inflammation control were lower for patients with juvenile idiopathic arthritis (JIA)-associated uveitis (OR, 0.14; CI, 0.02-0.81, P = 0.03) compared to patients without JIA-associated uveitis. Eight of the 11 patients (73%) who were taking concomitant prednisone were able to taper their dose to methotrexate. The odds of inflammation control were less in patients with the diagnoses of scleritis and JIA.

  12. Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis.

    Science.gov (United States)

    Ramanan, Athimalaipet V; Dick, Andrew D; Jones, Ashley P; McKay, Andrew; Williamson, Paula R; Compeyrot-Lacassagne, Sandrine; Hardwick, Ben; Hickey, Helen; Hughes, Dyfrig; Woo, Patricia; Benton, Diana; Edelsten, Clive; Beresford, Michael W

    2017-04-27

    Adalimumab, a fully human anti-tumor necrosis factor α monoclonal antibody, is effective in the treatment of juvenile idiopathic arthritis (JIA). We tested the efficacy of adalimumab in the treatment of JIA-associated uveitis. In this multicenter, double-blind, randomized, placebo-controlled trial, we assessed the efficacy and safety of adalimumab in children and adolescents 2 years of age or older who had active JIA-associated uveitis. Patients who were taking a stable dose of methotrexate were randomly assigned in a 2:1 ratio to receive either adalimumab (at a dose of 20 mg or 40 mg, according to body weight) or placebo, administered subcutaneously every 2 weeks. Patients continued the trial regimen until treatment failure or until 18 months had elapsed. They were followed for up to 2 years after randomization. The primary end point was the time to treatment failure, defined according to a multicomponent intraocular inflammation score that was based on the Standardization of Uveitis Nomenclature criteria. The prespecified stopping criteria were met after the enrollment of 90 of 114 patients. We observed 16 treatment failures in 60 patients (27%) in the adalimumab group versus 18 treatment failures in 30 patients (60%) in the placebo group (hazard ratio, 0.25; 95% confidence interval [CI], 0.12 to 0.49; Ptreatment failure than placebo among children and adolescents with active JIA-associated uveitis who were taking a stable dose of methotrexate. Patients who received adalimumab had a much higher incidence of adverse events and serious adverse events than those who received placebo. (Funded by the NIHR Health Technology Assessment Programme and Arthritis Research UK; SYCAMORE EudraCT number, 2010-021141-41 .).

  13. Monitoring methotrexate-induced liver fibrosis in patients with psoriasis: utility of transient elastography

    Directory of Open Access Journals (Sweden)

    Cheng HS

    2018-05-01

    Full Text Available Harriet S Cheng,1 Marius Rademaker2 1Dermatology Service, Auckland City Hospital, Auckland, New Zealand; 2Waikato Clinical Campus, Auckland University Medical School, Hamilton, New Zealand Abstract: Increasingly, existing evidence indicates that methotrexate-associated liver injury is related to comorbid risk factors such as diabetes, alcoholism, and obesity, rather than to methotrexate itself. Despite this fact, significant effort continues to be expended in the monitoring of low-dose methotrexate in patients with psoriasis. The gold standard investigation has been liver biopsy, but this is associated with significant morbidity and mortality. As methotrexate-induced liver injury is uncommon, the risk/benefit ratio of liver biopsy has been questioned. Fortunately, a number of new technologies have been developed for the diagnosis of chronic liver disease, including transient elastography (TE. TE is a type of shear wave ultrasound elastography, which measures the speed of shear waves used to estimate hepatic tissue stiffness. Several meta-analyses show very high pooled sensitivity and specificity for the diagnosis of hepatic cirrhosis (87% and 91%, respectively in a variety of chronic liver disorders. It has a negative predictive value for cirrhosis of >90% and a positive predictive value of 75%. Recent European guidelines now advocate the use of TE as the first-line test for the assessment of fibrosis in alcohol- or hepatitis-related liver disease, including nonalcoholic fatty liver disease (NAFLD. As the prevalence of obesity and metabolic syndrome, including NAFLD, is significantly elevated in patients with psoriasis, TE may be worth considering as a routine investigation for any patient with psoriasis. Although high-quality studies comparing TE with standard liver biopsy in the monitoring of psoriatics on low-dose methotrexate are lacking, the evidence from multiple small cohort studies and case series demonstrates its effectiveness. A recent

  14. Methotrexate: Revisited efficiency and safety of drug administration in psoriasis patients

    Directory of Open Access Journals (Sweden)

    A. L. Bakulev

    2017-01-01

    Full Text Available The article presents the current data of the literature on methotrexate, which is now one of the most commonly used preparation for the systemic treatment of patients with moderate to severe psoriasis. The following problems are under consideration: estimation by specialists of response to systemic psoriasis therapy and possible therapeutic strategies; selecting initial doses of methotrexate for the treatment of patients with psoriasis; the possibilities of combined use with genetically engineered biological agents and monitoring of therapy. The data from randomized clinical trials on the long-term continuous treatment with methotrexate (efficacy, safety; methods of its administration to patients and time and criteria for long-term effecasy are reported. There are presented the data on the mechanisms of methotrexate action and the new data about the impact on the adenosine metabolism and the ability of the preparation to modulate the inflammatory response in the skin of patients by inhibiting the cellular components of the inflammatory infiltrate in the skin (dendritic antigen-producing cells and T-lymphocytes, as well as the suppression of expression of some proinflammatory cytokines (IFN-y and IL17A.

  15. Enzymatic assay for methotrexate in erythrocytes

    DEFF Research Database (Denmark)

    Schrøder, H; Heinsvig, E M

    1985-01-01

    Methotrexate (MTX) accumulates in erythrocytes in MTX-treated patients. We present a modified enzymatic assay measuring MTX concentrations between 10 and 60 nmol/l in erythrocytes, adapted for a centrifugal analyser (Cobas Bio). About 40 patient's samples could be analysed within 1 h. The detection...

  16. Discovery – Methotrexate: Chemotherapy Treatment for Cancer

    Science.gov (United States)

    Prior to the 1950s, treatment for the majority of cancers was limited to either surgery or the use of radiation. The discovery of the use of methotrexate in curing a rare cancer marked the first time a cancer had been cured. This led to the development of many of today’s common cancer treatments.

  17. Adherence to methotrexate in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Bliddal, Henning; Eriksen, Stine A; Christensen, Robin

    2015-01-01

    Objectives. To study adherence to methotrexate (MTX) and factors of importance thereof in patients with rheumatoid arthritis (RA). Methods. Patients with a hospital diagnosis of RA (ICD10 codes M05.X or M06.X) after January 1, 1997, and aged ≥18 years at the date of first diagnosis...

  18. Enhancement effect of irradiation by methotrexate

    International Nuclear Information System (INIS)

    Shehata, W.M.; Meyer, R.L.

    1980-01-01

    Three cases are described in which complications developed which were believed to be due to the enhancement effect of irradiation by methotrexate during the course of therapy for lung, kidney, and bladder cancer. These included esophageal and large bowel complications. In two of these cases, the patients improved with conservative therapy

  19. Divergent Cumulative Cultural Evolution

    OpenAIRE

    Marriott, Chris; Chebib, Jobran

    2016-01-01

    Divergent cumulative cultural evolution occurs when the cultural evolutionary trajectory diverges from the biological evolutionary trajectory. We consider the conditions under which divergent cumulative cultural evolution can occur. We hypothesize that two conditions are necessary. First that genetic and cultural information are stored separately in the agent. Second cultural information must be transferred horizontally between agents of different generations. We implement a model with these ...

  20. Methotrexate: the emerging drug of choice for serious rheumatoid arthritis.

    Science.gov (United States)

    Salach, R H; Cash, J M

    1994-01-01

    The recently recognized high morbidity and unexpected mortality associated with rheumatoid arthritis (RA) has spurred new interest in more aggressive, early treatment of this disease. Methotrexate (MTX) has rapidly become the rheumatologist's drug of choice for serious RA because of its favorable efficacy to toxicity ratio and rapid onset of action compared with other second-line agents. The initial concerns about hepatic fibrosis and cirrhosis in psoriatic patients has subsided somewhat as long-term liver toxicity data are accumulating in patients with RA. Routine liver biopsy with incremental doses of MTX is no longer recommended. Potential for severe lung, hematologic, and infectious complications exists, mandating careful monitoring of RA patients taking MTX.

  1. Neurologic sequelae of methotrexate and ionizing radiation: a new classification

    International Nuclear Information System (INIS)

    Bleyer, W.A.

    1981-01-01

    Therapy for prevention of central nervous system (CNS) leukemia has had a dramatic effect on disease-free survival in children with acute lymphoblastic leukemia (ALL). Now, a majority of children may be in complete remission indefinitely, having completed therapy years ago. Unfortunately, some of these long-term survivors have residual neurologic dysfunction, varying in severity from the not uncommon occurrence of mild intellectual deficit to the fortunately rare instance of debilitating leukoencephalopathy. To help identify inciting factors and ultimately render CNS prophylaxis less neurotoxic, this article attempts to categorize the types of neurotoxicities reported in patients treated with methotrexate (MTX) and ionizing radiation. A variety of clinical syndromes are described and related temporally to these treatment modalities. Analyzed in this way, combinations including CNS irradiation appear to be the most neurotoxic. The safest methods are the single modalities, of which high-dose iv MTX may be the least neurotoxic

  2. Intraocular methotrexate can induce extended remission in some patients in noninfectious uveitis.

    Science.gov (United States)

    Taylor, Simon R J; Banker, Alay; Schlaen, Ariel; Couto, Cristobal; Matthe, Egbert; Joshi, Lavnish; Menezo, Victor; Nguyen, Ethan; Tomkins-Netzer, Oren; Bar, Asaf; Morarji, Jiten; McCluskey, Peter; Lightman, Sue

    2013-01-01

    To assess the outcomes of the intravitreal administration of methotrexate in uveitis. Multicenter, retrospective interventional case series of patients with noninfectious uveitis. Thirty-eight eyes of 30 patients were enrolled, including a total of 54 intravitreal injections of methotrexate at a dose of 400 µg in 0.1 mL. The primary outcome measure was visual acuity. Secondary outcome measures included control of intraocular inflammation and cystoid macular edema, time to relapse, development of adverse events, and levels of systemic corticosteroid and immunosuppressive therapy. Methotrexate proved effective in controlling intraocular inflammation and improving vision in 30 of 38 eyes (79%). The side effect profile was good, with no reported serious ocular adverse events and only one patient having an intraocular pressure of >21 mmHg. Of the 30 eyes that responded to treatment, 8 relapsed, but 22 (73%) entered an extended period of remission, with the Kaplan-Meier estimate of median time to relapse for the whole group being 17 months. The eight eyes that relapsed were reinjected and all responded to treatment. One eye relapsed at 3 months, but 7 eyes again entered extended remission. Of the 14 patients on systemic therapy at the start of the study, 8 (57%) were able to significantly reduce this following intravitreal methotrexate injection. In patients with uveitis and uveitic cystoid macular edema, intravitreal MTX can effectively improve visual acuity and reduce cystoid macular edema and, in some patients, allows the reduction of immunosuppressive therapy. Some patients relapse at 3 to 4 months, but a large proportion (73%) enter an extended period of remission of up to 18 months. This larger study extends the results obtained from previous smaller studies suggesting the viability of intravitreal methotrexate as a treatment option in uveitis.

  3. Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol

    Energy Technology Data Exchange (ETDEWEB)

    Stojanov, Dragan A. [University of Nis, Faculty of Medicine, Nis (Serbia); Clinical Center Nis, Center for Radiology, Nis (Serbia); Aracki-Trenkic, Aleksandra [Clinical Center Nis, Center for Radiology, Nis (Serbia); Vojinovic, Slobodan; Ljubisavljevic, Srdjan [University of Nis, Faculty of Medicine, Nis (Serbia); Clinical Center Nis, Clinic for Neurology, Nis (Serbia); Benedeto-Stojanov, Daniela [University of Nis, Faculty of Medicine, Nis (Serbia)

    2016-03-15

    To evaluate correlation between cumulative dose of gadobutrol and signal intensity (SI) within dentate nucleus and globus pallidus on unenhanced T1-weighted images in patients with relapsing-remitting multiple sclerosis (RRMS). Dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios, and renal and liver functions, were evaluated after multiple intravenous administrations of 0.1 mmol/kg gadobutrol at 27, 96-98, and 168 weeks. We compared SI ratios based on the number of administrations, total amount of gadobutrol administered, and time between injections. Globus pallidus-to-thalamus (p = 0.025) and dentate nucleus-to-pons (p < 0.001) SI ratios increased after multiple gadobutrol administrations, correlated with the number of administrations (ρ = 0.263, p = 0.046, respectively) and depended on the length of administration (p = 0.017, p = 0.037, respectively). Patients receiving gadobutrol at 27 weeks showed the greatest increase in both SI ratios (p = 0.006; p = 0.014, respectively, versus 96-98 weeks). GGT increased at the end of the study (p = 0.004). In patients with RRMS, SI within the dentate nucleus and globus pallidus increased on unenhanced T1-weighted images after multiple gadobutrol injections. Administration of the same total amount of gadobutrol over a shorter period caused greater SI increase. (orig.)

  4. Does methotrexate administration for ectopic pregnancy after in vitro fertilization impact ovarian reserve or ovarian responsiveness?

    Science.gov (United States)

    Boots, Christina E; Gustofson, Robert L; Feinberg, Eve C

    2013-12-01

    To evaluate the effects of methotrexate (MTX) on the future fertility of women undergoing IVF by comparing ovarian reserve and ovarian responsiveness in the IVF cycle before and after an ectopic pregnancy (EP) treated with MTX. Retrospective cohort study. Private reproductive endocrinology and infertility practice. Sixty-six women undergoing IVF before and after receiving MTX for an EP. Methotrexate administration and ovarian stimulation. Markers of ovarian reserve (day 3 FSH, antral follicle count), measures of ovarian responsiveness (duration of stimulation, peak E2 level, total dose of gonadotropins, number of oocytes retrieved, fertilization rate), and time from MTX administration to subsequent IVF cycle. There were no differences after MTX administration in body mass index (BMI), FSH, or antral follicle count. A greater dose of gonadotropins was used in the cycle after MTX, but there were no differences in numbers of oocytes retrieved or high quality embryos transferred. As expected, there was a slight increase in age in the subsequent IVF cycle. The pregnancy rates (PR) were comparable to the average PRs within the practice when combining all age groups. Methotrexate remains the first line of therapy for medical management of asymptomatic EP and does not compromise ovarian reserve, ovarian responsiveness, or IVF success in subsequent cycles. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  5. Folate overproduction in Lactobacillus plantarum WCFS1 causes methotrexate resistance

    NARCIS (Netherlands)

    Wegkamp, H.B.A.; Vos, de W.M.; Smid, E.J.

    2009-01-01

    Folate overproduction can serve as a mode of resistance against the folate antagonist methotrexate in Lactobacillus plantarum WCFS1. When compared with a wild-type control strain, an engineered high folate-producing strain was found to be insensitive to methotrexate. The growth rate and the viable

  6. Methotrexate use in allergic contact dermatitis: a retrospective study.

    Science.gov (United States)

    Patel, Ashaki; Burns, Erin; Burkemper, Nicole M

    2018-03-01

    Methotrexate, a folate antimetabolite, is used to treat atopic dermatitis and psoriasis. Although methotrexate's therapeutic efficacy has been noted in the literature, there are few data on the efficacy of methotrexate treatment for allergic contact dermatitis. To evaluate the efficacy and tolerability of methotrexate in treating allergic contact dermatitis at a single institution, and also to assess methotrexate efficacy in patients with chronic, unavoidable allergen exposure. We performed a retrospective chart review of 32 patients diagnosed with allergic contact dermatitis by positive patch test reactions, and who received treatment with methotrexate from November 2010 to November 2014. Demographic and treatment-associated data were collected from electronic medical records. Ten patients were identified as allergen non-avoiders secondary to their occupation, and were subgrouped as such. Seventy-eight per cent (25/32) of patients showed either a partial or a complete response. Methotrexate had a comparable efficacy rate in the allergen non-avoiders subset, at 10 of 10. Of the 32 patients, 23% (5/22) had complete clearance of their dermatitis, and 1/10 of allergen non-avoiders had complete clearance of their dermatitis. Methotrexate is a well-tolerated and effective treatment for allergic contact dermatitis, and shows comparable efficacy to immunomodulatory agents such as cyclosporine and azathioprine, with robust efficacy despite persistent allergen exposure in patients with allergic contact dermatitis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Superior outcome using cyclosporin A alone versus cyclosporin A plus methotrexate for post-transplant immunosuppression in children with acute leukemia undergoing sibling hematopoietic stem cell transplantation.

    Science.gov (United States)

    Weiss, Melissa; Steinbach, Daniel; Zintl, Felix; Beck, James; Gruhn, Bernd

    2015-06-01

    The outcome of cyclosporin A (CSA) alone (n = 19) as graft-versus-host disease (GVHD) prophylaxis was compared to that of CSA combined with methotrexate (MTX) (n = 43) in children with acute leukemia who underwent hematopoietic stem cell transplantation. All respective donors were HLA-identical siblings. All patients received CSA at a dose of 3 mg/kg/day starting on day -1. A CSA level of 80-130 ng/ml was aimed for. The 43 patients in the historical control were given an additional 10 mg/m(2) dosage of MTX on days 1, 3, 6, and 11. Patients who received CSA alone had a significantly reduced cumulative incidence of relapse (5 vs. 40 %; p = 0.002), a significantly increased 5-year event-free survival (84 vs. 35 %; p = 0.001), and a significantly increased 5-year overall survival (84 vs. 42 %; p = 0.004). The incidence of acute GVHD grade II-IV and chronic GVHD in patients in the CSA group was equivalent to the CSA+MTX group (26 vs. 19 %; p = 0.440, and 32 vs. 23 %; p = 0.428). In conclusion, post-transplant immunosuppression consisting of CSA alone is well tolerated and may contribute to a superior outcome.

  8. Enhanced antitumor efficacy of poly(D,L-lactide-co-glycolide-based methotrexate-loaded implants on sarcoma 180 tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Gao L

    2017-10-01

    Full Text Available Li Gao,1,2 Lunyang Xia,3 Ruhui Zhang,1 Dandan Duan,3 Xiuxiu Liu,2 Jianjian Xu,2 Lan Luo1 1State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 2School of Biological and Medical Engineering, Hefei University of Technology, Hefei, 3Laboratory of Pharmaceutical Research, Anhui Zhongren Science and Technology Co., Ltd., Hefei, People’s Republic of China Purpose: Methotrexate is widely used in chemotherapy for a variety of malignancies. However, severe toxicity, poor pharmacokinetics, and narrow safety margin of methotrexate limit its clinical application. The aim of this study was to develop sustained-release methotrexate-loaded implants and evaluate antitumor activity of the implants after intratumoral implantation. Materials and methods: We prepared the implants containing methotrexate, poly(D,L-lactide-co-glycolide, and polyethylene glycol 4000 with the melt-molding technique. The implants were characterized with regards to drug content, morphology, in vitro, and in vivo release profiles. Differential scanning calorimetry (DSC and Fourier transform infrared spectroscopy (FTIR were carried out to investigate the physicochemical properties of the implants. Furthermore, the antitumor activity of the implants was tested in a sarcoma 180 mouse model. Results: The implants were prepared as solid rods. Scanning electron microscopy images showed a smooth surface of the implant, suggesting that methotrexate was homogeneously dispersed in the polymeric matrix. The results of DSC and FTIR indicated that no significant interaction between methotrexate and the polymer was observed in the implants. Both in vitro and in vivo release profiles of the implants were characterized by burst release followed by sustained release of methotrexate. Intratumoral implantation of methotrexate-loaded implants could efficiently delay tumor growth. Moreover, an increase in the dose of implants led to a higher tumor

  9. Cumulative radiation exposure in children with cystic fibrosis.

    LENUS (Irish Health Repository)

    O'Reilly, R

    2010-02-01

    This retrospective study calculated the cumulative radiation dose for children with cystic fibrosis (CF) attending a tertiary CF centre. Information on 77 children with a mean age of 9.5 years, a follow up time of 658 person years and 1757 studies including 1485 chest radiographs, 215 abdominal radiographs and 57 computed tomography (CT) scans, of which 51 were thoracic CT scans, were analysed. The average cumulative radiation dose was 6.2 (0.04-25) mSv per CF patient. Cumulative radiation dose increased with increasing age and number of CT scans and was greater in children who presented with meconium ileus. No correlation was identified between cumulative radiation dose and either lung function or patient microbiology cultures. Radiation carries a risk of malignancy and children are particularly susceptible. Every effort must be made to avoid unnecessary radiation exposure in these patients whose life expectancy is increasing.

  10. The combination of etanercept and methotrexate increases the effectiveness of treatment in active psoriasis despite inadequate effect of methotrexate therapy

    DEFF Research Database (Denmark)

    Zachariae, Claus; Mørk, Nils-Jørgen; Reunala, Timo

    2008-01-01

    Many patients with moderate-to-severe plaque psoriasis do not respond adequately to methotrexate monotherapy. This pilot study, with a small patient population, was performed to evaluate the effectiveness and safety of etanercept and methotrexate combination in patients with plaque psoriasis...

  11. Four-year experience with methotrexate exposures.

    Science.gov (United States)

    LoVecchio, Frank; Katz, Kenneth; Watts, David; Wood, Ian

    2008-09-01

    Unintentional methotrexate (MTX) acute oral overdose is rarely reported. We conducted a retrospective chart review of all human exposure calls (>150,000 charts) for MTX ingestions reported to our Poison Center during 2000-2003. Thirteen patients met the criteria. The average amount of MTX ingested was 13.03 mg (data from 7 cases), and the average patient age was 43 years (20 months to 80 years). No significant toxicities occurred. Although intravenous MTX toxicity can be severe, this does not appear to be a phenomenon associated with either acute unintentional or suicidal oral ingestion.

  12. Evaluation of the Efficacy of Combined Therapy of Methotrexate and Etanercept versus Methotrexate as a Mono-Therapy.

    Science.gov (United States)

    Rexhepi, Sylejman; Rexhepi, Mjellma; Rexhepi, Blerta; Sahatçiu-Meka, Vjollca; Mahmutaj, Vigan

    2018-05-20

    This study aims to evaluate the efficacy of Methotrexate (MTX) alone and combined therapy with Etanercept (ETN) and Methotrexate in patients with active rheumatoid arthritis (RA). In the randomised control study, conducted in the period from March 2014 until March 2016, we evaluated the efficacy of the treatment of patients with RA with MTX as monotherapy and combination treatment with MTX and ETN. In the Clinic of Rheumatology in Prishtina, 90 adult patients with RA were treated in combination with ETN (doses of 50 mg subcutaneously/weekly), with oral MTX (doses up to 20 mg weekly), and MTX alone (doses up to 20 mg weekly) during this period of two years. Clinical response was assessed using European League against Rheumatism (EULAR)/American College of Rheumatology (ACR) Criteria and the Disease Activity Score (DAS28). Radiographic changes were measured in the beginning and at the end of the study using Larsen's method. Of the cohort groups of 90 patients, mean age of 55.63, 15 patients, (16.6 %) were treated with combined therapy (ETN plus MTX) and 75 patients (83.3%) with monotherapy (MTX). After two years of treatment the group with combined therapy resulted with improvement of acute phase reactants as erythrocyte sedimentation rate (ESR) for the first hour (41.1 vs. 10.3 mm/hour) and C - reactive protein (CRP) (40.8 vs. 6 mg/liter), and compared to the group treated with monotherapy, there were no significant changes (ESR: 45.7 vs 34.3 mm/hour; CRP: 48 vs 24 mg/liter). Before the treatment, the severity of the disease was high, wherein the group with combined therapy DAS28 was 5.32, compared to the monotherapy group whom DAS28 was 5.90. After 2 years of treatment, we had significant changes in the results of DAS28, wherein the group treated with ETN plus MTX DAS28 was 2.12 ± 0.15, while in the group of patients treated with MTX DAS28 were 3.75 ± 0.39 (t = 13.03; df = 58; p < 0.0001). The group with combined therapy showed no evidence of radiographic

  13. Screening of cytoprotectors against methotrexate-induced cytogenotoxicity from bioactive phytochemicals.

    Science.gov (United States)

    Gu, Shaobin; Wu, Ying; Yang, Jianbo

    2016-01-01

    As a well known anti-neoplastic drug, the cytogenotoxicity of methotrexate (MTX) has received more attention in recent years. To develop a new cytoprotector to reduce the risk of second cancers caused by methotrexate, an umu test combined with a micronucleus assay was employed to estimate the cytoprotective effects of ten kinds of bioactive phytochemicals and their combinations. The results showed that allicin, proanthocyanidins, polyphenols, eleutherosides and isoflavones had higher antimutagenic activities than other phytochemicals. At the highest dose tested, the MTX genetoxicity was suppressed by 34.03%∼67.12%. Of all the bioactive phytochemical combinations, the combination of grape seed proanthocyanidins and eleutherosides from Siberian ginseng as well as green tea polyphenols and eleutherosides exhibited stronger antimutagenic effects; the inhibition rate of methotrexate-induced genotoxicity separately reached 74.7 ± 6.5% and 71.8 ± 4.7%. Pretreatment of Kunming mice with phytochemical combinations revealed an obvious reduction in micronucleus and sperm abnormality rates following exposure to MTX (p phytochemicals combinations had the potential to be used as new cytoprotectors.

  14. CUMBIN - CUMULATIVE BINOMIAL PROGRAMS

    Science.gov (United States)

    Bowerman, P. N.

    1994-01-01

    The cumulative binomial program, CUMBIN, is one of a set of three programs which calculate cumulative binomial probability distributions for arbitrary inputs. The three programs, CUMBIN, NEWTONP (NPO-17556), and CROSSER (NPO-17557), can be used independently of one another. CUMBIN can be used by statisticians and users of statistical procedures, test planners, designers, and numerical analysts. The program has been used for reliability/availability calculations. CUMBIN calculates the probability that a system of n components has at least k operating if the probability that any one operating is p and the components are independent. Equivalently, this is the reliability of a k-out-of-n system having independent components with common reliability p. CUMBIN can evaluate the incomplete beta distribution for two positive integer arguments. CUMBIN can also evaluate the cumulative F distribution and the negative binomial distribution, and can determine the sample size in a test design. CUMBIN is designed to work well with all integer values 0 < k <= n. To run the program, the user simply runs the executable version and inputs the information requested by the program. The program is not designed to weed out incorrect inputs, so the user must take care to make sure the inputs are correct. Once all input has been entered, the program calculates and lists the result. The CUMBIN program is written in C. It was developed on an IBM AT with a numeric co-processor using Microsoft C 5.0. Because the source code is written using standard C structures and functions, it should compile correctly with most C compilers. The program format is interactive. It has been implemented under DOS 3.2 and has a memory requirement of 26K. CUMBIN was developed in 1988.

  15. Cumulation of light nuclei

    International Nuclear Information System (INIS)

    Baldin, A.M.; Bondarev, V.K.; Golovanov, L.B.

    1977-01-01

    Limit fragmentation of light nuclei (deuterium, helium) bombarded with 8,6 GeV/c protons was investigated. Fragments (pions, protons and deuterons) were detected within the emission angle 50-150 deg with regard to primary protons and within the pulse range 150-180 MeV/c. By the kinematics of collision of a primary proton with a target at rest the fragments observed correspond to a target mass upto 3 GeV. Thus, the data obtained correspond to teh cumulation upto the third order

  16. CROSSER - CUMULATIVE BINOMIAL PROGRAMS

    Science.gov (United States)

    Bowerman, P. N.

    1994-01-01

    The cumulative binomial program, CROSSER, is one of a set of three programs which calculate cumulative binomial probability distributions for arbitrary inputs. The three programs, CROSSER, CUMBIN (NPO-17555), and NEWTONP (NPO-17556), can be used independently of one another. CROSSER can be used by statisticians and users of statistical procedures, test planners, designers, and numerical analysts. The program has been used for reliability/availability calculations. CROSSER calculates the point at which the reliability of a k-out-of-n system equals the common reliability of the n components. It is designed to work well with all integer values 0 < k <= n. To run the program, the user simply runs the executable version and inputs the information requested by the program. The program is not designed to weed out incorrect inputs, so the user must take care to make sure the inputs are correct. Once all input has been entered, the program calculates and lists the result. It also lists the number of iterations of Newton's method required to calculate the answer within the given error. The CROSSER program is written in C. It was developed on an IBM AT with a numeric co-processor using Microsoft C 5.0. Because the source code is written using standard C structures and functions, it should compile correctly with most C compilers. The program format is interactive. It has been implemented under DOS 3.2 and has a memory requirement of 26K. CROSSER was developed in 1988.

  17. Extracorporeal photochemotherapy and methotrexate in the treatment of atypical oral lichen planus

    Directory of Open Access Journals (Sweden)

    A. V. Molochkov

    2017-01-01

    Full Text Available Background: Some authors have successfully used methotrexate in the treatment of atypical oral lichen planus (LP and noted its good tolerability. High clinical efficacy of the extracorporeal photochemotherapy (ECP has been also reported in the treatment of such patients. However, there is no information on the long-term results of methotrexate and ECP and their combination in the treatment of atypical LP. Aim: To study clinical efficacy and long-term results of the combination of routine therapy with the ECP course and a single injection of methotrexate at a dose of 10 mg in patients with atypical LP of the oral cavity and the skin. Materials and methods: This was a prospective study with an active control. Eighteen (18 patients with various forms of atypical LP of the oral cavity (hypertrophic, erosive/ulcerative, exudative/hyperemic forms and the skin (hypertrophic, pigmented, atrophic, follicular forms were administered the combination of routine therapy (chloroquine, doxycycline, vitamin B6, topical corticosteroids, an ECP course, and a single injection of methotrexate at a dose of 10 mg. Two hours before the ECP session all patients were given 8-methoxypsoralen. Peripheral mononuclear cells were isolated with a cell separator and treated with ultraviolet radiation (λ = 320–400 nm, then the monocyte cell mass was re-infused to the patient. The treatment course included 4 sessions performed every other day. A single injection of methotrexate was given in the middle of the ECP course. Clinical efficacy was assessed with the Thongprasom scale of activity of the disease and by visual analog scale (VAS for pain assessment in patients with oral lesions. Results: The treatment was well tolerated and was not associated with methotrexate-related immune abnormalities. At one month after the 4th ECP session, the mean Thongprasom score was decreased from 5 to 2.2 ± 1.2 (p < 0.001. At Week 24 after the treatment, 15 (83.2% of

  18. Comparison of central nervous system prophylaxis with cranial radiation and intrathecal methotrexate versus intrathecal methotrexate alone in acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Muriel, F.S.; Svarch, E.; Pavlovsky, S.

    1983-01-01

    In acute lymphoblastic leukemia, central nervous system prophylaxis with irradiation plus intrathecal methotrexate (i.t. MTX) reduces the incidence of CNS relapse to 7%-15%. However, increased evidence of CNS delayed toxicity was recognized mainly in children as CT scan abnormalities and neuropsychologic alterations. Two questions were analyzed: (1) Will further doses of i.t. methotraxate and dexamethasone (i.t. MTX-DMT) decrease the incidence of CNS relapse. (2) Is i.t. MTX-DMT given during induction and maintenance as effective as cranium irradiation plus i.t. MTX-DMT. Incidence of primary CNS relapse in i.t. MTX-DMT-treated patients with a WBC count 50,000, it was 16% in the treated group and 19% in the control group. These patients were compared with patients which had received 3 doses of i.t. MTX-DMT alone during induction, 3 doses weekly during the first month of remission, and quarterly thereafter. The incidence of leukemia at 60 mo in patients with a WBC count 50,000 at 48 mo was 28% and 42% in the irradiated and nonirradiated group respectively. Complete remission remained at 15% and 16% respectively of patients disease-free at 48 mo. We conclude that (A) after cranial irradiation plus i.t. MTX-DMT X 5, the use of additional doses of i.t. MTX-DMT is not of further benefit in preventing CNS relapse; (B) use of i.t. MTX-DMT alone compares with cranial irradiation plus i.t. MTX-DMT in incidence of CNS relapse; and (C) relapse-free survival and survival in patients with a WBC count < 50.000 were significantly longer in those without cranial irradiation

  19. The Impact of Methylenetetrahydrofolate Reductase C677T Polymorphism on Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation with Methotrexate Prophylaxis.

    Directory of Open Access Journals (Sweden)

    Ja Min Byun

    Full Text Available Pharmacogenomics can explain the inter-individual differences in response to drugs, including methotrexate (MTX used for acute graft-versus-host disease (aGVHD prophylaxis during hematopoietic stem cell transplantation (HSCT. In real-world practice, preplanned MTX dose is arbitrarily modified according to observed toxicity which can lead to unexpected and severe aGVHD development. We aimed to validate the influence of MTHFR C677T polymorphism on the outcomes of allogenic HSCT in a relatively under-represented homogenous Asian population. A total of 177 patients were divided into 677TT group versus 677C-carriers (677CT+677CC, and clinical outcomes along with baseline characteristics were analyzed and compared. Although there was a tendency towards increased peak liver function test results and accordingly greater delta values between the highest and the baseline in 677TT group, we found no associations between genotypes and hepatotoxicity. However, the incidence of acute liver GVHD (≥ grade 2 was significantly higher in the 677TT group than in the 677CC + 677CT group (P = 0.016. A total of 25 patients (14.1% expired due to transplantation related mortality (TRM during the first 180 days after HSCT. Patients carrying 677TT genotype were more likely to experience early TRM than 677C-carriers. The same pattern was observed in the cumulative TRM rate, and 677TT genotype patients were more prone to cumulative TRM (P = 0.010. This translated into shorter OS for patients with 677TT compared to 677C-carriers (P = 0.010. The 3-year survival after HSCT was 29.9% for 677TT cases and 47.1% for 677C-carriers. The multivariate analysis identified 677TT genotype (HR = 1.775. 95% CI 1.122-2.808, P = 0.014 and non-CR state (HR = 2.841. 95% CI 1.627-4.960, P<0.001 as predictors for survival. In conclusion, the MTHFR 677TT genotype appears to be associated with acute liver GVHD, and represent a risk factor for TRM and survival in patients undergoing HSCT with MTX

  20. Cumulative environmental effects. Summary

    International Nuclear Information System (INIS)

    2012-01-01

    This report presents a compilation of knowledge about the state of the environment and human activity in the Norwegian part of the North Sea and Skagerrak. The report gives an overview of pressures and impacts on the environment from normal activity and in the event of accidents. This is used to assess the cumulative environmental effects, which factors have most impact and where the impacts are greatest, and to indicate which problems are expected to be most serious in the future. The report is intended to provide relevant information that can be used in the management of the marine area in the future. It also provides input for the identification of environmental targets and management measures for the North Sea and Skagerrak.(Author)

  1. Cumulative environmental effects. Summary

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-07-01

    This report presents a compilation of knowledge about the state of the environment and human activity in the Norwegian part of the North Sea and Skagerrak. The report gives an overview of pressures and impacts on the environment from normal activity and in the event of accidents. This is used to assess the cumulative environmental effects, which factors have most impact and where the impacts are greatest, and to indicate which problems are expected to be most serious in the future. The report is intended to provide relevant information that can be used in the management of the marine area in the future. It also provides input for the identification of environmental targets and management measures for the North Sea and Skagerrak.(Author)

  2. NEWTONP - CUMULATIVE BINOMIAL PROGRAMS

    Science.gov (United States)

    Bowerman, P. N.

    1994-01-01

    The cumulative binomial program, NEWTONP, is one of a set of three programs which calculate cumulative binomial probability distributions for arbitrary inputs. The three programs, NEWTONP, CUMBIN (NPO-17555), and CROSSER (NPO-17557), can be used independently of one another. NEWTONP can be used by statisticians and users of statistical procedures, test planners, designers, and numerical analysts. The program has been used for reliability/availability calculations. NEWTONP calculates the probably p required to yield a given system reliability V for a k-out-of-n system. It can also be used to determine the Clopper-Pearson confidence limits (either one-sided or two-sided) for the parameter p of a Bernoulli distribution. NEWTONP can determine Bayesian probability limits for a proportion (if the beta prior has positive integer parameters). It can determine the percentiles of incomplete beta distributions with positive integer parameters. It can also determine the percentiles of F distributions and the midian plotting positions in probability plotting. NEWTONP is designed to work well with all integer values 0 < k <= n. To run the program, the user simply runs the executable version and inputs the information requested by the program. NEWTONP is not designed to weed out incorrect inputs, so the user must take care to make sure the inputs are correct. Once all input has been entered, the program calculates and lists the result. It also lists the number of iterations of Newton's method required to calculate the answer within the given error. The NEWTONP program is written in C. It was developed on an IBM AT with a numeric co-processor using Microsoft C 5.0. Because the source code is written using standard C structures and functions, it should compile correctly with most C compilers. The program format is interactive. It has been implemented under DOS 3.2 and has a memory requirement of 26K. NEWTONP was developed in 1988.

  3. A U-HPLC-ESI-MS/MS-based stable isotope dilution method for the detection and quantitation of methotrexate in plasma

    NARCIS (Netherlands)

    E. den Boer (Ethan); S.G. Heil (Sandra); B.D. van Zelst (Bertrand); P. Schneider (Petra); B.C.P. Koch (Birgit); M.L. te Winkel (Mariël Lizet); M.M. van den Heuvel-Eibrink (Marry); T.M. Luider (Theo); R. de Jonge (Robert)

    2012-01-01

    textabstractINTRODUCTION: High-dose methotrexate (MTX) is used in the treatment of proliferative diseases such as acute lymphoblastic leukemia. Therapeutic drug monitoring of plasma MTX is important to monitor efficacy and adverse events. The authors aimed to develop a liquid chromatography,

  4. Cerebral venous and sinus thrombosis with cerebrospinal fluid circulation block after the first methotrexate administration by lumbar puncture

    International Nuclear Information System (INIS)

    Bienfait, H.P.; Gijtenbeek, J.M.M.; Bent, M.J. van; Bruin, H.G. de; Voogt, P.J.; Pillay, M.

    2002-01-01

    We report a patient treated for small lymphocytic lymphoma/leukemia with cerebral venous and sinus thrombosis (CVST) after lumbar puncture with intrathecal administration of methotrexate (MTX). He also developed a cerebrospinal fluid flow block. This is the first report of an association between lumbar puncture and intrathecally administered MTX and the development of CVST. Intrathecal treatment in this patient was discontinued and he was successfully treated with high-dose low-molecular-weight heparin subcutaneously. (orig.)

  5. Ameliorative Effects of Hydroalcoholic Extract of Lavandula officinalis L. on Methotrexate-Induced Oxidative Stress in Rats

    Directory of Open Access Journals (Sweden)

    Mojtaba Kalantar, Saeed Shirali, Amin Hasanvand , Masoud Valizadeh , Ramin Tavakoli , Marzieh Asadi , Mehdi Goudarzi

    2017-03-01

    Full Text Available Background: Methotrexate as a chemotherapy drug can causes chronic liver damage and oxidative stress. The aim of this study was to evaluate the protective effect of hydroalcoholic extract of Lavandula officinalis on methotrexate-induced oxidative stress in rats. Methods: In this experimental study, thirty five Wistar male rats weighting 200-250 g were randomly divided into 5 groups (n = 7 in each group. Negative control group (normal saline 5ml/kg; positive control group received normal salin orally for 10 days, and a single dose of methotrexate (MTX, 20mg/kg, i.p. was administrated on the 9th day. Groups 3-5 received respectively 100, 200 and 400 mg/kg of Lavandula officinalis extract (LOE orally for 10 days, and a single dose of MTX was injected on the 9th day. 24 h after the last injection, animals were sacrificed. Blood samples were collected to determine serum AST, ALT and ALP levels. Malondialdehyde (MDA, glutathione (GSH levels and catalase (CAT, superoxide dismutase (SOD and glutathione peroxidase (GPx activity were assayed in liver tissue. A portion of liver was maintained in 10% formalin for Hematoxylin and Eosin (H&E staining and histological examination. Results: The result obtained from current study was showed a significant increase in the levels of AST, ALT, ALP, MDA and decrease of GSH, CAT and SOD by MTX administration. Pre-treatment with LOE showed reduction in the levels of AST, ALT, ALP, MDA and increase of GSH, CAT and SOD in all doses but the most significant alteration was observed in doses of 200 and 400 mg/kg (P<0.05. Histological results showed that methotrexate could lead to liver damage. Also the hepatoprotective effect of the LOE was confirmed by the histological examination of the liver. Conclusion: Our results indicate that hydroalcoholic extract of Lavandula officinalis have produced amelioration in biochemical and oxidative stress parameters against MTX -induced oxidative stress.

  6. Pure methotrexate encephalopathy presenting with seizures: CT and MRI features

    Energy Technology Data Exchange (ETDEWEB)

    Loevblad, K.O.; Kelkar, P.; Ozdoba, C.; Remonda, L.; Schroth, G. [Department of Neuroradiology, Institute of Diagnostic Radiology, Inselspital, University of Bern, CH-3010 Bern (Switzerland); Ramelli, G. [Department of Pediatrics, Inselspital, University of Bern, Bern (Switzerland)

    1998-02-01

    With the advent of chemotherapy, mortality rates in acute lymphoblastic leukaemia (ALL) have decreased, but complications in the central nervous system have appeared. These include direct involvement of the brain itself and the development of chemotherapy-related encephalopathy as a delayed reaction. In most reported cases, this encephalopathy is believed to be due to necrotising angiitis arising from the combination of chemotherapy with adjuvant radiotherapy. We report the cases of four children with ALL who had been treated with high-dose intravenous and intrathecal chemotherapy but no radiation therapy, and who were admitted to hospital because of seizures. CT of the brain revealed the presence of diffuse periventricular white matter hypodensities in all cases and subcortical hyperdense foci in three cases. MRI showed diffuse hyperintense white matter lesions on T2-weighted images in all four patients; hypointense changes were observed on susceptibility-sensitive FLASH sequences in the hyperdense foci seen on CT as well as changes that were hyperintense on T1-weighted images. It was, therefore, concluded that the lesions corresponded to a leukoencephalopathy with calcific deposits. These findings are of a pure form of methotrexate encephalopathy causing seizures. (orig.) With 2 figs., 17 refs.

  7. Methotrexate pharmacogenetics in Uruguayan adults with hematological malignant diseases.

    Science.gov (United States)

    Giletti, Andrea; Vital, Marcelo; Lorenzo, Mariana; Cardozo, Patricia; Borelli, Gabriel; Gabus, Raúl; Martínez, Lem; Díaz, Lilian; Assar, Rodrigo; Rodriguez, María Noel; Esperón, Patricia

    2017-11-15

    Individual variability is among the causes of toxicity and interruption of treatment in acute lymphoblastic leukemia (ALL) and severe non-Hodgkin lymphoma (NHL) patients under protocols including Methotrexate (MTX): 2,4-diamino-N10-methyl propyl-glutamic acid. 41 Uruguayan patients were recruited. Gene polymorphisms involved in MTX pathway were analyzed and their association with treatment toxicities and outcome was evaluated. Genotype distribution and allele frequency were determined for SLC19A1 G 80 A, MTHFR C 677 T and A 1298 C, TYMS 28bp copy number variation, SLCO1B1 T 521 C, DHFR C -1610 G/T, DHFR C -680 A, DHFR A -317 G and DHFR 19bp indel. Multivariate analysis showed that DHFR -1610 G/T (OR=0.107, p=0.018) and MTHFR 677 T alleles (OR=0.12, p=0.026) had a strong protective effect against hematologic toxicity, while DHFR -1610 CC genotype increased this toxicity (OR=9, p=0.045). No more associations were found. The associations found between gene polymorphisms and toxicities in this small cohort are encouraging for a more extensive research to gain a better dose individualization in adult ALL and NHL patients. Besides, genotype distribution showed to be different from other populations, reinforcing the idea that genotype data from other populations should not be extrapolated to ours. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Pure methotrexate encephalopathy presenting with seizures: CT and MRI features

    International Nuclear Information System (INIS)

    Loevblad, K.O.; Kelkar, P.; Ozdoba, C.; Remonda, L.; Schroth, G.; Ramelli, G.

    1998-01-01

    With the advent of chemotherapy, mortality rates in acute lymphoblastic leukaemia (ALL) have decreased, but complications in the central nervous system have appeared. These include direct involvement of the brain itself and the development of chemotherapy-related encephalopathy as a delayed reaction. In most reported cases, this encephalopathy is believed to be due to necrotising angiitis arising from the combination of chemotherapy with adjuvant radiotherapy. We report the cases of four children with ALL who had been treated with high-dose intravenous and intrathecal chemotherapy but no radiation therapy, and who were admitted to hospital because of seizures. CT of the brain revealed the presence of diffuse periventricular white matter hypodensities in all cases and subcortical hyperdense foci in three cases. MRI showed diffuse hyperintense white matter lesions on T2-weighted images in all four patients; hypointense changes were observed on susceptibility-sensitive FLASH sequences in the hyperdense foci seen on CT as well as changes that were hyperintense on T1-weighted images. It was, therefore, concluded that the lesions corresponded to a leukoencephalopathy with calcific deposits. These findings are of a pure form of methotrexate encephalopathy causing seizures. (orig.)

  9. Vorinostat plus tacrolimus/methotrexate to prevent GVHD after myeloablative conditioning, unrelated donor HCT.

    Science.gov (United States)

    Choi, Sung Won; Braun, Thomas; Henig, Israel; Gatza, Erin; Magenau, John; Parkin, Brian; Pawarode, Attaphol; Riwes, Mary; Yanik, Greg; Dinarello, Charles A; Reddy, Pavan

    2017-10-12

    The oral histone deacetylase (HDAC) inhibitor (vorinostat) is safe and results in low incidence of acute graft-versus-host disease (GVHD) after reduced-intensity conditioning, related donor hematopoietic cell transplantation (HCT). However, its safety and efficacy in preventing acute GVHD in settings of heightened clinical risk that use myeloablative conditioning, unrelated donor (URD), and methotrexate are not known. We conducted a prospective, phase 2 study in this higher-risk setting. We enrolled 37 patients to provide 80% power to detect a significant difference in grade 2 to 4 acute GVHD of 50% compared with a reduction in target to 28%. Eligibility included adults with a hematological malignancy to receive myeloablative HCT from an available 8/8-HLA matched URD. Patients received GVHD prophylaxis with tacrolimus and methotrexate. Vorinostat (100 mg twice daily) was started on day -10 and continued through day +100 post-HCT. Median age was 56 years (range, 18-69 years), and 95% had acute myelogenous leukemia or high-risk myelodysplastic syndrome. Vorinostat was safe and tolerable. The cumulative incidence of grade 2 to 4 acute GVHD at day 100 was 22%, and for grade 3 to 4 it was 8%. The cumulative incidence of chronic GVHD was 29%; relapse, nonrelapse mortality, GVHD-free relapse-free survival, and overall survival at 1 year were 19%, 16%, 47%, and 76%, respectively. Correlative analyses showed enhanced histone (H3) acetylation in peripheral blood mononuclear cells and reduced interleukin 6 ( P = .028) and GVHD biomarkers (Reg3, P = .041; ST2, P = .002) at day 30 post-HCT in vorinostat-treated subjects compared with similarly treated patients who did not receive vorinostat. Vorinostat for GVHD prevention is an effective strategy that should be confirmed in a randomized phase 3 study. This trial was registered at www.clinicaltrials.gov as #NCT01790568. © 2017 by The American Society of Hematology.

  10. Cumulative radiation effect

    International Nuclear Information System (INIS)

    Kirk, J.; Gray, W.M.; Watson, E.R.

    1977-01-01

    In five previous papers, the concept of Cumulative Radiation Effect (CRE) has been presented as a scale of accumulative sub-tolerance radiation damage, with a unique value of the CRE describing a specific level of radiation effect. Simple nomographic and tabular methods for the solution of practical problems in radiotherapy are now described. An essential feature of solving a CRE problem is firstly to present it in a concise and readily appreciated form, and, to do this, nomenclature has been introduced to describe schedules and regimes as compactly as possible. Simple algebraic equations have been derived to describe the CRE achieved by multi-schedule regimes. In these equations, the equivalence conditions existing at the junctions between schedules are not explicit and the equations are based on the CREs of the constituent schedules assessed individually without reference to their context in the regime as a whole. This independent evaluation of CREs for each schedule has resulted in a considerable simplification in the calculation of complex problems. The calculations are further simplified by the use of suitable tables and nomograms, so that the mathematics involved is reduced to simple arithmetical operations which require at the most the use of a slide rule but can be done by hand. The order of procedure in the presentation and calculation of CRE problems can be summarised in an evaluation procedure sheet. The resulting simple methods for solving practical problems of any complexity on the CRE-system are demonstrated by a number of examples. (author)

  11. Maintenance hemodialysis patients have high cumulative radiation exposure.

    LENUS (Irish Health Repository)

    Kinsella, Sinead M

    2010-10-01

    Hemodialysis is associated with an increased risk of neoplasms which may result, at least in part, from exposure to ionizing radiation associated with frequent radiographic procedures. In order to estimate the average radiation exposure of those on hemodialysis, we conducted a retrospective study of 100 patients in a university-based dialysis unit followed for a median of 3.4 years. The number and type of radiological procedures were obtained from a central radiology database, and the cumulative effective radiation dose was calculated using standardized, procedure-specific radiation levels. The median annual radiation dose was 6.9 millisieverts (mSv) per patient-year. However, 14 patients had an annual cumulative effective radiation dose over 20 mSv, the upper averaged annual limit for occupational exposure. The median total cumulative effective radiation dose per patient over the study period was 21.7 mSv, in which 13 patients had a total cumulative effective radiation dose over 75 mSv, a value reported to be associated with a 7% increased risk of cancer-related mortality. Two-thirds of the total cumulative effective radiation dose was due to CT scanning. The average radiation exposure was significantly associated with the cause of end-stage renal disease, history of ischemic heart disease, transplant waitlist status, number of in-patient hospital days over follow-up, and death during the study period. These results highlight the substantial exposure to ionizing radiation in hemodialysis patients.

  12. Microbubbles coupled to methotrexate-loaded liposomes for ultrasound-mediated delivery of methotrexate across the blood–brain barrier

    Directory of Open Access Journals (Sweden)

    Wang X

    2014-10-01

    Full Text Available Xiang Wang,1 Ping Liu,1 Weixiao Yang,1 Lu Li,1 Peijing Li,2 Zheng Liu,1 Zhongxiong Zhuo,1 Yunhua Gao1 1Department of Ultrasound, Xinqiao Hospital of the Third Military Medical University, Chongqing, 2Department of Ultrasound, General Hospital of the Jinan Military Area, Jinan, People’s Republic of China Abstract: Methotrexate (MTX is the single most effective agent for the treatment of primary central nervous system lymphoma. Currently, the delivery of MTX to the brain is achieved by high systemic doses, which cause severe long-term neurotoxicity, or intrathecal administration, which is highly invasive and may lead to infections or hemorrhagic complications. Acoustically active microbubbles have been developed as drug carriers for the noninvasive and brain-targeted delivery of therapeutics. However, their application is limited by their low drug-loading capacity. To overcome this limitation, we prepared microbubbles coupled to MTX-loaded liposomes using ZHIFUXIAN, a novel type of microbubbles with a superior safety profile and long circulation time. MTX-liposome-coupled microbubbles had a high drug-loading capacity of 8.91%±0.86%, and their size (2.64±0.93 µm in diameter was suitable for intravenous injection. When used with ultrasound, they showed more potent in vitro cytotoxicity against Walker-256 cancer cells than MTX alone or MTX-loaded liposomes. When Sprague-Dawley rats were exposed to sonication, administration of these MTX-liposome-coupled microbubbles via the tail vein led to targeted disruption of the blood–brain barrier without noticeable tissue or capillary damage. High-performance liquid chromatography analysis of the brain MTX concentration showed that MTX delivery to the brain followed the order of MTX-liposome-coupled microbubbles + ultrasound (25.3±2.4 µg/g > unmodified ZHIFUXIAN + MTX + ultrasound (18.6±2.2 µg/g > MTX alone (6.97±0.75 µg/g > MTX-liposome-coupled microbubbles (2.92±0.39 µg/g. Therefore

  13. Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.

    Science.gov (United States)

    Sankrityayan, Himanshu; Majumdar, Anuradha S

    2016-01-01

    Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 μg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels.

  14. High prevalence of methotrexate intolerance in juvenile idiopathic arthritis : development and validation of a methotrexate intolerance severity score

    NARCIS (Netherlands)

    Bulatović, Maja; Heijstek, Marloes W; Verkaaik, Marleen; van Dijkhuizen, E H Pieter; Armbrust, Wineke; Hoppenreijs, Esther P A; Kamphuis, Sylvia; Kuis, Wietse; Egberts, Toine C G; Sinnema, Gerben; Rademaker, Carin M A; Wulffraat, Nico M

    OBJECTIVE: To design and validate a new questionnaire for identifying patients with methotrexate (MTX) intolerance, and to determine the prevalence of MTX intolerance in patients with juvenile idiopathic arthritis (JIA) using this questionnaire. METHODS: The MTX Intolerance Severity Score (MISS)

  15. High prevalence of methotrexate intolerance in juvenile idiopathic arthritis: development and validation of a methotrexate intolerance severity score

    NARCIS (Netherlands)

    Bulatovic, M.; Heijstek, M.W.; Verkaaik, M.; Dijkhuizen, E.H. van; Armbrust, W.; Hoppenreijs, E.P.A.H.; Kamphuis, S.; Kuis, W.; Egberts, T.C.; Sinnema, G.; Rademaker, C.M.A.; Wulffraat, N.M.

    2011-01-01

    OBJECTIVE: To design and validate a new questionnaire for identifying patients with methotrexate (MTX) intolerance, and to determine the prevalence of MTX intolerance in patients with juvenile idiopathic arthritis (JIA) using this questionnaire. METHODS: The MTX Intolerance Severity Score (MISS)

  16. Adipose-derived stem cells retain their regenerative potential after methotrexate treatment

    International Nuclear Information System (INIS)

    Beane, Olivia S.; Fonseca, Vera C.; Darling, Eric M.

    2014-01-01

    In musculoskeletal tissues like bone, chemotherapy can impair progenitor cell differentiation and proliferation, resulting in decreased bone growth and mineralization throughout a patient's lifetime. In the current study, we investigated the effects of chemotherapeutics on adipose-derived stem cell (ASC) function to determine whether this cell source could be a candidate for repairing, or even preventing, chemotherapy-induced tissue damage. Dose-dependent proliferation rates of ASCs and normal human fibroblasts (NHFs) were quantified after treatment with cytarabine (CY), etoposide (ETO), methotrexate (MTX), and vincristine (VIN) using a fluorescence-based assay. The influence of MTX on the multipotency of ASCs and freshly isolated stromal vascular fraction (SVF) cells was also evaluated using lineage-specific stains and spectrophotometry. ASC and NHF proliferation were equally inhibited by exposure to CY and ETO; however, when treated with MTX and VIN, ASCs exhibited greater resistance. This was especially apparent for MTX-treated samples, with ASC proliferation showing no inhibition for clinically relevant MTX doses ranging from 0.1 to 50 μM. Additional experiments revealed that the differentiation potential of ASCs was not affected by MTX treatment and that upregulation of dihydrofolate reductase possibly contributed to this response. Moreover, SVF cells, which include ASCs, exhibited similar resistance to MTX impairment, with respect to cellular proliferation, clonogenicity, and differentiation capability. Therefore, we have shown that the regenerative properties of ASCs resist the cytotoxicity of MTX, identifying these cells as a potential key for repairing musculoskeletal damage in patients undergoing chemotherapy. - Highlights: • Long-term effects of chemotherapeutics can include musculoskeletal dysfunction. • A screen of common drugs showed disparate effects on ASCs and fibroblasts. • One drug, methotrexate, did not impair ASC growth

  17. Adipose-derived stem cells retain their regenerative potential after methotrexate treatment

    Energy Technology Data Exchange (ETDEWEB)

    Beane, Olivia S. [Center for Biomedical Engineering, Brown University, Providence, RI (United States); Fonseca, Vera C. [Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI (United States); Darling, Eric M., E-mail: Eric_Darling@brown.edu [Center for Biomedical Engineering, Brown University, Providence, RI (United States); Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI (United States); Department of Orthopaedics, Brown University, Providence, RI (United States); School of Engineering, Brown University, Providence, RI (United States)

    2014-10-01

    In musculoskeletal tissues like bone, chemotherapy can impair progenitor cell differentiation and proliferation, resulting in decreased bone growth and mineralization throughout a patient's lifetime. In the current study, we investigated the effects of chemotherapeutics on adipose-derived stem cell (ASC) function to determine whether this cell source could be a candidate for repairing, or even preventing, chemotherapy-induced tissue damage. Dose-dependent proliferation rates of ASCs and normal human fibroblasts (NHFs) were quantified after treatment with cytarabine (CY), etoposide (ETO), methotrexate (MTX), and vincristine (VIN) using a fluorescence-based assay. The influence of MTX on the multipotency of ASCs and freshly isolated stromal vascular fraction (SVF) cells was also evaluated using lineage-specific stains and spectrophotometry. ASC and NHF proliferation were equally inhibited by exposure to CY and ETO; however, when treated with MTX and VIN, ASCs exhibited greater resistance. This was especially apparent for MTX-treated samples, with ASC proliferation showing no inhibition for clinically relevant MTX doses ranging from 0.1 to 50 μM. Additional experiments revealed that the differentiation potential of ASCs was not affected by MTX treatment and that upregulation of dihydrofolate reductase possibly contributed to this response. Moreover, SVF cells, which include ASCs, exhibited similar resistance to MTX impairment, with respect to cellular proliferation, clonogenicity, and differentiation capability. Therefore, we have shown that the regenerative properties of ASCs resist the cytotoxicity of MTX, identifying these cells as a potential key for repairing musculoskeletal damage in patients undergoing chemotherapy. - Highlights: • Long-term effects of chemotherapeutics can include musculoskeletal dysfunction. • A screen of common drugs showed disparate effects on ASCs and fibroblasts. • One drug, methotrexate, did not impair ASC growth

  18. Effects of repeated administration of chemotherapeutic agents tamoxifen, methotrexate, and 5-fluorouracil on the acquisition and retention of a learned response in mice

    Science.gov (United States)

    Foley, John J.; Clark-Vetri, Rachel; Raffa, Robert B.

    2011-01-01

    Rationale A number of cancer chemotherapeutic agents have been associated with a loss of memory in breast cancer patients although little is known of the causality of this effect. Objectives To assess the potential cognitive effects of repeated exposure to chemotherapeutic agents, we administered the selective estrogen receptor modulator tamoxifen or the antimetabolite chemotherapy, methotrexate, and 5-fluorouracil, alone and in combination to mice and tested them in a learning and memory assay. Methods Swiss-Webster male mice were injected with saline, 32 mg/kg tamoxifen, 3.2 or 32 mg/kg methotrexate, 75 mg/kg 5-fluorouracil, 3.2 or 32 mg/kg methotrexate in combination with 75 mg/kg 5-fluorouracil once per week for 3 weeks. On days 23 and 24, mice were tested for acquisition and retention of a nose-poke response in a learning procedure called autoshaping. In addition, the acute effects of tamoxifen were assessed in additional mice in a similar procedure. Results The chemotherapeutic agents alone and in combination reduced body weight relative to saline treatment over the course of 4 weeks. Repeated treatment with tamoxifen produced both acquisition and retention effects relative to the saline-treated group although acute tamoxifen was without effect except at a behaviorally toxic dose. Repeated treatment with methotrexate in combination with 5-fluorouracil produced effects on retention, but the magnitude of these changes depended on the methotrexate dose. Conclusions These data demonstrate that repeated administration of tamoxifen or certain combination of methotrexate and 5-fluorouracil may produce deficits in the acquisition or retention of learned responses which suggest potential strategies for prevention or remediation might be considered in vulnerable patient populations. PMID:21537942

  19. Secant cumulants and toric geometry

    NARCIS (Netherlands)

    Michalek, M.; Oeding, L.; Zwiernik, P.W.

    2012-01-01

    We study the secant line variety of the Segre product of projective spaces using special cumulant coordinates adapted for secant varieties. We show that the secant variety is covered by open normal toric varieties. We prove that in cumulant coordinates its ideal is generated by binomial quadrics. We

  20. Utilization of Subcutaneous Methotrexate in Rheumatoid Arthritis Patients After Failure or Intolerance to Oral Methotrexate: A Multicenter Cohort Study.

    Science.gov (United States)

    Branco, Jaime C; Barcelos, Anabela; de Araújo, Filipe Pombo; Sequeira, Graça; Cunha, Inês; Patto, José Vaz; Oliveira, Margarida; Mateus, Margarida Pratas; Couto, Maura; Nero, Patrícia; Pinto, Patrícia; Monteiro, Paulo; Castelão, Walter; Félix, Jorge; Ferreira, Diana; Almeida, João; Silva, Maria João

    2016-01-01

    Low-dose weekly methotrexate (MTX) is the mainstay in the therapy of rheumatoid arthritis (RA). It can be given via oral, intramuscular or subcutaneous (SC) route. This study sought to determine the real-world pattern of treatment with SC MTX in Portuguese adult patients with active RA. Utilization of Metoject(®) in Rheumatoid Arthritis (UMAR) was a non-interventional, cohort multicenter study with retrospective data collection. Eligible patients had active RA, at least 18 years of age, and started SC MTX treatment in 2009 or 2010 after failure or intolerance to oral MTX. Data were collected from patient's clinical records. Both non-parametric and parametric survival methods were used to obtain a detailed understanding of SC MTX treatment duration. Fifty patients were included, of which only 9 discontinued SC MTX during the study follow-up period. The probability of discontinuation after 1, 2, and 3 years of treatment of SC MTX treatment is expected to be 6.10%, 8.50%, and 23.20%, respectively. The extrapolated median duration of SC MTX using an exponential model was 106.4 months/8.87 years. Mean dose of SC MTX was 18.36 mg. The reasons for treatment discontinuation were occurrence of adverse events in six patients and lack of efficacy in three. The long treatment duration of SC MTX highlights its excellent tolerability compared to oral MTX, especially concerning the frequent adverse gastrointestinal events of MTX. Furthermore, long MTX treatment duration provides the opportunity to postpone or even avoid expensive therapies with biologics. The results obtained from the UMAR study provide important information for the utilization and public financing of SC MTX in Portugal.

  1. Taurine protects against methotrexate-induced toxicity and inhibits leukocyte death

    International Nuclear Information System (INIS)

    Cetiner, Mustafa; Sener, Goeksel; Sehirli, A. Ozer; Eksioglu-Demiralp, Emel; Ercan, Feriha; Sirvanci, Serap; Gedik, Nursal; Akpulat, Sertac; Tecimer, Tuelay; Yegen, Berrak C.

    2005-01-01

    The efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, is often limited by severe side effects and toxic sequelae. Regarding the mechanisms of these side effects, several hypotheses have been put forward, among which oxidative stress is noticeable. The present study was undertaken to determine whether taurine, a potent free radical scavenger, could ameliorate MTX-induced oxidative injury and modulate immune response. Following a single dose of methotrexate (20 mg/kg), either saline or taurine (50 mg/kg) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the ileum, liver, and kidney were removed to measure malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen content, as well as histological examination. Our results showed that MTX administration increased the MDA, MPO activity, and collagen contents and decreased GSH levels in all tissues (P < 0.001), while these alterations were reversed in taurine-treated group (P < 0.05-0.01). Elevated (P < 0.001) TNF-α level observed following MTX treatment was depressed with taurine (P < 0.01). Oxidative burst of neutrophils stimulated by phorbol myristate acetate was reduced in saline-treated MTX group (P < 0.001), while taurine abolished this effect. Similarly, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in MTX-treated animals, while taurine reversed these effects (P < 0.05). Reduced cellularity in bone marrow samples of MTX-treated group (P < 0.01) was reversed back to control levels in taurine-treated rats. Severe degeneration of the intestinal mucosa, liver parenchyma, glomerular, and tubular epithelium observed in saline-treated group was improved by taurine treatment. In conclusion, it appears that taurine protects against methotrexate-induced oxidant organ injury and inhibits leukocyte apoptosis and may be of therapeutic potential in alleviating the systemic

  2. Overview and guidelines of off-label use of methotrexate in ectopic pregnancy: report by CNGOF.

    Science.gov (United States)

    Marret, Henri; Fauconnier, Arnaud; Dubernard, Gil; Misme, Hélène; Lagarce, Laurence; Lesavre, Magali; Fernandez, Hervé; Mimoun, Camille; Tourette, Claire; Curinier, Sandra; Rabishong, Benoit; Agostini, Aubert

    2016-10-01

    Our objective is to describe off-label use of methotrexate in ectopic pregnancy treatment using evidence based medicine. The patient group includes all women with a pregnancy outside the usual endometrium, or of unknown location. Method used was a Medline search on ectopic pregnancy managed using methotrexate treatment; evidence synthesis was done based on this current literature analysis. Level of evidence (LE) were given according to the centre for evidence base medicine rules. Grade was proposed for guidelines but no recommendation was possible as misoprostol is off label use for all the indications studied. In the absence of any contraindication, the protocol recommended for medical treatment of ectopic pregnancy is a single intramuscular injection of methotrexate (MTX) at a dosage of 1mg/kg or 50mg/m(2) (Grade A). It can be repeated once at the same dose should the hCG concentration not fall sufficiently. Pretreatment laboratory results must include a complete blood count and kidney and liver function tests (in accordance with its marketing authorization). MTX is an alternative to conservative treatment such as laparoscopic salpingotomy for uncomplicated tubal pregnancy (Grade A) with pretreatment hCG levels≤5000IU/l (Grade B). Expectant management is preferred for hCG levelslocation persisting more than 10days in an asymptomatic woman who has an hCG level>2000IU/l, routine MTX treatment is an option. MTX is not indicated for combination with treatments such as mifepristone or potassium. Copyright © 2016. Published by Elsevier Ireland Ltd.

  3. Comparison of central nervous system prophylaxis with cranial radiation and intrathecal methotrexate versus intrathecal methotrexate alone in acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Muriel, F.S.; Svarch, E.; Pavlovsky, S.; Eppinger-Helft, M.; Braier, J.; Vergara, B.; Garay, G.; Kvicala, R.; Divito, J.M.; Failace, R.

    1983-08-01

    In acute lymphoblastic leukemia, central nervous system prophylaxis with irradiation plus intrathecal methotrexate (i.t. MTX) reduces the incidence of CNS relapse to 7%-15%. However, increased evidence of CNS delayed toxicity was recognized mainly in children as CT scan abnormalities and neuropsychologic alterations. Two questions were analyzed: (1) Will further doses of i.t. methotraxate and dexamethasone (i.t. MTX-DMT) decrease the incidence of CNS relapse. (2) Is i.t. MTX-DMT given during induction and maintenance as effective as cranium irradiation plus i.t. MTX-DMT. Incidence of primary CNS relapse in i.t. MTX-DMT-treated patients with a WBC count < 50,000 and in the untreated group was 11%. In patients with a WBC count > 50,000, it was 16% in the treated group and 19% in the control group. These patients were compared with patients which had received 3 doses of i.t. MTX-DMT alone during induction, 3 doses weekly during the first month of remission, and quarterly thereafter. The incidence of leukemia at 60 mo in patients with a WBC count < 50,000 was 20% in the irradiated group and 32% in the group with i.t. MTX-DMT alone. The relapse-free survival at 60 mo was 26% and 41%, respectively, (p < 0.0005). The incidence in patients with a WBC count > 50,000 at 48 mo was 28% and 42% in the irradiated and nonirradiated group respectively. Complete remission remained at 15% and 16% respectively of patients disease-free at 48 mo. We conclude that (A) after cranial irradiation plus i.t. MTX-DMT X 5, the use of additional doses of i.t. MTX-DMT is not of further benefit in preventing CNS relapse; (B) use of i.t. MTX-DMT alone compares with cranial irradiation plus i.t. MTX-DMT in incidence of CNS relapse; and (C) relapse-free survival and survival in patients with a WBC count < 50.000 were significantly longer in those without cranial irradiation.

  4. Long-term survival of methotrexate in psoriatic arthritis

    Directory of Open Access Journals (Sweden)

    N. Battafarano

    2011-06-01

    Full Text Available Objective. The purpose of this study was to evaluate the long-term survival rate of Methotrexate (MTX in the peripheral joint involvement of psoriatic arthritis (PsA in a setting of everyday clinical practice. Methods. This was an observational restrospective study performed using the data from a dermatological-rheumatological PsA clinic. All of the patients evaluated at this clinic from March 1997 to December 2007 who were started on MTX alone, had a three-year follow-up time or had discontinued the therapy were included into the survey. Results. Of the 174 evaluable patients, 104 (59.8% were still taking MTX after three years of treament. The reasons of therapy discontinuation in the remaining 70 (40.2% patients were: 34 (19.5% lost-to-follow-up, 18 (10.3% adverse events, 14 (8% inefficacies, and 4 (2.3% deaths (none related to the therapy. MTX was effective in controlling joint inflammation but not in preventing their deterioration. Overall, adverse events were recorded in 43 patients (36.4% of the 114 patients with a three-year follow-up. No serious side effect occurred in the study population. Conclusions. The results of this study showed that, in a setting of clinical pratice, MTX had a good three-year performance in patients with peripheral PsA. Almost 60% of them were still taking this drug at the end of the study period and the toxicity was more than acceptable. In our opinion, MTX might be considered the non-biological DMARD of choice for the treatment of this condition. However it should be used earlier and at higher doses.

  5. An indirect comparison and cost per responder analysis of adalimumab, methotrexate and apremilast in the treatment of methotrexate-naïve patients with psoriatic arthritis.

    Science.gov (United States)

    Betts, Keith A; Griffith, Jenny; Friedman, Alan; Zhou, Zheng-Yi; Signorovitch, James E; Ganguli, Arijit

    2016-01-01

    Apremilast was recently approved for the treatment of active psoriatic arthritis (PsA). However, no studies compare apremilast with methotrexate or biologic therapies, so its relative comparative efficacy remains unknown. This study compared the response rates and incremental costs per responder associated with methotrexate, apremilast, and biologics for the treatment of active PsA. A systematic literature review was performed to identify phase 3 randomized controlled clinical trials of approved biologics, methotrexate, and apremilast in the methotrexate-naïve PsA population. Using Bayesian methods, a network meta-analysis was conducted to indirectly compare rates of achieving a ≥20% improvement in American College of Rheumatology component scores (ACR20). The number needed to treat (NNT) and the incremental costs per ACR20 responder (2014 US$) relative to placebo were estimated for each of the therapies. Three trials (MIPA for methotrexate, PALACE-4 for apremilast, and ADEPT for adalimumab) met all inclusion criteria. The NNTs relative to placebo were 2.63 for adalimumab, 6.69 for apremilast, and 8.31 for methotrexate. Among methotrexate-naïve PsA patients, the 16 week incremental costs per ACR20 responder were $3622 for methotrexate, $26,316 for adalimumab, and $45,808 for apremilast. The incremental costs per ACR20 responder were $222,488 for apremilast vs. methotrexate. Among methotrexate-naive PsA patients, adalimumab was found to have the lowest NNT for one additional ACR20 response and methotrexate was found to have the lowest incremental costs per ACR20 responder. There was no statistical evidence of greater efficacy for apremilast vs. methotrexate. A head-to-head trial between apremilast and methotrexate is recommended to confirm this finding.

  6. The challenge of cumulative impacts

    Energy Technology Data Exchange (ETDEWEB)

    Masden, Elisabeth

    2011-07-01

    Full text: As governments pledge to combat climate change, wind turbines are becoming a common feature of terrestrial and marine environments. Although wind power is a renewable energy source and a means of reducing carbon emissions, there is a need to ensure that the wind farms themselves do not damage the environment. There is particular concern over the impacts of wind farms on bird populations, and with increasing numbers of wind farm proposals, the concern focuses on cumulative impacts. Individually, a wind farm, or indeed any activity/action, may have minor effects on the environment, but collectively these may be significant, potentially greater than the sum of the individual parts acting alone. Cumulative impact assessment is a legislative requirement of environmental impact assessment but such assessments are rarely adequate restricting the acquisition of basic knowledge about the cumulative impacts of wind farms on bird populations. Reasons for this are numerous but a recurring theme is the lack of clear definitions and guidance on how to perform cumulative assessments. Here we present a conceptual framework and include illustrative examples to demonstrate how the framework can be used to improve the planning and execution of cumulative impact assessments. The core concept is that explicit definitions of impacts, actions and scales of assessment are required to reduce uncertainty in the process of assessment and improve communication between stake holders. Only when it is clear what has been included within a cumulative assessment, is it possible to make comparisons between developments. Our framework requires improved legislative guidance on the actions to include in assessments, and advice on the appropriate baselines against which to assess impacts. Cumulative impacts are currently considered on restricted scales (spatial and temporal) relating to individual development assessments. We propose that benefits would be gained from elevating cumulative

  7. Treatment efficacy and methotrexate-related toxicity in patients with rheumatoid arthritis receiving methotrexate in combination with adalimumab.

    Science.gov (United States)

    Burmester, Gerd R; Kaeley, Gurjit S; Kavanaugh, Arthur F; Gabay, Cem; MacCarter, Daryl K; Nash, Peter; Takeuchi, Tsutomu; Goss, Sandra L; Rodila, Ramona; Chen, Kun; Kupper, Hartmut; Kalabic, Jasmina

    2017-01-01

    Treatment of rheumatoid arthritis (RA) with a combination of methotrexate (MTX)+adalimumab (ADA) is more effective than ADA monotherapy. We assessed the toxicity of different doses of MTX and treatment efficacy of ADA+MTX in two trials. Data originated from CONCERTO, in patients with early RA initiating ADA+ 2.5, 5, 10 or 20 mg/week MTX for 26 weeks; and MUSICA, in patients with an inadequate response to MTX initiating ADA+ 7.5 or 20 mg/week MTX for 24 weeks. Efficacy was assessed by the American College of Rheumatology 50 (ACR50). Patient-reported MTX-related toxicity information was collected at each visit on 18 prespecified MTX-related adverse events (AE) in the MTX label. In CONCERTO, ACR50 rates increased over time, ranging from 54% to 68% at week 26, while AE rates remained steady, ranging from 2.4% to 17.8% at week 26. Of 395 patients, 113 (28.6%) reported 345 MTX-related AEs, including one serious AE (SAE, excessive fatigue and/or malaise); 10 AEs (in two patients) led to study discontinuation. In MUSICA, ACR50 rates increased over time, and were 32.3% and 37.5% at week 24, while MTX-related AE rates remained steady and were 6.5% at week 24. Of 309 patients, 71 (23%) reported 185 MTX-related AEs, including 5 SAEs (four infections and one fever/chills); six AEs (in four patients) led to study discontinuation. In patients with RA initiating ADA+MTX combination, treatment efficacy was achieved and increased throughout both trials, while rates of MTX-related AEs remained steady. MTX-related AEs were observed in up to 30% of patients and most were mild. MTX was discontinued by 0.5%-1.3% of patients. MUSICA (NCT01185288), CONCERTO (NCT01185301), Post results.

  8. Intravitreal methotrexate infusion for proliferative vitreoretinopathy

    Directory of Open Access Journals (Sweden)

    Sadaka A

    2016-09-01

    Full Text Available Ama Sadaka,1 Robert A Sisk,1–3 James M Osher,1,3 Okan Toygar,4 Melinda K Duncan,5 Christopher D Riemann1,3 1Department of Ophthalmology, University of Cincinnati College of Medicine, 2Department of Opthalmology, Cincinnati Children’s Hospital Medical Center, 3Cincinnati Eye Institute, Cincinnati, OH, USA; 4Department of Ophthalmology, Bahcesehir University Medical Faculty, Istanbul, Turkey; 5Department of Biological Sciences, University of Delaware, Newark, DE, USA Purpose: The purpose of this study was to evaluate intravitreal methotrexate infusion (IMI during pars plana vitrectomy (PPV for retinal detachment in patients with high risk for the development of proliferative vitreoretinopathy (PVR.Methods: Patients presenting with severe recurrent PVR with tractional retinal detachment and/or a history of severe ocular inflammation were treated with IMI. Clinical outcomes were determined from a retrospective medical chart review.Results: Twenty-nine eyes presenting with either tractional retinal detachment and recurrent PVR (n=22 or a history of severe inflammation associated with high PVR risk (n=7 received IMI during PPV. Best-corrected visual acuity at 6 months was ≥20/200 in 19 of 29 eyes (66% and remained stable or improved compared with initial presentation in 24 of 29 eyes (83%. At the last follow-up examination, the retinas of 26 of 29 eyes (90% remained attached after IMI while three eyes required another reattachment procedure. Three additional eyes (10% developed recurrent limited PVR without recurrent RD and were observed. No complications attributable to IMI occurred during a mean follow-up of 27 months.Conclusion: Eyes at high risk for PVR development due to a history of prior PVR or intraocular inflammation had a low incidence of PVR following IMI at the time of PPV for RD repair. No significant safety issues from IMI were observed in this series. Keywords: tractional retinal detachment, recurrent retinal detachment, pars

  9. EFFECACY OF PULSE-THERAPY WIHT GLUCOCORTICOSTEROIDS AND METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    N YU Lashina

    2000-01-01

    Full Text Available Summary Aim of study: Comparative study of clinical efficacy and tolerability of pulse-therapy (PT by glucocorticosteroids and methotrexate in RA pts and frequency of side effects and aggravations. Material and methods: 31 pts with seropositive RA (M:F=4:27 with disease activity 2-3 were examined. 16 pts had pulse-therapy by dexaven in dosage of 2 mg/kg of weight for 3 consecutive days, 15 pts of the 2nd group had methypred in classic dose of1000 mg No3. After PT on the 7th and 30th day pts had PT by methotrexate 100 mg and dexaven 16 mg. Therapy effect was evaluated after PT, in a month, 6 month and a year. During examination the following parameters were registered: severity of arthralgia, morning stiffness duration, grip strength, number of inflamedjoints, Ritchie's, Li, Landsbery indices, extra-articular manifestations. ESR, hemoglobin content, leukocytes, fibrinogen, seromucoid, C-reactive protein, CIC, RF were determined. Results: After PT in both groups arthralgia, morning stiffness, number of inflamed joints considerably subsided. Dynamics of medial indices of activity decreased by 2-3 times. Side effects after the procedures were minimal and were stopped without additional treatment.

  10. Methotrexate/6-mercaptopurine maintenance therapy influences the risk of a second malignant neoplasm after childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Al-Modhwahi, Ibrahim; Andersen, Mette Klarskov

    2009-01-01

    Among 1614 children with acute lymphoblastic leukemia (ALL) treated with the Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL-92 protocol, 20 patients developed a second malignant neoplasm (SMN) with a cumulative risk of 1.6% at 12 years from the diagnosis of ALL. Nine of the 16...... acute myeloid leukemias or myelodysplastic syndromes had monosomy 7 (n = 7) or 7q deletions (n = 2). In Cox multivariate analysis, longer duration of oral 6-mercaptopurine (6MP)/methotrexate (MTX) maintenance therapy (P = .02; longest for standard-risk patients) and presence of high hyperdiploidy (P...

  11. USE OF SUBCUTANEOUS METHOTREXATE FOR THE TREATMENT OF PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS: THE REMARCA TRIAL

    Directory of Open Access Journals (Sweden)

    D. E. Karateev

    2016-01-01

    Full Text Available The early administration of methotrexate (MTX and the use of its high (by the rheumatology practice standards doses contribute to the enhanced efficiency of therapy and the reduced severity of rheumatoid arthritis (RA. One of the important merits of MTX in the treatment of RA is the possibility of adjusting its dose and choosing its (oral or subcutaneous administration routes, which makes it possible to individualize treatment. Particular emphasis has been recently placed just on a subcutaneous MTX formulation that creates prerequisites for substantially improving the efficiency of RA therapy. The paper gives the data of the REMARCA (Russian investigation of methotrexate and biologicals for early active arthritis trial assessing the results of RA treatment in the use of the subcutaneous MTX dosage form as a first-line drug and in the elaboration of management tactics for this disease.Subjects and methods. The investigation included 191 patients (34 men and 157 women with active RA; of whom 51.8% had very early RA (< 6 months' disease duration. 115 patients with RA completed a 24-month follow-up period; and their data were analyzed in more detail.Results and discussion. The findings may substantiate treatment policy based on the prescription of subcutaneous MTX (without previously administering its oral formulation in patients with early RA and high disease activity, starting the drug at 15 mg/week and rapidly escalating with the highest tolerable doses during 4-8 weeks, which allows remission (or low disease activity in the majority of patients without using glucocorticoids and biological agents.

  12. Short time administration of antirheumatic drugs - Methotrexate as a strong inhibitor of osteoblast's proliferation in vitro

    Directory of Open Access Journals (Sweden)

    Annussek Tobias

    2012-09-01

    Full Text Available Abstract Introduction Due to increasing use of disease modifying antirheumatic drugs (DMARDs as first line therapy in rheumatic diseases, dental and maxillofacial practitioner should be aware of drug related adverse events. Especially effects on bone-metabolism and its cells are discussed controversially. Therefore we investigate the in vitro effect of short time administration of low dose methotrexate (MTX on osteoblasts as essential part of bone remodelling cells. Methods Primary bovine osteoblasts (OBs were incubated with various concentrations of MTX, related to tissue concentrations, over a period of fourteen days by using a previously established standard protocol. The effect on cell proliferation as well as mitochondrial activity was assessed by using 3-(4, 5-dimethylthiazol-2-yl 2, 5-diphenyltetrazolium bromide (MTT assay, imaging and counting of living cells. Additionally, immunostaining of extracellular matrix proteins was used to survey osteogenic differentiation. Results All methods indicate a strong inhibition of osteoblast`s proliferation by short time administration of low dose MTX within therapeutically relevant concentrations of 1 to 1000nM, without affecting cell differentiation of middle-stage differentiated OBs in general. More over a significant decrease of cell numbers and mitochondrial activity was found at these MTX concentrations. The most sensitive method seems to be the MTT-assay. MTX-concentration of 0,01nM and concentrations below had no inhibitory effects anymore. Conclusion Even low dose methotrexate acts as a potent inhibitor of osteoblast’s proliferation and mitochondrial metabolism in vitro, without affecting main differentiation of pre-differentiated osteoblasts. These results suggest possible negative effects of DMARDs concerning bone healing and for example osseointegration of dental implants. Especially the specifics of the jaw bone with its high vascularisation and physiological high tissue metabolism

  13. Birth outcomes after preconception paternal exposure to methotrexate

    DEFF Research Database (Denmark)

    Winter, Rachel W; Larsen, Michael Due; Magnussen, Bjarne

    2017-01-01

    BACKGROUND: Methotrexate (MTX), a folic acid antagonist, is often prescribed for moderate to severe inflammatory related diseases. The safety of paternal MTX use prior to conception is unknown. This study, using the National Danish Registries, aimed to examine the association between paternal MTX...

  14. Methotrexate in Alopecia Areata: A Report of Three Cases

    OpenAIRE

    Batalla, Ana; Fl?rez, ?ngeles; Abalde, Teresa; V?zquez-Veiga, Hugo

    2016-01-01

    There are few studies about systemic treatment in severe cases of alopecia areata (AA), especially in the pediatric population. Although there is more experience with systemic corticosteroids, recent reports have suggested methotrexate (MTX) as an alternative treatment, with a relatively good outcome. We describe three cases of AA in children treated with MTX, two of them with successful results.

  15. Advances in individual prediction of methotrexate toxicity: a review

    DEFF Research Database (Denmark)

    Schmiegelow, K.

    2009-01-01

    pathways. In the coming years pharmacogenomics is expected to change our approaches to individualised therapy with methotrexate. However, genetic polymorphisms affect the pharmacokinetics and dynamics of all the drugs a patient receive as well as the normal tissues tolerance to a given drug exposure. Thus...

  16. Efficacy of royal jelly on methotrexate-induced systemic oxidative ...

    African Journals Online (AJOL)

    The aim of this present study is to investigate the mucositis caused by methotrexate (MTX), as well as whether the application of royal jelly (RJ) has a protective effect on oxidative stress. This present study included six groups each consisted of 12 Wistar rats. Distilled water (po: peroral) was given to the 1st group as placebo ...

  17. Carrier-bound Methotrexate. IV. Antiproliferative Activity of ...

    African Journals Online (AJOL)

    NJD

    Polymeric conjugates of methotrexate (MTX) with macromolecular carriers, ... The water-soluble conjugates, crudely fractionated by aqueous dialysis, possess mass-average molecular masses in ..... for 20 h in an ice bath and another 3 h at room temperature. ... with excess Et2O-hexane (2:1) afforded a resinous product,.

  18. Methotrexate-Associated Nonalcoholic Fatty Liver Disease with Transaminitis in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Rajalingham Sakthiswary

    2014-01-01

    Full Text Available Background. The aim of this study was to determine the risk factors of MTX-associated nonalcoholic fatty liver disease (NAFLD with transaminitis in a cohort of rheumatoid arthritis (RA patients from Singapore. Methods. Patients who developed ultrasound proven NAFLD with transaminitis while on MTX therapy were identified. The demographic and clinical characteristics of the above patients (cases were compiled and compared with age- and gender-matched controls who were RA patients on long standing MTX therapy without any episode of transaminitis. Results. Among the 978 patients who had received MTX, the prevalence of MTX-associated NAFLD was 4.7% (46 patients. Compared to the controls, the cases had significantly higher mean cumulative dose of MTX (4.03 ± 2.25 g versus 10.04 ± 9.94 g, P≤0.05, weekly dose of MTX (11.3 ± 4.8 mg versus 13.1 ± 4.4 mg weekly, P=0.033, and fasting blood glucose (P=0.029. Following multivariate regression analysis, only cumulative dose of MTX remained significant (P=0.015. Among the cases, the cumulative dose of MTX was found to have a significant positive correlation with the alanine transaminase (ALT level (P<0.05, standardised beta coefficient 0.512. Conclusion. The cumulative dose of MTX was the only independent predictor of MTX-associated NAFLD with transaminitis.

  19. Cumulative risk, cumulative outcome: a 20-year longitudinal study.

    Directory of Open Access Journals (Sweden)

    Leslie Atkinson

    Full Text Available Cumulative risk (CR models provide some of the most robust findings in the developmental literature, predicting numerous and varied outcomes. Typically, however, these outcomes are predicted one at a time, across different samples, using concurrent designs, longitudinal designs of short duration, or retrospective designs. We predicted that a single CR index, applied within a single sample, would prospectively predict diverse outcomes, i.e., depression, intelligence, school dropout, arrest, smoking, and physical disease from childhood to adulthood. Further, we predicted that number of risk factors would predict number of adverse outcomes (cumulative outcome; CO. We also predicted that early CR (assessed at age 5/6 explains variance in CO above and beyond that explained by subsequent risk (assessed at ages 12/13 and 19/20. The sample consisted of 284 individuals, 48% of whom were diagnosed with a speech/language disorder. Cumulative risk, assessed at 5/6-, 12/13-, and 19/20-years-old, predicted aforementioned outcomes at age 25/26 in every instance. Furthermore, number of risk factors was positively associated with number of negative outcomes. Finally, early risk accounted for variance beyond that explained by later risk in the prediction of CO. We discuss these findings in terms of five criteria posed by these data, positing a "mediated net of adversity" model, suggesting that CR may increase some central integrative factor, simultaneously augmenting risk across cognitive, quality of life, psychiatric and physical health outcomes.

  20. Pharmacogenomics of Methotrexate Membrane Transport Pathway: Can Clinical Response to Methotrexate in Rheumatoid Arthritis Be Predicted?

    Directory of Open Access Journals (Sweden)

    Aurea Lima

    2015-06-01

    Full Text Available Background: Methotrexate (MTX is widely used for rheumatoid arthritis (RA treatment. Single nucleotide polymorphisms (SNPs could be used as predictors of patients’ therapeutic outcome variability. Therefore, this study aims to evaluate the influence of SNPs in genes encoding for MTX membrane transport proteins in order to predict clinical response to MTX. Methods: Clinicopathological data from 233 RA patients treated with MTX were collected, clinical response defined, and patients genotyped for 23 SNPs. Genotype and haplotype analyses were performed using multivariate methods and a genetic risk index (GRI for non-response was created. Results: Increased risk for non-response was associated to SLC22A11 rs11231809 T carriers; ABCC1 rs246240 G carriers; ABCC1 rs3784864 G carriers; CGG haplotype for ABCC1 rs35592, rs2074087 and rs3784864; and CGG haplotype for ABCC1 rs35592, rs246240 and rs3784864. GRI demonstrated that patients with Index 3 were 16-fold more likely to be non-responders than those with Index 1. Conclusions: This study revealed that SLC22A11 and ABCC1 may be important to identify those patients who will not benefit from MTX treatment, highlighting the relevance in translating these results to clinical practice. However, further validation by independent studies is needed to develop the field of personalized medicine to predict clinical response to MTX treatment.

  1. 78 FR 25440 - Request for Information and Citations on Methods for Cumulative Risk Assessment

    Science.gov (United States)

    2013-05-01

    ... Citations on Methods for Cumulative Risk Assessment AGENCY: Office of the Science Advisor, Environmental... influence exposures, dose-response or risk/hazard posed by environmental contaminant exposures, and methods... who wish to receive further information about submitting information on methods for cumulative risk...

  2. Methotrexate for the treatment of juvenile idiopathic arthritis: process to approval for JIA indication in Japan.

    Science.gov (United States)

    Mori, Masaaki; Naruto, Takuya; Imagawa, Tomoyuki; Murata, Takuji; Takei, Syuji; Tomiita, Minako; Itoh, Yasuhiko; Fujikawa, Satoshi; Yokota, Shumpei

    2009-01-01

    Methotrexate (MTX), the primary treatment for the articular-type juvenile idiopathic arthritis (JIA), is effective and brings about radiological improvement. Patient compliance is good, and it is recognized that its known side effects, namely, disruption of liver function and induction of pulmonary lesions, are unlikely to be severe at the low MTX doses that are administered. In Japan, MTX was granted approval in 1999 by the then Ministry of Health and Welfare specifically for treating rheumatoid arthritis in adult patients, allowing it be generally used in medical institutions for patients having National Health Insurance. However, in the pediatric field, its use outside the indications has so far been unavoidable, and has been left to the discretion of the physician. Finally, at the present conference, expansion of the indications of MTX for JIA was approved in Japan. It is noteworthy that this expansion of indications was achieved without requiring clinical trials on children sponsored by the pharmaceutical company: it was achieved rather by collecting necessary information through ongoing efforts (including collection and analysis of information about approval status in foreign countries, adequate evidence from the literature, implementation of a clinical use survey in Japan, etc.). It also merits attention that the maximum dose (10 mg/m2) was set on the basis of pharmacokinetic data from children, rather than relying on the dosing method and dose for adults.

  3. Methotrexate-induced Pancytopenia in Two Patients with Renal Dysfunction

    OpenAIRE

    Yusuf OĞUZ; Tayfun EYİLETEN; Murat KARAMAN; Seyid Ahmet AY; Mahmut İlker YILMAZ

    2011-01-01

    Methotrexate (MTX) is cleared primarily by renal excretion. The excretion of MTX is delayed in subjects with renal dysfunction and elevated plasma MTX concentrations develop which lead to bone marrow toxicities and possible pancytopenia. In this case report, we presented two advanced age patients with MTX-induced pancytopenia. The first patient on hemodialysis was diagnosed with seronegative arthritis while the second patient with congestive heart failure was diagnosed with rheumatoid arthrit...

  4. Interaction of methotrexate with trypsin analyzed by spectroscopic and molecular modeling methods

    Science.gov (United States)

    Wang, Yanqing; Zhang, Hongmei; Cao, Jian; Zhou, Qiuhua

    2013-11-01

    Trypsin is one of important digestive enzymes that have intimate correlation with human health and illness. In this work, the interaction of trypsin with methotrexate was investigated by spectroscopic and molecular modeling methods. The results revealed that methotrexate could interact with trypsin with about one binding site. Methotrexate molecule could enter into the primary substrate-binding pocket, resulting in inhibition of trypsin activity. Furthermore, the thermodynamic analysis implied that electrostatic force, hydrogen bonding, van der Waals and hydrophobic interactions were the main interactions for stabilizing the trypsin-methotrexate system, which agreed well with the results from the molecular modeling study.

  5. Methotrexate in the treatment of peripheral arthritis in ulcerative colitis

    Directory of Open Access Journals (Sweden)

    R. Scarpa

    2011-06-01

    Full Text Available Objective: To evaluate efficacy of methotrexate treatment in peripheral arthritis of ulcerative colitis. Methods: We studied 18 patients (10/8 M/F; mean age: 38.90 yrs; range: 21-65 yrs, with peripheral arthritis (14 with polyarticular, 4 with oligoarticular subset associate ulcerative colitis. Methotrexate 20 mg/week was administered in our patients, who were already receiving mesalazina for inflammatory bowel disease. At baseline, after 3 (T1, 6 (T2 and 12 months (T3 serological parameters (ESR and CRP, functional status (HAQ and disease activity (VAS, GH, Ritchie articular index were evaluated. Results: During the therapy a significant improvement was observed in disease activity, functional status and serological parameters since T1. ESR and CRP did not change at T2 and T3. Instead VAS, GH, Ritchie articular index and HAQ had a significant and gradual improvement from T1 to T3. Conclusion: Methotrexate treatment was efficacious in the treatment of peripheral arthritis associate ulcerative colitis. This drug induced improvement in disease activity, functional status and serological parameters after 3 months of therapy.

  6. The Algebra of the Cumulative Percent Operation.

    Science.gov (United States)

    Berry, Andrew J.

    2002-01-01

    Discusses how to help students avoid some pervasive reasoning errors in solving cumulative percent problems. Discusses the meaning of ."%+b%." the additive inverse of ."%." and other useful applications. Emphasizes the operational aspect of the cumulative percent concept. (KHR)

  7. Adaptive strategies for cumulative cultural learning.

    Science.gov (United States)

    Ehn, Micael; Laland, Kevin

    2012-05-21

    The demographic and ecological success of our species is frequently attributed to our capacity for cumulative culture. However, it is not yet known how humans combine social and asocial learning to generate effective strategies for learning in a cumulative cultural context. Here we explore how cumulative culture influences the relative merits of various pure and conditional learning strategies, including pure asocial and social learning, critical social learning, conditional social learning and individual refiner strategies. We replicate the Rogers' paradox in the cumulative setting. However, our analysis suggests that strategies that resolved Rogers' paradox in a non-cumulative setting may not necessarily evolve in a cumulative setting, thus different strategies will optimize cumulative and non-cumulative cultural learning. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. The Influence of Methotrexate Treatment on Male Fertility and Pregnancy Outcome After Paternal Exposure.

    Science.gov (United States)

    Grosen, Anne; Kelsen, Jens; Hvas, Christian Lodberg; Bellaguarda, Emanuelle; Hanauer, Stephen B

    2017-04-01

    Inflammatory bowel disease incidence peaks during the reproductive years. Methotrexate (MTX) is frequently used for inflammatory bowel disease, but its use during pregnancy is contraindicated in women because of teratogenic effects. The aim of this review is to investigate the influence of MTX on male fertility and pregnancy outcomes after paternal MTX exposure. A systematic literature search was performed by applying 2 focus areas, "methotrexate" and "male fertility or pregnancy outcome." Terms and keywords were used both as MeSH terms and free-text searches. Pertinent articles were searched for additional relevant references. In animal studies, MTX induces aberrations in sperm DNA that have not been identified in humans. The effects of MTX on human sperm quality have only been described in case reports. A transient adverse effect on sperm quality with low-dose MTX has been reported, but several other cases have not found harmful effects of MTX. MTX has not been measured in human sperm ejaculates; yet, the risk of a direct toxic effect on the fetus through MTX-contaminated seminal plasma seems negligible. Until now, 284 pregnancies with paternal MTX exposure have been reported. The outcomes were 248 live births and a total of 13 malformations, with no overt indication of MTX embryopathy. This review reveals the lack of studies on the safety of MTX with regard to male reproduction. It is not clear whether MTX transiently influences male fertility and sperm DNA integrity, and more studies are needed. Comparative cohort studies found no increased risk of adverse pregnancy outcomes.

  9. 32 CFR 651.16 - Cumulative impacts.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Cumulative impacts. 651.16 Section 651.16... § 651.16 Cumulative impacts. (a) NEPA analyses must assess cumulative effects, which are the impact on the environment resulting from the incremental impact of the action when added to other past, present...

  10. Time to treatment as an important factor for the response to methotrexate in juvenile idiopathic arthritis.

    Science.gov (United States)

    Albers, H M; Wessels, J A M; van der Straaten, R J H M; Brinkman, D M C; Suijlekom-Smit, L W A; Kamphuis, S S M; Girschick, H J; Wouters, C; Schilham, M W; le Cessie, S; Huizinga, T W J; Ten Cate, R; Guchelaar, H J

    2009-01-15

    Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug in juvenile idiopathic arthritis (JIA). Currently, individual response to MTX cannot be reliably predicted. Identification of clinical and genetic factors that influence the response to MTX could be helpful in realizing the optimal treatment for individual patients. A cohort of 128 JIA patients treated with MTX were studied retrospectively. Eleven clinical parameters and genotypes of 6 single nucleotide polymorphisms in 5 genes related to the mechanism of action of MTX were compared between MTX responders and nonresponders using a multivariate regression analysis. The time from diagnosis to start of MTX treatment, physician's global assessment at baseline, and the starting dose were significantly associated with the response to MTX at 6 months after initiation. Patients with a shorter time from diagnosis to start of MTX and a higher disease activity according to the physician but with a lower MTX dose showed an increased response. The effect of the starting dose on MTX response seemed to be mainly due to the influence of the systemic JIA subtype. The time from diagnosis to start of MTX treatment and physician's global assessment at baseline were highly correlated. Therefore, the precise effect size of each independent variable could not be determined. In children with JIA, the time from diagnosis to start of MTX appears to be an important factor for MTX response. Our results suggest that an earlier start of MTX treatment will lead to an increased response.

  11. High Efficacy of Methotrexate in Patients with Recurrent Idiopathic Acute Anterior Uveitis: a Prospective Study.

    Science.gov (United States)

    Bachta, Artur; Kisiel, Bartłomiej; Tłustochowicz, Mateusz; Raczkiewicz, Anna; Rękas, Marek; Tłustochowicz, Witold

    2017-02-01

    To evaluate prospectively the efficacy of methotrexate (MTX) in the treatment of recurrent idiopathic acute anterior uveitis (RIAAU). Nineteen out of 22 RIAAU patients completed the study (two patients withdrew their consent shortly after study initiation, one patient discontinued after 4 weeks because of the adverse effects). All patients were treated with MTX in a starting dose of 15 mg/week, increased to target dose of 25 mg/week after 4 weeks. In patients taking systemic corticosteroids (CS) the dose was gradually tapered (by 2.5 mg every week) until discontinuation. The mean follow-up period was 3.3 years (19-59 months). Sixteen patients (84 %) remained flare-free on MTX therapy. In the remaining three patients the mean interval between flares increased from 4.8 to 18.3 months. Systemic CS were tapered off in all patients. The number of acute anterior uveitis flares in the whole cohort decreased from 2.12 to 0.11/patient-year (p treatment of RIAAU.

  12. Agreement between Rheumatologist and Patient-reported Adherence to Methotrexate in a US Rheumatoid Arthritis Registry.

    Science.gov (United States)

    Curtis, Jeffrey R; Bharat, Aseem; Chen, Lang; Greenberg, Jeffrey D; Harrold, Leslie; Kremer, Joel M; Sommers, Tanya; Pappas, Dimitrios

    2016-06-01

    Rheumatologists have limited tools to assess medication adherence. The extent to which methotrexate (MTX) adherence is overestimated by rheumatologists is unknown. We deployed an Internet survey to patients with rheumatoid arthritis (RA) participating in a US registry. Patient self-report was the gold standard compared to MTX recorded in the registry. Response rate to the survey was 44%. Of 228 patients whose rheumatologist reported current MTX at the time of the most recent registry visit, 45 (19.7%) had discontinued (n = 19, 8.3%) or missed ≥ 1 dose in the last month (n = 26, 11.4%). For the subgroup whose rheumatologist also confirmed at the next visit that they were still taking MTX (n = 149), only 2.6% reported not taking it, and 10.7% had missed at least 1 dose. MTX use was misclassified for 13%-20% of patients, mainly because of 1 or more missed doses rather than overt discontinuation. Clinicians should be aware of suboptimal adherence when assessing MTX response.

  13. A paradox of cumulative culture.

    Science.gov (United States)

    Kobayashi, Yutaka; Wakano, Joe Yuichiro; Ohtsuki, Hisashi

    2015-08-21

    Culture can grow cumulatively if socially learnt behaviors are improved by individual learning before being passed on to the next generation. Previous authors showed that this kind of learning strategy is unlikely to be evolutionarily stable in the presence of a trade-off between learning and reproduction. This is because culture is a public good that is freely exploited by any member of the population in their model (cultural social dilemma). In this paper, we investigate the effect of vertical transmission (transmission from parents to offspring), which decreases the publicness of culture, on the evolution of cumulative culture in both infinite and finite population models. In the infinite population model, we confirm that culture accumulates largely as long as transmission is purely vertical. It turns out, however, that introduction of even slight oblique transmission drastically reduces the equilibrium level of culture. Even more surprisingly, if the population size is finite, culture hardly accumulates even under purely vertical transmission. This occurs because stochastic extinction due to random genetic drift prevents a learning strategy from accumulating enough culture. Overall, our theoretical results suggest that introducing vertical transmission alone does not really help solve the cultural social dilemma problem. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia: Clinical Facts and Fiction

    Science.gov (United States)

    Nielsen, Stine N.; Frandsen, Thomas L.; Nersting, Jacob

    2014-01-01

    The antileukemic mechanisms of 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy are poorly understood, but the benefits of several years of myelosuppressive maintenance therapy for acute lymphoblastic leukemia are well proven. Currently, there is no international consensus on drug dosing. Because of significant interindividual and intraindividual variations in drug disposition and pharmacodynamics, vigorous dose adjustments are needed to obtain a target degree of myelosuppression. As the normal white blood cell counts vary by patients’ ages and ethnicity, and also within age groups, identical white blood cell levels for 2 patients may not reflect the same treatment intensity. Measurements of intracellular levels of cytotoxic metabolites of 6MP and MTX can identify nonadherent patients, but therapeutic target levels remains to be established. A rise in serum aminotransferase levels during maintenance therapy is common and often related to high levels of methylated 6MP metabolites. However, except for episodes of hypoglycemia, serious liver dysfunction is rare, the risk of permanent liver damage is low, and aminotransferase levels usually normalize within a few weeks after discontinuation of therapy. 6MP and MTX dose increments should lead to either leukopenia or a rise in aminotransferases, and if neither is experienced, poor treatment adherence should be considered. The many genetic polymorphisms that determine 6MP and MTX disposition, efficacy, and toxicity have precluded implementation of pharmacogenomics into treatment, the sole exception being dramatic 6MP dose reductions in patients who are homozygous deficient for thiopurine methyltransferase, the enzyme that methylates 6MP and several of its metabolites. In conclusion, maintenance therapy is as important as the more intensive and toxic earlier treatment phases, and often more challenging. Ongoing research address the applicability of drug metabolite measurements for dose adjustments

  15. Methotrexate in patients with rheumatoid arthritis in Spain: Subanalysis of the AR Excellence project.

    Science.gov (United States)

    Tornero-Molina, Jesús; Andreu, José Luis; Martín-Martínez, María-Auxiliadora; Corominas, Héctor; Pérez Venegas, José Javier; Román-Ivorra, José Andrés; Sánchez-Alonso, Fernando

    2017-12-19

    The AR Excellence project evaluates clinical monitoring in patients with rheumatoid arthritis (RA) in Spain. The aim of the study was to analyze the use of methotrexate (MTX) in the AR Excellence cohort and to compare it with current recommendations. We collected data from RA patients who initiated treatment with MTX. They included demographics, dose and routes of administration, switching among them, highest dose in each route, combinations with other disease-modifying antirheumatic drugs (DMARDs), time to combination with another DMARD (either conventional or biological) and adverse events. Six hundred twenty-five patients with RA (mean age 55 years; 70.6% women) were included, with an average disease duration of 21 months. Ninety percent of the patients initiated treatment with MTX. Therapy was begun with a mean dose of 11mg per week; this initial dose was increased in 58% of the individuals. The average time to reach the full dose of MTX (20mg a week) was 6,67 months. Time to combination of MTX with another DMARD, either synthetic or biological, was 3 months. In all, 67.4% of the patients received oral MTX and the route was subcutaneous in 18.6%. In 12% of the cases, there was a change in the route of administration after a period of 6 months. In 544 patients, folate supplements were added to MTX; MTX-related adverse events were detected in 17.3% of the patients. MTX is currently the pivotal treatment in RA. The subanalysis of the AR Excellence project demonstrates that MTX escalation to its full doses is not done with adequate speed. The subcutaneous route is used in a small proportion of patients. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  16. Relationship of peak serum methotrexate concentration to prognosis and drug tolerance in non-metastatic extremity osteosarcomas.

    Science.gov (United States)

    Wang, Bo; Yao, Hao; Xie, Xianbiao; Yin, Junqiang; Zou, Changye; Huang, Gang; Shen, Jingnan

    2018-05-28

    This study aimed to explore whether peak serum methotrexate concentration (C max ) correlated with adverse events, overall survival (OS) and event-free survival (EFS) in patients with primary extremity osteosarcoma. Patients with extremity osteosarcoma who were treated at our center between 2005 and 2015 were retrospectively studied. All the patients were Enneking stage II and had received standard perioperative chemotherapy composed of high-dose methotrexate, doxorubicin, cisplatin and ifosfamide. C max and treatment-associated toxicities of each cycle were recorded. OS and EFS were estimated and compared by Kaplan-Meier survival analysis, and Cox regression models were performed for univariate comparisons. In total, 567 patients were followed for an average of 53 months (24-104 months). The estimated 3- and 5-year EFS were 71.7 and 63.1%, and the 3- and 5-year OS were 78.2 and 72.9%, respectively. C max ranged from 527 to 2495 µmol/L with a mean value of 931 ± 106 µmol/L. No significant differences in EFS and OS (p = 0.18 and p = 0.28) were observed among patients with a mean C max  > 1500, > 1000, > 700 and  1500 µmol/L had significantly increased rates of grade 3-5 toxicity. In the univariate analysis, C max was not a prognostic factor for EFS (p = 0.08) or OS (p = 0.16). C max did not correlate significantly with the oncologic prognosis of non-metastatic extremity osteosarcoma patients treated by multi-agent chemotherapy; however, C max correlated closely with toxicities and complications. The persistent inclusion of methotrexate in classical multidisciplinary chemotherapy was questioned and should be examined in future trials.

  17. Evidence-based recommendations for treatment with methotrexate in rheumatic disorders

    DEFF Research Database (Denmark)

    Madsen, Ole Rintek; Faurschou, Mikkel; Loft, Anne Gitte

    2010-01-01

    The aim of this study was to develop 3E (Evidence, Expertise, Exchange) recommendations (RCs) on the use of methotrexate in rheumatic disorders and to assess the agreement among Danish rheumatologists.......The aim of this study was to develop 3E (Evidence, Expertise, Exchange) recommendations (RCs) on the use of methotrexate in rheumatic disorders and to assess the agreement among Danish rheumatologists....

  18. Chromatic response of polydiacetylene vesicle induced by the permeation of methotrexate.

    Science.gov (United States)

    Shin, Min Jae; Kim, Ye Jin; Kim, Jong-Duk

    2015-07-07

    The noble vesicular system of polydiacetylene showed a red shift using two types of detecting systems. One of the systems involves the absorption of target materials from the outer side of the vesicle, and the other system involves the permeation through the vesicular layers from within the vesicle. The chromatic mixed vesicles of N-(2-aminoethyl)pentacosa-10,12-diynamide (AEPCDA) and dimethyldioctadecylammonium chloride (DODAC) were fabricated by sonication, followed by polymerization by UV irradiation. The stability of monomeric vesicles was observed to increase with the polymerization of the vesicles. Methotrexate was used as a target material. The polymerized mixed vesicles having a blue color were exposed to a concentration gradient of methotrexate, and a red shift was observed indicating the adsorption of methotrexate on the polydiacetylene bilayer. In order to check the chromatic change by the permeation of methotrexate, we separated the vesicle portion, which contained methotrexate inside the vesicle, and checked chromatic change during the permeation of methotrexate through the vesicle. The red shift apparently indicates the disturbance in the bilayer induced by the permeation of methotrexate. The maximum contrast of color appeared at the equal molar ratio of AEPCDA and DODAC, indicating that the formation of flexible and deformable vesicular layers is important for red shift. Therefore, it is hypothesized that the system can be applicable for the chromatic detection of the permeation of methotrexate through the polydiacetylene layer.

  19. Review of dextromethorphan administration in 18 patients with subacute methotrexate central nervous system toxicity.

    Science.gov (United States)

    Afshar, Maryam; Birnbaum, Daniel; Golden, Carla

    2014-06-01

    The pathogenesis of methotrexate central nervous system toxicity is multifactorial, but it is likely related to central nervous system folate homeostasis. The use of folinate rescue has been described to decrease toxicity in patients who had received intrathecal methotrexate. It has also been described in previous studies that there is an elevated level of homocysteine in plasma and cerebrospinal fluid of patients who had received intrathecal methotrexate. Homocysteine is an N-methyl-D-aspartate receptor agonist. The use of dextromethorphan, noncompetitive N-methyl-D-aspartate receptor receptor antagonist, has been used in the treatment of sudden onset of neurological dysfunction associated with methotrexate toxicity. It remains unclear whether the dextromethorphan impacted the speed of recovery, and its use remains controversial. This study reviews the use of dextromethorphan in the setting of subacute methotrexate central nervous system toxicity. Charts of 18 patients who had sudden onset of neurological impairments after receiving methotrexate and were treated with dextromethorphan were reviewed. The use of dextromethorphan in most of our patients resulted in symptomatic improvement. In this patient population, earlier administration of dextromethorphan resulted in faster improvement of impairments and led to prevention of recurrence of seizure activity induced by methotrexate central nervous system toxicity. Our study provides support for the use of dextromethorphan in patients with subacute methotrexate central nervous system toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Changes in serum lipids in patients with rheumatoid arthritis treated with a combination of tocilizumab and methotrexate compared with methotrexate alone for 24 weeks of observation

    Directory of Open Access Journals (Sweden)

    E. V. Udachkina

    2015-11-01

    Full Text Available Background. According to the some studies tocilizumab therapy (TCZ in patients with rheumatoid arthritis (RA is accompanied by deterioration of blood lipid profile. Aim. To study changes in serum lipid parameters in patients with RA treated with a combination of tocilizumab and methotrexate compared with methotrexate alone for 24 weeks of observation. Material and methods. Patients (n=72 with RA were included into the pilot non-randomized 24-week study and divided in two groups: 1 TCZ+MTX group (n=39; women 30; median age 51 [43-55] years; 6 i.v. infusions of TCZ 8 mg/kg + МТX 10-20 mg/week; 2 MTX group (n=33; women 23; mеdian age 56 [48-63] years; MTX 7.5-20 mg/week. Results. At the baseline, similar proatherogenic blood profile was observed in both groups. The patients of MTX group more frequently took statins (n=19; 57.6% compared with the group TCZ+MTX (n=7; 18%, (p<0.05. The lipid levels correlated positively with traditional risk factors (p<0.05. RA activity and duration correlated negatively with high density lipoprotein cholesterol (HDL-C, (p<0.05. Good/satisfactory anti-inflammatory effect was achieved in both groups after 24 weeks of treatment. Patients of TCZ+MTX group showed an increase in total cholesterol and HDL-C levels by 11% and 110%, respectively and decrease in plasma atherogenic index (PAI by 47%, (p<0.05. HDL-C level increased by 22% and PAI decreased by 16% in patients of MTX group (p<0.05. Among patients of MTX group without statin therapy HDL-C as well as non-HDL-C levels were increased by 24% and 27%, respectively (p<0.05; PAI did not change significantly in this subgroup. Among patients of MTX group treated with statins isolated increase in HDL-C level by 22% and decrease in PAI by 37.3% (p<0.05 were observed. A number of patients with achieved target levels of all studied lipid parameters did not change significantly in both groups. Conclusions. TCZ+MTX combined therapy as well as MTX monotherapy are associated

  1. Success and spontaneous pregnancy rates following systemic methotrexate versus laparoscopic surgery for tubal pregnancies: A randomized trial

    DEFF Research Database (Denmark)

    Krag Moeller, Lars Bo; Moeller, Charlotte; Thomsen, Sten Grove

    2009-01-01

    . A total of 106 women diagnosed with ectopic pregnancy (EP). Methods. Between March 1997 and September 2000, 1,265 women were diagnosed with EP, 395 (31%) were eligible, 109 (9%) were randomized of whom 106 had an EP. The study was originally powered to a sample size of 422 patients. The women were......Objective. To determine which treatment should be offered to women with a non-ruptured tubal pregnancy: a single dose of methotrexate (MTX) or laparoscopic surgery. Design. Prospective, randomized, open multicenter study. Setting. Seven Danish departments of obstetrics and gynecology. Sample...... (n.s.). Conclusions. In women with an EP, who are hemodynamically stable and wishing to preserve their fertility, medical treatment with single dose MTX tends to be equal to treatment with laparoscopic surgery regarding success rate, complications, and subsequent fertility. Although the two treatment...

  2. Methotrexate-induced nonhealing cutaneous ulcers in a nonpsoriatic patient without pancytopenia

    Directory of Open Access Journals (Sweden)

    Venkatesh Krishnamurthy Tekur

    2016-01-01

    Full Text Available Methotrexate forms one of the main drugs in the pharmacological management of rheumatoid arthritis, psoriasis, and some neoplastic diseases. Methotrexate rarely causes cutaneous ulceration and most cases are reported in patients with psoriasis and have been accompanied by pancytopenia. The author here reports occurrence of multiple (two cutaneous ulcers due to methotrexate in a nonpsoriatic patient. The patient was on methotrexate for seronegative rheumatoid arthritis for 10 years. To the best of the Author's knowledge, this is a rare case of cutaneous ulceration due to methotrexate in a nonpsoriatic patient reported in the literature so far, and probably one of its kind without pancytopenia or other hematological abnormalities. Stopping this medication led to complete healing of the ulcerated lesion in about four to six weeks.

  3. Rapid, radiochemical-ligand binding assay for methotrexate

    International Nuclear Information System (INIS)

    Caston, J.D.

    1976-01-01

    A radiochemical ligand binding assay for methotrexate is provided. A binder factor comprising a partially purified dihydrofolic acid reductase preparation is employed. The binder factor is conveniently prepared by homogenizing a factor containing animal organ such as liver, and extracting with isotonic saline and ammonium sulfate. A binder cofactor, NADPH 2 , is also employed in the binding reaction. The procedure contemplates both direct and sequential assay techniques, and it is not interfered with by vast excesses of many natural folate derivatives. 12 claims, 6 drawing figures

  4. Anti-tumor Study of Chondroitin Sulfate-Methotrexate Nanogels

    Science.gov (United States)

    Wang, Jinyu; Zhao, Weibo; Chen, Haixiao; Qin, An; Zhu, Peizhi

    2017-10-01

    Self-assembly nanogels (NGs) were formed by bioconjugating methotrexate (MTX) with chondroitin sulfate (CS). MTX-CS NGs can greatly enhance the solubility and improve the delivery efficacy of MTX due to the CD44 binding property of CS. Vivo experiments revealed that MTX-CS NGs showed less toxicity than MTX. MTX-CS NGs can improve the anti-tumor effect while reducing the side effects of MTX. Due to their CD44 binding property, chondroitin sulfate-drug conjugates could be a promising and efficient platform for improving the solubility of sparingly soluble drug molecules as well as targeted delivery to cancer cells and tumor tissues.

  5. Cumulative trauma disorders: A review.

    Science.gov (United States)

    Iqbal, Zaheen A; Alghadir, Ahmad H

    2017-08-03

    Cumulative trauma disorder (CTD) is a term for various injuries of the musculoskeletal and nervous systems that are caused by repetitive tasks, forceful exertions, vibrations, mechanical compression or sustained postures. Although there are many studies citing incidence of CTDs, there are fewer articles about its etiology, pathology and management. The aim of our study was to discuss the etiology, pathogenesis, prevention and management of CTDs. A literature search was performed using various electronic databases. The search was limited to articles in English language pertaining to randomized clinical trials, cohort studies and systematic reviews of CTDs. A total of 180 papers were identified to be relevant published since 1959. Out of these, 125 papers reported about its incidence and 50 about its conservative treatment. Workplace environment, same task repeatability and little variability, decreased time for rest, increase in expectations are major factors for developing CTDs. Prevention of its etiology and early diagnosis can be the best to decrease its incidence and severity. For effective management of CTDs, its treatment should be divided into Primordial, Primary, Secondary and Tertiary prevention.

  6. Complete cumulative index (1963-1983)

    International Nuclear Information System (INIS)

    1983-01-01

    This complete cumulative index covers all regular and special issues and supplements published by Atomic Energy Review (AER) during its lifetime (1963-1983). The complete cumulative index consists of six Indexes: the Index of Abstracts, the Subject Index, the Title Index, the Author Index, the Country Index and the Table of Elements Index. The complete cumulative index supersedes the Cumulative Indexes for Volumes 1-7: 1963-1969 (1970), and for Volumes 1-10: 1963-1972 (1972); this Index also finalizes Atomic Energy Review, the publication of which has recently been terminated by the IAEA

  7. The effect of methotrexate on the bone healing of mandibular condylar process fracture: an experimental study in rats.

    Science.gov (United States)

    Cavalcanti, Samantha Cristine Santos X B; Corrêa, Luciana; Mello, Suzana Beatriz Veríssimo; Luz, João Gualberto C

    2014-10-01

    Methotrexate (MTX) is an anti-metabolite used in rheumatology and oncology. High doses are indicated for oncological treatment, whereas low doses are indicated for chronic inflammatory diseases. This study evaluated the effect of two MTX treatment schedules on the bone healing of the temporomandibular joint fracture in rats. Seventy-five adult male Wistar rats were used to generate an experimental unilateral medially rotated condylar fracture model that allows an evaluation of bone healing and the articular structures. The animals were subdivided into three groups that each received one of the following treatments intraperitoneally: saline (1 mL/week), low-dose MTX (3 mg/kg/week) and high-dose MTX (30 mg/kg). The histological study comprised fracture site and temporomandibular joint evaluations and bone neoformation was evaluated by histomorphometric analysis. A biochemical parameter of bone formation was also assessed. When compared with saline, high-dose MTX delayed bone fracture repairs. In this latter group, after 90 days, the histological analysis revealed atrophy of the fibrocartilage and the presence of fibrous tissue in the joint space. The histomorphometric analysis revealed diminished bone neoformation. The alkaline phosphatase levels also decreased after MTX treatment. It was concluded that high-dose MTX impaired mandibular condyle repair and induced degenerative articular changes. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  8. Etanercept in methotrexate-resistant JIA-related uveitis.

    Science.gov (United States)

    Saeed, Muhammad Usman; Raza, Syed Hamid; Goyal, Sudeshna; Cleary, Gavin; Newman, William David; Chandna, Arvind

    2014-01-01

    We report our results with systemic Etanercept in patients with juvenile idiopathic arthritis in a joint ophthalmology-rheumatology clinic at a tertiary hospital. Patients with JIA on Etanercept were identified from a dedicated uveitis database. A retrospective review of electronic and paper-based patient records was performed. Nine patients with JIA and current or previous treatment with Etanercept were identified, including six females and three males. Five patients with previous or current uveitis were noted. A further four were under observation for uveitis and required Etanercept for their joint disease. All nine patients had previously been taking Methotrexate, which had a suboptimal response in controlling arthritis or uveitis. Six out of nine patients did not show any uveitis activity at their last follow-up. Eyes of three patients still show signs of active inflammation in the anterior chamber (two on Etanercept and one off Etanercept). Severely impaired visual acuity (PL) was recorded in both eyes of one patient with long-standing persistent uveitis. Moderate visual loss in one eye of one patient was seen. The remaining seven patients did not show any significant loss of vision. Intraocular inflammation was not induced in any patient started on Etanercept. Etanercept may be useful in controlling JIA-related uveitis or arthritis in a pediatric patient when Methotrexate has had a suboptimal response in controlling the inflammatory activity.

  9. Collateral methotrexate resistance in cisplatin-selected murine leukemia cells

    Directory of Open Access Journals (Sweden)

    Bhushan A.

    1999-01-01

    Full Text Available Resistance to anticancer drugs is a major cause of failure of many therapeutic protocols. A variety of mechanisms have been proposed to explain this phenomenon. The exact mechanism depends upon the drug of interest as well as the tumor type treated. While studying a cell line selected for its resistance to cisplatin we noted that the cells expressed a >25,000-fold collateral resistance to methotrexate. Given the magnitude of this resistance we elected to investigate this intriguing collateral resistance. From a series of investigations we have identified an alteration in a membrane protein of the resistant cell as compared to the sensitive cells that could be the primary mechanism of resistance. Our studies reviewed here indicate decreased tyrosine phosphorylation of a protein (molecular mass = 66 in the resistant cells, which results in little or no transfer of methotrexate from the medium into the cell. Since this is a relatively novel function for tyrosine phosphorylation, this information may provide insight into possible pharmacological approaches to modify therapeutic regimens by analyzing the status of this protein in tumor samples for a better survival of the cancer patients.

  10. Nanoparticles of Conjugated Methotrexate-Human Serum Albumin: Preparation and Cytotoxicity Evaluations

    Directory of Open Access Journals (Sweden)

    Azade Taheri

    2011-01-01

    Full Text Available Methotrexate-human serum albumin conjugates were developed by a simple carbodiimide reaction. Methotrexate-human serum albumin conjugates were then crosslinked with 1-ethyl-3-(3-dimethylaminopropyl carbodiimide HCl (EDC to form nanoparticles. The size of nanoparticles determined by laser light scattering and TEM was between 90–150 nm. Nanoparticles were very stable at physiologic conditions (PBS pH 7.4, 37∘C and after incubation with serum. The effect of amount of EDC used for crosslinking on the particle size and free amino groups of nanoparticles was examined. The amount of crosslinker showed no significant effect on the size of nanoparticles but free amino groups of nanoparticles were decreased by increasing the crosslinker. The physicochemical interactions between methotrexate and human serum albumin were investigated by differential scanning calorimetry (DSC. Nanoparticles were more cytotoxic on T47D cells compared to free methotrexate. Moreover, methotrexate-human serum albumin nanoparticles decreased the IC50 value of methotrexate on T47D cells in comparison with free methotrexate.

  11. Nanoparticles of Conjugated Methotrexate-Human Serum Albumin: Preparation and Cytotoxicity Evaluations

    International Nuclear Information System (INIS)

    Taheri, A.; Atyabi, F.; Nouri, F.S.; Ahadi, F.; Derakhshan, M.A.; Dinarvand, R.; Atyabi, F.; Ghahremani, M.H.; Ostad, S.N.; Dinarvand, R.; Amini, M.; Ghahremani, M.H.; Ostad, S.N.; Mansoori, P.

    2011-01-01

    Methotrexate-human serum albumin conjugates were developed by a simple carbodiimide reaction. Methotrexate-human serum albumin conjugates were then crosslinked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide HCl (EDC) to form nanoparticles. The size of nanoparticles determined by laser light scattering and TEM was between 90 150 nm. Nanoparticles were very stable at physiologic conditions (PBS pH 7.4, 37 degree C) and after incubation with serum. The effect of amount of EDC used for crosslinking on the particle size and free amino groups of nanoparticles was examined. The amount of cross linker showed no significant effect on the size of nanoparticles but free amino groups of nanoparticles were decreased by increasing the cross linker. The physicochemical interactions between methotrexate and human serum albumin were investigated by differential scanning calorimetry (DSC). Nanoparticles were more cytotoxic on T 47 D cells compared to free methotrexate. Moreover, methotrexate-human serum albumin nanoparticles decreased the C50 value of methotrexate on T 47 D cells in comparison with free methotrexate.

  12. Pharmacogenetic markers to predict the clinical response to methotrexate in south Indian Tamil patients with psoriasis.

    Science.gov (United States)

    Indhumathi, S; Rajappa, Medha; Chandrashekar, Laxmisha; Ananthanarayanan, P H; Thappa, D M; Negi, V S

    2017-08-01

    Despite the advent of several new systemic therapies, methotrexate remains the gold standard for the treatment of moderate to severe psoriasis. However, there exists a significant heterogeneity in individual response to methotrexate. There are no consistently reliable markers to predict methotrexate treatment response till date. We aimed to demonstrate the association of certain genetic variants in the HLA (HLA-A2, HLA-B17, and HLA-Cw6) and the non-HLA genes including T-helper (Th)-1, Th-2, Th-17 cytokine genes (IFN-γ, IL-2, IL-4, IL-10, IL-12B, and IL-23R), and T-regulatory gene (FOXP3) with the methotrexate treatment response in South Indian Tamil patients with psoriasis. Of the 360 patients recruited, 189 patients with moderate to severe psoriasis were treated with methotrexate. Of the 189 patients, 132 patients responded to methotrexate and the remaining 57 patients were non-responders. We analyzed the association of aforesaid polymorphisms with the methotrexate treatment outcome using binary logistic regression. We observed that there were significant differences between genotype frequencies of HLA-Cw6 and FOXP3 (rs3761548) among the responders compared to non-responders, with conservative estimation. We observed that pro-inflammatory cytokines such as IFN-γ, IL-2, IL-12, and IL-23 were markedly reduced with the use of methotrexate, in comparison to the baseline levels, while the plasma IL-4 levels were increased posttreatment. Our results serve as preliminary evidence for the clinical use of genetic markers as predictors of response to methotrexate in psoriasis. This might aid in the future in the development of a point-of-care testing (POCT) gene chip, to predict optimal treatment response in patients with psoriasis, based on their individual genotypic profile.

  13. System-Reliability Cumulative-Binomial Program

    Science.gov (United States)

    Scheuer, Ernest M.; Bowerman, Paul N.

    1989-01-01

    Cumulative-binomial computer program, NEWTONP, one of set of three programs, calculates cumulative binomial probability distributions for arbitrary inputs. NEWTONP, CUMBIN (NPO-17555), and CROSSER (NPO-17557), used independently of one another. Program finds probability required to yield given system reliability. Used by statisticians and users of statistical procedures, test planners, designers, and numerical analysts. Program written in C.

  14. Common-Reliability Cumulative-Binomial Program

    Science.gov (United States)

    Scheuer, Ernest, M.; Bowerman, Paul N.

    1989-01-01

    Cumulative-binomial computer program, CROSSER, one of set of three programs, calculates cumulative binomial probability distributions for arbitrary inputs. CROSSER, CUMBIN (NPO-17555), and NEWTONP (NPO-17556), used independently of one another. Point of equality between reliability of system and common reliability of components found. Used by statisticians and users of statistical procedures, test planners, designers, and numerical analysts. Program written in C.

  15. Cumulative human impacts on marine predators

    DEFF Research Database (Denmark)

    Maxwell, Sara M; Hazen, Elliott L; Bograd, Steven J

    2013-01-01

    Stressors associated with human activities interact in complex ways to affect marine ecosystems, yet we lack spatially explicit assessments of cumulative impacts on ecologically and economically key components such as marine predators. Here we develop a metric of cumulative utilization and impact...

  16. Cumulative Student Loan Debt in Minnesota, 2015

    Science.gov (United States)

    Williams-Wyche, Shaun

    2016-01-01

    To better understand student debt in Minnesota, the Minnesota Office of Higher Education (the Office) gathers information on cumulative student loan debt from Minnesota degree-granting institutions. These data detail the number of students with loans by institution, the cumulative student loan debt incurred at that institution, and the percentage…

  17. Yellow fever vaccine used in a psoriatic arthritis patient treated with methotrexate: a case report.

    Science.gov (United States)

    Stuhec, Matej

    2014-01-01

    The yellow fever vaccines on the market are contraindicated for immunocompromised and elderly patients. A case of yellow fever vaccine used in a 27-year-old Slovenian male with psoriatic arthritis during treatment with methotrexate is described. We demonstrate a positive case, since there were no adverse effects in concurrent administration of yellow fever vaccine and methotrexate. This patient did not show severe adverse reactions and did not contract yellow fever despite potential exposure. More research is needed on possible adverse effects of concurrent administration of yellow fever vaccine and methotrexate to determine the potential of this method for more frequent use.

  18. [Recommendations for the use of methotrexate in patients with juvenile idiopathic arthritis].

    Science.gov (United States)

    Calvo, I; Antón, J; López Robledillo, J C; de Inocencio, J; Gamir, M L; Merino, R; Lacruz, L; Camacho, M; Rua, M J; Bustabad, S; Díaz Cordovés-Rego, G

    2016-03-01

    To develop a consensus document of recommendations for the use of methotrexate (MTX) in patients with juvenile idiopathic arthritis (JIA). A group of eleven experts proposed several clinical questions on the use of MTX in patients with JIA. A systematic review was conducted and the evidence and recommendations for each question were extracted. The results were discussed and validated by the experts in a work session to establish the final recommendations. MTX is recommended as the first drug for inducing remission in JIA, and its indication should be made according to the clinical category of the patient. Prior to treatment, it is recommended to perform a complete blood count, including white cells, levels of liver enzymes, serum creatinine, and other analytical parameters according to specific risk factors. Treatment should be initiated with a dose of 10-15 mg/m(2)/week. In cases of uveitis or polyarthritis, an initial dose of 15 mg/m(2)/week should be considered. For a better bioavailability and tolerability, it is preferable to administer MTX parenterally if the dose is ≥15 mg/m(2)/week. It is necessary to periodically perform an analytical monitoring of the patient and to assess possible alterations in liver enzymes to make changes if necessary. Combinations with biological agents may be necessary, as well as the concomitant addition of folic or folinic acid. This document describes the main recommendations for the appropriate use of MTX in JIA patients, according to scientific evidence and clinical experience. Copyright © 2015 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  19. The Australasian Psoriasis Collaboration view on methotrexate for psoriasis in the Australasian setting.

    Science.gov (United States)

    Rademaker, Marius; Gupta, Monisha; Andrews, Megan; Armour, Katherine; Baker, Chris; Foley, Peter; Gebauer, Kurt; George, Jacob; Rubel, Diana; Sullivan, John

    2017-08-01

    The Australasian Psoriasis Collaboration reviewed methotrexate (MTX) in the management of psoriasis in the Australian and New Zealand setting. The following comments are based on expert opinion and a literature review. Low-dose MTX (< 0.4 mg/kg per week) has a slow onset of action and has moderate to good efficacy, together with an acceptable safety profile. The mechanism of action is anti-inflammatory, rather than immunosuppressive. For pretreatment, consider testing full blood count (FBC), liver and renal function, non-fasting lipids, hepatitis serology, HbA1c and glucose. Body mass index and abdominal circumference should also be measured. Optional investigations in at-risk groups include an HIV test, a QuantiFERON-TB Gold test and a chest X-ray. In patients without complications, repeat the FBC at 2-4 weeks, then every 3-6 months and the liver/renal function test at 3 months and then every 6 months. There is little evidence that a MTX test dose is of value. Low-dose MTX rarely causes clinically significant hepatotoxicity in psoriasis. Most treatment-emergent liver toxicity is related to underlying metabolic syndrome and non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. Alcohol itself is not contraindicated, but should be limited to < 20 gm/day. [Correction added on 6 January 2017, after first online publication: '20 mg/day' has been corrected to '20 gm/day'.] Although MTX is a potential teratogen post-conception, there is little evidence for this pre-conception. MTX does not affect the quality of sperm. There is no evidence that MTX reduces healing, so there is no specific need to stop MTX peri-surgery. MTX may be used in combination with cyclosporine, acitretin, prednisone and anti-tumour necrosis factor biologics. © 2016 The Australasian College of Dermatologists.

  20. Double-modulation of 5-Fluorouracil by methotrexate and leucovorin in advanced colorectal-carcinoma.

    Science.gov (United States)

    Leone, B; Romero, A; Rabinovich, M; Vallejo, C; Bianco, A; Perez, J; Rodriguez, R; Cuevas, M; Machiavelli, M; Paris, A; Lacava, J

    1993-11-01

    A phase II trial was performed to evaluate the efficacy and toxicity of a double modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and leucovorin (LV) as first line chemotherapy in advanced colorectal carcinoma. Between January 1990, and April 1992, 42 patients with metastatic or advanced recurrent (inoperable) colorectal cancer were entered into the study. Therapy consisted of a sequential combination of MTX, LV and 5-FU. MTX was administered at a dose of 150 mg/m2 over 20 minutes I.V. infusion at hour (h) 0, followed 19 h later by LV 50 mg/m2 over 2 h infusion. 5-FU 900 mg/m2 was given by I.V. push injection at h 20. Starting 24 h after MTX administration all patients received LV 15 mg/m2 intramuscularly every 6 h for six doses. Treatment was repeated every 15 days until progressive disease, severe toxicity, or death. Four patients were considered not evaluable for response. Objective regression (OR) was observed in 14 of 38 patients (37%, 95% confidence interval 23-53%). Two patients (5%) obtained complete response (CR) and 12 (32%) partial response (PR). Median time to treatment failure was 6 months (range 1-21). Median survival for the whole group of patients was 13 months (range 1-27). Toxicity was within acceptable limits but one therapy-related death due to severe leukopenia and sepsis was observed. Double modulation of 5-FU with MTX and low dose of LV is an active regimen against advanced colorectal carcinoma and represents a promising strategy that should be further explored.

  1. Carvacrol and Pomegranate Extract in Treating Methotrexate-Induced Lung Oxidative Injury in Rats

    Science.gov (United States)

    Şen, Hadice Selimoğlu; Şen, Velat; Bozkurt, Mehtap; Türkçü, Gül; Güzel, Abdulmenap; Sezgi, Cengizhan; Abakay, Özlem; Kaplan, Ibrahim

    2014-01-01

    Background This study was designed to evaluate the effects of carvacrol (CRV) and pomegranate extract (PE) on methotrexate (MTX)-induced lung injury in rats. Material/Methods A total of 32 male rats were subdivided into 4 groups: control (group I), MTX treated (group II), MTX+CRV treated (group III), and MTX+PE treated (group IV). A single dose of 73 mg/kg CRV was administered intraperitoneally to rats in group III on Day 1 of the investigation. To group IV, a dose of 225 mg/kg of PE was administered via orogastric gavage once daily over 7 days. A single dose of 20 mg/kg of MTX was given intraperitoneally to groups II, III, and IV on Day 2. The total duration of experiment was 8 days. Malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) were measured from rat lung tissues and cardiac blood samples. Results Serum and lung specimen analyses demonstrated that MDA, TOS, and OSI levels were significantly greater in group II relative to controls. Conversely, the TAC level was significantly reduced in group II when compared to the control group. Pre-administering either CRV or PE was associated with decreased MDA, TOS, and OSI levels and increased TAC levels compared to rats treated with MTX alone. Histopathological examination revealed that lung injury was less severe in group III and IV relative to group II. Conclusions MTX treatment results in rat lung oxidative damage that is partially counteracted by pretreatment with either CRV or PE. PMID:25326861

  2. Microfluidic platform for dynamic in vitro optimization of methotrexate-loaded lipid nanoparticle delivery for personalized osteosarcoma treatment

    Energy Technology Data Exchange (ETDEWEB)

    Muñoz-Hernando, M.; Macias, P.; Abella, M.; Desco, M.; Sharpe, S.; Vaquero, J.J.; Muñoz-Barrutia, M.

    2016-07-01

    Cancer is a leading cause of mortality in the world, with osteosarcoma being one of the most common types among children between 1 and 14 years old. The use of lipid nanoparticles as biodegradable shells for controlled drug delivery shows promise as a more effective and targeted tumor treatment. However, current techniques for in vitro testing of these vehicles have shown little validity due to their static nature, in which nanoparticles sediment onto the bottom of the wells and kill the cells via asphyxiation, hiding the real effect achieved by the nanoparticles. In this work, a microfluidic platform capable of determining the optimum dose of methotrexate-loaded lipid nanoparticles in osteosarcoma treatment is presented as a promising alternative to current nanoparticle characterization assays. (Author)

  3. Methotrexate is an effective treatment for chronic uveitis associated with juvenile idiopathic arthritis.

    Science.gov (United States)

    Foeldvari, Ivan; Wierk, Angela

    2005-02-01

    To assess the effectiveness of methotrexate (MTX) in the treatment of juvenile idiopathic arthritis (JIA) associated uveitis, which is still one of the most common causes of visual impairment. A retrospective chart review of patients with the diagnosis of uveitis associated with JIA between July 1, 2002, and December 31, 2002. Four hundred sixty-seven patients with JIA were followed. Thirty-eight had uveitis: 31 associated with oligoarticular JIA and 7 with psoriatic JIA. Twenty-five of the 38 patients received MTX; in 23 patients uveitis was the indication for MTX therapy. In the MTX treated group 46/50 eyes had uveitis, the mean (range) age at onset of uveitis was 7.82 years (1.8-15.8), and the mean age at onset of arthritis was 7.25 years (1.25-15.7). MTX treatment was started an average of 11.4 months (0-72) after the onset of uveitis. The mean MTX dose was 15.6 mg/m2. Remission occurred after 4.25 months (1-12). Mean duration of remission was 10.3 months (3-27). The total duration of MTX therapy was 661 months and patients were in remission for 417/661 months. In 6 patients MTX was discontinued after 12 months of remission. Four patients were still in remission after 7.5 months (1-14). MTX seems to be an effective therapy for JIA associated uveitis.

  4. Marrow transplantation for leukemia following fractionated total body irradiation. A comparative trial of methotrexate and cyclosporine

    International Nuclear Information System (INIS)

    Irle, C.; Deeg, H.J.; Buckner, C.D.; Swedish Hospital Medical Center, Seattle, WA; Veterans Administration Hospital, Seattle, WA; Washington Univ., Seattle

    1985-01-01

    Fifty-six patients, 30-47 yr of age, with leukemia in relapse received allogeneic marrow transplants from HLA-identical siblings. All patients were treated with cyclophosphamide (120 mg/kg) and 7 daily fractions of 2.25 Gy of total body irradiation (TBI) for seven consecutive days. Nine patients (16%) are currently alive, free of disease, 324-845 days from transplantation. Actuarial relapse and survival rates at 2 yr were 56% and 9.5% respectively. These data were not remarkably different from those in previous studies using 10 Gy of TBI administered as a single dose. Thirty patients were randomized to receive methotrexate (MTX) and 26 to receive cyclosporine (CSP) as postgrafting prophylaxis for acute graft-versus-host disease (GVHD). Probability of developing significant acute GVHD by day 100 post-transplant was 71% for patients in the MTX group and 45% for patients in the CSP group (p<0.05). Probability of relapse was 37% for patients in the MTX group and 70% for patients in the CSP group (p<0.05). Transplant-related deaths were more frequent in the MTX group and leukemic deaths more frequent in the CSP group although this may have been related to an uneven distribution of high-risk patients. Long term disease-free survival was comparable. (author)

  5. Laser-assisted delivery of topical methotrexate - in vitro investigations

    DEFF Research Database (Denmark)

    Taudorf, Elisabeth Hjardem

    2016-01-01

    of the correlation between laser parameters and tissue effects was used to deliver methotrexate (MTX) topically through microscopic ablation zones (MAZs) of precise dimensions. MTX is a well-known chemotherapeutic and anti-inflammatory drug that may cause systemic adverse effects, and topical delivery is thus......Ablative fractional lasers (AFXL) are increasingly used to treat dermatological disorders and to facilitate laser-assisted topical drug delivery. In this thesis, laser-tissue interactions generated by stacked pulses with a miniaturized low-power 2,940 nm AFXL were characterized (study I). Knowledge...... zones of varying thickness. The ratio of skin deposition versus transdermal permeation was constant, regardless of MAZ depth. Impact of transport kinetics on AFXL-assisted topical MTX delivery: MTX accumulated rapidly in AFXL-processed skin. MTX was detectable in mid-dermis after 15 min. and saturated...

  6. Adverse effects of methotrexate in three psoriatic arthritis patients.

    Science.gov (United States)

    Maejima, Hideki; Watarai, Akira; Nakano, Toshiaki; Katayama, Chieko; Nishiyama, Hiromi; Katsuoka, Kensei

    2014-04-01

    Methotrexate, a folic acid analogue with anti-proliferative and anti-inflammatory effects, is commonly used to treat patients with severe destructive psoriatic arthritis and has considerable efficacy. Combined anti-tumor necrosis factor and MTX therapy result in less treatment discontinuation due to adverse events. Despite its efficacy, MTX may result in adverse effects including hepatic, pulmonary, and renal toxicity as well as lymphoproliferative disorders and predisposition to infection. We herein report rare adverse effects of MTX treatment, specifically asymptomatic pulmonary tuberculosis, renal cell carcinoma, and lateral uveitis, in three psoriatic arthritis patients treated with MTX. MTX is an important drug for the treatment for psoriatic arthritis patient, but an awareness of the possible adverse effects is needed.

  7. Fast analysis procedure of radiochemical coordinat uptake for methotrexate

    International Nuclear Information System (INIS)

    Caston, J.D.; Kamen, B.A.

    1976-01-01

    Under this invention, a radio-chemical analysis is submitted to determine the concentration of methotrexate or its equivalents in analysis in a biological medium. The amounts taken up of the labelled compound and the known concentrations of the unlabelled compound to be determined are radio-isotopically related to a first system containing a pre-determined amount of the labelled compound and a pre-determined amount of the unlabelled compound. In a second system, identical to the first, save that the sample of the biological medium to be analyzed takes the place of the unlabelled compound, the amount of labelled compound taken up is determined radio-isotopically. The concentration of the compound in the sample is then determined by correlation of the labelled compound uptake determined in the second system with the relation determined in the first system. The radio-isotopic relations and determinations may be made by direct and sequential analytical techniques [fr

  8. Pharmacology and optimization of thiopurines and methotrexate in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Steenholdt, Casper; de Boer, Nanne K.

    2016-01-01

    Improving the efficacy and reducing the toxicity of thiopurines and methotrexate (MTX) have been areas of intense basic and clinical research. An increased knowledge on pharmacodynamics and pharmacokinetics of these immunomodulators has optimized treatment strategies in inflammatory bowel disease...

  9. Effect of minimal enteral feeding on recovery in a methotrexate-induced gastrointestinal mucositis rat model

    NARCIS (Netherlands)

    Kuiken, Nicoline S. S.; Rings, Edmond H. H. M.; Havinga, Rick; Groen, Albert K.; Tissing, Wim J. E.

    Patients suffering from gastrointestinal mucositis often receive parenteral nutrition as nutritional support. However, the absence of enteral nutrition might not be beneficial for the intestine. We aimed to determine the feasibility of minimal enteral feeding (MEF) administration in a methotrexate

  10. HER2 specific delivery of methotrexate by dendrimer conjugated anti-HER2 mAb

    International Nuclear Information System (INIS)

    Shukla, Rameshwer; Thomas, Thommey P; Desai, Ankur M; Kotlyar, Alina; Park, Steve J; Baker, James R Jr

    2008-01-01

    Herceptin, a humanized monoclonal antibody that binds to human growth factor receptor-2 (HER2), was covalently attached to a fifth-generation (G5) polyamidoamine dendrimer containing the cytotoxic drug methotrexate. The specific binding and internalization of this conjugate labeled with FITC was clearly demonstrated in cell lines overexpressing HER2 by flow cytometry as well as confocal microscopic analysis. In addition, binding and uptake of antibody conjugated dendrimers was completely blocked by excess non-conjugated herceptin. The dendrimer conjugate was also shown to inhibit the dihydrofolate reductase with similar activity to methotrexate. Co-localization experiments with lysotracker red indicate that antibody conjugate, although internalized efficiently into cells, has an unusually long residence time in the lysosome. Somewhat lower cytotoxicity of the conjugate in comparison to free methotrexate was attributed to the slow release of methotrexate from the conjugate and its long retention in the lysosomal pocket

  11. Selective sparing of goblet cells and paneth cells in the intestine of methotrexate-treated rats

    NARCIS (Netherlands)

    M. Verburg (Melissa); I.B. Renes (Ingrid); H.P. Meijer; J.A. Taminiau; H.A. Büller (Hans); A.W.C. Einerhand (Sandra); J. Dekker (Jan)

    2000-01-01

    textabstractProliferation, differentiation, and cell death were studied in small intestinal and colonic epithelia of rats after treatment with methotrexate. Days 1-2 after treatment were characterized by decreased proliferation, increased apoptosis, and decreased numbers and depths

  12. Transporter-mediated interaction of indican and methotrexate in rats

    Directory of Open Access Journals (Sweden)

    Shiuan-Pey Lin

    2018-04-01

    Full Text Available Indican (indoxyl-β-D-glucoside is present in several Chinese herbs e.g. Isatis indigotica, Polygonum tinctorium and Polygonum perfoliatum. The major metabolite of indican was indoxyl sulfate (IS, an uremic toxin which was a known substrate/inhibitor of organic anion transporter (OAT 1, OAT 3 and multidrug resistance-associated protein (MRP 4. Methotrexate (MTX, an important immunosuppressant with narrow therapeutic window, is a substrate of OAT 1, 2, 3, 4 and MRP 1, 2, 3, 4. We hypothesized that IS, the major metabolite of oral indican, might inhibit the renal excretion of MTX mediated by OAT 1, OAT 3 and MRP 4. Therefore, this study investigated the effect of oral indican on the pharmacokinetics of MTX. Rats were orally given MTX with and without indican (20.0 and 40.0 mg/kg in a parallel design. The serum MTX concentration was determined by a fluorescence polarization immunoassay. For mechanism clarification, phenolsulfonphthalein (PSP, 5.0 mg/kg, a probe substrate of OAT 1, OAT 3, MRP 2 and MRP 4, was intravenously given to rats with and without a intravenous bolus of IS (10.0 mg/kg to measure the effect of IS on the elimination of PSP. The results indicated that 20.0 and 40.0 mg/kg of oral indican significantly increased the area under concentration–time curve0-t (AUC0-t of MTX by 231% and 259%, prolonged the mean residence time (MRT by 223% and 204%, respectively. Furthermore, intravenous IS significantly increased the AUC0-t of PSP by 204% and decreased the Cl by 68%. In conclusion, oral indican increased the systemic exposure and MRT of MTX through inhibition on multiple anion transporters including OAT 1, OAT 3 and MRP 4 by the major metabolite IS. Keywords: Indican, Indoxyl sulfate, Methotrexate, Anion transporters, Pharmacokinetics

  13. Methotrexate: an effective monotherapy for refractory generalized morphea

    Directory of Open Access Journals (Sweden)

    Platsidaki E

    2017-05-01

    Full Text Available Eftychia Platsidaki, Vassiliki Tzanetakou, Anargyros Kouris, Panagiotis G Stavropoulos Department of Dermatology and Venereology, Andreas Syggros Hospital, University of Athens, Athens, Greece Introduction: Morphea is an inflammatory skin disorder characterized by excessive collagen deposition. Although treatment algorithms for morphea subtypes have been suggested, no consistent recommendations are available. This study attempts to evaluate the clinical efficacy of methotrexate (MTX as monotherapy in refractory generalized morphea. Methods: It is a retrospective study, including 20 patients who had already been treated with various topical and systemic therapies with minimal clinical improvement. Patients received orally MTX at a of dosage 15 mg once weekly. Duration of the use, dosage of MTX, and adverse events were recorded. Clinical assessment of skin lesions was performed and documented. Results: The mean disease duration was 27 months before the initiation of MTX treatment. After 12 months of therapy, very good response was achieved in 6 patients (30%, good response in 10 patients (50%, and fair response in 2 patients (10%, while 2 patients (10% had failed treatment. Patients were followed up for a mean time interval of 21 months. No serious adverse event was recorded. Conclusion: MTX has been already proved to be an effective and well-tolerated treatment in pediatric patients with morphea. The majority of the group of adult patients showed very good and good improvement when treated with MTX. Although this is an uncontrolled study, MTX monotherapy was considered a safe and effective treatment for the management of this specific clinical subset of morphea in adults. Keywords: methotrexate, adults, generalized morphea

  14. Yellow fever vaccine used in a psoriatic arthritis patient treated with methotrexate: a case report:

    OpenAIRE

    Štuhec, Matej

    2014-01-01

    The yellow fever vaccines on the market are contraindicated for immunocompromised and elderly patients. A case of yellow fever vaccine used in a 27-year-old Slovenian male with psoriatic arthritis during treatment with methotrexate is described. We demonstrate a positive case, since there were noadverse effects in concurrent administration of yellow fever vaccine and methotrexate. This patient did not show severe adverse reactions and did not contract yellow fever despite potential exposure. ...

  15. Yellow fever vaccine used in a psoriatic arthritis patient treated with methotrexate

    OpenAIRE

    Štuhec, Matej

    2015-01-01

    The yellow fever vaccines on the market are contraindicated for immunocompromised and elderly patients. A case of yellow fever vaccine used in a 27-year-old Slovenian male with psoriatic arthritis during treatment with methotrexate is described. We demonstrate a positive case, since there were noadverse effects in concurrent administration of yellow fever vaccine and methotrexate. This patient did not show severe adverse reactions and did not contract yellow fever despite potential exposure. ...

  16. Plasma MicroRNA Profiles in Patients with Early Rheumatoid Arthritis Responding to Adalimumab plus Methotrexate vs Methotrexate Alone

    DEFF Research Database (Denmark)

    Sode, Jacob; Krintel, Sophine B; Carlsen, Anting Liu

    2018-01-01

    OBJECTIVE: The aim was to identify plasma (i.e., cell-free) microRNA (miRNA) predicting antitumor necrosis and/or methotrexate (MTX) treatment response in patients enrolled in an investigator-initiated, prospective, double-blinded, placebo-controlled trial (The OPERA study, NCT00660647). METHODS......: We included 180 disease-modifying antirheumatic drug-naive patients with early rheumatoid arthritis (RA) randomized to adalimumab (ADA; n = 89) or placebo (n = 91) in combination with MTX. Plasma samples before and 3 months after treatment initiation were analyzed for 91 specific mi...... multivariate miRNA models were able to predict response to ADA treatment after 3 and 12 months, with 63% and 82% area under the ROC curves, respectively. CONCLUSION: We identified miR-27a-3p as a potential predictive biomarker of ACR/EULAR remission in patients with early RA treated with ADA in combination...

  17. The Relationship between Gender, Cumulative Adversities and ...

    African Journals Online (AJOL)

    The Relationship between Gender, Cumulative Adversities and Mental Health of Employees in ... CAs were measured in three forms (family adversities (CAFam), personal adversities ... Age of employees ranged between 18-65 years.

  18. Cumulative cultural learning: Development and diversity

    Science.gov (United States)

    2017-01-01

    The complexity and variability of human culture is unmatched by any other species. Humans live in culturally constructed niches filled with artifacts, skills, beliefs, and practices that have been inherited, accumulated, and modified over generations. A causal account of the complexity of human culture must explain its distinguishing characteristics: It is cumulative and highly variable within and across populations. I propose that the psychological adaptations supporting cumulative cultural transmission are universal but are sufficiently flexible to support the acquisition of highly variable behavioral repertoires. This paper describes variation in the transmission practices (teaching) and acquisition strategies (imitation) that support cumulative cultural learning in childhood. Examining flexibility and variation in caregiver socialization and children’s learning extends our understanding of evolution in living systems by providing insight into the psychological foundations of cumulative cultural transmission—the cornerstone of human cultural diversity. PMID:28739945

  19. Complexity and demographic explanations of cumulative culture

    NARCIS (Netherlands)

    Querbes, A.; Vaesen, K.; Houkes, W.N.

    2014-01-01

    Formal models have linked prehistoric and historical instances of technological change (e.g., the Upper Paleolithic transition, cultural loss in Holocene Tasmania, scientific progress since the late nineteenth century) to demographic change. According to these models, cumulation of technological

  20. Cumulative human impacts on marine predators.

    Science.gov (United States)

    Maxwell, Sara M; Hazen, Elliott L; Bograd, Steven J; Halpern, Benjamin S; Breed, Greg A; Nickel, Barry; Teutschel, Nicole M; Crowder, Larry B; Benson, Scott; Dutton, Peter H; Bailey, Helen; Kappes, Michelle A; Kuhn, Carey E; Weise, Michael J; Mate, Bruce; Shaffer, Scott A; Hassrick, Jason L; Henry, Robert W; Irvine, Ladd; McDonald, Birgitte I; Robinson, Patrick W; Block, Barbara A; Costa, Daniel P

    2013-01-01

    Stressors associated with human activities interact in complex ways to affect marine ecosystems, yet we lack spatially explicit assessments of cumulative impacts on ecologically and economically key components such as marine predators. Here we develop a metric of cumulative utilization and impact (CUI) on marine predators by combining electronic tracking data of eight protected predator species (n=685 individuals) in the California Current Ecosystem with data on 24 anthropogenic stressors. We show significant variation in CUI with some of the highest impacts within US National Marine Sanctuaries. High variation in underlying species and cumulative impact distributions means that neither alone is sufficient for effective spatial management. Instead, comprehensive management approaches accounting for both cumulative human impacts and trade-offs among multiple stressors must be applied in planning the use of marine resources.

  1. Cumulative cultural learning: Development and diversity.

    Science.gov (United States)

    Legare, Cristine H

    2017-07-24

    The complexity and variability of human culture is unmatched by any other species. Humans live in culturally constructed niches filled with artifacts, skills, beliefs, and practices that have been inherited, accumulated, and modified over generations. A causal account of the complexity of human culture must explain its distinguishing characteristics: It is cumulative and highly variable within and across populations. I propose that the psychological adaptations supporting cumulative cultural transmission are universal but are sufficiently flexible to support the acquisition of highly variable behavioral repertoires. This paper describes variation in the transmission practices (teaching) and acquisition strategies (imitation) that support cumulative cultural learning in childhood. Examining flexibility and variation in caregiver socialization and children's learning extends our understanding of evolution in living systems by providing insight into the psychological foundations of cumulative cultural transmission-the cornerstone of human cultural diversity.

  2. Calculating Cumulative Binomial-Distribution Probabilities

    Science.gov (United States)

    Scheuer, Ernest M.; Bowerman, Paul N.

    1989-01-01

    Cumulative-binomial computer program, CUMBIN, one of set of three programs, calculates cumulative binomial probability distributions for arbitrary inputs. CUMBIN, NEWTONP (NPO-17556), and CROSSER (NPO-17557), used independently of one another. Reliabilities and availabilities of k-out-of-n systems analyzed. Used by statisticians and users of statistical procedures, test planners, designers, and numerical analysts. Used for calculations of reliability and availability. Program written in C.

  3. About the cumulants of periodic signals

    Science.gov (United States)

    Barrau, Axel; El Badaoui, Mohammed

    2018-01-01

    This note studies cumulants of time series. These functions originating from the probability theory being commonly used as features of deterministic signals, their classical properties are examined in this modified framework. We show additivity of cumulants, ensured in the case of independent random variables, requires here a different hypothesis. Practical applications are proposed, in particular an analysis of the failure of the JADE algorithm to separate some specific periodic signals.

  4. Cumulative effects assessment: Does scale matter?

    International Nuclear Information System (INIS)

    Therivel, Riki; Ross, Bill

    2007-01-01

    Cumulative effects assessment (CEA) is (or should be) an integral part of environmental assessment at both the project and the more strategic level. CEA helps to link the different scales of environmental assessment in that it focuses on how a given receptor is affected by the totality of plans, projects and activities, rather than on the effects of a particular plan or project. This article reviews how CEAs consider, and could consider, scale issues: spatial extent, level of detail, and temporal issues. It is based on an analysis of Canadian project-level CEAs and UK strategic-level CEAs. Based on a review of literature and, especially, case studies with which the authors are familiar, it concludes that scale issues are poorly considered at both levels, with particular problems being unclear or non-existing cumulative effects scoping methodologies; poor consideration of past or likely future human activities beyond the plan or project in question; attempts to apportion 'blame' for cumulative effects; and, at the plan level, limited management of cumulative effects caused particularly by the absence of consent regimes. Scale issues are important in most of these problems. However both strategic-level and project-level CEA have much potential for managing cumulative effects through better siting and phasing of development, demand reduction and other behavioural changes, and particularly through setting development consent rules for projects. The lack of strategic resource-based thresholds constrains the robust management of strategic-level cumulative effects

  5. The impact of gallic acid on the methotrexate-induced kidney damage in rats

    Directory of Open Access Journals (Sweden)

    Halil Asci

    2017-10-01

    Full Text Available Prolonged use of an antineoplastic agent methotrexate (MTX, can cause numerous side effects such as nephrotoxicity. The aim of this study was to examine the effects of MTX on kidneys and demonstrate the protective effects of gallic acid (GA. Twenty-four, male, rats distributed into three groups. Each groups consisted eight rats and only saline was administered to the control group. The MTX group received a single dose (20 mg/kg MTX intraperitoneally. The MTX + GA group received same dose MTX and 100 mg/kg GA orally during the 7 days. Renal functions, oxidative stress markers, histopathological and immunohistochemical changes were evaluated at the end of the experiment. Blood urea nitrogen, creatinine, uric acid levels and tissue oxidative stress markers, total oxidant status and oxidative stress index levels significantly increased and total antioxidant status levels significantly decreased in MTX group compared with the control group. At the histopathological examination hemorrhages, tubular cell necrosis, glomerulosclerosis, inflammatory cell infiltrations and proteinous materials in tubules were noticed in MTX group. Immunohistochemical examination revealed that increased expressions of serum amyloid A (SAA, tumor necrosis factor alpha (TNF-α, prostaglandin E2 (PGE-2 and C-reactive protein (CRP in tubular epithelial cells of kidneys in this group. There were no immunoreaction with SAA and CRP, only small number of PGE-2 and TNF-α positive tubular epithelial cells were observed in MTX + GA group. In conclusion, all evidence suggested that oxidative stress caused MTX-induced nephrotoxicity and GA prevent the kidney from the nephrotoxicity due to its antioxidant and anti-inflammatory activities.

  6. Systemic methotrexate to treat ectopic pregnancy does not affect ovarian reserve.

    Science.gov (United States)

    Oriol, Bárbara; Barrio, Ana; Pacheco, Alberto; Serna, José; Zuzuarregui, José Luis; Garcia-Velasco, Juan A

    2008-11-01

    To evaluate whether methotrexate (MTX) compromises ovarian reserve and future reproductive outcome in women undergoing assisted reproductive technology (ART), when it is used as first-line treatment for ectopic pregnancy (EP). Prospective, observational study. University-affiliated private IVF unit. Twenty-five women undergoing IVF-ICSI who were treated with MTX (1 mg/kg IM) for an EP after ART. Evaluation of reproductive outcome and serum anti-Müllerian hormone (AMH) levels. Serum AMH was evaluated before administering MTX and >or=1 week after the resolution of the EP. Reproductive outcome was evaluated by comparing subsequent IVF-ICSI cycles after EP resolution. Serum AMH levels, cycle length, gonadotropin dose required, peak serum E(2) level, oocytes collected, and embryos obtained. Serum AMH levels before MTX were not statistically significantly different from those after treatment (3.7 +/- 0.3 ng/mL vs. 3.9 +/- 0.3 ng/mL). Patients undergoing a subsequent cycle after systemic treatment for EP had similar cycle durations (10.3 vs. 10.8 d), gonadotropin requirements (2,775 vs. 2,630.3 IU), peak E(2) levels (1,884.3 vs. 1,523.6 pg/mL), number of oocytes retrieved (12.1 vs. 10.5), and total number of embryos obtained (7.1 vs. 6.5). Single-dose MTX is a safe first-treatment choice that does not compromise future reproductive outcomes in women who are diagnosed with EP after ART.

  7. Use of biotin targeted methotrexate–human serum albumin conjugated nanoparticles to enhance methotrexate antitumor efficacy

    Science.gov (United States)

    Taheri, Azade; Dinarvand, Rassoul; Nouri, Faranak Salman; Khorramizadeh, Mohammad Reza; Borougeni, Atefeh Taheri; Mansoori, Pooria; Atyabi, Fatemeh

    2011-01-01

    Biotin molecules could be used as suitable targeting moieties in targeted drug delivery systems against tumors. To develop a biotin targeted drug delivery system, we employed human serum albumin (HSA) as a carrier. Methotrexate (MTX) molecules were conjugated to HSA. MTX-HSA nanoparticles (MTX-HSA NPs) were prepared from these conjugates by cross-linking the HSA molecules. Biotin molecules were then conjugated on the surface of MTX-HSA NPs. The anticancer efficacy of biotin targeted MTX-HSA NPs was evaluated in mice bearing 4T1 breast carcinoma. A single dose of biotin targeted MTX-HSA NPs showed stronger in vivo antitumor activity than non-targeted MTX-HSA NPs and free MTX. By 7 days after treatment, average tumor volume in the biotin targeted MTX-HSA NPs-treated group decreased to 17.6% of the initial tumor volume when the number of attached biotin molecules on MTX-HSA-NPs was the highest. Average tumor volume in non-targeted MTX-HSA NPs-treated mice grew rapidly and reached 250.7% of the initial tumor volume. Biotin targeted MTX-HSA NPs increased the survival of tumor-bearing mice to 47.5 ± 0.71 days and increased their life span up to 216.7%. Mice treated with biotin targeted MTX-HSA NPs showed slight body weight loss (8%) 21 days after treatment, whereas non-targeted MTX-HSA NPs treatment at the same dose caused a body weight loss of 27.05% ± 3.1%. PMID:21931482

  8. Biochemical modulation of 5-fluorouracil by methotrexate in patients with advanced gastric carcinoma.

    Science.gov (United States)

    Pérez, J E; Lacava, J A; Dominguez, M E; Rodriguez, R; Barbieri, M R; Ortiz, E H; Romero Acuña, L A; Langhi, M J; Romero Acuña, J M; Vallejo, C T; Leone, B A; Machiavelli, M R; Romero, A O

    1998-10-01

    A phase II trial was conducted to evaluate the efficacy and toxicity of a modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) (with leucovorin (LV) rescue) as first-line chemotherapy in patients with locally advanced (inoperable) or metastatic gastric carcinoma. From July 1993 through August 1996, 36 patients with advanced gastric carcinoma received a regimen that consisted of: MTX 200 mg/m2 diluted in 250 ml normal saline by intravenous infusion over 20 minutes at hour 0; 5-FU 1,200 mg/m2 intravenous push injection at hour 20. Beginning 24 hours after MTX administration all patients received LV 15 mg/m2 intramuscularly every 6 hours for six doses. Cycles were repeated every 15 days. One patient was not assessable for response. Objective regression was observed in 15 of 37 patients (43%; 95% confidence interval, 26%-60%). One patient (3%) achieved complete response and 14 (40%) achieved partial response. No change was recorded in 14 patients (40%) and progressive disease was noted in six patients (17%). The median time to treatment failure was 7 months and the median survival was 12 months. Toxicity was within acceptable limits but one therapy-related death resulting from severe leukopenia occurred. The dose-limiting toxicity was mucositis. Five episodes of grade 3 or 4 stomatitis were observed and caused dosage modifications of MTX and 5-FU. Biochemical modulation of 5-FU by MTX appears as an attractive modality in patients with advanced gastric cancer. Further investigation both in experimental and clinical fields is needed to clearly define its role and to design the best modulatory strategy.

  9. Acute and Cumulative Effects of Unmodified 50-nm Nano-ZnO on Mice.

    Science.gov (United States)

    Kong, Tao; Zhang, Shu-Hui; Zhang, Ji-Liang; Hao, Xue-Qin; Yang, Fan; Zhang, Cai; Yang, Zi-Jun; Zhang, Meng-Yu; Wang, Jie

    2018-01-02

    Nanometer zinc oxide (nano-ZnO) is widely used in diverse industrial and agricultural fields. Due to the extensive contact humans have with these particles, it is crucial to understand the potential effects that nano-ZnO have on human health. Currently, information related to the toxicity and mechanisms of nano-ZnO is limited. The aim of the present study was to investigate acute and cumulative toxic effects of 50-nm unmodified ZnO in mice. This investigation will seek to establish median lethal dose (LD50), a cumulative coefficient, and target organs. The acute and cumulative toxicity was investigated by Karber's method and via a dose-increasing method, respectively. During the experiment, clinical signs, mortality, body weights, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. The LD50 was 5177-mg/kg·bw; the 95% confidence limits for the LD50 were 5116-5238-mg/kg·bw. It could be concluded that the liver, kidney, lung, and gastrointestinal tract were target organs for the 50-nm nano-ZnO acute oral treatment. The cumulative coefficient (K) was 1.9 which indicated that the cumulative toxicity was apparent. The results also indicated that the liver, kidney, lung, and pancrea were target organs for 50-nm nano-ZnO cumulative oral exposure and might be target organs for subchronic and chronic toxicity of oral administered 50-nm ZnO.

  10. A decrease in vitamin D levels is associated with methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    Oosterom, N; Dirks, N F; Heil, S G; de Jonge, R; Tissing, W J E; Pieters, R; van den Heuvel-Eibrink, M M; Heijboer, A C; Pluijm, S M F

    2018-06-19

    Children with acute lymphoblastic leukemia (ALL) are at increased risk of vitamin D deficiency, which might make them more susceptible to developing adverse events. Previous studies showed that low vitamin D levels were associated with an increased inflammatory mucosal state and impaired mucosal tissue barriers. We examined the prevalence of vitamin D deficiency and studied the association between vitamin D levels and methotrexate (MTX)-induced oral mucositis in pediatric ALL. We assessed 25-hydroxyvitamin D (25(OH)D 3 ) and 24,25-dihydroxyvitamin D (24,25(OH) 2 D 3 ) levels in 99 children with ALL before the start of 4 × 5 g/m 2 high-dose methotrexate (HD-MTX) (T0) and in 81/99 children after discontinuation of HD-MTX (T1). Two cutoff values for vitamin D deficiency exist: 25(OH)D 3 levels D deficiency occurred in respectively 8% ( 4 years of age as compared to children between 1 and 4 years of age. A decrease in 25(OH)D 3 levels during HD-MTX therapy was associated with developing severe oral mucositis (OR 1.6; 95% CI [1.1-2.4]). 25(OH)D 3 and 24,25(OH) 2 D 3 levels at T0 and the change in 24,25(OH) 2 D 3 levels during therapy were not associated with the development of severe oral mucositis. This study showed that vitamin D deficiency occurs frequently in pediatric ALL patients above the age of 4 years. A decrease in 25(OH)D 3 levels during MTX therapy was observed in children with ALL that developed severe oral mucositis.

  11. Predicting Cumulative Incidence Probability: Marginal and Cause-Specific Modelling

    DEFF Research Database (Denmark)

    Scheike, Thomas H.; Zhang, Mei-Jie

    2005-01-01

    cumulative incidence probability; cause-specific hazards; subdistribution hazard; binomial modelling......cumulative incidence probability; cause-specific hazards; subdistribution hazard; binomial modelling...

  12. Predicting Cumulative Incidence Probability by Direct Binomial Regression

    DEFF Research Database (Denmark)

    Scheike, Thomas H.; Zhang, Mei-Jie

    Binomial modelling; cumulative incidence probability; cause-specific hazards; subdistribution hazard......Binomial modelling; cumulative incidence probability; cause-specific hazards; subdistribution hazard...

  13. Managing cumulative impacts: A key to sustainability?

    Energy Technology Data Exchange (ETDEWEB)

    Hunsaker, C.T.

    1994-12-31

    This paper addresses how science can be more effectively used in creating policy to manage cumulative effects on ecosystems. The paper focuses on the scientific techniques that we have to identify and to assess cumulative impacts on ecosystems. The term ``sustainable development`` was brought into common use by the World Commission on Environment and Development (The Brundtland Commission) in 1987. The Brundtland Commission report highlighted the need to simultaneously address developmental and environmental imperatives simultaneously by calling for development that ``meets the needs of the present generation without compromising the needs of future generations.`` We cannot claim to be working toward sustainable development until we can quantitatively assess cumulative impacts on the environment: The two concepts are inextricibally linked in that the elusiveness of cumulative effects likely has the greatest potential of keeping us from achieving sustainability. In this paper, assessment and management frameworks relevant to cumulative impacts are discussed along with recent literature on how to improve such assessments. When possible, examples are given for marine ecosystems.

  14. The injury and cumulative effects on human skin by UV exposure from artificial fluorescence emission.

    Science.gov (United States)

    Tian, Yan; Liu, Wei; Niu, TianHui; Dai, CaiHong; Li, Xiaoxin; Cui, Caijuan; Zhao, Xinyan; E, Yaping; Lu, Hui

    2014-01-01

    The injury and cumulative effects of UV emission from fluorescence lamp were studied. UV intensity from fluorescence lamp was measured, and human skin samples (hips, 10 volunteers) were exposed to low-dose UV irradiation (three times per week for 13 consecutive weeks). Three groups were examined: control group without UV radiation; low-dose group with a cumulative dose of 50 J cm(-2) which was equivalent to irradiation of the face during indoor work for 1.5 years; and high-dose group with 1000 J cm(-2) cumulative dose equivalent to irradiation of the face during outdoor activities for 1 year. Specific indicators were measured before and after UVA irradiation. The findings showed that extending the low-dose UVA exposure decreased the skin moisture content and increased the transepidermal water loss as well as induced skin color changes (decreased L* value, increased M index). Furthermore, irradiated skin showed an increased thickness of cuticle and epidermis, skin edema, light color and unclear staining collagen fibers in the dermis, and elastic fiber fragmentation. In addition, MMP-1, p53 and SIRT1 expression was also increased. Long-term exposure of low-dose UVA radiation enhanced skin photoaging. The safety of the fluorescent lamp needs our attention. © 2014 The American Society of Photobiology.

  15. Perspectives on cumulative risks and impacts.

    Science.gov (United States)

    Faust, John B

    2010-01-01

    Cumulative risks and impacts have taken on different meanings in different regulatory and programmatic contexts at federal and state government levels. Traditional risk assessment methodologies, with considerable limitations, can provide a framework for the evaluation of cumulative risks from chemicals. Under an environmental justice program in California, cumulative impacts are defined to include exposures, public health effects, or environmental effects in a geographic area from the emission or discharge of environmental pollution from all sources, through all media. Furthermore, the evaluation of these effects should take into account sensitive populations and socioeconomic factors where possible and to the extent data are available. Key aspects to this potential approach include the consideration of exposures (versus risk), socioeconomic factors, the geographic or community-level assessment scale, and the inclusion of not only health effects but also environmental effects as contributors to impact. Assessments of this type extend the boundaries of the types of information that toxicologists generally provide for risk management decisions.

  16. Cumulative processes and quark distribution in nuclei

    International Nuclear Information System (INIS)

    Kondratyuk, L.; Shmatikov, M.

    1984-01-01

    Assuming existence of multiquark (mainly 12q) bags in nuclei the spectra of cumulative nucleons and mesons produced in high-energy particle-nucleus collisions are discussed. The exponential form of quark momentum distribution in 12q-bag (agreeing well with the experimental data on lepton-nucleus interactions at large q 2 ) is shown to result in quasi-exponential distribution of cumulative particles over the light-cone variable αsub(B). The dependence of f(αsub(B); psub(perpendicular)) (where psub(perpendicular) is the transverse momentum of the bag) upon psub(perpendicular) is considered. The yields of cumulative resonances as well as effects related to the u- and d-quark distributions in N > Z nuclei being different are dicscussed

  17. Methotrexate and epirubicin conjugates as potential antitumor drugs

    Directory of Open Access Journals (Sweden)

    Szymon Wojciech Kmiecik

    2017-07-01

    Full Text Available Introduction: The use of hybrid molecules has become one of the most significant approaches in new cytotoxic drug design. This study describes synthesis and characterization of conjugates consisting of two well-known and characterized chemotherapeutic agents: methotrexate (MTX and epirubicin (EPR. The synthesized conjugates combine two significant anticancer strategies: combinatory therapy and targeted therapy. These two drugs were chosen because they have different mechanisms of action, which can increase the anticancer effect of the obtained conjugates. MTX, which is a folic acid analog, has high cytotoxic properties and can serve as a targeting moiety that can reach folate receptors (FRs overexpresing tumor cells. Combination of nonselective drugs such as EPR with MTX can increase the selectivity of the obtained conjugates, while maintaining the high cytotoxic properties.Materials and methods: Conjugates were purified by RP-HPLC and the structure was investigated by MS and MS/MS methods. The effect of the conjugates on proliferation of LoVo, LoVo/Dx, MCF-7 and MV-4-11 human cancer cell lines was determined by SRB or MTT assay.Results: The conjugation reaction results in the formation of monosubstituted (α, γ and disubstituted MTX derivatives. In vitro proliferation data demonstrate that the conjugates synthesized in our study show lower cytotoxic properties than both chemotherapeutics used alone.Discussion: Epirubicin cytotoxicity was not observed in obtained conjugates. Effective drugs release after internalization needs further investigation.

  18. Methotrexate treatment provokes apoptosis of proliferating keratinocyte in psoriasis patients.

    Science.gov (United States)

    Elango, Tamilselvi; Thirupathi, Anand; Subramanian, Swapna; Ethiraj, Purushoth; Dayalan, Haripriya; Gnanaraj, Pushpa

    2017-08-01

    Psoriasis is a chronic inflammatory skin disease characterized by hyper proliferation of keratinocytes. Recent data show that the epidermis thickening in psoriasis may be related to imbalance of homeostasis caused by abnormal apoptotic process. Maintenance of keratinocyte apoptotic process is very important in psoriasis. Methotrexate (MTX) has been used for many years to restore the normal skin in psoriasis condition. However, the exact mechanism of MTX in psoriasis condition is poorly understood. The aim of this study was to examine the role of MTX on keratinocyte apoptosis pathway in psoriasis patients. A total of 58 psoriasis vulgaris patients were recruited for this study. Nonlesional skin biopsies served as control. Skin biopsies of psoriatic patients were collected and analyzed for cytosolic, mitochondria and total cytochrome c by ELISA. Expression of caspase-9, NFκBp65, pAkt1 by western blot, real-time PCR and immunohistochemical analysis of c-FLIP protein was analyzed in nonlesional and lesional skin biopsies before (day 0) and after (at the end of 6 and 12 weeks) MTX treatment. After MTX treatment, a significant increase in cytochrome c was observed when compared with before MTX treatment in psoriasis patients (p psoriasis by controlling the acanthosis.

  19. Microwave hyperthermia enhancement of methotrexate absorption in rat brains

    International Nuclear Information System (INIS)

    Lin, J.C.; Yuen, M.K.; Jung, D.T.

    1987-01-01

    The author studied enhanced absorption of methotrexate (MTX) in brains of male Wistar (10 weeks old, 500g) subjected to microwave hyperthermia. The rat was anesthetized using 40 mg/kg of sodium pentobarbital, IP and was placed in a stereotaxic head holder. Microwave energy (2450 MHz, 2.6 W/cm/sup 2/, CW) were applied directly to the left side of the rat's head by a coaxial applicator for 20 min. The body temperature was kept at 37.8 0 C. The brain temperature recorded in a similar group of animals using a Vitek probe was about 45 0 C. Three different MTX dosages, 50, 100 and 200 mg/kg, were injected intravenously immediately following microwave irradiation into three groups of rats in 1.5, 3 and 6 min., respectively. MTX was allowed to circulate for five min. before brains were removed for analysis. Standard HPLC procedures were applied to samples from anterior and posterior left hemisphere of the cerebrum, and the cerebellum. Samples from the right hemisphere were used for controls. The average absorption at the posterior left hemisphere was found to be 2.4, 9.6 and 12.4μg of MTX/g of brain tissue for 50, 100 and 200 mg/kg, respectively. These results indicate that MTX absorption is significantly increased in rat brains subjected to microwave hyperthermia treatment

  20. Radiolabeling, biodistribution and tumor imaging of stealth liposomes containing methotrexate

    International Nuclear Information System (INIS)

    Subramanian, N; Arulsudar, N; Chuttani, K; Mishra, P; Sharma, R.K; Murthy, R.S.R

    2003-01-01

    To study the utility of sterically stabilized liposomes (stealth liposomes) in tumor scintigraphy by studying its biodistribution and accumulation in target tissue after radiolabeling with Technetium-99m (99mTC). Conventional and Stealth liposomes were prepared by lipid film hydration method using methotrexate as model anticancer drug. Radiolabeling of the liposomes was carried out by direct labeling using reduced 99mTc. Experimental conditions for maximum labeling yield were optimized. The stability studies were carried out to check binding strength of the radiolabeled complexes. The blood kinetic study was carried out in rabbits after giving the labeled complex by intravenous administration through ear vein. The biodistribution studies were carried out in the Ehrlich ascites tumor (EAT) bearing mice after intravenous administration through tail vein, showed prolonged circulation in blood and significant increase in the accumulation in tumor for the sterically stabilized liposomes compared to the conventional liposomes. The gamma scintigraphic image shows the distribution of the stealth liposomes in liver, spleen, kidney and tumor. The study gives precise idea about the use of stealth liposomes in tumor scintigraphy and organ distribution studies (Au)

  1. Cumulative Culture and Future Thinking: Is Mental Time Travel a Prerequisite to Cumulative Cultural Evolution?

    Science.gov (United States)

    Vale, G. L.; Flynn, E. G.; Kendal, R. L.

    2012-01-01

    Cumulative culture denotes the, arguably, human capacity to build on the cultural behaviors of one's predecessors, allowing increases in cultural complexity to occur such that many of our cultural artifacts, products and technologies have progressed beyond what a single individual could invent alone. This process of cumulative cultural evolution…

  2. EXAFS cumulants of CdSe

    International Nuclear Information System (INIS)

    Diop, D.

    1997-04-01

    EXAFS functions had been extracted from measurements on the K edge of Se at different temperatures between 20 and 300 K. The analysis of the EXAFS of the filtered first two shells has been done in the wavevector range laying between 2 and 15.5 A -1 in terms of the cumulants of the effective distribution of distances. The cumulants C 3 and C 4 obtained from the phase difference and the amplitude ratio methods have shown the anharmonicity in the vibrations of atoms around their equilibrium position. (author). 13 refs, 3 figs

  3. Tofacitinib, an oral Janus kinase inhibitor, as monotherapy or with background methotrexate, in Japanese patients with rheumatoid arthritis: an open-label, long-term extension study.

    Science.gov (United States)

    Yamanaka, Hisashi; Tanaka, Yoshiya; Takeuchi, Tsutomu; Sugiyama, Naonobu; Yuasa, Hirotoshi; Toyoizumi, Shigeyuki; Morishima, Yosuke; Hirose, Tomohiro; Zwillich, Samuel

    2016-01-28

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Here, tofacitinib safety and efficacy data from a long-term extension study in Japanese patients are presented. Study A3921041 was a multi-centre, open-label, long-term extension study that included Japanese patients who had participated in a prior Phase 2 or Phase 3 study of tofacitinib as monotherapy or with background methotrexate. Patients received tofacitinib 5 mg twice daily (BID) or tofacitinib 10 mg BID. Dose adjustment of tofacitinib during treatment period, and concomitant usage of disease-modifying antirheumatic drugs including methotrexate after week 12 were permitted. Primary endpoints were adverse events, laboratory parameters and vital signs. Secondary efficacy endpoints included American College of Rheumatology (ACR)20/50/70 response rates, Disease Activity Score (DAS)28-4(erythrocyte sedimentation rate (ESR))tofacitinib-treated patients, the incidence rate (patients with events per 100 patient-years) was 10.7 for serious adverse events, 3.3 for serious infections, 7.4 for herpes zoster (serious and non-serious) and 1.2 for malignancies (excluding non-melanoma skin cancer). Mean changes from baseline (start of the index study) in laboratory parameters were consistent with those seen in previously reported studies of tofacitinib. ACR20/50/70 response rates, DAS-defined remission rates and HAQ-DI scores were sustained through to study completion. Tofacitinib (with or without background methotrexate) demonstrated a stable safety profile and sustained efficacy in Japanese patients with active rheumatoid arthritis. The risk of herpes zoster appears to be higher in Japanese patients treated with tofacitinib than in the global population. Clinicaltrials.gov NCT00661661 . Registered 7 February 2008.

  4. Cumulative effects of wind turbines. A guide to assessing the cumulative effects of wind energy development

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-07-01

    This guidance provides advice on how to assess the cumulative effects of wind energy developments in an area and is aimed at developers, planners, and stakeholders interested in the development of wind energy in the UK. The principles of cumulative assessment, wind energy development in the UK, cumulative assessment of wind energy development, and best practice conclusions are discussed. The identification and assessment of the cumulative effects is examined in terms of global environmental sustainability, local environmental quality and socio-economic activity. Supplementary guidance for assessing the principle cumulative effects on the landscape, on birds, and on the visual effect is provided. The consensus building approach behind the preparation of this guidance is outlined in the annexes of the report.

  5. Methotrexate therapy for chronic noninfectious uveitis: analysis of a case series of 160 patients.

    Science.gov (United States)

    Samson, C M; Waheed, N; Baltatzis, S; Foster, C S

    2001-06-01

    To evaluate the outcomes of patients with chronic noninfectious uveitis unresponsive to conventional antiinflammatory therapy who were treated with methotrexate. Retrospective noncomparative interventional case series. All patients with chronic noninfectious uveitis treated with methotrexate at a single institution from 1985 to 1999. Charts of patients seen on the Ocular Immunology & Uveitis Service at the Massachusetts Eye & Ear Infirmary were reviewed. Patients with chronic uveitis of noninfectious origin treated with methotrexate were included in the study. Control of inflammation, steroid-sparing effect, visual acuity, adverse reactions. A total of 160 patients met the inclusion criteria. Control of inflammation was achieved in 76.2% of patients. Steroid-sparing effect was achieved in 56% of patients. Visual acuity was maintained or improved in 90% of patients. Side effects requiring discontinuation of medication occurred in 18% of patients. Potentially serious adverse reactions occurred in only 8.1% of patients. There was neither long-term morbidity nor mortality caused by methotrexate. Methotrexate is effective in the treatment of chronic noninfectious uveitis that fails to respond to conventional steroid treatment. It is an effective steroid-sparing immunomodulator, is a safe medication, and is well tolerated.

  6. Effect of biologic therapy on radiological progression in rheumatoid arthritis: what does it add to methotrexate?

    Directory of Open Access Journals (Sweden)

    Jones G

    2012-07-01

    Full Text Available Graeme Jones, Erica Darian-Smith, Michael Kwok, Tania WinzenbergMenzies Research Institute, University of Tasmania, Tasmania, AustraliaAbstract: There have been substantial advances in the treatment of rheumatoid arthritis in recent years. Traditional disease-modifying antirheumatic drugs (DMARDs have been shown to have small effects on the progression of radiographic damage. This quantitative overview summarizes the evidence for biologic DMARDS and radiographic damage either alone or in combination with methotrexate. Two outcomes were used (standardized mean difference and odds of progression. A total of 21 trials were identified of which 18 had useable data. For biologic monotherapy, tocilizumab, adalimumab, and etanercept were significantly better than methotrexate, with tocilizumab ranking first in both outcomes while golimumab was ineffective in both outcomes. For a biologic in combination with methotrexate compared with methotrexate alone, most therapies studied (etanercept, adalimumab, infliximab, certolizumab, tocilizumab, and rituximab were effective at slowing X-ray progression using either outcome, with infliximab ranking first in both outcomes. The exceptions to this were golimumab (no effect on standardized mean difference and abatacept (no effect on odds of progression. This effect was additional to methotrexate; thus, the overall benefit is moderate to large in magnitude, which is clearly of major clinical significance for sufferers of rheumatoid arthritis and supports the use of biologic DMARDs in those with a poor disease prognosis.Keywords: rheumatoid, trials, meta-analysis, radiographs, biologic, disease-modifying antirheumatic drugs, DMARDs

  7. Countermeasures against methotrexate intolerance in juvenile idiopathic arthritis instituted by parents show no effect.

    Science.gov (United States)

    Scheuern, Andrea; Tyrrell, Pascal N; Haas, Johannes-Peter; Hügle, Boris

    2017-06-01

    A high proportion of children with JIA will develop intolerance to MTX with anticipatory and associative gastrointestinal adverse effects. Parents and physicians frequently try to alleviate these symptoms with a variety of countermeasures. The objective of this study was to investigate the course of MTX intolerance within a 6 month period, and the effects of countermeasures on MTX intolerance severity. We performed a prospective study of 196 consecutive JIA patients treated with MTX. Intolerance was determined using the Methotrexate Intolerance Severity Score (MISS) questionnaire. MISS and countermeasures instituted by parents or physicians were determined at four time points, each 2 months apart. Countermeasures, classified into four types (antiemetic drugs, covert dosing, taste masking and complementary medicine), were analysed using non-parametric statistics and mixed linear modelling, adjusted by propensity scoring for use of countermeasures. Ninety patients (46%) showed MTX intolerance, with 58 (64%) using countermeasures at time of inclusion. Median MISS at inclusion was 11 (interquartile range = 8.0-14.25), and did not change significantly over time. No significant difference in MISS score was observed between patients receiving countermeasures and those who did not. For specific countermeasures, MISS did not change significantly after introduction. Sensitivity analysis adjusting for propensity score indicated no significant association of MISS severity on parents' decision to implement any countermeasures. MTX intolerance was present in many children with JIA and symptoms decreased little in the short term. Various modalities used as countermeasures against nausea by parents showed no discernible effect. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  8. Endogenous metabolites that are substrates of organic anion transporter's (OATs) predict methotrexate clearance.

    Science.gov (United States)

    Muhrez, Kienana; Benz-de Bretagne, Isabelle; Nadal-Desbarats, Lydie; Blasco, Hélène; Gyan, Emmanuel; Choquet, Sylvain; Montigny, Frédéric; Emond, Patrick; Barin-Le Guellec, Chantal

    2017-04-01

    Variable pharmacokinetics of high-dose-methotrexate (MTX) is responsible for severe toxicities. Unpredictable overexposure still occurs during some courses despite having controlled the main factors known to play a role in its elimination. The aim of our study was to evaluate whether the urine metabolomic profile measured at the time of MTX administration is predictive of the drug's clearance and/or of treatment-related toxicity. We analyzed the urine content of endogenous metabolites before MTX administration in a cohort of adult patients treated for lymphoid malignancies. Individual MTX clearance (MTX CL ) was estimated from population pharmacokinetic analyses of therapeutic drug monitoring data. We determined the urine metabolite content by gas chromatography-mass spectrometry (GC-MS) and applied Partial Least Square (PLS) analysis to assess the relationship between the urine metabolome and MTX CL . External validation was applied to evaluate the performances of the PLS model. We used orthogonal partial least squares discriminant analysis (OPLS-DA) to distinguish patients with normal or delayed elimination, and patients with or without toxicity. Sixty-two patients were studied. We obtained a very good prediction of individual MTX clearance using a set of 28 metabolites present in patient urine at baseline. The mean prediction error and precision were -0.36% and 21.4%, respectively, for patients not included in the model. The model included a set of endogenous organic anions, of which the tubular secretion depends on organic anion transporter (OAT) function. Our analyses did not allow us to discriminate between patients with or without delayed elimination or those who did or did not experience toxicity. Urinary metabolomics can be informative about an individual's ability to clear MTX. More broadly, it paves the way for the development of a biomarker of tubular secretion, easily measurable from endogenous substances. Copyright © 2016 Elsevier Ltd. All rights

  9. Protective Effects of Thymoquinone against Methotrexate-Induced Germ Cell Apoptosis in Male Mice

    Directory of Open Access Journals (Sweden)

    Fatemeh Sheikhbahaei

    2016-12-01

    Full Text Available Background: Toxic effects of anti-cancer and other drugs on the normal tissues could be reduced by the herbal plants and their fractions. This study investigated the protective effect of thymoquinone (TQ as a fraction of Nigella sativa on methotrexate (MTX- induced germ cell apoptosis in male mice. Materials and Methods: In this experimental study, thirty male Balb/c mice were divided randomly into 5 groups (n=6. A single dose of MTX (20 mg/kg and different concentrations of TQ were administrated for 4 consecutive days. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay was performed on paraffin embedded tissue sections to analysis the occurrence of apoptosis in the testis. Reverse transcription polymerase chain reaction (RT-PCR of apoptosis-related genes was performed with RNA extracted from testes of the mice. Statistical analysis was done using one-way ANOVA. Results: In the MTX group, there was a significant increase in morphologic sign of germ cell degeneration of tubules (48 ± 0.6%, apoptotic index (AI; 2.3 ± 0.6%, as well as mRNA expression of p53 (P=0.008, caspase 8 (P=0.002, caspase 3 (P=0.005, caspase 9 (P=0.000, bax (P=0.004 and the ratio of bax/bcl-2 (P=0.000, whereas there was an decrease in the expression of bcl-2 (P=0.003, as compared to control group. In MTX+TQ groups, the data showed that different concentrations of TQ could improve the harmful effects caused by the MTX. The best protective effects were achieved in MTX+TQ (10 mg/kg. Conclusion: TQ protects testicular germ cell against MTX-induced apoptosis by affecting related genes regulation.

  10. Methotrexate induces DNA damage and inhibits homologous recombination repair in choriocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Xie L

    2016-11-01

    Full Text Available Lisha Xie,1,* Tiancen Zhao,1,2,* Jing Cai,1 You Su,1 Zehua Wang,1 Weihong Dong1 1Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 2Department of Obstetrics and Gynecology, Central Hospital of Wuhan, Wuhan, China *These authors contributed equally to this work Objective: The objective of this study was to investigate the mechanism of sensitivity to methotrexate (MTX in human choriocarcinoma cells regarding DNA damage response. Methods: Two choriocarcinoma cancer cell lines, JAR and JEG-3, were utilized in this study. An MTX-sensitive osteosarcoma cell line MG63, an MTX-resistant epithelial ovarian cancer cell line A2780 and an MTX-resistant cervical adenocarcinoma cell line Hela served as controls. Cell viability assay was carried out to assess MTX sensitivity of cell lines. MTX-induced DNA damage was evaluated by comet assay. Quantitative reverse transcription polymerase chain reaction was used to detect the mRNA levels of BRCA1, BRCA2, RAD51 and RAD52. The protein levels of γH2AX, RAD 51 and p53 were analyzed by Western blot. Results: Remarkable DNA strand breaks were observed in MTX-sensitive cell lines (JAR, JEG-3 and MG63 but not in MTX-resistant cancer cells (A2780 and Hela after 48 h of MTX treatment. Only in the choriocarcinoma cells, the expression of homologous recombination (HR repair gene RAD51 was dramatically suppressed by MTX in a dose- and time-dependent manner, accompanied with the increase in p53. Conclusion: The MTX-induced DNA strand breaks accompanied by deficiencies in HR repair may contribute to the hypersensitivity to chemotherapy in choriocarcinoma. Keywords: choriocarcinoma, chemotherapy hypersensitivity, DNA double-strand break, RAD51, p53

  11. Saccharomyces boulardii ameliorates clarithromycin- and methotrexate-induced intestinal and hepatic injury in rats.

    Science.gov (United States)

    Duman, Deniz Güney; Kumral, Zarife Nigâr Özdemir; Ercan, Feriha; Deniz, Mustafa; Can, Güray; Cağlayan Yeğen, Berrak

    2013-08-28

    Saccharomyces boulardii is a probiotic used for the prevention of antibiotic-associated diarrhoea. We aimed to investigate whether S. boulardii could alter the effects of clarithromycin (CLA) and methotrexate (MTX) on oro-caecal intestinal transit and oxidative damage in rats. Rats were divided into two groups receiving a single dose of MTX (20 mg/kg) or CLA (20 mg/kg per d) for 1 week. Groups were treated with either saline or S. boulardii (500 mg/kg) twice per d throughout the experiment. The control group was administered only saline. Following decapitation, intestinal transit and inflammation markers of glutathione (GSH), malondialdehyde and myeloperoxidase were measured in intestinal and hepatic tissues. CLA and MTX increased intestinal transit, while S. boulardii treatment slowed down CLA-facilitated transit back to control level. Both MTX and CLA increased lipid peroxidation while depleting the antioxidant GSH content in the hepatic and ileal tissues. Conversely, lipid peroxidation was depressed and GSH levels were increased in the ileal and hepatic tissues of S. boulardii-treated rats. Increased ileal neutrophil infiltration due to MTX and CLA treatments was also reduced by S. boulardii treatment. Histological analysis supported that S. boulardii protected intestinal tissues against the inflammatory effects of both agents. These findings suggest that S. boulardii ameliorates intestinal injury and the accompanying hepatic inflammation by supporting the antioxidant state of the tissues and by inhibiting the recruitment of neutrophils. Moreover, a preventive effect on MTXinduced toxicity is a novel finding of S. boulardii, proposing it as an adjunct to chemotherapy regimens.

  12. High cumulative insulin exposure: a risk factor of atherosclerosis in type 1 diabetes?

    NARCIS (Netherlands)

    Muis, Marian J.; Bots, Michiel L.; Bilo, Henk J. G.; Hoogma, Roel P. L. M.; Hoekstra, Joost B. L.; Grobbee, Diederick E.; Stolk, Ronald P.

    2005-01-01

    Background: Since insulin therapy might have an atherogenic effect, we studied the relationship between cumulative insulin dose and atherosclerosis in type 1 diabetes. We have focused on patients with type 1 diabetes instead of type 2 diabetes to minimise the effect of insulin resistance as a

  13. High cumulative insulin exposure : a risk factor of atherosclerosis in type 1 diabetes?

    NARCIS (Netherlands)

    Muis, MJ; Bots, ML; Bilo, HJG; Hoogma, RPLM; Hoekstra, JBL; Grobbee, DE; Stolk, RP

    Background: Since insulin therapy might have an atherogenic effect, we studied the relationship between cumulative insulin dose and atherosclerosis in type 1 diabetes. We have focused on patients with type 1 diabetes instead of type 2 diabetes to minimise the effect of insulin resistance as a

  14. Effect of methotrexate combined with ginger, silymarin or propolis on ...

    African Journals Online (AJOL)

    aghomotsegin

    2015-02-16

    Feb 16, 2015 ... the same MTX dose combined with ginger, silymarin or propolis oral administration. The doses of ... Propolis (bee glue) is a natural antioxidant produced .... labeled by VIC fluorescent dye and the three target gene cDNA.

  15. Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis

    DEFF Research Database (Denmark)

    Visser, K; Katchamart, W; Loza, E

    2009-01-01

    the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid...

  16. Multiparty correlation measure based on the cumulant

    International Nuclear Information System (INIS)

    Zhou, D. L.; Zeng, B.; Xu, Z.; You, L.

    2006-01-01

    We propose a genuine multiparty correlation measure for a multiparty quantum system as the trace norm of the cumulant of the state. The legitimacy of our multiparty correlation measure is explicitly demonstrated by proving it satisfies the five basic conditions required for a correlation measure. As an application we construct an efficient algorithm for the calculation of our measures for all stabilizer states

  17. Decision analysis with cumulative prospect theory.

    Science.gov (United States)

    Bayoumi, A M; Redelmeier, D A

    2000-01-01

    Individuals sometimes express preferences that do not follow expected utility theory. Cumulative prospect theory adjusts for some phenomena by using decision weights rather than probabilities when analyzing a decision tree. The authors examined how probability transformations from cumulative prospect theory might alter a decision analysis of a prophylactic therapy in AIDS, eliciting utilities from patients with HIV infection (n = 75) and calculating expected outcomes using an established Markov model. They next focused on transformations of three sets of probabilities: 1) the probabilities used in calculating standard-gamble utility scores; 2) the probabilities of being in discrete Markov states; 3) the probabilities of transitioning between Markov states. The same prophylaxis strategy yielded the highest quality-adjusted survival under all transformations. For the average patient, prophylaxis appeared relatively less advantageous when standard-gamble utilities were transformed. Prophylaxis appeared relatively more advantageous when state probabilities were transformed and relatively less advantageous when transition probabilities were transformed. Transforming standard-gamble and transition probabilities simultaneously decreased the gain from prophylaxis by almost half. Sensitivity analysis indicated that even near-linear probability weighting transformations could substantially alter quality-adjusted survival estimates. The magnitude of benefit estimated in a decision-analytic model can change significantly after using cumulative prospect theory. Incorporating cumulative prospect theory into decision analysis can provide a form of sensitivity analysis and may help describe when people deviate from expected utility theory.

  18. Cumulative watershed effects: a research perspective

    Science.gov (United States)

    Leslie M. Reid; Robert R. Ziemer

    1989-01-01

    A cumulative watershed effect (CWE) is any response to multiple land-use activities that is caused by, or results in, altered watershed function. The CWE issue is politically defined, as is the significance of particular impacts. But the processes generating CWEs are the traditional focus of geomorphology and ecology, and have thus been studied for decades. The CWE...

  19. Hypoxia-induced resistance to doxorubicin and methotrexate in human melanoma cell lines in vitro.

    Science.gov (United States)

    Sanna, K; Rofstad, E K

    1994-07-15

    Rodent cell lines can develop resistance to doxorubicin and methotrexate during hypoxic stress. This has so far not been observed in human tumor cell lines. The purpose of our communication is to show that doxorubicin and methotrexate resistance can also develop in human melanoma cells during exposure to hypoxia. Four cell lines (BEX-c, COX-c, SAX-c, WIX-c) have been studied. Cells were exposed to hypoxia (O2 concentration WIX-c. BEX-c and SAX-c were sensitive to methotrexate without hypoxia pre-treatment, whereas COX-c and WIX-c were resistant initially. Hypoxia-induced drug resistance was present immediately after reoxygenation and tended to decrease with time but remained statistically significant even 42 hr after reoxygenation.

  20. Pharmacological and therapeutic properties of carrier bound methotrexate against tumor confined to a third space body compartment.

    Science.gov (United States)

    Chu, B C; Howell, S B

    1981-11-01

    The pharmacokinetics and therapeutic effectiveness of methotrexate (MTX) and MTX covalently bound to bovine serum albumin (MTX-BSA) and poly-l-lysine, MW 3,000 (MTX-PLL 3K) or MW 40,000 to 60,000 (MTX-PLL 40-60K) were compared when these drugs were injected directly into the pleural cavities of BDF1 mice containing the L1210 tumor. Simultaneous measurements od drug levels in both pleural fluid and blood after a single dose demonstrated that free MTX and MTX-PLL 3K were cleared from the pleural cavity and blood within 4 hr, MTX-PLL 40K-60K was cleared within 2 hr, and MTX-BSA was still present in the tumor compartment at 48 hr. The coupling of MTX to these carriers increased its toxicity by extending the half-life of MTX-BSA within the animal and by incorporating a toxic PLL derivative as a carrier. At equitoxic doses, a single dose of MTX-BSA gave a peak increase in lifespan (ILS) of 50% (at 35 mg/kg) compared with a peak ILS of 30 to 35% for both free drug (at 95 mg/kg) and the MTX-PLL derivatives (at 1.4-6 mg/kg). Systemic administration of sufficient leucovorin to provide partial marrow protection compromised the antitumor activity of both MTX and MTX-BSA in the pleural cavity, and although leucovorin permitted higher doses to be used, this resulted in only a small increase in peak ILS for MTX-BSA on a single dose schedule.

  1. An evaluation paradigm for cumulative impact analysis

    Science.gov (United States)

    Stakhiv, Eugene Z.

    1988-09-01

    Cumulative impact analysis is examined from a conceptual decision-making perspective, focusing on its implicit and explicit purposes as suggested within the policy and procedures for environmental impact analysis of the National Environmental Policy Act of 1969 (NEPA) and its implementing regulations. In this article it is also linked to different evaluation and decision-making conventions, contrasting a regulatory context with a comprehensive planning framework. The specific problems that make the application of cumulative impact analysis a virtually intractable evaluation requirement are discussed in connection with the federal regulation of wetlands uses. The relatively familiar US Army Corps of Engineers' (the Corps) permit program, in conjunction with the Environmental Protection Agency's (EPA) responsibilities in managing its share of the Section 404 regulatory program requirements, is used throughout as the realistic context for highlighting certain pragmatic evaluation aspects of cumulative impact assessment. To understand the purposes of cumulative impact analysis (CIA), a key distinction must be made between the implied comprehensive and multiobjective evaluation purposes of CIA, promoted through the principles and policies contained in NEPA, and the more commonly conducted and limited assessment of cumulative effects (ACE), which focuses largely on the ecological effects of human actions. Based on current evaluation practices within the Corps' and EPA's permit programs, it is shown that the commonly used screening approach to regulating wetlands uses is not compatible with the purposes of CIA, nor is the environmental impact statement (EIS) an appropriate vehicle for evaluating the variety of objectives and trade-offs needed as part of CIA. A heuristic model that incorporates the basic elements of CIA is developed, including the idea of trade-offs among social, economic, and environmental protection goals carried out within the context of environmental

  2. Delayed High-dose Methotrexate Excretion and Influencing Factors in Osteosarcoma Patients

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2016-01-01

    Conclusions: Precaution of delayed excretion of MTX is needed during osteosarcoma treatment using HD-MTX. An optimal individualized rescue strategy can be created with consideration of gender, age, and C24 h.

  3. Affinity labeling of the folate-methotrexate transporter from Leishmania donovani

    International Nuclear Information System (INIS)

    Beck, J.T.; Ullman, B.

    1989-01-01

    An affinity labeling technique has been developed to identify the folate-methotrexate transporter of Leishmania donovani promastigotes using activated derivatives of the ligands. These activated derivatives were synthesized by incubating folate and methotrexate with a 10-fold excess of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) for 10 min at ambient temperature in dimethyl sulfoxide. When intact wild-type (DI700) Leishmania donovani or preparations of their membranes were incubated with a 0.4 μM concentration of either activated [ 3 H]folate or activated [ 3 H]methotrexate, the radiolabeled ligands were covalently incorporated into a polypeptide with a molecular weight of approximately 46,000, as demonstrated by SDS-polyacrylamide gel electrophoresis. No affinity labeling of a 46,000-dalton protein was observed when equimolar concentrations of activated radiolabeled ligands were incubated with intact cells or membranes prepared from a methotrexate-resistant mutant clone of Leishmania donovani, MTXA5, that is genetically defective in folate-methotrexate transport capability. Time course studies indicated that maximal labeling of the 46,000-dalton protein occurred within 5-10 min of incubation of intact cells with activated ligand. These studies provide biochemical evidence that the folate-methotrexate transporter of Leishmania donovani can be identified in crude extracts by an affinity labeling technique and serve as a prerequisite to further analysis of the transport protein by providing a vehicle for subsequent purification of this membrane carrier. Moreover, these investigations suggest that the affinity labeling technique using EDC-activated ligands may be exploitable to analyze other cell surface binding proteins in Leishmania donovani, as well as in other organisms

  4. Reversible acute methotrexate leukoencephalopathy: atypical brain MR imaging features

    International Nuclear Information System (INIS)

    Ziereisen, France; Damry, Nash; Christophe, Catherine; Dan, Bernard; Azzi, Nadira; Ferster, Alina

    2006-01-01

    Unusual acute symptomatic and reversible early-delayed leukoencephalopathy has been reported to be induced by methotrexate (MTX). We aimed to identify the occurrence of such atypical MTX neurotoxicity in children and document its MR presentation. We retrospectively reviewed the clinical findings and brain MRI obtained in 90 children treated with MTX for acute lymphoblastic leukaemia or non-B malignant non-Hodgkin lymphoma. All 90 patients had normal brain imaging before treatment. In these patients, brain imaging was performed after treatment completion and/or relapse and/or occurrence of neurological symptoms. Of the 90 patients, 15 (16.7%) showed signs of MTX neurotoxicity on brain MRI, 9 (10%) were asymptomatic, and 6 (6.7%) showed signs of acute leukoencephalopathy. On the routine brain MRI performed at the end of treatment, all asymptomatic patients had classical MR findings of reversible MTX neurotoxicity, such as abnormal high-intensity areas localized in the deep periventricular white matter on T2-weighted images. In contrast, the six symptomatic patients had atypical brain MRI characterized by T2 high-intensity areas in the supratentorial cortex and subcortical white matter (n=6), cerebellar cortex and white matter (n=4), deep periventricular white matter (n=2) and thalamus (n=1). MR normalization occurred later than clinical recovery in these six patients. In addition to mostly asymptomatic classical MTX neurotoxicity, MTX may induce severe but reversible unusual leukoencephalopathy. It is important to recognize this clinicoradiological presentation in the differential diagnosis of acute neurological deterioration in children treated with MTX. (orig.)

  5. Delayed methotrexate excretion in infants and young children with primary central nervous system tumors and postoperative fluid collections.

    Science.gov (United States)

    Wright, Karen D; Panetta, John C; Onar-Thomas, Arzu; Reddick, Wilburn E; Patay, Zoltan; Qaddoumi, Ibrahim; Broniscer, Alberto; Robinson, Giles; Boop, Frederick A; Klimo, Paul; Ward, Deborah; Gajjar, Amar; Stewart, Clinton F

    2015-01-01

    High-dose methotrexate (HD-MTX) has been used to treat children with central nervous system tumors. Accumulation of MTX within pleural, peritoneal, or cardiac effusions has led to delayed excretion and increased risk of systemic toxicity. This retrospective study analyzed the association of intracranial post-resection fluid collections with MTX plasma disposition in infants and young children with brain tumors. Brain MRI findings were analyzed for postoperative intracranial fluid collections in 75 pediatric patients treated with HD-MTX and for whom serial MTX plasma concentrations (MTX) were collected. Delayed plasma excretion was defined as (MTX) ≥1 μM at 42 hours (h). Leucovorin was administered at 42 h and then every 6 h until (MTX) collections present. Population average (inter-individual variation) MTX clearance was 96.0 ml/min/m² (41.1 CV %) and increased with age. Of the patients with intracranial fluid collections, 24 had delayed excretion; only 2 of the 17 without fluid collections (P collection, total leucovorin dosing, or hydration fluids between those with and without toxicity. Although an intracranial fluid collection is associated with delayed MTX excretion, HD-MTX can be safely administered with monitoring of infants and young children with intracranial fluid collections. Infants younger than 1 year may need additional monitoring to avoid toxicity.

  6. Case report: AREB in a patient with rheumatoid arthritis treated with methotrexate and infliximab

    Directory of Open Access Journals (Sweden)

    Giuseppe Rossi

    2011-09-01

    Full Text Available Anti TNF-a drugs seem to be the new frontier of Rheumatoid Arthritis (RA therapy. The association infliximab methotrexate has been approved for the treatment of RA not responding to the classic therapy, but the short clinical experience in using antiTNF-a molecules brings to segnalation of new risks or adverse events. We describe a case of a patient, treated for many years with classic RA therapy, which developed a refractory anemia after treatment with association infliximab-methotrexate.

  7. Risk of Adverse Pregnancy Outcome After Paternal Exposure to Methotrexate Within 90 Days Before Pregnancy

    DEFF Research Database (Denmark)

    Eck, Lasse Karlsen; Jensen, Thomas Bo; Mastrogiannis, Dimitrios

    2017-01-01

    OBJECTIVE: To study the association between paternal exposure to methotrexate within the 90-day period before pregnancy and congenital malformations and stillbirth in the offspring. METHODS: We conducted a nationwide register study. Our cohort consisted of all live births in Denmark between 1997...... group and no increased risk of preterm birth (adjusted OR 1.31, 95% CI 0.66-2.59) among the children from exposed fathers. CONCLUSION: We found no association between paternal exposure to methotrexate within 90 days before pregnancy and congenital malformations, stillbirths, or preterm birth. Available...

  8. Sequential Proximal Tibial Stress Fractures associated with Prolonged usage of Methotrexate and Corticosteroids: A Case Report

    Directory of Open Access Journals (Sweden)

    Tan TJL

    2015-11-01

    Full Text Available Stress fractures of the proximal tibia metaphysis are rare in the elderly. We present a case of a 65-year old male who developed sequential proximal tibia stress fractures associated with prolonged usage of methotrexate and prednisolone within a span of 18 months. Magnetic Resonance Imaging revealed an incomplete stress fracture involving the medial proximal tibial region. The patient was treated with stemmed total knee arthroplasty (TKA bilaterally. Stress fractures should be considered in patients with atypical knee pain who have a history of methotrexate and prednisolone usage. TKA is an effective treatment in stress fractures of the proximal tibia.

  9. Cumulative keyboard strokes: a possible risk factor for carpal tunnel syndrome

    Directory of Open Access Journals (Sweden)

    Eleftheriou Andreas

    2012-08-01

    Full Text Available Abstract Background Contradictory reports have been published regarding the association of Carpal Tunnel Syndrome (CTS and the use of computer keyboard. Previous studies did not take into account the cumulative exposure to keyboard strokes among computer workers. The aim of the present study was to investigate the association between cumulative keyboard use (keyboard strokes and CTS. Methods Employees (461 from a Governmental data entry & processing unit agreed to participate (response rate: 84.1 % in a cross-sectional study. Α questionnaire was distributed to the participants to obtain information on socio-demographics and risk factors for CTS. The participants were examined for signs and symptoms related to CTS and were asked if they had previous history or surgery for CTS. The cumulative amount of the keyboard strokes per worker per year was calculated by the use of payroll’s registry. Two case definitions for CTS were used. The first included subjects with personal history/surgery for CTS while the second included subjects that belonged to the first case definition plus those participants were identified through clinical examination. Results Multivariate analysis used for both case definitions, indicated that those employees with high cumulative exposure to keyboard strokes were at increased risk of CTS (case definition A: OR = 2.23;95 % CI = 1.09-4.52 and case definition B: OR = 2.41; 95%CI = 1.36-4.25. A dose response pattern between cumulative exposure to keyboard strokes and CTS has been revealed (p  Conclusions The present study indicated a possible association between cumulative exposure to keyboard strokes and development of CTS. Cumulative exposure to key-board strokes would be taken into account as an exposure indicator regarding exposure assessment of computer workers. Further research is needed in order to test the results of the current study and assess causality between cumulative keyboard strokes and

  10. Efficacy of combination therapy of anti-TNF-α antibody infliximab and methotrexate in refractory entero-Behçet's disease.

    Science.gov (United States)

    Iwata, Shigeru; Saito, Kazuyoshi; Yamaoka, Kunihiro; Tsujimura, Shizuyo; Nawata, Masao; Hanami, Kentaro; Tanaka, Yoshiya

    2011-04-01

    It is often difficult to manage refractory gastrointestinal tract complications of Behçet's disease (entero-BD) by conventional therapy. In this study, we assessed the short- and long-term efficacy and safety of the combination therapy of infliximab, an anti-tumor-necrosis-factor (TNF)-α antibody, and methotrexate in ten patients with refractory entero-BD refractory to conventional therapies. The short- (weeks) and long-term (by 2 years) effects of infliximab at 3-5 mg/kg body weight every 8 weeks on the clinical course and intestinal manifestations were assessed by abdominal computed tomography (CT) and colonoscopy. The primary endpoint was the rate of disappearance of ileocecal ulceration at 12 months of therapy. All patients showed improvement of gastrointestinal symptoms and disease-associated complications within 4 weeks. Furthermore, the rate of disappearance of ileocecal ulcerations was 50% (5/10 patients) at 6 months and 90% (9/10 patients) at 12 months, and, therefore 90% of patients were satisfied with the primary endpoint. Furthermore, corticosteroid dose was significantly reduced from 22.0 to 1.8 mg/day at 24 months. No severe adverse effects were observed during the 24 months of follow-up. We provide evidence for the rapid and excellent efficacy of infliximab in patients with refractory entero-BD and that the combination of infliximab and methotrexate brings about long-term alleviation of entero-BD and excellent tolerability.

  11. Dose intensity of standard adjuvant CMF with granulocyte colony-stimulating factor for premenopausal patients with node-positive breast cancer

    NARCIS (Netherlands)

    deGraaf, H; Willemse, PHB; Bong, SB; Piersma, H; Tjabbes, T; vanVeelen, H; Coenen, JLLM; deVries, EGE

    1996-01-01

    The effects of granulocyte colony-stimulating factor (G-CSF) on total dose and dose intensity of standard oral adjuvant CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy were studied in premenopausal patients with node-positive breast cancer. Treatment consisted of standard CMF

  12. Uterine Artery Embolization Combined with Local Methotrexate and Systemic Methotrexate for Treatment of Cesarean Scar Pregnancy with Different Ultrasonographic Pattern

    International Nuclear Information System (INIS)

    Lian Fan; Wang Yu; Chen Wei; Li Jiaping; Zhan Zhongping; Ye Yujin; Zhu, Yunxiao; Huang Jia; Xu Hanshi; Yang Xiuyan; Liang Liuqin; Yang Jianyong

    2012-01-01

    Purpose: This study was designed to compare the effectiveness of systemic methotrexate (MTX) with uterine artery embolization (UAE) combined with local MTX for the treatment of cesarean scar pregnancy (CSP) with different ultrasonographic pattern, and to indicate the preferable therapy in CSP patients. Methods: The results of 21 CSP cases were reviewed. All subjects were initially administrated with systemic MTX (50 mg/m 2 body surface area). UAE combined with local MTX was added to the patients who had failed systemic MTX. The transvaginal ultrasonography data were retrospectively assessed, and two different ultrasonographic patterns were found: surface implantation and deep implantation of amniotic sac. The management and its effectiveness for patients with the two ultrasonographic patterns were studied retrospectively. Ultrasound scan and serum β-hCG were monitored during follow-up. Data were analyzed with the Student’s t test. Results: Nine patients were successfully treated with systemic MTX. The remaining 12 cases were successfully treated with additional UAE combined with local MTX. According to the classification by Vial et al. of CSP on ultrasonography, most surface implanted CSPs (8/11, 72.7%) could be successfully treated with systemic MTX, whereas most deeply implanted CSPs (9/10, 90%) had failed systemic MTX but still could be successfully treated with additional UAE combined with local MTX. All patients recovered without severe side effects. Most patients with a future desire for reproduction achieved subsequent pregnancy. Conclusions: For CSP patients suitable for nonsurgical treatment, UAE combined with local MTX would be the superior option compared with systemic MTX in the cases with deep implantation of amniotic sac.

  13. Cyclosporin-Methotrexate Compared with Cyclosporin-Methotrexate-Methylprednisolone Therapy for the Prophylaxis of Acute Graft-Versus Host Disease

    International Nuclear Information System (INIS)

    Khattab, N.F.

    2010-01-01

    Acute graft-versus host (GVHD) disease is a common immunologic complication, which occurs in 40-50% of the recipients of allogenic stem cell transplantation (SCT). The role of corticosteroid in the prevention of GVHD is not well established. We report here a study to determine whether the addition of methylprednisolone to the combination of cyclosporine (CSA) and methotrexate (MTX), methylp-rednisolone (MP) for the prophylaxis of acute GVHD would further decrease the incidence of acute GVHD. A group of patients (25 patients with acute myeloid leukemia (AML) and 12 patients with acute lymphocytic leukemia (ALL) that received CSA/MTX/MP started from 2004 to 2008, were compared to a historical group of patients (19 patient with acute myeloid leukemia (AML) and 12 patients with acute lymphocytic leukemia (ALL) that received GVHD prophylaxis in the form of CSA/MTX only from 1999 to 2003). The primary endpoint in this study was the develop-ment of GVHD and the secondary end point was overall and disease free survival. Both groups of patients were matched for age, sex, donor recipient sex, low risk patients and high risk patients. Although the incidence of acute GVHD in the MP -ve group was 35% versus 24% in the MP+ve group, there was no significant difference between them. The overall survival showed a significant difference between the 2 groups (p<0.05). It was 48% for the 2 drug regimen (CSA/MTX) vs. 81% for the three drug regimen (CSA/MTX/MP). There was a significant decrease in the relapse rate in patients on CSA/MTX/MP (p<0.05). In conclusion, the addition of MP (methylprednis-olone) to the combination of CSA/MTX did not affect the incidence of acute GVHD significantly in allogeneic SCT but surprisingly the incidence of survival and relapse was markedly increased and decreased respectively

  14. Sharing a quota on cumulative carbon emissions

    International Nuclear Information System (INIS)

    Raupach, Michael R.; Davis, Steven J.; Peters, Glen P.; Andrew, Robbie M.; Canadell, Josep G.; Ciais, Philippe

    2014-01-01

    Any limit on future global warming is associated with a quota on cumulative global CO 2 emissions. We translate this global carbon quota to regional and national scales, on a spectrum of sharing principles that extends from continuation of the present distribution of emissions to an equal per-capita distribution of cumulative emissions. A blend of these endpoints emerges as the most viable option. For a carbon quota consistent with a 2 C warming limit (relative to pre-industrial levels), the necessary long-term mitigation rates are very challenging (typically over 5% per year), both because of strong limits on future emissions from the global carbon quota and also the likely short-term persistence in emissions growth in many regions. (authors)

  15. Complexity and demographic explanations of cumulative culture.

    Science.gov (United States)

    Querbes, Adrien; Vaesen, Krist; Houkes, Wybo

    2014-01-01

    Formal models have linked prehistoric and historical instances of technological change (e.g., the Upper Paleolithic transition, cultural loss in Holocene Tasmania, scientific progress since the late nineteenth century) to demographic change. According to these models, cumulation of technological complexity is inhibited by decreasing--while favoured by increasing--population levels. Here we show that these findings are contingent on how complexity is defined: demography plays a much more limited role in sustaining cumulative culture in case formal models deploy Herbert Simon's definition of complexity rather than the particular definitions of complexity hitherto assumed. Given that currently available empirical evidence doesn't afford discriminating proper from improper definitions of complexity, our robustness analyses put into question the force of recent demographic explanations of particular episodes of cultural change.

  16. Complexity and demographic explanations of cumulative culture.

    Directory of Open Access Journals (Sweden)

    Adrien Querbes

    Full Text Available Formal models have linked prehistoric and historical instances of technological change (e.g., the Upper Paleolithic transition, cultural loss in Holocene Tasmania, scientific progress since the late nineteenth century to demographic change. According to these models, cumulation of technological complexity is inhibited by decreasing--while favoured by increasing--population levels. Here we show that these findings are contingent on how complexity is defined: demography plays a much more limited role in sustaining cumulative culture in case formal models deploy Herbert Simon's definition of complexity rather than the particular definitions of complexity hitherto assumed. Given that currently available empirical evidence doesn't afford discriminating proper from improper definitions of complexity, our robustness analyses put into question the force of recent demographic explanations of particular episodes of cultural change.

  17. Conceptual models for cumulative risk assessment.

    Science.gov (United States)

    Linder, Stephen H; Sexton, Ken

    2011-12-01

    In the absence of scientific consensus on an appropriate theoretical framework, cumulative risk assessment and related research have relied on speculative conceptual models. We argue for the importance of theoretical backing for such models and discuss 3 relevant theoretical frameworks, each supporting a distinctive "family" of models. Social determinant models postulate that unequal health outcomes are caused by structural inequalities; health disparity models envision social and contextual factors acting through individual behaviors and biological mechanisms; and multiple stressor models incorporate environmental agents, emphasizing the intermediary role of these and other stressors. The conclusion is that more careful reliance on established frameworks will lead directly to improvements in characterizing cumulative risk burdens and accounting for disproportionate adverse health effects.

  18. Childhood Cumulative Risk and Later Allostatic Load

    DEFF Research Database (Denmark)

    Doan, Stacey N; Dich, Nadya; Evans, Gary W

    2014-01-01

    State, followed for 8 years (between the ages 9 and 17). Poverty- related stress was computed using the cumulative risk approach, assessing stressors across 9 domains, including environmental, psychosocial, and demographic factors. Allostatic load captured a range of physiological responses, including......Objective: The present study investigated the long-term impact of exposure to poverty-related stressors during childhood on allostatic load, an index of physiological dysregulation, and the potential mediating role of substance use. Method: Participants (n = 162) were rural children from New York...... cardiovascular, hypothalamic pituitary adrenal axis, sympathetic adrenal medullary system, and metabolic activity. Smoking and alcohol/drug use were tested as mediators of the hypothesized childhood risk-adolescent allostatic load relationship. Results: Cumulative risk exposure at age 9 predicted increases...

  19. A single center experience of methotrexate in the treatment of Crohn's disease and ulcerative colitis: a case for subcutaneous administration.

    Science.gov (United States)

    Nathan, Debbie M; Iser, John H; Gibson, Peter R

    2008-06-01

    Methotrexate (MTX) is used as a second-line immuno-modulator in patients with inflammatory bowel disease when purine analogs are not tolerated or lack efficacy. High-level evidence indicates efficacy for intramuscular administration in Crohn's disease, but there are few reports of experience with subcutaneous delivery. This study aimed to evaluate the response to and tolerance of MTX where subcutaneous administration was the preferred option. The records of all patients treated with MTX were evaluated with regard to the dose, duration, response, and tolerance to MTX. Remission was defined as improvement in symptoms with no corticosteroid requirement for 3 months or ability to wean off steroids. MTX was initiated in 45 patients with Crohn's disease and 23 ulcerative colitis (median age, 46 years; range, 20-80 years; 54% men) because of intolerance (69%) or resistance (31%) to purine analogues. MTX was initiated in 74% of patients in doses of 25 mg (33) or 20 mg (17), administered by subcutaneous self-injection in 90% of subjects. Remission was achieved in 24 of 45 (53%) with Crohn's disease and 11 of 23 (48%) with ulcerative colitis. An additional four (9%) patients with Crohn's disease and three patients (13%) with ulcerative colitis demonstrated symptomatic improvement and/or ability to decrease corticosteroid dose. While nine patients ceased therapy and nine successfully reduced their doses due to intolerance, three of four patients had no adverse effects. Subcutaneous delivery was well accepted. Subcutaneously administered MTX exhibits apparent efficacy, acceptance, tolerance, and safety in patients with Crohn's disease or ulcerative colitis who are steroid-dependent and where purine analogs have been ineffective or intolerable.

  20. Fuzzy set theory for cumulative trauma prediction

    OpenAIRE

    Fonseca, Daniel J.; Merritt, Thomas W.; Moynihan, Gary P.

    2001-01-01

    A widely used fuzzy reasoning algorithm was modified and implemented via an expert system to assess the potential risk of employee repetitive strain injury in the workplace. This fuzzy relational model, known as the Priority First Cover Algorithm (PFC), was adapted to describe the relationship between 12 cumulative trauma disorders (CTDs) of the upper extremity, and 29 identified risk factors. The algorithm, which finds a suboptimal subset from a group of variables based on the criterion of...

  1. Sikap Kerja Duduk Terhadap Cumulative Trauma Disorder

    OpenAIRE

    Rahmawati, Yulita; Sugiharto, -

    2011-01-01

    Permasalahan yang diteliti adalah adakah hubungan antara sikap kerja duduk dengan kejadian Cumulative Trauma Disorder (CTD) pada pekerja bagian pengamplasan di PT. Geromar Jepara. Tujuan yang ingin dicapai adalah untuk mengetahui hubungan antara sikap kerja duduk dengan kejadian CTD pada pekerja bagian pengamplasan. Metode penelitian ini bersifat explanatory dengan menggunakan pendekatan belah lintang. Populasi dalam penelitian ini adalah pekerja bagian pengamplasan sebanyak 30 orang. Teknik ...

  2. Power Reactor Docket Information. Annual cumulation (citations)

    International Nuclear Information System (INIS)

    1977-12-01

    An annual cumulation of the citations to the documentation associated with civilian nuclear power plants is presented. This material is that which is submitted to the U.S. Nuclear Regulatory Commission in support of applications for construction and operating licenses. Citations are listed by Docket number in accession number sequence. The Table of Contents is arranged both by Docket number and by nuclear power plant name

  3. Cumulative Effect of Depression on Dementia Risk

    OpenAIRE

    Olazarán, J.; Trincado, R.; Bermejo-Pareja, F.

    2013-01-01

    Objective. To analyze a potential cumulative effect of life-time depression on dementia and Alzheimer's disease (AD), with control of vascular factors (VFs). Methods. This study was a subanalysis of the Neurological Disorders in Central Spain (NEDICES) study. Past and present depression, VFs, dementia status, and dementia due to AD were documented at study inception. Dementia status was also documented after three years. Four groups were created according to baseline data: never depression (n...

  4. Cumulative release to the accessible environment

    International Nuclear Information System (INIS)

    Kanehiro, B.

    1985-01-01

    The Containment and Isolation Working Group considered issues related to the postclosure behavior of repositories in crystalline rock. This working group was further divided into subgroups to consider the progress since the 1978 GAIN Symposium and identify research needs in the individual areas of regional ground-water flow, ground-water travel time, fractional release, and cumulative release. The analysis and findings of the Fractional Release Subgroup are presented

  5. EPA Workshop on Epigenetics and Cumulative Risk ...

    Science.gov (United States)

    Agenda Download the Workshop Agenda (PDF) The workshop included presentations and discussions by scientific experts pertaining to three topics (i.e., epigenetic changes associated with diverse stressors, key science considerations in understanding epigenetic changes, and practical application of epigenetic tools to address cumulative risks from environmental stressors), to address several questions under each topic, and included an opportunity for attendees to participate in break-out groups, provide comments and ask questions. Workshop Goals The workshop seeks to examine the opportunity for use of aggregate epigenetic change as an indicator in cumulative risk assessment for populations exposed to multiple stressors that affect epigenetic status. Epigenetic changes are specific molecular changes around DNA that alter expression of genes. Epigenetic changes include DNA methylation, formation of histone adducts, and changes in micro RNAs. Research today indicates that epigenetic changes are involved in many chronic diseases (cancer, cardiovascular disease, obesity, diabetes, mental health disorders, and asthma). Research has also linked a wide range of stressors including pollution and social factors with occurrence of epigenetic alterations. Epigenetic changes have the potential to reflect impacts of risk factors across multiple stages of life. Only recently receiving attention is the nexus between the factors of cumulative exposure to environmental

  6. Higher order cumulants in colorless partonic plasma

    Energy Technology Data Exchange (ETDEWEB)

    Cherif, S. [Sciences and Technologies Department, University of Ghardaia, Ghardaia, Algiers (Algeria); Laboratoire de Physique et de Mathématiques Appliquées (LPMA), ENS-Kouba (Bachir El-Ibrahimi), Algiers (Algeria); Ahmed, M. A. A. [Department of Physics, College of Science, Taibah University Al-Madinah Al-Mounawwarah KSA (Saudi Arabia); Department of Physics, Taiz University in Turba, Taiz (Yemen); Laboratoire de Physique et de Mathématiques Appliquées (LPMA), ENS-Kouba (Bachir El-Ibrahimi), Algiers (Algeria); Ladrem, M., E-mail: mladrem@yahoo.fr [Department of Physics, College of Science, Taibah University Al-Madinah Al-Mounawwarah KSA (Saudi Arabia); Laboratoire de Physique et de Mathématiques Appliquées (LPMA), ENS-Kouba (Bachir El-Ibrahimi), Algiers (Algeria)

    2016-06-10

    Any physical system considered to study the QCD deconfinement phase transition certainly has a finite volume, so the finite size effects are inevitably present. This renders the location of the phase transition and the determination of its order as an extremely difficult task, even in the simplest known cases. In order to identify and locate the colorless QCD deconfinement transition point in finite volume T{sub 0}(V), a new approach based on the finite-size cumulant expansion of the order parameter and the ℒ{sub m,n}-Method is used. We have shown that both cumulants of higher order and their ratios, associated to the thermodynamical fluctuations of the order parameter, in QCD deconfinement phase transition behave in a particular enough way revealing pronounced oscillations in the transition region. The sign structure and the oscillatory behavior of these in the vicinity of the deconfinement phase transition point might be a sensitive probe and may allow one to elucidate their relation to the QCD phase transition point. In the context of our model, we have shown that the finite volume transition point is always associated to the appearance of a particular point in whole higher order cumulants under consideration.

  7. Cumulative irritation potential of topical retinoid formulations.

    Science.gov (United States)

    Leyden, James J; Grossman, Rachel; Nighland, Marge

    2008-08-01

    Localized irritation can limit treatment success with topical retinoids such as tretinoin and adapalene. The factors that influence irritant reactions have been shown to include individual skin sensitivity, the particular retinoid and concentration used, and the vehicle formulation. To compare the cutaneous tolerability of tretinoin 0.04% microsphere gel (TMG) with that of adapalene 0.3% gel and a standard tretinoin 0.025% cream. The results of 2 randomized, investigator-blinded studies of 2 to 3 weeks' duration, which utilized a split-face method to compare cumulative irritation scores induced by topical retinoids in subjects with healthy skin, were combined. Study 1 compared TMG 0.04% with adapalene 0.3% gel over 2 weeks, while study 2 compared TMG 0.04% with tretinoin 0.025% cream over 3 weeks. In study 1, TMG 0.04% was associated with significantly lower cumulative scores for erythema, dryness, and burning/stinging than adapalene 0.3% gel. However, in study 2, there were no significant differences in cumulative irritation scores between TMG 0.04% and tretinoin 0.025% cream. Measurements of erythema by a chromameter showed no significant differences between the test formulations in either study. Cutaneous tolerance of TMG 0.04% on the face was superior to that of adapalene 0.3% gel and similar to that of a standard tretinoin cream containing a lower concentration of the drug (0.025%).

  8. Methotrexate loaded polyether-copolyester dendrimers for the treatment of gliomas: enhanced efficacy and intratumoral transport capability.

    Science.gov (United States)

    Dhanikula, Renu Singh; Argaw, Anteneh; Bouchard, Jean-Francois; Hildgen, Patrice

    2008-01-01

    Therapeutic benefit in glial tumors is often limited due to low permeability of delivery systems across the blood-brain barrier (BBB), drug resistance, and poor penetration into the tumor tissue. In an attempt to overcome these hurdles, polyether-copolyester (PEPE) dendrimers were evaluated as drug carriers for the treatment of gliomas. Dendrimers were conjugated to d-glucosamine as the ligand for enhancing BBB permeability and tumor targeting. The efficacy of methotrexate (MTX)-loaded dendrimers was established against U87 MG and U 343 MGa cells. Permeability of rhodamine-labeled dendrimers and MTX-loaded dendrimers across the in vitro BBB model and their distribution into avascular human glioma tumor spheroids was also studied. Glucosylated dendrimers were found to be endocytosed in significantly higher amounts than nonglucosylated dendrimers by both the cell lines. IC 50 of MTX after loading in dendrimers was lower than that of the free MTX, suggesting that loading MTX in PEPE dendrimers increased its potency. Similar higher activity of MTX-loaded glucosylated and nonglucosylated dendrimers was found in the reduction of tumor spheroid size. These MTX-loaded dendrimers were able to kill even MTX-resistant cells highlighting their ability to overcome MTX resistance. In addition, the amount of MTX-transported across BBB was three to five times more after loading in the dendrimers. Glucosylation further increased the cumulative permeation of dendrimers across BBB and hence increased the amount of MTX available across it. Glucosylated dendrimers distributed through out the avascular tumor spheroids within 6 h, while nonglucosylated dendrimers could do so in 12 h. The results show that glucosamine can be used as an effective ligand not only for targeting glial tumors but also for enhanced permeability across BBB. Thus, glucosylated PEPE dendrimers can serve as potential delivery system for the treatment of gliomas.

  9. Effects of methotrexate on rat parotid and submandibular glands and their secretions

    International Nuclear Information System (INIS)

    McBride, R.K.

    1986-01-01

    Experimental animals were injected intraperitoneally with methotrexate for 3 days. Parotid and submandibular main ducts were cannulated and saliva flow was evoked by either intravenous infusion of acetylcholine or an intravenous injection of benthanechol. Methotrexate was found to reduce significantly mean food consumption, body weight, and parotid gland wet weights. Experimental animal salivary total gland DNA levels were not different, but total parotid gland RNA, protein, amylase and water content, and submandibular gland RNA were significantly lower compared to control. Acetylcholine, but not bethanechol, evoked parotid protein and amylase outputs and submandibular protein output from experimental animals were significantly higher than the control groups'. The increased outputs were apparently linked to β-adrenergic receptor activation, since hexamethonium or propranolol eliminated the significant increases while phenoxybenzamine did not. Plasma catecholamine levels were significantly higher in the methotrexate treated animals and probably played a role in the salivary gland β-adrenergic activation. Methotrexate treatment significantly increased the submandibular gland β-adrenergic receptor concentration as determined by [ 3 H]-dihydroalprenolol receptor binding assays. Muscarinic receptor concentrations determined with [ 3 H]-quinuclidninyl benzilate were not changed

  10. St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats

    International Nuclear Information System (INIS)

    Yang, Shih-Ying; Juang, Shin-Hun; Tsai, Shang-Yuan; Chao, Pei-Dawn Lee; Hou, Yu-Chi

    2012-01-01

    St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window. This study investigated the effect of SJW on MTX pharmacokinetics in rats. Rats were orally given MTX alone and coadministered with 300 and 150 mg/kg of SJW, and 25 mg/kg of diclofenac, respectively. Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method. The results showed that 300 mg/kg of SJW significantly increased the AUC 0−t and C max of MTX by 163% and 60%, respectively, and 150 mg/kg of SJW significantly increased the AUC 0−t of MTX by 55%. In addition, diclofenac enhanced the C max of MTX by 110%. The mortality of rats treated with SJW was higher than that of controls. In conclusion, coadministration of SJW significantly increased the systemic exposure and toxicity of MTX. The combined use of MTX with SJW would need to be with caution. -- Highlights: ► St. John's wort significantly increased the AUC 0−t and C max of methotrexate. ► Coadministration of St. John's wort increased the exposure and toxicity of methotrexate. ► The combined use of methotrexate with St. John's wort will need to be with caution.

  11. Comparison of weakness progression in inclusion body myositis during treatment with methotrexate or placebo

    NARCIS (Netherlands)

    Badrising, UA; Maat-Schieman, MLC; Ferrari, MD; Zwinderman, AH; Wessels, JAM; Breedveld, FC; van Doorn, PA; van Engelen, BGM; Hoogendijk, JE; Howeler, CJ; de Jager, AE; Jennekens, FGI; Koehler, PJ; de Visser, M; Viddeleer, A; Verschuuren, JJ; Wintzen, AR

    We investigated whether 5 to 20mg per week oral methotrexate could slow down disease progression in 44 patients with inclusion body myositis in a randomized double-blind placebo-controlled study over 48 weeks. Mean change of quantitative muscle strength testing sum scores was the primary study

  12. Effects of methotrexate on rat parotid and submandibular glands and their secretions

    Energy Technology Data Exchange (ETDEWEB)

    McBride, R.K.

    1986-01-01

    Experimental animals were injected intraperitoneally with methotrexate for 3 days. Parotid and submandibular main ducts were cannulated and saliva flow was evoked by either intravenous infusion of acetylcholine or an intravenous injection of benthanechol. Methotrexate was found to reduce significantly mean food consumption, body weight, and parotid gland wet weights. Experimental animal salivary total gland DNA levels were not different, but total parotid gland RNA, protein, amylase and water content, and submandibular gland RNA were significantly lower compared to control. Acetylcholine, but not bethanechol, evoked parotid protein and amylase outputs and submandibular protein output from experimental animals were significantly higher than the control groups'. The increased outputs were apparently linked to ..beta..-adrenergic receptor activation, since hexamethonium or propranolol eliminated the significant increases while phenoxybenzamine did not. Plasma catecholamine levels were significantly higher in the methotrexate treated animals and probably played a role in the salivary gland ..beta..-adrenergic activation. Methotrexate treatment significantly increased the submandibular gland ..beta..-adrenergic receptor concentration as determined by (/sup 3/H)-dihydroalprenolol receptor binding assays. Muscarinic receptor concentrations determined with (/sup 3/H)-quinuclidninyl benzilate were not changed.

  13. Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis.

    NARCIS (Netherlands)

    Gerards, A.H.; Lathouder, de S; Groot, E.R.; Dijkmans, B.A.C.; Aarden, L.A.

    2003-01-01

    OBJECTIVES: To analyse whether the beneficial effects of methotrexate in rheumatoid arthritis (RA) could be due to inhibition of inflammatory cytokine production. METHODS: Cytokine production was studied using whole blood (WB) and mononuclear cells (MNC) of healthy volunteers and RA patients.

  14. Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Gerards, A. H.; de Lathouder, S.; de Groot, E. R.; Dijkmans, B. A. C.; Aarden, L. A.

    2003-01-01

    Objectives. To analyse whether the beneficial effects of methotrexate in rheumatoid arthritis (RA) could be due to inhibition of inflammatory cytokine production. Methods. Cytokine production was studied using whole blood (WB) and mononuclear cells (MNC) of healthy volunteers and RA patients.

  15. Measures of 6-mercaptopurine and methotrexate maintenance therapy intensity in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Nielsen, Stine Nygaard; Grell, Kathrine; Nersting, Jacob

    2016-01-01

    PURPOSE: Normal white blood cell counts (WBC) are unknown in children with acute lymphoblastic leukemia (ALL). Accordingly, 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy is adjusted by a common WBC target of 1.5-3.0 × 10(9)/L. Consequently, the absolute degree...

  16. Liposomal Cytarabine Induces Less Neurocognitive Dysfunction Than Intrathecal Methotrexate in an Animal Model

    DEFF Research Database (Denmark)

    Thomsen, Anna M; Gulinello, Maria E; Wen, Jing

    2018-01-01

    Liposomal cytarabine is currently being tested clinically as an alternative to intrathecal (IT) methotrexate (MTX) for preventing relapse within the central nervous system among patients with acute lymphoblastic leukemia. To compare the toxicity and cognitive deficits caused by IT MTX versus lipo...

  17. Bisphosphonate-associated osteonecrosis of jaw reoccurrence after methotrexate therapy: a case report.

    Science.gov (United States)

    Alsalleeh, Fahd; Keippel, Jeffery; Adams, Lyde; Bavitz, Bruce

    2014-09-01

    Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a well-known complication caused by amino-bisphosphonate therapy. We document one case of BRONJ associated with oral administration of methotrexate, a known immunosuppressive drug used to treat rheumatoid arthritis. A 66-year-old woman was referred for evaluation and endodontic surgery of recently re-treated tooth 13. Tooth 14 was extracted 3 months prior, and the extraction site had not completely healed. Her medical history revealed rheumatoid arthritis and osteoporosis. She had been taking Fosamax (alendronate) 70 mg daily. Because of adequate root canal therapy of tooth 13, endodontic surgery was performed. Five months after apicoectomy, her symptoms had not changed. Tooth 13 was extracted, and the socket healed without complications. The socket of extracted tooth 14 was also healing. At the 3-month recall visit, bone exposure and purulent discharge at the site of extracted tooth 14 were noted. The patient had recently received methotrexate. The methotrexate was discontinued, and she was given course of amoxicillin. At the 18-month follow-up, the healing progressed, and the wound was closed. A medication that suppresses the immune system such as methotrexate may complicate the management of BRONJ. Once a diagnosis of BRONJ is made, a closely monitored conservative approach is recommended. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  18. The acitretin and methotrexate combination therapy for psoriasis vulgaris achieves higher effectiveness and less liver fibrosis.

    Science.gov (United States)

    An, Jingang; Zhang, Dingwei; Wu, Jiawen; Li, Jiong; Teng, Xiu; Gao, Xiaomin; Li, Ruilian; Wang, Xiuying; Xia, Linlin; Xia, Yumin

    2017-07-01

    Both acitretin and methotrexate are effective in ameliorating psoriatic lesion. However, their combination has been seldom reported in the treatment of psoriasis because of the warning regarding the potential hepatotoxicity of the drug interactions. This study was designed to investigate the effectiveness of such combination therapy for psoriasis vulgaris, and the potential benefit as well as side effect during the treatment. Thirty-nine patients with psoriasis vulgaris were treated with acitretin, methotrexate or their combination or as control. Similarly, K14-VEGF transgenic psoriasis-like mice were treated with these drugs. Human primary keratinocytes and hepatic stellate cells were used for analyzing their effect in vitro. The results showed that the combination therapy exhibited higher effectiveness in remitting skin lesion, but did not significantly affect the liver function of both patients and mice. Moreover, the combination groups showed less elevation of profibrotic factors in sera when compared with methotrexate alone groups accordingly. Furthermore, primary keratinocytes expressed more involucrin as well as loricrin and proliferated more slowly on the combined stimulation. Interestingly, such combination treatment induced lower expression of profibrotic factors in hepatic stellate cells. In conclusion, the acitretin-methotrexate combination therapy for psoriasis vulgaris can achieve higher effectiveness and result in less liver fibrosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis

    NARCIS (Netherlands)

    Fleischmann, Roy M.; Huizinga, Tom W. J.; Kavanaugh, Arthur F.; Wilkinson, Bethanie; Kwok, Kenneth; DeMasi, Ryan; van Vollenhoven, Ronald F.

    2016-01-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24 months in methotrexate (MTX)-naive adult

  20. Use of mycophenolate mofetil in patients with severe localized scleroderma resistant or intolerant to methotrexate

    NARCIS (Netherlands)

    Mertens, Jorre S.; Marsman, Diane; van de Kerkhof, Peter C M; Hoppenreijs, Esther P A H; Knaapen, Hanneke K A; Radstake, Timothy R D; de Jong, Elke M G J; Seyger, Marieke M B

    2016-01-01

    To assess the efficacy and safety of mycophenolate mofetil (MMF) in patients with localized scleroderma (LoS) resistant or intolerant to previous treatment with methotrexate (MTX). A case series of patients with LoS treated with MMF. Outcome was assessed through clinical examination. Adverse events

  1. N-feruloylserotonin in preventive combination therapy with methotrexate reduced inflammation in adjuvant arthritis

    Czech Academy of Sciences Publication Activity Database

    Kuncírová, V.; Poništ, S.; Mihalová, D.; Dráfi, F.; Nosáľ, R.; Acquaviva, A.; Gardi, C.; Harmatha, Juraj; Hrádková, I.; Bauerová, K.

    2014-01-01

    Roč. 28, č. 6 (2014), s. 616-626 ISSN 0767-3981 Institutional support: RVO:61388963 Keywords : arthritis * inflammation * oxidative stress * combination therapy * methotrexate * N-feruloylserotonin Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.121, year: 2014

  2. Voltammetric Behavior of Methotrexate Using Mercury Meniscus Modified Silver Solid Amalgam Electrode

    Czech Academy of Sciences Publication Activity Database

    Šelešovská, R.; Bandžuchová, L.; Navrátil, Tomáš

    2011-01-01

    Roč. 23, č. 1 (2011), s. 177-178 ISSN 1040-0397 R&D Projects: GA AV ČR IAA400400806 Institutional research plan: CEZ:AV0Z40400503 Keywords : methotrexate * voltammetry * determination Subject RIV: CG - Electrochemistry Impact factor: 2.872, year: 2011

  3. A Randomized Clinical Trial Comparing Methotrexate and Mycophenolate Mofetil for Non-Infectious Uveitis

    Science.gov (United States)

    Rathinam, Sivakumar R; Babu, Manohar; Thundikandy, Radhika; Kanakath, Anuradha; Nardone, Natalie; Esterberg, Elizabeth; Lee, Salena M; Enanoria, Wayne TA; Porco, Travis C; Browne, Erica N; Weinrib, Rachel; Acharya, Nisha R

    2014-01-01

    Objective To compare the relative effectiveness of methotrexate and mycophenolate mofetil for non-infectious intermediate uveitis, posterior uveitis, or panuveitis. Design Multicenter, block-randomized, observer-masked clinical trial Participants Eighty patients with non-infectious intermediate, posterior or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. Intervention Patients were randomized to receive 25mg weekly oral methotrexate or 1g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. Main Outcome Measures Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤ 10 mg of prednisone and ≤ 2 drops of prednisolone acetate 1% a day and (3) no declaration of treatment failure due to intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. Results Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (p=0.09). Treatment failure due to adverse events or tolerability was not significantly different by treatment arm (p=0.99). There were no statistically significant differences between treatment groups in time to corticosteroid-sparing control of inflammation (p=0.44), change in best spectacle-corrected visual acuity (p=0.68), and resolution of macular

  4. A randomized clinical trial comparing methotrexate and mycophenolate mofetil for noninfectious uveitis.

    Science.gov (United States)

    Rathinam, Sivakumar R; Babu, Manohar; Thundikandy, Radhika; Kanakath, Anuradha; Nardone, Natalie; Esterberg, Elizabeth; Lee, Salena M; Enanoria, Wayne T A; Porco, Travis C; Browne, Erica N; Weinrib, Rachel; Acharya, Nisha R

    2014-10-01

    To compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis. Multicenter, block-randomized, observer-masked clinical trial. Eighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. Patients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31). There was no statistically significant difference in corticosteroid-sparing control of

  5. Methotrexate-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses.

    Science.gov (United States)

    Campbell, Jared M; Bateman, Emma; Stephenson, Matthew D; Bowen, Joanne M; Keefe, Dorothy M; Peters, Micah D J

    2016-07-01

    Methotrexate chemotherapy is associated with various toxicities which can result in the interruption or discontinuation of treatment and a subsequently raised risk of relapse. This umbrella systematic review was conducted to synthesize the results of all existing systematic reviews that investigate the pharmacogenetics of methotrexate-induced toxicity, with the aim of developing a comprehensive reference for personalized medicine. Databases searched were PubMed, Embase, JBI Database of Systematic Reviews and Implementation Reports, DARE, and ProQuest. Papers were critically appraised by two reviewers, and data were extracted using a standardized tool. Three systematic reviews on methotrexate-induced toxicity were included in the review. Meta-analyses were reported across Asian, Caucasian, pediatric and adult patients for the MTHFR C677T and A1298C polymorphisms. Toxicity outcomes included different forms of hematologic, ectodermal and hepatic toxicities. Results varied considerably depending on the patient groups and subgroups investigated in the different systematic reviews, as well as the genetic models utilized. However, significant associations were found between the MTHFR C677T allele and; hepatic toxicity, myelosuppression, oral mucositis, gastrointestinal toxicity, and skin toxicity. Additionally, limited evidence suggests that the MTHFR A1298C polymorphism may be associated with decreased risk of skin toxicity and leukopenia. This umbrella systematic review has synthesized the best available evidence on the pharmacogenetics of methotrexate toxicity. The next step in making personalized medicine for methotrexate therapy a clinical reality is research on the effectiveness and cost-effectiveness of MTHFR genotype testing to enable the close monitoring of at-risk patients for the timely initiation of rescue therapies.

  6. A bivariate optimal replacement policy with cumulative repair cost ...

    Indian Academy of Sciences (India)

    Min-Tsai Lai

    Shock model; cumulative damage model; cumulative repair cost limit; preventive maintenance model. 1. Introduction ... with two types of shocks: one type is failure shock, and the other type is damage ...... Theory, methods and applications.

  7. On interference of cumulative proton production mechanisms

    International Nuclear Information System (INIS)

    Braun, M.A.; Vechernin, V.V.

    1993-01-01

    The dynamical picture of the cumulative proton production in hA-collisions by means of diagram analysis with NN interaction described by a non-relativistic NN potential is considered. The contributions of the various mechanisms (spectator, direct and rescattering) for backward hemisphere proton production within the framework of this common approach is calculated. The emphasis is on the comparison of the relative contributions of these mechanisms for various angles, taking into account the interference of these contributions. Comparison with experimental data is also presented. (author)

  8. Preserved cumulative semantic interference despite amnesia

    Directory of Open Access Journals (Sweden)

    Gary Michael Oppenheim

    2015-05-01

    As predicted by Oppenheim et al’s (2010 implicit incremental learning account, WRP’s BCN RTs demonstrated strong (and significant repetition priming and semantic blocking effects (Figure 1. Similar to typical results from neurally intact undergraduates, WRP took longer to name pictures presented in semantically homogeneous blocks than in heterogeneous blocks, an effect that increased with each cycle. This result challenges accounts that ascribe cumulative semantic interference in this task to explicit memory mechanisms, instead suggesting that the effect has the sort of implicit learning bases that are typically spared in hippocampal amnesia.

  9. Is cumulated pyrethroid exposure associated with prediabetes?

    DEFF Research Database (Denmark)

    Hansen, Martin Rune; Jørs, Erik; Lander, Flemming

    2014-01-01

    was to investigate an association between exposure to pyrethroids and abnormal glucose regulation (prediabetes or diabetes). A cross-sectional study was performed among 116 pesticide sprayers from public vector control programs in Bolivia and 92 nonexposed controls. Pesticide exposure (duration, intensity...... pyrethroids, a significant positive trend was observed between cumulative pesticide exposure (total number of hours sprayed) and adjusted OR of abnormal glucose regulation, with OR 14.7 [0.9-235] in the third exposure quintile. The study found a severely increased prevalence of prediabetes among Bolivian...

  10. Methotrexate Toxicity in Growing Long Bones of Young Rats: A Model for Studying Cancer Chemotherapy-Induced Bone Growth Defects in Children

    Directory of Open Access Journals (Sweden)

    Chiaming Fan

    2011-01-01

    Full Text Available The advancement and intensive use of chemotherapy in treating childhood cancers has led to a growing population of young cancer survivors who face increased bone health risks. However, the underlying mechanisms for chemotherapy-induced skeletal defects remain largely unclear. Methotrexate (MTX, the most commonly used antimetabolite in paediatric cancer treatment, is known to cause bone growth defects in children undergoing chemotherapy. Animal studies not only have confirmed the clinical observations but also have increased our understanding of the mechanisms underlying chemotherapy-induced skeletal damage. These models revealed that high-dose MTX can cause growth plate dysfunction, damage osteoprogenitor cells, suppress bone formation, and increase bone resorption and marrow adipogenesis, resulting in overall bone loss. While recent rat studies have shown that antidote folinic acid can reduce MTX damage in the growth plate and bone, future studies should investigate potential adjuvant treatments to reduce chemotherapy-induced skeletal toxicities.

  11. Chapter 19. Cumulative watershed effects and watershed analysis

    Science.gov (United States)

    Leslie M. Reid

    1998-01-01

    Cumulative watershed effects are environmental changes that are affected by more than.one land-use activity and that are influenced by.processes involving the generation or transport.of water. Almost all environmental changes are.cumulative effects, and almost all land-use.activities contribute to cumulative effects

  12. Original and cumulative prospect theory: a discussion of empirical differences

    NARCIS (Netherlands)

    Wakker, P.P.; Fennema, H.

    1997-01-01

    This note discusses differences between prospect theory and cumulative prospect theory. It shows that cumulative prospect theory is not merely a formal correction of some theoretical problems in prospect theory, but it also gives different predictions. Experiments are described that favor cumulative

  13. Metronomic Cyclophosphamide and Methotrexate Chemotherapy Combined with 1E10 Anti-Idiotype Vaccine in Metastatic Breast Cancer

    International Nuclear Information System (INIS)

    Soriano, J.L.; Batista, N.; Lima, M.; Gonzalez, J.; Garcia, R.; Zarza, Y.; Lopez, M.V.; Rodriguez, M.; Loys, J.L.; Montejo, N.; Santiesteban, E.; Aguirre, F.; Macias, A.; Vazquez, A.M.

    2011-01-01

    The use of low doses of cytotoxic agents continuously for prolonged periods is an alternative for the treatment of patients with metastatic breast cancer who have developed resistance to conventional chemotherapy. The combination of metronomic chemotherapy with therapeutic vaccines might increase the efficacy of the treatment. Twenty one patients with metastatic breast cancer in progression and a Karnosky index =60%, were treated with metronomic chemotherapy (50?mg of cyclophosphamide orally daily and 2.5 mg of methotrexate orally bi-daily), in combination with five bi-weekly subcutaneous injections of 1 mg of aluminum hydroxide-precipitated 1E10 anti-idiotype MAb (1E10-Alum), followed by re immunizations every 28 days. Five patients achieved objective response, eight showed stable disease and eight had disease progression. Median time to progression was 9,8 months, while median overall survival time was 12,93 months. The median duration of the response (CR+PR+SD) was 18,43 months (12,20-24,10 months), being higher than 12 months in 76,9% of the patients. Overall toxicity was generally mild. Metronomic chemotherapy combined with 1E10-Alum vaccine immunotherapy might be a useful therapeutic option for the treatment of metastatic breast cancer due to its potential impact on survival and patient quality of live, low toxicity and advantages of the administration.

  14. Reduction of oxidative stress by an ethanolic extract of leaves of Piper betle (Paan) Linn. decreased methotrexate-induced toxicity.

    Science.gov (United States)

    De, Soumita; Sen, Tuhinadri; Chatterjee, Mitali

    2015-11-01

    Methotrexate (MTX), a folate antagonist, is currently used as first line therapy for autoimmune diseases like rheumatoid arthritis and psoriasis, but its use is limited by the associated hepatotoxicity. As leaves of Piper betle, belonging to family Piperaceae, have antioxidant and anti-inflammatory properties, the present study was undertaken to investigate the potential of Piper betle leaf extract (PB) in attenuating MTX-induced hepatotoxicity. Rats pre-treated with PB (50 or 100 mg kg(-1) b.w., p.o.) were administered with a single dose of MTX (20 mg kg(-1), b.w., i.p.) and its hepatoprotective efficacy was compared with folic acid (1 mg kg(-1) b.w., i.p.), conventionally used to minimize MTX-induced toxicity. MTX-induced hepatotoxicity was confirmed by increased activities of marker enzymes, alanine transaminase, aspartate transaminase, and alkaline phosphatase which were remitted by pre-treatment with PB and corroborated with histopathology. Additionally, MTX-induced hepatic oxidative stress which included increased generation of reactive oxygen species, enhanced lipid peroxidation, depleted levels of glutathione and decreased activities of antioxidant enzymes was effectively mitigated by PB, indicative that its promising antioxidant-mediated hepatoprotective activity was worthy of future pharmacological consideration.

  15. Weekly vs. daily administration of oral methotrexate (MTX) for generalized plaque psoriasis: a randomized controlled clinical trial.

    Science.gov (United States)

    Radmanesh, Mohammad; Rafiei, Behnam; Moosavi, Zahra-Beigum; Sina, Niloofar

    2011-10-01

    Methotrexate (MTX) treatment for psoriasis is most often administered weekly, because the drug has been considered more hepatotoxic when taken daily. However, some patients may tolerate smaller, more frequent doses better. To study the efficacy and toxicity of daily vs. weekly MTX. In a randomized controlled trial, 101 patients with generalized plaque psoriasis received oral MTX 2.5 mg daily for weeks, 4 weeks and monthly for a total of 4 months. Changes in PASI scores were classified into three categories: >75% improvement was considered significant; 25-75% moderate; and <25% poor. Sixty Group 1 patients and 81 Group 2 patients showed a significant response (P-value 0.001); 19 patients in Group 1 and 14 in Group 2 responded moderately; 22 patients in Group 1 and six patients from Group 2 responded poorly. Forty-five patients in Group 1 and 33 in Group 2 developed transient increases in liver enzymes (P-value 0.11). Nausea, headache, fatigue, and gastrointestinal upset were noted in four Group 1 patients and 30 Group 2 patients (P-value 0.0001). Nausea, vomiting, headache, and fatigue were significantly less common side effects in our patients who received MTX daily, but liver enzyme abnormalities were less common, and clinical efficacy was greater in the patients who received MTX weekly. © 2011 The International Society of Dermatology.

  16. Self-Delivery Nanoparticles of Amphiphilic Methotrexate-Gemcitabine Prodrug for Synergistic Combination Chemotherapy via Effect of Deoxyribonucleotide Pools.

    Science.gov (United States)

    Wang, Yao; Huang, Ping; Hu, Minxi; Huang, Wei; Zhu, Xinyuan; Yan, Deyue

    2016-11-16

    The distinct and complementary biochemical mechanisms of folic acid analog methotrexate (MTX) and cytidine analog gemcitabine (GEM) make their synergistic combination effective. Unfortunately, such a combination faces severe pharmacokinetic problems and several transportation barriers. To overcome these problems, a new strategy of amphiphilic small molecule prodrug (ASMP) is developed to improve their synergistic combination effect. The ASMP was prepared by the amidation of the hydrophilic GEM with the hydrophobic MTX at a fixed ratio. Owing to its inherent amphiphilicity, the MTX-GEM ASMP self-assembled into stable nanoparticles (ASMP-NPs) with high drug loading capacity (100%), in which the MTX and GEM could self-deliver without any carriers and release synchronously in cancer cells. In vitro studies showed that the MTX-GEM ASMP-NPs could greatly improve the synergistic combination effects by the reason of arresting more S phase of the cell cycle and reducing levels of deoxythymidine triphosphate (dTTP), deoxyadenosine triphosphate (dATP), and deoxycytidine triphosphate (dCTP). The stronger synergistic effects caused the higher cell cytotoxicity and apoptotic ratio, and circumvented the multidrug resistance (MDR) of tumor cells. Additionally, MTX-GEM ASMP-NPs could achieve the same anticancer effect with the greatly reduced dosage compared with the free drugs according to the dose-reduction index (DRI) values of MTX and GEM in MTX-GEM ASMP-NPs, which may be beneficial for reducing the side effects.

  17. Diosmin Attenuates Methotrexate-Induced Hepatic, Renal, and Cardiac Injury: A Biochemical and Histopathological Study in Mice

    Science.gov (United States)

    Khalifa, Hesham A.; Al-Quraishy, Saleh A.

    2017-01-01

    The current study was designed to investigate the beneficial role of diosmin, a biologically active flavonoid, against methotrexate- (MTX-) induced hepatic, renal, and cardiac injuries in mice. Male Swiss albino mice received a single intraperitoneal injection of MTX (at 20 mg/kg, body weight) either alone or in combination with oral diosmin (at 50 or 100 mg/kg body weight, for 10 days). Serum was used to evaluate tissue injury markers, while hepatic, renal, and cardiac tissue samples were obtained for determination of antioxidant activity as well as histopathological examination. Diosmin treatment ameliorated the MTX-induced elevation of serum alkaline phosphatase, aminotransferases, urea, creatinine, lactate dehydrogenase, and creatine kinases as well as plasma proinflammatory cytokines (interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha). Additionally, both diosmin doses significantly reduced tissue levels of malondialdehyde and nitric oxide and increased those of glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase, and catalase, compared to the MTX-intoxicated group. Histopathological examination showed that diosmin significantly minimized the MTX-induced histological alterations and nearly restored the normal architecture of hepatic, renal, and cardiac tissues. Based on these findings, diosmin may be a promising agent for protection against MTX-induced cytotoxicity in patients with cancer and autoimmune diseases. PMID:28819543

  18. Protective effect of Chlorogenic acid against methotrexate induced oxidative stress, inflammation and apoptosis in rat liver: An experimental approach.

    Science.gov (United States)

    Ali, Nemat; Rashid, Summya; Nafees, Sana; Hasan, Syed Kazim; Shahid, Ayaz; Majed, Ferial; Sultana, Sarwat

    2017-06-25

    Methotrexate (MTX) is a drug which is used to treat different types of cancers but hepatotoxicity limits its clinical use. Chlorogenic acid (CGA) is one of the most abundant naturally occurring polyphenols in the human diet. Here, we assessed the effect of CGA against MTX-induced hepatotoxicity and investigated the underlying possible mechanisms in Wistar Rats. Rats were pre-treated with CGA (50 or 100 mg kg/b.w) and administered a single dose of MTX (20 mg/kg, b.w.). MTX caused hepatotoxicity as evidenced by significant increase in serum toxicity markers, histopathological changes. decreased activities of anti-oxidant armory (SOD, CAT, GPx, GR) and GSH content. MTX significantly causes upregulation of iNOS, Cox-2, Bax and downregulation of Bcl-2 expressions, it causes higher caspase 3, 9 activities. However CGA pretreatment alleviates the hepatotoxicity by decreasing the oxidative stress. CGA inhibited Cox-2, iNOS, Bax, Bcl-2 and Caspases 3, 9 mediated inflammation and apoptosis, and improve the histology induced by MTX. Thus, these findings demonstrated the hepatoprotective nature of CGA by attenuating the pro-inflammatory and apoptotic mediators and improving antioxidant competence in hepatic tissue. These results imply that CGA has perfective effect against MTX-induced liver injury. Hence CGA supplementation might be helpful in abrogation of MTX toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Cumulative Environmental Management Association : Wood Buffalo Region

    International Nuclear Information System (INIS)

    Friesen, B.

    2001-01-01

    The recently announced oil sands development of the Wood Buffalo Region in Alberta was the focus of this power point presentation. Both mining and in situ development is expected to total $26 billion and 2.6 million barrels per day of bitumen production. This paper described the economic, social and environmental challenges facing the resource development of this region. In addition to the proposed oil sands projects, this region will accommodate the needs of conventional oil and gas production, forestry, building of pipelines and power lines, municipal development, recreation, tourism, mining exploration and open cast mining. The Cumulative Environmental Management Association (CEMA) was inaugurated as a non-profit association in April 2000, and includes 41 members from all sectors. Its major role is to ensure a sustainable ecosystem and to avoid any cumulative impacts on wildlife. Other work underway includes the study of soil and plant species diversity, and the effects of air emissions on human health, wildlife and vegetation. The bioaccumulation of heavy metals and their impacts on surface water and fish is also under consideration to ensure the quality and quantity of surface water and ground water. 3 figs

  20. Stability study of methotrexate in 0.9% sodium chloride injection and 5% dextrose injection with limit tests for impurities

    DEFF Research Database (Denmark)

    Nissen, Klaus; Bogedal Jorgensen, Lene; Lindegaard Berg, Dorthe

    2017-01-01

    Purpose. Results of an evaluation of the stability of methotrexate in 0.9% sodium chloride injection and 5% dextrose injection are presented. Methods. Methotrexate concentrated solution (100 mg/mL) was diluted to nominal concentrations of 0.2 and 20 mg/mL in infusion bags containing 0.9% sodium...... chloride injection or 5% dextrose injection. The filled bags were stored for 28 days at 25 °C and 60% relative humidity and protected from light. Samples were withdrawn for analysis on the day of preparation and after 3, 7, 14, 21, and 28 days. The test program included visual inspections, measurements...... in amounts of known and unknown degradation products were detected. In 5% dextrose injection, methotrexate at the higher concentration was stable for 28 days, with minor formation of degradation products; in the 0.2-mg/mL solution, however, methotrexate was stable for only 3 days. At later time points...

  1. Circulating levels of osteoprotegerin and sRANKL and the effect of methotrexate in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Aadhaar Dhooria

    2018-01-01

    Conclusions: OPG levels are higher in RA patients and normalize in response to treatment with methotrexate. The initial higher levels of OPG may represent a compensatory mechanism to osteoclast activation; they normalize on reduction of disease activity.

  2. Successful combination treatment of a patient with progressive juvenile localized scleroderma (morphea) using imatinib, corticosteroids, and methotrexate.

    Science.gov (United States)

    Inamo, Yasuji; Ochiai, Toyoko

    2013-01-01

    We report a case of progressive juvenile localized scleroderma (JLS or morphea) treated with a combination of imatinib, corticosteroids, and methotrexate. This therapy halted the progressive skin thickening and the hand and finger joint deformity in the early stages of the disease. We conclude that imatinib used in addition to standard treatment with systemic corticosteroids and methotrexate may be of therapeutic benefit for individuals with JLS. © 2012 Wiley Periodicals, Inc.

  3. Cumulative ionizing radiation exposure in patients with end stage kidney disease: a 6-year retrospective analysis.

    LENUS (Irish Health Repository)

    Coyle, Joe

    2011-08-13

    OBJECTIVE: To quantify cumulative exposure to ionizing radiation in patients with end stage kidney disease (ESKD). To investigate factors which may be independently associated with risk of high cumulative effective dose (CED). MATERIALS AND METHODS: The study had local institutional review board ethical approval. We conducted a retrospective study of 394 period prevalent ESKD patients attending a single tertiary referral centre between 2004 and 2009. Patient demographics were obtained from case records. Details of radiological investigations were obtained from the institutional radiology computerized database. CED was calculated using standard procedure specific radiation levels. High exposure was defined as CED > 50 mSv, an exposure which has been reported to increase cancer mortality by 5%. Data were compared using Pearson χ(2) and Mann-Whitney U test or Kruskal-Wallis tests. RESULTS: 394 patients were followed for a median of 4 years (1518 patient years follow-up). Of these 63% were male. Seventeen percent of patients had a CED of >50 mSv. Computed tomography (CT) accounted for 9% of total radiological studies\\/procedures while contributing 61.4% of total study dose. Median cumulative dose and median dose per patient year were significantly higher in the hemodialysis (HD) group (15.13 and 5.79 mSv, respectively) compared to the post-transplant group (2.9 and 0.52 mSv, respectively) (P < 0.001). CONCLUSION: ESKD patients are at risk of cumulative exposure to significant levels of diagnostic radiation. The majority of this exposure is imparted as a result of CT examinations to patients in the HD group.

  4. Repeated Radionuclide therapy in metastatic paraganglioma leading to the highest reported cumulative activity of 131I-MIBG

    International Nuclear Information System (INIS)

    Ezziddin, Samer; Sabet, Amir; Ko, Yon-Dschun; Xun, Sunny; Matthies, Alexander; Biersack, Hans-Jürgen

    2012-01-01

    131 I-MIBG therapy for neuroendocrine tumours may be dose limited. The common range of applied cumulative activities is 10-40 GBq. We report the uneventful cumulative administration of 111 GBq (= 3 Ci) 131 I-MIBG in a patient with metastatic paraganglioma. Ten courses of 131 I-MIBG therapy were given within six years, accomplishing symptomatic, hormonal and tumour responses with no serious adverse effects. Chemotherapy with cisplatin/vinblastine/dacarbazine was the final treatment modality with temporary control of disease, but eventually the patient died of progression. The observed cumulative activity of 131 I-MIBG represents the highest value reported to our knowledge, and even though 12.6 GBq of 90 Y-DOTATOC were added intermediately, no associated relevant bone marrow, hepatic or other toxicity were observed. In an individual attempt to palliate metastatic disease high cumulative activity alone should not preclude the patient from repeat treatment

  5. Dynamics of Destructive Joint Changes in Juvenile Idiopathic Arthritis in Children who Received Methotrexate or Methotrexate-Tocilizumab Combination: a Cohort Study

    Directory of Open Access Journals (Sweden)

    Maria A. Davydova

    2017-01-01

    Full Text Available Background. Destructive joint damages in juvenile arthritis inevitably lead to persistent disability in adulthood. These consequences can be avoided by resorting to early therapy of the disease.Objective. Our aim was to assess the dynamics of destructive joint changes in juvenile idiopathic arthritis (JIA in children, depending on a basic therapy.Methods. We studied the treatment results of children with systemic-onset JIA with active joint syndrome without active  systemic manifestations hospitalized in the regional clinical  cardiological health center. JIA activity criteria at the time of  hospitalization: 3 joints with active arthritis; the assessment of the disease activity by a doctor 3 points out of 10; the assessment of  wellbeing by the patient or a parent 3 points out of 10; the  appointment of basic therapy no later than 6 months from the  disease onset. Treatment results were compared in the groups of  methotrexate (hospitalization from January 2008 to December 2010 and methotrexate + tocilizumab (January 2014 — September 2016. The main outcome of JIA therapy was the severity of joint  destruction in 6, 12 and 24 months as determined by the modified  Sharpe ratio according to radiographs obtained from patients' medical records.Results. The study groups were comparable in terms of sex and age of the patients, JIA onset age, the disease activity at the time of  hospitalization, and the initial assessment of joint destruction —  (median 165 (131; 187 and 162 (124; 171 (p = 0.116. Under  pressure of therapy, the modified Sharpe score in the group of  methotrexate monotherapy was higher than in the group of combined therapy: in 6 months — 142 (126; 163 and 87 (72; 112 (p < 0.001; in 12 months — 166 (121; 210 and 75 (29; 89 (p <  0.001; in 24 months — 165 (113; 198 and 52 (26; 73 (p <  0.001. At the first administration of tocilizumab, 4 children had nausea and abdominal pain, and 3 children had

  6. Evolution model with a cumulative feedback coupling

    Science.gov (United States)

    Trimper, Steffen; Zabrocki, Knud; Schulz, Michael

    2002-05-01

    The paper is concerned with a toy model that generalizes the standard Lotka-Volterra equation for a certain population by introducing a competition between instantaneous and accumulative, history-dependent nonlinear feedback the origin of which could be a contribution from any kind of mismanagement in the past. The results depend on the sign of that additional cumulative loss or gain term of strength λ. In case of a positive coupling the system offers a maximum gain achieved after a finite time but the population will die out in the long time limit. In this case the instantaneous loss term of strength u is irrelevant and the model exhibits an exact solution. In the opposite case λ<0 the time evolution of the system is terminated in a crash after ts provided u=0. This singularity after a finite time can be avoided if u≠0. The approach may well be of relevance for the qualitative understanding of more realistic descriptions.

  7. Psychometric properties of the Cumulated Ambulation Score

    DEFF Research Database (Denmark)

    Ferriero, Giorgio; Kristensen, Morten T; Invernizzi, Marco

    2018-01-01

    INTRODUCTION: In the geriatric population, independent mobility is a key factor in determining readiness for discharge following acute hospitalization. The Cumulated Ambulation Score (CAS) is a potentially valuable score that allows day-to-day measurements of basic mobility. The CAS was developed...... and validated in older patients with hip fracture as an early postoperative predictor of short-term outcome, but it is also used to assess geriatric in-patients with acute medical illness. Despite the fast- accumulating literature on the CAS, to date no systematic review synthesizing its psychometric properties....... Of 49 studies identified, 17 examined the psychometric properties of the CAS. EVIDENCE SYNTHESIS: Most papers dealt with patients after hip fracture surgery, and only 4 studies assessed the CAS psychometric characteristics also in geriatric in-patients with acute medical illness. Two versions of CAS...

  8. Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Nielsen, Stine N; Frandsen, Thomas L

    2014-01-01

    implementation of pharmacogenomics into treatment, the sole exception being dramatic 6MP dose reductions in patients who are homozygous deficient for thiopurine methyltransferase, the enzyme that methylates 6MP and several of its metabolites. In conclusion, maintenance therapy is as important as the more...

  9. Novel methotrexate soft nanocarrier/fractional erbium YAG laser combination for clinical treatment of plaque psoriasis.

    Science.gov (United States)

    Ramez, Shahenda A; Soliman, Mona M; Fadel, Maha; Nour El-Deen, Faisal; Nasr, Maha; Youness, Eman R; Aboel-Fadl, Dalea M

    2018-02-15

    Psoriasis is a commonly encountered chronic dermatological disease, presenting with inflammatory symptoms in patients. Systemic treatment of psoriasis is associated with several adverse effects, therefore the development of a customized topical treatment modality for psoriasis would be an interesting alternative to systemic delivery. The therapeutic modality explored in this article was the comparative treatment of psoriatic patients using nanoparticulated methotrexate in the form of jojoba oil-based microemulsion with or without fractional erbium YAG laser. Assessment parameters included follow-up photography for up to 8 weeks of treatment, estimation of the psoriasis severity [TES (thickness, erythema, scales)] score, and histopathological skin evaluation. The prepared methotrexate microemulsion was clinically beneficial and safe in treatment of psoriasis vulgaris. The concomitant use of the fractional laser provided improvement in the psoriatic plaques within shorter time duration (3 weeks compared to 8 weeks of treatment), presenting an alternative topical treatment modality for psoriasis vulgaris.

  10. Effects of growth hormone plus a hyperproteic diet on methotrexate-induced injury in rat intestines.

    Science.gov (United States)

    Ortega, M; Gomez-de-Segura, I A; Vázquez, I; López, J M; de Guevara, C L; De-Miguel, E

    2001-01-01

    The aim of this study was to determine whether growth hormone treatment reduces injury to the intestinal mucosa induced by methotrexate (MTX). Wistar rats with intestinal injury induced by methotrexate were treated with daily growth hormone, beginning 3 days before MTX treatment until 3 or 4 days after MTX administration. The rats were killed at 3 or 7 days post-MTX administration. The rats were fed with either a normoproteic diet or a hyperproteic diet. Body weight, mortality, bacterial translocation, intestinal morphometry, proliferation and apoptosis and blood somatostatin and IGF-1 were determined. Combined administration of growth hormone and a hyperproteic diet reduces MTX-induced mortality. This effect was accompanied by increased cell proliferation and decreased apoptosis within the crypt. Morphometric data showed complete recovery of the mucosa by day 7 post-MTX administration. These results indicate a synergistic protective action of growth hormone combined with a hyperproteic diet to MTX-induced injury.

  11. [Fiessinger-Leroy-Reiter syndrome with non-obstructive cardiomyopathy treated with methotrexate].

    Science.gov (United States)

    Blétry, O; De Prost, Y; Scheuble, C; Frank, R; Godeau, P

    1979-07-01

    The case of a 50 year old male with the Fiessinger-Leroy-Reiter syndrome, ankylosing spondylitis and generalised pustular psoriasis is reported. This condition wax complicated by non-obstructive cardiomyopathy, congestive cardiac failure and first-degree atrioventricular block, the site of which was localised by electrophysiological studies (nodal block with an infrahisian conduction defect). After failure of several therapeutic regimes, a spectacular improvement was obtained with Methotrexate associated with a diuretic; the signs of heart failure regressed and the cardiomyopathy stablised. A parallel improvement was seen in the skin, cardiac and articular lesions and has been maintained with an 18 months follow-up. Left ventricular performance was studied by echocardiography. The mechanism of the beneficial effect of Methotrexate is unclear; this therapeutic trial is to be extended to include other cases of primary cardiomyopathy without obstruction.

  12. Actuarial risk of isolated CNS involvement in Ewing's sarcoma following prophylactic cranial irradiation and intrathecal methotrexate

    International Nuclear Information System (INIS)

    Trigg, M.E.; Makuch, R.; Glaubiger, D.

    1985-01-01

    Records of 154 patients with Ewing's sarcoma treated at the National Cancer Institute were reviewed to assess the incidence and risk of developing isolated central nervous system (CNS) Ewing's sarcoma. Sixty-two of the 154 patients had received CNS irradiation and intrathecal (i.t.) methotrexate as part of their initial therapy to prevent the occurrence of isolated CNS Ewing's sarcoma. The risk of developing isolate CNS Ewing's sarcoma was greatest within the first two years after diagnosis and was approximately 10%. The overall risk of CNS recurrence in the group of patients receiving DNS treatment was similar to the group receiving no therapy directed to the CNS. The occurrence of isolated CNS involvement was not prevented by the use of CNS irradiation and i.t. methotrexate. Because of a lack of efficacy to the CNS irradiation regimen, current treatment regimens do not include therapy directed to CNS

  13. A Combination of Surgery And Methotrexate for Successful Treatment of a Caesarean Scar Ectopic Pregnancy.

    LENUS (Irish Health Repository)

    Tadesse, WG

    2018-06-01

    Caesarean scar ectopic pregnancy (CSEP) is one of the rarest forms of ectopic pregnancies. With rising caesarean delivery (CD) rates worldwide, there is an increase in the incidence of CSEP. Patients usually present with painless vaginal bleeding and often misdiagnosed as spontaneous miscarriage. The use of ultrasonography with colour flow Doppler helps in the differential diagnosis. Different treatment options are described in the literature, although there is insufficient evidence regarding the best approach. We report the diagnosis and management of a case of CSEP in a woman with four previous CD who presented with vaginal bleeding and lower abdominal cramps at six weeks of gestation. She was treated with laparoscopic and ultrasound guided aspiration of the gestational sac and local injection of methotrexate supplemented by intramuscular methotrexate injection.

  14. Successful Management of Cervical Ectopic Pregnancy with Bilateral Uterine Artery Embolization and Methotrexate

    Directory of Open Access Journals (Sweden)

    Keitaroh Takeda

    2018-01-01

    Full Text Available Cervical ectopic pregnancy (CEP is a rare form of ectopic pregnancy. Cases diagnosed early in pregnancy can be managed medically, but more advanced pregnancies often require hysterectomy. Uterine artery embolization (UAE is a novel approach to CEP for those who wish to preserve fertility. Here we present the case of a 44-year-old female with a 2-week history of vaginal bleeding and abdominal pain who was diagnosed with CEP and successfully treated with bilateral UAE (BUAE in combination with methotrexate. A 44-year-old female presented to the emergency department with a 2-week history of vaginal bleeding. Serum beta-hCG was 71,964 mIU/ml. The transvaginal ultrasound confirmed CEP. The patient was referred to obstetrics and interventional radiology and ultimately treated with BUAE and methotrexate. Symptoms resolved quickly and she was discharged after 3 days.

  15. Preliminary study for predicting better methotrexate efficacy in Japanese patients with rheumatoid arthritis

    OpenAIRE

    Hashiguchi, Masayuki; Tsuru, Tomomi; Miyawaki, Kumika; Suzaki, Midori; Hakamata, Jun; Shimizu, Mikiko; Irie, Shin; Mochizuki, Mayumi

    2016-01-01

    Background Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammatory status, joint destruction, disability, and pain. Methotrexate (MTX) has been confirmed to reduce disease activity and delay or stabilize the development of bone erosions. However, major drawbacks are that patients show great interindividual variability in response to MTX and the unpredictable occurrence of side effects. A strategy for personalized MTX treatment to predict its efficacy a...

  16. Multicenter study of environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in 48 Canadian hospitals.

    Science.gov (United States)

    Poupeau, Céline; Tanguay, Cynthia; Caron, Nicolas J; Bussières, Jean-François

    2018-01-01

    Context Oncology workers are occupationally exposed to antineoplastic drugs. This exposure can induce adverse health effects. In order to reduce their exposure, contamination on surfaces should be kept as low as possible. Objectives To monitor environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in oncology pharmacy and patient care areas in Canadian hospitals. To describe the impact of some factors that may limit contamination. Methods This is a descriptive study. Twelve standardized sites were sampled in each participating center (six in the pharmacy and six in patient care areas). Samples were analyzed for the presence of cyclophosphamide, ifosfamide, and methotrexate by ultra-performance liquid chromatography tandem mass spectrometry technology. Descriptive statistical analyses were done and results were compared with a Kolmogorov-Smirnov test for independent samples. Results In 2015, 48 hospitals participated in this study (48/202, 24%). Overall, 34% (181/525) of the samples were positive for cyclophosphamide, 8% (41/525) for ifosfamide, and 6% (31/525) for methotrexate. The 75th percentile value of cyclophosphamide surface concentration was 6.9 pg/cm 2 . For ifosfamide and methotrexate, they were lower than the limit of detection. Centers who prepared more antineoplastic drugs per year and centers who used more cyclophosphamide per year showed significantly higher surface contamination ( p contamination. Conclusion In comparison with other multicenter studies that were conducted in Canada, the concentration of antineoplastic drugs measured on surfaces is decreasing. Regular environmental monitoring is a good practice in order to maintain contamination as low as reasonably achievable.

  17. Outpatient endometrial aspiration: an alternative to methotrexate for pregnancy of unknown location.

    Science.gov (United States)

    Insogna, Iris G; Farland, Leslie V; Missmer, Stacey A; Ginsburg, Elizabeth S; Brady, Paula C

    2017-08-01

    Pregnancies of unknown location with abnormal beta-human chorionic gonadotropin trends are frequently treated as presumed ectopic pregnancies with methotrexate. Preliminary data suggest that outpatient endometrial aspiration may be an effective tool to diagnose pregnancy location, while also sparing women exposure to methotrexate. The purpose of this study was to evaluate the utility of an endometrial sampling protocol for the diagnosis of pregnancies of unknown location after in vitro fertilization. A retrospective cohort study of 14,505 autologous fresh and frozen in vitro fertilization cycles from October 2007 to September 2015 was performed; 110 patients were diagnosed with pregnancy of unknown location, defined as a positive beta-human chorionic gonadotropin without ultrasound evidence of intrauterine or ectopic pregnancy and an abnormal beta-human chorionic gonadotropin trend (location, failed intrauterine pregnancy was diagnosed in 46 patients (42%), and ectopic pregnancy was diagnosed in 64 patients (58%). Clinical variables that included fresh or frozen embryo transfer, day of embryo transfer, serum beta-human chorionic gonadotropin at the time of sampling, endometrial thickness, and presence of an adnexal mass were not significantly different between patients with failed intrauterine pregnancy or ectopic pregnancy. In patients with failed intrauterine pregnancy, 100% demonstrated adequate postsampling beta-human chorionic gonadotropin declines; villi were identified in just 46% (n=21 patients). Patients with failed intrauterine pregnancy had significantly shorter time to resolution (negative serum beta-human chorionic gonadotropin) after sampling compared with patients with ectopic pregnancy (12.6 vs 26.3 days; Plocation are spared methotrexate, with a shorter time to pregnancy resolution than those who receive methotrexate. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Quantifying the hepatotoxic risk of alcohol consumption in patients with rheumatoid arthritis taking methotrexate

    OpenAIRE

    Humphreys, Jenny H; Warner, Alexander; Costello, Ruth; Lunt, Mark; Verstappen, Suzanne M M; Dixon, William G

    2017-01-01

    Background Patients with rheumatoid arthritis (RA) who take methotrexate (MTX) are advised to limit their alcohol intake due to potential combined hepatotoxicity. However, data are limited to support this. The aim of this study was to quantify the risk of developing abnormal liver blood tests at different levels of alcohol consumption, using routinely collected data from primary care. Methods Patients with RA in the Clinical Practice Research Datalink starting MTX between 1987 and 2016 were i...

  19. Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis.

    OpenAIRE

    Gerards, A.H.; Lathouder, de, S; Groot, E.R.; Dijkmans, B.A.C.; Aarden, L.A.

    2003-01-01

    OBJECTIVES: To analyse whether the beneficial effects of methotrexate in rheumatoid arthritis (RA) could be due to inhibition of inflammatory cytokine production. METHODS: Cytokine production was studied using whole blood (WB) and mononuclear cells (MNC) of healthy volunteers and RA patients. Cultures were stimulated with either bacterial products such as lipo-oligosaccharide (LOS) or Staphylococcus aureus Cowan I (SAC) to activate monocytes or with monoclonal antibodies to CD3 and CD28 to in...

  20. Methotrexate for the Treatment of Pediatric Crohn's Disease: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Colman, Ruben J; Lawton, Rachel C; Dubinsky, Marla C; Rubin, David T

    2018-04-23

    Methotrexate (MTX) is an immunomodulator used for the treatment of pediatric inflammatory bowel disease (IBD). There are currently no RCTs that assess the treatment efficacy of methotrexate within the pediatric IBD patient population. This systematic review and meta-analysis assesses the efficacy of MTX therapy among the existing pediatric literature. A systematic literature search was performed using MEDLINE and the Cochrane library from inception until March 2016. Synonyms for 'pediatric', 'methotrexate' and 'IBD' were utilized as both free text and MESH search terms. The studies included contained clinical remission (CR) rates for MTX treatment of pediatric IBD patients 18 yrs old, as mono- or combination therapy. Case studies with <10 patients were excluded. Quality assessment was performed with the Newcastle-Ottawa Scale. Meta-analysis calculated pooled CR rates. A random-effects meta-analysis with forest plots was performed using R. Fourteen (11 monotherapy, 1 combination therapy, 2 both; n = 886 patients) observational studies were eligible out of 202 studies. No interventional studies were identified. The pooled achieved CR rate for pediatric CD patients on monotherapy within 3-6 months was 57.7% (95% CI 48.2-66.6%), (P =0.22; I2 = 29.8%). The CR was 37.1% (95% CI 29.5-45.5%), (P = 0.20; I2 = 37.4%) for maintenance therapy at 12 months. Sub-analysis could not identify CR differences between MTX administration types, thiopurine exposure. This meta-analysis demonstrated that, over 50% of pediatric Crohn's disease patients induced with methotrexate achieved clinical remission, while 12-month remission rate was only 37%. Prospective controlled interventional trials should assess treatment efficacy among patient subgroups. 10.1093/ibd/izy078_video1izy078.video15774883936001.

  1. Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis

    OpenAIRE

    Fleischmann, Roy M; Huizinga, Tom W J; Kavanaugh, Arthur F; Wilkinson, Bethanie; Kwok, Kenneth; DeMasi, Ryan; van Vollenhoven, Ronald F

    2016-01-01

    Introduction Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24?months in methotrexate (MTX)-naive adult patients with RA. In this post hoc analysis, we compared efficacy and safety of tofacitinib in patients with early (disease duration

  2. Evaluation of Protective Activity of Curcumin in Reducing Methotrexate Induced Liver Cells Injury: An Experimental Study on Iraqi White Domestic Rabbits

    Directory of Open Access Journals (Sweden)

    Hussain Abady Aljebori

    2018-03-01

    Full Text Available Background: Hepatotoxicity is a common problem in medical practice, most of the commonly used drugs are potentially hepatotoxic. Although Methotrexate is a hepa- toxic drug, it is widely used in the treatment of many cancerous and non-cancerous conditions because of its cytotoxic and immunosuppressant activity. Curcumin con- tains a variety of natural substances with antioxidant properties, it is widely used in  folk medicine.Antioxidant activity of Curcumin can reduce liver cell injury induced by Methotrexate administration. Objective: The research aims to study the methotrexate hepatoxicity on rabbits, and the hepatoprotective activity of Curcumin. Materials and Methods: Thirty white domestic rabbits were bought from animal market and grouped randomly into three groups; control group received intraperitoneal normal saline, methotrexate group received 6.5 mg/Kgm body weight intraperitoneal methotrexate, and curcumin group received oral Curcumin in addition to intraperitoneal methotrexate. Results: The study showed abnormal liver function tests, INR, liver tissues oxida- tive markers, and liver cell injury on histopathology in Methotrexate group, and normal findings in Curcumin groups. Conclusion: It is concluded that the Methotrexate is a hepatotoxic drug. The results also shoe that the concomitant administration of Curcumin reduced hepatotoxicity. Recommendation: It is recommended to use of Curcumin in clinical practice as a food supplement to patient receiving methotrexate to reduce hepatotoxicity.

  3. PEG capped methotrexate silver nanoparticles for efficient anticancer activity and biocompatibility.

    Science.gov (United States)

    Muhammad, Zarmina; Raza, Abida; Ghafoor, Sana; Naeem, Ayesha; Naz, Syeda Sohaila; Riaz, Sundus; Ahmed, Wajiha; Rana, Nosheen Fatima

    2016-08-25

    Nanocarriers endow tremendous benefits to the drug delivery systems depending upon the specific properties of either component. These benefits include, increase in the drug blood retention time, reduced efflux, additional toxicity and targeted delivery. Methotrexate (MTX) is clinically used for cancer treatment. Higher dosage of MTX results in hepatic and renal toxicity. In this study methotrexate silver nanoparticles (Ag-MTX) coated with polyethylene glycol (PEG) are synthesized and characterized. Their anticancer activity and biocompatibility is also evaluated. Ag-MTX nanoparticles are synthesized by chemical reduction method. They are characterized by Ultraviolet-Visible Spectroscopy and Fourier Transform Infrared Spectroscopy. Average size of PEG coated Ag-MTX nanoparticles (PEG-Ag-MTX nanoparticles) is 12nm. These particles exhibited improved anticancer activity against MCF-7 cell line. Hemolytic activity of these particles was significantly less than MTX. PEG-Ag-MTX nanoparticles are potential nanocarrier of methotrexate which may offer MTX based cancer treatment with reduced side effects. In-vivo investigations should be carried out to explore them in detail. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats

    International Nuclear Information System (INIS)

    Chiang, H.-M.; Fang, S.-H.; Wen, K.-C.; Hsiu, S.-L.; Tsai, Shang-Yuan; Hou, Y.-C.; Chi, Y.-C.; Lee Chao, Pei-Dawn

    2005-01-01

    Isoflavone supplements are nowadays widely used as alternative for hormone replacement therapy. However, the safety remains unanswered. This study attempted to investigate the effect of Pueraria lobata root decoction (PLRD), an isoflavone-rich herb, on the pharmacokinetics of methotrexate (MTX), a bicarboxylate antimetabolite with narrow therapeutic window. Rats were orally and intravenously given methotrexate alone and coadministered with PLRD. Blood samples were withdrawn via cardiopuncture at specific time points after drug administration. Serum methotrexate concentrations were assayed by specific monoclonal fluorescence polarization immunoassay method. Pharmacokinetic parameters were calculated using noncompartment model of WINNONLIN for both oral and intravenous data of MTX. Our results showed that coadministration of 4.0 g/kg and 2.0 g/kg of PLRD significantly increased the AUC 0-t by 207.8% and 127.9%, prolonged the mean residence time (MRT) by 237.8 and 155.2%, respectively, finally resulted in surprisingly high mortalities of 57.1% and 14.3% in rats. When MTX was given intravenously, the coadministration of PLRD at 4.0 g/kg significantly increased the half-life by 53.9% and decreased the clearance by 47.9%. In conclusion, the coadministration of PLRD significantly decreased the elimination and resulted in markedly increased exposure of MTX in rats

  5. A qualitative analysis of methotrexate self-injection education videos on YouTube.

    Science.gov (United States)

    Rittberg, Rebekah; Dissanayake, Tharindri; Katz, Steven J

    2016-05-01

    The aim of this study is to identify and evaluate the quality of videos for patients available on YouTube for learning to self-administer subcutaneous methotrexate. Using the search term "Methotrexate injection," two clinical reviewers analyzed the first 60 videos on YouTube. Source and search rank of video, audience interaction, video duration, and time since video was uploaded on YouTube were recorded. Videos were classified as useful, misleading, or a personal patient view. Videos were rated for reliability, comprehensiveness, and global quality scale (GQS). Reasons for misleading videos were documented, and patient videos were documented as being either positive or negative towards methotrexate (MTX) injection. Fifty-one English videos overlapped between the two geographic locations; 10 videos were classified as useful (19.6 %), 14 misleading (27.5 %), and 27 personal patient view (52.9 %). Total views of videos were 161,028: 19.2 % useful, 72.8 % patient, and 8.0 % misleading. Mean GQS: 4.2 (±1.0) useful, 1.6 (±1.1) misleading, and 2.0 (±0.9) for patient videos (p tool available, clinicians need to be familiar with specific resources to help guide and educate their patients to ensure best outcomes.

  6. Delivery of Methotrexate and Characterization of Skin Treated by Fabricated PLGA Microneedles and Fractional Ablative Laser.

    Science.gov (United States)

    Nguyen, Hiep X; Banga, Ajay K

    2018-02-21

    This study investigated in vitro transdermal delivery of methotrexate through dermatomed porcine ear and cadaver human skin treated with poly (D,L-lactide-co-glycolide) acid microneedles or fractional ablative laser. PLGA microneedles were fabricated and characterized using scanning electron microscopy and mechanical assessment techniques. The integrity of treated skin was evaluated by rheometer, transepidermal water loss, and skin electrical resistance measurements. Successful skin microporation was demonstrated by dye binding, histology, pore uniformity, confocal laser microscopy, and DermaScan studies. In vitro permeation experiment was performed on Franz diffusion cells to determine drug delivery into and across the skin. Both physical treatments resulted in a considerable decrease in skin resistance and an increase in transepidermal water loss value. The laser-created microchannels were significantly larger than those formed by microneedles (p < 0.05). An effective force of 41.04 ± 18.33 N was required to achieve 100% penetration efficiency of the microneedles. For both porcine ear and human skin, laser ablation provided a significantly higher methotrexate permeability into the receptor chamber and skin layers compared to microneedle poration and untreated skin (p < 0.05). Both fractional ablative laser and polymeric microneedles markedly enhanced in vitro transdermal delivery of methotrexate into and across skin. Graphical Abstract ᅟ.

  7. Mechanisms and Implications of Dual-Acting Methotrexate in Folate-Targeted Nanotherapeutic Delivery

    Directory of Open Access Journals (Sweden)

    Pamela T. Wong

    2015-01-01

    Full Text Available The rational design of a nanoplatform in drug delivery plays a crucial role in determining its targeting specificity and efficacy in vivo. A conventional approach relies on the surface conjugation of a nanometer-sized particle with two functionally distinct types of molecules, one as a targeting ligand, and the other as a therapeutic agent to be delivered to the diseased cell. However, an alternative simplified approach can be used, in which a single type of molecule displaying dual function as both a targeting ligand and therapeutic agent is conjugated to the nanoparticle. In this review, we evaluate the validity of this new strategy by using methotrexate, which displays multifunctional mechanisms of action. Methotrexate binds to the folate receptor, a surface biomarker frequently overexpressed in tumor cells, and also inhibits dihydrofolate reductase, an enzyme critical for cell survival and division. Thus we describe a series of fifth generation poly(amido amine dendrimers conjugated with methotrexate, and discuss several lines of evidence supporting the efficacy of this new platform strategy based on surface plasmon resonance spectroscopy, enzyme activity assays, and cell-based studies with folate receptor (+ KB cancer cells.

  8. Synchronized dynamic dose reconstruction

    International Nuclear Information System (INIS)

    Litzenberg, Dale W.; Hadley, Scott W.; Tyagi, Neelam; Balter, James M.; Ten Haken, Randall K.; Chetty, Indrin J.

    2007-01-01

    Variations in target volume position between and during treatment fractions can lead to measurable differences in the dose distribution delivered to each patient. Current methods to estimate the ongoing cumulative delivered dose distribution make idealized assumptions about individual patient motion based on average motions observed in a population of patients. In the delivery of intensity modulated radiation therapy (IMRT) with a multi-leaf collimator (MLC), errors are introduced in both the implementation and delivery processes. In addition, target motion and MLC motion can lead to dosimetric errors from interplay effects. All of these effects may be of clinical importance. Here we present a method to compute delivered dose distributions for each treatment beam and fraction, which explicitly incorporates synchronized real-time patient motion data and real-time fluence and machine configuration data. This synchronized dynamic dose reconstruction method properly accounts for the two primary classes of errors that arise from delivering IMRT with an MLC: (a) Interplay errors between target volume motion and MLC motion, and (b) Implementation errors, such as dropped segments, dose over/under shoot, faulty leaf motors, tongue-and-groove effect, rounded leaf ends, and communications delays. These reconstructed dose fractions can then be combined to produce high-quality determinations of the dose distribution actually received to date, from which individualized adaptive treatment strategies can be determined

  9. The cumulative effect of air pollutants on the acute exacerbation of COPD in Shanghai, China.

    Science.gov (United States)

    Sun, Xian Wen; Chen, Pei Li; Ren, Lei; Lin, Ying Ni; Zhou, Jian Ping; Ni, Lei; Li, Qing Yun

    2018-05-01

    Epidemiologic studies have shown the effect of air pollutants on acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, little is known regarding the dose-response relationship. This study aimed to investigate the cumulative effect of air pollutants on AECOPD. We collected 101 patients with AECOPD from November 2010 through August 2011 in Shanghai. Multiple logistic regression was used to estimate associations between air pollutants and AECOPD. Poisson regression was then applied to determine the cumulative effect of air pollutants including particulate matter 10 (PM10), PM2.5, nitrogen dioxide (NO 2 ), sulphur dioxide (SO 2 ) and ozone (O 3 ) on AECOPD, of which the seasonal variation was further explored. The monthly episodes of AECOPD were associated with the concentrations of PM2.5 (r=0.884, peffect in cold season, whereas 7days in warm season. The RR for AECOPD for per 10μg/m 3 increment in NO 2 was 1.07, with a 5-day cumulative effect without seasonal variation. High consecutive levels of PM2.5 and NO 2 increase the risk of developing AECOPD. Cumulative effect of PM2.5 and NO 2 appears before the exacerbation onset. These gradations were more evident in the PM2.5 during different seasons. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. 7 CFR 42.132 - Determining cumulative sum values.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Determining cumulative sum values. 42.132 Section 42... Determining cumulative sum values. (a) The parameters for the on-line cumulative sum sampling plans for AQL's... 3 1 2.5 3 1 2 1 (b) At the beginning of the basic inspection period, the CuSum value is set equal to...

  11. Improving cumulative effects assessment in Alberta: Regional strategic assessment

    International Nuclear Information System (INIS)

    Johnson, Dallas; Lalonde, Kim; McEachern, Menzie; Kenney, John; Mendoza, Gustavo; Buffin, Andrew; Rich, Kate

    2011-01-01

    The Government of Alberta, Canada is developing a regulatory framework to better manage cumulative environmental effects from development in the province. A key component of this effort is regional planning, which will lay the primary foundation for cumulative effects management into the future. Alberta Environment has considered the information needs of regional planning and has concluded that Regional Strategic Assessment may offer significant advantages if integrated into the planning process, including the overall improvement of cumulative environmental effects assessment in the province.

  12. Children neglected: Where cumulative risk theory fails.

    Science.gov (United States)

    O'Hara, Mandy; Legano, Lori; Homel, Peter; Walker-Descartes, Ingrid; Rojas, Mary; Laraque, Danielle

    2015-07-01

    Neglected children, by far the majority of children maltreated, experience an environment most deficient in cognitive stimulation and language exchange. When physical abuse co-occurs with neglect, there is more stimulation through negative parent-child interaction, which may lead to better cognitive outcomes, contrary to Cumulative Risk Theory. The purpose of the current study was to assess whether children only neglected perform worse on cognitive tasks than children neglected and physically abused. Utilizing LONGSCAN archived data, 271 children only neglected and 101 children neglected and physically abused in the first four years of life were compared. The two groups were assessed at age 6 on the WPPSI-R vocabulary and block design subtests, correlates of cognitive intelligence. Regression analyses were performed, controlling for additional predictors of poor cognitive outcome, including socioeconomic variables and caregiver depression. Children only neglected scored significantly worse than children neglected and abused on the WPPSI-R vocabulary subtest (p=0.03). The groups did not differ on the block design subtest (p=0.4). This study shows that for neglected children, additional abuse may not additively accumulate risk when considering intelligence outcomes. Children experiencing only neglect may need to be referred for services that address cognitive development, with emphasis on the linguistic environment, in order to best support the developmental challenges of neglected children. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Standardization of the cumulative absolute velocity

    International Nuclear Information System (INIS)

    O'Hara, T.F.; Jacobson, J.P.

    1991-12-01

    EPRI NP-5930, ''A Criterion for Determining Exceedance of the Operating Basis Earthquake,'' was published in July 1988. As defined in that report, the Operating Basis Earthquake (OBE) is exceeded when both a response spectrum parameter and a second damage parameter, referred to as the Cumulative Absolute Velocity (CAV), are exceeded. In the review process of the above report, it was noted that the calculation of CAV could be confounded by time history records of long duration containing low (nondamaging) acceleration. Therefore, it is necessary to standardize the method of calculating CAV to account for record length. This standardized methodology allows consistent comparisons between future CAV calculations and the adjusted CAV threshold value based upon applying the standardized methodology to the data set presented in EPRI NP-5930. The recommended method to standardize the CAV calculation is to window its calculation on a second-by-second basis for a given time history. If the absolute acceleration exceeds 0.025g at any time during each one second interval, the earthquake records used in EPRI NP-5930 have been reanalyzed and the adjusted threshold of damage for CAV was found to be 0.16g-set

  14. Analysis of Memory Codes and Cumulative Rehearsal in Observational Learning

    Science.gov (United States)

    Bandura, Albert; And Others

    1974-01-01

    The present study examined the influence of memory codes varying in meaningfulness and retrievability and cumulative rehearsal on retention of observationally learned responses over increasing temporal intervals. (Editor)

  15. Immunogenicity and safety of the inactivated hepatitis A vaccine in children with juvenile idiopathic arthritis on methotrexate treatment: a matched case-control study.

    Science.gov (United States)

    Maritsi, Despoina N; Coffin, Susan E; Argyri, Ioanna; Vartzelis, George; Spyridis, Nick; Tsolia, Maria N

    2017-01-01

    To describe the immunogenicity and side effects of immunisation against hepatitis A virus (HAV) in JIA patients on methotrexate treatment, who have not been previously exposed to HAV. Case-control study performed in JIA patients and healthy controls matched on age and gender. The subjects received two doses of inactivated anti-HAV vaccine (720 mIU/ml) intramuscularly at 0 and 6 months. Seroconversion, seroprotection rates and anti-HAV-IgG titres were measured at 1, 7 and 18 months. Children were monitored for adverse events. 83 JIA patients and 76 controls were enrolled in the study. At one month, seroprotection rates were lower in children with, as compared to those without JIA (48.2% vs. 65%; p=0.05). At 7 and 18 months, rates of seroprotection rose significantly and were similar in both groups. The titre of anti-HAV-IgG was lower in children with JIA than healthy children at all time points (pVaccines were well tolerated. Two doses of inactivated HAV vaccine were well tolerated and immunogenic in most immunosuppressed children with JIA; however, a single dose of HAV vaccine was insufficient to induce seroprotection in half of the patients. Further studies are required to analyse the long-term immunity against HAV in this population and optimal HAV immunisation regimen.

  16. The influence of folate pathway polymorphisms on high-dose methotrexaterelated toxicity and survival in children with non-Hodgkin malignant lymphoma

    Directory of Open Access Journals (Sweden)

    Erculj Nina

    2014-09-01

    Full Text Available Background. We evaluated the influence of folate pathway polymorphisms on high-dose methotrexate (HD-MTX related toxicity in paediatric patients with T-cell non-Hodgkin lymphoma (NHL. Patients and methods. In total, 30 NHL patients were genotyped for selected folate pathway polymorphisms.

  17. Feasibility of a dose-intensive CMF regimen with granulocyte colony-stimulating factor as adjuvant therapy in premenopausal patients with node-positive breast cancer

    NARCIS (Netherlands)

    Bos, AME; de Graaf, H; de Vries, EGE; Piersma, H; Willemse, PHB

    Our aim was to study the feasibility of an intensified intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) schedule with the aim to escalate dose intensity (DI). Twenty-three premenopausal breast cancer patients received 6 cycles of adjuvant CMF intravenously on days 1. and 8 every 3

  18. Methotrexate as a first-line corticosteroid-sparing therapy in a cohort of uveitis and scleritis.

    Science.gov (United States)

    Kaplan-Messas, Audrey; Barkana, Yaniv; Avni, Isaac; Neumann, Ron

    2003-06-01

    To evaluate the clinical experience with methotrexate as a first-line corticosteroid-sparing drug in patients with resistant ocular inflammation. We retrospectively studied 39 consecutive patients with uveitis (n = 36) or scleritis (n = 3) who were treated with methotrexate following inadequate control with corticosteroids lasting five years. Criteria for initiating treatment with methotrexate and defining outcome were strictly defined. The cohort included 21 females and 18 males, all Caucasians, with a mean age of 26.6 years (range: 3-73 years). Patients were followed up for 21.5 +/- 12.6 months. Treatment was discontinued due to side effects in 10 patients (26%). Of the remaining 29 patients, full or partial control of inflammation was achieved in 23 (79%). Response to treatment was observed after a mean of 2.4 +/- 0.8 months. Ten patients were fully controlled and discontinued methotrexate therapy after a mean of 20.9 +/- 9.2 months, with no recurrence of inflammation. Use of topical and systemic corticosteroids was markedly reduced in responsive patients. Methotrexate is recommended as a first-line adjunct to or replacement of systemic corticosteroids in the treatment of ocular inflammation.

  19. Cumulative Effect of Depression on Dementia Risk

    Directory of Open Access Journals (Sweden)

    J. Olazarán

    2013-01-01

    Full Text Available Objective. To analyze a potential cumulative effect of life-time depression on dementia and Alzheimer’s disease (AD, with control of vascular factors (VFs. Methods. This study was a subanalysis of the Neurological Disorders in Central Spain (NEDICES study. Past and present depression, VFs, dementia status, and dementia due to AD were documented at study inception. Dementia status was also documented after three years. Four groups were created according to baseline data: never depression (nD, past depression (pD, present depression (prD, and present and past depression (prpD. Logistic regression was used. Results. Data of 1,807 subjects were investigated at baseline (mean age 74.3, 59.3% women, and 1,376 (81.6% subjects were evaluated after three years. The prevalence of dementia at baseline was 6.7%, and dementia incidence was 6.3%. An effect of depression was observed on dementia prevalence (OR [CI 95%] 1.84 [1.01–3.35] for prD and 2.73 [1.08–6.87] for prpD, and on dementia due to AD (OR 1.98 [0.98–3.99] for prD and OR 3.98 [1.48–10.71] for prpD (fully adjusted models, nD as reference. Depression did not influence dementia incidence. Conclusions. Present depression and, particularly, present and past depression are associated with dementia at old age. Multiple mechanisms, including toxic effect of depression on hippocampal neurons, plausibly explain these associations.

  20. Quantitative cumulative biodistribution of antibodies in mice

    Science.gov (United States)

    Yip, Victor; Palma, Enzo; Tesar, Devin B; Mundo, Eduardo E; Bumbaca, Daniela; Torres, Elizabeth K; Reyes, Noe A; Shen, Ben Q; Fielder, Paul J; Prabhu, Saileta; Khawli, Leslie A; Boswell, C Andrew

    2014-01-01

    The neonatal Fc receptor (FcRn) plays an important and well-known role in antibody recycling in endothelial and hematopoietic cells and thus it influences the systemic pharmacokinetics (PK) of immunoglobulin G (IgG). However, considerably less is known about FcRn’s role in the metabolism of IgG within individual tissues after intravenous administration. To elucidate the organ distribution and gain insight into the metabolism of humanized IgG1 antibodies with different binding affinities FcRn, comparative biodistribution studies in normal CD-1 mice were conducted. Here, we generated variants of herpes simplex virus glycoprotein D-specific antibody (humanized anti-gD) with increased and decreased FcRn binding affinity by genetic engineering without affecting antigen specificity. These antibodies were expressed in Chinese hamster ovary cell lines, purified and paired radiolabeled with iodine-125 and indium-111. Equal amounts of I-125-labeled and In-111-labeled antibodies were mixed and intravenously administered into mice at 5 mg/kg. This approach allowed us to measure both the real-time IgG uptake (I-125) and cumulative uptake of IgG and catabolites (In-111) in individual tissues up to 1 week post-injection. The PK and distribution of the wild-type IgG and the variant with enhanced binding for FcRn were largely similar to each other, but vastly different for the rapidly cleared low-FcRn-binding variant. Uptake in individual tissues varied across time, FcRn binding affinity, and radiolabeling method. The liver and spleen emerged as the most concentrated sites of IgG catabolism in the absence of FcRn protection. These data provide an increased understanding of FcRn’s role in antibody PK and catabolism at the tissue level. PMID:24572100

  1. Endogenous inspired biomineral-installed hyaluronan nanoparticles as pH-responsive carrier of methotrexate for rheumatoid arthritis.

    Science.gov (United States)

    Alam, Md Mahmudul; Han, Hwa Seung; Sung, Shijin; Kang, Jin Hee; Sa, Keum Hee; Al Faruque, Hasan; Hong, Jungwan; Nam, Eon Jeong; Kim, In San; Park, Jae Hyung; Kang, Young Mo

    2017-04-28

    Methotrexate (MTX), an anchor drug for rheumatoid arthritis (RA), has been suffered from refractoriness and high toxicity limiting effective dosage. To mitigate these challenges, the ability to selectively deliver MTX to arthritis tissue is a much sought-after modality for the treatment of RA. In this study, we prepared mineralized nanoparticles (MP-HANPs), composed of PEGylated hyaluronic acid (P-HA) as the hydrophilic shell, 5β-cholanic acid as the hydrophobic core, and calcium phosphate (CaP) as the pH-responsive mineral. Owing to the presence of CaP as the diffusion barrier, mineralized HANPs revealed the pH-responsiveness of release kinetics of MTX across neutral to acidic conditions. HANPs were internalized via receptor-mediated endocytosis in macrophages which involved molecular redundancy among major hyaladherins, including CD44, stabilin-2, and RHAMM. Following endocytosis, MP-HANPs loaded with doxorubicin revealed pH-dependent demineralization followed by dramatic acceleration of drug release into the cytosol compared to other HANPs. Furthermore, an in vivo study showed a significantly high paw-to-liver ratio of fluorescent intensity after systemic administration of MP-HANP-Cy5.5, indicating improved biodistribution of nanoparticles into arthritic paws in collagen-induced arthritis mice. Treatment with MTX-loaded MP-HANPs ameliorated inflammatory arthritis with remarkable safety at high dose of MTX. We highlight the distinct advantages of combining key benefits of biomineralization and PEGylation with HA-based nanoparticles for arthritis-selective targeting, thus suggesting MP-HANPs as a promising carrier of MTX for treatment of RA. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. The role of Wnt/β-catenin signaling in enterocyte turnover during methotrexate-induced intestinal mucositis in a rat.

    Directory of Open Access Journals (Sweden)

    Igor Sukhotnik

    Full Text Available BACKGROUND/AIMS: Intestinal mucositis is a common side-effect in patients who receive aggressive chemotherapy. The Wnt signaling pathway is critical for establishing and maintaining the proliferative compartment of the intestine. In the present study, we tested whether Wnt/β-catenin signaling is involved in methotrexate (MTX-induced intestinal damage in a rat model. METHODS: Non-pretreated and pretreated with MTX Caco-2 cells were evaluated for cell proliferation and apoptosis using FACS analysis. Adult rats were divided into three experimental groups: Control rats; MTX-2 animals were treated with a single dose of MTX given IP and were sacrificed on day 2, and MTX-4 rats were treated with MTX similar to group B and were sacrificed on day 4. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation, and enterocyte apoptosis were measured at sacrifice. Real Time PCR and Western blot was used to determine the level of Wnt/β-catenin related genes and protein expression. RESULTS: In the vitro experiment, treatment with MTX resulted in marked decrease in early cell proliferation rates following by a 17-fold increase in late cell proliferation rates compared to early proliferation. Treatment with MTX resulted in a significant increase in early and late apoptosis compared to Caco-2 untreated cells. In the vivo experiment, MTX-2 and MTX-4 rats demonstrated intestinal mucosal hypoplasia. MTX-2 rats demonstrated a significant decrease in FRZ-2, Wnt 3A Wnt 5A, β-catenin, c-myc mRNA expression and a significant decrease in β-catenin and Akt protein levels compared to control animals. Four days following MTX administration, rats demonstrated a trend toward a restoration of Wnt/β-catenin signaling especially in ileum. CONCLUSIONS: Wnt/β-catenin signaling is involved in enterocyte turnover during MTX-induced intestinal mucositis in a rat.

  3. A Framework for Treating Cumulative Trauma with Art Therapy

    Science.gov (United States)

    Naff, Kristina

    2014-01-01

    Cumulative trauma is relatively undocumented in art therapy practice, although there is growing evidence that art therapy provides distinct benefits for resolving various traumas. This qualitative study proposes an art therapy treatment framework for cumulative trauma derived from semi-structured interviews with three art therapists and artistic…

  4. Cumulative effects of forest management activities: how might they occur?

    Science.gov (United States)

    R. M. Rice; R. B. Thomas

    1985-01-01

    Concerns are often voiced about possible environmental damage as the result of the cumulative sedimentation effects of logging and forest road construction. In response to these concerns, National Forests are developing procedures to reduce the possibility that their activities may lead to unacceptable cumulative effects

  5. Cumulative effect in multiple production processes on nuclei

    International Nuclear Information System (INIS)

    Golubyatnikova, E.S.; Shmonin, V.L.; Kalinkin, B.N.

    1989-01-01

    It is shown that the cumulative effect is a natural result of the process of hadron multiple production in nuclear reactions. Interpretation is made of the universality of slopes of inclusive spectra and other characteristics of cumulative hadrons. The character of information from such reactions is discussed, which could be helpful in studying the mechanism of multiparticle production. 27 refs.; 4 figs

  6. Cumulative particle production in the quark recombination model

    International Nuclear Information System (INIS)

    Gavrilov, V.B.; Leksin, G.A.

    1987-01-01

    Production of cumulative particles in hadron-nuclear inteactions at high energies is considered within the framework of recombination quark model. Predictions for inclusive cross sections of production of cumulative particles and different resonances containing quarks in s state are made

  7. Assessment by MRI of inflammation and damage in rheumatoid arthritis patients with methotrexate inadequate response receiving golimumab: results of the GO-FORWARD trial

    DEFF Research Database (Denmark)

    Conaghan, Philip G; Emery, Paul; Østergaard, Mikkel

    2011-01-01

    To evaluate golimumab's effect on MRI-detected inflammation and structural damage in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX).......To evaluate golimumab's effect on MRI-detected inflammation and structural damage in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX)....

  8. High cumulants of conserved charges and their statistical uncertainties

    Science.gov (United States)

    Li-Zhu, Chen; Ye-Yin, Zhao; Xue, Pan; Zhi-Ming, Li; Yuan-Fang, Wu

    2017-10-01

    We study the influence of measured high cumulants of conserved charges on their associated statistical uncertainties in relativistic heavy-ion collisions. With a given number of events, the measured cumulants randomly fluctuate with an approximately normal distribution, while the estimated statistical uncertainties are found to be correlated with corresponding values of the obtained cumulants. Generally, with a given number of events, the larger the cumulants we measure, the larger the statistical uncertainties that are estimated. The error-weighted averaged cumulants are dependent on statistics. Despite this effect, however, it is found that the three sigma rule of thumb is still applicable when the statistics are above one million. Supported by NSFC (11405088, 11521064, 11647093), Major State Basic Research Development Program of China (2014CB845402) and Ministry of Science and Technology (MoST) (2016YFE0104800)

  9. Radiation dose monitoring in the clinical routine

    Energy Technology Data Exchange (ETDEWEB)

    Guberina, Nika [UK Essen (Germany). Radiology

    2017-04-15

    Here we describe the first clinical experiences regarding the use of an automated radiation dose management software to monitor the radiation dose of patients during routine examinations. Many software solutions for monitoring radiation dose have emerged in the last decade. The continuous progress in radiological techniques, new scan features, scanner generations and protocols are the primary challenge for radiation dose monitoring software systems. To simulate valid dose calculations, radiation dose monitoring systems have to follow current trends and stay constantly up-to-date. The dose management software is connected to all devices at our institute and conducts automatic data acquisition and radiation dose calculation. The system incorporates 18 virtual phantoms based on the Cristy phantom family, estimating doses in newborns to adults. Dose calculation relies on a Monte Carlo simulation engine. Our first practical experiences demonstrate that the software is capable of dose estimation in the clinical routine. Its implementation and use have some limitations that can be overcome. The software is promising and allows assessment of radiation doses, like organ and effective doses according to ICRP 60 and ICRP 103, patient radiation dose history and cumulative radiation doses. Furthermore, we are able to determine local diagnostic reference doses. The radiation dose monitoring software systems can facilitate networking between hospitals and radiological departments, thus refining radiation doses and implementing reference doses at substantially lower levels.

  10. Towards Greenland Glaciation: cumulative or abrupt transition?

    Science.gov (United States)

    Ramstein, Gilles; Tan, Ning; Ladant, Jean-baptiste; Dumas, Christophe; Contoux, Camille

    2017-04-01

    During the mid-Pliocene warming period (3-3.3 Ma BP), the global annual mean temperatures inferred by data and model studies were 2-3° warmer than pre-industrial values. Accordingly, Greenland ice sheet volume is supposed to reach at the most, only half of that of present-day [Haywood et al. 2010]. Around 2.7-2.6 Ma BP, just ˜ 500 kyr after the warming peak of mid-Pliocene, the Greenland ice sheet has reached its full size [Lunt et al. 2008]. A crucial question concerns the evolution of the Greenland ice sheet from half to full size during the 3 - 2.5 Ma period. Data show a decreasing trend of atmospheric CO2 concentration from 3 Ma to 2.5 Ma [Seki et al.2010; Bartoli et al. 2011; Martinez et al. 2015]. However, a recent study [Contoux et al. 2015] suggests that a lowering of CO2 is not sufficient to initiate a perennial glaciation on Greenland and must be combined with low summer insolation to preserve the ice sheet during insolation maxima. This suggests rather a cumulative process than an abrupt event. In order to diagnose the evolution of the ice sheet build-up, we carry on, for the first time, a transient simulation of climate and ice sheet evolutions from 3 Ma to 2.5 Ma. This strategy enables us to investigate the waxing and waning of the ice sheet during several orbital cycles. We use a tri-dimensional interpolation method designed by Ladant et al. (2014), which allows the evolution of CO2 concentration and of orbital parameters, and the evolution of the Greenland ice sheet size to be taken into account. By interpolating climatic snapshot simulations ran with various possible combinations of CO2, orbits and ice sheet sizes, we can build a continuous climatic forcing that is then used to provide 500 kyrs-long ice sheet simulations. With such a tool, we may offer a physically based answer to different CO2 reconstructions scenarios and analyse which one is the most consistent with Greenland ice sheet buildup.

  11. Dose gradient curve: A new tool for evaluating dose gradient.

    Science.gov (United States)

    Sung, KiHoon; Choi, Young Eun

    2018-01-01

    Stereotactic radiotherapy, which delivers an ablative high radiation dose to a target volume for maximum local tumor control, requires a rapid dose fall-off outside the target volume to prevent extensive damage to nearby normal tissue. Currently, there is no tool to comprehensively evaluate the dose gradient near the target volume. We propose the dose gradient curve (DGC) as a new tool to evaluate the quality of a treatment plan with respect to the dose fall-off characteristics. The average distance between two isodose surfaces was represented by the dose gradient index (DGI) estimated by a simple equation using the volume and surface area of isodose levels. The surface area was calculated by mesh generation and surface triangulation. The DGC was defined as a plot of the DGI of each dose interval as a function of the dose. Two types of DGCs, differential and cumulative, were generated. The performance of the DGC was evaluated using stereotactic radiosurgery plans for virtual targets. Over the range of dose distributions, the dose gradient of each dose interval was well-characterized by the DGC in an easily understandable graph format. Significant changes in the DGC were observed reflecting the differences in planning situations and various prescription doses. The DGC is a rational method for visualizing the dose gradient as the average distance between two isodose surfaces; the shorter the distance, the steeper the dose gradient. By combining the DGC with the dose-volume histogram (DVH) in a single plot, the DGC can be utilized to evaluate not only the dose gradient but also the target coverage in routine clinical practice.

  12. Curcumin Attenuates Methotrexate-Induced Hepatic Oxidative Damage in Rats

    International Nuclear Information System (INIS)

    HEMEIDA, R.A.M.; MOHAFEZ, O.M.

    2008-01-01

    In the present study, we have addressed the ability of curcumin to suppress MTX-induced liver damage. Hepatotoxicity was induced by injection of a single dose of MTX (20 mg/kg I.P.). MTX challenge induced liver damage that was well characterized histopathologically and biochemically. MTX increased relative liver/body weight ratio. Histologically, MTX produced fatty changes in hepatocytes and sinusoidal lining cells, mild necrosis and inflammation. Biochemically, the test battery entailed elevated activities of serum ALT and AST. Liver activities of superoxide dismutase (SOD), catalase (CAT) and level of reduced glutathione (GSH), were notably reduced, while lipid peroxidation, expressed as malondialdhyde (MDA) level was significantly increased. Administration of curcumin (100mg/kg, I.P.) once daily for 5 consecutive days after MTX challenge mitigated the injurious effects of MTX and ameliorated all the altered biochemical parameters. These results showed that administration of curcumin decreases MTX-induced liver damage probably via regulation of oxidant/anti-oxidant balance. In conclusion, the present study indicates that curcumin may be of therapeutic benefit against MTX-cytotoxicity.

  13. An Analysis of Cumulative Risks Indicated by Biomonitoring Data of Six Phthalates Using the Maximum Cumulative Ratio

    Science.gov (United States)

    The Maximum Cumulative Ratio (MCR) quantifies the degree to which a single component of a chemical mixture drives the cumulative risk of a receptor.1 This study used the MCR, the Hazard Index (HI) and Hazard Quotient (HQ) to evaluate co-exposures to six phthalates using biomonito...

  14. An analysis of cumulative risks based on biomonitoring data for six phthalates using the Maximum Cumulative Ratio

    Science.gov (United States)

    The Maximum Cumulative Ratio (MCR) quantifies the degree to which a single chemical drives the cumulative risk of an individual exposed to multiple chemicals. Phthalates are a class of chemicals with ubiquitous exposures in the general population that have the potential to cause ...

  15. Methotrexate in ocular manifestations of Behcet's disease: a longitudinal study up to 15 years.

    Science.gov (United States)

    Davatchi, Fereydoun; Shams, Hormoz; Shahram, Farhad; Nadji, Abdolhadi; Chams-Davatchi, Cheyda; Sadeghi Abdollahi, Bahar; Faezi, Tahereh; Akhlaghi, Massoomeh; Ashofteh, Farimah

    2013-10-01

    Ocular manifestations of Behcet's disease (BD) need aggressive treatment to prevent severe loss of vision or blindness. Cytotoxic drugs are the main therapeutic agents and the first line treatment. Methotrexate is the least toxic, used mainly for posterior uveitis. We present here the outcome of eye lesions with methotrexate and prednisolone, in a longitudinal study of up to 15 years, on 682 patients (5447 eye-years of follow-up). Methotrexate was started at 7.5-15 mg/week. Prednisolone was added at 0.5 mg/kg/daily, then adjusted as needed. (i) fulfilling the International Criteria for Behcet's Disease; and (ii) having active posterior uveitis (PU). Visual acuity (VA) was calculated on a scale of 10. Activity indexes were calculated for PU and retinal vasculitis (RV) for each eye. Total Inflammatory Activity Index (TIAI) demonstrating the inflammatory index of both eyes of the patient, and Total Adjusted Disease Activity Index (TADAI) showing both TIAI + VA were also calculated. Overall results: the mean VA improvement was 0.4 (P < 001), PU 1.2 (P < 0.001) and RV 0.6 (P < 0.001). VA improved in 46.5%, PU in 75.4%, and RV in 53.7% of eyes. TIAI improved in 74% of patients and TADAI in 69.4%. VA was aggravated in 37.2%, PU in 11.1%, and RV in 30.3% of eyes. TIAI was aggravated in 17.4% and TADAI in 21.6% of the patients. The remaining kept their baseline values. All parameters improved, PU better than RV. Improvement of VA was the least, mainly due to secondary cataracts. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  16. The role of nanoparticles in the albumin-cytarabine and albumin-methotrexate interactions

    Energy Technology Data Exchange (ETDEWEB)

    Pentak, Danuta, E-mail: danuta.pentak@us.edu.pl [Department of Materials Chemistry and Chemical Technology, Institute of Chemistry, University of Silesia, Szkolna 9, 40-006 Katowice (Poland); Maciążek-Jurczyk, Małgorzata; Zawada, Zygmunt H. [School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Department of Physical Pharmacy, Jagiellońska 4, 41-200 Sosnowiec (Poland)

    2017-04-01

    Understanding the interactions which occur between nanomaterials and biomolecules is one of the most important issues in nanotechnology. Determining the properties of nanoparticles obtained through the use of novel methods and defining the scope of their application as drug carriers has important practical significance. Nanoparticles containing methotrexate and cytarabine obtained by a modified reverse-phase evaporation method (mREV) were characterized through the use of the UV/Vis and NMR methods. Obtained results confirmed high degree of analysed drugs encapsulation. The encapsulation efficiencies of cytarabine (AraC) and methotrexate (MTX) in L{sub DPPC/AraC/MTX} were found to be 86.30% (AraC) and 86.00% (MTX). The increased permeability of the phospholipid membranes, resulting from physico-chemical properties and the location of the drug, as well as from the physico-chemical properties of the phospholipids themselves, has been confirmed by increase in the length of the T1 relaxation time of protons in the −N{sup +}(CH{sub 3}){sub 3} group. The study of analysed drugs release process from the liposomes has been made for bovine serum albumin, both in the absence (dBSA) and in the presence of fatty acid (BSA). Moreover two types of kinetic models (Bhaskar equation and Rigter-Peppas equation) have been used. Based on the study it has been concluded that mathematical modelling of drug release can be very helpful in speeding up product development and in better understanding the mechanisms controlling drug release from advanced delivery systems. - Graphical abstract: In vitro drug release profiles of different liposomal formulation. - Highlights: • Liposomes containing tested drugs can be obtained by mREV method. • High degree of encapsulation characterizes obtained liposomes. • Cytarabine and methotrexate release from liposomes followed both: diffusion and controlled mechanisms.

  17. Dose estimation from residual and fallout radioactivity, 1

    International Nuclear Information System (INIS)

    Takeshita, Kenji

    1975-01-01

    External dose rates and cumulative doses for early entrants from areal surveys and simulated experiments are reviewed. The average cumulative doses to infinity at the hypocenters were 101 rad in Hiroshima and 32 rad in Nagasaki, with a variation of about 60 percent. Radioactive fallout areas nearly matched the ''black rain'' areas in Nagasaki and in Hiroshima. Radioactivity in the fallout areas was affected by radioactive decay and by the leaching and dissipation by rains. Considering these factors, the cumulative dose to infinity in the fallout area of Hiroshima was estimated to be 13 rad, excluding internal radiation doses from inhaled and ingested radionuclides. Attempts to estimate radiation dose from internally deposited radionuclides are also described. (auth.)

  18. Can the Methotrexate Therapy Prevent the Development of Uveitis in Patients with Juvenile Idiopathic Arthritis: Results of a Retrospective Study

    Directory of Open Access Journals (Sweden)

    M. M. Kostik

    2015-01-01

    Full Text Available Background: Uveitis is one of the most common extra-articular manifestations of juvenile idiopathic arthritis (JIA. Currently, the possibility of reducing the risk of uveitis in children with JIA by using methotrexate has been studied.Objective: Our aim was to analyze the results of treatment of children with JIA by studying the relation between the use of methotrexate and the risk of uveitis.Methods: A retrospective uncontrolled study. The case histories of patients with JIA who were treated for at least 2 years after the onset of the disease were studied. The results of treatment of patients who received and who did not receive methotrexate were studied (standard therapy — non-steroidal anti-inflammatory drugs and intra-articular injections of glucocorticoids. The established cases of uveitis were taken into account.Results: The study analyzed the results of observation of 281 children with JIA. In the methotrexate group, uveitis was detected in 22/191 (11.5%, and in the control group — in 42/90 (46.7% of patients (OR 6.7; 95% CI 3.7–12.3. The time period between the onset of JIA and development of uveitis in two groups under study was the same and equal to 24 (12; 67 and 17 months (7; 35, respectively (p = 0.232. Multivariate regression analysis showed that the main predictors of uveitis were oligoarticular course of JIA (HR = 1.89, positive antinuclear antibody test (HR = 2.14, onset of JIA under the age of 5 (HR = 2.56, female gender (HR = 1.82,and the absence of methotrexate in the therapy (HR = 0.24.Conclusion: The treatment with methotrexate may reduce the risk of uveitis in patients with JIA. To confirm this hypothesis, randomized studies are needed.

  19. Synthesis of protein-coated biocompatible methotrexate-loaded PLA-PEG-PLA nanoparticles for breast cancer treatment

    Directory of Open Access Journals (Sweden)

    Salam Massadeh

    2016-06-01

    Full Text Available Background: PLA-PEG-PLA triblock polymer nanoparticles are promising tools for targeted dug delivery. The main aim in designing polymeric nanoparticles for drug delivery is achieving a controlled and targeted release of a specific drug at the therapeutically optimal rate and choosing a suitable preparation method to encapsulate the drug efficiently, which depends mainly on the nature of the drug (hydrophilic or hydrophobic. In this study, methotrexate (MTX-loaded nanoparticles were prepared by the double emulsion method. Method: Biodegradable polymer polyethylene glycol-polylactide acid tri-block was used with poly(vinyl alcohol as emulsifier. The resulting methotrexate polymer nanoparticles were coated with bovine serum albumin in order to improve their biocompatibility. This study focused on particle size distribution, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release at various concentrations of PVA (0.5%, 1%, 2%, and 3%. Results: Reduced particle size of methotrexate-loaded nanoparticles was obtained using lower PVA concentrations. Enhanced encapsulation efficiency and loading capacity was obtained using 1% PVA. FT-IR characterization was conducted for the void polymer nanoparticles and for drug-loaded nanoparticles with methotrexate, and the protein-coated nanoparticles in solid state showed the structure of the plain PEG-PLA and the drug-loaded nanoparticles with methotrexate. The methotrexate-loaded PLA-PEG-PLA nanoparticles have been studied in vitro; the drug release, drug loading, and yield are reported. Conclusion: The drug release profile was monitored over a period of 168 hours, and was free of burst effect before the protein coating. The results obtained from this work are promising; this work can be taken further to develop MTX based therapies.

  20. Synthesis of protein-coated biocompatible methotrexate-loaded PLA-PEG-PLA nanoparticles for breast cancer treatment

    Science.gov (United States)

    Massadeh, Salam; Alaamery, Manal; Al-Qatanani, Shatha; Alarifi, Saqer; Bawazeer, Shahad; Alyafee, Yusra

    2016-01-01

    Background PLA-PEG-PLA triblock polymer nanoparticles are promising tools for targeted dug delivery. The main aim in designing polymeric nanoparticles for drug delivery is achieving a controlled and targeted release of a specific drug at the therapeutically optimal rate and choosing a suitable preparation method to encapsulate the drug efficiently, which depends mainly on the nature of the drug (hydrophilic or hydrophobic). In this study, methotrexate (MTX)-loaded nanoparticles were prepared by the double emulsion method. Method Biodegradable polymer polyethylene glycol-polylactide acid tri-block was used with poly(vinyl alcohol) as emulsifier. The resulting methotrexate polymer nanoparticles were coated with bovine serum albumin in order to improve their biocompatibility. This study focused on particle size distribution, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release at various concentrations of PVA (0.5%, 1%, 2%, and 3%). Results Reduced particle size of methotrexate-loaded nanoparticles was obtained using lower PVA concentrations. Enhanced encapsulation efficiency and loading capacity was obtained using 1% PVA. FT-IR characterization was conducted for the void polymer nanoparticles and for drug-loaded nanoparticles with methotrexate, and the protein-coated nanoparticles in solid state showed the structure of the plain PEG-PLA and the drug-loaded nanoparticles with methotrexate. The methotrexate-loaded PLA-PEG-PLA nanoparticles have been studied in vitro; the drug release, drug loading, and yield are reported. Conclusion The drug release profile was monitored over a period of 168 hours, and was free of burst effect before the protein coating. The results obtained from this work are promising; this work can be taken further to develop MTX based therapies.

  1. Topically applied methotrexate is rapidly delivered into skin by fractional laser ablation

    DEFF Research Database (Denmark)

    Taudorf, Elisabeth Hjardem; Lerche, Catharina; Vissing, Anne-Cathrine

    2015-01-01

    Objectives: Methotrexate (MTX) is a chemotherapeutic and anti-inflammatory drug that may cause systemic adverse effects. This study investigated kinetics and biodistribution of MTX delivered topically by ablative fractional laser (AFXL). Methods: In vitro passive diffusion of 10 mg/ml MTX (1 w...... sections, donor and receiver compartments. Fluorescence microscopy of UVC-activated MTX-fluorescence and desorption electro-spray ionization mass spectrometry imaging (DESI-MSI) evaluated MTX biodistribution. Results: AFXL-processed skin facilitated rapid MTX delivery through cone-shaped microchannels.......30 mg/cm3, p = 0.002). Transdermal permeation was

  2. Computed tomographic diagnosis of methotrexate leukoencephalopathy, developed in children with acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Seguchi, Michiko

    1983-01-01

    The difference of Hounsfield units between the white and gray matter are highly reliable indexes for the numerical analysis of infant cranial CT. These indexes were evaluated in 239 healthy children at ages ranging from 1 to 15 years. CT findings of white matter changes due to methotrexate were evaluated numerically in 80 children with acute lymphatic leukemia. This analysis resulted in detection of transient, or preclinical, slight pathological changes in the white matter. This method was also considered to give objectivity to evaluation of the changes in CT. (Ueda, J.)

  3. In vivo pharmacological evaluation and efficacy study of methotrexate-encapsulated polymer-coated layered double hydroxide nanoparticles for possible application in the treatment of osteosarcoma.

    Science.gov (United States)

    Ray, Sayantan; Saha, Suman; Sa, Biswanath; Chakraborty, Jui

    2017-04-01

    Considering the existing drawbacks of methotrexate (MTX) with respect to its solubility and toxicity, we incorporated it in a nanoceramic matrix, Mg-Al-layered double hydroxide (LDH) to form LDH-MTX nanoparticles, and the same was in turn encapsulated in a nontoxic and biodegradable polymer, poly (D,L-lactide-co-glycolide) (PLGA), to arrest the initial burst release and dose-dumping-related toxicity, already reported by our group. Our present study was designed to evaluate the pharmacokinetics, tissue distribution, survival rate of the test animals, and antitumor efficacy of the PLGA-LDH-MTX nanoparticles and its counterpart without LDH, PLGA-MTX nanoparticles compared with bare MTX. The median lethal dose (LD 50 ) of the former was higher, compared with bare MTX, using Balb/c nude mice, indicating it to be completely safe for use. Also, a comparative pharmacokinetic and antitumour efficacy study using MTX, PLGA-MTX, and PLGA-LDH-MTX nanoparticles in osteosarcoma-induced Balb/c nude mice in vivo demonstrated superiority of PLGA-LDH-MTX as compared to PLGA-MTX and bare MTX. The results suggest that PLGA-LDH-MTX nanoparticles might exhibit potential advantages over the present-day chemotherapy over bare MTX, for the possibility of treatment of osteosarcoma.

  4. Can the Methotrexate Therapy Prevent the Development of Uveitis in Patients with Juvenile Idiopathic Arthritis: Results of a Retrospective Study

    OpenAIRE

    M. M. Kostik; E. V. Gaydar; M. F. Dubko; V. V. Masalova; L. S. Snegireva; I. A. Chikova; E. A. Isupova; T. N. Nikitina; E. D. Serogodskaya; O. V. Kalashnikova; A. Ravelli; V. G. Chasnyk

    2015-01-01

    Background: Uveitis is one of the most common extra-articular manifestations of juvenile idiopathic arthritis (JIA). Currently, the possibility of reducing the risk of uveitis in children with JIA by using methotrexate has been studied.Objective: Our aim was to analyze the results of treatment of children with JIA by studying the relation between the use of methotrexate and the risk of uveitis.Methods: A retrospective uncontrolled study. The case histories of patients with JIA who were treate...

  5. Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials.

    Science.gov (United States)

    Lee, Shing M; Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

    2016-04-20

    The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. © 2016 by American Society of Clinical Oncology.

  6. Cumulative stress and autonomic dysregulation in a community sample.

    Science.gov (United States)

    Lampert, Rachel; Tuit, Keri; Hong, Kwang-Ik; Donovan, Theresa; Lee, Forrester; Sinha, Rajita

    2016-05-01

    Whether cumulative stress, including both chronic stress and adverse life events, is associated with decreased heart rate variability (HRV), a non-invasive measure of autonomic status which predicts poor cardiovascular outcomes, is unknown. Healthy community dwelling volunteers (N = 157, mean age 29 years) participated in the Cumulative Stress/Adversity Interview (CAI), a 140-item event interview measuring cumulative adversity including major life events, life trauma, recent life events and chronic stressors, and underwent 24-h ambulatory ECG monitoring. HRV was analyzed in the frequency domain and standard deviation of NN intervals (SDNN) calculated. Initial simple regression analyses revealed that total cumulative stress score, chronic stressors and cumulative adverse life events (CALE) were all inversely associated with ultra low-frequency (ULF), very low-frequency (VLF) and low-frequency (LF) power and SDNN (all p accounting for additional appreciable variance. For VLF and LF, both total cumulative stress and chronic stress significantly contributed to the variance alone but were not longer significant after adjusting for race and health behaviors. In summary, total cumulative stress, and its components of adverse life events and chronic stress were associated with decreased cardiac autonomic function as measured by HRV. Findings suggest one potential mechanism by which stress may exert adverse effects on mortality in healthy individuals. Primary preventive strategies including stress management may prove beneficial.

  7. Cumulants in perturbation expansions for non-equilibrium field theory

    International Nuclear Information System (INIS)

    Fauser, R.

    1995-11-01

    The formulation of perturbation expansions for a quantum field theory of strongly interacting systems in a general non-equilibrium state is discussed. Non-vanishing initial correlations are included in the formulation of the perturbation expansion in terms of cumulants. The cumulants are shown to be the suitable candidate for summing up the perturbation expansion. Also a linked-cluster theorem for the perturbation series with cumulants is presented. Finally a generating functional of the perturbation series with initial correlations is studied. We apply the methods to a simple model of a fermion-boson system. (orig.)

  8. Estimating a population cumulative incidence under calendar time trends

    DEFF Research Database (Denmark)

    Hansen, Stefan N; Overgaard, Morten; Andersen, Per K

    2017-01-01

    BACKGROUND: The risk of a disease or psychiatric disorder is frequently measured by the age-specific cumulative incidence. Cumulative incidence estimates are often derived in cohort studies with individuals recruited over calendar time and with the end of follow-up governed by a specific date....... It is common practice to apply the Kaplan-Meier or Aalen-Johansen estimator to the total sample and report either the estimated cumulative incidence curve or just a single point on the curve as a description of the disease risk. METHODS: We argue that, whenever the disease or disorder of interest is influenced...

  9. [Pharmacokinetic monitoring of 24-hour infusion of methotrexate in an adult population with non-Hodgkin lymphoma].

    Science.gov (United States)

    Fernández Megía, M J; Alós Almiñana, M; Esquer Borrás, J

    2004-01-01

    To describe the behavior and variability of methotrexate (MTX) pharmacokinetic parameters in patients with non-Hodgkin lymphoma (NHL) and to suggest a monitoring system to optimize sample collection using a bayesian method. Two adult patient groups diagnosed with different NHL types were studied. Group I was made up of 9 patients aged 53 +/- 16 years who received MTX at a mean dose of 1.652 +/- 327 mg per course. Group II was made up of 7 patients aged 53 +/- 14 years who received MTX at a mean dose of 1.862 +/- 220 mg per course. No statistically significant differences between groups were seen. Serum MTX measurements were performed using polarized immunofluorescence (TDx system). The pharmacokinetic analysis was performed using Abbottbase Pharmacokinetics Systems (PKS) software, adjusting experimental data according to a bicompartmental linear model for intravenous delivery using non-linear regression in Group I and Bayesian estimates in Group II. By estimating mean square error and linear regression between predicted and experimental concentrations, the capability of the Bayesian method implemented in PKS to predict plasma MTX concentration at 48 hours post-infusion was evaluated. The safety of MTX therapy was assessed using patient medical histories and then scoring toxicity using the WHO scale. Pharmacokinetic parameters obtained for group I included: alpha (h(-1)) = 0.38 +/- 0.12; beta (h(-1)) = 0.07 +/- 0.03; K12 (h(-1)) = 0.02 +/- 0.02; K21 (h(-1)) = 0.09 +/- 0.09; K13 (h(-1)) = 0.34 +/- 0.12; Vc (l/kg) = 0.53 +/- 0.23; Vss (l/kg) = 0.62 +/- 0.26; Cl (l/kg.h) = 0.16 +/- 0.06. The error for the PKS population model in measuring plasma MTX concentration at 48 hours post-infusion in Group II was calculated in accordance with three sampling schemes -12 h, 24 h, and both. It was -14.58 x 10(-3), -15.70 x 10(-3) and -14.67 x 10(-3), respectively. Eqm was 9.58 x 10(-3), 2.39 x 10(-3), and 1.02 x 10(-3), respectively. An MTX monitoring scheme is suggested based on

  10. Advanced colorectal carcinoma. A prospective randomized trial of sequential methotrexate, 5-fluorouracil, and leucovorin versus 5-fluorouracil alone.

    Science.gov (United States)

    Machiavelli, M; Leone, B A; Romero, A; Rabinovich, M G; Vallejo, C T; Bianco, A; Pérez, J E; Rodríguez, R; Cuevas, M A; Alvarez, L A

    1991-06-01

    One hundred and twenty-five previously untreated patients bearing metastatic or advanced recurrent (inoperable) colorectal carcinoma and measurable disease were prospectively randomized. Those in arm A received 5-fluorouracil (5-FU), 1,200 mg/m2 i.v. infusion over 2 h, while those in arm B received methotrexate (MTX), 200 mg/m2 i.v. (push injection), followed 20 h later by 5-FU, 1,200 mg/m2 i.v. infusion over 2 h, plus calcium leucovorin (LV), 25 mg i.m. every 6 h for eight doses beginning 24 h after MTX administration. Cycles were repeated every 15 days. All patients receiving treatment were evaluable for toxicity and survival, and 118 patients were evaluable for response. The objective regression rate (complete plus partial response) was 12% (7 of 58) in arm A and 28% (17 of 60) in arm B (p = 0.049). No change was observed in 24% (14 of 58) in arm A and in 35% (21 of 60) in arm B (p = 0.28), while progressive disease was registered in 64% (37 of 58) and 37% (22 of 60) in arms A and B, respectively (p = 0.006). Median duration of response was 3 months in arm A and 5 months in arm B (p = 0.39). The median survival was 8.3 months in arm A and 11.2 months in arm B (p = 0.25). No statistically significant differences were found when objective regression and survival were related to site of primary tumor, performance status, and number of involved organs. There were two drug-related deaths in arm B due to severe myelosuppression followed by mucositis and sepsis. Of nonhematologic toxicities, diarrhea was more frequently observed in arm B, as were mucositis and infectious complications. Our results indicate that the sequential schedule MTX-5-FU-LV with 20-h intervals between MTX and 5-FU is superior in terms of objective regression to 5-FU alone given at the dose and schedule used in the present study. However, MTX-5-FU-LV did not have a significant impact on survival.

  11. A histological evaluation on osteogenesis and resorption of methotrexate-loaded calcium phosphate cement in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Li Dong; Yang Zhiping; Li Xin; Li Zhenfeng; Li Jianmin [Department of Orthopedics, Qilu Hospital of Shandong University, Shandong (China); Yang Jingyan, E-mail: yangzhiping@medmail.com.c [Department of Pathology, 2nd Affiliated Hospital of Shandong University, Shandong (China)

    2010-04-15

    In this study, we investigated the resorption of in vivo methotrexate-loaded calcium phosphate cement (MTX-CPC) implants and their effect on osteogenesis. MTX-CPC implants containing 1% methotrexate (MTX) (weight/weight) were preset and implanted into the femoral condyle of rabbits. Calcium phosphate cement (CPC) without MTX was used as the control. The femurs were harvested at day 1 and at 1, 3 and 6 months after implantation and radiological examination were performed. Decalcified sections were examined by hematoxylin and eosin (HE) staining, alkaline phosphatase (ALPase) immunohistochemistry and tartrate-resistant acid phosphatase (TRAPase) enzyme histochemistry. Then, we performed histomorphometric analysis, including determination of the percentage of newly formed bone and osteoblast and osteoclast counts. The results indicated that MTX-CPC implants were biocompatible, biodegradable and osteoconducive. However, MTX release from the implantation site inhibited osteogenesis in the initial period; this inhibition weakened with time, and no difference was observed between CPC and MTX-CPC at 6 months after implantation. Hence, MTX-CPC is an excellent material for filling defects and can be used for preparing effective drug delivery systems to achieve local control of invasive bone tumors.

  12. Methotrexate and Cytarabine—Loaded Nanocarriers for Multidrug Cancer Therapy. Spectroscopic Study

    Directory of Open Access Journals (Sweden)

    Danuta Pentak

    2016-12-01

    Full Text Available Determining the properties of nanoparticles obtained by novel methods and defining the scope of their application as drug carriers has important practical significance. This article presents the pioneering studies concerning high degree incorporation of cytarabine (AraC and methotrexate (MTX into liposome vesicles. The main focus of this study were cytarabine-methotrexate-dipalmitoylphosphatidylcholine (DPPC interactions observed in the gel and fluid phases of DPPC bilayers. The proposed new method of use the Transmittance2919/2850 ratio presented in our research is sensitive to subtle changes in conformational order resulting from rotations, kinks and bends of the lipid chains. The transition temperatures characterized by Fourier Transform Infrared Spectroscopy (FT-IR were consistent with the results obtained by Differential Scanning Calorimetry (DSC. Transmission Electron Microscopy (TEM was used in order to determine the size and shape of the liposomes obtained. The mutual interactions occurring between the drugs studied and the phospholipids were analyzed using the Nuclear Magnetic Resonance (NMR.

  13. Cumulative Environmental Impacts: Science and Policy to Protect Communities.

    Science.gov (United States)

    Solomon, Gina M; Morello-Frosch, Rachel; Zeise, Lauren; Faust, John B

    2016-01-01

    Many communities are located near multiple sources of pollution, including current and former industrial sites, major roadways, and agricultural operations. Populations in such locations are predominantly low-income, with a large percentage of minorities and non-English speakers. These communities face challenges that can affect the health of their residents, including limited access to health care, a shortage of grocery stores, poor housing quality, and a lack of parks and open spaces. Environmental exposures may interact with social stressors, thereby worsening health outcomes. Age, genetic characteristics, and preexisting health conditions increase the risk of adverse health effects from exposure to pollutants. There are existing approaches for characterizing cumulative exposures, cumulative risks, and cumulative health impacts. Although such approaches have merit, they also have significant constraints. New developments in exposure monitoring, mapping, toxicology, and epidemiology, especially when informed by community participation, have the potential to advance the science on cumulative impacts and to improve decision making.

  14. Pesticide Cumulative Risk Assessment: Framework for Screening Analysis

    Science.gov (United States)

    This document provides guidance on how to screen groups of pesticides for cumulative evaluation using a two-step approach: begin with evaluation of available toxicological information and, if necessary, follow up with a risk-based screening approach.

  15. Online Scheduling in Manufacturing A Cumulative Delay Approach

    CERN Document Server

    Suwa, Haruhiko

    2013-01-01

    Online scheduling is recognized as the crucial decision-making process of production control at a phase of “being in production" according to the released shop floor schedule. Online scheduling can be also considered as one of key enablers to realize prompt capable-to-promise as well as available-to-promise to customers along with reducing production lead times under recent globalized competitive markets. Online Scheduling in Manufacturing introduces new approaches to online scheduling based on a concept of cumulative delay. The cumulative delay is regarded as consolidated information of uncertainties under a dynamic environment in manufacturing and can be collected constantly without much effort at any points in time during a schedule execution. In this approach, the cumulative delay of the schedule has the important role of a criterion for making a decision whether or not a schedule revision is carried out. The cumulative delay approach to trigger schedule revisions has the following capabilities for the ...

  16. Considering Environmental and Occupational Stressors in Cumulative Risk Assessments

    Science.gov (United States)

    While definitions vary across the global scientific community, cumulative risk assessments (CRAs) typically are described as exhibiting a population focus and analyzing the combined risks posed by multiple stressors. CRAs also may consider risk management alternatives as an anal...

  17. Peer tutors as learning and teaching partners: a cumulative ...

    African Journals Online (AJOL)

    ... paper explores the kinds of development in tutors' thinking and action that are possible when training and development is theoretically informed, coherent, and oriented towards improving practice. Keywords: academic development, academic literacies, cumulative learning, higher education, peer tutoring, writing centres.