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Sample records for high-dose radioiodine therapy

  1. The Effect of High Dose Radioiodine Therapy on Formation of Radiation Retinopathy During Thyroid Cancer Treatment

    PubMed Central

    Kaçar Güveli, Tülay; Özkan, Sezer; Öner Tamam, Müge; Uyanık, Ercan; Ediz, Nurcan; Mülazımoğlu, Mehmet; Özpaçacı, Tevfik

    2014-01-01

    Objective: Non-thyroidal complication of high-dose radioiodine therapy for thyroid carcinoma might cause salivary and lacrimal gland dysfunction, which may be transient or permanent in a dose-dependent manner. However, radiation retinopathy complicating 131I therapy, has not been previously well characterized. The aim of this study was to evaluate the extent of retinal damage among patients who had received high doses of radioiodine treatment. Methods: Forty eyes of 20 patients (3 male, 17 female) who received 250-1000 mCi during 131I therapy and on ophthalmological follow up for a year after the last treatment were included in the study. Mean age of the study group was 50 years (range 25-70 years). In ophthalmologic examination, visual acuity was measured in order to determine visual loss. Intraocular pressure was measured in all the patients. Then lens examination was carried out with slit lamp biomicroscopy in order to investigate cataract or partial lens opacities. Fundus observation was carried out through the dilated pupil with slit lamp biomicroscopy using 90 D noncontact lens. Result: The best corrected visual aquity with Snellen chart was found as 1.0 in 36 eyes (90%) and between 0.6 and 0.9 (10%) in 4 eyes (10%). At the biomicroscopic fundus examination, retinal hemorrhage consistent with radiation retinopathy, microaneurysm, microinfarction, edema or exudation, vitreus hemorrhage, partial or total optical disc pallor indicating papillopathy in the optic disc were not observed in any of the eyes. Conclusion: This result indicates that there is not any significant correlation between repeated high-dose radioiodine therapy and radiation retinopathy in differentiated thyroid carcinomas. Even though there is not a significant restriction in use of higher doses of radioiodine therapy in differentiated thyroid carcinoma, more extensive studies are needed in order to obtain more accurate data on possible occurrence of retinopathy. PMID:25541931

  2. High-dose radioiodine treatment for differentiated thyroid carcinoma is not associated with change in female fertility or any genetic risk to the offspring

    SciTech Connect

    Bal, Chandrasekhar . E-mail: csbal@hotmail.com; Kumar, Ajay; Tripathi, Madhavi; Chandrashekar, Narayana; Phom, Hentok; Murali, Nadig R.; Chandra, Prem; Pant, Gauri S.

    2005-10-01

    Background: We tried to evaluate the female fertility and genetic risk to the offspring from the exposure to high-dose {sup 131}I by assessing the pregnancy outcomes and health status of the children of female patients with differentiated thyroid cancer who had received therapeutic doses of {sup 131}I. Materials and Methods: From 1967 to 2002, a total of 1,282 women had been treated with {sup 131}I. Of these patients, 692 (54%) were in the reproductive age group (18-45 years). Forty women had a total of 50 pregnancies after high-dose {sup 131}I. Age at presentation ranged from 16 to 36 years (mean, 23 {+-} 4 years). Histopathology was papillary thyroid cancer in 32 cases and follicular thyroid cancer in 8 cases. Results: Single high-dose therapy was given in 30 cases, 2 doses were given in 7 cases, 3 doses were given in 2 cases, and four doses were given in 1 case in which lung metastases had occurred. In 37 patients (92%), disease was successfully ablated before pregnancy. Ovarian absorbed-radiation dose calculated by the MIRD method ranged from 3.5 to 60 cGy (mean, 12 {+-} 11 cGy). The interval between {sup 131}I therapy and pregnancy varied from 7 to 120 months (37.4 {+-} 28.2 months). Three spontaneous abortions occurred in 2 women. Forty-seven babies (20 females and 27 males) were born. Forty-four babies were healthy with normal birth weight and normal developmental milestones. Twenty women delivered their first baby after {sup 131}I therapy. The youngest child in our series is 11 months of age, and the oldest is 8.5 years of age. Conclusions: Female fertility is not affected by high-dose radioiodine treatment, and the therapy does not appear to be associated with any genetic risks to the offspring.

  3. [Radioiodine therapy for Graves' disease: problems and new developments].

    PubMed

    Reiners, Christoph

    2004-05-01

    In Germany, patients with Graves' disease are usually treated with radioiodine after unsuccessful antithyroid drug medication, occurrence of side effects from antithyroid drugs or an increased risk from surgery. In patients with normal or only slightly enlarged thyroid glands (volume < or = 50 ml), radioiodine therapy is particularly effective. Radioiodine is the preferential treatment for Graves' patients with high titres of TSH-receptor antibodies and cigarette smoking. Children are still rarely treated with radioiodine in Germany. In contrast, treatment with radioiodine should be more liberally applied in elderly patients with subclinical hyperthyroidism and cardiac symptoms. Individual dosimetry to determine the therapeutic activity is mandatory in Germany. Patients with large goitres obviously need higher organ doses than patients with smaller goitres or normal thyroid glands. Antithyroid drug treatment may interfere with radioiodine therapy. Therefore, it is recommendable to withdraw antithyroid drugs several days before treatment with radioiodine is initiated (and a preceding radioiodine uptake test is performed). In patients with Graves' orbitopathy prophylaxis with corticosteroids can prevent the worsening of symptoms that may be induced by radioiodine treatment. Currently, a risk adapted procedure is recommended according to which prophylactic medication with corticosteroids before applying radioiodine treatment is not necessary in patients with symptoms of orbitopathy and lack of other risk factors (cigarette smoking, in particular). Present results suggest that the risks of radioiodine treatment in Graves' disease patients are very low, while at the same time the cost-effectiveness of this treatment regimen is high. PMID:15255314

  4. High-Dose Radioiodine Outpatient Treatment: An Initial Experience in Thailand

    PubMed Central

    Nantajit, Danupon; Saengsuda, Sureerat; NaNakorn, Pattama; Saengsuda, Yuthana

    2015-01-01

    Objective(s): The aim of this study was to determine whether high-dose radioactive iodine (Na131I) outpatient treatment of patients with thyroid carcinoma is a pragmatically safe approach, particularly for the safety of caregivers. Methods: A total of 79 patients completed the radiation-safety questionnaires prior to receiving high-dose radioactive iodine treatment. The questionnaire studied the subjects’ willingness to be treated as outpatients, along with the radiation safety status of their caregivers and family members. In patients, who were selected to be treated as outpatients, both internal and external radiation exposures of their primary caregivers were measured, using thyroid uptake system and electronic dosimeter, respectively. Results: Overall, 62 out of 79 patients were willing to be treated as outpatients; however, only 44 cases were eligible for the treatment. The primary reason was that the patients did not use exclusive, separated bathrooms. The caregivers of 10 subjects, treated as outpatients, received an average radiation dose of 138.1 microsievert (mSv), which was almost entirely from external exposure; the internal radiation exposures were mostly at negligible values. Therefore, radiation exposure to caregivers was significantly below the public exposure limit (1 mSv) and the recommended limit for caregivers (5 mSv). Conclusion: A safe 131I outpatient treatment in patients with thyroid carcinoma could be achieved by selective screening and providing instructions for patients and their caregivers.

  5. High dose bystander effects in spatially fractionated radiation therapy

    PubMed Central

    Asur, Rajalakshmi; Butterworth, Karl T.; Penagaricano, Jose A.; Prise, Kevin M.; Griffin, Robert J.

    2014-01-01

    Traditional radiotherapy of bulky tumors has certain limitations. Spatially fractionated radiation therapy (GRID) and intensity modulated radiotherapy (IMRT) are examples of advanced modulated beam therapies that help in significant reductions in normal tissue damage. GRID refers to the delivery of a single high dose of radiation to a large treatment area that is divided into several smaller fields, while IMRT allows improved dose conformity to the tumor target compared to conventional three-dimensional conformal radiotherapy. In this review, we consider spatially fractionated radiotherapy approaches focusing on GRID and IMRT, and present complementary evidence from different studies which support the role of radiation induced signaling effects in the overall radiobiological rationale for these treatments. PMID:24246848

  6. High-dose enzyme replacement therapy in murine Hurler syndrome.

    PubMed

    Ou, Li; Herzog, Tyler; Koniar, Brenda L; Gunther, Roland; Whitley, Chester B

    2014-02-01

    Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease that is systemic, including progressive neurodegeneration, mental retardation and death before the age of 10 years. MPS I results from deficiency of α-L-iduronidase (IDUA) in lysosomes and subsequent accumulation of glycosaminoglycans (GAG). Clinical enzyme replacement therapy (ERT) with intravenous laronidase reverses some aspects of MPS I disease (e.g., hepatomegaly, splenomegaly, glycosaminoglycanuria) and ameliorates others (e.g., pulmonary function, cardiac disease, arthropathy, exercise tolerance). However, neurologic benefits are thought to be negligible because the blood-brain barrier (BBB) blocks enzyme from reaching the central nervous system (CNS). We considered the possibility that a very high dose of intravenous laronidase might be able to traverse the BBB in small quantities, and provide some metabolic correction in the brain. To address this question, high-dose laronidase was administered (11.6 mg/kg, once per week, 4 weeks) to adult MPS I mice. IDUA enzyme activity in the cortex of treated mice increased to 97% of that in wild type mice (p<0.01). GAG levels in cortex were reduced by 63% of that from untreated MPS I mice (p<0.05). Further, immunohistochemical analysis showed that treatment reduced secondary GM3-ganglioside accumulation in treated MPS I mice. Water T-maze tests showed that the learning abnormality in MPS I mice was reduced (p<0.0001). In summary, repeated, high-dose ERT facilitated laronidase transit across the BBB, reduced GAG accumulation within the CNS, and rescued cognitive impairment. PMID:24100243

  7. Assessments for High Dose Radionuclide Therapy Treatment Planning

    SciTech Connect

    Fisher, Darrell R.

    2003-10-01

    Advances in the biotechnology of cell-specific targeting of cancer, and the increased number of clinical trials involving treatment of cancer patients with radiolabeled antibodies, peptides, and similar delivery vehicles have led to an increase in the number of high-dose radionuclide therapy procedures. Optimized radionuclide therapy for cancer treatment is based on the concept of absorbed dose to the dose-limiting normal organ or tissue. The limiting normal tissue is often the red marrow, but it may sometimes be lungs, liver, intestinal tract, or kidneys. Appropriate treatment planning requires assessment of radiation dose to several internal organs and tissues, and usually involves biodistribution studies in the patient using a tracer amount of radionuclide bound to the targeting agent and imaged at sequential time points using a planar gamma camera. Time-activity curves are developed from the imaging data for the major organs tissues of concern, for the whole body, and sometimes for selected tumors. Patient-specific factors often require that dose estimates be customized for each patient. The Food and Drug Administration regulates the experimental use of investigational new drugs and requires reasonable calculation of radiation absorbed dose to the whole body and to critical organs using methods prescribed by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine. Review of high-dose studies in the U.S. and elsewhere shows that 1) some studies are conducted with minimal dosimetry, 2) the marrow dose is difficult to establish and is subject to large uncertainties, and 3) despite the general availability of MIRD software, internal dosimetry methods are often inconsistent from one clinical center to another.

  8. Wernicke's encephalopathy in a child with high dose thiamine therapy

    PubMed Central

    Park, So Won; Yi, Yoon Young; Han, Jung Woo; Kim, Heung Dong; Lee, Joon Soo

    2014-01-01

    Wernicke's encephalopathy is an acute neurological disorder characterized by mental confusion, oculomotor dysfunction, and ataxia. It has been reported in individuals with alcohol dependence, hyperemesis gravidarum, and prolonged parenteral nutrition without vitamin supplementation. Here we present the case of a 13-year-old male patient with neuroblastoma and a history of poor oral intake and nausea for 3 months. After admission, he showed gait disturbances, nystagmus, and excessive dizziness; his mental state, however, indicated he was alert, which did not fit the classical triad of Wernicke's encephalopathy. A diagnosis of Wernicke's encephalopathy was made only after brain magnetic resonance imaging and serum thiamine level analyses were performed. The patient's symptoms remained after 5 days of treatment with 100-mg thiamine once daily; thus, we increased the dosage to 500 mg 3 times daily, 1,500 mg per day. His symptoms then improved after 20 days of replacement therapy. This case report describes a pediatric patient who was promptly diagnosed with Wernicke's encephalopathy, despite only 2 suspicious symptoms, and who completely recovered after high doses of thiamine were given intravenously. PMID:25550705

  9. Radioiodine therapy of hyperthyroidism precludes thallium-201 myocardial scintigraphy

    SciTech Connect

    Orzel, J.A.; Kruyer, W.B.; Borchert, R.D.

    1987-02-01

    The authors attempted to perform Tl-201 myocardial perfusion scintigraphy in a 42-year-old man 23 and 35 days after he received 9.8 mCi of oral I-131 for documented Graves' disease. Interference from primary and scattered photons from residual thyroid I-131 made Tl-201 myocardial scintigraphy technically impossible. A series of phantom and patient studies using I-131 and Tl-201 were performed, yielding guidelines for planning Tl-201 myocardial scintigraphy following radioiodine therapy.

  10. Acute and long-term effects of radioiodine therapy on serum levels of calcitonin

    SciTech Connect

    Franke, A.; Oeff, K.

    1984-01-01

    The purpose of this study is to establish data on the radiosensitivity of thyroid C cells and medullary carcinoma of the thyroid (MCT) as reflected by the alterations in serum concentrations of calcitonin (Ct) after radioiodine therapy. Serum levels of Ct were measured by radioimmunoassay in 1437 patients subjected to diagnostic and therapeutic procedures for thyroid diseases. The effect of low dose and of high dose radioiodine therapy (RLO, RHI) was studied in 158 patients with hyperthyroidism and in 84 patients with thyroid cancer, respectively. RLO and RHI were followed by significant alterations in the distribution of Ct values. RLO decreased the occurrence of high values. RHI was followed by the absence of high concentrations and a substantial reduction in normal levels. The effect of RLO was confirmed in 47 patients by comparing their individual levels before and 8 weeks after RLO, the means +- SD being 24.3+-8.3 and 12.6+-5.7 pmol/l, respectively (p<0.001). In 30 patients followed up for late onset hypothyroidism who had been treated by RLO 10-25 years ago, the concentrations of Ct were almost normal (mean +- SD 16.6 +- 5.7 pmol/l).

  11. Response to Radioiodine Therapy for Thyrotoxicosis: Disparate Outcomes for an Indigenous Population.

    PubMed

    Tamatea, Jade A U; Conaglen, John V; Elston, Marianne S

    2016-01-01

    Despite 70 years of experience treating thyrotoxic patients with radioiodine not all patients are successfully treated by a single dose. Multiple factors predicting radioiodine efficacy have been reported. The aim of this study was to assess whether ethnicity was associated with radioiodine response. A retrospective review was performed of patients who received radioiodine therapy for thyrotoxicosis from 1 January 2008 to 31 December 2010 and had follow-up available of a minimum of 12 months. 224 patients were included, 82.4% female, and 63.7% had Graves's disease. Radioiodine failed in 21.5% of patients overall, with a higher failure rate in the indigenous population (35.2%). When controlling for other influencing factors by logistic regression, there continued to be an increased risk for the indigenous group (OR 2.82) and those treated with antithyroid drugs following radioiodine (OR 2.04). Younger age was also associated with an increased risk of failing radioiodine therapy (OR 0.97 for each year of age). Cure rates following radioiodine were lower for indigenes independent of factors known to affect radioiodine outcome. This is the first report demonstrating ethnicity as a possible independent variable for radioiodine efficacy. Further work is needed to investigate the cause of this difference. PMID:27446210

  12. Response to Radioiodine Therapy for Thyrotoxicosis: Disparate Outcomes for an Indigenous Population

    PubMed Central

    Conaglen, John V.

    2016-01-01

    Despite 70 years of experience treating thyrotoxic patients with radioiodine not all patients are successfully treated by a single dose. Multiple factors predicting radioiodine efficacy have been reported. The aim of this study was to assess whether ethnicity was associated with radioiodine response. A retrospective review was performed of patients who received radioiodine therapy for thyrotoxicosis from 1 January 2008 to 31 December 2010 and had follow-up available of a minimum of 12 months. 224 patients were included, 82.4% female, and 63.7% had Graves's disease. Radioiodine failed in 21.5% of patients overall, with a higher failure rate in the indigenous population (35.2%). When controlling for other influencing factors by logistic regression, there continued to be an increased risk for the indigenous group (OR 2.82) and those treated with antithyroid drugs following radioiodine (OR 2.04). Younger age was also associated with an increased risk of failing radioiodine therapy (OR 0.97 for each year of age). Cure rates following radioiodine were lower for indigenes independent of factors known to affect radioiodine outcome. This is the first report demonstrating ethnicity as a possible independent variable for radioiodine efficacy. Further work is needed to investigate the cause of this difference. PMID:27446210

  13. [High-dose buprenorphine for outpatient palliative pain therapy].

    PubMed

    Gastmeier, K; Freye, E

    2009-04-01

    The case of a 78-year-old patient with cancer-related pain and additionally mixed-pain syndrome is presented. Pain therapy with buprenorphine TTS 210 microg/h every 3 days was sufficient in the beginning, later the therapy was changed because of increasing problems of tape fixing during fever periods under chemotherapy to a continuous infusion of buprenorphine intravenously via an external medication pump. During the course of therapy it became necessary to increase the dose to 99.9 mg/day buprenorphine. Under this medication a sufficient pain reduction (median NRS 2-3) over a period of 135 days could be achieved. At the same time the patient was vigilant and cooperative without signs of intoxication until the end of life at home in the presence of his family.If no signs of intoxication occur under extreme opioid therapy and a sufficient pain therapy can be achieved, a rotation to another opioid is not necessary. However, outpatient palliative care requires a frequent adaptation to the individually varying opioid demand of the patient and time-consuming nursing care. PMID:19066981

  14. Thyroid cancer radioiodine therapy: health service performance and radiation safety.

    PubMed

    Vogiatzi, S; Liossis, A; Lamprinakou, M

    2015-07-01

    Greek Atomic Energy Commission collected data related to radioiodine I-131 therapy (RAIT) delivery to differentiated thyroid carcinoma patients, for the period 2003-13, corresponding to 100 % of hospitals at national level. Radiation safety and health service performance outcome indicators were assessed. The numbers of hospitals and nuclear medicine (NM) therapy wards, as well as RAIT annual frequencies, have increased. Geographical inhomogeneous distribution of existing infrastructure is recorded. In some cases, the observed inefficient use of NM therapy wards seems to be due to lack of human resources (e.g. nurses). Regular assessment of appropriate key indicators could serve as a useful tool for radiation safety monitoring and health service performance improvement. PMID:25809109

  15. Efficacy of high-dose methylprednisolone pulse therapy in the treatment of enterovirus 71 encephalitis.

    PubMed

    Zhang, Guangyou; Wang, Jiwen; Yao, Guo; Shi, Baohai

    2016-07-01

    To investigate the efficacy of high-dose methylprednisolone pulse therapy in the treatment of Enterovirus 71 (EV71) encephalitis. To determine whether high-dose methylprednisolone pulse therapy should be used, 80 cases of pediatric patients with EV71 encephalitis were randomly divided into steroid pulse therapy group and non-steroid pulse therapy group and their clinical information was compared using statistic analysis. There was no statistical difference in the duration of fever, duration of nervous system involvement, duration of hospital stay, blood pressure, and cure rates between the two groups (p>0.05). The heart rate, respiratory rate, white blood cell counts and blood glucose of the steroid pulse therapy group were significantly higher than those of the non-steroid pulse therapy group (p<0.05). High-dose steroid pulse therapy to treat EV71 encephalitis can't shorten the course or improve the prognosis of the disease. In contrast, it has side effects and might aggravate disease condition or interfere with disease diagnosis. Our study suggested that there is no beneficial effect to use high-dose steroid pulse therapy for the treatment of EV71 encephalitis. PMID:27592493

  16. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning.

    PubMed

    Engebretsen, Kristin M; Kaczmarek, Kathleen M; Morgan, Jenifer; Holger, Joel S

    2011-04-01

    INTRODUCTION. High-dose insulin therapy, along with glucose supplementation, has emerged as an effective treatment for severe beta-blocker and calcium channel-blocker poisoning. We review the experimental data and clinical experience that suggests high-dose insulin is superior to conventional therapies for these poisonings. PRESENTATION AND GENERAL MANAGEMENT. Hypotension, bradycardia, decreased systemic vascular resistance (SVR), and cardiogenic shock are characteristic features of beta-blocker and calcium-channel blocker poisoning. Initial treatment is primarily supportive and includes saline fluid resuscitation which is essential to correct vasodilation and low cardiac filling pressures. Conventional therapies such as atropine, glucagon and calcium often fail to improve hemodynamic status in severely poisoned patients. Catecholamines can increase blood pressure and heart rate, but they also increase SVR which may result in decreases in cardiac output and perfusion of vascular beds. The increased myocardial oxygen demand that results from catecholamines and vasopressors may be deleterious in the setting of hypotension and decreased coronary perfusion. METHODS. The Medline, Embase, Toxnet, and Google Scholar databases were searched for the years 1975-2010 using the terms: high-dose insulin, hyperinsulinemia-euglycemia, beta-blocker, calcium-channel blocker, toxicology, poisoning, antidote, toxin-induced cardiovascular shock, and overdose. In addition, a manual search of the Abstracts of the North American Congress of Clinical Toxicology and the Congress of the European Association of Poisons Centres and Clinical Toxicologists published in Clinical Toxicology for the years 1996-2010 was undertaken. These searches identified 485 articles of which 72 were considered relevant. MECHANISMS OF HIGH-DOSE INSULIN BENEFIT. There are three main mechanisms of benefit: increased inotropy, increased intracellular glucose transport, and vascular dilatation. EFFICACY OF HIGH-DOSE

  17. Comparison between conventional salvage therapy and high-dose therapy with autografting for recurrent or refractory Hodgkin's disease.

    PubMed

    Yuen, A R; Rosenberg, S A; Hoppe, R T; Halpern, J D; Horning, S J

    1997-02-01

    Sixty patients with Hodgkin's disease, refractory to or at first recurrence after chemotherapy, received cytoreductive therapy followed by high-dose etoposide, cyclophosphamide and either total body irradiation or carmustine and autografting (median follow-up, 3.6 years; range, 1.1 to 7.5 years). A matched conventional salvage group of 103 patients was selected from patients treated at Stanford University Medical Center between January 1976 and January 1989 (median follow-up, 10.3 years; range, 3.0 to 15.7 years). Overall survival (OS), event-free survival (EFS), and freedom from progression (FFP) at 4 years follow-up favored patients who received high-dose therapy compared with conventional salvage treatment (OS: 54% v 47%, P = .25; EFS: 53% v 27%, P < .01; FFP: 62% v 32%, P < .01). In Cox regression analysis, response to cytoreductive or salvage therapy and B symptoms at relapse were the most important predictors of OS. The use of high-dose therapy at relapse, a longer duration of remission, and favorable response to cytoreductive or salvage therapy were most predictive of superior FFP and EFS. These data from a single institution comparing conventional and high-dose therapy in matched patients demonstrate an advantage for high-dose therapy and autografting in the sustained control of Hodgkin's disease. As with primary therapy, it is difficult to demonstrate a statistically significant survival advantage, despite an apparently superior cure rate. However, patients failing induction therapy or relapsing within 1 year benefited significantly from high-dose therapy by all outcome measures (OS, EFS, FFP). As the transplant-related mortality rates decline in Hodgkin's disease, it is predicted that cure rates and late effects will become ultimate determinants of the success of high-dose therapy and autografting. PMID:9028312

  18. Peripheral blood progenitor cell transplantation in multiple myeloma following high-dose melphalan-based therapy.

    PubMed

    Goldschmidt, H; Hegenbart, U; Wallmeier, M; Hohaus, S; Engenhart, R; Wannenmacher, M; Haas, R

    1998-01-01

    The objective of our study was to evaluate the efficacy and toxicity of a high-dose melphalan-based therapy with or without total body irradiation (TBI) followed by peripheral blood progenitor cell (PBPC) transplantation in patients with multiple myeloma. Between June 1992 and June 1996, 104 patients (71 male, 33 female) with a median age of 51 years (range 30-65 years) underwent transplantation at our center. PBPC were mobilized using high-dose chemotherapy followed by treatment with G-CSF. Fifty patients were treated with TBI+melphalan 140 mg/m2 while 54 patients received melphalan 200 mg/m2. Following PBPC autografting, the median time to attainment of platelets > or = 20 x 10(9)/l and neutrophils > or = 0.5 x 10(9)/l was 11 and 14 days, with no difference between the treatment groups. In the TBI group significantly longer periods of total parenteral nutrition were required due to the occurrence of severe mucositis. Two patients from the TBI group died of transplantation-related complications. Following high-dose treatment, remission state improved in 43 out of 102 patients. No statistically significant advantage in reaching complete or partial remission was observed with TBI+high-dose melphalan compared to the treatment with high-dose melphalan alone. The optimal high-dose treatment, with particular reference to the inclusion or omission of TBI, should be prospectively investigated. PMID:9304704

  19. Transient radiation effects following high dose I-131 therapy for differentiated thyroid cancer (DTC)

    SciTech Connect

    Khan, S.; Waxman, A.; Ramanna, L.

    1994-05-01

    There is limited information regarding the incidence of post-I-131 therapeutic side effects in pts. undergoing high-dose I-131 therapy for DTC. The purpose of the current study is to characterize side effects experienced by patients following 150 mCi.

  20. Early Angiographic Resolution of Cerebral Vasospasm with High Dose Intravenous Milrinone Therapy

    PubMed Central

    Zeiler, F. A.; Silvaggio, J.

    2015-01-01

    Background. Treatment of symptomatic delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) is difficult. Recent studies suggest intravenous (IV) high dose milrinone as a potential therapy. The timing to angiographic response with this is unclear. Methods. We reviewed the chart of one patient admitted for SAH who developed symptomatic DCI and was treated with high dose IV milrinone. Results. A 66-year-old female was admitted with a Hunt and Hess clinical grade 4, World Federation of Neurological Surgeons (WFNS) clinical grade 4, and SAH secondary to a left anterior choroidal artery aneurysm which was clipped. After bleed day 6, the patient developed symptomatic DCI. We planned for angioplasty of the proximal segments. We administered high dose IV milrinone bolus followed by continuous infusion which led to clinical improvement prior to angiography. The angiogram performed 1.5 hours after milrinone administration displayed resolution of the CT angiogram and MRI based cerebral vasospasm such that further intra-arterial therapy was aborted. She completed 6 days of continuous IV milrinone therapy, was transferred to the ward, and subsequently rehabilitated. Conclusions. High dose IV milrinone therapy for symptomatic DCI after SAH can lead to rapid neurological improvement with dramatic early angiographic improvement of cerebral vasospasm. PMID:26457209

  1. Can peptide receptor radionuclide therapy (PRRT) be useful in radioiodine-refractory differentiated thyroid cancer?

    PubMed

    Campennì, Alfredo; Pignata, Salvatore A; Baldari, Sergio

    2015-11-01

    We report on a 70-year-old man affected by radioiodine-refractory differentiated thyroid cancer (DTC) in whom metastases were treated by peptide receptor radionuclide therapy (PRRT). Seven years before, patient had undergone total thyroidectomy. Pathological examination was conclusive for DTC. The patient underwent some radioiodine treatments (RaIT). The last post-therapy whole body scan (pT-WBS) performed five days after RaIT did not show abnormal radioiodine uptake but serum thyroglobulin (Tg) value was high in absence of thyroglobulin-antibodies (Tg-Ab). In-111 DTPA-pentetreotide scintigraphy showed several lung lesions with high somatostatin receptor density. Patient underwent PRRT using Lu-177 DOTATOC. pT-WBS scan confirmed the metastases already demonstrated by In-111 DTPA pentetreotide but radioiodine negative. PMID:25471282

  2. Outcome of Radioiodine Therapy in a West African Population

    PubMed Central

    Onimode, Yetunde A.; Ankrah, Alfred; Adedapo, Kayode S.

    2016-01-01

    Hyperthyroidism continues to be a pressing public health concern in West Africa. Its prevalence in Africa has been quoted as 1.2%-9.9%, with Graves’ disease as its most common cause. Radioiodine-131 (RAI) therapy of hyperthyroidism recently commenced in two government hospitals in Ghana and Nigeria. This is a retrospective analysis of consecutive patients treated with RAI for primary hyperthyroidism at the National Centre for Radiotherapy and Nuclear Medicine (NCRNM) from 2008-2013, and in the University College Hospital (UCH) from 2006-2013. Cure was defined as euthyroidism or hypothyroidism occurring at 6 months post-RAI. Data were analysed using SPSS version 21 and Epi Info version, categorical data were evaluated with the Chi-square test and Fisher's exact test. 94 patients were studied, aged 20-74 years; 78 were females, and 16 were males. 38 were Ghanaian and 56 Nigerian. The presence of thyroid-associated ophthalmopathy (TAO) made cure less likely (χ2 P = 0.006, odds ratio = 0.118; 95% confidence interval, 0.027-0.518). Other factors assessed proved to be insignificant. Our findings suggest that hyperthyroid patients with TAO will benefit from a higher RAI dose than their counterparts without TAO. PMID:26912975

  3. Outcome of Radioiodine Therapy in a West African Population.

    PubMed

    Onimode, Yetunde A; Ankrah, Alfred; Adedapo, Kayode S

    2016-01-01

    Hyperthyroidism continues to be a pressing public health concern in West Africa. Its prevalence in Africa has been quoted as 1.2%-9.9%, with Graves' disease as its most common cause. Radioiodine-131 (RAI) therapy of hyperthyroidism recently commenced in two government hospitals in Ghana and Nigeria. This is a retrospective analysis of consecutive patients treated with RAI for primary hyperthyroidism at the National Centre for Radiotherapy and Nuclear Medicine (NCRNM) from 2008-2013, and in the University College Hospital (UCH) from 2006-2013. Cure was defined as euthyroidism or hypothyroidism occurring at 6 months post-RAI. Data were analysed using SPSS version 21 and Epi Info version, categorical data were evaluated with the Chi-square test and Fisher's exact test. 94 patients were studied, aged 20-74 years; 78 were females, and 16 were males. 38 were Ghanaian and 56 Nigerian. The presence of thyroid-associated ophthalmopathy (TAO) made cure less likely (χ(2) P = 0.006, odds ratio = 0.118; 95% confidence interval, 0.027-0.518). Other factors assessed proved to be insignificant. Our findings suggest that hyperthyroid patients with TAO will benefit from a higher RAI dose than their counterparts without TAO. PMID:26912975

  4. Spatially resolved measurement of high doses in microbeam radiation therapy using samarium doped fluorophosphate glasses

    SciTech Connect

    Okada, Go; Morrell, Brian; Koughia, Cyril; Kasap, Safa; Edgar, Andy; Varoy, Chris; Belev, George; Wysokinski, Tomasz; Chapman, Dean

    2011-09-19

    The measurement of spatially resolved high doses in microbeam radiation therapy has always been a challenging task, where a combination of high dose response and high spatial resolution (microns) is required for synchrotron radiation peaked around 50 keV. The x-ray induced Sm{sup 3+}{yields} Sm{sup 2+} valence conversion in Sm{sup 3+} doped fluorophosphates glasses has been tested for use in x-ray dosimetry for microbeam radiation therapy. The conversion efficiency depends almost linearly on the dose of irradiation up to {approx}5 Gy and saturates at doses exceeding {approx}80 Gy. The conversion shows strong correlation with x-ray induced absorbance of the glass which is related to the formation of phosphorus-oxygen hole centers. When irradiated through a microslit collimator, a good spatial resolution and high ''peak-to-valley'' contrast have been observed by means of confocal photoluminescence microscopy.

  5. Treatment of Graves' ophthalmopathy with high-dose intravenous methylprednisolone pulse therapy.

    PubMed

    Nagayama, Y; Izumi, M; Kiriyama, T; Yokoyama, N; Morita, S; Kakezono, F; Ohtakara, S; Morimoto, I; Okamoto, S; Nagataki, S

    1987-12-01

    This preliminary study was undertaken to investigate the efficacy of high-dose iv methylprednisolone pulse therapy in 5 patients with Graves' ophthalmopathy. One gram of methylprednisolone sodium succinate was given iv daily for 3 successive days. The 3-day infusion was repeated 3 to 7 times at intervals of 1 week; total duration of pulse therapy was 3 to 7 weeks. The clinical improvement of eye involvements by pulse therapy was assessed immediately after the last pulse therapy. The clinical assessment of the effect of pulse therapy for Graves' ophthalmopathy showed a good response in 3 patients, a fair response in one, and no response in one. However, in one patient, who was judged to show no response, complete improvement of the enlarged extraocular muscle was observed on orbital computed tomography. Moreover, two patients, who have been followed without any other therapies, showed no relapse of eye involvements for 32 and 10 months, respectively. Although it is impossible to determine whether pulse therapy is more effective than other immunosuppressive therapies, the results of this preliminary study suggest that pulse therapy may be a good immunosuppressive therapy for Graves' ophthalmopathy too. Controlled studies are desired. PMID:3321820

  6. Challenges of Using High-Dose Fractionation Radiotherapy in Combination Therapy

    PubMed Central

    Yang, Ying-Chieh; Chiang, Chi-Shiun

    2016-01-01

    Radiotherapy is crucial and substantially contributes to multimodal cancer treatment. The combination of conventional fractionation radiotherapy (CFRT) and systemic therapy has been established as the standard treatment for many cancer types. With advances in linear accelerators and image-guided techniques, high-dose fractionation radiotherapy (HFRT) is increasingly introduced in cancer centers. Clinicians are currently integrating HFRT into multimodality treatment. The shift from CFRT to HFRT reveals different effects on the tumor microenvironment and responses, particularly the immune response. Furthermore, the combination of HFRT and drugs yields different results in different types of tumors or using different treatment schemes. We have reviewed clinical trials and preclinical evidence on the combination of HFRT with drugs, such as chemotherapy, targeted therapy, and immune therapy. Notably, HFRT apparently enhances tumor cell killing and antigen presentation, thus providing opportunities and challenges in treating cancer. PMID:27446811

  7. Impact of cytogenetic classification on outcomes following early high-dose therapy in multiple myeloma.

    PubMed

    Kaufman, G P; Gertz, M A; Dispenzieri, A; Lacy, M Q; Buadi, F K; Dingli, D; Hayman, S R; Kapoor, P; Lust, J A; Russell, S; Go, R S; Hwa, Y L; Kyle, R A; Rajkumar, S V; Kumar, S K

    2016-03-01

    Early high-dose therapy (HDT), consisting of high-dose melphalan and autologous stem cell transplantation following doublet or triplet novel agent induction, is a preferred management strategy for transplant-eligible myeloma patients. We set out to examine the utility of the current fluorescence in situ hybridization (FISH)-based risk stratification in a homogenously treated population of transplant-eligible myeloma patients receiving novel induction regimens and early HDT with or without posttransplant maintenance therapy. FISH was available in 409 patients at the time of diagnosis for patients receiving HDT within 12 months of diagnosis. We present comprehensive outcomes for chromosome 14 translocations and 17p abnormalities that both support and refute current risk stratification models. In contrast to its current classification as a marker of 'standard risk' (SR), t(11;14) was associated with inferior overall survival (OS) when compared with the classical SR cohort. The use of novel agent maintenance therapy (bortezomib or lenalidomide) following early HDT ameliorates the negative prognostic value of high-risk (HR) cytogenetic markers. HR patients who received maintenance following early HDT had similar OS compared with the SR cohort at 5 years. PMID:26487275

  8. Combined methotrexate and high-dose vincristine chemotherapy with radiation therapy for small cell bronchogenic carcinoma

    SciTech Connect

    Holoye, P.Y.; Libnoch, J.A.; Anderson, T.; Cox, J.D.; Byhardt, R.W.; Hoffmann, R.G.

    1985-04-01

    The addition of methotrexate to a previously described regimen of cyclophosphamide, Adriamycin (doxorubicin), and high-dose vincristine (VAC) was tested in 50 evaluable patients with small cell bronchogenic carcinoma. Prophylactic whole brain radiation therapy was given during the first chemotherapy course and consolidation radiation therapy was given to the mediastinum and primary site after achieving partial or complete remission. The addition of methotrexate did not improve the incidence of complete remission as compared to a previous regimen without it. The addition of radiation therapy improved the local control rate. The high-dose vincristine in this and a previous CAV study improved the incidence of complete remission in both limited and extensive disease presentation as compared with the authors previous experience and induced an acceptable and reversible neurotoxicity. Moderate dose consolidation radiotherapy to the lung primary and mediastinum was effective in improving local control. The distinction between limited and extensive disease was found to be vague, as 22% of the patients could be shifted from one group to the other depending on definition. The evaluation of the various staging procedures indicates that bone scan gave a small number of truly abnormal tests. Isotopic brain and liver-spleen scan could be duplicated by computerized axial tomography (CAT). CAT scan of abdomen disclosed unexpected extension to the retroperitoneal nodes and adrenals.

  9. Economic and social effects of high-dose buprenorphine substitution therapy. Six-month results.

    PubMed

    Lavignasse, Pierre; Lowenstein, William; Batel, Philippe; Constant, Marie-Véronique; Jourdain, Jean-Jacques; Kopp, Pierre; Reynaud-Maurupt, Catherine; Riff, Bertrand; Videau, Benjamin; Mucchielli, Alain

    2002-05-01

    The purpose of this study was to analyze the impact of high-dose buprenorphine substitution therapy in opiate-dependent patients in terms of use of psychoactive substances, associated risks, social integration, and the social cost generated by the use of these substances. This was a longitudinal quantitative survey carried out in 1083 patients who were evaluated at three times: at the beginning of substitution therapy (D0), at 6 months and then at 12 months follow up (M6, M12). Data were collected with an anonymous self-administered questionnaire, completed in the presence of an investigating physician. Results demonstrated that patients treated with high-dose buprenorphine for 6 months, consumed fewer psychoactive drugs (heroin, cocaine, benzodiazepines) and had fewer associated risks. Additionally, several criteria involved in social integration showed improvement; morbidity and mortality decreased after the first 6 months of substitution therapy. These improvements were followed by a reduction in the social cost of drug use generated by the group of patients considered. These initial results require confirmation in the final analysis of the study taking into account the 12-month follow up. PMID:12218879

  10. Radioprotective agents for the prevention of side effects induced by radioiodine-131 therapy.

    PubMed

    Noaparast, Zohreh; Hosseinimehr, Seyed Jalal

    2013-08-01

    Radioiodine 131 ((131)I) has been used worldwide for the ablation of remnant thyroidal tissue after surgery or as the first-line treatment for Graves' disease. Although the use of (131)I is becoming increasingly prevalent, there is evidence suggesting that this treatment is associated with side effects such as salivary gland dysfunction and an increased risk of leukemia. This article aims to review the potential use of radioprotective agents and the side effects induced by (131)I therapy. Several synthetic and natural compounds have been investigated in preclinical and clinical studies. The protective agents reduced the toxicity of (131)I, mainly in the salivary glands, and mitigated the genetic damage through different mechanisms. There are limited clinical studies evaluating the use of radioprotective agents in patients undergoing radioiodine therapy. However, lemon candies, lemon juice and sugarless chewing gum have been proposed to be beneficial for minimizing the side effects of radioiodine within the salivary glands. PMID:23902246

  11. Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies

    PubMed Central

    Leyvraz, S; Herrmann, R; Guillou, L; Honegger, H P; Christinat, A; Fey, M F; Sessa, C; Wernli, M; Cerny, T; Dietrich, D; Pestalozzi, B

    2006-01-01

    Having determined in a phase I study the maximum tolerated dose of high-dose ifosfamide combined with high-dose doxorubicin, we now report the long-term results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients with locally advanced or metastatic soft-tissue sarcomas were included, with age <60 years and all except one in good performance status (0 or 1). The chemotherapy treatment consisted of ifosfamide 10 g m−2 (continuous infusion for 5 days), doxorubicin 30 mg m−2 day−1 × 3 (total dose 90 mg m−2), mesna and granulocyte-colony stimulating factor. Cycles were repeated every 21 days. A median of 4 (1–6) cycles per patient was administered. Twenty-two patients responded to therapy, including three complete responders and 19 partial responders for an overall response rate of 48% (95% CI: 33–63%). The response rate was not different between localised and metastatic diseases or between histological types, but was higher in grade 3 tumours. Median overall survival was 19 months. Salvage therapies (surgery and/or radiotherapy) were performed in 43% of patients and found to be the most significant predictor for favourable survival (exploratory multivariate analysis). Haematological toxicity was severe, including grade ⩾3 neutropenia in 59%, thrombopenia in 39% and anaemia in 27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient died of septic shock. This high-dose regimen is toxic but nonetheless feasible in multicentre settings in non elderly patients with good performance status. A high response rate was obtained. Prolonged survival was mainly a function of salvage therapies. PMID:17031396

  12. High-dose Daptomycin Therapy for Staphylococcal Endocarditis and When to Apply It

    PubMed Central

    Smith, Jordan R.; Claeys, Kimberly; Barber, Katie E.; Rybak, Michael J.

    2014-01-01

    Infective endocarditis (IE) continues to present a large burden to the healthcare system. Staphylococcus aureus, the leading pathogen associated with the disease, has always proven difficult to treat. Increasing numbers of S. aureus isolates are demonstrating reduced susceptibility to vancomycin, and therapeutic options are limited. Daptomycin is frequently employed when vancomycin therapy proves unsuccessful or when vancomycin MIC values rise above 1 mg/L. Currently, daptomycin is FDA-approved at a dose of 6 mg/kg/day for the treatment of S. aureus bacteremia and associated right-sided endocarditis. However, numerous in vitro and clinical studies suggest that daptomycin doses up to 12 mg/kg/day may provide improved efficacy and resistance prevention. Additionally, high-dose daptomycin has demonstrated excellent safety. Together, these data suggest a role for high-dose daptomycin in staphylococcal IE patients who are severely ill, previously failed therapy with vancomycin, or possess a S. aureus isolate with an elevated vancomycin MIC. PMID:25165017

  13. High-dose MVCT image guidance for stereotactic body radiation therapy

    SciTech Connect

    Westerly, David C.; Schefter, Tracey E.; Kavanagh, Brian D.; Chao, Edward; Lucas, Dan; Flynn, Ryan T.; Miften, Moyed

    2012-08-15

    Purpose: Stereotactic body radiation therapy (SBRT) is a potent treatment for early stage primary and limited metastatic disease. Accurate tumor localization is essential to administer SBRT safely and effectively. Tomotherapy combines helical IMRT with onboard megavoltage CT (MVCT) imaging and is well suited for SBRT; however, MVCT results in reduced soft tissue contrast and increased image noise compared with kilovoltage CT. The goal of this work was to investigate the use of increased imaging doses on a clinical tomotherapy machine to improve image quality for SBRT image guidance. Methods: Two nonstandard, high-dose imaging modes were created on a tomotherapy machine by increasing the linear accelerator (LINAC) pulse rate from the nominal setting of 80 Hz, to 160 Hz and 300 Hz, respectively. Weighted CT dose indexes (wCTDIs) were measured for the standard, medium, and high-dose modes in a 30 cm solid water phantom using a calibrated A1SL ion chamber. Image quality was assessed from scans of a customized image quality phantom. Metrics evaluated include: contrast-to-noise ratios (CNRs), high-contrast spatial resolution, image uniformity, and percent image noise. In addition, two patients receiving SBRT were localized using high-dose MVCT scans. Raw detector data collected after each scan were used to reconstruct standard-dose images for comparison. Results: MVCT scans acquired using a pitch of 1.0 resulted in wCTDI values of 2.2, 4.7, and 8.5 cGy for the standard, medium, and high-dose modes respectively. CNR values for both low and high-contrast materials were found to increase with the square root of dose. Axial high-contrast spatial resolution was comparable for all imaging modes at 0.5 lp/mm. Image uniformity was improved and percent noise decreased as the imaging dose increased. Similar improvements in image quality were observed in patient images, with decreases in image noise being the most notable. Conclusions: High-dose imaging modes are made possible on a

  14. [Procedure guidelines for radioiodine therapy of differentiated thyroid cancer. Version 4].

    PubMed

    Dietlein, Markus; Eschner, Wolfgang; Grünwald, Frank; Lassmann, Michael; Verburg, Frederik A; Luster, Markus

    2016-06-28

    The procedure guideline for radioiodine therapy of differentiated thyroid cancer (version 4) was developed in the consensus of a representative expert group. This fulfils the level S1 (first step) within the AWMF classification of Clinical Practice Guidelines (AWMF, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, Germany). This procedure guideline completed the guideline for surgical management of thyroid cancer (level S2) with the aspects from nuclear medicine. Controversies over ablative radioiodine therapy in small papillary thyroid cancers and in minimally invasive follicular cancer without angioinvasion, over empirical standard doses for ablative radioiodine therapy, and over the kind of TSH-stimulation were described and the guideline formulated a corridor of good clinical practice. The text has included the recent results from the National Cancer database and the SEER database (both from the USA), indicating that the ablative radioiodine therapy has improved the survival rate even in low risk patients. Such a statistically significant benefit can be detected only by a national cancer registry with long-term follow-up data. PMID:27350004

  15. High-dose statin therapy and risk of intracerebral hemorrhage: a meta-analysis.

    PubMed

    Pandit, A K; Kumar, P; Kumar, A; Chakravarty, K; Misra, S; Prasad, K

    2016-07-01

    Statin plays a major role in the primary and secondary prevention of cardiovascular disease (CVD). Inconsistent findings in the studies have been observed toward the risk of intracerebral hemorrhage (ICH) using higher dose of statin. To examine this issue, we performed a meta-analysis of randomized controlled trials (RCTs) to assess the association between higher dose of various statins and risk of ICH among patients with CVD. Literature was searched for studies published before June 10, 2015, using electronic database 'PubMed', 'EMBASE', and 'Google Scholar' as well as from many trial databases. The following search terms were used: 'Statin therapy' AND 'Cardiovascular Disease', AND 'Dose' AND 'Intracerebral hemorrhage', AND 'Randomized Controlled Trials' AND 'High Dose Statin'. High dose of statins was defined as atorvastatin 80 mg, simvastatin 80 mg, pravastatin 40 mg, rosuvastatin 20 mg per day. Fixed-effect model was used to estimate the risk ratio (RR) and 95% confidence interval (CI) if heterogeneity was <50%; otherwise, random-effect model was used. Begg's funnel plot was used to assess the publication bias. Seven RCTs involving 31,099 subjects receiving high-dose statin and 31,105 subjects receiving placebo were analyzed in our meta-analysis. A significant risk of ICH was observed in subjects with higher dose of statin (RR = 1.53; 95% CI: 1.16-2.01; P = 0.002). There was no difference in all-cause mortality between the two groups (RR = 0.95; 95% CI: 0.86-1.06; P = 0.36). No publication bias was observed through Begg's funnel plot. Higher dose of statins was found to be associated with the risk of ICH. Future studies are needed to confirm these findings. PMID:26647879

  16. Influence of prophylactic anticonvulsant therapy on high-dose busulphan kinetics.

    PubMed

    Hassan, M; Oberg, G; Björkholm, M; Wallin, I; Lindgren, M

    1993-01-01

    The pharmacokinetics of high-dose busulphan was studied in 17 patients during conditioning prior to bone marrow transplantation using deuterium-labeled busulphan (d8-BU). About 50% of busulphan doses 1 and 16 was replaced with d8-BU. Patients were treated with phenytoin or diazepam as prophylactic anticonvulsant therapy. Patients who received phenytoin demonstrated significantly higher clearance (mean +/- SD, 3.32 +/- 0.99 ml min-1 kg-1), a lower area under the concentration-time curve (AUC, 5,412 +/- 1,534 ng h ml-1; corrected for dose/kilogram) and a shorter elimination half-life (3.03 +/- 0.57 h) for the last dose of d8-BU (dose 16) as compared with the first dose (2.80 +/- 0.78 ml min-1 kg-1, 6,475 +/- 2,223 ng h ml-1 and 3.94 +/- 1.10 h, respectively). No difference in the above mentioned pharmacokinetic parameters was seen in patients treated with diazepam. Moreover, a continuous decrease in the steady-state level of busulphan was observed in four of seven patients in the phenytoin-treated group, whereas in the diazepam group, such a decrease was seen in only one of eight patients. We conclude that phenytoin used as prophylactic anticonvulsant therapy alters busulphan pharmacokinetics and, most probably, its pharmacodynamics. For adequate prophylactic therapy, anticonvulsants with fewer enzyme-inductive properties than phenytoin should be used. PMID:8269597

  17. Use of corticosteroids to prevent progression of Graves' ophthalmopathy after radioiodine therapy for hyperthyroidism

    SciTech Connect

    Bartalena, L.; Marcocci, C.; Bogazzi, F.; Panicucci, M.; Lepri, A.; Pinchera, A. )

    1989-11-16

    We studied the effects of radioiodine treatment of hyperthyroidism due to Graves' disease on Graves' ophthalmopathy and the possible protective role of corticosteroids. Between June 1985 and June 1988, 26 patients were randomly assigned to treatment with radioiodine alone (group 1) and 26 to treatment with this agent and concomitant administration of systemic prednisone for four months (group 2). The initial dose of prednisone was 0.4 to 0.5 mg per kilogram of body weight for one month; the drug was gradually withdrawn over the next three months. All patients were evaluated at 3-month intervals for 18 months after they underwent radioiodine therapy. Ocular changes were assessed with the ophthalmopathy index; patients with moderate-to-severe changes (scores greater than or equal to 4) were excluded from the study. Before treatment, 10 patients in group 1 and 5 in group 2 had no evidence of ophthalmopathy: in none of them did ocular symptoms appear after radioiodine therapy. Among the patients in group 1 with an initial ophthalmopathy index greater than or equal to 1, ocular disease worsened in 56 percent (mostly involving soft-tissue changes and extraocular-muscle function) and did not change in 44 percent. In contrast, ophthalmopathy improved in 52 percent and did not change in 48 percent of group 2. The mean ophthalmopathy index increased from 1.5 to 3.0 in group 1 (P less than 0.005) and decreased from 2.2 to 1.3 in group 2 (P less than 0.05). We conclude that systemic corticosteroid treatment prevents the exacerbations of Graves' ophthalmopathy that occur after radioiodine therapy in a substantial proportion of patients with hyperthyroidism who have some degree of ocular involvement before treatment.

  18. High Dose Simvastatin Exhibits Enhanced Lipid Lowering Effects Relative to Simvastatin/Ezetimibe Combination Therapy

    PubMed Central

    Settergren, Magnus; D'Alexandri, Fabio Luiz; Haeggström, Jesper Z.; Fiehn, Oliver; Hyötyläinen, Tuulia; Pedersen, Theresa L.; Newman, John W.; Orešič, Matej; Pernow, John; Wheelock, Craig E.

    2014-01-01

    Statins are the frontline in cholesterol reduction therapies; however use in combination with agents that possess complimentary mechanisms of action may achieve further reductions in LDL-C. Thirty-nine patients were treated with either 80mg simvastatin (n=20) or 10mg simvastatin plus 10mg ezetimibe (n=19) for 6 weeks. Dosing was designed to produce comparable LDL-C reductions, while enabling assessment of potential simvastatin-associated pleiotropic effects. Baseline and post-treatment plasma were analyzed for lipid mediators (e.g., eicosanoids, endocannabinoids) and structural lipids by liquid chromatography tandem mass spectrometry. Following statistical analysis and orthogonal projections to latent structures (OPLS) multivariate modeling, no changes were observed in lipid mediator levels, while global structural lipids were reduced in response to both mono- (R2Y=0.74, Q2=0.66, CV-ANOVA p=7.0×10-8) and combination therapy (R2Y=0.67, Q2=0.54, CV-ANOVA p=2.6×10−5). OPLS modeling identified a subset of 12 lipids that classified the two treatment groups after 6 weeks (R2Y=0.65, Q2=0.61, CV-ANOVA p=5.4×10−8). Decreases in the lipid species PC(15:0/18:2) and HexCer(d18:1/24:0) were the strongest discriminators of LDL-C reductions for both treatment groups (q<0.00005), while PE(36:3e) contributed most to distinguishing treatment groups (q=0.017). Shifts in lipid composition were similar for high-dose simvastatin and simvastatin/ezetimibe combination therapy, but the magnitude of the reduction was linked to simvastatin dosage. Simvastatin therapy did not affect circulating levels of lipid mediators, suggesting that pleiotropic effects are not associated with eicosanoid production. Only high-dose simvastatin reduced the relative proportion of sphingomyelin and ceramide to phosphatidylcholine (q=0.008), suggesting a pleiotropic effect previously associated with a reduced risk of cardiovascular disease. PMID:25516625

  19. External beam radiation therapy followed by high-dose-rate brachytherapy for inoperable superficial esophageal carcinoma

    SciTech Connect

    Pasquier, David . E-mail: d-pasquier@o-lambret.fr; Mirabel, Xavier; Adenis, Antoine; Rezvoy, Nicolas; Hecquet, Genevieve; Fournier, Charles; Coche-Dequeant, Bernard; Prevost, Bernard; Castelain, Bernard; Lartigau, Eric

    2006-08-01

    Purpose: The aim of this study was to retrospectively evaluate the feasibility, efficacy, and tolerance of external beam radiotherapy followed by high-dose-rate brachytherapy in inoperable patients with superficial esophageal cancer. Patients and Methods: From November 1992 to May 1999, 66 patients with superficial esophageal cancer were treated with exclusive radiotherapy. The median age was 60 years (range, 41-85). Fifty-three percent of them were ineligible for surgery owing to synchronous or previously treated head-and-neck cancer. Most of the patients (n = 49) were evaluated with endoscopic ultrasonography (EUS) or computed tomography (CT). The mean doses of external beam radiotherapy and high-dose rate brachytherapy were 57.1 Gy ({+-}4.83) and 8.82 Gy ({+-}3.98), respectively. The most frequently used regimen was 60 Gy followed by 7 Gy at 5 mm depth in two applications. Results: Among patients evaluated with EUS or CT, the complete response rate was 98%. The 3-, 5-, and 7-year survival rates were 57.9%, 35.6%, and 26.6%, respectively. Median overall survival was 3.8 years. The 5-year relapse-free survival and cause-specific survival were 54.6% and 76.9%. The 5-year overall, relapse-free, and cause-specific survival of the whole population of 66 patients was 33%, 53%, and 77%, respectively. Local failure occurred in 15 of 66 patients; 6 were treated with brachytherapy. Severe late toxicity (mostly esophageal stenosis) rated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale occurred in 6 of 66 patients (9%). Conclusion: This well tolerated regimen may be a therapeutic alternative for inoperable patients with superficial esophageal cancer. Only a randomized study could be able to check the potential benefit of brachytherapy after external beam radiation in superficial esophageal cancer.

  20. Radioiodine therapy in patients with hyperthyroid disorder: standard versus dosimetric activity application.

    PubMed

    Reinartz, P; Zimny, M; Schaefer, W; Mueller, B; Buell, U; Sabri, O

    2003-12-01

    Due to its high success rate and non-invasive character, an increasing demand for radioiodine therapy can be seen. This study was conducted to determine whether standardized 131I activities can be used to facilitate management of patients with hyperthyroid disorder or whether a pre-therapeutic radioiodine test is advisable to determine an adequate therapeutic activity. The therapeutic uptake of 218 patients with benign thyroid disorders were determined and compared with 24 h and 48 h test uptake measurements as well as with calculated standard uptake values. Since there is a linear relationship between iodine uptake and delivered radiation dose, the effect of the different therapeutic approaches on the latter parameter was analysed. Special care was taken to assess possible differences between the various thyroid disorders. A mean deviation between pre-therapeutic test uptake and actual therapeutic uptake of 14.7% was observed in contrast to one of 29.1% when using disease specific standard values per millilitre of thyroid tissue. Furthermore, the proportion of patients with large deviations of more than 40% increased drastically when using standard uptake values (with radioiodine test, 4.1%; with standard values, 18.8%). In conclusion, the dosimetric approach with a pre-therapeutic radioiodine test proved to be the most accurate therapeutic procedure. Both the 24 h and 48 h test uptake measurements gave analogous results and yielded a correlation coefficient of 0.91 when compared with the therapeutic uptake. While it may be tempting to use standard activities to facilitate patient management, the findings of this study confirm that, for precise therapy planning, a pre-therapeutic radioiodine test is advised. Since no significant difference could be found between the 24 h and 48 h test uptake values, an early measurement 24 h after administration of the test activity is recommended. PMID:14627852

  1. Radioiodine Therapy Does Not Change the Atherosclerotic Burden of the Carotid Arteries

    PubMed Central

    Andersen, Ulrik Bjørn; Sørensen, Christian Hjort; Nygaard, Birte; Jensen, Lars Thorbjørn

    2016-01-01

    Background and aim: Atherosclerosis evolves or accelerates when arteries are exposed to ionizing radiation, both early and late after exposure. Radioiodine therapy of benign thyroid disease exposes the carotid arteries to 4–50 Gy, and may thereby increase the risk of atherosclerosis. Increased risk of cerebrovascular events has been reported after radioiodine therapy. This study aimed to examine whether atherosclerosis develops early or late after radioiodine therapy of benign thyroid disease. Method: Patients treated for benign thyroid disorders (nontoxic goiter, adenoma, and hyperthyroidism) were examined with ultrasound for the main outcome, carotid intima media thickness (CIMT), and for plaque presence (plaque presence only in late damage). Signs of early damage from radioiodine were studied in 39 radioiodine-treated patients, who were examined before treatment and at 1, 3, 6, and 12 months after treatment. Late changes were studied in a cross-sectional case-control design, with radioiodine-treated patients as cases (n = 193) and patients treated with surgery as controls (n = 95). Data were analyzed with repeated measurement for longitudinal data, and with multivariate regression for cross-sectional data. Results were adjusted for age, sex, cholesterol, smoking status, known atherosclerotic disease, and body mass index. Results: No changes in CIMT were found in the patients followed prospectively for one year after treatment with radioactive iodine for benign thyroid disease (p = 0.58). In the study on late effects, there was no difference in CIMT (p = 0.25) or presence of plaques (p = 0.70) between those treated with radioactive iodine and those treated with surgery (9.8 and 5.6 years since treatment, respectively). Furthermore, the level of thyrotropin (TSH) did not influence these atherosclerosis markers. Conclusion: No early changes in CIMT were detected in patients treated with radioactive iodine for benign thyroid disease. No signs

  2. Is High Dose Therapy Superior to Conventional Dose Therapy as Initial Treatment for Relapsed Germ Cell Tumors? The TIGER Trial

    PubMed Central

    Feldman, Darren R.; Huddart, Robert; Hall, Emma; Beyer, Jörg; Powles, Thomas

    2011-01-01

    Metastatic germ cell tumours (GCTs) are usually cured with cisplatin based chemotherapy and standard treatment algorithms are established. However when this treatment fails and the disease relapses, standard treatment is much more uncertain. Both conventional dose therapy (CDT) and high dose therapy (HDT) are widely used, due to the lack of conclusive data supporting one specific approach. A recent retrospective analysis focusing on this population suggested a significant benefit for HDT. Retrospective analyses are prone to bias, and therefore while this data is provocative it is by no mean conclusive. For this reason the international community is supporting a prospective randomised trial in this area comparing CDT(TIP) with sequential HDT (TICE). The planned open labelled randomised phase III study (TIGER) is due to open in 2011 and will recruit 390 patients to detect a 13% difference in 2 year progression free survival (primary endpoint). It is hoped that this large study will conclusively resolve the uncertainty which currently exists. PMID:21750688

  3. High-Dose-Rate Intraoperative Radiation Therapy for Recurrent Head-and-Neck Cancer

    SciTech Connect

    Perry, David J.; Chan, Kelvin; Wolden, Suzanne; Zelefsky, Michael J.; Chiu, Johnny; Cohen, Gilad; Zaider, Marco; Kraus, Dennis; Shah, Jatin; Lee, Nancy

    2010-03-15

    Purpose: To report the use of high-dose-rate intraoperative radiation therapy (HDR-IORT) for recurrent head-and-neck cancer (HNC) at a single institution. Methods and Materials: Between July 1998 and February 2007, 34 patients with recurrent HNC received 38 HDR-IORT treatments using a Harrison-Anderson-Mick applicator with Iridium-192. A single fraction (median, 15 Gy; range, 10-20 Gy) was delivered intraoperatively after surgical resection to the region considered at risk for close or positive margins. In all patients, the target region was previously treated with external beam radiation therapy (median dose, 63 Gy; range, 24-74 Gy). The 1- and 2-year estimates for in-field local progression-free survival (LPFS), locoregional progression-free survival (LRPFS), distant metastases-free survival (DMFS), and overall survival (OS) were calculated. Results: With a median follow-up for surviving patients of 23 months (range, 6-54 months), 8 patients (24%) are alive and without evidence of disease. The 1- and 2-year LPFS rates are 66% and 56%, respectively, with 13 (34%) in-field recurrences. The 1- and 2-year DMFS rates are 81% and 62%, respectively, with 10 patients (29%) developing distant failure. The 1- and 2-year OS rates are 73% and 55%, respectively, with a median time to OS of 24 months. Severe complications included cellulitis (5 patients), fistula or wound complications (3 patients), osteoradionecrosis (1 patient), and radiation-induced trigeminal neuralgia (1 patient). Conclusions: HDR-IORT has shown encouraging local control outcomes in patients with recurrent HNC with acceptable rates of treatment-related morbidity. Longer follow-up with a larger cohort of patients is needed to fully assess the benefit of this procedure.

  4. Cardiovascular Safety Profile and Clinical Experience With High-Dose Domperidone Therapy for Nausea and Vomiting

    PubMed Central

    Ortiz, Arleen; Cooper, Chad J.; Alvarez, Alicia; Gomez, Yvette; Sarosiek, Irene

    2015-01-01

    Abstract: Introduction: Domperidone is a dopamine receptor antagonist with peripheral prokinetic and central antiemetic properties. Prolongation of the QTc interval with chronic use of oral domperidone in standard doses has been reported in the literature. Our goal was to investigate cardiac toxicity in patients receiving 2-fold greater doses than in previous reports. Methods: A retrospective chart review was conducted of patients with nausea (N) and vomiting (V) receiving domperidone from 2009 to 2013 under an Investigational New Drug (IND) protocol. Patient demographics, indications for therapy, clinical outcomes, cardiac symptoms and electrocardiogram tracings were reviewed. Prolonged QTc was verified if >470 milliseconds in females (F) and >450 milliseconds in males (M). Results: A total of 64 patients, 44 female (37% Hispanic, 60% white, 3% African American), were taking domperidone for diabetic gastroparesis 45%; idiopathic gastroparesis 36%; chronic N&V 8%; dumping syndrome 5%; cyclic vomiting 5% and conditioned vomiting 1%. Mean duration of therapy was 8 months (range, 3 months to 4 years). Doses ranged from 40 to 120 mg/d with 90% receiving 80 to 120 mg compared with the standard dose of 40 mg. Of note, 73% of subjects benefited from treatment with reduced nausea and vomiting. Thirty-seven patients had follow-up electrocardiograms available, and they showed that the mean QTc at baseline was 424 milliseconds ± 28.4 (SD) compared with 435 milliseconds ± 27.2 (SD) at follow-up (not significant). Ten of these patients had prolonged QTc at F/U ranging from 453 to 509 milliseconds, without any cardiovascular complaints. There was no relationship between prolonged QTc and daily dose of domperidone, body mass index or age. Conclusions: Our data indicate that at very high dosing, the prokinetic/antiemetic agent domperidone has a low risk of adverse cardiovascular events while exhibiting good clinical efficacy. PMID:25828198

  5. Evaluation of high-dose daptomycin for therapy of experimental Staphylococcus aureus foreign body infection

    PubMed Central

    Schaad, Heinz J; Bento, Manuela; Lew, Daniel P; Vaudaux, Pierre

    2006-01-01

    Background Daptomycin is a novel cyclic lipopeptide whose bactericidal activity is not affected by current antibiotic resistance mechanisms displayed by S. aureus clinical isolates. This study reports the therapeutic activity of high-dose daptomycin compared to standard regimens of oxacillin and vancomycin in a difficult-to-treat, rat tissue cage model of experimental therapy of chronic S. aureus foreign body infection. Methods The methicillin-susceptible S. aureus (MSSA) strain I20 is a clinical isolate from catheter-related sepsis. MICs, MBCs, and time-kill curves of each antibiotic were evaluated as recommended by NCCLS, including supplementation with physiological levels (50 mg/L) of Ca2+ for daptomycin. Two weeks after local infection of subcutaneously implanted tissue cages with MSSA I20, each animal received (i.p.) twice-daily doses of daptomycin, oxacillin, or vancomycin for 7 days, or was left untreated. The reductions of CFU counts in each treatment group were analysed by ANOVA and Newman-Keuls multiple comparisons procedures. Results The MICs and MBCs of daptomycin, oxacillin, or vancomycin for MSSA strain I20 were 0.5 and 1, 0.5 and 1, or 1 and 2 mg/L, respectively. In vitro elimination of strain I20 was more rapid with 8 mg/L of daptomycin compared to oxacillin or vancomycin. Twice-daily administered daptomycin (30 mg/kg), oxacillin (200 mg/kg), or vancomycin (50 mg/kg vancomycin) yielded bactericidal antibiotic levels in infected cage fluids throughout therapy. Before therapy, mean (± SEM) viable counts of strain I20 were 6.68 ± 0.10 log10 CFU/mL of cage fluid (n = 74). After 7 days of therapy, the mean (± SEM) reduction in viable counts of MSSA I20 was 2.62 (± 0.30) log10 CFU/mL in cages (n = 18) of daptomycin-treated rats, exceeding by >2-fold (P < 0.01) the viable count reductions of 0.92 (± 0.23; n = 19) and 0.96 (± 0.24; n = 18) log10 CFU/mL in cages of oxacillin-treated and vancomycin-treated rats, respectively. Viable counts in cage

  6. Short and long-term effects of high-dose intravenous methylprednisolone pulse therapy on thyroid-associated ophthalmopathy

    PubMed Central

    Liu, Xiaomei; Wang, Shu; Qin, Li; Qiang, Wei; Dahal, Mahesh; Fan, Ping; Gao, Shan; Shi, Bingyin

    2016-01-01

    The majority of previous studies on high-dose intravenous methylprednisolone pulse (IVMP) therapy have observed the clinical conditions of patients prior to and following treatment without any long-term follow-up, and these studies have predominantly focused on combined treatment. The present prospective clinical study aimed to assess the long-term effects and safety of high-dose IVMP therapy in thyroid-associated ophthalmopathy (TAO), as well as the significance of thyrotropin receptor antibody (TRAb) and soluble intercellular adhesion molecule-l (sICAM-1) during IVMP therapy. A total of 58 patients with TAO were treated with high-dose IVMP therapy, and their clinical characteristics and indices were recorded before, during and after therapy, with a 12–57 month (mean, 28.4 months) follow-up. Before treatment and on the second day after each IVMP therapy, serum TRAb and sICAM-1 levels were evaluated in 23 patients with TAO via a competitive radioimmunoassay and enzyme-linked immunosorbent assay, respectively. The results of the present study demonstrated that the symptoms of eyelid swelling, ophthalmodynia, photophobia, lacrimation and diplopia, and visual acuity, ocular motility, proptosis and clinical activity score (CAS) indices were all significantly improved after IVMP therapy. In addition, analysis of covariance demonstrated that alterations in the levels of serum TRAb during the course of treatment were associated with CAS of TAO, whereas the change in serum sICAM-1 was not. In conclusion, high-dose IVMP therapy is an effective, safe, stable and well-tolerated treatment for TAO, which is associated with rare, minor adverse effects. Furthermore, serum TRAb levels are correlated with the CAS of TAO and may serve as a predictor of the response to methylprednisolone therapy. PMID:27446294

  7. Pretreatment with betamethasone of patients with Graves' disease given radioiodine therapy: thyroid autoantibody responses and outcome of therapy

    SciTech Connect

    Gamstedt, A.; Karlsson, A. )

    1991-07-01

    The effects of betamethasone on thyroid autoantibody responses and outcome of radioiodine therapy were determined over a period of 1 yr in a prospective randomized study of 40 patients with Graves' disease. Twenty patients were given placebo tablets, and 20 patients were treated with betamethasone from 3 weeks before until 4 weeks after {sup 131}I therapy. At the time of inclusion in the study, the mean serum concentrations of TSH receptor antibodies, thyroid peroxidase antibodies, and thyroglobulin antibodies (TgAb) were increased in both groups. Three weeks of treatment with betamethasone reduced the thyroid peroxidase antibody and TgAb titers as well as the serum concentrations of thyroid hormones. A decrease in the TSH receptor antibody level was not statistically significant. After radioiodine therapy, transient increases in thyroid autoantibody levels were observed. The titers of the different antibodies generally changed in parallel. In some patients a detectable level of a given antibody was found only after the radioiodine treatment, and in two cases, TgAb did not appear at all, although the two other antibodies increased temporarily. Betamethasone delayed, but did not abolish, the {sup 131}I-induced antibody peaks. Betamethasone also caused a reduction in the total serum immunoglobulin G, a reduction which persisted throughout the study period. When the study ended, 17 patients given placebo and 9 patients given betamethasone were receiving replacement therapy due to the development of hypothyroidism. These patients at this point in time had lower antibody levels than those not requiring T4. The results of this study demonstrate that betamethasone reduces and modifies the thyroid autoantibody responses as well as the outcome of radioiodine therapy in patients with Graves' disease.

  8. Focal takotsubo cardiomyopathy with high-dose interleukin-2 therapy for malignant melanoma.

    PubMed

    Damodaran, Senthil; Mrozek, Ewa; Liebner, David; Kendra, Kari

    2014-12-01

    High-dose interleukin-2 (IL-2) is an available treatment option for patients with metastatic melanoma or renal cell carcinoma, and is associated with sustained complete and partial responses in a subset of patients. IL-2, however, is not devoid of toxicities, most of which involve the cardiovascular system and manifest as hypotension, arrhythmias, and cardiomyopathy. This report describes an unusual presentation of takotsubo cardiomyopathy in a postmenopausal woman receiving high-dose IL-2 for metastatic melanoma. PMID:25505207

  9. Optically erasable samarium-doped fluorophosphate glasses for high-dose measurements in microbeam radiation therapy

    NASA Astrophysics Data System (ADS)

    Morrell, B.; Okada, G.; Vahedi, S.; Koughia, C.; Edgar, A.; Varoy, C.; Belev, G.; Wysokinski, T.; Chapman, D.; Sammynaiken, R.; Kasap, S. O.

    2014-02-01

    Previous work has demonstrated that fluorophosphate (FP) glasses doped with trivalent samarium (Sm3+) can be used as a dosimetric detector in microbeam radiation therapy (MRT) to measure high radiation doses and large dose variations with a resolution in the micrometer range. The present work addresses the use of intense optical radiation at 405 nm to erase the recorded dose information in Sm3+-doped FP glass plates and examines the underlying physics. We have evaluated both the conversion and optical erasure of Sm3+-doped FP glasses using synchrotron-generated high-dose x-rays at the Canadian Light Source. The Sm-ion valency conversion is accompanied by the appearance of x-ray induced optical absorbance due to the trapping of holes and electrons into phosphorus-oxygen hole (POHC) and electron (POEC) capture centers. Nearly complete Sm2+ to Sm3+ reconversion (erasure) may be achieved by intense optical illumination. Combined analysis of absorbance and electron spin resonance measurements indicates that the optical illumination causes partial disappearance of the POHC and the appearance of new POEC. The suggested model for the observed phenomena is based on the release of electrons during the Sm2+ to Sm3+ reconversion process, the capture of these electrons by POHC (and hence their disappearance), or by PO groups, with the appearance of new and/or additional POEC. Optical erasure may be used as a practical means to erase the recorded data and permits the reuse of these Sm-doped FP glasses in monitoring dose in MRT.

  10. Optically erasable samarium-doped fluorophosphate glasses for high-dose measurements in microbeam radiation therapy

    SciTech Connect

    Morrell, B.; Okada, G.; Vahedi, S.; Koughia, C. Kasap, S. O.; Edgar, A.; Varoy, C.; Belev, G.; Wysokinski, T.; Chapman, D.; Sammynaiken, R.

    2014-02-14

    Previous work has demonstrated that fluorophosphate (FP) glasses doped with trivalent samarium (Sm{sup 3+}) can be used as a dosimetric detector in microbeam radiation therapy (MRT) to measure high radiation doses and large dose variations with a resolution in the micrometer range. The present work addresses the use of intense optical radiation at 405 nm to erase the recorded dose information in Sm{sup 3+}-doped FP glass plates and examines the underlying physics. We have evaluated both the conversion and optical erasure of Sm{sup 3+}-doped FP glasses using synchrotron-generated high-dose x-rays at the Canadian Light Source. The Sm-ion valency conversion is accompanied by the appearance of x-ray induced optical absorbance due to the trapping of holes and electrons into phosphorus-oxygen hole (POHC) and electron (POEC) capture centers. Nearly complete Sm{sup 2+} to Sm{sup 3+} reconversion (erasure) may be achieved by intense optical illumination. Combined analysis of absorbance and electron spin resonance measurements indicates that the optical illumination causes partial disappearance of the POHC and the appearance of new POEC. The suggested model for the observed phenomena is based on the release of electrons during the Sm{sup 2+} to Sm{sup 3+} reconversion process, the capture of these electrons by POHC (and hence their disappearance), or by PO groups, with the appearance of new and/or additional POEC. Optical erasure may be used as a practical means to erase the recorded data and permits the reuse of these Sm-doped FP glasses in monitoring dose in MRT.

  11. Treatment results of high dose cabergoline as an adjuvant therapy in six patients with established severe ovarian hyper stimulation syndrome

    PubMed Central

    Saharkhiz, Nasrin; Akbari Sene, Azadeh; Salehpour, Saghar; Tamimi, Maryam; Vasheghani Farahani, Masoumeh; Sheibani, Kourosh

    2014-01-01

    Background: The beneficial role of cabergoline as a prophylactic agent to prevent ovarian hyper stimulation syndrome (OHSS) among high-risk patients has been demonstrated in previous studies. But data for its role as a treatment for established severe OHSS is still limited. We represent the treatment results of high dose oral cabergoline in management of six patients after the syndrome is established. Case: High-dose oral cabergoline (1 mg daily for eight days) was prescribed as an adjuvant to symptomatic treatment for six hospitalized patients with established severe OHSS following infertility treatment cycles. In two cases OHSS resolved rapidly despite the occurrence of ongoing pregnancy. Conclusion: Considering the treatment outcomes of our patients, high dose cabergoline did not eliminate the need for traditional treatments, but it was a relatively effective and safe therapy in management of established severe OHSS, and prevented the increase in its severity following the occurrence of pregnancy. PMID:25469130

  12. High-dose esomeprazole and amoxicillin dual therapy for first-line Helicobacter pylori eradication: a proof of concept study

    PubMed Central

    Zullo, Angelo; Ridola, Lorenzo; Francesco, Vincenzo De; Gatta, Luigi; Hassan, Cesare; Alvaro, Domenico; Bellesia, Annamaria; de Nucci, Germana; Manes, Gianpiero

    2015-01-01

    Background The prevalence of resistance to clarithromycin and metronidazole has considerably increased, with a corresponding decrease in the eradication rate for Helicobacter pylori (H. pylori) infection. Primary resistance to amoxicillin is extremely low, and esomeprazole was found to exert a noteworthy antimicrobial activity in vitro against H. pylori. A dual therapy with high-dose of esomeprazole coupled with high-dose amoxicillin might be therefore an ideal first-line treatment for H. pylori eradication. We aimed to assess the efficacy of a first-line 10-day, high-dose dual therapy consisting of amoxicillin and esomeprazole to eradicate H. pylori infection. Methods Consecutive naïve H. pylori-infected patients, who underwent an upper endoscopy in 4 Italian hospitals due to dyspeptic symptoms and found to be infected at routine histological assessment, were invited to participate. Patients enrolled received a 10-day, high-dose dual therapy comprising esomeprazole (40 mg t.i.d) and amoxicillin (1 g t.i.d.). At least 4 weeks after the end of the treatment a 13C-urea breath test was performed to evaluate the eradication. Results A total of 56 patients agreed to participate in the study and were all followed-up. The overall eradication was 87.5% (95% CI=78.8•96.2), without a statistically significant difference among centres. Overall, 5 (8.9%; 1.5•16.4%) patients complained of side-effects. Conclusions The 10-day, high-dose dual therapy with esomeprazole and amoxicillin might be an effective and safe first-line regimen. The efficacy of a longer 14-day regimen should be tested. PMID:26423014

  13. Psychiatric side effects of acute high-dose corticosteroid therapy in neurological conditions.

    PubMed

    Lotan, Itay; Fireman, Liora; Benninger, Felix; Weizman, Abraham; Steiner, Israel

    2016-07-01

    It has been implied that high-dose corticosteroids (CSs) commonly cause psychiatric side effects. Here, we examined the rate and risk factors of psychiatric side effects during high-dose CS treatment in patients with neurological disorders. Patients treated with high-dose intravenous CSs for neurological disorders were evaluated for depression, mania, and psychosis using the Beck Depression Inventory, the Geriatric Depression Scale, the Young Mania Rating Scale, and the Brief Psychiatric Rating Scale before CS treatment, immediately after, and 1 month following treatment. Forty-nine consecutive patients were monitored. There was a reduction in the Beck Depression Inventory and Geriatric Depression Scale scores as well as in the Brief Psychiatric Rating Scale scores throughout the study period and a transitory increase in the Young Mania Rating Scale score immediately after CS administration. Thus, a tendency to develop transient mild euphoria during high-dose CS treatment exists, but is reversible at 1 month, whereas a reduction in depressive symptoms tended to persist. Overall, our data indicate that high-dose CS treatment for neurological diseases is relatively safe with respect to psychiatric complications. PMID:26938038

  14. Nebuhaler or nebulizer for high dose bronchodilator therapy in chronic bronchitis: a comparison.

    PubMed

    Allen, M B; Pugh, J; Wilson, R S

    1988-10-01

    We have compared the clinical efficacy of high dose terbutaline sulphate (10 mg four times daily) delivered by either a Nebuhaler or jet nebulizer in 13 patients with chronic bronchitis in a 2-week, open, crossover study. Both treatment regimens improved run-in symptom scores but no significant changes were recorded in peak flow and spirometry. Side-effects were more common with the Nebuhaler and more patients preferred the nebulizer. However, the Nebuhaler is an alternative therapeutic option for delivery of high doses of bronchodilators in patients with chronic bronchitis. PMID:3076792

  15. High-Dose Adjuvant Radiotherapy After Radical Prostatectomy With or Without Androgen Deprivation Therapy

    SciTech Connect

    Ost, Piet; Cozzarini, Cesare; De Meerleer, Gert; Fiorino, Claudio; De Potter, Bruno; Briganti, Alberto; Nagler, Evi V.T.; Montorsi, Francesco; Fonteyne, Valerie; Di Muzio, Nadia

    2012-07-01

    Purpose: To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (>69 Gy) adjuvant radiotherapy (HD-ART) and the impact of androgen deprivation therapy (ADT). Methods and Materials: Between 1999 and 2008, 225 node-negative patients were referred for HD-ART with or without ADT to two large academic institutions. Indications for HD-ART were extracapsular extension, seminal vesicle invasion (SVI), and/or positive surgical margins at radical prostatectomy (RP). A dose of at least 69.1 Gy was prescribed to the prostate bed and seminal vesicle bed. The ADT consisted of a luteinizing hormone-releasing hormone analog. The duration and indication of ADT was left at the discretion of the treating physician. The effect of HD-ART and ADT on biochemical (bRFS) and clinical (cRFS) relapse-free survival was examined through univariate and multivariate analysis, with correction for known patient- and treatment-related variables. Interaction terms were introduced to evaluate effect modification. Results: After a median follow-up time of 5 years, the 7-year bRFS and cRFS were 84% and 88%, respectively. On multivariate analysis, the addition of ADT was independently associated with an improved bRFS (hazard ratio [HR] 0.4, p = 0.02) and cRFS (HR 0.2, p = 0.008). Higher Gleason scores and SVI were associated with decreased bRFS and cRFS. A lymphadenectomy at the time of RP independently improved cRFS (HR 0.09, p = 0.009). The 7-year probability of late Grade 2-3 toxicity was 29% and 5% for genitourinary (GU) and gastrointestinal (GI) symptoms, respectively. The absolute incidence of Grade 3 toxicity was <1% and 10% for GI and GU symptoms, respectively. The study is limited by its retrospective design and the lack of a standardized use of ADT. Conclusions: This retrospective study shows significantly improved bRFS and cRFS rates with the addition of ADT to HD-ART, with low Grade 3 gastrointestinal toxicity and 10% Grade 3 genitourinary toxicity.

  16. Graves Disease Induced by Radioiodine Therapy for Toxic Nodular Goiter: A Case Report.

    PubMed

    Yürekli, Yakup; Cengiz, Arzu; Güney, Engin

    2015-10-01

    Graves' disease (GD) may be observed as an infrequent adverse effect after radioiodine therapy (RAIT) for toxic thyroid adenoma (TA) and toxic multi nodular goiter (MNG). We present a case of a 55-year-old male with a toxic nodule who was treated with RAI. After therapy, the patient's serum free triiodothyronine (fT3) and free thyroxine (fT4) levels gradually increased. Antithyroid peroxidase (TPOAb), antithyroglobulin (TgAb) and TSH-receptor antibodies (TRAb) were also positive. Thyroid scintigraphy revealed diffuse intense uptake after four months of RAIT. Radiation-induced GD should be considered in patients with aggravated hyperthyroidism 3-4 months after therapy. PMID:27529890

  17. Graves Disease Induced by Radioiodine Therapy for Toxic Nodular Goiter: A Case Report

    PubMed Central

    Yürekli, Yakup; Cengiz, Arzu; Güney, Engin

    2015-01-01

    Graves’ disease (GD) may be observed as an infrequent adverse effect after radioiodine therapy (RAIT) for toxic thyroid adenoma (TA) and toxic multi nodular goiter (MNG). We present a case of a 55-year-old male with a toxic nodule who was treated with RAI. After therapy, the patient’s serum free triiodothyronine (fT3) and free thyroxine (fT4) levels gradually increased. Antithyroid peroxidase (TPOAb), antithyroglobulin (TgAb) and TSH-receptor antibodies (TRAb) were also positive. Thyroid scintigraphy revealed diffuse intense uptake after four months of RAIT. Radiation-induced GD should be considered in patients with aggravated hyperthyroidism 3-4 months after therapy.

  18. Graves' disease radioiodine-therapy: Choosing target absorbed doses for therapy planning

    SciTech Connect

    Willegaignon, J. Sapienza, M. T.; Coura-Filho, G. B.; Buchpiguel, C. A.; Watanabe, T.; Traino, A. C.

    2014-01-15

    Purpose: The precise determination of organ mass (m{sub th}) and total number of disintegrations within the thyroid gland (A{sup ~}) are essential for thyroid absorbed-dose calculations for radioiodine therapy. Nevertheless, these parameters may vary according to the method employed for their estimation, thus introducing uncertainty in the estimated thyroid absorbed dose and in any dose–response relationship derived using such estimates. In consideration of these points, thyroid absorbed doses for Graves’ disease (GD) treatment planning were calculated using different approaches to estimating the m{sub th} and the A{sup ~}. Methods: Fifty patients were included in the study. Thyroid{sup 131}I uptake measurements were performed at 2, 6, 24, 48, 96, and 220 h postadministration of a tracer activity in order to estimate the effective half-time (T{sub eff}) of {sup 131}I in the thyroid; the thyroid cumulated activity was then estimated using the T{sub eff} thus determined or, alternatively, calculated by numeric integration of the measured time-activity data. Thyroid mass was estimated by ultrasonography (USG) and scintigraphy (SCTG). Absorbed doses were calculated with the OLINDA/EXM software. The relationships between thyroid absorbed dose and therapy response were evaluated at 3 months and 1 year after therapy. Results: The average ratio (±1 standard deviation) betweenm{sub th} estimated by SCTG and USG was 1.74 (±0.64) and that between A{sup ~} obtained by T{sub eff} and the integration of measured activity in the gland was 1.71 (±0.14). These differences affect the calculated absorbed dose. Overall, therapeutic success, corresponding to induction of durable hypothyroidism or euthyroidism, was achieved in 72% of all patients at 3 months and in 90% at 1 year. A therapeutic success rate of at least 95% was found in the group of patients receiving doses of 200 Gy (p = 0.0483) and 330 Gy (p = 0.0131) when m{sub th} was measured by either USG or SCTG and A

  19. Repeated high-dose chemotherapy followed by purged autologous bone marrow transplantation as consolidation therapy in metastatic neuroblastoma.

    PubMed

    Hartmann, O; Benhamou, E; Beaujean, F; Kalifa, C; Lejars, O; Patte, C; Behard, C; Flamant, F; Thyss, A; Deville, A

    1987-08-01

    Among 62 children over 1 year of age at diagnosis, who were treated for stage IV neuroblastoma, 33 entered complete remission (CR) or good partial remission (GPR) after conventional therapy and received high-dose chemotherapy (HDC) with in vitro purged autologous bone marrow transplantation (ABMT) as consolidation therapy. The HDC was a combination of carmustine (BCNU), teniposide (VM-26), and melphalan. Thirty-three patients received one course of this regimen, and 18 received two courses. At present, 16 of the 33 grafted patients are alive in continuous CR, with a median follow-up of 28 months. Toxicity of this regimen was tolerable, principally marked by bone marrow depression and gastrointestinal (GI) tract complications. Four complication-related deaths were observed. Relapse post-ABMT occurred most often in the bone marrow. Under this treatment, actuarial disease-free survival is improved compared with that observed under conventional therapy. PMID:3305792

  20. High-dose therapy with peripheral blood progenitor cell transplantation in low-grade non-Hodgkin's lymphoma.

    PubMed

    Haas, R; Moos, M; Möhle, R; Döhner, H; Witt, B; Goldschmidt, H; Murea, S; Flentje, M; Wannenmacher, M; Hunstein, W

    1996-02-01

    It was the objective of our study to evaluate the efficacy of a sequential high-dose therapy with peripheral blood progenitor cell (PBPC) support in patients with low-grade non-Hodgkin's lymphoma (NHL). Since July 1991, 48 patients (23 male/25 female) with a median age of 43 years (range 26-55) were included in the study. At the time of entry, 28 patients were in first and seven in second or higher remission. Twelve patients had relapse of disease and one patient had tumor progression. PBPC were collected during granulocyte colony-stimulating factor (G-CSF)-enhanced leukocyte recovery following treatment with high-dose cytarabine and mitoxantrone (HAM). A median of two leukaphereses (range 2-7) resulted in 6.9 x 10(6) CD34+ cells/kg (median, range 2.1 x 10(6)-38.8 x 10(6)). A comparison was made between the harvests obtained from patients in first remission and those from patients in second remission, in relapse or progressive disease. Patients mobilized in first remission tended to have a greater collection efficiency for CD34+ cells comprising a significantly greater proportion of more primitive CD34+/Thy-1+ progenitor cells. Conversely, leukapheresis (LP) products collected during first remission contained a significantly smaller proportion of CD34+/CD45RA+ cells and CD34+/c-kit+ cells, subsets which reflect a more differentiated progenitor cell stage. Following high-dose therapy and PBPC autografting, the median time to reach platelets > or = 20 x 10(9)/l and neutrophils > or = 0.5 x 10(9)/l and 12 and 13 days, respectively. Two patients died of treatment-related toxic organ failure. Thirty-nine patients are alive in remission after a median follow-up time of 15 months (range 1-31), while seven patients relapsed between 5 and 29 months post-transplantation. Except for one patient autografted in first remission, the patients with relapse had a history of previous relapse or progressive disease. Since the probability of disease-free survival appears to be related

  1. Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe

    PubMed Central

    Garcia, Maristela Magnavita Oliveira; Varela, Carolina Garcez; Silva, Patricia Fontes; Lima, Paulo Roberto Passos; Góes, Paulo Meira; Rodrigues, Marilia Galeffi; Silva, Maria de Lourdes Lima Souza e; Ladeia, Ana Marice Teixeira; Guimarães, Armênio Costa; Correia, Luis Claudio Lemos

    2016-01-01

    Background The effect of statins on the endothelial function in humans remains under discussion. Particularly, it is still unclear if the improvement in endothelial function is due to a reduction in LDL-cholesterol or to an arterial pleiotropic effect. Objective To test the hypothesis that modulation of the endothelial function promoted by statins is primarily mediated by the degree of reduction in LDL-cholesterol, independent of the dose of statin administered. Methods Randomized clinical trial with two groups of lipid-lowering treatment (16 patients/each) and one placebo group (14 patients). The two active groups were designed to promote a similar degree of reduction in LDL-cholesterol: the first used statin at a high dose (80 mg, simvastatin 80 group) and the second used statin at a low dose (10 mg) associated with ezetimibe (10 mg, simvastatin 10/ezetimibe group) to optimize the hypolipidemic effect. The endothelial function was assessed by flow-mediated vasodilation (FMV) before and 8 weeks after treatment. Results The decrease in LDL-cholesterol was similar between the groups simvastatin 80 and simvastatin 10/ezetimibe (27% ± 31% and 30% ± 29%, respectively, p = 0.75). The simvastatin 80 group presented an increase in FMV from 8.4% ± 4.3% at baseline to 11% ± 4.2% after 8 weeks (p = 0.02). Similarly, the group simvastatin 10/ezetimibe showed improvement in FMV from 7.3% ± 3.9% to 12% ± 4.4% (p = 0.001). The placebo group showed no variation in LDL-cholesterol level or endothelial function. Conclusion The improvement in endothelial function with statin seems to depend more on a reduction in LDL-cholesterol levels, independent of the dose of statin administered, than on pleiotropic mechanisms. PMID:27142792

  2. Endocrine function following high dose proton therapy for tumors of the upper clivus

    SciTech Connect

    Slater, J.D.; Austin-Seymour, M.; Munzenrider, J.; Birnbaum, S.; Carroll, R.; Klibanski, A.; Riskind, P.; Urie, M.; Verhey, L.; Goitein, M.

    1988-09-01

    The endocrine status of patients receiving proton radiation for tumors of the upper clivus was reviewed to evaluate the effect of high dose treatment on the pituitary gland. The fourteen patients had chordomas or low grade chondrosarcomas and were all treated by the same techniques. The median tumor dose was 69.7 Cobalt Gray Equivalent (CGE) with a range from 66.6 to 74.4 CGE. (CGE is used because modulated protons have an RBE of 1.1 compared to 60Co). The daily fraction size was 1.8-2.1 CGE. The median follow-up time is 48 months, ranging from 30 to 68 months. All treatments were planned using a computerized multi-dimensional system with the position of the pituitary outlined on the planning CT scan. Review of the dose distribution indicated that the dose to the pituitary ranged from 60.5 to 72.3 CGE, with a median of 67.6 CGE. One female patient had decreased thyroid and gonadotropin function at the time of diagnosis and has been on hormone replacement since that time. The other three females were all pre-menopausal at the time of radiotherapy. At this time four patients (3 males and 1 female) have developed endocrine abnormalities 14 to 45 months after irradiation. All four had evidence of hypothyroidism and two have also developed corticotropin deficiency. The three males had decreased testosterone levels; the female patient developed amenorrhea and hyperprolactinemia. All four are asymptomatic with ongoing hormone replacement.

  3. The protection conferred by chelation therapy in post-MI diabetics might be replicated by high-dose zinc supplementation.

    PubMed

    McCarty, Mark F; DiNicolantonio, James J

    2015-05-01

    The recent Trial to Assess Chelation Therapy (TACT) study, enrolling subjects who had previously experienced a myocardial infarction, has provided strong evidence that intravenous chelation therapy can markedly reduce risk for mortality and vascular events in diabetics, whereas no discernible benefit was observed in non-diabetics. It has plausibly been suggested that this reflects a role for transition metal ions--iron or copper--in the genesis of advanced glycation end products, key mediators of diabetic complications that can destabilize plaque. Since phlebotomy therapy fails to prevent vascular events in diabetics, we hypothesize that labile copper may be the chief culprit whose removal by chelation mediated the benefit observed in TACT. If so, strategies less time and labor intensive than chelation therapy might provide comparable benefit. A number of recent studies report that the copper-specific orally-active chelator trientine can reduce risk for range of diabetic complications in rodents; a clinical trial with this agent demonstrated some decrease in left ventricular mass in diabetics with ventricular hypertrophy. However, until this agent becomes less expensive, supplementation with high-dose zinc may represent a more feasible alternative. Zinc opposes the absorption and redox activity of copper via induction of the antioxidant protein metallothionein, which binds copper tightly. A great many studies demonstrate that increased expression of metallothionein decreases risk for tissue damage in diabetic rodents, and in some of these studies metallothionein expression was boosted by supplemental zinc. Zinc supplementation also modestly improves glycemic control in type 2 diabetics, and might reduce risk for diabetes by protecting pancreatic beta cells from oxidative stress. A long term study assessing the impact of supplementing diabetics with high-dose zinc, assessing risk for mortality, vascular events, and diabetic complications, may be warranted. Histidine

  4. High dose simvastatin exhibits enhanced lipid lowering effects relative to simvastatin/ezetimibe combination therapy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Technical Abstract: Background: Statins are the frontline in cholesterol reduction therapies; however use in combination with agents that possess complimentary mechanisms of action may achieve further reduce in LDL-C. Methods and Results: Thirty-nine patients were treated with either 80mg simvasta...

  5. High-dose radiation therapy alone by moderate hypofractionation for patients with thoracic esophageal squamous cell carcinoma.

    PubMed

    Oh, Dongryul; Noh, Jae Myoung; Nam, Heerim; Lee, Hyebin; Kim, Tae Gyu; Ahn, Yong Chan

    2016-08-01

    We conducted retrospective analyses to investigate the clinical outcome of thoracic esophageal cancer patients who were treated with high-dose radiation therapy (RT) alone by moderate hypofractionation due to medical unfitness or refusal to receive either surgery or chemo-radiotherapy.Between May 2003 and April 2013, 70 patients were treated with high-dose RT alone with curative aim. The planned total RT dose was 60 Gy in daily 3.0 Gy per fraction. We evaluated the survival outcome, toxicities, and prognostic factors affecting patients' survival.At the time of analysis, 32 patients experienced disease progression. The 2-year overall survival (OS), cancer-specific survival (CSS) and local control (LC) rates were 52.1%, 57.8%, and 68.2%, respectively. Among them, 25 patients had superficial (cT1a-b) esophageal cancers, and the 2-year OS, CSS, and LC rates were 80.0%, 87.3%, and 81.6%, respectively. Multivariate analysis revealed that cT disease (P < 0.001) and tumor location (P = 0.022) were the significant factors for OS. The incidence of grade 3 or higher toxicities were 9.9%, including grade 3 esophagitis (2 patients, 2.8%) and grade 4 or 5 trachea-esophageal fistula (5 patients, 7.1%).High-dose RT alone by moderate hypofractionation had led to reasonable clinical outcomes at acceptable toxicity risk in thoracic esophageal cancer patients who are medically unfit or refuse surgery or chemotherapy, especially for the patients having superficial lesion. PMID:27537591

  6. Nasal Symptoms After Radioiodine Therapy: A Rarely Described Side Effect with Similar Frequency to Lacrimal Dysfunction

    PubMed Central

    2014-01-01

    Background: Salivary and lacrimal side effects of radioiodine therapy have been carefully described. However, nasal side effects are rarely described. The objective of this study was to document the frequency of nasal side effects in comparison to the already well-documented lacrimal side effects and to determine contributing risk factors. Methods: A retrospective review of the medical records of 807 patients with differentiated thyroid cancer who received care at an academic medical center was conducted. Four hundred eleven patients who received treatment with radioactive iodine (RAI) were identified and included in the analysis. The frequency of both nasal and lacrimal side effects was ascertained. Factors that may have contributed to patients sustaining nasal damage after RAI therapy were also documented. These factors included radioactive iodine dose, method of preparation for receiving RAI therapy, and patient characteristics. Results: The mean dose of RAI administered was 109 mCi. Forty-three patients (10.5%) and 40 patients (9.7%) developed nasal and lacrimal side effects, respectively, following RAI treatment. The mean time of onset of nasal symptoms was 11 days, compared with 10 months for lacrimal symptoms. Radioiodine dose and body mass index were significantly positively and negatively correlated, respectively, with sustaining nasal side effects (p values of 0.04 and 0.01, respectively). Similarly, both RAI dose and body mass index were significantly correlated, positively and negatively, respectively, with sustaining lacrimal side effects (p values of 0.02 and 0.01). Preparation for treatment using a withdrawal protocol was associated with increased risk of both nasal and lacrimal side effects, compared with a recombinant human thyrotropin (rhTSH) protocol (p values of <0.01 and 0.01). The odds ratios (95% confidence interval [CI]) for nasal and lacrimal side effects with recombinant rhTSH preparation were 0.22 [0.11–0.44] and 0.37 [0.18–0

  7. A novel triple therapy for ITP using high-dose dexamethasone, low-dose rituximab, and cyclosporine (TT4)

    PubMed Central

    Choi, Philip Young-Ill; Roncolato, Fernando; Badoux, Xavier; Ramanathan, Sundra; Ho, Shir-Jing

    2015-01-01

    Promising reports of combination immunosuppression with high-dose dexamethasone and rituximab for the treatment of primary immune thrombocytopenia (ITP) have recently emerged. They suggest a potential to further optimize the efficacy of therapy. We investigate the use of a novel combination of conventional therapies in ITP given over 4 weeks. From 2011 to 2014, 20 patients were prospectively enrolled onto a single-arm phase 2b study to describe the safety, efficacy, and tolerability of oral dexamethasone 40 mg for days 1 to 4, oral cyclosporine 2.5 to 3 mg/kg daily for day 1 to 28, and intravenous low-dose rituximab 100 mg for days 7, 14, 21, and 28. There were no therapy-related serious adverse side effects, 6-month response rate was 60%, and treatment was well tolerated. Responders enjoyed relapse-free survivals of 92% and 76%, respectively, at 12 and 24 months. This study highlights the possibility of achieving an enduring remission from 4 weeks of therapy. This study is registered at www.anzctr.org.au (#ANZCTRN12611000015943). PMID:25972158

  8. High dose sapropterin dihydrochloride therapy improves monoamine neurotransmitter turnover in murine phenylketonuria (PKU).

    PubMed

    Winn, Shelley R; Scherer, Tanja; Thöny, Beat; Harding, Cary O

    2016-01-01

    Central nervous system (CNS) deficiencies of the monoamine neurotransmitters, dopamine and serotonin, have been implicated in the pathophysiology of neuropsychiatric dysfunction in phenylketonuria (PKU). Increased brain phenylalanine concentration likely competitively inhibits the activities of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), the rate limiting steps in dopamine and serotonin synthesis respectively. Tetrahydrobiopterin (BH4) is a required cofactor for TH and TPH activity. Our hypothesis was that treatment of hyperphenylalaninemic Pah(enu2/enu2) mice, a model of human PKU, with sapropterin dihydrochloride, a synthetic form of BH4, would stimulate TH and TPH activities leading to improved dopamine and serotonin synthesis despite persistently elevated brain phenylalanine. Sapropterin (20, 40, or 100mg/kg body weight in 1% ascorbic acid) was administered daily for 4 days by oral gavage to Pah(enu2/enu2) mice followed by measurement of brain biopterin, phenylalanine, tyrosine, tryptophan and monoamine neurotransmitter content. A significant increase in brain biopterin content was detected only in mice that had received the highest sapropterin dose, 100mg/kg. Blood and brain phenylalanine concentrations were unchanged by sapropterin therapy. Sapropterin therapy also did not alter the absolute amounts of dopamine and serotonin in brain but was associated with increased homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), dopamine and serotonin metabolites respectively, in both wild type and Pah(enu2/enu2) mice. Oral sapropterin therapy likely does not directly affect central nervous system monoamine synthesis in either wild type or hyperphenylalaninemic mice but may stimulate synaptic neurotransmitter release and subsequent metabolism. PMID:26653793

  9. [A Case of a Multidisciplinary Team Approach to Serious Hand-Foot Syndrome Induced by High-Dose Cytarabine Therapy].

    PubMed

    Sakurada, Hiroaki; Aoi, Miki; Yuge, Masaaki; Sugimura, Yuriko; Kitamura, Kunio; Yamamura, Masumi; Tachi, Tomoya; Teramachi, Hitomi

    2016-07-01

    A 40's year-old female patient with acute myeloblastic leukemia received high-dose cytarabine(HD-Ara-C)as her third induction therapy. Because the pharmacist in charge noticed on a prior interview that she had experienced a mild skin eruption similar to hand-foot syndrome(HFS)in the previous round oftherapy(idarubicin and cytarabine), heparinoid lotion and hypoallergenic soap were used to prevent HFS. However, HFS occurred on day 3, and further developed on day 6 to grade 3 with painful erythema, swelling, and paresthesia affecting the entire surface of both hands. We cared for her with moisturization, lifestyle guidance, rotation of steroid ointment, and occlusive dressing techniques according to a multidisciplinary team approach composed ofa hematologist, dermatologist, pharmacist, and nurse. Her symptoms resolved on day 40. PMID:27431642

  10. Step-down from high dose fixed combination therapy in asthma patients: a randomized controlled trial

    PubMed Central

    2012-01-01

    Background Asthma guidelines suggest that therapy can be reduced once asthma is controlled. Despite these recommendations, asthmatic patients are seldom stepped down in clinical practice, and questions remain about when and how to reduce asthma therapy. The purpose of the present study was to evaluate lung function and asthma control in patients who were stepped down from the highest recommended dose of inhaled corticosteroid/long acting β2 agonist combination therapy. Methods This was a prospective, randomised, controlled, two-arm parallel group study. Asthmatic patients who were fully controlled with a high daily dose (1000/100 μg) of fluticasone/salmeterol were randomly assigned to 6 months of open-label treatment with either 500/100 μg fluticasone/salmeterol Diskus daily or 400/24 μg extrafine beclomethasone/formoterol pMDI daily. The primary outcome was the change in morning peak expiratory flow (PEF) values between baseline and the end of treatment. The secondary outcomes included asthma control and exacerbation frequency. Results Four hundred twenty-two patients were included in the analysis. The PEF values remained above 95% of the predicted values throughout the study. The end-study morning PEF rates showed equivalence between the groups (difference between means, 2.49 L/min; 95% CI, -13.43 to 18.42). No changes from baseline were detected in PEF and forced expiratory volume in 1 second measured at the clinics, in the symptom scores or in the use of rescue medication. Asthma control was maintained in 95.2% of the patients at 6 months. No significant differences between the groups were detected in any other parameter, including exacerbation frequency and adverse events. Conclusions Stepping down patients whose asthma is controlled with the highest recommended dose of fluticasone/salmeterol to either 500/100 μg fluticasone/salmeterol daily or 400/24 μg extra-fine beclomethasone/formoterol daily provides comparable maintenance of lung

  11. Adjuvant Therapy with High-Dose Medroxyprogesterone Acetate for Operable Breast Cancer.

    PubMed

    Koyama

    1999-04-25

    BACKGROUND: Medroxyprogesterone acetate (MPA) produces a comparable or higherresponse rate in metastatic breast cancer compared with tamoxifen which is alsocommonly used for adjuvant endocrine therapy. Several studies in the West have indicated the efficacy of MPA when used as an adjuvant to surgery in certain subsets of patients. The present study was undertaken as a multicenter open study in Japan to investigate the safety and efficacy of MPA in adjuvant endocrine therapy. Method and Patients: A combination of 800 mg/day MPA and a fluorouracil compound for 6 months was given postoperatively to 119 patients with stage II or IIIabreast cancer in 32 participating hospitals between June 1987 and June 1989. RESULTS: Among the 119 patients, 59 patients (49.6%) experienced some kind ofadverse reaction. The major adverse reaction was abnormal menstruation, seen in 13 (25.0%) of the 52 premenopausal patients. Vaginal bleeding was a major adverse reaction in the 67 postmenopausal patients (8/67 or 11.9%). An increase in body weight and moon face were observed in 23 (19.3%) and 9 (7.6%) of the 119 patients, respectively. Administration of drugs was discontinued because of adversereaction in 17 patients (14.3%), and dose reduction or temporary suspension wasnecessary in 7 patients (5.9%). Increase in body weight was the main reason fordiscontinuation of the treatment. No severe adverse reactions were observed. After a median follow-up of 74.5 months (range, 2.2-90.0 months), 84 of the 119 patients are alive with no evidence of disease. The 3-year and 5-year disease-freesurvival rates were 88.2% and 82.6% in stage II patients, and 64.7% and 52.9% in stage IIIa patients, respectively. The 3-year and 5-year disease-free survivalrates according to age were 87.8% and 79.3% in patients aged 50 years or more, and 78.6% and 71.4% in patients aged under 50 years. CONCLUSION: These results show that 800 mg/day MPA plus a fluorouracil compound can be administered with acceptable

  12. Efficient multicistronic co-expression of hNIS and hTPO in prostate cancer cells for nonthyroidal tumor radioiodine therapy.

    PubMed

    Li, Guoquan; Xiang, Lei; Yang, Weidong; Wang, Zhe; Wang, Jing; Chen, Kai

    2012-01-01

    Radioiodine therapy has proven to be a safe and effective approach in the treatment of differentiated thyroid cancer. Similar treatment strategies have been exploited in nonthyroidal malignancies by transfecting hNIS gene into tumor cells or xenografts. However, rapid radioiodine efflux is often observed after radioiodine uptake, limiting the overall antitumor effects. In this study, we aimed at constructing multicistronic co-expression of hNIS and hTPO genes in tumor cells to enhance the radioiodine uptake and prolong the radioiodine retention. Driven by the cytomegalovirus promoter, hNIS and hTPO were simultaneously inserted into the expression cassette of adenoviral vector. An Ad5 viral vector (Ad-CMV-hTPO-T2A-hNIS) was assembled as a gene therapy vehicle by Gateway technology and 2A method. The co-expression of hNIS and hTPO genes was confirmed by a double-label immunofluorescence assay. The radioiodine ((125)I) uptake and efflux effects induced by co-expression of hNIS and hTPO genes were determined in transfected and non-transfected PC-3 cells. Significantly higher uptake (6.58 ± 0.56 fold, at 1 h post-incubation) and prolonged retention (5.47 ± 0.36 fold, at 1 h of cell efflux) of radioiodine ((125)I) were observed in hNIS and hTPO co-expressed PC-3 cells as compared to non-transfected PC-3 cells. We concluded that the new virus vector displayed favorable radioiodine uptake and retention properties in hNIS-hTPO transfected PC-3 cells. Our study will provide valuable information on improving the efficacy of hNIS-hTPO co-mediated radioiodine gene therapy. PMID:23145364

  13. Does Radioiodine Therapy in Patients with Differentiated Thyroid Cancer Increase the Frequency of Another Malignant Neoplasm?

    PubMed Central

    Hirosawa, Renata Midori; Marivo, Monica; Luengo, Juliana de Moura Leite; Tagliarini, Jose Vicente; Castilho, Emanuel Cellice; Marques, Mariangela de Alencar; Kiy, Yoshio; Marone, Marilia Martins Silveira; Silveira, Liciana Vaz de Arruda; Mazeto, Glaucia Maria Ferreira da Silva

    2011-01-01

    Objectives. To compare the frequency of another primary malignancy in patients with differentiated thyroid carcinoma (DTC) who received radioiodine therapy or not (131I). Material and Methods. 168 cases of DTC patients were retrospectively evaluated as to the frequency of another neoplasia by comparing patients with and without it, taking into account clinical, laboratory, and therapeutic parameters. Results. Another primary malignancy occurred in 8.9% of patients. Of these, 53.3% showed the malignancy before 131I and 46.7% after it. By comparing both groups, the age at the moment of diagnosis of another neoplasia was 46.1 ± 20.2 years for the group before 131I therapy and of 69.4 ± 11.4 years for the group after it (P = 0.02). Of the 148 patients treated with 131I, 4.7% developed another malignancy. The latter were older (61 ± 17 years) than those who did not show another cancer type (44.1 ± 14.2 years) (P < 0.05). Conclusion. The frequency of another neoplasia found after 131I was similar to that found before 131I. PMID:22084737

  14. High-Dose Vitamin D and Calcium Attenuates Bone Loss with Antiretroviral Therapy Initiation

    PubMed Central

    Overton, Edgar Turner; Chan, Ellen S.; Brown, Todd T.; Tebas, Pablo; McComsey, Grace A.; Melbourne, Kathleen M.; Napoli, Andrew; Hardin, William Royce; Ribaudo, Heather J.; Yin, Michael T.

    2015-01-01

    Background Antiretroviral therapy (ART) initiation for HIV-1 infection is associated with 2-6% loss in bone mineral density (BMD). Objective To evaluate vitamin D3 (4000 IU daily) plus calcium (1000 mg calcium carbonate daily) supplementation on bone loss associated with ART initiation. Design 48-week prospective, randomized, double-blind, placebo-controlled study. Setting Thirty nine AIDS Clinical Trials Network research units. Participants ART-naïve HIV-infected adults. Measurements BMD by dual-energy X-ray absorptiometry (DXA); 25-hydroxy vitamin D (25(OH)D) levels, parathyroid hormone (PTH), phosphate metabolism, markers of bone turnover and systemic inflammation. Results 165 eligible subjects were randomized (79 Vitamin D/calcium (VitD/Cal); 86 placebo); 142 subjects with evaluable DXA data were included in the primary analysis. The study arms were well-balanced at baseline: median age 33 years; 90% male; 33% non-Hispanic black; median CD4 count 341 cells/mm3; and median 25(OH)D 23 ng/mL (57 nmol/L). At 48 weeks, subjects receiving placebo had greater decline in total hip BMD than VitD/Cal: −3.19% median change (1st-3rd quartile (Q1, Q3) −5.12%, −1.02%) vs. (−1.46% −3.16%,−0.40%). respectively (p=0.001). Lumbar spine BMD loss for the two groups was similar: −2.91% (−4.84%, −1.06%) vs. −1.41% (−3.78%, 0.00%), (p=0.085). At week 48, 90% of participants achieved HIV-1 RNA <50 copies/mL. Levels of 25(OH)D3 increased in the VitD/Cal but not the placebo group: median change of 24.5 (14.6, 37.8) vs. 0.7 (−5.3, 4.3) ng/mL, respectively (p<0.001). Additionally, increases in markers of bone turnover were blunted in the VitD/Cal group. Limitations No international sites were included; only 48 weeks of follow up Conclusion Vitamin D/calcium supplementation mitigates the loss of BMD seen with initiation of efavirenz/emtricitabine/tenofovir, particularly at the total hip, which is the site of greatest concern for fragility fracture. Primary Funding

  15. The effect of high dose atorvastatin therapy on lipids and lipoprotein subfractions in overweight patients with type 2 diabetes.

    PubMed

    Lawrence, J M; Reid, J; Taylor, G J; Stirling, C; Reckless, J P D

    2004-05-01

    Few data are available on the effects of high dose statin therapy on lipoprotein subfractions in type 2 diabetes. In a double blind randomised placebo-controlled trial we have studied the effects of 80 mg atorvastatin over 8 weeks on LDL, VLDL and HDL subfractions in 40 overweight type 2 diabetes patients. VLDL and LDL subfractions were prepared by density gradient ultracentrifugation. Triglycerides, cholesterol, total protein and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. Atorvastatin 80 mg produced significant falls in LDL subfractions (LDL(1) 66.2 mg/dl:36.6 mg/dl, LDL(2) 118:56.6 mg/dl, LDL(3) 36.9:19.9 mg/dl all P < 0.01 relative to placebo) and VLDL subfractions (VLDL(1) 55:22.1 mg/dl, VLDL(2) 40.1:19.1 mg/dl, VLDL(3) 52.6:30 mg/dl all P < 0.01 relative to placebo). There was no change in the proportion of LDL present as LDL(3). There was a reduction in the proportion of VLDL as VLDL(1) and a reciprocal increase in the proportion as VLDL(3). Changes in VLDL subfractions were associated with changes in lipid composition, particularly a reduction in cholesterol ester and a reduction in the cholesterol ester/triglyceride ratio. Effects on HDL subfractions were largely neutral. High dose atorvastatin produces favourable effects on lipoprotein subfractions in type 2 diabetes which may enhance antiatherogenic potential. PMID:15135263

  16. Role of Maintenance Therapy after High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation in Aggressive Lymphomas: A Systematic Review.

    PubMed

    Taverna, Josephine A; Yun, Seongseok; Jonnadula, Jayasree; Saleh, Ahlam; Riaz, Irbaz Bin; Abraham, Ivo; Yeager, Andrew M; Persky, Daniel O; McBride, Ali; Haldar, Subrata; Anwer, Faiz

    2016-07-01

    Significant uncertainty exists in regard to the efficacy of maintenance therapy after high-dose chemotherapy (HDC) as well as autologous stem cell transplantation (ASCT) for the treatment of patients with aggressive lymphoma. A systematic review was performed to evaluate the effectiveness of post-ASCT maintenance therapy in patients with relapsed/refractory lymphoma. A comprehensive literature search yielded 4476 studies and a total of 42 studies (11 randomized controlled trials [RCT], 9 retrospective comparative studies, and 22 single-arm studies) were included in the systematic review. There was significant heterogeneity in study design, chemotherapeutic regimens, post-ASCT maintenance strategies, patient enrollment criteria, and study endpoints. Our findings suggest that post-ASCT maintenance immune-targeting strategies, including PD-1/PD-L1 blocking antibodies, rituximab, and brentuximab, may improve progression-free survival but not overall survival. Collectively, the results indicate a need for testing new strategies with well-designed and adequately powered RCTs to better address the role of post-ASCT maintenance in relapsed/refractory lymphomas. PMID:26899562

  17. Assessment of radioiodine therapy efficacy for treatment of differentiated thyroid cancer patients with pulmonary metastasis undetected by chest computed tomography

    PubMed Central

    LONG, BIN; YANG, MENGDI; YANG, ZHIWEN; YI, HEQING; LI, LINFA

    2016-01-01

    Radioiodine therapy (RAI) has proven effective for the treatment of patients exhibiting differentiated thyroid cancer (DTC) with pulmonary metastases. However, the early detection of metastasis remains challenging, and various studies have reported variations in radioiodine treatment efficacy. The present study investigated whether RAI is an effective method for the treatment of DTC with pulmonary metastases undetected by computed tomography (CT). A retrospective study was performed, analyzing iodine-131 (131I) therapy in 21 DTC patients with lung metastases that were undetected by CT. All 21 patients were initially treated with radioiodine ablation of thyroid remnants. Routine chest CT was performed prior to 131I treatment without diagnostic radioiodine whole-body scanning (DxWBS), and post-therapeutic WBS was performed 3–5 days subsequent to oral administration of 131I. The overall effectiveness rate was 95.2% (20/21). The rates for complete response (CR), partial response and no response were 23.8 (5/21), 71.4 (15/21) and 4.8% (1/21), respectively. There were 12 patients with diffuse uptake, and the remaining 9 patients demonstrated focused and low uptake. The difference in CR rate between diffuse uptake and focused uptake patients was not statistically significant (P=0.123). A correlation was observed between thyroglobulin (Tg) levels and extrapulmonary metastases. All patients exhibited extrapulmonary metastases when Tg levels were >87.5 ng/ml (area under receiver operating characteristic curve, 1.0; P<0.001). Overall, DTC patients with lung metastases undetected by CT imaging responded well to 131I radiotherapy and demonstrated a positive prognosis. Serum Tg levels prior to 131I treatment may correlate with metastasis, and this may suggest a requirement for the performance of DxWBS prior to radiotherapy. PMID:26893676

  18. Estimation of patient attenuation factor for iodine-131 based on direct dose rate measurements from radioiodine therapy patients.

    PubMed

    Soliman, Khaled; Alenezi, Ahmed

    2015-02-01

    The aim of the study was to measure the actual dose at 1 m from the patients per unit activity with the aim of providing a more accurate prediction of the dose levels around radioiodine patients in the hospital, as well as to compare our results with the literature. In this work the demonstration of a patient body tissue attenuation factor is verified by comparing the dose rates measured from the patients with those measured from the unshielded radioiodine capsules immediately after administration of the radioactivity. The normalized dose rate per unit activity is therefore proposed as an operational quantity that can be used to predict exposure rates to staff and patients' relatives. The average dose rate measured from our patient per unit activity was 38.4±11.8 μSv/h/GBq. The calculated attenuation correction factor based on our measurements was 0.55±0.17. The calculated dose rate from a radioiodine therapy patient should normally include a factor accounting for patient body tissue attenuation and scatter. The attenuation factor is currently neglected and not applied in operational radiation protection. Realistic estimation of radiation dose levels from radioiodine therapy patients when properly performed will reduce the operational cost and optimize institutional radiation protection practice. It is recommended to include patient attenuation factors in risk assessment exercises - in particular, when accurate estimates of total effective doses to exposed individuals are required when direct measurements are not possible. The information provided about patient attenuation might benefit radiation protection specialists and regulators. PMID:25279710

  19. A randomized trial of high-dose ciprofloxacin versus azlocillin and netilmicin in the empirical therapy of febrile neutropenic patients.

    PubMed

    Johnson, P R; Liu Yin, J A; Tooth, J A

    1992-08-01

    A prospective, randomized trial comparing monotherapy with high-dose ciprofloxacin versus a standard combination regimen of azlocillin and netilmicin in the empirical treatment of febrile episodes in neutropenic patients was performed. One hundred and forty-six patient episodes were randomized, but ten (seven ciprofloxacin and three azlocillin/netilmicin) were considered unevaluable for efficacy, and three episodes were withdrawn due to incorrect randomization or non-neutropenia. Of the remaining 133 episodes, infections resolved without modification of therapy in 25/66 (38%) versus 28/67 (42%) of ciprofloxacin and azlocillin/netilmicin treated groups respectively (P = 0.72). Considering all randomized episodes, therapy was modified in 46/73 (63%) episodes with ciprofloxacin and 39/70 (56%) with azlocillin/netilmicin (P = 0.40). Of 73 patient episodes randomized to ciprofloxacin, 25 (34%) received oral follow-on therapy after a median of three days of intravenous therapy. Infections were microbiologically documented in 31/73 (42%) ciprofloxacin and 32/70 (46%) azlocillin/netilmicin, of which 8/27 (30%) and 14/31 (45%) of evaluable episodes resolved without modification of therapy respectively (P = 0.28). Gram-positive organisms accounted for 78% of all organisms cultured with 36% coagulase-negative staphylococci. Bacteriological eradication was recorded in 18/24 (75%) and 26/29 (90%) evaluable patient episodes treated with ciprofloxacin and azlocillin/netilmicin respectively (P = 0.27). Superinfections were seen in 14% of episodes in both groups, and subsequent infections in 12% ciprofloxacin and 14% azlocillin/netilmicin treated patients. Two patients (one ciprofloxacin and one azlocillin/netilmicin) died within 48 h of randomization, and a further 13 patients (four ciprofloxacin and nine azlocillin/netilmicin) died before resolution of neutropenia. Adverse events were recorded in 9% and 15% of ciprofloxacin and azlocillin/netilmicin treated patients respectively

  20. Thiotepa-based high-dose therapy for autologous stem cell transplantation in lymphoma: a retrospective study from the EBMT.

    PubMed

    Sellner, L; Boumendil, A; Finel, H; Choquet, S; de Rosa, G; Falzetti, F; Scime, R; Kobbe, G; Ferrara, F; Delmer, A; Sayer, H; Amorim, S; Bouabdallah, R; Finke, J; Salles, G; Yakoub-Agha, I; Faber, E; Nicolas-Virelizier, E; Facchini, L; Vallisa, D; Zuffa, E; Sureda, A; Dreger, P

    2016-02-01

    Clinical information about thiotepa-based autologous stem cell transplantation (auto-SCT) outside the primary central nervous system lymphoma (PCNSL) field is sparse. In this registry-based retrospective study, we evaluated potential risks and benefits of thiotepa-based preparative regimens compared with BEAM (carmustine, etoposide, cytarabine, melphalan) in auto-SCT for diffuse large B-cell lymphoma (DLBCL, excluding PCNSL), follicular lymphoma (FL) or Hodgkin lymphoma (HL). A total of 14 544 patients (589 thiotepa and 13 955 BEAM) met the eligibility criteria, and 535 thiotepa- and 1031 BEAM-treated patients were matched in a 1:2 ratio for final comparison. No significant differences between thiotepa and BEAM groups for any survival end point were identified in the whole sample or disease entity subsets. For a more detailed analysis, 47 TEAM (thiotepa, etoposide, cytarabine, melphalan)-treated patients were compared with 75 matched BEAM patients with additional collection of toxicity data. Again, there were no significant differences between the two groups for any survival end point. In addition, the frequency of common infectious and non-infectious complications including secondary malignancies was comparable between TEAM and BEAM. These results indicate that thiotepa-based high-dose therapy might be a valuable alternative to BEAM in DLBCL, HL and FL. Further evaluation by prospective clinical trials is warranted. PMID:26569093

  1. Clinical Studies of Nonpharmacological Methods to Minimize Salivary Gland Damage after Radioiodine Therapy of Differentiated Thyroid Carcinoma: Systematic Review.

    PubMed

    Christou, Andri; Papastavrou, Evridiki; Merkouris, Anastasios; Frangos, Savvas; Tamana, Panayiota; Charalambous, Andreas

    2016-01-01

    Purpose. To systematically review clinical studies examining the effectiveness of nonpharmacological methods to prevent/minimize salivary gland damage due to radioiodine treatment of differentiated thyroid carcinoma (DTC). Methods. Reports on relevant trials were identified by searching the PubMed, CINHAL, Cochrane, and Scopus electronic databases covering the period 01/2000-10/2015. Inclusion/exclusion criteria were prespecified. Search yielded eight studies that were reviewed by four of the present authors. Results. Nonpharmacological methods used in trials may reduce salivary gland damage induced by radioiodine. Sialogogues such as lemon candy, vitamin E, lemon juice, and lemon slice reduced such damage significantly (p < 0.0001, p < 0.05, p < 0.10, and p < 0.05, resp.). Parotid gland massage also reduced the salivary damage significantly (p < 0.001). Additionally, vitamin C had some limited effect (p = 0.37), whereas no effect was present in the case of chewing gum (p = 0.99). Conclusion. The review showed that, among nonpharmacological interventions, sialogogues and parotid gland massage had the greatest impact on reducing salivary damage induced by radioiodine therapy of DTC. However, the studies retrieved were limited in number, sample size, strength of evidence, and generalizability. More randomized controlled trials of these methods with multicenter scope and larger sample sizes will provide more systematic and reliable results allowing more definitive conclusions. PMID:27446226

  2. Clinical Studies of Nonpharmacological Methods to Minimize Salivary Gland Damage after Radioiodine Therapy of Differentiated Thyroid Carcinoma: Systematic Review

    PubMed Central

    Papastavrou, Evridiki; Frangos, Savvas; Tamana, Panayiota

    2016-01-01

    Purpose. To systematically review clinical studies examining the effectiveness of nonpharmacological methods to prevent/minimize salivary gland damage due to radioiodine treatment of differentiated thyroid carcinoma (DTC). Methods. Reports on relevant trials were identified by searching the PubMed, CINHAL, Cochrane, and Scopus electronic databases covering the period 01/2000–10/2015. Inclusion/exclusion criteria were prespecified. Search yielded eight studies that were reviewed by four of the present authors. Results. Nonpharmacological methods used in trials may reduce salivary gland damage induced by radioiodine. Sialogogues such as lemon candy, vitamin E, lemon juice, and lemon slice reduced such damage significantly (p < 0.0001, p < 0.05, p < 0.10, and p < 0.05, resp.). Parotid gland massage also reduced the salivary damage significantly (p < 0.001). Additionally, vitamin C had some limited effect (p = 0.37), whereas no effect was present in the case of chewing gum (p = 0.99). Conclusion. The review showed that, among nonpharmacological interventions, sialogogues and parotid gland massage had the greatest impact on reducing salivary damage induced by radioiodine therapy of DTC. However, the studies retrieved were limited in number, sample size, strength of evidence, and generalizability. More randomized controlled trials of these methods with multicenter scope and larger sample sizes will provide more systematic and reliable results allowing more definitive conclusions. PMID:27446226

  3. Verification of the agreement of two dosimetric methods with radioiodine therapy in hyperthyroid patients

    SciTech Connect

    Canzi, Cristina; Zito, Felicia; Voltini, Franco; Reschini, Eugenio; Gerundini, Paolo

    2006-08-15

    The aim of this study was to verify the capability of an MIRD formula-based dosimetric method to predict radioiodine kinetics (fraction of administered iodine transferred to the thyroid, U{sub 0}, and effective clearance rate, {lambda}{sub eff}) and absorbed dose after oral therapeutic {sup 131}I administration. The method is based on {sup 123}I intravenous administration and five subsequent gamma camera measured uptake values determined separately on different structures within the thyroid. Another dosimetric method based on only the {sup 123}I 24-h uptake and a fixed {lambda}{sub eff} value was also considered. Eighty-nine hyperthyroid patients (10 with Graves' disease and 79 with autonomously functioning nodules) were studied and 132 thyroidal structures were evaluated. The mean time interval between dosimetry and therapy was 20{+-}10d. Uptake values were measured at 2, 4, 24, 48, and 120 h during dosimetry and at 2, 4, 24, 48, 96, and 168 h during therapy. The value 0.125d{sup -1} was chosen in the fixed-{lambda}{sub eff} method. The planned doses to the target ranged from 120 to 250 Gy depending on the type and severity of hyperthyroidism. The following significant correlations between therapeutic and dosimetric parameters were found: U{sub 0}ther=0.88U{sub 0}dos (r=0.97,p<0.01), {lambda}{sub eff}ther=1.01{lambda}{sub eff}dos (r=0.85,p<0.01), and D{sub estimated}=0.85D{sub planned} (r=0.88,p<0.01). The percent difference between U{sub 0}ther and U{sub 0}dos ranged from -44 to 32% and between {lambda}{sub eff}ther and {lambda}{sub eff}dos from -32 to 48%. U{sub 0}ther was lower than U{sub 0}dos in 74% of cases: this can be explained by the self-stunning effect of {sup 131}I therapeutic activity that produced a dose of about 20 Gy with a maximum dose rate of 0.6 Gy/h over the initial 24-48 h. The differences, {delta}D, between the estimated and the planned doses ranged from -42% (-87 Gy) to 32% (59 Gy); in 73% of cases the difference was within {+-}35 Gy

  4. Determination of Organ Doses in Radioiodine Therapy using Monte Carlo Simulation

    PubMed Central

    Shahbazi-Gahrouei, Daryoush; Ayat, Saba

    2015-01-01

    Radioactive iodine treatment is a type of internal radiotherapy that has been used effectively for the treatment of differentiated thyroid cancer after thyroidectomy. The limit of this method is its affects on critical organs, and hence dosimetry is necessary to consider the risk of this treatment. Scope of this work is the measurement of absorbed doses of critical organs by Monte Carlo simulation and comparing the results with other methods of dosimetry such as direct dosimetry and Medical Internal Radiation Dose (MIRD) method. To calculate absorbed doses of vital organs (thyroid, sternum and cervical vertebrae) via Monte Carlo, a mathematical phantom was used. Since iodine 131 (131I) emmits photon and beta particle, *F8 tallies, which give results in MeV were applied and the results were later converted to cGy by dividing by the mass within the cell and multiplying by 1.6E-8. The absorbed dose obtained by Monte Carlo simulations for 100, 150 and 175 mCi administered 131I was found to be 388.0, 427.9 and 444.8 cGy for thyroid, 208.7, 230.1 and 239.3 cGy for sternum and 272.1, 299.9 and 312.1 cGy for cervical vertebrae. The results of Monte Carlo simulation method had no significant difference with the results obtained via direct dosimetry using thermoluminescent dosimeter-100 and MIRD method. Hence, Monte Carlo is a suitable method for dosimetry in radioiodine therapy. PMID:25709539

  5. Differential cytotoxic responses to low- and high-dose photodynamic therapy in human gastric and bladder cancer cells.

    PubMed

    Yoo, Je-Ok; Lim, Young-Cheol; Kim, Young-Myeong; Ha, Kwon-Soo

    2011-10-01

    Here, we present differential cytotoxic responses to two different doses of photodynamic therapies (PDTs; low-dose PDT [LDP] and high-dose PDT [HDP]) using a chlorin-based photosensitizer, DH-II-24, in human gastric and bladder cancer cells. Fluorescence-activated cell sorting analysis using Annexin V and propidium iodide (PI) showed that LDP induced apoptotic cell death, whereas HDP predominantly caused necrotic cell death. The differential cytotoxic responses to the two PDTs were further confirmed by a DiOC(6) and PI double-staining assay via confocal microscopy. LDP, but not HDP, activated caspase-3, which was inhibited by Z-VAD, Trolox, and BAPTA-AM. LDP and HDP demonstrated opposite effects on intracellular reactive oxygen species (ROS)/Ca(2+) signals; LDP stimulated intracellular ROS production, contributing to a transient increase of intracellular Ca(2+) , whereas HDP induced a massive and prolonged elevation of intracellular Ca(2+) responsible for the transient production of intracellular ROS. In addition, the two PDTs also increased in situ transglutaminase 2 (TG2) activity, with a higher stimulation by HDP, and this increase in activity was prevented by Trolox, BAPTA-AM, and TG2-siRNA. LDP-induced apoptotic cell death was strongly inhibited by Trolox and TG2-siRNA and moderately suppressed by BAPTA-AM. However, HDP-mediated necrotic cell death was partially inhibited by BAPTA-AM but not by TG2-siRNA. Thus, these results demonstrate that LDP and HDP induced apoptotic and necrotic cell death by differential signaling mechanisms involving intracellular Ca(2+) , ROS, and TG2. PMID:21678478

  6. Impact of Conditioning Regimen on Outcomes for Patients with Lymphoma Undergoing High-Dose Therapy with Autologous Hematopoietic Cell Transplantation

    PubMed Central

    Logan, Brent; Zhu, Xiaochun; Akpek, Görgün; Aljurf, Mahmoud; Artz, Andrew; Bredeson, Christopher N.; Cooke, Kenneth R.; Ho, Vincent T.; Lazarus, Hillard M.; Olsson, Richard; Saber, Wael; McCarthy, Philip; Pasquini, Marcelo C.

    2015-01-01

    There are limited data to guide the choice of high-dose therapy (HDT) regimen prior to autologous hematopoietic cell transplantation (AHCT) for patients with Hodgkin (HL) and non-Hodgkin lymphoma (NHL). We studied 4,917 patients (NHL n=3,905; HL n=1,012) who underwent AHCT from 1995-2008 using the most common HDT platforms: BEAM (n=1730), CBV (n=1853), BuCy (n=789), and TBI-containing (n=545). CBV was divided into CBVhigh and CBVlow based on BCNU dose. We analyzed the impact of regimen on development of idiopathic pulmonary syndrome (IPS), transplant-related mortality (TRM), progression free and overall survival (PFS and OS). The 1-year incidence of IPS was 3-6% and was highest in recipients of CBVhigh (HR 1.9) and TBI (HR 2.0) compared to BEAM. 1-year TRM was 4-8% and was similar between regimens. Among patients with NHL, there was a significant interaction between histology, HDT regimen, and outcome. Compared to BEAM, CBVlow (HR 0.63) was associated with lower mortality in follicular lymphoma (p<0.001), and CBVhigh (HR1.44) with higher mortality in diffuse large B-cell lymphoma (p=0.001). For patients with HL, CBVhigh (HR1.54), CBVlow (HR1.53), BuCy (HR1.77) and TBI (HR 3.39) were associated with higher mortality compared to BEAM (p<0.001). The impact of specific AHCT regimen on post transplant survival is different depending on histology; therefore, further studies are required to define the best regimen for specific diseases. PMID:25687795

  7. Favorable outcomes in elderly patients undergoing high-dose therapy and autologous stem cell transplantation for non-Hodgkin lymphoma.

    PubMed

    Dahi, Parastoo B; Tamari, Roni; Devlin, Sean M; Maloy, Molly; Bhatt, Valkal; Scordo, Michael; Goldberg, Jenna; Zelenetz, Andrew D; Hamlin, Paul A; Matasar, Matthew J; Maragulia, Jocelyn; Giralt, Sergio A; Perales, Miguel-Angel; Moskowitz, Craig H; Sauter, Craig S

    2014-12-01

    High-dose therapy and autologous stem cell transplantation (HDT-ASCT) can offer potential long-term remission or cure in patients with non-Hodgkin lymphoma (NHL). Limited experience is available on the safety and efficacy of HDT-ASCT in elderly patients. This is a single-center, retrospective study examining outcomes of HDT-ASCT for 202 NHL patients, ages 60 years and older, between January 2001 and December 2012. Overall survival (OS) and progression-free survival (PFS) were analyzed according to age at HDT-ASCT, hematopoietic cell transplantation comorbidity index (HCT-CI), NHL histology, and remission status at the time of HDT-ASCT. The median age was 65 years (range, 60 to 74) and the majority had either diffuse large B cell lymphoma (n = 73, 37%) or mantle cell lymphoma (n = 69, 34%). One hundred and fifteen patients (57%) had high HCT-CI scores at the time of HDT-ASCT. With a median follow-up of 3.6 years (range, 4 to 11.9 years) for survivors, PFS and OS at 3 years were 60% (95% confidence interval [CI], 53% to 68%) and 73% (95% CI, 67% to 80%), respectively. Transplantation-related mortality (TRM) was 4% both at 100 days and at 1 year after HDT-ASCT. Age and HCT-CI score were not associated with OS or PFS, and high HCT-CI did not correlate with TRM. Seven patients (4%) developed secondary myelodysplastic syndrome or acute myeloid leukemia at a median of 35 months (range, 6 to 48) after HDT-ASCT. In this single-center cohort of elderly patients with NHL undergoing HDT-ASCT, this intervention was proven tolerable and effective, with results similar to those of historic controls in younger patients. Our data suggest that age alone should not preclude HDT-ASCT in elderly patients. PMID:25175794

  8. Effect of a Low Iodine Diet vs. Restricted Iodine Diet on Postsurgical Preparation for Radioiodine Ablation Therapy in Thyroid Carcinoma Patients

    PubMed Central

    Lim, Chi Young; Kim, Jung-Yeon; Yoon, Mi-Jin; Chang, Hang Seok; Park, Cheong Soo

    2015-01-01

    Purpose The radioiodine ablation therapy is required for patients who underwent a total thyroidectomy. Through a comparative review of a low iodine diet (LID) and a restricted iodine diet (RID), the study aims to suggest guidelines that are suitable for the conditions of Korea. Materials and Methods The study was conducted with 101 patients. With 24-hour urine samples from the patients after a 2-week restricted diet and after a 4-week restricted diet, the amount of iodine in the urine was estimated. The consumed radioiodine amounts for 2 hours and 24 hours were calculated. Results This study was conducted with 47 LID patients and 54 RID patients. The amounts of iodine in urine, the 2-week case and 4-week case for each group showed no significant differences. The amounts of iodine in urine between the two groups were both included in the range of the criteria for radioiodine ablation therapy. Also, 2 hours and 24 hours radioiodine consumption measured after 4-week restrictive diet did not show statistical differences between two groups. Conclusion A 2-week RID can be considered as a type of radioiodine ablation therapy after patients undergo a total thyroidectomy. PMID:26069126

  9. Image guided radiation therapy boost in combination with high-dose-rate intracavitary brachytherapy for the treatment of cervical cancer

    PubMed Central

    Wang, Xianliang; Li, Jie; Yuan, Ke; Yin, Gang; Wan, Bin

    2016-01-01

    Purpose The purpose of this study was to demonstrate the dosimetric and clinical feasibility of image guided radiation therapy (IGRT) combined with high-dose-rate (HDR) intracavitary brachytherapy (ICBT) to improve dose distribution in cervical cancer treatment. Material and methods For 42 cervical cancer patients, magnetic resonance imaging (MRI) scans were acquired after completion of whole pelvic irradiation 45-46 Gy and 5 fractions of B + I (ICBT + IGRT) treatment were subsequently received. The high risk clinical target volume (HRCTV), intermediate risk clinical target volume (IRCTV), bladder, rectum, and sigmoid were contoured on the computed tomography (CT) scans. The total planning aim doses for HRCTV was D90% > 85 Gy, whilst constraints for rectum and sigmoid were D2cc < 75 Gy and D2cc < 90 Gy for bladder in terms of an equivalent dose in 2 Gy (EQD2) for external beam radiotherapy (EBRT) and brachytherapy boost. The IGRT plan was optimized on top of the ICBT dose distribution. A dosimetric comparison was made between B + I and optimized ICBT (O-ICBT) only. Results The mean D90% of HRCTV was comparable for B + I and O-ICBT (p = 0.82). For B + I plan, HRCTV D100%, IRCTV D100%, and IRCTV D90% were significantly increased by a mean of 10.52 Gy, 5.61 Gy, and 2.70 Gy, respectively (p < 0.01). The D2cc for bladder, rectum, and sigmoid were lower by a mean of 21.36, 6.78, and 10.65 Gy, respectively (p < 0.01). The mean rectum V60 Gy value over 42 patients was almost the same for both techniques but for bladder and sigmoid B + I had higher V60 Gy mean values as compared with the O-ICBT. Conclusions B + I can improve dose distribution in cervical cancer treatment; it could be useful for tumors extended beyond the reach of intracavitary/interstitial brachytherapy (IC/ISBT) or for centers that are inexperienced or ill-equipped with IC/ISBT techniques. Additional confirmatory prospective studies with larger numbers of patients and longer follow-up are required to

  10. Losartan/hydrochlorothiazide combination therapy surpasses high-dose angiotensin receptor blocker in the reduction of morning home blood pressure in patients with morning hypertension.

    PubMed

    Hanayama, Yoshihisa; Uchida, Haruhito Adam; Nakamura, Yoshio; Makino, Hirofumi

    2012-01-01

    Angiotensin receptor blockers (ARBs) are the first-line antihypertensive agents. In clinical practice, it is often difficult to achieve the recommended blood pressure level by ARBs in their ordinal dosages alone. This study examined the practical efficacy of a combination therapy of ARB with thiazide diuretics for lowering morning home blood pressure (MHBP) in comparison to high-dose ARB therapy in patients with morning hypertension administered an ordinal dosage of ARB. This study was performed in a prospective, randomized, open-labeled and blind-endpoint fashion. Patients were considered to have morning hypertension when their self-measured systolic MHBPs were 135mmHg or higher, irrespective of their diastolic MHBP and office blood pressures (OBPs). Forty-eight outpatients with morning hypertension receiving the ordinal dosage of ARB were given either losartan/hydrochlorothiazide (n = 26) or high-dose ARB (n = 22) in place of their previously prescribed ARB. No change in any medication was permitted during this period. Decreases of both systolic and diastolic MHBP after 3 months of treatment were significantly greater in the losartan/hydrochlorothiazide group than in the high-dose ARB group (p < 0.05, respectively). The ratio of adverse events was somewhat high (23.1% in the losartan/hydrochlorothiazide group, 9.1% in the high-dose ARB group, respectively). However, there were no significant differences in any particular adverse event between groups. This study suggested losartan/hydrochlorothiazide might be superior to high-dose ARB for reducing morning home blood pressure. PMID:23254579

  11. Survival outcome of radioiodine therapy in post thyroidectomy thyroid carcinoma patients: Outcome of long term follow up

    NASA Astrophysics Data System (ADS)

    Haque, F.; Nahar, N.; Sultana, S.; Nasreen, F.; Jabin, Z.; Alam, A. S. M. M.

    2016-03-01

    The overall prognosis of patients with thyroid carcinoma is excellent whenever managed following best practice guidelines. Objective: To calculate sex and age group affected by thyroid cancer; to compare between single or multiple dose of radio ablation needed after thyroidectomy and to determine the percentage of patients become disease free during their follow up. Methods: This was a retrospective study done in NINMAS, Bangladesh on 687 patients from 1984 to 2004. In all cases total or near total thyroidectomy was done before commencing radioiodine therapy. Patients TG level, neck ultrasonography, thyroid scan, whole body I131 scans, neck examination were done every six monthly/yearly. Results: Among 687 patients, female were more sufferers (68.1%) and female to male ratio was 2:1. Age group 19-40 years was mostly affected (57.8%). Most common type seen was papillary carcinoma (81.8%). After ablation 100 patients did not follow-up. Total 237 patients discontinued within 4 years. Remaining 450 patients undergone regular follow-up for 5 years and more, 394 were disease free (87.6%). Total recurrence of metastasis was 23 and 12 patients expired at different times. Conclusions: Long-term regular follow-up is necessary after radioiodine ablation to become free of disease.

  12. Ion recombination correction factors (P(ion)) for Varian TrueBeam high-dose-rate therapy beams.

    PubMed

    Kry, Stephen F; Popple, Richard; Molineu, Andrea; Followill, David S

    2012-01-01

    Ion recombination is approximately corrected for in the Task Group 51 protocol by Pion, which is calculated by a two-voltage measurement. This measurement approach may be a poor estimate of the true recombination, particularly if Pion is large (greater than 1.05). Concern exists that Pion in high-dose-per-pulse beams, such as flattening filter free (FFF) beams, may be unacceptably high, rendering the two-voltage measurement technique inappropriate. Therefore, Pion was measured for flattened beams of 6, 10, 15, and 18 MV and for FFF beams of 6 and 10 MV. The values for the FFF beams were verified with 1/V versus 1/Q curves (Jaffé plots). Pion was also measured for electron beams of 6, 12, 16, 18, and 20 MeV on a traditional accelerator, as well as on the high-dose-rate Varian TrueBeam accelerator. The measurements were made at a range of depths and with PTW, NEL, and Exradin Farmer-type chambers. Consistent with the increased dose per pulse, Pion was higher for FFF beams than for flattening filter beams. However, for all beams, measurement locations, and chambers examined, Pion never exceeded 1.018. Additionally, Pion was always within 0.3% of the recombination calculated from the Jaffé plots. We conclude that ion recombination can be adequately accounted for in high-dose-rate FFF beams using Pion determined with the standard two-voltage technique. PMID:23149774

  13. High-Dose Estradiol-Replacement Therapy Enhances the Renal Vascular Response to Angiotensin II via an AT2-Receptor Dependent Mechanism

    PubMed Central

    Safari, Tahereh; Nematbakhsh, Mehdi; Evans, Roger G.; Denton, Kate M.

    2015-01-01

    Physiological levels of estrogen appear to enhance angiotensin type 2 receptor- (AT2R-) mediated vasodilatation. However, the effects of supraphysiological levels of estrogen, analogous to those achieved with high-dose estrogen replacement therapy in postmenopausal women, remain unknown. Therefore, we pretreated ovariectomized rats with a relatively high dose of estrogen (0.5 mg/kg/week) for two weeks. Subsequently, renal hemodynamic responses to intravenous angiotensin II (Ang II, 30–300 ng/kg/min) were tested under anesthesia, while renal perfusion pressure was held constant. The role of AT2R was examined by pretreating groups of rats with PD123319 or its vehicle. Renal blood flow (RBF) decreased in a dose-related manner in response to Ang II. Responses to Ang II were enhanced by pretreatment with estradiol. For example, at 300 ng kg−1 min−1, Ang II reduced RBF by 45.7 ± 1.9% in estradiol-treated rats but only by 27.3 ± 5.1% in vehicle-treated rats. Pretreatment with PD123319 blunted the response of RBF to Ang II in estradiol-treated rats, so that reductions in RBF were similar to those in rats not treated with estradiol. We conclude that supraphysiological levels of estrogen promote AT2R-mediated renal vasoconstriction. This mechanism could potentially contribute to the increased risk of cardiovascular disease associated with hormone replacement therapy using high-dose estrogen. PMID:26681937

  14. High-dose chemotherapy and autologous stem cell support followed by posttransplantation doxorubicin as initial therapy for metastatic breast cancer.

    PubMed

    deMagalhaes-Silverman, M; Bloom, E; Lembersky, B; Lister, J; Pincus, S; Rybka, W; Voloshin, M; Wilson, J; Ball, E

    1997-02-01

    High-dose chemotherapy is associated with a high complete response rate and possibly some survival advantage in patients with metastatic breast cancer. We designed a clinical trial consisting of a two-step high-dose chemotherapy regimen followed by posttransplantation doxorubicin as the first chemotherapy treatment for metastatic disease. Twenty-one patients with metastatic breast cancer and no previous chemotherapy for metastatic disease were treated with high-dose cyclophosphamide (Cy; 5000 mg/m2), followed by granulocyte colony-stimulating factor. Peripheral blood stem cells were collected. Subsequently, patients received Cy (6000 mg/m2), thiotepa (500 mg/m2), and carboplatin (800 mg/m2) (CTCb) with hematopoietic rescue. Upon recovery of hematopoietic and gastrointestinal toxicity, three cycles of doxorubicin (Dox; 60 mg/m2) were delivered. After Cy, nine patients (45%) developed neutropenic fevers. There were no episodes of bacteremia. Patients received CTCb 37 days after starting Cy and had a hospital stay of 19 days. After CTCb, the median number of days to an absolute neutrophil count >5 x 10(9)/liter was 8, and the median number of days to a platelet count >20 x 10(9)/liter was 9. Neutropenic fevers occurred in 12 patients. There were no hemorrhagic complications. Fifty-five of the 63 planned courses of Dox were delivered. The median time from peripheral blood stem cell infusion to the first Dox cycle was 38 days. The median time to the second Dox cycle was 28 days, and to the last cycle was 30 days. Three episodes of neutropenic fevers were observed. Two patients developed herpes zoster. This regimen is feasible, with acceptable toxicity. PMID:9815672

  15. Hypofractionated High-Dose Proton Beam Therapy for Stage I Non-Small-Cell Lung Cancer: Preliminary Results of A Phase I/II Clinical Study

    SciTech Connect

    Hata, Masaharu . E-mail: mhata@syd.odn.ne.jp; Tokuuye, Koichi; Kagei, Kenji; Sugahara, Shinji; Nakayama, Hidetsugu; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Mizumoto, Masashi; Ohara, Kiyoshi; Akine, Yasuyuki

    2007-07-01

    Purpose: To present treatment outcomes of hypofractionated high-dose proton beam therapy for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Twenty-one patients with Stage I NSCLC (11 with Stage IA and 10 with Stage IB) underwent hypofractionated high-dose proton beam therapy. At the time of irradiation, patient age ranged from 51 to 85 years (median, 74 years). Nine patients were medically inoperable because of comorbidities, and 12 patients refused surgical resection. Histology was squamous cell carcinoma in 6 patients, adenocarcinoma in 14, and large cell carcinoma in 1. Tumor size ranged from 10 to 42 mm (median, 25 mm) in maximum diameter. Three and 18 patients received proton beam irradiation with total doses of 50 Gy and 60 Gy in 10 fractions, respectively, to primary tumor sites. Results: Of 21 patients, 2 died of cancer and 2 died of pneumonia at a median follow-up period of 25 months. The 2-year overall and cause-specific survival rates were 74% and 86%, respectively. All but one of the irradiated tumors were controlled during the follow-up period. Five patients showed recurrences 6-29 months after treatment, including local progression and new lung lesions outside of the irradiated volume in 1 and 4 patients, respectively. The local progression-free and disease-free rates were 95% and 79% at 2 years, respectively. No therapy-related toxicity of Grade {>=}3 was observed. Conclusions: Hypofractionated high-dose proton beam therapy seems feasible and effective for Stage I NSCLC. Proton beams may contribute to enhanced efficacy and lower toxicity in the treatment of patients with Stage I NSCLC.

  16. A New Formulation of Calcitriol (DN-101) for High-Dose Pulse Administration in Prostate Cancer Therapy

    PubMed Central

    Henner, William David; Beer, Tomasz M

    2003-01-01

    Although the antineoplastic activity of calcitriol in prostate cancer has been known for many years, the agent’s use in oncology has been prevented because of the occurrence of hypercalcemia with daily administration. High-dose pulse administration of calcitriol has the potential to improve the therapeutic index of calcitriol. Results of a phase II study of calcitriol and docetaxel (Taxotere®) suggest that this combination may have utility in androgen-independent prostate cancer (AIPC). DN-101, a high-dose (15 μg) formulation of calcitriol suitable for use in oncology, is now being tested in a randomized trial (AIPC Study of Calcitriol Enhancing Taxotere). This formulation of calcitriol could become an important new tool for improving the efficacy of docetaxel in the treatment of AIPC and would join the ranks of other nuclear receptor ligands in cancer treatment. Investigations of DN-101 in the treatment of a broad range of tumor types and in combination with a variety of agents are an exciting new area of research. PMID:16985949

  17. A New Formulation of Calcitriol (DN-101) for High-Dose Pulse Administration in Prostate Cancer Therapy.

    PubMed

    Henner, William David; Beer, Tomasz M

    2003-01-01

    Although the antineoplastic activity of calcitriol in prostate cancer has been known for many years, the agent's use in oncology has been prevented because of the occurrence of hypercalcemia with daily administration. High-dose pulse administration of calcitriol has the potential to improve the therapeutic index of calcitriol. Results of a phase II study of calcitriol and docetaxel (Taxotere(R)) suggest that this combination may have utility in androgen-independent prostate cancer (AIPC). DN-101, a high-dose (15 mug) formulation of calcitriol suitable for use in oncology, is now being tested in a randomized trial (AIPC Study of Calcitriol Enhancing Taxotere). This formulation of calcitriol could become an important new tool for improving the efficacy of docetaxel in the treatment of AIPC and would join the ranks of other nuclear receptor ligands in cancer treatment. Investigations of DN-101 in the treatment of a broad range of tumor types and in combination with a variety of agents are an exciting new area of research. PMID:16985949

  18. Hyperthyroidism and radio-iodine therapy in a district general hospital.

    PubMed Central

    Child, D F; Mughni, M A; Hudson, P; Williams, C P; Harvey, J N

    1994-01-01

    A retrospective analysis was performed of 48 patients with hyperthyroidism (41 women aged 35-80, mean 56.6 years; 7 men aged 31-77, mean 52.1 years) treated with a fixed dose of 550 MBq 131I during a 12 month period May 1991-April 1992. Weight loss was common at presentation but 28.57% of women aged 35-49 years weighed over 80 kg compared to 9.98% in a standard UK population P < 0.05. Patients treated with carbimazole (73%) prior to 131I had higher FT3 levels at presentation (14.0 +/- 4.4 pmol/l) compared to those (27%) who were considered not to require such treatment (8.9 +/- 1.4 pmol/l, P < 0.001). Four months following radio-iodine, 67% were hypothyroid, 25% were euthyroid and 8% remained thyrotoxic and were retreated. Another patient became hypothyroid during 1 year of follow-up. Pre-treatment with carbimazole did not protect against the development of hypothyroidism (carbimazole treated 69% hypothyroid at 4 months, untreated 62% hypothyroid at 4 months). Patients with continuing thyrotoxicosis had very high FT3 levels at presentation (18.6, 21.1, 20 and in one patient reported only as > 10 pmol/l). A rationalized programme of follow-up assessments at 2, 3, 4, 8 and 12 months is suggested for patients treated with this dose of radio-iodine. PMID:7966101

  19. High-dose hepatitis B immunoglobulin therapy in hepatocellular carcinoma with hepatitis B virus-DNA/hepatitis B e antigen-positive patients after living donor liver transplantation

    PubMed Central

    Lee, Eung Chang; Kim, Seong Hoon; Lee, Seung Duk; Park, Hyeongmin; Lee, Soon-Ae; Park, Sang-Jae

    2016-01-01

    AIM: To investigate the impact of high-dose hepatitis B immunoglobulin (HBIG) on hepatocellular carcinoma (HCC) and hepatitis B virus (HBV) recurrence and overall survival after living donor liver transplantation (LDLT). METHODS: We investigated 168 patients who underwent LDLT due to HCC, and who were HBV-DNA/hepatitis B e antigen (HBeAg) -positive, from January 2008 to December 2013. After assessing whether the patients met the Milan criteria, they were assigned to the low-dose HBIG group and high-dose HBIG group. Using the propensity score 1:1 matching method, 38 and 18 pairs were defined as adhering to and not adhering to the Milan criteria. For each pair, HCC recurrence, HBV recurrence and overall survival were analyzed by the Kaplan-Meier method and the log rank test according to the HBIG dose. RESULTS: Among those who met the Milan criteria, the 6-mo, 1-year, and 3-year HCC recurrence-free survival rates were 88.9%, 83.2%, and 83.2% in the low-dose HBIG group and 97.2%, 97.2%, and 97.2% in the high-dose HBIG group, respectively (P = 0.042). In contrast, among those who did not meet the Milan criteria, HCC recurrence did not differ according to the HBIG dose (P = 0.937). Moreover, HBV recurrence and overall survival did not differ according to the HBIG dose among those who met (P = 0.317 and 0.190, respectively) and did not meet (P = 0.350 and 0.987, respectively) the Milan criteria. CONCLUSION: High-dose HBIG therapy can reduce HCC recurrence in HBV-DNA/HBeAg-positive patients after LDLT. PMID:27076765

  20. Reduction in relapse rate of radioiodine therapy in patients of toxic multinodular goiter: A quality improvement project

    PubMed Central

    Mitra, Sujata; Muthu, Sonai G

    2012-01-01

    Introduction: Radioiodine (I-131) therapy is the definitive treatment of toxic multinodular goiter (TMNG). Treatment failure may result in relapse after I-131 therapy. The present study was undertaken to reduce treatment failure rate of I-131 therapy in TMNG patients. Materials and Methods: Multiple causes may have lead to treatment failure of I-131 in TMNG patients making it difficult to establish a direct cause–effect relationship and take corrective action. Therefore, the JURAN methodology of quality improvement was applied. The treatment failure rate in 80 TMNG patients treated with I-131 in the period 2003–06 was 29%. The root cause analysis identified delay in decision to radioablate and concomitant antithyroid drugs (ATD) with I-131 therapy as factors leading to relapse. In 2007, a change in management was introduced with decision to radioablate all TMNG patients not remitting at 1 year of ATD and to withdraw ATD for 2 weeks prior to I-131 therapy. A total of 63 patients of TMNG followed the changed protocol between 2007 and 2009. Further analysis showed that one of the factors identified in the initial brainstorming (high iodide pool in the patient) had not been addressed in the protocol currently followed. The protocol was modified to include patient preparation and implemented after standardization. Results: The post-I-131 relapse rate in patients treated after implementation of the new protocol from 2007 to 2009 was 18% which further reduced to 16% in 2011 after modification of the protocol. Conclusion: The failure rate of I-131 therapy in TMNG reduced from 29% to 16% through standardization of the treatment procedure achieved by the use of Juran Methodology that helped to identify process-related defects. PMID:23599590

  1. Correlation of stress with outcome of radioiodine therapy for Graves disease

    SciTech Connect

    Stewart, T.; Rochon, J.; Lenfestey, R.; Wise, P.

    1985-06-01

    Between November 1965 and December 1983, 293 patients were treated for Graves disease using /sup 131/I. All patients were asked to identify a stressful event antedating the onset of overt clinical symptoms. Eighty-one patients were able to do this (27.6%). Two hundred forty-four patients received a single treatment, 49 required two or more treatments. Patients with stress initiating the symptoms of Graves disease became hypothyroid earlier, 50% at 12 mo compared with 36 mo for the nonstress group. At 10 yr 5% of the stress group remained euthyroid compared with 17% nonstress. The authors conclude that stress in the 12 mo or less before the onset of clinical symptoms potentiates the development of hypothyroidism induced by a standard dose of radioiodine.

  2. Effects of substitution and high-dose thyroid hormone therapy on deiodination, sulfoconjugation, and tissue thyroid hormone levels in prolonged critically ill rabbits.

    PubMed

    Debaveye, Yves; Ellger, Björn; Mebis, Liese; Visser, Theo J; Darras, Veerle M; Van den Berghe, Greet

    2008-08-01

    To delineate the metabolic fate of thyroid hormone in prolonged critically ill rabbits, we investigated the impact of two dose regimes of thyroid hormone on plasma 3,3'-diiodothyronine (T(2)) and T(4)S, deiodinase type 1 (D1) and D3 activity, and tissue iodothyronine levels in liver and kidney, as compared with saline and TRH. D2-expressing tissues were ignored. The regimens comprised either substitution dose or a 3- to 5- fold higher dose of T(4) and T(3), either alone or combined, targeted to achieve plasma thyroid hormone levels obtained by TRH. Compared with healthy animals, saline-treated ill rabbits revealed lower plasma T(3) (P=0.006), hepatic T(3) (P=0.02), and hepatic D1 activity (P=0.01). Substitution-dosed thyroid hormone therapy did not affect these changes except a further decline in plasma (P=0.0006) and tissue T(4) (P=0.04). High-dosed thyroid hormone therapy elevated plasma and tissue iodothyronine levels and hepatic D1 activity, as did TRH. Changes in iodothyronine tissue levels mimicked changes in plasma. Tissue T(3) and tissue T(3)/reverse T(3) ratio correlated with deiodinase activities. Neither substitution- nor high-dose treatment altered plasma T(2). Plasma T(4)S was increased only by T(4) in high dose. We conclude that in prolonged critically ill rabbits, low plasma T(3) levels were associated with low liver and kidney T(3) levels. Restoration of plasma and liver and kidney tissue iodothyronine levels was not achieved by thyroid hormone in substitution dose but instead required severalfold this dose. This indicates thyroid hormone hypermetabolism, which in this model of critical illness is not entirely explained by deiodination or by sulfoconjugation. PMID:18450965

  3. Drug associated acute interstitial nephritis: clinical and pathological features and the response to high dose steroid therapy.

    PubMed

    Pusey, C D; Saltissi, D; Bloodworth, L; Rainford, D J; Christie, J L

    1983-01-01

    Nine episodes of drug associated acute interstitial nephritis, in seven patients, were treated between 1972 and 1980. The drugs implicated were cotrimoxazole (three times), ampicillin, Magnapen (ampicillin and flucloxacillin), penicillin, gentamicin, paracetamol and bendrofluazide. The time from exposure to the onset of symptoms ranged from one to 30 days. Presentation was with acute renal failure, which was non-oliguric in five cases, accompanied by rash (four), fever (four), and loin pain (two). Renal biopsy was carried out in all cases, and showed a characteristic interstitial infiltrate comprising substantial numbers of lymphocytes and plasma cells, with a variable number of neutrophils, eosinophils and histiocytes. Immunofluorescence was negative in all four cases studied in the acute phase, and showed scattered deposits of IgG, IgM, IgA and C3 on the tubular basement membrane in one patient during recovery. Significant proteinuria and an abnormal urine deposit were present in all cases, and seven of nine had radiological evidence of enlarged kidneys. Seven episodes were treated with high doses of methyl prednisolone and in all there was a response with a diuresis or spontaneous fall in serum creatinine within 72 hrs, and recovery of virtually normal renal function. Of two cases who did not initially receive steroids, one improved more slowly and one developed chronic renal impairment. PMID:6604293

  4. Diagnosis of prolactinoma in two male-to-female transsexual subjects following high-dose cross-sex hormone therapy.

    PubMed

    Cunha, F S; Domenice, S; Câmara, V L; Sircili, M H P; Gooren, L J G; Mendonça, B B; Costa, E M F

    2015-08-01

    Male-to-female transsexual persons use oestrogens + antiandrogens to adapt their physical bodies to the female sex. Doses are usually somewhat higher than those used by hypogonadal women receiving oestrogen replacement. Particularly in cases of self-administration of cross-sex hormones, doses may be very high. Oestrogens are powerful stimulators of synthesis and release of prolactin and serum prolactin levels are usually somewhat increased following oestrogen treatment. Prolactinomas have been reported in male-to-female transsexual persons, both after use of high and conventional doses of oestrogens but remain rare events. We report two new cases of prolactinomas in male-to-female transsexual persons, one in a 41-year-old subject who had used nonsupervised high-dose oestrogen treatment since the age of 23 years and another one in a 42 year old who had initiated oestrogen treatment at the age of 17 years. Their serum prolactin levels were strongly increased, and the diagnosis of a pituitary tumour was confirmed by imaging techniques. Both cases responded well to treatment with cabergoline treatment whereupon serum prolactin normalised. Our two cases are added to the three cases of prolactinomas in the literature in persons who had used supraphysiological doses of oestrogens. PMID:25059808

  5. Randomized Phase II Trial of High-Dose Melatonin and Radiation Therapy for RPA Class 2 Patients With Brain Metastases (RTOG 0119)

    SciTech Connect

    Berk, Lawrence . E-mail: Berklb@moffitt.usf.edu; Berkey, Brian; Rich, Tyvin; Hrushesky, William; Gallagher, Michael; Kudrimoti, Mahesh; McGarry, Ronald C.; Suh, John; Mehta, Minesh

    2007-07-01

    Purpose: To determine if high-dose melatonin for Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) Class 2 patients with brain metastases improved survival over historical controls, and to determine if the time of day melatonin was given affected its toxicity or efficacy. RTOG 0119 was a phase II randomized trial for this group of patients. Methods and Materials: RTOG RPA Class 2 patients with brain metastases were randomized to 20 mg of melatonin, given either in the morning (8-9 AM) or in the evening (8-9 PM). All patients received radiation therapy (30 Gy in 10 fractions) in the afternoon. Melatonin was continued until neurologic deterioration or death. The primary endpoint was overall survival time. Neurologic deterioration, as reflected by the Mini-Mental Status Examination, was also measured. Results: Neither of the randomized groups had survival distributions that differed significantly from the historic controls of patients treated with whole-brain radiotherapy. The median survivals of the morning and evening melatonin treatments were 3.4 and 2.8 months, while the RTOG historical control survival was 4.1 months. Conclusions: High-dose melatonin did not show any beneficial effect in this group of patients.

  6. High-dose radiotherapy in inoperable nonsmall cell lung cancer: comparison of volumetric modulated arc therapy, dynamic IMRT and 3D conformal radiotherapy.

    PubMed

    Bree, Ingrid de; van Hinsberg, Mariëlle G E; van Veelen, Lieneke R

    2012-01-01

    Conformal 3D radiotherapy (3D-CRT) combined with chemotherapy for inoperable non-small cell lung cancer (NSCLC) to the preferable high dose is often not achievable because of dose-limiting organs. This reduces the probability of regional tumor control. Therefore, the surplus value of using intensity-modulated radiation therapy (IMRT) techniques, specifically volumetric modulated arc therapy (RapidArc [RA]) and dynamic IMRT (d-IMRT) has been investigated. RA and d-IMRT plans were compared with 3D-CRT treatment plans for 20 patients eligible for concurrent high-dose chemoradiotherapy, in whom a dose of 60 Gy was not achievable. Comparison of dose delivery in the target volume and organs at risk was carried out by evaluating 3D dose distributions and dose-volume histograms. Quality of the dose distribution was assessed using the inhomogeneity and conformity index. For most patients, a higher dose to the target volume can be delivered using RA or d-IMRT; in 15% of the patients a dose ≥60 Gy was possible. Both IMRT techniques result in a better conformity of the dose (p < 0.001). There are no significant differences in homogeneity of dose in the target volume. IMRT techniques for NSCLC patients allow higher dose to the target volume, thus improving regional tumor control. PMID:22459649

  7. Statin therapy and thromboxane generation in patients with coronary artery disease treated with high-dose aspirin.

    PubMed

    Bliden, K P; Singla, A; Gesheff, M G; Toth, P P; Tabrizchi, A; Ens, G; Guyer, K; Singh, M; Franzese, C J; Stapleton, D; Tantry, U S; Gurbel, P A

    2014-08-01

    Aspirin and statin therapy are mainstay treatments in patients with coronary artery disease (CAD). The relation between statin therapy, in vivo thromboxane (Tx) generation; a marker of inflammation, and blood thrombogenicity has never been explored. Urinary 11-dehydro (dh) TxB2 was determined in patients with suspected CAD on 325 mg daily aspirin therapy prior to undergoing cardiac catheterisation (n=281). Thrombogenicity was estimated by thrombelastographic measurement of thrombin-induced platelet-fibrin clot strength (TIP-FCS) and lipids/lipoproteins were determined by vertical density gradient ultracentrifugation/ELISA. The influence of statin therapy and dose was analysed by the atorvastatin equivalent dose (5-10 mg, 20-40 mg, or 80 mg daily). Statin therapy (n=186) was associated with a dose-dependent reduction in urinary 11-dh TxB2 (p=0.046) that was independent of LDL and apo B100 levels but was strongly related to TIP-FCS (p=0.006). By multivariate analysis, no statin therapy (n=95) and female gender were independently associated with high urinary 11-dh TxB2 [OR=2.95 (0.1.57-5.50, p=0.0007); OR=2.25 (1.24-4.05, p=0.007)], respectively. In aspirin-treated patients, statin therapy was independently and inversely associated with inflammation in a dose-dependent manner. Elevated 11-dh TxB2 was associated with a prothrombotic state indicated by high TIP-FCS. Our data suggest that measurement of urinary 11-dTxB2 may be a useful method to optimise statin dosing in order to reduce thrombotic risk. PMID:24763965

  8. High-Dose Daptomycin Therapy for Left-Sided Infective Endocarditis: a Prospective Study from the International Collaboration on Endocarditis

    PubMed Central

    Bayer, Arnold S.; Miró, Josè M.; Park, Lawrence P.; Guimarães, Armenio C.; Skoutelis, Athanasios; Fortes, Claudio Q.; Durante-Mangoni, Emanuele; Hannan, Margaret M.; Nacinovich, Francisco; Fernández-Hidalgo, Nuria; Grossi, Paolo; Tan, Ru-San; Holland, Thomas; Fowler, Vance G.; Corey, Ralph G.; Chu, Vivian H.

    2013-01-01

    The use of daptomycin in Gram-positive left-sided infective endocarditis (IE) has significantly increased. The purpose of this study was to assess the influence of high-dose daptomycin on the outcome of left-sided IE due to Gram-positive pathogens. This was a prospective cohort study based on 1,112 cases from the International Collaboration on Endocarditis (ICE)-Plus database and the ICE-Daptomycin Substudy database from 2008 to 2010. Among patients with left-sided IE due to Staphylococcus aureus, coagulase-negative staphylococci, and Enterococcus faecalis, we compared those treated with daptomycin (cohort A) to those treated with standard-of-care (SOC) antibiotics (cohort B). The primary outcome was in-hospital mortality. Time to clearance of bacteremia, 6-month mortality, and adverse events (AEs) ascribable to daptomycin were also assessed. There were 29 and 149 patients included in cohort A and cohort B, respectively. Baseline comorbidities did not differ between the two cohorts, except for a significantly higher prevalence of diabetes and previous episodes of IE among patients treated with daptomycin. The median daptomycin dose was 9.2 mg/kg of body weight/day. Two-thirds of the patients treated with daptomycin had failed a previous antibiotic regimen. In-hospital and 6-month mortalities were similar in the two cohorts. In cohort A, median time to clearance of methicillin-resistant S. aureus (MRSA) bacteremia was 1.0 day, irrespective of daptomycin dose, representing a significantly faster bacteremia clearance compared to SOC (1.0 versus 5.0 days; P < 0.01). Regimens with higher daptomycin doses were not associated with increased incidence of AEs. In conclusion, higher-dose daptomycin may be an effective and safe alternative to SOC in the treatment of left-sided IE due to common Gram-positive pathogens. PMID:24080644

  9. Brachial Plexus-Associated Neuropathy After High-Dose Radiation Therapy for Head-and-Neck Cancer

    SciTech Connect

    Chen, Allen M.; Hall, William H.; Li, Judy; Beckett, Laurel; Farwell, D. Gregory; Lau, Derick H.; Purdy, James A.

    2012-09-01

    Purpose: To identify clinical and treatment-related predictors of brachial plexus-associated neuropathies after radiation therapy for head-and-neck cancer. Methods and Materials: Three hundred thirty patients who had previously completed radiation therapy for head-and-neck cancer were prospectively screened using a standardized instrument for symptoms of neuropathy thought to be related to brachial plexus injury. All patients were disease-free at the time of screening. The median time from completion of radiation therapy was 56 months (range, 6-135 months). One-hundred fifty-five patients (47%) were treated by definitive radiation therapy, and 175 (53%) were treated postoperatively. Radiation doses ranged from 50 to 74 Gy (median, 66 Gy). Intensity-modulated radiation therapy was used in 62% of cases, and 133 patients (40%) received concurrent chemotherapy. Results: Forty patients (12%) reported neuropathic symptoms, with the most common being ipsilateral pain (50%), numbness/tingling (40%), motor weakness, and/or muscle atrophy (25%). When patients with <5 years of follow-up were excluded, the rate of positive symptoms increased to 22%. On univariate analysis, the following factors were significantly associated with brachial plexus symptoms: prior neck dissection (p = 0.01), concurrent chemotherapy (p = 0.01), and radiation maximum dose (p < 0.001). Cox regression analysis confirmed that both neck dissection (p < 0.001) and radiation maximum dose (p < 0.001) were independently predictive of symptoms. Conclusion: The incidence of brachial plexus-associated neuropathies after radiation therapy for head-and-neck cancer may be underreported. In view of the dose-response relationship identified, limiting radiation dose to the brachial plexus should be considered when possible.

  10. Radioiodine Treatment and Thyroid Hormone Suppression Therapy for Differentiated Thyroid Carcinoma: Adverse Effects Support the Trend toward Less Aggressive Treatment for Low-Risk Patients

    PubMed Central

    Klein Hesselink, E.N.; Links, T.P.

    2015-01-01

    Over the past decades, the incidence of differentiated thyroid carcinoma (DTC) has steadily increased, with especially a growing number of low-risk patients. Whereas DTC used to be treated rather aggressively, it is now acknowledged that aggressive treatment does not affect outcome for low-risk patients and that it can induce adverse effects. In this review an overview of the most clinically relevant adverse effects of radioiodine treatment and thyroid hormone suppression therapy (THST) is presented, and the trend toward less aggressive treatment for low-risk patients is outlined. Salivary gland dysfunction occurs in roughly 30% of patients, and is probably due to the concentration of radioiodine in the salivary glands by the sodium/iodide symporter. Beta radiation from radioiodine can result in sialoadenitis and eventually fibrosis and loss of salivary function. Furthermore, patients can experience bone marrow dysfunction following radioiodine treatment. Although this is in general subclinical and transient, patients that receive very high cumulative radioiodine doses may be at risk for more severe bone marrow dysfunction. THST can induce adverse cardiovascular effects in patients with DTC, such as diastolic and systolic dysfunction, and also adverse vascular and prothrombotic effects have been described. Finally, the effects of THST on bone formation and resorption are outlined; especially postmenopausal women with DTC on THST seem to be at risk of bone loss. In the past years, advances have been made in preventing low-risk patients from being overtreated. Improved biomarkers are still needed to further optimize risk stratification and personalize medicine. PMID:26279993

  11. Clinical Outcome of Radioiodine Therapy in Low-intermediate Risk Papillary Thyroid Carcinoma with BRAF(V600E) Mutation.

    PubMed

    Jiao, L I; Tao, Yang; Teng, Zhao; Jun, Liang; Yan-Song, Lin

    2016-06-10

    Objective To evaluate the impact of BRAF(V600E) gene status on clinical outcome of radioiodine((131)I) therapy in low-intermediate risk recurrent papillary thyroid carcinoma (PTC). Methods Totally 135 PTC patients were enrolled and divided into two groups according to BRAF(V600E) gene status:BRAF(V600E) mutation group(n=105) and BRAF(V600E) wild group(n=30). The median follow-up time was 2.16 years(1.03-4.06 years),and clinical outcome after initial (131)I ablation therapy was divided into excellent response(ER),acceptable response(AR),and incomplete response(IR) according to the serological and imageological follow-up results. The cinical outcomes were then compared between these two groups. Results There was no significant difference in clinicopathological features and initial radioactive iodine dose between BRAF(V600E) mutation and wild groups (P>0.05). ER,AR,and IR after (131)I ablation therapy accounted for 74.3%,20.0%,and 5.7% in BRAF(V600E) mutation group and 73.3%,20.0%,and 6.7% in BRAF(V600E) wild group,and no statistical difference was found (P=0.891). Conclusion For low-intermediate risk recurrent PTC,BRAF(V600E) gene status may have no impact on the response to (131)I ablation therapy,and thus this molecular feature should not be used as an independent weighting factor for risk assessment in this population. PMID:27544995

  12. [A case of advanced breast cancer with multiple bone metastases responding to docetaxel and high-dose toremifene as fourth-line chemo-endocrine therapy].

    PubMed

    Minamoto, Kanji; Ikeda, Toshio

    2009-12-01

    A 55-year old woman, who underwent left mastectomy (Bt+Ax), was revealed to have sternum metastasis by postoperative 99mTc bone scanning(T1bN1M1). She received daily aromatase inhibitor (anastrozole), as a primary systemic endocrine therapy, and biweekly pamidronate for metastatic breast cancer. However, she depended on folk medicine a year later, at which time the primary treatment was discontinued. Another year later, the bone metastases developed with increased serum levels of tumor markers (CEA, CA19-9, and NCC-ST-439). Then, she underwent three different regimens of systemic chemo-endocrine therapy over the following three years, including CAF+MPA as the first-line, paclitaxel (PTX) + anastrozole as the second-line, and S-1+anastrozole as the third-line regimen. She recently completed 10 courses of the fourth-line regimen[tri-weekly docetaxel (DOC) and high-dose toremifene (TOR 120 mg/day)], which reduced levels of 99mTc accumulation in the multiple bone metastases and levels of the serum tumor markers to the normal range. No severe adverse events occurred except peripheral thrombovasculitis (grade 2) in her left anterior arm during the fourth regimen. She recently maintains the current status by taking a regular dose (40 mg/day) of toremifene for 5 months. Combination treatment with DOC and high-dose TOR can be one of the worthwhile regimens as systemic chemo-endocrine therapy for patients with advanced breast cancer who develop bone metastases. PMID:20009468

  13. Salvage therapy with high dose Intravenous Immunoglobulins in acquired Von Willebrand Syndrome and unresponsive severe intestinal bleeding

    PubMed Central

    2014-01-01

    A 91-year-old woman affected with acquired Von Willebrand (VW) syndrome and intestinal angiodysplasias presented with severe gastrointestinal bleeding (hemoglobin 5 g/dl). Despite replacement therapy with VW factor/factor VIII concentrate qid, bleeding did not stop (eleven packed red blood cell units were transfused over three days). High circulating levels of anti-VW factor immunoglobulin M were documented immunoenzimatically. Heart ultrasound showed abnormalities of the mitral and aortic valves with severe flow alterations. When intravenous immunoglobulins were added to therapy, prompt clinical and laboratory responses occurred: complete cessation of bleeding, raise in hemoglobin, VW factor antigen, VW ristocetin cofactor and factor VIII levels as well as progressive reduction of the anti-VWF autoantibody levels. PMID:24926417

  14. Phase 2 Trial of Hypofractionated High-Dose Intensity Modulated Radiation Therapy With Concurrent and Adjuvant Temozolomide for Newly Diagnosed Glioblastoma

    SciTech Connect

    Iuchi, Toshihiko; Hatano, Kazuo; Kodama, Takashi; Sakaida, Tsukasa; Yokoi, Sana; Kawasaki, Koichiro; Hasegawa, Yuzo; Hara, Ryusuke

    2014-03-15

    Purpose/Objectives: To assess the effect and toxicity of hypofractionated high-dose intensity modulated radiation therapy (IMRT) with concurrent and adjuvant temozolomide (TMZ) in 46 patients with newly diagnosed glioblastoma multiforme (GBM). Methods and Materials: All patients underwent postsurgical hypofractionated high-dose IMRT. Three layered planning target volumes (PTVs) were contoured. PTV1 was the surgical cavity and residual tumor on T1-weighted magnetic resonance images with 5-mm margins, PTV2 was the area with 15-mm margins surrounding the PTV1, and PTV3 was the high-intensity area on fluid-attenuated inversion recovery images. Irradiation was performed in 8 fractions at total doses of 68, 40, and 32 Gy for PTV1, PTV2, and PTV3, respectively. Concurrent TMZ was given at 75 mg/m{sup 2}/day for 42 consecutive days. Adjuvant TMZ was given at 150 to 200 mg/m{sup 2}/day for 5 days every 28 days. Overall and progression-free survivals were evaluated. Results: No acute IMRT-related toxicity was observed. The dominant posttreatment failure pattern was dissemination. During a median follow-up time of 16.3 months (range, 4.3-80.8 months) for all patients and 23.7 months (range, 12.4-80.8 months) for living patients, the median overall survival was 20.0 months after treatment. Radiation necrosis was diagnosed in 20 patients and was observed not only in the high-dose field but also in the subventricular zone (SVZ). Necrosis in the SVZ was significantly correlated with prolonged survival (hazard ratio, 4.08; P=.007) but caused deterioration in the performance status of long-term survivors. Conclusions: Hypofractionated high-dose IMRT with concurrent and adjuvant TMZ altered the dominant failure pattern from localized to disseminated and prolonged the survival of patients with GBM. Necrosis in the SVZ was associated with better patient survival, but the benefit of radiation to this area remains controversial.

  15. The Sonographic Features of the Thyroid Gland After Treatment with Radioiodine Therapy in Patients with Graves' Disease.

    PubMed

    English, Collette; Casey, Ruth; Bell, Marcia; Bergin, Diane; Murphy, Joseph

    2016-01-01

    The aim of the study was to describe the typical sonographic features of the thyroid gland in patients with Graves' hyperthyroidism after radioiodine therapy (RIT). Thirty patients (21 female and 9 male) with a mean age of 53 y (standard deviation [SD] ± 11.3) and with previous Graves' disease who had been successfully treated with RIT were enrolled in the study. All were hypothyroid or euthyroid after treatment. The thyroid ultrasound was carried out by a single experienced operator with an 8-MHz linear transducer. Volume, vascularity, echogenicity and echotexture of the glands were noted. The presence of nodules and lymph nodes was also documented. The mean volumes of the right lobe were 2.4 mL ± 2.9 SD (0.6-14) and the left lobe were 1.8 mL ± 1.9 SD (0.4-9.1), with a mean total volume of 4.2 mL ± 4.7 SD (1.3-19.1). Of those who had a pre-treatment ultrasound (23%), the percentage reduction in volume was 87% (p < 0.05); 93% of the glands were hypovascular, with the remaining 7% showing normal vascularity. The glands were hyperechoic and of coarse echotexture. Overall, the sonographic features of the post-RIT gland included a significantly reduced mean total volume of 4.2 mL, hypovascularity, coarse echotexture and hyperechogenicity. PMID:26603660

  16. Prognostic Factors of the Efficacy of High-dose Corticosteroid Therapy in Hemolysis, Elevated Liver Enzymes, and Low Platelet Count Syndrome During Pregnancy: A Meta-analysis.

    PubMed

    Yang, Li; Ren, Chenchen; Mao, Minhong; Cui, Shihong

    2016-03-01

    The aim of this study was to identify the factors which can affect the efficacy of corticosteroid (CORT) therapy in the management of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome.Research articles reporting the efficacy of CORT therapy to HELLP syndrome patients were searched in several electronic databases including EMBASE, Google Scholar, Ovid SP, PubMed, and Web of Science. Study selection was based on predefined eligibility criteria. Efficacy was defined by the changes from baseline in HELLP syndrome indicators after CORT therapy. Meta-analyses were carried out with Stata software.Data of 778 CORT-treated HELLP syndrome patients recruited in 22 studies were used in the analyses. Corticosteroid treatment to HELLP syndrome patients was associated with significant changes from baseline in platelet count; serum levels of aspartate aminotransaminase, alanine transaminase, and lactic dehydrogenase (LDH); mean blood pressure; and urinary output. Lower baseline platelet count predicted higher change in platelet count after CORT therapy. Lower baseline platelet count and lower baseline urinary output predicted greater changes in LDH levels after CORT therapy. There was also an inverse relationship between the change from baseline in LDH levels and intensive care duration. Higher CORT doses were associated with greater declines in the aspartate aminotransaminase, alanine transaminase, and LDH levels. Incidence of cesarean delivery was inversely associated with the gestation age. The percentage of nulliparous women had a positive association with the intensive care stay duration.High-dose CORT therapy to HELLP syndrome patients provides benefits in improving disease markers and reducing intensive care duration, especially in cases such as mothers with much lower baseline platelet count and LDH levels. PMID:27043683

  17. Prognostic Factors of the Efficacy of High-dose Corticosteroid Therapy in Hemolysis, Elevated Liver Enzymes, and Low Platelet Count Syndrome During Pregnancy

    PubMed Central

    Yang, Li; Ren, Chenchen; Mao, Minhong; Cui, Shihong

    2016-01-01

    Abstract The aim of this study was to identify the factors which can affect the efficacy of corticosteroid (CORT) therapy in the management of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Research articles reporting the efficacy of CORT therapy to HELLP syndrome patients were searched in several electronic databases including EMBASE, Google Scholar, Ovid SP, PubMed, and Web of Science. Study selection was based on predefined eligibility criteria. Efficacy was defined by the changes from baseline in HELLP syndrome indicators after CORT therapy. Meta-analyses were carried out with Stata software. Data of 778 CORT-treated HELLP syndrome patients recruited in 22 studies were used in the analyses. Corticosteroid treatment to HELLP syndrome patients was associated with significant changes from baseline in platelet count; serum levels of aspartate aminotransaminase, alanine transaminase, and lactic dehydrogenase (LDH); mean blood pressure; and urinary output. Lower baseline platelet count predicted higher change in platelet count after CORT therapy. Lower baseline platelet count and lower baseline urinary output predicted greater changes in LDH levels after CORT therapy. There was also an inverse relationship between the change from baseline in LDH levels and intensive care duration. Higher CORT doses were associated with greater declines in the aspartate aminotransaminase, alanine transaminase, and LDH levels. Incidence of cesarean delivery was inversely associated with the gestation age. The percentage of nulliparous women had a positive association with the intensive care stay duration. High-dose CORT therapy to HELLP syndrome patients provides benefits in improving disease markers and reducing intensive care duration, especially in cases such as mothers with much lower baseline platelet count and LDH levels. PMID:27043683

  18. High-Dose Split-Course Radiation Therapy for Anal Cancer: Outcome Analysis Regarding the Boost Strategy (CORS-03 Study)

    SciTech Connect

    Hannoun-Levi, Jean-Michel; Ortholan, Cecile; Resbeut, Michel; Teissier, Eric; Ronchin, Philippe; Cowen, Didier; Zaccariotto, Audrey; Benezery, Karen; Francois, Eric; Salem, Naji; Ellis, Steve; Azria, David; Gerard, Jean-Pierre

    2011-07-01

    Purpose: To retrospectively assess the clinical outcome in anal cancer patients treated with split-course radiation therapy and boosted through external-beam radiation therapy (EBRT) or brachytherapy (BCT). Methods and Materials: From January 2000 to December 2004, a selected group (162 patients) with invasive nonmetastatic anal squamous cell carcinoma was studied. Tumor staging reported was T1 = 31 patients (19%), T2 = 77 patients (48%), T3 = 42 patients (26%), and T4= 12 patients (7%). Lymph node status was N0-1 (86%) and N2-3 (14%). Patients underwent a first course of EBRT: mean dose 45.1 Gy (range, 39.5-50) followed by a boost: mean dose 17.9 Gy (range, 8-25) using EBRT (76 patients, 47%) or BCT (86 patients, 53%). All characteristics of patients and tumors were well balanced between the BCT and EBRT groups. Results: The mean overall treatment time (OTT) was 82 days (range, 45-143) and 67 days (range, 37-128) for the EBRT and BCT groups, respectively (p < 0.001). The median follow-up was 62 months (range, 2-108). The 5-year cumulative rate of local recurrence (CRLR) was 21%. In the univariate analysis, the prognostic factors for CRLR were as follows: T stage (T1-2 = 15% vs. T3-4 = 36%, p = 0.03), boost technique (BCT = 12% vs. EBRT = 33%, p = 0.002) and OTT (OTT <80 days = 14%, OTT {>=}80 days = 34%, p = 0.005). In the multivariate analysis, BCT boost was the unique prognostic factor (hazard ratio = 0.62 (0.41-0.92). In the subgroup of patients with OTT <80 days, the 5-year CRLR was significantly increased with the BCT boost (BC = 9% vs. EBRT = 28%, p = 0.03). In the case of OTT {>=}80 days, the 5-year CRLR was not affected by the boost technique (BCT = 29% vs. EBRT = 38%, p = 0.21). Conclusion: In anal cancer, when OTT is <80 days, BCT boost is superior to EBRT boost for CRLR. These results suggest investigating the benefit of BCT boost in prospective trials.

  19. Hypofractionated High-Dose Radiation Therapy for Prostate Cancer: Long-Term Results of a Multi-Institutional Phase II Trial

    SciTech Connect

    Fonteyne, Valerie; Soete, Guy; Arcangeli, Stefano; De Neve, Wilfried; Rappe, Bernard; Storme, Guy; Strigari, Lidia; Arcangeli, Giorgio; De Meerleer, Gert

    2012-11-15

    Purpose: To report late gastrointestinal (GI) and genitourinary (GU) toxicity, biochemical and clinical outcomes, and overall survival after hypofractionated radiation therapy for prostate cancer (PC). Methods and Materials: Three institutions included 113 patients with T1 to T3N0M0 PC in a phase II study. Patients were treated with 56 Gy in 16 fractions over 4 weeks. Late toxicity was scored using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria extended with additional symptoms. Biochemical outcome was reported according to the Phoenix definition for biochemical failure. Results: The incidence of late GI and GU toxicity was low. The 3-year actuarial risk of developing late GU and GI toxicity of grade {>=}2 was 13% and 8% respectively. Five-year biochemical non-evidence of disease (bNED) was 94%. Risk group, T stage, and deviation from planned hormone treatment were significant predictive factors for bNED. Deviation from hormone treatment remained significant in multivariate analysis. Five-year clinical non evidence of disease and overall survival was 95% and 91% respectively. No patient died from PC. Conclusions: Hypofractionated high-dose radiation therapy is a valuable treatment option for patients with PC, with excellent biochemical and clinical outcome and low toxicity.

  20. High-dose cytarabine as salvage therapy for relapsed or refractory acute myeloid leukemia-is more better or more of the same?

    PubMed

    Wolach, Ofir; Itchaki, Gilad; Bar-Natan, Michal; Yeshurun, Moshe; Ram, Ron; Herscovici, Corina; Shpilberg, Ofer; Douer, Dan; Tallman, Martin S; Raanani, Pia

    2016-03-01

    Cytarabine is the backbone of most chemotherapeutic regimens for acute myeloid leukemia (AML), yet the optimal dose for salvage therapy of refractory or relapsed AML (RR-AML) has not been established. Very high dose single-agent cytarabine at 36 g/m(2) (ARA-36) was previously shown to be effective and tolerable in RR-AML. In this retrospective analysis, we aim to describe the toxicity and efficacy of ARA-36 as salvage therapy for patients with AML who are primary refractory to intensive daunorubicin-containing induction or those relapsing after allogeneic stem cell transplant (alloSCT). Fifteen patients, median age 53 years, were included in the analysis. Six patients were treated for induction failure, one had resistant APL, and eight relapsed after alloSCT. Complete remission was achieved in 60% of patients. Surviving patients were followed for a median of 8.5 months. One-year overall survival was 54% (95% CI 30%-86%), and relapse rate from remission (n = 9) was 56%. Grade III/IV pulmonary, infectious, ocular and gastrointestinal toxicities occurred in 26%, 20%, 20% and 20% of patients respectively. Salvage therapy with ARA-36 regimen for RR-AML has considerable efficacy with manageable toxicity in patients with induction failure or post-transplant relapse. Overall survival in these high-risk patients still remains poor. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25689584

  1. Use of PET for estimation of radiation dose variations within the thyroid from radioiodine therapy in thyrotoxic patients

    SciTech Connect

    Ott, R.J.; Batty, V.; Clack, R.; Flower, M.A.; Leach, M.O.; Marsden, P.; McCready, V.R.; Webb, S.

    1985-05-01

    A series of 22 patients have been studied using a prototype Multiwire Proportional Chamber Positron Camera to determine the accuracy of measurement of thyroid uptake of radioiodine. The patients being treated for thyrotoxicosis were given a solution containing 1.5 mCi of I-131 and 0.7 mCi of I-124. In a few case 0.3 mCi of I-124 was given prior to I-131 therapy. Data acquisition consisted of 8 contiguous views of the thyroid covering the full 360 degrees around the patient. Each study contained approximately 400,000 events. Data analysis consisted of a simple backprojection and 3D deconvolution of the point source response function to produce a 64x64x64 volume matrix using 0.27ml voxels. The volume of the thyroid was obtained using a simple thresholding technique to determine the number of voxels within the thyroid. Phantom measurements show that the functional volume and hence the radiation dose to the thyroid can be estimated to approx. =10%. From conventional imaging with a gamma camera plus pinhole collimator, 18 out of 22 patients were diagnosed as having uniform Graves disease. The high resolution tomographic information provided by PET imaging has shown that the uptake in 5 of these 18 patients was multinodular. In one case the volume of the nodules within the thyroid was estimated to be 45% of the organ volume. This non-uniform uptake of iodine within the thyroid has consequences for the overall management of hyperthyroidism in patients thought to have Graves disease. It may in part explain the cases of unexpected post therapy hypothyroidism.

  2. Ineffectiveness of daily standard and high-dose antiviral therapy in preventing short episodes of genital HSV-2 reactivation: three randomized, open-label cross-over trials

    PubMed Central

    Johnston, Christine; Saracino, Misty; Kuntz, Steve; Magaret, Amalia; Selke, Stacy; Huang, Meei-li; Schiffer, Joshua T.; Koelle, David M.; Corey, Lawrence; Wald, Anna

    2012-01-01

    Background Recent studies indicate that short subclinical episodes of herpes simplex virus type 2 (HSV-2) are the predominant form of skin and mucosal viral shedding. We evaluated whether standard or high-dose antiviral therapy reduced the frequency of such shedding. Methods To determine whether short episodes of genital HSV shedding are suppressed on standard dose (SD) and high-dose (HD) antiviral therapy, HSV-2 seropositive, HIV seronegative persons in Seattle, WA were enrolled into three separate but complementary randomized, open-label, cross-over studies comparing 1) no medication to aciclovir 400 mg twice daily (SD-ACV), 2) valaciclovir 500 mg daily (SD-VAL) to aciclovir 800 mg three times daily (TID) (HD-ACV), and 3) SD-VAL to HD-VAL (1 gm TID). Study arms lasted 4–7 weeks, separated by one week wash-out. Participants obtained genital swabs four times daily for quantitative HSV DNA PCR. The primary endpoint was within-person comparison of shedding rate on each study arm. Results Of 113 participants randomized, 90 were eligible for analysis of the primary endpoint. Participants collected 23,605 swabs; of these 1272 (5·4%) had HSV detected. HSV shedding was significantly higher during the no medication arm (18·1% of swabs) compared with SD-ACV (1.2% of swabs, IRR=0·05, 95% CI=0·03–0·08). Breakthrough reactivations occurred on all doses (SD-ACV 1·2%, SD-VAL 5·2%, HD-ACV 4·2%, and HD-VAL 3·3% of swabs). HD-VAL was associated with less shedding compared with SD-VAL (IRR=0·54, 95% CI=0·44–0·66), likely due to more rapid clearance of mucosal HSV (4·7 logs/6 hours on HD-VAL vs. 4·4 logs/6 hours on SD-VAL, (p=0·02)). However, the annualized breakthrough episodes was similar on SD-VAL (22·6) and HD-ACV (20·2, p=0·54) and SD-VAL (14.9) and HD-VAL (16·5, p=0·34). Regardless of dose, breakthrough episodes were short (median 7–10 hours) and 80% were subclinical. Studies were not designed to make inter-trial comparisons between antiviral doses

  3. A novel treatment planning methodology for high dose (166)Ho-DOTMP therapy in patients with multiple myeloma

    NASA Astrophysics Data System (ADS)

    McCullough, Steven Patrick

    2000-09-01

    patient without irrigation, will not significantly reduce the bladder wall dose. The results from this work will produce the most advanced treatment planning methodology for bone marrow ablation therapy using radioisotopes currently available. Treatments can be tailored specifically for each patient, including the addition of concomitant total body irradiation for patients with unfavorable dose distributions, to deliver a desired patient disease response, while minimizing the dose or toxicity to non- target organs.

  4. Combined 2-deoxy glucose and metformin improves therapeutic efficacy of sodium-iodide symporter-mediated targeted radioiodine therapy in breast cancer cells.

    PubMed

    Chatterjee, Sushmita; Thaker, Nirmal; De, Abhijit

    2015-01-01

    Radiosensitization using either metformin or 2-deoxy-d-glucose (2-DG) in various cancer cells has been reported. The present study reveals novel information on combining these drugs to enhance radiosensitization effect in breast cancer (BC) cells. Responses to low-dose Cobalt60 radiation, as well as a newly emerged radioiodine therapy target for BC, that is, sodium-iodide symporter (NIS or SLC5A5) protein, are tested. As therapeutic potential of NIS in BC is often limited due to low uptake and fast efflux rate of iodine, the scope of these two radiosensitizers to further improve NIS-mediated (131)I therapeutic efficacy is explored. Two BC cell lines, MCF-7, and MDA MB231 are tested to optimize minimal drug doses required for radiosensitization. A combination of 2 mM metformin and 20 mM 2-DG with 2 grey (Gy) Cobalt60 radiation shows significant radiosensitization effect (P=0.0002). In cells treated with the combination therapy, increased γH2A.X foci formation was noted. Further, MCF-7 BC cells overexpressing NIS (MCF-7 NIS) was established, and using the optimized drug concentrations, significant radiosensitization (P=0.0019) by 50 μ Ci (131)I usage was found to be the case as well. Apoptosis data corroborates with the result of clonogenic assay showing significant increase in apoptotic population upon dual drug-mediated radiosensitization. In case of metformin treatment, lowered adenosine triphosphate (ATP) content of the cell has been observed. The encouraging radiosensitization effect observed using combined 2-DG and metformin may aid in reducing Cobalt60 radiation exposure or for targeted radioiodine therapy in BC cells with NIS expression. This study indicates high potential of this drug combination in sensitizing BC cells for NIS-mediated-targeted radioiodine therapy, which otherwise may have lacked efficacy. PMID:26355636

  5. A Prospective Exploratory Analysis of Cardiac Biomarkers and Electrocardiogram Abnormalities in Patients Receiving Thoracic Radiation Therapy with High-Dose Heart Exposure

    PubMed Central

    Gomez, Daniel R.; Yusuf, Syed Wamique; Munsell, Mark; Welsh, James W.; Liao, Zhongxing; Lin, Steven H.; Pan, Hubert; Chang, Joe Y.; Komaki, Ritsuko; Cox, James D.; McAleer, Mary Frances; Grosshans, David R.

    2014-01-01

    Introduction Acute effects of incidental cardiac irradiation in patients treated for thoracic cancer are not well characterized. We evaluated longitudinal changes in cardiac biomarkers for patients undergoing conformal radiation therapy (RT) with thoracic malignancies with high-dose cardiac exposure. Methods Twenty-five patients enrolled in a prospective trial (February 2009–December 2012) received ≥45 Gy to the thorax, with pretreatment estimates of ≥20 Gy to the heart. Chemotherapy was allowed except for doxorubicin or fluorouracil. Electrocardiographic (ECG), troponin-I (TnI), and brain natriuretic peptide (BNP) measurements were obtained before RT, within 24 hours of the first fraction, at the end of RT, and at first follow-up (1–2 months). These biomarkers were quantified at specific times and changes from baseline were evaluated with paired t tests. Results The median heart dose was 25.9 Gy (range 10.1–35.1 Gy). After the first RT fraction, no changes were noted in ECG or median Tnl or BNP levels; at the end of RT, two patients had elevated TnI and BNP, but neither difference was statistically significant. At first follow-up, TnI had returned to normal but the median BNP remained elevated (P=0.042). BNP did not increase over time in the 18 patients who received only RT. Twelve patients experienced acute ECG changes during RT, which resolved in seven patients by the next measurement. No patients experienced clinically significant RT-related events. Conclusion Increases in BNP and ECG changes were observed during high doses of radiation to the heart. The findings of this pilot study warrant further investigation and validation. PMID:25521400

  6. Retrospective Analysis of the Safety and Efficacy of High-dose Interleukin-2 After Prior Tyrosine Kinase Inhibitor Therapy in Patients With Advanced Renal Cell Carcinoma

    PubMed Central

    Wong, Michael K. K.; Agarwal, Neeraj; Redman, Bruce G.; Logan, Theodore; Gao, Dexiang; Flaig, Thomas W.; Lewis, Karl; Poust, Jamie; Monk, Paul; Jarkowski, Anthony; Sendilnathan, Arun; Bolden, Marcus; Kuzel, Timothy M.; Olencki, Thomas

    2014-01-01

    Although tyrosine kinase inhibitors (TKI) are the most common first-line therapy for metastatic renal cell carcinoma, high-dose interleukin-2 (HD-IL2) remains the only agent that provides durable complete responses. The optimal sequence of these agents remains uncertain. This retrospective multi-institutional study examined the safety and efficacy of HD-IL2 following TKI therapy. After IRB approval at 7 HD-IL2 centers, data relating to patient, disease, and treatment characteristics among 40 consecutive patients with metastatic renal cell carcinoma who were treated with HD-IL2 after at least 1 prior TKI therapy were retrospectively collected. The most common cardiac adverse events were grade 3 hypotension and vascular leak syndrome. Six patients (15%) experienced other grade ≥3 cardiac adverse events. There were 2 treatment-related deaths due to congestive heart failure, occurring in 1 patient with short TKI to HD-IL2 interval and another patient with an abnormal baseline cardiac stress test. Best responses included 2 CRs (5%, duration 40+ and 62+ mo), 3 PRs (8%, duration 6, 11, and 24 mo), 13 SD (32%, median duration 12 mo), 20 PD (50%), and 2 not evaluable patients. Median overall survival was 22 months. Administration of HD-IL2 could be safe and effective after TKI therapy; however, careful selection of patients is critical. We recommend baseline cardiac risk factor assessment, screening with both cardiac stress test and echocardiogram, and allowing a TKI to HD-IL2 interval of at least 2 months. PMID:25075565

  7. Retrospective analysis of the safety and efficacy of high-dose interleukin-2 after prior tyrosine kinase inhibitor therapy in patients with advanced renal cell carcinoma.

    PubMed

    Lam, Elaine T; Wong, Michael K K; Agarwal, Neeraj; Redman, Bruce G; Logan, Theodore; Gao, Dexiang; Flaig, Thomas W; Lewis, Karl; Poust, Jamie; Monk, Paul; Jarkowski, Anthony; Sendilnathan, Arun; Bolden, Marcus; Kuzel, Timothy M; Olencki, Thomas

    2014-09-01

    Although tyrosine kinase inhibitors (TKI) are the most common first-line therapy for metastatic renal cell carcinoma, high-dose interleukin-2 (HD-IL2) remains the only agent that provides durable complete responses. The optimal sequence of these agents remains uncertain. This retrospective multi-institutional study examined the safety and efficacy of HD-IL2 following TKI therapy. After IRB approval at 7 HD-IL2 centers, data relating to patient, disease, and treatment characteristics among 40 consecutive patients with metastatic renal cell carcinoma who were treated with HD-IL2 after at least 1 prior TKI therapy were retrospectively collected. The most common cardiac adverse events were grade 3 hypotension and vascular leak syndrome. Six patients (15%) experienced other grade ≥3 cardiac adverse events. There were 2 treatment-related deaths due to congestive heart failure, occurring in 1 patient with short TKI to HD-IL2 interval and another patient with an abnormal baseline cardiac stress test. Best responses included 2 CRs (5%, duration 40+ and 62+ mo), 3 PRs (8%, duration 6, 11, and 24 mo), 13 SD (32%, median duration 12 mo), 20 PD (50%), and 2 not evaluable patients. Median overall survival was 22 months. Administration of HD-IL2 could be safe and effective after TKI therapy; however, careful selection of patients is critical. We recommend baseline cardiac risk factor assessment, screening with both cardiac stress test and echocardiogram, and allowing a TKI to HD-IL2 interval of at least 2 months. PMID:25075565

  8. Treatment with lithium prevents serum thyroid hormone increase after thionamide withdrawal and radioiodine therapy in patients with Graves' disease.

    PubMed

    Bogazzi, Fausto; Bartalena, Luigi; Campomori, Alberto; Brogioni, Sandra; Traino, Claudio; De Martino, Fabio; Rossi, Giuseppe; Lippi, Francesco; Pinchera, Aldo; Martino, Enio

    2002-10-01

    Serum thyroid hormone concentrations increase after radioiodine (RAI) therapy for Graves' disease. This phenomenon has been ascribed to either antithyroid drug withdrawal before RAI therapy or release of preformed thyroid hormones into the bloodstream from the RAI-damaged thyroid. Lithium blocks the release of iodine and thyroid hormones from the thyroid, thus enhancing the effectiveness of RAI therapy. Changes in serum-free thyroxine (FT4) and triiodothyronine (FT3) levels after methimazole (MMI) discontinuation and RAI therapy were evaluated in a prospective, randomized, control study of 36 patients with Graves' disease. After a 3- to 4-month course of MMI, patients were assigned to one of three groups: G1 (RAI alone); G2 (RAI plus lithium for 6 d starting on the day of RAI therapy); or G3 (RAI plus lithium for 19 d starting on the day of MMI withdrawal). G1-G2 patients had an increase in serum FT4 and FT3 levels from 13.5 +/- 6.5 to 19.8 +/- 9.2 pmol/liter and 5.0 +/- 2.0 to 8.0 +/- 4.8 pmol/liter, respectively (P < 0.0001), 2-5 d after MMI withdrawal, but G3 patients showed no changes. In the 30 d after RAI therapy, mean serum FT4 values increased in G1 patients (P = 0.02), peaking at 3-7 d (P < 0.05) but not in G2 and G3 patients. Serum FT3 levels decreased in G1, G2, and G3 (P = 0.03, P = 0.001, P = 0.02, respectively). Hyperthyroidism was cured in 8 of 12 G1 patients, 11 of 12 G2 patients, and 11 of 12 G3 patients (P = 0.31). Control of hyperthyroidism was prompter in G2 (P = 0.08) and G3 (P < 0.05) than in G1 patients. Patients in the three groups received a similar dose of RAI, but the committed radiation to the thyroid was higher in G3 (563 +/- 174 Gray) and G2 (588 +/- 347 Gray) than in G1 (429 +/- 204 Gray) (P < 0.03). In conclusion, the results of the present study demonstrate that: 1) MMI withdrawal is associated with a slight rise in serum thyroid hormone levels; 2) a further increase occurs after RAI therapy; 3) changes in serum thyroid hormone

  9. Is robotic arm stereotactic body radiation therapy “virtual high dose ratebrachytherapy” for prostate cancer? An analysis of comparative effectiveness using published data [corrected].

    PubMed

    Zaorsky, Nicholas George; Hurwitz, Mark D; Dicker, Adam P; Showalter, Timothy N; Den, Robert B

    2015-05-01

    High-dose rate brachytherapy (HDR-BT) monotherapy and robotic arm (i.e., CyberKnife) stereotactic body radiation therapy (SBRT) are emerging technologies that have become popular treatment options for prostate cancer. Proponents of both HDR-BT monotherapy and robotic arm SBRT claim that these modalities are as efficacious as intensity-modulated radiation therapy in treating prostate cancer. Moreover, proponents of robotic arm SBRT believe it is more effective than HDR-BT monotherapy because SBRT is non-invasive, touting it as 'virtual HDR-BT.' We perform a comparative effective analysis of the two technologies. The tumor control rates and toxicities of HDR-BT monotherapy and robotic arm SBRT are promising. However, at present, it would be inappropriate to state that HDR-BT monotherapy and robotic arm SBRT are as efficacious or effective as other treatment modalities for prostate cancer, which have stronger foundations of evidence. Studies reporting on these technologies have relatively short follow-up time, few patients and are largely retrospective. PMID:25540018

  10. Impaired immune regulation after radioiodine therapy for Graves' disease and the protective effect of Methimazole.

    PubMed

    Côté-Bigras, Sarah; Tran, Viet; Turcotte, Sylvie; Rola-Pleszczynski, Marek; Verreault, Jean; Rottembourg, Diane

    2016-06-01

    Both therapies for Graves' disease (GD), radioactive iodine (RAI) and antithyroid drugs (ATD), were reported to have specific immune effects. We aimed at investigating the effects of RAI therapy on cellular subsets involved in immune regulation. We conducted a thirty day follow-up prospective cohort study of adult patients. Patients eligible for RAI therapy at our centre were approached. Twenty seven patients with GD were recruited, among whom 11 were treated with ATD. Twenty-two healthy subjects (HS) were also studied. Over time, frequency of regulatory T cells (Treg) and of invariant natural killer T cells (iNKT), along with Treg cell-mediated suppression and underlying mechanisms, were monitored in the peripheral blood. Variance in frequency of Treg and iNKT after RAI therapy was higher in GD patients than in HS over time (p < 0.0001). Reduced Treg suppressive function was observed after RAI therapy in GD patients (p = 0.002). ATD medication prior to RAI dampened these outcomes: less variation of Treg frequency (p = 0.0394), a trend toward less impaired Treg function, and prevention of reduced levels of suppressive cytokines (p < 0.05). Shortly after RAI therapy, alterations in immunoregulatory cells in patients with GD were observed and partially prevented by an ATD pretreatment. Worsening of autoimmunity after RAI was explained in previous studies by enhanced immune activity. This study adds new highlights on immune regulation deficiencies after therapeutic interventions in thyroid autoimmunity. PMID:26701678

  11. Long-term Survival and Toxicity in Patients Treated With High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

    SciTech Connect

    Spratt, Daniel E.; Pei, Xin; Yamada, Josh; Kollmeier, Marisa A.; Cox, Brett; Zelefsky, Michael J.

    2013-03-01

    Purpose: To report long-term survival and toxicity outcomes with the use of high-dose intensity modulated radiation therapy (IMRT) to 86.4 Gy for patients with localized prostate cancer. Methods and Materials: Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5-7 field IMRT technique. Patients were stratified by prognostic risk group based on National Comprehensive Cancer Network risk classification criteria. A total of 587 patients (59%) were treated with neoadjuvant and concurrent androgen deprivation therapy. The median follow-up for the entire cohort was 5.5 years (range, 1-14 years). Results: For low-, intermediate-, and high-risk groups, 7-year biochemical relapse-free survival outcomes were 98.8%, 85.6%, and 67.9%, respectively (P<.001), and distant metastasis-free survival rates were 99.4%, 94.1%, and 82.0% (P<.001), respectively. On multivariate analysis, T stage (P<.001), Gleason score (P<.001), and >50% of initial biopsy positive core (P=.001) were predictive for distant mestastases. No prostate cancer-related deaths were observed in the low-risk group. The 7-year prostate cancer-specific mortality (PCSM) rates, using competing risk analysis for intermediate- and high-risk groups, were 3.3% and 8.1%, respectively (P=.008). On multivariate analysis, Gleason score (P=.004), percentage of biopsy core positivity (P=.003), and T-stage (P=.033) were predictive for PCSM. Actuarial 7-year grade 2 or higher late gastrointestinal and genitourinary toxicities were 4.4% and 21.1%, respectively. Late grade 3 gastrointestinal and genitourinary toxicity was experienced by 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. Conclusions: This study represents the largest cohort of patients treated with high-dose radiation to 86.4 Gy, using IMRT for localized prostate cancer, with the longest follow-up to date

  12. Paclitaxel and Trastuzumab as Maintenance Therapy in Patients with HER2-Positive Metastatic Breast Cancer Who Underwent High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation.

    PubMed

    Cheng, Yee Chung; Rondón, Gabriela; Anderlini, Paolo; Khouri, Issa F; Champlin, Richard E; Ueno, Naoto T

    2013-01-01

    We examined the feasibility and safety of using paclitaxel and trastuzumab as maintenance therapy after high-dose chemotherapy (HDC) with autologous hematopoietic stem cell transplantation (AHST) for patients with HER2-positive metastatic breast cancer. Ten patients (9 women and 1 man) were enrolled in the study. The median age was 46.5 years (range, 27-65 years). The median follow-up time was 1003 days (range, 216-2526 days). All patients had metastatic disease, but 2 had only bone metastasis. One patient had complete response, 6 had partial response and 3 had stable disease to the standard-dose chemotherapy prior to transplantation. The conditioning regimen consisted of cyclophosphamide, carmustine, and thiotepa. After AHST, patients received weekly paclitaxel for 12 doses and trastuzumab every 3 weeks for 1 year as maintenance therapy. All patients experienced successful engraftment. The only grade 4 toxic effects observed were leukopenia and thrombocytopenia. The most common grade 3 toxic effect was neutropenic fever. No treatment-related deaths were observed. The median progression-free survival time was 441 days, and the median overall survival time was 955 days. Two patients died in accidents while their disease remained in remission. Five patients died with disease progression. At the time of this report, 3 patients are alive with stable disease, 1 of whom has remained free of disease progression for 2526 days since transplantation. Our findings indicate that paclitaxel plus trastuzumab as maintenance therapy after HDC with AHST for patients with HER2-positive metastatic breast cancer not only is feasible and safe but also results in survival outcomes similar to historical results. PMID:24155780

  13. Results of combined photodynamic therapy (PDT) and high dose rate brachytherapy (HDR) in treatment of obstructive endobronchial non-small cell lung cancer

    NASA Astrophysics Data System (ADS)

    Weinberg, Benjamin D.; Allison, Ron R.; Sibata, Claudio; Parent, Teresa; Downie, Gordon

    2009-06-01

    We reviewed the outcome of combined photodynamic therapy (PDT) and high dose rate brachytherapy (HDR) for patients with symptomatic obstruction from endobronchial non-small cell lung cancer. Methods: Nine patients who received combined PDT and HDR for endobronchial cancers were identified and their charts reviewed. The patients were eight males and one female aged 52-73 at diagnosis, initially presenting with various stages of disease: stage IA (N=1), stage IIA (N=1), stage III (N=6), and stage IV (N=1). Intervention was with HDR (500 cGy to 5 mm once weekly for 3 weeks) and PDT (2 mg/kg Photofrin, followed by 200 J/cm2 illumination 48 hours post infusion). Treatment group 1 (TG-1, N=7) received HDR first; Treatment group 2 (TG-2, N=2) received PDT first. Patients were followed by regular bronchoscopies. Results: Treatments were well tolerated, all patients completed therapy, and none were lost to follow-up. In TG-1, local tumor control was achieved in six of seven patients for: 3 months (until death), 15 months, 2+ years (until death), 2+ years (ongoing), and 5+ years (ongoing, N=2). In TG-2, local control was achieved in only one patient, for 84 days. Morbidities included: stenosis and/or other reversible benign local tissue reactions (N=8); photosensitivity reaction (N=2), and self-limited pleural effusion (N=2). Conclusions: Combined HDR/PDT treatment for endobronchial tumors is well tolerated and can achieve prolonged local control with acceptable morbidity when PDT follows HDR and when the spacing between treatments is one month or less. This treatment regimen should be studied in a larger patient population.

  14. Salvage therapy with high-dose chemotherapy and peripheral blood stem cell transplant in patients with primary mediastinal nonseminomatous germ cell tumors.

    PubMed

    Suleiman, Yaman; Siddiqui, Bilal K; Brames, Mary J; Abonour, Rafat; Einhorn, Lawrence H

    2013-01-01

    Salvage therapy with high-dose chemotherapy (HDCT) and bone marrow transplant (BMT) or peripheral blood stem cell transplant (PBSCT) has curative potential in patients with recurrent germ cell tumor. However, patients with primary mediastinal nonseminomatous germ cell tumors (PMNSGCTs) have had poor results with any form of salvage chemotherapy including HDCT. We switched from BMT to PBSCT in 1996. One hundred sixteen of 184 patients (63%) with recurrent or refractory germ cell tumors treated from 1996 to 2004 were alive and continuously disease-free. PMNSGCTs were excluded from that study because of poor results in the patient population with HDCT and BMTs. In 2006, we resumed treating patients with recurrent PMNSGCT with 2 consecutive courses of HDCT consisting of carboplatin 700 mg/m(2) × 3 plus etoposide 750 mg/m(2) × 3 and each followed by an infusion of autologous peripheral-blood hematopoietic stem cells with a second course 3 to 4 weeks later. Twelve patients were treated: 11 as initial salvage chemotherapy and 1 as fourth-line therapy. Eight of the 12 patients had major thoracic resections at the time of the relapse after initial chemotherapy. Three of the 12 patients achieved complete remission (CR; 10, 15, and 50 months' duration). One patient remains continuously with no evidence of disease (NED) at 50 months. An additional patient is currently NED at 52 months with HDCT and subsequent surgery. Median survival for the 12 patients was 11 months (range, 4-52 months). Results with tandem transplant for recurrent PMNSGCT remain poor compared to primary testis cancer, but durable CR and probable cure can be achieved in a small subset of patients with PMNSGCT. In our opinion, salvage surgical resection if anatomically feasible is the preferred option for patients with PMNSGT progressing after initial chemotherapy. PMID:22892555

  15. Redefining High-Risk Prostate Cancer Based on Distant Metastases and Mortality After High-Dose Radiotherapy With Androgen Deprivation Therapy

    SciTech Connect

    Tendulkar, Rahul D.; Reddy, Chandana A.; Stephans, Kevin L.; Ciezki, Jay P.; Klein, Eric A.; Mahadevan, Arul; Kupelian, Patrick A.

    2012-03-15

    Purpose: Modern outcomes of high-dose external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT) for high-risk (HR) prostate cancer are not well described. Methods and Materials: We identified 585 patients who met HR criteria by 2010 National Comprehensive Cancer Network guidelines, who were treated with EBRT consisting of {>=}74 Gy from 1996 to 2008 at Cleveland Clinic, of whom 95% received ADT. We analyzed biochemical relapse-free survival (bRFS), distant metastases-free survival (DMFS), and prostate cancer-specific mortality (PCSM). Results: The median EBRT dose was 78 Gy, and median ADT duration was 6 months. At 10 years, the bRFS was 50.2%, the DMFS was 71.6%, and the PCSM was 14.4%. On multivariate analysis, significant predictors of bRFS were biopsy Gleason score (bGS) of 8 to 10, stage T3, and prostate-specific antigen (PSA) concentration; predictors of DMFS were bGS of 8 to 10 and stage T3; the only predictor of PCSM was bGS of 8 to 10. The duration of ADT was not predictive of any endpoint. We identified an unfavorable high-risk (UHR) group of stage T1-T2 tumors consisting of bGS of 8 with PSA of >10 ng/ml or bGS of 9 to 10 with any PSA level; the remaining clinically localized cancers comprised the favorable high-risk (FHR) group. Comparing FHR, UHR, and stage T3 groups, the DMFS rates were 81.4%, 57.8%, and 59.1% (p < 0.0001), and the PCSM rates were 7.5%, 28.4%, and 20.6% at 10 years, respectively (p = 0.006). Conclusion: A bGS of 8 to 10 is the strongest predictor of bRFS, DMFS, and PCSM after high-dose EBRT with ADT. The duration of ADT did not correlate with outcome. Future studies should account for the heterogeneity in HR prostate cancer.

  16. Comparison of High-Dose Corticosteroid Pulse Therapy and Combination Therapy Using Oral Cyclosporine with Low-Dose Corticosteroid in Severe Alopecia Areata

    PubMed Central

    Yeo, In Kwon; Ko, Eun Jung; No, Yeon A; Lim, Ee Seok; Park, Kui Young; Li, Kapsok; Kim, Beom Joon; Seo, Seong Jun; Kim, Myeung Nam

    2015-01-01

    Background Severe alopecia areata (AA) is resistant to conventional treatment. Although systemic oral corticosteroids are an effective treatment for patients with severe AA, those drugs have many adverse effects. Corticosteroid pulse therapy has been introduced to increase therapeutic effects and reduce adverse effects. However, the treatment modality in severe AA is still controversial. Objective To evaluate the effectiveness of corticosteroid pulse therapy in patients with severe AA compared with treatment with oral cyclosporine with corticosteroid. Methods A total of 82 patients with severe AA were treated with corticosteroid pulse therapy, and 60 patients were treated with oral cyclosporine with corticosteroid. Both groups were retrospectively evaluated for therapeutic efficacy according to AA type and disease duration. Results In 82 patients treated with corticosteroid pulse therapy, 53 (64.6%) were good responders (>50% hair regrowth). Patients with the plurifocal (PF) type of AA and those with a short disease duration (≤3 months) showed better responses. In 60 patients treated with oral cyclosporine with corticosteroid, 30 (50.0%) patients showed a good response. The AA type or disease duration, however, did not significantly affect the response to treatment. Conclusion Corticosteroid pulse therapy may be a better treatment option than combination therapy in severe AA patients with the PF type. PMID:26719635

  17. Iodine kinetics and dosimetry in the salivary glands during repeated courses of radioiodine therapy for thyroid cancer

    SciTech Connect

    Liu, B.; Huang, R.; Kuang, A.; Zhao, Z.; Zeng, Y.; Wang, J.; Tian, R.

    2011-10-15

    Purpose: The present study was conducted to investigate salivary iodine kinetics and dosimetry during repeated courses of radioiodine ({sup 131}I) therapy for differentiated thyroid cancer (DTC). Such data could provide a better understanding of the mechanisms of {sup 131}I induced salivary toxicity and help to develop appropriate methods to reduce this injury. Methods: Seventy-eight consecutive DTC patients (mean age 45 {+-} 17 years, 60%, female) undergoing {sup 131}I therapy for remnant ablation or metastatic tumors were prospectively recruited. Planar quantitative scintigraphy of head-neck images was serially acquired after administration of 2.9-7.4 GBq of {sup 131}I to assess kinetics in the salivary glands of patients. Salivary absorbed doses were calculated based on the schema of Medical Internal Radiation Dosimetry. Results: The maximum uptakes in percentage of administered {sup 131}I activity per kilogram of gland tissue (%/kg) were 12.9% {+-} 6.5%/kg (range, 0.4%-37.3%/kg) and 12.3% {+-} 6.2%/kg (range, 0.4%-35.1%/kg) for the parotid and submandibular glands, respectively. Statistically significant correlations of maximum uptake versus cumulative activity (r = -0.74, P < 0.01, for the parotid glands; r = -0.71, P < 0.01, for the submandibular glands) and treatment cycle (P < 0.001, for both gland types) were found. The effective half-lives of {sup 131}I in the parotid and submandibular glands were 9.3 {+-} 3.5 h (range, 1.5-19.8 h) and 8.6 {+-} 3.2 h (range, 0.8-18.0 h), respectively. A statistically significant correlation was observed between effective half-life with cumulative activity (r = 0.37, P < 0.01) and treatment cycle (P = 0.03) only for the parotid glands. The calculated absorbed doses were 0.20 {+-} 0.10 mGy/MBq (range, 0.01-0.92 mGy/MBq) and 0.25 {+-} 0.09 mGy/MBq (range, 0.01-1.52 mGy/MBq) for the parotid and submandibular glands, respectively. The photon contribution to the salivary absorbed dose was minimal in relation to the beta dose

  18. Rituximab-CHOP-ESHAP vs CHOP-ESHAP-high-dose therapy vs conventional CHOP chemotherapy in high-intermediate and high-risk aggressive non-Hodgkin's lymphoma.

    PubMed

    Intragumtornchai, Tanin; Bunworasate, Udomsak; Nakorn, Thanyaphong Na; Rojnuckarin, Ponlapat

    2006-07-01

    With currently available combination chemotherapy regimens, the outcome of the patients newly diagnosed with aggressive non-Hodgkin's lymphoma (NHL) identified as 'high' and 'high-intermediate' risk groups according to the international prognostic index (IPI) is still unsatisfactory and a more innovative therapy is urgently required to improve the survival of the patients. The purpose of this study was to compare the efficacy of rituximab given in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and ESHAP (etoposide, methylprednisolone, high-dose Ara-C, cisplatin) vs CHOP-ESHAP and upfront high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) vs standard CHOP in patients aged < or = 65 years old newly diagnosed with 'high' and 'high-intermediate' risk aggressive lymphoma enrolled onto two consecutive treatment trials at the institute. Between May 1995 - July 2002, 84 patients, aged 15 - 65 years old, with newly diagnosed aggressive NHL and an age-adjusted IPI of 2 or 3 were enrolled. The median age of the patients was 38 years (range 15 - 65). The baseline demographic features, in particular the major prognostic variables, were similar between the treatment groups. Patients treated with rituximab-CHOP-ESHAP received eight cycles of rituximab (375 mg m(-2) on day 1 of cycles 1 - 6 and days 21 and 28 of cycle 7) plus CHOP (day 3 of cycles 1, 3 and 5) and ESHAP (day 3 of cycles 2, 4 and 6 and day 1 of cycle 7) at 21-day intervals. Patients enrolled onto the CHOP-ESHAP-HDT arm (n = 23) were treated with three courses of CHOP and then switched to two or four cycles of ESHAP followed by HDT. Patients treated with CHOP alone (n = 25) were treated with the standard eight cycles of CHOP. The rate of complete remission was significantly improved with rituximab-CHOP-ESHAP compared with either CHOP-ESHAP-HDT or CHOP alone (67% compared with 44% and 36%, respectively; p = 0.043). With a median follow-up time of 53 months, the 5

  19. High-Dose Terazosin Therapy (5 mg) in Korean Patients with Lower Urinary Tract Symptoms with or without Concomitant Hypertension: A Prospective, Open-Label Study

    PubMed Central

    Kwak, Cheol; Lee, Jeong Ki

    2007-01-01

    Purpose We determined the efficacy and safety of a relatively high dose of terazosin (5 mg) in Korean patients with lower urinary tract symptoms (LUTS), with or without concomitant hypertension. Materials and Methods From July to December 2006, 200 men who consecutively presented with LUTS were prospectively studied. Eight weeks after treatment, blood pressure (BP), uroflowmetry, and International Prostate Symptom Score (I-PSS) were assessed. For analysis purposes, patients were stratified according to concomitant hypertension. Of the 200 patients, 173 completed the scheduled eight-week treatment period. Results At baseline, no differences were evident in the two groups in terms of I-PSS, Qmax, PVR and BP. After eight weeks of treatment-although I-PSS and uroflowmetry parameters were not significantly different in the two groups-systolic and diastolic BP in the non-hypertensive control group were higher than in the hypertensive group (p= 0.001 and p = 0.0100, respectively). Changes in I-PSS, uroflowmetry parameters, and BPs measured at week eight post-treatment commencement did not significantly differ between the two groups. Moreover, the addition of 5 mg of terazosin to antihypertensives did not cause a significant reduction in either systolic or diastolic BP in either group. Conclusion Adding terazosin to existing antihypertensive regimens did not seem to increase the incidence of adverse events. Our findings suggest that 5 mg terazosin is effective and that it has an acceptable safety profile as an add-on therapy for patients with LUTS and concomitant hypertension. PMID:18159592

  20. Single-Fraction High-Dose-Rate Brachytherapy and Hypofractionated External Beam Radiation Therapy in the Treatment of Intermediate-Risk Prostate Cancer - Long Term Results

    SciTech Connect

    Cury, Fabio L.; Duclos, Marie; Aprikian, Armen; Patrocinio, Horacio; Kassouf, Wassim; Shenouda, George; Faria, Sergio; David, Marc; Souhami, Luis

    2012-03-15

    Purpose: We present the long-term results of a cohort of patients with intermediate-risk prostate cancer (PC) treated with single-fraction high-dose-rate brachytherapy (HDRB) combined with hypofractionated external beam radiation therapy (HypoRT). Methods and Materials: Patients were treated exclusively with HDRB and HypoRT. HDRB delivered a dose of 10 Gy to the prostate surface and HypoRT consisted of 50 Gy delivered in 20 daily fractions. The first 121 consecutive patients with a minimum of 2 years posttreatment follow-up were assessed for toxicity and disease control. Results: The median follow-up was 65.2 months. No acute Grade III or higher toxicity was seen. Late Grade II gastrointestinal toxicity was seen in 9 patients (7.4%) and Grade III in 2 (1.6%). Late Grade III genitourinary toxicity was seen in 2 patients (1.6%). After a 24-month follow-up, a rebiopsy was offered to the first 58 consecutively treated patients, and 44 patients agreed with the procedure. Negative biopsies were found in 40 patients (91%). The 5-year biochemical relapse-free survival rate was 90.7% (95% CI, 84.5-96.9%), with 13 patients presenting biochemical failure. Among them, 9 were diagnosed with distant metastasis. Prostate cancer-specific and overall survival rates at 5 years were 100% and 98.8% (95% CI, 96.4-100%), respectively. Conclusion: The combination of HDRB and HypoRT is well tolerated, with acceptable toxicity rates. Furthermore, results from rebiopsies revealed an encouraging rate of local control. These results confirm that the use of conformal RT techniques, adapted to specific biological tumor characteristics, have the potential to improve the therapeutic ratio in intermediate-risk PC patients.

  1. An oral high dose of cholecalciferol restores vitamin D status in deficient postmenopausal HIV-1-infected women independently of protease inhibitors therapy: a pilot study.

    PubMed

    Pepe, Jessica; Mezzaroma, Ivano; Fantauzzi, Alessandra; Falciano, Mario; Salotti, Alessandra; Di Traglia, Mario; Diacinti, Daniele; Biondi, Piergianni; Cipriani, Cristiana; Cilli, Mirella; Minisola, Salvatore

    2016-07-01

    The best repletion and maintenance dosing regimens with cholecalciferol in vitamin D-deficient HIV-1 patients remain unknown. Protease inhibitors (PIs) have been shown to inhibit vitamin D 1α- and 25α-hydroxylation in hepatocyte and monocyte cultures. We therefore evaluated the effect of a single high dose of cholecalciferol in vitamin D-deficient HIV-1 postmenopausal women undergoing treatment with highly active anti-retroviral therapy (cART), with and without PIs. Forty HIV-1 postmenopausal women treated with cART, with hypovitaminosis D (<20 ng/ml), were enrolled. We measured serum changes of 25-hydroxyvitamin D [25(OH)D]; 1,25-dihydroxyvitamin D [1,25(OH)2D], parathyroid hormone (PTH), serum calcium, and urinary calcium excretion following a loading dose of 600,000 IU of cholecalciferol after 3, 30, 60, 90, and 120 days. Patients were divided into two groups, whether or not they were taking PI. A significant increase in mean 25(OH)D and 1,25(OH)2D levels at day 3 and throughout the entire observation period was found in both groups (p < 0.001). PTH levels concomitantly decreased in both groups (p < 0.001). Mean albumin-adjusted serum calcium increases with respect to baseline were significant only at day 3 and day 30 for both groups (p < 0.01). Considering remaining parameters, there were no significant differences between the groups at any time, by two-way RM ANOVA. An oral dose of 600,000 IU of cholecalciferol in HIV-1 postmenopausal women rapidly increases 25(OH)D and 1,25(OH)2D levels reducing PTH levels, regardless of the presence of PIs in the cART scheme. PMID:26254790

  2. High Doses of Daunorubicin during Induction Therapy of Newly Diagnosed Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis of Prospective Clinical Trials

    PubMed Central

    Gong, Qiang; Zhou, Lixin; Xu, Shuangnian; Li, Xi; Zou, Yunding; Chen, Jieping

    2015-01-01

    The right dose of daunorubicin (DNR) for the treatment of newly diagnosed acute myeloid leukemia (AML) is uncertain. Previous trials have shown conflicting results concerning the efficacy of high or low doses of daunorubicin to induction chemotherapy for newly diagnosed AML. A systematic review and meta-analysis was conducted to resolve this controversial issue. We compared the efficacy and safety of high doses of daunorubicin (HD-DNR) and traditional low doses of daunorubicin (LD-DNR) or idarubicin (IDA) during induction therapy of newly diagnosed AML. Data of 3,824 patients from 1,796 articles in the literature were retrieved and six randomized controlled trials were analyzed. The primary outcomes were overall survival (OS), disease-free survival (DFS), and event-free survival (EFS). The secondary outcomes included complete remission (CR), relapse, and toxicity. The meta-analysis results suggest that comparing HD-DNR with LD-DNR, there were significant differences in CR (RR = 1.19, 95%CI[1.12,1.18], p<0.00001), OS(HR = 0.88, 95%CI[0.79,0.99], p = 0.002), and EFS (HR = 0.86, 95%CI [0.74, 1.00], p = 0.008), but not in DFS, relapse, and toxicity. There were no statistically significant differences in any other outcomes between HD-DNR and IDA. The analysis indicates that compared with LD-DNR, HD-DNR can significantly improve CR, OS and EFS but not DFS, and did not increase occurrence of relapse and toxicity. PMID:25993000

  3. High-Dose and Extended-Field Intensity Modulated Radiation Therapy for Early-Stage NK/T-Cell Lymphoma of Waldeyer's Ring: Dosimetric Analysis and Clinical Outcome

    SciTech Connect

    Bi, Xi-Wen; Li, Ye-Xiong Fang, Hui; Jin, Jing; Wang, Wei-Hu; Wang, Shu-Lian; Liu, Yue-Ping; Song, Yong-Wen; Ren, Hua; Dai, Jian-Rong

    2013-12-01

    Purpose: To assess the dosimetric benefit, treatment outcome, and toxicity of high-dose and extended-field intensity modulated radiation therapy (IMRT) in patients with early-stage NK/T-cell lymphoma of Waldeyer's ring (WR-NKTCL). Methods and Materials: Thirty patients with early-stage WR-NKTCL who received extended-field IMRT were retrospectively reviewed. The prescribed dose was 50 Gy to the primary involved regions and positive cervical lymph nodes (planning target volume requiring radical irradiation [PTV{sub 50}]) and 40 Gy to the negative cervical nodes (PTV{sub 40}). Dosimetric parameters for the target volume and critical normal structures were evaluated. Locoregional control (LRC), overall survival (OS), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Results: The median mean doses to the PTV{sub 50} and PTV{sub 40} were 53.2 Gy and 43.0 Gy, respectively. Only 1.4% of the PTV{sub 50} and 0.9% of the PTV{sub 40} received less than 95% of the prescribed dose, indicating excellent target coverage. The average mean doses to the left and right parotid glands were 27.7 and 28.4 Gy, respectively. The 2-year OS, PFS, and LRC rates were 71.2%, 57.4%, and 87.8%. Most acute toxicities were grade 1 to 2, except for grade ≥3 dysphagia and mucositis. The most common late toxicity was grade 1-2 xerostomia, and no patient developed any ≥grade 3 late toxicities. A correlation between the mean dose to the parotid glands and the degree of late xerostomia was observed. Conclusions: IMRT achieves excellent target coverage and dose conformity, as well as favorable survival and locoregional control rates with acceptable toxicities in patients with WR-NKTCL.

  4. Modified total body irradiation as a planned second high-dose therapy with stem cell infusion for patients with bone-based malignancies

    SciTech Connect

    Zaucha, Renata E.; Buckner, Dean C.; Barnett, Todd; Holmberg, Leona A.; Gooley, Ted; Hooper, Heather A. P.A.-C.; Maloney, David G.; Appelbaum, Frederick; Bensinger, William I. . E-mail: wbensing@fhcrc.org

    2006-01-01

    Purpose: To estimate the maximum tolerated dose of hyperfractionated total marrow irradiation (TMI) as a second consolidation after high-dose chemotherapy with autologous or syngeneic blood stem cell transfusion for patients with bone/bone marrow-based malignant disease. Patients and Methods: Fifty-seven patients aged 3-65 years (median, 45 years), including 21 with multiple myeloma, 24 with breast cancer, 10 with sarcoma, and 2 with lymphoma, were treated with 1.5 Gy administered twice daily to a total dose of 12 Gy (n = 27), 13.5 Gy (n = 12), and 15 Gy (n = 18). Median time between the 2 transplants was 105 days (range, 63-162 days). Results: All patients engrafted neutrophils (median, Day 11; range, Day 9-23) and became platelet independent (median, Day 9; range, Day 7-36). There were 5 cases of Grade 3-4 regimen-related pulmonary toxicity, 1 at 12 Gy, and 4 at 15 Gy. Complete responses, partial responses, and stabilizations were achieved in 33%, 26%, and 41% of patients, respectively. Kaplan-Meier estimates of 5-year progression-free survival and overall survival for 56 evaluable patients are 24% and 36%, respectively. Median time of follow-up among survivors was 96 months (range, 77-136 months). Conclusion: Total marrow irradiation as a second myeloablative therapy is feasible. The estimated maximum tolerated dose for TMI in a tandem transplant setting was 13.5 Gy. Because 20% of patients are surviving at 8 years free of disease, further studies of TMI are warranted.

  5. Dosimetric and radiobiological comparison of volumetric modulated arc therapy, high-dose rate brachytherapy, and low-dose rate permanent seeds implant for localized prostate cancer.

    PubMed

    Yang, Ruijie; Zhao, Nan; Liao, Anyan; Wang, Hao; Qu, Ang

    2016-01-01

    To investigate the dosimetric and radiobiological differences among volumetric modulated arc therapy (VMAT), high-dose rate (HDR) brachytherapy, and low-dose rate (LDR) permanent seeds implant for localized prostate cancer. A total of 10 patients with localized prostate cancer were selected for this study. VMAT, HDR brachytherapy, and LDR permanent seeds implant plans were created for each patient. For VMAT, planning target volume (PTV) was defined as the clinical target volume plus a margin of 5mm. Rectum, bladder, urethra, and femoral heads were considered as organs at risk. A 78Gy in 39 fractions were prescribed for PTV. For HDR and LDR plans, the dose prescription was D90 of 34Gy in 8.5Gy per fraction, and 145Gy to clinical target volume, respectively. The dose and dose volume parameters were evaluated for target, organs at risk, and normal tissue. Physical dose was converted to dose based on 2-Gy fractions (equivalent dose in 2Gy per fraction, EQD2) for comparison of 3 techniques. HDR and LDR significantly reduced the dose to rectum and bladder compared with VMAT. The Dmean (EQD2) of rectum decreased 22.36Gy in HDR and 17.01Gy in LDR from 30.24Gy in VMAT, respectively. The Dmean (EQD2) of bladder decreased 6.91Gy in HDR and 2.53Gy in LDR from 13.46Gy in VMAT. For the femoral heads and normal tissue, the mean doses were also significantly reduced in both HDR and LDR compared with VMAT. For the urethra, the mean dose (EQD2) was 80.26, 70.23, and 104.91Gy in VMAT, HDR, and LDR brachytherapy, respectively. For localized prostate cancer, both HDR and LDR brachytherapy were clearly superior in the sparing of rectum, bladder, femoral heads, and normal tissue compared with VMAT. HDR provided the advantage in sparing of urethra compared with VMAT and LDR. PMID:27400663

  6. Comparison of radioiodine with radioiodine plus lithium in the treatment of Graves' hyperthyroidism.

    PubMed

    Bogazzi, F; Bartalena, L; Brogioni, S; Scarcello, G; Burelli, A; Campomori, A; Manetti, L; Rossi, G; Pinchera, A; Martino, E

    1999-02-01

    Effectiveness of radioiodine for Graves' hyperthyroidism depends also on its intrathyroidal persistence. The latter is enhanced by lithium by blocking iodine release from the thyroid. One hundred ten patients with Graves' hyperthyroidism were randomly assigned to treatment with radioiodine or radioiodine plus lithium, stratified according to goiter size (< or =40 or >40 mL) and evaluated for changes in thyroid function and goiter size, at monthly intervals, for 12 months. Cure of hyperthyroidism occurred in 33 of 46 patients (72%) treated with radioiodine and in 45 of 54 patients (83%) treated with radioiodine plus lithium. The probability of curing hyperthyroidism was higher and its control prompter (P = 0.02) in the radioiodine-plus-lithium group. Patients with < or =40-mL goiters had similar persistence of hyperthyroidism (13%), but lithium-treated patients had hyperthyroidism controlled earlier (P = 0.04). Among patients with >40-mL goiters, hyperthyroidism was cured in 6 of 15 patients (40%) treated with radioiodine alone and in 12 of 16 patients (75%) treated with radioiodine plus lithium (P = 0.07), and cure occurred earlier in the latter (P = 0.05). Goiters shrank in both groups (P < 0.0001), more effectively and promptly (P < 0.0005) in the radioiodine-plus-lithium group. Serum free T4 and T3 levels increased shortly after therapy only in the radioiodine group (P < 0.01). Lithium carbonate enhances the effectiveness of radioiodine therapy, in terms of prompter control of hyperthyroidism, in patients with small or large goiters. In the latter group, lithium also increases the rate of permanent control of hyperthyroidism. PMID:10022407

  7. Impact of Dose to the Bladder Trigone on Long-Term Urinary Function After High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

    SciTech Connect

    Ghadjar, Pirus; Zelefsky, Michael J.; Spratt, Daniel E.; Munck af Rosenschöld, Per; Oh, Jung Hun; Hunt, Margie; Kollmeier, Marisa; Happersett, Laura; Yorke, Ellen; Deasy, Joseph O.; Jackson, Andrew

    2014-02-01

    Purpose: To determine the potential association between genitourinary (GU) toxicity and planning dose–volume parameters for GU pelvic structures after high-dose intensity modulated radiation therapy in localized prostate cancer patients. Methods and Materials: A total of 268 patients who underwent intensity modulated radiation therapy to a prescribed dose of 86.4 Gy in 48 fractions during June 2004-December 2008 were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Dose–volume histograms of the whole bladder, bladder wall, urethra, and bladder trigone were analyzed. The primary endpoint for GU toxicity was an IPSS sum increase ≥10 points over baseline. Univariate and multivariate analyses were done by the Kaplan-Meier method and Cox proportional hazard models, respectively. Results: Median follow-up was 5 years (range, 3-7.7 years). Thirty-nine patients experienced an IPSS sum increase ≥10 during follow-up; 84% remained event free at 5 years. After univariate analysis, lower baseline IPSS sum (P=.006), the V90 of the trigone (P=.006), and the maximal dose to the trigone (P=.003) were significantly associated with an IPSS sum increase ≥10. After multivariate analysis, lower baseline IPSS sum (P=.009) and increased maximal dose to the trigone (P=.005) remained significantly associated. Seventy-two patients had both a lower baseline IPSS sum and a higher maximal dose to the trigone and were defined as high risk, and 68 patients had both a higher baseline IPSS sum and a lower maximal dose to the trigone and were defined as low risk for development of an IPSS sum increase ≥10. Twenty-one of 72 high-risk patients (29%) and 5 of 68 low-risk patients (7%) experienced an IPSS sum increase ≥10 (P=.001; odds ratio 5.19). Conclusions: The application of hot spots to the bladder trigone was significantly associated with relevant changes in IPSS during follow-up. Reduction of radiation dose to the lower bladder and specifically the

  8. Radioactive Iodine (Radioiodine) Therapy

    MedlinePlus

    ... low thyroid hormone levels (a condition known as hypothyroidism ), which in turn causes the pituitary gland to release more TSH. This intentional hypothyroidism is temporary, but it often causes symptoms like ...

  9. High-Dose Radiotherapy With or Without Androgen Deprivation Therapy for Intermediate-Risk Prostate Cancer: Cancer Control and Toxicity Outcomes

    SciTech Connect

    Edelman, Scott; Liauw, Stanley L.; Rossi, Peter J.; Cooper, Sherrie; Jani, Ashesh B.

    2012-08-01

    Purpose: To evaluate the impact of short-course androgen deprivation therapy (ADT) on cancer control outcomes and toxicity in intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (high-dose radiotherapy [HDRT]). Methods and Materials: Demographic, disease, and treatment characteristics of prostate cancer patients at 2 institution consortiums were charted. Of 296 men with intermediate-risk prostate cancer (defined as {>=}T2b, prostate-specific antigen level >10 ng/mL, or Gleason score [GS] of 7, with none of the following: {>=}T3, prostate-specific antigen level >20 ng/mL, GS {>=}8, or positive nodes) treated with HDRT to a dose of 72 Gy or greater, 123 received short-course ADT and 173 did not. Univariate and multivariate analyses on biochemical failure-free survival (BFFS) (including subset analysis by disease factors) and on overall survival (OS) were performed, as were comparisons of gastrointestinal (GI) and genitourinary (GU) toxicity rates. Results: For the whole group, the median dose was 75.6 Gy; the minimum follow-up was 2 years, and the median follow-up was 47.4 months. For ADT vs. no ADT, the 5-year BFFS rate was 86% vs. 79% (p = 0.138) and the 5-year OS rate was 87% vs. 80% (p = 0.159). On multivariate analysis, percent positive cores (PPC) (p = 0.002) and GS (p = 0.008) were significantly associated with BFFS, with ADT showing a trend (p = 0.055). The impact of ADT was highest in the subsets with PPC greater than 50% (p = 0.019), GS 4+3 (p = 0.078), and number of risk factors greater than 1 (p = 0.022). Only intensity-modulated radiotherapy use (p = 0.012) and GS (p = 0.023) reached significance for OS, and there were no significant differences in GU or GI toxicity. Conclusions: Although the use of ADT with HDRT did not influence BFFS, our study suggests a benefit in patients with PPC greater than 50%, GS 4+3, or multiple risk factors. No OS benefit was shown, and ADT was not associated with additional radiotherapy

  10. Phase II Study of Accelerated High-Dose Radiotherapy With Concurrent Chemotherapy for Patients With Limited Small-Cell Lung Cancer: Radiation Therapy Oncology Group Protocol 0239

    SciTech Connect

    Komaki, Ritsuko; Paulus, Rebecca; Ettinger, David S.; Videtic, Gregory M.M.; Bradley, Jeffrey D.; Glisson, Bonnie S.; Sause, William T.; Curran, Walter J.; Choy, Hak

    2012-07-15

    Purpose: To investigate whether high-dose thoracic radiation given twice daily during cisplatin-etoposide chemotherapy for limited small-cell lung cancer (LSCLC) improves survival, acute esophagitis, and local control rates relative to findings from Intergroup trial 0096 (47%, 27%, and 64%). Patients and Methods: Patients were accrued over a 3-year period from 22 US and Canadian institutions. Patients with LSCLC and good performance status were given thoracic radiation to 61.2 Gy over 5 weeks (daily 1.8-Gy fractions on days 1-22, then twice-daily 1.8-Gy fractions on days 23-33). Cisplatin (60 mg/m{sup 2} IV) was given on day 1 and etoposide (120 mg/m{sup 2} IV) on days 1-3 and days 22-24, followed by 2 cycles of cisplatin plus etoposide alone. Patients who achieved complete response were offered prophylactic cranial irradiation. Endpoints included overall and progression-free survival; severe esophagitis (Common Toxicity Criteria v 2.0) and treatment-related fatalities; response (Response Evaluation Criteria in Solid Tumors); and local control. Results: Seventy-two patients were accrued from June 2003 through May 2006; 71 were evaluable (median age 63 years; 52% female; 58% Zubrod 0). Median survival time was 19 months; at 2 years, the overall survival rate was 36.6% (95% confidence interval [CI] 25.6%-47.7%), and progression-free survival 19.7% (95% CI 11.4%-29.6%). Thirteen patients (18%) experienced severe acute esophagitis, and 2 (3%) died of treatment-related causes; 41% achieved complete response, 39% partial response, 10% stable disease, and 6% progressive disease. The local control rate was 73%. Forty-three patients (61%) received prophylactic cranial irradiation. Conclusions: The overall survival rate did not reach the projected goal; however, rates of esophagitis were lower, and local control higher, than projected. This treatment strategy is now one of three arms of a prospective trial of chemoradiation for LSCLC (Radiation Therapy Oncology Group 0538

  11. Preliminary Toxicity Analysis of 3-Dimensional Conformal Radiation Therapy Versus Intensity Modulated Radiation Therapy on the High-Dose Arm of the Radiation Therapy Oncology Group 0126 Prostate Cancer Trial

    SciTech Connect

    Michalski, Jeff M.; Yan, Yan; Watkins-Bruner, Deborah; Bosch, Walter R.; Winter, Kathryn; Galvin, James M.; Bahary, Jean-Paul; Morton, Gerard C.; Parliament, Matthew B.; Sandler, Howard M.

    2013-12-01

    Purpose: To give a preliminary report of clinical and treatment factors associated with toxicity in men receiving high-dose radiation therapy (RT) on a phase 3 dose-escalation trial. Methods and Materials: The trial was initiated with 3-dimensional conformal RT (3D-CRT) and amended after 1 year to allow intensity modulated RT (IMRT). Patients treated with 3D-CRT received 55.8 Gy to a planning target volume that included the prostate and seminal vesicles, then 23.4 Gy to prostate only. The IMRT patients were treated to the prostate and proximal seminal vesicles to 79.2 Gy. Common Toxicity Criteria, version 2.0, and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late morbidity scores were used for acute and late effects. Results: Of 763 patients randomized to the 79.2-Gy arm of Radiation Therapy Oncology Group 0126 protocol, 748 were eligible and evaluable: 491 and 257 were treated with 3D-CRT and IMRT, respectively. For both bladder and rectum, the volumes receiving 65, 70, and 75 Gy were significantly lower with IMRT (all P<.0001). For grade (G) 2+ acute gastrointestinal/genitourinary (GI/GU) toxicity, both univariate and multivariate analyses showed a statistically significant decrease in G2+ acute collective GI/GU toxicity for IMRT. There were no significant differences with 3D-CRT or IMRT for acute or late G2+ or 3+ GU toxicities. Univariate analysis showed a statistically significant decrease in late G2+ GI toxicity for IMRT (P=.039). On multivariate analysis, IMRT showed a 26% reduction in G2+ late GI toxicity (P=.099). Acute G2+ toxicity was associated with late G3+ toxicity (P=.005). With dose–volume histogram data in the multivariate analysis, RT modality was not significant, whereas white race (P=.001) and rectal V70 ≥15% were associated with G2+ rectal toxicity (P=.034). Conclusions: Intensity modulated RT is associated with a significant reduction in acute G2+ GI/GU toxicity. There is a trend for a

  12. Investigation of the level of safety for out-patients treated with high dose of 131I in Sudan

    NASA Astrophysics Data System (ADS)

    Saeed, M. K.

    2014-10-01

    The aim of this study was to describe and analyze the patterns of radiation exposure of contacts of Sudanese patients treated with radioactive 131I on an out-patient basis and post discharge after high dose 131I therapy, and also to compare the family members' results with dose constraints proposed by the European Commission (EC). Thermoluminiscent dosimeters (Model TLD-100 H) were used to estimate the effective doses for 40 family members of fifteen patients treated with 131I. The family members wore a TLD in front of the chest for 10 days. The effective dose ranged from 0.23 to 6.74 mSv (mean 1.75 mSv). These findings may be considered when establishing new national guidelines concerning radiation protection and release of patients after a treatment with radioiodine therapy.

  13. The costs of peripheral blood progenitor cell reinfusion mobilised by granulocyte colony-stimulating factor following high dose melphalan as compared with conventional therapy in multiple myeloma.

    PubMed

    Uyl-de Groot, C A; Ossenkoppele, G J; van Riet, A A; Rutten, F F

    1994-01-01

    In a retrospective study, we calculated the treatment costs of 26 patients, who received either high dose melphalan combined with granulocyte colony-stimulating factor (G-CSF; filgrastim)(n = 7) or without G-CSF (n = 11) or alternatively, peripheral blood progenitor cell reinfusion (PBPC) mobilised by G-CSF following high dose melphalan. In comparison with the control group, a shortening of the pancytopenic period and platelet recovery was noticed in the PBPC group. This resulted in a reduction in hospital costs, diagnostics, laboratory services, total parenteral nutrition and transfusions. The average costs per treatment in the PBPC group amounted to about US$ 17,908 as compared to US$ 32,223 in the control group, implying a cost reduction of 44% when changing to PBPC reinfusion. PMID:7517149

  14. Salvage therapy with high-dose cytarabine and mitoxantrone in combination with all-trans retinoic acid and gemtuzumab ozogamicin in acute myeloid leukemia refractory to first induction therapy

    PubMed Central

    Hütter-Krönke, Marie-Luise; Benner, Axel; Döhner, Konstanze; Krauter, Jürgen; Weber, Daniela; Moessner, Margit; Köhne, Claus-Henning; Horst, Heinz A.; Schmidt-Wolf, Ingo G.H.; Rummel, Mathias; Götze, Katharina; Koller, Elisabeth; Petzer, Andreas L.; Salwender, Hans; Fiedler, Walter; Kirchen, Heinz; Haase, Detlef; Kremers, Stephan; Theobald, Matthias; Matzdorff, Axel C.; Ganser, Arnold; Döhner, Hartmut; Schlenk, Richard F.

    2016-01-01

    Outcome of patients with primary refractory acute myeloid leukemia remains unsatisfactory. We conducted a prospective phase II clinical trial with gemtuzumab ozogamicin (3 mg/m2 intravenously on day 1), all-trans retinoic acid (45 mg/m2 orally on days 4–6 and 15 mg/m2 orally on days 7–28), high-dose cytarabine (3 g/m2/12 h intravenously on days 1–3) and mitoxantrone (12 mg/m2 intravenously on days 2–3) in 93 patients aged 18–60 years refractory to one cycle of induction therapy. Primary end point of the study was response to therapy; secondary end points included evaluation of toxicities, in particular, rate of sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation. Complete remission or complete remission with incomplete blood count recovery was achieved in 47 (51%) and partial remission in 10 (11%) patients resulting in an overall response rate of 61.5%; 33 (35.5%) patients had refractory disease and 3 patients (3%) died. Allogeneic hematopoietic cell transplantation was performed in 71 (76%) patients; 6 of the 71 (8.5%) patients developed moderate or severe sinusoidal obstruction syndrome after transplantation. Four-year overall survival rate was 32% (95% confidence interval 24%-43%). Patients responding to salvage therapy and undergoing allogeneic hematopoietic cell transplantation (n=51) had a 4-year survival rate of 49% (95% confidence intervaI 37%-64%). Patients with fms-like tyrosine kinase internal tandem duplication positive acute myeloid leukemia had a poor outcome despite transplantation. In conclusion, the described regimen is an effective and tolerable salvage therapy for patients who are primary refractory to one cycle of conventional intensive induction therapy. (clinicaltrials.gov identifier: 00143975) PMID:27036160

  15. Salvage therapy with high-dose cytarabine and mitoxantrone in combination with all-trans retinoic acid and gemtuzumab ozogamicin in acute myeloid leukemia refractory to first induction therapy.

    PubMed

    Hütter-Krönke, Marie-Luise; Benner, Axel; Döhner, Konstanze; Krauter, Jürgen; Weber, Daniela; Moessner, Margit; Köhne, Claus-Henning; Horst, Heinz A; Schmidt-Wolf, Ingo G H; Rummel, Mathias; Götze, Katharina; Koller, Elisabeth; Petzer, Andreas L; Salwender, Hans; Fiedler, Walter; Kirchen, Heinz; Haase, Detlef; Kremers, Stephan; Theobald, Matthias; Matzdorff, Axel C; Ganser, Arnold; Döhner, Hartmut; Schlenk, Richard F

    2016-07-01

    Outcome of patients with primary refractory acute myeloid leukemia remains unsatisfactory. We conducted a prospective phase II clinical trial with gemtuzumab ozogamicin (3 mg/m(2) intravenously on day 1), all-trans retinoic acid (45 mg/m(2) orally on days 4-6 and 15 mg/m(2) orally on days 7-28), high-dose cytarabine (3 g/m(2)/12 h intravenously on days 1-3) and mitoxantrone (12 mg/m(2) intravenously on days 2-3) in 93 patients aged 18-60 years refractory to one cycle of induction therapy. Primary end point of the study was response to therapy; secondary end points included evaluation of toxicities, in particular, rate of sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation. Complete remission or complete remission with incomplete blood count recovery was achieved in 47 (51%) and partial remission in 10 (11%) patients resulting in an overall response rate of 61.5%; 33 (35.5%) patients had refractory disease and 3 patients (3%) died. Allogeneic hematopoietic cell transplantation was performed in 71 (76%) patients; 6 of the 71 (8.5%) patients developed moderate or severe sinusoidal obstruction syndrome after transplantation. Four-year overall survival rate was 32% (95% confidence interval 24%-43%). Patients responding to salvage therapy and undergoing allogeneic hematopoietic cell transplantation (n=51) had a 4-year survival rate of 49% (95% confidence intervaI 37%-64%). Patients with fms-like tyrosine kinase internal tandem duplication positive acute myeloid leukemia had a poor outcome despite transplantation. In conclusion, the described regimen is an effective and tolerable salvage therapy for patients who are primary refractory to one cycle of conventional intensive induction therapy. (clinicaltrials.gov identifier: 00143975). PMID:27036160

  16. {sup 18}F-Choline Positron Emission Tomography/Computed Tomography–Driven High-Dose Salvage Radiation Therapy in Patients With Biochemical Progression After Radical Prostatectomy: Feasibility Study in 60 Patients

    SciTech Connect

    D'Angelillo, Rolando M.; Sciuto, Rosa; Ramella, Sara; Papalia, Rocco; Jereczek-Fossa, Barbara A.; Trodella, Luca E.; Fiore, Michele; Gallucci, Michele; Maini, Carlo L.; Trodella, Lucio

    2014-10-01

    Purpose: To retrospectively review data of a cohort of patients with biochemical progression after radical prostatectomy, treated according to a uniform institutional treatment policy, to evaluate toxicity and feasibility of high-dose salvage radiation therapy (80 Gy). Methods and Materials: Data on 60 patients with biochemical progression after radical prostatectomy between January 2009 and September 2011 were reviewed. The median value of prostate-specific antigen before radiation therapy was 0.9 ng/mL. All patients at time of diagnosis of biochemical recurrence underwent dynamic {sup 18}F-choline positron emission tomography/computed tomography (PET/CT), which revealed in all cases a local recurrence. High-dose salvage radiation therapy was delivered up to total dose of 80 Gy to 18F-choline PET/CT-positive area. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events, version 3.0, scale. Results: Treatment was generally well tolerated: 54 patients (90%) completed salvage radiation therapy without any interruption. Gastrointestinal grade ≥2 acute toxicity was recorded in 6 patients (10%), whereas no patient experienced a grade ≥2 genitourinary toxicity. No grade 4 acute toxicity events were recorded. Only 1 patient (1.7%) experienced a grade 2 gastrointestinal late toxicity. With a mean follow-up of 31.2 months, 46 of 60 patients (76.6%) were free of recurrence. The 3-year biochemical progression-free survival rate was 72.5%. Conclusions: At early follow-up, {sup 18}F-choline PET/CT-driven high-dose salvage radiation therapy seems to be feasible and well tolerated, with a low rate of toxicity.

  17. Dosimetric Considerations to Determine the Optimal Technique for Localized Prostate Cancer Among External Photon, Proton, or Carbon-Ion Therapy and High-Dose-Rate or Low-Dose-Rate Brachytherapy

    SciTech Connect

    Georg, Dietmar

    2014-03-01

    Purpose: To assess the dosimetric differences among volumetric modulated arc therapy (VMAT), scanned proton therapy (intensity-modulated proton therapy, IMPT), scanned carbon-ion therapy (intensity-modulated carbon-ion therapy, IMIT), and low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy (BT) treatment of localized prostate cancer. Methods and Materials: Ten patients were considered for this planning study. For external beam radiation therapy (EBRT), planning target volume was created by adding a margin of 5 mm (lateral/anterior–posterior) and 8 mm (superior–inferior) to the clinical target volume. Bladder wall (BW), rectal wall (RW), femoral heads, urethra, and pelvic tissue were considered as organs at risk. For VMAT and IMPT, 78 Gy(relative biological effectiveness, RBE)/2 Gy were prescribed. The IMIT was based on 66 Gy(RBE)/20 fractions. The clinical target volume planning aims for HDR-BT ({sup 192}Ir) and LDR-BT ({sup 125}I) were D{sub 90%} ≥34 Gy in 8.5 Gy per fraction and D{sub 90%} ≥145 Gy. Both physical and RBE-weighted dose distributions for protons and carbon-ions were converted to dose distributions based on 2-Gy(IsoE) fractions. From these dose distributions various dose and dose–volume parameters were extracted. Results: Rectal wall exposure 30-70 Gy(IsoE) was reduced for IMIT, LDR-BT, and HDR-BT when compared with VMAT and IMPT. The high-dose region of the BW dose–volume histogram above 50 Gy(IsoE) of IMPT resembled the VMAT shape, whereas all other techniques showed a significantly lower high-dose region. For all 3 EBRT techniques similar urethra D{sub mean} around 74 Gy(IsoE) were obtained. The LDR-BT results were approximately 30 Gy(IsoE) higher, HDR-BT 10 Gy(IsoE) lower. Normal tissue and femoral head sparing was best with BT. Conclusion: Despite the different EBRT prescription and fractionation schemes, the high-dose regions of BW and RW expressed in Gy(IsoE) were on the same order of magnitude. Brachytherapy techniques

  18. Both F-18 FDG-avidity and Malignant Shape of Cervical Lymph Nodes on PET/CT after Total Thyroidectomy Predict Resistance to High-dose I-131 Therapy in Patients with Papillary Thyroid Cancer

    PubMed Central

    Byun, Byung Hyun; Kwon, Seong Young; Chong, Ari; Kim, Jahae; Yoo, Su Woong; Min, Jung-Joon; Song, Ho-Chun; Bom, Henry Hee-Seung

    2013-01-01

    Objective: Resistance of metastatic lymph nodes (LNs) to high dose I-131 therapy is associated with high morbidity in patients with differentiated thyroid cancer. We evaluated the role of F-18 FDG PET/CT in the prediction of resistance to high dose I-131 therapy in patients with papillary thyroid cancer. Methods: The subjects were 307 patients who underwent total or near total thyroidectomy followed by high dose (5.55-6.66 GBq) I-131 therapy. We divided the patients into three subgroups by visual assessment of regional LNs: FDG-avid LNs with a malignant shape on CT (PET/CT-positive group), FDG-avid LNs with a benign shape on CT (PET/CT-intermediate group) and no FDG-avid lesion (PET/CT-negative group). We measured the maximum SUV (SUVmax) of FDG-avid LNs in each patient. The presence or absence of focal increased uptake of I-131 was evaluated by whole body scan (WBS), and was denoted as WBS-positive group or WBS-negative group, respectively. Resistance to therapy was defined as presence of thyroglobulin (Tg) in serum (Tg ≥1.0 ng/ml) 3-6 months after I-131 therapy. Univariate and multivariate analyses were performed to determine the relationship between resistance to I-131 therapy and various clinico-pathologic variables. Results: PET/CT-positive, intermediate, and negative groups included 20 (6.5%), 44 (14.3%) and 243 (79.2%) patients, respectively. The mean SUVmax was significantly higher in the PET/CT-positive group than that of the PET/CT-intermediate group (4.6 vs. 2.7, P <0.001). Univariate analysis revealed that the PET/CT-positive group (P <0.001), T2-4 stage (P <0.001), N1b stage (P = 0.001), lower dose (5.55 GBq) of I-131 (P <0.001), and the WBS-positive group (P = 0.029) were associated with resistance to therapy. In multivariate analysis, the PET/CT-positive group, lower dose of I-131, N1b stage, and T2-4 stage remained significant with odds ratios of 10.07 (P <0.001), 3.82 (P <0.001), 3.58 (P = 0.001), and 2.53 (P = 0.009), respectively. Conclusion

  19. Single high-dose etoposide and melphalan with non-cryopreserved autologous marrow rescue as primary therapy for relapsed, refractory and poor-prognosis Hodgkin's disease.

    PubMed Central

    Seymour, L. K.; Dansey, R. D.; Bezwoda, W. R.

    1994-01-01

    A simplified schedule of high-dose chemotherapy (HDC) consisting of melphalan (140 mg m-2) plus VP16 (2.5 g m-2) given over 12-18 h together with autologous non-cryopreserved autologous bone marrow transplant (ABMT) was used for treatment of relapsed (37 patients) and refractory (seven patients) patients and as first-line treatment (four patients) for poor-prognosis Hodgkin's disease. Two patients had a second HDC-ABMT after relapse following prior HDC-ABMT, giving a total of 50 procedures among 48 patients. The haematological recovery rate was 98% with a complete response rate of the Hodgkin's disease of > 90%. Factors significantly influencing response rate were performance status and the presence of liver involvement. Thirty-nine patients are alive, with 37 in continuous complete remission. The median duration of survival and median duration of remission have not been reached at a median follow-up time of 45 months. Adverse prognostic factors for survival were disease status at the time of HDC-ABMT (refractory versus relapse, with primarily refractory patients showing significantly poor survival) and the presence of liver involvement. High-dose chemotherapy with short-duration chemotherapy and non-cryopreserved bone marrow is an effective and safe treatment modality for patients with relapsed and poor-prognosis Hodgkin's disease. PMID:8080741

  20. High-dose caspofungin as a component of combination antifungal therapy in 91 patients with neoplastic diseases and hematopoietic stem cell transplantation: a critical review of short-term and long-term adverse events.

    PubMed

    Safdar, Amar; Rodriguez, Gilhen; Zuniga, Jorge; Al Akhrass, Fadi; Pande, Anupam

    2015-04-01

    The antifungal activity of echinocandins is concentration dependent. Previously, we demonstrated that high-dose caspofungin (HD-CSP; 100 mg daily) was well tolerated in 34 immunosuppressed patients with cancer and may have favorably influenced outcomes. We retrospectively assessed all 91 patients in whom HD-CSP was given for the treatment of invasive fungal disease (IFD). The median number of doses was 18.5 ± 21.5, and in 8 (9%) patients more than 40 doses were given. Most (62%) of the patients had leukemia. A total of 45 (49%) patients had undergone stem cell transplantation; 80% received allogeneic grafts and 47% had graft-versus-host disease. High-dose corticosteroids were given during antifungal therapy in 26 (29%) patients. In all, 8 (9%) patients had new elevation in serum bilirubin during HD-CSP therapy; normalization occurred after voriconazole and HD-CSP were discontinued in 4 patients each. No other short-term or delayed adverse events were observed. In all, 40 (44%) patients died of IFD. High-dose corticosteroids during HD-CSP (odds ratio [OR] 8, 95% confidence interval [CI] 2.1-30.4; P < .002) and starting HD-CSP in the critical care unit (OR 67.5, 95% CI 5.25-868.9; P < .001) were associated with death from fungal disease. Prolonged HD-CSP therapy was well tolerated. Drug-induced hyperbilirubinemia may pose a potential limitation for continued HD-CSP use in highly susceptible patients with hematologic neoplasms and stem cell transplantation. PMID:24366977

  1. [A case of an elderly patient having advanced hepatocellular carcinoma with tumor thrombus in the inferior vena cava treated with chemo-radio-therapy--intraarterial infusion of weekly high dose 5-FU (WHF)].

    PubMed

    Yabuuchi, Shinichi; Katayose, Yu; Rikiyama, Toshiki; Oikawa, Masaya; Yamamoto, Kuniharu; Onogawa, Toru; Hayashi, Hiroki; Muto, Mitsuhisa; Unno, Michiaki

    2006-11-01

    The patient was an 81-year-old man, diagnosed with advanced huge hepatocellular carcinoma (HCC) with tumor thrombus extending into the inferior vena cava (Vv3), for which resection was judged impossible. The radio therapy (51 Gy) for tumor thrombus was carried out, and he received a weekly hepatic arterial infusion therapy (weekly high-dose 5-fluorouracil (5-FU)) for these legions. After 8 cycles, the CT scan revealed a minor response of the tumor (SD), and,the tumor marker reduced. After 10 months, these legions had markedly regressed (PR), the tumor thrombus in the inferior vena cava was not detectable. There were no severe side effects. Ten months since the start of chemo-radio therapy, the positron emission tomography (PET) revealed a metastatic tumor of the femoral bone in recurrence. In conclusion, some elderly patients of advanced HCC with tumor thrombus may obtain a long term survival through this treatment. PMID:17212102

  2. Comparison of three methods of calculation, experimental and monte carlo simulation in investigation of organ doses (thyroid, sternum, cervical vertebra) in radioiodine therapy.

    PubMed

    Shahbazi-Gahrouei, Daryoush; Ayat, Saba

    2012-07-01

    Radioiodine therapy is an effective method for treating thyroid cancer carcinoma, but it has some affects on normal tissues, hence dosimetry of vital organs is important to weigh the risks and benefits of this method. The aim of this study is to measure the absorbed doses of important organs by Monte Carlo N Particle (MCNP) simulation and comparing the results of different methods of dosimetry by performing a t-paired test. To calculate the absorbed dose of thyroid, sternum, and cervical vertebra using the MCNP code, *F8 tally was used. Organs were simulated by using a neck phantom and Medical Internal Radiation Dosimetry (MIRD) method. Finally, the results of MCNP, MIRD, and Thermoluminescent dosimeter (TLD) measurements were compared by SPSS software. The absorbed dose obtained by Monte Carlo simulations for 100, 150, and 175 mCi administered (131)I was found to be 388.0, 427.9, and 444.8 cGy for thyroid, 208.7, 230.1, and 239.3 cGy for sternum and 272.1, 299.9, and 312.1 cGy for cervical vertebra. The results of paired t-test were 0.24 for comparing TLD dosimetry and MIRD calculation, 0.80 for MCNP simulation and MIRD, and 0.19 for TLD and MCNP. The results showed no significant differences among three methods of Monte Carlo simulations, MIRD calculation and direct experimental dosimetry using TLD. PMID:23717806

  3. Comparison of Three Methods of Calculation, Experimental and Monte Carlo Simulation in Investigation of Organ Doses (Thyroid, Sternum, Cervical Vertebra) in Radioiodine Therapy

    PubMed Central

    Shahbazi-Gahrouei, Daryoush; Ayat, Saba

    2012-01-01

    Radioiodine therapy is an effective method for treating thyroid cancer carcinoma, but it has some affects on normal tissues, hence dosimetry of vital organs is important to weigh the risks and benefits of this method. The aim of this study is to measure the absorbed doses of important organs by Monte Carlo N Particle (MCNP) simulation and comparing the results of different methods of dosimetry by performing a t-paired test. To calculate the absorbed dose of thyroid, sternum, and cervical vertebra using the MCNP code, *F8 tally was used. Organs were simulated by using a neck phantom and Medical Internal Radiation Dosimetry (MIRD) method. Finally, the results of MCNP, MIRD, and Thermoluminescent dosimeter (TLD) measurements were compared by SPSS software. The absorbed dose obtained by Monte Carlo simulations for 100, 150, and 175 mCi administered 131I was found to be 388.0, 427.9, and 444.8 cGy for thyroid, 208.7, 230.1, and 239.3 cGy for sternum and 272.1, 299.9, and 312.1 cGy for cervical vertebra. The results of paired t-test were 0.24 for comparing TLD dosimetry and MIRD calculation, 0.80 for MCNP simulation and MIRD, and 0.19 for TLD and MCNP. The results showed no significant differences among three methods of Monte Carlo simulations, MIRD calculation and direct experimental dosimetry using TLD. PMID:23717806

  4. Results of a prospective phase II trial evaluating interim positron emission tomography-guided high dose therapy for poor prognosis diffuse large B-cell lymphoma.

    PubMed

    Stewart, Douglas A; Kloiber, Reinhard; Owen, Carolyn; Bahlis, Nizar J; Duggan, Peter; Mansoor, Adnan; Bence-Bruckler, Isabelle

    2014-09-01

    Patients with diffuse large B-cell lymphoma (DLBCL) with a poor prognosis based upon advanced stage and elevated serum lactate dehydrogenase achieve a 3-4-year progression-free survival (PFS) of only 55%. The role of interim fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) to guide use of upfront high dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) for patients with poor prognosis DLBCL is unproven. A prospective phase II clinical trial was designed to evaluate the outcomes of HDCT/ASCT for patients with poor prognosis DLBCL aged 18-65 years who had unfavorable interim restaging PET scans. Of the 70 eligible patients, 36 had unfavorable and 34 favorable interim PET responses, with 3-year PFS rates of 65.2% and 52.7%, respectively. In conclusion, favorable interim PET response as defined in this study is not associated with improved PFS rates for patients with poor prognosis DLBCL treated with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). A phase III trial evaluating this PET-guided approach is not warranted. PMID:24188476

  5. Prophylaxis for Pneumocystis jiroveci pneumonia: is it a necessity in pulmonary patients on high-dose, chronic corticosteroid therapy without AIDS?

    PubMed

    Liebling, Maryjane; Rubio, Edmundo; Ie, Susanti

    2015-04-01

    The benefit of prophylaxis for Pneumocystis jirovecii pneumonia (PJP) is well documented in immunocompromised patients, particularly those with HIV and/or AIDS; therefore, guidelines dictate this as standard of care. However, there is a paucity of literature regarding those without HIV and/or AIDS who are potentially predisposed to PJP, including patients with sarcoidosis, cryptogenic organizing pneumonia, interstitial lung disease, asthma and chronic obstructive pulmonary disease, who may require high dose of prolonged corticosteroids for disease maintenance or to prevent relapses. In this review, the authors examine the available literature regarding prophylaxis in these groups, elaborate on the pathogenesis of PJP, when to suspect PJP in these patients, as well as explore current recommendations that guide clinical practice regarding implementation of PJP prophylaxis, namely with trimethoprim/sulfamethoxazole being the preferred agent. In summary, the role of PJP prophylaxis in non-HIV patients on chronic steroids remains controversial. The authors present a review of the literature to provide better guidance to the clinician regarding the need to initiate PJP prophylaxis in this patient population. PMID:25771943

  6. International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100).

    PubMed

    Giralt, S; Stadtmauer, E A; Harousseau, J L; Palumbo, A; Bensinger, W; Comenzo, R L; Kumar, S; Munshi, N C; Dispenzieri, A; Kyle, R; Merlini, G; San Miguel, J; Ludwig, H; Hajek, R; Jagannath, S; Blade, J; Lonial, S; Dimopoulos, M A; Einsele, H; Barlogie, B; Anderson, K C; Gertz, M; Attal, M; Tosi, P; Sonneveld, P; Boccadoro, M; Morgan, G; Sezer, O; Mateos, M V; Cavo, M; Joshua, D; Turesson, I; Chen, W; Shimizu, K; Powles, R; Richardson, P G; Niesvizky, R; Rajkumar, S V; Durie, B G M

    2009-10-01

    Multiple myeloma is the most common indication for high-dose chemotherapy with autologous stem cell support (ASCT) in North America today. Stem cell procurement for ASCT has most commonly been performed with stem cell mobilization using colony-stimulating factors with or without prior chemotherapy. The target CD34+ cell dose to be collected as well as the number of apheresis performed varies throughout the country, but a minimum of 2 million CD34+ cells/kg has been traditionally used for the support of one cycle of high-dose therapy. With the advent of plerixafor (AMD3100) (a novel stem cell mobilization agent), it is pertinent to review the current status of stem cell mobilization for myeloma as well as the role of autologous stem cell transplantation in this disease. On June 1, 2008, a panel of experts was convened by the International Myeloma Foundation to address issues regarding stem cell mobilization and autologous transplantation in myeloma in the context of new therapies. The panel was asked to discuss a variety of issues regarding stem cell collection and transplantation in myeloma especially with the arrival of plerixafor. Herein, is a summary of their deliberations and conclusions. PMID:19554029

  7. Early Intervention with High-Dose Steroid Pulse Therapy Prolongs Disease-Free Interval of Severe Alopecia Areata: A Retrospective Study

    PubMed Central

    Yang, Chao-Chun; Lee, Chun-Te; Hsu, Chao-Kai; Lee, Yi-Pei; Wong, Tak-Wah; Chao, Sheau-Chiou; Lee, Julia Yu-Yun; Sheu, Hamm-Ming

    2013-01-01

    Background Spontaneous recovery of severe alopecia areata is rare and the condition is difficult to treat. Objective The aim of this study is to investigate and compare the effects and safety of steroid pulse therapy between oral and intravenous administrations between 1999 and 2010 at the Department of Dermatology, National Cheng Kung University Hospital. Methods Data were retrospectively retrieved. A satisfactory response was defined as more than 75% hair regrowth in the balding area. Results A total of 85 patients with more than 50% hair loss were identified and treated, with an overall satisfactory response rate of 51.8%. The mean follow-up time was 37.6 months, with a relapse rate of 22.7%. Patients with alopecia areata (hereafter, AA) of recent onset within one year showed higher response rates (p<0.001) and lower relapse rates compared to patients with AA persisting for more than 1 year. Further, even in patients with alopecia totalis, alopecia universalis or ophiasis type, early treatment resulted in a satisfactory response rate of 47% among the treated patients. In general, oral therapy was as effective and well-tolerated as intravenous therapy. Conclusion The response rate is determined by disease severity and time of intervention, not by the administration form of steroid pulse therapy. Oral steroid pulse therapy can be considered as the first-line treatment for patients with severe AA of recent onset within one year. PMID:24371395

  8. Dosimetry analyses comparing high-dose-rate brachytherapy, administered as monotherapy for localized prostate cancer, with stereotactic body radiation therapy simulated using CyberKnife.

    PubMed

    Fukuda, Shoichi; Seo, Yuji; Shiomi, Hiroya; Yamada, Yuji; Ogata, Toshiyuki; Morimoto, Masahiro; Konishi, Koji; Yoshioka, Yasuo; Ogawa, Kazuhiko

    2014-11-01

    The purpose of this study was to perform dosimetry analyses comparing high-dose-rate brachytherapy (HDR-BT) with simulated stereotactic body radiotherapy (SBRT). We selected six consecutive patients treated with HDR-BT monotherapy in 2010, and a CyberKnife SBRT plan was simulated for each patient using computed tomography images and the contouring set used in the HDR-BT plan for the actual treatment, but adding appropriate planning target volume (PTV) margins for SBRT. Then, dosimetric profiles for PTVs of the rectum, bladder and urethra were compared between the two modalities. The SBRT plan was more homogenous and provided lower dose concentration but better coverage for the PTV. The maximum doses in the rectum were higher in the HDR-BT plans. However, the HDR-BT plan provided a sharper dose fall-off around the PTV, resulting in a significant and considerable difference in volume sparing of the rectum with the appropriate PTV margins added for SBRT. While the rectum D5cm(3) for HDR-BT and SBRT was 30.7 and 38.3 Gy (P < 0.01) and V40 was 16.3 and 20.8 cm(3) (P < 0.01), respectively, SBRT was significantly superior in almost all dosimetric profiles for the bladder and urethra. These results suggest that SBRT as an alternative to HDR-BT in hypofractionated radiotherapy for prostate cancer might have an advantage for bladder and urethra dose sparing, but for the rectum only when proper PTV margins for SBRT are adopted. PMID:24957754

  9. A dosimetric analysis of intensity-modulated radiation therapy (IMRT) as an alternative to adjuvant high-dose-rate (HDR) brachytherapy in early endometrial cancer patients

    SciTech Connect

    Aydogan, Bulent . E-mail: baydogan@radonc.uchicago.edu; Mundt, Arno J.; Smith, Brett D.; Mell, Loren K.; Wang, Steve; Sutton, Harold; Roeske, John C.

    2006-05-01

    Purpose: To evaluate the role of intensity-modulated radiation treatment (IMRT) as an alternative to high-dose-rate (HDR) brachytherapy in the treatment of the vagina in postoperative early endometrial cancer patients after surgery. Methods and Materials: Planning computed tomography (CT) scans of 10 patients previously treated with HDR were used in this study. In all cases, a dose of 700 cGy/fraction was prescribed at a distance of 0.5 cm from the cylinder surface. The same CT scans were then used in IMRT planning. In this paradigm, the vaginal cylinder represents a component of a hypothetical immobilization system that would be indexed to the linac treatment table. Results: Our study showed that IMRT provided relatively lower rectal doses than HDR when treatment was prescribed at a distance of 0.5 cm away from the cylinder surface. Maximum rectal doses were lower with IMRT compared with HDR (average: 89.0% vs. 142.6%, respectively, p < 0.05). Moreover, the mean rectal dose was lower in IMRT plans compared with HDR plans with treatment prescribed either to the surface (average: 14.8% vs. 21.4%, respectively, p < 0.05) or to 0.5 cm (average: 19.6% vs. 33.5%, respectively, p < 0.05). IMRT plans had planning target volume (PTV) coverage comparable with HDR (average PTV minimum for treatment prescribed to 0.5 cm: 93.9% vs. 92.1%, p = 0.71, respectively) with less inhomogeneity (average PTV maximum: 110.8% vs. 381.6%, p < 0.05). Conclusion: Our dosimetric analysis suggests that when used in conjunction with a suitable immobilization system, IMRT may provide an alternative to HDR brachytherapy in women with early endometrial cancer after hysterectomy. However, more studies are needed to evaluate the clinical merit of the IMRT in these patients.

  10. High-dose chemotherapy and autologous stem cell support followed by post-transplant doxorubicin and taxol as initial therapy for metastatic breast cancer: hematopoietic tolerance and efficacy.

    PubMed

    deMagalhaes-Silverman, M; Hammert, L; Lembersky, B; Lister, J; Rybka, W; Ball, E

    1998-06-01

    A multistep HDC regimen was designed as first-line chemotherapy for MBC. Twenty-four patients with MBC and no previous chemotherapy for metastatic disease were treated with high-dose cyclophosphamide (5000 mg/m2), and etoposide (1000 mg/m2) (CyVP16), followed by granulocyte colony-stimulating factor (G-CSF). Peripheral blood stem cells (PBSCs) were collected. Subsequently patients received cyclophosphamide (6000 mg/m2), thiotepa (500 mg/m2) and carboplatin (800 mg/m2) (CTCb) with hematopoietic rescue. Upon recovery from hematopoietic and gastrointestinal toxicity three cycles of doxorubicin (50 mg/m2) and taxol (150 mg/m2) were delivered. After CyVP16 42% of patients developed neutropenic fevers. There was one documented episode of bacteremia. Patients received CTCb 32 days after starting CyVP16. After CTCb the median number of days to ANC >5 x 10(9)/l was 10 and to a platelet count >20 x 10(9)/l was 14. Neutropenic fevers developed in 16 patients. There were no hemorrhagic episodes. A total of 69 cycles of doxorubicin and taxol were delivered (87% of planned). The median time from PBSC infusion to the first cycle was 38 days. The median time to the second cycle was 27 days and to the last cycle was 24 days. One patient developed congestive heart failure. Two episodes of neutropenic fevers were observed. No toxicity-related deaths were observed. Grafts are stable at 6 months post transplantation. This multistep regimen is feasible with acceptable toxicity. PMID:9674853

  11. The Impact of Dose to the Bladder Trigone on Long-Term Urinary function after High-Dose Intensity-Modulated Radiation Therapy for Localized Prostate Cancer

    PubMed Central

    Ghadjar, Pirus; Zelefsky, Michael J.; Spratt, Daniel E.; af Rosenschöld, Per Munck; Oh, Jung Hun; Hunt, Margie; Kollmeier, Marisa; Happersett, Laura; Yorke, Ellen; Deasy, Joseph O.; Jackson, Andrew

    2015-01-01

    Purpose To determine the potential association between genitourinary (GU) toxicity and planning dose-volume parameters for GU pelvic structures after high-dose intensity-modulated radiotherapy (IMRT) in localized prostate cancer patients. Methods and Materials 268 patients who underwent IMRT to a prescribed dose of 86.4 Gy in 48 fractions during 06/2004–12/2008 were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Dose volume histograms of the whole bladder, bladder wall, urethra, and bladder trigone were analyzed. The primary endpoint for GU toxicity was an IPSS sum increase ≥10 points over baseline. Univariate and multivariate analyses were done by Kaplan-Meier method and Cox proportional hazard models, respectively. Results Median follow-up was 5 years (range, 3–7.7 years). Thirty-nine patients experienced an IPSS sum increase ≥10 during follow-up; 84% remained event free at 5 years. After univariate analysis, lower baseline IPSS sum (P=0.006), the V90 of the trigone (P=0.006), and the maximal dose to the trigone (P=0.003) were significantly associated with an IPSS sum increase ≥10. After multivariate analysis, lower baseline IPSS sum (P=0.009) and increased maximal dose to the trigone (P=0.005) remained significantly associated. Seventy-two patients had both a lower baseline IPSS sum and a higher maximal dose to the trigone and were defined as high-risk and 68 patients had both a higher baseline IPSS sum and a lower maximal dose to the trigone and were defined as low-risk for development of an IPSS sum increase ≥10. Twenty-one of 72 high-risk (29%) and 5 of 68 low-risk (7%) patients experienced an IPSS sum increase ≥10 (P=0.001; odds ratio, 5.19). Conclusions The application of hot spots to the bladder trigone was significantly associated with relevant changes in IPSS during follow-up. Reduction of radiation dose to the lower bladder and specifically the bladder trigone appears to be associated with a reduction in late

  12. Evaluation of intranasal vaccine administration and high-dose interferon- α2b therapy for treatment of chronic upper respiratory tract infections in shelter cats.

    PubMed

    Fenimore, Audra; Carter, Kasey; Fankhauser, Jeffrey; Hawley, Jennifer R; Lappin, Michael R

    2016-08-01

    Clinical signs of upper respiratory tract infection can be hard to manage in cats, particularly those in shelters. In this study, clinical data were collected from chronically ill (3-4 weeks' duration) cats with suspected feline herpesvirus-1 (FHV-1) or feline calicivirus (FCV) infections after administration of one of two novel therapies. Group A cats were administered a commercially available formulation of human interferon-α2b at 10,000 U/kg subcutaneously for 14 days, and group B cats were administered one dose of a FHV-1 and FCV intranasal vaccine. Molecular assays for FHV-1 and FCV were performed on pharyngeal samples, and a number of cytokines were measured in the blood of some cats. A clinical score was determined daily for 14 days, with cats that developed an acceptable response by day 14 returning to the shelter for adoption. Those failing the first treatment protocol were entered into the alternate treatment group. During the first treatment period, 8/13 cats in group A (61.5%) and all 12 cats in group B (100%) had apparent responses. The seven cats positive for nucleic acids of FHV-1 or FCV responded favorably, independent of the treatment group. There were no differences in cytokine levels between cats that responded to therapy or failed therapy. Either protocol assessed here may be beneficial in alleviating chronic clinical signs of suspected feline viral upper respiratory tract disease in some cats that have failed other, more conventional, therapies. The results of this study warrant additional research involving these protocols. PMID:26269455

  13. Feasibility and efficacy of high-dose three-dimensional-conformal radiotherapy in cirrhotic patients with small-size hepatocellular carcinoma non-eligible for curative therapies-mature results of the French Phase II RTF-1 trial

    SciTech Connect

    Mornex, Francoise . E-mail: francoise.mornex@chu-lyon.fr; Girard, Nicolas; Beziat, Christophe; Kubas, Abdul; Khodri, Mustapha; Trepo, Christian; Merle, Philippe

    2006-11-15

    Purpose: Hepatocellular carcinoma (HCC) is a poor prognosis tumor, and only 20% of patients will benefit from curative therapies (surgery, liver transplantation, percutaneous ablation). Although conventional radiotherapy has been traditionally regarded as inefficient and toxic for cirrhotic patients, three-dimensional conformal radiotherapy (3DCRT) has provided promising preliminary data for the treatment of HCC. Methods and Materials: Prospective phase II trial including Child-Pugh A/B cirrhotic patients with small-size HCC (1 nodule {<=}5 cm, or 2 nodules {<=}3 cm) nonsuitable for curative treatments, to assess tolerance and efficacy of high-dose (66 Gy, 2 Gy/fraction) 3DCRT. Results: Twenty-seven patients were enrolled. Among the 25 assessable patients, tumor response was observed for 23 patients (92%), with complete response for 20 patients (80%), and partial response for 3 patients (12%). Stable disease was observed in 2 patients (8%). Grade 4 toxicities occurred in 2 of 11 (22%) Child-Pugh B patients only. Child-Pugh A patients tolerated treatment well, and 3/16 (19%) developed asymptomatic Grade 3 toxicities. Conclusion: High-dose 3DCRT is a noninvasive, well-tolerated modality that is highly suitable for the treatment of small HCCs in cirrhotic patients, with promising results. However, additional trials are needed to optimize this technique and formally compare it with the usual curative approaches.

  14. Randomized Noninferiority Trial of Reduced High-Dose Volume Versus Standard Volume Radiation Therapy for Muscle-Invasive Bladder Cancer: Results of the BC2001 Trial (CRUK/01/004)

    SciTech Connect

    Huddart, Robert A.; Hall, Emma; Hussain, Syed A.; Jenkins, Peter; Rawlings, Christine; Tremlett, Jean; Crundwell, Malcolm; Adab, Fawzi A.; Sheehan, Denise; Syndikus, Isabel; Hendron, Carey; Lewis, Rebecca; Waters, Rachel; James, Nicholas D.

    2013-10-01

    Purpose: To test whether reducing radiation dose to uninvolved bladder while maintaining dose to the tumor would reduce side effects without impairing local control in the treatment of muscle-invasive bladder cancer. Methods and Materials: In this phase III multicenter trial, 219 patients were randomized to standard whole-bladder radiation therapy (sRT) or reduced high-dose volume radiation therapy (RHDVRT) that aimed to deliver full radiation dose to the tumor and 80% of maximum dose to the uninvolved bladder. Participants were also randomly assigned to receive radiation therapy alone or radiation therapy plus chemotherapy in a partial 2 × 2 factorial design. The primary endpoints for the radiation therapy volume comparison were late toxicity and time to locoregional recurrence (with a noninferiority margin of 10% at 2 years). Results: Overall incidence of late toxicity was less than predicted, with a cumulative 2-year Radiation Therapy Oncology Group grade 3/4 toxicity rate of 13% (95% confidence interval 8%, 20%) and no statistically significant differences between groups. The difference in 2-year locoregional recurrence free rate (RHDVRT − sRT) was 6.4% (95% confidence interval −7.3%, 16.8%) under an intention to treat analysis and 2.6% (−12.8%, 14.6%) in the “per-protocol” population. Conclusions: In this study RHDVRT did not result in a statistically significant reduction in late side effects compared with sRT, and noninferiority of locoregional control could not be concluded formally. However, overall low rates of clinically significant toxicity combined with low rates of invasive bladder cancer relapse confirm that (chemo)radiation therapy is a valid option for the treatment of muscle-invasive bladder cancer.

  15. Serum PCSK9 Levels Distinguish Individuals Who Do Not Respond to High-Dose Statin Therapy with the Expected Reduction in LDL-C

    PubMed Central

    Taylor, Beth A.; Panza, Gregory; Pescatello, Linda S.; Chipkin, Stuart; Gipe, Daniel; Shao, Weiping; White, C. Michael; Thompson, Paul D.

    2014-01-01

    The purpose of the present report was to examine whether proprotein convertase subtilisin/kexin type 9 (PCSK9) levels differ in individuals who do not exhibit expected reductions in low density lipoprotein cholesterol (LDL-C) with statin therapy. Eighteen nonresponder subjects treated with 80 mg atorvastatin treatment for 6 months without substantial reductions in LDL-C (ΔLDL-C: 2.6 ± 11.4%) were compared to age- and gender-matched atorvastatin responders (ΔLDL-C: 50.7 ± 8.5%) and placebo-treated subjects (ΔLDL-C: 9.9 ± 21.5%). Free PCSK9 was marginally higher in nonresponders at baseline (P = 0.07) and significantly higher in atorvastatin responders after 6 months of treatment (P = 0.04). The change in free PCSK9 over 6 months with statin treatment was higher (P < 0.01) in atorvastatin responders (134.2 ± 131.5 ng/mL post- versus prestudy) than in either the nonresponders (39.9 ± 87.8 ng/mL) or placebo subjects (27.8 ± 97.6 ng/mL). Drug compliance was not lower in the nonresponders as assessed by pill counts and poststudy plasma atorvastatin levels. Serum PCSK9 levels, both at baseline and in response to statin therapy, may differentiate individuals who do versus those who do not respond to statin treatment. PMID:25136459

  16. Radioiodine and radiotherapy in the management of thyroid cancers

    SciTech Connect

    Simpson, W.J. )

    1990-06-01

    Radioiodine is an important adjuvant treatment in the management of resectable papillary and follicular thyroid cancers in all patients except those with the best prognostic features. External radiation is also an important adjuvant therapy in these patients, especially those with tumors that extend beyond the thyroid gland and invade the trachea, esophagus, nerves, and blood vessels; it is especially important in treating patients whose tumors do not concentrate radioiodine. Radioiodine may be curative in patients with microscopic distant metastases demonstrated by radioiodine scanning. Even unresectable primary papillary and follicular cancers may be eradicated by combined therapy with radioiodine and radiotherapy. Radioiodine plays no significant role in the treatment of medullary or anaplastic thyroid cancers, but external radiation may eradicate microscopic thyroid bed or nodal disease when persistent disease is indicated by elevated calcitonin levels in medullary thyroid cancer patients. Anaplastic thyroid cancers are usually unresectable and are not eradicated by conventional radiotherapy or by any of the novel radiation techniques, with or without chemotherapy. In all types of thyroid cancer, external radiotherapy may produce beneficial palliative results in patients with distant metastases, but the use of radioiodine should always be explored in papillary and follicular thyroid cancer patients. 30 references.

  17. Direct exposure of mouse ovaries and oocytes to high doses of an adenovirus gene therapy vector fails to lead to germ cell transduction.

    PubMed

    Gordon, J W

    2001-04-01

    The risk of insertion of adenovirus gene therapy DNA into female germ cells during the course of somatic gene therapy was stringently tested in the mouse by injecting up to 10(10) infectious particles directly into the ovary and by incubating naked oocytes in a solution of 2 x 10(8) particles/ml for 1 h prior to in vitro fertilization (IVF). The vector used was a recombinant adenovirus carrying the bacterial lacZ gene driven by the cytomegalovirus promoter (Adbeta-gal). Ovaries were stained for LacZ activity, or immunochemically for LacZ, 5-7 days after injection. Although very large amounts of LacZ activity and protein were detected, all positive staining was in the thecal portion of the ovary, with no staining seen in oocytes. In another series of experiments, mice with injected ovaries were mated, and preimplantation embryos or fetuses were analyzed either for LacZ expression or by PCR for lacZ DNA. None of 202 preimplantation embryos stained positively for LacZ and none of 58 fetuses were positive for DNA by PCR analysis. Finally, more than 1400 eggs were fertilized after exposure to the vector prior to IVF and stained as morulae for LacZ activity. Fewer than 2% of the embryos stained positively for LacZ, and experiments indicated that the staining was due to incomplete washing of the eggs prior to IVF. These data provide strong evidence that adenoviruses cannot infect oocytes and that the risk of female germ-line transduction with such vectors is very low. PMID:11319918

  18. External-Beam Radiation Therapy and High-Dose Rate Brachytherapy Combined With Long-Term Androgen Deprivation Therapy in High and Very High Prostate Cancer: Preliminary Data on Clinical Outcome

    SciTech Connect

    Martinez-Monge, Rafael; Moreno, Marta; Ciervide, Raquel; Cambeiro, Mauricio; Perez-Gracia, Jose Luis; Gil-Bazo, Ignacio; Gaztanaga, Miren; Arbea, Leire; Pascual, Ignacio; Aristu, Javier

    2012-03-01

    Purpose: To determine the feasibility of combined long-term androgen deprivation therapy (ADT) and dose escalation with high-dose-rate (HDR) brachytherapy. Methods and Materials: Between 2001 and 2007, 200 patients with high-risk prostate cancer (32.5%) or very high-risk prostate cancer (67.5%) were prospectively enrolled in this Phase II trial. Tumor characteristics included a median pretreatment prostate-specific antigen of 15.2 ng/mL, a clinical stage of T2c, and a Gleason score of 7. Treatment consisted of 54 Gy of external irradiation (three-dimensional conformal radiotherapy [3DCRT]) followed by 19 Gy of HDR brachytherapy in four twice-daily treatments. ADT started 0-3 months before 3DCRT and continued for 2 years. Results: One hundred and ninety patients (95%) received 2 years of ADT. After a median follow-up of 3.7 years (range, 2-9), late Grade {>=}2 urinary toxicity was observed in 18% of the patients and Grade {>=}3 was observed in 5%. Prior transurethral resection of the prostate (p = 0.013) and bladder D{sub 50} {>=}1.19 Gy (p = 0.014) were associated with increased Grade {>=}2 urinary complications; age {>=}70 (p = 0.05) was associated with Grade {>=}3 urinary complications. Late Grade {>=}2 gastrointestinal toxicity was observed in 9% of the patients and Grade {>=}3 in 1.5%. CTV size {>=}35.8 cc (p = 0.007) and D{sub 100} {>=}3.05 Gy (p = 0.01) were significant for increased Grade {>=}2 complications. The 5-year and 9-year biochemical relapse-free survival (nadir + 2) rates were 85.1% and 75.7%, respectively. Patients with Gleason score of 7-10 had a decreased biochemical relapse-free survival (p = 0.007). Conclusions: Intermediate-term results at the 5-year time point indicate a favorable outcome without an increase in the rate of late complications.

  19. X-ray induced Sm3+ to Sm2+ conversion in fluorophosphate and fluoroaluminate glasses for the monitoring of high-doses in microbeam radiation therapy

    NASA Astrophysics Data System (ADS)

    Vahedi, Shahrzad; Okada, Go; Morrell, Brian; Muzar, Edward; Koughia, Cyril; Edgar, Andy; Varoy, Chris; Belev, George; Wysokinski, Tomasz; Chapman, Dean; Kasap, Safa

    2012-10-01

    Fluorophosphate and fluoroaluminate glasses doped with trivalent samarium were evaluated as sensors of x-ray radiation for microbeam radiation therapy at the Canadian Light Source using the conversion of trivalent Sm3+ to the divalent form Sm2+. Both types of glasses show similar conversion rates and may be used as a linear sensor up to ˜150 Gy and as a nonlinear sensor up to ˜2400 Gy, where saturation is reached. Experiments with a multi-slit collimator show high spatial resolution of the conversion pattern; the pattern was acquired by a confocal fluorescence microscopy technique. The effects of previous x-ray exposure may be erased by annealing at temperatures exceeding the glass transition temperature Tg while annealing at TA < Tg enhances the Sm conversion. This enhancement is explained by a thermally stimulated relaxation of host glass ionic matrix surrounding x-ray induced Sm2+ ions. In addition, some of the Sm3+-doped glasses were codoped with Eu2+-ions but the results show that there is no marked improvement in the conversion efficiency by the introduction of Eu2+.

  20. Radioiodine-induced thyroid storm. Case report and literature review

    SciTech Connect

    McDermott, M.T.; Kidd, G.S.; Dodson, L.E. Jr.; Hofeldt, F.D.

    1983-08-01

    Thyroid storm developed following radioiodine therapy in a 43-year-old man with Graves' disease, weight loss, myopathy, severe thyrotoxic hypercalcemia, and a pituitary adenoma. The hypercalcemia may have been a significant, and previously unreported, predisposing factor for the radioiodine-associated thyroid storm. This case and 15 other well-documented cases of radioiodine-associated storm found in the literature are reviewed, as are several other cases of less severe exacerbations of thyrotoxicosis associated with radioiodine therapy. Although not often seen, these complications are often fatal. High-risk patients, such as the elderly, those with severe thyrotoxicosis, and those with significant underlying diseases, may benefit from preventive measures such as the judicious use of thyrostatic medications during the periods before and after isotope administration.

  1. High-Dose Hypofractionated Proton Beam Radiation Therapy Is Safe and Effective for Central and Peripheral Early-Stage Non-Small Cell Lung Cancer: Results of a 12-Year Experience at Loma Linda University Medical Center

    SciTech Connect

    Bush, David A.; Cheek, Gregory; Zaheer, Salman; Wallen, Jason; Mirshahidi, Hamid; Katerelos, Ari; Grove, Roger; Slater, Jerry D.

    2013-08-01

    Purpose: We update our previous reports on the use of hypofractionated proton beam radiation therapy for early-stage lung cancer patients. Methods and Materials: Eligible subjects had biopsy-proven non-small cell carcinoma of the lung and were medically inoperable or refused surgery. Clinical workup required staging of T1 or T2, N0, M0. Subjects received hypofractionated proton beam therapy to the primary tumor only. The dose delivered was sequentially escalated from 51 to 60 Gy, then to 70 Gy in 10 fractions over 2 weeks. Endpoints included toxicity, pulmonary function, overall survival (OS), disease-specific survival (DSS), and local control (LC). Results: One hundred eleven subjects were analyzed for treatment outcomes. The patient population had the following average characteristics; age 73.2 years, tumor size 3.6 cm, and 1.33 L forced expiratory volume in 1 second. The entire group showed improved OS with increasing dose level (51, 60, and 70 Gy) with a 4-year OS of 18%, 32%, and 51%, respectively (P=.006). Peripheral T1 tumors exhibited LC of 96%, DSS of 88%, and OS of 60% at 4 years. Patients with T2 tumors showed a trend toward improved LC and survival with the 70-Gy dose level. On multivariate analysis, larger tumor size was strongly associated with increased local recurrence and decreased survival. Central versus peripheral location did not correlate with any outcome measures. Clinical radiation pneumonitis was not found to be a significant complication, and no patient required steroid therapy after treatment for radiation pneumonitis. Pulmonary function was well maintained 1 year after treatment. Conclusions: High-dose hypofractionated proton therapy achieves excellent outcomes for lung carcinomas that are peripherally or centrally located. The 70-Gy regimen has been adopted as standard therapy for T1 tumors at our institution. Larger T2 tumors show a trend toward improved outcomes with higher doses, suggesting that better results could be seen with

  2. Computer-aided detection of therapy-induced leukoencephalopathy in pediatric acute lymphoblastic leukemia patients treated with intravenous high-dose methotrexate.

    PubMed

    Glass, John O; Reddick, Wilburn E; Li, Chin-Shang; Laningham, Fred H; Helton, Kathleen J; Pui, Ching-Hon

    2006-07-01

    The purpose of this study was to use objective quantitative magnetic resonance imaging (MRI) methods to develop a computer-aided detection (CAD) tool to differentiate white matter (WM) hyperintensities into either leukoencephalopathy (LE) induced by chemotherapy or normal maturational processes in children treated for acute lymphoblastic leukemia without irradiation. A combined MRI set consisting of T1-weighted, T2-weighted, proton-density-weighted and fluid-attenuated inversion recovery images and WM, gray matter and cerebrospinal fluid proportional volume maps from a spatially normalized atlas were analyzed with a neural network segmentation based on a Kohonen self-organizing map (SOM). Segmented maps were manually classified to identify the most hyperintense WM region and the normal-appearing genu region. Signal intensity differences normalized to the genu within each examination were generated for four time points in 228 children. A second Kohonen SOM was trained on the first examination data and divided the WM into normal-appearing or LE groups. Reviewing labels from the CAD tool revealed a consistency measure of 89.8% (167 of 186) within patients. The overall agreement between the CAD tool and the consensus reading of two trained observers was 84.1% (535 of 636), with 84.2% (170 of 202) agreement in the training set and 84.1% (365 of 434) agreement in the testing set. These results suggest that subtle therapy-induced LE can be objectively and reproducibly detected in children treated for cancer using this CAD approach based on relative differences in quantitative signal intensity measures normalized within each examination. PMID:16824973

  3. High-dose cytosine-arabinoside and cisplatin regimens as salvage therapy for refractory or relapsed AIDS-related non-Hodgkin's lymphoma.

    PubMed

    Bi, J; Espina, B M; Tulpule, A; Boswell, W; Levine, A M

    2001-12-15

    No effective salvage regimen has been defined for patients with AIDS-related non-Hodgkin's lymphoma (AIDS-NHL) who do not respond to first-line chemotherapy that contains anthracycline. Combined dexamethasone, cytosine arabinoside, and cisplatin (DHAP) and etoposide, methylprednisolone, cytosine arabinoside, and cisplatin (ESHAP) have shown good response rates in HIV-negative patients with relapsed lymphomas. We retrospectively analyzed patients with refractory or relapsed AIDS-NHL who had been treated with either DHAP or ESHAP to evaluate the feasibility and efficacy of these regimens. Twenty-six patients with refractory or relapsed AIDS-NHL were treated between 1990 and 1999 either with DHAP ( n = 13) or with ESHAP ( n = 13). Only 1 patient from each group (8%) had achieved complete remission with any previous therapy, and most had progressive disease after the regimen immediately preceding DHAP or ESHAP. In the ESHAP group, 4 patients (31%) achieved complete remission (CR) and 3 patients (23%) attained partial remission (PR) for an overall response rate of 54%. The median survival was 7.1 months (range, 1-58.9+ months) from the time ESHAP was begun. Among the 3 patients with primary refractory lymphoma, there was 1 CR, 1 PR, and one patient with stable disease. In contrast, only 1 PR (7%) was observed with DHAP; the median survival was 3 months. Myelosuppression was the most significant toxicity with grade 4 neutropenia occurring in all who received ESHAP and in 54% of patients treated with DHAP. Neutropenic fever occurred in 8 (62%) ESHAP-treated and 6 (46%) DHAP-treated patients. Although hematologic toxicity is profound, ESHAP appears to be an active salvage regimen for patients with relapsed or refractory AIDS-NHL. PMID:11744828

  4. Indirect Tumor Cell Death After High-Dose Hypofractionated Irradiation: Implications for Stereotactic Body Radiation Therapy and Stereotactic Radiation Surgery

    SciTech Connect

    Song, Chang W.; Lee, Yoon-Jin; Griffin, Robert J.; Park, Inhwan; Koonce, Nathan A.; Hui, Susanta; Kim, Mi-Sook; Dusenbery, Kathryn E.; Sperduto, Paul W.; Cho, L. Chinsoo

    2015-09-01

    Purpose: The purpose of this study was to reveal the biological mechanisms underlying stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS). Methods and Materials: FSaII fibrosarcomas grown subcutaneously in the hind limbs of C3H mice were irradiated with 10 to 30 Gy of X rays in a single fraction, and the clonogenic cell survival was determined with in vivo–in vitro excision assay immediately or 2 to 5 days after irradiation. The effects of radiation on the intratumor microenvironment were studied using immunohistochemical methods. Results: After cells were irradiated with 15 or 20 Gy, cell survival in FSaII tumors declined for 2 to 3 days and began to recover thereafter in some but not all tumors. After irradiation with 30 Gy, cell survival declined continuously for 5 days. Cell survival in some tumors 5 days after 20 to 30 Gy irradiation was 2 to 3 logs less than that immediately after irradiation. Irradiation with 20 Gy markedly reduced blood perfusion, upregulated HIF-1α, and increased carbonic anhydrase-9 expression, indicating that irradiation increased tumor hypoxia. In addition, expression of VEGF also increased in the tumor tissue after 20 Gy irradiation, probably due to the increase in HIF-1α activity. Conclusions: Irradiation of FSaII tumors with 15 to 30 Gy in a single dose caused dose-dependent secondary cell death, most likely by causing vascular damage accompanied by deterioration of intratumor microenvironment. Such indirect tumor cell death may play a crucial role in the control of human tumors with SBRT and SRS.

  5. Effective method of measuring the radioactivity of [131I]-capsule prior to radioiodine therapy with significant reduction of the radiation exposure to the medical staff.

    PubMed

    Lützen, Ulf; Zhao, Yi; Marx, Malies; Imme, Thea; Assam, Isong; Siebert, Frank-Andre; Culman, Juaraj; Zuhayra, Maaz

    2016-01-01

    Radiation Protection in Radiology, Nuclear Medicine and Radio Oncology is of the utmost importance. Radioiodine therapy is a frequently used and effective method for the treatment of thyroid disease. Prior to each therapy the radioactivity of the [131I]-capsule must be determined to prevent misadministration. This leads to a significant radiation exposure to the staff. We describe an alternative method, allowing a considerable reduction of the radiation exposure. Two [131I]-capsules (A01 = 2818.5; A02 = 7355.0 MBq) were measured multiple times in their own delivery lead containers - that is to say, [131I]-capsules remain inside the containers during the measurements (shielded measurement) using a dose calibrator and a well-type and a thyroid uptake probe. The results of the shielded measurements were correlated linearly with the [131I]-capsules radioactivity to create calibration curves for the used devices. Additional radioactivity measurements of 50 [131I]-capsules of different radioactivities were done to validate the shielded measuring method. The personal skin dose rate (HP(0.07)) was determined using calibrated thermo luminescent dosimeters. The determination coefficients for the calibration curves were R2 > 0.9980 for all devices. The relative uncertainty of the shielded measurement was < 6.8%. At a distance of 10 cm from the unshielded capsule the HP(0.07) was 46.18 μSv/(GBq•s), and on the surface of the lead container containing the [131I]-capsule the HP(0.07) was 2.99 and 0.27 μSv/(GBq•s) for the two used container sizes. The calculated reduction of the effective dose by using the shielded measuring method was, depending on the used container size, 74.0% and 97.4%, compared to the measurement of the unshielded [131I]-capsule using a dose calibrator. The measured reduction of the effective radiation dose in the practice was 56.6% and 94.9 for size I and size II containers. The shielded [131I]-capsule measurement reduces the radiation exposure to the

  6. The incidence of ophthalmopathy after radioiodine therapy for Graves` disease: Prognostic factors and the role of methimazole

    SciTech Connect

    Kung, A.W.C.; Cheng, A.

    1994-08-01

    Radioactive iodine-131 (RAI) has been reported to be associated with a high incidence of development or exacerbation of Graves` ophthalmopathy (GO). This is thought to be associated with a surge of autoantibodies after RAI therapy. The role of methimazole (MMI), which possesses immunomodulatory action, in the prevention of GO was explored by studying 114 patients with Graves` disease. They were assigned randomly to receive either RAI alone or adjunctive antithyroid drugs, which consisted of MMI and L-T{sub 4} as a block-replacement therapy for 12 months and were followed for 2 yr. Thirty-five patients (30.7%) had GO at presentation. Twenty-one (18%) patients developed new GO, and six had worsening of preexisting GO. The development of hypothyroidism (P < 0.01) and an elevation of TSH (P < 0.05) were associated with increased risk of development or exacerbation of GO. The chance of development or exacerbation of GO is higher in those with no ophthalmopathy than in those with preexisting GO at presentation (P = 0.002). The incidence of development or exacerbation of GO was similar in the two treatment groups (RAI, 22.8%; adjunctive antithyroid drugs, 23.7%; P = NS). MMI was able to suppress the surge of TSH receptor antibody (TRAB) after RAI, but a surge in TRAB was not of prognostic significance for the development of GO after RAI. Patients who developed or had exacerbation of GO actually had lower TRAB at presentation (P = 0.02). The authors conclude that hypothyroidism with elevated TSH is an important adverse factor for the development or exacerbation of GO, and MMI was unable to prevent the development or exacerbation of GO after RAI. 35 refs., 4 tabs.

  7. Modification of a motel-type room to accommodate patients receiving radioiodine therapy: reduction of environmental exposure.

    PubMed

    Pickering, Charles A; Dykes, James N; Domingo, Michelle T; Patricko, Joseph; Yamauchi, Dave M; Williams, Lawrence E

    2012-08-01

    Patients receiving ¹³¹I-based therapies are generally restricted in leaving the medical institution. In the U.S., the U.S. Nuclear Regulatory Commission (U.S. NRC) has developed the rule that a ≤ 7 mR h⁻¹ reading at 1 m from the patient (or 33 mCi) is sufficient to allow unrestricted release. Because of home situations and other constraints, it is preferable that a patient-specific release level be determined by the radiation safety staff. Locally, the City of Hope has instituted a general release criterion of ≤ 2 mR h⁻¹ at 1 m. While contributing to a reduction in public exposure, this as low as reasonably achievable (ALARA) approach is difficult to justify on a cost basis due to the expense of maintaining the radioactive individual in a hospital room. Instead, it was determined that a motel-type room already on the campus be modified to allow the patient to remain on-site until at or below a locally permitted release level. By adding lead to the bathroom area and sealing the tile surfaces, the room may be converted for less than $5,000. Daily cost for the patient is $65. In comparing the use of this facility for thyroid cancer patients from 2006 to 2010, it was found that the public exposure at 1 m was reduced by approximately 70% as compared to release at the 7 mR h level. In addition, controlling the release reduces the likelihood of a radiation incident in the public environment such as on public transportation or in a hotel. PMID:22739966

  8. Radioiodinated branched carbohydrates

    DOEpatents

    Goodman, Mark M.; Knapp, Jr., Furn F.

    1989-01-01

    A radioiodinated branched carbohydrate for tissue imaging. Iodine-123 is stabilized in the compound by attaching it to a vinyl functional group that is on the carbohydrate. The compound exhibits good uptake and retention and is promising in the development of radiopharmaceuticals for brain, heart and tumor imaging.

  9. Radioiodine: the classic theranostic agent.

    PubMed

    Silberstein, Edward B

    2012-05-01

    Radioiodine has the distinction of being the first theranostic agent in our armamentarium. Millennia were required to discover that the agent in orally administered seaweed and its extracts, which had been shown to cure neck swelling due to thyromegaly, was iodine, first demonstrated to be a new element in 1813. Treatment of goiter with iodine began at once, but its prophylactic value to prevent a common form of goiter took another century. After Enrico Fermi produced the first radioiodine, (128)I, in 1934, active experimentation in the United States and France delineated the crucial role of iodine in thyroid metabolism and disease. (130)I and (131)I were first employed to treat thyrotoxicosis by 1941, and thyroid cancer in 1943. After World War II, (131)I became widely available at a reasonable price for diagnostic testing and therapy. The rectilinear scanner of Cassen and Curtis (Science 1949;110:94-95), and a dedicated gamma camera invented by Anger (Nature 1952;170:200-201), finally permitted the diagnostic imaging of thyroid disease, with (131)I again the radioisotope of choice, although there were short-lived attempts to employ (125)I and (132)I for this purpose. (123)I was first produced in 1949 but did not become widely available until about 1982, 10 years after a production technique eliminated high-energy (124)I contamination. I continues to be the radioiodine of choice for the diagnosis of benign thyroid disease, whereas (123)I and (131)I are employed in the staging and detection of functioning thyroid cancer. (124)I, a positron emitter, can produce excellent anatomically correlated images employing positron emission tomography/computed tomography equipment and has the potential to enhance heretofore imperfect dosimetric studies in determining the appropriate administered activity to ablate/treat thyroid cancer. Issues of acceptable measuring error in thyroid cancer dosimetry and the role in (131)I therapy of tumor heterogeneity, tumor hypoxia, and

  10. High-dose-rate brachytherapy and hypofractionated external beam radiotherapy combined with long-term hormonal therapy for high-risk and very high-risk prostate cancer: outcomes after 5-year follow-up

    PubMed Central

    Ishiyama, Hiromichi; Satoh, Takefumi; Kitano, Masashi; Tabata, Ken-ichi; Komori, Shouko; Ikeda, Masaomi; Soda, Itaru; Kurosaka, Shinji; Sekiguchi, Akane; Kimura, Masaki; Kawakami, Shogo; Iwamura, Masatsugu; Hayakawa, Kazushige

    2014-01-01

    The purpose of this study was to report the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT) for National Comprehensive Cancer Network (NCCN) criteria-defined high-risk (HR) and very high-risk (VHR) prostate cancer. Data from 178 HR (n = 96, 54%) and VHR (n = 82, 46%) prostate cancer patients who underwent 192Ir-HDR brachytherapy and hypofractionated EBRT with long-term ADT between 2003 and 2008 were retrospectively analyzed. The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After five fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administered. All patients initially underwent ≥6 months of neoadjuvant ADT, and adjuvant ADT was continued for 36 months after EBRT. The median follow-up was 61 months (range, 25–94 months) from the start of radiotherapy. The 5-year biochemical non-evidence of disease, freedom from clinical failure and overall survival rates were 90.6% (HR, 97.8%; VHR, 81.9%), 95.2% (HR, 97.7%; VHR, 92.1%), and 96.9% (HR, 100%; VHR, 93.3%), respectively. The highest Radiation Therapy Oncology Group-defined late genitourinary toxicities were Grade 2 in 7.3% of patients and Grade 3 in 9.6%. The highest late gastrointestinal toxicities were Grade 2 in 2.8% of patients and Grade 3 in 0%. Although the 5-year outcome of this tri-modality approach seems favorable, further follow-up is necessary to validate clinical and survival advantages of this intensive approach compared with the standard EBRT approach. PMID:24222312

  11. Impact of high-dose chemotherapy and autologous transplantation as first-line therapy on the survival of high-risk diffuse large B cell lymphoma patients: a single-center study in Japan.

    PubMed

    Inano, Shojiro; Iwasaki, Makoto; Iwamoto, Yoshihiro; Sueki, Yuki; Fukunaga, Akiko; Yanagita, Soshi; Arima, Nobuyoshi

    2014-02-01

    High-dose chemotherapy (HDT), together with autologous stem cell transplantation (ASCT), plays an important role in the treatment of diffuse large B cell lymphoma (DLBCL), especially as second-line therapy. However, its significance in up-front settings remains to be elucidated. In our institute, patients with DLBCL in both the high-intermediate and high international prognostic index (IPI) groups initially underwent CHOP/R-CHOP treatment followed by HDT/ASCT at upfront settings between 2002 and 2011. We retrospectively analyzed 25 patients who were all treated with upfront HDT/ASCT. We excluded one patient who failed to undergo transplantation because of primary refractory disease from the analysis. The median follow-up was 77 months (range 17-110 months). Five-year overall survival (OS) and progression-free survival (PFS) were 91.7 and 79.2 %, respectively, which were higher than the equivalents in previous studies. The OS and PFS in the high-risk group were lower than those in the high-intermediate group. Treatment-related mortalities or fatal complication were not observed. Our results confirm that HDT/ASCT for high-risk aggressive lymphoma is a feasible and promising therapy, but patients with high IPI continued to have poor prognoses; improvements in treatment strategy are clearly needed. Since HDT/ASCT is an aggressive treatment option associated with long-term complications, we need to identify patient groups that will gain the maximum benefit from HDT/ASCT in the upfront setting. PMID:24338743

  12. CHOP versus CHOP plus ESHAP and high-dose therapy with autologous peripheral blood progenitor cell transplantation for high-intermediate-risk and high-risk aggressive non-Hodgkin's lymphoma.

    PubMed

    Intragumtornchai, T; Prayoonwiwat, W; Numbenjapon, T; Assawametha, N; O'Charoen, R; Swasdikul, D

    2000-12-01

    The purpose of the study was to compare conventional cyclophosphamide/doxorubicin/vincristine/prednisolone (CHOP) chemotherapy with CHOP (3 courses) plus etoposide/methylprednisolone/high-dose cytarabine/cisplatin (ESHAP), high-dose therapy (HDT), and autologous peripheral blood progenitor cell transplantation (PBPCT) as front-line treatment for poor-prognosis aggressive non-Hodgkin's lymphoma (NHL). Between May 1, 1995, and April 30, 1998, 58 patients, aged 15-55 years, newly diagnosed with poor-prognosis aggressive NHL (category F-H by the Working Formulation) were enrolled. According to the age-adjusted international prognostic index, 65% of the patients were high-risk cases and 35% made up the high-intermediate group. After 3 courses of CHOP, 25 of 48 patients were randomized to continue with CHOP, and 23 were randomized to receive 2-4 cycles of ESHAP followed by HDT and PBPCT. There was no significant difference in the rate of complete remission between the two groups (36%, 95% confidence interval [CI]: 18%-57% in CHOP vs. 43%, 95% CI: 23%-65% in ESHAP/HDT) (P = 0.77). With a median follow-up duration of 39 months, the 4-year failure-free survival (FFS) was superior in the ESHAP/HDT group (38%, 95% CI: 18%-58% vs. 15%, 95% CI: 4%-32%) (P = 0.04). The disease-free survival was marginally different in favor of the ESHAP/HDT arm (90%, 95% CI: 47%-98% vs. 37%, 95% CI: 7%-69%) (P = 0.06). The 4-year overall survival between the two treatment arms was comparable (51%, 95% CI: 28%-70% for ESHAP/HDT vs. 30%, 95% CI: 13%-48% for CHOP) (P = 0.25). Treatment-related mortalities were not significantly different between both groups (17%, 95% CI: 5%-39% for ESHAP/HDT vs. 8%, 95% CI: 1%-26% for CHOP) (P = 0.41). However, only 61% of the patients assigned to the ESHAP/HDT arm underwent HDT and PBPCT. As compared with CHOP, the corporate regimen of CHOP/ESHAP/HDT seems to improve the FFS in patients with newly diagnosed, poor-prognosis aggressive NHL. PMID:11707834

  13. Patterns and Predictors of Amelioration of Genitourinary Toxicity after High-Dose Intensity-Modulated Radiation Therapy for Localized Prostate Cancer: Implications for Defining Post-Radiotherapy Urinary Toxicity

    PubMed Central

    Ghadjar, Pirus; Jackson, Andrew; Spratt, Daniel E.; Oh, Jung Hun; Rosenschöld, Per Munck af; Kollmeier, Marisa; Yorke, Ellen; Hunt, Margie; Deasy, Joseph O.; Zelefsky, Michael J.

    2016-01-01

    Background Treatment-related toxicity and quality of life (QoL) considerations are important when counseling patients with localized prostate cancer. Objective To determine the incidence and longitudinal pattern of late genitourinary (GU) toxicity and QoL after high-dose intensity-modulated radiotherapy (IMRT). Design, setting, and participants A total of 268 patients with localized prostate cancer were treated between 06/2004 and 12/2008 at a tertiary referral center. Median follow-up was 5 (range, 3–7.7) years. Intervention Patients underwent IMRT to a total dose of 86.4 Gy, 50% of patients underwent neoadjuvant and concurrent androgen-deprivation therapy. Outcome measurements and statistical analysis Patients were evaluated with the prospectively obtained International Prostate Symptom Score (IPSS) questionnaire. GU toxicity was also scored using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0; toxicity events were defined as increase over baseline. Differences in increases in IPSS sums and QoL index between baseline IPSS sum and QoL index groups were analyzed using the Kruskal-Wallis and Mann-Whitney tests. Univariate and multivariate Cox regression models were applied. Results and limitations The overall median IPSS sum increase during follow-up was 3, and was less pronounced among patients with severe compared with mild baseline symptoms (median increase 0 vs. 4; p < 0.0001). Overall, QoL index was unchanged after IMRT but appeared to improve in patients with dissatisfied baseline QoL compared with satisfied baseline QoL (p < 0.0001). Fifty-five (20%) and 2 (1%) patients developed grade 2 and 3 late GU toxicity; however, 28/57 (49%) of these resolved during follow-up. Even though the IPSS data was prospectively obtained, most patients were not treated within a prospective protocol. Conclusions Late GU toxicity after high-dose IMRT was mild and severe late GU toxicity was rare. Changes in IPSS sum and QoL index were dependent on the baseline

  14. (Radioiodinated free fatty acids)

    SciTech Connect

    Knapp, Jr., F. F.

    1987-12-11

    The traveler participated in the Second International Workshop on Radioiodinated Free Fatty Acids in Amsterdam, The Netherlands where he presented an invited paper describing the pioneering work at the Oak Ridge National Laboratory (ORNL) involving the design, development and testing of new radioiodinated methyl-branched fatty acids for evaluation of heart disease. He also chaired a technical session on the testing of new agents in various in vitro and in vivo systems. He also visited the Institute for Clinical and Experimental Nuclear Medicine in Bonn, West Germany, to review, discuss, plan and coordinate collaborative investigations with that institution. In addition, he visited the Cyclotron Research Center in Liege, Belgium, to discuss continuing collaborative studies with the Osmium-191/Iridium-191m radionuclide generator system, and to complete manuscripts and plan future studies.

  15. [High-dose intravenous immunoglobulin treatment].

    PubMed

    Taneichi, Hiromichi; Miyawaki, Toshio

    2011-03-01

    Intravenous immunoglobulin treatment was introduced as replacement therapy for patients with congenital agammaglobulinemia. For the last three decades, high-dose intravenous immunoglobulin (HD-IVIg) has been used for autoimmune diseases and systemic inflammatory diseases, such as idiopathic thrombocytopenic purpura, Kawasaki disease, myasthenia gravis and Guillain-Barré/syndrome. Although the immunomodulatory mechanisms of HD-IVIg remains unclear. Its use in many other diseases have been expected. Acute encephalitis/encephalopathy is a complex neurological syndrome associated with significant morbidity and mortality. The pathogenicity of brain dysfunction is still unknown. This review provides an overview and discussion of mechanisms that may be responsible for HD-IVIg effects in acute encephalitis/encephalopathy. PMID:21400848

  16. Randomized trial of high-dose interferon-alpha-2b combined with ribavirin in patients with chronic hepatitis C: Correlation between amino acid substitutions in the core/NS5A region and virological response to interferon therapy.

    PubMed

    Mori, Nami; Imamura, Michio; Kawakami, Yoshiiku; Saneto, Hiromi; Kawaoka, Tomokazu; Takaki, Shintaro; Aikata, Hiroshi; Takahashi, Shoichi; Chayama, Kazuaki

    2009-04-01

    The aim of this study was to compare the efficacy of high-dose interferon (IFN)-alpha-2b with standard dose of IFN-alpha-2b in combination with ribavirin (RBV) for patients with chronic hepatitis C virus (HCV) infection, and to investigate the predictive factors associated with virological response. Two hundred Japanese patients with high HCV viral load (>100 KIU/ml) were randomized to 6 or 10 mega units (MU) of 24-week IFN-alpha-2b with RBV. Predictive factors were investigated; including pretreatment amino acid (aa) sequences of the core region and the IFN-sensitive determining region (ISDR). The sustained virological response rate was not different in the two groups (24% vs. 30%) but the incidence of depression was significantly higher in the 10 MU group than 6 MU group (7% vs. 0%, P = 0.02). Younger age (<60) and HCV genotype (2a/b) were significant predictors of sustained virological response. In patients infected with genotype 1b, substitutions of core aa 70 and/or 91 were predictive for non-virological response (P < 0.001), and substitutions in the ISDR was observed frequently in virological responders. Early viral kinetics study showed that serum HCV core antigen decreased more slowly in both patients with aa 70 and/or 91 substitutions in the core and with absence of substitutions in the ISDR. In conclusion, the use of a higher dose of IFN-alpha-2b in combination with RBV did not improve virological response but resulted in higher incidence of depression. Amino acid substitutions in the core and ISDR are predictive of virological response to the therapy in patients with genotype 1b and high viral load. PMID:19235866

  17. Computed Tomography–Guided Interstitial High-Dose-Rate Brachytherapy in Combination With Regional Positive Lymph Node Intensity-Modulated Radiation Therapy in Locally Advanced Peripheral Non–Small Cell Lung Cancer: A Phase 1 Clinical Trial

    SciTech Connect

    Xiang, Li; Zhang, Jian-wen; Lin, Sheng; Luo, Hui-Qun; Wen, Qing-Lian; He, Li-Jia; Shang, Chang-Ling; Ren, Pei-Rong; Yang, Hong-Ru; Pang, Hao-Wen; Yang, Bo; He, Huai-Lin; Chen, Yue; Wu, Jing-Bo

    2015-08-01

    Purpose: To assess the technical safety, adverse events, and efficacy of computed tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy in combination with regional positive lymph node intensity modulated radiation therapy in patients with locally advanced peripheral non–small cell lung cancer (NSCLC). Methods and Materials: Twenty-six patients with histologically confirmed NSCLC were enrolled in a prospective, officially approved phase 1 trial. Primary tumors were treated with HDR brachytherapy. A single 30-Gy dose was delivered to the 90% isodose line of the gross lung tumor volume. A total dose of at least 70 Gy was administered to the 95% isodose line of the planning target volume of malignant lymph nodes using 6-MV X-rays. The patients received concurrent or sequential chemotherapy. We assessed treatment efficacy, adverse events, and radiation toxicity. Results: The median follow-up time was 28 months (range, 7-44 months). There were 3 cases of mild pneumothorax but no cases of hemothorax, dyspnea, or pyothorax after the procedure. Grade 3 or 4 acute hematologic toxicity was observed in 5 patients. During follow-up, mild fibrosis around the puncture point was observed on the CT scans of 2 patients, but both patients were asymptomatic. The overall response rates (complete and partial) for the primary mass and positive lymph nodes were 100% and 92.3%, respectively. The 1-year and 2-year overall survival (OS) rates were 90.9% and 67%, respectively, with a median OS of 22.5 months. Conclusion: Our findings suggest that HDR brachytherapy is safe and feasible for peripheral locally advanced NSCLC, justifying a phase 2 clinical trial.

  18. Radioiodine and thyroid disease: the beginning.

    PubMed

    Becker, D V; Sawin, C T

    1996-07-01

    In 1936, Karl Compton, then president of the Massachusetts Institute of Technology (MIT) and the thyroid group of the Massachusetts General Hospital (MGH), undertook a joint study that led to the production of small amounts of short-lived radioiodine (iodine 128, half-life, 25 min). The original intent was to use it for diagnosis and treatment of thyroid disease, but in order to explore the underlying physiology, their first work was performed in rabbits and published in 1938. It clearly showed that the radioiodine was selectively and avidly taken up by the thyroid gland. It was immediately apparent to the MGH-MIT group and another team working at the Berkeley, CA cyclotron that longer-lasting iodine isotopes were needed, and soon both developed procedures for cyclotron-produced 130 (half-life, 12.5 hr) and 131I (half-life, 8 d). In 1939, the Berkeley group, using 131I, was the first to show that the normal human thyroid gland accumulated radioiodine. By 1941, the MGH-MIT team, using mainly 130I, was able to successfully treat a few patients with hyperthyroidism, and so achieved their original goal. The Berkeley group did the same a few months later, using mainly 131I. Both presented results at the same meeting of the American Society for Clinical Investigation in Atlantic City, NJ in the spring of 1942. This was in the midst of World War II and it was not easy to get much 130I or 131I, so experience was limited. Although effective, radioiodine treatment of hyperthyroidism had not been widely adopted by the end of the war in 1945, partly because radioiodine remained in short supply and partly because another medical therapy for hyperthyroidism, antithyroid drugs, had been invented. However, by 1946, fission-derived radioiodine became readily available as a by-product of the Manhattan project in Oak Ridge, TN; hundreds of patients were treated within a few years, both for hyperthyroidism and for thyroid cancer. A new treatment, based on the physiological application

  19. The impurity of radioiodinated triolein

    PubMed Central

    Kennedy, J. A.; Kinloch, J. D.

    1964-01-01

    Commercially supplied radioiodinated triolein has been shown by thin-layer chromatography and silicic acid column chromatography to contain impurities, consisting mainly of diglycerides and monoglycerides, but also a small amount of free fatty acid. The effect of these impurities on the radioiodinated triolein absorption test requires further investigation. Images PMID:14149942

  20. [Treatment of multiple myeloma with high-dose chemotherapy and transplantation of autologous hematopoietic stem cells and subsequent maintenance therapy with interferon alfa-2b or interferon alfa 2b and dexamethasone. Report of the ongoing study of the "4W" Czech Myeloma Group].

    PubMed

    Adam, Z; Krejcí, M; Bacovský, J; Hejlová, N; Kuca, B; Svojgrová, M; Franková, H; Gumulec, J; Janca, J; Veprek, K; Januska, B; Lehanka, F; Rezek, Z; Praskac, P; Cahová, S; Vránová, M; Papajík, T; Králová, E; Novotná, J; Scudla, V; Koza, V; Drbal, J; Faber, E; Mareschová, I; Hájek, R

    1998-07-01

    We report our results with high-dose chemotherapy in previously untreated multiple myeloma patients (4 courses of VAD chemotherapy, collection of PBSC after priming with cyclophosphamide, 5 g/m2, high-dose chemotherapy with melphalan, 200 mg/m2). Second transplantation was indicated only for patients who did not achieve remission after the first high-dose therapy (paraprotein lower than 25% of the pretreatment value). For the second transplantation melphalan (200 mg/m2) with methylprednisolone (1.5 g for 5 days) were used as conditioning regimen. After high-dose therapy all patients were randomized into two arms of maintenance therapy: interferon alpha-2b or sequential maintenance therapy (interferon alpha-2b for 3 months followed after 4 week pause by 40 mg of dexamethasone days 1-4, 10-13 and 20-23. The administration of interferon alpha was resumed four weeks after the last dexamethasone for next three months. The maintenance therapy continued for 48 months or until the progression. Fifty-five patients were enrolled in the study from January 1996 to August 1997. Thirty-five patients have undergone the first transplantation and 57% of them reached complete remission. There were 10% of non-responders after the first high-dose regimen. The mean time to reach white blood cell count above 1 x 10(9)/L after the application of high dose melphalan and platelets more than 50 x 10(9)/L were 12.2 (range 6-16 days) and 12.4 (range 0-25 days), respectively. Grade 4 mucositis according to SWOG classification requiring total parenteral nutrition was presented in 40% of the patients. The mean number of 1 unit of platelets and 2 units of packed red blood cells transfusions were given within the posttransplant period. Early transplant related mortality was 3%. This paper describes the response and tolerance of each particular step of therapy. The follow-up has been too short to evaluate event-free and overall survivals. PMID:9748876

  1. Ocular toxicity following high dose chemotherapy and autologous transplant.

    PubMed

    Rubin, P; Hulette, C; Khawly, J A; Elkordy, M; Hussein, A; Vredenburgh, J J; Jaffe, G J; Peters, W P

    1996-07-01

    A 49-year-old woman received an autologous transplant for breast cancer. Six weeks later she noticed visual disturbance of the left eye which correlated with a visual field abnormality. There was a milder degree of visual disturbance in the right eye. Treatment with high-dose steroids partially stabilized the problem, which was felt to be an ischemic optic neuropathy. She ultimately died of respiratory failure. Pathology of the optic nerves revealed demyelination. Visual disturbances following high-dose chemotherapy are uncommon; the pathology to date has not been elucidated. Steroid therapy may be useful. PMID:8832031

  2. Cervical Gross Tumor Volume Dose Predicts Local Control Using Magnetic Resonance Imaging/Diffusion-Weighted Imaging—Guided High-Dose-Rate and Positron Emission Tomography/Computed Tomography—Guided Intensity Modulated Radiation Therapy

    SciTech Connect

    Dyk, Pawel; Jiang, Naomi; Sun, Baozhou; DeWees, Todd A.; Fowler, Kathryn J.; Narra, Vamsi; Garcia-Ramirez, Jose L.; Schwarz, Julie K.; Grigsby, Perry W.

    2014-11-15

    Purpose: Magnetic resonance imaging/diffusion weighted-imaging (MRI/DWI)-guided high-dose-rate (HDR) brachytherapy and {sup 18}F-fluorodeoxyglucose (FDG) — positron emission tomography/computed tomography (PET/CT)-guided intensity modulated radiation therapy (IMRT) for the definitive treatment of cervical cancer is a novel treatment technique. The purpose of this study was to report our analysis of dose-volume parameters predicting gross tumor volume (GTV) control. Methods and Materials: We analyzed the records of 134 patients with International Federation of Gynecology and Obstetrics stages IB1-IVB cervical cancer treated with combined MRI-guided HDR and IMRT from July 2009 to July 2011. IMRT was targeted to the metabolic tumor volume and lymph nodes by use of FDG-PET/CT simulation. The GTV for each HDR fraction was delineated by use of T2-weighted or apparent diffusion coefficient maps from diffusion-weighted sequences. The D100, D90, and Dmean delivered to the GTV from HDR and IMRT were summed to EQD2. Results: One hundred twenty-five patients received all irradiation treatment as planned, and 9 did not complete treatment. All 134 patients are included in this analysis. Treatment failure in the cervix occurred in 24 patients (18.0%). Patients with cervix failures had a lower D100, D90, and Dmean than those who did not experience failure in the cervix. The respective doses to the GTV were 41, 58, and 136 Gy for failures compared with 67, 99, and 236 Gy for those who did not experience failure (P<.001). Probit analysis estimated the minimum D100, D90, and Dmean doses required for ≥90% local control to be 69, 98, and 260 Gy (P<.001). Conclusions: Total dose delivered to the GTV from combined MRI-guided HDR and PET/CT-guided IMRT is highly correlated with local tumor control. The findings can be directly applied in the clinic for dose adaptation to maximize local control.

  3. High-dose thiamine as initial treatment for Parkinson's disease

    PubMed Central

    Costantini, Antonio; Pala, Maria Immacolata; Compagnoni, Laura; Colangeli, Marco

    2013-01-01

    Parkinson's disease (PD) is a systemic disease with motor and non-motor deficits. We recruited three patients with newly diagnosed PD. They were not under anti-Parkinson's therapy. Plasmatic thiamine was within healthy reference range. We performed the Unified Parkinson's Disease Rating Scale (UPDRS) and started a parenteral therapy with high doses of thiamine. The therapy led to a considerable improvement in the motor part of the UPDRS ranging from 31.3% to 77.3%. From this clinical observation, it is reasonable to infer that a focal, severe thiamine deficiency due to a dysfunction of thiamine metabolism could cause a selective neuronal damage in the centres that are typically hit in this disease. Injection of high doses of thiamine was effective in reversing the symptoms, suggesting that the abnormalities in thiamine-dependent processes could be overcome by diffusion-mediated transport at supranormal thiamine concentrations. PMID:23986125

  4. METASTATIC RADIOIODINE AVID STRUMA OVARII ASSOCIATED WITH PSEUDO-MEIGS' SYNDROME.

    PubMed

    Riaz, Saima; Bashir, Humayun; Hassan, Aamna; Syed, Aamir Ali; Hussain, Mudassar; Imtiaz, Saba

    2015-01-01

    We report a case of 21 years old lady who presented with ascites, left adnexal mass and elevated CA-125. With suspicion of ovarian malignancy, she underwent left salpingo-oophorectomy with omental biopsy. Histopathology revealed: 'follicular variant of papillary thyroid carcinoma arising in struma ovarii' with metastatic papillary thyroid carcinoma in omental and peritoneal nodules. Patient underwent total thyroidectomy followed by radioactive iodine therapy for metastatic omental and peritoneal disease. Post-therapy whole body scan, revealed extensive I-131 avid disease metastatic disease involving the chest, abdomen, pelvis and the musculoskeletal system. Patient was treated with multiple doses of high dose radioactive iodine. She became symptom free on supra-physiologic doses of oral thyroxin however her high thyroglobulin levels and residual radioiodine avid metastatic disease required further treatment. In literature a few cases of struma ovarii have been reported with elevated CA-125 and associated pseudo-Meigs' syndrome. The treatment for this rare disease is still not standardized and poses a therapeutic challenge. Our case emphasizes the need for a multidisciplinary approach for managing struma ovarii. PMID:26721055

  5. Novel radioiodinated neuroreceptor ligands

    SciTech Connect

    Musachio, J.L.

    1993-01-01

    Since many bioactive compounds do not readily undergo direct labeling with radioisotopes of iodine, the novel prosthetic groups, p-toluenesulfonate esters of (E)- and (Z)-3-(tri-n-butylstannyl)prop-2-en-1-ol, were designed to complement existing methods for radioiodine incorporation. The preparation and synthetic utility of these bifunctional reagents are described. These vinylstannylated alkylating agents were coupled with nucleophilic functionalities (amide nitrogen, secondary amine, tertiary alcohol) in acceptable to excellent yields. Regio- and stereospecific radioiododestannylation with retention of configuration occurred under mild, no-carrier-added conditions to give the corresponding radiolabeled N- or O-iodoallyl analogs in good radiochemical yields with high specific radioactivities. The methodology is versatile and well-suited to selective labeling of small molecules with radioisotopes of iodine. Of particular importance are the N-iodoallyl analogs of spiperone and the O-iodoallyl analog of diprenorphine for in vitro and in vivo studies of dopamine D[sub 2] and opioid receptors. For in vivo studies of central serotonin 5-HT[sub 2] receptors via single photon emission computed tomography (SPECT), novel radioiodinated N1-alkyl-2-iodo-LSD derivatives were synthesized. These target radioligands were prepared in moderate radiochemical yields. D-(+)-N1-ethyl-2-iodo-LSD, EIL, was identified as the most promising candidate of this series. [[sup 125]I]-EIL binds to central 5-HT[sub 2] receptors with high affinity and selectivity in vitro and labels 5-HT[sub 2] receptors in vivo with high specificity. For preparation of EIL labeled with [sup 123]I, an optimized procedure was developed that gave [[sup 123]I]-EIL in acceptable yields. This radioligand allowed visualization of serotonin 5-HT[sub 2] sites in living baboon brain via SPECT. [[sup 123]I]-EIL may serve as an agent for tomographic studies of human cerebral 5-HT[sub 2] receptors in normal and disease states.

  6. Prospective Evaluation of Subretinal Vessel Location in Polypoidal Choroidal Vasculopathy (PCV) and Response of Hemorrhagic and Exudative PCV to High-Dose Antiangiogenic Therapy (An American Ophthalmological Society Thesis)

    PubMed Central

    Kokame, Gregg T.

    2014-01-01

    Purpose: The purpose of this study was to determine the following: (1) Is polypoidal choroidal vasculopathy (PCV) a subretinal neovascular process, rather than a choroidal vascular anomaly? and (2) Is a higher dose of ranibizumab (2.0 mg/0.05 mL) more effective in treating PCV than the current dose (0.5 mg/0.05 mL) approved for treatment of age-related macular degeneration? Methods: Retrospective evaluation of PCV in 104 eyes of 86 patients was accomplished with use of indocyanine green angiography plus optical coherence tomography to localize the branching vascular network and the polyps. Nineteen eyes of 19 patients with active leaking and exudation underwent a prospective open-label trial of monthly high-dose intravitreal ranibizumab (2.0 mg/0.05 mL). The primary outcome was prevention of major vision loss (≤15 ETDRS letters). Secondary outcomes included adverse events, improved vision, and changes in subretinal hemorrhage, subretinal fluid, macular edema, and polypoidal complexes at 6 months. Results: The PCV vessels were localized beneath the retinal pigment epithelium (RPE) and above Bruch’s membrane in 103 (99%) of 104 eyes. In the high-dose ranibizumab trial at 6 months, none of the patients lost ≥15 letters in visual acuity, and 5 (26%) of 19 gained ≥15 letters. Decreases were noted in subretinal fluid in 14 (82%) of 17 eyes, subretinal hemorrhage in 12 (100%) of 12, RPE detachment in 14 (88%) of 16, macular edema in 11 (92%) of 12, and polyps in 15 (79%) of 19 eyes. Conclusions: PCV vessels are a subtype of subretinal neovascularization located above Bruch’s membrane and below RPE. High-dose ranibizumab (2.0 mg/0.05 mL) decreased exudation and hemorrhage and resulted in significant polyp regression, although branching vascular networks persisted. PMID:25646029

  7. An Unusual False-Positive Uptake of Radioiodine in Pericardial Effusion on Posttherapy Scan.

    PubMed

    Malhotra, Gaurav; Moghe, Surendra H; Ranade, Rohit; Asopa, R Ramesh V

    2016-07-01

    Posttherapy scan in a 21-year-old woman with papillary carcinoma of thyroid with lymph node metastasis, who received 5.55 GBq of radioiodine (I), revealed halo-like diffuse tracer uptake in the pericardial region. Echocardiography showed no abnormality except pericardial effusion, which subsided after reinstitution of levothyroxine therapy. Although rare, false-positive radioiodine uptake can occur in pericardial effusion secondary to thyroxine withdrawal-related hypothyroidism and needs close monitoring of the patient. PMID:27055143

  8. Post-radioiodine De Novo Onset Graves' Ophthalmopathy: Case Reports and a Review of the Literature.

    PubMed

    Batra, Ruchika; Krishnasamy, Senthil Kumar; Buch, Harit; Sandramouli, Soupramanien

    2015-05-01

    New-onset Graves' ophthalmopathy (GO) following radioiodine treatment (RAI) and worsening of existing GO are well-described in the endocrinology literature. These phenomena are recognized by ophthalmologists, yet poorly documented in the ophthalmology literature. Two male patients, aged 43 and 62 years, respectively, with Graves' disease without GO, received RAI. Four months later, one patient developed acute GO with unilateral reduction in visual acuity, conjunctival chemosis, lagophthalmos, bilateral severely restricted ocular motility, and lid retraction. High-dose intravenous steroids, followed by oral steroids, led to a dramatic clinical improvement. The second patient received a second dose of RAI for persistent hyperthyroidism and subsequently developed acute GO-comprising restricted ocular motility, peri-orbital swelling, and conjunctival chemosis. Symptoms gradually resolved on continued carbimazole treatment. Neither patient received pre-RAI prophylactic glucocorticoids, as currently they are only recommended for patients with pre-existing GO or multiple risk factors. We discuss the limitations of using this risk-based approach in preventing new-onset GO following RAI therapy. PMID:24409943

  9. Objective and Longitudinal Assessment of Dermatitis After Postoperative Accelerated Partial Breast Irradiation Using High-Dose-Rate Interstitial Brachytherapy in Patients With Breast Cancer Treated With Breast Conserving Therapy: Reduction of Moisture Deterioration by APBI

    SciTech Connect

    Tanaka, Eiichi; Yamazaki, Hideya; Yoshida, Ken; Takenaka, Tadashi; Masuda, Norikazu; Kotsuma, Tadayuki; Yoshioka, Yasuo; Inoue, Takehiro

    2011-11-15

    Purpose: To objectively evaluate the radiation dermatitis caused by accelerated partial breast irradiation (APBI) using high-dose-rate interstitial brachytherapy. Patients and Methods: The skin color and moisture changes were examined using a newly installed spectrophotometer and corneometer in 22 patients who had undergone APBI using open cavity implant high-dose-rate interstitial brachytherapy (36 Gy in six fractions) and compared with the corresponding values for 44 patients in an external beam radiotherapy (EBRT) control group (50-60 Gy in 25-30 fractions within 5-6 weeks) after breast conserving surgery. Results: All values changed significantly as a result of APBI. The extent of elevation in a Asterisk-Operator (reddish) and reduction in L Asterisk-Operator (black) values caused by APBI were similar to those for EBRT, with slightly delayed recovery for 6-12 months after treatment owing to the surgical procedure. In contrast, only APBI caused a change in the b Asterisk-Operator values, and EBRT did not, demonstrating that the reduction in b Asterisk-Operator values (yellowish) depends largely on the surgical procedure. The changes in moisture were less severe after APBI than after EBRT, and the recovery was more rapid. The toxicity assessment using the Common Toxicity Criteria, version 3, showed that all dermatitis caused by APBI was Grade 2 or less. Conclusion: An objective analysis can quantify the effects of APBI procedures on color and moisture cosmesis. The radiation dermatitis caused by APBI using the present schedule showed an equivalent effect on skin color and a less severe effect on moisture than the effects caused by standard EBRT.

  10. [Radioiodine versus surgery in the treatment of Graves' hyperthyroidism].

    PubMed

    Jukić, Tomislav; Stanicić, Josip; Petric, Vlado; Kusić, Zvonko

    2010-01-01

    The most common etiologic cause of thyrotoxicosis in children and adults is autoimmune Graves' (Basedow's) disease. Antithyroid medications, surgery and radioactive iodine have been used in the treatment of Graves' hyperthyroidism for more than six decades. The use of antithyroid drugs is the most common therapeutic approach. However, long-term remission with antithyroid drugs can be expected in 20-50% of adults and 20-30% of children. The methods for definitive treatment of Graves' hyperthyroidism are iodine-131 (radioiodine) and surgery. Both treatment modalities have benefits and risks and the decision is made according to the age, patient preference and the presence of other co-morbidities, individual characteristics of patients and the availability of certain treatment modality. Radioiodine is simple, safe, effective and economic procedure for definitive treatment of Graves' hyperthyroidism. It is administered ambulatory and can be given to the patient in thyrotoxicosis. Due to many benefits, radioiodine is preferred in most of the adult patients with Graves' hyperthyroidism while only small proportion of patients is sent to surgery. Radioiodine is especially the treatment of choice in elderly patients and patients with heart disease. In these patients radioiodine is indicated immediately after reaching euthyroidism with antithyroid drugs. Surgery is mainly indicated in younger patients, in the case of patient preference or in special indications. Clear indications for surgical treatment of Graves' hyperthyroidism are: suspected or confirmed malignancy, coexisting pathology that demands surgical treatment, pregnancy and breastfeeding, large goiter (> 80 grams) or goiter with symptoms and signs of compression, severe toxic side effects of antithyroid medications, requirement for immediate control of disease, age younger than 5 years and active ophtalmopathy. The risk of surgical treatment is negatively correlated with the surgeon's experience and nowadays

  11. Sequential multiagent chemotherapy is not superior to high-dose cytarabine alone as postremission intensification therapy for acute myeloid leukemia in adults under 60 years of age: Cancer and Leukemia Group B Study 9222

    PubMed Central

    Moore, Joseph O.; George, Stephen L.; Dodge, Richard K.; Amrein, Philip C.; Powell, Bayard L.; Kolitz, Jonathan E.; Baer, Maria R.; Davey, Frederick R.; Bloomfield, Clara D.; Larson, Richard A.; Schiffer, Charles A.

    2005-01-01

    The Cancer and Leukemia Group B (CALGB) study 9222 tested the hypothesis that treatment intensification of acute myeloid leukemia (AML) in first remission with multiple chemotherapy agents is superior to high-dose cytarabine (HiDAC) alone. We enrolled 474 patients younger than 60 years old with untreated de novo AML. Daunorubicin and cytarabine resulted in complete remission (CR) in 342 patients (72%), and 309 of these patients were randomized to receive one of 2 different intensification regimens. The first regimen consisted of 3 courses of HiDAC. The second regimen consisted of one course of HiDAC, a second course with etoposide and cyclophosphamide, and a third course with diaziquone and mitoxantrone. After a median follow-up time of 8.3 years, the median survival for all randomized patients was 2.8 years (95% CI, 1.9-6.8 years). There was no difference in disease-free survival (DFS) between the 2 regimens (P = .66). The median DFS was 1.1 years (95% CI, 0.9-1.7 years) for patients receiving HiDAC and 1.0 year (95% CI, 0.9-1.3 years) for those receiving multiagent chemotherapy. Cytogenetics was the only pretreatment characteristic prognostic for DFS, but there was no evidence of a differential treatment effect within cytogenetic risk groups. Toxicity was greater with multiagent chemotherapy. These 2 postremission regimens produced similar outcomes. PMID:15572587

  12. The use of SPECT-CT improves accuracy of post-radioiodine therapy imaging and changes the management strategy in a case of advanced follicular thyroid carcinoma.

    PubMed

    Wong, T H; Amir Hassan, S Z

    2015-12-01

    This is a case of follicular thyroid carcinoma with extensive lung, bone and brain metastases. Multi-modality treatments including total thyroidectomy, modified radical neck dissection, cranial radiotherapy and Iodine-131 (RAI) therapy were instituted. Post RAI therapy planar whole body scan showed RAI avid metastases in the skull, cervical spine, bilateral lungs and abdomen. With the use of SPECTCT imaging, rare adrenal metastasis and additional rib metastasis were identified. Besides, management strategy was altered due to detection of non-RAI avid brain and lung metastatic lesions. PMID:26988209

  13. High-Dose Intravenous Corticosteroids for Ocular Inflammatory Diseases

    PubMed Central

    Charkoudian, Leon D.; Ying, Gui-shuang; Pujari, Siddharth S.; Gangaputra, Sapna; Thorne, Jennifer E.; Foster, C. Stephen; Jabs, Douglas A.; Levy-Clarke, Grace A.; Nussenblatt, Robert B.; Rosenbaum, James T.; Suhler, Eric B.; Kempen, John H.

    2011-01-01

    Purpose To evaluate the effectiveness and risk of complications of high-dose intravenous pulsed corticosteroids for non-infectious ocular inflammatory diseases. Methods Retrospective cohort study. One hundred four eyes of seventy patients who received high-dose intravenous corticosteroids for treatment of active ocular inflammation were identified from five centers. The main outcome measures were control of inflammation and occurrence of ocular or systemic complications within one month after treatment. Results Within ≤1 month of starting treatment, 57% of eyes achieved complete control of inflammation (95% confidence interval (CI): 33-83%), improving to 82% when near-complete control was included (95% CI: 61-96%). Most eyes (85%; 95% CI: 70-95%) gained clinically significant improvement in anterior chamber inflammation. One patient developed a colon perforation during treatment. No other major complications were recorded. Conclusions Treatment of ocular inflammation with high-dose intravenous corticosteroids resulted in substantial clinical improvement for most cases within one month. Complications of therapy were infrequent. PMID:22409561

  14. Autophagy activity is associated with membranous sodium iodide symporter expression and clinical response to radioiodine therapy in non-medullary thyroid cancer.

    PubMed

    Plantinga, Theo S; Tesselaar, Marika H; Morreau, Hans; Corssmit, Eleonora P M; Willemsen, Brigith K; Kusters, Benno; van Engen-van Grunsven, A C H; Smit, Johannes W A; Netea-Maier, Romana T

    2016-07-01

    Although non-medullary thyroid cancer (NMTC) generally has a good prognosis, 30-40% of patients with distant metastases develop resistance to radioactive iodine (RAI) therapy due to tumor dedifferentiation. For these patients, treatment options are limited and prognosis is poor. In the present study, expression and activity of autophagy was assessed in large sets of normal, benign and malignant tissues and was correlated with pathology, SLC5A5/hNIS (solute carrier family 5 member 5) protein expression, and with clinical response to RAI ablation therapy in NMTC patients. Fluorescent immunostaining for the autophagy marker LC3 was performed on 100 benign and 80 malignant thyroid tissues. Semiquantitative scoring was generated for both diffuse LC3-I intensity and number of LC3-II-positive puncta and was correlated with SLC5A5 protein expression and clinical parameters. Degree of diffuse LC3-I intensity and number of LC3-II-positive puncta scoring were not discriminative for benign vs. malignant thyroid lesions. Interestingly, however, in NMTC patients significant associations were observed between diffuse LC3-I intensity and LC3-II-positive puncta scoring on the one hand and clinical response to RAI therapy on the other hand (odds ratio [OR] = 3.13, 95% confidence interval [CI] =1.91-5.12, P = 0.01; OR = 5.68, 95%CI = 3.02-10.05, P = 0.002, respectively). Mechanistically, the number of LC3-II-positive puncta correlated with membranous SLC5A5 expression (OR = 7.71, 95%CI = 4.15-11.75, P<0.001), number of RAI treatments required to reach remission (P = 0.014), cumulative RAI dose (P = 0.026) and with overall remission and recurrence rates (P = 0.031). In conclusion, autophagy activity strongly correlates with clinical response of NMTC patients to RAI therapy, potentially by its capacity to maintain tumor cell differentiation and to preserve functional iodide uptake. PMID:27105307

  15. Total rod ERG suppression with high dose compassionate Fenretinide usage.

    PubMed

    Marmor, Michael F; Jain, Atul; Moshfeghi, Darius

    2008-11-01

    Fenretinide is a synthetic retinoid that interferes with the attachment of retinol to retinol binding protein. It may inhibit accumulation of A2E and lipofuscin, and is proposed as therapy for Stargardt disease. It is currently used for cancer therapy, and mild depression of rod function and dark adaptation is a side effect at standard dosage. We studied two youngsters (aged between 12 and 13) receiving high doses as compassionate treatment for neuroblastoma: 800 mg daily for 1 out of every 3 weeks, for roughly 2 years. Goldmann-Weekers dark adaptometry, ISCEV standard ERG and mfERG were performed, and blood was analyzed for vitamin A. Neither child complained of night blindness or showed retinal fundus abnormalities. On initial exam, dark adaptation thresholds were elevated by 3 log units, and there were no detectable rod ERG responses. However, cone responses and mfERG were normal. Retesting one subject 3 months after stopping the drug revealed normal rod thresholds (slightly delayed) and low normal rod ERG responses. Serum vitamin A levels were normal from both subjects, but there is no record of whether the samples were drawn during cycles on or off drug. Our study demonstrates that high dose Fenretinide can suppress rod function quite completely, although serum vitamin A and rod function apparently return to normal or near normal levels rapidly once the drug is stopped. It is intriguing that cone function and access to vitamin A seems largely independent of Fenretinide effects on retinol availability. PMID:18523815

  16. Abnormal radioiodine uptake on post-therapy whole body scan and sodium/iodine symporter expression in a dermoid cyst of the ovary: report of a case and review of the literature.

    PubMed

    Campennì, Alfredo; Giovinazzo, Salvatore; Tuccari, Giovanni; Fogliani, Simone; Ruggeri, Rosaria M; Baldari, Sergio

    2015-08-01

    In patients affected by differentiated thyroid cancer, the whole-body scan (WBS) with 131-radioiodine, especially when performed after a therapeutic activity of 131I, represents a sensitive procedure for detecting thyroid remnant and/or metastatic disease. Nevertheless, a wide spectrum of potentially pitfalls has been reported. Herein we describe a 63-year-old woman affected by follicular thyroid cancer, who was accidentally found to have an abdominal mass at post-dose WBS (pWBS). pWBS showed abnormal radioiodine uptake in the upper mediastinum, consistent with lymph-node metastases, and a slight radioiodine uptake in an abdominal focal area. Computed tomography revealed an inhomogeneous mass in the pelvis, previously unrecognized. The lesion, surgically removed, was found to be a typical dermoid cyst of the ovary, without any evidence of thyroid tissue. By immunohistochemistry, a moderate expression of the sodium-iodine symporter (NIS) was demonstrated in the epithelial cells, suggesting a NIS-dependent uptake of radioiodine by the cyst. PMID:26331324

  17. Radioiodine Remnant Ablation: A Critical Review

    PubMed Central

    Bal, Chandra Sekhar; Padhy, Ajit Kumar

    2015-01-01

    Radioiodine remnant ablation (RRA) is considered a safe and effective method for eliminating residual thyroid tissue, as well as microscopic disease if at all present in thyroid bed following thyroidectomy. The rationale of RRA is that in the absence of thyroid tissue, serum thyroglobulin (Tg) measurement can be used as an excellent tumor marker. Other considerations are like the presence of significant remnant thyroid tissue makes detection and treatment of nodal or distant metastases difficult. Rarely, microscopic disease in the thyroid bed if not ablated, in the future, could be a source of anaplastic transformation. On the other hand, microscopic tumor emboli in distant sites could be the cause of distant metastasis too. The ablation of remnant tissue would in all probability eliminate these theoretical risks. It may be noted that all these are unproven contentious issues except postablation serum Tg estimation that could be a good tumor marker for detecting early biochemical recurrence in long-term follow-up strategy. Radioactive iodine is administered as a form of “adjuvant therapy” for remnant ablation. There have been several reports with regard to the administered dose for remnant ablation. The first report of a prospective randomized clinical trial was published from India by a prospective randomized study conducted at the All India Institute of Medical Sciences, New Delhi in the year 1996. The study reported that increasing the empirical 131I initial dose to more than 50 mCi results in plateauing of the dose-response curve and thus, conventional high-dose remnant ablation needs critical evaluation. Recently, two important studies were published: One from French group and the other from UK on a similar line. Interestingly, all three studies conducted in three different geographical regions of the world showed exactly similar conclusion. The new era of low-dose remnant ablation has taken a firm scientific footing across the continents. PMID:26420983

  18. Long-Term Results of Fixed High-Dose I-131 Treatment for Toxic Nodular Goiter: Higher Euthyroidism Rates in Geriatric Patients

    PubMed Central

    Aktaş, Gül Ege; Turoğlu, Halil Turgut; Erdil, Tanju Yusuf; İnanır, Sabahat; Dede, Fuat

    2015-01-01

    Objective: Geriatric patient population has special importance due to particular challenges. In addition to the increase in incidence of toxic nodular goiter (TNG) with age, it has a high incidence in the regions of low-medium iodine intake such as in our country. The aim of this study was to evaluate the overall outcome of high fixed dose radioiodine (RAI) therapy, and investigate the particular differences in the geriatric patient population. Methods: One hundred and three TNG patients treated with high dose I-131 (370-740 MBq) were retrospectively reviewed. The baseline characteristics; age, gender, scintigraphic patterns and thyroid function tests before and after treatment, as well as follow-up, duration of antithyroid drug (ATD) medication and achievement of euthyroid or hypothyroid state were evaluated. The patient population was divided into two groups as those=>65 years and those who were younger, in order to assess the effect of age. Results: Treatment success was 90% with single dose RAI therapy. Hyperthyroidism was treated in 7±7, 2 months after RAI administration. At the end of the first year, overall hypothyroidism rate was 30% and euthyroid state was achieved in 70% of patients. Age was found to be the only statistically significant variable effecting outcome. A higher ratio of euthyroidism was achieved in the geriatric patient population. Conclusion: High fixed dose I-131 treatment should be preferred in geriatric TNG patients in order to treat persistent hyperthyroidism rapidly. The result of this study suggests that high fixed dose RAI therapy is a successful modality in treating TNG, and high rates of euthyroidism can be achieved in geriatric patients.

  19. Lower-dose (6 mg Daily) versus High-dose (30 mg Daily) Oral Estradiol Therapy of Hormone-receptor-positive, Aromatase-inhibitor-resistant Advanced Breast Cancer: A Randomized Phase 2 Study

    PubMed Central

    Ellis, Matthew J.; Gao, Feng; Dehdashti, Farrokh; Jeffe, Donna B.; Marcom, P. Kelly; Carey, Lisa A.; Dickler, Maura N.; Silverman, Paula; Fleming, Gini F.; Kommareddy, Aruna; Jamalabadi-Majidi, Shohreh; Crowder, Robert; Siegel, Barry A

    2012-01-01

    Context Estrogen deprivation therapy with aromatase inhibitors (AI) has been hypothesized to paradoxically sensitize hormone-receptor-positive breast cancer tumor cells to low-dose estradiol therapy. Objective To determine if estradiol 6-mg daily is a viable endocrine therapy for postmenopausal women with advanced AI-resistant hormone-receptor-positive breast cancer. Design, Setting and Patients A randomized Phase 2 trial of 6-mg versus 30-mg oral estradiol daily opened in April 2004 and was closed to enrollment in February 2008 (NCT00324259). Eligible patients had metastatic breast cancer treated with an AI with at least 24 weeks progression-free survival, or relapse after two or more years of adjuvant AI. Patients at high risk of estradiol-related adverse events were excluded. Main Outcome Measures The primary endpoint was clinical benefit rate – CBR (response plus stable disease at 24 weeks). Secondary outcomes included toxicity, progression-free survival (PFS), time to treatment failure (TTF), quality of life (QOL) and the predictive properties of the FDG-PET metabolic flare reaction. Results 66 patients were enrolled. The grade 3+ adverse event rate on the 30-mg arm (11/32; 95% CI: 23%–47%) was higher than that in 6-mg arm (4/34; 95% CI: 5%–22%) (P=.03). CBRs were 28% (9/32; 95% CI: 18% – 41%) on the 30-mg arm and 29% (10/34; 95% CI: 19% – 42%) on the 6-mg arm. An estradiol44 stimulated increase in FDG uptake of ≥12% (prospectively defined) was predictive of response (positive predictive value of 80%; 95% CI: 61%–92%). Seven patients with estradiol-sensitive disease were retreated with AI upon estradiol progression, with two PR and one SD, suggesting resensitization to estrogen deprivation. Conclusions In women with advanced breast cancer and acquired resistance to AI, an estradiol dose of 6-mg daily provided a similar CBR as 30-mg daily, with fewer serious adverse events. The efficacy of treatment with the lower dose should be further examined

  20. Pre-therapeutic 124I PET(/CT) dosimetry confirms low average absorbed doses per administered 131I activity to the salivary glands in radioiodine therapy of differentiated thyroid cancer

    PubMed Central

    Hobbs, Robert F.; Stahl, Alexander; Knust, Jochen; Sgouros, George; Bockisch, Andreas

    2010-01-01

    Purpose Salivary gland impairment following high activity radioiodine therapy of differentiated thyroid cancer (DTC) is a severe side effect. Dosimetric calculations using planar gamma camera scintigraphy (GCS) with 131I and ultrasonography (US) provided evidence that the average organ dose per administered 131I activity (ODpA) is too low to account for observed radiation damages to the salivary glands. The objective of this work was to re-estimate the ODpA using 124I PET(/CT) as a more reliable approach than 131I GCS/US. Methods Ten DTC patients underwent a series of six (or seven) PET scans and one PET/CT scan after administration of ~23 MBq 124I-iodide. Volumes of interest (VOIs) drawn on the CT and serial PET images were used to determine the glandular volumes and the imaged 124I activities. To enable identical VOIs to be drawn on serial PET images, each PET was co-registered with the CT image. To correct for partial volume effect and for the artificial bias in the activity concentration due to cascading gamma coincidences occurring in 124I decay, the imaged activity was effectively corrected using isovolume recovery coefficients (RCs) based on recovery phantom measurements. A head-neck phantom, which contained 124I-filled spheres, was manufactured to validate the isovolume recovery correction method with a realistic patient-based phantom geometry and for a range of activity concentration regimes. The mean±standard deviation (range) ODpA projected for 131I was calculated using the absorbed dose fraction method. Results The ODpAs (in Gy/GBq) for the submandibular and parotid glands were 0.32±0.13 (0.18–0.55) and 0.31±0.10 (0.13–0.46), respectively. No significant differences (p>0.2) in the mean ODpA between 124I PET(/CT) and 131I GCS/US dosimetry was found. The validation experiment showed that the percentage deviations between RC-corrected and true activity concentrations were <10%. Conclusion 124I PET(/CT) dosimetry also corroborates the low ODpAs to

  1. Molecularly Targeted Therapy of Human Hepatocellular Carcinoma Xenografts with Radio-iodinated Anti-VEGFR2 Murine-Human Chimeric Fab

    PubMed Central

    Huang, Jianfei; Tang, Qi; Wang, Changjun; Yu, Huixin; Feng, Zhenqing; Zhu, Jin

    2015-01-01

    Vascular endothelial growth factor receptor 2 (VEGFR2) is traditionally regarded as an important therapeutic target in a wide variety of malignancies, such as hepatocellular carcinoma (HCC). We previously generated a murine-human anti-VEGFR2 chimeric Fab (cFab), named FA8H1, which has the potential to treat VEGFR2-overexpressing solid tumors. Here, we investigated whether FA8H1 can be used as a carrier in molecularly targeted therapy in HCC xenograft models. FA8H1 was labeled with 131I, and two HCC xenograft models were generated using BEL-7402 (high VEGFR2-expressing) and SMMC-7721 (low VEGFR2-expressing) cells, which were selected from five HCC cell lines. The biodistribution of 131I-FA8H1 was determined in both models by Single-Photon Emission Computed Tomography and therapeutic effects were monitored in nude mice bearing BEL-7402 xenografts. Finally, we determined the involvement of necrosis and apoptotic pathways in treated mice using immunohistochemistry. 131I-FA8H1 levels were dramatically reduced in blood and other viscera. The therapeutic effect of 131I-labeled FA8H1 in the BEL-7402 model was significantly better than that by 131I and FA8H1 alone. We observed extensive necrosis in the treated tumors, and both FasL and caspase 3 were up-regulated. Thus, 131I-anti-VEGFR2 cFab has the potential to be used for molecularly targeted treatment of HCC overexpressing VEGFR2. PMID:26021484

  2. High dose rate intraluminal irradiation in recurrent endobronchial carcinoma

    SciTech Connect

    Seagren, S.L.; Harrell, J.H.; Horn, R.A.

    1985-12-01

    Palliative therapy for previously irradiated patients with symptomatic recurrent endobronchial malignancy is a difficult problem. We have had the opportunity to treat 20 such patients with high dose rate (50-100 rad/min) endobronchial brachytherapy. Eligible patients had received previous high dose thoracic irradiation (TDF greater than or equal to 90), a performance status of greater than or equal to 50, and symptoms caused by a bronchoscopically defined and implantable lesion. The radiation is produced by a small cobalt-60 source (0.7 Ci) remotely afterloaded by cable control. The source is fed into a 4 mm diameter catheter which is placed with bronchoscopic guidance; it may oscillate if necessary to cover the lesion. A dose of 1,000 rad at 1 cm from the source is delivered. We have performed 22 procedures in 20 patients, four following YAG laser debulking. Most had cough, some with hemoptysis. Eight had dyspnea secondary to obstruction and three had obstructive pneumonitis. In 12, symptoms recurred with a mean time to recurrence of 4.3 months (range 1-9 months). Eighteen patients were followed-up and reexamined via bronchoscope 1-2.5 months following the procedure; two were lost to follow-up. All had at least 50 percent clearance of tumor, and six had complete clearance; most regressions were documented on film or videotape. In six, the palliation was durable. The procedure has been well tolerated with no toxicity. We conclude that palliative endobronchial high dose rate brachytherapy is a useful palliative modality in patients with recurrent endobronchial symptomatic carcinoma.

  3. Prognostic impact of progression to induction chemotherapy and prior paclitaxel therapy in patients with germ cell tumors receiving salvage high-dose chemotherapy in the last 10 years: a study of the European Society for Blood and Marrow Transplantation Solid Tumors Working Party.

    PubMed

    Necchi, A; Miceli, R; Bregni, M; Bokemeyer, C; Berger, L A; Oechsle, K; Schumacher, K; Kanfer, E; Bourhis, J H; Massard, C; Laszlo, D; Montoro, J; Flechon, A; Arpaci, F; Secondino, S; Wuchter, P; Dreger, P; Crysandt, M; Worel, N; Kruger, W; Ringhoffer, M; Unal, A; Nagler, A; Campos, A; Wahlin, A; Michieli, M; Sucak, G; Donnini, I; Schots, R; Ifrah, N; Badoglio, M; Martino, M; Raggi, D; Giannatempo, P; Rosti, G; Pedrazzoli, P; Lanza, F

    2016-03-01

    Little is known about the prognostic impact of prior paclitaxel therapy and response to induction chemotherapy defined as the regimen preceding high-dose chemotherapy (HDCT) for the salvage therapy of advanced germ cell tumors. Twenty European Society for Blood and Marrow Transplantation centers contributed data on patients treated between 2002 and 2012. Paclitaxel used in either prior lines of therapy or in induction-mobilization regimens was considered. Multivariable Cox analyses of prespecified factors were undertaken on PFS and overall survival (OS). As of October 2013, data for 324 patients had been contributed to this study. One hundred and ninety-two patients (59.3%) had received paclitaxel. Sixty-one patients (19%) had a progression to induction chemotherapy, 234 (72%) a response (29 (9%) missing or granulocyte colony-stimulating factor without chemotherapy). Both progression to induction chemotherapy and prior paclitaxel were significantly associated with shorter OS univariably (P<0.001 and P=0.032). On multivariable analysis from the model with fully available data (N=216) progression to induction was significantly prognostic for PFS and OS (P=0.003), but prior paclitaxel was not (P=0.674 and P=0.739). These results were confirmed after multiple imputation of missing data. Progression to induction chemotherapy could be demonstrated as an independent prognostic factor, in contrast to prior paclitaxel. PMID:26642334

  4. X-ray induced Sm{sup 3+} to Sm{sup 2+} conversion in fluorophosphate and fluoroaluminate glasses for the monitoring of high-doses in microbeam radiation therapy

    SciTech Connect

    Vahedi, Shahrzad; Okada, Go; Morrell, Brian; Muzar, Edward; Koughia, Cyril; Kasap, Safa; Edgar, Andy; Varoy, Chris; Belev, George; Wysokinski, Tomasz; Chapman, Dean

    2012-10-01

    Fluorophosphate and fluoroaluminate glasses doped with trivalent samarium were evaluated as sensors of x-ray radiation for microbeam radiation therapy at the Canadian Light Source using the conversion of trivalent Sm{sup 3+} to the divalent form Sm{sup 2+}. Both types of glasses show similar conversion rates and may be used as a linear sensor up to {approx}150 Gy and as a nonlinear sensor up to {approx}2400 Gy, where saturation is reached. Experiments with a multi-slit collimator show high spatial resolution of the conversion pattern; the pattern was acquired by a confocal fluorescence microscopy technique. The effects of previous x-ray exposure may be erased by annealing at temperatures exceeding the glass transition temperature T{sub g} while annealing at T{sub A} < T{sub g} enhances the Sm conversion. This enhancement is explained by a thermally stimulated relaxation of host glass ionic matrix surrounding x-ray induced Sm{sup 2+} ions. In addition, some of the Sm{sup 3+}-doped glasses were codoped with Eu{sup 2+}-ions but the results show that there is no marked improvement in the conversion efficiency by the introduction of Eu{sup 2+}.

  5. Rituximab plus gemcitabine and oxaliplatin in patients with refractory/relapsed diffuse large B-cell lymphoma who are not candidates for high-dose therapy. A phase II Lymphoma Study Association trial.

    PubMed

    Mounier, Nicolas; El Gnaoui, Taoufik; Tilly, Hervé; Canioni, Danièle; Sebban, Catherine; Casasnovas, René-Olivier; Delarue, Richard; Sonet, Anne; Beaussart, Pauline; Petrella, Tony; Castaigne, Sylvie; Bologna, Serge; Salles, Gilles; Rahmouni, Alain; Gaulard, Philippe; Haioun, Corinne

    2013-11-01

    A previous pilot study with rituximab, gemcitabine and oxaliplatin showed promising activity in patients with refractory/relapsed B-cell lymphoma. We, therefore, conducted a phase II study to determine whether these results could be reproduced in a multi-institutional setting. This phase II study included 49 patients with refractory (n=6) or relapsing (n=43) diffuse large B-cell lymphoma. The median age of the patients was 69 years. Prior treatment included rituximab in 31 (63%) and autologous transplantation in 17 (35%) patients. International Prognostic Index at enrollment was >2 in 34 patients (71%). The primary endpoint was overall response rate after four cycles of treatment. Patients were planned to receive eight cycles if they reached at least partial remission after four cycles. After four cycles 21 patients (44%) were in complete remission and 8 (17%) in partial remission, resulting in an overall response rate of 61%. Factors significantly affecting overall response rate were early (<1 year) progression/relapse (18% versus 54%; P=0.001) and prior exposure to rituximab (23% versus 65%; P=0.004). Five-year progression-free and overall survival rates were 12.8% and 13.9%, respectively. Rituximab, gemcitabine and oxaliplatin were well tolerated with grade 3-4 infectious episodes in 22% of the cycles. These results are the first confirmation from a multicenter study that rituximab, gemcitabine and oxaliplatin provide a consistent response rate in patients with refractory/relapsed diffuse large B-cell lymphoma. This therapy can now be considered as a platform for new combinations with targeted treatments. This trial was registered at clinicaltrial.gov under #NCT00169195. PMID:23753028

  6. Rituximab plus gemcitabine and oxaliplatin in patients with refractory/relapsed diffuse large B-cell lymphoma who are not candidates for high-dose therapy. A phase II Lymphoma Study Association trial

    PubMed Central

    Mounier, Nicolas; El Gnaoui, Taoufik; Tilly, Hervé; Canioni, Danièle; Sebban, Catherine; Casasnovas, René-Olivier; Delarue, Richard; Sonet, Anne; Beaussart, Pauline; Petrella, Tony; Castaigne, Sylvie; Bologna, Serge; Salles, Gilles; Rahmouni, Alain; Gaulard, Philippe; Haioun, Corinne

    2013-01-01

    A previous pilot study with rituximab, gemcitabine and oxaliplatin showed promising activity in patients with refractory/relapsed B-cell lymphoma. We, therefore, conducted a phase II study to determine whether these results could be reproduced in a multi-institutional setting. This phase II study included 49 patients with refractory (n=6) or relapsing (n=43) diffuse large B-cell lymphoma. The median age of the patients was 69 years. Prior treatment included rituximab in 31 (63%) and autologous transplantation in 17 (35%) patients. International Prognostic Index at enrollment was >2 in 34 patients (71%). The primary endpoint was overall response rate after four cycles of treatment. Patients were planned to receive eight cycles if they reached at least partial remission after four cycles. After four cycles 21 patients (44%) were in complete remission and 8 (17%) in partial remission, resulting in an overall response rate of 61%. Factors significantly affecting overall response rate were early (<1 year) progression/relapse (18% versus 54%; P=0.001) and prior exposure to rituximab (23% versus 65%; P=0.004). Five-year progression-free and overall survival rates were 12.8% and 13.9%, respectively. Rituximab, gemcitabine and oxaliplatin were well tolerated with grade 3–4 infectious episodes in 22% of the cycles. These results are the first confirmation from a multicenter study that rituximab, gemcitabine and oxaliplatin provide a consistent response rate in patients with refractory/relapsed diffuse large B-cell lymphoma. This therapy can now be considered as a platform for new combinations with targeted treatments. This trial was registered at clinicaltrial.gov under #NCT00169195. PMID:23753028

  7. [Clinical trials of ultra-high-dose methylcobalamin in ALS].

    PubMed

    Izumi, Yuishin; Kaji, Ryuji

    2007-10-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting both upper and lower motor neurons. Weakness may begin in the legs, hands, proximal arms, or pharynx. The course is relentless and progressive without remissions, relapses, or even stable plateaus. There is no effective drug therapy for ALS, although riluzole has been shown to prolong life in sufferers, without tracheostomy. A vitamin B12 analog, methylcobalamin, has a protective effect on cultured cortical neurons against glutamate-induced cytotoxicity. We have shown the ultra-high-dose methylcobalamin (25 mg/day i.m.) slows down the progressive reduction of the CMAP (compound muscle action potential) amplitudes in ALS in the short term (4 weeks). The latencies of SSR (sympathetic skin response) were shorter after treatment (50 mg/day i.v., 2 weeks). In the long-term effect of methylcobalamin (50 mg/day i.m., twice a week), the survival time (or the period to become respirator-bound) was significantly longer in the treated group than in the untreated. Larger-scale randomized double blind trial was started in Japan in order to evaluate the long-term efficacy and the safety of ultra-high-dose methylcobalamin for sporadic or familial cases of ALS. PMID:17969354

  8. High sensitive airborne radioiodine monitor.

    PubMed

    Ogata, Yoshimune; Yamasaki, Tadashi; Hanafusa, Ryuji

    2013-11-01

    Airborne radioiodine monitoring includes a problem in that commercial radioactive gas monitors have inadequate sensitivity. To solve this problem, we designed a highly sensitive monitoring system. The higher counting efficiency and lower background made it possible to perform the low-level monitoring. The characteristics of the system were investigated using gaseous (125)I. The minimum detectable activity concentration was 1 × 10(-4)Bq cm(-3) for 1 min counting, which is one tenth of the legal limit for the radiation controlled areas in Japan. PMID:23602709

  9. A Logical levothyroxine dose Individualization: Optimization Approach at discharge from Radioiodine therapy ward and during follow-up in patients of Differentiated Thyroid Carcinoma: Balancing the Risk based strategy and the practical issues and challenges: Experience and Views of a large volume referral centre in India

    PubMed Central

    Basu, Sandip; Abhyankar, Amit; Asopa, Ramesh; Chaukar, Devendra; DCruz, Anil K

    2013-01-01

    In this communication, the authors discuss the issue of individualization of thyrotropin suppressive therapy in differentiated thyroid carcinoma (DTC) patients and share their views with respect to optimizing the dose of levothyroxine (LT) prescription both during discharge from radioiodine therapy ward and during follow-up. The changing management paradigm at our Institute during post-thyroidectomy period and during the preparation for radioiodine scan is also briefly highlighted. Five factors can be identified as important determinants for the dose individualization approach: (1) Persistence or absence of metastatic disease, (2) the risk characteristics of the patient and the tumor (3) patient's clinical profile, symptomatology, and contraindications (4) the feasibility to ensure a proper thyroid stimulating hormone TSH suppression level (depends on patient's socio-economic and educational background, the connectivity with the local physician and his expertise) (5) time period elapsed since initial diagnosis. While discussing each individual case scenario, the authors, based upon their experience in one of the busiest thyroid cancer referral centers in the country, discuss certain unaddressed points in the current guideline recommendations, deviations made and some challenges toward employing them into practice, which could be situation and center specific. In addition to these, the value of clinical examination, patient profile and detailed enquiry about clinical symptomatology by the attending physician in each follow-up visit cannot be overemphasized. According to the authors, this aspect, quite important for dose determination in an individual, is relatively underrepresented in the present guidelines. It would also be worthwhile to follow a conservative approach (till clear data emerges) in patients who have characteristics of “high-risk” disease, but are clinically and biochemically disease free, if no medical contraindications exist and patient

  10. High-dose naloxone in tardive dyskinesia.

    PubMed

    Lindenmayer, J P; Gardner, E; Goldberg, E; Opler, L A; Kay, S R; van Praag, H M; Weiner, M; Zukin, S

    1988-10-01

    Tardive dyskinesia (TD) is thought to result from nigrostriatal dopaminergic supersensitivity secondary to prolonged neuroleptic exposure. Preclinical studies have demonstrated that the opiate antagonist naloxone can acutely reverse a haloperidol-induced hyperdopaminergic state. In a trial of high-dose naloxone, 20 patients with TD received i.v. naloxone (20 mg, 40 mg, and placebo) under double-blind conditions. At baseline and at regular postdrug intervals, patients were evaluated using a battery of motor, clinical, and neuropsychological measures to study effects on neurological, behavioral, and cognitive functions. There was a significant improvement in involuntary movements at 30 min postnaloxone, together with improvement in clinical ratings at that time point, as well as some cognitive changes. The implications of these findings for the putative functional relationship between dopaminergic and enkephalinergic systems in the nigrostriatal area are discussed. PMID:3070611

  11. High-dose thiamine improves the symptoms of fibromyalgia.

    PubMed

    Costantini, Antonio; Pala, Maria Immacolata; Tundo, Silvia; Matteucci, Pietro

    2013-01-01

    Living with fibromyalgia means living with chronic pain, fatigue, sleep disorders and other associated key symptoms. To date, pharmacotherapy generally produces modest benefits. Some observations indicate that the large majority of symptoms of fibromyalgia could be the clinical manifestation of a mild thiamine deficiency due to a dysfunction of the active transport of thiamine from the blood to the mitochondria or to enzymatic abnormalities. Between June and July 2011, we recruited three female patients affected by fibromyalgia. We proceeded with the study of the patients' history, a physical examination, an evaluation of chronic widespread pain using the Visual Numeric Scale and an evaluation of the fatigue using the Fatigue Severity Scale were also performed. The levels of thiamine and thiamine pyrophosphate in the blood were determined. After the therapy with high doses of thiamine, in the patients, there was an appreciable improvement of the symptoms. PMID:23696141

  12. High-dose thiamine improves the symptoms of Friedreich's ataxia

    PubMed Central

    Costantini, Antonio; Giorgi, Rafaela; D'Agostino, Sonia; Pala, Maria Immacolata

    2013-01-01

    Friedreich's ataxia (FRDA) is an autosomal recessive inherited disorder characterised by progressive gait and limb ataxia, dysarthria, areflexia, loss of position sense and a progressive motor weakness of central origin. Some observations indicate that all symptoms of FRDA ataxia could be the manifestation of a thiamine deficiency because of enzymatic abnormalities. Two patients with FRDA were under rehabilitative treatment from February 2012 to February 2013. The scale for assessment and rating of ataxia was performed. The patient began an intramuscular therapy with 100 mg of thiamine every 3–5  days. Injection of high-dose thiamine was effective in reversing the motor failure. From this clinical observation, it is reasonable to infer that a thiamine deficiency due to enzymatic abnormalities could cause a selective neuronal damage in the centres that are typically affected by this disease. PMID:23704441

  13. High dose thiamine improves fatigue in multiple sclerosis

    PubMed Central

    Costantini, Antonio; Nappo, Agostino; Pala, Maria Immacolata; Zappone, Antonietta

    2013-01-01

    The majority of the patients with multiple sclerosis (MS) experience fatigue. Some observations indicate that fatigue and related manifestations concomitant with MS could be associated with an intracellular mild thiamine deficiency. We recruited 15 patients with MS who also experience fatigue and assessed the severity of the fatigue using the Fatigue Severity Scale. Although blood thiamine and thiamine pyrophosphate levels were within normal limit in all the patients, high-dose thiamine therapy administered orally or parenterally led to an appreciable improvement of the fatigue. The absence of apparent decrease in blood thiamine despite the presence of symptoms referable to a mild thiamine deficiency suggests that these patients may have a dysfunction of the mechanisms of intracellular transport or structural enzymatic abnormalities. The administration of large quantities of thiamine was effective in reversing the fatigue in MS, suggesting that the abnormalities in thiamine-dependent processes could be overcome by diffusion-mediated transport at supranormal thiamine concentrations. PMID:23861280

  14. High-dose thiamine improves the symptoms of fibromyalgia

    PubMed Central

    Costantini, Antonio; Pala, Maria Immacolata; Tundo, Silvia; Matteucci, Pietro

    2013-01-01

    Living with fibromyalgia means living with chronic pain, fatigue, sleep disorders and other associated key symptoms. To date, pharmacotherapy generally produces modest benefits. Some observations indicate that the large majority of symptoms of fibromyalgia could be the clinical manifestation of a mild thiamine deficiency due to a dysfunction of the active transport of thiamine from the blood to the mitochondria or to enzymatic abnormalities. Between June and July 2011, we recruited three female patients affected by fibromyalgia. We proceeded with the study of the patients’ history, a physical examination, an evaluation of chronic widespread pain using the Visual Numeric Scale and an evaluation of the fatigue using the Fatigue Severity Scale were also performed. The levels of thiamine and thiamine pyrophosphate in the blood were determined. After the therapy with high doses of thiamine, in the patients, there was an appreciable improvement of the symptoms. PMID:23696141

  15. Modern trends and development in high-dose luminescent measurements

    NASA Astrophysics Data System (ADS)

    Kortov, V.

    2014-11-01

    Main application areas of high-dose dosimetry are described. The requirements to the materials for high-dose luminescent detectors are set. The examples of successful high-dose measurements using radiation-resistant phosphors are given. Viability of using materials with deep traps to detect intensive radiation flows is grounded. Characteristics of high-dose measurements using highly sensitive detectors TLD-500 (Al2O3:C) and LiF:Mg,Cu,P are discussed.

  16. Radioiodine in the Savannah River Site environment

    SciTech Connect

    Kantelo, M.V.; Bauer, L.R.; Marter, W.L.; Murphy, C.E. Jr.; Zeigler, C.C.

    1993-01-15

    Radioiodine, which is the collective term for all radioactive isotopes of the element iodine, is formed at the Savannah River Site (SRS) principally as a by-product of nuclear reactor operations. Part of the radioiodine is released to the environment during reactor and reprocessing operations at the site. The purpose of this report is to provide an introduction to radioiodine production and disposition, its status in the environment, and the radiation dose and health risks as a consequence of its release to the environment around the Savannah River Plant. A rigorous dose reconstruction study is to be completed by thee Center for Disease Control during the 1990s.

  17. Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer

    PubMed Central

    2016-01-01

    Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term “theranostics” was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging. PMID:27239470

  18. Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer.

    PubMed

    Ahn, Byeong-Cheol

    2016-01-01

    Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term "theranostics" was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging. PMID:27239470

  19. Administration of high-dose interleukin-2 in a 2-year-old with metastatic melanoma.

    PubMed

    Bernhardt, M Brooke; Hicks, M John; Pappo, Alberto S

    2009-12-15

    Malignant melanoma is rare in pediatrics, and therapies for patients with disseminated disease have not been well studied. This report describes our experience with the use of high-dose interleukin 2 (aldesleukin, IL-2) in a 2-year-old child with metastatic melanoma and describes our approach for the administration of this agent to young patients. PMID:19731326

  20. Ketobemidone may alter busulfan pharmacokinetics during high-dose therapy.

    PubMed

    Hassan, M; Svensson, J O; Nilsson, C; Hentschke, P; Al-Shurbaji, A; Aschan, J; Ljungman, P; Ringdén, O

    2000-08-01

    The authors report a possible interaction between ketobemidone and busulfan during myeloablative treatment of a patient with acute myeloid leukemia. At the time of admission, the patient was receiving ketobemidone 1,000 mg/d as analgesic for a rectal fissure. The patient started conditioning prior to bone marrow transplantation with busulfan (1 mg/kg x 4 for 4 days). High busulfan plasma concentrations were observed after the first dose and the next doses were reduced to 0.7 mg/kg. The kinetics of both drugs revealed that an increase in ketobemidone concentration was followed by an increase in busulfan levels. Substituting ketobemidone with morphine resulted in a decrease in busulfan concentration despite increasing the dose once more to 1 mg/kg. PMID:10942175

  1. No Salvage Using High-Dose Chemotherapy Plus/Minus Reirradiation for Relapsing Previously Irradiated Medulloblastoma

    SciTech Connect

    Massimino, Maura Gandola, Lorenza; Spreafico, Filippo; Biassoni, Veronica; Luksch, Roberto; Collini, Paola; Solero, Carlo N.; Simonetti, Fabio; Pignoli, Emanuele; Cefalo, Graziella; Poggi, Geraldina; Modena, Piergiorgio Ph.D.; Mariani, Luigi; Potepan, Paolo; Podda, Marta; Casanova, Michela; Pecori, Emilia; Acerno, Stefania; Ferrari, Andrea; Terenziani, Monica

    2009-04-01

    Purpose: Myeloablative regimens were frequently used for medulloblastoma relapsing after craniospinal irradiation (CSI): in 1997-2002, we used repeated surgery, standard-dose and myeloablative chemotherapy, and reirradiation. Methods and Materials: In 10 patients, reinduction included sequential high-dose etoposide, high-dose cyclophosphamide/vincristine, and high-dose carboplatin/vincristine, then two myeloablative courses with high-dose thiotepa ({+-} carboplatin); 6 other patients received two of four courses of cisplatin/etoposide. Hematopoietic precursor mobilization followed high-dose etoposide or high-dose cyclophosphamide or cisplatin/etoposide therapy. After the overall chemotherapy program, reirradiation was prescribed when possible. Results: Seventeen patients were treated: previous treatment included CSI of 19.5-36 Gy with posterior fossa/tumor boost and chemotherapy in 16 patients. Fifteen patients were in their first and 2 in their second and third relapses, respectively. First progression-free survival had lasted a median of 26 months. Relapse sites included leptomeninges in 9 patients, spine in 4 patients, posterior fossa in 3 patients, and brain in 1 patient. Three patients underwent complete resection of recurrence, and 10 underwent reirradiation. Twelve of 14 patients with assessable tumor had an objective response after reinduction; 2 experienced progression and were not given the myeloablative courses. Remission lasted a median of 16 months. Additional relapses appeared in 13 patients continuing the treatment. Fifteen patients died of progression and 1 died of pneumonia 13 months after relapse. The only survivor at 93 months had a single spinal metastasis that was excised and irradiated. Survival for the series as a whole was 11-93 months, with a median of 41 months. Conclusions: Despite responses being obtained and ample use of surgery and reirradiation, second-line therapy with myeloablative schedules was not curative, barring a few

  2. High dose intravenous ciprofloxacin in febrile neutropenic patients.

    PubMed

    Johnson, P R; Yin, J A; Tooth, J A

    1990-12-01

    We have evaluated the use of high-dose intravenous ciprofloxacin as monotherapy in the empirical therapy of febrile episodes in neutropenic patients during the course of a randomized trial comparing ciprofloxacin with a standard combination regimen. Sixty-four episodes of fever were studied in a high risk population of 42 patients mostly undergoing intensive chemotherapy for leukaemia. Ciprofloxacin achieved clinical responses as follows: completely successful in 39%, partially successful in 20%, and unsuccessful in 41%. Infections were microbiologically documented in 37 (58%), with Gram-positive bacteria (of which 37% were coagulase negative staphylococci and 34% were streptococci) accounting for 81% of all organisms cultured. Responses in documented infections were as follows; completely successful in 32%, partially successful in 27%, and unsuccessful in 41%. One infection-related death occurred 30 h after starting ciprofloxacin, and a further three patients died before the resolution of neutropenia. The early death was caused by fulminant infection with a ciprofloxacin-resistant Pseudomonas aeruginosa. No other ciprofloxacin resistance was seen amongst eight Gram-negative isolates. There was no evidence of emerging ciprofloxacin resistance during the course of the study. Ciprofloxacin was associated with a low incidence of adverse events with skin rash (five cases) and nausea (one case) being reported as possibly or probably related to ciprofloxacin. We conclude that high-dose intravenous ciprofloxacin may be safely employed as monotherapy in the empirical treatment of febrile episodes in neutropenic patients. It has the additional advantages of twice daily administration, the availability of intravenous and oral presentations, and absence of cross-allergy in beta-lactam antibiotic hypersensitive patients. PMID:2292537

  3. Radiation Therapy

    MedlinePlus

    Radiation therapy is a cancer treatment. It uses high doses of radiation to kill cancer cells and stop them ... places inside your body. The type of radiation therapy you receive depends on many factors, including The ...

  4. Radioactive Iodine (I-131) Therapy for Hyperthyroidism

    MedlinePlus

    ... Iodine (I-131) Therapy Radioiodine therapy is a nuclear medicine treatment for an overactive thyroid, a condition ... locally overactive in producing too much thyroid hormone. Nuclear medicine is a branch of medical imaging that ...

  5. Radioiodine thyroid ablation in graves' hyperthyroidism: merits and pitfalls.

    PubMed

    Nwatsock, J F; Taieb, D; Tessonnier, L; Mancini, J; Dong-A-Zok, F; Mundler, O

    2012-01-01

    Ablative approaches using radioiodine are increasingly proposed for the treatment of Graves' disease (GD) but their ophthalmologic and biological autoimmune responses remain controversial and data concerning clinical and biochemical outcomes are limited. The aim of this study was to evaluate thyroid function, TSH-receptor antibodies (TRAb) and Graves' ophthalmopathy (GO) occurrence after radioiodine thyroid ablation in GD. We reviewed 162 patients treated for GD by iodine-131 ((131)I) with doses ranging from 370 to 740 MBq, adjusted to thyroid uptake and sex, over a 6-year period in a tertiary referral center. Collected data were compared for outcomes, including effectiveness of radioiodine therapy (RIT) as primary endpoint, evolution of TRAb, and occurrence of GO as secondary endpoints. The success rate was 88.3% within the first 6 months after the treatment. The RIT failure was increased in the presence of goiter (adjusted odds ratio = 4.1, 95% confidence interval 1.4-12.0, P = 0.010). The TRAb values regressed with time (r = -0.147; P = 0.042) and patients with a favorable outcome had a lower TRAb value (6.5 ± 16.4 U/L) than those with treatment failure (23.7 ± 24.2 U/L, P < 0.001). At the final status, 48.1% of patients achieved normalization of serum TRAb. GO occurred for the first time in 5 patients (3.7%) who were successfully cured for hyperthyroidism but developed early and prolonged period of hypothyroidism in the context of antithyroid drugs (ATD) intolerance (P = 0.003) and high TRAb level (P = 0.012). On the basis the results of this study we conclude that ablative RIT is effective in eradicating Graves' hyperthyroidism but may be accompanied by GO occurrence, particularly in patients with early hypothyroidism and high pretreatment TRAb and/or ATD intolerance. In these patients, we recommend an early introduction of LT4 to reduce the duration and the degree of the radioiodine-induced hypothyroidism. PMID:22942775

  6. Benefits of automated surface decontamination of a radioiodine ward.

    PubMed

    Westcott, Eliza; Broadhurst, Alicia; Crossley, Steven; Lee, Lloyd; Phan, Xuyen; Scharli, Rainer; Xu, Yan

    2012-02-01

    A floor-washing robot has been acquired to assist physicists with decontamination of radioiodine therapy ward rooms after discharge of the patient at Sir Charles Gairdner Hospital. The effectiveness of the robot in decontaminating the ward has been evaluated. A controlled experiment was performed by deliberately contaminating a polyvinyl chloride flooring offcut with 131I followed by automated decontamination with the robot. The extent of fixed and removable contamination was assessed before and after decontamination by two methods: (1) direct Geiger-Mueller counting and (2) beta-counting wipe tests. Surface contamination was also assessed in situ on the ward by Geiger-Mueller counting and wipe testing. Contamination maps confirmed that contamination was removed rather than spread around by the robot. Wipe testing revealed that the robot was successful in clearing approximately 60-80% of removable contamination. The robotic floor-washing device was considered suitable to provide effective automated decontamination of the radioiodine ward. In addition, the robot affords other benefits: the time spent by the physicists decontaminating the room is greatly reduced offering financial and occupational safety and health benefits. The robot has also found utility in other decontamination applications in the healthcare environment. PMID:22249471

  7. DMSO Increases Radioiodination Yield of Radiopharmaceuticals

    PubMed Central

    Wang, Ketai; Adelstein, S. James; Kassis, Amin I.

    2007-01-01

    A high-yield radioiodination method for various types of molecules is described. The approach employs DMSO as precursor solvent, a reaction ratio of 2–5 precursor molecules per iodine atom, 5–10 μg oxidant, and a 10–25-μl reaction volume. The solution is vortexed at room temperature for 1–5 min and progress of the reaction is assessed by HPLC. Radioiodinated products are obtained in ≥95% yield and meet the requirements for radiotracer imaging, biodistribution studies, and molecular and cellular biology research. PMID:17931872

  8. Mammary radioiodine accumulation due to functional sodium iodide symporter expression in a benign fibroadenoma

    SciTech Connect

    Berger, F.; Unterholzner, S.; Diebold, J.; Knesewitsch, P.; Hahn, K.; Spitzweg, C. . E-mail: Christine.Spitzweg@med.uni-muenchen.de

    2006-11-03

    The sodium iodide symporter (NIS) has been characterized to mediate the active transport of iodide not only in the thyroid gland but also in various non-thyroidal tissues, including lactating mammary gland and the majority of breast cancers, thereby offering the possibility of diagnostic and therapeutic radioiodine application in breast cancer. In this report, we present a 57-year-old patient with multifocal papillary thyroid carcinoma, who showed focal radioiodine accumulation in a lesion in the right breast on a posttherapy {sup 131}I scan following radioiodine therapy. CT and MR-mammography showed a focal solid lesion in the right breast suggestive of a fibroadenoma, which was confirmed by histological examination. Immunostaining of paraffin-embedded tumor tissue sections using a human NIS antibody demonstrated NIS-specific immunoreactivity confined to epithelial cells of mammary ducts. In conclusion, in a thyroid cancer patient we identified a benign fibroadenoma of the breast expressing high levels of functionally active NIS protein as underlying cause of focal mammary radioiodine accumulation on a posttherapy {sup 131}I scan. These data show for the first time that functional NIS expression is not restricted to lactating mammary gland and malignant breast tissue, but can also be detected in benign breast lesions, such as fibroadenomata of the breast.

  9. Response of osteosarcoma to preoperative intravenous high-dose methotrexate chemotherapy: CT evaluation

    SciTech Connect

    Mail, J.T.; Cohen, M.D.; Mirkin, L.D.; Provisor, A.J.

    1985-01-01

    The histologic response of an osteosarcoma to preamputation high-dose methotrexate therapy can be used to determine the optimum maintenance chemotherapy regimen to be administered after amputation. This study evaluates computed tomography (CT) as a method of assessing the response of the tumor to the methotrexate therapy. Nine patients with nonmetastatic osteosarcoma of an extremity had a CT scan of the tumor at initial presentation. This was compared with a second CT scan after four courses of high-dose intravenous methotrexate. Each set of scans was evaluated for changes in bony destruction, soft-tissue mass, pattern of calcification, and extent of tumor involvement of the marrow cavity. These findings were correlated with the histologic response of the tumor as measured by the degree of tumor necrosis. The changes seen on CT correlated well with the degree of the histologic response in seven of the nine patients.

  10. Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions.

    PubMed Central

    Naderer, O; Nafziger, A N; Bertino, J S

    1997-01-01

    The effects of a 10-day course of moderate-dose (10 mg/kg/day) or high-dose (20 mg/kg/day) trimethoprim therapy on serum creatinine, measured creatinine clearance, urinary creatinine excretion, and serum folate were studied in 20 healthy volunteers. Serum creatinine concentrations increased significantly during trimethoprim therapy, began to decrease near day 10, and returned to baseline during the washout phase at both dosage levels. At the same time, measured creatinine clearance and urine creatinine changed in the opposite direction. No clinical or statistical differences were noted between changes in the moderate- versus the high-dose phases. Serum folate concentration decreases during high-dose trimethoprim therapy were statistically significant. Adverse drug reactions in the two groups were statistically different during the first study period, with the high-dose group having a 75% incidence rate and the moderate-dose group having an 11% incidence rate (P < 0.02). Serum creatinine, measured creatinine clearance, and urinary creatinine excretion demonstrated statistically, but not clinically, significant changes during trimethoprim therapy. In addition, high-dose trimethoprim caused significantly more adverse drug reactions than moderate-dose trimethoprim in normal volunteers. PMID:9371351

  11. Salvage high-dose-rate interstitial brachytherapy for locally recurrent rectal cancer*

    PubMed Central

    Pellizzon, Antônio Cássio Assis

    2016-01-01

    For tumors of the lower third of the rectum, the only safe surgical procedure is abdominal-perineal resection. High-dose-rate interstitial brachytherapy is a promising treatment for local recurrence of previously irradiated lower rectal cancer, due to the extremely high concentrated dose delivered to the tumor and the sparing of normal tissue, when compared with a course of external beam radiation therapy. PMID:27403021

  12. Oxalate Nephropathy After Continuous Infusion of High-Dose Vitamin C as an Adjunct to Burn Resuscitation

    PubMed Central

    Pamplin, Jeremy; Studer, Lynette; Hughes, Rhome L.; King, Booker T.; Graybill, John C.; Chung, Kevin K.

    2016-01-01

    Fluid resuscitation is the foundation of management in burn patients and is the topic of considerable research. One adjunct in burn resuscitation is continuous, high-dose vitamin C (ascorbic acid) infusion, which may reduce fluid requirements and thus decrease the risk for over resuscitation. Research in preclinical studies and clinical trials has shown continuous infusions of high-dose vitamin C to be beneficial with decrease in resuscitative volumes and limited adverse effects. However, high-dose and low-dose vitamin C supplementation has been shown to cause secondary calcium oxalate nephropathy, worsen acute kidney injury, and delay renal recovery in non-burn patients. To the best of our knowledge, the authors present the first case series in burn patients in whom calcium oxalate nephropathy has been identified after high-dose vitamin C therapy. PMID:25812044

  13. Oxalate Nephropathy After Continuous Infusion of High-Dose Vitamin C as an Adjunct to Burn Resuscitation.

    PubMed

    Buehner, Michelle; Pamplin, Jeremy; Studer, Lynette; Hughes, Rhome L; King, Booker T; Graybill, John C; Chung, Kevin K

    2016-01-01

    Fluid resuscitation is the foundation of management in burn patients and is the topic of considerable research. One adjunct in burn resuscitation is continuous, high-dose vitamin C (ascorbic acid) infusion, which may reduce fluid requirements and thus decrease the risk for over resuscitation. Research in preclinical studies and clinical trials has shown continuous infusions of high-dose vitamin C to be beneficial with decrease in resuscitative volumes and limited adverse effects. However, high-dose and low-dose vitamin C supplementation has been shown to cause secondary calcium oxalate nephropathy, worsen acute kidney injury, and delay renal recovery in non-burn patients. To the best of our knowledge, the authors present the first case series in burn patients in whom calcium oxalate nephropathy has been identified after high-dose vitamin C therapy. PMID:25812044

  14. Immobilization of radioiodine in synthetic boracite

    DOEpatents

    Babad, H.; Strachan, D.M.

    1982-09-23

    A nuclear waste storage product is disclosed in which radioiodine is incorporated in a synthetic boracite. The boracite may be prepared by reacting a transition metal iodide with an alkali horate under mild hydrothermal conditions, drying the reaction product, and then hot pressing.

  15. Radioiodine concentrated in a wetland.

    PubMed

    Kaplan, Daniel I; Zhang, Saijin; Roberts, Kimberly A; Schwehr, Kathy; Xu, Chen; Creeley, Danielle; Ho, Yi-Fang; Li, Hsiu-Ping; Yeager, Chris M; Santschi, Peter H

    2014-05-01

    Most subsurface environmental radioactivity contamination is expected to eventually resurface in riparian zones, or wetlands. There are a number of extremely sharp biogeochemical interfaces in wetlands that could alter radionuclide speciation and promote accumulation. The objective of this study was to determine if a wetland concentrated (129)I emanating from a former waste disposal basin located on the Savannah River Site (SRS) in South Carolina, USA. Additionally, studies were conducted to evaluate the role of sediment organic matter in immobilizing the radioiodine. Groundwater samples were collected along a 0.7-km transect away from the seepage basin and in the downstream wetlands. The samples were analyzed for (129)I speciation (iodide (I(-)), iodate (IO3(-)), and organo-I). Groundwater (129)I concentrations in many locations in the wetlands (as high as 59.9 Bq L(-1)(129)I) were greatly elevated with respect to the source term (5.9 Bq L(-1)(129)I). (129)I concentration profiles in sediment cores were closely correlated to organic matter concentrations (r(2) = 0.992; n = 5). While the sediment organic matter promoted the uptake of (129)I to the wetland sediment, it also promoted the formation of a soluble organic fraction: 74% of the wetland groundwater (129)I could pass through a 1 kDa (<1 nm) membrane and only 26% of the (129)I was colloidal. Of that fraction that could pass through a 1 kDa membrane, 39% of the (129)I was organo-I. Therefore, while wetlands may be highly effective at immobilizing aqueous (129)I, they may also promote the formation of a low-molecular-weight organic species that does not partition to sediments. This study provides a rare example of radioactivity concentrations increasing rather than decreasing as it migrates from a point source and brings into question assumptions in risk models regarding continuous dilution of released contaminants. PMID:24075117

  16. Preclinical efficacy of the oncolytic measles virus expressing the sodium iodide symporter in iodine non-avid anaplastic thyroid cancer: a novel therapeutic agent allowing noninvasive imaging and radioiodine therapy.

    PubMed

    Reddi, H V; Madde, P; McDonough, S J; Trujillo, M A; Morris, J C; Myers, R M; Peng, K W; Russell, S J; McIver, B; Eberhardt, N L

    2012-09-01

    Anaplastic thyroid cancer is an extremely aggressive disease resistant to radioiodine treatment because of loss of sodium iodide symporter (NIS) expression. To enhance prognosis of this fatal cancer, we validated the preclinical efficacy of measles virus (MV)-NIS, the vaccine strain of the oncolytic MV (MV-Edm), modified to include the NIS gene. Western blotting analysis confirmed that a panel of eight anaplastic thyroid cancer (ATC)-derived cell lines do not express NIS protein, but do express CD46, the MV receptor. In vitro cell death assays and in vivo xenograft studies demonstrate the oncolytic efficacy of MV-NIS in BHT-101 and KTC-3, ATC-derived cell lines. Radioactive iodine uptake along with single-photon emission computed tomography (SPECT)-computed tomography imaging of KTC-3 xenografts after (99)Tc(m) administration confirmed NIS expression in vitro and in vivo, respectively, after virus treatment. Adjuvant administration of RAI, to MV-NIS-treated KTC-3 tumors showed a trend for increased tumor cell killing. As current treatment for ATC is only palliative, and MV-NIS is currently Food and Drug Administration approved for human clinical trials in myeloma, our data indicate that targeting ATC with MV-NIS could prove to be a novel therapeutic strategy for effective treatment of iodine-resistant ATC and will expedite its testing in clinical trials for this aggressive disease. PMID:22790962

  17. Respective roles of thyroglobulin, radioiodine imaging, and positron emission tomography in the assessment of thyroid cancer.

    PubMed

    Lind, Peter; Kohlfürst, Susanne

    2006-07-01

    Depending on the iodine supply of an area, the incidence of thyroid cancer ranges between 4 and 12/100,000 per year. To detect thyroid cancer in an early stage, the assessment of thyroid nodules includes ultrasonography, ultrasonography-guided fine-needle aspiration biopsy, and conventional scintigraphic methods using (99m)Tc-pertechnetate, (99m)Tc-sestamibi or -tetrofosmin, and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in selected cases. After treatment of thyroid cancer, a consequent follow-up is necessary over a period of several years. For following up low-risk patients, recombinant thyroid-stimulating hormone-stimulated thyroglobulin and ultrasonography is sufficient in most cases. After total thyroidectomy and radioiodine ablation therapy, thyroid-stimulating hormone-stimulated thyroglobulin should be below the detection limit (eg, <0.5 ng/mL, R: 70-130). An increase of thyroglobulin over time is suspicious for recurrent or metastatic disease. Especially in high-risk patients, aside from the use of ultrasonography for the detection of local recurrence and cervial lymph node metastases, nuclear medicine methods such as radioiodine imaging and FDG-PET are the methods of choice for localizing metastatic disease. Radioiodine imaging detects well-differentiated recurrences and metastases with a high specificity but only moderate sensitivity. The sensitivity of radioiodine imaging depends on the activity administered. Therefore a low activity diagnostic (131)I whole-body scan (74-185 MBq) has a lower detection rate than a high activity post-therapy scan (3700-7400 MBq). In patients with low or dedifferentiated thyroid cancer and after several courses of radioiodine therapy caused by metastatic disease, iodine negative metastases may develop. In these cases, despite clearly elevated levels of thyroglobulin, radioiodine imaging is negative or demonstrates only faint iodine uptake. The method of choice to image these iodine negative metastases is

  18. Comparison of Fixed versus Calculated Activity of Radioiodine for the Treatment of Graves Disease in Adults

    PubMed Central

    Dominguez, Paulette N.; Jimeno, Cecilia A.; Obaldo, Jerry M.; Ogbac, Ruben V.

    2016-01-01

    Background Radioactive iodine as a treatment modality has been shown in several studies to be a safe and effective therapy for Graves disease. However, there is still no uniformity regarding optimal dosing method. The aim of this study is to compare the efficacy of calculated and fixed dosing of radioiodine for the treatment of Graves disease. Methods A hundred twenty-two patients diagnosed with Graves disease were randomized to receive either fixed or calculated dose of radioiodine. Those randomized to fixed activity received either low fixed activity at 9.9 mCi for thyroid gland size <40 g or high fixed activity at 14.9 mCi for thyroid gland size 40 to 80 g, and those grouped to calculated activity received 160 µCi/g of thyroid tissue adjusted for 24 hours radioiodine uptake. Thyroid function tests (free thyroxine [T4] and thyroid stimulating hormone [TSH]) were monitored at 10, 16, and 24 weeks after radioactive iodine therapy. The primary outcome, treatment failure was defined as persistently elevated free T4 and low TSH. Results Of the 122 patients randomized, 56 in the fixed dose group and 56 in the calculated dose group completed the follow-up. At the end of 6 months, the percentage of treatment failure was 37.50% in the calculated dose group versus 19.64% in the fixed dose group with a relative risk of 0.53 (95% confidence interval, 0.28 to 0.98) favoring the fixed dose group. Conclusion Fixed dose radioiodine has a significantly lower incidence of persistent hyperthyroidism at 6 months post-radioactive therapy. PMID:26996425

  19. High Dose Ilaprazole/Amoxicillin as First-Line Regimen for Helicobacter pylori Infection in Korea

    PubMed Central

    Graham, David Y.

    2016-01-01

    Objective. The eradication rate of Helicobacter pylori (H. pylori) following standard triple therapy has declined over the past few decades. This study has determined whether high dose dual therapy (PPI and amoxicillin) is adequate for eradicating H. pylori in Korea. Methods. This was an open-labeled study of H. pylori infected treatment-naive patients. Subjects received dual therapy for 14 days: ilaprazole 40 mg tablets given twice a day and amoxicillin 750 mg tablets given 4 times a day. At the end of the therapy, the subjects visited the clinic to confirm compliance and monitor for any side effects. Subjects visited again after 4–6 weeks to confirm H. pylori status through a urea breath test. Results. The cure rate of H. pylori was 79.3% (23 of 29) (95% confidence interval: 61.6–90.2) in the intention-to-treat analysis and 82.1% (23 of 28) in the per-protocol analysis. Compliance rates were high (96.6%) and side effects were minimal and tolerable. Conclusion. A high dose of ilaprazole + amoxicillin was ineffective as the first-line therapy for eradicating H. pylori in Korea. Future studies should focus on intragastric pH measurements and assess amoxicillin resistance. PMID:27413365

  20. High-Dose Vitamin C Promotes Regression of Multiple Pulmonary Metastases Originating from Hepatocellular Carcinoma

    PubMed Central

    Seo, Min-Seok; Kim, Ja-Kyung

    2015-01-01

    We report a case of regression of multiple pulmonary metastases, which originated from hepatocellular carcinoma after treatment with intravenous administration of high-dose vitamin C. A 74-year-old woman presented to the clinic for her cancer-related symptoms such as general weakness and anorexia. After undergoing initial transarterial chemoembolization (TACE), local recurrence with multiple pulmonary metastases was found. She refused further conventional therapy, including sorafenib tosylate (Nexavar). She did receive high doses of vitamin C (70 g), which were administered into a peripheral vein twice a week for 10 months, and multiple pulmonary metastases were observed to have completely regressed. She then underwent subsequent TACE, resulting in remission of her primary hepatocellular carcinoma. PMID:26256994

  1. Relative safety profiles of high dose statin regimens

    PubMed Central

    Escobar, Carlos; Echarri, Rocio; Barrios, Vivencio

    2008-01-01

    Recent clinical trials recommend achieving a low-density lipoprotein cholesterol level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To attain these goals, however, many patients will need statins at high doses. The most frequent side effects related to the use of statins, myopathy, rhabdomyolysis, and increased levels of transaminases, are unusual. Although low and moderate doses show a favourable profile, there is concern about the tolerability of higher doses. During recent years, numerous trials to analyze the efficacy and tolerability of high doses of statins have been published. This paper updates the published data on the safety of statins at high doses. PMID:18827903

  2. Synthesis and biodistribution of radioiodinated nicotine analogs

    SciTech Connect

    Chan, S.M.; Basmadjian, G.P.; Marten, D.F.; Sadek, S.; Magarian, R.A.; Grunder, J.R.; Ice, R.D.

    1984-01-01

    The authors reported previously on the synthesis and biodistribution of radioiodinated 5-iodonicotine. In their continuous effort to search for a potential brain as well as adrenal medulla imaging agent, the authors synthesized four radioiodinated nicotine analogs. The labeled compounds were prepared by brominating nicotinic acid, and reacting the acylated product with the appropriate amines to give the respective amides which were then reduced with diborane to the amines. I-125 labeling was done by halogen exchange. Biodistribution studies performed in female Sprague-Dawley rats showed that all these compounds were taken up rapidly by the brain and the adrenal. The highest uptake of all these compounds in both organs occurred at 2 minutes after tail vein injections. The organ:blood ratios at 2 minutes and the T/sub 1/3/ (min.) of radioactivity in these organs were compared.

  3. Trends in Any and High-Dose Opioid Analgesic Receipt Among Aging Patients With and Without HIV

    PubMed Central

    Gordon, Kirsha; Edelman, E. Jennifer; Kerns, Robert D.; Crystal, Stephen; Dziura, James D.; Fiellin, Lynn E.; Gordon, Adam J.; Goulet, Joseph L.; Justice, Amy C.; Fiellin, David A.

    2016-01-01

    Harms of opioid analgesics, especially high-dose therapy among individuals with comorbidities and older age, are increasingly recognized. However, trends in opioid receipt among HIV-infected patients are not well characterized. We examined trends, from 1999 to 2010, in any and high-dose (≥120 mg/day) opioid receipt among patients with and without HIV, by age strata, controlling for demographic and clinical correlates. Of 127,216 patients, 64 % received at least one opioid prescription. Opioid receipt increased substantially among HIV-infected and uninfected patients over the study; high-dose therapy was more prevalent among HIV-infected patients. Trends in high-dose receipt stratified by three age groups revealed an increasing trend in each age strata, higher among HIV-infected patients. Correlates of any opioid receipt included HIV, PTSD and major depression. Correlates of high-dose receipt included HIV, PTSD, major depression and drug use disorders. These findings suggest a need for appropriate balance of risks and benefits, especially as these populations age. PMID:26384973

  4. Severe complications of ulcerative colitis after high-dose prednisolone and azathioprine treatment.

    PubMed

    Matsuda, K; Watanabe, T; Abo, Y; Uchida, H; Kawamura, Y J; Masaki, T; Muto, T

    1999-06-01

    We report a rare case of ulcerative colitis (UC) associated with methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa infections in multiple organs, and with compressive fracture from osteoporosis after the administration of high-dose prednisolone and azathioprine. A 25-year-old man had been treated with high-dose prednisolone for UC. He suddenly experienced severe lumbago, which prevented him from walking. Plain X-ray demonstrated compressive fractures of the thoracic and the lumbar vertebrae, which were thought to be due to osteoporosis as a side effect of the high-dose prednisolone. At this admission, in another hospital, he also had a bloody discharge from the rectum, and azathioprine was started; however, the patient's condition still did not show any improvement. The total doses of azathioprine and prednisolone he had received were 3150 mg and more than 15,000 mg, respectively. Considering the presence of the serious complications, surgical intervention was the treatment selected. Culture study revealed MRSA in the feces and nasal cavity, and P. aeruginosa in the feces and urine. Vancomycin hydrochloride and gentamicin were administered, and were effective, with a subsequent negative culture study. Subtotal colectomy with mucus fistula was performed. After the operation, culture studies remained negative. Major steroid side effects such as bone fracture and osteoporosis should be considered as an indication for surgery in UC patients. MRSA and P. aeruginosa are a menace, especially for UC immunosuppressed patients on steroid or immunosuppressive therapy. When these bacteria are detected, there should be prompt and adequate antimicrobial therapy against the organisms and the immunosuppressive therapy should be immediately discontinued. We conclude that surgical therapy should be considered in the earlier stage for patients with intractable UC, rather than continuing long-term administration of steroid or azathioprine, which may lead to

  5. Radiation Therapy

    MedlinePlus

    Radiation therapy is a cancer treatment. It uses high doses of radiation to kill cancer cells and stop them from ... half of all cancer patients receive it. The radiation may be external, from special machines, or internal, ...

  6. Does High-Dose Antimicrobial Chemotherapy Prevent the Evolution of Resistance?

    PubMed Central

    Day, Troy; Read, Andrew F.

    2016-01-01

    High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view. We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology. We use this framework to show how high-dose chemotherapy engenders opposing evolutionary processes involving the mutational input of resistant strains and their release from ecological competition. Whether such therapy provides the best approach for controlling resistance therefore depends on the relative strengths of these processes. These opposing processes typically lead to a unimodal relationship between drug pressure and resistance emergence. As a result, the optimal drug dose lies at either end of the therapeutic window of clinically acceptable concentrations. We illustrate our findings with a simple model that shows how a seemingly minor change in parameter values can alter the outcome from one where high-dose chemotherapy is optimal to one where using the smallest clinically effective dose is best. A review of the available empirical evidence provides broad support for these general conclusions. Our analysis opens up treatment options not currently considered as resistance management strategies, and it also simplifies the experiments required to determine the drug doses which best retard resistance emergence in patients. PMID:26820986

  7. Dynamics of chronic myeloid leukemia response to dasatinib, nilotinib, and high-dose imatinib.

    PubMed

    Olshen, Adam; Tang, Min; Cortes, Jorge; Gonen, Mithat; Hughes, Timothy; Branford, Susan; Quintás-Cardama, Alfonso; Michor, Franziska

    2014-11-01

    Treatment with the tyrosine kinase inhibitor imatinib is the standard of care for newly diagnosed patients with chronic myeloid leukemia. In recent years, several second-generation inhibitors - such as dasatinib and nilotinib - have become available: these promise to overcome some of the mutations associated with acquired resistance to imatinib. Despite eliciting similar clinical responses, the molecular effects of these agents on different subpopulations of leukemic cells remain incompletely understood. Furthermore, the consequences of using high-dose imatinib therapy have not been investigated in detail. Here we utilized clinical data from patients treated with dasatinib, nilotinib, or high-dose imatinib, together with a statistical data analysis and mathematical modeling approach, to investigate the molecular treatment response of leukemic cells to these agents. We found that these drugs elicit very similar responses if administered front-line. However, patients display significantly different kinetics when treated second-line, both in terms of differences between front-line and second-line treatment for the same drug, and among agents when used as second-line. We then utilized a mathematical framework describing the behavior of four differentiation levels of leukemic cells during therapy to predict the treatment response kinetics for the different cohorts of patients. The dynamics of BCR-ABL1 clearance observed in our study suggest that the use of standard or high-dose imatinib or a second-generation tyrosine kinase inhibitor such as nilotinib or dasatinib elicits similar responses when administered as front-line therapy for patients with chronic myeloid leukemia in chronic phase. PMID:25216683

  8. Dynamics of chronic myeloid leukemia response to dasatinib, nilotinib, and high-dose imatinib

    PubMed Central

    Olshen, Adam; Tang, Min; Cortes, Jorge; Gonen, Mithat; Hughes, Timothy; Branford, Susan; Quintás-Cardama, Alfonso; Michor, Franziska

    2014-01-01

    Treatment with the tyrosine kinase inhibitor imatinib is the standard of care for newly diagnosed patients with chronic myeloid leukemia. In recent years, several second-generation inhibitors – such as dasatinib and nilotinib – have become available: these promise to overcome some of the mutations associated with acquired resistance to imatinib. Despite eliciting similar clinical responses, the molecular effects of these agents on different subpopulations of leukemic cells remain incompletely understood. Furthermore, the consequences of using high-dose imatinib therapy have not been investigated in detail. Here we utilized clinical data from patients treated with dasatinib, nilotinib, or high-dose imatinib, together with a statistical data analysis and mathematical modeling approach, to investigate the molecular treatment response of leukemic cells to these agents. We found that these drugs elicit very similar responses if administered front-line. However, patients display significantly different kinetics when treated second-line, both in terms of differences between front-line and second-line treatment for the same drug, and among agents when used as second-line. We then utilized a mathematical framework describing the behavior of four differentiation levels of leukemic cells during therapy to predict the treatment response kinetics for the different cohorts of patients. The dynamics of BCR-ABL1 clearance observed in our study suggest that the use of standard or high-dose imatinib or a second-generation tyrosine kinase inhibitor such as nilotinib or dasatinib elicits similar responses when administered as front-line therapy for patients with chronic myeloid leukemia in chronic phase. PMID:25216683

  9. Primary central nervous system lymphoma: implication of high-dose chemotherapy followed by auto-SCT

    PubMed Central

    Reddy, N; Savani, BN

    2016-01-01

    Primary central nervous system lymphoma is a rare and distinct subtype of non-Hodgkin's lymphoma that is sensitive to radiation and chemotherapy. Decisions regarding the initial therapeutic approach are influenced by age and risk of therapy-related neurotoxicity. Despite several albeit small phase II studies, and the acknowledged need for larger prospective trials, there is supporting evidence to consider auto-SCT following induction chemotherapy in patients with good performance status. The international extranodal lymphoma study group is conducting a randomized phase II study comparing consolidative radiation therapy to high-dose therapy. Novel therapeutic options including early aggressive approach with upfront auto-SCT and strategies to prevent relapse following transplantation is an area of focus. PMID:22002486

  10. Not too little, not too much-just right! (Better ways to give high dose melphalan).

    PubMed

    Shaw, P J; Nath, C E; Lazarus, H M

    2014-12-01

    Of the 13 286 autologous haematopoietic cell transplant procedures reported in the US in 2010-2012 for plasma cell disorders, 10 557 used single agent, high-dose melphalan. Despite 30 years of clinical and pharmacokinetic (PK) experience with high-dose melphalan, and its continuing central role as cytoreductive therapy for large numbers of patients with myeloma, the pharmacodynamics and pharmacogenomics of melphalan are still in their infancy. The addition of protectant agents such as amifostine and palifermin allows dose escalation to 280 mg/m(2), but at these doses it is cardiac, rather than gut, toxicity that is dose-limiting. Although combination with additional alkylating agents is feasible, the additional TRM may not be justified when so many post-consolidation therapies are available for myeloma patients. Current research should optimise the delivery of this single-agent chemotherapy. This includes the use of newer formulations and real-time PKs. These strategies may allow a safe and effective platform for adding synergistic novel therapies and provide a window of lymphodepletion for the addition of immunotherapies. PMID:25133893

  11. Novel application of high-dose rate brachytherapy for severe, recalcitrant palmoplantar pustulosis.

    PubMed

    Timerman, D; Devlin, P M; Nambudiri, V E; Wright, N A; Vleugels, R A; Clark, R A; Kupper, T S; Merola, J F; Patel, M

    2016-07-01

    Palmoplantar pustulosis (PPP) is a chronic pustular dermatitis of the palms and soles, which is frequently associated with significant pruritus and pain, often limiting daily activities. We present the case of a 36-year-old man with severe PPP who had treatment failure with multiple medical therapies but showed marked improvement with high-dose rate brachytherapy. Brachytherapy has the advantage of providing a conformal dose distribution over complex curved surfaces, such as the foot and ankle. Our observations suggest that brachytherapy may be a well-tolerated treatment option for patients with severe, refractory PPP. PMID:26848819

  12. Microbial copper reduction method to scavenge anthropogenic radioiodine

    NASA Astrophysics Data System (ADS)

    Lee, Seung Yeop; Lee, Ji Young; Min, Je Ho; Kim, Seung Soo; Baik, Min Hoon; Chung, Sang Yong; Lee, Minhee; Lee, Yongjae

    2016-06-01

    Unexpected reactor accidents and radioisotope production and consumption have led to a continuous increase in the global-scale contamination of radionuclides. In particular, anthropogenic radioiodine has become critical due to its highly volatile mobilization and recycling in global environments, resulting in widespread, negative impact on nature. We report a novel biostimulant method to effectively scavenge radioiodine that exhibits remarkable selectivity for the highly difficult-to-capture radioiodine of >500-fold over other anions, even under circumneutral pH. We discovered a useful mechanism by which microbially reducible copper (i.e., Cu2+ to Cu+) acts as a strong binder for iodide-iodide anions to form a crystalline halide salt of CuI that is highly insoluble in wastewater. The biocatalytic crystallization of radioiodine is a promising way to remove radioiodine in a great capacity with robust growth momentum, further ensuring its long-term stability through nuclear I‑ fixation via microcrystal formation.

  13. Microbial copper reduction method to scavenge anthropogenic radioiodine

    PubMed Central

    Lee, Seung Yeop; Lee, Ji Young; Min, Je Ho; Kim, Seung Soo; Baik, Min Hoon; Chung, Sang Yong; Lee, Minhee; Lee, Yongjae

    2016-01-01

    Unexpected reactor accidents and radioisotope production and consumption have led to a continuous increase in the global-scale contamination of radionuclides. In particular, anthropogenic radioiodine has become critical due to its highly volatile mobilization and recycling in global environments, resulting in widespread, negative impact on nature. We report a novel biostimulant method to effectively scavenge radioiodine that exhibits remarkable selectivity for the highly difficult-to-capture radioiodine of >500-fold over other anions, even under circumneutral pH. We discovered a useful mechanism by which microbially reducible copper (i.e., Cu2+ to Cu+) acts as a strong binder for iodide-iodide anions to form a crystalline halide salt of CuI that is highly insoluble in wastewater. The biocatalytic crystallization of radioiodine is a promising way to remove radioiodine in a great capacity with robust growth momentum, further ensuring its long-term stability through nuclear I− fixation via microcrystal formation. PMID:27311370

  14. Microbial copper reduction method to scavenge anthropogenic radioiodine.

    PubMed

    Lee, Seung Yeop; Lee, Ji Young; Min, Je Ho; Kim, Seung Soo; Baik, Min Hoon; Chung, Sang Yong; Lee, Minhee; Lee, Yongjae

    2016-01-01

    Unexpected reactor accidents and radioisotope production and consumption have led to a continuous increase in the global-scale contamination of radionuclides. In particular, anthropogenic radioiodine has become critical due to its highly volatile mobilization and recycling in global environments, resulting in widespread, negative impact on nature. We report a novel biostimulant method to effectively scavenge radioiodine that exhibits remarkable selectivity for the highly difficult-to-capture radioiodine of >500-fold over other anions, even under circumneutral pH. We discovered a useful mechanism by which microbially reducible copper (i.e., Cu(2+) to Cu(+)) acts as a strong binder for iodide-iodide anions to form a crystalline halide salt of CuI that is highly insoluble in wastewater. The biocatalytic crystallization of radioiodine is a promising way to remove radioiodine in a great capacity with robust growth momentum, further ensuring its long-term stability through nuclear I(-) fixation via microcrystal formation. PMID:27311370

  15. A NTCP approach for estimating the outcome in radioiodine treatment of hyperthyroidism

    SciTech Connect

    Strigari, L.; Sciuto, R.; Benassi, M.; Bergomi, S.; Nocentini, S.; Maini, C. L.

    2008-09-15

    Radioiodine has been in use for over 60 years as a treatment for hyperthyroidism. Major changes in clinical practice have led to accurate dosimetry capable of avoiding the risks of adverse effects and the optimization of the treatment. The aim of this study was to test the capability of a radiobiological model, based on normal tissue complication probability (NTCP), to predict the outcome after oral therapeutic {sup 131}I administration. Following dosimetric study, 79 patients underwent treatment for hyperthyroidism using radioiodine and then 67 had at least a one-year follow up. The delivered dose was calculated using the MIRD formula, taking into account the measured maximum uptake of administered iodine transferred to the thyroid, U0, and the effective clearance rate, T{sub eff} and target mass. The dose was converted to normalized total dose delivered at 2 Gy per fraction (NTD{sub 2}). Furthermore, the method to take into account the reduction of the mass of the gland during radioiodine therapy was also applied. The clinical outcome and dosimetric parameters were analyzed in order to study the dose-response relationship for hypothyroidism. The TD{sub 50} and m parameters of the NTCP model approach were then estimated using the likelihood method. The TD{sub 50}, expressed as NTD{sub 2}, resulted in 60 Gy (95% C.I.: 45-75 Gy) and 96 Gy (95% C.I.: 86-109 Gy) for patients affected by Graves or autonomous/multinodular disease, respectively. This supports the clinical evidence that Graves' disease should be characterized by more radiosensitive cells compared to autonomous nodules. The m parameter for all patients was 0.27 (95% C.I.: 0.22-0.36). These parameters were compared with those reported in the literature for hypothyroidism induced after external beam radiotherapy. The NTCP model correctly predicted the clinical outcome after the therapeutic administration of radioiodine in our series.

  16. High-dose secondary calibration laboratory accreditation program

    SciTech Connect

    Humphreys, J.C.

    1993-12-31

    There is a need for high-dose secondary calibration laboratories to serve the multi-billion dollar radiation processing industry. This need is driven by the desires of industry for less costly calibrations and faster calibration-cycle response time. Services needed include calibration irradiations of routine processing dosimeters and the supply of reference standard transfer dosimeters for irradiation in the production processing facility. In order to provide measurement quality assurance and to demonstrate consistency with national standards, the high-dose secondary laboratories would be accredited by means of an expansion of an existing National Voluntary Laboratory Accreditation Program. A laboratory performance criteria document is under development to implement the new program.

  17. Finnish spectrolite as high-dose gamma detector

    NASA Astrophysics Data System (ADS)

    Antonio, Patrícia L.; Caldas, Linda V. E.

    2015-11-01

    A natural material called spectrolite, from Finland, was studied in this work. The purpose was to test it in gamma radiation beams to verify its performance as a high-dose detector. From this material, pellets were manufactured with two different concentrations of Teflon and spectrolite, and their responses were verified using two luminescent techniques: thermoluminescence (TL) and optically stimulated luminescence (OSL). The TL and OSL signals were evaluated by means of characterization tests of the material response, after exposure to a nominal absorbed dose interval of 5 Gy to 10 kGy. The results obtained, for both concentrations, showed a good performance of this material in beams of high-dose gamma radiation. Both techniques were utilized in order to investigate the properties of the spectrolite+Teflon samples for different applications.

  18. High-dose-rate brachytherapy in uterine cervical carcinoma

    SciTech Connect

    Patel, Firuza D. . E-mail: patelfd@glide.net.in; Rai, Bhavana; Mallick, Indranil; Sharma, Suresh C.

    2005-05-01

    Purpose: High-dose-rate (HDR) brachytherapy is in wide use for curative treatment of cervical cancer. The American Brachytherapy Society has recommended that the individual fraction size be <7.5 Gy and the range of fractions should be four to eight; however, many fractionation schedules, varying from institution to institution, are in use. We use 9 Gy/fraction of HDR in two to five fractions in patients with carcinoma of the uterine cervix. We found that our results and toxicity were comparable to those reported in the literature and hereby present our experience with this fractionation schedule. Methods and Materials: A total of 121 patients with Stage I-III carcinoma of the uterine cervix were treated with HDR brachytherapy between 1996 and 2000. The total number of patients analyzed was 113. The median patient age was 53 years, and the histopathologic type was squamous cell carcinoma in 93% of patients. The patients were subdivided into Groups 1 and 2. In Group 1, 18 patients with Stage Ib-IIb disease, tumor size <4 cm, and preserved cervical anatomy underwent simultaneous external beam radiotherapy to the pelvis to a dose of 40 Gy in 20 fractions within 4 weeks with central shielding and HDR brachytherapy of 9 Gy/fraction, given weekly, and interdigitated with external beam radiotherapy. The 95 patients in Group 2, who had Stage IIb-IIIb disease underwent external beam radiotherapy to the pelvis to a dose of 46 Gy in 23 fractions within 4.5 weeks followed by two sessions of HDR intracavitary brachytherapy of 9 Gy each given 1 week apart. The follow-up range was 3-7 years (median, 36.4 months). Late toxicity was graded according to the Radiation Therapy Oncology Group criteria. Results: The 5-year actuarial local control and disease-free survival rate was 74.5% and 62.0%, respectively. The actuarial local control rate at 5 years was 100% for Stage I, 80% for Stage II, and 67.2% for Stage III patients. The 5-year actuarial disease-free survival rate was 88.8% for

  19. Guidelines for radioiodinated MIBG scintigraphy in children.

    PubMed

    Olivier, Pierre; Colarinha, Paula; Fettich, Jure; Fischer, Sibylle; Frökier, Jörgen; Giammarile, Francesco; Gordon, Isky; Hahn, Klaus; Kabasakal, Levent; Mann, Mike; Mitjavila, Mercedes; Piepsz, Amy; Porn, Ute; Sixt, Rune; van Velzen, Jeannette

    2003-05-01

    These guidelines on the use of radioiodinated (99m)Tc-MIBG scintigraphy in children, which summarise the views of the Paediatric Committee of the European Association of Nuclear Medicine, provide a framework which may prove helpful to nuclear medicine teams in daily practice. They have been influenced by the conclusions of the "Consensus Guidelines for MIBG Scintigraphy" (Paris, November 6, 1997) of the European Neuroblastoma Group and by those of the Oncological Committee of the French Society of Nuclear Medicine. The guidelines should be taken in the context of "good practice" and any local/national rules which apply to nuclear medicine examinations. PMID:12658506

  20. High dose cytosine arabinoside in the initial treatment of adults with acute lymphoblastic leukaemia.

    PubMed Central

    Rohatiner, A. Z.; Bassan, R.; Battista, R.; Barnett, M. J.; Gregory, W.; Lim, J.; Amess, J.; Oza, A.; Barbui, T.; Horton, M.

    1990-01-01

    In a study conducted at St Bartholomew's Hospital between 1972 and 1982, using moderately intensive therapy (OPAL/HEAV'D), a low blast count at presentation (less than 10 x 10(9) 1(-1)) and common ALL (C-ALL) phenotype correlated favourably with duration of remission. Fifty-four patients (age range 15-57, median 32) subsequently received a modification of the previous treatment programme which included high-dose ara-C 2 g m-2 b.d. for 6 days as cycle 3 (OPAL + HD ARA-C). CR was achieved in 36/54 (67%) patients, response correlating favourably with younger age (15-30 years vs 31-57 years, P = 0.02). Three patients died in CR. Overall, there was no difference in survival or remission duration between patients who received high dose ara-C and those in the control group. However, in contrast to the early results, there was a reversal in the relevance of the prognostic factors with a trend in favour of high blast count (greater than 10 x 10(9) 1(-1)) and T-cell phenotype in terms of remission duration. Moreover, comparison of duration of remission for the previously defined prognostic groups according to therapy suggests that the prognosis of patients with 'high risk' disease (T, B, null ALL or high blast count) is improved with more intensive therapy. In contrast, those with 'low risk' disease (C-ALL and low blast count) have a better prognosis with less intensive therapy. These observations confirm those of others and allow for individualization of therapy on the basis of pre-treatment variables. PMID:2206954

  1. Precision, high dose radiotherapy: helium ion treatment of uveal melanoma

    SciTech Connect

    Saunders, W.M.; Char, D.H.; Quivey, J.M.; Castro, J.R.; Chen, G.T.Y.; Collier, J.M.; Cartigny, A.; Blakely, E.A.; Lyman, J.T.; Zink, S.R.

    1985-02-01

    The authors report on 75 patients with uveal melanoma who were treated by placing the Bragg peak of a helium ion beam over the tumor volume. The technique localizes the high dose region very tightly around the tumor volume. This allows critical structures, such as the optic disc and the macula, to be excluded from the high dose region as long as they are 3 to 4 mm away from the edge of the tumor. Careful attention to tumor localization, treatment planning, patient immobilization and treatment verification is required. With a mean follow-up of 22 months (3 to 60 months) the authors have had only five patients with a local recurrence, all of whom were salvaged with another treatment. Pretreatment visual acuity has generally been preserved as long as the tumor edge is at least 4 mm away from the macula and optic disc. The only serious complication to date has been an 18% incidence of neovascular glaucoma in the patients treated at our highest dose level. Clinical results and details of the technique are presented to illustrate potential clinical precision in administering high dose radiotherapy with charged particles such as helium ions or protons.

  2. Reciprocal changes in parathyroid hormone and thyroid function after radioiodine treatment of hyperthyroidism

    SciTech Connect

    Ross, D.S.; Nussbaum, S.R.

    1989-06-01

    Hyperthyroidism is associated with negative calcium balance, normal to increased serum calcium concentrations, and decreased cortical bone mass. There is no agreement concerning serum PTH levels in such patients. In this study, we measured serum PTH concentrations using a newly developed sensitive 2-site immunoradiometric assay in 17 hyperthyroid patients before and after radioiodine therapy. The mean serum PTH and calcium concentrations were 28 +/- 15 (+/- SD) ng/L (normal range, 12-65 ng/L) and 2.4 +/- 0.5 mmol/L (normal range, 2.1-2.6 mmol/L) before therapy. After therapy serum PTH concentrations increased in 16 of the 17 patients. The increase in serum PTH was greater in the 9 patients who became hypothyroid rapidly (29 +/- 15 to 75 +/- 29 ng/L) compared with that in the 8 patients who became euthyroid gradually (26 +/- 16 to 45 +/- 24 ng/L). Serum PTH rose along with TSH as the patients became hypothyroid after radioiodine, and both serum PTH and TSH fell when L-T4 therapy was given. The reciprocal changes in serum PTH concentrations and thyroid function over time suggest a strong association of bone mineral metabolism and thyroid status.

  3. High dose chemotherapy with peripheral blood stem cells transplantation in patients with relapsed or refractory lymphomas preliminary reports.

    PubMed

    Chang, C S; Lin, S F; Huang, S M; Liu, T C; Chen, T P; Yeh, C J

    1997-03-01

    High dose chemotherapy with peripheral blood stem cells transplantation (PBSCT) has been used worldwide in the treatment of patients with various hematological malignancies and other solid tumors. It has just come into use as a salvage therapy in various malignancies in Taiwan in recent years. We report eight cases with relapsed or refractory lymphoma treated with high dose chemotherapy and PBSCT. Our results showed all cases but one achieved complete remission. The mean days of white cell recovery were 10 days to > 500/microliter (ranges, 8-16 days) and 12 days to > 1,000/microliter (ranges, 9-19 days). The mean days to platelet transfusion independent, i.e. platelet > 20,000/microliters, was 14 days. No specific side effect was noted except death in one case on D+9 during cytopenia state. Four patients relapsed and died during the follow-up after PBSCT. From our preliminary results we suggest that high dose chemotherapy with PBSCT could be used as a salvage therapy in patients with relapsed or refractory lymphomas with favorable and sustained hematological recovery. Most cases were tolerable with myeloablative chemotherapy and re-achieved remission, however, remission duration was still short and relapse remained the main problem to be overcome. The long term effects of high dose chemotherapy with PBSCT still need further study. PMID:9109301

  4. Influence of genetic polymorphisms in the folate pathway on toxicity after high-dose methotrexate treatment in pediatric osteosarcoma

    PubMed Central

    Park, Jeong A

    2016-01-01

    Background Methotrexate (MTX), one of the main drugs used to treat osteosarcoma, is a representative folic acid antagonist. Polymorphisms of various enzymes involved in the metabolism of MTX could contribute to differences in response to MTX in pediatric osteosarcoma patients. Methods Blood and tissue samples were obtained from 37 pediatric osteosarcoma patients who were treated with high-dose MTX therapy. The following 4 single nucleotide polymorphisms (SNPs) were analyzed: ATIC 347C>G, MTHFR 677C>T, MTHFR 1298A>C and SLC19A1 80G>A. Serial plasma MTX concentrations after high-dose MTX therapy and MTX-induced toxicities were evaluated. Correlations among polymorphisms, MTX concentrations and treatment-induced toxicities were assessed. Results Plasma MTX levels at 48 hours after high-dose MTX infusion were significantly associated with SLC19A1 80G>A (P=0.031). Higher plasma levels of MTX at 48 and 72 hours were significantly associated with MTX-induced mucositis (P=0.007 and P=0.046) and renal toxicity (P=0.002), respectively. SNP of SLC19A1 gene was associated with development of severe mucositis (P=0.026). Conclusion This study suggests that plasma levels of MTX are associated with GI and renal toxicities after high-dose MTX therapy, and genetic polymorphisms that affect the metabolism of MTX may influence drug concentrations and development of significant side effects in pediatric patients treated with high-dose MTX. PMID:27104192

  5. Refractory immune thrombocytopenia successfully treated with high-dose vitamin D supplementation and hydroxychloroquine: two case reports

    PubMed Central

    2013-01-01

    Introduction Immune thrombocytopenic purpura is thought to be characterized by an immune response against the host’s own platelets. If the thrombocytopenia is severe, patients are initially treated with high-dose steroids. Other more toxic second line treatments are considered if steroids fail. Here, we report the case of two patients in whom conventional treatment was unsuccessful but who responded to hydroxychloroquine and high-dose vitamin D replacement therapy. To the best of our knowledge, this is the first description of successful treatment for immune thrombocytopenia with high-dose vitamin D and hydroxychloroquine. Case presentation Case 1: We report the case of a 79-year-old Caucasian man who presented with high titer antinuclear antibodies, positive anti-SSA/Ro autoantibodies and clinically was felt to have an overlap of systemic lupus erythematosus and/or Sjögren’s syndrome with profound life-threatening thrombocytopenia. There was no evidence of underlying malignancy. The patient’s platelet count significantly increased with vitamin D and hydroxychloroquine treatment, but upon vitamin D discontinuation his platelet levels plummeted. Hydroxychloroquine therapy was maintained throughout treatment. With reinstitution of high-dose vitamin D therapy, platelet counts were restored to normal levels. Case 2: We also report the case of an 87-year-old Caucasian woman who presented with high titer antinuclear antibodies, positive anti-SSA/Ro autoantibodies and was felt to have an overlap of systemic lupus erythematosus and/or Sjögren’s syndrome with immune thrombocytopenia; she also had severely low levels of 25-hydroxy vitamin D (17ng/mL). There was no evidence of underlying malignancy. She responded to high-dose vitamin D replacement and hydroxychloroquine treatment, thereby alleviating the need for high-dose steroid treatment. She remains in remission while taking vitamin D, hydroxychloroquine and very low-dose prednisone. No untoward side effects

  6. Effect of high-dose intravenous vitamin C on inflammation in cancer patients

    PubMed Central

    2012-01-01

    Background An inflammatory component is present in the microenvironment of most neoplastic tissues. Inflammation and elevated C-reactive protein (CRP) are associated with poor prognosis and decreased survival in many types of cancer. Vitamin C has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at much higher-than-recommended dietary allowance levels. Since in vitro studies demonstrated inhibition of pro-inflammatory pathways by millimolar concentrations of vitamin C, we decided to analyze the effects of high dose IVC therapy in suppression of inflammation in cancer patients. Methods 45 patients with prostate cancer, breast cancer, bladder cancer, pancreatic cancer, lung cancer, thyroid cancer, skin cancer and B-cell lymphoma were treated at the Riordan Clinic by high doses of vitamin C (7.5 g -50 g) after standard treatments by conventional methods. CRP and tumor markers were measured in serum or heparin-plasma as a routine analysis. In addition, serum samples were collected before and after the IVCs for the cytokine kit tests. Results According to our data positive response to treatment, which was demonstrated by measurements of C- reactive protein, was found in 75% of patients and progression of the inflammation in 25% of patients. IVC treatments on all aggressive stage cancer patients showed the poor response of treatment. There was correlation between tumor markers (PSA, CEA, CA27.29 and CA15-3) and changes in the levels of C-reactive protein. Our test of the effect of IVC on pro-inflammatory cytokines demonstrated that inflammation cytokines IL-1α, IL-2, IL-8, TNF-α, chemokine eotaxin and CRP were reduced significantly after treatments. Conclusions The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients. In our study, we found that modulation of inflammation by IVC correlated with decreases in tumor marker levels. In

  7. High-dose chemotherapy in small-cell lung cancer.

    PubMed

    Pasini, F; Durante, E; De Manzoni, D; Rosti, G; Pelosi, G

    2002-01-01

    Small cell lung cancer (SCLC) is highly sensitive both to radiotherapy and chemotherapy. Given its high chemo sensitivity, even two decades ago, SCLC was one of the first malignancies deemed suitable for maximising the dose and dose intensity with the support of autologous bone marrow (ABMT). On the whole, results were disappointing and the procedure was practically abandoned. Nowadays some interest is again emerging due to improvements in supportive care, such as the availability of hematopoietic growth factors and the peripheral blood progenitor cells (PBPC). Data of 505 patients included in 26 studies were reviewed. About two thirds of these patients had LD (limited disease). Late intensification protocols were used in 311 patients who, however, represented only the 30% of the population initially given conventional chemotherapy. Of the patients not achieving complete remission (CR) after induction, high-dose induced a CR in 39% of the cases. The use of early intensification was reported in 8 studies including 194 patients. The CR rate was 51.5%. Overall, the probability of achieving the CR was 2-3 times higher in LD than in ED (extensive disease). Relapses occurred at the site of the primary in more than half of the cases, showing that the course of the disease was not modified by the use of high-dose chemotherapy. Toxic deaths occurred in 7% of the treated patients, without difference in the two treatment methods. Though the schedules were too variable to draw firm conclusions, the ICE (ifosfamide, carboplatin, etoposide) and the CBP (cyclophosphamide, cisplatin, carmustine) regimens apparently provided better results, with a 2-year survival rate of 30-50% in the LD subset. An european multicenter randomized trial is ongoing. At the present time high-dose chemotherapy is still to be considered experimental treatment, since major problems such as the selection of the patients, doses and timing of chemotherapy and radiotherapy remain unsolved. PMID:12552940

  8. On carbon nitride synthesis at high-dose ion implantation

    NASA Astrophysics Data System (ADS)

    Romanovsky, E. A.; Bespalova, O. V.; Borisov, A. M.; Goryaga, N. G.; Kulikauskas, V. S.; Sukharev, V. G.; Zatekin, V. V.

    1998-04-01

    Rutherford backscattering spectrometry was used for the study of high dose 35 keV nitrogen ions implantation into graphites and glassy carbon. Quantitative data on depth profiles and its dependencies on irradiation fluence and ion beam density were obtained. The stationary dome-shaped depth profile with maximum nitrogen concentration 22-27 at.% and half-width more than twice exceeding projected range of ions is reached at fluence Φ ˜10 18 cm -2. The dependence of the maximum concentration in the profile on ion current density was studied. The largest concentration was obtained at reduced ion current density.

  9. High dose calcitriol may reduce thrombosis in cancer patients.

    PubMed

    Beer, Tomasz M; Venner, Peter M; Ryan, Christopher W; Petrylak, Daniel P; Chatta, Gurkamal; Dean Ruether, J; Chi, Kim N; Curd, John G; DeLoughery, Thomas G

    2006-11-01

    The incidence of venous and arterial thrombosis in a placebo-controlled randomised trial of DN-101 (high dose calcitriol) with docetaxel versus docetaxel was compared. Of the 13 thrombotic events observed in the 250 patients enroled in this study, two occurred in DN-101 and 11 in placebo-treated patients (P = 0.01). This difference remained significant after adjustment for baseline history of thrombosis, atrial fibrillation and use of anti-thrombotic agents. In vitro and vitamin D receptor (VDR) knockout mouse studies predict that nanomolar concentrations of calcitriol may act as an antithrombotic agent. We report the first clinical observation that supports this hypothesis in humans. PMID:16984385

  10. Pharmacokinetic interaction between high-dose methotrexate and oxacillin.

    PubMed

    Titier, Karine; Lagrange, Fabrice; Péhourcq, Fabienne; Moore, Nicholas; Molimard, Mathieu

    2002-08-01

    An 18-year-old man received two high-dose methotrexate cycles for the treatment of an osteosarcoma. Fifteen grams of methotrexate were infused over 6 hours. During the second cycle, co-administration of oxacillin (1g/8h) resulted in prolonged and marked elevation of methotrexate plasma concentrations. The patient experienced acute toxicity with renal failure, myelosuppression, mucitis, fever, and dermatologic abnormalities. After an initial improvement with folinic acid rescue and hemodialysis, the patient died. Oxacillin may thus inhibit the elimination of methotrexate. PMID:12142645

  11. Failure of High-Dose Daptomycin for Bacteremia Caused by Daptomycin-Susceptible Enterococcus faecium Harboring LiaSR Substitutions

    PubMed Central

    Munita, Jose M.; Mishra, Nagendra N.; Alvarez, Danya; Tran, Truc T.; Diaz, Lorena; Panesso, Diana; Reyes, Jinnethe; Murray, Barbara E.; Adachi, Javier A.; Bayer, Arnold S.; Arias, Cesar A.

    2014-01-01

    High-dose daptomycin (DAP) therapy failed in a neutropenic patient with bloodstream infection caused by a DAP-susceptible Enterococcus faecium (minimum inhibitory concentration, 3 µg/mL) harboring genetic changes associated with DAP resistance, with persistent bacteremia and selection of additional resistances. Daptomycin monotherapy should be used cautiously against DAP-susceptible E. faecium strains with minimum inhibitory concentrations >2 µg/mL. PMID:25107294

  12. High-dose chemotherapy in relapsed or refractory Hodgkin lymphoma patients: a reappraisal of prognostic factors.

    PubMed

    Cocorocchio, E; Peccatori, F; Vanazzi, A; Piperno, G; Calabrese, L; Botteri, E; Travaini, L; Preda, L; Martinelli, G

    2013-03-01

    High-dose chemotherapy (HDCT) has a consolidated role in the treatment of patients with refractory or relapsed Hodgkin lymphoma (HL). We report clinical results of 97 HL patients who underwent HDCT for refractory (62 patients) or relapsed (35 patients) diseases in Istituto Europeo di Oncologia, from 1995 to 2009. Treatment included high-dose carmustine, etoposide, cytarabine and melphalan in 84 patients and high-dose idarubicin and melphalan in 13 patients with subsequent peripheral hemopoietic stem cells transplant. Outcomes were evaluated in terms of progression-free survival (PFS) and overall survival (OS). In order to identify prognostic factors for outcome, a multivariate analysis for age, sex, disease status (refractory/relapsed), disease stage, B symptoms, presence of extranodal involvement, bulky disease, elevated lactate dehydrogenase, number of previous chemotherapy lines, remission status before transplant, 18F-fluoro-deoxy-d-glucose positron emission tomography ((18) FDG-PET) status before and after transplant was done. A clinical response was achieved in 91% of patients, with complete remissions in 76/97 patients. With a median follow-up of 45 months (range 1-164 months), 5-year PFS and OS were 64% and 71%, respectively. Remission status after induction therapy, 18F-fluoro-deoxy-d-glucose positron emission tomography status before and after transplant were the most important prognostic factors for PFS and OS in univariate or multivariate analyses. HDCT is able to induce a high remission rate and a prolonged PFS in more than 50% of the patients with refractory and relapsed HL. PMID:22473680

  13. Administration of high-dose continuous infusion interleukin-2 to patients age 70 or over.

    PubMed

    Quan, Walter; Ramirez, Maria; Taylor, Chris; Quan, Francine; Vinogradov, Mikhail; Walker, Paul

    2005-02-01

    High-dose bolus or continuous infusion interleukin-2-based therapy can cause capillary leak syndrome. Significant cardiovascular/hemodynamic events, including myocardial infarction, hypotension, pulmonary edema, and cardiac arrhythmia, have been described with such therapy. Concern over the toxicity of highdose interleukin-2 (IL-2) therapy has led to some clinicians excluding patients 70 years of age or over. We have treated 15 patients 70 years of age or over having an Eastern Conference Oncology Group (ECOG) performance status of 0 or 1, with therapy based on continuous infusion IL-2 18 MIU/sq m/24 hours for 72 hours. All patients underwent a pretreatment evaluation of cardiac status with a low-level stress or adenosine stress test. Cycles were typically repeated every 3 weeks for 4 cycles, then every 3-4 weeks thereafter. Patients were treated by oncology nurses in either the stem cell transplant (intermediate unit) or the oncology inpatient unit. Patient characteristics were: median age, 72 years (range, 70-83 years); tumor types: melanoma (10), kidney cancer (5); most common sites of disease: lung (11), lymph nodes (6), subcutaneous (3), liver (2); prior therapy included: none (8), outpatient IL-2 (5), other immunotherapy (4). Median number of cycles received: 3 (1-10). Most common toxicities were: fever, rigors, nausea, emesis, hypophosphatemia, and hypomagnesemia. Three patients required the use of dopamine for blood pressure support. Two patients declined further therapy. There were no treatment-related deaths. No patients required endotracheal intubation or transfer to an intensive care unit. One complete and 8 partial responses (60% response rate) have been seen. Responding sites include the lung, lymph node, intact kidney primary, and liver. Median survival has not been reached at over 14 months (range 3+-26+ months). Patients who are 70 years of age and older with an ECOG performance status of 0 or 1 are able to tolerate high-dose continuous infusion IL

  14. Pharmacokinetics of high-dose busulfan in children.

    PubMed

    Vassal, G; Gouyette, A; Hartmann, O; Pico, J L; Lemerle, J

    1989-01-01

    The pharmacokinetics of high-dose busulfan given orally at 1 mg/kg every 6 h over 4 days (total dose, 16 mg/kg) in combined chemotherapy followed by autologous bone marrow transplantation was studied in 12 children with a mean age of 7 years (range, 4-14 years). Busulfan levels in biological fluids were measured by a gas chromatographic assay with mass fragmentographic detection, using a deuterated analogue as the internal standard. In a high-dose regimen, busulfan followed one-compartment model kinetics with zero-order absorption. A mean maximal concentration of 803 +/- 228 ng/ml was achieved at 92-255 min after dosing. The mean elimination half-life was 2.33 h, and the mean total clearance was 119 +/- 54 ml/min per m2, with an apparent distribution volume of 27.10 +/- 11.50 l/m2. A mean trough level of 370 ng/ml was found throughout the 4 days of the chemotherapy course. There were no significant variations in pharmacokinetic parameters measured after the first and last doses. Busulfan was monitored in the CSF of nine children at 3.25-7 h after the last dose and was detected in all patients, with a mean CSF-to-plasma concentration ratio of 0.95 (range, 0.5-1.4). PMID:2791192

  15. ELDRS Characterization for a Very High Dose Mission

    NASA Technical Reports Server (NTRS)

    Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Kenna, Aaron J.; Thorbourn, Dennis O.; Clark, Karla B.; Yan, Tsun-Yee

    2010-01-01

    Evaluation of bipolar linear parts which may have Enhanced Low Dose Rate Sensitivity (ELDRS) is problematic for missions that have very high dose radiation requirements. The accepted standards for evaluating parts that display ELDRS require testing at a very low dose rate which could be prohibitively long for very high dose missions. In this work, a methodology for ELDRS characterization of bipolar parts for mission doses up to 1 Mrad(Si) is evaluated. The procedure employs an initial dose rate of 0.01 rad(Si)/s to a total dose of 50 krad(Si) and then changes to 0.04 rad(Si)/s to a total dose of 1 Mrad(Si). This procedure appears to work well. No change in rate of degradation with dose has been observed when the dose rate is changed from 0.01 to 0.04 rad(Si)/s. This is taken as an indication that the degradation due to the higher dose rate is equivalent to that at the lower dose rate at the higher dose levels, at least for the parts studied to date. In several cases, significant parameter degradation or functional failure not observed at HDR was observed at fairly high total doses (50 to 250 krad(Si)) at LDR. This behavior calls into question the use of dose rate trend data and enhancement factors to predict LDR performance.

  16. Spectroscopic gamma camera for use in high dose environments

    NASA Astrophysics Data System (ADS)

    Ueno, Yuichiro; Takahashi, Isao; Ishitsu, Takafumi; Tadokoro, Takahiro; Okada, Koichi; Nagumo, Yasushi; Fujishima, Yasutake; Kometani, Yutaka; Suzuki, Yasuhiko; Umegaki, Kikuo

    2016-06-01

    We developed a pinhole gamma camera to measure distributions of radioactive material contaminants and to identify radionuclides in extraordinarily high dose regions (1000 mSv/h). The developed gamma camera is characterized by: (1) tolerance for high dose rate environments; (2) high spatial and spectral resolution for identifying unknown contaminating sources; and (3) good usability for being carried on a robot and remotely controlled. These are achieved by using a compact pixelated detector module with CdTe semiconductors, efficient shielding, and a fine resolution pinhole collimator. The gamma camera weighs less than 100 kg, and its field of view is an 8 m square in the case of a distance of 10 m and its image is divided into 256 (16×16) pixels. From the laboratory test, we found the energy resolution at the 662 keV photopeak was 2.3% FWHM, which is enough to identify the radionuclides. We found that the count rate per background dose rate was 220 cps h/mSv and the maximum count rate was 300 kcps, so the maximum dose rate of the environment where the gamma camera can be operated was calculated as 1400 mSv/h. We investigated the reactor building of Unit 1 at the Fukushima Dai-ichi Nuclear Power Plant using the gamma camera and could identify the unknown contaminating source in the dose rate environment that was as high as 659 mSv/h.

  17. Uninhibited thyroidal uptake of radioiodine despite iodine excess in amiodarone-induced hypothyroidism

    SciTech Connect

    Wiersinga, W.M.; Touber, J.L.; Trip, M.D.; van Royen, E.A.

    1986-08-01

    Iodine excess is associated with a low thyroidal radioiodine uptake due to dilution of the radioisotope by the increased stable iodide pool. We studied thyroidal uptake of radioisotopes in cardiac patients with iodine excess due to amiodarone treatment. /sup 99m/Tc-pertechnetate scintigraphy was performed in 13 patients receiving long term amiodarone therapy. Five patients had a clearly visible thyroid gland, and 8 patients had no or a very faint thyroid image. All patients with positive scans had an increased plasma TSH level, whereas all patients with negative scans had a normal or absent TSH response to TRH. Thyroidal uptake and discharge of 123I were studied in 30 other patients. Group I (n = 11) had normal plasma TSH responses to TRH and no iodine excess, group II (n = 7) had normal TSH responses to TRH and excess iodine from metrizoate angiography in the previous month, group III (n = 7) had normal or decreased TSH responses to TRH while receiving long term amiodarone therapy, and group IV (n = 5) had increased TSH responses to TRH while receiving long term amiodarone therapy. The mean radioiodine uptake value in group I (5.4 +/- 0.8% (+/- SE) at 60 min) was higher than those in group II (2.3 +/- 0.7%; P = 0.009) and group III (0.8 +/- 0.3%; P = 0.0005), but not different from that in group IV (5.3 +/- 1.2%; P = NS). Radioiodine discharge after perchlorate (expressed as a percentage of the 60 min uptake) in group I (10.1 +/- 2.2%) was lower than those in group II (24.9 +/- 10.6%; P = 0.05) and group III (28.8 +/- 5.3%; P less than 0.005), whereas discharge in group IV (58.0 +/- 6.1%) was greater than those in group II (P less than 0.05) and group III (P less than 0.01). In conclusion, 1) thyroid visualization by /sup 99m/Tc-pertechnetate and thyroid radioiodine uptake during iodine excess are decreased in euthyroid and hyperthyroid patients, but preserved in hypothyroid patients.

  18. May early intervention with high dose intravenous immunoglobulin pose a potentially successful treatment for severe cases of tick-borne encephalitis?

    PubMed Central

    2013-01-01

    Background Arthropod-borne viral encephalitis of diverse origins shows similar clinical symptoms, histopathology and magnetic resonance imaging, indicating that the patho mechanisms may be similar. There is no specific therapy to date. However, vaccination remains the best prophylaxis against a selected few. Regardless of these shortcomings, there are an increasing number of case reports that successfully treat arboviral encephalitis with high doses of intravenous immunoglobulins. Discussion To our knowledge, high dose intravenous immunoglobulin has not been tested systematically for treating severe cases of tick-borne encephalitis. Antibody-dependent enhancement has been suspected, but not proven, in several juvenile cases of tick-borne encephalitis. Although antibody-dependent enhancement during secondary infection with dengue virus has been documented, no adverse effects were noticed in a controlled study of high dose intravenous immunoglobulin therapy for dengue-associated thrombocytopenia. The inflammation-dampening therapeutic effects of generic high dose intravenous immunoglobulins may override the antibody-dependent enhancement effects that are potentially induced by cross-reactive antibodies or by virus-specific antibodies at sub-neutralizing levels. Summary Analogous to the increasing number of case reports on the successful treatment of other arboviral encephalitides with high dose intravenous immunoglobulins, we postulate whether it may be possible to also treat severe cases of tick-borne encephalitis with high dose intravenous immunoglobulins as early in the course of the disease as possible. PMID:23822550

  19. Effect of high dose vitamin C on Epstein-Barr viral infection

    PubMed Central

    Mikirova, Nina A.; Hunninghake, Ronald

    2014-01-01

    Background Many natural compounds were tested for the ability to suppress viral replication. The present manuscript details an analysis of high dose vitamin C therapy on patients with EBV infection. Material/Methods The data were obtained from the patient history database at the Riordan Clinic. Among people in our database who were treated with intravenous vitamin C (7.5 g to 50 g infusions) between 1997 and 2006, 178 patients showed elevated levels of EBV EA IgG (range 25 to 211 AU) and 40 showed elevated levels of EBV VCA IgM (range 25 to 140 AU). Most of these patients had a diagnosis of chronic fatigue syndrome, with the rest being diagnosed as having mononucleosis, fatigue, or EBV infection. Results Our data provide evidence that high dose intravenous vitamin C therapy has a positive effect on disease duration and reduction of viral antibody levels. Plasma levels of ascorbic acid and vitamin D were correlated with levels of antibodies to EBV. We found an inverse correlation between EBV VCA IgM and vitamin C in plasma in patients with mononucleosis and CFS meaning that patients with high levels of vitamin C tended to have lower levels of antigens in the acute state of disease. In addition, a relation was found between vitamin D levels and EBV EA IgG with lower levels of EBV early antigen IgG for higher levels of vitamin D. Conclusions The clinical study of ascorbic acid and EBV infection showed the reduction in EBV EA IgG and EBV VCA IgM antibody levels over time during IVC therapy that is consistent with observations from the literature that millimolar levels of ascorbate hinder viral infection and replication in vitro. PMID:24793092

  20. Radioiodine in kelp from western Australia

    SciTech Connect

    Marsh, K.V.; Buddemeier, R.W.; Wood, W.; Smith, C.

    1987-03-25

    As part of a program to survey low levels of radioactivity in the marine environment of the southern hemisphere, we have studied the distribution and uptake of /sup 131/I found in the subtidal kelp Ecklonia radiata, on the west coast of Australia. Concentrations of 5 to 75 fCi/g of /sup 131/I exist in this species over a considerable distance along the coast. We have characterized the principal source of the /sup 131/I and found a general temporal correlation between the amount of radioiodine discharged from sewer outfalls and its concentration in kelp. Transplant experiments have enabled us to estimate uptake and depuration rates, and our results are consistent with laboratory measurements made by others.

  1. Molten Hydroxide Trapping Process for Radioiodine

    SciTech Connect

    Trowbridge, L.D.

    2003-01-28

    A molten hydroxide trapping process has been considered for removing radioiodine species from off-gas streams whereby iodine is reacted directly with molten hydroxides such as NaOH or KOH. The resulting product is the corresponding iodide, which can be separated by simple cooling of the molten mixture to grow the iodide primary phase once the mixture reaches 70-80 mol% in the iodide component. Thermodynamic analysis indicates that such a chemical process is highly favorable. Experimental testing of the trapping process using molecular iodine showed trapping of up to 96% of the volatile iodine. The trapping efficiency was dependent on operational parameters such as temperature and gas-melt contact efficiency, and higher efficiencies are expected as the process is further developed. While an iodide phase could be effectively isolated by slow cooling of a molten iodide-hydroxide mixture, the persistent appearance of hydroxide indicated that an appreciable solubility of hydroxide occurred in the iodide phase.

  2. Patterns of radioiodine uptake by the lactating breast.

    PubMed

    Bakheet, S M; Hammami, M M

    1994-07-01

    Breast uptake of radioiodine, if not suspected, may be misinterpreted as thyroid cancer metastasis to the lung. To characterize the patterns of radioiodine breast uptake, we retrospectively studied 20 radioiodine scans that were performed within 1 week of cessation of breast feeding. Four patterns of uptake were identified: "full", "focal", "crescent" and "irregular". The uptake was asymmetric in 60% (left > right in 45%, right > left in 15%), symmetric in 25% and unilateral in 15% of cases. A characteristic full bilateral uptake was present in 40% of cases. In three cases with the irregular pattern, caused in part by external contamination with radioactive milk, the uptake closely mimicked lung metastases. Delayed images, obtained in one case, showed an apparent radioiodine shift from the breast to the thyroid, suggesting that the presence of breast uptake can modulate radioiodine uptake by thyroid tissue. In a case of unilateral breast uptake, a history of mastitis was obtained, which to our knowledge has not been previously reported. Breast uptake of radioiodine may take several scintigraphic patterns that are not always characteristic of the lactating breast and may affect the apparent extent of thyroid remnant/metastasis. PMID:7957345

  3. High-dose continuous infusion plus pulse interleukin-2 and famotidine in melanoma.

    PubMed

    Quan, Walter; Ramirez, Maria; Taylor, W Chris; Vinogradov, Mikhail; Khan, Nawazish; Jackson, Shawn

    2004-12-01

    High-dose, continuous infusion interleukin-2 (IL-2) regimens generate greater Lymphokine Activated Killer cell (LAK) cytotoxicity in vitro and a higher rebound lymphocytosis in vivo than do bolus IL-2 regimens. Lymphocytes initially activated by continuous infusion IL-2 then subsequently pulsed with IL-2 have increased cytotoxicity against cancer cells. Famotidine may enhance the lysis of tumors by cytotoxic lymphocytes. Fourteen patients with melanoma were treated with famotidine 20 mg intravenously twice per day and continuous infusion IL-2 (18 MIU/sq m/24 hours) for 72 hours, followed by a 24-hour rest, then IL-2 18 MIU/sq m over 15-30 minutes for 1 dose (12 patients) or daily for 3 doses (2 patients). Most common toxicities were fever, nausea/emesis, hypophosphatemia, hypomagnesemia, and rigors. Nine partial responses (64% response rate; 95% Confidence Interval: 39%-84%) have been seen. Median survival has not been reached at greater than 10 months. Two patients responding to therapy showed an increase in detectable CD 56(+) cells in serial subcutaneous or lymph node biopsies, while 1 patient undergoing progression of disease had no such infiltrate. High-dose, 72-hour continuous infusion plus pulse interleukin-2 with famotidine has activity in melanoma. CD 56(+) cells may play a role in responding patients. PMID:15665626

  4. High-Dose Hook Effect in 17-Hydroxyprogesterone Assay in a Patient with 21-Hydroxylase Deficiency.

    PubMed

    Parlak, Mesut; Ellidağ, Hamit Yaşar; Türkkahraman, Doğa

    2015-12-01

    Congenital adrenal hyperplasia (CAH) describes a group of disorders characterized by enzyme defects in adrenal steroidogenesis. 21-hydroxylase deficiency (21-OHD) is the most commonly encountered form. The analysis of steroids in pediatric cases requires high-sensitivity assays. A 14-year-old Syrian girl was referred for evaluation of short stature, amenorrhea, and hirsutism. On physical examination, breast development was Tanner stage 1. She had a phallic clitoris with a single urogenital orifice. Laboratory findings revealed primary adrenal deficiency with high androgen levels and low levels of 17-hydroxyprogesterone (17-OHP), (<0.05 ng/mL) and estrogen. This unexpected result led to suspicion of a high-dose hook effect. The measurement was repeated after 1/10 dilution of serum, and a high level of 17-OHP (115.4 ng/mL) was detected with the same test-enzyme-linked immunosorbent assay (ELISA). Simple virilizing form of CAH (21-OHD) was suspected and confirmed with genetic analysis. After initiation of glucocorticoid therapy, breast development was noted along with a decrease in testosterone level and an increase in estrogen level. To our knowledge, this is the first case report of hook effect for 17-OHP immunoassay in a patient with 21-OHD. High-dose hook effect should be suspected in patients with CAH when the test results are incompatible with one another. Additionally, this case demonstrates that a high testosterone level can block aromatase activity and consequently also estrogen production and breast development. PMID:26777045

  5. High dose chemotherapy with stem cell support in the treatment of testicular cancer

    PubMed Central

    Popovic, Lazar; Matovina-Brko, Gorana; Popovic, Milica; Petrovic, Dragana; Cvetanovic, Ana; Vukojevic, Jelena; Jovanovic, Darjana

    2015-01-01

    Testicular germ cell cancer (TGCC) is rare form of malignant disease that occurs mostly in young man between age 15 and 40. The worldwide incidence of TGCC is 1.5 per 100000 man with the highest rates in North Europe. After discovery of cisplatin cure rates of TGCC are very favorable between 90%-95% and unlike most solid tumors, cure rate for metastatic TGCC is around 80%. Metastatic TGCC is usually treated with 3-4 cycles of bleomycin, etoposide, cisplatinum chemotherapy with or without retroperitoneal surgery and cure rates with this approach are between 41% in poor risk group and 92% in good risk group of patients. Cure rates are lower in relapsed and refractory patients and many of them will die from the disease if not cured with first line chemotherapy. High dose chemotherapy (HDCT) approach was used for the first time during the 1980s. Progress in hematology allowed the possibility to keep autologous haematopoietic stem cells alive ex-vivo at very low temperatures and use them to repopulate the bone marrow after sub-lethal dose of intesive myeloablative chemotherapy. Despite the fact that there is no positive randomized study to prove HDCT concept, cure rates in relapsed TGCC are higher after high dose therapy then in historical controls in studies with conventional treatment. Here we review clinical studies in HDCT for TGCC, possibilities of mobilising sufficient number of stem cells and future directions in the treatment of this disease. PMID:26730267

  6. High dose chemotherapy with stem cell support in the treatment of testicular cancer.

    PubMed

    Popovic, Lazar; Matovina-Brko, Gorana; Popovic, Milica; Petrovic, Dragana; Cvetanovic, Ana; Vukojevic, Jelena; Jovanovic, Darjana

    2015-12-26

    Testicular germ cell cancer (TGCC) is rare form of malignant disease that occurs mostly in young man between age 15 and 40. The worldwide incidence of TGCC is 1.5 per 100000 man with the highest rates in North Europe. After discovery of cisplatin cure rates of TGCC are very favorable between 90%-95% and unlike most solid tumors, cure rate for metastatic TGCC is around 80%. Metastatic TGCC is usually treated with 3-4 cycles of bleomycin, etoposide, cisplatinum chemotherapy with or without retroperitoneal surgery and cure rates with this approach are between 41% in poor risk group and 92% in good risk group of patients. Cure rates are lower in relapsed and refractory patients and many of them will die from the disease if not cured with first line chemotherapy. High dose chemotherapy (HDCT) approach was used for the first time during the 1980s. Progress in hematology allowed the possibility to keep autologous haematopoietic stem cells alive ex-vivo at very low temperatures and use them to repopulate the bone marrow after sub-lethal dose of intesive myeloablative chemotherapy. Despite the fact that there is no positive randomized study to prove HDCT concept, cure rates in relapsed TGCC are higher after high dose therapy then in historical controls in studies with conventional treatment. Here we review clinical studies in HDCT for TGCC, possibilities of mobilising sufficient number of stem cells and future directions in the treatment of this disease. PMID:26730267

  7. Evaluation of Rectal Dose During High-Dose-Rate Intracavitary Brachytherapy for Cervical Carcinoma

    SciTech Connect

    Sha, Rajib Lochan; Reddy, Palreddy Yadagiri; Rao, Ramakrishna; Muralidhar, Kanaparthy R.; Kudchadker, Rajat J.

    2011-01-01

    High-dose-rate intracavitary brachytherapy (HDR-ICBT) for carcinoma of the uterine cervix often results in high doses being delivered to surrounding organs at risk (OARs) such as the rectum and bladder. Therefore, it is important to accurately determine and closely monitor the dose delivered to these OARs. In this study, we measured the dose delivered to the rectum by intracavitary applications and compared this measured dose to the International Commission on Radiation Units and Measurements rectal reference point dose calculated by the treatment planning system (TPS). To measure the dose, we inserted a miniature (0.1 cm{sup 3}) ionization chamber into the rectum of 86 patients undergoing radiation therapy for cervical carcinoma. The response of the miniature chamber modified by 3 thin lead marker rings for identification purposes during imaging was also characterized. The difference between the TPS-calculated maximum dose and the measured dose was <5% in 52 patients, 5-10% in 26 patients, and 10-14% in 8 patients. The TPS-calculated maximum dose was typically higher than the measured dose. Our study indicates that it is possible to measure the rectal dose for cervical carcinoma patients undergoing HDR-ICBT. We also conclude that the dose delivered to the rectum can be reasonably predicted by the TPS-calculated dose.

  8. Systemic effects of local treatment with high doses of potent corticosteroids in psoriatics.

    PubMed

    Nilsson, J E; Gip, L J

    1979-01-01

    The risk of systemic effects of high doses of potent topical corticosteroids was evaluated in 6 psoriatics with lesions on more than 50% of the body surface. Before the examinations the patients had been treated for 3-4 months with 35-65 g fluorinated corticosteroids daily. General clinical examination, plasma cortisol determinations, and tetracosactrin tests were carried out. One patient showed clinical signs of Cushing's syndrome including diabetes mellitus, another had a slight Cushingoid appearance. The plasma cortisol levels were depressed in 5 of the 6 patients on the first post-treatment day. A subnormal plasmacortisol response to tetracosactrin stimulation was noted in 3 of the patients. In these cases the potent corticosteroid therapy was discontinued. One month later a follow-up was performed, which showed a clinical and laboratory normalization except for the tetracosactrin test in one case. The study emphasizes the risk of serious systemic effects of the absorbed corticosteroids, if high doses are used for long periods. PMID:87083

  9. High dose intravitreal foscarnet in the treatment of cytomegalovirus retinitis in AIDS.

    PubMed Central

    Diaz-Llopis, M; España, E; Muñoz, G; Navea, A; Chipont, E; Cano, J; Menezo, J L; Romero, F J

    1994-01-01

    The efficacy and tolerance of high dose intravitreal foscarnet for cytomegalovirus retinitis in patients with AIDS was studied. Foscarnet in a dose of 2400 micrograms was injected directly into the vitreous of 11 patients (15 eyes). Five patients had active retinitis (eight eyes, 53.3%), and received a 3 week induction therapy of six injections as the first step. Six patients had initial inactive retinitis (seven eyes, 46.7%), and received only maintenance therapy which consisted of a weekly injection. The main indications for intravitreal therapy were: myelosuppression, kidney toxicity, catheter related sepsis, or refusal of intravenous therapy. The patients were followed for a mean period of 16 weeks (range 8-28 weeks) and received a total of 304 injections. Vitreous foscarnet levels were measured by high performance liquid chromatography. After a 3 week course of induction therapy, complete resolution of the active retinitis was seen in 62.5% (5/8 cases), while 37.5% (3/8 cases) had partial resolution. No cases failed to respond or progress. The rate of relapse on maintenance therapy was 33% (five of 15 eyes) by 20 weeks, and two of these eyes did not respond to reinduction and progressed in involvement of the macula or optic nerve. Neither important local complications nor intraocular drug toxicity were observed. Vitreous foscarnet levels in two different patients were 896 mumol/l and 74.9 mumol/l at 22 3/4 hours and 42 1/2 hours after the injection. Intravitreal foscarnet appears to be a safe, effective, and useful alternative in patients with intolerance to intravenous and viral therapy. PMID:8123619

  10. High doses of corticosteroids in the treatment of septic shock.

    PubMed

    Hellman, A; Alestig, K

    1985-01-01

    High doses of corticosteroids are reported to be beneficial in the treatment of septic shock in many animal species, e.g. dog, rat and rabbit. Recent findings in baboons subjected to E. coli shock indicate that early treatment with a combination of antibiotics and steroids strongly enhance survival rate. In clinical studies the protective effects of steroids are more ambiguous, however. In part this may be explained by variations in the amount of steroids used or by the fact that in some studies the steroid is administered late in shock. The dose recommended, 30 mg/kg bw of methylprednisolone or an equivalent amount of another glucocorticoid given once or twice, is based on animal as well as clinical documentation. PMID:3911703

  11. Oxidation of silicon implanted with high-dose aluminum

    SciTech Connect

    Yang, Zunde; Du, Honghua; Withrow, S.P.

    1994-12-31

    Si(100) wafers were implanted with Al at 500 C to high doses at multi-energies and were oxidized in 1 atm flowing oxygen at 1000-1200 C. Morphology, structure, and oxidation behavior of the implanted and oxidized Si were studied using optical microscopy, atomic force microscopy, and cross-sectional transmission electron microscopy in conjunction with selected area electron diffraction and energy dispersive x-ray analysis. Large Al precipitates were formed and embedded near the surface region of the implanted Si. Oxidation rate of the Al-implanted Si wafers was lower than that of virgin Si. The unique morphology of the implanted Si results from rpaid Al diffusion and segregation promoted by hot implantation. Reduction of the oxidation rate of Si by Al implantation is attributed to preferential oxidation of Al and formation of a continuous diffusion barrier of Al{sub 2}O{sub 3}.

  12. Anti-angiogenic effect of high doses of ascorbic acid

    PubMed Central

    Mikirova, Nina A; Ichim, Thomas E; Riordan, Neil H

    2008-01-01

    Pharmaceutical doses of ascorbic acid (AA, vitamin C, or its salts) have been reported to exert anticancer activity in vitro and in vivo. One proposed mechanism involves direct cytotoxicity mediated by accumulation of ascorbic acid radicals and hydrogen peroxide in the extracellular environment of tumor cells. However, therapeutic effects have been reported at concentrations insufficient to induce direct tumor cell death. We hypothesized that AA may exert anti-angiogenic effects. To test this, we expanded endothelial progenitor cells (EPCs) from peripheral blood and assessed, whether or not high dose AA would inhibit EPC ability to migrate, change energy metabolism, and tube formation ability. We also evaluated the effects of high dose AA on angiogenic activities of HUVECs (human umbilical vein endothelial cells) and HUAECs (human umbilical arterial endothelial cells). According to our data, concentrations of AA higher than 100 mg/dl suppressed capillary-like tube formation on Matrigel for all cells tested and the effect was more pronounced for progenitor cells in comparison with mature cells. Co-culture of differentiated endothelial cells with progenitor cells showed that there was incorporation of EPCs in vessels formed by HUVECs and HUAECs. Cell migration was assessed using an in vitro wound healing model. The results of these experiments showed an inverse correlation between AA concentrations relative to both cell migration and gap filling capacity. Suppression of NO (nitric oxide) generation appeared to be one of the mechanisms by which AA mediated angiostatic effects. This study supports further investigation into non-cytotoxic antitumor activities of AA. PMID:18789157

  13. Dosimetric investigation of high dose rate, gated IMRT

    SciTech Connect

    Lin, Teh; Chen Yan; Hossain, Murshed; Li, Jinsheng; Ma, C.-M.

    2008-11-15

    Increasing the dose rate offers time saving for IMRT delivery but the dosimetric accuracy is a concern, especially in the case of treating a moving target. The objective of this work is to determine the effect of dose rate associated with organ motion and gated treatment using step-and-shoot IMRT delivery. Both measurements and analytical simulation on clinical plans are performed to study the dosimetric differences between high dose rate and low dose rate gated IMRT step-and-shoot delivery. Various sites of IMRT plans for liver, lung, pancreas, and breast cancers were delivered to a custom-made motorized phantom, which simulated sinusoidal movement. Repeated measurements were taken for gated and nongated delivery with different gating settings and three dose rates, 100, 500, and 1000 MU/min using ion chambers and extended dose range films. For the study of the residual motion effect for individual segment dose and composite dose of IMRT plans, our measurements with 30%-60% phase gating and without gating for various dose rates were compared. A small but clinically acceptable difference in delivered dose was observed between 1000, 500, and 100 MU/min at 30%-60% phase gating. A simulation is presented, which can be used for predicting dose profiles for patient cases in the presence of motion and gating to confirm that IMRT step-and-shoot delivery with gating for 1000 MU/min are not much different from 500 MU/min. Based on the authors sample plan analyses, our preliminary results suggest that using 1000 MU/Min dose rate is dosimetrically accurate and efficient for IMRT treatment delivery with gating. Nonetheless, for the concern of patient care and safety, a patient specific QA should be performed as usual for IMRT plans for high dose rate deliveries.

  14. Randomized trials of high-dose chemotherapy in breast cancer: fraud, the press and the data (or lessons learned in medical policy governing clinical research).

    PubMed Central

    Antman, Karen

    2002-01-01

    High dose therapy for breast cancer remains controversial. Of the 15 randomized trials of high dose therapy in breast cancer reported to date, two South African studies have been discredited leaving 13 remaining studies. Mortality was consistently low, in the 0 to 2.5% range, except for the BCNU containing American Intergroup study, which had a 7.4% toxic mortality rate. Seven of the remaining 13 studies randomized fewer than 200 patients. Three of these small studies have significant differences in disease free survival, and a fourth study has a trend in favor of high dose therapy. The other three small studies cannot exclude a survival difference of 20%. Of the 6 remaining moderately large trials of 219 to 885 randomized patients, 5 are adjuvant studies and one included patients with metastatic disease. Of the five adjuvant trials, four have significant differences in relapse rate favoring the high dose arm, and the remaining study has a trend (with a high dose sequential single agent design rather than combination therapy as in the other studies). A planned subset analysis of the first 284 patients in the largest study funded by the Dutch insurance industry showed a significant advantage for high dose therapy. Given the 2-year median time to relapse and an addition 2-year median to death after relapse, the follow up for survival of 3-5 years on these studies is still short. In the only moderately sized metastatic trial from the National Cancer Institute of Canada with a very short median follow-up of 19 months, a significant difference in disease free survival has emerged, with no difference in survival. PMID:12053718

  15. [Proton Pump Inhibitor and High-dose Methotrexate: Two Cases Reports].

    PubMed

    Evrard, Julien; Farnier, Elodie; Carcel, Corine; Lachenal, Florence; Vial, Thierry; Pont, Emmanuelle

    2015-01-01

    Methotrexate (MTX) is a cytotoxic agent prescribed at high dose in treatment of malignancy. Association of MTX to proton pump inhibitor (PPI) is not recommended if doses are more than 20 mg per weeks and only to take into account for smaller doses. Review relate some cases of delayed elimination of methotrexate in patients taking PPI, which increase risk of toxic event. However, currently there is no status quo on interaction between PPI and MTX according to available data. We report two clinical cases illustrating one more time a toxic event to MTX in presence of PPI. In absence of risk/benefit ratio set correctly, an assessment of appropriateness of PPI prescription before MTX therapy can limit an iatrogenic risk. PMID:26242498

  16. Recurrent myelitis in common variable immunodeficiency successfully managed with high-dose subcutaneous immunoglobulin

    PubMed Central

    Danieli, Maria Giovanna; Pettinari, Lucia; Marinangeli, Lucia; Logullo, Francesco

    2012-01-01

    Acute myelitis is an aetiologically heterogeneous inflammatory disorder of the spinal cord. We report on a 71-year-old woman with a recurrent cervical and thoracic myelitis who presented with a new relapse of the disease. Neuromyelitis optica was ruled out such as other possible causes of acute and/or recurrent myelopathy. Serum immunoglobulin levels and specific antibody responses were consistent with the diagnosis of common variable immunodeficiency (CVID). She was treated with high-dose methylprednisolone and intravenous immunoglobulin. As a remission-maintaining drug, we decided to treat her with subcutaneous immunoglobulin (CSL Behring) at 0.2 g/kg/week at doses higher than usually employed in replacement therapy in CVID. At 3-year follow-up, the response to treatment was good. No relapses occurred. Our case suggests the effectiveness and safety of subcutaneous immunoglobulin in maintaining remission and in sparing prednisone in a woman with recurrent myelitis associated with CVID. PMID:22878981

  17. Recurrent myelitis in common variable immunodeficiency successfully managed with high-dose subcutaneous immunoglobulin.

    PubMed

    Danieli, Maria Giovanna; Pettinari, Lucia; Marinangeli, Lucia; Logullo, Francesco

    2012-01-01

    Acute myelitis is an aetiologically heterogeneous inflammatory disorder of the spinal cord. We report on a 71-year-old woman with a recurrent cervical and thoracic myelitis who presented with a new relapse of the disease. Neuromyelitis optica was ruled out such as other possible causes of acute and/or recurrent myelopathy. Serum immunoglobulin levels and specific antibody responses were consistent with the diagnosis of common variable immunodeficiency (CVID). She was treated with high-dose methylprednisolone and intravenous immunoglobulin. As a remission-maintaining drug, we decided to treat her with subcutaneous immunoglobulin (CSL Behring) at 0.2 g/kg/week at doses higher than usually employed in replacement therapy in CVID. At 3-year follow-up, the response to treatment was good. No relapses occurred. Our case suggests the effectiveness and safety of subcutaneous immunoglobulin in maintaining remission and in sparing prednisone in a woman with recurrent myelitis associated with CVID. PMID:22878981

  18. [Successful anesthetic management of a patient with giant pheochromocytoma using high-dose landiolol hydrochloride].

    PubMed

    Kitano, Manabu; Komasawa, Nobuyasu; Sawai, Toshiyuki; Minami, Toshiaki

    2014-08-01

    We report successful anesthetic management of a patient with pheochromocytoma using high-dose landiolol hydrochloride. A 55-year-old man was scheduled to undergo resection of giant pheochromocytoma. Epidural anesthesia was not performed due to anticoagulant therapy for lower limb thrombus. Tracheal intubation was performed with the Pentax-AWS Airwayscope. Preoperative screening revealed urine adrenaline 2.567.0 microg x day(-1) urine noradrenaline 1,734.0 microg x day(-1), and a tumor diameter of 96 x 60 mm. Catecholamine surge was controlled with 50 microg x kg(-1) x min(-1) continuous infusion of landiolol hydrochloride and IV bolus phentolamine. On tumor resection, although systemic blood pressure increased to 294 mmHg and was unresponsive to repeated phentolamine administration, the heart rate remained at 70-105 beats x min(-1) and there were no significant ST changes. PMID:25199327

  19. Five-Year Outcomes of High-Dose Single-Fraction Spinal Stereotactic Radiosurgery

    SciTech Connect

    Moussazadeh, Nelson; Lis, Eric; Katsoulakis, Evangelia; Kahn, Sweena; Svoboda, Marek; DiStefano, Natalie M.; McLaughlin, Lily; Bilsky, Mark H.; Yamada, Yoshiya; Laufer, Ilya

    2015-10-01

    Purpose: To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. Methods and Materials: The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included disease progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. Results: Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen

  20. Effect of folate status and methylenetetrahydrofolate reductase genotypes on the complications and outcome of high dose methotrexate chemotherapy in north Indian children with acute lymphoblastic leukemia

    PubMed Central

    Moulik, Nirmalya Roy; Kumar, Archana; Agrawal, Suraksha; Mahdi, Abbas Ali; Kumar, Ashutosh

    2016-01-01

    Purpose: The genes of the folate metabolic pathway have been associated with toxicities during high dose methotrexate therapy for childhood ALL, however, the importance of intrinsic folate status in this regard is unclear. Methods: In the present study the effect of precourse folate levels and MTHFR genotypes on the complications during high dose methotrexate chemotherapy in children with ALL were examined. Results: Twenty-one children were studied. Folate deficiency was associated with higher incidence of neutropenia (P = 0.03) and longer duration of chemotherapy interruption (P = 0.009). Children with MTHFR1298 mutations needed more red cell transfusion (P = 0.03). All 3 deaths encountered were seen in folate deficient children. Conclusions: Folate deficiency was associated with higher complications during high dose methotrexate therapy, the implications of which are important especially in resource poor settings with high prevalence of folate deficiency. PMID:27168705

  1. Treatment of hyperthyroidism with radioiodine targeted activity: A comparison between two dosimetric methods.

    PubMed

    Amato, Ernesto; Campennì, Alfredo; Leotta, Salvatore; Ruggeri, Rosaria M; Baldari, Sergio

    2016-06-01

    Radioiodine therapy is an effective and safe treatment of hyperthyroidism due to Graves' disease, toxic adenoma, toxic multinodular goiter. We compared the outcomes of a traditional calculation method based on an analytical fit of the uptake curve and subsequent dose calculation with the MIRD approach, and an alternative computation approach based on a formulation implemented in a public-access website, searching for the best timing of radioiodine uptake measurements in pre-therapeutic dosimetry. We report about sixty-nine hyperthyroid patients that were treated after performing a pre-therapeutic dosimetry calculated by fitting a six-point uptake curve (3-168h). In order to evaluate the results of the radioiodine treatment, patients were followed up to sixty-four months after treatment (mean 47.4±16.9). Patient dosimetry was then retrospectively recalculated with the two above-mentioned methods. Several time schedules for uptake measurements were considered, with different timings and total number of points. Early time schedules, sampling uptake up to 48h, do not allow to set-up an accurate treatment plan, while schedules including the measurement at one week give significantly better results. The analytical fit procedure applied to the three-point time schedule 3(6)-24-168h gave results significantly more accurate than the website approach exploiting either the same schedule, or the single measurement at 168h. Consequently, the best strategy among the ones considered is to sample the uptake at 3(6)-24-168h, and carry out an analytical fit of the curve, while extra measurements at 48 and 72h lead only marginal improvements in the accuracy of therapeutic activity determination. PMID:27245300

  2. Epidermal growth factor inhibits radioiodine uptake but stimulates deoxyribonucleic acid synthesis in newborn rat thyroids grown in nude mice

    SciTech Connect

    Ozawa, S.; Spaulding, S.W. )

    1990-08-01

    We have studied the effect of altering the level of circulating epidermal growth factor (EGF) on the function and growth of newborn rat thyroids transplanted into nude mice. Preliminary studies confirmed that sialoadenectomy reduced circulating EGF levels in nude mice (from 0.17 +/- 0.02 to 0.09 +/- 0.02 ng/ml), and that ip injection of 5 micrograms EGF raised EGF levels (the peak level of 91.7 +/- 3.3 ng/ml was achieved at 30 min, with a subsequent half-life of about 1 h). The radioiodine uptake by newborn rat thyroid transplants in the sialoadenectomized and sham-operated animals correlated inversely with the circulating EGF levels determined when the mice were killed (r = -0.99). Low-dose TSH treatment (0.1 microU/day) generally stimulated the radioiodine uptake, but high-dose TSH groups (100 microU/day) were not significantly different from the control group. The 5-day nuclear (3H)thymidine labeling index was 6.8 +/- 0.5% IN newborn rat thyroid transplants grown in sialoadenectomized animals, 13.1 +/- 0.3% in sham-operated animals, and 16.8 +/- 0.5% in nude mice receiving 5 micrograms EGF ip daily. In general, both low-dose and high-dose TSH promoted DNA synthesis under low EGF conditions but were ineffective in the presence of higher levels of EGF. Adult rat thyroid transplants showed no significant responses. Although sialoadenectomy may alter other factors besides EGF, it appears that changes in the levels of circulating EGF within the physiological range affect the function and growth of newborn rat thyroid transplants. Circulating EGF may play a role in thyroid maturation and may also be involved in the regulation of thyroid function throughout life.

  3. Radioiodine Biogeochemistry and Prevalence in Groundwater.

    PubMed

    Kaplan, D I; Denham, M E; Zhang, S; Yeager, C; Xu, C; Schwehr, K A; Li, H P; Ho, Y F; Wellman, D; Santschi, P H

    2014-10-18

    (129)I is commonly either the top or among the top risk drivers, along with (99)Tc, at radiological waste disposal sites and contaminated groundwater sites where nuclear material fabrication or reprocessing has occurred. The risk stems largely from (129)I having a high toxicity, a high bioaccumulation factor (90% of all the body's iodine concentrates in the thyroid), a high inventory at source terms (due to its high fission yield), an extremely long half-life (16M years), and rapid mobility in the subsurface environment. Another important reason that (129)I is a key risk driver is that there is uncertainty regarding its biogeochemical fate and transport in the environment. We typically can define (129)I mass balance and flux at sites, but cannot predict accurately its response to changes in the environment. As a consequence of some of these characteristics, (129)I has a very low drinking water standard, which is set at 1 pCi/L, the lowest of all radionuclides in the Federal Register. Recently, significant advancements have been made in detecting iodine species at ambient groundwater concentrations, defining the nature of the organic matter and iodine bond, and quantifying the role of naturally occurring sediment microbes to promote iodine oxidation and reduction. These recent studies have led to a more mechanistic understanding of radioiodine biogeochemistry. The objective of this review is to describe these advances and to provide a state of the science of radioiodine biogeochemistry relevant to its fate and transport in the terrestrial environment and provide information useful for making decisions regarding the stewardship and remediation of (129)I contaminated sites. As part of this review, knowledge gaps were identified that would significantly advance the goals of basic and applied research programs for accelerating (129)I environmental remediation and reducing uncertainty associated with disposal of (129)I waste. Together the information gained from

  4. Radioiodine Biogeochemistry and Prevalence in Groundwater

    SciTech Connect

    Kaplan, Daniel I.; Denham, Miles E.; Zhang, Saijin; Yeager, Chris; Xu, Chen; Schwehr, Kathy; Li, Hsiu-Ping; Ho, Yi-Fang; Wellman, Dawn M.; Santschi, Peter H.

    2014-08-03

    129I is commonly either the top or among the top risk drivers, along with 99Tc, at radiological waste disposal sites and contaminated groundwater sites where nuclear material fabrication or reprocessing has occurred. The risk stems largely from 129I having a high toxicity, a high bioaccumulation factor (90% of all the body’s iodine concentrates in the thyroid), a high inventory at source terms (due to its high fission yield), an extremely long half-life (16M yr), and rapid mobility in the subsurface environment. Another important reason that 129I is a key risk driver is that there is the uncertainty regarding its biogeochemical fate and transport in the environment. We typically can define 129I mass balance and flux at sites, but cannot predict accurately its response to changes in the environment. As a consequence of some of these characteristics, 129I has a very low Drinking Water Standard, DWS, which is set at 1 pCi/L, the lowest of all radionuclides in the Federal Register. Recently, significant advancements have been made in detecting iodine species at ambient groundwater concentrations, defining the nature of the organic matter and iodine bond, and quantifying the role of naturally occurring sediment microbes to promote iodine oxidation and reduction. These recent studies have led to a more mechanistic understanding of radioiodine biogeochemistry. The objective of this review is to describe these advances and to provide a state of the science of radioiodine biogeochemistry relevant to its fate and transport in the terrestrial environment and provide information useful for making decisions regarding the stewardship and remediation of 129I contaminated sites. As part of this review, knowledge gaps were identified that would significantly advance the goals of basic and applied research programs for accelerating 129I environmental remediation and reducing uncertainty associated with disposal of 129I waste. Together the information gained from addressing these

  5. Radioiodine Biogeochemistry and Prevalence in Groundwater

    PubMed Central

    Kaplan, D. I.; Denham, M. E.; Zhang, S.; Yeager, C.; Xu, C.; Schwehr, K. A.; Li, H. P.; Ho, Y. F.; Wellman, D.; Santschi, P. H.

    2014-01-01

    129I is commonly either the top or among the top risk drivers, along with 99Tc, at radiological waste disposal sites and contaminated groundwater sites where nuclear material fabrication or reprocessing has occurred. The risk stems largely from 129I having a high toxicity, a high bioaccumulation factor (90% of all the body's iodine concentrates in the thyroid), a high inventory at source terms (due to its high fission yield), an extremely long half-life (16M years), and rapid mobility in the subsurface environment. Another important reason that 129I is a key risk driver is that there is uncertainty regarding its biogeochemical fate and transport in the environment. We typically can define 129I mass balance and flux at sites, but cannot predict accurately its response to changes in the environment. As a consequence of some of these characteristics, 129I has a very low drinking water standard, which is set at 1 pCi/L, the lowest of all radionuclides in the Federal Register. Recently, significant advancements have been made in detecting iodine species at ambient groundwater concentrations, defining the nature of the organic matter and iodine bond, and quantifying the role of naturally occurring sediment microbes to promote iodine oxidation and reduction. These recent studies have led to a more mechanistic understanding of radioiodine biogeochemistry. The objective of this review is to describe these advances and to provide a state of the science of radioiodine biogeochemistry relevant to its fate and transport in the terrestrial environment and provide information useful for making decisions regarding the stewardship and remediation of 129I contaminated sites. As part of this review, knowledge gaps were identified that would significantly advance the goals of basic and applied research programs for accelerating 129I environmental remediation and reducing uncertainty associated with disposal of 129I waste. Together the information gained from addressing these knowledge

  6. Tumour response following high-dose intratumoural application of Viscum album on a patient with adenoid cystic carcinoma

    PubMed Central

    Werthmann, Paul Georg; Helling, Dieter; Heusser, Peter; Kienle, Gunver Sophia

    2014-01-01

    Adenoid cystic carcinoma (ACC) is a rare type of cancer that typically originates in the salivary glands. Surgical removal can lead to functional loss and psychological distress. Viscum album extract (VAE) is a herbal remedy with dose-dependent cytotoxic, apoptogenic and immunological effects. In some case reports, tumour regression has been observed following high-dose local applications of VAE. An active 88-year-old man with fast-growing ACC of the hard palate refused surgical removal and received high-dose intratumoural injections of VAE (alone) over a 10-month period. The tumour decreased in size, softened and loosened from its surroundings. A biopsy during the course showed inflammation. The patient remained well and without functional limitations during the therapy and follow-up period (5 months). VAE produced no reported side effects. This aged patient exemplifies a satisfying course of ACC under VAE resulting in good quality of life and partial tumour regression. PMID:25082867

  7. High-dose, post-transplantation cyclophosphamide to promote graft-host tolerance after allogeneic hematopoietic stem cell transplantation

    PubMed Central

    Luznik, Leo

    2010-01-01

    Graft-versus-host disease, or GVHD, is a major complication of allogeneic hematopoietic stem cell transplantation (alloHSCT) for the treatment of hematologic malignancies. Here, we describe a novel method for preventing GVHD after alloHSCT using high-dose, post-transplantation cyclophosphamide (Cy). Post-transplantation Cy promotes tolerance in alloreactive host and donor T cells, leading to suppression of both graft rejection and GVHD after alloHSCT. High-dose, post-transplantation Cy facilitates partially HLA-mismatched HSCT without severe GVHD and is effective as sole prophylaxis of GVHD after HLA-matched alloHSCT. By reducing the morbidity and mortality of alloHSCT, post-transplantation Cy may expand the applications of this therapy to the treatment of autoimmune diseases and non-malignant hematologic disorders such as sickle cell disease. PMID:20066512

  8. Radioiodination of chicken luteinizing hormone without affecting receptor binding potency

    SciTech Connect

    Kikuchi, M.; Ishii, S. )

    1989-12-01

    By improving the currently used lactoperoxidase method, we were able to obtain radioiodinated chicken luteinizing hormone (LH) that shows high specific binding and low nonspecific binding to a crude plasma membrane fraction of testicular cells of the domestic fowl and the Japanese quail, and to the ovarian granulosa cells of the Japanese quail. The change we made from the original method consisted of (1) using chicken LH for radioiodination that was not only highly purified but also retained a high receptor binding potency; (2) controlling the level of incorporation of radioiodine into chicken LH molecules by employing a short reaction time and low temperature; and (3) fractionating radioiodinated chicken LH further by gel filtration using high-performance liquid chromatography. Specific radioactivity of the final {sup 125}I-labeled chicken LH preparation was 14 microCi/micrograms. When specific binding was 12-16%, nonspecific binding was as low as 2-4% in the gonadal receptors. {sup 125}I-Labeled chicken LH was displaced by chicken LH and ovine LH but not by chicken follicle-stimulating hormone. The equilibrium association constant of quail testicular receptor was 3.6 x 10(9) M-1. We concluded that chicken LH radioiodinated by the present method is useful for studies of avian LH receptors.

  9. Effect of reserpine on salivary gland radioiodine uptake in thyroid cancer

    SciTech Connect

    Levy, H.A.; Park, C.H.

    1987-04-01

    Nine patients with thyroid cancer were treated with reserpine in an attempt to reduce radiation exposure to the salivary glands from 100-150 mCi doses of I-131 therapy to thyroid remnants or metastases. Three control patients were not treated with reserpine but did receive 100-150 mCi of I-131. Parotid/background ratios of activity after radioablative doses of I-131 in patients not treated with reserpine were significantly higher than the patients treated with reserpine, and this was also true seven days after the radioablative dose. Combined therapy with reserpine, chewing gum, lemon candies, and hydration is suggested for the prevention of sialadenitis and xerostomia due to large doses of radioiodine.

  10. Salvage high-dose-rate (HDR) brachytherapy for recurrent head-and-neck cancer

    SciTech Connect

    Hepel, Jaroslaw T.; Syed, A.M. Nisar . E-mail: bvigil@memnet.org; Puthawala, Ajmel; Sharma, Anil; Frankel, Paul

    2005-08-01

    Background: A significant portion of head-and-neck cancer patients will develop persistent or recurrent disease after definitive treatment. Radiation therapy is often used as definitive therapy or as an adjunct to surgery. Recurrent cancer of the head and neck in the previously irradiated field is, thus, a common occurrence and poses a therapeutic challenge. Some studies have evaluated low-dose-rate (LDR) brachytherapy as a therapeutic option, including a large case series with long-term follow-up by our own institution. High-dose-rate (HDR) brachytherapy offers therapeutic advantages over LDR brachytherapy. This study evaluates the local control and outcomes of patients with previously irradiated recurrent head-and-neck cancer treated with HDR interstitial brachytherapy. Methods and Materials: Between 1997 and 2002, 30 patients who received prior radiation therapy for primary tumors of the head and neck were treated for biopsy-proven recurrent disease. All patients received previous radiation as definitive therapy alone or as adjunct to surgery. All patients were inoperable, refused surgery, or had gross residual disease after salvage surgery for their recurrent disease. Thirty-six sites on the 30 patients were implanted by application of high-dose-rate interstitial brachytherapy techniques with mean tumor dose of 34 Gy (18-48 Gy) in twice daily fractions of 300 to 400cGy per fraction. Results: At a minimum follow-up of 12 months, local tumor control was achieved in 69% of implanted sites. Disease-specific survival at 1 and 2 years was 54% and 45%, respectively. Overall survival at 1 and 2 years was 56% and 37%, respectively. Grade 3/4 late complications occurred in 16% of the patients. No fatal complications occurred. Conclusion: HDR brachytherapy can play an important role in the salvage treatment of previously irradiated recurrent head-and-neck cancer. This study shows that comparable results are obtained by HDR brachytherapy with fewer late complications than

  11. The Acute Gastrointestinal Syndrome in High-Dose Irradiated Mice

    PubMed Central

    Booth, Catherine; Tudor, Gregory; Tudor, Julie; Katz, Barry P; MacVittie, Thomas

    2012-01-01

    The most detailed reports of the response of the gastrointestinal system to high dose acute radiation have focused mainly on understanding the histopathology. However, to enable medical countermeasure assessment under the animal rule criteria, it is necessary to have a robust model in which the relationship between radiation dose and intestinal radiation syndrome incidence, timing and severity are established and correlated with histopathology. Although many mortality studies have been published, they have used a variety of mouse strains, ages, radiation sources and husbandry conditions, all of which influence the dose response. Further, it is clear that the level of bone marrow irradiation and supportive care can influence endpoints. In order to create robust baseline data we have generated dose response data in adult male mice, maintained under identical conditions, and exposed to either total or partial-body irradiation. Partial-body irradiation includes both extensive (40%) and minimal (5%) bone marrow sparing models, the latter designed to correlate with an established primate model and allow assessment of effects of any medical countermeasure on all three major radiation syndromes (intestinal, bone marrow and lung) in the surviving mice. Lethal dose (LD30, LD50 and LD70) data are described in the various models, along with the impact of enteric flora and response to supportive care. Correlation with diarrhea severity and histopathology are also described. This data can be used to aid the design of good laboratory practice (GLP) compliant Animal Rule studies that are reflective of the conditions following accidental radiation exposure. PMID:23091876

  12. Treatment of myasthenia gravis with high-dose intravenous immunoglobulin.

    PubMed

    Cosi, V; Lombardi, M; Piccolo, G; Erbetta, A

    1991-08-01

    We treated 37 patients affected by autoimmune generalized myasthenia gravis (MG) with high-dose intravenous gammaglobulin (HDIVIg), 400 mg/kg per day on 5 consecutive days. A one-degree improvement of Oosterhuis global clinical classification of myasthenic severity (OGCCMS), the disappearance of bulbar involvement or both were recorded 12 days after the beginning of the treatment in 70.3% of the patients and persisted up to 60 days in 58.7%. A two-degree improvement of OGCCMS was recorded in 54.1% of the patients and it was maintained up to 60 days in 37.8%. The percentage of improvement did not significantly differ between patients entering the treatment in a long-standing, drug-refractory stationary phase of the illness (n = 26) and patients who received HDIVIg in an acute phase of MG (n = 11). None of the patients experienced side effects. Our data indicates that HDIVIg is an interesting, virtually riskless therapeutic choice for MG patients, and allows the planning of a controlled trial versus plasma-exchange. PMID:1950455

  13. High-dose processing and application to Korean space foods

    NASA Astrophysics Data System (ADS)

    Song, Beom-Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Kang, Sang-Wook; Choi, Gi-Hyuk; Lee, Ju-Woon

    2009-07-01

    Nutrition bar, Ramen (ready-to-cook noodle), and two Korean traditional foods ( Kimchi, fermented vegetable; Sujeonggwa, cinnamon beverage) have been developed as space foods using high-dose gamma irradiation. Addition of calcium lactate and vitamin C, a mild heating, deep-freezing, and gamma irradiation at 25 kGy were conducted to prepare Kimchi as a ready-to-eat space food. Sterilization of Space Kimchi (SK) was confirmed by a microbiological test. The hardness of the Space Kimchi was lower than the untreated Kimchi (CON), but higher than the irradiated only Kimchi. Sensory attributes of the SK were similar to CON, and maintained during preservation at 35 °C for 30 days. The optimal doses for eliminating the contaminated microbes and maintaining the qualities of the Nutrition bars, Ramen, and Sujeonggwa were determined at 15, 10 and 6 kGy, respectively. All the Korean space food were certificated for use in space flight conditions of 30 days by the Russian Institute for Biomedical Problems.

  14. High-Dose Resveratrol Supplementation in Obese Men

    PubMed Central

    Poulsen, Morten M.; Vestergaard, Poul F.; Clasen, Berthil F.; Radko, Yulia; Christensen, Lars P.; Stødkilde-Jørgensen, Hans; Møller, Niels; Jessen, Niels; Pedersen, Steen B.; Jørgensen, Jens Otto L.

    2013-01-01

    Obesity, diabetes, hypertension, and hyperlipidemia constitute risk factors for morbidity and premature mortality. Based on animal and in vitro studies, resveratrol reverts these risk factors via stimulation of silent mating type information regulation 2 homolog 1 (SIRT1), but data in human subjects are scarce. The objective of this study was to examine the metabolic effects of high-dose resveratrol in obese human subjects. In a randomized, placebo-controlled, double-blinded, and parallel-group design, 24 obese but otherwise healthy men were randomly assigned to 4 weeks of resveratrol or placebo treatment. Extensive metabolic examinations including assessment of glucose turnover and insulin sensitivity (hyperinsulinemic euglycemic clamp) were performed before and after the treatment. Insulin sensitivity, the primary outcome measure, deteriorated insignificantly in both groups. Endogenous glucose production and the turnover and oxidation rates of glucose remained unchanged. Resveratrol supplementation also had no effect on blood pressure; resting energy expenditure; oxidation rates of lipid; ectopic or visceral fat content; or inflammatory and metabolic biomarkers. The lack of effect disagrees with persuasive data obtained from rodent models and raises doubt about the justification of resveratrol as a human nutritional supplement in metabolic disorders. PMID:23193181

  15. Formation of vanadium silicide by high dose ion implantation

    NASA Astrophysics Data System (ADS)

    Salvi, V. P.; Narsale, A. M.; Vidwans, S. V.; Rangwala, A. A.; Guzman, L.; Dapor, M.; Giunta, G.; Calliari, L.; Marchetti, F.

    1987-10-01

    The vanadium silicide system has been found to be of increasing interest because one of the silicide phases viz. V 3Si with the A-15 structure is often accompanied by a high temperature superconductivity. We have studied the formation of vanadium silicide layers by high dose ion implantation. 30 keV 51V + ions were implanted at room temperature onto thermally evaporated a-Si films on thermally grown SiO 2 substrates. The samples were annealed in vacuum to study the possible evolution of V-Si phases. Both Seeman-Bohlin X-ray diffraction and Auger/sputter profiling techniques were used to analyse these samples. The observed Auger depth profile of the annealed samples shows a more uniform vanadium distribution as compared to the vanadium distribution in as-implanted samples, along with the changes in the Si L 2,3VV lineshape. The X-ray diffraction results show the formation of V 3Si, V 5Si 3 and VSi 2 phases. After annealing the sample in vacuum, a more ordered growth of V 3Si phase is found to be accompanied by an increase in VSi 2 phase. This has been related to the possible changes ocurring in the a-Si layers due to annealing of the sample.

  16. The effects of radioiodination and fluorescent labelling on albumin

    SciTech Connect

    Crandall, R.E.; Janatova, J.; Andrade, J.D.

    1981-01-01

    The preparation and characterization of fluorescamine -, fluorescein isothiocyanate (FITC) -, and radioiodine-labelled bovine serum albumin is critically evaluated. Electrophoretic mobility and ion-exchange chromatography, together with measures of degree of conjugation and sulfhydryl content, are used to assess the changes due to conjugation. Fluorescamine labelling results in drastic changes in chromatographic behavior and electrophoretic mobility. FITC labelling also results in significant changes in chromatographic and electrophoretic properties. Radioiodination leads to minor changes in chromatographic properties and oxydation of sulfhydryl groups, with little or no change in electrophoretic properties. All three labels have some degree of lability and show increased levels of free label with time, even after extensive initial purification. It is concluded that the two fluorescent labels and possibly the radioiodine labelling method used here are unsuitable for certain studies of BSA, such as its adsorption at solid-liquid interfaces.

  17. Inhibition of miR-146b expression increases radioiodine-sensitivity in poorly differential thyroid carcinoma via positively regulating NIS expression

    SciTech Connect

    Li, Luchuan; Lv, Bin; Chen, Bo; Guan, Ming; Sun, Yongfeng; Li, Haipeng; Zhang, Binbin; Ding, Changyuan; He, Shan; Zeng, Qingdong

    2015-07-10

    Dedifferentiated thyroid carcinoma (DTC) with the loss of radioiodine uptake (RAIU) is often observed in clinical practice under radioiodine therapy, indicating the challenge for poor prognosis. MicroRNA (miRNA) has emerged as a promising therapeutic target in many diseases; yet, the role of miRNAs in RAIU has not been generally investigated. Based on recent studies about miRNA expression in papillary or follicular thyroid carcinomas, the expression profiles of several thyroid relative miRNAs were investigated in one DTC cell line, derived from normal DTC cells by radioiodine treatment. The top candidate miR-146b, with the most significant overexpression profiles in dedifferentiated cells, was picked up. Further research found that miR-146b could be negatively regulated by histone deacetylase 3 (HDAC3) in normal cells, indicating the correlation between miR-146b and Na{sup +}/I{sup −} symporter (NIS)-mediated RAIU. Fortunately, it was confirmed that miR-146b could regulate NIS expression/activity; what is more important, miR-146b interference would contribute to the recovery of radioiodine-sensitivity in dedifferentiated cells via positively regulating NIS. In the present study, it was concluded that NIS-mediated RAIU could be modulated by miR-146b; accordingly, miR-146b might serve as one of targets to enhance efficacy of radioactive therapy against poorly differential thyroid carcinoma (PDTC). - Highlights: • Significant upregulated miR-146b was picked up from thyroid relative miRNAs in DTC. • MiR-146b was negatively regulated by HDAC3 in normal thyroid carcinoma cells. • NIS activity and expression could be regulated by miR-146b in thyroid carcinoma. • MiR-146b inhibition could recover the decreased radioiodine-sensitivity of DTC cells.

  18. Radioiodine remnant ablation in low-risk differentiated thyroid cancer patients who had R0 dissection is an over treatment

    PubMed Central

    Bal, Chandrasekhar; Ballal, Sanjana; Soundararajan, Ramya; Chopra, Saurav; Garg, Aayushi

    2015-01-01

    Low-risk (LR) differentiated thyroid cancer (DTC) patients should be ablated or not, albeit, with small dose of radioiodine is highly controversial. We hypothesized that those LR DTC patients who were surgically ablated need no radioiodine remnant ablation (RRA). This study aims to evaluate the long-term outcome in these two groups of patients. Retrospective cohort study conducted from January 1991 to December 2012. Based on extent of surgical resection and histopathology, LR DTC patients were classified as Gr-1: 169 patients, who were surgically ablated; Gr-2: 153 patients, who had significant remnant in thyroid bed. Basal parameters were comparable between two groups except pretherapy 24 h radioiodine uptake (0.16 ± 0.01% vs. 5.64 ± 0.46%; P < 0.001). No patient received RRA in Gr-1; Gr-2 patients were administered 30 mCi 131I. Total number of events (recurrence, persistent, and progression of disease), with median follow up of 10.3 years, was observed in 10/322 (3.1%) of LR DTC patients. Only one patient had disease recurrence from Gr-1, who became disease-free after radioiodine therapy. Similarly, one patient from 126, who was ablated with single dose of RRA, had recurrence from Gr-2. However, 8/27 (29.7%) patients from Gr-2 had persistent disease; even two of them subsequently developed disease progression, who failed first-dose of RRA. The event-free survival rates were 99.4% and 94.1% (P = 0.006) in Gr-1 and Gr-2, respectively. RRA is an overtreatment in surgically ablated LR DTC patients. Successfully ablated RRA patients also had similar long-term outcome, however, those who failed, should be re-stratified as intermediate-risk category, and managed aggressively. PMID:25755077

  19. High dose intravenous immunoglobulin in autoimmune rheumatic disorders.

    PubMed

    Zeuner, R A; Euler, H H; Schroeder, J O

    1997-11-01

    Since the effectiveness of high dose intravenous immunoglobulin (IVIg) was first demonstrated in autoimmune thrombocytopenia, IVIg has been investigated in the treatment of various autoimmune rheumatic disorders. Controlled randomised studies have established the efficacy of IVIg in Kawasaki's syndrome, for which combined IVIg and aspirin (acetylsalicylic acid) now constitutes the standard treatment. Another controlled study has demonstrated the benefit of IVIg in dermatomyositis. IVIg treatment in juvenile rheumatoid arthritis has produced contradictory results. Uncontrolled studies and case reports on the application of IVIg in systemic lupus erythematosus, ANCA-associated vasculitides and adult rheumatoid arthritis generally describe short term positive effects. Various mechanisms are thought to underlie the effect of IVIg on autoimmune rheumatic diseases, such as: blockade of Fc receptors;immunomodulation via anti-idiotypic interactions;inhibition of complement-mediated tissue damage;modulation of cytokine expression by leucocytes and endothelial cells; andinhibition of superantigen-mediated T cell activation. IVIg is considered to be a low-risk form of treatment. Reported adverse effects include headache, aseptic meningitis and transient impairment of renal function. Haemolysis and anaphylactic reactions are rare. The effect profile of IVIg makes it a relevant, although still experimental, form of treatment in autoimmune rheumatic disorders, but its high cost renders it unsuitable as a first-line treatment. Because IVIg does not weaken patients' resistance to infection, it might serve as a therapeutic option in bridging clinical situations where immunosuppressive or cytotoxic approaches are contraindicated in patients with autoimmune disorders, such as intercurrent infection or in the period immediately before and after surgery. PMID:18020527

  20. High-dose neutron irradiation performance of dielectric mirrors

    SciTech Connect

    Nimishakavi Anantha Phani Kiran Kumar; Leonard, Keith J.; Jellison, Jr., Gerald Earle; Snead, Lance Lewis

    2015-05-01

    The study presents the high-dose behavior of dielectric mirrors specifically engineered for radiation-tolerance: alternating layers of Al2O3/SiO2 and HfO2/SiO2 were grown on sapphire substrates and exposed to neutron doses of 1 and 4 dpa at 458 10K in the High Flux Isotope Reactor (HFIR). In comparison to previously reported results, these higher doses of 1 and 4 dpa results in a drastic drop in optical reflectance, caused by a failure of the multilayer coating. HfO2/SiO2 mirrors failed completely when exposed to 1 dpa, whereas the reflectance of Al2O3/SiO2 mirrors reduced to 44%, eventually failing at 4 dpa. Transmission electron microscopy (TEM) observation of the Al2O3/SiO2 specimens showed SiO2 layer defects which increases size with irradiation dose. The typical size of each defect was 8 nm in 1 dpa and 42 nm in 4 dpa specimens. Buckling type delamination of the interface between the substrate and first layer was typically observed in both 1 and 4 dpa HfO2/SiO2 specimens. Composition changes across the layers were measured in high resolution scanning-TEM mode using energy dispersive spectroscopy. A significant interdiffusion between the film layers was observed in Al2O3/SiO2 mirror, though less evident in HfO2/SiO2 system. Lastly, the ultimate goal of this work is the provide insight into the radiation-induced failure mechanisms of these mirrors.

  1. High-dose neutron irradiation performance of dielectric mirrors

    DOE PAGESBeta

    Nimishakavi Anantha Phani Kiran Kumar; Leonard, Keith J.; Jellison, Jr., Gerald Earle; Snead, Lance Lewis

    2015-05-01

    The study presents the high-dose behavior of dielectric mirrors specifically engineered for radiation-tolerance: alternating layers of Al2O3/SiO2 and HfO2/SiO2 were grown on sapphire substrates and exposed to neutron doses of 1 and 4 dpa at 458 10K in the High Flux Isotope Reactor (HFIR). In comparison to previously reported results, these higher doses of 1 and 4 dpa results in a drastic drop in optical reflectance, caused by a failure of the multilayer coating. HfO2/SiO2 mirrors failed completely when exposed to 1 dpa, whereas the reflectance of Al2O3/SiO2 mirrors reduced to 44%, eventually failing at 4 dpa. Transmission electron microscopymore » (TEM) observation of the Al2O3/SiO2 specimens showed SiO2 layer defects which increases size with irradiation dose. The typical size of each defect was 8 nm in 1 dpa and 42 nm in 4 dpa specimens. Buckling type delamination of the interface between the substrate and first layer was typically observed in both 1 and 4 dpa HfO2/SiO2 specimens. Composition changes across the layers were measured in high resolution scanning-TEM mode using energy dispersive spectroscopy. A significant interdiffusion between the film layers was observed in Al2O3/SiO2 mirror, though less evident in HfO2/SiO2 system. Lastly, the ultimate goal of this work is the provide insight into the radiation-induced failure mechanisms of these mirrors.« less

  2. Molecular Mechanisms Linking High Dose Medroxyprogesterone with HIV-1 Risk

    PubMed Central

    Irvin, Susan C.; Herold, Betsy C.

    2015-01-01

    Background Epidemiological studies suggest that medroxyprogesterone acetate (MPA) may increase the risk of HIV-1. The current studies were designed to identify potential underlying biological mechanisms. Methods Human vaginal epithelial (VK2/E6E7), peripheral blood mononuclear (PBMC), and polarized endometrial (HEC-1-A) cells were treated with a range of concentrations of MPA (0.015-150 μg/ml) and the impact on gene expression, protein secretion, and HIV infection was evaluated. Results Treatment of VK2/E6E7 cells with high doses (>15μg/ml] of MPA significantly upregulated proinflammatory cytokines, which resulted in a significant increase in HIV p24 levels secreted by latently infected U1 cells following exposure to culture supernatants harvested from MPA compared to mock-treated cells. MPA also increased syndecan expression by VK2/E6E7 cells and cells treated with 15 μg/ml of MPA bound and transferred more HIV-1 to T cells compared to mock-treated cells. Moreover, MPA treatment of epithelial cells and PBMC significantly decreased cell proliferation resulting in disruption of the epithelial barrier and decreased cytokine responses to phytohaemagglutinin, respectively. Conclusion We identified several molecular mechanisms that could contribute to an association between DMPA and HIV including proinflammatory cytokine and chemokine responses that could activate the HIV promoter and recruit immune targets, increased expression of syndecans to facilitate the transfer of virus from epithelial to immune cells and decreased cell proliferation. The latter could impede the ability to maintain an effective epithelial barrier and adversely impact immune cell function. However, these responses were observed primarily following exposure to high (15-150 μg/ml) MPA concentrations. Clinical correlation is needed to determine whether the prolonged MPA exposure associated with contraception activates these mechanisms in vivo. PMID:25798593

  3. High-dose-rate (HDR) brachytherapy for the treatment of benign obstructive endobronchial granulation tissue

    SciTech Connect

    Madu, Chika N. . E-mail: chikam@xrt.upenn.edu; Machuzak, Michael S.; Sterman, Daniel H.; Musani, Ali; Ahya, Vivek; McDonough, James; Metz, James M.

    2006-12-01

    Background: Severe airway obstruction can occur in the setting of benign granulation tissue forming at bronchial anastomotic sites after lung transplantation in up to 20% of patients. Many of these benign lesions respond to stent placement, laser ablation, or balloon bronchoplasty. However, in certain cases, proliferation of granulation tissue may persist despite all therapeutic attempts. This study describes a series of refractory patients treated with high-dose-rate (HDR) brachytherapy for benign proliferation of granulation tissue, causing airway compromise. Methods and Materials: Between April 2002 and June 2005, 5 patients with significant airway compromise from recurrent granulation tissue were treated with HDR brachytherapy. All patients had previously failed to maintain a patent airway despite multiple bronchoscopic interventions. Treatment was delivered using an HDR brachytherapy afterloader with {sup 192}Ir. Dose prescription was to a depth of 1 cm. All patients were treated weekly, with total doses ranging from 10 Gy to 21 Gy in two to three fractions. Results: The median follow-up was 12 months. All patients experienced a reduction in therapeutic bronchoscopic procedures after HDR brachytherapy compared with the pretreatment period. With the exception of possible radiation-induced bronchitis in 1 patient, there were no other treatment related complications. At the time of this report, 2 patients have died and the other 3 are alive with marked symptomatic improvement and reduced bronchoscopic procedures. Conclusion: High-dose-rate brachytherapy is an effective treatment for benign proliferation of granulation tissue causing airway obstruction. The early response to therapy is encouraging and further follow-up is necessary to determine long-term durability and late effects.

  4. Effect of high-dose Ascorbic acid on vasopressor's requirement in septic shock

    PubMed Central

    Zabet, Mohadeseh Hosseini; Mohammadi, Mostafa; Ramezani, Masoud; Khalili, Hossein

    2016-01-01

    Objective: Effects of ascorbic acid on hemodynamic parameters of septic shock were evaluated in nonsurgical critically ill patients in limited previous studies. In this study, the effect of high-dose ascorbic acid on vasopressor drug requirement was evaluated in surgical critically ill patients with septic shock. Methods: Patients with septic shock who required a vasopressor drug to maintain mean arterial pressure >65 mmHg were assigned to receive either 25 mg/kg intravenous ascorbic acid every 6 h or matching placebo for 72 h. Vasopressor dose and duration were considered as the primary outcomes. Duration of Intensive Care Unit (ICU) stay and 28-day mortality has been defined as secondary outcomes. Findings: During the study period, 28 patients (14 in each group) completed the trial. Mean dose of norepinephrine during the study period (7.44 ± 3.65 vs. 13.79 ± 6.48 mcg/min, P = 0.004) and duration of norepinephrine administration (49.64 ± 25.67 vs. 71.57 ± 1.60 h, P = 0.007) were significantly lower in the ascorbic acid than the placebo group. No statistically significant difference was detected between the groups regarding the length of ICU stay. However, 28-day mortality was significantly lower in the ascorbic acid than the placebo group (14.28% vs. 64.28%, respectively; P = 0.009). Conclusion: High-dose ascorbic acid may be considered as an effective and safe adjuvant therapy in surgical critically ill patients with septic shock. The most effective dose of ascorbic acid and the best time for its administration should be determined in future studies. PMID:27162802

  5. Nalbuphine Sedation in a Patient with Long Term, High Dose Chemotherapeutically Controlled Psychosis

    PubMed Central

    Kelly, Maureen; Howell, Robert M.

    1985-01-01

    Consideration of which pharmacologic agent to use when a patient requires sedation prior to an oral surgery procedure entails a number of factors, including past medical history, current medications and dose level, duration of administration, pharmacologic interactions, and the dental needs of the patient. The case described in this report illustrates the importance of consideration of these factors in a patient who required sedation prior to oral surgery while taking 800 mg chlorpromazine, 300 mg amantadine hydrochloride, and 900 mg of cimetidine daily. The possible pharmacologic interactions which could occur from concomitantly administering either diazepam or a narcotic in the presence of these agents are numerous and significant. The choice of sedative agent was further complicated by the fact that the patient was prescribed chlorpromazine and amantadine in doses which far exceeded the usual therapeutic levels and had been maintained for an extended period of time, over 8 months. Consequently, any adverse reactions that may have resulted when sedating a patient taking chlorapromazine and amantadine hydrochloride in lower doses for a shorter duration would be more likely to occur with greater speed and severity in a patient receiving such high-dose, long-term therapy. Also, unusual reactions which have not been reported with usual therapeutic dose levels might also occur since these high doses approach toxic levels for some patients. Additionally, a sedative agent had to be used which would not interfere with the antipsychotic effects of chlorpromazine since the patient's psychiatric condition required maintenance of these unusually high therapeutic levels. The following case report gives the rationale and outcome of utilizing nalbuphine for obtunding pain and producing sedation during an oral surgery procedure under such complex therapeutic conditions. PMID:3866505

  6. Nalbuphine sedation in a patient with long-term, high-dose chemotherapeutically controlled psychosis.

    PubMed

    Kelly, M; Howell, R M

    1985-01-01

    Consideration of which pharmacologic agent to use when a patient requires sedation prior to an oral surgery procedure entails a number of factors, including past medical history, current medications and dose level, duration of administration, pharmacologic interactions, and the dental needs of the patient. The case described in this report illustrates the importance of consideration of these factors in a patient who required sedation prior to oral surgery while taking 800 mg chlorpromazine, 300 mg amantadine hydrochloride, and 900 mg of cimetidine daily. The possible pharmacologic interactions which could occur from concomitantly administering either diazepam or a narcotic in the presence of these agents are numerous and significant. The choice of sedative agent was further complicated by the fact that the patient was prescribed chlorpromazine and amantadine in doses which far exceeded the usual therapeutic levels and had been maintained for an extended period of time, over 8 months. Consequently, any adverse reactions that may have resulted when sedating a patient taking chlorapromazine and amantadine hydrochloride in lower doses for a shorter duration would be more likely to occur with greater speed and severity in a patient receiving such high-dose, long-term therapy. Also, unusual reactions which have not been reported with usual therapeutic dose levels might also occur since these high doses approach toxic levels for some patients. Additionally, a sedative agent had to be used which would not interfere with the antipsychotic effects of chlorpromazine since the patient's psychiatric condition required maintenance of these unusually high therapeutic levels. The following case report gives the rationale and outcome of utilizing nalbuphine for obtunding pain and producing sedation during an oral surgery procedure under such complex therapeutic conditions. PMID:3866505

  7. Safety of high-dose doripenem in adult patients with cystic fibrosis

    PubMed Central

    Strawbridge, Seth; Nailor, Michael D.

    2016-01-01

    Background: High doses of β-lactam antibiotics have been advocated for acute pulmonary exacerbations caused by Pseudomonas aeruginosa in patients with cystic fibrosis (CF) secondary to high minimum inhibitory concentrations (MIC) of the infecting organisms. Some β-lactam antibiotics have increased elimination in CF patients. This case series examines the safety of high-dose doripenem (HDD), 2 g intravenously every 8 hours, which is 4 times the labeled dose, in CF patients. Methods: This was a retrospective, single site, chart review of all CF patients given HDD during a 3-year period. Adverse events were prospectively defined using labeled definitions within the package insert and the medical literature. A standard case report form was used to collect demographic details, antibiotic lengths of therapy and adverse events. Results: A total of 17 patients (9 males), with a median age of 24 years, contributed 43 unique visits and 382 HDD exposure days. Mean duration of inpatient doripenem use was 8.9 days. Concurrent antibiotics were common, with a median number of additional antibiotics per admission of three. The median number of adverse effects documented was two. The most common adverse event was anemia, which was identified in 41 of 43 visits, but was present on admission in 31 instances. One patient developed leukopenia for 1 day, but returned to normal without dose adjustment. There were three instances of Clostridium difficile infection. One patient was documented to have an allergic reaction that led to discontinuation, but was ultimately rechallenged without adverse effect. Other common adverse events were gastrointestinal in origin. No other possible adverse effects led to discontinuation of the drug. Conclusions: In adult patients with CF, HDD in combination with other antibiotics did not lead to adverse effects necessitating discontinuation. HDD should be considered in this selected patient population, particularly when high MIC organisms are identified

  8. Dosimetric Effects of Air Pockets Around High-Dose Rate Brachytherapy Vaginal Cylinders

    SciTech Connect

    Richardson, Susan; Palaniswaamy, Geethpriya; Grigsby, Perry W.

    2010-09-01

    Purpose: Most physicians use a single-channel vaginal cylinder for postoperative endometrial cancer brachytherapy. Recent published data have identified air pockets between the vaginal cylinders and the vaginal mucosa. The purpose of this research was to evaluate the incidence, size, and dosimetric effects of these air pockets. Methods and Materials: 25 patients receiving postoperative vaginal cuff brachytherapy with a high-dose rate vaginal cylinders were enrolled in this prospective data collection study. Patients were treated with 6 fractions of 200 to 400 cGy per fraction prescribed at 5 mm depth. Computed tomography simulation for brachytherapy treatment planning was performed for each fraction. The quantity, volume, and dosimetric impact of the air pockets surrounding the cylinder were quantified. Results: In 25 patients, a total of 90 air pockets were present in 150 procedures (60%). Five patients had no air pockets present during any of their treatments. The average number of air pockets per patient was 3.6, with the average total air pocket volume being 0.34 cm{sup 3} (range, 0.01-1.32 cm{sup 3}). The average dose reduction to the vaginal mucosa at the air pocket was 27% (range, 9-58%). Ten patients had no air pockets on their first fraction but air pockets occurred in subsequent fractions. Conclusion: Air pockets between high-dose rate vaginal cylinder applicators and the vaginal mucosa are present in the majority of fractions of therapy, and their presence varies from patient to patient and fraction to fraction. The existence of air pockets results in reduced radiation dose to the vaginal mucosa.

  9. Cytoprotective responses in HaCaT keratinocytes exposed to high doses of curcumin.

    PubMed

    Lundvig, Ditte M S; Pennings, Sebastiaan W C; Brouwer, Katrien M; Mtaya-Mlangwa, Matilda; Mugonzibwa, Emeria; Kuijpers-Jagtman, Anne Marie; Wagener, Frank A D T G; Von den Hoff, Johannes W

    2015-08-15

    Wound healing is a complex process that involves the well-coordinated interactions of different cell types. Topical application of high doses of curcumin, a plant-derived polyphenol, enhances both normal and diabetic cutaneous wound healing in rodents. For optimal tissue repair interactions between epidermal keratinocytes and dermal fibroblasts are essential. We previously demonstrated that curcumin increased reactive oxygen species (ROS) formation and apoptosis in dermal fibroblasts, which could be prevented by pre-induction of the cytoprotective enzyme heme oxygenase (HO)-1. To better understand the effects of curcumin on wound repair, we now assessed the effects of high doses of curcumin on the survival of HaCaT keratinocytes and the role of the HO system. We exposed HaCaT keratinocytes to curcumin in the presence or absence of the HO-1 inducers heme (FePP) and cobalt protoporphyrin (CoPP). We then assessed cell survival, ROS formation, and caspase activation. Curcumin induced caspase-dependent apoptosis in HaCaT keratinocytes via a ROS-dependent mechanism. Both FePP and CoPP induced HO-1 expression, but only FePP protected against curcumin-induced ROS formation and caspase-mediated apoptosis. In the presence of curcumin, FePP but not CoPP induced the expression of the iron scavenger ferritin. Together, our data show that the induction of ferritin, but not HO, protects HaCaT keratinocytes against cytotoxic doses of curcumin. The differential response of fibroblasts and keratinocytes to high curcumin doses may provide the basis for improving curcumin-based wound healing therapies. PMID:26071936

  10. Adverse reactions and tolerability of high-dose sublingual allergen immunotherapy

    PubMed Central

    Moral, Angel; Moreno, Victoria; Girón, Francisco; El-Qutob, David; Moure, José D; Alcántara, Manuel; Padial, Antonia; Oehling, Alberto G; Millán, Carmen; de la Torre, Fernando

    2016-01-01

    Background Sublingual allergen immunotherapy is an effective treatment against allergic respiratory disease. Many studies have shown the safety of this type of therapy, although the factors that might affect the tolerability of high-dose sublingual immunotherapy have not been well established. The aim of this study was to determine the factors that affect the tolerability of sublingual allergen immunotherapy. Patients and methods A total of 183 subjects aged ≥5 years, diagnosed with allergic rhinitis with/without mild to moderate asthma due to sensitization to grass, olive pollen, or mites, were included in this open, retrospective, multicentric, noninterventional study. Sublingual immunotherapy was administered for at least 3 months. Results The most frequent adverse reaction was oral pruritus (13.7% of the patients). Most of the reactions were local (84.7%) and immediate (93.5%) and occurred during the initiation phase (60.6%). All reactions were mild to moderate in severity. No serious adverse reactions were registered. When comparing factors with potential influence on the occurrence of adverse reactions, the results between the groups of subjects with and without adverse reactions showed no statistically significant differences in sex (P=0.6417), age (P=0.1801), years since the disease was first diagnosed (P=0.3800), treatment composition (P=0.6946), polysensitization (P=0.1730), or clinical diagnosis (P=0.3354). However, it was found that treatment duration had a statistically significant influence (3 months, >3 months: P=0.0442) and the presence of asthma was close to statistical significance (P=0.0847). Conclusion In our study, treatment duration is significantly associated with the occurrence of adverse reactions after the administration of high doses of sublingual allergen immunotherapy. PMID:27418842

  11. The high-dose aldesleukin (IL-2) "select" trial: a trial designed to prospectively validate predictive models of response to high-dose IL-2 treatment in patients with metastatic renal cell carcinoma.

    PubMed

    Clement, Jessica M; McDermott, David F

    2009-08-01

    For patients with metastatic renal cell carcinoma (RCC), the prognosis is poor. Despite the recent approval of drugs such as sorafenib, sunitinib, and temsirolimus, durable remissions of metastatic disease are rare. This is largely due to the fact that these drugs, while effective, do not result in the eradication of disease. In 1992, the FDA approved the use of high-dose interleukin-2 (IL-2) for the treatment of patients with metastatic RCC because of a small number of patients that achieved durable responses. However, IL-2 has not become a mainstay of treatment because of the expense and toxicity associated with this therapy. This review article discusses a phase II trial that investigates predictive biomarkers that might help clinicians identify the patient population with metastatic RCC that would benefit from IL-2 therapy and therefore limit patients who receive this toxic therapy to those most likely to benefit. PMID:19692326

  12. Mixed species radioiodine air sampling readout and dose assessment system

    DOEpatents

    Distenfeld, Carl H.; Klemish, Jr., Joseph R.

    1978-01-01

    This invention provides a simple, reliable, inexpensive and portable means and method for determining the thyroid dose rate of mixed airborne species of solid and gaseous radioiodine without requiring highly skilled personnel, such as health physicists or electronics technicians. To this end, this invention provides a means and method for sampling a gas from a source of a mixed species of solid and gaseous radioiodine for collection of the mixed species and readout and assessment of the emissions therefrom by cylindrically, concentrically and annularly molding the respective species around a cylindrical passage for receiving a conventional probe-type Geiger-Mueller radiation detector.

  13. Survival of tumor cells after proton irradiation with ultra-high dose rates

    PubMed Central

    2011-01-01

    Background Laser acceleration of protons and heavy ions may in the future be used in radiation therapy. Laser-driven particle beams are pulsed and ultra high dose rates of >109 Gy s-1may be achieved. Here we compare the radiobiological effects of pulsed and continuous proton beams. Methods The ion microbeam SNAKE at the Munich tandem accelerator was used to directly compare a pulsed and a continuous 20 MeV proton beam, which delivered a dose of 3 Gy to a HeLa cell monolayer within < 1 ns or 100 ms, respectively. Investigated endpoints were G2 phase cell cycle arrest, apoptosis, and colony formation. Results At 10 h after pulsed irradiation, the fraction of G2 cells was significantly lower than after irradiation with the continuous beam, while all other endpoints including colony formation were not significantly different. We determined the relative biological effectiveness (RBE) for pulsed and continuous proton beams relative to x-irradiation as 0.91 ± 0.26 and 0.86 ± 0.33 (mean and SD), respectively. Conclusions At the dose rates investigated here, which are expected to correspond to those in radiation therapy using laser-driven particles, the RBE of the pulsed and the (conventional) continuous irradiation mode do not differ significantly. PMID:22008289

  14. Proposed strategy for the use of high-dose chemotherapy with stem cell rescue and intrathecal topotecan without whole-brain irradiation for infantile classic medulloblastoma.

    PubMed

    Yamada, Ai; Moritake, Hiroshi; Kamimura, Sachiyo; Yamashita, Shinji; Takeshima, Hideo; Nunoi, Hiroyuki

    2014-12-01

    We describe a 6-month-old infant with classic medulloblastoma. Gross total resection of the left cerebellar tumor was performed; however, relapse occurred during the administration of intrathecal and intravenous methotrexate-based chemotherapy. After undergoing resection, high-dose chemotherapy was administered consisting of topotecan, melphalan, and cyclophosphamide with autologous peripheral stem cell rescue followed by local irradiation and intrathecal topotecan, which resulted in a complete response for more than two years. The administration of high-dose chemotherapy followed by intrathecal topotecan as maintenance therapy is an effective strategy, without losses in the cognitive function, for avoiding the use of whole-brain irradiation for infantile classic medulloblastoma. PMID:25174961

  15. 5-Azacitidine Monotherapy Followed by Related Haploidentical Hematopoietic Stem Cell Transplantation Achieves Durable Remission in a Pediatric Patient With Acute Undifferentiated Leukemia Refractory to High-Dose Chemotherapy.

    PubMed

    Polishchuk, Veronika; Khazal, Sajad; Berulava, Giorgi; Roth, Michael; Mahadeo, Kris M

    2016-06-01

    Patients with acute leukemias of undifferentiated lineage (AUL) generally have guarded prognosis. Here, we describe the first reported pediatric patient with AUL refractory to high-dose chemotherapy who achieved clinical remission with ALL maintenance therapy and 5-azacitidine. His induction remission was followed by consolidation with reduced toxicity haploidentical hematopoietic stem cell transplant (HSCT). At 9 months post-HSCT, the patient is alive and in remission. This combination therapy of remission induction with ALL maintenance therapy and 5-azacitidine and consolidation with reduced toxicity haploidentical HSCT is novel and promising for patients who lack conventional donors and are not candidates for myeloablative therapy. PMID:26914221

  16. A multicentre evaluation of the effectiveness and safety of high-dose daptomycin for the treatment of infective endocarditis

    PubMed Central

    Kullar, Ravina; Casapao, Anthony M.; Davis, Susan L.; Levine, Donald P.; Zhao, Jing J.; Crank, Christopher W.; Segreti, John; Sakoulas, George; Cosgrove, Sara E.; Rybak, Michael J.

    2013-01-01

    Objectives Despite significant medical advances, infective endocarditis (IE) remains an infection associated with high morbidity and mortality. The objective was to assess the safety and efficacy of high-dose daptomycin, defined as ≥8 mg/kg/day, in patients with confirmed or suspected staphylococcal and/or enterococcal IE. Methods This was a multicentre, retrospective observational study (2005–11). Adult patients, not undergoing haemodialysis, with blood cultures positive for staphylococci or enterococci and a definitive or possible diagnosis of IE, who received daptomycin ≥8 mg/kg/day (based on total body weight) for ≥72 h were included. Results Seventy patients met the inclusion criteria and comprised 33 (47.1%) with right-sided IE (RIE), 35 (50%) with left-sided IE (LIE) and 2 with both RIE and LIE. Several patients had concomitant sites of infection, with bone/joint infection being most prevalent (12.9%). Sixty-five patients received daptomycin as salvage therapy. Pathogens were isolated from 64 patients, with methicillin-resistant Staphylococcus aureus as the most common organism (84.4%), followed by vancomycin-resistant Enterococcus faecium (7.8%). The median (IQR) daptomycin dose was 9.8 mg/kg/day (8.2–10.0 mg/kg/day), and was similar in RIE and LIE patients (9.8 and 9.3 mg/kg/day, respectively). A total of 24 (34.3%) received combination therapy. For those patients with pathogens isolated (n = 64), the organism was eradicated in 57 (89.1%) patients. Among 64 clinically evaluable patients, 55 (85.9%) achieved clinical success. No patients required discontinuation of high-dose daptomycin due to creatine phosphokinase elevations. Conclusions Patients with both RIE and LIE had successful outcomes with high-dose daptomycin therapy. Additional clinical trials evaluating high daptomycin dosages in patients with IE are warranted. PMID:23928022

  17. High-dose short-term chlorambucil for intractable sympathetic ophthalmia and Behçet's disease.

    PubMed Central

    Tessler, H H; Jennings, T

    1990-01-01

    We treated five patients with intractable sympathetic ophthalmia and six patients with severe Behçet's disease by high-dose, short-term chlorambucil therapy. We used a total dose ranging from 306 mg to 4.2 g and a duration of therapy no longer than 36 weeks and in most cases less than 24 weeks. After termination of therapy all 11 patients had a sustained remission of their eye disease. Unless subretinal neovascularisation was present, all had a final visual acuity of 20/50 or better. Malignancy has not developed in any of our cases, with a follow-up ranging from 6 months to 12 years (mean, 4.5 years). Although 30- and 40-year follow-ups and larger numbers of patients may be necessary fully to realise the risks of chlorambucil, we believe that our high-dose, short-term regimen (Behçet's disease: average duration, 23 weeks; average total dose 2.2 g; sympathetic ophthalmia: average duration, 11 weeks; total average dose, 0.9 g) may be safer than previously reported chlorambucil regimens of one to two years or longer. In addition we fulfilled our aim of discontinuing all concomitant systemic corticosteroids within a relatively short time (usually six to eight weeks). PMID:2378842

  18. High-Dose Rifapentine with Moxifloxacin for Pulmonary Tuberculosis

    PubMed Central

    Jindani, Amina; Harrison, Thomas S.; Nunn, Andrew J.; Phillips, Patrick P.J.; Churchyard, Gavin J.; Charalambous, Salome; Hatherill, Mark; Geldenhuys, Hennie; McIlleron, Helen M.; Zvada, Simbarashe P.; Mungofa, Stanley; Shah, Nasir A.; Zizhou, Simukai; Magweta, Lloyd; Shepherd, James; Nyirenda, Sambayawo; van Dijk, Janneke H.; Clouting, Heather E.; Coleman, David; Bateson, Anna L.E.; McHugh, Timothy D.; Butcher, Philip D.; Mitchison, Denny A.

    2014-01-01

    BACKGROUND Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed. METHODS We randomly assigned patients with newly diagnosed, smear-positive, drug-sensitive tuberculosis to one of three regimens: a control regimen that included 2 months of ethambutol, isoniazid, rifampicin, and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months. Sputum specimens were examined on microscopy and after culture at regular intervals. The primary end point was a composite treatment failure and relapse, with noninferiority based on a margin of 6 percentage points and 90% confidence intervals. RESULTS We enrolled a total of 827 patients from South Africa, Zimbabwe, Botswana, and Zambia; 28% of patients were coinfected with the human immunodefiency virus. In the per-protocol analysis, the proportion of patients with an unfavorable response was 4.9% in the control group, 3.2% in the 6-month group (adjusted difference from control, −1.8 percentage points; 90% confidence interval [CI], −6.1 to 2.4), and 18.2% in the 4-month group (adjusted difference from control, 13.6 percentage points; 90% CI, 8.1 to 19.1). In the modified intention-to-treat analysis these proportions were 14.4% in the control group, 13.7% in the 6-month group (adjusted difference from control, 0.4 percentage points; 90% CI, −4.7 to 5.6), and 26.9% in the 4-month group (adjusted difference from control, 13.1 percentage points; 90% CI, 6.8 to 19.4). CONCLUSIONS The 6-month regimen that included weekly administration of high-dose rifapentine and

  19. High-dose methotrexate: pharmacokinetics in children and young adults.

    PubMed

    Raude, E; Oellerich, M; Weinel, P; Freund, M; Schrappe, M; Riehm, H; Poliwoda, H

    1988-07-01

    Pharmacokinetics of methotrexate (MTX) was studied in 34 patients (age 1-25 years, median 12 years) predominantly with primary brain tumors and osteosarcoma, who received a total of 64 high-dose infusions (12 g/m2/4 h, maximum dose 20 g), followed by leucovorin rescue (COSS 82). Serum samples were collected over a period of at least 72 h after the end of infusion and MTX was measured by enzyme immunoassay (EMIT). The data were fitted to a biexponential equation using a nonlinear regression analysis. The concentration-time decay of MTX in serum observed in 29/34 patients receiving 4 x 15 mg/m2/d p.o. leucovorin up to 5 days was biphasic with mean half-lives (+/- SD) of 2.42 +/- 0.45 h for t1/2 alpha and 19.9 +/- 7.6 h for t1/2 beta. The steady-state volume of distribution (Vss) was 0.56 +/- 0.18 l/kg and the total body clearance (CL) 71 +/- 20 ml/min/m2 (mean +/- SD). Peak serum concentrations ranged from 674-1778 mumol/l (mean +/- SD, 1201 +/- 293 mumol/l). In 5/34 patients who received a prolonged leucovorin rescue due to a delayed MTX elimination t1/2 alpha was greater than 3.1 h. The data of this study suggest that patients with MTX serum concentrations of less than or equal to 6.3 mumol/l at 24 h, less than or equal to 0.77 mumol/l at 48 h, and less than or equal to 0.33 mumol/l at 72 h after the end of infusion, and a t1/2 alpha of less than or equal to 3.1 h (97.5th percentiles) are at low risk of toxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3209285

  20. Image-guided high-dose-rate brachytherapy of malignancies in various inner organs – technique, indications, and perspectives

    PubMed Central

    Bretschneider, Tina; Ricke, Jens; Gebauer, Bernhard

    2016-01-01

    In the last few years, minimally invasive tumor ablation performed by interventional radiologists has gained increasing relevance in oncologic patient care. Limitations of thermal ablation techniques such as radiofrequency ablation (RFA), microwave ablation (MWA), and laser-induced thermotherapy (LITT), including large tumor size, cooling effects of adjacent vessels, and tumor location near thermosensitive structures, have led to the development of image-guided high-dose-rate (HDR) brachytherapy, especially for the treatment of liver malignancies. This article reviews technical properties of image-guided brachytherapy, indications and its current clinical role in multimodal cancer treatment. Furthermore, perspectives of this novel therapy option will be discussed. PMID:27504135

  1. Image-guided high-dose-rate brachytherapy of malignancies in various inner organs - technique, indications, and perspectives.

    PubMed

    Bretschneider, Tina; Ricke, Jens; Gebauer, Bernhard; Streitparth, Florian

    2016-06-01

    In the last few years, minimally invasive tumor ablation performed by interventional radiologists has gained increasing relevance in oncologic patient care. Limitations of thermal ablation techniques such as radiofrequency ablation (RFA), microwave ablation (MWA), and laser-induced thermotherapy (LITT), including large tumor size, cooling effects of adjacent vessels, and tumor location near thermosensitive structures, have led to the development of image-guided high-dose-rate (HDR) brachytherapy, especially for the treatment of liver malignancies. This article reviews technical properties of image-guided brachytherapy, indications and its current clinical role in multimodal cancer treatment. Furthermore, perspectives of this novel therapy option will be discussed. PMID:27504135

  2. High Dose Atorvastatin Associated with Increased Risk of Significant Hepatotoxicity in Comparison to Simvastatin in UK GPRD Cohort

    PubMed Central

    Clarke, Alan T.; Johnson, Paul C. D.; Hall, Gillian C.; Ford, Ian; Mills, Peter R.

    2016-01-01

    Background & Aims Occasional risk of serious liver dysfunction and autoimmune hepatitis during atorvastatin therapy has been reported. We compared the risk of hepatotoxicity in atorvastatin relative to simvastatin treatment. Methods The UK GPRD identified patients with a first prescription for simvastatin [164,407] or atorvastatin [76,411] between 1997 and 2006, but with no prior record of liver disease, alcohol-related diagnosis, or liver dysfunction. Incident liver dysfunction in the following six months was identified by biochemical value and compared between statin groups by Cox regression model adjusting for age, sex, year treatment started, dose, alcohol consumption, smoking, body mass index and comorbid conditions. Results Moderate to severe hepatotoxicity [bilirubin >60μmol/L, AST or ALT >200U/L or alkaline phosphatase >1200U/L] developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio [AHR] for all atorvastatin relative to simvastatin was 1.9 [95% confidence interval 1.4–2.6]. High dose was classified as 40–80mg daily and low dose 10–20mg daily. Hepatotoxicity occurred in 0.44% of 4075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS]. AHRs compared to LDS were 7.3 [4.2–12.7] for HDA, 1.4 [0.9–2.0] for LDA and 1.5 [1.0–2.2] for HDS. Conclusions The risk of hepatotoxicity was increased in the first six months of atorvastatin compared to simvastatin treatment, with the greatest difference between high dose atorvastatin and low dose simvastatin. The numbers of events in the analyses were small. PMID:26983033

  3. High-dose versus low-dose antivenom in the treatment of poisonous snake bites: A systematic review

    PubMed Central

    Das, Rashmi Ranjan; Sankar, Jhuma; Dev, Nishanth

    2015-01-01

    Though snake antivenom (SAV) is the mainstay of therapy for poisonous snake bites, there is no universally accepted standard regimen regarding the optimum dose (low vs. high). We therefore, undertook this systematic review to address this important research question. We searched all the published literature through the major electronic databases till August 2014. Randomized clinical trials (RCTs) were included. Eligible trials compared low versus high dose SAV in poisonous snake bite. The review has been registered at PROSPERO (Registration number: CRD42014009700). Of 36 citations retrieved, a total of 5 RCTs (n = 473) were included in the final analyses. Three trials were open-label, 4 conducted in Indian sub-continent and 1 in Brazil. The doses of SAV varied in the high dose group from 40 ml to 550 ml, and in the low dose group from 20 ml to 220 ml. There was no significant difference between the two groups for any of the outcomes except duration of hospital stay, which was lower in the low dose group. The GRADE evidence generated was of “very low quality.” Low-dose SAV is equivalent or may be superior to high-dose SAV in management of poisonous snake bite. Low dose is also highly cost-effective as compared to the high dose. But the GRADE evidence generated was of “very low quality” as most were open label trials. Further trials are needed to make definitive recommendations regarding the dose and these should also include children <9 years of age. PMID:26195860

  4. High-dose rifampicin kills persisters, shortens treatment duration, and reduces relapse rate in vitro and in vivo.

    PubMed

    Hu, Yanmin; Liu, Alexander; Ortega-Muro, Fatima; Alameda-Martin, Laura; Mitchison, Denis; Coates, Anthony

    2015-01-01

    Although high-dose rifampicin holds promise for improving tuberculosis control by potentially shortening treatment duration, these effects attributed to eradication of persistent bacteria are unclear. The presence of persistent Mycobacterium tuberculosis was examined using resuscitation promoting factors (RPFs) in both in vitro hypoxia and in vivo murine tuberculosis models before and after treatment with incremental doses of rifampicin. Pharmacokinetic parameters and dose-dependent profile of rifampicin in the murine model were determined. The Cornell mouse model was used to test efficacy of high-dose rifampicin in combination with isoniazid and pyrazinamide and to measure relapse rate. There were large numbers of RPF-dependent persisters in vitro and in vivo. Stationary phase cultures were tolerant to rifampicin while higher concentrations of rifampicin eradicated plate count positive but not RPF-dependent persistent bacteria. In murine infection model, incremental doses of rifampicin exhibited a dose-dependent eradication of RPF-dependent persisters. Increasing the dose of rifampicin significantly reduced the risk of antibiotic resistance emergence. In Cornell model, mice treated with high-dose rifampicin regimen resulted in faster visceral clearance; organs were M. tuberculosis free 8 weeks post-treatment compared to 14 weeks with standard-dose rifampicin regimen. Organ sterility, plate count and RPF-dependent persister negative, was achieved. There was no disease relapse compared to the standard dose regimen (87.5%). High-dose rifampicin therapy results in eradication of RPF-dependent persisters, allowing shorter treatment duration without disease relapse. Optimizing rifampicin to its maximal efficacy with acceptable side-effect profiles will provide valuable information in human studies and can potentially improve current tuberculosis chemotherapy. PMID:26157437

  5. Therapeutic Strategies for High-Dose Vasopressor-Dependent Shock

    PubMed Central

    Bassi, Estevão; Park, Marcelo; Azevedo, Luciano Cesar Pontes

    2013-01-01

    There is no consensual definition of refractory shock. The use of more than 0.5 mcg/kg/min of norepinephrine or epinephrine to maintain target blood pressure is often used in clinical trials as a threshold. Nearly 6% of critically ill patients will develop refractory shock, which accounts for 18% of deaths in intensive care unit. Mortality rates are usually greater than 50%. The assessment of fluid responsiveness and cardiac function can help to guide therapy, and inotropes may be used if hypoperfusion signs persist after initial resuscitation. Arginine vasopressin is frequently used in refractory shock, although definite evidence to support this practice is still missing. Its associations with corticosteroids improved outcome in observational studies and are therefore promising alternatives. Other rescue therapies such as terlipressin, methylene blue, and high-volume isovolemic hemofiltration await more evidence before use in routine practice. PMID:24151551

  6. Synthesis of N-(2-diethylamino-ethyl)-4-(4-fluoro-benzamido)-2-methoxybenzamide (desiodo-MIP-1145) by coupling technique and its radioiodination: a potential melanoma imaging agent.

    PubMed

    Aglan, H; Kandil, S A; El-Kafrawy, A F; Seddik, U

    2016-07-01

    Radioiodinated MIP-1145, which specifically targets melanin, is an ideal candidate for targeted therapy of melanoma. An analogue of MIP-1145 lacking the iodo-substituent (desiodo-MIP-1145) was synthesized as a labeling precursor in three simple steps. The radioiodination of desiodo-MIP-1145 by iodine-125 was carried out via an electrophilic substitution reaction. An optimization study for the iodination reaction was carried out. The labeled compound was isolated and purified by means of electrophoresis and HPLC. The maximum radiochemical yield, 76%, was obtained with radiochemical purity greater than 99%. The log P value for [(125) I]MIP-1145 was measured as 4.5. PMID:27313146

  7. Radioiodinated glucose analogues for use as imaging agents

    DOEpatents

    Goodman, Mark M.; Knapp, Jr., Furn F.

    1988-01-01

    A radioiodinated branched carbohydrate for tissue imaging. Iodine-123 is stabilized in the compound by attaching it to a vinyl functional group that is on the carbohydrate. The compound exhibits good uptake and retention and is promising in the development of radiopharmaceuticals for brain, heart and tumor imaging.

  8. Limits of fetal thyroid risk from radioiodine exposure

    SciTech Connect

    Lloyd, R.D.; Tripp, D.A.; Kerber, R.A.

    1996-04-01

    An incident in which a young women became pregnant soon after being treated with 444 MBq {sup 131}I for Graves disease prompted us to search local records for the occurrence of thyroid abnormalities among people exposed in utero to fallout radioiodine. The data base from the Utah Fallout Study indicated that there had been 480 cohort subjects for whom dose to thyroid from fallout radioiodine had been calculated and who could have received any thyroid dose before birth (2473 subjects had been re-examined in 1985-86 of the 4818 examined in 1965-70). Of these 480 subjects in this category, 403 of them could be located in the 1980`s and were examined for abnormalities. Although nodules, thyroiditis, hypothyroidism and goiter were seen among the 375 persons with in utero thyroid doses from fallout radioiodine below 0.42 Gy, no thyroid abnormalities of any kind occurred in the 4 persons with in utero thyroid doses of 0.5 to 2.6 Gy. In addition, no neoplasia was found in any of the 403 subjects examined about 3 decades after in utero fallout exposure. These limited data do not indicate that the fetal thyroid is more sensitive than the postnatal thyroid by more than about a factor of about 4 when thyroid dose is considered and by not much more than unity when the comparison is based on dose equivalent (x-ray vs. radioiodine). 21 refs., 1 tab.

  9. Implementation of High-Dose-Rate Brachytherapy and Androgen Deprivation in Patients With Prostate Cancer

    SciTech Connect

    Lilleby, Wolfgang; Tafjord, Gunnar; Raabe, Nils K.

    2012-07-01

    Purpose: To evaluate outcome (overall survival [OS], the actuarial 5-year cancer-specific survival [CSS], disease-free survival [DFS], biochemical failure-free survival [BFS]), complications and morbidity in patients treated with high-dose-rate brachytherapy (HDR-BT) boost and hormonal treatment with curative aims. Methods: Between 2004 and 2009, 275 prospectively followed pN0/N0M0 patients were included: 19 patients (7%) with T2, Gleason score 7 and prostate-specific antigen (PSA) <10 and 256 patients (93%) with T3 or Gleason score 8-10 or PSA >20 received multimodal treatment with conformal four-field radiotherapy (prostate/vesiculae 2 Gy Multiplication-Sign 25) combined with HDR-BT (iridium 192; prostate 10 Gy Multiplication-Sign 2) with long-term androgen deprivation therapy (ADT). Results: After a median observation time of 44.2 months (range, 10.4-90.5 months) 12 patients had relapsed clinically and/or biochemically and 10 patients were dead, of which 2 patients died from prostate cancer. Five-year estimates of BFS, CSS, DFS, and OS rates were 98.5%, 99.3%, 95.6%, and 96.3%, respectively. None of the patients with either Gleason score <8 or with intermediate risk profile had relapsed. The number of HDR-BT treatments was not related to outcome. Despite of age (median, 65.7 years; range, 45.7-77 years) and considerable pretreatment comorbidity in 39 of 275 patients, Genitourinary treatment-related morbidity was moderate with long-lasting Radiation Therapy Oncology Group Grade 2 voiding problems in 26 patients (9.5%) and occasionally mucous discharge in 20 patients (7%), none with Grade >2 for gastrointestinal at follow-up. Complications during implantations were related to pubic arch interference (4 patients) and lithotomy time, causing 2 patients to develop compartment syndrome. Conclusion: Despite still preliminary observations, our 5-year outcome estimates favor the implementation of high-dose-rate brachytherapy in high-risk patients combined with conformal

  10. Single fraction multimodal image guided focal salvage high-dose-rate brachytherapy for recurrent prostate cancer

    PubMed Central

    Rischke, Hans-Christian; Meyer, Philipp Tobias; Knobe, Sven; Volgeova-Neher, Natalja; Kollefrath, Michael; Jilg, Cordula Annette; Grosu, Anca Ligia; Baltas, Dimos; Kroenig, Malte

    2016-01-01

    Purpose We present a novel method for treatment of locally recurrent prostate cancer (PCa) following radiation therapy: focal, multimodal image guided high-dose-rate (HDR) brachytherapy. Material and methods We treated two patients with recurrent PCa after primary (#1) or adjuvant (#2) external beam radiation therapy. Multiparametric magnetic resonance imaging (mpMRI), choline, positron emission tomography combined with computed tomography (PET/CT), or prostate-specific membrane antigen (PSMA)-PET combined with CT identified a single intraprostatic lesion. Positron emission tomography or magnetic resonance imaging – transrectal ultrasound (MRI-TRUS) fusion guided transperineal biopsy confirmed PCa within each target lesion. We defined a PET and mpMRI based gross tumor volume (GTV). A 5 mm isotropic margin was applied additionally to each lesion to generate a planning target volume (PTV), which accounts for technical fusion inaccuracies. A D90 of 18 Gy was intended in one fraction to each PTV using ultrasound guided HDR brachytherapy. Results Six month follow-up showed adequate prostate specific antygen (PSA) decline in both patients (ΔPSA 83% in patient 1 and ΔPSA 59.3% in patient 2). Follow-up 3-tesla MRI revealed regressive disease in both patients and PSMA-PET/CT showed no evidence of active disease in patient #1. No acute or late toxicities occurred. Conclusions Single fraction, focal, multimodal image guided salvage HDR brachytherapy for recurrent prostate cancer is a feasible therapy for selected patients with single lesions. This approach has to be evaluated in larger clinical trials. PMID:27504134

  11. Clinical, patient-related, and economic outcomes of home-based high-dose hemodialysis versus conventional in-center hemodialysis

    PubMed Central

    Mitsides, Nicos; Mitra, Sandip; Cornelis, Tom

    2016-01-01

    Despite technological advances in renal replacement therapy, the preservation of health and quality of life for individuals on dialysis still remains a challenge. The high morbidity and mortality in dialysis warrant further research and insight into the clinical domains of the technique and practice of this therapy. In the last 20 years, the focus of development in the field of hemodialysis (HD) has centered around adequate removal of urea and other associated toxins. High-dose HD offers an opportunity to improve mortality, morbidity, and quality of life of patients with end-stage kidney disease. However, the uptake of this modality is low, and the risk associated with the therapy is not fully understood. Recent studies have highlighted the evidence base and improved our understanding of this technique of dialysis. This article provides a review of high-dose and home HD, its clinical impact on patient outcome, and the controversies that exist. PMID:27462173

  12. The impact of high-dose vitamin C on blood glucose testing in ¹⁸F-FDG PET imaging.

    PubMed

    Bahr, Rebekah L; Wilson, Don C

    2015-03-01

    Complementary and alternative therapies in addition to standard oncology protocols are commonly sought by cancer patients; however, few patients disclose their complementary treatments to their cancer care team. A lack of communication may result in unforeseen side effects and the potential for some alternative therapies to interfere with or inhibit conventional treatment. High-dose vitamin C therapy, in particular, may lead to an inability to measure a patient's blood glucose level before (18)F-FDG injection for PET/CT scanning. We report a case of a 52-y-old woman referred for (18)F-FDG PET/CT to evaluate the extent of recurrent colorectal cancer. The PET/CT scan immediately followed a single intravenous dose of 25 g of ascorbic acid from her naturopath. A glucometer that applies the glucose oxidase method for measuring fasting blood glucose was used, for which high doses of vitamin C are listed as a contraindication. The high concentration of ascorbic acid in the patient's blood sample interfered with the chemical reaction on the glucose strip, and therefore no blood glucose measurement could be attained. With more patients receiving alternative and complementary cancer therapies, it is important to know what the implications of orthomolecular therapy might be on routine blood glucose testing for (18)F-FDG PET scans. (18)F-FDG is in direct competition with glucose; therefore, elevated blood glucose levels will cause a decrease in (18)F-FDG absorption and may lead to a false-negative scan. PMID:25104819

  13. Persistent Psychosis after Abuse of High Dose of Zolpidem

    PubMed Central

    Eslami-Shahrbabaki, Mahin; Barfeh, Babak; Nasirian, Mansoureh

    2014-01-01

    Background Zolpidem is a non-benzodiazepine medication which selectively affects GABA A receptors and treats insomnia. There are numerous reports of psychosis following the consumption of zolpidem all of which recovered after stopping the medication. Case Report A 27 year old male law student, who was treated with 10 mg zolpidem due to insomnia, increased the dosage to 500 mg during 3 months. Not only was his insomnia remained untreated, but also he gradually became isolated, suspicious, and aggressive, and dropped out of university. He was then hospitalized in a psychiatric ward for 2 months, and was treated with antipsychotics and gradual discontinuation of zolpidem. With no improvement in psychosis and sleep improvement he was discharged. After two weeks he was hospitalized again and went under electroconvulsive therapy (ECT) and antipsychotic therapy, and was discharged with relative improvement. Now, after three years, he is diagnosed with schizophrenia and with modest improvements he is under care and treatment. Conclusion Zolpidem is a fairly useful medication for treating sleep problems, especially improving beginning of sleep. However, physicians ýand clinicians should consider the conditions, predispositions, and personal and family history of types of psychosis, alcohol and drug abuse in the comprehensive assessment and treatment plan for patients with insomnia. PMID:25984284

  14. Monitoring of gefitinib sensitivity with radioiodinated PHY based on EGFR expression.

    PubMed

    Yoshimoto, Mitsuyoshi; Hirata, Masahiko; Kanai, Yasukazu; Naka, Sadahiro; Nishii, Ryuichi; Kagawa, Shinya; Kawai, Keiichi; Ohmomo, Yoshiro

    2014-01-01

    Epidermal growth factor receptor (EGFR) is attractive target for tumor diagnosis and therapy, as it is specifically and abundantly expressed in tumor cells. EGFR-tyrosine kinase (TK) inhibitors such as gefitinib and erlotinib are widely used in the treatment of non-small cell lung cancer (NSCLC). In this study, we investigated whether radioiodinated 4-(3-iodo-phenoxy)-6,7-diethoxy-quinazoline (PHY), which is a candidate EGFR-TK imaging agent for single photon emission computed tomography (SPECT) is able to predict gefitinib sensitivity. We used four NSCLC cell lines-A549 (wild-type EGFR), H1650 (mutant EGFR; del E746_A750), H1975 (mutant EGFR; L858R, T790M) and H3255 (mutant EGFR; L858R)-and one epidermoid carcinoma cell line, A431 (wild-type EGFR). Cell proliferation assay and Western blotting revealed that A431 and H3255 with high EGFR expression showed high sensitivity to gefitinib. On the other hand, A549, H1650 and H1975 showed much lower sensitivity to gefitinib. The blocking study revealed that gefitinib decreased tumor uptake in (125)I-PHY in A431-bearing mice. Moreover, in vivo tumor uptake of (125)I-PHY was correlated with the IC50 of gefitinib for cell proliferation. In the present study, tumor uptake of (125)I-PHY was correlated with the gefitinib sensitivity and this uptake was based on expression levels of EGFR, but not on mutation status. Although the mutation status is the most important factor for predicting gefitinib sensitivity, the abundant expression of EGFR is essential for therapy with EGFR-TK inhibitors. Therefore, radioiodinated PHY is a potential imaging agent to predict gefitinib sensitivity based on EGFR expression levels though further modifications of the imaging agent is needed to accurately estimate the mutation status. PMID:24583857

  15. High-dose recombinant human erythropoietin for treatment of anemia in myelodysplastic syndromes and paroxysmal nocturnal hemoglobinuria: a pilot study.

    PubMed

    Stebler, C; Tichelli, A; Dazzi, H; Gratwohl, A; Nissen, C; Speck, B

    1990-12-01

    In a dose escalation study we tested the feasibility and tolerance of high-dose recombinant human erythropoietin (r-HuEPO) therapy in four patients with ineffective erythropoiesis due to myelodysplastic syndromes (MDS) or paroxysmal nocturnal hemoglobinuria (PNH). Recombinant human EPO was administered i.v. with an initial dose of 50 U/kg body weight (BW) three times per week. The dose was increased by steps of 25 or 50 U/kg bW with intervals of 1-4 weeks up to a maximum dose of 500 U/kg BW three times per week. All patients were treated as outpatients. Pre-study treatment with cyclosporin A and/or Danazol was continued in three patients. In one patient r-HuEPO was discontinued after 20 weeks because of relapse of severe aplastic anemia. No major side effects were observed even at the maximum dose. One patient with PNH showed an increase of hemoglobin from 89 to 139 g/liter that permitted monthly phlebotomies to reduce his iron overload. In one patient with MDS the reticulocyte count increased from 2.5 to 50 x 10(9)/liter, and the transfusion requirement decreased to 2 U every 3-4 weeks instead of every 2 weeks. Two patients did not complete the whole treatment period and showed no rise in reticulocyte count. We conclude that high dose r-HuEPO therapy is feasible in patients with anemia due to MDS or PNH. High-dose r-HuEPO appears to have some effect on anemia due to ineffective erythropoiesis in a subgroup of patients. Further studies are needed to identify potential responders and to define the optimal administration of r-HuEPO. PMID:2226680

  16. Oral mucositis and outcomes of autologous hematopoietic stem-cell transplantation following high-dose melphalan conditioning for multiple myeloma.

    PubMed

    Vera-Llonch, Montserrat; Oster, Gerry; Ford, Colleen M; Lu, John; Sonis, Stephen

    2007-05-01

    The purpose of this study was to assess the relationship between oral mucositis (OM) and adverse clinical and economic outcomes of autologous hematopoietic stem-cell transplantation (HSCT) following high-dose melphalan (Alkeran) conditioning in patients with multiple myeloma. A retrospective study of 115 consecutive autologous HSCT recipients with multiple myeloma who received high-dose melphalan conditioning before transplantation was undertaken at a single academic center. OM severity was assessed twice weekly using a validated scale beginning 3-4 days following conditioning and continuing until hospital discharge or day 28, whichever occurred first. OM was graded, based on presence/extent of erythema/ulceration across eight oropharyngeal sites, as follows: 0 = no erythema or ulceration; I = erythema but no ulceration; II = ulceration, 1 site; III = ulceration, 2 sites; IV = ulceration, 3 sites; and V = ulceration, > or = 4 sites. Analyses examined the relationship between worst OM grade and selected clinical and economic outcomes, including days with fever, days of total parenteral nutrition (TPN),days of parenteral narcotic therapy, incidence of significant infection, and inpatient days and charges. The mean age of study subjects was 54 years; 19 patients (17%) received total-body irradiation, and 55 patients (48%) experienced OM grade > or = II (ie, ulceration). The worst OM grade was significantly (P < 0.05) associated with numbers of days of TPN and parenteral narcotic therapy, length of hospitalization, and total inpatient charges. Worst OM grade was not associated with the number of febrile days or the risk of significant infection. OM is associated with worse clinical and economic outcomes in multiple myeloma patients undergoing autologous HSCT following high-dose melphalan conditioning. PMID:17564153

  17. TMPyP4 promotes cancer cell migration at low doses, but induces cell death at high doses

    PubMed Central

    Zheng, Xiao-Hui; Nie, Xin; Liu, Hai-Ying; Fang, Yi-Ming; Zhao, Yong; Xia, Li-Xin

    2016-01-01

    TMPyP4 is widely considered as a potential photosensitizer in photodynamic therapy and a G-quadruplex stabilizer for telomerase-based cancer therapeutics. However, its biological effects including a possible adverse-effect are poorly understood. In this study, whole genome RNA-seq analysis was used to explore the alteration in gene expression induced by TMPyP4. Unexpectedly, we find that 27.67% of changed genes were functionally related to cell adhesion. Experimental evidences from cell adhesion assay, scratch-wound and transwell assay indicate that TMPyP4 at conventional doses (≤0.5 μM) increases cell-matrix adhesion and promotes the migration of tumor cells. In contrast, a high dose of TMPyP4 (≥2 μM) inhibits cell proliferation and induces cell death. The unintended “side-effect” of TMPyP4 on promoting cell migration suggests that a relative high dose of TMPyP4 is preferred for therapeutic purpose. These findings contribute to better understanding of biological effects induced by TMPyP4 and provide a new insight into the complexity and implication for TMPyP4 based cancer therapy. PMID:27221067

  18. Reduced fluid volume requirement for resuscitation of third-degree burns with high-dose vitamin C.

    PubMed

    Matsuda, T; Tanaka, H; Williams, S; Hanumadass, M; Abcarian, H; Reyes, H

    1991-01-01

    The effects of high-dose vitamin C therapy (170 mg, 340 mg, and 680 mg/kg/day) were evaluated in 70% body surface area third-degree burns in guinea pigs that were resuscitated with 1 ml/kg/%burn Ringer's lactate solution. The water content measurements of the burned skin at 24 hours after burn injury in the vitamin C-treated groups were significantly lower than those of the control group (1 ml/kg/%burn) and those of the standard resuscitation group (4 ml/kg/%burn). The cardiac outputs in the group that received 340 mg vitamin C were significantly higher than those of the control group but not significantly different than those of the standard therapy group at 2 hours after burn injury and thereafter. In comparison with the regimen of 340 mg vitamin C, the regimen of 680 mg vitamin C was no more beneficial, and the regimen of 170 mg was less effective. With administration of adjuvant high-dose vitamin C, we were able to reduce the total 24-hour resuscitation volume from 4 ml/kg/%burn to 1 ml/kg/%burn, while a comparable cardiac output was maintained. PMID:1779006

  19. TMPyP4 promotes cancer cell migration at low doses, but induces cell death at high doses.

    PubMed

    Zheng, Xiao-Hui; Nie, Xin; Liu, Hai-Ying; Fang, Yi-Ming; Zhao, Yong; Xia, Li-Xin

    2016-01-01

    TMPyP4 is widely considered as a potential photosensitizer in photodynamic therapy and a G-quadruplex stabilizer for telomerase-based cancer therapeutics. However, its biological effects including a possible adverse-effect are poorly understood. In this study, whole genome RNA-seq analysis was used to explore the alteration in gene expression induced by TMPyP4. Unexpectedly, we find that 27.67% of changed genes were functionally related to cell adhesion. Experimental evidences from cell adhesion assay, scratch-wound and transwell assay indicate that TMPyP4 at conventional doses (≤0.5 μM) increases cell-matrix adhesion and promotes the migration of tumor cells. In contrast, a high dose of TMPyP4 (≥2 μM) inhibits cell proliferation and induces cell death. The unintended "side-effect" of TMPyP4 on promoting cell migration suggests that a relative high dose of TMPyP4 is preferred for therapeutic purpose. These findings contribute to better understanding of biological effects induced by TMPyP4 and provide a new insight into the complexity and implication for TMPyP4 based cancer therapy. PMID:27221067

  20. Three Patients Needing High Doses of Valproic Acid to Get Therapeutic Concentrations

    PubMed Central

    Jackson, James; McCollum, Betsy; Ognibene, Judy; Diaz, Francisco J.; de Leon, Jose

    2015-01-01

    Valproic acid (VPA) can autoinduce its own metabolism. Cases requiring VPA doses >4000 mg/day to obtain therapeutic plasma concentrations, such as these 3 cases, have never been published. Case 1 received VPA for seizures and schizophrenia and had >50 VPA concentrations in 4 years. A high dose of 5,250 mg/day of VPA concentrate was prescribed for years but this dose led to an intoxication when switched to the enterocoated divalproex sodium formulation, requiring a normal dose of 2000 mg/day. VPA metabolic capacity was significantly higher (t = −9.6; df = 6.3, p < 0.001) during the VPA concentrate therapy, possibly due to autoinduction in that formulation. Case 2 had VPA for schizoaffective psychosis with 10 VPA concentrations during an 8-week admission. To maintain a VPA level ≥50 μg/mL, VPA doses increased from 1500 to 4000 mg/day. Case 3 had tuberous sclerosis and epilepsy and was followed up for >4 years with 137 VPA concentrations. To maintain VPA concentrations ≥50 μg/mL, VPA doses increased from 3,375 to 10,500 mg/day. In Cases 2 and 3, the duration of admission and the VPA dose were strongly correlated (r around 0.90; p < 0.001) with almost no change after controlling for VPA concentrations, indicating progressive autoinduction that increased with time. PMID:26000191

  1. Novel Use of the Contura for High Dose Rate Cranial Brachytherapy

    SciTech Connect

    Scanderbeg, Daniel J.; Alksne, John F.; Lawson, Joshua D.; Murphy, Kevin T.

    2011-01-01

    A popular choice for treatment of recurrent gliomas was cranial brachytherapy using the GliaSite Radiation Therapy System. However, this device was taken off the market in late 2008, thus leaving a treatment void. This case study presents our experience treating a cranial lesion for the first time using a Contura multilumen, high-dose-rate (HDR) brachytherapy balloon applicator. The patient was a 47-year-old male who was diagnosed with a recurrent right frontal anaplastic oligodendroglioma. Previous radiosurgery made him a good candidate for brachytherapy. An intracavitary HDR balloon brachytherapy device (Contura) was placed in the resection cavity and treated with a single fraction of 20 Gy. The implant, treatment, and removal of the device were all completed without incident. Dosimetry of the device was excellent because the dose conformed very well to the target. V90, V100, V150, and V200 were 98.9%, 95.7%, 27.2, and 8.8 cc, respectively. This patient was treated successfully using the Contura multilumen balloon. Contura was originally designed for deployment in a postlumpectomy breast for treatment by accelerated partial breast irradiation. Being an intracavitary balloon device, its similarity to the GliaSite system makes it a viable replacement candidate. Multiple lumens in the device also make it possible to shape the dose delivered to the target, something not possible before with the GliaSite applicator.

  2. High-dose interleukin 2-induced myocarditis: can myocardial damage reversibility be assessed by cardiac MRI?

    PubMed

    Chow, Shien; Cove-Smith, Laura; Schmitt, Matthias; Hawkins, Robert

    2014-06-01

    High-dose interleukin 2 (HD-IL2) is one of the therapeutic options for patients with metastatic renal cell carcinoma. In well-selected patients with favorable clinical and pathologic features, it offers impressive response and potential long-term remission. It also has a place for treatment for metastatic malignant melanoma and in adoptive cell therapy. However, it is known for its intensive course and toxicities. Myocarditis is one of the known complications of this treatment and can pose a diagnostic challenge to treating oncologists because of its nonspecific and similar presentation to acute coronary syndrome (ACS). We report 3 short cases of HD-IL2-related myocarditis, which were either missed or misdiagnosed as ACS using conventional assessment but subsequently accurately diagnosed by cardiac magnetic resonant imaging (CMR). We discussed the clinical presentation of these cases and demonstrated the diagnostic advantage of CMR compared with standard investigations including its superior capability to assess myocardial reversibility, which has important short-term and long-term implications. The use of CMR also avoided unnecessary invasive intervention such as coronary angiogram in all 3 patients. These example cases call for effort to conduct prospective research to assess and confirm the utility of CMR, thus informing a more effective management pathway for immune-related myocarditis in HD-IL2 and other cancer immunotherapy. PMID:24810642

  3. The effect of prior antithyroid drug use on delaying remission in high uptake Graves' disease following radioiodine ablation

    PubMed Central

    Subramanian, Muthiah; Baby, Manu Kurian; Seshadri, Krishna G

    2016-01-01

    Antithyroid drugs (ATDs) have been shown to attenuate the effectiveness of radioiodine (radioiodine ablation, RIA) therapy in Graves' disease. We undertook a study to look at the impact of iodine uptakes on the outcome of 131I therapy. To determine the effect of prior ATD use on the duration of time to achieve cure in patients with high vs intermediate uptake Graves' disease who received a fixed dose (15 mCi) of 131I radioiodine. In a retrospective study of patients with Graves' disease, 475 patients who underwent RIA were followed-up on a two-monthly basis with thyroid function tests. Of the 123 patients with a documented preablation RAIU and consistent follow-up it was observed that 40 patients had an intermediate RAIU (10–30%) and 83 subjects had a distinctly increased uptake (>30%). Successful cure was defined as the elimination of thyrotoxicosis in the form of low free thyroxin and rising TSH levels. When a standard dose of 15 mCi 131I was administered, a cure rate of 93% was achieved. The median duration of time to cure (TC) was 129 days. Surprisingly, a direct proportional linear relationship (R 2=0.92) was established between time to cure and radioiodine uptake (TC> 3 0%=172days, TC10 – 3 0%=105 days, P<0.001). Patients who used ATD medications took a proportionately longer duration to achieve remission (TCNO ATD=102days, TCATD=253days, P<0.001). The effect of prior ATD therapy in delaying remission was amplified in the subset of patients with higher uptakes (TC> 3 0% + ATD=310days, TC> 3 0% + NO ATD=102days, P<0.001) compared to those with the intermediate uptakes (TC10 – 3 0% + ATD=126 days, TC10 – 3 0% + NO ATD=99 days, P<0.001). RIA, using a dose of 15 mCi achieved a high cure rate. Higher uptakes predicted longer time to achieve remission, with prior ATD use amplifying this effect. PMID:26772754

  4. Enhanced Interaction between Warfarin and High-Dose Ketoconazole: A Case Report

    PubMed Central

    Jackevicius, Cynthia A.; Ton, Mannhu N.

    2009-01-01

    This case describes the increased anticoagulation effect associated with the use of high-dose ketoconazole. A 59-year-old man treated with warfarin for aortic valve replacement was prescribed high-dose ketoconazole and hydrocortisone for the treatment of prostate cancer. Despite lowering the warfarin dosage by 35% during the start of high dose ketoconazole, an additional dose reduction was required subsequently when the INR rose from 2.62 to 3.82 within nine days. After a total dose reduction of 43%, the INR returned to therapeutic range within two weeks. The Naranjo probability scale revealed a probable adverse reaction of increased anticoagulant effect associated with high dose ketoconazole. Due to the inhibition of warfarin metabolism by ketoconazole, patients taking high dose ketoconazole concomitantly with warfarin may need their warfarin dosage reduced by more than is currently recommended, as well as receive more frequent INR monitoring to avoid over anticoagulation. PMID:20029646

  5. Clinical Characteristics of Veterans Prescribed High Doses of Opioid Medications for Chronic Non-Cancer Pain

    PubMed Central

    Morasco, Benjamin J.; Duckart, Jonathan P.; Carr, Thomas P.; Deyo, Richard A.; Dobscha, Steven K.

    2010-01-01

    Little is known about patients prescribed high doses of opioids to treat chronic non-cancer pain, though these patients may be at higher risk for medication-related complications. We describe the prevalence of high-dose opioid use and associated demographic and clinical characteristics among veterans treated in a VA regional healthcare network. Veterans with chronic non-cancer pain prescribed high doses of opioids (>=180 mg/day morphine equivalent; n=478) for 90+ consecutive days were compared to two groups with chronic pain: Traditional-dose (5–179 mg/day; n=500) or no opioid (n=500). High-dose opioid use occurred in 2.4% of all chronic pain patients and in 3.4% of all chronic pain patients prescribed opioids long-term. The average dose in the high-dose group was 324.9 (SD=285.1) mg/day. The only significant demographic difference among groups was race (p=0.03) with black veterans less likely to receive high doses. High-dose patients were more likely to have four or more pain diagnoses and the highest rates of medical, psychiatric, and substance use disorders. After controlling for demographic factors and VA facility, neuropathy, low back pain, and nicotine dependence diagnoses were associated with increased likelihood of high-dose prescriptions. High-dose patients frequently did not receive care consistent with treatment guidelines: there was frequent use of short-acting opioids, urine drug screens were administered to only 40.8% of patients in the prior year, and 32.0% received concurrent benzodiazepine prescriptions, which may increase risk for overdose and death. Further study is needed to identify better predictors of high-dose usage, as well as the efficacy and safety of such dosing. PMID:20801580

  6. Late onset radioiodine-induced hypothyroidism presenting with psychosis 14 years after treatment: a rare case

    PubMed Central

    Er, Chaozer; Sule, Ashish Anil

    2016-01-01

    Radioiodine treatment-induced hypothyroid psychosis is uncommon. Our literature search shows only three cases of hypothyroid psychosis developed within 3 months after the radioiodine treatment. Our case represents the first case of radioiodine-induced hypothyroidism presenting as psychosis much later (14 years) after the radioiodine treatment. A 60-year-old Chinese lady, with long-standing primary hypothyroidism due to the radioiodine treatment performed 14 years ago, presented with a 1-week history of hallucination, delusion and agitation. She was not on thyroid replacement. Thyroid function test done 14 years ago and again upon her admission to our facility was consistent with primary hypothyroidism. General blood tests and brain imaging were unremarkable. Her psychotic features resolved within 1 week with thyroid replacement and 9 days of antipsychotics. No further relapse of psychosis was noted. This emphasizes that radioiodine-induced hypothyroidism can go unnoticed for many years and present much later solely as psychosis. PMID:27099771

  7. Late onset radioiodine-induced hypothyroidism presenting with psychosis 14 years after treatment: a rare case.

    PubMed

    Er, Chaozer; Sule, Ashish Anil

    2016-04-01

    Radioiodine treatment-induced hypothyroid psychosis is uncommon. Our literature search shows only three cases of hypothyroid psychosis developed within 3 months after the radioiodine treatment. Our case represents the first case of radioiodine-induced hypothyroidism presenting as psychosis much later (14 years) after the radioiodine treatment. A 60-year-old Chinese lady, with long-standing primary hypothyroidism due to the radioiodine treatment performed 14 years ago, presented with a 1-week history of hallucination, delusion and agitation. She was not on thyroid replacement. Thyroid function test done 14 years ago and again upon her admission to our facility was consistent with primary hypothyroidism. General blood tests and brain imaging were unremarkable. Her psychotic features resolved within 1 week with thyroid replacement and 9 days of antipsychotics. No further relapse of psychosis was noted. This emphasizes that radioiodine-induced hypothyroidism can go unnoticed for many years and present much later solely as psychosis. PMID:27099771

  8. High-dose-rate interstitial brachytherapy for female peri-urethral cancer

    PubMed Central

    Gandhi, Ajeet Kumar; Bhatla, Neerja; Kumar, Sunesh; Rath, Goura Kisor

    2016-01-01

    Purpose Peri-urethral cancer (PUC) in females is a rare malignancy. Surgery is not usually contemplated due to associated morbidity. Radiation therapy (RT) can be employed in the form of interstitial brachytherapy (IBT) alone for early lesions, and external beam radiation therapy (EBRT) with or without IBT for advanced lesions. We report our first experience in the literature to evaluate the role of high-dose-rate (HDR) IBT in female PUC. Material and methods Between 2008 and 2013, 10 female patients with PUC (5 primary and 5 recurrent) were treated with HDR-IBT with or without EBRT at our center. Size of the lesion ranged from 1.5 cm to 5.0 cm. A 2-3 plane free-hand implant was performed using plastic catheters. The prescribed dose of HDR-IBT was 42 Gy in 14 fractions for brachytherapy alone (5 patients), and 18-21 Gy for the boost along with EBRT (5 patients). Patients were followed up regularly for assessment of disease control and toxicity. Results At a median follow up of 25 months, six patients were disease free at their last follow up. Four patients developed recurrence: 2 at inguinal nodes, 1 at local site, and 1 at both local as well as inguinal nodes. Moist desquamation was the commonest acute toxicity observed in all 5 patients treated with IBT alone, which healed within 4 weeks’ time. Overall, grade II delayed complication rate was 30%. Conclusions Though small sample size, the results of our study have shown that HDR-IBT provides good loco-regional control with acceptable toxicity for female PUC. PMID:26985196

  9. RADIOIODINE GEOCHEMISTRY IN THE SRS SUBSURFACE ENVIRONMENT

    SciTech Connect

    Kaplan, D.; Emerson, H.; Powell, B.; Roberts, K.; Zhang, S.; Xu, C.; Schwer, K.; Li, H.; Ho, Y.; Denham, M.; Yeager, C.; Santschi, P.

    2013-05-16

    Iodine-129 is one of the key risk drivers for several Savannah River Site (SRS) performance assessments (PA), including that for the Low-Level Waste Disposal Facility in E-Area. In an effort to reduce the uncertainty associated with the conceptual model and the input values used in PA, several studies have recently been conducted dealing with radioiodine geochemistry at the SRS. The objective of this report was to review these recent studies and evaluate their implications on SRS PA calculations. For the first time, these studies measured iodine speciation in SRS groundwater and provided technical justification for assuming the presence of more strongly sorbing species (iodate and organo-iodine), and measured greater iodine sediment sorption when experiments included these newly identified species; specifically they measured greater sorption coefficients (K{sub d} values: the concentration ratio of iodine on the solid phase divided by the concentration in the aqueous phase). Based on these recent studies, new best estimates were proposed for future PA calculations. The new K{sub d} values are greater than previous recommended values. These proposed K{sub d} values reflect a better understanding of iodine geochemistry in the SRS subsurface environment, which permits reducing the associated conservatism included in the original estimates to account for uncertainty. Among the key contributing discoveries supporting the contention that the K{sub d} values should be increased are that: 1) not only iodide (I{sup -}), but also the more strongly sorbing iodate (IO{sub 3}{sup -}) species exists in SRS groundwater (average total iodine = 15% iodide, 42% iodate, and 43% organoiodine), 2) when iodine was added as iodate, the measured K{sub d} values were 2 to 6 times greater than when the iodine was added as iodide, and perhaps most importantly, 3) higher desorption (10 to 20 mL/g) than (ad)sorption (all previous studies) K{sub d} values were measured. The implications of this

  10. Targeting C-reactive protein levels using high-dose atorvastatin before coronary artery bypass graft surgery

    PubMed Central

    Krivoy, Norberto; Adler, Zvi; Saloma, Ronen; Hawadie, Ashraf; Azzam, Zaher S

    2008-01-01

    BACKGROUND: Statin medication exhibits pleiotropic properties, such as improvement of endothelial function. AIM: To determine whether a high loading dose of atorvastatin prescribed before and after coronary artery bypass graft (CABG) surgery will attenuate the inflammatory response reflected in kinetic concentrations of C-reactive protein (CRP). METHODS: The individual area under the concentration-time curve (AUC) of CRP concentration was calculated for the first five days after CABG surgery and compared among three groups of patients: group A patients (n=16), who were on chronic statin therapy, were switched to an equivalent therapy of 20 mg atorvastatin daily for 120 h; group B patients (n=15), who were on chronic statin therapy, were switched to 80 mg atorvastatin daily (one dose 24 h before CABG surgery, one on the day of surgery and two further doses after surgery) followed by 40 mg/day up to 120 h after surgery; and group C patients (n=10), who were naive to statin therapy, underwent elective CABG surgery. RESULTS: The three groups were comparable according to measurements of their intra- and postoperative variables, except for their mean weight. The mean (± SEM) AUC-CRP for group B was 13,545±959.9 mg/L·h, significantly smaller (P=0.01) than that for group A (17,085±858.4 mg/L·h). In group C (statin-naïve patients), the AUC-CRP was 16,191±1447 mg/L·h, which was not significantly different from groups A and B, respectively. CONCLUSIONS: High loading doses of atorvastatin before CABG surgery reduced CRP concentration, expressed as AUC-CRP. This effect supports the idea that a high dose of atorvastatin is needed to attenuate the ‘negative’ inflammatory response. The present study also lends support to the possibility that high-dose atorvastatin positively improves post-open-heart surgery results. PMID:19343161

  11. Decrease in cerebral metabolic rate of glucose after high-dose methotrexate in childhood acute lymphocytic leukemia

    SciTech Connect

    Komatsu, K.; Takada, G.; Uemura, K.; Shishido, F.; Kanno, I. )

    1990-09-01

    We measured changes in the regional cerebral metabolic rate of glucose (rCMRGlu) using {sup 18}F-fluorodeoxyglucose and positron emission tomography for the assessment of neurotoxicity in childhood acute lymphocytic leukemia treated with high-dose methotrexate (HD-MTX) therapy. We studied 8 children with acute lymphocytic leukemia (mean age: 9.6 years) treated with HD-MTX (200 mg/kg or 2,000 mg/M2) therapy. CMRGlu after HD-MTX therapy was most reduced (40%) in the patient who had central nervous system leukemia and was treated with the largest total doses of both intrathecal MTX (IT-MTX) and HD-MTX. CMRGlu in the whole brain after HD-MTX therapy was reduced by an average of 21% (P less than 0.05). The reductions of CMRGlu in 8 patients were correlated with total doses of both IT-MTX (r = 0.717; P less than 0.05) and systemic HD-MTX (r = 0.784; P less than 0.05). CMRGlu of the cerebral cortex, especially the frontal and occipital cortex, was reduced more noticeably than that of the basal ganglia and white matter. We suggest that the measurement of changes in rCMRGlu after HD-MTX therapy is useful for detecting accumulated MTX neurotoxicity.

  12. Choice of therapy in young adults with hyperthyroidism of Graves' disease. A brief, case-directed poll of fifty-four thyroidologists

    SciTech Connect

    Dunn, J.T.

    1984-06-01

    We asked 54 thyroidologists how they would treat each of four patients having moderate hyperthyroidism of Graves' disease and a thyroid gland weighing 70 g (three to four times normal). For a 19-year-old woman, 67% of thyroidologists recommended an initial course of therapy with antithyroid drugs, usually for 1 year; 24% favored radioiodine treatments; and 9%, surgery. Choices for treating a 19-year-old man were similar. For a 29-year-old man, 44% of thyroidologists preferred drug therapy; 50%, radioiodine; and 6%, surgery. For a 29-year-old woman, choices were similar to those for the 29-year-old man, except for a slight preference for drugs over radioiodine. If hyperthyroidism recurred after a first course of antithyroid drugs, the consultants favored radioiodine treatments and surgery about equally, except in the 29-year-old man, in whom radioiodine was preferred. This survey shows considerable variation among experts in treating hyperthyroidism in young adults.

  13. Childhood thyroid cancers and radioactive iodine therapy: necessity of precautious radiation health risk management.

    PubMed

    Kumagai, Atsushi; Reiners, Christoph; Drozd, Valentina; Yamashita, Shunichi

    2007-12-01

    One of the lessons from Chernobyl's legacy on health impact beyond 20 years is not only how to detect and treat the patients with radiation-associated thyroid cancers but how to follow up those who received radioactive iodine treatment repetitively after surgery in order to monitor any recurrence/worsening and also how to predict the risk of secondary primary cancers for their lifetime period. To evaluate the possibility of second primary tumors after radioactive iodine treatment, we reviewed the reports on risks from both external and internal radiation exposure, especially at high doses during childhood through an internet service of the National Library of Medicine and the National Institutes of Health, PubMed by the end of June, 2007, together with our own experience of Chernobyl childhood thyroid cancers. Children who were internally exposed after Chernobyl accident have a long-term risk of well differentiated thyroid cancers. Once they have disease, ironically radioactive iodine ablation is one of the useful therapies after surgical treatment. Elevated risks of solid cancers and leukemia have been found in radioiodine-treated patients, however, so far precious few reports from Chernobyl thyroid cancer patient were published. To reduce the adverse effects of radioactive iodine therapy on non-target tissues, recombinant human TSH has been applied and proved effective. Period of latency of second primary cancers may be very long. Therefore patients treated with high activities of radioactive iodine, especially children cases, should be carefully followed up during their whole lifespan. PMID:17938505

  14. Better retention of Malaysian opiate dependents treated with high dose methadone in methadone maintenance therapy

    PubMed Central

    2010-01-01

    Background Methadone is a synthetic opiate mu receptor agonist that is widely used to substitute for illicit opiates in the management of opiate dependence. It helps prevent opiate users from injecting and sharing needles which are vehicles for the spread of HIV and other blood borne viruses. This study has the objective of determining the utility of daily methadone dose to predict retention rates and re-injecting behaviour among opiate dependents. Methods Subjects comprised opiate dependent individuals who met study criteria. They took methadone based on the Malaysian guidelines and were monitored according to the study protocols. At six months, data was collected for analyses. The sensitivity and specificity daily methadone doses to predict retention rates and re-injecting behaviour were evaluated. Results Sixty-four patients volunteered to participate but only 35 (54.69%) remained active and 29 (45.31%) were inactive at 6 months of treatment. Higher doses were significantly correlated with retention rate (p < 0.0001) and re-injecting behaviour (p < 0.001). Of those retained, 80.0% were on 80 mg or more methadone per day doses with 20.0% on receiving 40 mg -79 mg. Conclusions We concluded that a daily dose of at least 40 mg was required to retain patients in treatment and to prevent re-injecting behaviour. A dose of at least 80 mg per day was associated with best results. PMID:21167035

  15. Reevaluation of the newborn thyroid dose from radioiodines

    SciTech Connect

    Hedrick, W.R.; Milavickas, L.R.

    1987-07-01

    The basis for the current thyroid absorbed dose estimates for radioiodines has been examined. The values for the newborn thyroid dose were found to underestimate the dose by a factor of 3. This underestimation of the dose was caused by the assumption that the biokinetic distribution of iodine is the same for the newborn and the adult. Increased thyroid uptake by the newborn requires that higher cumulated activities be incorporated into the dose determinations for the newborn.

  16. Stokes radius determination of radioiodinated polypeptide hormones by gel filtration

    SciTech Connect

    Ribela, M.T.; Bartolini, P.

    1988-11-01

    A simple technique for determination of the molecular (Stokes) radius of radioiodinated proteins was developed using the same column and chromatographic conditions employed in routine radioimmunoassay tracer purification. The calibration curve for five radioiodinated standard proteins presented a highly significant correlation (r = -0.996; P less than 0.001) and allowed precise molecular radius determination for labeled human growth hormone (hGH), luteotropin (hLH), follicle-stimulating hormone (hFSH), thyrotropin (hTSH), prolactin (hPRL), and corticotropin (hACTH), enabling detection of differences of the order of +/- 3%. The validity of the method was verified by determining the molecular radius of hGH in both ''cold'' (unlabeled standards and unknowns) and ''hot'' (radioiodinated standards and unknowns) systems. The technique can be applied in a very simple manner, requiring just one simple additional calibration run before Sephadex G-100 tracer purification. Furthermore, it can be applied to any protein, even when only extremely limited amounts are available. Since the standards and unknowns are labeled and chromatographed under identical conditions, potential common alterations of the molecule due to oxidation, iodine incorporation, tracer-carrier interactions, etc., are automatically corrected for.

  17. A Phase I trial of high dose gefitinib for patients with leptomeningeal metastases from non-small cell lung cancer

    PubMed Central

    Cioffredi, Leigh A.; Jacobs, Lorraine; Sharmeen, Farhana; Morse, Linda K.; Lucca, Joan; Plotkin, Scott R.; Marcoux, Paul J.; Rabin, Michael S.; Lynch, Thomas J.; Johnson, Bruce E.

    2015-01-01

    Introduction There are few effective treatment options for leptomeningeal metastasis (LM) in non-small-cell lung cancer (NSCLC). This study assessed the feasibility of high-dose gefitinib in patients with LM from NSCLC harboring EGFR mutations or prior systemic response to EGFR-TKI. Methods This phase I open-label trial of a novel gefitinib dosing schedule employed a 3+3 design. Eligible NSCLC patients with LM had known EGFR mutations and/or prior response to EGFR-TKI. Patients alternated 2 weeks of high-dose daily gefitinib (dose levels: 750 mg, 1000 mg, 1250 mg) with 2 weeks of maintenance therapy (500 mg daily). Primary endpoints were safety and toxicity. Secondary endpoints included overall survival (OS), neurological progression-free survival, radiological response, and cytological response in cerebrospinal fluid (CSF). Results Seven patients were treated: 3 at 750 mg dose level, 4 at 1000 mg dose level. There were no DLTs at the 750 mg dose level, and one DLT (toxic epidermal necrolysis) at the 1000 mg dose level. The study was closed due to slow accrual. Median neurological PFS was 2.3months (range 1.6–4.0 months); median OS was 3.5months (range 1.6–5.1months). Though there were no radiologically documented remissions of LM disease, four patients had improvement in neurological symptoms. One patient cleared their CSF of NSCLC cells, while 2 others had decrease in malignant cells in CSF. Conclusion Although the MTD was not defined due to slow accrual, this study provides important information about the tolerability and CSF penetration of high-dose gefitinib as a therapeutic option for modest palliation for NSCLC patients with LM and a known EGFR mutation. PMID:25784657

  18. Long-Term Outcomes After High-Dose Postprostatectomy Salvage Radiation Treatment

    SciTech Connect

    Goenka, Anuj; Magsanoc, Juan Martin; Pei Xin; Schechter, Michael; Kollmeier, Marisa; Cox, Brett; Scardino, Peter T.; Eastham, James A.; Zelefsky, Michael J.

    2012-09-01

    Purpose: To review the impact of high-dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases-free survival, and to identify clinical and pathologic predictors of outcomes. Methods and Materials: During 1988-2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose {>=}66 Gy, of whom 205 (72%) received doses {>=}70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response. Results: The median follow-up time after SRT was 60 months. Seven-year actuarial prostate-specific antigen (PSA) relapse-free survival and distant metastases-free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p < 0.01), negative surgical margins (p < 0.01), presalvage PSA level >0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score {>=}7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose {>=}70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose {>=}70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7 years: 90% vs. 79.1%, p = 0.07). Conclusion: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in

  19. High-Dose Vincristine Sulfate Liposome Injection for Advanced, Relapsed, and Refractory Adult Philadelphia Chromosome–Negative Acute Lymphoblastic Leukemia

    PubMed Central

    O'Brien, Susan; Schiller, Gary; Lister, John; Damon, Lloyd; Goldberg, Stuart; Aulitzky, Walter; Ben-Yehuda, Dina; Stock, Wendy; Coutre, Steven; Douer, Dan; Heffner, Leonard T.; Larson, Melissa; Seiter, Karen; Smith, Scott; Assouline, Sarit; Kuriakose, Philip; Maness, Lori; Nagler, Arnon; Rowe, Jacob; Schaich, Markus; Shpilberg, Ofer; Yee, Karen; Schmieder, Guenter; Silverman, Jeffrey A.; Thomas, Deborah; Deitcher, Steven R.; Kantarjian, Hagop

    2013-01-01

    Purpose Relapsed adult acute lymphoblastic leukemia (ALL) is associated with high reinduction mortality, chemotherapy resistance, and rapid progression leading to death. Vincristine sulfate liposome injection (VSLI), sphingomyelin and cholesterol nanoparticle vincristine (VCR), facilitates VCR dose-intensification and densification plus enhances target tissue delivery. We evaluated high-dose VSLI monotherapy in adults with Philadelphia chromosome (Ph) –negative ALL that was multiply relapsed, relapsed and refractory to reinduction, and/or relapsed after hematopoietic cell transplantation (HCT). Patients and Methods Sixty-five adults with Ph-negative ALL in second or greater relapse or whose disease had progressed following two or more leukemia therapies were treated in this pivotal phase II, multinational trial. Intravenous VSLI 2.25 mg/m2, without dose capping, was administered once per week until response, progression, toxicity, or pursuit of HCT. The primary end point was achievement of complete response (CR) or CR with incomplete hematologic recovery (CRi). Results The CR/CRi rate was 20% and overall response rate was 35%. VSLI monotherapy was effective as third-, fourth-, and fifth-line therapy and in patients refractory to other single- and multiagent reinduction therapies. Median CR/CRi duration was 23 weeks (range, 5 to 66 weeks); 12 patients bridged to a post-VSLI HCT, and five patients were long-term survivors. VSLI was generally well tolerated and associated with a low 30-day mortality rate (12%). Conclusion High-dose VSLI monotherapy resulted in meaningful clinical outcomes including durable responses and bridging to HCT in advanced ALL settings. The toxicity profile of VSLI was predictable, manageable, and comparable to standard VCR despite the delivery of large, normally unachievable, individual and cumulative doses of VCR. PMID:23169518

  20. Accuracy and optimal timing of activity measurements in estimating the absorbed dose of radioiodine in the treatment of Graves' disease

    NASA Astrophysics Data System (ADS)

    Merrill, S.; Horowitz, J.; Traino, A. C.; Chipkin, S. R.; Hollot, C. V.; Chait, Y.

    2011-02-01

    Calculation of the therapeutic activity of radioiodine 131I for individualized dosimetry in the treatment of Graves' disease requires an accurate estimate of the thyroid absorbed radiation dose based on a tracer activity administration of 131I. Common approaches (Marinelli-Quimby formula, MIRD algorithm) use, respectively, the effective half-life of radioiodine in the thyroid and the time-integrated activity. Many physicians perform one, two, or at most three tracer dose activity measurements at various times and calculate the required therapeutic activity by ad hoc methods. In this paper, we study the accuracy of estimates of four 'target variables': time-integrated activity coefficient, time of maximum activity, maximum activity, and effective half-life in the gland. Clinical data from 41 patients who underwent 131I therapy for Graves' disease at the University Hospital in Pisa, Italy, are used for analysis. The radioiodine kinetics are described using a nonlinear mixed-effects model. The distributions of the target variables in the patient population are characterized. Using minimum root mean squared error as the criterion, optimal 1-, 2-, and 3-point sampling schedules are determined for estimation of the target variables, and probabilistic bounds are given for the errors under the optimal times. An algorithm is developed for computing the optimal 1-, 2-, and 3-point sampling schedules for the target variables. This algorithm is implemented in a freely available software tool. Taking into consideration 131I effective half-life in the thyroid and measurement noise, the optimal 1-point time for time-integrated activity coefficient is a measurement 1 week following the tracer dose. Additional measurements give only a slight improvement in accuracy.

  1. An Alternative to the Use of High-Dose Estrogens for Postcoital Contraception.

    ERIC Educational Resources Information Center

    Schilling, Lee H.

    1979-01-01

    Research is reported on the use of ethinyl estradiol and norgestrel for contraception after intercourse. This treatment is offered as an alternative to high doses of estrogen and appears to be successful in preventing unwanted pregnancies. (JMF)

  2. High Doses of Fish Oil Might Help Healing After Heart Attack

    MedlinePlus

    ... Doses of Fish Oil Might Help Healing After Heart Attack Study found improved heart function, less scarring To ... 2, 2016 MONDAY, Aug. 1, 2016 (HealthDay News) -- Heart attack patients who took high doses of fish oil ...

  3. High-Dose Induced Thermoluminescence of Light-Colored Lithology in Chelyabinsk Meteorite

    NASA Astrophysics Data System (ADS)

    Weinstein, I. A.; Vokhmintsev, A. S.; Ishchenko, A. V.; Grokhovsky, V. I.

    2015-07-01

    This work presents the study results of high-dose irradiation effects on the laboratory TL parameters in Chelyabinsk LL5 chondrite fragments with light-colored lithology. Obtained data are analyzed in terms of the general order kinetic formalism.

  4. Cardiac toxicity of trastuzumab in metastatic breast cancer patients previously treated with high-dose chemotherapy: a retrospective study

    PubMed Central

    Bengala, C; Zamagni, C; Pedrazzoli, P; Matteucci, P; Ballestrero, A; Da Prada, G; Martino, M; Rosti, G; Danova, M; Bregni, M; Jovic, G; Guarneri, V; Maur, M; Conte, P F

    2006-01-01

    HER-2 overexpression is associated to a poor prognosis in high-risk and metastatic breast cancer (MBC) patients treated with high-dose chemotherapy (HDC). HER-2 status is also a predictive factor and when trastuzumab is administered in combination with or sequentially to chemotherapy, a significant disease-free and/or overall survival improvement has been observed in HER-2+ early and MBC. Unfortunately, in both settings, trastuzumab is associated with an increased risk of cardiac dysfunction (CD). We have reviewed the clinical charts of HER-2-overexpressing MBC patients treated with trastuzumab after HDC. Age, baseline left ventricular ejection fraction (LVEF), radiation therapy on cardiac area, exposure to anthracycline, single or multiple transplant, high-dose agents, trastuzumab treatment duration were recorded as potential risk factors. In total, 53 patients have been included in the analysis. Median LVEF at baseline was 60.5%; at the end of trastuzumab (data available for 28 patients only), it was 55% (P=0.01). Five out of the 28 (17.9%) patients experienced CD. Two out of 53 (3.8%) patients developed a congestive heart failure. Age ⩾50 years and multiple transplant procedure were potential risk factors for CD. The overall incidence of CD observed in this population of HER-2+ MBC patients treated with trastuzumab after HDC is not superior to that reported with concomitant trastuzumab and anthracyclines. However, patients with age ⩾50 years or receiving multiple course of HDC should be considered at risk for CD. PMID:16570045

  5. Early use of high-dose riboflavin in a case of Brown-Vialetto-Van Laere syndrome.

    PubMed

    Anand, Geetha; Hasan, Nadeem; Jayapal, Sathiya; Huma, Zilla; Ali, Tariq; Hull, Jeremy; Blair, Edward; McShane, Tony; Jayawant, Sandeep

    2012-02-01

    Brown-Vialetto-Van Laere syndrome (BVVLS) is a genetic condition caused by a mutation in the C20orf54 gene, which also codes for an intestinal riboflavin transporter. We report the case of a female who presented at 22 months with acute-onset stridor and generalized muscle weakness, in whom a genetic diagnosis of BVVLS was made, and whose symptoms improved on therapy with high-dose riboflavin. She had previously been developing normally and was able to walk at 11 months, then developed progressive muscle weakness at 22 months, and within 2 weeks was unable to sit without support. She also demonstrated stridor and paradoxical breathing indicating diaphragmatic weakness, and required continuous non-invasive ventilation (NIV) through a tracheostomy. After treatment with riboflavin she was able to walk unaided, and her Gross Motor Functional Classification level improved from level IV to level I, having fully regained the motor function she showed before symptom onset. There were no longer signs of diaphragmatic paralysis while on NIV, and she was able to tolerate 10-minute periods off NIV before paradoxical breathing again became apparent. We therefore recommend that in all cases suspected to be in the BVVLS or Fazio-Londe spectrum, early treatment with high-dose riboflavin must be considered. PMID:22098162

  6. Continuous high-dose antigen exposure preferentially induces IL-10, but intermittent antigen exposure induces IL-4.

    PubMed

    Yamanaka, Keiichi; Nakanishi, Takehisa; Watanabe, Jun; Kondo, Makoto; Yamagiwa, Akisa; Gabazza, Esteban C; Mizutani, Hitoshi

    2014-01-01

    IL-10 plays a critical role in the induction of specific T-cell tolerance. To date, whether IL-10 induction by antigen application is dose- or time-dependent remains unclear. In this study, IL-10 induction by allergen exposure was investigated in the several schedules. Oxazolone was repeatedly applied to mouse ear, and mRNA of inflammatory cytokines in lesional skins was measured. The results indicated that continuous high-dose antigen exposure induces IL-4 as well as abundant IL-10 production. Monocytes/dendritic cells and T cells are major source of IL-10. Allergen-specific immunotherapy is resumed before antigen scattering: preseason. We evaluated safe-loading dose of allergens in preseasonal therapy focusing Tr1 induction. Restarting immunotherapy with high dose effectively augmented IL-10 expression accompanied with further induction of IL-4 and inflammatory cytokines. Therefore, the protocol restarting with low-dose antigen is preferential to obviate the risk of exacerbation or anaphylaxis. PMID:24299227

  7. A child presenting with acute renal failure secondary to a high dose of indomethacin: a case report

    PubMed Central

    2009-01-01

    Introduction Acute renal failure caused by nonsteroidal anti-inflammatory drugs administered at therapeutic doses is generally mild, non-anuric and transitory. There are no publications on indomethacin toxicity secondary to high doses in children. The aim of this article is to describe acute renal failure secondary to a high dose of indomethacin in a child and to review an error in a supervised drug prescription and administration system. Case presentation Due to a medication error, a 20-day-old infant in the postoperative period of surgery for Fallot's tetralogy received a dose of 10 mg/kg of indomethacin, 50 to 100 times higher than the therapeutic dose. The child presented with acute, oligo-anuric renal failure requiring treatment with continuous venovenous renal replacement therapy, achieving complete recovery of renal function with no sequelae. Conclusion In order to reduce medication errors in critically ill children, it is necessary to develop a supervised drug prescription and administration system, with controls at various levels. PMID:19192282

  8. Early supradiaphragmatic Hodgkin's disease. High-dose gallium scanning obviates the need for staging laparotomy

    SciTech Connect

    Blackwell, E.A.; Joshua, D.E.; McLaughlin, A.F.; Green, D.; Kronenberg, H.; May, J.

    1986-08-15

    Experience with 16 sequential patients with Stage IA/IIA supradiaphragmatic Hodgkin's disease who had no evidence of intra-abdominal disease using high-dose gallium and computerized tomography scanning is reported. Subsequent staging laparotomy also was negative in all these patients and did not alter management decisions. It is suggested that high-dose, whole-body gallium scanning and other noninvasive staging procedures give reliable data for therapeutic decisions.

  9. An automated optimization tool for high-dose-rate (HDR) prostate brachytherapy with divergent needle pattern.

    PubMed

    Borot de Battisti, M; Maenhout, M; Denis de Senneville, B; Hautvast, G; Binnekamp, D; Lagendijk, J J W; van Vulpen, M; Moerland, M A

    2015-10-01

    Focal high-dose-rate (HDR) for prostate cancer has gained increasing interest as an alternative to whole gland therapy as it may contribute to the reduction of treatment related toxicity. For focal treatment, optimal needle guidance and placement is warranted. This can be achieved under MR guidance. However, MR-guided needle placement is currently not possible due to space restrictions in the closed MR bore. To overcome this problem, a MR-compatible, single-divergent needle-implant robotic device is under development at the University Medical Centre, Utrecht: placed between the legs of the patient inside the MR bore, this robot will tap the needle in a divergent pattern from a single rotation point into the tissue. This rotation point is just beneath the perineal skin to have access to the focal prostate tumor lesion. Currently, there is no treatment planning system commercially available which allows optimization of the dose distribution with such needle arrangement. The aim of this work is to develop an automatic inverse dose planning optimization tool for focal HDR prostate brachytherapy with needle insertions in a divergent configuration. A complete optimizer workflow is proposed which includes the determination of (1) the position of the center of rotation, (2) the needle angulations and (3) the dwell times. Unlike most currently used optimizers, no prior selection or adjustment of input parameters such as minimum or maximum dose or weight coefficients for treatment region and organs at risk is required. To test this optimizer, a planning study was performed on ten patients (treatment volumes ranged from 8.5 cm(3)to 23.3 cm(3)) by using 2-14 needle insertions. The total computation time of the optimizer workflow was below 20 min and a clinically acceptable plan was reached on average using only four needle insertions. PMID:26378657

  10. High-Dose-Rate Brachytherapy Boost for Prostate Cancer: Comparison of Two Different Fractionation Schemes

    SciTech Connect

    Kaprealian, Tania; Weinberg, Vivian; Speight, Joycelyn L.; Gottschalk, Alexander R.; Roach, Mack; Shinohara, Katsuto; Hsu, I.-Chow

    2012-01-01

    Purpose: This is a retrospective study comparing our experience with high-dose-rate (HDR) brachytherapy boost for prostate cancer, using two different fractionation schemes, 600 cGy Multiplication-Sign 3 fractions (patient group 1) and 950 cGy Multiplication-Sign 2 fractions (patient group 2). Methods and Materials: A total of 165 patients were treated for prostate cancer using external beam radiation therapy up to a dose of 45 Gy, followed by an HDR brachytherapy prostate radiation boost. Between July 1997 and Nov 1999, 64 patients were treated with an HDR boost of 600 cGy Multiplication-Sign 3 fractions; and between June 2000 and Nov 2005, 101 patients were treated with an HDR boost of 950 cGy Multiplication-Sign 2 fractions. All but 9 patients had at least one of the following risk features: pretreatment prostate-specific antigen (PSA) level >10, a Gleason score {>=}7, and/or clinical stage T3 disease. Results: Median follow-up was 105 months for group 1 and 43 months for group 2. Patients in group 2 had a greater number of high-risk features than group 1 (p = 0.02). Adjusted for comparable follow-up, there was no difference in biochemical no-evidence-of-disease (bNED) rate between the two fractionation scheme approaches, with 5-year Kaplan-Meier estimates of 93.5% in group 1 and 87.3% in group 2 (p = 0.19). The 5-year estimates of progression-free survival were 86% for group 1 and 83% for group 2 (p = 0.53). Among high-risk patients, there were no differences in bNED or PFS rate due to fractionation. Conclusions: Results were excellent for both groups. Adjusted for comparable follow-up, no differences were found between groups.

  11. High-dose ifosfamide and mitoxantrone (HDIM) in patients with relapsed or refractory Hodgkin's lymphoma.

    PubMed

    Aurer, Igor; Nemet, Damir; Mitrović, Zdravko; Dujmović, Dino; Bašić-Kinda, Sandra; Radman, Ivo; Sertić, Dubravka; Šantek, Fedor; Kralik, Marko; Dotlić, Snježana; Mazić, Sanja; Labar, Boris

    2016-06-01

    Relapsed/refractory Hodgkin's lymphoma (HL) is treated with salvage chemotherapy and autologous stem cell transplantation (ASCT). Optimal chemotherapy is unknown. We retrospectively analyzed outcomes of 58 patients treated with 2 cycles of high-dose ifosfamide and mitoxantrone (HDIM). HDIM consisted of ifosfamide 5 g/m(2)/day and MESNA 5 g/m(2)/day in continuous 24-h infusion (days 1 and 2), MESNA 2.5 g/m(2) over 12 h (day 3), and mitoxantrone 20 mg/m(2) (day 1) administered every 2 weeks. Stem cells were collected after the first cycle. Responding patients proceeded to ASCT. Toxicity was acceptable. Stem cell mobilization was successful in 96 % of patients. Overall response rate was 74 % (89 % in relapsing and 45 % in refractory patients) with 31 % complete remissions. After a median follow-up of 54 months, 5-year event-free survival was 56 % (69 % for relapsing and 35 % for refractory patients), and 5-year overall survival was 67 % (73 % for relapsing and 55 % for refractory patients). Significant adverse prognostic factors were refractoriness to previous therapy and HDIM failure. No differences in outcomes were noted between patients with early and late relapses or between complete and partial responders. HDIM is a well-tolerated and effective regimen for relapsed and refractory HL with excellent stem cell mobilizing properties. Patients failing HDIM may still benefit from other salvage options. PMID:27103009

  12. An automated optimization tool for high-dose-rate (HDR) prostate brachytherapy with divergent needle pattern

    NASA Astrophysics Data System (ADS)

    Borot de Battisti, M.; Maenhout, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; van Vulpen, M.; Moerland, M. A.

    2015-10-01

    Focal high-dose-rate (HDR) for prostate cancer has gained increasing interest as an alternative to whole gland therapy as it may contribute to the reduction of treatment related toxicity. For focal treatment, optimal needle guidance and placement is warranted. This can be achieved under MR guidance. However, MR-guided needle placement is currently not possible due to space restrictions in the closed MR bore. To overcome this problem, a MR-compatible, single-divergent needle-implant robotic device is under development at the University Medical Centre, Utrecht: placed between the legs of the patient inside the MR bore, this robot will tap the needle in a divergent pattern from a single rotation point into the tissue. This rotation point is just beneath the perineal skin to have access to the focal prostate tumor lesion. Currently, there is no treatment planning system commercially available which allows optimization of the dose distribution with such needle arrangement. The aim of this work is to develop an automatic inverse dose planning optimization tool for focal HDR prostate brachytherapy with needle insertions in a divergent configuration. A complete optimizer workflow is proposed which includes the determination of (1) the position of the center of rotation, (2) the needle angulations and (3) the dwell times. Unlike most currently used optimizers, no prior selection or adjustment of input parameters such as minimum or maximum dose or weight coefficients for treatment region and organs at risk is required. To test this optimizer, a planning study was performed on ten patients (treatment volumes ranged from 8.5 cm3to 23.3 cm3) by using 2-14 needle insertions. The total computation time of the optimizer workflow was below 20 min and a clinically acceptable plan was reached on average using only four needle insertions.

  13. Clinical results and pharmacokinetics of high-dose cytosine arabinoside (HD ARA-C).

    PubMed

    Breithaupt, H; Pralle, H; Eckhardt, T; von Hattingberg, M; Schick, J; Löffler, H

    1982-10-01

    Four patients with acute nonlymphoblastic leukemia and one malignant teratoma refractory to conventional chemotherapy were treated with high doses of cytosine arabinoside (HD ARA-C). They received up to 12 cycles of 1.8 to 3 g/m2 every 12 hours applied by 2-hour infusions. A total of 55 HD ARA-C infusions was performed. All leukemic patients responded. A complete clearance of blasts from the bone marrow was observed in two patients following 8-12 cycles of 3 g/m2. However, relapses occurred after three and seven weeks, in one case with resistance to HD ARA-C. The patient with malignant teratoma did not respond. No severe toxicity emerged even after repeated applications. Adverse reactions included moderate nausea and vomiting (4 patients), diarrhea (2 patients), hepatic dysfunction (1 patient), bone pain (1 patient), blurred vision (1 patient), conjunctivitis (1 patient), and exanthema with partial epidermiolysis (1 patient). Granulocytopenia occurring between 3-8 days after having started the therapy, subsided within 4-25 days. Plasma levels of ARA-C and the metabolite uracil arabinoside (ARA-U) were monitored. At steady state plasma concentrations of ARA-C were 32-97 microM (8-24 micrograms/ml). ARA-C disappeared from the plasma mono- or biphasic with a terminal half-life (t50%) of 7.8-12.6 minutes. The total clearance (Cl) of ARA-C varied between 1.7 and 2.9 liters/kg . h, and the distribution volume (Vss) between 0.44 and 0.86 liters/kg. Cerebrospinal fluid (CSF) levels of ARA-C reached 10-15% of steady state concentrations in plasma. PMID:7104969

  14. High-Dose-Rate Monotherapy: Safe and Effective Brachytherapy for Patients With Localized Prostate Cancer

    SciTech Connect

    Demanes, D. Jeffrey; Martinez, Alvaro A.; Ghilezan, Michel; Hill, Dennis R.; Schour, Lionel; Brandt, David; Gustafson, Gary

    2011-12-01

    Purpose: High-dose-rate (HDR) brachytherapy used as the only treatment (monotherapy) for early prostate cancer is consistent with current concepts in prostate radiobiology, and the dose is reliably delivered in a prospectively defined anatomic distribution that meets all the requirements for safe and effective therapy. We report the disease control and toxicity of HDR monotherapy from California Endocurietherapy (CET) and William Beaumont Hospital (WBH) in low- and intermediate-risk prostate cancer patients. Methods and Materials: There were 298 patients with localized prostate cancer treated with HDR monotherapy between 1996 and 2005. Two biologically equivalent hypofractionation protocols were used. At CET the dose was 42 Gy in six fractions (two implantations 1 week apart) delivered to a computed tomography-defined planning treatment volume. At WBH the dose was 38 Gy in four fractions (one implantation) based on intraoperative transrectal ultrasound real-time treatment planning. The bladder, urethral, and rectal dose constraints were similar. Toxicity was scored with the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 5.2 years. The median age of the patients was 63 years, and the median value of the pretreatment prostate-specific antigen was 6.0 ng/mL. The 8-year results were 99% local control, 97% biochemical control (nadir +2), 99% distant metastasis-free survival, 99% cause-specific survival, and 95% overall survival. Toxicity was scored per event, meaning that an individual patient with more than one symptom was represented repeatedly in the morbidity data table. Genitourinary toxicity consisted of 10% transient Grade 2 urinary frequency or urgency and 3% Grade 3 episode of urinary retention. Gastrointestinal toxicity was <1%. Conclusions: High disease control rates and low morbidity demonstrate that HDR monotherapy is safe and effective for patients with localized prostate cancer.

  15. High-dose methotrexate with or without rituximab in newly diagnosed primary CNS lymphoma

    PubMed Central

    Ambady, Prakash; Abdelaziz, Ahmed; Sarai, Guneet; Bonekamp, David; Blakeley, Jaishri; Grossman, Stuart A.; Ye, Xiaobu

    2014-01-01

    Objective: To evaluate the efficacy of rituximab (R) when added to high-dose methotrexate (HD-MTX) in patients with newly diagnosed immunocompetent primary CNS lymphomas (PCNSLs). Methods: Immunocompetent adults with newly diagnosed PCNSL treated at The Johns Hopkins Hospital between 1995 and 2012 were investigated. From 1995 to 2008, patients received HD-MTX monotherapy (8 g/m2 initially every 2 weeks and after complete response [CR] monthly to complete 12 months of therapy). From 2008 to 2012, patients received the same HD-MTX with rituximab (375 mg/m2) with each HD-MTX treatment. CR rates and median overall and progression-free survival were analyzed for each patient cohort in this single-institution, retrospective study. Results: A total of 81 patients were identified: 54 received HD-MTX (median age 66 years) while 27 received HD-MTX/R (median age 65 years). CR rates were 36% in the HD-MTX cohort and 73% in the HD-MTX/R cohort (p = 0.0145). Median progression-free survival was 4.5 months in the HD-MTX cohort and 26.7 months in the HD-MTX/R cohort (p = 0.003). Median overall survival was 16.3 months in the HD-MTX cohort and has not yet been reached in the HD-MTX/R cohort (p = 0.01). Conclusions: The addition of rituximab to HD-MTX appears to improve CR rates as well as overall and progression-free survival in patients with newly diagnosed PCNSL. Comparisons of long-term survival in the 2 cohorts await further maturation of the data. Classification of evidence: This study provides Class III evidence that in immunocompetent patients with PCNSL, HD-MTX plus rituximab compared with HD-MTX alone improves CR and overall survival rates. PMID:24928128

  16. Adequacy of high-dose cefepime regimen in febrile neutropenic patients with hematological malignancies.

    PubMed

    Sime, Fekade Bruck; Roberts, Michael S; Tiong, Ing Soo; Gardner, Julia H; Lehman, Sheila; Peake, Sandra L; Hahn, Uwe; Warner, Morgyn S; Roberts, Jason A

    2015-09-01

    While guidelines recommend empirical cefepime therapy in febrile neutropenia, the mortality benefit of cefepime has been controversial. In light of this, recent reports on pharmacokinetic changes for several antibiotics in febrile neutropenia and the consequent suboptimal exposure call for a pharmacokinetic/pharmacodynamic evaluation of current dosing. This study aimed to assess pharmacokinetic/pharmacodynamic target attainment from a 2-g intravenous (i.v.) every 8 h (q8h) cefepime regimen in febrile neutropenic patients with hematological malignancies. Cefepime plasma concentrations were measured in the 3rd, 6th, and 9th dosing intervals at 60% of the interval and/or trough point. The selected pharmacokinetic/pharmacodynamic targets were the proportion of the dosing interval (60% and 100%) for which the free drug concentration remains above the MIC (fT>MIC). Target attainment was assessed in reference to the MIC of isolated organisms if available or empirical breakpoints if not. The percentage of fT>MIC was also estimated by log-linear regression analysis. All patients achieved >60% fT>MIC in the 3rd and 6th dosing intervals. A 100% fT>MIC was not attained in 6/12, 4/10, and 4/9 patients in the 3rd, 6th, and 9th dose intervals, respectively, or in 14/31 (45%) of the dosing intervals investigated. On the other hand, 29/31 (94%) of trough concentrations were at or above 4 mg/liter. In conclusion, for patients with normal renal function, a high-dose 2-g i.v. q8h cefepime regimen appears to provide appropriate exposure if the MIC of the organism is ≤4 mg/liter but may fail to cover less susceptible organisms. PMID:26124158

  17. Calibration of 192Ir high dose rate brachytherapy source using different calibration procedures

    PubMed Central

    Bondel, Shwetha; Ravikumar, Manickham; Supe, Sanjay Sudhakar; Reddy, Buchuppudi Rekha

    2013-01-01

    Aim To calibrate Ir-192 high dose rate (HDR) brachytherapy source using different calibration methods and to determine the accuracy and suitability of each method for routine calibrations. Background The source calibration is an essential part of the quality assurance programme for dosimetry of brachytherapy sources. The clinical use of brachytherapy source requires an independent measurement of the air kerma strength according to the recommendations of medical physics societies. Materials and methods The Ir-192 HDR brachytherapy source from Gammamed plus machine (Varian Medical Systems, Palo Alto, CA) was calibrated using three different procedures, one using the well-type ionization chamber, second by the in-air calibration method and third using solid water phantoms. The reference air kerma rate (RAKR) of the source was determined using Deutsche Gesellschaft fur Medizinische Physik (DGMP) recommendations. Results The RAKR determined using different calibration methods are in good agreement with the manufacturer stated value. The mean percentage variations of 0.21, −0.94, −0.62 and 0.58 in RAKR values with respect to the manufacturer quoted values were observed with the well-type chamber, in-air calibration, cylindrical phantom and slab phantom measurements, respectively. Conclusion Measurements with a well-type chamber are relatively simple to perform. For in-air measurements, the indigenously designed calibration jig provides an accurate positioning of the source and chamber with minimum scatter contribution. The slab phantom system has an advantage that no additional phantom and chamber are required other than those used for external beam therapy dosimetry. All the methods of calibration discussed in this study are effective to be used for routine calibration purposes. PMID:24944818

  18. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups.

    PubMed

    Luskin, Marlise R; Lee, Ju-Whei; Fernandez, Hugo F; Abdel-Wahab, Omar; Bennett, John M; Ketterling, Rhett P; Lazarus, Hillard M; Levine, Ross L; Litzow, Mark R; Paietta, Elisabeth M; Patel, Jay P; Racevskis, Janis; Rowe, Jacob M; Tallman, Martin S; Sun, Zhuoxin; Luger, Selina M

    2016-03-24

    The initial report of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group trial E1900 (#NCT00049517) showed that induction therapy with high-dose (HD) daunorubicin (90 mg/m(2)) improved overall survival in adults <60 years old with acute myeloid leukemia (AML); however, at initial analysis, the benefit was restricted to younger patients (<50 years) and patients without unfavorable cytogenetics or aFLT3-ITD mutation. Here, we update the results of E1900 after longer follow-up (median, 80.1 months among survivors), focusing on the benefit of HD daunorubicin on common genetic subgroups. Compared with standard-dose daunorubicin (45 mg/m(2)), HD daunorubicin is associated with a hazard ratio (HR) for death of 0.74 (P= .001). Younger patients (<50 years) benefited from HD daunorubicin (HR, 0.66;P= .002), as did patients with favorable and intermediate cytogenetics (HR, 0.51;P= .03 and HR, 0.68;P= .01, respectively). Patients with unfavorable cytogenetics were shown to benefit from HD daunorubicin on multivariable analysis (adjusted HR, 0.66;P= .04). Patients withFLT3-ITD (24%),DNMT3A(24%), andNPM1(26%) mutant AML all benefited from HD daunorubicin (HR, 0.61,P= .009; HR, 0.62,P= .02; and HR, 0.50,P= .002; respectively). HD benefit was seen in the subgroup of older patients (50-60 years) with theFLT3-ITD orNPM1mutation. Additionally, the presence of anNPM1mutation confers a favorable prognosis only for patients receiving anthracycline dose intensification during induction. PMID:26755712

  19. Safety of high-dose intravenous immunoglobulin in systemic autoimmune diseases.

    PubMed

    Tufan, Fatih; Kamali, Sevil; Erer, Burak; Gul, Ahmet; Inanc, Murat; Ocal, Lale; Konice, Meral; Aral, Orhan

    2007-11-01

    It is reported that the usage of high-dose intravenous immunoglobulin (HD-IVIG) in systemic autoimmune diseases is associated with various adverse events in a wide range of severity. We aimed to investigate the frequency and profile of adverse events in a group of patients with diffuse connective tissue diseases and Wegener's granulomatosis (WG) who were administrated HD-IVIG for different indications. We recorded the data of 38 patients (25 females and 13 males) aged 38 +/- 15 (12-75) years who were followed up with the diagnosis of systemic autoimmune diseases between 1994 and 2006 according to a predefined protocol. Patients with active disease were treated with HD-IVIG and standard immunosuppressives concomitantly. We evaluated the occurrence of allergy, acute renal failure, thromboembolic events, neutropenia, hemolytic anemia, aseptic meningitis, and vasculitis during infusion therapy of HD-IVIG and in the following 3 weeks. We commenced a total of 130 infusions of HD-IVIG. Patients were administrated 1-12 (3.4 +/- 2.6) infusions of HD-IVIG as needed. Indications for HD-IVIG were unresponsiveness or partial response to standard treatment, severe infections along with disease activity, and severe thrombocytopenia in the preoperative period in 97, 23, and 5% of patients, respectively. Minor adverse events were seen in two patients during HD-IVIG infusions. One patient with WG developed rapidly progressive renal failure during severe disease flare between HD-IVIG infusions. Another patient with WG developed recurrence of deep-vein thrombosis during severe disease flare 3 months after HD-IVIG. Both events were attributed to severe disease activity. Adverse events like allergy, acute renal failure, thromboembolic events, hematological problems, aseptic meningitis, and vasculitis are reported in different frequencies (1-81%) in patients who were administered HD-IVIG for systemic autoimmune diseases. HD-IVIG is considered a safe treatment in selected patients

  20. Adequacy of High-Dose Cefepime Regimen in Febrile Neutropenic Patients with Hematological Malignancies

    PubMed Central

    Roberts, Michael S.; Tiong, Ing Soo; Gardner, Julia H.; Lehman, Sheila; Peake, Sandra L.; Hahn, Uwe; Warner, Morgyn S.; Roberts, Jason A.

    2015-01-01

    While guidelines recommend empirical cefepime therapy in febrile neutropenia, the mortality benefit of cefepime has been controversial. In light of this, recent reports on pharmacokinetic changes for several antibiotics in febrile neutropenia and the consequent suboptimal exposure call for a pharmacokinetic/pharmacodynamic evaluation of current dosing. This study aimed to assess pharmacokinetic/pharmacodynamic target attainment from a 2-g intravenous (i.v.) every 8 h (q8h) cefepime regimen in febrile neutropenic patients with hematological malignancies. Cefepime plasma concentrations were measured in the 3rd, 6th, and 9th dosing intervals at 60% of the interval and/or trough point. The selected pharmacokinetic/pharmacodynamic targets were the proportion of the dosing interval (60% and 100%) for which the free drug concentration remains above the MIC (fT>MIC). Target attainment was assessed in reference to the MIC of isolated organisms if available or empirical breakpoints if not. The percentage of fT>MIC was also estimated by log-linear regression analysis. All patients achieved >60% fT>MIC in the 3rd and 6th dosing intervals. A 100% fT>MIC was not attained in 6/12, 4/10, and 4/9 patients in the 3rd, 6th, and 9th dose intervals, respectively, or in 14/31 (45%) of the dosing intervals investigated. On the other hand, 29/31 (94%) of trough concentrations were at or above 4 mg/liter. In conclusion, for patients with normal renal function, a high-dose 2-g i.v. q8h cefepime regimen appears to provide appropriate exposure if the MIC of the organism is ≤4 mg/liter but may fail to cover less susceptible organisms. PMID:26124158

  1. High Dose-Rate Intracavitary Brachytherapy for Cervical Carcinomas With Lower Vaginal Infiltration

    SciTech Connect

    Kazumoto, Tomoko Kato, Shingo; Tabushi, Katsuyoshi; Kutsutani-Nakamura, Yuzuru; Mizuno, Hideyuki; Takahashi, Michiko; Shiromizu, Kenji; Saito, Yoshihiro

    2007-11-15

    Purpose: This report presents the clinical applications of an automated treatment-planning program of high-dose-rate intracavitary brachytherapy (HDR-ICBT) for advanced uterine cervical cancer infiltrating the parametrium and the lower vagina. Methods and Materials: We adopted HDR-ICBT under optimized dose distribution for 22 cervical cancer patients with tumor infiltration of the lower half of the vagina. All patients had squamous cell carcinoma with International Federation of Gynecology and Obstetrics clinical stages IIB-IVA. After whole pelvic external beam irradiation with a median dose of 30.6 Gy, a conventional ICBT was applied as 'pear-shaped' isodose curve. Then 3-4 more sessions per week of this new method of ICBT were performed. With a simple determination of the treatment volume, the cervix-parametrium, and the lower vagina were covered automatically and simultaneously by this program, that was designated as 'utero-vaginal brachytherapy'. The mean follow-up period was 87.4 months (range, 51.8-147.9 months). Results: Isodose curve for this program was 'galaxy-shaped'. Five-year local-progression-free survival and overall survival rates were 90.7% and 81.8%, respectively. Among those patients with late complications higher than Grade 2 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer morbidity score, only one (4.5%) developed severe proctitis. Conclusions: Because of the favorable treatment outcomes, this treatment-planning program with a simplified target-volume based dosimetry was proposed for cervical cancer with lower vaginal infiltration.

  2. Comparison of efficacy and adverse effect profile of high dose versus standard dose atorvastatin in acute ST elevation myocardial infarction patients

    PubMed Central

    Sebastian, Gailin B; Anoop, T M; Thomas, Joby K; George, Raju

    2011-01-01

    Objective To compare the efficacy and adverse effects of high and standard dose atorvastatin in ST elevation myocardial infarction (STEMI) patients. Design A prospective, single-centre, randomised, double blind study. Setting A tertiary care centre in Kerala, India, from January to June 2009. Patients 121 consecutive acute STEMI patients eligible for thrombolytic therapy. Interventions Pharmacological thrombolysis and atorvastatin therapy. Main outcome measures Primary end points were mean change in low density lipoprotein and total cholesterol, serum glutamic pyruvic transaminase (SGPT), creatine phosphokinase (CPK) at 3 months of high dose (80 mg) and standard dose (20 mg) of atorvastatin. Results There was no significant difference in the mean cholesterol levels at 3 months of therapy (mean reduction in total cholesterol and low density lipoprotein cholesterol were 48 mg%, 49 mg% in the 20 mg group compared with 54 mg% and 53 mg%, respectively, in the 80 mg group; p 0.39 and 0.4). There was a significant increase in SGPT at 1 week in the 80 mg group and atorvastatin was stopped in a significantly higher number of patients due to the increase in SGPT and CPK at 1 week in the high dose group (12% and 7% of patients; (p=0.04 and p=0.06, respectively). Conclusion In acute STEMI patients treated with pharmacological thrombolysis, standard dose atorvastatin is equally effective as high dose atorvastatin in terms of reduction in cholesterol, with higher and earlier incidence of asymptomatic SGPT and CPK elevation in the high dose group.

  3. Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation.

    PubMed

    Jeong, Jong Cheol; Jambaldorj, Enkthuya; Kwon, Hyuk Yong; Kim, Myung-Gyu; Im, Hye Jin; Jeon, Hee Jung; In, Ji Won; Han, Miyeun; Koo, Tai Yeon; Chung, Junho; Song, Eun Young; Ahn, Curie; Yang, Jaeseok

    2016-02-01

    Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate.This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2  g/kg), a single dose of rituximab (375  mg/m), and 4 doses of bortezomib (1.3  mg/m). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients.There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83  ±  16.0 (14952  ±  5820) and 63  ±  36.0 (10321  ±  7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468-634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group.In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients. PMID:26844479

  4. Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation

    PubMed Central

    Jeong, Jong Cheol; Jambaldorj, Enkthuya; Kwon, Hyuk Yong; Kim, Myung-Gyu; Im, Hye Jin; Jeon, Hee Jung; In, Ji Won; Han, Miyeun; Koo, Tai Yeon; Chung, Junho; Song, Eun Young; Ahn, Curie; Yang, Jaeseok

    2016-01-01

    Abstract Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate. This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2 g/kg), a single dose of rituximab (375 mg/m2), and 4 doses of bortezomib (1.3 mg/m2). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients. There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83 ± 16.0 (14952 ± 5820) and 63 ± 36.0 (10321 ± 7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468–634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group. In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients. PMID:26844479

  5. Renal function in high dose chemotherapy and autologous hematopoietic cell support treatment for breast cancer.

    PubMed

    Merouani, A; Shpall, E J; Jones, R B; Archer, P G; Schrier, R W

    1996-09-01

    Autologous and allogeneic bone marrow grafting both require cytoreductive therapy but only the allogeneic procedure requires immunosuppressive agents. Allogeneic bone marrow transplantation has been reported to be associated with a high incidence of both renal failure and veno-occlusive disease (VOD) of the liver, the combination of which is associated with a high morbidity and mortality. There is less known about the frequency and severity of these complications in patients undergoing autologous bone marrow transplantation. In the present study renal, hepatic and other complications were examined in 232 patients with Stages II/III and IV breast cancer who were treated with high-dose chemotherapy and autologous hematopoietic cell support with either marrow or peripheral blood progenitor cells. The post-treatment severity of the renal dysfunction was classified as follows: Grade 0, normal renal function [< 25% decrement in glomerular filtration rate (GFR)]; Grade 1. mild renal dysfunction (> 25% decrement in GFR but < a twofold increase in serum creatinine); Grade 2, > twofold rise in serum creatinine but no need for dialysis; Grade 3 > than twofold rise in serum creatinine and need for dialysis. There were 102 patients (44%) who were classified as Grade 0 and 81 patients (35%) who were classified as Grade 1 renal dysfunction. Severe renal dysfunction (Grades 2 and 3) was observed in 49 of the 232 patients (21%). This severe renal dysfunction of 21% compares with a previously reported 53% incidence of severe renal dysfunction for allogeneic bone marrow transplantation. Similarly, the frequency of hepatic VOD was less (4.7% or 11 of 232 patients) in this autologous bone marrow transplant study as compared to a reported incidence of hepatic VOD ranging from 22 to 53% in large series of allogeneic bone marrow transplant patients. The severe renal dysfunction (Grades 2 and 3) in the present autologous hematopoietic cell support study correlated most significantly with

  6. Constitutive gene expression profile segregates toxicity in locally advanced breast cancer patients treated with high-dose hyperfractionated radical radiotherapy

    PubMed Central

    Henríquez Hernández, Luis Alberto; Lara, Pedro Carlos; Pinar, Beatriz; Bordón, Elisa; Gallego, Carlos Rodríguez; Bilbao, Cristina; Pérez, Leandro Fernández; Morales, Amílcar Flores

    2009-01-01

    Breast cancer patients show a wide variation in normal tissue reactions after radiotherapy. The individual sensitivity to x-rays limits the efficiency of the therapy. Prediction of individual sensitivity to radiotherapy could help to select the radiation protocol and to improve treatment results. The aim of this study was to assess the relationship between gene expression profiles of ex vivo un-irradiated and irradiated lymphocytes and the development of toxicity due to high-dose hyperfractionated radiotherapy in patients with locally advanced breast cancer. Raw data from microarray experiments were uploaded to the Gene Expression Omnibus Database (GEO accession GSE15341). We obtained a small group of 81 genes significantly regulated by radiotherapy, lumped in 50 relevant pathways. Using ANOVA and t-test statistical tools we found 20 and 26 constitutive genes (0 Gy) that segregate patients with and without acute and late toxicity, respectively. Non-supervised hierarchical clustering was used for the visualization of results. Six and 9 pathways were significantly regulated respectively. Concerning to irradiated lymphocytes (2 Gy), we founded 29 genes that separate patients with acute toxicity and without it. Those genes were gathered in 4 significant pathways. We could not identify a set of genes that segregates patients with and without late toxicity. In conclusion, we have found an association between the constitutive gene expression profile of peripheral blood lymphocytes and the development of acute and late toxicity in consecutive, unselected patients. These observations suggest the possibility of predicting normal tissue response to irradiation in high-dose non-conventional radiation therapy regimens. Prospective studies with higher number of patients are needed to validate these preliminary results. PMID:19497124

  7. High-Dose Weekly AmBisome Antifungal Prophylaxis in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation: A Pharmacokinetic Study

    PubMed Central

    Mehta, Parinda; Vinks, Alexander; Filipovich, Alexandra; Vaughn, Gretchen; Fearing, Deborah; Sper, Christine; Davies, Stella

    2016-01-01

    Disseminated fungal infection causes significant morbidity and mortality in children undergoing hematopoietic stem cell transplantation (HSCT). The widespread use of prophylactic oral triazoles has limitations of poor absorption, interindividual variability in metabolism, and hepatic toxicity. AmBisome (amphotericin B liposomal complex) has a better safety profile than the parent drug amphotericin B and produces higher plasma and tissue concentrations. We hypothesized that once-weekly high-dose AmBisome therapy could provide adequate fungal prophylaxis for immunocompromised children undergoing HSCT. We performed a pharmacokinetic pilot study to determine whether once-weekly high-dose AmBisome administration would result in effective concentrations throughout the dosing interval. A total of 14 children (median age, 3 years, 1 month; range, 4.5 months–9 years, 9 months) undergoing HSCT received once-weekly intravenous AmBisome prophylaxis (10 mg/kg as a 2-hour infusion). Blood samples for pharmacokinetic measurements were drawn around the first and the fourth weekly doses. The concentration of non–lipid-complexed amphotericin in plasma was determined by a validated bioassay. Pharmacokinetic parameters after single doses and during steady state were calculated using standard noncompartmental methods. AmBisome was well tolerated at this dose. Complete pharmacokinetic profiles for weeks 1 and 4 were obtained in 12 patients. The half-life calculated in this pediatric population was shorter on average than reported in adults (45 hours vs 152 hours). The volume of distribution correlated best with body weight (R2 = .55), and clearance was best predicted by initial serum creatinine level (R2 = .19). Mean (± standard deviation) individual plasma trough concentrations were 0.23 (0.13) mg/L after single doses and 0.47 (0.41) mg/L after multiple doses. Mean steady-state area under the curve was higher at week 4 than after a single dose (P < .05). Single-dose and steady

  8. Tandem high-dose chemotherapy strategy as first-line treatment of primary disseminated multifocal Ewing sarcomas in children, adolescents and young adults.

    PubMed

    Loschi, S; Dufour, C; Oberlin, O; Goma, G; Valteau-Couanet, D; Gaspar, N

    2015-08-01

    The prognosis of primary disseminated multifocal metastatic Ewing's sarcoma (PDMES) is poor even if a slight improvement has been achieved with high-dose alkylating agent-containing chemotherapy. To enhance treatment efficacy, we assessed the feasibility, safety and efficacy of a tandem high-dose chemotherapy (HDC) regimen. In a single institution, patients with PDMES received six courses of vincristine/ifosfamide/doxorubicin/etoposide induction therapy, followed by high-dose thiotepa, and then melphalan-busulfan, 8 weeks apart. Surgical resection of primary tumour was carried out between the two HDC regimens and 70 days after the last HDC regimen for post-operative radiotherapy or irradiation alone. From October 2002 to 2009, 13 of the 18 consecutive patients with PDMES (72%) received the full treatment programme. The other five patients experienced early progression and died. Among the 13 patients, 11 relapsed after the end of the treatment programme within 6 months (2.2-11.9) from end of therapy. Only two patients are still alive in first complete remission after 9 years. The 3-year event-free survival (EFS) and overall survival (OS) rates were 11 and 22%, respectively. The median EFS and OS duration from the diagnosis were 13.4 and 17.3 months, respectively. Neither major complications nor treatment-related death occurred. The tandem-HDC regimen was feasible, with expected side effects, but it did not improve the outcome of patients with PDMES. PMID:26030048

  9. Salmonella Typhi–Induced Septic Shock and Acute Respiratory Distress Syndrome in a Previously Healthy Teenage Patient Treated With High-Dose Dexamethasone

    PubMed Central

    Ugas, Melissa Brosset; Carroll, Timothy; Kovar, Lacey; Chavez-Bueno, Susana

    2016-01-01

    Typhoid fever is commonly characterized by fever and abdominal pain. Rare complications include intestinal hemorrhage, bowel perforation, delirium, obtundation, and septic shock. Herein we describe the case of a previously healthy 16-year-old male without history of travel, diagnosed with typhoid fever complicated by septic shock and acute respiratory distress syndrome treated with high-dose dexamethasone. This case details severe complications of typhoid fever that are uncommonly seen in developed countries, and the successful response to high-dose dexamethasone as adjunct therapy. High-dose dexamethasone treatment has reportedly decreased Salmonella Typhi mortality, but controlled studies specifically performed in children are lacking, and most reports of its use are over 30 years old and all have originated in developing countries. Providers should include Salmonella Typhi in the differential diagnosis of the pediatric patient with fever, severe abdominal pain, and enteritis, and be aware of its potentially severe complications and the limited data on safety and efficacy of adjunctive therapies that can be considered in addition to antibiotics. PMID:27294165

  10. Salmonella Typhi-Induced Septic Shock and Acute Respiratory Distress Syndrome in a Previously Healthy Teenage Patient Treated With High-Dose Dexamethasone.

    PubMed

    Ugas, Melissa Brosset; Carroll, Timothy; Kovar, Lacey; Chavez-Bueno, Susana

    2016-01-01

    Typhoid fever is commonly characterized by fever and abdominal pain. Rare complications include intestinal hemorrhage, bowel perforation, delirium, obtundation, and septic shock. Herein we describe the case of a previously healthy 16-year-old male without history of travel, diagnosed with typhoid fever complicated by septic shock and acute respiratory distress syndrome treated with high-dose dexamethasone. This case details severe complications of typhoid fever that are uncommonly seen in developed countries, and the successful response to high-dose dexamethasone as adjunct therapy. High-dose dexamethasone treatment has reportedly decreased Salmonella Typhi mortality, but controlled studies specifically performed in children are lacking, and most reports of its use are over 30 years old and all have originated in developing countries. Providers should include Salmonella Typhi in the differential diagnosis of the pediatric patient with fever, severe abdominal pain, and enteritis, and be aware of its potentially severe complications and the limited data on safety and efficacy of adjunctive therapies that can be considered in addition to antibiotics. PMID:27294165

  11. Radioiodinated O6-Benzylguanine Derivatives Containing an Azido Function

    PubMed Central

    Vaidyanathan, Ganesan; White, Benjamin; Affleck, Donna J.; McDougald, Darryl; Zalutsky, Michael R.

    2010-01-01

    Introduction Drug resistance to alkylator chemotherapy has been primarily attributed to the DNA repair protein alkylguanine-DNA alkyltransferase (AGT); thus, personalizing chemotherapy could be facilitated if tumor AGT content could be quantified prior to administering chemotherapy. We have been investigating the use of radiolabeled O6-benzylguanine (BG) analogues to label and quantify AGT in vivo. BG derivatives containing an azido function were sought to potentially enhance the targeting of these analogues to AGT, which is primarily present in the cell nucleus, either by conjugating them to nuclear localization sequence (NLS) peptides or by pretargeting via bioorthogonal approaches. Methods Two O6-(3-iodobenzyl)guanine (IBG) derivatives containing an azido moiety—O6-(4-azidohexyloxymethyl-3-iodobenzyl)guanine (AHOMIBG) and O6-(4-azido-3-iodobenzyl)guanine (AIBG)—and their tin precursors were synthesized in multiple steps and the tin precursors were converted to radioiodinated AHOMIBG and AIBG, respectively. Both unlabeled and radioiodinated AHOMIBG analogues were conjugated to alkyne-derivatized NLS peptide heptynoyl-PK3RKV. The ability of these radioiodinated compounds to bind to AGT was determined by a trichloroacetic acid precipitation assays and gel electrophoresis/phosphor imaging. Labeling of an AGT-AIBG conjugate via Staudinger ligation using the 131I-labeled phosphine ligand, 2-(diphenylphosphino)phenyl 4-[131I]iodobenzoate, also was investigated. Results [131I]AHOMIBG was synthesized in two steps from its tin precursor in 52.2 ± 7.5% (n = 5) radiochemical yield and conjugated to the NLS peptide via click reaction in 50.7 ± 4.9% (n = 6) yield. The protected tin precursor of AIBG was radioiodinated in an average radiochemical yield of 69.6 ± 4.5% (n = 7); deprotection of the intermediate gave [131I]AIBG in 17.8 ± 4.2% (n = 9) yield. While both [131I]AHOMIBG and its NLS conjugate bound to AGT pure protein, their potency as a substrate for AGT was

  12. Juvenile hypothyroidism among two populations exposed to radioiodine.

    PubMed Central

    Goldsmith, J R; Grossman, C M; Morton, W E; Nussbaum, R H; Kordysh, E A; Quastel, M R; Sobel, R B; Nussbaum, F D

    1999-01-01

    We found an epidemic of juvenile hypothyroidism among a population of self-defined "downwinders" living near the Hanford nuclear facility located in southeast Washington State. The episode followed massive releases of 131I. Self-reported data on 60 cases of juvenile hypothyroidism (<20 years of age) among a group of 801 Hanford downwinders are presented, as well as data concerning the thyroid status of approximately 160,000 children exposed to radioiodine before 10 years of age as a result of the 26 April 1986 Chernobyl explosion in the former Soviet Union. These children were residents of five regions near Chernobyl. They were examined by standardized screening protocols over a period of 5 years from 1991 to 1996. They are a well-defined group of 10 samples. Fifty-six cases of hypothyroidism were found among boys and 92 among girls. Body burdens of 137Cs have been correlated with hypothyroidism prevalence rates. On the other hand, the group of juvenile (<20 years of age) Hanford downwinders is not a representative sample. Most of the 77 cases of juvenile hypothyroidism in the Hanford group were diagnosed from 1945 to 1970. However, the ratio of reported cases to the county population under 20 years of age is roughly correlated with officially estimated mean levels of cumulative thyroid 131I uptake in these counties, providing evidence that juvenile hypothyroidism was associated with radioiodine exposures. Because even subtle hypothyroidism may be of clinical significance in childhood and can be treated, it may be useful to screen for the condition in populations exposed to radioiodine fallout. Although radiation exposure is associated with hypothyroidism, its excess among fallout-exposed children has not been previously quantified. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:10090710

  13. Extraction, radioiodination, and in vivo catabolism of equine fibrinogen

    SciTech Connect

    Coyne, C.P.; Hornof, W.J.; Kelly, A.B.; O'Brien, T.R.; DeNardo, S.J.

    1985-12-01

    Equine fibrinogen was isolated and aliquots were stored frozen at -70 C before radiolabeling with 125I (half-life = 60.2 days; gamma = 35 keV, using monochloroiodine reagent. Radioiodination efficiencies were 49% to 53%, resulting in a labeled product with 98% protein-bound activity and 91% clottable radioactivity. In 6 equine in vivo investigations, plasma half-lives of 125I-labeled fibrinogen were from 4.1 to 5.2 days, corresponding to a mean daily plasma elimination rate of approximately 15%.

  14. From prophylaxis to atomic cocktail: circulation of radioiodine.

    PubMed

    Santesmases, María Jesús

    2009-01-01

    This paper is a history of iodine. To trace the trajectory of this element, goiter is used as a guideline for the articulation of a historical account, as a representation of thyroid disorders and of the spaces of knowledge and practices related to iodine. Iodine's journey from goiter treatment and prophylaxis in the late interwar period took on a new course after WWII by including the element's radioactive isotopes. I intend to show how the introduction of radioiodine contributed to stabilize the epistemic role of iodine, in both its non-radioactive and radioactive form, in thyroid gland studies and in the treatment of its disorders. PMID:19852395

  15. [Radionuclide therapy for cancer--what's new?].

    PubMed

    Hanna, Mäenpää; Mikko, Tenhunen

    2012-01-01

    Radionuclide therapy is radiation therapy, the effect of which is based on radiation damage in cancer cells. The most common radionuclide therapy for cancer is radioiodine therapy for thyroid cancer. Two new forms of treatment have recently been initiated in Finland: 177lutetium octreotate therapy for neuroendocrine tumors, pheochromocytoma and paraganglioma as well as radioembolization (selective internal radiation therapy, SIRT) with 90yttrium-coated resin beads against liver metastases. Still in experimental use, 223radium chloride is a drug prolonging survival in prostate cancer that has metastasized to bone. The treatments require special knowledge and collaboration between several units. PMID:23210283

  16. Implementation of a High-Dose-Rate Brachytherapy Program for Carcinoma of the Cervix in Senegal: A Pragmatic Model for the Developing World

    SciTech Connect

    Einck, John P.; Hudson, Alana; Shulman, Adam C.; Yashar, Catheryn M.; Dieng, Mamadou M.; Diagne, Magatte; Gueye, Latifatou; Gningue, Fama; Gaye, Pape M.; Fisher, Brandon J.; Mundt, Arno J.; Brown, Derek W.

    2014-07-01

    West Africa has one of the highest incidence rates of carcinoma of the cervix in the world. The vast majority of women do not have access to screening or disease treatment, leading to presentation at advanced stages and to high mortality rates. Compounding this problem is the lack of radiation treatment facilities in Senegal and many other parts of the African continent. Senegal, a country of 13 million people, had a single {sup 60}Co teletherapy unit before our involvement and no brachytherapy capabilities. Radiating Hope, a nonprofit organization whose mission is to provide radiation therapy equipment to countries in the developing world, provided a high-dose-rate afterloading unit to the cancer center for curative cervical cancer treatment. Here we describe the implementation of high-dose-rate brachytherapy in Senegal requiring a nonstandard fractionation schedule and a novel treatment planning approach as a possible blueprint to providing this technology to other developing countries.

  17. False-positive uptake on radioiodine whole-body scintigraphy: physiologic and pathologic variants unrelated to thyroid cancer

    PubMed Central

    Oh, Jong-Ryool; Ahn, Byeong-Cheol

    2012-01-01

    Radioiodine whole-body scintigraphy (WBS), which takes advantage of the high avidity of radioiodine in the functioning thyroid tissues, has been used for detection of differentiated thyroid cancer. Radioiodine is a sensitive marker for detection of thyroid cancer; however, radioiodine uptake is not specific for thyroid tissue. It can also be seen in healthy tissue, including thymus, breast, liver, and gastrointestinal tract, or in benign diseases, such as cysts and inflammation, or in a variety of benign and malignant non-thyroidal tumors, which could be mistaken for thyroid cancer. In order to accurately interpret radioiodine scintigraphy results, one must be familiar with the normal physiologic distribution of the tracer and frequently encountered physiologic and pathologic variants of radioiodine uptake. This article will provide a systematic overview of potential false-positive uptake of radioiodine in the whole body and illustrate how such unexpected findings can be appropriately evaluated. PMID:23133823

  18. Testicular function in patients with differentiated thyroid carcinoma treated with radioiodine

    SciTech Connect

    Pacini, F.; Gasperi, M.; Fugazzola, L.

    1994-09-01

    The aim of the present study was to assess whether {sup 131}I therapy for differentiated thyroid carcinoma (DTC) can affect endocrine testicular function. Serum follicle-stimulating hormone (FSH) and testosterone (T) concentrations were measured in 103 patients periodically submitted for radioiodine therapy for residual or metastatic disease. Mean follow-up was 93.7{+-}54 mo (range 10-243 mo). Mean FSH values in {sup 131}I-treated patients tested after their last treatment were 15.3{+-}9.9 mU/ml, significantly higher than those of 19 untreated patients (6.5{+-}3.1 mU/ml). Considering the mean +3 s.d. FSH of untreated subjects as the upper limit of normal range, 36.8% of the patients had an abnormal increase in serum FSH. Longitudinal analysis performed in 21 patients showed that the behavior of FSH in response to {sup 131}I therapy was not universal. Six patients had no change or a slight increase in serum FSH after {sup 131}I administration; eleven patients had a transient increase above normal values 6-12 mo after {sup 131}I treatment, with return to normal levels in subsequent months. The administration of a second dose was followed by a similar increase in FSH levels. Finally, four patients, followed for a long period of time and treated with several {sup 131}I doses, showed a progressive increase in serum FSH, which eventually became permanent. Semen analysis, performed in a small subgroup of patients, showed a consistent reduction in the number of normokinetic sperm. No change was found in serum T levels between treated and untreated patients. The results indicate that {sup 131}I therapy for thyroid carcinoma is associated with transient impairment of testicular germinal cell function. The damage may become permanent for high-radiation activities delivered year after year and might pose a significant risk of infertility. 14 refs., 8 figs., 1 tab.

  19. Acute and late toxicity following adjuvant high-dose chemotherapy for high-risk primary operable breast cancer--a quality assessment study.

    PubMed

    Svane, Inge M; Homburg, Keld M; Kamby, Claus; Nielsen, Dorte L; Roer, Ole; Sliffsgaard, Dorte; Johnsen, Hans E; Hansen, Steen W

    2002-01-01

    From 1996 to 2000, high-dose chemotherapy with haematopoietic stem-cell support was used as an adjuvant treatment strategy for management of primary high-risk breast cancer patients with more than five positive nodes. This single institution study included 52 women aged < or = 56 years with primary operable breast cancer and > or = 6 tumour-positive axillary lymph nodes. The treatment regimen consisted of at least three initial courses of FEC (5-fluorouracil, epirubicin, cyclophosphamide) followed by high-dose chemotherapy (cyclophosphamide, thiotepa, carboplatin) supported by autologous peripheral blood stem-cell reinfusion. This study focuses on quality control including evaluation of toxicity, supportive therapy and assessment of the stem-cell products. Cytokeratin 19 positive cells were found in the stem-cell product from 3/37 patients. Data regarding organ toxicity were used for evaluation of short- and long-term side effects. Substantial acute toxicity and frequent catheter-related infections were found. Long-term toxicities included reduced lung diffusion capacity (n = 36), fatigue (n = 14), arthralgia/myalgia (n = 10), neurotoxicity (n = 9) and memory loss (n = 4). However, most toxicities were grade 1-2 and reversible within two years. No treatment-related death occurred. Within a median follow-up of 30 months (range, 11-57), 25% of the patients had relapsed. Recurrence-free survival was 75% and overall survival was 88% three years after the start of treatment. Overall, high-dose chemotherapy was relatively well tolerated, with manageable toxicity and an acceptable requirement of supportive therapy. Until now, high-dose chemotherapy has not proven superior to conventional-dose adjuvant chemotherapy, therefore it is necessary in the future to focus on well-designed randomized studies. PMID:14651213

  20. High dose rate sources in remote afterloading brachytherapy: Implications for intracavitary and interstitial treatment of carcinoma

    SciTech Connect

    Syzek, E.J.; Bogardus, C.R. Jr. )

    1990-11-01

    Remote afterloading brachytherapy provides effective cancer treatment with zero personnel radiation exposure compared to conventional low dose rate systems requiring inpatient use of iridium, radium, or cesium sources. Clinical use of high dose rate brachytherapy is broadened to encompass curative treatment of cervical, endometrial, endobronchial, head and neck, esophageal, rectal, and prostatic carcinomas as well as palliation of intra-abdominal metastasis intraoperatively. Complications encountered with high dose rate sources will be compared to those of low dose rate systems commonly used in conjunction with external beam irradiation. Radiobiological effectiveness and economic benefits will be addressed to provide support for use of remote afterloading using high dose rate brachytherapy in palliative and curative treatment of selected carcinoma. 36 refs.

  1. Gene expression profiling in undifferentiated thyroid carcinoma induced by high-dose radiation.

    PubMed

    Bang, Hyun Soon; Choi, Moo Hyun; Kim, Cha Soon; Choi, Seung Jin

    2016-06-01

    Published gene expression studies for radiation-induced thyroid carcinogenesis have used various methodologies. In this study, we identified differential gene expression in a human thyroid epithelial cell line after exposure to high-dose γ-radiation. HTori-3 cells were exposed to 5 or 10 Gy of ionizing radiation using two dose rates (high-dose rate: 4.68 Gy/min, and low-dose rate: 40 mGy/h) and then implanted into the backs of BALB/c nude mice after 4 (10 Gy) or 5 weeks (5 Gy). Decreases in cell viability, increases in giant cell frequency, anchorage-independent growth in vitro, and tumorigenicity in vivo were observed. Particularly, the cells irradiated with 5 Gy at the high-dose rate or 10 Gy at the low-dose rate demonstrated more prominent tumorigenicity. Gene expression profiling was analyzed via microarray. Numerous genes that were significantly altered by a fold-change of >50% following irradiation were identified in each group. Gene expression analysis identified six commonly misregulated genes, including CRYAB, IL-18, ZNF845, CYP24A1, OR4N4 and VN1R4, at all doses. These genes involve apoptosis, the immune response, regulation of transcription, and receptor signaling pathways. Overall, the altered genes in high-dose rate (HDR) 5 Gy and low-dose rate (LDR) 10 Gy were more than those of LDR 5 Gy and HDR 10 Gy. Thus, we investigated genes associated with aggressive tumor development using the two dosage treatments. In this study, the identified gene expression profiles reflect the molecular response following high doses of external radiation exposure and may provide helpful information about radiation-induced thyroid tumors in the high-dose range. PMID:27006382

  2. Gene expression profiling in undifferentiated thyroid carcinoma induced by high-dose radiation

    PubMed Central

    Bang, Hyun Soon; Choi, Moo Hyun; Kim, Cha Soon; Choi, Seung Jin

    2016-01-01

    Published gene expression studies for radiation-induced thyroid carcinogenesis have used various methodologies. In this study, we identified differential gene expression in a human thyroid epithelial cell line after exposure to high-dose γ-radiation. HTori-3 cells were exposed to 5 or 10 Gy of ionizing radiation using two dose rates (high-dose rate: 4.68 Gy/min, and low-dose rate: 40 mGy/h) and then implanted into the backs of BALB/c nude mice after 4 (10 Gy) or 5 weeks (5 Gy). Decreases in cell viability, increases in giant cell frequency, anchorage-independent growth in vitro, and tumorigenicity in vivo were observed. Particularly, the cells irradiated with 5 Gy at the high-dose rate or 10 Gy at the low-dose rate demonstrated more prominent tumorigenicity. Gene expression profiling was analyzed via microarray. Numerous genes that were significantly altered by a fold-change of >50% following irradiation were identified in each group. Gene expression analysis identified six commonly misregulated genes, including CRYAB, IL-18, ZNF845, CYP24A1, OR4N4 and VN1R4, at all doses. These genes involve apoptosis, the immune response, regulation of transcription, and receptor signaling pathways. Overall, the altered genes in high-dose rate (HDR) 5 Gy and low-dose rate (LDR) 10 Gy were more than those of LDR 5 Gy and HDR 10 Gy. Thus, we investigated genes associated with aggressive tumor development using the two dosage treatments. In this study, the identified gene expression profiles reflect the molecular response following high doses of external radiation exposure and may provide helpful information about radiation-induced thyroid tumors in the high-dose range. PMID:27006382

  3. High-dose gammaglobulin (IVIG) followed by intrauterine transfusions (IUTs): a new alternative for the treatment of severe fetal hemolytic disease.

    PubMed

    Voto, L S; Mathet, E R; Zapaterio, J L; Orti, J; Lede, R L; Margulies, M

    1997-01-01

    Intrauterine fetal transfusion is currently the therapy of choice in cases of severe anti-D isoimmunisation. However, its efficacy is reduced in patients with early severe hydrops fetalis due to the technical difficulties in performing this procedure before 20 weeks' gestation. The purpose of this study was to determine whether early onset of high-dose gammaglobulin therapy followed by intrauterine transfusions (IUTs) is more effective than IUTs alone in the treatment of very severe isoimmunised fetuses. The population studied in this retrospective clinical research was assigned to one of the following two groups: 1) Gamma group: 30 patients receiving gammaglobulin therapy before 21 weeks' gestation and IUTs after 20 weeks; or 2) IUT group: 39 patients receiving IUT treatment starting at a gestational age of 20-25 weeks. Both groups were statistically similar regarding history of perinatal deaths and anti-D antibody titers. The number of hydropic fetuses at the first IUT and of fetal deaths were significantly higher in the IUT than in the Gamma group. No significant differences were observed between the groups in fetal hematocrit at first IUT and at birth. However, the percentage of severely anemic fetuses was higher in the IUT group. Fetal mortality rate was 36% less in the Gamma group. Our results suggest that high-dose gammaglobulin therapy followed by IUTs may improve fetal survival in these severe cases. Further randomised clinical trials are needed to confirm these results. PMID:9085208

  4. Experiment and DFT studies on radioiodine removal and storage mechanism by imidazolium-based ionic liquid.

    PubMed

    Cao, Bobo; Liu, Shuangyue; Du, Dongmei; Xue, Zhimin; Fu, Hui; Sun, Haitao

    2016-03-01

    In order to remove and store radioactive substances effectively, studies on the mechanisms of radioiodine captured by ionic liquids (ILs) with a fixed cation (1-butyl-3-methyl-imidazolium cation [Bmim]+) were carried out in experimental and theoretical methods. Fourier transform infrared attenuated total reflectance (FT-IR ATR) spectra of 2BP8HQ and ultraviolet-visible (UV/vis) spectroscopy were used to investigate the kinetic process of radioiodine removal by ILs in experiment. Corresponding theoretical investigations on the structures and formation mechanisms of ILs, bare anions and complexes as well as hydrogen bonds was carried using density functional theory. The electrostatic potential was used in configuration design and construction. Charge distribution was used to show the variation of atom charge density, Interaction energy and vibration frequency change were performed to explore possible mechanisms on the halogen bond formation between radioiodine molecule and bare anion or anion in ILs when radioiodine captured by ILs. In order to characterize halogen bonds both natural bond orbital analysis and atoms in molecules analysis were performed. Both experimental and computational results showed that radioiodine could be captured by ILs with a 1:1mol stoichiometry. It was noteworthy that [Bmim][Br], [Bmim][I] and [Bmim][Cl], containing high radioiodine capture efficiency anions, were better candidates in removal and reliable storage of radioiodine for their capture efficiencies of over 80% in 5h. PMID:26774640

  5. SPECT/CT evaluation of unusual physiologic radioiodine biodistributions: pearls and pitfalls in image interpretation.

    PubMed

    Glazer, Daniel I; Brown, Richard K J; Wong, Ka Kit; Savas, Hatice; Gross, Milton D; Avram, Anca M

    2013-01-01

    Radioiodine imaging has a well-established role in depicting metastatic disease after thyroidectomy in patients with well-differentiated thyroid cancer. Uptake of radioiodine in thyroid metastases depends on expression of sodium-iodide symporter (NIS) by tumor tissues. However, because radioiodine may also accumulate in normal structures and tissues, it is important to distinguish physiologic radioiodine activity from metastatic disease. Furthermore, secretions that contain radioiodine may also simulate pathologic uptake. A spectrum of physiologic distributions, normal variants, and benign mimics of disease have been described in the literature; yet, even when armed with a comprehensive knowledge of these patterns, interpreting radiologists and nuclear physicians may still encounter diagnostic uncertainty. Single-photon emission computed tomography (SPECT) with integrated computed tomography (CT) is a novel technology that, when applied to diagnostic iodine 123 or iodine 131 ((131)I) radioiodine scintigraphy, may accurately localize and help distinguish benign mimics of disease, with the potential to alter the management plan. SPECT/CT is increasingly being used with radioiodine scintigraphy to evaluate patients with thyroid cancer and shows promise for improving imaging specificity and reducing false-positive results. PMID:23479704

  6. Dose rate in brachytherapy using after-loading machine: pulsed or high-dose rate?

    PubMed

    Hannoun-Lévi, J-M; Peiffert, D

    2014-10-01

    Since February 2014, it is no longer possible to use low-dose rate 192 iridium wires due to the end of industrial production of IRF1 and IRF2 sources. The Brachytherapy Group of the French society of radiation oncology (GC-SFRO) has recommended switching from iridium wires to after-loading machines. Two types of after-loading machines are currently available, based on the dose rate used: pulsed-dose rate or high-dose rate. In this article, we propose a comparative analysis between pulsed-dose rate and high-dose rate brachytherapy, based on biological, technological, organizational and financial considerations. PMID:25195117

  7. High-dose neuroleptics: uncontrolled clinical practice confirms controlled clinical trials.

    PubMed

    Bollini, P; Andreani, A; Colombo, F; Bellantuono, C; Beretta, P; Arduini, A; Galli, T; Tognoni, G

    1984-01-01

    The strategy of high-dose intramuscular haloperidol as routinely applied in a general hospital psychiatric ward to 74 successive patients, 33 of whom stayed only up to seven days, and a further 34 up to 15 days, led to a complete recovery in only six, and complete lack of change in 23. Adverse reactions were recorded in 42, severe enough to stop treatment in eight; there were three deaths. In view of this risk-benefit analysis, systematic application of this high dose strategy to get a more rapid turnover of patients is unjustified. PMID:6692073

  8. Efficacy of High-Dose Baclofen for Alcohol Use Disorder and Comorbid Bulimia: A Case Report.

    PubMed

    Weibel, Sébastien; Lalanne, Laurence; Riegert, Myriam; Bertschy, Gilles

    2015-01-01

    High-dose baclofen is a promising treatment for alcohol use disorder, with a specific action on craving. A more general action on craving in other addictive disorders has been suggested based on the hypothesis of a common neurobiological pathway in addictions. We report the case of a woman with both alcohol use disorder and bulimia nervosa. There was a positive response to high-dose baclofen on alcohol craving, but no response on food craving. The case illustrates that craving could be differentially responsive to anti-craving drugs. PMID:26457456

  9. Vitamin E ameliorates high dose trans-dehydrocrotonin-associated hepatic damage in mice.

    PubMed

    Rabelo, Alana Fontales Lima; Guedes, Marjorie Moreira; Tomé, Adriana da Rocha; Lima, Patricia Rodrigues; Maciel, Maria Aparecida; Lira, Silveria Regina de Sousa; Carvalho, Ana Carla da Silva; Santos, Flávia Almeida; Rao, Vietla Satyanarayana

    2010-04-01

    trans-Dehydrocrotonin (t-DCTN), the diterpenoid from Croton cajucara Bentham, exhibits hypoglycemic and hypolipidemic activities, but in high doses is associated with a discrete hepatotoxicity. In the search for measures to mitigate this, pretreatment with the antioxidants N-acetylcysteine and vitamin E has been examined. Mice that received a high dose t-DCTN (100 mg/kg) manifested hepatic damage, as evidenced by significant elevations in serum ALT and AST, and hepatic GSH, and histological alterations, which could be obliterated by pretreatment with vitamin E, but not with N-acetylcysteine, possibly by creating an effective antioxidant balance. PMID:20433064

  10. Predictors of Toxicity After Image-guided High-dose-rate Interstitial Brachytherapy for Gynecologic Cancer

    SciTech Connect

    Lee, Larissa J.; Viswanathan, Akila N.

    2012-12-01

    Purpose: To identify predictors of grade 3-4 complications and grade 2-4 rectal toxicity after three-dimensional image-guided high-dose-rate (HDR) interstitial brachytherapy for gynecologic cancer. Methods and Materials: Records were reviewed for 51 women (22 with primary disease and 29 with recurrence) treated with HDR interstitial brachytherapy. A single interstitial insertion was performed with image guidance by computed tomography (n = 43) or magnetic resonance imaging (n = 8). The median delivered dose in equivalent 2-Gy fractions was 72.0 Gy (45 Gy for external-beam radiation therapy and 24 Gy for brachytherapy). Toxicity was reported according to the Common Toxicity Criteria for Adverse Events. Actuarial toxicity estimates were calculated by the Kaplan-Meier method. Results: At diagnosis, the median patient age was 62 years and the median tumor size was 3.8 cm. The median D90 and V100 were 71.4 Gy and 89.5%; the median D2cc for the bladder, rectum, and sigmoid were 64.6 Gy, 61.0 Gy, and 52.7 Gy, respectively. The actuarial rates of all grade 3-4 complications at 2 years were 20% gastrointestinal, 9% vaginal, 6% skin, 3% musculoskeletal, and 2% lymphatic. There were no grade 3-4 genitourinary complications and no grade 5 toxicities. Grade 2-4 rectal toxicity was observed in 10 patients, and grade 3-4 complications in 4; all cases were proctitis with the exception of 1 rectal fistula. D2cc for rectum was higher for patients with grade 2-4 (68 Gy vs 57 Gy for grade 0-1, P=.03) and grade 3-4 (73 Gy vs 58 Gy for grade 0-2, P=.02) rectal toxicity. The estimated dose that resulted in a 10% risk of grade 2-4 rectal toxicity was 61.8 Gy (95% confidence interval, 51.5-72.2 Gy). Discussion: Image-guided HDR interstitial brachytherapy results in acceptable toxicity for women with primary or recurrent gynecologic cancer. D2cc for the rectum is a reliable predictor of late rectal complications. Three-dimensional-based treatment planning should be performed to ensure

  11. Monte Carlo Study of Radiation Dose Enhancement by Gadolinium in Megavoltage and High Dose Rate Radiotherapy

    PubMed Central

    Zhang, Daniel G.; Feygelman, Vladimir; Moros, Eduardo G.; Latifi, Kujtim; Zhang, Geoffrey G.

    2014-01-01

    MRI is often used in tumor localization for radiotherapy treatment planning, with gadolinium (Gd)-containing materials often introduced as a contrast agent. Motexafin gadolinium is a novel radiosensitizer currently being studied in clinical trials. The nanoparticle technologies can target tumors with high concentration of high-Z materials. This Monte Carlo study is the first detailed quantitative investigation of high-Z material Gd-induced dose enhancement in megavoltage external beam photon therapy. BEAMnrc, a radiotherapy Monte Carlo simulation package, was used to calculate dose enhancement as a function of Gd concentration. Published phase space files for the TrueBeam flattening filter free (FFF) and conventional flattened 6MV photon beams were used. High dose rate (HDR) brachytherapy with Ir-192 source was also investigated as a reference. The energy spectra difference caused a dose enhancement difference between the two beams. Since the Ir-192 photons have lower energy yet, the photoelectric effect in the presence of Gd leads to even higher dose enhancement in HDR. At depth of 1.8 cm, the percent mean dose enhancement for the FFF beam was 0.38±0.12, 1.39±0.21, 2.51±0.34, 3.59±0.26, and 4.59±0.34 for Gd concentrations of 1, 5, 10, 15, and 20 mg/mL, respectively. The corresponding values for the flattened beam were 0.09±0.14, 0.50±0.28, 1.19±0.29, 1.68±0.39, and 2.34±0.24. For Ir-192 with direct contact, the enhanced were 0.50±0.14, 2.79±0.17, 5.49±0.12, 8.19±0.14, and 10.80±0.13. Gd-containing materials used in MRI as contrast agents can also potentially serve as radiosensitizers in radiotherapy. This study demonstrates that Gd can be used to enhance radiation dose in target volumes not only in HDR brachytherapy, but also in 6 MV FFF external beam radiotherapy, but higher than the currently used clinical concentration (>5 mg/mL) would be needed. PMID:25275550

  12. Concomitant cervical and transperineal parametrial high-dose-rate brachytherapy boost for locally advanced cervical cancer

    PubMed Central

    Bailleux, Caroline; Falk, Alexander Tuan; Chand-Fouche, Marie-Eve; Gautier, Mathieu; Barranger, Emmanuel

    2016-01-01

    Purpose There is no consensus for parametrial boost technic while both transvaginal and transperineal approaches are discussed. A prototype was developed consisting of a perineal template, allowing transperineal needle insertion. This study analyzed acute toxicity of concomitant cervical and transperineal parametrial high-dose-rate brachytherapy (HDRB) boost for locally advanced cervical cancer. Material and methods From 01.2011 to 12.2014, 33 patients (pts) presenting a locally advanced cervical cancer with parametrial invasion were treated. After the first course of external beam radiation therapy with cisplatinum, HDRB was performed combining endocavitary and interstitial technique for cervical and parametrial disease. Post-operative delineation (CTV, bladder, rectum, sigmoid) and planification were based on CT-scan/MRI. HDRB was delivered in 3-5 fractions over 2-3 consecutive days. Acute toxicities occurring within 6 months after HDRB were retrospectively reviewed. Results Median age was 56.4 years (27-79). Clinical stages were: T2b = 23 pts (69.7%), T3a = 1 pt (3%), T3b = 6 pts (18.2%), and T4a = 3 pts (9.1%). Median HDRB prescribed dose was 21 Gy (21-27). Median CTVCT (16 pts) and HR-CTVMRI (17 pts) were 52.6 cc (28.5-74.3), 31.9 cc (17.1-58), respectively. Median EQD2αβ10 for D90CTV and D90HR-CTV were 82.9 Gy (78.2-96.5), 84.8 Gy (80.6-91.4), respectively. Median EQD2αβ3 (CT/MRI) for D2cc bladder, rectum and sigmoid were 75.5 Gy (66.6-90.9), 64.4 Gy (51.9-77.4), and 60.4 Gy (50.9-81.1), respectively. Median follow-up was 14 months (ranged 6-51). Among the 24 pts with MFU = 24 months, 2-year LRFS rate, RRFS, and OS were 86.8%, 88.8%, and 94.1%, respectively. The rates of acute genitourinary and gastrointestinal toxicities were 36% (G1 dysuria = 8 pts, G2 infection = 2 pts, G3 infection = 2 pts), and 27% (G1 diarrhea = 9 pts), respectively. One patient presented vaginal bleeding at the time of applicator withdrawal (G3-blood transfusion); no bleeding was

  13. Savannah River Site radioiodine atmospheric releases and offsite maximum doses

    SciTech Connect

    Marter, W.L.

    1990-11-01

    Radioisotopes of iodine have been released to the atmosphere from the Savannah River Site since 1955. The releases, mostly from the 200-F and 200-H Chemical Separations areas, consist of the isotopes, I-129 and 1-131. Small amounts of 1-131 and 1-133 have also been released from reactor facilities and the Savannah River Laboratory. This reference memorandum was issued to summarize our current knowledge of releases of radioiodines and resultant maximum offsite doses. This memorandum supplements the reference memorandum by providing more detailed supporting technical information. Doses reported in this memorandum from consumption of the milk containing the highest I-131 concentration following the 1961 1-131 release incident are about 1% higher than reported in the reference memorandum. This is the result of using unrounded 1-131 concentrations of I-131 in milk in this memo. It is emphasized here that this technical report does not constitute a dose reconstruction in the same sense as the dose reconstruction effort currently underway at Hanford. This report uses existing published data for radioiodine releases and existing transport and dosimetry models.

  14. The acute effect of high-dose intravenous vitamin C and other nutrients on blood pressure: a cohort study

    PubMed Central

    Travica, Nikolaj; Sali, Avni

    2016-01-01

    Background Regular intake of vitamin C/ascorbate reduces blood pressure (BP) in hypertensives. High-dose intravenous vitamin C (IVC) achieves higher plasma levels; however, there is a paucity of research on acute BP effects. Our study is the first to investigate the effect of high-dose IVC, with or without concomitant i.v. nutrients, on BP during i.v. treatment. Methods A cohort of adult patients scheduled to receive IVC treatment for infection, cancer or fatigue, as prescribed by their treating doctor, participated at a Melbourne clinic, Australia. Ambulatory BP was assessed every 10 min over 90 min during i.v. treatment. Patients received 15–100 g of IVC alone or in addition to i.v. vitamin B, glutathione, magnesium or zinc. BP change over time adjusted for baseline BP, IVC dosage, i.v. treatment and BMI was analysed. Results A total of 77 mostly normotensive patients participated, with a third receiving IVC alone (42±20 g), and two-thirds also received other i.v. nutrients. IVC alone (>30 g) reduced the mean BP up to 8–9 mmHg in prehypertensive patients. In contrast, concomitant intravenous vitamin B12 (IVB12) significantly increased the mean BP by 11–13 mmHg. Comparison of BP change during IVC versus IVC+IVB12 indicated a highly significant difference [systolic blood pressure: mean difference (SD)=16.6 (17.8) mmHg, P<0.001; diastolic blood pressure: mean difference (SD)=12.5 (16.7) mmHg, P=0.003]. Conclusion Our study suggests an acute BP-reducing effect of high-dose IVC, particularly with dosages above 30 g, and in patients with prehypertension and normal BMI. Furthermore, our study indicated a marked and clinically relevant hypertensive effect of IVB12, suggesting routine BP monitoring during i.v. therapy in clinical practice. PMID:26910646

  15. Prolongation of survival for high-grade malignant gliomas with adjuvant high-dose BCNU and autologous bone marrow transplantation.

    PubMed

    Johnson, D B; Thompson, J M; Corwin, J A; Mosley, K R; Smith, M T; de los Reyes, R A; Daly, M B; Petty, A M; Lamaster, D; Pierson, W P

    1987-05-01

    projected median survival of 26 months (P = .007). This new approach using early postoperative intensive therapy consisting of high-dose BCNU, autologous bone marrow transplantation, and whole brain irradiation appears to significantly improve survival. PMID:3553437

  16. Investigations of DNA damage induction and repair resulting from cellular exposure to high dose-rate pulsed proton beams

    NASA Astrophysics Data System (ADS)

    Renis, M.; Borghesi, M.; Favetta, M.; Malfa, G.; Manti, L.; Romano, F.; Schettino, G.; Tomasello, B.; Cirrone, G. A. P.

    2013-07-01

    Studies regarding the radiobiological effects of low dose radiation, microbeam irradiation services have been developed in the world and today laser acceleration of protons and heavy ions may be used in radiation therapy. The application of different facilities is essential for studying bystander effects and relating signalling phenomena in different cells or tissues. In particular the use of ion beams results advantageous in cancer radiotherapy compared to more commonly used X-rays, since the ability of ions in delivering lethal amount of doses into the target tumour avoiding or limiting damage to the contiguous healthy tissues. At the INFN-LNS in Catania, a multidisciplinary radiobiology group is strategically structured aimed to develop radiobiological research, finalised to therapeutic applications, compatible with the use of high dose laser-driven ion beams. The characteristic non-continuous dose rates with several orders of magnitude of laser-driven ion beams makes this facility very interesting in the cellular systems' response to ultra-high dose rates wit